Comparative proteomics analysis of Arabidopsis thaliana response to light-emitting diode of narrow wavelength 450 nm, 595 nm, and 650 nm.
Incident light is a central modulator of plant growth and development. However, there are still open questions surrounding wavelength-specific plant proteomic responses. Here we applied tandem mass tag based quantitative proteomics technology to acquire an in-depth view of proteome changes in Arabidopsis thaliana response to narrow wavelength blue (B; 450 nm), amber (A; 595 nm), and red (R; 650 nm) light treatments. A total of 16,707 proteins were identified with 9120 proteins quantified across all three light treatments in three biological replicates. This enabled examination of changes in the abundance for proteins with low abundance and important regulatory roles including transcription factors and hormone signaling. Importantly, 18% (1631 proteins) of the A. thaliana proteome is differentially abundant in response to narrow wavelength lights, and changes in proteome correlate well with different morphologies exhibited by plants. To showcase the usefulness of this resource, data were placed in the context of more than thirty published datasets, providing orthogonal validation and further insights into light-specific biological pathways, including Systemic Acquired Resistance and Shade Avoidance Syndrome. This high-resolution resource for A. thaliana provides baseline data and a tool for defining molecular mechanisms that control fundamental aspects of plant response to changing light conditions, with implications in plant development and adaptation. SIGNIFICANCE: Understanding of molecular mechanisms involved in wavelength-specific response of plant is question of widespread interest both to basic researchers and to those interested in applying such knowledge to the engineering of novel proteins, as well as targeted lighting systems. Here we sought to generate a high-resolution proteomic profile of plant leaves, based on exposure to specific narrow-wavelength lights. Although changes in plant physiology in response to light spectral composition is well documented, there is limited knowledge on the roles of specific light wavelengths and their impact. Most previous studies have utilized relatively broad wavebands in their experiments. Such multi-wavelengths lights trigger diverse and complex signaling networks that pose major challenges in inference of wavelength-specific molecular processes that underly the plant response. Moreover, most studies have compared the effect of blue and red wavelengths comparing with FL, as control. As FL light consists the mixed spectra composition of both red and blue as well as numerous other wavelengths, comparing undeniably results in inconsistent and overlapping responses that will hamper effects to elucidate the plant response to specific wavelengths [1, 2]. Monitoring plant proteome response to specific wavelengths and further contrasting the changes with one another, rather than comparing plants proteome to FL, is thus necessary to gain detailed insights on underlying biological pathways and their consequences in plant physiology. Here, we employed narrow wavelength LED lights in our design to eliminate a potential overlap in molecular responses by ensuring non-overlapping wavelengths in the light treatments. We further applied TMT-labeling technology to gain a high-resolution view on the proteome changes. Our proteomics data provides an in-depth coverage suitable for system-wide analyses, providing deep insights on plant molecular response particularly because of the tremendous increase in the coverage of identified proteins which outreach the other biological data.


Optimizing disease progression study designs for drug effect discrimination.
Investigate the possibility to directly optimize a clinical trial design for statistical power to detect a drug effect and compare to optimal designs that focus on parameter precision. An improved statistic derived from the general formulation of the Wald approximation was used to predict the statistical power for given trial designs of a disease progression study. The predicted value was compared, together with the classical Wald statistic, to a type I error-corrected model-based power determined via clinical trial simulations. In a second step, a study design for maximal power was determined by directly maximizing the new statistic. The resulting power-optimal designs and their corresponding performance based on empirical power calculations were compared to designs focusing on parameter precision. Comparisons of empirically determined power and the newly developed statistic, showed excellent agreement across all scenarios investigated. This was in contrast to the classical Wald statistic, which consistently over-predicted the reference power with deviations of up to 90 %. Designs maximized using the proposed metric differed from traditional optimal designs and showed equal or up to 20 % higher power in the subsequent clinical trial simulations. Furthermore, the proposed method was used to minimize the number of individuals required to achieve 80 % power through a simultaneous optimization of study size and study design. The targeted power of 80 % was confirmed in subsequent simulation study. A new statistic was developed, allowing for the explicit optimization of a clinical trial design with respect to statistical power.


Retracted: The Use of Internet of Things and Cloud Computing Technology in the Performance Appraisal Management of Innovation Capability of University Scientific Research Team.
[This retracts the article DOI: 10.1155/2022/9423718.].


Vitellogenin-derived fragment in embryos of Japanese flounder Paralichthys olivaceus with binding and bactericidal activities against an infectious bacterium via an interaction with saccharides.
Thirty- and 90-kDa proteins with binding ability to Edwardsiella tarda, a causative bacterium of Edwardsiellosis in fish, were purified from the embryo of Japanese flounder Paralichthys olivaceus. The proteins were isolated with affinity chromatography, in which the bacterium was used as a ligand and galactose, mannose, and ethylenediaminetetraacetic acid (EDTA) were used as elution agents, followed by gel filtration chromatography. N-terminal amino acid sequencing and liquid chromatography with quadrupole time-of-flight tandem mass spectrometry (LC/Q-TOF-MS) analysis revealed that the 90-kDa protein was lipovitellin heavy-chain (LvH), which is one of the proteolytically cleaved products of maternal vitellogenin (Vg) and represents the main precursor of the egg yolk in teleosts, and the 30-kDa protein was an N-terminal bit of LvH. On the other hand, Vg in the serum of the mother fish did not bind to E. tarda. While the 90-kDa protein did not show anti-bacterial activity, the 30-kDa protein strongly exhibited activity toward E. tarda, with a minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) below 0.06 μM, suggesting that the latter protein plays an important role during embryogenesis in the flounder. This is the first report showing that Vg-derived products have monosaccharides-binding activity and a fragment derived from LvH exhibits bactericidal activity.


Endoscopic Management of Anastomotic Esophageal Strictures Secondary to Esophageal Atresia.
The reported incidence of anastomotic stricture after esophageal atresia repair has varied in case series from as low as 9% to as high as 80%. The cornerstone of esophageal stricture treatment is dilation with either balloon or bougie. The goal of esophageal dilation is to increase the luminal diameter of the esophagus while also improving dysphagia symptoms. Once a stricture becomes refractory to esophageal dilation, there are several treatment therapies available as adjuncts to dilation therapy. These therapies include intralesional steroid injection, mitomycin C, esophageal stent placement, and endoscopic incisional therapy.


[Polyorchidism: report of 2 cases and review of the literature].
Polyorchidism is a rare urogenital abnormality. The authors report two cases in children aged 3 years and 5 years with left ectopic testis. Surgical exploration demonstrated two testes on the left side with a third testis on the right. Descent of the two testes into the left hemi-scrotum was performed. The authors review the management of polyorchidism in the light of these two cases.


Changes of synaptosomal energy metabolism induced by hypoxia during aging.
Synaptosomes were isolated from the motor area of the cerebral cortex of normoxic or hypoxic (PaO2 = 17-19 mmHg, for 15 min) beagle dogs of different ages. Synaptosomes were incubated in Krebs-Henseleit-Hepes buffer (for 10 min at 24 degrees C) and the energetic state was defined by: the balance of the labile phosphates (ATP, ADP, AMP, and creatine phosphate); the respiratory rate; the redox state of the intramitochondrial NAD-couple. By the present experimental model, it is possible to evaluate the potential damage (induced by the "in vivo" hypoxic insult) that synaptosomes cannot reverse under optimal incubation. Aging affected the phosphorylation state of the post-hypoxic incubated synaptosomes. The oxygen consumption rate was quite similar in the synaptosomal fractions from the motor area of hypoxic beagle dogs of different ages, but the cytochrome c and a contents were lower in the preparations from hypoxic older brains. In dogs of different ages, hypoxia always lowered the respiration of the synaptosomes, but aging affected the oxygen consumption rates only in post-hypoxic synaptosomes incubated with succinate. The synaptosomal energetic state was defined also by the redox state of the intramitochondrial NAD-couple (delta Gox-red) and the phosphorylation state of adenine nucleotide system (delta GATP). The free-energy change (delta delta G) for the coupled reactions was calculated, too. In synaptosomes isolated from the cerebral cortex of dogs submitted to hypoxia, the equilibrium (calculated for the mitochondrial electron transfer chain and the phosphorylation of adenine nucleotides) was markedly altered as function of aging.(ABSTRACT TRUNCATED AT 250 WORDS)


Efficacy of different treatment regimens of marbofloxacin in canine visceral leishmaniosis: a pilot study.
This phase II, randomized, open-label field trial was designed to evaluate and compare the safety and efficacy of four treatment durations (10, 20, 28 or 40 days) with marbofloxacin administered orally at the dosage of 2mg/kg once a day for canine visceral leishmaniosis. Twenty-four dogs naturally infected with visceral leishmaniosis and without biochemical disorder evidences of renal insufficiency, were recruited by two Greek veterinarian clinics. They were also randomly assigned to one of the four treatment duration groups, and have been clinically, haematologically, biochemically and parasitologically followed-up regularly for 9 months. Efficacy was achieved for 5/6 dogs treated for 28 days, 4/6 dogs treated for 10 or 20 days and for 3/6 dogs treated for 40 days. Moreover, efficacy was reached more quickly (58.4 days) in dogs treated for 28 days. Improvement of clinical signs tended to be better and faster in the 28 days treatment group too. After 9 months of follow-up, a total of three cases could be considered as relapsing (two dogs treated for 40 days and one dog treated for 28 days). There was a significant reduction in amastigotes density in macrophages after 3 months in the four groups when compared with the parasite density at inclusion. No adverse effects were noticed during this 9 months study. Results obtained with marbofloxacin at the dosage of 2mg/kg once a day for 28 days seem encouraging and may offer a safe alternative for treating canine visceral leishmaniosis.


Pluripotent Conversion of Muscle Stem Cells Without Reprogramming Factors or Small Molecules.
Muscle derived stem cells (MDSCs) are multipotent stem cells that can differentiate into several lineages including skeletal muscle precursor cells. Here, we show that MDSCs from myostatin null mice (Mstn (-/-) ) can be readily induced into pluripotent stem cells without using reprogramming factors. Microarray studies revealed a strong upregulation of markers like Leukemia Inhibitory factor (LIF) and Leukemia Inhibitory factor receptor (LIFR) in Mstn (-/-) MDSCs as compared to wild type MDSCs (WT-MDSCs). Furthermore when cultured in mouse embryonic stem cell media with LIF for 95 days, Mstn (-/-) MDSCs formed embryonic stem cell (ES) like colonies. We termed such ES like cells as the culture-induced pluripotent stem cells (CiPSC). CiPSCs from Mstn (-/-) MDSCs were phenotypically similar to ESCs, expressed high levels of Oct4, Nanog, Sox2 and SSEA-1, maintained a normal karyotype. Furthermore, CiPSCs formed embryoid bodies and teratomas when injected into immunocompromised mice. In addition, CiPSCs differentiated into somatic cells of all three lineages. We further show that culturing in ES cell media, resulted in hypermethylation and downregulation of BMP2 in Mstn(-/-) MDSCs. Western blot further confirmed a down regulation of BMP2 signaling in Mstn (-/-) MDSCs in supportive of pluripotent reprogramming. Given that down regulation of BMP2 has been shown to induce pluripotency in cells, we propose that lack of myostatin epigenetically reprograms the MDSCs to become pluripotent stem cells. Thus, here we report the successful establishment of ES-like cells from adult stem cells of the non-germline origin under culture-induced conditions without introducing reprogramming genes.


Biracial perception in black and white: How Black and White perceivers respond to phenotype and racial identity cues.
This study investigates how racial identity and phenotypicality (i.e., racial ambiguity) shape the perception of biracial individuals in both White and Black perceivers. We investigated complex racial categorization and its downstream consequences, such as perceptions of discrimination. We manipulated racial phenotypicality (Black or racially ambiguous) and racial identity (Black or biracial) to test these cues' influence on Black and White race categorizations in a sample of both White (n = 145) and Black (n = 152) identified individuals. Though racial identity and phenotypicality information influenced deliberate racial categorization, White and Black participants used the cues in different ways. For White perceivers, racial identity and phenotypicality additively influenced Black categorization. For Black perceivers, however, racial identity was only used in Black categorization when racial ambiguity was high. Perceived discrimination was related to White (but not Black) perceivers' distribution of minority resources to targets, however Black categorization related to perceived discrimination for Black perceivers only. By demonstrating how Black and White individuals use identity and phenotype information in race perceptions, we provide a more complete view of the complexities of racial categorization and its downstream consequences. (PsycINFO Database Record


In vitro culture increases mechanical stability of human tissue engineered cartilage constructs by prevention of microscale scaffold buckling.
Many studies have measured the global compressive properties of tissue engineered (TE) cartilage grown on porous scaffolds. Such scaffolds are known to exhibit strain softening due to local buckling under loading. As matrix is deposited onto these scaffolds, the global compressive properties increase. However the relationship between the amount and distribution of matrix in the scaffold and local buckling is unknown. To address this knowledge gap, we studied how local strain and construct buckling in human TE constructs changes over culture times and GAG content. Confocal elastography techniques and digital image correlation (DIC) were used to measure and record buckling modes and local strains. Receiver operating characteristic (ROC) curves were used to quantify construct buckling. The results from the ROC analysis were placed into Kaplan-Meier survival function curves to establish the probability that any point in a construct buckled. These analysis techniques revealed the presence of buckling at early time points, but bending at later time points. An inverse correlation was observed between the probability of buckling and the total GAG content of each construct. This data suggests that increased GAG content prevents the onset of construct buckling and improves the microscale compressive tissue properties. This increase in GAG deposition leads to enhanced global compressive properties by prevention of microscale buckling.


Inhibitory role of the zona incerta in the pilocarpine model of epilepsy.
Recent experiments have suggested that the zona incerta might be regarded as a highly sensitive structure for seizure induction. This sensitivity has been linked to this structure's abundant expression of cholinergic receptors. Here we have decided to investigate the participation of the GABAergic system of the zona incerta, one of its major neurotransmitters with widespread projections to the neocortex, in the pilocarpine (Pilo) model of epilepsy. Stereotaxic administration of a GABA(A) agonist (muscimol), antagonist (bicuculline) or saline (controls) bilaterally into the zona incerta of adult male Wistar rats was performed 30 min prior to the systemic injection of pilocarpine. Animals were electroencephalographically and behaviorally monitored for seizure activity. Administration of muscimol had a pro-convulsant effect characterised by a higher percentage of animals developing SE with a shorter latency. Conversely, administration of bicuculline had a dose dependent anticonvulsant effect, with no animals displaying SE. Our results contribute to the further characterisation of the regulatory role of the zona incerta in seizure-related phenomena, suggesting that its modulation might be a relevant target for anticonvulsant strategies.


New organosilicon maxillofacial prosthetic materials.
The silicone elastomer A-2186 is a widely used maxillofacial prosthetic material. It is a pourable two-component silicone rubber cured by a platinum catalyst. Used as a prosthetic material, A-2186 has short working time and because of its hydrophobic nature, poor adhesion to non-silicone based adhesives. The purpose of this study is to evaluate the physical properties of new prosthetic materials based on methacryloxypropyl-terminated polydimethylsiloxane (MPDS-MF), and to compare the properties with those of A-2186. Hardness, tensile strength, ultimate elongation, tear strength and adhesive bonding strength of MPDS-MF and A-2186 with and without additives were determined and compared. The bonding strengths of the extrinsic colorant carrier with the prosthetic materials were also determined. Statistical analyses were done using a two-way analysis of variance (ANOVA). For significant effects, post-hoc tests were done using the Bonferroni correction. The hardness of MPDS-MF is similar to A-2186. However, tensile strength, tear strength, ultimate elongation, and adhesive bonding strength of MPDS-MF are higher than those of A-2186. MPDS-MF is cured by free radical thermal polymerization and crosslinking. The working time of MPDS-MF, unlike A-2186, is long. The presence of methacrylate groups in MPDS-MF enhances its adhesion to non-silicone based adhesive. Based on the present study, it appears that MPDS-MF is suitable for use in fabricating of clinical prostheses.


Characterization of bovine parainfluenza virus type 3.
Bovine parainfluenza virus type 3 (PIV-3) has a buoyant density of 1.197. The RNA of PIV-3, like that of Sendai virus, is a single continuous chain which lacks polyadenylic acid sequences and tends to self-anneal to a marked extent. It has a sedimentation coefficient of 42S and a molecular weight of 4.5 X 10(6), being slightly smaller than Sendai virus RNA (47S, 5.3 X 10(6)). PIV-3 has 5 main structural proteins, of which 2 are glycoproteins. The molecular weights of protein 1, protein 2, protein 3, glycoprotein 1, and glycoprotein 2 were estimated to be 79,000, 68,000, 35,000, 69,000, and 55,000, respectively. Protein 2 was suggested to be nucleocapsid protein.


Cell cycle dependence of transformation expression in mouse cells transformed by a thermosensitive mutant (Ts-121) of polyoma virus.
Change in division capability as a phenotypic expression of cellular transformation was investigated by using one of the temperature-sensitive (ts) mutants of the polyoma virus-transformed cell line, the 121-6-5 cells of BALB/3T3. When contact -inhibited cells were treated with hyaluronidase at 39 degrees C, a single round of cell division was induced after which cell growth was inhibited by cell density. However, if the cells were incubated at 35 degrees C, after the enzyme treatment, density-inhibition block disappeared and the cells entered a second division. This indicates that the release of cells from density-inhibition depends on the low temperature incubation. The ability of cells to complete a second division was examined by shifting the cells from 39 degrees C to 35 degrees C during different phases of the first division cycle after the enzyme-treatment. A 6-hour incubation of S phase cells at 35 degrees C resulted in a second cycle of division, while the 24-hour incubation of G1 cells at 35 degrees C did not induce a second round of division. These results suggest that expression of the transformed phenotype in 121-6-5 cells is clearly dependent upon both the temperature and the phase of the division cycle.


The First Neuroethics Meeting: Then and Now.
It wasn't until 2002 that more than 150 neuroscientists, bioethicists, doctors of psychiatry and psychology, philosophers, and professors of law and public policy came together to chart the boundaries, define the issues, and raise some of the ethical implications tied to advances in brain research. On the 15 th anniversary of the Neuroethics: Mapping the Field conference in San Francisco, we asked three of the original speakers to reflect on how far the neuroethics field has come in 15 years-and where the field may be going in the next 15.


Increase of pulmonary vascular resistance during cold provocation in patients with variant angina.
This study was performed to evaluate pulmonary vascular reactivity in patients with angiographically documented coronary vasospasm. Right heart catheterization was performed in 8 subjects with vasospastic angina without evidence of Raynaud's phenomenon: heart rate, systemic and pulmonary arterial pressure as well as cardiac output were determined at rest, during cold provocation and after 20 minutes recovery. Data were obtained both before and during treatment with nifedipine. During cold provocation pulmonary vascular resistance was elevated significantly (P less than 0.02 compared with baseline); systemic vascular resistance tended to increase; nifedipine blunted both vasoconstrictor effects. Our results indicate an abnormal vascular response of the pulmonary arteries to cold provocation in patients with symptomatic coronary artery spasm and suggest a primary vasospastic disorder with coronary and pulmonary manifestation.


Structural and biochemical features of acidic α-amylase of Bacillus acidicola.
The investigation is aimed at understanding structure-function aspect of α-amylase of an acidophilic bacterium Bacillus acidicola (BAamy), which is Ca(2+)-independent and active at acidic pH of native starch, and thus, suits better in starch saccharification process. The CD spectroscopic data analysis revealed that the enzyme has 30% α-helices, 14.2% β-sheets, and 55.8% random coils at 60 °C and pH 4.0. Using Bacillus stearothermophilus α-amylase (BStA) as the template, 3-D structure of rBAamy has been proposed. A complete loss in α-amylase activity was recorded when the amino acid residues (D231, E261 and D328) were substituted that confirmed their role in catalysis. The CD studies indicated a decrease in the α-helices content below and beyond the optimum pH and temperature that suggests a critical role of α-helix in maintaining the structural conformation of the enzyme. Fluorescence-quenching by N-bromosuccinimide (NBS) suggested the role of tryptophan in maintaining structural integrity of α-amylase and that by acrylamide indicated interaction by simple collision process.


Effect of Helicobacter pylori infection on gastric cell proliferation and genomic instability in a paediatric population of southern Italy.
The incidence of gastric cancer is high in areas with a high prevalence of Helicobacter pylori infection. Cell transformation and tumour progression occur over a long period of time and markers of genomic instability usually precede morphological changes. To evaluate the effect of Helicobacter pylori infection on cell proliferation, DNA status and oncogene expression in children. Morphometric and immunohistochemical techniques were used to analyse DNA content, p53 and c-myc oncogene expression and cell proliferation on gastric biopsies of 53 children (27 Helicobacter pylori-negative and 26 Helicobacter pylori-positive). Gastric mucosa was normal in 11% of Helicobacter pylori-positive and in 33% of Helicobacter pylori-negative subjects. Most children had chronic non-atrophic gastritis regardless of Helicobacter pylori infection, and only a minority of children affected by Helicobacter pylori had mild atrophic gastritis. Cell proliferation was significantly higher in children with Helicobacter pylori-positive gastritis than in those with Helicobacter pylori-negative gastritis. No metaplasia, dysplasia, p53 overexpression or altered DNA content was found in any child. Interestingly, 46% of children with and 29% without Helicobacter pylori infection had c-myc overexpression closely related to the cell proliferation rate. Helicobacter pylori infection in children may coexist with a normal gastric mucosa, and it is not associated with genomic instability markers in cases of chronic gastritis.


Child extrafamilial sexual abuse: predicting parent and child functioning.
This study evaluated the emotional and behavioral adjustment of parents and children within 3 months and 1 year after the discovery of child extrafamilial sexual abuse. Ninety-two case parents (63 mothers, 29 fathers) and 56 children were compared to a nonclinical comparison group of 136 parents (74 mothers, 62 fathers) and 75 children. Parent adjustment was assessed using self-report measures while child functioning was assessed using a combination of child-, parent- and teacher-report measures. Mothers, fathers and sexually abused children experienced clinically significant effects both initially and at 12 months post-disclosure. Children's perceptions of self-blame and guilt for the abuse and the extent of traumatization predicted their self-reported symtomatology at 3 months and 1 year post-disclosure. Child age and gender also significantly contributed to the prediction of many of the child outcome measures. No abuse-related variable was related to any child self-report measure. Mothers' satisfaction in the parenting role, perceived support and intrusive symptoms predicted their initial emotional functioning. Avoidant symptoms, child's internalizing behavior and mothers' initial emotional functioning were significant predictors of longer-term emotional functioning. Results emphasize the need to address children's abuse-related attributions and underscore the need to expand our focus beyond the child victims to the traumatized families.


Urethane anesthesia blocks the development and expression of kindled seizures.
The effect of anesthetic and subanesthetic doses of urethane on the development of amygdala kindled seizures and on the expression of previously kindled seizures was studied in hooded rats. An anesthetic dose of urethane (1.5 g/kg) almost completely eliminated evoked afterdischarge and completely eliminated convulsive behavior in both groups. It also eliminated the seizure response to pentylenetetrazol. Subanesthetic doses of urethane (0.25 and 0.5 g/kg) strongly attenuated the expression of previously kindled seizures. These results suggest that urethane may not be an appropriate anesthetic for the study of epileptiform phenomena.


The anomalous splenic vein: a case report and review of the literature.
The spleen arises from a mesenchymal bulge at the 6-mm stage of development. There are a wide variety of splenic anomalies and variations that range from benign to clinically significant, and this article presents a brief review of splenic embryology and a case report of an anomalous splenic vein that precluded the formation of a Nissen fundoplication.


Mitochondrial damage are involved in Aflatoxin B1-induced testicular damage and spermatogenesis disorder in mice.
Aflatoxin B1 (AFB1) is an unavoidable environmental pollutants, which seriously endangers human and animal health. AFB1 has male reproductive toxicity, yet the underlying mechanisms remain inconclusive. Mitochondra are a kind of crucial organelle for maintaining spermatogenesis in testis. Thus, we hypothesized that AFB1 can impair mitochondria to aggravate testicular damage and spermatogenesis disorder. To verify this hypothesis, 48 male mice were intragastrically administered with 0, 0.375, 0.75 or 1.5 mg/kg body weight AFB1 for 30 days, respectively. In this study, we found AFB1 caused testicular histopathological lesions and spermatogenesis abnormalities, with the elevation of oxidative stress (increased H2O2, whereas decreased SOD and GSH). Significant mitochondria structure damage of germ cells and Leydig cells, MMP loss, ATP contents reduction, and inhibited activities of mitochondrial complexes I-IV in mice testis were found in AFB1 treatment groups. Besides, AFB1 inhibited mitochondrial biogenesis and mitochondrial dynamics, presenting as the decreased mRNA and protein expressions of PGC-1α, Nrf1, Tfam, Drp1, Fis1, Mfn1 and Opa1. The results revealed that the mitochondrial damage were involved in AFB1-induced testicular damage and spermatogenesis disorder, providing a considerable direction to clarify potential mechanisms of AFB1 reproductive toxicity.


The distribution of a dopamine D2 receptor mRNA in rat brain.
Based on the recently reported sequence of a dopamine D2 receptor cloned from rat brain, we prepared a series of cDNA probes to determine the distribution of mRNA encoding this receptor. Within the forebrain, D2 receptor mRNA is abundant in the caudate-putamen, accumbens nucleus and olfactory tubercle. Moderate to low levels of mRNA are observed in the medial habenular nucleus, diagonal band, lateral septal nucleus, claustrum, dorsal endopiriform nucleus, and entorhinal cortex. In the mesencephalon, D2 receptor mRNA is abundant within the substantia nigra, pars compacta, and the ventral tegmental area. Comparison of the distribution of the mRNA and ligand binding indicates that both presynaptic and postsynaptic D2 receptors of the nigrostriatal, mesolimbic and mesocortical pathways are derived from the same mRNA.


The mitochondrial genome of the basidiomycete Agrocybe aegerita: molecular cloning, physical mapping and gene location.
The mtDNA of a wild-type strain of Agrocybe aegerita was purified from mitochondria isolated by cellular fractionation. A representative library was constructed in E. coli by molecular cloning at the HindIII restriction site of pBR322. Southern hybridizations between total DNA of the fungal strain and cloned mitochondrial insert probes were used to establish the restriction map of the mtDNA molecule. Its size was assessed at about 80,500 bp. Four structural genes (for Cox 1, Cox 2, Atp 6, and Atp 8) were located on the map by heterologous hybridizations with oligonucleote probes specific for yeast mitochondrial genes. The location of the genes coding for the large and the small RNAs of the mitochondrial ribosome was determined by hybridization with the E. coli rrnB operon. A comparison of A. aegerita mtDNA organization with that of both phylogenetically close and distant fungi is discussed.


Accuracy of Nurse-Performed Lung Ultrasound in Patients With Acute Dyspnea: A Prospective Observational Study.
In clinical practice lung ultrasound (LUS) is becoming an easy and reliable noninvasive tool for the evaluation of dyspnea. The aim of this study was to assess the accuracy of nurse-performed LUS, in particular, in the diagnosis of acute cardiogenic pulmonary congestion. We prospectively evaluated all the consecutive patients admitted for dyspnea in our Medicine Department between April and July 2014. At admission, serum brain natriuretic peptide (BNP) levels and LUS was performed by trained nurses blinded to clinical and laboratory data. The accuracy of nurse-performed LUS alone and combined with BNP for the diagnosis of acute cardiogenic dyspnea was calculated. Two hundred twenty-six patients (41.6% men, mean age 78.7 ± 12.7 years) were included in the study. Nurse-performed LUS alone had a sensitivity of 95.3% (95% CI: 92.6-98.1%), a specificity of 88.2% (95% CI: 84.0-92.4%), a positive predictive value of 87.9% (95% CI: 83.7-92.2%) and a negative predictive value of 95.5% (95% CI: 92.7-98.2%). The combination of nurse-performed LUS with BNP level (cut-off 400 pg/mL) resulted in a higher sensitivity (98.9%, 95% CI: 97.4-100%), negative predictive value (98.8%, 95% CI: 97.2-100%), and corresponding negative likelihood ratio (0.01, 95% CI: 0.0, 0.07). Nurse-performed LUS had a good accuracy in the diagnosis of acute cardiogenic dyspnea. Use of this technique in combination with BNP seems to be useful in ruling out cardiogenic dyspnea. Other studies are warranted to confirm our preliminary findings and to establish the role of this tool in other settings.


An observational study on body mass index during rehabilitation and follow-up in people with spinal cord injury in Denmark.
Observational study OBJECTIVE: To describe body mass index (BMI) during rehabilitation in people with a newly sustained spinal cord injury (SCI). Inpatient SCI rehabilitation in Denmark. Inpatients, >18 years, having sustained a SCI within the last 12 months at admission to primary rehabilitation, inclusive of various SCI etiology, neurological level, completeness of the lesion or mobility status. Measures of BMI were obtained at admission and discharge as part of standard care. At one SCI center measures of BMI were sampled at follow up 9.5 months after discharge as well. BMI was described by mean and standard deviation (SD). Paired t-test was used to test difference in BMI between admission and discharge. Repeated measures Analysis of Variance (ANOVA) was used for analyzing BMI deriving from three time points. Overall BMI was stable with no change (25.4 kg/m2 at admission and 25.6 kg/m2 at discharge) during rehabilitation at the two national centers. In participants with an American Spinal Injury Association (ASIA) Impairment Scale (AIS) D classification, BMI was higher during rehabilitation compared to the other groups and increased significantly (p = 0.008) from discharge to follow up. Overall BMI was stable but higher than recommended in people with SCI undergoing rehabilitation at the two national centers in Denmark. Participants with an AIS D SCI were obese according to SCI adjusted BMI and the World Health Organization (WHO) recommendations during rehabilitation and at follow up.


Incorporating digital scans of diagnostic casts into computed tomography for virtual implant treatment planning.
The success of implant treatment depends on the accuracy of the diagnosis and planning. Accurate diagnosis can be achieved with clinician experience and proper diagnostic methods. Cone beam computerized tomography (CBCT) helps to develop and implement a comprehensive treatment plan for the surgeon, restorative team, and patient in order to minimize complications. Radiographic stents are used during CBCT scans; however, they are not problem-free. This article describes a technique for incorporating digital scans of diagnostic casts into CBCT scans for virtual treatment planning.


Contamination risk for operators performing semi-closed HIPEC procedure using cisplatin.
Aim of this study was to assess operators' safety while performing a semi-closed HIPEC procedure for peritoneal carcinomatosis using cisplatin drugs. Environmental air, theater personnel urine, operators' gloves and hand skin contamination were assessed during two non-consecutive working days. Six operating surgeons, two anesthesiologists and two theater nurses were included in the study. Glove samples were collected from the inner surface of the external glove and from the external surface of the inner glove from operating surgeons wearing a double pair of gloves. Personnel urine samples were collected before, after and 24 h from the procedure. Air and urine samples permanently resulted below detectable levels for cisplatin presence on all the tested sources and sessions. Cisplatin contamination was detected on the inner surface of the external gloves and on the outer surface of the inner gloves, but in a lower concentration for the latter. Skin wipe samples were below detectable levels for platinum presence. The results suggest that two pairs of gloves are adequate to protect the skin from antiblastic drugs. No sign of direct contact or systemic absorption of drugs was ever detected from the inspected samples. Semi-closed HIPEC technique appears to be a safe procedure for operators.


Development and Evaluation of a Disease Large Animal Model for Preclinical Assessment of Renal Denervation Therapies.
New-generation catheters-based renal denervation (RDN) is under investigation for the treatment of uncontrolled hypertension (HTN). We assessed the feasibility of a large animal model of HTN to accommodate the human RDN devices. Ten minipigs were instrumented to measure blood pressure (BP) in an awake-state. HTN was induced with subcutaneous 11-deoxycorticosterone (DOCA, 100 mg/kg) implants. Five months after, the surviving animals underwent RDN with the Symplicity® system. Norepinephrine (NE) renal gradients were determined before and 1 month after RDN. Renal arteries were processed for histological (hematoxylin-eosin, Movat pentachrome) and immunohistochemical (S100, tyrosine-hydroxylase) analyses. BP significantly rose after DOCA implants. Six animals died prematurely, mainly from infectious causes. The surviving animals showed stable BP levels after 5 months. One month after RDN, nerve damage was showed in three animals, with impedance drop >10%, NE gradient drop and reduction in BP. The fourth animal showed no nerve damage, impedance drop <10%, NE gradient increase and no change in BP. In conclusion, the minipig model of DOCA-induced HTN is feasible, showing durable effects. High mortality should be addressed in next iterations of this model. RDN may partially offset the DOCA-induced HTN. Impedance drop and NE renal gradient could be markers of RDN success.


HPV vaccine completion and dose adherence among commercially insured females aged 9 through 26 years in the US.
Although HPV vaccination has been recommended for use in girls and young women since 2007, HPV vaccine uptake is low in the US. We conducted a retrospective cohort study using the 2008-2011 MarketScan data to examine HPV vaccine completion and dose adherence among commercially insured females aged 9-26 years. We performed multivariable logistic regression models to examine factors related to HPV vaccine completion and HPV vaccine dose adherence. Among 378,484 females aged 9-26 years who initiated HPV vaccination, only 29.4% completed HPV vaccination. Compared with females receiving vaccines from primary care providers, those receiving vaccines from OB/GYN providers were more likely to complete the vaccine series. Age at HPV vaccine initiation, health insurance plan, seasonal pattern, and flu vaccination were also significantly associated with vaccine completion. Among 111,286 females who completed HPV vaccination, 62.4% received all doses within 30 days of the recommended schedules. Similar factors relating to HPV vaccine completion were consistently associated with HPV vaccine dose adherence. However, younger age (<22 years) and receipt of flu vaccine were negatively related to HPV vaccine dose adherence. Intervention programs to improve HPV vaccine reminding system and reduce logistic barriers for both physicians and patients are warranted.


An 8-year review of barium studies in the diagnosis of gastroparesis.
To determine the utility of barium studies for diagnosing gastroparesis in patients with nausea, vomiting, or other related symptoms. Radiology files revealed gastroparesis without gastric outlet obstruction on upper gastrointestinal tract barium studies in 50 patients with nausea, vomiting, and other related symptoms. Original reports and images were reviewed to determine whether gastric peristalsis was decreased/absent and to investigate gastric dilatation, fluid or debris, and delayed emptying of barium. Twenty patients (40%) had nuclear gastric emptying studies. Medical records were reviewed to determine the presentation, treatment, and course. The diagnosis of gastroparesis was considered accurate if patients with gastroparesis on barium studies responded to treatment. Forty-six patients (92%) had predisposing factors for gastroparesis, including narcotics and diabetes. Forty-five patients (90%) presented with nausea or vomiting, and 40 patients (80%) had one or more other symptoms, including bloating, early satiety, postprandial fullness, and abdominal pain. Barium studies revealed decreased gastric peristalsis in 46 (92%) of the 50 patients and absent peristalsis in four (8%); 46 patients (92%) had additional findings, including gastric dilatation in 30 (60%), delayed emptying of barium in 27 (54%), debris in 28 (56%; bezoars in three), and retained fluid in 13 (26%). Thirteen (65%) of 20 patients with nuclear gastric emptying studies had delayed emptying of solids and seven (35%) had normal emptying. Thirty-five (83%) of 42 patients treated for gastroparesis had symptomatic improvement versus two (25%) of eight patients not treated. Patients with nausea, vomiting, or other related symptoms who have gastroparesis without gastric outlet obstruction on barium studies can be treated for this condition on the basis of the clinical and radiographic findings.


Factors influencing adolescents' healthy pregnancy preparation behavior: a cross-sectional gender comparison applying the health belief model.
Interventions to prepare for a healthy pregnancy from an early age can ensure the health of both mother and child. This study aims to compare the factors associated with healthy pregnancy preparation behavior (HPPB) among male and female adolescents. A total of 690 Korean adolescents participated in this cross-sectional study from July 11 to August 24, 2018. Determinants of the likelihood of engaging in HPPB were described using hierarchical regression about the importance of and confidence in HPPB, the gender equality related to pregnancy and birth, and the health belief model (HBM) constructs about HPPB. Smoking experience (β = - 0.18, p < 0.001 for boys, β = - 0.25, p < 0.001 for girls), and HBM constructs were identified as factors correlated with HPPB in both genders. The significant factors in boys were perceived susceptibility (β = - 0.13, p = 0.005), perceived severity (β = 0.12, p = 0.015), perceived benefits (β = 0.23, p < 0.001), and perceived barriers (β = - 0.18, p < 0.001), whereas the corresponding factors in girls were perceived severity (β = 0.20, p = 0.001), and perceived barriers (β = - 0.23, p < 0.001). The importance of HPPB was identified as a factor only among girls (β = 0.19, p = 0.005), while confidence in HPPB (β = 0.12, p = 0.401), gender equality related to pregnancy and childbirth (β = - 0.20, p = 0.001 for women's responsibility variable, β = 0.14, p = 0.018 for men's responsibility variable), and alcohol (β = - 0.10, p = 0.022) were factors identified only among boys. The gender differences in opinions on HPPB identified in this study can help nurses and community health care professionals recognize issues for which they can develop and implement preventive interventions. For healthy pregnancy preparation, interventions based on HBM constructs and smoking should be presented for both male and female adolescents. Imparting education to females on the importance of HPPB and to males on confidence in HPPB, gender equality related to pregnancy and childbirth, and alcohol consumption, should be emphasized. In addition, as perceived susceptibility may be low in a disease prevention model using the health belief model, it is necessary to prioritize increasing the perceived susceptibility of school-age children as an intervention.


The protein interactome of collapsin response mediator protein-2 (CRMP2/DPYSL2) reveals novel partner proteins in brain tissue.
Collapsin response mediator protein-2 (CRMP2) is a CNS protein involved in neuronal development, axonal and neuronal growth, cell migration, and protein trafficking. Recent studies have linked perturbations in CRMP2 function to neurodegenerative disorders such as Alzheimer's disease, neuropathic pain, and Batten disease, and to psychiatric disorders such as schizophrenia. Like most proteins, CRMP2 functions though interactions with a molecular network of proteins and other molecules. Here, we have attempted to identify additional proteins of the CRMP2 interactome to provide further leads about its roles in neurological functions. We used a combined co-immunoprecipitation and shotgun proteomic approach in order to identify CRMP2 protein partners. We identified 78 CRMP2 protein partners not previously reported in public protein interaction databases. These were involved in seven biological processes, which included cell signaling, growth, metabolism, trafficking, and immune function, according to Gene Ontology classifications. Furthermore, 32 different molecular functions were found to be associated with these proteins, such as RNA binding, ribosomal functions, transporter activity, receptor activity, serine/threonine phosphatase activity, cell adhesion, cytoskeletal protein binding and catalytic activity. In silico pathway interactome construction revealed a highly connected network with the most overrepresented functions corresponding to semaphorin interactions, along with axon guidance and WNT5A signaling. Taken together, these findings suggest that the CRMP2 pathway is critical for regulating neuronal and synaptic architecture. Further studies along these lines might uncover novel biomarkers and drug targets for use in drug discovery.


A frontal transcallosal inhibition loop mediates interhemispheric balance in visuospatial processing.
Interhemispheric communication through the corpus callosum is required for both sensory and cognitive processes. Impaired transcallosal inhibition causing interhemispheric imbalance is believed to underlie visuospatial bias after frontoparietal cortical damage, but the synaptic circuits involved remain largely unknown. Here, we show that lesions in the mouse anterior cingulate area (ACA) cause severe visuospatial bias mediated by a transcallosal inhibition loop. In a visual-change-detection task, ACA callosal-projection neurons (CPNs) were more active with contralateral visual field changes than with ipsilateral changes. Unilateral CPN inactivation impaired contralateral change detection but improved ipsilateral detection by altering interhemispheric interaction through callosal projections. CPNs strongly activated contralateral parvalbumin-positive (PV+) neurons, and callosal-input-driven PV+ neurons preferentially inhibited ipsilateral CPNs, thus mediating transcallosal inhibition. Unilateral PV+ neuron activation caused a similar behavioral bias to contralateral CPN activation and ipsilateral CPN inactivation, and bilateral PV+ neuron activation eliminated this bias. Notably, restoring interhemispheric balance by activating contralesional PV+ neurons significantly improved contralesional detection in ACA-lesioned animals. Thus, a frontal transcallosal inhibition loop comprising CPNs and callosal-input-driven PV+ neurons mediates interhemispheric balance in visuospatial processing, and enhancing contralesional transcallosal inhibition restores interhemispheric balance while also reversing lesion-induced bias.


Alterations in the blood brain barrier in ageing cerebral cortex in relationship to Alzheimer-type pathology: a study in the MRC-CFAS population neuropathology cohort.
Impairment of the blood brain barrier (BBB) in human brain ageing and its relationship to Alzheimer-type pathology remains poorly defined. We have investigated the BBB in temporal cortex of brain donations from a population-representative sample of 92 participants from the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS), a longitudinal study with a programme of brain donation. BBB alteration was investigated by immunohistochemistry to albumin and fibrinogen and to the tight junction proteins claudin-5, zonula occludens-1 (ZO-1) and occludin. BBB leakage showed wide population-variation and increased with progression of Alzheimer-type pathology, though with considerable overlap between different levels of Alzheimer-type pathology. This was accompanied by increased mean vascular density, but not by down-regulation of tight junction proteins. ZO-1 and occludin were also expressed in glia. Mechanisms leading to BBB leakage in brain ageing remain to be defined, but the population-variation in BBB changes and its early increase in relationship to Alzheimer-type pathology progression suggest that BBB dysfunction contributes to brain ageing.


Water stress assessment integrated with virtual water trade and physical transfer water: A case study of Beijing, China.
With the increase in population and economic development, urban water demand has increased significantly over the past decades, and physical transfer water (i.e., freshwater transported from water source regions to water intake regions through channels or pipelines) and virtual water (i.e., freshwater used in the production of goods and services along their supply chains, abbreviated as VW) have gradually become viable water sources for many cities to relieve water stress. This study used Beijing as the research object and systematically analyzed the impact of physical transfer water, VW, and local water on urban water stress from 2000 to 2016. The results show that VW inflow related to food trade has increased from 3.55 billion m3 in 2000 to 16.76 billion m3 in 2016, and that energy's VW inflow increased from 52.76 million m3 to 137.47 million m3 over the same period. Before 2011, Beijing's water demand was largely met by local water resources; however, after 2011, external water resources (including physical transfer water and VW) accounted for majority of the city's water demand, and VW's contribution increased from 47% in 2011 to 53% in 2016. Although Beijing has significantly reduced local water use in favor of external sources, its water stress index in 2016 remained considerable, far exceeding the upper limit of available water. This study also proposes some measures to ensure Beijing's water security based on the sustainability of external water supply.


Identification of potentially functional circRNAs and prediction of circRNA-miRNA-mRNA regulatory network in periodontitis: Bridging the gap between bioinformatics and clinical needs.
Periodontitis is a multifactorial chronic inflammatory disease that can lead to the irreversible destruction of dental support tissues. As an epigenetic factor, the expression of circRNA is tissue-dependent and disease-dependent. This study aimed to identify novel periodontitis-associated circRNAs and predict relevant circRNA-periodontitis regulatory network by using recently developed bioinformatic tools and integrating sequencing profiling with clinical information for getting a better and more thorough image of periodontitis pathogenesis, from gene to clinic. High-throughput sequencing and RT-qPCR were conducted to identify differentially expressed circRNAs in gingival tissues from periodontitis patients. The relationship between upregulated circRNAs expression and probing depth (PD) was performed using Spearman's correlation analysis. Bioinformatic analyses including GO analysis, circRNA-disease association prediction, and circRNA-miRNA-mRNA network prediction were performed to clarify potential regulatory functions of identified circRNAs in periodontitis. A receiver-operating characteristic (ROC) curve was established to assess the diagnostic significance of identified circRNAs. High-throughput sequencing identified 70 differentially expressed circRNAs (68 upregulated and 2 downregulated circRNAs) in human periodontitis (fold change >2.0 and p < .05). The top five upregulated circRNAs were validated by RT-qPCR that had strong associations with multiple human diseases, including periodontitis. The upregulation of circRNAs were positively correlated with PD (R = .40-.69, p < .05, moderate). A circRNA-miRNA-mRNA network with the top five upregulated circRNAs, differentially expressed mRNAs, and overlapped predicted miRNAs indicated potential roles of circRNAs in immune response, cell apoptosis, migration, adhesion, and reaction to oxidative stress. The ROC curve showed that circRNAs had potential value in periodontitis diagnosis (AUC = 0.7321-0.8667, p < .05). CircRNA-disease associations were predicted by online bioinformatic tools. Positive correlation between upregulated circRNAs, circPTP4A2, chr22:23101560-23135351+, circARHGEF28, circBARD1 and circRASA2, and PD suggested function of circRNAs in periodontitis. Network prediction further focused on downstream targets regulated by circRNAs during periodontitis pathogenesis.


Thirty day postoperative outcomes following anterior lumbar interbody fusion using the National Surgical Quality Improvement Program database.
Anterior lumbar interbody fusion (ALIF) is a common procedure used to treat various lumbar degenerative pathologies. The purpose of this study is to describe 30-day postoperative outcomes following ALIF on a national scale. The American College of Surgeons National Surgery Quality Improvement Program (ACS NSQIP) was searched for ALIF patients between 2005 and 2011. The top preoperative diagnoses were determined using ICD-9 codes. All available 30-day complications were grouped as overall composite morbidity and were compared between preoperative diagnosis groups by univariable and multivariable analyses. There were a total of 1352 ALIF patients. Overall, 6.73% of patients experienced a postoperative complication. Unplanned reoperations (2.48%), urinary tract infection (1.55%), superficial surgical site infection (1.41%), and sepsis (1.11%) were the most common morbidity events. The morbidity rates for each sub-group were: intervertebral disc degeneration (4.41%), spondylosis (6.72%), lumbosacral spinal stenosis(8.21%), and spondylolisthesis (8.41%). After extensive adjustment for patient characteristics and preoperative morbidities, multivariable analysis revealed spondylolisthesis (OR=3.29; 95% CI:1.04-10.46) and spinal stenosis (OR=3.76; 95% CI:1.33-10.63) to be associated with significantly higher overall morbidity odds when compared with lumbar disc degeneration. Lumbosacral spondylosis was associated with similar outcomes as degenerative disc disease (OR =1.70; 95% CI:0.48-6.06). Diverse postoperative complications need to be managed following ALIF. Patients with spondylolisthesis and spinal stenosis may carry increased 30-day postoperative morbidity profiles in ALIF when compared to those with degenerative disc disease. Prospective studies are needed to better delineate the outcomes of ALIF procedures, particularly in the spondylolisthesis and spinal stenosis patient populations.


Direct formation of peritectic phase but no primary phase appearance within Ni83.25Zr16.75 peritectic alloy during free fall.
Ni83.25Zr16.75 peritectic alloy was containerlessly solidified in a drop tube. When the droplet diameter exceeds a critical value (Dcrit), Ni7Zr2 phase primarily solidifies, followed by the peritectic reaction of Ni7Zr2 + L → Ni5Zr. Once the droplet diameter is smaller than the critical value (Dcrit), peritectic phase Ni5Zr directly solidifies from the undercooled melt by completely suppressing the nucleation and growth of Ni7Zr2 phase, which is ascribed to high undercooling and cooling rate. Additionally, peritectic phase Ni5Zr grows equiaxially in the sample solidified in a DSC at a cooling rate of 0.167 K/s.


Violence Risk Assessment in the Emergency Department.
Workplace violence is a prevalent problem in health care, with mental health and emergency departments being the most at-risk settings. The aim of this evidence-based practice project was to pilot use of a violence risk assessment tool, the Broset Violence Checklist, to assess for risk of type II violence and record the interventions that nurses chose to implement to mitigate the situation. Additionally, reports made to the hospital reporting system were tracked and compared to previous reporting frequency. Following staff education, nurses were instructed to complete checklists for all patients who have a score of 1 or higher, which indicates the presence of at least 1 high-risk behavior, and continue hourly scoring until the score returned to 0 or the patient was dispositioned. The number of incidents recorded, time of day, scores, interventions applied to mitigate violence, and change in scores after interventions were evaluated. The number of Broset Violence Checklist scoring sheets submitted and reports made via the hospital reporting system were compared. Incidents were most frequent from 11 am until 3 am. The highest scores occurred in the late evening and early morning hours. There were significantly more incidents captured with the use of the Broset Violence Checklist as compared to the hospital reporting system. Incidents significantly associated with higher scores included providing comfort measures, addressing concerns, and applying restraints. The Broset Violence Checklist was used successfully in the emergency department setting to identify behaviors associated with violence. Under-reporting to the hospital report system was identified in this project, consistent with reports in the literature. Specific interventions were not associated with a decrease in Broset Violence Checklist scores.


Botrytis cinerea chitin synthase BcChsVI is required for normal growth and pathogenicity.
Fungal chitin synthase of classes V and VI (or VII), which contain an additional N-terminal myosin motor domain, have been shown to play important roles in pathogenesis. To study the function of BcChsVI in Botrytis cinerea, BcChs6 gene was disrupted through Agrobacterium tumefaciens-mediated transformation. The Bcchs6 disruption mutant exhibited a 45.5 % increasing in its chitin content when compared with wild strain. The qRT-PCR analysis revealed that in Bcchs6 mutant the expression of BcChs6 was significantly decreased, while the expression of BcChs2 and BcChs3a was increased when compared with wild type. It is probable that the disruption of this gene provoked a compensatory mechanism regulating the cellular response to cell wall damage. Interestingly, the radial growth of Bcchs6 mutant was drastically reduced when 50 % solute was removed from the regular PDA medium, and they were more sensitive to Calcofluor white and other cell wall disturbing chemicals. Pathogenicity assays on tomato leaves indicated that they were significantly reduced in their ability to cause disease. Our results demonstrated that BcChs6 is necessary for proper hyphal growth and pathogenicity of B. cinerea on tomato leaves.


Abnormal expression of E-cadherin in tumor cells is associated with poor prognosis of gastric carcinoma.
The purpose of this study was to clarify the relationship of hepatocyte growth factor (HGF), c-Met, and E-cadherin with clinicopathological parameters and prognosis in gastric carcinoma (GC). 114 specimens were collected from GC patients and expression of HGF, c-Met, and E-cadherin in tissue microarray was evaluated by immunohistochemical staining. Correlation between immunostainings and clinicopathological parameters, follow-up data of patients, was analyzed statistically. Abnormal E-cadherin expression was found in 60.5% (69/114) and associated with tumor depth (P = 0.003), lymph node metastasis (P = 0.001) and advanced clinical stage (P = 0.001). High-expression of HGF and c-Met were found in 64.0% (73/114) and 82.4% (94/114), respectively. High c-Met expression was significantly associated with advanced clinical stage (P = 0.001) and lymph node metastasis (P = 0.011) of GC. In univariate survival analysis, high-expression of HGF and c-Met, and abnormal E-cadherin were significantly associated with poor prognosis of GC patients. However, only abnormal E-cadherin expression (P = 0.001) and tumor depth (P = 0.010) emerged as strong independent prognostic factors for overall survival of GC patients. We found significant correlation among HGF/c-Met, E-cadherin expression and worse prognosis of patients with GC. Abnormal E-cadherin expression may serve as an independent predictive factor for prognosis of GC patients.


Pentoxifylline and insulin-like growth factor-I (IGF-I) abrogate kainic acid-induced cognitive impairment in mice.
Hippocampal insults involving neuroimmune mechanisms can impair learning and memory in a variety of tasks. The present study was designed to assess the effect of pentoxifylline, an inhibitor of tumor necrosis factor alpha (TNFalpha), and insulin-like growth factor-I (IGF-I) on kainate (KA)-induced impairment in spatial memory. Male mice received a subcutaneous injection of a dose of KA (15 mg/kg) that had no cytotoxic effect on hippocampal neurons as confirmed by Fluorojade B staining. This dose resulted in an impairment of spatial memory in a two-trial recognition task 11 days later. Intraperitoneal administration of pentoxifylline (200 mg/kg) abrogated this effect. Repeated intracerebroventricular injection of IGF-I (2 microg/mouse on day 1 followed by 1 microg/mouse on days 2-5) abrogated KA-induced deficits in spatial memory whereas acute IGF-I (2 microg/mouse on day 1 only) had mixed effects. These findings indicate that endogenous TNFalpha is probably involved in the detrimental effects of kainate on cognition and that exogenous IGF-I can oppose these effects, probably by antagonizing TNFalpha-induced neurotoxicity.


Synaptic instability in a neuronal population as an element of encoding information.
An unexpected and novel finding is described and discussed here concerning the synaptic physiology of hippocampal slices during the period of recovery after brain dissection. Contrary to the common notion that the amplitude of synaptic responses recovers in a single exponential rising fashion, we found that synaptic response amplitude displayed an oscillatory pattern. The period of oscillation was of 6h and its frequency depended on the input frequency of stimulation. Based on these preliminary data we can make an assumption that the recovery-associated oscillatory behavior of synaptic responses may be hippocampus specific. These data suggest the existence of a previously undescribed element that modifies the electrical properties underlying the modulation of synaptic responses in a neuronal population. The article hypothesizes a mechanism for this phenomenon.


Photochemical degradation of 1,3-dinitrobenzene in aqueous solution in the presence of hydrogen peroxide.
A study on the destruction of 1,3-dinitrobenzene (1,3-DNB) in aqueous solution was carried out under ultraviolet (UV) irradiation alone and UV irradiation in the presence of hydrogen peroxide (H2O2). The combination of UV and H2O2 is significantly effective in degrading 1,3-DNB in terms of initial reaction rate and the mineralization of organic carbons. The photodegradation process can be influenced in certain extent by increasing the content of H2O2 and the acidity of reaction matrices. It was found that a variety of phenolic intermediates and inorganic acid were formed via hydroxyl radicals attacking the parent compound. The UV/H2O2 oxidation of 1,3-DNB was characterized by pseudo-zero order reaction for the degradation of 1,3-DNB with a 20 times enhanced rate constant of 1.36 x 10(-7) Ms(-1) and the initial rate constant was dependent on the initial concentration of 1,3-DNB.


Viral deletions among healthy young Chinese adults with occult hepatitis B virus infection.
To investigate the mechanism and prognosis of occult hepatitis B virus (HBV) infection (OBI) at a molecular level among healthy young adults, the presence of HBV DNA in 1176 sera samples collected from healthy young people after neonatal vaccination was assessed by nested polymerase chain reaction (PCR) using specific primers designed for the X and S regions of the HBV genome. Full-length HBV DNA from 9 patients with OBI (OB1-OB9) was cloned and sequenced. Deletions in the pre-S, basal core promoter (BCP), core (C) and polymerase (P) regions were observed. The data indicate that there is still a substantial risk of OBI in China despite neonatal vaccination. All deletions that were observed in the pre-S, BCP, C and P regions play a direct or indirect role in OBI. The presence of a deletion mutation in the pre-S1 region was considered to play a pivotal role in hepatocarcinogenesis and was found to increase the risk of hepatocellular carcinoma in the cohorts studied.


Obesity Affects Short-Term Renal Function After Renal Transplantation.
The literature has shown a significant association between body mass index (BMI) and patient and graft outcomes after renal transplantation. The purpose of this study was to reveal the effect of obesity on graft function in a Taiwanese kidney transplant cohort. Two hundred consecutive patients who received kidney transplantation were enrolled in our study. Eight pediatric cases were excluded due to differing definitions of BMI among children. According to the national obesity criteria, these patients were divided into underweight, normal, overweight, and obese groups. Their estimated glomerular filtration rate (eGFR) was compared accordingly using t tests. Cumulative graft and patient survivals were calculated using Kaplan-Meier analysis. A P value of ≤ .05 was considered significant. The mean age of our cohort (105 men and 87 women) was 45.3 years. There was no significant difference comparing biopsy-proven acute rejection, acute tubular necrosis, and delayed graft function between the obese and nonobese groups (P values: .293, .787, and .304, respectively). Short-term eGFR was inferior in the overweight group, but this effect was insignificant beyond 1 month. The 1-month and 3-month eGFR were found to be correlated with BMI groups (P = .012 and P = .008, respectively) but not significant after 6 months post-kidney transplantation. Our study found that short-term renal function was affected by obesity and being overweight, possibly due to the higher prevalence of diabetes and dyslipidemia in obese patients and the increased surgical difficulty.


Bifurcation of Toll-like receptor 9 signaling by adaptor protein 3.
Endosomal Toll-like receptors (TLRs) 7 and 9 recognize viral pathogens and induce signals leading to the activation of nuclear factor κB (NF-κB)-dependent proinflammatory cytokines and interferon regulatory factor 7 (IRF7)-dependent type I interferons (IFNs). Recognition of viral nucleic acids by TLR9 requires its cleavage in the endolysosomal compartment. Here, we show that TLR9 signals leading to the activation of type I IFN, but not proinflammatory cytokine genes, require TLR9 trafficking from endosomes to a specialized lysosome-related organelle. Furthermore, we identify adapter protein-3 as the protein complex responsible for the trafficking of TLR9 to this subcellular compartment. Our results reveal an intracellular mechanism for bifurcation of TLR9 signals by selective receptor trafficking within the endosomal system.


Erythrocyte Alloimmunity and Genetic Variance: Results from the Collaborative Study of Alloimmunity to Antigen Diversity in Asian Populations (All ADP).
As an East-Asian international study, we evaluated erythrocyte alloimmunity by gender and history of transfusion or pregnancy. In total, data from more than 1,826,000 patients were analyzed, from whom 26,170 irregular erythrocyte antibodies were detected in 22,653 cases. Antibody frequencies in these cases were as follows: anti-E, 26.8%; anti-Lea, 20.0%; anti-P1, 7.1%; anti-M, 6.4%; anti-Mia, 5.6%; anti-c + E, 5.6%; anti-Leb, 4.6%; anti-D, 2.8%; anti-Fyb, 2.6%; anti-Lea+Leb, 2.5%; anti-Dia, 2.0%; and others. For pregnant patients, anti-D (12.7%) was statistically more frequent. For transfused patients, anti-E (37.3%), anti-c + E (9.5%), anti-C + e (3.3%) and anti-Jka (3.1%) were significantly more frequent.


Surgical treatment of the massively dilated ureter in children. Part I. management by cutaneous ureterostomy.
One of the major therapeutic challenges facing the pediatric urologist is the massively dilated ureter. When conservative measures, such as relief of obstruction or treatment of infection, have failed or are likely to fail, surgical treatment must be directed at the massive dilatation itself. These circumstances were encountered in 366 massively dilated ureters in 244 children during a 10-year period. Loop and/or terminal cutaneous ureterostomy was used to manage 125 of these ureters in 74 children. Indications for temporary non-intubated proximal urinary diversion included uncontrolled infection, sepsis, azotemia, significant ureteral redundancy and tortuosity, and questionable over-all renal function. Advantages of loop ureterostomy included more proximal drainage and less stomal problems but terminal ureterostomy required a significantly lesser number of surgical procedures in reconstructing the urinary tract. Temporary splinting of the ureter in dry ureteral reimplantations has diminished markedly the incidence of ureterovesical complications. No instances of permanent vesical contracture were noted after long periods of defunctionalization. After initial reconstruction of 47 cutaneous ureterostomies good results by all parameters were obtained in 68 per cent. Additional surgical procedures in selected initial failures have resulted in a final success rate of 85 per cent.


Identification of potential biomarkers of gout through competitive endogenous RNA network analysis.
Gout is a widespread inflammatory arthritis. The present study aimed to identify potential biomarkers of gout and explore their underlying mechanisms through bioinformatics methods. The microarray data was downloaded from the GSE160170 dataset from the Gene Expression Omnibus (GEO) database, and the GEO2R online tool was used to obtain differentially expressed genes (DEGs). We searched for gout-related genes through the DisGeNET and GeneCards databases, and the final DEGs was acquired by intersection with the DEGs obtained from the microarray dataset. Tissue- and organ-specific genes were identified by the BioGPS online tool. Enrichment analysis was performed using GSEA4.1.0 and KOBAS3.0, and a protein-protein interaction (PPI) network was constructed using STRING to understand the biological functions and enrichment pathways of the DEGs as well as to identify their hub genes. Cytoscape was used to construct the competitive endogenous RNA (ceRNA) networks. A total of 653 differentially expressed lncRNAs (DElncRNAs) and 818 differentially expressed mRNAs (DEmRNAs) were identified in the present study. After intersecting the differential DEGs from the dataset, 85 DEGs were obtained. Enrichment analyses showed that the DEGs were mainly enriched in the following biological processes (BPs): inflammation and regulation; immune response; and cell proliferation and apoptosis. Moreover, the DEGs were mainly enriched in rheumatoid arthritis (RA), osteoclast differentiation, interleukin (IL)-17 signaling pathway, nuclear factor kappa B (NF-κB) signaling pathway, Toll-like receptor signaling pathway and tumor necrosis factor (TNF) signaling pathway. Cytoscape software identified 15 hub genes, and the following 9 hub genes were obtained after intersecting with genes specifically expressed in the blood/immune and bone/muscle systems: TNF, JUN, PTGS2, STAT1, IL6, FOS, IL1β, CXCL8 and CD80. In addition, the lncRNA-NEAT1-miR-142-3p-IL-6 pathway may be a key regulatory pathway in the pathogenesis of gout. The present study indicated that the identified 9 hub genes may be potential biomarkers for the diagnosis and treatment of gout. In addition, the results suggested that the lncRNA-NEAT1-miR-142-3p-IL-6 pathway may be a potential RNA regulatory pathway that controls the progression of gout disease.


Posttraumatic stress disorder and psychosocial functioning within two samples of MVA survivors.
To examine criterion F variables of PTSD, the psychosocial functioning of two samples of motor vehicle accident (MVA) survivors was investigated. Within each sample, comparisons between MVA survivors with and without PTSD were conducted on four psychosocial functioning indices at three time points. In addition, the relationships between specific PTSD symptom clusters and psychosocial functioning indices were examined. The study revealed that, in general, MVA survivors with PTSD evidenced poorer psychosocial functioning than did survivors without PTSD. The emotional numbing symptoms of PTSD emerged as the most consistent predictors of the psychosocial functioning indices. The implications of these findings to the comprehensive treatment of PTSD are discussed.


Drink and drug driving: what's the skipper up to?
Since the introduction of random breath testing (RBT) in Australia there has been a significant reduction in drink driving, as measured by alcohol-related crashes. In contrast, the prevalence of drug-related road fatalities is on the increase. One strategy that targets drink- and/or drug-driving is the promotion of a designated driver or 'skipper'. This paper determines to what extent the 'skipper' is driving alcohol or drug-free. A convenience sample of university students from The University of Western Australia completed a questionnaire that included questions on drug and alcohol use while driving as the designated 'skipper'. The mean age of the 286 participants was 21 years. Among the students who reported acting as the designated 'skipper' during the past 12 months, 26% of the students drove, as the designated 'skipper,' while feeling the effects of alcohol. Similarly, 18% of students who reported using drugs drove, as the 'skipper', while feeling the effects of the drug. Multivariate analysis identified that the presence of random drug testing would act as a deterrent for drug driving while the designated 'skipper'. Although three-quarters of designated 'skippers' do not drink and/or drug drive, a sizeable proportion of young drivers continue to place themselves and, more importantly, their passengers and the entire community at an elevated risk of injury. Campaigns that target the responsibility of the 'skipper' and that are included as part of drink-driving campaigns would be beneficial. It is premature to be making recommendations on random drug testing for drivers.


Transcranial direct current stimulation for bipolar depression: systematic reviews of clinical evidence and biological underpinnings.
Despite multiple available treatments for bipolar depression (BD), many patients face sub-optimal responses. Transcranial direct current stimulation (tDCS) has been advocated in the management of different conditions, including BD, especially in treatment-resistant cases. The optimal dose and timing of tDCS, the mutual influence with other concurrently administered interventions, long-term efficacy, overall safety, and biological underpinnings nonetheless deserve additional assessment. The present study appraised the existing clinical evidence about tDCS for bipolar depression, delving into the putative biological underpinnings with a special emphasis on cellular and molecular levels, with the ultimate goal of providing a translational perspective on the matter. Two separate systematic reviews across the PubMed database since inception up to August 8th 2022 were performed, with fourteen clinical and nineteen neurobiological eligible studies. The included clinical studies encompass 207 bipolar depression patients overall and consistently document the efficacy of tDCS, with a reduction in depression scores after treatment ranging from 18% to 92%. The RCT with the largest sample clearly showed a significant superiority of active stimulation over sham. Mild-to-moderate and transient adverse effects are attributed to tDCS across these studies. The review of neurobiological literature indicates that several molecular mechanisms may account for the antidepressant effect of tDCS in BD patients, including the action on calcium homeostasis in glial cells, the enhancement of LTP, the regulation of neurotrophic factors and inflammatory mediators, and the modulation of the expression of plasticity-related genes. To the best of our knowledge, this is the first study on the matter to concurrently provide a synthesis of the clinical evidence and an in-depth appraisal of the putative biological underpinnings, providing consistent support for the efficacy, safety, and tolerability of tDCS.


Primary empty sella turcica in children. Report of two familial cases.
The authors describe cranio-facial deformities found in two sisters and associated with spinal anomalies, short stature and delayed skeletal maturation. The principal radiological features were an enlarged J-shaped sella turcica and intrasellar cisternal herniation. Enlargement of optic foramina and internal acoustic canals were also present. These asymptomatic cases of "empty sella" seem to be part of a general dysplastic syndrome rather than a local disease.


Ethyl 2-(1,3-benzodioxol-5-yl)-1-[3-(1H-imidazol-1-yl)prop-yl]-1H-benzimidazole-5-carboxyl-ate.
In the title compound, C(23)H(22)N(4)O(4), the essentially planar [maximum deviation = 0.022 (1) Å] benzimidazole ring system forms dihedral angles of 86.16 (7) and 37.38 (6)°, respectively, with the imidazole and benzene rings. The dioxolane ring adopts an envelope conformation with the methyl-ene C atom at the flap. In the crystal, C-H⋯O and C-H⋯N inter-actions link the mol-ecules into a ribbon along the a axis. The crystal packing is further stabilized by weak π-π stacking inter-actions [centroid-centroid distances = 3.5954 (8) and 3.7134 (8) Å] and C-H⋯π inter-actions.


Identification and properties of steroid-binding proteins in nesting Chelonia mydas plasma.
We report for the first time the presence of a sex steroid-binding protein in the plasma of green sea turtles Chelonia mydas, which provides an insight into reproductive status. A high affinity, low capacity sex hormone steroid-binding protein was identified in nesting C. mydas and its thermal profile was established. In nesting C. mydas testosterone and oestradiol bind at 4 degrees C with high affinity (K (a) = 1.49 +/- 0.09 x 10(9) M(-1); 0.17 +/- 0.02 x 10(7) M(-1)) and low binding capacity (B (max) = 3.24 +/- 0.84 x 10(-5) M; 0.33 +/- 0.06 x 10(-4) M). The binding affinity and capacity of testosterone at 23 and 36 degrees C, respectively were similar to those determined at 4 degrees C. However, oestradiol showed no binding activity at 36 degrees C. With competition studies we showed that oestradiol and oestrone do not compete for binding sites. Furthermore, in nesting C. mydas plasma no high-affinity binding was observed for adrenocortical steroids (cortisol and corticosterone) and progesterone. Our results indicate that in nesting C. mydas plasma temperature has a minimal effect on the high-affinity binding of testosterone to sex steroid-binding protein, however, the high affinity binding of oestradiol to sex steroid-binding protein is abolished at a hypothetically high (36 degrees C) sea/ambient/body temperature. This suggests that at high core body temperatures most of the oestradiol becomes biologically available to the tissues rather than remaining bound to a high-affinity carrier.


Efficacy and safety of paclitaxel with or without targeted therapy as second-line therapy in advanced gastric cancer: A meta-analysis.
Paclitaxel (PTX) has become a widely used second-line therapy for advanced gastric cancer. There exists controversy whether targeted therapy combined with PTX can provide additional benefit over PTX alone. Therefore, a meta-analysis was carried out to evaluate the efficacy and safety of the two therapy regimes. We searched systematically for studies from the databases of PubMed, Embase, Web of Science and the Cochrane Library published between January 2000 and August 2019. Only randomized controlled trials were eligible. Statistical analysis was performed by meta-analysis. The primary end points were progression-free survival and overall survival, objective response rate and adverse events were the secondary end points. A total of 4 randomized controlled trials with 1574 patients (PTX + targeted therapy, n = 786; PTX, n = 788) were included for the final analysis. As compared with PTX monotherapy, PTX + targeted therapy significantly improved progression-free survival (hazard ratio = 0.88, 95% confidence interval [CI] 0.84-0.92, P < .001), overall survival (hazard ratio = 0.90, 95% CI: 0.86-0.95, P < .001) and was associated with a better objective response rate (RR = 1.80; 95% CI: 1.45-2.24; P < .001). PTX+targeted therapy group significantly increased incidences of grade 3 to 5 neutropenia, fatigue and neuropathy (P < .05). No statistically significant differences were observed in the incidences of grade 3 to 5 anemia, decreased appetite, nausea, diarrhea and abdominal pain between the two treatments (P >.05). Second-line PTX+targeted therapy is a more effective treatment option with tolerable safety profile for advanced gastric cancer as a result of improved survival, though with additional toxicity.


Transection or electrical stimulation of the hypoglossal nerve increases glial fibrillary acidic protein immunoreactivity in the hypoglossal nucleus.
Glial fibrillary acidic protein (GFAP) immunoreactivity within rat hypoglossal (XIIth) nuclei was examined 1-50 days following either unilateral nerve transection or modest electrical stimulation using indirect immunofluorescence and PAP immunohistochemistry. Both nerve transection and stimulation provoked an increase in the immunodetected GFAP within the XIIth nucleus.


Using artificial intelligence to make sustainable development decisions considering VUCA: a systematic literature review and bibliometric analysis.
Sustainable development emergent subfields have been rapidly evolving, and their popularity increased in recent years. Sustainable development is a broad concept having numerous sub-concepts including, but not limited to, circular economy, sustainability, renewable energy, green supply chain, reverse logistics, and waste management. This polymorphism makes decision-making in this field to be an abstruse task. In this perplexing circumstance, the presence of VUCA conditions makes decision-making even more challenging. By taking advantage of artificial intelligence tools and approaches, this paper aims to study with a concentration on sustainable development-related decision-making under VUCA phenomena elements using bibliometric and network analyses which can propose numerous novel insights into the most recent research trends in this area by analyzing the most influential and cited research articles, keywords, author collaboration network, institutions, and countries that finally provides results not previously fully comprehended or assessed by other studies on this topic. In this study, an extensive systematic literature review and bibliometric analysis are conducted using 534 research articles out of more than 3600. From the content analysis part, four clusters have been found. The decision parameters, presumptions, and research goal(s) for each model are pointed out too. The findings contribute to both conceptual and practical managerial aspects and provide a powerful roadmap for future research directions in this field, such as how real-life multidimensionality can be considered in sustainable development-related decision-making, or what are the effects of the VUCA in sustainable development considering the circular economy and waste management intersection.


Territoriality and changes in resource use by sunbirds at Leonotis leonurus (Labiatae).
Leonotis leonurus was studied with the aim of characterising nectar quality and quantity, and of monitoring the sunbirds' response to the resource. The flowers produced high quality nectar in low quantities. Nectar quality remained constant during the day and averaged 23.4% sucrose equivalents (an energy content of 3.8j/μl). Nectar production was highest during the morning when flow rates reached a peak of 3.3 μl/h. L. leonurus was visited by four species of sunbirds. In 1977 there were 7.8 visits/h to the flowers. The clump was defended by a single Olive Sunbird (Nectarinia olivacea) who defended the flowers intra- and interspecifically. On one day the territorial bird obtained approximately 57.1 kJ from the Leonotis flowers and expended 5.4 kJ on defence and 13.6 kJ overall while on the territory. Territorial behaviour and intruder pressure was a function of resource availability. When Leonotis nectar levels were high intruder pressure was intense and the territorial bird employed long chases as a defence behaviour. When nectar levels desreased intruder pressure was lower, the territorial bird chased less and employed vocalisations as a relatively inexpensive form of territorial behaviour.In 1978 there was an abundance of nectar sources in the study area due to the late onset of the dry season. Sunbirds were not territorial at Leonotis and visiting rates were lower than in 1977, averaging only 1.7 visits per hour. Instead the sunbirds concentrated on contemporaneously flowering plant species, particularly Halleria lucida.


The rapidly growing mycobacteria--Mycobacterium fortuitum and Mycobacterium chelonei.
In summary, rapidly growing mycobacteria, M. fortuitum and M. chelonei, are pathogens of increasing importance which are often hospital-acquired and can infect patients with iatrogenic immunosuppression. They readily grow on routine mycobacterial culture media and must be distinguished from non-pathogenic rapidly growing species and slowly growing mycobacteria. Widely distributed in nature, they are often present in hospital environments, especially in water. Compared to M. tuberculosis they are weak pathogens, and infected patients are not considered contagious. Disease is probably acquired from environmental sources by direct entry of the organisms through traumatized skin or mucous membranes or by aspiration into previously abnormal lungs. They are usually resistant to antituberculous agents but are susceptible to several commonly used antibacterial agents. Treatment generally requires one or more active antibiotics plus adjunctive surgery in many cases. Prevention of nosocomial infection lies in proper disinfection of potentially contaminated medical devices and elimination of contaminated water.


Autophosphorylation of the two C-terminal tyrosine residues Tyr1316 and Tyr1322 modulates the activity of the insulin receptor kinase in vitro.
Previously, several studies have demonstrated that autophosphorylation of the C-terminal tyrosine residues (Tyr1316 and Tyr1322) affects the signaling properties of the insulin receptor in vivo. To assess the biochemical consequences of the C-terminal phosphorylation in vitro, we have constructed, purified and characterized 45 kDa soluble insulin receptor kinase domains (IRKD), either with (IRKD) or without (IRKD-Y2F) the two C-terminal tyrosine phosphorylation sites, respectively. According to HPLC phosphopeptide mapping, autophosphorylation of the three tyrosines in the activation loop of the IRKD-Y2F kinase (Tyr1146, Tyr1150, and Tyr1151) was not affected by the mutation. In addition, the Y2F mutation did not significantly change the Km values for exogenous substrates. However, the mutation in IRKD-Y2F resulted in a decrease in the maximum velocities of the phosphotransferase reaction in substrate phosphorylation reactions. Moreover, the exchange of the tyrosines in IRKD-Y2F led to an increase in the apparent Km values for ATP, suggesting a cross-talk of the C-terminus and the catalytic domain of the enzyme. In addition, as judged by size exclusion chromatography, conformational changes of the enzyme following autophosphorylation were abolished by the removal of the two C-terminal tyrosines. These data suggest a regulatory role of the two C-terminal phosphorylation sites in the phosphotransferase activity of the insulin receptor.


Effect of spasmolytic analgesic drugs on the motility patterns of the equine small intestine.
The effect of acepromazine, Buscopan (Crown Chemicals), pethidine and methadone was evaluated in ponies prepared with Thiry-Vella (T-V) loops. Motility was assessed by electrophysiological means (bipolar electrodes and strain gauge transducers) and by the passage through the T-V loop of a fluid test meal. Results were obtained from 26 experiments in three ponies and compared with six control experiments, in which saline had been administered to the same ponies. Each pony acted as its own control in each experiment and pre and post treatment values for slow wave frequency, spiking activity, delivery rate and flow rate were compared. Acepromazine reduced electrical activity, but increased volume transport. Buscopan produced little change, while pethidine and methadone both decreased electrical activity, but increased volume transit. These effects may be due to a decrease in tone with resulting increase in luminal volume of the intestine.


Physiological consequences of mitochondrial antibiotic-resistant mutations in Paramecium: growth-rates, cytochromic defects and cyanide-insensitive respiration of mutant and erythromycin-treated wild-type strains.
A set of mitochondrial antibiotic-resistant mutants of Paramecium have been analyzed with respect to their growth-rates, cytochromic content and respiratory properties. The mutants could be arranged in a continuous series ranging from strains equivalent to wild-type to severely affected ones; affected strains display longer generation times, reduced amount of cytochrome oxidase and very high levels of cyanideinsensitive respiration. Perfect phenocopies of the mutants were obtained by treating wild-type cells with low concentrations of erythromycin suggesting that the mutations exert their pleiotropic effect by perturbating mitochondria protein synthesis in agreement with the idea that these mutations affect the mitochondrial ribosomes. In the mitochondria of some of the mutants, electrons can be channelled with equal efficiency into the "classical" cyanide-sensitive pathway and the alternate cyanide insensitive (and SHAM-sensitive) one, providing direct demonstration of the branching of these two respiratory pathways. In the absence of any added inhibitor, however, electrons tend to be channelled in the cyanide-sensitive pathway. All the physiological data fit perfectly the genetic data concerning the "stability" of the various mutations in "mixed mitochondrial populations", i.e., markers that were known to be strongly counter-selected with respect to wild-type in such populations correspond to severely affected strains, while markers that were known to be "stable" correspond to "healthy" strains. A more quantitative analysis of the data shows that that there is little or no "complementation" between wild-type and mutated mitochondria in mixed cells indicating a high extent of functional autonomy of mitochondria in Paramecium.


Divergent T-cell receptor delta chains from marsupials.
Complementary DNAs (cDNAs) encoding T-cell receptor delta (TRD) chains from the northern brown bandicoot, Isoodon macrourus, were identified while sequencing expressed sequence tags (ESTs) from a thymus cDNA library. Surprisingly, the I. macrourus TRD sequences were not orthologous to previously published TRD sequences from another Australian marsupial, the tammar wallaby, Macropus eugenii. Identification of TRD genes in the recently completed whole genome sequence of the South American opossum, Monodelphis domestica, revealed the presence of two highly divergent TRD loci. To determine whether the presence of multiple TRD loci accounts for the lack of orthology between the I. macrourus and M. eugenii cDNAs, additional TRD sequences were obtained from both species of marsupials. The results of this analysis revealed that, unlike eutherian mammals, all three species of marsupials have multiple, highly divergent TRD loci. One group of marsupial TRD sequences was closely related to TR sequences from eutherian mammals. A second group of TRD sequences formed a unique marsupial-specific clade, separate from TR sequences from eutherians. An interesting expression pattern of TRD variable (TRDV) and constant (TRDC) segments was evident in cDNAs from I. macrourus and M. eugenii. TRDV and TRDC sequences that were closely related to TRD genes from eutherian mammals were only found in association with each other in cDNAs from both marsupial species. A similar pattern was seen between TRDV and TRDC sequences that were most closely related to other marsupial TRD genes.


Impact of 24-month treatment with etanercept, adalimumab, or methotrexate on metabolic syndrome components in a cohort of 210 psoriatic arthritis patients.
Psoriatic arthritis (PsA) is a chronic inflammatory condition, characterized by an excess of metabolic disorders. Metabolic syndrome (MetS) is a cluster of classic cardiovascular risk factors, due to an imbalance between pro- and anti-inflammatory adipokines. Tumor necrosis factor (TNF)-α is a pro-inflammatory adipocytokine mainly produced by monocytes and macrophages with a central role in inflammatory responses, but it also induces adipocytes apoptosis, promotes insulin resistance, and stimulates lipolysis. The aim of this study was to evaluate the impact of therapy with etanercept (ETN), adalimumab (ADA), and methotrexate (MTX) on MetS components in a cohort of PsA patients with a follow-up period of 24 months. A retrospective study has been conducted in a cohort of PsA patients. On the basis of the inclusion criteria, we identified the first 70 consecutive patients, respectively, on ADA, ETN, and MTX, for a total of 210 patients achieving PsARC criteria during the observation period. As part of the routine clinical practice, assessment of metabolic parameters and of disease activity was recorded at baseline (T0), at 12 months (T1), and at 24 months (T2). The results show that when the specific components of the MetS were considered, taking also into account by regression analysis the effect of the confounding factors, the patients on etN and ADA show a significant improvement of the metabolic syndrome components (in detail, waist circumference, triglycerides, high-density lipoprotein cholesterol, and glucose) as compared to the MTX group. In conclusion, these data suggest that the biologic treatment in PsA can no longer be taken into consideration only for its positive effect on articular and cutaneous symptoms but also on the various aspects of this complex picture.


Vitreous fluorophotometry in patients with cataract surgery.
Cystoid macular edema frequently complicates recovery from cataract surgery. Our understanding of this disease would be enhanced by more sensitive and quantitative methods to evaluate it. We performed vitreous fluorophotometry in 66 nondiabetic patients who had recently undergone cataract surgery. Eyes with definite macular edema on fluorescein angiography were ranked according to the severity of the leakage. The rank of the leakage correlated significantly with the vitreous fluorophotometry values (P less than 0.01). The mean fluorophotometry result in the eyes with cystoid macular edema was greater than that in the phakic, control group (P less than 0.01). However, eyes with minimal or no leakage visible on fluorescein angiography had fluorophotometry values indistinguishable from normal. The quantitative vitreous fluorophotometry results provided an indicator of cystoid macular edema that may prove useful in following this problem and evaluating therapy for it.


Outcome of day treatment for older adults with affective disorders: An observational pre-post design of two transdiagnostic approaches.
First, to evaluate the outcome of 2 transdiagnostic day treatment programs. A 20-week psychotherapeutic day treatment (PDT) and an activating day treatment (ADT) program delivered in blocks of 4 weeks with a maximum of 24 weeks with respect to depression, anxiety, and hypochondriasis. Second, to explore the impact of cognitive impairment and personality pathology on treatment outcome. The course of depression (Inventory of Depressive Symptoms), anxiety (Geriatric Anxiety Inventory), and hypochondriasis (Whitley Index) were evaluated by linear mixed models adjusted for age, sex, level of education, and alcohol usage among 49 patients (mean age 65 years, 67% females) receiving PDT and among 61 patients (mean age 67.1, 61% females) receiving ADT. Pre-post effect-sizes were expressed as Cohen's d. Subsequently, cognitive impairment (no, suspected, established) and personality pathology (DSM-IV criteria as well as the Big Five personality traits) were examined as potential moderators of treatment outcome. Among patients receiving PDT, large improvements were found for depression (d = 1.1) and anxiety (d = 1.2) but not for hypochondriasis (d = 0.0). Patients receiving ADT showed moderate treatment effects for depression (d = 0.6), anxiety (d = 0.6), as well as hypochondriasis (d = 0.6). Personality pathology moderates treatment outcome of neither PDT nor ADT. Cognitive impairment negatively interfered with the course of depressive symptoms among patients receiving PDT. Transdiagnostic day treatment is promising for older adults with affective disorders with high feasibility.