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A homeostatic control mechanism that monitors and reacts to the need for sleep has been thought to function independently of the brain's circadian clock in previous studies. Now simultaneous recordings of sleep stages and electrical activity in the suprachiasmatic nucleus in behaving animals reveal feedback from sleep centers to the circadian pacemaker. | Suprachiasmatic Nucleus |
Biocatalytic membrane reactors have been widely used in different industries including food, fine chemicals, biological, biomedical, pharmaceuticals, environmental treatment and so on. This article gives an overview of the different immobilized enzymatic processes and their advantages over the conventional chemical catalysts. The application of a membrane bioreactor (MBR) reduces the energy consumption, and system size, in line with process intensification. The performances of MBR are considerably influenced by substrate concentration, immobilized matrix material, types of immobilization and the type of reactor. Advantages of a membrane associated bioreactor over a free-enzyme biochemical reaction, and a packed bed reactor are, large surface area of immobilization matrix, reuse of enzymes, better product recovery along with heterogeneous reactions, and continuous operation of the reactor. The present research work highlights immobilization techniques, reactor setup, enzyme stability under immobilized conditions, the hydrodynamics of MBR, and its application, particularly, in the field of sugar, starch, drinks, milk, pharmaceutical industries and energy generation. | Enzymes, Immobilized |
Notch signalling, SoxB and Group A bHLH 'proneural' genes are conserved regulators of the neurogenic program in many bilaterians. However, the ancestry of their functions and interactions is not well understood. We address this question in the sea anemone Nematostella vectensis, a representative of the Cnidaria, the sister clade to the Bilateria. It has previously been found that the SoxB orthologue NvSoxB(2) is expressed in neural progenitor cells (NPCs) in Nematostella and promotes the development of both neurons and nematocytes, whereas Notch signalling has been implicated in the negative regulation of neurons and the positive regulation of nematocytes. Here, we clarify the role of Notch by reporting that inhibition of Notch signalling increases the numbers of both neurons and nematocytes, as well as increasing the number of NvSoxB(2)-expressing cells. This suggests that Notch restricts neurogenesis by limiting the generation of NPCs. We then characterise NvAth-like (Atonal/Neurogenin family) as a positive regulator of neurogenesis that is co-expressed with NvSoxB(2) in a subset of dividing NPCs, while we find that NvAshA (Achaete-scute family) and NvSoxB(2) are co-expressed in non-dividing cells only. Reciprocal knockdown experiments reveal a mutual requirement for NvSoxB(2) and NvAth-like in neural differentiation; however, the primary expression of each gene is independent of the other. Together, these data demonstrate that Notch signalling and NvSoxB(2) regulate Nematostella neural progenitors via parallel yet interacting mechanisms; with different aspects of these interactions being shared with Drosophila and/or vertebrate neurogenesis. | Sea Anemones |
INTRODUCTION: Left paraduodenal hernia is an internal herniation that develops due to anomalous fetal development. If incarcerated, it becomes an unusual cause of acute abdomen. CASE REPORT: This case report presents an uncommon case of a 39-year-old man with acute abdominal pain with vomiting. The patients medical history included recurrent subileous events and Crohn s disease in long-term remission. CT scan of abdominal cavity indicated a possible mechanical obstruction of small bowel loops in the upper left abdominal quadrant. Incarcerated left paraduodenal herniation was identified during surgery. Repositioned small bowel loops did not require resection and the entrance of Landzert s fossa was sutured. CONCLUSION: Left paraduodenal hernia is the most common congenital internal herniation. Although rare, it should be considered in the differential diagnosis of acute abdomen. | Paraduodenal Hernia |
Rhizoctonia solan Kuhn (teleomorph: Thanatephorus cucumeris (Frank) Donk (R. solani) is a soil-borne phytopathogenic species complex as well as a necrotic fungus that causes significant crop yield losses worldwide. Agronomic practices (crop rotation), resistant cultivars, and chemical pesticides are widely used to control R. solani. However, these practices are insufficient to control the pest. Moreover, the application of chemical pesticides is harmful to both the environment and human health. Therefore, the use of biocontrol agents (BCAs) and that of plant-growth promoting bacteria (PGPB) are considered to be potentially sustainable, cost-effective, efficient, and eco-friendly ways to control R. solani. Several microorganisms have been used as biocontrol agents (BCAs) to manage R. solani. Among these, biocontrol agents (BCAs) Bacillus spp. are used to promote plant growth. Furthermore, due to its broad range of antibiotic-producing abilities, Bacillus spp. is widely used against R. solani. In this review, current and previous studies about the ability of Bacillus spp. to control diseases caused by R. solani are reported. It also focuses on the plant-growth promotion attributes of Bacillus spp. in response to the deleterious effects of R. solani. | Plant Physiological Phenomena |
Macroautophagy/autophagy is a key process in the maintenance of cellular homeostasis. The age-dependent decline in retinal autophagy has been associated with photoreceptor degeneration. Retinal dysfunction can also result from damage to the retinal pigment epithelium (RPE), as the RPE-retina constitutes an important metabolic ecosystem that must be finely tuned to preserve visual function. While studies of mice lacking essential autophagy genes have revealed a predisposition to retinal degeneration, the consequences of a moderate reduction in autophagy, similar to that which occurs during physiological aging, remain unclear. Here, we described a retinal phenotype consistent with accelerated aging in mice carrying a haploinsufficiency for Ambra1, a pro-autophagic gene. These mice showed protein aggregation in the retina and RPE, metabolic underperformance, and premature vision loss. Moreover, Ambra1(+/gt) mice were more prone to retinal degeneration after RPE stress. These findings indicate that autophagy provides crucial support to RPE-retinal metabolism and protects the retina against stress and physiological aging.Abbreviations : 4-HNE: 4-hydroxynonenal; AMBRA1: autophagy and beclin 1 regulator 1, AMD: age-related macular degeneration;; GCL: ganglion cell layer; GFAP: glial fibrillary acidic protein; GLUL: glutamine synthetase/glutamate-ammonia ligase; HCL: hierarchical clustering; INL: inner nuclear layer; IPL: inner plexiform layer; LC/GC-MS: liquid chromatography/gas chromatography-mass spectrometry; MA: middle-aged; MTDR: MitoTracker Deep Red; MFI: mean fluorescence intensity; NL: NH(4)Cl and leupeptin; Nqo: NAD(P)H quinone dehydrogenase; ONL: outer nuclear layer; OPL: outer plexiform layer; OP: oscillatory potentials; OXPHOS: oxidative phosphorylation; PCR: polymerase chain reaction; PRKC/PKCalpha: protein kinase C; POS: photoreceptor outer segment; RGC: retinal ganglion cells; RPE: retinal pigment epithelium; SI: sodium iodate; TCA: tricarboxylic acid. | Haploinsufficiency |
In mammalian cross-species hybrids, parameters of voice calls, produced by vocal fold vibrations, are intermediate between parental species. Inheritance of ultrasonic calls, produced by whistle mechanism, is unstudied for hybrids. We examined 4000 pup ultrasonic isolation-induced calls for peak power of call fundamental frequency and for call duration in 4-8-day-old captive hamsters of four Study Groups: pure Phodopus sungorus; pure P. campbelli of two populations (Mongolian and Kosh-Agach) and hybrids between male P. sungorus and female P. campbelli (Kosh-Agach). All Study Groups produced two categories of ultrasonic calls: Low-Frequency centered around 41 kHz and High-Frequency centered around 60 kHz, but in different percentages. Between populations, only Low-Frequency calls were shorter and higher-frequency in Mongolian P. campbelli. Between species, only High-Frequency calls were shorter and higher-frequency in P. sungorus. In hybrids, Low-Frequency calls were shorter and lower-frequency than in either parental species, whereas High-Frequency calls were longer and lower-frequency in hybrids than in pure P. sungorus but similar with another parental species. We discuss that interspecific hybridization may give rise to offspring with new properties of ultrasonic calls. | Phodopus |
This article reviews the pathophysiology and management of bleeding peptic ulcer. Ulcers bleed when and because they erode into a blood vessel, and bleed massively when they erode into a medium- or large-sized artery. Focal pathology at the bleeding point (such as arteritis, aneurysmal dilatation or recanalized thrombus) contributes to the timing and clinical pattern of ulcer bleeding. Big bleeds are probably associated with erosion into big arteries. The identification of a visible vessel in the floor of an ulcer that has recently bled is predictive of further bleeding, while the absence of a visible vessel or stigmata of recent haemorrhage is strongly predictive that further bleeding will not occur. Unfortunately, no conventional method of managing gastrointestinal bleeding from ulcers has been convincingly shown to be better than placebo in controlled clinical trials. The value of transfusion and surgery has never been tested in controlled trials, while many small studies of drug therapy, especially of H2-receptor blocking agents, and a few small studies of early surgery afford generally negative or equivocal results. There is some evidence that new physical methods such as lasers or bipolar probes applied at endoscopy are superior to placebo though negative trials have also been reported. Studies randomizing larger numbers of patients with bleeding ulcers are required if therapeutic benefit of any aspect of management is to be demonstrated or refuted. | Peptic Ulcer Hemorrhage |
Neonatal mortality rate in India is high and stagnant. Special Care Newborn Units (SCNUs) are being set up to provide quality level II newborn care services in district hospitals of several districts to meet this challenge. The units are located in some of the remotest districts where the burden of neonatal deaths and accessibility to special care is a concern. A recently concluded evaluation of these units indicates that it is possible to provide quality level II newborn care in district hospitals. However, there are critical constraints such as availability and skills of human resources, maintenance of equipment and bed occupancy. It is not the SCNU alone but an active network of SCNU (level II care), neonatal stabilization units (level I care) and newborn care corners can impact neonatal mortality rate reduction higher. Number of beds is also not sufficient to cater to the increasing demand of such services. Available number of nurses is a problem in many such units. An effective and sustainable system to maintain and repair the equipment is essential. Scaling up these units would require squarely addressing these issues. | Hospital Units |
In interphase, chromosomes occupy defined nuclear volumes known as chromosome territories. To probe the biological consequences of the described nonrandom spatial positioning of chromosome territories in human lymphocytes, we performed an extensive FISH-based analysis of ionizing radiation-induced interchanges involving chromosomes 1, 4, 18 and 19. Since the probability of exchange formation depends strongly on the spatial distance between the damage sites in the genome, a preferential formation of exchanges between proximally positioned chromosomes is expected. Here we show that the spectrum of interchanges deviates significantly from one expected based on random chromosome positioning. Moreover, the observed exchange interactions between specific chromosome pairs as well as the interactions between homologous chromosomes are consistent with the proposed gene density-related radial distribution of chromosome territories. The differences between expected and observed exchange frequencies are more pronounced after exposure to densely ionizing neutrons than after exposure to sparsely ionizing X rays. These experiments demonstrate that the spatial positioning of interphase chromosomes affects the spectrum of chromosome rearrangements. | Chromosomes, Human, Pair 1 |
It is suggested that personal construct theory not only has the potential as a model for nursing, but also for complementary therapies, thus allowing complementary therapies or procedures from the therapies and nursing to blend, promoting a seamless integration that enables nurses to offer a wider range of interventions in their nursing care. By coming together in a therapeutic relationship using personal construct theory, it is possible for nurses to enhance the process of healing which is an integral part of nursing care. | Personal Construct Theory |
Although founder effect speciation has been a popular theoretical model for the speciation of geographically isolated taxa, its empirical importance has remained difficult to evaluate due to the intractability of past demography, which in a founder effect speciation scenario would involve a speciational bottleneck in the emergent species and the complete cessation of gene flow following divergence. Using regression-weighted approximate Bayesian computation, we tested the validity of these two fundamental conditions of founder effect speciation in a pair of sister species with disjunct distributions: the royal spoonbill Platalea regia in Australasia and the black-faced spoonbill Pl. minor in eastern Asia. When compared with genetic polymorphism observed at 20 nuclear loci in the two species, simulations showed that the founder effect speciation model had an extremely low posterior probability (1.55 x 10(-8)) of producing the extant genetic pattern. In contrast, speciation models that allowed for postdivergence gene flow were much more probable (posterior probabilities were 0.37 and 0.50 for the bottleneck with gene flow and the gene flow models, respectively) and postdivergence gene flow persisted for a considerable period of time (more than 80% of the divergence history in both models) following initial divergence (median = 197,000 generations, 95% credible interval [CI]: 50,000-478,000, for the bottleneck with gene flow model; and 186,000 generations, 95% CI: 45,000-477,000, for the gene flow model). Furthermore, the estimated population size reduction in Pl. regia to 7,000 individuals (median, 95% CI: 487-12,000, according to the bottleneck with gene flow model) was unlikely to have been severe enough to be considered a bottleneck. Therefore, these results do not support founder effect speciation in Pl. regia but indicate instead that the divergence between Pl. regia and Pl. minor was probably driven by selection despite continuous gene flow. In this light, we discuss the potential importance of evolutionarily labile traits with significant fitness consequences, such as migratory behavior and habitat preference, in facilitating divergence of the spoonbills. | Founder Effect |
In 1896 the so-called Department X" of the "Association for Public Welfare" was founded and turned to be the first organisation of the "fight against consumption" in the town of Halle. Under the guidance of PUTTER and REINEBOTH a first dispensary for tuberculous patients was established and became the prototype of similar institutions in Germany and other countries." | Tuberculosis Societies |
There are currently two commonly used approaches to assessing economic impacts of health damage resulting from environmental pollution: human capital approach (HCA) and willingness-to-pay (WTP). WTP can be further divided into averted expenditure approach (AEA), hedonic wage approach (HWA), contingent valuation approach (CVA) and hedonic price approach (HPA). A general review of the principles behind these approaches by the authors indicates that these methods are incapable of unveiling the mechanism of health impact from the point of view of national economy. On a basis of economic system, the shocks brought about by health effects of environmental pollution change the labor supply and medical expenditure, which in turn affects the level of production activity in each sector and the total final consumption pattern of the society. The general equilibrium approach within the framework of macroeconomic theory is able to estimate the health impact on national economy comprehensively and objectively. Its mechanism and applicability are discussed in detail by the authors. | Environmental Health |
OBJECTIVE: Study familial and pre- and perinatal factors in Asperger Syndrome (AS). METHODS: One hundred boys with AS had their records reviewed. Pathogenetic subgroups" were defined according to presence of medical syndromes/chromosomal abnormalities, indices of familiality, and pre- and perinatal risk factors predisposing to brain damage. RESULTS: No major index of pathogenetic factors was found in 13%, a syndrome/chromosomal abnormality in 8%, pre- or perinatal risk 13%, combined pre- or perinatal risk and family history in 11%, and family history only in 55%. COMMENT: About 50% of all boys with AS have a paternal family history of autism spectrum disorder. Pre- and perinatal risks appear to be important in about 25% of cases." | Asperger Syndrome |
Granulocyte colony stimulating factor (G-CSF) is used to prevent febrile neutropenia post chemotherapy. Usually well tolerated with minimal side effects but aortitis is an extremely rare side effect previously reported. A 64-year-old woman treated with adjuvant chemotherapy including G-CSF for left breast cancer was admitted with fevers, neutropenia and markedly raised inflammatory markers after 7 days of her first cycle. Initially diagnosed with neutropenic sepsis, she did not respond to broad spectrum antibiotics with subsequent CT imaging revealing marked periaortic inflammatory changes consistent with aortitis and periaortitis. Extensive investigations for other causes of large vessel vasculitis were negative and G-CSF was the only causative factor. She rapidly responded to steroids with almost complete resolution of inflammatory changes on repeat imaging within 4 weeks and no recurrence on tapering of steroids. This diagnosis must be considered in patients presenting with fever and raised inflammatory markers post G-CSF treatment. | Aortitis |
Blackwater fever was typically reported after quinine administration, although it is poor recognized in patients receiving artesunate. This case describes a blackwater fever in a non-immune patient after artesunate for severe malaria. It highlights the importance of monitoring haemolytic parameters in severe malaria to avoid renal impairment or severe anaemia. | Blackwater Fever |
Herbicide resistance or tolerance in weeds mediated by cytochrome P450 monooxygenase is a considerable problem. However, cytochrome P450 mediated resistance or tolerance in weeds was less studied. Thus, in this work, the role of the cytochrome P450 monooxygenase in the different responses of Poa annua and Alopecurus aequalis to fenoxaprop-P-ethyl was studied. We found that the effect of fenoxaprop-P-ethyl could be synergized by piperonyl butoxide (PBO) in P. annua, but not by malathion. After being treated with fenoxaprop-P-ethyl (containing mefenpyr-diethyl), the contents of cytochrome P450 and cytochrome b5 in P. annua increased significantly compared to plants treated with mefenpyr-diethyl only or untreated plants. However, the increase was less in A. aequalis, which was susceptible to fenoxaprop-P-ethyl. The activities of rho-nitroanisole O-demethylase (PNOD), ethoxyresorufin O-deethylase (EROD), ethoxycoumarin oxidase (ECOD) and NADPH-dependent cytochrome P450 reductase mediated by cytochrome P450 monooxygenase increased in P. annua after treatment with fenoxaprop-P-ethyl, especially the activities of ECOD and cytochrome P450 reductase. Besides this, cytochrome P450 monooxygenase activity toward fenoxaprop-P-ethyl in P. annua increased significantly compared to untreated or treated with mefenpyr-diethyl plants and treated or untreated A. aequalis. Cytochrome P450 monooxygenase may play an important role in the different responses to fenoxaprop-P-ethyl in P. annua and A. aequalis. | Poa |
OBJECTIVES: To assess emergency contraception (EC) service provision by California's family planning clinics. STUDY DESIGN: We made 2 scripted calls to a random sample of 309 family planning clinics. RESULTS: We reached one hundred ninety-four clinics on 2 occasions, although only 183 (59%) could be reached with the information provided online by California's office of family planning. Of these 194 clinics, 27% responded that the clinic did not provide EC and 43% offered only levonorgestrel EC. Only 1 clinic asked about recent sexual assault and one other about their weight. CONCLUSIONS: Prompt access to effective EC remains challenging in California. Clinic staff responding to requests for EC should provide trauma-informed care. | Contraception, Postcoital |
We examined the effects of early rearing experience on the development of dominance status in 53 juvenile (age 3) and then in 38 adult (ages 5-8) rhesus macaques. Based on previous research investigating the behavioral outcomes of nursery-rearing, we predicted that mother-reared (MR) monkeys would outrank peer-only reared (PR) monkeys, which would in turn outrank surrogate/peer-reared (SPR) subjects. Juvenile MR and PR subjects did not differ in ranks, but monkeys from both rearing backgrounds outranked SPR cage-mates at age 3. Independent of rearing condition, high-ranking juveniles gained the most weight between ages 1-3, suggesting that low status may be associated with decreases in early weight gain. Adult MR subjects outranked both PR and SPR subjects, with PR animals occupying intermediate ranks. These results indicate that impoverished early experiences, such as adult absence and limited social interaction, are useful predictors of future social success in rhesus macaques. | Maternal Behavior |
Recently, we have found that calcium binding proteins of the EF-hand superfamily (i.e., a large family of proteins containing helix-loop-helix calcium binding motif or EF-hand) contain two types of conserved clusters called cluster I ('black' cluster) and cluster II ('grey' cluster), which provide a supporting scaffold for the Ca(2+) binding loops and contribute to the hydrophobic core of the EF-hand domains. Cluster I is more conservative and mostly incorporates aromatic amino acids, whereas cluster II includes a mix of aromatic, hydrophobic, and polar amino acids of different sizes. Recoverin is EF-hand Ca(2+)-binding protein containing two 'black' clusters comprised of F35, F83, Y86 (N-terminal domain) and F106, E169, F172 (C-terminal domain) as well as two 'gray' clusters comprised of F70, Q46, F49 (N-terminal domain) and W156, K119, V122 (C-terminal domain). To understand a role of these residues in structure and function of human recoverin, we sequentially substituted them for alanine and studied the resulting mutants by a set of biophysical methods. Under metal-free conditions, the 'black' clusters mutants (except for F35A and E169A) were characterized by an increase in the alpha-helical content, whereas the 'gray' cluster mutants (except for K119A) exhibited the opposite behavior. By contrast, in Ca(2+)-loaded mutants the alpha-helical content was always elevated. In the absence of calcium, the substitutions only slightly affected multimerization of recoverin regardless of their localization (except for K119A). Meanwhile, in the presence of calcium mutations in N-terminal domain of the protein significantly suppressed this process, indicating that surface properties of Ca(2+)-bound recoverin are highly affected by N-terminal cluster residues. The substitutions in C-terminal clusters generally reduced thermal stability of recoverin with F172A ('black' cluster) as well as W156A and K119A ('gray' cluster) being the most efficacious in this respect. In contrast, the mutations in the N-terminal clusters caused less pronounced differently directed changes in thermal stability of the protein. The substitutions of F172, W156, and K119 in C-terminal domain of recoverin together with substitution of Q46 in its N-terminal domain provoked significant but diverse changes in free energy associated with Ca(2+) binding to the protein: the mutant K119A demonstrated significantly improved calcium binding, whereas F172A and W156A showed decrease in the calcium affinity and Q46A exhibited no ion coordination in one of the Ca(2+)-binding sites. The most of the N-terminal clusters mutations suppressed membrane binding of recoverin and its inhibitory activity towards rhodopsin kinase (GRK1). Surprisingly, the mutant W156A aberrantly activated rhodopsin phosphorylation regardless of the presence of calcium. Taken together, these data confirm the scaffolding function of several cluster-forming residues and point to their critical role in supporting physiological activity of recoverin." | Neuronal Calcium-Sensor Proteins |
The mucus layer protects airway epithelia from damage by noxious agents. Intriguingly, Bordetella pertussis bacteria provoke massive mucus production by nasopharyngeal epithelia during the initial coryza-like catarrhal stage of human pertussis and the pathogen transmits in mucus-containing aerosol droplets expelled by sneezing and post-nasal drip-triggered cough. We investigated the role of the cAMP-elevating adenylate cyclase (CyaA) and pertussis (PT) toxins in the upregulation of mucin production in B. pertussis-infected airway epithelia. Using human pseudostratified airway epithelial cell layers cultured at air-liquid interface (ALI), we show that purified CyaA and PT toxins (100 ng/mL) can trigger production of the major airway mucins Muc5AC and Muc5B. Upregulation of mucin secretion involved activation of the cAMP response element binding protein (CREB) and was blocked by the 666-15-Calbiochem inhibitor of CREB-mediated gene transcription. Intriguingly, a B. pertussis mutant strain secreting only active PT and producing the enzymatically inactive CyaA-AC(-) toxoid failed to trigger any important mucus production in infected epithelial cell layers in vitro or in vivo in the tracheal epithelia of intranasally infected mice. In contrast, the PT(-) toxoid-producing B. pertussis mutant secreting the active CyaA toxin elicited a comparable mucin production as infection of epithelial cell layers or tracheal epithelia of infected mice by the wild-type B. pertussis secreting both PT and CyaA toxins. Hence, the cAMP-elevating activity of B. pertussis-secreted CyaA was alone sufficient for activation of mucin production through a CREB-dependent mechanism in B. pertussis-infected airway epithelia in vivo. | Adenylate Cyclase Toxin |
Genotoxicity of B. officinalis, G. officinalis, V. luteum and V. hirundinaria extracts, which demonstrated strong antioxidant capacity, was tested using chromosome aberration, sister chromatid exchange (SCE), cytokinesis-block micronucleus and alkaline single-cell gel electrophoresis (comet) assays in human lymphocytes in vitro and Ames Salmonella/microsome test. All tested extracts were not mutagenic in S. typhimurium strains TA98 and TA100 with and without metabolic activation and did not induce chromosome aberrations in human lymphocytes in vitro. Extract from G. officinalis was the only one, which induced significant increase in micronuclei, indicating possible aneugenic effect. All investigated plant extracts induced DNA damage evaluated by the comet assay, while B. officinalis and V. luteum extracts induced slight increase in SCE values. The determined variation in response might be due to the plant extract tested and donor susceptibility. | Vincetoxicum |
Mikania glomerata and Mikania laevigata are medicinal plants popularly used in Brazil for colds and asthma. Although several studies report differences in their composition, they are frequently used indistinctly, which may be due to misidentification of the species or the plant part used. Herein, the chemical, anatomical, and morphological profiles of both species were evaluated, seeking to differentiate them. Due to the pattern of secondary metabolites found in M. glomerata and M. laevigata, the chemical profile of the leaves was the characteristic that best differentiated the two species. Coumarin was present in all the leaf samples of M. laevigata but absent or in low concentration in leaf samples of M. glomerata. The stems presented coumarin in both species, albeit in different concentrations. The quantification of chlorogenic and dicaffeoylquinic acids was crucial for the separation of the two species, as higher concentrations are found in M. glomerata. The anatomic structure of the leaves, stem, and petioles of both species was conserved, even when exposed to different environments, but presented only subtle differences between species. The morphology of the leaves presented different characteristics for each species but altered when exposed to shade. Therefore, the chemical analysis together with the morphological characteristics of plants grown in full sunlight may be used for the correct identification of these species. | Asteraceae |
DDX5, XRN2, and PRMT5 have been shown to resolve DNA/RNA hybrids (R-loops) at RNA polymerase II transcription termination sites at few genomic loci. Herein, we perform genome-wide R-loop mapping using classical DNA/RNA immunoprecipitation and high-throughput sequencing (DRIP-seq) of loci regulated by DDX5, XRN2, and PRMT5. We observed hundreds to thousands of R-loop gains and losses at transcribed loci in DDX5-, XRN2-, and PRMT5-deficient U2OS cells. R-loop gains were characteristic of highly transcribed genes located at gene-rich regions, whereas R-loop losses were observed in low-density gene areas. DDX5, XRN2, and PRMT5 shared many R-loop gain loci at transcription termination sites, consistent with their coordinated role in RNA polymerase II transcription termination. DDX5-depleted cells had unique R-loop gain peaks near the transcription start site that did not overlap with those of siXRN2 and siPRMT5 cells, suggesting a role for DDX5 in transcription initiation independent of XRN2 and PRMT5. Moreover, we observed that the accumulated R-loops at certain loci in siDDX5, siXRN2, and siPRMT5 cells near the transcription start site of genes led to antisense intergenic transcription. Our findings define unique and shared roles of DDX5, XRN2, and PRMT5 in DNA/RNA hybrid regulation." | Transcription Termination, Genetic |
In this age of easy access to non-invasive computed tomography and magnetic resonance imaging, the clinician is faced with the dilemma of whether or not to remove the patient's intervertebral disc herniation in order to relieve the pain caused by lumbosacral nerve root compromise. This review outlines the rationale for instituting a series of epidural injection techniques, before resorting to surgery. | Sciatica |
Recent studies demonstrate that eyes-closed rest benefits memory consolidation, perhaps due to reduced attention to environmental stimuli. Here, we asked whether focusing attention to internal thoughts and feelings after learning similarly blocks memory consolidation. Verbal memory was tested following an eyes-closed consolidation period filled with either focused attention to breath or quiet rest. Although breath-focus did not impair memory relative to quiet rest overall, participants who reported being more successful in maintaining breath-focus during this condition showed increased forgetting. We interpret these findings as incompatible with a simple sensory-interference-based account of rest's effect on memory. | Memory Consolidation |
Squirrel monkeys (Saimiri sciureus) have a striking color-vision polymorphism; each animal has one of six different types of color vision. These arise from individual variation in the presence of three different middle- to long-wavelength cone pigments. The distribution of cone phenotypes was established for a large sample of squirrel monkeys, including several families, through analysis of a retinal gross potential. The results indicate that the inheritance of color vision in the squirrel monkey can be explained by assuming that the three middle- to long-wavelength cone pigments are specified by three alleles at a single locus on the X chromosome. This arrangement is discretely different from that found in Old World monkeys and humans. | Saimiri |
The paper presents a network coded cooperative communication (NC-CC) enabled wireless hospital sensor network architecture for monitoring health as well as postural activities of a patient. A wearable device, referred as a smartband is interfaced with pulse rate, body temperature sensors and an accelerometer along with wireless protocol services, such as Bluetooth and Radio-Frequency transceiver and Wi-Fi. The energy efficiency of wearable device is improved by embedding a linear acceleration based transmission duty cycling algorithm (NC-DRDC). The real-time demonstration is carried-out in a hospital environment to evaluate the performance characteristics, such as power spectral density, energy consumption, signal to noise ratio, packet delivery ratio and transmission offset. The resource sharing and energy efficiency features of network coding technique are improved by proposing an algorithm referred as network coding based dynamic retransmit/rebroadcast decision control (LA-TDC). From the experimental results, it is observed that the proposed LA-TDC algorithm reduces network traffic and end-to-end delay by an average of 27.8% and 21.6%, respectively than traditional network coded wireless transmission. The wireless architecture is deployed in a hospital environment and results are then successfully validated." | Hospital Communication Systems |
RNA-seq analysis of Cupriavidus necator NH9, a 3-chlorobenzoate degradative bacterium, cultured with 3-chlorobenzaote and benzoate, revealed strong induction of genes encoding enzymes in degradation pathways of the respective compound, including the genes to convert 3-chlorobenzaote and benzoate to chlorocatechol and catechol, respectively, and the genes of chlorocatechol ortho-cleavage pathway for conversion to central metabolites. The genes encoding transporters, components of the stress response, flagellar proteins, and chemotaxis proteins showed altered expression patterns between 3-chlorobenzoate and benzoate. Gene Ontology enrichment analysis revealed that chemotaxis-related terms were significantly upregulated by benzoate compared with 3-chlorobenzoate. Consistent with this, in semisolid agar plate assays, NH9 cells showed stronger chemotaxis to benzoate than to 3-chlorobenzoate. These results, combined with the absence of genes related to uptake/chemotaxis for 3-chlorobenzoate located closely to the degradation genes of 3-chlorobenzoate, suggested that NH9 has not fully adapted to the utilization of chlorinated benzoate, unlike benzoate, in nature. | Cupriavidus necator |
Most signals in genome-wide association studies (GWAS) of complex traits implicate noncoding genetic variants with putative gene regulatory effects. However, currently identified regulatory variants, notably expression quantitative trait loci (eQTLs), explain only a small fraction of GWAS signals. Here, we show that GWAS and cis-eQTL hits are systematically different: eQTLs cluster strongly near transcription start sites, whereas GWAS hits do not. Genes near GWAS hits are enriched in key functional annotations, are under strong selective constraint and have complex regulatory landscapes across different tissue/cell types, whereas genes near eQTLs are depleted of most functional annotations, show relaxed constraint, and have simpler regulatory landscapes. We describe a model to understand these observations, including how natural selection on complex traits hinders discovery of functionally relevant eQTLs. Our results imply that GWAS and eQTL studies are systematically biased toward different types of variant, and support the use of complementary functional approaches alongside the next generation of eQTL studies. | Quantitative Trait Loci |
The retinoblastoma tumor suppressor (RB) is a critical regulator of E2F-dependent transcription, controlling a multitude of protumorigenic networks including but not limited to cell-cycle control. Here, genome-wide assessment of E2F1 function after RB loss in isogenic models of prostate cancer revealed unexpected repositioning and cooperation with oncogenic transcription factors, including the major driver of disease progression, the androgen receptor (AR). Further investigation revealed that observed AR/E2F1 cooperation elicited novel transcriptional networks that promote cancer phenotypes, especially as related to evasion of cell death. These observations were reflected in assessment of human disease, indicating the clinical relevance of the AR/E2F1 cooperome in prostate cancer. Together, these studies reveal new mechanisms by which RB loss induces cancer progression and highlight the importance of understanding the targets of E2F1 function. SIGNIFICANCE: This study identifies that RB loss in prostate cancer drives cooperation between AR and E2F1 as coregulators of transcription, which is linked to the progression of advanced disease." | Retinoblastoma Binding Proteins |
BACKGROUND: Seafarers enable 90% of global commerce, working in isolation from social support and medical care. While occupational conditions of isolation may suggest possible excess risk of mental illness and suicide, research on seafarer mental illness is limited. AIMS: To describe seafarers with mental illness and associated incidence rates in a large population of international seafarers. METHODS: We used mental illness claims data from a large international marine insurance provider arising from working seafarers during the years 2007-15. We used descriptive statistics and calculated mental illness incidence rates in this seafarer population. RESULTS: There were 278 seafarer mental illness claims in the study data. Claims were more often reported in deck workers (46%) and ratings (58%). The crude mental illness rate was 3.9 per 100 000 person-years. CONCLUSIONS: Using objective data on a large seafaring population, our analysis highlights the important issue of mental illness in this isolated and underserved international workforce. The low observed mental illness claims rate is likely due to the high threshold for claims reporting. | Insurance Benefits |
Low-cost, easy-to-use cell concentration tools are in urgent demand for biomedical diagnosis in resource-poor settings. Herein, we propose a novel inertial microfluidic syringe cell (IMSC) concentrator that employs inertial focusing to increase cell concentration through ordering the cell and removing the cell-free fluid. A three-part structure, consisting of a cap-shaped upper housing, a circular gasket, and a lower housing with a spiral channel, is adopted for simple fabricating and assembling, which enables the seamless translation of our IMSC concentrator into commercial outcomes without additional redesigning. The performance characterization indicates that our IMSC concentrator is capable of processing samples with different initial concentrations over a broad flow rate range. The satisfactory concentration performances over a broad driving flow rate range make it possible for our IMSC concentrator to be driven by pushing the syringe with single hand. Finally, pollen particles and MCF-7 cells are successfully concentrated at a high throughput of 3.0 mL/min (up to 4.2 x 10(7) counts/mL) under the hand-powered drive. We envision wide applications of our IMSC concentrator as centrifugation on a syringe tip" to various cell concentration pretreatments in resource-poor settings." | MCF-7 Cells |
The host-protective immune response to infection with gastrointestinal (GI) nematodes involves a range of interacting processes that begin with recognition of the parasite's antigens and culminate in an inflammatory reaction in the intestinal mucosa. Precisely which immune effectors are responsible for the loss of specific worms is still not known although many candidate effectors have been proposed. However, it is now clear that many different genes regulate the response and that differences between hosts (fast or strong versus slow or weak responses) can be explained by allelic variation in crucial genes associated with the gene cascade that accompanies the immune response and/or genes encoding constitutively expressed receptor/signalling molecules. Major histocompatibility complex (MHC) genes have been recognized for some time as decisive in controlling immunity, and evidence that non-MHC genes are equally, if not more important in this respect has also been available for two decades. Nevertheless, whilst the former have been mapped in mice, only two candidate loci have been proposed for non-MHC genes and relatively little is known about their roles. Now, with the availability of microsatellite markers, it is possible to exploit linkage mapping techniques to identify quantitative trait loci (QTL) responsible for resistance to GI nematodes. Four QTL for resistance to Heligmosomoides polygyrus, and additional QTL affecting faecal egg production by the worms and the accompanying immune responses, have been identified. Fine mapping and eventually the identification of the genes (and their alleles) underlying QTL for resistance/susceptibility will permit informed searches for homologues in domestic animals, and human beings, through comparative genomic maps. This information in turn will facilitate targeted breeding to improve resistance in domestic animals and, in human beings, focused application of treatment and control strategies for GI nematodes. | Nematospiroides |
Psychiatric disorders are amongst the most prevalent and impairing conditions in childhood and adolescence. Unfortunately, it is well known that general practitioners (GPs) and other frontline health providers (i.e., child protection workers, public health nurses, and pediatricians) are not adequately trained to address these ubiquitous problems (Braddick et al. Child and Adolescent mental health in Europe: infrastructures, policy and programmes, European Communities, 2009; Levav et al. Eur Child Adolesc Psychiatry 13:395-401, 2004). Advances in technology may offer a solution to this problem with clinical decision support systems (CDSS) that are designed to help professionals make sound clinical decisions in real time. This paper offers a systematic review of currently available CDSS for child and adolescent mental health disorders prepared according to the PRISMA-Protocols (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols). Applying strict eligibility criteria, the identified studies (n = 5048) were screened. Ten studies, describing eight original clinical decision support systems for child and adolescent psychiatric disorders, fulfilled inclusion criteria. Based on this systematic review, there appears to be a need for a new, readily available CDSS for child neuropsychiatric disorder which promotes evidence-based, best practices, while enabling consideration of national variation in practices by leveraging data-reuse to generate predictions regarding treatment outcome, addressing a broader cluster of clinical disorders, and targeting frontline practice environments. | Adolescent Psychiatry |
Two new quinolizidine-based alkaloids (2 and 12), along with ten known ones (1, 3-11) were isolated from the roots of S. tonkinensis. Their structures were determined by spectroscopic data (including NMR, MS, IR, and UV), X-ray single crystal diffraction, electronic circular dichroism analyses (ECD), and comparing with related literatures. Compounds 1, 3-12 at non-toxic concentrations exhibited potent anti-inflammatory activities according to in vitro and in vivo anti-inflammatory tests. Among them, (-)-anagyrine (4), sophocarpine (8), 14beta-hydroxymatrine (10), and 7beta-sophoramine (12) showed more potent in vitro anti-inflammatory activities, and 5alpha,14beta-dihydroxymatrine (2), (-)-anagyrine (4), sophocarpine (8), and 5alpha-hydroxymatrine (9) exhibited better in vivo anti-inflammatory effects. | Sophora |
A peptide corresponding to position 32-47 in tyrosine hydroxylase was synthesized (TH-16) and polyclonal antibodies against this peptide were raised in rabbits (anti-TH-16). The effects of anti-TH-16 on modulation of tyrosine hydroxylase activity were investigated. Anti-TH-16 enhanced the enzymatic activity in a concentration-dependent manner, and the antigen TH-16 inhibited the stimulatory activity of the antiserum in a concentration-dependent manner. The activated enzyme had a lower Km app for the cofactor 2-amino-4-hydroxy-6-methyl-5,6,7,8-tetrahydropterin and a higher Vmax app than the nonactivated enzyme. Anti-TH-16 was characterized further by its ability to immunoprecipitate the enzyme activity by labeling tyrosine hydroxylase after Western blotting and by immunohistochemical labeling of catecholaminergic neurons. Anti-TH-16 did not block activation of tyrosine hydroxylase by phosphorylation catalyzed by cyclic AMP-dependent protein kinase. Exposure of the enzyme to anti-TH-16 and subsequent phosphorylation of the enzyme resulted in a greater activation of the enzyme than the sum of activation produced by these two treatments separately. However, the activation was less than additive when the enzyme was first phosphorylated and subsequently exposed to anti-TH-16. The present study demonstrates the utility of anti-TH-16 in investigating the molecular aspects of the enzyme activation. | Tyrosine 3-Monooxygenase |
The chromosomal high-mobility group A (HMGA) proteins, composed of HMGA1a, HMGA1b and HMGA2, play important roles in the regulation of numerous processes in eukaryotic cells, such as transcriptional regulation, DNA repair, RNA processing, and chromatin remodeling. The biological activities of HMGA1 proteins are highly regulated by their post-translational modifications (PTMs), including acetylation, methylation, and phosphorylation. Recently, it was found that the homeodomain-interacting protein kinase-2 (HIPK2), a newly identified serine/threonine kinase, co-immunoprecipitated with, and phosphorylated, HMGA1 proteins. However, the sites and the biological significance of the phosphorylation have not been elucidated. Here, we found that HIPK2 phosphorylates HMGA1a at Ser-35, Thr-52, and Thr-77, and HMGA1b at Thr-41 and Thr-66. In addition, we demonstrated that cdc2, which is known to phosphorylate HMGA1 proteins, could induce the phosphorylation of HMGA1 proteins at the same Ser/Thr sites. The two kinases, however, exhibited different site preferences for the phosphorylation: The preference for HIPK2 phosphorylation followed the order of Thr-77 > Thr-52 > Ser-35, whereas the order for cdc2 phosphorylation was Thr-52 > Thr-77 > Ser-35. Moreover, we found that the HIPK2-phosphorylated HMGA1a reduced the binding affinity of HMGA1a to human germ line promoter, and the drop in binding affinity induced by HIPK2 phosphorylation was lower than that introduced by cdc2 phosphorylation, which is consistent with the notion that the second AT-hook in HMGA1a is more important for DNA binding than the third AT-hook. | HMGA1b Protein |
Previous studies from this laboratory reported that 3H-labeled metabolites with half-lives of more than 24 hours may remain in the plasmaa of women receiving an intravenous injection of 3H norethindrone or 3H mestranol. To confirm the presence of these metabolites, blood samples were collected for five days after injection of 3H norethindrone or 3H mestranol; 3H representing metabolites of norethindrone disappeared with half-life values of 42 to 84 hours (mean 67 hours), while 3H representing metabolites of mestranol declined with an average half-life of 45 hours (range 37 to 65 hours). When the 3H-labeled drugs were administered orally, metabolites of similar half-life were formed. Because these compounds exist for several days after a single administration and since oral contraceptive drugs are normally taken daily, the possiblity of the accumulation of 3H in the plasm of women receiving several consecutive doses of 3H norethindrone was investigated. The results of this study show a stepwise accumulation of the 3H metabolites when 3H norethindrone was administered in six daily oral doses. However, the 3H levels declined from the peak on the sixth and last day of the treatment at a rate equivalent to those previously measured after intravenous or oral administration. | Mestranol |
Physical rehabilitation for individuals coping with neurological deficits is evolving in response to a paradigm shift in thinking about the injured nervous system and using evidence as a basis for clinical decisions. Functional recovery from paralysis was generally believed to be nearly impossible, based on traditional expert opinion, and the priority was to develop compensation strategies to achieve functional goals in the home and community. Research, which began in animal models of neurological insult and is currently being translated to the clinic, has challenged these assumptions. The nervous system, whether intact or injured, has enormous potential for adaptation and modification, which can be harnessed to facilitate recovery. In this chapter we will briefly outline the history of physical rehabilitation as it concerns the development of strategies aimed at compensation, rather than functional recovery. Then we will discuss how new activity-based therapies are being developed, based on evidence from basic science and clinical evidence. One of these activity-based therapies is locomotor training, a program which relies on the intrinsic, automatic, control of locomotion by lower" neural centers. A brief description of the program, including the four foundational principles, will be followed by an introduction to the use of robotics in these programs. Finally, we will discuss a second activity-based therapy, functional electrical stimulation (FES), and the future of physical rehabilitation for spinal cord injury and other neurological disorders." | Recovery of Function |
Metallochaperones are metal-binding proteins designed to deliver the appropriate metal to a target protein. The metal is usually transferred between different proteins. In this study, we discovered that metal was transferred between the same subunit of a mutant nitrile hydratase (NHase). Various activator proteins" mediate the trafficking of metal ions into NHases. We constructed fusion NHases by fusing the beta- and alpha-subunits and/or the "activator proteins" of the NHase from Pseudomonas putida. The fusion NHases exhibited higher thermostability and tolerance to high concentrations of the product amide. The mechanism of the cobalt incorporation changed from a self-subunit swapping pattern to an apoprotein-specific molecular chaperone pattern in vivo and a metallochaperone pattern in vitro. Notably, the cobalt transfer occurred between the same alpha-subunit in the metallochaperone pattern. These results not only demonstrated the superiority of fusion-type NHases, but also revealed an innovative metal ion transfer pattern in metalloprotein biosynthesis." | Carbon-Oxygen Lyases |
The increasing incidence and rapid spread of bacterial resistance to conventional antibiotics are a serious global threat to public health, highlighting the need to develop new antimicrobial alternatives. Antimicrobial peptides (AMPs) represent a class of promising natural antibiotic candidates due to their broad-spectrum activity and low tendency to induce resistance. However, the development of AMPs for medical use is hampered by several obstacles, such as moderate activity, lability to proteolytic degradation, and low bioavailability. To date, many researchers have focussed on the optimization or design of novel artificial AMPs with desired properties. Unnatural amino acids (UAAs) are valuable building blocks in the manufacture of a variety of pharmaceuticals, and have been used to develop artificial AMPs with specific structural and physicochemical properties. Rational incorporation of UAAs has become a very promising approach to endow AMPs with strong and long-lasting activity but no toxicity. This review aims to summarize key approaches that have been used to incorporate UAAs to develop novel AMPs with improved properties and better performance. It is anticipated that this review will guide future design considerations for UAA-based antimicrobial applications. | Antimicrobial Peptides |
Antarctic krill (Euphausia superba) plays a central role in the Antarctic marine food web and biogeochemical cycles and has been identified as a species that is potentially vulnerable to plastic pollution. While plastic pollution has been acknowledged as a potential threat to Southern Ocean marine ecosystems, the effect of nanoplastics (<1000 nm) is poorly understood. Deleterious impacts of nanoplastic are predicted to be higher than that of larger plastics, due to their small size which enables their permeation of cell membranes and potentially provokes toxicity. Here, we investigated the intergenerational impact of exposing Antarctic krill to nanoplastics. We focused on whether embryonic energy resources were affected when gravid female krill were exposed to nanoplastic by determining lipid and fatty acid compositions of embryos produced in incubation. Embryos were collected from females who had spawned under three different exposure treatments (control, nanoplastic, nanoplastic + algae). Embryos collected from each maternal treatment were incubated for a further 6 days under three nanoplastic exposure treatments (control, low concentration nanoplastic, and high concentration nanoplastic). Nanoplastic additions to seawater did not impact lipid metabolism (total lipid or fatty acid composition) across the maternal or direct embryo treatments, and no interactive effects were observed. The provision of a food source during maternal exposure to nanoplastic had a positive effect on key fatty acids identified as important during embryogenesis, including higher total polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) when compared to the control and nanoplastic treatments. Whilst the short exposure time was ample for lipids from maternally digested algae to be incorporated into embryos, we discuss why the nanoplastic-fatty acid relationship may be more complex. Our study is the first to scope intergeneration effects of nanoplastic on Antarctic krill lipid and fatty acid reserves. From this, we suggest directions for future research including long term exposures, multi-stressor scenarios and exploring other critical energy reserves such as proteins. | Euphausiacea |
In a recent paper, we described our efforts in search for evidence supporting epigenetic transgenerational inheritance caused by endocrine disrupter chemicals. One aspect of our study was to compare genome-wide DNA methylation changes in the vinclozolin-exposed fetal male germ cells (n = 3) to control samples (n = 3), their counterparts in the next, unexposed, generation (n = 3 + 3) and also in adult spermatozoa (n = 2 + 2) in both generations. We reported finding zero common hits in the intersection of these four comparisons. In our interpretation, this result did not support the notion that DNA methylation provides a mechanism for a vinclozolin-induced transgenerational male infertility phenotype. In response to criticism by Guerrero-Bosagna regarding our statistical power in the above study, here we provide power calculations to clarify the statistical power of our study and to show the validity of our conclusions. We also explain here how our data is misinterpreted in the commentary by Guerrero-Bosagna by leaving out important data points from consideration.Please see related Correspondence article: xxx (13059_2016_982) and related Research article: http://genomebiology.biomedcentral.com/articles/10.1186/s13059-015-0619-z. | Embryonic Germ Cells |
The dual agent antibiotic, trimethoprim/sulfamethoxazole (TMP-SMX), has been prescribed to treat or prevent infections for over 50 years. However, there are no published validated analytical methods for the measurement of TMP metabolites in humans. We developed methodology enabling reliable quantification of TMP and 5 metabolites in human plasma. Chromatographic separation was achieved in less than 8 min using a biphenyl column. Analytes were detected in positive electrospray mode using a tandem Waters Xevo-TQ-XS mass spectrometer. Precision and accuracy values for all analytes were within 15% of nominal values during assay validation. | Trimethoprim |
Oxysarcodexia is one of the Neotropical richest genera within the Sarcophagidae family. Medical, veterinary and forensic importance of these flies are due to their association with corpses, cases of myiasis in humans and domestic animals, and being pathogen carriers. Regarding morphological identification, molecular techniques, especially the DNA-based ones, arise as useful alternatives or complementary methodologies for species identification. Thus, in this study we aimed to investigate the potential of the COI marker (barcode region) to delimit Oxysarcodexia species in comparison with the morphological identification criteria. A COI fragment was amplified and the length of the sequences after alignment were of 648bp (149 parsimoniously informative variable sites). According to the Neighbor-Joining phylogenetic tree, specimens of the same morphological species were clustered in monophyletic clades (82-100% bootstrap branch support). Species-level resolution thus achieved was successful, despite low interspecific divergence (1.8-2.3%) and since interspecific variation was higher than intraspecific divergence (0.1-1.2%). Therefore, the use of COI barcode sequences supports differentiation and identification of the Oxysarcodexia species studied. | Sarcophagidae |
Methacholine, atrial natriuretic peptide (ANP), nitroprusside (nitric oxide), angiotensin II, and bradykinin raised cyclic GMP (cGMP) levels in cultured bovine adrenal chromaffin cells. The role of cGMP in secretion from chromaffin cells was examined using 8-bromo-cGMP. This analogue had no effect on basal secretion or secretion due to angiotensin II, bradykinin, or a high K+ level but potentiated secretion due to low doses of nicotine. At supramaximal doses of nicotine, 8-bromo-cGMP inhibited secretion. These effects of 8-bromo-cGMP were not due to changes in the nicotine-induced rise in cytosolic calcium concentration. A potentiation of secretion due to low doses of nicotine was also found following simultaneous addition of ANP or nitroprusside, a result suggesting that ANP and nitric oxide (endothelium-derived relaxing factor) could be important regulators of secretion from adrenal chromaffin cells. | Cyclic GMP |
Plant diseases caused by Phytophthora species will remain an ever increasing threat to agriculture and natural ecosystems. Phytophthora literally means plant destroyer, a name coined in the 19th century by Anton de Bary when he investigated the potato disease that set the stage for the Great Irish Famine. Phytophthora infestans, the causal agent of potato late blight, was the first species in a genus that at present has over 100 recognized members. In the last decade, the number of recognized Phytophthora species has nearly doubled and new species are added almost on a monthly basis. Here we present an overview of the 10 clades that are currently distinguished within the genus Phytophthora with special emphasis on new species that have been described since 1996 when Erwin and Ribeiro published the valuable monograph 'Phytophthora diseases worldwide' (35). | Stramenopiles |
PURPOSE: To report coinfection with Acanthamoeba and Pseudomonas aeruginosa in a case with contact lens-associated keratitis. CASE REPORT: A 20-year-old woman presented to the emergency department of our hospital with a 4-day history of progressively increasing pain, redness, photophobia, mucopurulent discharge, and diminution of vision in her right eye. She was being treated for contact lens-related Pseudomonas keratitis in another hospital before presentation. Gram stain of corneal scrapings revealed gram-negative bacilli. Both Gram stain and 10% KOH wet mount showed the presence of Acanthamoeba cysts. Microbiological cultures obtained from contact lenses and contact lens storage case showed the presence of Pseudomonas aeruginosa and Acanthamoeba. Topical therapy was started in the form of hourly gentamycin 1.3%, cefazolin 5%, chlorhexidine 0.02%, propamidine 0.1%, polymyxin B 30,000 IU eye drops, and neosporin (neomycin, bacitracin, polymyxin) eye ointment four times a day. Symptomatic improvement was observed within 48 hours, along with a decrease in the density of infiltrates and a reduction in the anterior chamber reaction. Repeat corneal scrapings on day 10 showed Acanthamoeba but no bacilli. Progressive resolution of the infiltrate was noted during the next few days. Epithelialization was complete by day 24, following which the amoebicidal therapy was tapered during the next 4 weeks. Complete resolution of keratitis was achieved after 7 weeks of treatment. CONCLUSIONS: Both P. aeruginosa and Acanthamoeba are potentially devastating causes of microbial keratitis. Our case highlights the importance of considering the possibility of a concurrent infection in cases with contact lens-related keratitis. | Acanthamoeba Keratitis |
BACKGROUND: Antithyroid drug (ATD)-induced agranulocytosis is rare but may cause fatal complications in patients with thyrotoxicosis during treatment with thionamide-derived drugs. From our previous experience, we note that 2 of 11 such patients died in a 10-year retrospective study. METHODS: We reviewed thirteen patients who developed agranulocytosis from 7,466 patients with hyperthyroidism while they were being treated with ATD from July 1989 to November 2003. RESULTS: The incidence of ATD-induced agranulocytosis (absolute neutrophil counts < 500/mm3) was 0.17%. The age of the 13 patients (female: male = 10:3) was 28 to 61 years (mean +/- SD: 39.6 +/- 10.0 years). The most common clinical manifestations were fever (100%), sore throat (76.9%) and chills (46.1%). At the time of agranulocytosis attack, ATD had been administered for 12 to 66 days (mean +/- SD: 36.4 +/- 18.7 days) and the duration of symptoms was 1 to 14 days (mean +/- SD: 4.6 +/- 3.7 days). Intravenous infusion of 300 microg granulocyte colony-stimulating factor (G-CSF) per day was administered to 3 patients simultaneously with intravenous empirical broad-spectrum antibiotics. After intensive and supportive treatment in hospital, all the patients recovered with absolute neutrophil counts of more than 500/mm3 in 2 to 13 days (mean +/- SD: 7.6 +/- 3.4 days). CONCLUSIONS: In our 25-year clinical experience, the most cost-effective method of managing agranulocytosis induced by thionamide-derived ATD is that all patients with thyrotoxicosis must be warned that their white blood cells and differential counts should be checked immediately whenever the common cold" symptoms occur during treatment, especially within the first 3 months of medication." | Agranulocytosis |
The care of patients with diagnoses on the somatoform spectrum represents a challenge to all primary care physicians and is a matter of frustration to some. These patients tend to doctor shop," and studies indicate that they generate health care costs that are at least six to 14 times higher than health care costs generated by control subjects. For all disorders on the somatoform spectrum, the most effective management is regular follow-up with the primary care physician. To accomplish this goal, a therapeutic delivery of the diagnosis to the patient is essential to firmly establish the therapeutic alliance. An approach is suggested for "administering" the diagnosis as the first step in treatment for patients with several types of somatoform and related disorders. These techniques allow the patient's emotional needs to be met, enable the patient to save face when necessary and solidify the doctor-patient relationship. A good relationship allows the physician to provide long-term management with empathetic, safe and cost-effective medical care. Physicians may at times dread somatic patients, and these useful techniques can help them begin a more satisfying relationship with their very challenging patients." | Somatoform Disorders |
Interconnected pore structures of scaffolds are important to control the cell functions for cartilage tissue engineering. In this study, collagen scaffolds with interconnected pore structures were prepared using poly(D,L-lactide-co-glycolide) (PLGA) sponges as sacrificial templates. Six types of PLGA sponges of different pore sizes and porosities were prepared by the solvent casting/particulate leaching method and used to regulate the interconnectivity of the collagen scaffolds. The integral and continuous templating structure of PLGA sponges generated well-interconnected pore structures in the collagen scaffolds. Bovine articular chondrocytes cultured in collagen scaffolds showed homogenous distribution, fast proliferation, high expression of cartilaginous genes and high secretion of cartilaginous extracellular matrix. In particular, the collagen scaffold templated by the PLGA sacrificial sponge that was prepared with a high weight ratio of PLGA and large salt particulates showed the most promotive effect on cartilage tissue formation. The interconnected pore structure facilitated cell distribution, cell-cell interaction and cartilage tissue regeneration." | Polylactic Acid-Polyglycolic Acid Copolymer |
Wildfire regimes are being altered in ecosystems worldwide. The density of reptiles responds to fires and changes to habitat structure. Some of the most vulnerable ecosystems to human-increased fire frequency are old-growth Araucaria araucana forests of the southern Andes. We investigated the effects of wildfires on the density and richness of a lizard community in these ecosystems, considering fire frequency and elapsed time since last fire. During the 2018/2019 southern summer season, we conducted 71 distance sampling transects to detect lizards in Araucaria forests of Chile in four fire treatments": (1) unburned control, (2) long-term recovery, (3) short-term recovery, and (4) burned twice. We detected 713 lizards from 7 species. We found that the density and richness of lizards are impacted by wildfire frequency and time of recovery, mediated by the modification of habitat structure. The lizard community varied from a dominant arboreal species (L. pictus) in unburned and long-recovered stands, to a combination of ground-dwelling species (L. lemniscatus and L. araucaniensis) in areas affected by two fires. Araucaria forests provided key habitat features to forest reptiles after fires, but the persistence of these old-growth forests and associated biodiversity may be threatened given the increase in fire frequency." | Araucaria |
AIMS: The purpose of this study was to review the treatment policy for locally advanced stage III and IV squamous cell carcinoma (SCC) of the tonsil at the Princess Alexandra Hospital Head and Neck Unit, Brisbane, Australia. MATERIALS AND METHODS: The records of 148 patients with curable stage III and IV SCC of the tonsil were reviewed from the years 1992 to 2004 inclusive. During this period, patients were treated with surgery and postoperative radiotherapy and only offered definitive radiation if they were medically or surgically inoperable. There were 102 patients treated with surgery +/- postoperative radiotherapy (group 1) and 46 patients treated with definitive radiotherapy +/- chemotherapy (group 2). The endpoints of locoregional control (LRC), disease specific survival (DSS), and overall survival (OS) were studied and prognostic factors were investigated with univariate and multivariate analyses. RESULTS: The 5-year OS, DSS, and LRC were 57%, 69%, and 84%, respectively. Univariate analyses showed that patients in group 1 had a superior OS (69% vs. 41%, P = .007), a trend toward improvement in LRC (88% vs. 73%, P = .08), and a nonsignificant improvement in DSS (75% vs. 56%, P = .14). There was a greater percentage of patients with an Eastern Cooperative Oncology Group (ECOG) score of 2 or less in group 1, suggesting selection bias toward the surgical group. Multivariate analyses, which adjusted for known prognostic factors, showed that treatment group was significant for OS but not for LRC or DSS. CONCLUSIONS: Surgery and postoperative radiotherapy continues to provide a superior outcome in locally advanced tonsil SCC in patients with surgically resectable disease, good ECOG performance status, and medically operable. | Tonsillar Neoplasms |
Affiliation with a health maintenance organization (HMO) can offer significant advantages for a hospital, including new sources of patients and revenue. When considering HMO affiliation, the board and the administration should consider such issues as the compatibility of the affiliation with the hospital's mission and programs, the effect of the affiliation on the hospital's relationships with other parties, the implications of negotiating a contractual relationship with a payer, and the degree to which the hospital wishes to accommodate the HMO. | Prepaid Health Plans |
Photobacterium damselae subsp. piscicida, a causative agent of pseudotuberculosis, often harbours resistance plasmids (R plasmids) that facilitate horizontal gene transfer of drug resistance genes. R plasmid pP9014 was isolated from P. damselae subsp. piscicida and its complete nucleotide sequence was determined using Next Generation Sequencing technology. A protein network analysis was conducted to determine the relatedness of protein coding sequences, and ClustalW was used for the full nucleotide sequences. The occurrence of pP9014-like plasmids compared with pP99-018-like plasmids in a specific region was determined using probes for their transfer regions. pP9014 is 55851bp long with an overall GC content of 44.4% encoding 61 open reading frames (ORFs) including antimicrobial resistance genes and two conjugative transfer regions (Tra and Trb). The backbone showed highest similarity to Marinobacter adhaerens pHP-42 and Methylophaga sp. JAM7. pP9014 is similar to several IncP plasmids but forms a different subgroup. pP9014 is a unique plasmid in P. damselae subsp. piscicida and was not commonly found in drug-resistant P. damselae subsp. piscicida isolated from different areas and years in Japan. Plasmids similar to the previously reported pP99-018 are more widely distributed. This rarity suggests that plasmids similar to pP99-018 are more compatible with gamma-proteobacteria. pP9014 is the first reported IncP-1 plasmid from fish pathogens. Its similarity to other IncP plasmids isolated from soil and human pathogens suggests that plasmids of the IncP-1 incompatibility group are vectors for the transfer of drug resistance genes among diverse environments. | Photobacterium |
Recently, many studies have evaluated HPV vaccine safety and adverse effects. Two vaccines have been recently evaluated in randomized controlled trials: the bivalent vaccine for HPV 16 and 18 (Cervarix, GlaxoSmithKline Biologicals, Rixensart, Belgium) and the quadrivalent vaccine for HPV 6, 11, 16, and 18 (Gardasil, Merck and Co., Inc., Whitehouse Station, NJ). We have performed a systematic review of all randomized controlled trials in which HPV vaccines were compared with placebo regarding safety, tolerability and adverse effects. Studies were searched up to March 2013 in the databases: Pubmed, Embase, Scielo and Cancerlit. Odds Ratios (OR) of most incident adverse effects were obtained. Twelve reports, involving 29,540 subjects, were included. In the HPV 16/18 group, the most frequently reported events related to the vaccine were pain (OR 3.29; 95% CI: 3.00-3.60), swelling (OR 3.14; 95% CI: 2.79-3.53) and redness (OR 2.41; 95% CI: 2.17-2.68). For the HPV 6/11/16/18 group the events were pain (OR 2.88; 95% CI: 2.42-3.43) and swelling (OR 2.65; 95% CI: 2.0-3.44). Concerning the HPV 16/18 vaccine, pain was the most common outcome detected. These effects can be due to a possible VLP-related inflammation process. Fatigue was the most relevant general effect observed followed by fever, gastrointestinal symptoms, and headache. In the HPV 6/11/16/18 group, only general symptoms, pain and swelling were observed. Pain and swelling were the most frequent. Comparing HPV 16/18 to HPV 6/11/16/18 vaccines, the former presented more adverse effects, perhaps because there are many more trials evaluating the bivalent vaccine. Other studies are needed to clarify this issue. | Papillomavirus Vaccines |
Ingrown toenail, or onychocryptosis, is a common inflammatory disease of the hallux. It results from the alteration of fit of the nail plate in the lateral nail fold. Ingrown toenails are usually seen in adolescents and young adults and can affect daily activities and social life. Generally, ingrown toenails are classified into three stages, including the inflammatory stage, the abscess stage, and the granulation stage. In this article, we present the rare case of a man with a diagnosis of paronychia with sporangium formation causing an ingrown toenail. | Nails, Ingrown |
Etidocaine and bupivacaine are long acting local anesthetics with contrasting effects on motor and sensory function. The effect of these drugs on fast-conducting (large, motor) and slow-conducting nerve fibers (small, pain) in the isolated rabbit vagus nerve was examined. Both drugs had an equivalent effect on slow fibers. Etidocaine had a short latency and bupivacaine a prolonged latency of effect on fast fibers. During this long latency of effect by bupivacaine on fast fibers, only the slow fibers were blocked. This period of differential effect on fast and slow fibers is believed to be the explanation for the early effect of bupivacaine on pain fibers followed by a later block of motor function. This difference is believed to be due to the lower lipid solubility solubility and greater ionization of bupivacaine, which impedes diffusion across the permeability barriers present in fast-conducting A fiber. | Etidocaine |
Pralidoxime chloride (PAM) hydrolyzes acetylthiocholine, the substrate used in the assay of red cell cholinesterase. The thiocholine that is produced forms a yellow complex when Ellman's reagent is used in the assay. This was tested in blood samples of patients who were treated with PAM after organophosphorus (OP) poisoning and after the observation of an immediate increase in absorption of light at 412 nm. | Thiocholine |
Bacteriophage phi6 has a double-stranded RNA genome composed of three linear segments, L, M, and S. The innermost particle in the virion of phi6, like in the other dsRNA viruses, is an RNA-dependent RNA polymerase complex, which carries out all the functions needed for the replication of the viral genome. Empty polymerase complexes can package the single-stranded copies of the viral genome segments, replicate the packaged segments into double-stranded form (minus strand synthesis), and then produce new plus strands (transcripts) from the double-stranded RNA templates. The three viral genomic segments contain unique packaging signals at their 5' ends, and minus strand synthesis initiation is dependent on the sequence at the 3' end. Here we have constructed chimeric segments that have the packaging signal from one segment and the minus strand synthesis initiation signal from another segment. Using purified recombinant polymerase complexes and single-stranded/chimeric and original RNA segments, we have analyzed the packaging and replication regulation operating in in vitro conditions. We show that the 5' end of the L genome segment in single-stranded form is needed to switch from the packaging to the minus strand synthesis and the same sequence is required in double-stranded form to switch on plus strand synthesis. In addition we have constructed deletions to the M segment to analyze the possible regulatory role of the internal noncoding area of this segment. | Bacteriophage phi 6 |
Many different types of virus particles are able to non-specifically impede the ability of human peripheral blood lymphocytes to respond to mitogenic ro alloantigenic stimuli. This result is not obtained if ultra-purified virus is employed, although virus which has been banded only once through sucrose generally retains inhibitory potential. Ultra-pure virus is relatively unable to bind to cell surfaces, suggesting the importance of physical contact between viruses and cells in order for the observed inhibition to occur. Addition of exogenous T-cell growth factor (TCGF) to cultures containing virus, cells and stimulus causes a dose-dependent reversal of the usual inhibitory effect. | Alpharetrovirus |
In the assessment of autonomic function by heart rate variability (HRV), the framework that the power of high-frequency component or its surrogate indices reflects parasympathetic activity, while the power of low-frequency component or LF/HF reflects sympathetic activity has been used as the theoretical basis for the interpretation of HRV. Although this classical framework has contributed greatly to the widespread use of HRV for the assessment of autonomic function, it was obtained from studies of short-term HRV (typically 5âÂÂ10 min) under tightly controlled conditions. If it is applied to long-term HRV (typically 24 h) under free-running conditions in daily life, erroneous conclusions could be drawn. Also, long-term HRV could contain untapped useful information that is not revealed in the classical framework. In this review, we discuss the limitations of the classical framework and present studies that extracted autonomic function indicators and other useful biomedical information from long-term HRV using novel approaches beyond the classical framework. Those methods include non-Gaussianity index, HRV sleep index, heart rate turbulence, and the frequency and amplitude of cyclic variation of heart rate. | Heart Rate |
Circular dichroism (CD) is an excellent tool for examining the interactions and stability of proteins. This protocol covers methods to obtain and analyze circular dichroism spectra to measure changes in the folding of proteins as a function of denaturants, osmolytes or ligands. Applications include determination of the free energy of folding of a protein, the effects of mutations on protein stability and the estimation of binding constants for the interactions of proteins with other proteins, DNA or ligands, such as substrates or inhibitors. The experiments require 2-5 h. | Circular Dichroism |
BACKGROUND: Although dogs are a commonly owned companion animal in the UK, the species experiences many health problems that are predictable from demographic information. This study aimed to use anonymised veterinary clinical data from the VetCompass Programme to report the frequency of common disorders of dogs under primary veterinary care in the UK during 2016 and to explore effects associated with age, sex and neuter status. RESULTS: From an available population of 905,543 dogs under veterinary care at 886 veterinary clinics during 2016, the current study included a random sample of 22,333 (2.47 %) dogs from 784 clinics. Prevalence for each disorder was calculated at the most refined level of diagnostic certainty (precise-level precision) and after grouping to a more general level of diagnostic precision (grouped-level precision). The most prevalent precise-level precision disorders recorded were periodontal disease (prevalence 12.52 %, 95 % CI: 12.09-12.97), otitis externa (7.30 %, 95 % CI: 6.97-7.65) and obesity (7.07 %, 95 % CI: 6.74-7.42). The most prevalent grouped-level disorders were dental disorder (14.10 %, 95 % CI: 13.64-14.56), skin disorder (12.58 %, 95 % CI: 12.15-13.02) and enteropathy (10.43 %, 95 % CI: 10.04-10.84). Associations were identified for many common disorders with age, sex and neuter. CONCLUSIONS: The overall findings can assist veterinarians and owners to prioritise preventive care and to understand demographic risk factors in order to facilitate earlier diagnosis of common disorders in dogs. The information on associations with age, sex and neuter status provides additional contextual background to the complexity of disorder occurrence and supports targeted health controls for demographic subsets of dogs. | Castration |
The Rainbow trout gill cell-line (RTgill-W1) has been accepted by the Organisation for Economic Co-operation and Development (OECD TG249) as a replacement for fish in acute toxicity tests. In these tests cells are exposed under static conditions. In contrast, in vivo, water moves over fish gills generating fluid shear stress (FSS) that alters cell physiology and response to toxicants. The current study uses a specialised 3D printed chamber designed to house inserts and allows for the flow (0.2 dynes cm(2)) of water over the cells. This system was used to assess RTgill-W1 cell responses to FSS in the absence and presence of copper (Cu) over 24 h. FSS caused increased gene expression of mechanosensitive channel peizo1 and the Cu-transporter atp7a, elevated reactive oxygen species generation and increased expression of superoxidase dismutase. Cell metabolism was unaffected by Cu (0.163 muM to 2.6 muM Cu) under static conditions but significantly reduced by FSS + Cu above 1.3 muM. Differential expression of metallothionein (mt) a and b was observed with increased expression of mta under static conditions and mtb under FSS on exposure to Cu. These findings highlight toxicologically relevant mechanosensory responses by RTgill-W1 to FSS that may influence toxicological responses. | Oncorhynchus mykiss |
Leuconostoc gasicomitatum is a psychrotrophic lactic acid bacterium causing spoilage of cold-stored, modified-atmosphere-packaged (MAP), nutrient-rich foods. Its role has been verified by challenge tests in gas and slime formation, development of pungent acidic and buttery off odors, and greening of beef. MAP meats have especially been prone to L. gasicomitatum spoilage. In addition, spoilage of vacuum-packaged vegetable sausages and marinated herring has been reported. The genomic sequencing project of L. gasicomitatum LMG 18811T was prompted by a need to understand the growth and spoilage potentials of L. gasicomitatum, to study its phylogeny, and to be able to knock out and overexpress the genes. Comparative genomic analysis was done within L. gasicomitatum LMG 18811T and the three fully assembled Leuconostoc genomes (those of Leuconostoc mesenteroides, Leuconostoc citreum, and Leuconostoc kimchii) available. The genome of L. gasicomitatum LMG 18811T is plasmid-free and contains a 1,954,080-bp circular chromosome with an average GC content of 36.7%. It includes genes for the phosphoketolase pathway and alternative pathways for pyruvate utilization. As interesting features associated with the growth and spoilage potential, LMG 18811T possesses utilization strategies for ribose, external nucleotides, nucleosides, and nucleobases and it has a functional electron transport chain requiring only externally supplied heme for respiration. In respect of the documented specific spoilage reactions, the pathways/genes associated with a buttery off odor, meat greening, and slime formation were recognized. Unexpectedly, genes associated with platelet binding and collagen adhesion were detected, but their functionality and role in food spoilage and processing environment contamination need further study. | Leuconostocaceae |
With the development of high-density and high-rise buildings on both sides of the street, widespread attention has been paid to the applicability of the traditional greening model of 'the more trees, the better atmospheric environment' in dealing with air pollution in urban street canyons. Clarifying the characteristics of street canyons greening and its planting design pattern on the reduction of emission pollutants by vehicles is an important prerequisite for the improvement of air quality in the street canyons. Based on literature review, we compared the applicability and limitations of the three methods, including field observation, wind tunnel test, and numerical simulation. We further analyzed the effects of roadside trees and hedges on the dispersion and deposition of air pollutants, and put forward a framework of adaptive greening design for air quality improvement. Finally, we proposed that future studies should address the creation of graphic languages for roadside greening design, the development of technical guidelines for evaluating the exposure of air pollution, and the optimization of parameterization schemes for the physical processes of greening effect in computational fluid dynamics models. Overall, our review could provide ideas and reference for the subsequent research. | Vehicle Emissions |
BACKGROUND: There remains a paucity of epidemiologic data from recent years on the incidence of shoulder arthroplasty. We aimed to examine the recent trends and predict future projections of hemiarthroplasty (HA), anatomic (aTSA), and reverse shoulder arthroplasty (RSA), as well as compare these predictions to those for total hip (THA) and knee arthroplasty (TKA). METHODS: The National Inpatient Sample was queried from 2011 to 2017 for HA, aTSA, and RSA, as well as TKA and THA. Linear and Poisson regression was performed to project annual procedural incidence and volume to the year 2025. RESULTS: Between 2011 and 2017, the number of primary shoulder arthroplasties increased by 103.7%. In particular, RSA increased by 191.3%, with 63,845 RSAs performed in 2017. All projection models demonstrated significant increases in shoulder arthroplasty volume and incidence from 2017 to 2025. By 2025, the linear model predicts that shoulder arthroplasty volume will increase by 67.2% to 174,810 procedures whereas the Poisson model predicts a 235.2% increase, to 350,558 procedures by 2025. These growth rate projections outpace those of THA and TKA. CONCLUSIONS: The number of shoulder arthroplasties has been increasing in recent years, largely because of the exponential increases in RSA. The overall incidence is increasing at a greater rate than TKA or THA, with projections continuing to rise over the next decade. These data and projections can be used by policy makers and hospitals to drive initiatives aimed at meeting these projected future demands. | Arthroplasty |
B cell receptor (BCR)-mediated tonic signals are important for B cell survival and development. In this issue of Immunity, Treanor et al. (2010) show that triggering of downstream responses is kept in check with BCR immobilization by actin. | CD79 Antigens |
A 1-year-old boy with no underlying disorder presented with non-bilious vomiting since 4 days before admission. He was referred to our hospital and was diagnosed with a small bowel obstruction due to an intraabdominal tumor. Laparotomy revealed an intestinal volvulus with a soft and lobulated tumor arising from the mesentery. The resected tumor with a small part of the small bowel was diagnosed as lipoblastoma histologically. From a literature review, mesenteric lipoblastoma with an intestinal volvulus showed different characteristics such as greater frequency of vomiting and less frequency of abdominal mass as clinical symptoms, and the size of the tumor was smaller than that of the tumor without the intestinal volvulus. | Lipoblastoma |
Gelotology, or the science of laughter, is developing as a complementary field of medicine. Laughter therapy has been shown to have multifaceted physiological and endocrine benefits, and is being used to help manage various chronic diseases. This communication describes some aspects of laughter therapy, and reviews evidence related to its therapeutic potential in diabetes care. | Laughter Therapy |
BACKGROUND: Intra-operative assessment is not routinely performed in the UK due to poor sensitivity of available methods and overburdened pathology resources. We conducted a prospective clinical feasibility study of the GeneSearch Breast Lymph Node (BLN) Assay (Veridex, LLC, Warren, NJ) to confirm its potential usefulness within the UK healthcare system. METHODS: In the assay 50% of the lymph node was processed to detect the presence of cytokeratin-19 and mammaglobin mRNA. The assay was calibrated to detect metastases >0.2 mm. Assay results were compared to H&E performed on each face of approximately 2 mm alternating node slabs and 3 additional sections cut at approximately 150 microm interval from each face of the node slab. RESULTS: 124 sentinel lymph nodes were removed from 82 breast cancer patients. The assay correctly identified all 6 patients with sentinel node macrometastases (>2.0 mm), and 2 of 3 patients with sentinel node micrometastases (0.2-2.0 mm). Sentinel lymph nodes in 4 patients were assay positive but histology negative. Two of these four patients had isolated tumor cells seen by histology. The overall concordance with histology was 93.9% (77/82), with sensitivity of 88.9% (8/9, 95% CI 56.5-98%), specificity of 94.6% (69/73, 95% CI 86.7-97.8%), positive predictive value of 66.7% (8/12, 95% CI 39.1-86.2%) and negative predictive value of 98.6% (69/70, 95% CI 92.3-99.7%). The assay was performed in a median time of 32 min (range 26-69 min). CONCLUSION: Intra-operative assessment of sentinel lymph node can be performed rapidly and accurately using the GeneSearch BLN Assay. | Mammaglobin A |
In children it is often necessary to ligate the splenic artery and the main collateral supply to the spleen during liver transplantation. The complication of splenic infarction has been observed on postoperative CT in such patients. The purpose of our study was to determine the incidence and CT appearance of splenic infarction and to correlate its occurrence with a vascular cause related to the operative procedure. During a 2 year period, 26 of 94 (28%) children receiving liver transplants developed splenic infarction as shown by CT. Infarction generally occurred within 2 weeks of transplantation. Computed tomography demonstrated variable portions of splenic involvement with hypodense lesions. Twenty-two of 39 (56%) patients whose splenic artery was ligated developed splenic infarctions. Only 4 of 55 (7%) patients whose splenic artery was left intact had splenic infarctions on postoperative CT. We conclude that there is an increased incidence of splenic infarction in pediatric liver transplant recipients. The incidence of infarction is related to ligation of the splenic artery and collateral pathways. | Splenic Infarction |
The purpose of this paper is to assess critically the results of treatment of slipped femoral capital epiphyses in patients seen over the past ten years at the Prince of Wales Hospital. The problems examined in this study include: (a) the indications for prophylactic pinning; (b) the number of Knowles pins necessary for fixation; and (c) the questions whether and when these should be removed. | Epiphyses, Slipped |
Opportunistic pathogen Vibrio vulnificus causes severe systemic infection in humans with high mortality. Although multiple exotoxins have been characterized in V. vulnificus, their interactions and potential synergistic roles in pathogen-induced host cell death have not been investigated previously. By employing a series of multiple exotoxin deletion mutants, we investigated whether specific exotoxins of the pathogen functioned together to achieve severe and rapid necrotic cell death. Human epithelial cells treated with V. vulnificus with a plpA deletion background exhibited an unusually prolonged cell blebbing, suggesting the importance of PlpA, a phospholipase A(2), in rapid necrotic cell death by this pathogen. Additional deletion of the rtxA gene encoding the multifunctional autoprocessing repeats-in-toxin (MARTX) toxin did not result in necrotic cell blebs. However, if the rtxA gene was engineered to produce an effector-free MARTX toxin, the cell blebbing was observed, indicating that the pore forming activity of the MARTX toxin is sufficient, but the MARTX toxin effector domains are not necessary, for the blebbing. When a recombinant PlpA was treated on the blebbed cells, the blebs were completely disrupted. Consistent with this, MARTX toxin-pendent rapid release of cytosolic lactate dehydrogenase was significantly delayed in the plpA deletion background. Mutations in other exotoxins such as elastase, cytolysin/hemolysin, and/or extracellular metalloprotease did not affect the bleb formation or disruption. Together, these findings indicate that the pore forming MARTX toxin and the phospholipase A(2), PlpA, cooperate sequentially to achieve rapid necrotic cell death by inducing cell blebbing and disrupting the blebs, respectively. | Vibrio vulnificus |
semiaza-Bambus[6]urils efficiently transport anions across lipid membranes. A systematic modification of their lipophilic side chains to include various alkyl groups and thioethers reveals that the most efficient chloride transporters are those that agree with Lipinski's rule-of-lipophilicity, exhibiting clog P(o/w) values close to 5. Furthermore, vesicle anion-transport assays show that the new anion-transporters are independent of the cation identity but exhibit high anion selectivity, NO(3)(-) > Br(-) > Cl(-) > SO(4)(2-), in agreement with the Hofmeister series. These findings will allow for the design of highly specific anion transporters for biomedical applications, particularly for managing anion channelopathies. | Organic Anion Transporters |
Today, axilla odours are socially stigmatized and are targeted with deodorants and antiperspirants representing a multi-billion market. Axilla odours aren't simple byproducts of our metabolism but specifically formed by an intricate interplay between i) specific glands, ii) secreted amino acid conjugates of highly specific odorants and iii) selective enzymes present in microorganisms colonizing our skin, providing a natural 'controlled-release' mechanism. Within a multidisciplinary research project, we were able to elucidate the structure of key body odorants, isolate and characterize secreted amino acid conjugates and identify the enzymes responsible for odour release. These enzymes then served as targets for the development of specific active compounds in an almost medicinal chemistry approach, an approach rarely used in the cosmetic field so far. Here we review the key new insights into the biochemistry of human body odour formation, with some remarks on the experimental steps undertaken and hurdles encountered. The development of deodorant actives and the difficult path to market for such specifically acting cosmetic actives is discussed. The basic insights into the biochemistry also opened the way to address some questions in population genetics: Why have large proportions of Asians lost the 'ability' to form body odours? Do twins smell the same? Are our typical body odours indeed influenced by the immune system as often claimed? After addressing these questions, I'll conclude with the key remaining challenges in this field on an ecological niche that is 'anatomically very close to our heart'. | Skin |
Mirizzi syndrome is a rare syndrome, caused by the compression of gall stones which may result in CBD obstruction or fistula formation. It may sometimes present without any prior symptoms. It has been classified into five types by Csendes. Usually open surgical approach is recommended for the condition, especially for Types III-V. We present the case of a patient who presented with right hypochondrial pain and was intra-operatively discovered to have type Va Mirrizi syndrome and was managed successfully laparoscopically. | Mirizzi Syndrome |
Two novel sequence-specific endonucleases have been isolated from Proteus vulgaris, ATCC 13315. PvuI recognizes the sequence: 5' C G A T decrease C G 3' 3' G C increase T A G C 5' and PvuII recognizes the sequence: 5' C A G decrease C T G 3' 3' G T C increase G A C 5' and cleave as indicated by the arrow (decrease). PvuI is an isoschizomer of XorII, RshI, and XniI. No enzyme with the specificity of PvuII has been described previously. | Proteus vulgaris |
We present our experience in the first 236 hysteroscopic procedures in Pontificia Universidad Catolica of Chile. 219 were performed as part of infertility study and 17 were performed for other reasons. The surgical technique, type of anesthesia, distension procedures and complications are described. The correlation between hysterosalpingographic diagnosis and endoscopic vision is established. The preoperative diagnosis was confirmed in 82% of the uterine cavity synechiae, 72% of the cervical synechiae, 67% of polyps and/or myomas, and in 100% of uterine malformations. Myomas and/or polyps were found in 12% of normal appearing hysterosalpingograms. | Hysteroscopy |
BACKGROUND: A neurodevelopmental syndrome was recently reported in four patients with SOX4 heterozygous missense variants in the high-mobility-group (HMG) DNA-binding domain. The present study aimed to consolidate clinical and genetic knowledge of this syndrome. METHODS: We newly identified 17 patients with SOX4 variants, predicted variant pathogenicity using in silico tests and in vitro functional assays and analysed the patients' phenotypes. RESULTS: All variants were novel, distinct and heterozygous. Seven HMG-domain missense and five stop-gain variants were classified as pathogenic or likely pathogenic variant (L/PV) as they precluded SOX4 transcriptional activity in vitro. Five HMG-domain and non-HMG-domain missense variants were classified as of uncertain significance (VUS) due to negative results from functional tests. When known, inheritance was de novo or from a mosaic unaffected or non-mosaic affected parent for patients with L/PV, and from a non-mosaic asymptomatic or affected parent for patients with VUS. All patients had neurodevelopmental, neurological and dysmorphic features, and at least one cardiovascular, ophthalmological, musculoskeletal or other somatic anomaly. Patients with L/PV were overall more affected than patients with VUS. They resembled patients with other neurodevelopmental diseases, including the SOX11-related and Coffin-Siris (CSS) syndromes, but lacked the most specific features of CSS. CONCLUSION: These findings consolidate evidence of a fairly non-specific neurodevelopmental syndrome due to SOX4 haploinsufficiency in neurogenesis and multiple other developmental processes. | SOXC Transcription Factors |
Maternal anxiety symptoms in the perinatal period might have long-term health effects on both the mother and the developing child. Valerian is a phytotherapeutic agent that is widely used for the treatment of anxiety. This study investigated the effects of valerian treatment in postpartum rats on maternal care, toxicity, and milk composition. Postnatal development, memory, and anxiety behavior in the offspring were also assessed. Postpartum Wistar rats received the valerian (500, 1000, or 2000 mg.kg-1.day-1) by oral gavage. Clinical and biochemical toxicity was evaluated with commercial kits. Maternal behavior was observed daily. Milk composition was analyzed by colorimetric methods. Physical and neuromotor tests were used to analyze postnatal development. Anxiolytic activity was assessed by the elevated plus maze, and memory was evaluated by the step-down inhibitory avoidance task. Maternal toxicity and care behavior were not altered by the treatment, while only the highest dose promoted a significant increase of lactose, and the doses 1000 and 2000 mg.kg-1.day-1 promoted a reduction of protein contents in milk. Postnatal development was similar in all offspring. Adult offspring did not display altered anxiety behavior, while long-term memory was impaired in the female adult offspring by maternal treatment with 1000 mg.kg-1.day-1. These results suggested that high doses of valerian had significant effects on important maternal milk components and can cause long-term alterations of offspring memory; thus, treatment with high doses of valerian is not safe for breastfeeding Wistar rat mothers. | Valerian |
PURPOSE: To study the effect of increasing grades of hypertensive retinopathy (HTR) on neonatal outcomes among preeclamptic women and assess the various maternal risk factors for HTR. METHODS: A prospective cohort study was conducted on 258 preeclamptic women. The systolic and diastolic blood pressure (SBP and DBP), liver, and renal function parameters were collected besides basic demographic details. Dilated fundus examination with the Keith-Wagner-Barker classification was used to grade HTR. Following delivery, neonatal outcomes were evaluated. RESULTS: Of the 258 preeclamptic women recruited, 53.1% had preeclampsia (PE), and 46.9% had severe preeclampsia. With increasing grades of HTR, a significant association with low birth weight (LBW) (p = 0.012) and preterm gestational age (p = 0.002) was noted but not with the Appearance, Pulse, Grimace, Activity and Respiration (APGAR) score (p = 0.062). Also, it did not increase the risk of retinopathy of prematurity (ROP), with most babies, even those born to mothers with high grades of HTR, showing no evidence of ROP (p = 0.025). Among the maternal factors, increasing age (p = 0.016), SBP (p < 0.001), DBP (p < 0.001), serum creatinine (p = 0.035), alanine aminotransferase (p = 0.008), lower hemoglobin (Hb) (p = 0.009), lower platelet (p < 0.001), and severe PE (p < 0.001) have been found to significantly affect the grade of HTR. CONCLUSION: Higher grades of HTR in the preeclamptic mother are associated with preterm delivery and LBW of the neonates but neither affect the APGAR score nor pose the risk of developing ROP. | Hypertensive Retinopathy |
A fixed-dose combination tablet of the cystic fibrosis transmembrane conductance regulator (CFTR) corrector tezacaftor and the CFTR potentiator ivacaftor with the next-generation CFTR corrector elexacaftor (hereafter referred to as elexacaftor/ivacaftor/tezacaftor) [Trikafta] has been developed by Vertex Pharmaceuticals Inc. to treat patients with the most common cystic fibrosis mutation (F508del). Its use has been associated with statistically significant and/or clinically meaningful improvements in lung function and respiratory-related quality of life compared with comparator regimens (placebo or ivacaftor/tezacaftor) in multinational phase II and III studies, and in October 2019 elexacaftor/ivacaftor/tezacaftor was approved by the US FDA for the treatment of cystic fibrosis in patients aged >/= 12 years who have >/= 1 F508del mutation in the CFTR gene. A regulatory assessment for elexacaftor/ivacaftor/tezacaftor as a treatment for cystic fibrosis is underway in the EU. This article summarizes the milestones in the development of elexacaftor/ivacaftor/tezacaftor leading to this first approval for the treatment of cystic fibrosis in patients aged >/= 12 years who have >/= 1 F508del mutation in the CFTR gene. | Chloride Channel Agonists |
Array-based biosensor technology offers the user the ability to detect and quantify multiple targets in multiple samples simultaneously (Analytical Sciences 23:5-10, 2007). The NRL Array Biosensor has been developed with the aim of creating a system for sensitive, rapid, on-site screening for multiple targets of interest. This system is fluorescence-based, using evanescent illumination of a waveguide, and has demonstrated the use of both sandwich and competitive immunoassays for the detection of both high and low molecular weight targets, respectively. The current portable, automated system has demonstrated detection of a wide variety of analytes ranging from simple chemical compounds to entire bacterial cells, with applications in food safety, disease diagnosis, homeland security and environmental monitoring. | Investigative Techniques |
The incidence of colon cancer increased worldwide in 2019 and its treatment is urgent from a quality of life perspective. A relationship has been reported between elevated numbers of tumor-associated macrophages (TAMs) in the tumor microenvironment and a poor prognosis in cancer patients, and M2 TAMs have been shown to promote tumor growth by immunosuppression through the stimulation of programmed death-1 (PD-1, an immune check point receptor), interleukin (IL)-1beta, and monocyte chemoattractant protein (MCP)-1. We herein examined the effects of three synthetic dihydroxystilbenes (2,3-, 3,4-, and 4,4'-dihydroxystilbenes) on colon carcinogenesis, colon tumor growth, and colon cytokines (IL-1beta, IL-6, and tumor necrosis factor (TNF)-alpha), a chemokine (MCP-1), vascular endothelial growth factor (VEGF), and PD-1 levels in azoxymethane (AOM) plus dextran sulfate sodium (DSS)-treated C57BL/6J mice. The three dihydroxystilbenes inhibited colon carcinogenesis and tumor growth as well as increases in colon IL-1beta, IL-6, MCP-1, and PD-1 levels in AOM/DDS-treated mice (in vivo). The three dihydroxystilbenes also suppressed COX-2 expression in colon tumors (in vivo). The results obtained also revealed that the three dihydroxystilbenes inhibited PD-1 elevations in M2-THP-1 macrophages (in vitro). Therefore, the inhibition of AOM/DSS-induced colon carcinogenesis and colon tumor growth by 2,3-, 3,4-, and 4,4'-dihydroxystilbenes appears to be due to the suppression of M2 TAM differentiation and activation and PD-1 expression (immunosuppression) via reductions in COX-2 expression levels in the colon tumor microenvironment. | Dihydrostilbenoids |
Hematologic abnormalities are not uncommon in patients with nonhematologic malignancies and may contribute significantly to morbidity and even to mortality. An appreciation for the spectrum of severity and etiology will allow the physician to anticipate and perhaps ameliorate some of these complications. This understanding will also provide sufficient information to decide when intervention is unnecessary. | Hematologic Diseases |
Gastrointestinal (GI) discomfort is a hallmark of most gut disorders and represents an important component of chronic visceral pain(1). For the growing population afflicted by irritable bowel syndrome, GI hypersensitivity and pain persist long after tissue injury has resolved(2). Irritable bowel syndrome also exhibits a strong sex bias, afflicting women three times more than men(1). Here, we focus on enterochromaffin (EC) cells, which are rare excitable, serotonergic neuroendocrine cells in the gut epithelium(3-5). EC cells detect and transduce noxious stimuli to nearby mucosal nerve endings(3,6) but involvement of this signalling pathway in visceral pain and attendant sex differences has not been assessed. By enhancing or suppressing EC cell function in vivo, we show that these cells are sufficient to elicit hypersensitivity to gut distension and necessary for the sensitizing actions of isovalerate, a bacterial short-chain fatty acid associated with GI inflammation(7,8). Remarkably, prolonged EC cell activation produced persistent visceral hypersensitivity, even in the absence of an instigating inflammatory episode. Furthermore, perturbing EC cell activity promoted anxiety-like behaviours which normalized after blockade of serotonergic signalling. Sex differences were noted across a range of paradigms, indicating that the EC cell-mucosal afferent circuit is tonically engaged in females. Our findings validate a critical role for EC cell-mucosal afferent signalling in acute and persistent GI pain, in addition to highlighting genetic models for studying visceral hypersensitivity and the sex bias of gut pain. | Visceral Pain |
To improve the sensory quality and promote the diversified development of duck meat, the identification and inhibition of key off-odorants in duck broth were comparatively characterized by using the sensomics approach and binary odor mixture analysis. Sensory evaluation results showed that Litsea pungens Hemsl (LPH) could strongly inhibit the duck broth off-odorants. Fifty-four aroma-active compounds with flavor dilution factors ranging from 1 to 2048 were identified in duck broth and duck broth stewed by LPH. Recombination and omission tests confirmed that trans-4,5-epoxy-(E)-2-decenal, (E)-2-octenal, p-cresol, 1-octen-3-ol, and 4-methyloctanoic acid were the key off-odorants in duck broth. Additionally, trans-4,5-epoxy-(E)-2-decenal (9.26 mug/L) and p-cresol (718.91 mug/L) were identified as the key off-odorants in duck meat for the first time. The results of binary odor mixture and off-odorants inhibition curves demonstrated that linalool with the lowest theoretical inhibitory concentration (109.65 mug/L) had the best aroma masking ability among the five off-odorants, followed by geraniol (123.03 mug/L), (Z)-3,7-dimethyl-2,6-octadien-1-ol (301.99 mug/L), (E)-3,7-dimethyl-2,6-octadienal (2187.76 mug/L), and (Z)-3,7-dimethyl-2,6-octadienal (2691.53 mug/L). The spiking test verified that these compounds with the lowest theoretical inhibitory concentrations effectively inhibited the off-odorants of duck broth. | Flavoring Agents |
4EBP1 is phosphorylated by the mTORC1 kinase. When mTORC1 activity is inhibited, hypophosphorylated 4EBP1 binds and sequesters eIF4E, a component of the mRNA cap-binding complex, and blocks translation. As a consequence, mTORC1 activity is needed to maintain active translation. The human cytomegalovirus pUL38 protein preserves mTORC1 activity, keeping most of the E4BP1 in the infected cell in a hyperphosphorylated, inactive state. Here we report that a second viral protein, pUL69, also antagonizes the activity of 4EBP1, but by a separate mechanism. pUL69 interacts directly with eIF4A1, an element of the cap-binding complex, and the poly(A)-binding protein, which binds to the complex. When pUL69 accumulates during infection with wild-type virus, 4EBP1 is excluded from the complex. However, 4EBP1 is present in the cap-binding complex after infection with a pUL69-deficient virus, coincident with reduced accumulation of several late virus-coded proteins. We propose that pUL69 supports translation in human cytomegalovirus-infected cells by excluding hypophosphorylated 4EBP1 from the cap-binding complex. | Poly(A)-Binding Protein I |
PURPOSE: To investigate the effect of COL8A2 repression on corneal endothelial cells (CECs) in vitro and in vivo. METHODS: Cultured human CECs (hCECs) were transfected with COL8A2 siRNA (siCOL8A2), and the cell viability and proliferation rate were measured. The expression of cell proliferation-associated molecules was evaluated by Western blotting and real-time reverse transcription PCR. Cell shape, Wingless-INT (WNT) signaling, and mitochondrial oxidative stress were also measured. For in vivo experiments, siCOL8A2 was transfected into rat CECs (rCECs), and corneal opacity and corneal endothelium were evaluated. RESULTS: After transfection with siCOL8A2, COL8A2 expression was reduced (80%). Cell viability, cell proliferation rate, cyclin D1 expression, and the number of cells in the S-phase were reduced in siCOL8A2-treated cells. The cell attained a fibroblast-like shape, and SNAI1, pSMAD2, and beta-catenin expression, along with mitochondrial mass and oxidative stress levels, were altered. Corneal opacity increased, and the CECs were changed in rats in the siCOL8A2 group. CONCLUSIONS: COL8A2 is required to maintain normal wound healing and CEC function. | Collagen Type VIII |
AIM: The aim of this study was to compare vaginal misoprostol with the Cook cervical ripening balloon (CCRB) for induction of labor in late-term nulliparous women. METHODS: This open, quasi-experimental, prospective study included 109 nulliparous women with late-term pregnancies and Bishop scores < 7. Fifty-five women were allocated to receive vaginal misoprostol 25 mcg and 54 received the CCRB to induce labor. The primary outcome was the time until delivery. Secondary outcomes included time to the onset of labor and obstetric and perinatal outcomes. RESULTS: Women in the misoprostol group experienced shorter time until delivery (25.41 h vs 31.26 h; P < 0.01) and in a greater percentage gave birth within the first 24 h. Time to active stage of labor was 19.5 h and 23.8 h (P < 0.01) for misoprostol and the CCRB, respectively. There were no differences in the rates of cesarean section or post-partum anemia. Additionally, there were no differences in rates of tachysystolia, intrapartum fever, or meconium. Perinatal outcomes, post-partum pH, Apgar scores, and neonatal admissions were similar in the two groups. CONCLUSION: Misoprostol 25 mcg reduces labor induction time compared with the CCRB with similar safety in late-term pregnancies. | Misoprostol |
The mitochondrial matrix ATPase associated with diverse cellular activities (m-AAA) protease spastic paraplegia 7 (SPG7) has been recently implicated as either a negative or positive regulatory component of the mitochondrial permeability transition pore (mPTP) by two research groups. To address this controversy, we investigated possible mechanisms that explain the discrepancies between these two studies. We found that loss of the SPG7 gene increased resistance to Ca(2+)-induced mPTP opening. However, this occurs independently of cyclophilin D (cyclosporine A insensitive) rather it is through decreased mitochondrial Ca(2+) concentrations and subsequent adaptations mediated by impaired formation of functional mitochondrial Ca(2+) uniporter complexes. We found that SPG7 directs the m-AAA complex to favor association with the mitochondrial Ca(2+) uniporter (MCU) and MCU processing regulates higher order MCU-complex formation. The results suggest that SPG7 does not constitute a core component of the mPTP but can modulate mPTP through regulation of the basal mitochondrial Ca(2+) concentration." | Mitochondrial Transmembrane Permeability-Driven Necrosis |
The biodiversity hypothesis postulates that the natural environment positively affects human physical and mental health. We evaluate the latest evidence and propose new tools to examine the halobiont environment. We chose to target our review at neuropsychiatric disorders, including depression, anxiety, autism, dementia, multiple sclerosis, etc. because a green prescription (exposure to green spaces) was shown to benefit patients with neuropsychiatric disorders. Specifically, our review consists of three mini reviews on the associations exploring: (1) ecological biodiversity and human microbiota; (2) human microbiota and neuropsychiatric disorders; (3) ecological biodiversity and neuropsychiatric disorders. We conclude that the environment could directly transfer microbes to humans and that human studies support the gut microbiota as part of the pathophysiology of neuropsychiatric disorders. Overall, the results from the three mini reviews consistently support the biodiversity hypothesis. These findings demonstrated the plausibility of biodiversity exerting mental health effects through biophysiological mechanisms instead of psychological mechanisms alone. The idea can be further tested with novel biodiversity measurements and research on the effects of a green prescription. | Biodiversity |
Adhesion molecules play important roles in airway hyperresponsiveness or airway inflammation. Our previous study indicated catenin alpha-like 1 (CTNNAL1), an alpha-catenin-related protein, was downregulated in asthma patients and animal model. In this study, we observed that the expression of CTNNAL1 was increased in lung tissue of the ozone-stressed Balb/c mice model and in acute ozone stressed human bronchial epithelial cells (HBEC). In order to identify the possible DNA-binding proteins regulating the transcription of CTNNAL1 gene in HBEC, we designed 8 oligo- nucleotide probes corresponding to various regions of the CTNNAL1 promoter in electrophoretic mobility shift assays (EMSA). We detected 5 putative transcription factors binding sites within CTNNAL1 promoter region that can recruit LEF-1, AP-2alpha and CREB respectively by EMSA and antibody supershift assay. Chromatin immunoprecipitation (ChIP) assay verified that AP-2 alpha and LEF-1 could be recruited to the CTNNAL1 promoter. Therefore we further analyzed the functions of putative AP-2 and LEF-1 sites within CTNNAL1 promoter by site-directed mutagenesis of those sites within pGL3/FR/luc. We observed a reduction in human CTNNAL1 promoter activity of mutants of both AP-2alpha and LEF-1 sites. Pre-treatment with ASOs targeting LEF-1and AP-2alpha yielded significant reduction of ozone-stress-induced CTNNAL1 expression. The activation of AP-2alpha and LEF-1, followed by CTNNAL1 expression, showed a correlation during a 16-hour time course. Our data suggest that a robust transcriptional CTNNAL1 up-regulation occurs during acute ozone-induced stress and is mediated at least in part by ozone-induced recruitments of LEF-1 and AP-2alpha to the human CTNNAL1 promoter." | Lymphoid Enhancer-Binding Factor 1 |
Recent advances in fluorescent dyes, methods, instruments and software for DNA melting analysis have created versatile new tools for variant scanning and genotyping. High resolution melting analysis (HRM or HRMA) is faster, simpler, and less expensive than alternative approaches requiring separations or labeled probes. With the addition of a saturating dye before PCR followed by rapid melting analysis of the PCR products, the sensitivity of heterozygote scanning approaches 100%. Specificity can be increased by identifying common polymorphisms with small amplicon melting, unlabeled probes or snapback primers to decrease the sequencing burden. However, some homozygotes require mixing for identification. Furthermore, different heterozygotes may produce melting curves so similar to each other that, although they clearly vary from homozygous variants, they are not differentiated from each other. Nevertheless, the experimental return for minimal effort is great. This focus issue of Human Mutation includes a concise, timely review on high resolution melting, a comparison to denaturing gradient gel electrophoresis, integration with qPCR for copy number assessment, combined amplicon scanning and unlabeled probe genotyping from a single melting curve, and applications to the mitochondrial genome and to BRCA1. | Genotype |
Thirteen compounds were isolated from the methanolic extract of the leaves of Androcymbium palaestinum Baker (Colchicaceae). Of these, three were new, two were new natural products, and eight were known. The new isolated compounds were (+)-1-demethylandrocine (5), (-)-andropalaestine (8), and (+)-2-demethyl-beta-lumicolchicone (10), while the new natural products were (+)-O-methylkreysigine-N-oxide (3) and (+)-O,O-dimethylautumnaline (9). Moreover, two known compounds are reported for the first time from this species, specifically (-)-colchicine (11) and (-)-3-demethyldemecolcine (13). The structures of the isolated compounds were elucidated using a series of spectroscopic and spectrometric techniques, principally HRESIMS, 1D-NMR ((1)H and (13)C NMR) and 2D-NMR (COSY, edited-HSQC, and HMBC). ECD spectroscopy was used for assigning the absolute configurations of compounds 3, 5, and 10. The cytotoxic activities of the isolated compounds were evaluated using the MDA-MB-435 (melanoma), MDA-MB-231 (breast), and OVCAR3 (ovary) cancer cell lines. Compound 11 was the most potent against all tested cell lines, with IC(50) values of 12, 95 and 23 nM, respectively. | Colchicaceae |
The subject of four-stranded nucleic acid structures is reviewed. Studies on gels formed by guanosine and its analogues have provided appropriate models for the structures of poly(I) and poly(G). The stabilizing influence of certain cations, in particular K+, on Guo-5'-P gels and poly(I) is discussed in the light of recent data on selective K+ stabilization of telomeric DNA structures. The topological possibilities these dG containing sequences could adopt are discussed. In particular the role of the glycosidic linkage (anti/syn), the polarity of the strands and the orientation of the G-tetrad stacks is highlighted. | Poly G |
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