text
stringlengths 11
9.77k
| label
stringlengths 2
104
|
|---|---|
The first International classification of headache disorders (ICHD-I) described migraine as a recurring headache disorder manifesting in attacks lasting 4-72 h. The headache frequency was not considered in these first diagnostic criteria of migraine. Thus, a chronic migraine with at least 15 migraine days per month was only included in the ICHD-II in 2004. Meanwhile, the diagnosis of chronic daily headache and transformed migraine had been established in the USA. The term transformed migraine describes the transformation of an episodic migraine into a chronic one, whether medication overuse had been present or not. Up till now a widely accepted definition of chronic migraine and medication overuse headache has not been established due to different views. An overview of the evolution of the diagnostic criteria for both headache disorders in recent years is provided. | Headache Disorders |
Although chlorinated organophosphate esters (Cl-OPEs) have been reported to be ubiquitously distributed in various anoxic environments, little information is available on their fate under anoxic conditions. In this study, we report two Dehalococcoides-containing enrichment cultures that transformed 3.88 +/- 0.22 mumol tris(2-chloroethyl) phosphate (TCEP) and 2.61 +/- 0.02 mumol tris(1-chloro-2-propyl) phosphate (TCPP) within 10 days. Based on the identification of the transformed products and deuteration experiments, we inferred that TCEP may be transformed to generate bis(2-chloroethyl) phosphate and ethene via one-electron transfer (radical mechanism), followed by C-O bond cleavage. Ethene was subsequently reduced to ethane. Similarly, TCPP was transformed to form bis(1-chloro-2-propyl) phosphate and propene. 16S rRNA gene amplicon sequencing and quantitative polymerase chain reaction analysis revealed that Dehalococcoides was the predominant contributor to the transformation of TCEP and TCPP. Two draft genomes of Dehalococcoides assembled from the metagenomes of the TCEP- and TCPP-transforming enrichment cultures contained 14 and 15 putative reductive dehalogenase (rdh) genes, respectively. Most of these rdh genes were actively transcribed, suggesting that they might contribute to the transformation of TCEP and TCPP. Taken together, this study provides insights into the role of Dehalococcoides during the transformation of representative Cl-OPEs. | Dehalococcoides |
Two new flavanol-flavonol C(4)(C) to C(5)(D) linked promelacacinidin dimers were isolated from the heartwood of Acacia nigrescens. Their structures were elucidated by extensive (1)H and (13)C NMR spectroscopic studies, and the main conformational features are discussed. | Acacia |
The definition of the node of the last universal common ancestor (LUCA) is justified in a topology of the unrooted universal tree. This definition allows previous analyses based on paralogous proteins to be extended to orthologous ones. In particular, the use of a thermophily index (based on the amino acids' propensity to enter the [hyper] thermophile proteins more frequently) and its correlation with the optimal growth temperature of the various organisms allow inferences to be made on the habitat in which the LUCA lived. The reconstruction of ancestral sequences by means of the maximum likelihood method and their attribution to the set of mesophilic or hyperthermophilic sequences have led to the following conclusions: the LUCA was a hyperthermophile organism," as were the ancestors of the Archaea and Bacteria domains, while the ancestor of the Eukarya domain was a mesophile. These conclusions are independent of the presence of hyperthermophile bacteria in the sample of sequences used in the analysis and are therefore independent of whether or not these are the first lines of divergence in the Bacteria domain, as observed in the topology of the universal tree of ribosomal RNA. These conclusions are thus more easily understood under the hypothesis that the origin of life took place at a high temperature." | Valine-tRNA Ligase |
A-64-year-old man was admitted to the emergency department because of dyspnea. Twelve-lead ECG revealed alternating QRS complexes. In consequence of diagnostic tests, i.e., chest tomography showed eventration of the left diaphragm. In this case, we present an unusual case of electrical alternans due to diaphragmatic eventration. | Diaphragmatic Eventration |
Sodium salicylate was administered to rabbits in order to compare its disposition with that in other major and minor agricultural species. A dose of 44 mg/kg was given orally (p.o.) or intravenously (i.v.), and plasma and urine samples were collected for 36 h and 96 h, respectively. The majority of the drug was excreted as salicylic acid (SA) within 12 h. The major metabolites following an oral dose were salicyluric acid (SUA) and the glucuronide conjugates of SA and SUA. Following i.v. dosing, sulfate conjugates of both SA and SUA were also evident. Both SA and SUA were detected in plasma. Following i.v. administration, SA was distributed with a Vss of 0.249 +/- 0.082 l/kg and cleared at a rate of 0.0432 +/- 0.006 l/h/kg. The biological half-life, calculated from the terminal disposition-rate constant, was 4.3 h (i.v.) or 9.7 h (p.o.). The urinary elimination pattern of SA and metabolites in the rabbit was similar to that previously reported by our laboratories for cattle and goats, although total recovery of the administered dose was not as high as for the latter two species. However, the volume of distribution was larger than for cattle and goats, and rabbits cleared the drug more slowly than those species. As a consequence, the biological half-life was eight to ten times longer than in the ruminants studied previously. | Salicylates |
Segmentectomy is gaining popularity for the treatment of lung cancer, especially in the early stages. Comprehensive understanding of segmental and subsegmental anatomy is required for the procedure to be successfully completed from a technical and oncological point of view. We hereby present a novel technique for delineating the intersegmental border, which can be widely reproduced because it is not time-consuming and does not require special equipment. | Insufflation |
Functional lesion studies have yielded new information about the cortical organization of speech perception in the human brain. We will review a number of recent findings, focusing on studies of speech perception that use the techniques of electrocortical mapping by cortical stimulation and hemispheric anesthetization by intracarotid amobarbital. Implications for recent developments in neuroimaging studies of speech perception will be discussed. This discussion will provide the framework for a developing model of the cortical circuitry critical for speech perception. | GABA Modulators |
Prostaglandin E1 is indicated for the temporary maintenance of patent ductus arteriosus in newborns with ductus-dependent congenital heart defects. Since the standard daily dose is smaller (0.2-0.4 ml) than one ampoule (1 ml), we performed a chemical stability study of prostaglandin E1 when it is fractioned into polypropylene syringes. Three concentrations were studied: 500 mg/ml (original), and 1:2 and 1:4 dilutions in sodium chloride 0.9%. Syringes were kept at 4 degrees C for 30 days. Prostaglandin E1 levels were determined by using high-pressure chromatography. In all three formulations, the concentrations underwent no statistically significant changes over time (p>0.05). CONCLUSION: PGE1 is chemically stable at 4 degrees C for 30 days when fractioned into polypropylene syringes, both in the original and the 1:2 and 1:4 diluted formulations. | Alprostadil |
The repair of critical-size bone defect remains a challenge for orthopedic surgeons. With the advent of an aging society and their accompanying chronic diseases, it is becoming more difficult to treat bone defects, especially large segmental bone defects that are caused by trauma, tumors, infections, and congenital malformations. New materials and technologies need to be developed to address these conditions. 3D bioprinting is a novel technology that bridges the biomaterial and living cells and is an important method in tissue engineering projects. 3D bioprinting has the advantages of replacing or repairing damaged tissue and organs. The progress in material science and 3D printing devices make 3D bioprinting a technology which can be used to create various scaffolds with a large range of advanced material and cell types. However, in regard to the widespread use of bioprinting, biosafety, immunogenicity and rising costs are rising to be concerned. This article reviews the developments and applications of 3D bioprinting and highlights newly applied techniques and materials and the recent achievements in the orthopedic field. This paper also briefly reviews the difference between the methods of 3D bioprinting. The challenges are also elaborated with the aim to research materials, manufacture scaffolds, promote vascularization and maintain cell viability. | Bioprinting |
Necrolytic migratory erythema is a rare paraneoplastic dermatosis that may be the first clinical manifestation of the glucagonoma syndrome, a disorder characterized by mucocutaneous rash, glucose intolerance, hypoaminoacidemia, hyperglucagonaemia and pancreatic glucagonoma. The clinical case of a 45-year-old woman is presented. She had been experiencing weight loss, polydipsia, polyphagia, postprandial emesis, excessive hair loss and abdominal pain for two months. Erythematous, scaly and migratory plaques with 20 days of evolution were found on her trunk, perineum, elbows, hands, feet, inframammary and antecubital folds. The skin biopsy revealed noticeable vacuolar changes in high epidermal cells, extensive necrosis and thin orthokeratotic cornified layer. These findings pointed to a diagnosis of necrolytic migratory erythema. A suggestion was made to investigate a pancreatic glucagonoma. Laboratory tests showed moderate anemia, hyperglycemia and marked hyperglucagonaemia. Abdominal ultrasound revealed a mass in the tail of the pancreas measuring 6 x 5 x 5 cm which was resected. The histopathological findings were compatible with a diagnosis of glucagonoma, as confirmed by immunohistochemistry. Skin symptoms disappeared 10 days after the tumor resection. We can conclude that the histological changes defined may be clues that can lead the search for a distant skin disease and allow for its diagnosis. The histological pattern of vacuolation and epidermal necrosis should arouse suspicion of pancreatic glucagonoma. | Necrolytic Migratory Erythema |
A main source of gene expression noise in prokaryotes is translational bursting. It arises from efficient translation of mRNAs with low copy numbers, which makes the production of protein copies highly variable and pulsatile. To obtain analytical solutions, previous models to capture this noise source had to assume translation to be initiation-limited, representing the burst size by a specific type of a long-tail distribution. However, there is increasing evidence suggesting that the initiation is not the rate-limiting step in certain settings, for example, under stress conditions. Here, to overcome the limitations imposed by the initiation-limited assumption, we present a new analytical approach that can evaluate biological consequences of the protein burst size with a general distribution. Since our new model can capture the contribution of other factors to the translational noise, it can be used to analyze the effects of gene expression noise in more general settings. We used this new model to analytically analyze the connection between the burst size and the stability of gene expression processes in various settings. We found that the burst size with different distributions can lead to quantitatively and qualitatively different stability characteristics of protein abundance and can have non-intuitive effects. By allowing analysis of how the stability of gene expression processes changes based on various distributions of translational noise, our analytical approach is expected to enable deeper insights into the control of cell fate decision-making, the evolution of cryptic genetic variations, and fine-tuning of gene circuits." | Peptide Chain Initiation, Translational |
BACKGROUND: Upper respiratory tract infections (URTIs) are one of the most common illnesses in humans. Unani medications are widely used for this indication and are considered effective in alleviating the symptoms. OBJECTIVE: This article aims to document the Unani medications used for URTIs under a single heading and to provide evidence of their efficacy. METHODS: A literature survey of classic Unani texts was conducted to screen for single and compound Unani formulations for URTIs. Electronic databases such as PubMed, ScienceDirect, Wiley Online Library, and Google Scholar were searched to obtain evidence regarding the efficacy of these recommended drugs in URTI treatment. RESULTS: In the Unani medicine literature, the authors found descriptions of 28 single herbs and 40 compound formulations for the treatment of URTIs. A search of electronic databases yielded 13 clinical studies confirming the efficacy of the recommended medications in URTI treatment. These trials demonstrated that the administration of Unani medications significantly accelerated clinical improvement in URTIs. CONCLUSIONS: The findings of the included studies led us to conclude that the use of Unani medicines significantly accelerates clinical improvement in URTIs, as demonstrated by various subjective and objective parameters. Hence, clinically validated Unani medications should be considered for the treatment of URTIs. | Medicine, Arabic |
The purpose of this study was to investigate a mechanism of action for the effect of vagal nerve stimulation on reducing seizures in patients with complex partial epilepsy. The hypothesis tested was that vagal nerve stimulation has an antikindling effect on epilepsy. The databases of two large clinical trials (E03, E05) were accessed, and statistical methods were applied using logarithmic transforms and regression analysis. Two parameters--duration of a patient's epilepsy before entering the clinical trial and the patient's seizure density before entering the clinical trial--were used as markers of subsequent seizure control during vagal nerve stimulation. In general, there was not a good fit to the regression lines, and the slope of the lines did not conform to the hypothesis. The hypothesis that vagal nerve stimulation may unkindle epileptic seizures was not supported. | Kindling, Neurologic |
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages have escaped most receptor-binding domain (RBD)-targeting therapeutic neutralizing antibodies (NAbs), which proves that previous NAb drug screening strategies are deficient against the fast-evolving SARS-CoV-2. Better broad NAb drug candidate selection methods are needed. Here, we describe a rational approach for identifying RBD-targeting broad SARS-CoV-2 NAb cocktails. Based on high-throughput epitope determination, we propose that broad NAb drugs should target non-immunodominant RBD epitopes to avoid herd-immunity-directed escape mutations. Also, their interacting antigen residues should focus on sarbecovirus conserved sites and associate with critical viral functions, making the antibody-escaping mutations less likely to appear. Following these criteria, a featured non-competing antibody cocktail, SA55+SA58, is identified from a large collection of broad sarbecovirus NAbs isolated from SARS-CoV-2-vaccinated SARS convalescents. SA55+SA58 potently neutralizes ACE2-utilizing sarbecoviruses, including circulating Omicron variants, and could serve as broad SARS-CoV-2 prophylactics to offer long-term protection, especially for individuals who are immunocompromised or with high-risk comorbidities." | Combined Antibody Therapeutics |
The morphological features of 23 patients with straddling or overriding mitral valve are presented. Levocardia was present in 20 of 23; visceroatrial situs solitisu in 20 of 23, with 3 patients, 2 with asplenia and 1 with polysplenia, having visceral heterotaxia. A concordant D-ventricular loop was present in the 20 patients with visceroatrial situs solitus. Six of these had double outlet right ventricle; 2 had asplenia syndrome; 1 had D-transposition of the great arteries, ventricular defect and pulmonary atresia; 1 with tricuspid atresia and double outlet-outlet chamber; 1 with polysplenia syndrome; and 12 had endocardial cushion defect with marked underdevelopment of the left ventricle, and normally related great arteries. Left ventricular size was related to the amount of mitral valve (or left-sided component of a common atrioventricular valve) connected to it. In those patients in whom little effective mitral orifice was connected to the left ventricle, the left ventricle was diminutive. Endocardial fibroelastosis of the left ventricle was noted in only a single patient. Six of the 7 patients with double outlet right ventricle (including one with double outlet bulbus) had subpulmonary obstruction, and in one of these, this was related in part to the straddling mitral valve. In 1 patient with double outlet right ventricle, there was a double orifice mitral valve, and it was the accessory mitral orifice that straddled. The diagnosis of overriding mitral valve should be suspected in any patient with significant conotruncal anomalies and underdeveloped left ventricle, especially the patient with double outlet right ventricle, and in the patient with endocardial cushion defect, hypoplasia of the left ventricle, and obstructive anomalies of the aortic arch. In certain patients, selective left atriography, left ventriculography, and single and two dimensional echocardiography may be diagnostic of this condition. | Levocardia |
L-serine has long been known to inhibit growth of Escherichia coli cells cultured in minimal medium supplemented with glucose, lactate, or another carbohydrate as the sole source of carbon. However, the target of serine inhibition was not known. The growth inhibition was released by adding isoleucine, 2-ketobutyric acid, threonine or homoserine, but not by aspartate. Thus the inhibition site must be between aspartate and homoserine in the isoleucine biosynthetic pathway. We found that homoserine dehydrogenase I was strongly inhibited by serine. We isolated serine-resistant mutants, and found that in these mutants homoserine dehydrogenase I was resistant to serine. Thus, we conclude that the target of serine inhibition in Escherichia coli is homoserine dehydrogenase I. | Homoserine Dehydrogenase |
BACKGROUND: Bicuspid anatomy of the aortic valve is a common reason for aortic regurgitation and is associated with aortic dilatation in more than 50% of patients. We have observed different patterns of aortic dilatation and used different approaches preserving the valve. METHODS: Between October 1995 and February 2006, a regurgitant bicuspid valve was repaired in 173 patients. The aorta was normal in 57 patients who underwent isolated repair. Aortic dilatation mainly above commissural level (n = 38) was treated by separate valve repair plus supracommissural aortic replacement. In 78 patients, aortic dilatation involved the root and was treated by root remodeling. RESULTS: Hospital mortality and perioperative morbidity were low in all three groups. Myocardial ischemia was significantly shorter in repair plus aortic replacement than remodeling (p < 0.001). Freedom from aortic regurgitation II or greater at 5 years varied between 91% and 96%. Freedom from reoperation at 5 years was 97% after remodeling, but only 53% after repair plus aortic replacement (p = 0.33). Symmetric prolapse was the most frequent cause for reoperation. CONCLUSIONS: The long-term stability of bicuspid aortic valve repair is excellent in the absence of aortic pathology. In the presence of aortic dilatation, root remodeling leads to equally stable valve durability. In patients with less pronounced root dilatation, separate valve repair plus aortic replacement may be a less complex alternative. Symmetric prolapse should be avoided if the ascending aorta is replaced. | Aortic Valve Prolapse |
BACKGROUND: Grass Carp Reovirus (GCRV), a highly virulent agent of aquatic animals, has an eleven segmented dsRNA genome encased in a multilayered capsid shell, which encodes twelve proteins including seven structural proteins (VP1-VP7), and five nonstructural proteins (NS80, NS38, NS31, NS26, and NS16). It has been suggested that the protein NS80 plays an important role in the viral replication cycle that is similar to that of its homologous protein muNS in the genus of Orthoreovirus. RESULTS: As a step to understanding the basis of the part played by NS80 in GCRV replication and particle assembly, we used the yeast two-hybrid (Y2H) system to identify NS80 interactions with proteins NS38, VP4, and VP6 as well as NS80 and NS38 self-interactions, while no interactions appeared in the four protein pairs NS38-VP4, NS38-VP6, VP4-VP4, and VP4-VP6. Bioinformatic analyses of NS80 with its corresponding proteins were performed with all currently available homologous protein sequences in ARVs (avian reoviruses) and MRVs (mammalian reoviruses) to predict further potential functional domains of NS80 that are related to VFLS (viral factory-like structures) formation and other roles in viral replication. Two conserved regions spanning from aa (amino acid) residues of 388 to 433, and 562 to 580 were discovered in this study. The second conserved region with corresponding conserved residues Tyr565, His569, Cys571, Asn573, and Glu576 located between the two coiled-coils regions (aa ~513-550 and aa ~615-690) in carboxyl-proximal terminus were supposed to be essential to form VFLS, so that aa residues ranging from 513 to 742 of NS80 was inferred to be the smallest region that is necessary for forming VFLS. The function of the first conserved region including Ala395, Gly419, Asp421, Pro422, Leu438, and Leu443 residues is unclear, but one-third of the amino-terminal region might be species specific, dominating interactions with other viral components. CONCLUSIONS: Our results in this study together with those from previous investigations indicate the protein NS80 might play a central role in VFLS formation and viral components recruitment in GCRV particle assembly, similar to the muNS protein in ARVs and MRVs. | Reoviridae |
Irritable bowel syndrome is a typical gastrointestinal disease that causes bloating, flatulence, abdominal pain, diarrhoea, constipation, or alteration of the last two in adults and children. A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) is one of the potential treatment strategies to reduce abdominal symptoms and increase the quality of life. The present narrative review aims to present a general overview of current studies that have evaluated the efficacy of a low-FODMAP diet against other diets in gastrointestinal symptoms, nutrient intake in adults and children, and lifestyle quality. The research was performed using seven searchable databases, which included the Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), Excerpta Medica Database (EMBASE), Medline, PubMed, Scopus, and Web of Science, up to March 2023. In conclusion, there is significant evidence that the follow-up of a low-FODMAP diet might be a feasible first-line therapeutic strategy to reduce stomach discomfort, pain, bloating, and quality of life for patients with irritable bowel syndrome. | FODMAP Diet |
Sarcoidosis, a granulomatous disorder of unknown etiology, characteristically involves multiple organs. However, pulmonary manifestations typically dominate. Chest radiographs are abnormal in 85 to 95% of patients. Abnormalities in pulmonary function tests are common and may be associated with cough, dyspnea, and exercise limitation. However, one third or more of patients are asymptomatic, with incidental abnormalities on chest radiographs. The clinical course and expression of pulmonary sarcoidosis are variable. Spontaneous remissions occur in nearly two thirds of patients. The course is chronic in up to 30% of patients. Chronic pulmonary sarcoidosis may result in progressive (sometimes life-threatening) loss of lung function. Fatalities ascribed to sarcoidosis occur in 1 to 4% of patients. Although the impact of treatment is controversial, corticosteroids may be highly effective in some patients. Immunosuppressive, cytotoxic, or immunomodulatory agents are reserved for patients failing or experiencing adverse effects from corticosteroids. Lung transplantation is a viable option for patients with life-threatening disease failing medical therapy. | Granuloma, Respiratory Tract |
School readiness includes the readiness of the individual child, the school's readiness for children, and the ability of the family and community to support optimal early child development. It is the responsibility of schools to meet the needs of all children at all levels of readiness. Children's readiness for kindergarten should become an outcome measure for a coordinated system of community-based programs and supports for the healthy development of young children. Our rapidly expanding insights into early brain and child development have revealed that modifiable factors in a child's early experience can greatly affect that child's health and learning trajectories. Many children in the United States enter kindergarten with limitations in their social, emotional, cognitive, and physical development that might have been significantly diminished or eliminated through early identification and attention to child and family needs. A strong correlation between social-emotional development and school and life success, combined with alarming rates of preschool expulsion, point toward the urgency of leveraging opportunities to support social-emotional development and address behavioral concerns early. Pediatric primary care providers have access to the youngest children and their families. Pediatricians can promote and use community supports, such as home visiting programs, quality early care and education programs, family support programs and resources, early intervention services, children's museums, and libraries, which are important for addressing school readiness and are too often underused by populations who can benefit most from them. When these are not available, pediatricians can support the development of such resources. The American Academy of Pediatrics affords pediatricians many opportunities to improve the physical, social-emotional, and educational health of young children, in conjunction with other advocacy groups. This technical report provides an updated version of the previous iteration from the American Academy of Pediatrics published in 2008." | Early Intervention, Educational |
This paper describes the synthesis of four novel bidentate metal(II) complexes having 2-aminobenzophenone precursor and a co-ligand (anthranilic acid). They are characterized by the usual spectral and analytical data. They adopt octahedral geometrical arrangements around the metal ions which have been confirmed by electronic absorption data. Moreover, the EPR study of Cu(II) complex has provided supportive evidence to the conclusion drawn on the basis of electronic spectrum and magnetic moment value. Powder XRD and SEM studies show that all the complexes are microcrystalline with homogenous morphology. The interaction of these complexes with CT-DNA has been explored by UV-absorption, fluorescence, viscosity, CV and CD techniques which reveal that the complexes could bind to CT-DNA through intercalation. The oxidative cleavage of the metal complexes with pBR322 DNA has also been investigated by gel electrophoresis. Moreover, the antimicrobial bustle shows that all metal chelates have superior activity than the free Schiff base ligand. The catalytic activity of the complexes has been evaluated towards the oxidation of aniline. All the complexes exhibit significant catalytic activity. Among them Cu(II) complex exhibits better catalytic activity than others. This catalytic process occurs at room temperature and it proceeds in water medium which suggests that this is an eco-friendly process. | Powder Diffraction |
Certain large DNA viruses (e.g. herpesviruses and poxviruses) encode proteins related to cellular protein-serine/threonine kinases, and Hepatitis B virus and vesicular stomatitis virus may encode structurally different protein kinases. Other viruses activate cellular protein kinases, e.g. interferon-induced eukaryotic initiation factor-2 kinase, growth factor-induced kinases and protein kinases that regulate mitosis. Protein phosphatases are encoded by vaccinia virus and bacteriophage lambda and must also play a role in viral infection--as do cellular protein phosphatases. The functions of many of these viral enzymes remain to be determined, but they represent possible new targets for anti-viral therapy. | Phosphoprotein Phosphatases |
A group of 177 women were asked, before and after child delivery, to state their preference for being alone or with other women. They were also asked to rank their level of anxiety. After delivery they filled out the Repression-Sensitization Scale of Byrne, Barry & Nelson (1963). Results show sensitizers to be more anxious than repressors before but not after delivery. Before delivery repressors preferred to be alone, while sensitizers wanted to stay with others. After delivery both groups show a significant preference for being with others. There is no significant correlation between anxiety and affiliation. | Repression-Sensitization |
Sulfadimethoxine is metabolized by O-dealkylation, N4-acetylation and N1-glucuronidation. In man, only N1-glucuronidation and N4-acetylation takes place, leading to the final double conjugate N4-acetylsulfadimethoxine-N1-glucuronide. The N1-glucuronides are directly measured by high pressure liquid chromatography. When N4-acetylsulfadimethoxine is administered as parent drug, 30% of the dose is N1-glucuronidated and excreted. Fast acetylators show a shorter half-life for sulfadimethoxine than slow acetylators (27.8 +/- 4.2 h versus 36.3 +/- 5.4 h; P = 0.013), similarly the half-life of the N4-acetyl conjugate is also shorter in fast acetylators (41.3 +/- 5.2 h versus 53.5 +/- 8.5 h, P = 0.036). No measurable plasma concentrations of the N1-glucuronides from sulfadimethoxine are found in plasma. N1-glucuronidation results in a 75% decrease in protein binding of sulfadimethoxine. N4-acetylsulfadimethoxine and its N1-glucuronide showed the same high protein binding of 99%. Approximately 50-60% of the oral dose of sulfadimethoxine is excreted in the urine, leaving 40-50% for excretion into bile and faeces. | Sulfadimethoxine |
BACKGROUND: Motor symptoms of Parkinson's disease (PD) are caused by degeneration and progressive loss of nigrostriatal dopamine neurons. Currently, no cure for this disease is available. Existing drugs alleviate PD symptoms but fail to halt neurodegeneration. Glial cell line-derived neurotrophic factor (GDNF) is able to protect and repair dopamine neurons in vitro and in animal models of PD, but the clinical use of GDNF is complicated by its pharmacokinetic properties. The present study aimed to evaluate the neuronal effects of a blood-brain-barrier penetrating small molecule GDNF receptor Rearranged in Transfection agonist, BT13, in the dopamine system. METHODS: We characterized the ability of BT13 to activate RET in immortalized cells, to support the survival of cultured dopamine neurons, to protect cultured dopamine neurons against neurotoxin-induced cell death, to activate intracellular signaling pathways both in vitro and in vivo, and to regulate dopamine release in the mouse striatum as well as BT13's distribution in the brain. RESULTS: BT13 potently activates RET and downstream signaling cascades such as Extracellular Signal Regulated Kinase and AKT in immortalized cells. It supports the survival of cultured dopamine neurons from wild-type but not from RET-knockout mice. BT13 protects cultured dopamine neurons from 6-Hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP(+) )-induced cell death only if they express RET. In addition, BT13 is absorbed in the brain, activates intracellular signaling cascades in dopamine neurons both in vitro and in vivo, and also stimulates the release of dopamine in the mouse striatum. CONCLUSION: The GDNF receptor RET agonist BT13 demonstrates the potential for further development of novel disease-modifying treatments against PD. (c) 2019 International Parkinson and Movement Disorder Society." | Glial Cell Line-Derived Neurotrophic Factor Receptors |
As sessile organisms, plants are unable to avoid being subjected to environmental stresses that negatively affect their growth and productivity. Instead, they utilize various mechanisms at the morphological, physiological, and biochemical levels to alleviate the deleterious effects of such stresses. Amongst these, secondary metabolites produced by plants represent an important component of the defense system. Secondary metabolites, namely phenolics, terpenes, and nitrogen-containing compounds, have been extensively demonstrated to protect plants against multiple stresses, both biotic (herbivores and pathogenic microorganisms) and abiotic (e.g. drought, salinity, and heavy metals). The regulation of secondary metabolism by beneficial elements such as silicon (Si) is an important topic. Silicon-mediated alleviation of both biotic and abiotic stresses has been well documented in numerous plant species. Recently, many studies have demonstrated the involvement of Si in strengthening stress tolerance through the modulation of secondary metabolism. In this review, we discuss Si-mediated regulation of the synthesis, metabolism, and modification of secondary metabolites that lead to enhanced stress tolerance, with a focus on physiological, biochemical, and molecular aspects. Whilst mechanisms involved in Si-mediated regulation of pathogen resistance via secondary metabolism have been established in plants, they are largely unknown in the case of abiotic stresses, thus leaving an important gap in our current knowledge. | Droughts |
With longer life expectancy, as well as better survival rates after myocardial infarction, the population of elderly patients with congestive heart failure steadily increases. Large, randomized, placebo-controlled studies have shown significant beneficial effects for several classes of drugs (angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers, aldosterone antagonists) in patients with congestive heart failure. In most of these studies, however, elderly patients were either excluded or represented only a minority of the study population. Therefore, the treatment benefit for the large population of patients aged 65 and older is still not very well documented. In this paper, we critically review the current literature with regard to outcome of heart failure therapy in this particular subpopulation. | Cardiovascular Agents |
The structural constituents of the large eukaryotic ribosomal subunit are 3 ribosomal RNAs, namely the 25S, 5.8S and 5S rRNA and about 46 ribosomal proteins (r-proteins). They assemble and mature in a highly dynamic process that involves more than 150 proteins and 70 small RNAs. Ribosome biogenesis starts in the nucleolus, continues in the nucleoplasm and is completed after nucleo-cytoplasmic translocation of the subunits in the cytoplasm. In this work we created 26 yeast strains, each of which conditionally expresses one of the large ribosomal subunit (LSU) proteins. In vivo depletion of the analysed LSU r-proteins was lethal and led to destabilisation and degradation of the LSU and/or its precursors. Detailed steady state and metabolic pulse labelling analyses of rRNA precursors in these mutant strains showed that LSU r-proteins can be grouped according to their requirement for efficient progression of different steps of large ribosomal subunit maturation. Comparative analyses of the observed phenotypes and the nature of r-protein-rRNA interactions as predicted by current atomic LSU structure models led us to discuss working hypotheses on i) how individual r-proteins control the productive processing of the major 5' end of 5.8S rRNA precursors by exonucleases Rat1p and Xrn1p, and ii) the nature of structural characteristics of nascent LSUs that are required for cytoplasmic accumulation of nascent subunits but are nonessential for most of the nuclear LSU pre-rRNA processing events. | RNA, Ribosomal, 5.8S |
Early region 4 (E4) of mouse adenovirus type 1 was analyzed by Northern blotting, cDNA sequencing, and S1 nuclease protection and primer extension assays. The transcription map of this region was dissimilar to the consensus human adenovirus E4 transcription map in which all transcripts have identical 5' and 3'-terminal sequences. Seven classes of mouse adenovirus type 1 mRNAs were identified; all shared the same 3' end. Three classes of unspliced mRNAs differed at their 5' start sites, two classes of spliced transcripts differed in the locations of their splice acceptors, and two classes of spliced messages differed in their splice donors and acceptors. From the structure of the various transcripts, translational products were predicted. In addition to a predicted polypeptide with similarity to the human adenovirus 2 E4 34K protein previously identified (A. O. Ball, C. W. Beard, P. Villegas, and K. R. Spindler, 1991, Virology 180, 257-265), two open reading frames with similarity to human adenovirus 2 E4 open reading frames 2 and 3 were found. | Oncogene Proteins, Viral |
Mesenchymal stem cells (MSCs) are multipotent adult stem cells that have regenerative capability and exert paracrine actions on damaged tissues. Since peritoneal fibrosis is a serious complication of peritoneal dialysis, we tested whether MSCs suppress this using a chlorhexidine gluconate model in rats. Although MSCs isolated from green fluorescent protein-positive rats were detected for only 3 days following their injection, immunohistochemical staining showed that MSCs suppressed the expression of mesenchymal cells, their effects on the deposition of extracellular matrix proteins, and the infiltration of macrophages for 14 days. Moreover, MSCs reduced the functional impairment of the peritoneal membrane. Cocultures of MSCs and human peritoneal mesothelial cells using a Transwell system indicated that the beneficial effects of MSCs on the glucose-induced upregulation of transforming growth factor-beta1(TGF-beta1) and fibronectin mRNA expression in the human cells were likely due to paracrine actions. Preincubation in MSC-conditioned medium suppressed TGF-beta1-induced epithelial-to-mesenchymal transition, alpha-smooth muscle actin, and the decrease in zonula occludens-1 in cultured human peritoneal mesothelial cells. Although bone morphogenic protein 7 was not detected, MSCs secreted hepatocyte growth factor and a neutralizing antibody to this inhibited TGF-beta1 signaling. Thus, our findings imply that MSCs ameliorate experimental peritoneal fibrosis by suppressing inflammation and TGF-beta1 signaling in a paracrine manner. | Peritoneal Fibrosis |
A novel pretreatment approach combined freeze with microwave was developed to promote the release of orthophosphate from excess sludge, and the phosphorus (P) was recovered from the produced supernatant by phosphate sedimentation. Batch tests examined the effects of freezing time, pH, and microwave time on the release of phosphate (PO(4)(3-)-P) of the excess sludge during the freezing-microwave pretreatment. The release amount of PO(4)(3-)-P reached 276 mg/L under the conditions of the freezing time of 23 h, microwave time of 5 min, and pH of 4. The optimal conditions for phosphate precipitation were pH of 9.5, the mole ratio of Mg/P of 1.8, and stirring speed of 200 rpm. The recovery efficiency of PO(4)(3-)-P reached 97.42% after the reaction of 20 min and the precipitation of 50 min. The precipitated sediment mainly consisted of amorphous calcium phosphate and magnesium ammonium phosphate (MAP) which can be used as a substitute for phosphorus minerals. | Phosphorus Acids |
OBJECTIVE: Antibodies against nodal-paranodal junction proteins have been detected in some patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), which is a crucial step to define the most effective treatment strategies. In this paper, we tested the positive rates of these antibodies in CIDP and characterized the clinical and electrophysiological features of the antibodies-positive patients. METHODS: We prospectively recruited 47 patients with CIDP. We detected IgG antibodies against human neurofascin-155 (NF155), neurofascin-186 (NF186), contactin-1 (CNTN1), contactin-2 (CNTN2) and contactin-associated protein-1 (Caspr1), and identified the IgG isotype with cell-based assay (CBA). We collected the demographic, clinical, laboratory, and electrophysiological information of the patients that were seropositive. RESULTS: Five patients (10.6 %) had IgG against NF155, 3 (6.4 %) against Caspr1, 2 (4.3 %) against NF186 and 1 (2.1 %) against CNTN1. All the 11 antibody-positive patients (8 males and 3 females) presented with typical clinical features. Five of them needed assistance in walking, 5 had cranial nerve impairments and 3 had autonomic disturbances. The age at onset of the patients that were anti-NF155-positive was younger (19.60 +/- 9.02 years vs. 55.33 +/- 11.93 years, P = 0.003) than those that were anti-Caspr1-positive. No significant difference in the functional status was observed between these two groups. The action potentials of 11/79 (13.9 %) motor nerves and 62/93 (66.7 %) sensory nerves exhibited no response. Moreover, 16/68 (23.5 %) nerves presented conduction block and 13/68 (19.1 %) nerves presented temporal dispersion. Distal motor latency (DML) of ulnar nerve and tibial nerve tended to be longer (p = 0.008 and p = 0.006, respectively) in anti-NF155-positive patients than that in anti-Caspr1-positive patients. Of the 11 patients that were antibody-positive patients, corticosteroids were effective in 3/7 (42.9 %), intravenous immunoglobins (IVIG) were effective in 1/7 (14.3 %), and rituximab was effective in 6/8 (75.0 %). CONCLUSIONS: Our findings validate the previous observation on the clinico-serological correlation between CIDP and antibodies against nodal-paranodal proteins. Of note, the damage on nerves is more severe in anti-NF155-positive patients than that in anti-Caspr1-positive patients during electrophysiological diagnosis. | Nodal Protein |
Cytokinesis controls the proper segregation of nuclear and cytoplasmic materials at the end of cell division. The chromosomal passenger complex (CPC) has been proposed to monitor the final separation of the two daughter cells at the end of cytokinesis in order to prevent cell abscission in the presence of DNA at the cleavage site, but the precise molecular basis for this is unclear. Recent studies indicate that abscission could be mediated by the assembly of filaments comprising components of the endosomal sorting complex required for transport-III (ESCRT-III). Here, we show that the CPC subunit Borealin interacts directly with the Snf7 components of ESCRT-III in both Drosophila and human cells. Moreover, we find that the CPC's catalytic subunit, Aurora B kinase, phosphorylates one of the three human Snf7 paralogues-CHMP4C-in its C-terminal tail, a region known to regulate its ability to form polymers and associate with membranes. Phosphorylation at these sites appears essential for CHMP4C function because their mutation leads to cytokinesis defects. We propose that CPC controls abscission timing through inhibition of ESCRT-III Snf7 polymerization and membrane association using two concurrent mechanisms: interaction of its Borealin component with Snf7 proteins and phosphorylation of CHMP4C by Aurora B." | Endosomal Sorting Complexes Required for Transport |
PURPOSE OF REVIEW: The treatments for inner ear diseases are evolving as the systemic administration of medication is replaced by novel intratympanic and intracochlear drug delivery. The current review explores the background and recent developments in this field. RECENT FINDINGS: Although still in various stages of clinical development, novel drug delivery techniques such as the Silverstein MicroWick, the round window microcatheter, biodegradable hydrogels, biopolymers, nanoparticles, newly designed cochlear implant arrays, osmotic mini/micro pumps, and reciprocating perfusion systems hold significant promise. Animal data suggest that sustained delivery systems have more reliable inner ear pharmacokinetics than both systemic administration and intratympanic injections. SUMMARY: As research scientists advance technologies for treating inner ear diseases, drug delivery techniques must keep pace. Viable treatment options for sensorineural hearing loss, tinnitus, and vestibular disorders are on the horizon and may usher in a new golden age for otology. | Round Window, Ear |
The immune system has evolved to respond to pathogens (nonself) and unresponsive to self-antigens (tolerance). During the development of T and B cells in the thymus and bone marrow, respectively, self-reactive T and B cells are deleted by a process of apoptosis (both T and B cells) and become unresponsive to self-antigen by receptor editing (for B cells). However, few self-reactive T cells are leaked into the periphery. A number of mechanisms are responsible to ensure that self-reactive T and B cells remain unresponsive to self-antigens. In the central tolerance, major mechanisms include apoptosis (for T cells) and receptor editing (for B cells), and in the peripheral tolerance, a major mechanism appears to be regulated by Treg cells. In T cell central tolerance, one of the most important molecules is a transcription factor, autoimmune regulator, which is selectively expressed in medullary thymic epithelial cells (mTECs) and constitutively regulates the transcription of hundreds of self-antigens in mTECs, thereby inducing central tolerance, negative selection, and Treg differentiation from some self-reactive thymocytes. Primary immunodeficiency diseases are a group of monogenic diseases where mutations of certain genes have resulted in the loss of central and/or peripheral tolerance. As a result autoimmunity and autoimmune diseases are common among patients with primary immunodeficiency diseases. Here, we have provided a comprehensive review of the mechanisms of central and peripheral tolerance and autoimmune manifestations and mechanisms of autoimmunity in primary immunodeficiency diseases. | Central Tolerance |
All the fractions of Phellinus linteus mycelia showed anti-tumor activity toward solid tumors planted in mice. The highest anti-tumor activity of 81.2% was observed in the protein-glucan complex obtained by precipitating the 24% NaOH extract at pH 6.0. This protein-glucan complex consisted of 39.3% polysaccharide and 49.4% protein. Its (13)C- and (1)H-NMR data showed that the main glucan part of the complex was simple alpha-1,3-glucan chains. | Sarcoma 180 |
BACKGROUND: Succinate dehydrogenase is an important target of fungicides. Succinate dehydrogenase inhibitors (SDHIs) have widely been used to combat destructive plant pathogenic fungi because they possess efficient and broad-spectrum antifungal activities and as well as unique mode of action. The research and development of novel SDHIs have been ongoing. RESULTS: Thirty-six novel quinolin-2(1H)-one derivatives were designed, synthesized and characterized. The single crystal structure of compound 3c was determined through the X-ray diffraction of single crystals. The bioassay results displayed that most compounds had good antifungal activities at 16 mug mL(-1) against Rhizoctonia cerealis, Erysiphe graminis, Botrytis cinerea, Penicillium italicum and Phytophthora infestans. Compounds 6o, 6p and 6r had better antifungal activities than the commercialized fungicide pyraziflumid against Botrytis cinerea. Their half maximal effective concentration (EC(50) ) values were 0.398, 0.513, 0.205 and 0.706 mug mL(-1) , respectively. Moreover, the inhibiting activities of the bioactive compounds were tested against succinate dehydrogenase. The results indicated that they possessed outstanding activities. Compounds 6o, 6p and 6r also exhibited better inhibiting activities than pyraziflumid against succinate dehydrogenase. Their half maximal inhibitory concentration (IC(50) ) values were 0.450, 0.672, 0.232 and 0.858 mug mL(-1) , respectively. The results of molecular dynamic (MD) simulations indicated that compound 6r displayed stronger affinity to succinate dehydrogenase than pyraziflumid. CONCLUSION: The results of the present study displayed that quinolin-2(1H)-one derivative could be one scaffold of potential SDHIs and will provide some valuable information for the research and development of new SDHIs. (c) 2022 Society of Chemical Industry. | Succinate Dehydrogenase |
PURPOSE: Our purpose was to demonstrate the feasibility of the routine aspiration of supernumerary follicles in infertile patients with imminent polyovulation after ovulation induction with gonadotropins and to examine its effect on the frequency of cycle cancellation and on the (multiple) pregnancy rate. METHODS: The data on 796 treatment cycles, performed between 1989 and 1996 on 410 infertile couples, were analyzed retrospectively. From October 1992, whenever necessary, supernumerary ovarian follicles were selectively aspirated transvaginally under ultrasound guidance to prevent the ovulation of more than three follicles. Thereafter, intrauterine insemination was performed. RESULTS: After the adoption of transvaginal ultrasound-guided aspiration of supernumerary follicles into the treatment protocol in October 1992, the number of canceled cycles (P < 0.0001) and the multiple pregnancy rate (P < 0.01) were significantly reduced compared to those previously. The overall pregnancy rate remained stable. No ovarian hyperstimulation syndrome requiring hospitalization was noted, and no complications resulting from the follicle aspiration were registered. CONCLUSIONS: Transvaginal ultrasound-guided aspiration of supernumerary ovarian follicles increases both the efficacy and the safety of ovulation induction with gonadotropins. Because of the limited equipment required, this method represents an alternative for conversion of overstimulated cycles to more costly alternatives such as in vitro fertilization. | Pregnancy, Multiple |
The first 2 years' experiences with Provox prostheses at the ENT Clinic of the University of Berne are discussed. Thirty-three prostheses were inserted after primary tracheoesophageal puncture and 5 after secondary puncture. Voice success was measured with the scale of Robillard Shultz and Harrison, which encompasses not only assessment of voice quality but also frequency of use and a patient's independence in prosthesis care. After primary puncture the percentage of functional" speakers increased progressively from 26% after 2 months to 56% after 1 year. After secondary puncture only 2 of 5 patients became functional speakers after 6 months. Because only a few of the previously laryngectomized patients who were informed about the possibility of a secondary puncture wished to receive a prosthesis, the reasons for their reservation were analyzed. Uneasiness about an additional operation and fear of complications were the most frequent motives. Further psychosocial aspects--including the unwillingness of some patients to use their fully functioning prosthesis--are discussed." | Laryngectomy |
BACKGROUND: A substantial number of patients with advanced HIV infection suffer from intractable diarrhoea. The aim of this study was to evaluate whether potent antiretroviral therapy could alleviate such diarrhoea. METHODS: In an open randomized study the effect of the HIV protease inhibitor indinavir in combination with nucleoside analogue reverse transcriptase inhibitors on chronic HIV-related diarrhoea was investigated in 14 late-stage (CD4+ lymphocyte count < or = 50 x 10(6) cells/l) HIV-infected patients. Data concerning stool frequency, stool consistency and antidiarrhoeal drug use were collected in daily diaries over a 24-week period. Endpoints of the study were reduction of stool frequency, improvement of stool consistency, weight gain, and in case of diarrhoea due to Enterocytozoon bieneusi or Cryptosporidium sp. disappearance of these parasites from stool. RESULTS: Thirteen patients started the study drug indinavir. One patient died after 1 week and one patient withdrew prematurely after 18 weeks. Median stool frequency declined from 5.8 daily at baseline to 2.3 daily after 24 weeks (P=0.04). Stool consistency improved considerably over the study period: before treatment 56% of stools were watery and 0% were formed; at week 24 these figures were 0 and 35%, respectively. Body weight increased significantly with a median increment of 6.6 kg at week 24 (P=0.0006). In two out of six patients with microsporidiosis and both patients with cryptosporidiosis, stools were free of parasites at week 24. Five out of six patients who used non-specific antidiarrhoeal medication on a regular basis prior to the study had ceased to do so at the end. CONCLUSION: The use of potent antiretroviral therapy in patients with advanced HIV infection can improve chronic HIV-related diarrhoea and in some cases lead to disappearance of E. bieneusi and Cryptosporidium sp. from the stools. | HIV Enteropathy |
Monoclonal antibodies constitute a major treatment option for many tumor patients. Due to their specific recognition sites in their constant Fc regions, antibodies are able to trigger antibody-dependent cell-mediated cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). While the contribution of ADCC to clinical efficacy has been strengthened by observations that patients with favorable Fcgamma receptor polymorphisms display better response rates to therapeutic antibodies, the contribution of CDC to their clinical efficacy remains controversial. In the background of high expression of complement-regulatory proteins on tumor cells as well as of the fact that some therapeutic antibodies lack the capacity to trigger efficient CDC, strategies have been implemented to improve either the capacity of antibodies to initiate the complement cascade or to interfere with tumor cells' resistance mechanisms. Although both strategies have demonstrated therapeutic benefit in vitro and in murine models, CDC-enhanced antibodies-to the best of our knowledge-have not been clinically tested, and evidence for the potential of CDC-optimizing approaches has yet to be generated in humans. Hence, the potency of complement activation and its impact on the clinical efficacy of therapeutic antibodies still remains to be elucidated in clinical trials encompassing novel complement-enhancing molecules. | Complement Activation |
The emergence of resistance to frontline antibiotics has called for novel strategies to combat serious pathogenic infections. Methicillin-resistant Staphylococcus aureus [MRSA] is one such pathogen. As opposed to traditional antibiotics, bacteriostatic anti-virulent agents disarm MRSA, without exerting pressure, that cause resistance. Herein, we employed a thermophilic Thermotoga maritima tryptophan synthase (TmTrpB1) enzyme followed by an isonitrile synthase and Fe(II)-alpha-ketoglutarate-dependent oxygenase, in sequence as biocatalysts to produce antivirulent indole vinyl isonitriles. We report on conversion of simple derivatives of indoles to their C3-vinyl isonitriles, as the enzymes employed here demonstrated broader substrate tolerance. In toto, eight distinct L-Tryptophan derived alpha-amino acids (7) were converted to their bioactive vinyl isonitriles (3) by action of an isonitrile synthase (WelI1) and an Fe(II)-alpha-ketoglutarate-dependent oxygenase (WelI3) yielding structural variants possessing antivirulence against MRSA. These indole vinyl isonitriles at 10 mug/mL are effective as antivirulent compounds against MRSA, as evidenced through analysis of rabbit blood hemolysis assay. Based on a homology modelling exercise, of enzyme-substrate complexes, we deduced potential three dimensional alignments of active sites and glean mechanistic insights into the substrate tolerance of the Fe(II)-alpha-ketoglutarate-dependent oxygenase. | Thermotoga |
PURPOSE OF REVIEW: At present, there is a debate as to the management of malrotation in pediatric patients. This review highlights recent literature including the role of laparoscopy, and the management of asymptomatic patients with and without congenital cardiac disease. RECENT FINDINGS: Symptomatic patients are still recommended to undergo open Ladd's procedure. Laparoscopic Ladd's procedure in asymptomatic patients confers a shorter time to tolerating feeds, shorter length of stay, and a decreased rate of bowel obstruction and other complications. It may, however, carry a higher risk of postoperative volvulus. Diagnostic laparoscopy is recommended in asymptomatic patients in whom the diagnosis is uncertain on upper gastrointestinal imaging. Asymptomatic patients with congenital heart disease may be managed with initial observation or operation, based upon individualized risk benefit assessment. If an elective Ladd's procedure is performed, it should take place after palliative cardiac operations have resulted in stable cardiac function. Screening upper gastrointestinal studies in heterotaxy patients may be unnecessary as the reported rates of volvulus in recent studies are low. SUMMARY: Laparoscopic Ladd's procedure may be an acceptable alternative to an open procedure for asymptomatic patients. Observation of asymptomatic patients with congenital cardiac disease is a reasonable alternative in selected patients. | Intestinal Volvulus |
The centriole and basal body (CBB) structure nucleates cilia and flagella, and is an essential component of the centrosome, underlying eukaryotic microtubule-based motility, cell division and polarity. In recent years, components of the CBB-assembly machinery have been identified, but little is known about their regulation and evolution. Given the diversity of cellular contexts encountered in eukaryotes, but the remarkable conservation of CBB morphology, we asked whether general mechanistic principles could explain CBB assembly. We analysed the distribution of each component of the human CBB-assembly machinery across eukaryotes as a strategy to generate testable hypotheses. We found an evolutionarily cohesive and ancestral module, which we term UNIMOD and is defined by three components (SAS6, SAS4/CPAP and BLD10/CEP135), that correlates with the occurrence of CBBs. Unexpectedly, other players (SAK/PLK4, SPD2/CEP192 and CP110) emerged in a taxon-specific manner. We report that gene duplication plays an important role in the evolution of CBB components and show that, in the case of BLD10/CEP135, this is a source of tissue specificity in CBB and flagella biogenesis. Moreover, we observe extreme protein divergence amongst CBB components and show experimentally that there is loss of cross-species complementation among SAK/PLK4 family members, suggesting species-specific adaptations in CBB assembly. We propose that the UNIMOD theory explains the conservation of CBB architecture and that taxon- and tissue-specific molecular innovations, gained through emergence, duplication and divergence, play important roles in coordinating CBB biogenesis and function in different cellular contexts. | Spindle Poles |
This study examined the changes in eggshell strength and the genetic parameters related to this trait throughout a hen's laying life using random regression. The data were collected from a crossbred population between 2011 and 2014, where the eggshell strength was determined repeatedly for 2260 hens. Using random regression models (RRMs), several Legendre polynomials were employed to estimate the fixed, direct genetic and permanent environment effects. The residual effects were treated as independently distributed with heterogeneous variance for each test week. The direct genetic variance was included with second-order Legendre polynomials and the permanent environment with third-order Legendre polynomials. The heritability of eggshell strength ranged from 0.26 to 0.43, the repeatability ranged between 0.47 and 0.69, and the estimated genetic correlations between test weeks was high at > 0.67. The first eigenvalue of the genetic covariance matrix accounted for about 97% of the sum of all the eigenvalues. The flexibility and statistical power of RRM suggest that this model could be an effective method to improve eggshell quality and to reduce losses due to cracked eggs in a breeding plan. | Chickens |
In the present work, nearly the entire 16S rRNA gene sequences of 46 clinical samples of Neisseria spp. were determined, and the aligned sequences were analyzed to investigate the diversity of 16S rRNA genes in each commensal Neisseria species. Two 16S rRNA types were identified in two Neisseria sicca strains, three 16S rRNA types in five Neisseria macacae strains, fourteen 16S rRNA types in twenty Neisseria flavescens isolates, and fourteen 16S rRNA types in nineteen Neisseria mucosa isolates. The number of nucleotides that were different between 16S rRNA sequences within specie ranged from 1 to 15. We found high intraspecific sequence variation in 16S rRNA genes of Neisseria spp. strains. | Neisseria |
PURPOSE: It has long been documented that patients may experience emotional reactions to a diagnosis of hearing impairment and recommendation of hearing aids. Because of this, patients may raise psychosocial concerns regarding their hearing rehabilitation during audiology appointments, particularly in relation to getting hearing aids. However, thus far there has been little systematic research exploring how patients' concerns about hearing aids are addressed by audiologists within appointments. METHOD: This study used conversation analysis to examine a corpus of 63 video-recorded initial audiology appointments with older adults with hearing impairment. RESULTS: The findings demonstrated that when patients expressed concerns regarding hearing aids, these concerns were typically psychosocial in nature and expressed in a way that carried a negative emotional stance. These types of turns thus invited an empathic response. However, patients' concerns were not typically addressed by audiologists during the appointment. As a consequence, patients persistently re-raised their concerns in subsequent turns, leading to expanded sequences of interaction during the management phase of the appointment. CONCLUSIONS: Older adults' psychosocial concerns regarding hearing aids may not always be sufficiently addressed within audiology appointments. A greater emphasis on emotionally focused communication within audiology could result in improved outcomes from hearing health care services. | Hearing Aids |
Biological systems are dynamic and display heterogeneity at all levels. Ubiquitous heterogeneity, here called for poikilosis, is an integral and important property of organisms and in molecules, systems and processes within them. Traditionally, heterogeneity in biology and experiments has been considered as unwanted noise, here poikilosis is shown to be the normal state. Acceptable variation ranges are called as lagom. Non-lagom, variations that are too extensive, have negative effects, which influence interconnected levels and once the variation is large enough cause a disease and can lead even to death. Poikilosis has numerous applications and consequences e.g. for how to design, analyze and report experiments, how to develop and apply prediction and modelling methods, and in diagnosis and treatment of diseases. Poikilosis-aware new and practical definitions are provided for life, death, senescence, disease, and lagom. Poikilosis is the first new unifying theory in biology since evolution and should be considered in every scientific study." | Biological Variation, Population |
Widely adopted while prospective validation was still under way, extracorporeal membrane oxygenation is now a clinically established treatment for reversing neonatal respiratory failure. The technique's accomplishments are impressive-83% survival in conditions otherwise associated with 80% mortality-but its problems include significant handicap in 20% of treated survivors." | Intensive Care Units, Neonatal |
A new species of hylid frog is described from Tapir Valley Nature Reserve, located on the Caribbean slope of Tenorio Volcano in Bijagua, Alajuela Province, Costa Rica. A molecular phylogenetic analysis supports its inclusion in the genus Tlalocohyla. Morphological, morphometric, larval, and acoustic characteristics further distinguish it from other species in the genus and support its uniqueness. The new species is closely related to T. picta and T. smithii, and is separated by at least 500 kilometers from the nearest known occurrence of a population of T. picta in southern Honduras. The new species is readily distinguished from all other Tlalocohyla by its brilliant green coloration marked with a pronounced, incomplete light dorsolateral stripe that is bordered above by a diffuse reddish-brown stripe. Its dorsum is marked with bold reddish brown spots and its ventral skin is fully transparent. This new Tlalocohyla is currently only known from the type locality, where it inhabits a lentic wetland system with an emergent herbaceous vegetation-dominated benthic zone, surrounded by tropical rainforest. A description of its bioacoustic repertoire and information on natural history, reproduction and habitat preference of this new species are provided. | Rana clamitans |
A newly developed solution is introduced, which makes it possible to design artificial bridges conditionally variable. Thus the frame is fixed on tangential bridges--departing from common techniques--by means of lateral assembled barriers. | Denture, Partial |
Forensic DNA analyses have become more and more sensitive in the past years. With the ability to generate DNA profiles even from minute amounts of cellular material also the possibility to detect DNA on trace material that originates from persons not linked to the crime event, such as crime scene investigators, increases. The contamination of crime scene samples can lead to false positive results and misinterpretation that can cause deceptive investigations. In this work we continue a study of 2010 that compared the number of detected contamination incidents that were caused in the pre-analytical phase of forensic DNA analysis with the number of crime scene samples analyzed by our laboratory. Within the past 17 years we were able to detect a total of 347 contamination incidents caused by police officers in approximately 46,000 trace samples to their origin (0.75%). Additionally we demonstrate the usefulness of reference profile databases that contain DNA profiles of police officers to detect contamination incidents of trace material. | Pre-Analytical Phase |
The growth of plant organs is a complex process powered by osmosis that attracts water inside the cells; this influx induces simultaneously an elastic extension of the walls and pressure in the cells, called turgor pressure; above a threshold, the walls yield and the cells grow. Based on Lockhart's seminal work, various models of plant morphogenesis have been proposed, either for single cells, or focusing on the wall mechanical properties. However, the synergistic coupling of fluxes and wall mechanics has not yet been fully addressed in a multicellular model. This work lays the foundations of such a model, by simplifying as much as possible each process and putting emphasis on the coupling itself. Its emergent properties are rich and can help to understand plant morphogenesis. In particular, we show that the model can display a new type of lateral inhibitory mechanism that amplifies growth heterogeneities due e.g to cell wall loosening. | Plant Development |
In the last decades, many surface modification technologies have been developed in an attempt to improve the function of medical device surfaces by adding or enhancing surface characteristics. These value-added processes included treatment to affect lubricity, hemocompatibility and drug delivery. A unique hydrophilic, lubricious coating was developed to treat hydrophobic polymer surfaces. The coating platforms described are composed of a polyelectrolyte molecular film containing hydrophilic, lubricant molecules. The molecular film is then further cross-linked with di-functional aldehyde molecules to form an interpenetrating network (IPN). The IPN entraps lubricant molecules in the matrix and provides for prolonged stability of the lubricity. This coating was applied to cartridges which were used to deliver intraocular lenses (IOLs) that replaced the cataractous crystalline lenses in patients In order to determine the safety and effectiveness of the coating, a rabbit in vivo study was designed to evaluate the ease of implantation and postoperative response to implantation of the foldable acrylic IOLs. The performance evaluation of the lubricious treated cartridges focused on the ease of insertion and post-IOL implantation response. It was found that the UNFOLDER Emerald Insertion System (Advanced Medical Optics) with lubricious treated cartridges generally required lower insertion forces than the standard UNFOLDER Emerald cartridges. The postoperative inflammatory response following lens extraction and posterior chamber implantation of low (6D), medium (20D) and high (30D) diopter foldable acrylic IOLs with both treated and standard cartridges was mild. Inflammation generally resolved by 3 weeks. Thus, in this animal study, the coating was shown to be effective in assisting the delivery of IOLs through cartridges, without causing any adverse effects." | Lens Implantation, Intraocular |
OBJECTIVE: To study the nature and mechanisms of airway inflammation in chronic bronchitis and observe the effects of inhaled glucocorticoids on inflammatory indices. METHODS: Rat chronic bronchitis model was established by intratracheal instillation of small dose of lipopolysaccharide (LPS, 1 g/L). Experiments were performed in 28 male Sprague-Dawley rats, which comprised four groups in random, i.e. chronic bronchitis model group, normal saline treated group, dexamethasone treated group and healthy control group. The levels of myeloperoxidase (MPO) of blood and lung tissues, and tumor necrosis factor (TNF)alpha and macrophage inflammatory protein-2 (MIP-2) of plasma, broncho-alveolar fluid (BALF) and lung tissues were determined by biochemical and ELISA methods. Total and differential white blood cell counts of BALFwere carried out. RESULTS: (1) The levels of TNFalpha and MIP-2 in BALF and lung tissues, and MPO in lung tissues of chronic bronchitis model group were significantly increased than those of control group (P < 0.05). (2) More significant increase in total white blood cell count and neutrophils in BALF was found in rat chronic bronchitis group than in control group (P < 0.001). (3) Significant positive correlations were observed between the level of MPO and MIP-2 of lung tissues, the level of MPO and TNFalpha of lung tissue and the total cell counts and the level of MIP-2 of BALF and lung tissue. (4) More significant decrease in total cell counts and neutrophils of BALF and levels of MPO in lung tissue was found in dexamethasone-treated group as compared to those of chronic bronchitis group. CONCLUSION: Recruitment and activation of neutrophils seem to be the characteristics of chronic bronchitis. TNFalpha and MIP-2 may be involved in the process of chemotaxis and activation in airway inflammation in chronic bronchitis. Inhaled steroids might have some effects on chronic bronchitis by limiting the airway inflammation. | Bronchitis, Chronic |
Intraocular lenses (IOLs) suitable for implantation were analyzed for the presence of refractile particles. These were found in lathe-cut and injection-molded lenses from various manufacturers. A YAG laser was focused 2 mm beyond the IOLs in a special test chamber and fired through them. The IOLs were then analyzed for damage. A photographically documented study of six IOLs using Q-switched and mode-locked lasers showed optical breakdown occurring within the IOLs; this was not clearly related to refractile particles. Optical breakdown did not occur in two IOLs with a similar number of refractile particles. Damage was seen with the mode-locked but not with the Q-switched laser. The optical breakdown occurred more frequently at high power (5.0 mJ) than at low power (1.2 mJ). | Lasers |
AIM: To evaluate the immunohistochemical localization of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) on tumor tissue specimens from patients with hepatocellular carcinoma (HCC) and the serum levels of IL-6 and sIL-6R in a group of patients with HCC as well as liver cirrhosis (LC) in a group of patients with LC alone and in a control group. METHODS: Three groups of subjects were studied: group I (n = 83) suffering from HCC and LC, group II (n = 72) suffering from LC alone and group III (n = 42) as healthy controls. All patients had hepatitis C virus infection. Serum IL-6 and IL-6R levels were determined using a commercially available ELISA kit. Immunohistochemistry was performed using the streptavidin-biotin complex and rabbit polyclonal antibodies against IL-6 and IL-6R. RESULTS: Immunohistochemistry analysis showed a medium to strong cytoplasmic and membrane reactivity for IL-6 and IL-6R respectively, in at least 40% of cases of HCC, whereas liver cirrhosis patients and controls were negative for IL-6 or showed a very mild and focal dot-like cytoplasmic reaction for IL-6R. Serum IL-6 levels in HCC group were significantly higher than those in LC and control groups (P < 0.0001). There was no significant difference in sIL-6R concentrations among 3 groups. When the patients with HCC were divided into groups according to Okuda's classification, a significant serum increase of IL-6 and sIL-6R level was observed from stage I to stage III (P < 0.02, P < 0.0005). When HCC and LC patients were divided into 3 classes of cirrhosis severity according to Child-Pugh, values in HCC patients were significantly higher than those in LC patients for each corresponding class (P < 0.01). CONCLUSION: IL-6 serum levels in HCC patients are higher than those in LC patients and controls, suggesting an increased production of this cytokine by neoplastic cells. sIL-6R values are similar in all groups, increasing only in stage III HCC patients. These data suggest that they have a closer relationship with the neoplastic mass rather than with the residual functioning hepatic mass. | Receptors, Interleukin-6 |
The present study aimed to morphologically examine the gingival microvascular network using a microvascular resin cast (MRC) technique, and to investigate how inflammatory disease functionally affects gingival microcirculation using laser Doppler flowmetry (LDF). We used four beagle dogs with healthy periodontal tissue as experimental animals. To cause periodontal inflammation, dental floss was placed around the cervical neck portions of the right premolars. The unmanipulated left premolars served as controls, and received plaque control every 7 days. After 90 days, gingivitis was induced in the experimental side, while the control side maintained healthy gingiva. To perform morphological examinations, we used an MRC method involving the injection of low-viscosity synthetic resin into the blood vessels, leading to peripheral soft-tissue dissolution and permitting observation of the bone, teeth, and vascular cast. Gingival blood flow was estimated using an LDF meter. The control gingival vasculature showed hairpin-loop-like networks along the tooth surface. The blood vessels had diameters of 20-40 mum and were regularly arranged around the cervical portion. On the other hand, the vasculature in the experimental group was twisted and gathered into spiral forms, with blood vessels that had uneven surfaces and smaller diameters of 8-10 mum. LDF revealed reduced gingival blood flow in the group with experimentally induced gingivitis compared to controls. The actual measurements of gingival blood flow by LDF were in agreement with the alterations that would be expected based on the gingivitis-induced morphological alterations observed with the MRC technique. | Corrosion Casting |
OBJECTIVE: To investigate the diagnostic performance of ultrasound in predicting birth-weight (BW) discordance in twin pregnancy. METHODS: Electronic databases PubMed, EMBASE and CINAHL were searched using combinations of MeSH terms 'birth weight', 'discordance', 'twins' and 'ultrasound'. Summary estimates of sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratios for the predictive accuracy of sonographically estimated fetal-weight (EFW) discordance and abdominal-circumference (AC) discordance in predicting BW discordance were computed using hierarchical summary receiver-operating characteristics curves. RESULTS: Twenty studies (including 5826 twin pregnancies) were included. EFW discordance >/= 20% had a sensitivity of 65.4% and specificity of 90.8% in predicting BW discordance >/= 20%. The predictive performance of ultrasound performed within 1 month, 2 weeks and 3 days before birth was 61.4%, 72.3% and 78.9%, respectively. EFW discordance >/= 25% had a sensitivity of 57.7% and specificity of 95.2% in predicting BW discordance >/= 25%. The sensitivity of EFW discordance >/= 25% detected within 1 month, 2 weeks and 3 days before birth was 60.0%, 75.0% and 60.3%, respectively, while the corresponding values for specificity were 97.7%, 96.2% and 87.3%, respectively. In view of the different cut-offs reported among studies, it was not possible to perform comprehensive data synthesis for each AC discordance cut-off. The optimal diagnostic performance of AC discordance was for prediction of BW discordance >/= 25%, with a sensitivity of 70.8% and specificity of 86.4%. CONCLUSION: Ultrasound EFW discordance has an overall moderate accuracy in predicting BW discordance in twin pregnancy. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. | Crown-Rump Length |
Unravelling the biosynthetic pathway of quinolizidine alkaloids (QAs), regarded as antinutritional compounds of narrow-leafed lupin (NLL) seeds, is fundamental to best exploit NLL as food or feed. We investigated 12 candidate genes connected to QA biosynthesis, selecting them by transcriptomic and genomic approaches, from the landscape of genes differentially expressed in leaves of the high- and low-alkaloid NLL accessions. Linkage analysis enabled the assessment of the location of the candidate genes in relation to iucundus, a major locus of unknown identity, that confers reduced QA content in seeds. The key finding was the identification of APETALA2/ethylene response transcription factor, RAP2-7, cosegregating with the iucundus locus and located within a region with highly significant QTLs that affect QA composition. We additionally identified a 4-hydroxy-tetrahydrodipicolinate synthase (DHDPS) gene involved in L-lysine biosynthesis as being closely linked to iucundus. The distributed location of other remaining candidates (including previously known QA genes) across different linkage groups, also indirectly supports the transcription factor as a possible regulator of lupin alkaloid biosynthesis. Our findings provide crucial insight into QA biosynthesis in NLL. Additionally, we evaluated and selected appropriate reference genes for qRT-PCRs to analyse the expression levels of QA genes in NLL. | Lupinus |
Since its conversion to a for-profit company in 1981, Maxicare has become a leader in the alternate health care delivery systems currently emerging in the United States. It has fostered a private practice physician network to provide care on a national scale to over 800,000 members and is currently entering the large New York City market." | Health Facilities, Proprietary |
The cardiovascular actions of cannbinoids are complex. In general they cause vasorelaxation in isolated blood vessels, while in anaesthetised animals they cause multiphasic responses which involve an early bradycardia and long-lasting hypotension. However, in conscious animals, the picture is one of bradycardia followed by pressor responses. Clearly, the responses to cannabinoids are dependent on the experimental conditions and synthetic cannabinoids and endocannabinoids exhibit different pharmacologies. In terms of mechanisms involved in the vascular responses to cannabinoids, the following have been implicated: the involvement of 'classical' cannabinoid receptors, the involvement of a novel endothelial cannabinoid receptor, the release of nitric oxide, the release of endothelium-derived hyperpolarising factor (EDHF), the activation of vanilloid receptors, metabolism of endocannabinoids to vasoactive molecules, and both peripheral inhibition and central excitation of the sympathetic nervous system. | Arachidonic Acids |
The tumor suppressor gene p53 induces growth arrest and/or apoptosis in response to DNA damage/hypoxia. Inactivation of p53 confers a selective advantage to tumor cells under a hypoxic microenvironment during tumor progression. The subterranean blind mole rat, Spalax, spends its life underground at low-oxygen tensions, hence developing a wide range of respiratory/molecular adaptations to hypoxic stress, including critical changes in p53 structure and signaling pathway. The highly conserved p53 Arg(R)-172 is substituted by lysine (K) in Spalax, identical with a tumor-associated mutation. Functionality assays revealed that Spalax p53 is unable to activate apoptotic target genes but is still capable of activating cell cycle arrest genes. Furthermore, we have shown that the transcription patterns of representative p53-induced genes (Apaf1 and Mdm2) in Spalax are influenced by hypoxia. Cell cycle arrest allows the cells to repair DNA damage via different DNA repair genes. We tested the transcription pattern of three p53-related DNA repair genes (p53R2, Mlh1, and Msh2) under normoxia and short-acute hypoxia in Spalax, C57BL/6 wild-type mice, and two strains of mutant C57BL/6 mice, each carrying a different mutation at the R172 position. Our results show that while wild-type/mutant mice exhibit strong hypoxia-induced reductions of repair gene transcript levels, no such inhibition is found in Spalax under hypoxia. Moreover, unlike mouse p53R2, Spalax p53R2 transcript levels are strongly elevated under hypoxia. These results suggest that critical repair functions, which are known to be inhibited under hypoxia in mice, remain active in Spalax, as part of its unique hypoxia tolerance mechanisms. | Spalax |
We report a case of substantial rebreathing which occurred during the thoracoscopic bulla resection despite a normal FICO2 reading on capnogram. Early detection of inspiratory unidirectional valve malfunction as the cause of the rebreathing was only possible by careful observation of the capnogram pattern. During the course of one lung anesthesia, a rising end-tidal CO2 concentration (FETCO2) and a change in the pattern of the capnogram were observed. However, the lowest FICO2 value in the late phase of inspiration stayed below the alarm limit setting of rebreathing. For this reason, the capnograph failed to identify the beginning of inspiration and perceived the high FICO2 value in early inspiration as part of expiratory plateau. In case of the inspiratory valve malfunction, it is possible that analysis of the capnogram reveals underestimated FICO2. | Anesthesia, Inhalation |
PET using FDG is a critical tool for evaluation of dementias, with characteristic patterns of hypometabolism suggesting specific diagnoses. Hypometabolism in the occipital region is recognized as an important finding associated with dementia with Lewy bodies and posterior cortical atrophy. We describe here the novel occipital tunnel" sign, which results from relative sparing of FDG uptake in the medial occipital (primary visual) cortex compared with more severe loss in the surrounding lateral occipital (visual association) cortex. This sign is useful for recognizing the occipital findings of dementia with Lewy bodies and posterior cortical atrophy, especially when viewing sagittal projections." | Occipital Lobe |
The TATA box-binding protein (TBP) is an essential component of the RNA polymerase II transcription apparatus in eukaryotic cells. Until recently, it was thought that the general transcriptional machinery was largely invariant and relied on a single TBP, whereas a large and diverse collection of activators and repressors were primarily responsible for imparting specificity to transcription initiation. However, it now appears that the basal" transcriptional machinery also contributes to specificity via tissue-specific versions of TBP-associated factors as well as a tissue-specific TBP-related factor (TRF1) responsible for gene selectivity in Drosophila. Here we report the cloning of a TBP-related factor (TRF2) that is found in humans, Drosophila, Caenorhabditis elegans, and other metazoans. Like TRF1 and TBP, TRF2 binds transcription factor IIA (TFIIA) and TFIIB and appears to be part of a larger protein complex. TRF2's primary amino acid structure suggests divergence in the putative DNA binding domain, and not surprisingly, it fails to bind to DNA containing canonical TATA boxes. Most importantly, TRF2 is associated with loci on Drosophila chromosomes distinct from either TBP or TRF1, so it may have different promoter specificity and regulate a select subset of genes. These findings suggest that metazoans have evolved multiple TBPs to accommodate the vast increase in genes and expression patterns during development and cellular differentiation." | TATA Box |
The Cytisus-Genista complex includes species that have become invasive following introduction into new geographic ranges as ornamental shrubs. Despite their impacts, the evolutionary relationships among invasives, ornamentals, and native-range species have never been investigated. Our objective was to examine relationships within the Cytisus-Genista complex to determine (1) the taxonomic identity of invasive French broom" and ornamental "sweet broom" and (2) whether "sweet broom" contributes to "French broom" populations directly or via hybridization. We used sequence data from chloroplast and nuclear regions to gain insight into evolutionary origins and to confirm taxonomic status. Our phylogenetic analyses suggest a complex evolutionary history that includes hybridization events. Placement of invasive and ornamental individuals within the Cytisus-Genista complex resolves taxonomic uncertainty in these groups, as our phylogenetic analyses recovered separate "French broom" and "sweet broom" clades within the G. monspessulana clade in the genus Genista. Extensive cloning and sequencing of the ITS region revealed that, although the majority of invasive "French broom" in California is Genista monspessulana, hybridization with individuals from the ornamental "sweet broom" clade likely occurs in populations throughout the state." | Genista |
AIM: To investigate the anti-obesity and antibacterial effects of Ligustrum robustum (L. robustum) in vivo and in vitro and its possible mechanisms. METHODS: The effects of L. robustum aqueous extract (LR) on various gut bacteria in vitro were evaluated. The effects of LR on high-fat diet-fed (HFD) rats in vivo were also assessed. Culture methods, quantitative polymerase chain reaction, and terminal-restriction fragment length polymorphism were used to analyze the effects of LR on gut bacteria. Biochemical tests were also performed to detect the changes in obesity-related indicators after LR treatment. RESULTS: LR treatment lowered adipose weight and decreased Lee's index, blood glucose, total cholesterol, and lipid in the tested groups relative to control (P < 0.05). To determine the reasons for these changes, we assessed the potential bacteriostatic and bactericidal effects of LR on specific bacterial species in vitro. LR affected the richness, diversity, and evenness of gut bacteria, increased fecal Lactobacillus, and decreased Enterococci in HFD rats (P < 0.05). CONCLUSION: L. robustum may be a safe and effective food for weight loss and obesity control, and the effects of L. robustum might be mediated by the regulation of gut bacteria. | Ligustrum |
As an attempt to utilize of rare earth elements as a novel method to activate the silent genes in fungus, the marine-derived fungus Penicillium citrinum was cultured under ordinary laboratory fermentation conditions in the presence of scandium chloride (ScCl(3), 50â¯muM), and chemical investigation led to the isolation and characterization of three new peptide derivatives (1-3), along with four known pyrrolidine alkaloids (4-7). Those structures were elucidated by spectroscopic data interpretation, as well as chemical reactions. Comparative metabolic profiling of the culture extracts (with/without scandium chloride) indicated that compounds 1-3 scarcely detected in the absence of ScCl(3). In addition, the antibacterial and cytotoxic activities of all isolated products were evaluated. | Petrosia |
The platinum-based chemotherapy is the standard treatment for several types of cancer. However, cancer cells often become refractory with time and most patients with serious cancers die of drug resistance. Recently, we have discovered a unique dissociative electron-transfer mechanism of action of cisplatin, the first and most widely used platinum-based anticancer drug. Here, we show that the combination of cisplatin with an exemplary biological electron donor, N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD), may overcome the resistance of cancer cells to cisplatin. Our steady-state absorption and fluorescence spectroscopic measurements confirm the effective dissociative electron-transfer reaction between TMPD and cisplatin. More significantly, we found that the combination of 100 muM TMPD with cisplatin enhances double-strand breaks of plasmid DNA by a factor of approximately 3.5 and dramatically reduces the viability of cisplatin-sensitive human cervical (HeLa) cancer cells and highly cisplatin-resistant human ovarian (NIH:OVCAR-3) and lung (A549) cancer cells. Furthermore, this combination enhances apoptosis and DNA fragmentation by factors of 2-5 compared with cisplatin alone. These results demonstrate that this combination treatment not only results in a strong synergetic effect, but also makes resistant cancer cells sensitive to cisplatin. Because cisplatin is the cornerstone agent for the treatment of a variety of human cancers (including testicular, ovarian, cervical, bladder, head/neck, and lung cancers), our results show both the potential to improve platinum-based chemotherapy of various human cancers and the promise of femtomedicine as an emerging frontier in advancing cancer therapy. | Tetramethylphenylenediamine |
IMPORTANCE OF THE FIELD: Alcohol abuse and dependence are major causes of morbidity and mortality and come with a high societal cost. The illness is notoriously difficult to treat and relapse is a common occurrence. Acamprosate represents an effective addition to the treatment options available for alcohol dependence with a novel mechanism of action. AREAS COVERED IN THIS REVIEW: We review the published acamprosate literature focusing on major and recent comparative clinical trials and meta-analyses. We included all studies found in National Library of Medicine's PubMed database searching on Mesh term: acamprosate excluded animal studies excluding non-English publications, and focusing on efficacy/effectiveness studies. Additionally, we discuss background information on alcohol dependence and acamprosate's putative mechanism of action. Safety and tolerability data are also presented. WHAT THE READER WILL GAIN: The reader will gain a better understanding of the role of acamprosate in the treatment of alcohol dependence and find a useful synopsis of the more recently published literature evaluating acamprosate's effectiveness based on what are not always identically defined primary study outcomes. TAKE HOME MESSAGE: Acamprosate is safe and effective in the maintenance of abstinence from alcohol use/abuse and is most commonly used in combination with nonpharmacologic therapeutic modalities. The effect size ranged from 1.3 to 2 for most of the studies included in this review. | Alkanesulfonic Acids |
Given the involvement of oxidative stress in liver-disease- or hepato-toxicant-induced hepatic damage and fibrosis, antioxidants are an effective preventive and therapeutic tool. The beneficial results of vitamin C, one of the physiological antioxidants, have been observed both in experimental animals and in humans. However, most of these studies have been concerned with supplementary vitamin C; the effects of under vitamin C insufficiency, which humans sometimes confront, have not been substantially investigated. In the present study, we established a vitamin C-insufficient animal model (half-to-normal serum vitamin C concentration) with gulo(-/-) mice that cannot synthesize vitamin C, and induced hepatotoxicity by means of thioacetamide (TAA) injections twice a week for 18 weeks. Additionally, we explored the direct effects of vitamin C both on immortalized human hepatic stellate LX-2 cells and on rat primary hepatic stellate cells. Vitamin C insufficiency resulted in a decreased survival rate and increased serum markers for hepatocyte damage, such as alanine aminotransferase and aspartate aminotransferase. Concomitantly, the levels of reactive oxygen species (ROS) and lipid peroxides in the liver were increased. Histological examinations of the vitamin C-insufficient liver revealed increases in collagen fiber deposition and activated-hepatic-stellate-cell number. Vitamin C, when directly applied to the LX-2 cells as well as the rat primary hepatic stellate cells, suppressed not only proliferation but hydrogen peroxide-induced collagen expression as well. In conclusion, vitamin C insufficiency exacerbated TAA-induced hepatotoxicity. These effects seem to be mainly from insufficient scavenging of ROS in the liver, and possibly in part, by directly affecting hepatic stellate cells. | L-Gulonolactone Oxidase |
Cryopyrin-associated periodic syndromes are categorized as a spectrum of three autoinflammatory diseases, namely familial cold auto-inflammatory syndrome, Muckle-Wells syndrome and chronic infantile neurological cutaneous articular syndrome. All are caused by mutations in the NLRP3 gene coding for cryopyrin and result in active interleukin-1 release: their rarity and shared clinical indicators involving skin, joints, central nervous system and eyes often mean that correct diagnosis is delayed. Onset occurs early in childhood, and life-long therapy with interleukin-1 blocking agents usually leads to tangible clinical remission and inflammatory marker normalization in a large number of patients, justifying the need to facilitate early diagnosis and thus avoid irreversible negative consequences for tissues and organs." | Cryopyrin-Associated Periodic Syndromes |
Multivesicular endosomes/bodies (MVBs) sort membrane proteins between recycling and degradative pathways. Segregation of membrane proteins onto intraluminal vesicles (ILVs) of MVBs removes them from the recycling pathway and facilitates their degradation following fusion of MVBs with lysosomes. Sorting of many cargos onto ILVs depends on the ESCRT (Endosomal Sorting Complex Required for Transport) machinery, although ESCRT-independent mechanisms also exist. In mammalian cells, efficient sorting of ligand-stimulated epidermal growth factor receptors onto ILVs also depends on the tyrosine phosphatase, PTP1B, an ER-localised enzyme that interacts with endosomal targets at membrane contacts between MVBs and the ER. This review focuses on the potential roles played by ER:MVB membrane contact sites in regulating ESCRT-dependent ILV formation. | Multivesicular Bodies |
Immunoassays, or assays that are using antibodies as the specific binding reagents, have become one of the most common methodologies in diagnostic laboratories. In this paper we review different configurations of immunoassays as applied to a variety of analytes and sensitivity limits, along with common detection techniques and strategies. Progress in developing of ultra high affinity antibodies as a direction to improved immunoassays is also reviewed. Finally, we specifically concentrate on determination of antibody binding constants and performing immunoassays at the single molecule level using Fluorescence Correlation Spectroscopy (FCS). This technique has become a powerful tool in molecular binding characterizations and assay development, and possibly will grow into a quantitative analytical method suitable for diagnostic tests. | Binding Sites, Antibody |
Epstein-Barr virus (EBV) is typically found in a latent, asymptomatic state in immunocompetent individuals. Perturbations of the host immune system can stimulate viral reactivation. Furthermore, there are a myriad of EBV-associated illnesses including various cancers, post-transplant lymphoproliferative disease, and autoimmune conditions. A thorough understanding of this virus, and the interplay between stress and the immune system, is essential to establish effective treatment. This review will provide a summary of the interaction between both psychological and cellular stressors resulting in EBV reactivation. It will examine mechanisms by which EBV establishes and maintains latency and will conclude with a brief overview of treatments targeting EBV. | Virus Latency |
A phenotypically female child, investigated because of short stature, had abnormally large, often bipartite Barr bodies and a mosaicism of 45, X cells and cells with 46 chromosomes which included an exceptionally large metacentric chromosome (Xp+). G- and C-banding established that the chromosome was derived from two substantially entire X chromosomes joined short arm-to-short arm, and was likely to be an isodicentric X with functional inactivation of one centromere. | Sex Chromatin |
PURPOSE: Uncorrected refractive error remains a leading cause of visual impairment (VI) across the globe with Mozambique being no exception. The establishment of an optometry profession in Mozambique that is integrated into the public health system denotes significant progress with refractive services becoming available to the population. As the foundations of a comprehensive refractive service have now been established, this article seeks to understand what barriers may limit their uptake by the general population and inform decision making on improved service delivery. METHODS: A community-based cross-sectional study using two-stage cluster sampling was conducted. Participants with VI were asked to identify barriers that were reflective of their experiences and perceptions of accessing refractive services. A total of 4601 participants were enumerated from 76 clusters in Nampula, Mozambique. RESULTS: A total of 1087 visually impaired participants were identified (884 with near and 203 with distance impairment). Cost was the most frequently cited barrier, identified by more than one in every two participants (53%). Other barriers identified included lack of felt need (20%), distance to travel (15%), and lack of awareness (13%). In general, no significant influence of sex or type of VI on barrier selection was found. Location had a significant impact on the selection of several barriers. Pearson chi analysis indicated that participants from rural areas were found to feel disadvantaged regarding the distance to services (p </= 0.001) and adequacy of hospital services (p = 0.001). CONCLUSIONS: For a comprehensive public sector refractive service to be successful in Mozambique, those planning its implementation must consider cost and affordability. A clear strategy for overcoming lack of felt need will also be needed, possibly in the form of improved advocacy and health promotion. The delivery of refractive services in more remote rural areas merits careful and comprehensive consideration. | Eyeglasses |
In this paper, Pd nanoplates were used as a kind of electrode materials for fabrication of an electrochemical immunosensor, which was applied for detection of cancer biomarker alpha-fetoprotein (AFP). Thanks to the unique structure and properties of Pd nanoplates, the antibody of AFP (Ab) was effectively immobilized onto the surface of the Pd nanoplates modified glassy carbon electrode (GCE). Moreover, the good electrochemical properties of Pd nanoplates greatly improved the electronic transmission rate and enhanced the electrochemical signal, which led to an increase of the detection sensitivity. Based on the specific antibody-antigen interaction, a label-free immunosensor based on Pd nanoplates was developed for sensing of AFP. The current method allows us to detect AFP over a wide concentration range from 0.01 to 75.0 ng/mL with a detection limit of 4 pg/mL. The proposed immunosensor has been used to determine AFP in human serum with satisfactory results. | alpha-Fetoproteins |
The state of microcirculation was studied by bulbar biomicroscopy in 18 healthy persons and 53 patients with dyscirculatory encephalopathy before and after treatment with vasoactive drugs (xanthinol nicotinate, Cavinton, Sermion). It was found that the microcirculation changes depended on the stage of the disease. It was found that the above drugs produced a positive effect on the microcirculation, the values of which normalized by the end of the course of treatment, especially after their direct administration. | Nicergoline |
OBJECTIVE: To assess the incidence of postoperative wound infections related to treatment with medicinal leeches at Ghent University Hospital. METHOD: A 2-year retrospective analysis of bacteriologic culture results of soft tissue infections in patients treated with medicinal leeches. RESULTS: Cultures of suspected wound infections were taken and susceptibility testing of isolates was performed on 17 of 47 patients (36.2%). Aeromonas was frequently isolated (18.5%). CONCLUSIONS: A high incidence of infection during and after application of medicinal leeches, despite their external decontamination, necessitates an antibiotic prophylaxis. In particular Aeromonas must be covered, as soft tissue infections with these bacteria can give serious complications. The prophylactic antibiotic should cover the most frequent isolated species taking into account the importance of Aeromonas and the susceptibility pattern. Based on the results, fluoroquinolones seem to be a good choice. The authors believe that practical recommendations to hospital pharmacists on prophylaxis during Hirudo medicinalis treatment, might enhance the safety of it's use by reducing the number of infections. | Hirudo medicinalis |
A 12-year-old female dog with a 3-month history of poor response to diabetes treatment had an acute worsening of symptoms, including weakness and blindness. The dog had elevated blood glucose, alkaline phosphatase and urea concentration, hyposthenuria, glycosuria, hematuria, and pyuria. Escherichia coli was isolated from the urine. Radiographs and ultrasound examination showed that the dog had unilateral emphysematous pyelitis and concurrent cystitis associated with vesicoureteral reflux. | Pyelocystitis |
Migratory insertion of benzylidene carbene ligands into arylpalladium(II) species generates eta(3)-benzylpalladium intermediates that can cyclize to generate five- and six-membered rings with new sp(3) centers. The reaction tolerates a range of arene functional groups and stabilized enolates. The products generated through this reaction are 1-arylindanes and 1-aryltetralins that are common to a range of natural products. | Tetrahydronaphthalenes |
AIMS: Brepocitinib is a tyrosine kinase 2/Janus kinase 1 inhibitor being investigated for the treatment of several autoimmune diseases. This study assessed the absorption, distribution, metabolism and excretion of oral brepocitinib, and the absolute oral bioavailability (F) and fraction absorbed (F(a) ) using a (14) C microtracer approach. METHODS: This was a phase 1 open-label, nonrandomized, fixed sequence, two-period, single-dose study of brepocitinib in healthy male participants. Participants received a single oral 60 mg dose of (14) C brepocitinib (~300 nCi) in Period A, then an unlabelled oral 60 mg dose followed by an intravenous (IV) 30 mug dose of (14) C labelled brepocitinib (~300 nCi) in Period B. Mass balance, pharmacokinetic parameters and safety were assessed. RESULTS: Six participants were enrolled. Brepocitinib was absorbed rapidly following oral administration. In Period A, total recovery of the oral dose was 96.7% +/- 6.3% (88.0% +/- 8.0% in urine, 8.7% +/- 2.1% in faeces). In Period B, a small fraction (6.0% of the oral dose) was recovered unchanged in urine. F and F(a) were 74.6% (90% confidence interval 67.3%, 82.8%) and 106.9%, respectively. Brepocitinib demonstrated an acceptable safety profile and was well tolerated following oral or oral then IV administrations. No deaths, serious adverse events or discontinuations were reported. CONCLUSION: Intestinal absorption of brepocitinib was essentially complete after oral administration, with F ~75%. Drug-related material recovery was high, with the majority excreted in urine. The major route of elimination of brepocitinib was renal excretion as metabolites, whereas urinary elimination of unchanged brepocitinib was minor. NCT: NCT03770039. | Renal Elimination |
The authors studied neuroleptic concentration-therapeutic response curves for butaperazine (BPZ), a piperazine phenothiazine, in 10 schizophrenic patients during the first 12 days of treatment. BPZ bound to red blood cells (RBC) was more strongly correlated with therapeutic response than was plasma BPZ. RBC BPZ concentrations could be used to define a therapeutic window", an optimun concentration for therapeutic response, above and below which favorable response diminishes. The authors emphasize the preliminary nature of the data but suggest that levels of RBC-bound neuroleptic may provide an important guide for dosage regulation in schizophrenic patients." | Phenothiazines |
The National Center for Advancing Translational Sciences (NCATS) defines translational science as "the field of investigation focused on understanding the scientific and operational principles underlying each step of the translational process." A major goal of translational science is to determine commonalities across projects to identify principles for addressing persistent bottlenecks in this process. To meet this goal, translational scientists must be conversant in multiple disciplines, work in teams, and understand the larger translational science ecosystem. The development of these skills through translational science training opportunities, such as the translational science training offered by the NCATS intramural research program, prepares fellows for a variety of career options. The unique structure of the NCATS intramural program and the career outcomes of its alumni are described herein to demonstrate the distinct features of this training environment, the productivity of fellows during their time in training, and how this prepares fellows to be competitive for a variety of science careers. To date, the NCATS intramural research program has trained 213 people, ranging from high school to postdoctoral levels. These alumni have transitioned into a wide array of career functions, types, and sectors." | National Center for Advancing Translational Sciences (U.S.) |
Exome sequencing is a powerful tool in prenatal and postnatal genetics and can help identify novel candidate genes critical to human development. We describe seven unpublished probands with rare likely pathogenic variants or variants of uncertain significance that segregate with recessive disease in TBC1D32, including four fetal probands in three unrelated pedigrees and three pediatric probands in unrelated pedigrees. We also report clinical comparisons with seven previously published patients. Index probands were identified through an ongoing prenatal exome sequencing study and through an online data sharing platform (Gene Matcher). A literature review was also completed. TBC1D32 is involved in the development and function of cilia and is expressed in the developing hypothalamus and pituitary gland. We provide additional data to expand the phenotype correlated with TBC1D32 variants, including a severe prenatal phenotype associated with life-limiting congenital anomalies. | Ciliopathies |
Chromochloris zofingiensis represents a potential algal producer of the value-added ketocarotenoid astaxanthin. Here, rutin, a low-cost flavonoid compound, was evaluated regarding its roles in C. zofingiensis production under astaxanthin-inducing conditions via physiological, biochemical, and transcriptomics analyses. The rutin treatment allowed C. zofingiensis to achieve 81.2% more biomass and 20.5% greater astaxanthin content under nitrogen deprivation, leading to more than doubled astaxanthin production. The rutin-treated C. zofingiensis had higher levels of chlorophylls, proteins, and lipids and lower carbohydrate level than the control. Rutin promoted the intracellular abscisic acid (ABA) level, which could be restored by the ABA biosynthesis inhibitor, accompanied by the restoration of biomass concentration and astaxanthin content. The application of exogenous ABA to C. zofingiensis also furthered biomass concentration and astaxanthin accumulation. Together with the comparative transcriptomics analysis, our study provides implications into the involvement of ABA in rutin-mediated stimulation of C. zofingiensis growth and astaxanthin accumulation and highlights a feasible strategy of combining stress and chemical induction for improved microalgal production. | Chlorophyceae |
Triggering of phagocyte apoptosis is a major virulence mechanism used by some successful bacterial pathogens. A central issue in the apoptotic death context is that fully developed apoptosis results in necrotic cell autolysis (secondary necrosis) with release of harmful cell components. In multicellular animals, this occurs when apoptosing cells are not removed by scavengers, mainly macrophages. Secondary necrotic lysis of neutrophils and macrophages may occur in infection when extensive phagocyte apoptosis is induced by bacterial cytotoxins and removal of apoptosing phagocytes is defective because the apoptotic process exceeds the available scavenging capacity or targets macrophages directly. Induction of phagocyte secondary necrosis is an important pathogenic mechanism, as it combines the pathogen evasion from phagocyte antimicrobial activities and the release of highly cytotoxic molecules, particularly of neutrophil origin, such as neutrophil elastase. This pathogenicity mechanism therefore promotes the unrestricted multiplication of the pathogen and contributes directly to the pathology of several necrotizing infections, where extensive apoptosis and necrosis of macrophages and neutrophils are present. Here, examples of necrotizing infectious diseases, where phagocyte secondary necrosis is implicated, are reviewed. | Phagocytes |
INTRODUCTION: Rheopheresis is an extracorporal selective double-filtration procedure with an initial separation of plasma from the whole blood and a further filtration of the plasma through a second filter in order to eliminate a certain number of high molecular weight proteins such LDL, Lp(a), fibrinogen, alpha2-macroglobulin, Factor von Willebrand, and IgM Immunoglobulin. METHODS: In this narrative review we discuss the available data on the effects of Rheopheresis in various clinical conditions. RESULTS: Rheopheresis is considerd to exert a rapid effect on clinical conditions associated with seriously affected microcirculation and rheologic parameters such as, the dry age-related macular degeneration (AMD), sudden sensorineural hearing loss (SSHS), peripheral artery disease (PAD), calciphylaxis, systemic sclerosis and diabetic foot. CONCLUSIONS: Rheopheresis is a promising technique for conditions associated with affected microcirculatory rheologic parameters. | Blood Component Removal |
AIM: We aimed to describe otogenic lateral sinovenous thrombosis (OLST), a rare, potentially life-threatening complication of otomastoiditis. METHODS: Children diagnosed with OLST in a tertiary-care Hospital from 2014 to 2019 was retrospectively selected. Clinical and radiological features, timing of diagnosis, treatment and outcome are reported. RESULTS: Seven children (5 males) were studied. Fever and neurological symptoms (headache, lethargy, diplopia, dizziness and papilledema) were always present. Otalgia and/or otorrhea were found in 6 children; none had signs of mastoiditis. Diagnosis was reached after 7 days (median) from clinical onset. Brain CT-scan was performed in 5 children being diagnostic for 3. Venography-MRI detected OLST and mastoiditis in all cases without parenchymal lesions. Treatment was based on intravenous rehydration, antibiotic and low-molecular weight heparin; acetazolamide was added in 3 children. Mastoidectomy and ventriculoperitoneal-shunting were selectively performed. Patients were discharged after 26 days (median). Follow-up neuroimaging showed sinus recanalization after a median time of 6 months. CONCLUSION: A multidisciplinary approach is needed to optimize diagnostic-therapeutic protocols of pediatric OLST. | Mastoidectomy |
With the rapid development of imaging modalities and surgical techniques, the clinical entity representing tumors that are intermediate between resectable and unresectable pancreatic adenocarcinoma has been identified has been termed borderline resectable" (BR). These tumors are generally amenable for resection but portend an increased risk for positive margins after surgery and commonly necessitate vascular resection and reconstruction. Although there is a lack of consensus regarding the appropriate definition of what constitutes a BR pancreatic tumor, it has been demonstrated that this intermediate category carries a particular prognosis that is in between resectable and unresectable disease. In order to downstage the tumor and increase the probability of clear surgical margins, neoadjuvant therapy is being increasingly utilized and studied. There is a lack of high-level evidence to establish the optimal treatment regimen for BR tumors. When resection with negative margins is achieved after neoadjuvant therapy, the prognosis for BR tumors approaches and even exceeds that for resectable disease. This review presents the current definitions, different treatment approaches, and the clinical outcomes of BR pancreatic cancer." | Induction Chemotherapy |
A field study was conducted in the boro season of 2011-12 and aman season of 2012 at Jessore, Bangladesh, to evaluate the performance of sequential applications of preemergence herbicides (oxadiargyl 80 g ai ha(-1), pendimethalin 850 g ai ha(-1), acetachlor + bensulfuranmethyl 240 g ai ha(-1), and pyrazosulfuron 15 g ai ha(-1)) followed by a postemergence herbicide (ethoxysulfuron 18 g ai ha(-1)) in dry-seeded rice. All evaluated herbicides reduced weed density and biomass by a significant amount. Among herbicides, pendimethalin, oxadiargyl, and acetachlor + bensulfuranmethyl performed very well against grasses; pyrazosulfuron, on the other hand, was not effective. The best herbicide for broadleaf weed control was oxadiargyl (65-85% control); pendimethalin and acetachlor + bensulfuraonmethyl were not effective for this purpose. The best combination for weed control was oxadiargyl followed by ethoxysulfuron in the boro season and oxadiargyl followed by a one-time hand weeding in the aman season. Compared with the partial weedy plots (hand weeded once), oxadiargyl followed by ethoxysulfuron (4.13 t ha(-1)) provided a 62% higher yield in the boro season while oxadiargyl followed by a one-time hand weeding (4.08 t ha(-1)) provided a 37% higher yield in the aman season. | Herbicides |
BACKGROUND: Tamoxifen is widely used for Cre-estrogen receptor-mediated genomic recombination in transgenic mouse models to mark cells for lineage tracing and to study gene function. However, recent studies have highlighted off-target effects of tamoxifen in various tissues and cell types when used for induction of Cre recombination. Despite the widespread use of these transgenic Cre models to assess gastrointestinal (GI) function, the effect of tamoxifen exposure on GI motility has not been described. METHODS: We examined the effects of tamoxifen on GI motility by measuring total GI transit, gastric emptying, small intestinal transit, and colonic contractility in wild-type adult mice. KEY RESULTS: We observed a significant delay in total GI transit in tamoxifen-treated mice, with unaltered gastric emptying, accelerated small intestinal transit, and abnormal colonic motility. CONCLUSION: Our findings highlight the importance of considering GI motility alterations induced by tamoxifen when designing protocols that utilize tamoxifen as a Cre-driver for studying GI function." | Digestive System Physiological Phenomena |
BACKGROUND: The 2019 novel coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently a major challenge threatening the global healthcare system. Respiratory virus infection is the most common cause of asthma attacks, and thus COVID-19 may contribute to an increase in asthma exacerbations. However, the mechanisms of COVID-19/asthma comorbidity remain unclear. METHODS: The "Limma" package or "DESeq2" package was used to screen differentially expressed genes (DEGs). Alveolar lavage fluid datasets of COVID-19 and asthma were obtained from the GEO and GSV database. A series of analyses of common host factors for COVID-19 and asthma were conducted, including PPI network construction, module analysis, enrichment analysis, inference of the upstream pathway activity of host factors, tissue-specific analysis and drug candidate prediction. Finally, the key host factors were verified in the GSE152418 and GSE164805 datasets. RESULTS: 192 overlapping host factors were obtained by analyzing the intersection of asthma and COVID-19. FN1, UBA52, EEF1A1, ITGB1, XPO1, NPM1, EGR1, EIF4E, SRSF1, CCR5, PXN, IRF8 and DDX5 as host factors were tightly connected in the PPI network. Module analysis identified five modules with different biological functions and pathways. According to the degree values ranking in the PPI network, EEF1A1, EGR1, UBA52, DDX5 and IRF8 were considered as the key cohost factors for COVID-19 and asthma. The H(2)O(2), VEGF, IL-1 and Wnt signaling pathways had the strongest activities in the upstream pathways. Tissue-specific enrichment analysis revealed the different expression levels of the five critical host factors. LY294002, wortmannin, PD98059 and heparin might have great potential to evolve into therapeutic drugs for COVID-19 and asthma comorbidity. Finally, the validation dataset confirmed that the expression of five key host factors were statistically significant among COVID-19 groups with different severity and healthy control subjects. CONCLUSIONS: This study constructed a network of common host factors between asthma and COVID-19 and predicted several drugs with therapeutic potential. Therefore, this study is likely to provide a reference for the management and treatment for COVID-19/asthma comorbidity." | Serine-Arginine Splicing Factors |
Microgels assembled from bio-based nanomaterials are a promising soft stabilizer for a Pickering system. In this study, nanocellulose microgels with foaming properties were constructed by electrostatic assembly between nisin and 2,2,6,6-tetramethyl piperidine-1-oxyl-oxidized cellulose nanocrystals (TOCNC). Pickering wet foam was prepared by using the microgels as a foaming stabilizer. Nanocellulose microgels exhibited better foaming ability and foam stability than TOCNCs. Quartz crystal microbalance with dissipation and transmission electron microscopy analyses confirmed that the nanocellulose microgels prepared under different nisin concentrations demonstrated significant differences in morphology, conformation, and structural strength. Microgel particles prepared at 0.03 and 0.06 wt % nisin concentrations had a unique dendritic microstructure. Microgels containing 0.06 wt % nisin displayed better foaming ability and foam stability. It was possible that the soft dendritic structure of the microgels could endow bubbles with sufficient thickness and strength to prevent coalescence. This novelty nanocellulose microgel is expected to be used for expanding the application of nanocellulose in the functional interfacial design of Pickering foams. | Microgels |
Psoriasis is a common chronic autoinflammatory/autoimmune skin disease associated with elevated pro-inflammatory cytokines. The pivotal role of interleukin (IL)-1beta and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome in the pathogenesis of psoriasis has been widely described. Accordingly, the suppression of NLRP3-dependent IL-1beta release is a potential therapy for psoriasis. Repurposing marketed drugs is a strategy for identifying new inhibitors of NLRP3 inflammasome activation. Herein, chlorquinaldol (CQD), a historic antimicrobial agent used as a topical treatment for skin and vaginal infections, was found to have a distinct effect by inhibiting NLRP3 inflammasome activation at concentrations ranging from 2 to 6 muM. CQD significantly suppressed apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) oligomerization, NLRP3-ASC interaction, and pyroptosis in macrophages. The levels of cleaved IL-1beta and caspase-1 were reduced by CQD in the cell lysates of macrophages, suggesting that CQD acted on upstream of pore formation in the cell membrane. Mechanistically, CQD reduced mitochondrial reactive oxygen species production but did not affect the nuclear factor-kappaB (NF-kappaB) pathway. Intraperitoneal administration of CQD (15 mg/kg) for 6 days was found to improve the skin lesions in the imiquimod-induced psoriatic mouse model (male C57BL/6 mice), while secretion of pro-inflammatory cytokines (IL-17 and IL-1beta) and keratinocyte proliferation were significantly suppressed by CQD. In conclusion, CQD exerted inhibitory effects on NLRP3 inflammasome activation in macrophages and decreased the severity of psoriatic response in vivo. Such findings indicate that the repurposing of the old drug, CQD, is a potential pharmacological approach for the treatment of psoriasis and other NLRP3-driven diseases. | Pyrin Domain |
Ionizing radiation is a ubiquitous feature of the Cosmos, from exogenous cosmic rays (CR) to the intrinsic mineral radioactivity of a habitable world, and its influences on the emergence and persistence of life are wide-ranging and profound. Much attention has already been focused on the deleterious effects of ionizing radiation on organisms and the complex molecules of life, but ionizing radiation also performs many crucial functions in the generation of habitable planetary environments and the origins of life. This review surveys the role of CR and mineral radioactivity in star formation, generation of biogenic elements, and the synthesis of organic molecules and driving of prebiotic chemistry. Another major theme is the multiple layers of shielding of planetary surfaces from the flux of cosmic radiation and the various effects on a biosphere of violent but rare astrophysical events such as supernovae and gamma-ray bursts. The influences of CR can also be duplicitous, such as limiting the survival of surface life on Mars while potentially supporting a subsurface biosphere in the ocean of Europa. This review highlights the common thread that ionizing radiation forms between the disparate component disciplines of astrobiology. | Extraterrestrial Environment |
Subsets and Splits
No saved queries yet
Save your SQL queries to embed, download, and access them later. Queries will appear here once saved.