Late cortical plasticity in motor and auditory cortex: role of met-allele in BDNF Val66Met polymorphism.
The brain-derived neurotropic factor (BDNF) Val66Met polymorphism has been associated with abnormalities of synaptic plasticity in animal models, and abnormalities in motor cortical plasticity have also been described in humans using transcranial direct current stimulation. No study has yet been done on plasticity in non-motor regions, and the effect of two Met alleles (i.e. 'Met dose') is not well understood. We studied the effect of the BDNF Val66Met polymorphism on the after-effects of transcranial direct current stimulation and tetanic auditory stimulation in 65 subjects (23; Val66Val, 22; Val66Met and 20; Met66Met genotypes). In the first session, motor evoked potentials (MEP) were recorded under stereotaxic guidance for 90 min after 9 min of anodal transcranial direct current stimulation (TDCS). In the second session, auditory-evoked potentials (AEP) were recorded before and after 2 min of auditory 13 Hz tetanic stimulation. There was a difference in MEP facilitation post-TDCS comparing Met carriers with non-Met carriers, with Met carriers having a modest late facilitation at 30-90 min. There was no difference in responses between Val66Met genotype and Met66Met genotype subjects. Tetanic auditory stimulation also produced late facilitation of N1-P2 AEP at 25 min, but there was no apparent effect of genetic status. This study indicates that Met66Met carriers behave like Val66Met carriers for TDCS-induced plasticity, and produce a late facilitation of MEPs. Auditory cortical plasticity was not affected by the BDNF Val66Met polymorphism. This study sheds light on the differences between auditory and motor cortical plasticity and the role of the BDNF Val66Met polymorphism.


Myeloid cells interact with a subset of thyrocytes to promote their migration and follicle formation through NF-κB.
The pathogenesis of thyroid dysgenesis (TD) is not well understood. Here, using a combination of single-cell RNA and spatial transcriptome sequencing, we identify a subgroup of NF-κB-activated thyrocytes located at the center of thyroid tissues in postnatal mice, which maintained a partially mesenchymal phenotype. These cells actively protruded out of the thyroid primordium and generated new follicles in zebrafish embryos through continuous tracing. Suppressing NF-κB signaling affected thyrocyte migration and follicle formation, leading to a TD-like phenotype in both mice and zebrafish. Interestingly, during thyroid folliculogenesis, myeloid cells played a crucial role in promoting thyrocyte migration by maintaining close contact and secreting TNF-α. We found that cebpa mutant zebrafish, in which all myeloid cells were depleted, exhibited thyrocyte migration defects. Taken together, our results suggest that myeloid-derived TNF-α-induced NF-κB activation plays a critical role in promoting the migration of vertebrate thyrocytes for follicle generation.


Bioinformatics analysis and genetic diversity of the poliovirus.
Poliomyelitis, a disease which can manifest as muscle paralysis, is caused by the poliovirus, which is a human enterovirus and member of the family Picornaviridae that usually transmits by the faecal-oral route. The viruses of the OPV (oral poliovirus attenuated-live vaccine) strains can mutate in the human intestine during replication and some of these mutations can lead to the recovery of serious neurovirulence. Informatics research of the poliovirus genome can be used to explain further the characteristics of this virus. In this study, sequences from 100 poliovirus isolates were acquired from GenBank. To determine the evolutionary relationship between the strains, we compared and analysed the sequences of the complete poliovirus genome and the VP1 region. The reconstructed phylogenetic trees for the complete sequences and the VP1 sequences were both divided into two branches, indicating that the genetic relationships of the whole poliovirus genome and the VP1 sequences are very similar. This branching indicates that the virulence and pathogenicity of poliomyelitis may be associated with the VP1 region. Sequence alignment of the VP1 region revealed numerous mutation sites in which mutation rates of >30 % were detected. In a group of strains recorded in the USA, mutation sites and mutation types were the same and this may be associated with their distribution in the evolutionary tree and their genetic relationship. In conclusion, the genetic evolutionary relationships of poliovirus isolate sequences are determined to a great extent by the VP1 protein, and poliovirus strains located on the same branch of the phylogenetic tree contain the same mutation spots and mutation types. Hence, the genetic characteristics of the VP1 region in the poliovirus genome should be analysed to identify the transmission route of poliovirus and provide the basis of viral immunity development.


The relationship between cardiorespiratory fitness and blood pressure among airline pilots: a mediation analysis of body composition.
Blood pressure (BP), cardiorespiratory fitness (CRF), and body composition are independently associated with health outcomes, yet the relationship between these variables has not been explored among airline pilots. The aim of this study was to evaluate the relationship between CRF and BP, and further examine whether the relationship is mediated by body composition. A cross-sectional study was conducted among 356 airline pilots in New Zealand. We measured height, body mass, BP, waist circumference, skinfolds, and CRF (via a WattBike cycle ergometer submaximal VO 2max test). Partial correlation coefficients were estimated to examine the relationships between all variables while controlling for age and sex. Haye's PROCESS macro and the Sobel test were utilized for the mediation analysis. All body composition variables (body mass index, waist circumference and body fat percentage) were positively correlated with all BP variables (systolic pressure, diastolic pressure and mean arterial pressure) ( P < 0.001). CRF was negatively correlated with all body composition and BP variables ( P < 0.001). The Sobel test and indirect effect were significant ( P < 0.001), confirming that all body composition variables partially mediate the relationship between CRF and all blood pressure variables. Lower CRF is associated with higher blood pressure, and body composition partially mediates the relationship between these health risk factors. These findings highlight the importance of physical fitness and healthy body composition in the management of blood pressure among this occupational group.


Cyclosporine A treatment for relapsed subcutaneous panniculitis-like T-cell lymphoma: a case with long-term follow-up.
Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a distinctive lymphoma characterized by an infiltration of subcutaneous tissue by neoplastic cytotoxic T cells. There was no distinction between TCR alpha/beta phenotype and TCR gamma/delta phenotype, and anthracycline-based chemotherapy was usually used for both. Here, we report a patient with recurrent SPTL who achieved a second long-term complete remission by repeated cyclosporine A (CsA) treatment. From 2000 to 2001, the patient received anthracycline-based combination chemotherapy. However, the treatment did not induce long-term remission. In 2002, he received cyclosporine treatment for about 6 months. This resulted in a 5-year remission that ended in relapse in 2008. He received CsA treatment once again and attained a second long-term remission. This case suggests that re-treatment with CsA can be a good option for relapsed SPTL cases and can result in long-term remission.


Vascular endothelial growth factor c regulates hematopoietic stem cell fate in the dorsal aorta.
Hematopoietic stem and progenitor cells (HSPCs) are multipotent cells that self-renew or differentiate to establish the entire blood hierarchy. HSPCs arise from the hemogenic endothelium of the dorsal aorta (DA) during development in a process called endothelial-to-hematopoietic transition. The factors and signals that control HSPC fate decisions from the hemogenic endothelium are not fully understood. We found that Vegfc has a role in HSPC emergence from the zebrafish DA. Using time-lapse live imaging, we show that some HSPCs in the DA of vegfc loss-of-function embryos display altered cellular behavior. Instead of typical budding from the DA, emergent HSPCs exhibit crawling behavior similar to myeloid cells. This was confirmed by increased myeloid cell marker expression in the ventral wall of the DA and the caudal hematopoietic tissue. This increase in myeloid cells corresponded with a decrease in HSPCs that persisted into larval stages. Together, our data suggest that Vegfc regulates HSPC emergence in the hemogenic endothelium, in part by suppressing a myeloid cell fate. Our study provides a potential signal for modulation of HSPC fate in stem cell differentiation protocols.


A Vitis vinifera basic helix-loop-helix transcription factor enhances plant cell size, vegetative biomass and reproductive yield.
Strategies for improving plant size are critical targets for plant biotechnology to increase vegetative biomass or reproductive yield. To improve biomass production, a codon-optimized helix-loop-helix transcription factor (VvCEB1opt ) from wine grape was overexpressed in Arabidopsis thaliana resulting in significantly increased leaf number, leaf and rosette area, fresh weight and dry weight. Cell size, but typically not cell number, was increased in all tissues resulting in increased vegetative biomass and reproductive organ size, number and seed yield. Ionomic analysis of leaves revealed the VvCEB1opt -overexpressing plants had significantly elevated, K, S and Mo contents relative to control lines. Increased K content likely drives increased osmotic potential within cells leading to greater cellular growth and expansion. To understand the mechanistic basis of VvCEB1opt action, one transgenic line was genotyped using RNA-Seq mRNA expression profiling and revealed a novel transcriptional reprogramming network with significant changes in mRNA abundance for genes with functions in delayed flowering, pathogen-defence responses, iron homeostasis, vesicle-mediated cell wall formation and auxin-mediated signalling and responses. Direct testing of VvCEB1opt -overexpressing plants showed that they had significantly elevated auxin content and a significantly increased number of lateral leaf primordia within meristems relative to controls, confirming that cell expansion and organ number proliferation were likely an auxin-mediated process. VvCEB1opt overexpression in Nicotiana sylvestris also showed larger cells, organ size and biomass demonstrating the potential applicability of this innovative strategy for improving plant biomass and reproductive yield in crops.


The exploration of novel Alzheimer's therapeutic agents from the pool of FDA approved medicines using drug repositioning, enzyme inhibition and kinetic mechanism approaches.
Novel drug development is onerous, time consuming and overpriced process with particularly low success and relatively high enfeebling rates. To overcome this burden, drug repositioning approach is being used to predict the possible therapeutic effects of FDA approved drugs in different diseases. Herein, we designed a computational and enzyme inhibitory mechanistic approach to fetch the promising drugs from the pool of FDA approved drugs against AD. The binding interaction patterns and conformations of screened drugs within active region of AChE were confirmed through molecular docking profiles. The possible associations of selected drugs with AD genes were predicted by pharmacogenomics analysis and confirmed through data mining. The stability behaviour of docked complexes (Drugs-AChE) were checked by MD simulations. The possible therapeutic potential of repositioned drugs against AChE were checked by in vitro analysis. Taken together, Cinitapride displayed a comparable results with standard and can be used as possible therapeutic agent in the treatment of AD.


Influence of air humidity on 248-nm ultraviolet laser pulse filamentation.
At first glance, the amount of water molecules naturally contained in humid air is negligibly small to affect filamentation of ultrashort laser pulses. However, here we show, both experimentally and numerically, that for ultraviolet laser pulses with 248 nm wavelength this is not true. We demonstrate that with increase of air humidity the plasma channels generated by the ultraviolet laser pulses in air become longer and wider, while the corresponding electron density in humid air can be up to one order of magnitude higher compared to dry air.


Reporting postpartum haemorrhage with transfusion: a comparison of NSW birth and hospital data.
Postpartum haemorrhage rates have been increasing in NSW and internationally, and blood transfusion is required in severe cases. Using routinely collected administrative data provides a convenient method with which to monitor trends in both postpartum haemorrhage and associated transfusion use. In order for this to be feasible however, the reliability of reporting of the conditions needs to be assessed. This study used linked data to compare the reporting of postpartum haemorrhage with transfusion as reported in the NSW Admitted Patient Data Collection (hospital data), with the same information obtained from the Perinatal Data Collection (birth data), for births in NSW from 2007 to 2010. The rate of postpartum haemorrhage requiring blood transfusion was 1.0% based on the hospital data and 1.1% based on the birth data, with a rate of 1.7% if identifying cases from either source. Agreement between the two sources improved from fair to moderate over the time period. Postpartum haemorrhage requiring transfusion recorded in the birth data shows only moderate agreement with hospital data, so caution is recommended when using this variable for analysis. Linkage of both datasets is recommended to identify birth information from birth data and postpartum haemorrhage with transfusion from hospital data until further validation work has been undertaken.


Irreversible oxidation of the active-site cysteine of peroxiredoxin to cysteine sulfonic acid for enhanced molecular chaperone activity.
The thiol (-SH) of the active cysteine residue in peroxiredoxin (Prx) is known to be reversibly hyperoxidized to cysteine sulfinic acid (-SO(2)H), which can be reduced back to thiol by sulfiredoxin/sestrin. However, hyperoxidized Prx of an irreversible nature has not been reported yet. Using an antibody developed against the sulfonylated (-SO(3)H) yeast Prx (Tsa1p) active-site peptide (AFTFVCPTEI), we observed an increase in the immunoblot intensity in proportion to the H(2)O(2) concentrations administered to the yeast cells. We identified two species of hyperoxidized Tsa1p: one can be reduced back (reversible) with sulfiredoxin, and the other cannot (irreversible). Irreversibly hyperoxidized Tsa1p was identified as containing the active-site cysteine sulfonic acid (Tsa1p-SO(3)H) by mass spectrometry. Tsa1p-SO(3)H was not an autoxidation product of Tsa1p-SO(2)H and was maintained in yeast cells even after two doubling cycles. Tsa1p-SO(3)H self-assembled into a ring-shaped multimeric form was shown by electron microscopy. Although the Tsa1p-SO(3)H multimer lost its peroxidase activity, it gained approximately 4-fold higher chaperone activity compared with Tsa1p-SH. In this study, we identify an irreversibly hyperoxidized Prx, Tsa1p-SO(3)H, with enhanced molecular chaperone activity and suggest that Tsa1p-SO(3)H is a marker of cumulative oxidative stress in cells.


Signatures of selection in five Italian cattle breeds detected by a 54K SNP panel.
In this study we used a medium density panel of SNP markers to perform population genetic analysis in five Italian cattle breeds. The BovineSNP50 BeadChip was used to genotype a total of 2,935 bulls of Piedmontese, Marchigiana, Italian Holstein, Italian Brown and Italian Pezzata Rossa breeds. To determine a genome-wide pattern of positive selection we mapped the F st values against genome location. The highest F st peaks were obtained on BTA6 and BTA13 where some candidate genes are located. We identified selection signatures peculiar of each breed which suggest selection for genes involved in milk or meat traits. The genetic structure was investigated by using a multidimensional scaling of the genetic distance matrix and a Bayesian approach implemented in the STRUCTURE software. The genotyping data showed a clear partitioning of the cattle genetic diversity into distinct breeds if a number of clusters equal to the number of populations were given. Assuming a lower number of clusters beef breeds group together. Both methods showed all five breeds separated in well defined clusters and the Bayesian approach assigned individuals to the breed of origin. The work is of interest not only because it enriches the knowledge on the process of evolution but also because the results generated could have implications for selective breeding programs.


Dynamic expressions of confidence within an evidence accumulation framework.
Human observers can reliably report their confidence in the choices they make. An influential framework conceptualizes decision confidence as the probability of a decision being correct, given the choice made and the evidence on which it was based. This framework accounts for three diagnostic signatures of human confidence reports, including an opposite dependence of confidence on evidence strength for correct and error trials. However, the framework does not account for the temporal evolution of these signatures, because it only describes the transformation of a static representation of evidence into choice and the associated confidence. Here, we combine this framework with another influential framework: dynamic accumulation of evidence over time, and build on the notion that confidence reflects the probability of being correct, given the choice and accumulated evidence up until that point. Critically, we show that such a dynamic model predicts that the diagnostic signatures of confidence depend on time; most critically, it predicts a stronger opposite dependence of confidence on evidence strength and choice correctness as a function of time. We tested, and confirmed, these predictions in human behaviour during random dot motion discrimination, in which confidence judgments were queried at different points in time. We conclude that human confidence reports reflect the dynamics of the probability of being correct given the accumulated evidence and choice.


BAFF maintains T-cell survival by inducing OPN expression in B cells.
Dysregulation of T-cell survival and apoptosis is the common cause of autoimmune diseases such as multiple sclerosis (MS). However, the factors inducing imbalance of T-cell survival and apoptosis in MS remains unclear. Here, we show that the resistance to apoptosis was associated with high levels of B-cell activating factor (BAFF). Blockade of BAFF with TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor)-IgG significantly reduced T-cell survival in myelin oligodendroglia glycoprotein (MOG)-induced chronic experimental allergic encephalitis (EAE). Furthermore, BAFF induced anti-apoptotic molecule Bcl2 expression in T cells by up-regulating osteopontin (OPN) secretion from B cells. BAFF mainly induced OPN expression in splenic CD21(-)CD23(+) B cells via a NF-kB dependent signaling pathway. In addition, we found that BAFF and OPN levels were increased in MS patients similar to the results obtained from our mice research. The study suggests that BAFF regulates T-cell survival by inducing OPN secretion in B cells in autoimmune diseases.


Avicennia germinans leaf traits in degraded, restored, and natural mangrove ecosystems of Guyana.
Mangrove leaves have unique features that enable them to cope with shifting environmental conditions while preserving their general functionality and efficiency. We examined the morphological characteristics and chlorophyll content (spectroscopically) of 600 mature Avicennia germinans leaves selected from 30 trees located in one degraded, one restored, and one natural mangrove ecosystem along Guyana's coastline. Systematic sampling was carried out using the closest individual sampling method in the wet and dry seasons. We hypothesized that both habitat type and seasonality influence the leaf traits and chlorophyll content of A. germinans. Our findings showed that A. germinans leaves are mesophyllous, and traits such as leaf perimeter, area, length, width, dry mass, wet mass, turgid mass, leaf-specific area, and relative water content showed fluctuations in ecosystems (one-way ANOVA, p < .05) as well as seasonally (paired t-test, p < .05). Substantial, positive correlations (p < .05, R > .75) were also established for over 10 leaf parameters in both seasons while PCA and multiple regression analyses further confirmed the strong relationships between leaf morphological features and their respective locations. Changes in chlorophyll concentration were most noticeable in the degraded ecosystem while variations in leaf traits were more pronounced in the restored mangrove area. This may be due to the various disturbances found in each ecosystem coupled with fluctuations in the seasons. Our results demonstrate that mangroves, to some extent, alter their plant structures to cope with environmental stressors present in the various ecosystems they thrive in to maintain their survival.


Interaction of oestrogen and progesterone receptors with specific subfractions of laying-hen oviduct chromatin.
Salt (NaCl)-extracted nuclear oestrogen receptor from hen oviduct was incubated with salt-depleted oviduct chromatin and dialysed to low salt. The oestrogen receptor (re)associated with chromatin to form a 13-14S-sedimenting fraction, as found in 'native' chromatin, and saturation of this interaction was obtained for very low receptor concentrations (approx. 0.04 nM). Similarly, purified progesterone receptor from chick oviduct cytosol associated with depleted chromatin to form an 11-12S-sedimenting fraction, as in 'native' chromatin; this interaction tended towards saturation for much higher concentrations of progesterone receptor (approx. 8 nM) than that observed for oestrogen receptor. When the two receptors were incubated with depleted chromatin from hen kidney or erythrocytes, their s values were as for oviduct chromatin. However, no saturation of these interactions was seen, even for high concentrations of receptor. Steroid-hormone receptors can therefore bind in vitro to particular subfractions of non-target-tissue chromatin, but with a much lower affinity than to target-tissue chromatin.


Transcriptome and Metabolome Analyses Reveal That Jasmonic Acids May Facilitate the Infection of Cucumber Green Mottle Mosaic Virus in Bottle Gourd.
Cucumber green mottle mosaic virus (CGMMV) is a typical seed-borne tobamovirus that mainly infects cucurbit crops. Due to the rapid growth of international trade, CGMMV has spread worldwide and become a significant threat to cucurbit industry. Despite various studies focusing on the interaction between CGMMV and host plants, the molecular mechanism of CGMMV infection is still unclear. In this study, we utilized transcriptome and metabolome analyses to investigate the antiviral response of bottle gourd (Lagenaria siceraria) under CGMMV stress. The transcriptome analysis revealed that in comparison to mock-inoculated bottle gourd, 1929 differently expressed genes (DEGs) were identified in CGMMV-inoculated bottle gourd. Among them, 1397 genes were upregulated while 532 genes were downregulated. KEGG pathway enrichment indicated that the DEGs were mainly involved in pathways including the metabolic pathway, the biosynthesis of secondary metabolites, plant hormone signal transduction, plant-pathogen interaction, and starch and sucrose metabolism. The metabolome result showed that there were 76 differentially accumulated metabolites (DAMs), of which 69 metabolites were up-accumulated, and 7 metabolites were down-accumulated. These DAMs were clustered into several pathways, including biosynthesis of secondary metabolites, tyrosine metabolism, flavonoid biosynthesis, carbon metabolism, and plant hormone signal transduction. Combining the transcriptome and metabolome results, the genes and metabolites involved in the jasmonic acid and its derivatives (JAs) synthesis pathway were significantly induced upon CGMMV infection. The silencing of the allene oxide synthase (AOS) gene, which is the key gene involved in JAs synthesis, reduced CGMMV accumulation. These findings suggest that JAs may facilitate CGMMV infection in bottle gourd.


Lights on for aminopeptidases in cystic kidney disease.
While erudite cell biologists have for many decades described singular immotile appendages known as primary cilia to be present on most cells in our bodies, cilial function(s) long remained an enigma. Driven largely by an ever increasing number of discoveries of genetic defects in primary cilia during the past decade, cilia were catapulted from a long lasting existence in obscurity into the bright spotlight in cell biology and medicine. The study by O'Toole et al. in this issue of the JCI adds a novel "enzymatic" facet to the rapidly growing information about these little cellular tails, by demonstrating that defects in the XPNPEP3 gene, which encodes mitochondrial and cytosolic splice variants of X-prolyl aminopeptidase 3, can cause nephronophthisis-like ciliopathy. Future studies are in order now to elucidate the cystogenic pathways affected by disrupted enzymatic function of XPNPEP3 in cilia-related cystogenic diseases.


MicroRNA function in the profibrogenic interplay upon chronic liver disease.
In chronic liver disease leading to fibrosis, hepatic stellate cells (HSC) differentiate into myofibroblasts. Myofibroblastic HSC have taken center stage during liver fibrogenesis, due to their remarkable synthesis of extracellular matrix proteins, their secretion of profibrogenic mediators and their contribution to hypertension, due to elevated contractility. MicroRNAs (miRNAs) are small, noncoding RNA molecules of 19-24 nucleotides in length. By either RNA interference or inhibition of translational initiation and elongation, each miRNA is able to inhibit the gene expression of a wide panel of targeted transcripts. Recently, it was shown that altered miRNA patterns after chronic liver disease highly affect the progression of fibrosis by their potential to target the expression of extracellular matrix proteins and the synthesis of mediators of profibrogenic pathways. Here, we underline the role of miRNAs in the interplay of the profibrogenic cell communication pathways upon myofibroblastic differentiation of hepatic stellate cells in the chronically injured liver.


Selective risk taking among needle exchange participants: implications for supplemental interventions.
This study characterized social network context of HIV risk behavior among injection drug users who participated in a needle exchange program. Interviews were conducted with 1184 injection drug users at the Baltimore Needle Exchange Program enrolled in an evaluation cohort. Analysis consisted of multiple logistic regression with statistical adjustment for the interdependence of observations. Of the 203 (17.1%) injection drug users who reported using a syringe after someone else, 78.3% reported sharing with close friends, and the adjusted odds ratio of any sharing and sharing with close friends was 30.9. Injection drug users were more likely to report sharing with a strong-tie close friend (adjusted odds ratio = 1.52) and less likely to report sharing with other close friends if those friends were weak ties and new to their network. Friendship ties were not stable, with fewer than 30% of the friends being repeat nominations. These data show that many injection drug users engage in selective risk taking that may minimize their disease risk exposure in the short term. The turnover in networks, however, suggests that programs need to emphasize the importance of exclusive use.


[Cognitive disorders in patients after surgical treatment of intracranial arterial aneurysms].
In the review of the literature the authors analyze the problem of neuropsychological disorders in patients after subarachnoid hemorrhage, particularly that caused by arterial aneurysm rupture. Currently available data on the epidemiology, clinical characteristics, and risk factors of cognitive disorders in patients operated on for intracranial aneurysm rupture are presented. Treatment strategies and timing of surgery are analyzed. The basic trends in evaluation and treatment of neuropsychological disorders in patients with subarachnoid hemorrhage are noted.


Nucleic acid-binding properties of a bacterially expressed potato virus Y helper component-proteinase.
The potyvirus helper component-proteinase (HC-Pro) is a multifunctional protein previously reported to have affinity for polyribonucleotides. To investigate further the ability of HC-Pro to bind nucleic acids, the potato virus Y (PVY) LYE84 isolate HC-Pro gene was amplified, cloned in an Escherichia coli expression vector and sequenced. HC-Pro was expressed as a fusion with the maltose-binding protein and purified by affinity chromatography. Electrophoretic mobility-shift assays demonstrated that HC-Pro acts as a sequence non-specific RNA-binding protein and suggest that more than one molecule of protein was bound per molecule of RNA. The HC-Pro RNA-binding activity was stable in 400 mm-NaCl and temperature sensitive. The recombinant protein preferentially bound ssRNA over DNA or dsRNA and showed little, if any, affinity for poly(A). The possible implications of the RNA-binding activity of HC-Pro in potyvirus replication and movement are discussed.


The effect of inflammation on Fos expression in the ferret trigeminal nucleus.
We have previously carried out detailed characterization and identification of Fos expression within the trigeminal nucleus after tooth pulp stimulation in ferrets. The aim of this study was to determine the effect of pulpal inflammation on the excitability of central trigeminal neurons following tooth pulp stimulation. Adult ferrets were prepared under anesthesia to allow tooth pulp stimulation, recording from the digastric muscle, and intravenous injections at a subsequent experiment. In some animals, pulpal inflammation was induced by introducing human caries into a deep buccal cavity. After 5 d, animals were re-anaethetized, and the teeth were stimulated at 10 times the threshold of the jaw-opening reflex. Stimulation of all tooth pulps induced ipsilateral Fos in the trigeminal subnuclei caudalis and oralis. All non-stimulated animals showed negligible Fos labeling, with no differences recorded between inflamed and non-inflamed groups. Following tooth pulp stimulation, Fos expression was greater in animals with inflamed teeth than in animals with non-inflamed teeth, with the greatest effect seen in the subnucleus caudalis. These results suggest that inflammation increases the number of trigeminal brainstem neurons activated by tooth pulp stimulation; this may be mediated by peripheral or central mechanisms.


Development of a neuromuscular electrical stimulation protocol for sprint training.
Sprint training is associated with several beneficial adaptations in skeletal muscle, including an enhancement of sarcoplasmic reticulum (SR) Ca(2+) release. Unfortunately, several patient populations (e.g., the elderly, those with cardiac dysfunction) that might derive great benefit from sprint exercise are unlikely to tolerate it. The purpose of this report was to describe the development of a tolerable neuromuscular electrical stimulation (NMES) protocol that induces skeletal muscle adaptations similar to those observed with sprint training. Our NMES protocol was modeled after a published sprint exercise protocol and used a novel electrode configuration and stimulation sequence to provide adequate training stimulus while maintaining subject tolerance. Nine young, healthy subjects (four men) began and completed the training protocol of the knee extensor muscles. All subjects completed the protocol, with ratings of discomfort far less than those reported in studies of traditional NMES. Training induced significant increases in SR Ca(2+) release and citrate synthase activity (~16% and 32%, respectively), but SR Ca(2+) uptake did not change. The percentage of myosin heavy chain IIx isoform was decreased significantly after training. At the whole muscle level, neither central activation nor maximum voluntary isometric contraction force were significantly altered, although isometric force did exhibit a trend toward an increase (~3%, P = 0.055). Surprisingly, the NMES training produced a significant increase in muscle cross-sectional area (~3%, P = 0.04). It seems that an appropriately designed NMES protocol can mimic many of the benefits of sprint exercise training, with a low overall time commitment and training volume. These findings suggest that NMES has the potential to bring the benefits of sprint exercise to individuals who are unable to tolerate traditional sprint training.


Expanding Collective Efficacy Theory to Reduce Violence Among African American Adolescents.
Community violence is a complex phenomenon, and many theories have been put forth to explain the causes of community violence and disparities in community violence across neighborhoods. One notable theory, collective efficacy theory (CET), posits that collective efficacy (i.e., a neighborhood's social cohesion and informal social control) mediates the association between concentrated disadvantage and community violence. As CET theorizes an inverse feedback loop between collective efficacy and community violence, collective efficacy could mitigate the link between neighborhood disadvantage and community violence. The current study examines the reciprocal association between collective efficacy and community violence exposure using data from 604 low-resourced, urban African American ninth-grade students from a large Midwestern city. Data were collected at 6-month intervals over 2 years. Significant cross-sectional associations were found between each of the collective efficacy constructs (social cohesion and informal social control) and community violence exposure, although no significant longitudinal cross-lagged associations were found. There were positive cross-sectional associations between (a) collective efficacy and community violence exposure and (b) informal social control and community violence exposure; however, the association between social cohesion and community violence exposure was negative. Associations between overall collective efficacy, as well as its subscales, and community violence exposure were consistent with hypothesized directions for social cohesion, but not for collective efficacy or informal social control. Findings support the use of collective efficacy as two constructs, rather than a single construct as proposed by Sampson et al. Implications for expanding original assumptions of CET are discussed.


Intracellular growth of Mycobacterium avium subspecies and global transcriptional responses in human macrophages after infection.
Mycobacterium avium subsp. avium (Maa) and M. avium subsp. hominissuis (Mah) are environmental mycobacteria and significant opportunistic pathogens. Mycobacterium avium infections in humans and pigs are mainly due to Mah. It is not known whether this is caused by a difference in virulence or difference in exposure to the two subspecies. The aim of the present study was to investigate the ability of the M. avium subspecies to replicate intracellularly and to characterise the gene expression program triggered by infection of human primary macrophages. All isolates were able to invade and persist within human macrophages. However, intracellular replication was only evident in cells infected with the two Maa isolates. Transcriptional responses to the isolates were characterized by upregulation of genes involved in apoptosis, immune- and inflammatory response, signal transduction and NF-kB signaling, cell proliferation and T-cell activation. Although similar pathways and networks were perturbed by the different isolates, the response to the Maa subspecies was exaggerated, and there was evidence of increased activation of type I and II interferon signaling pathways. Mycobacterium avium isolates of different genetic characteristics invaded monocytes and induced different degree of macrophage activation. Isolates of Maa were able to replicate intracellularly suggesting that differences in exposure, uptake or induction of adaptive immunity are more likely explanations for the difference in prevalence between M. avium subspecies.


Liver and brain tryptophan metabolism following hydrocortisone administration to rats and gerbils.
1 Liver tryptophan pyrrolase activity is low in the mongolian gerbil (Meriones unguiculatus) and is not induced by hydrocortisone (5 mg/kg). In contrast, there is measurable activity in the rat liver and this is induced by hydrocortisone. In vivo measurements confirmed the absence of induction in gerbils but suggested that they were able to metabolize tryptophan. However no detectable pyrrolase activity was found in any other tissues either before or after hydrocortisone. 2 In agreement with previous observations hydrocortisone decreased rat brain 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) 6 h after administration. Brain tryptophan concentrations were also decreased at this time. In contrast, hydrocortisone did not alter gerbil brain 5-HT, 5-HIAA or trytophan. alpha-Methyltryptophan activated hepatic tryptophan pyrrolase and decreased brain 5-HT and 5-HIAA in both animals. 3 Results suggest that the decrease in rat brain 5-HT and 5-HIAA following hydrocortisone may be associated with the rise in liver tryptophan pyrrolase and that the brain amine changes are mediated through the decrease in brain tryptophan concentration.


Speckle reducing anisotropic diffusion.
This paper provides the derivation of speckle reducing anisotropic diffusion (SRAD), a diffusion method tailored to ultrasonic and radar imaging applications. SRAD is the edge-sensitive diffusion for speckled images, in the same way that conventional anisotropic diffusion is the edge-sensitive diffusion for images corrupted with additive noise. We first show that the Lee and Frost filters can be cast as partial differential equations, and then we derive SRAD by allowing edge-sensitive anisotropic diffusion within this context. Just as the Lee and Frost filters utilize the coefficient of variation in adaptive filtering, SRAD exploits the instantaneous coefficient of variation, which is shown to be a function of the local gradient magnitude and Laplacian operators. We validate the new algorithm using both synthetic and real linear scan ultrasonic imagery of the carotid artery. We also demonstrate the algorithm performance with real SAR data. The performance measures obtained by means of computer simulation of carotid artery images are compared with three existing speckle reduction schemes. In the presence of speckle noise, speckle reducing anisotropic diffusion excels over the traditional speckle removal filters and over the conventional anisotropic diffusion method in terms of mean preservation, variance reduction, and edge localization.


Regional anesthesia for orthopedic procedures: What orthopedic surgeons need to know.
Regional anesthesia is an integral component of successful orthopedic surgery. Neuraxial anesthesia is commonly used for surgical anesthesia while peripheral nerve blocks are often used for postoperative analgesia. Patient evaluation for regional anesthesia should include neurological, pulmonary, cardiovascular, and hematological assessments. Neuraxial blocks include spinal, epidural, and combined spinal epidural. Upper extremity peripheral nerve blocks include interscalene, supraclavicular, infraclavicular, and axillary. Lower extremity peripheral nerve blocks include femoral nerve block, saphenous nerve block, sciatic nerve block, iPACK block, ankle block and lumbar plexus block. The choice of regional anesthesia is a unanimous decision made by the surgeon, the anesthesiologist, and the patient based on a risk-benefit assessment. The choice of the regional block depends on patient cooperation, patient positing, operative structures, operative manipulation, tourniquet use and the impact of post-operative motor blockade on initiation of physical therapy. Regional anesthesia is safe but has an inherent risk of failure and a relatively low incidence of complications such as local anesthetic systemic toxicity (LAST), nerve injury, falls, hematoma, infection and allergic reactions. Ultrasound should be used for regional anesthesia procedures to improve the efficacy and minimize complications. LAST treatment guidelines and rescue medications (intralipid) should be readily available during the regional anesthesia administration.


THIAMINE AND NICOTINIC ACID: ANAEROBIC GROWTH FACTORS FOR MUCOR ROUXII.
Bartnicki-Garcia, S. (Rutgers, the State University, New Brunswick, N. J.), and Walter J. Nickerson. Thiamine and nicotinic acid: Anaerobic growth factors for Mucor rouxii. J. Bacteriol. 82:142-148. 1961.-Mucor rouxii requires preformed thiamine and nicotinic acid for anaerobic growth. Such requirements are not manifested during aerobic incubation. Aerobically, the fungus was shown to be able to synthesize both vitamins. The yeastlike form and the filamentous form of anaerobically grown M. rouxii exhibit the same vitamin requirements. Thiamine can be substituted by its thiazole moiety. Under certain conditions, nicotinic acid was partly substituted by tryptophan, kynurenine, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid.Anaerobically. the fungus (thiamine requiring) was about ten times more susceptible to pyrithiamine antagonism than the same organism grown aerobically (thiamine independent).


Problems in defining cross-cultural "kinds of homosexuality" --and a solution.
Cross-cultural typologies of male homosexuality categorize widely different cultural expressions of same-sex behavior and orientation, but often without a deeper consideration of what it means for there to be kinds of homosexuality, or what the existence of separate kinds means for the category "homosexuality." In this paper the methods and results of these typologies are described and criticized, and a new interpretation of cultural expressions of homosexuality is offered in their place. The kinds of homosexuality are seen in terms of an activity of male consciousness, whereby male consciousness becomes progressively more oriented toward itself through each general kind. Finally a plan for a future systematic study of homosexuality is suggested, into which the reorganized typologies and other cultural material may be integrated.


Facial Acanthosis Nigricans: A Morphological Marker of Metabolic Syndrome.
Acanthosis nigricans (AN) is a frequently encountered entity. Facial AN (FAN) is a subset of AN which is being increasingly recognized. Recently, reports hypothesizing the association of FAN with features of metabolic syndrome have been published. The aim of this study was to study the clinicodemographic profile of patients with FAN, and to assess the correlation of hypertension, increased waist-hip ratio (WHR), increased body mass index (BMI), type 2 diabetes mellitus, deranged lipid profile, serum insulin, and impaired oral glucose tolerance test (OGTT) (parameters of metabolic syndrome) in these patients, as well as to determine the most significant predictor (highest relative risk) of development of FAN. A multicentric case-control study was conducted (123 cases in each group) over a period of 2 years. Data were obtained on the basis of history, examination, and relevant laboratory investigations. Statistical analysis was done using Statistica version 6 (StatSoft Inc., 2001, Tulsa, Oklahoma, USA), SPSS statistics version 17 (SPSS Inc., 2008, Illinois, Chicago, USA), and GraphPad Prism version 5 (GraphPad Software Inc., 2007, San Diego, California, USA). Mean age of the patients with FAN was 38.83 ± 8.62 years. Mean age of onset of the disease was 30.93 ± 8.18 years. The most common site of face involved was the forehead and temporal region. The most common pigmentation was brown-black. Male sex, positive OGTT, increased WHR, and increased BMI were most significantly related to FAN. Smoking was found to have a protective effect against the development of FAN. Here, we document a significant association between male patients with positive OGTT, increased WHR, and BMI and FAN. Thus, we propose that FAN could be considered a morphological marker of metabolic syndrome.


Regulation of the human cyclin C gene via multiple vitamin D3-responsive regions in its promoter.
The candidate human tumor suppressor gene cyclin C is a primary target of the anti-proliferative hormone 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3], but binding sites for the 1alpha,25(OH)2D3 receptor (VDR), so-called 1alpha,25(OH)2D3 response elements (VDREs), have not yet been identified in the promoter of this gene. We screened various cancer cell lines by quantitative PCR and found that the 1alpha,25(OH)2D3 inducibility of cyclin C mRNA expression, in relationship with the 24-hydroxylase (CYP24) gene, was best in MCF-7 human breast cancer cells. To characterize the molecular mechanisms, we analyzed 8.4 kb of the cyclin C promoter by using chromatin immunoprecipitation assays (ChIP) with antibodies against acetylated histone 4, VDR and its partner receptor, retinoid X receptor (RXR). The histone 4 acetylation status of all 23 investigated regions of the cyclin C promoter did not change significantly in response to 1alpha,25(OH)2D3, but four independent promoter regions showed a consistent, 1alpha,25(OH)2D3-dependent association with VDR and RXR over a time period of 240 min. Combined in silico/in vitro screening identified in each of these promoter regions a VDRE and reporter gene assays confirmed their functionality. Moreover, re-ChIP assays monitored simultaneous association of VDR with RXR, coactivator, mediator and RNA polymerase II proteins on these regions. Since cyclin C protein is associated with those mediator complexes that display transcriptional repressive properties, this study contributes to the understanding of the downregulation of a number of secondary 1alpha,25(OH)2D3-responding genes.


Outcome of thrombolysis and thrombectomy for thrombosed endografts inserted in the superficial femoral artery for occlusive disease.
To evaluate the efficacy and outcome of thrombolysis and thrombectomy for thrombosed polytetrafluoroethylene stent-grafts inserted in the superficial femoral artery (SFA) for occlusive disease. A retrospective review was conducted of 79 consecutive patients with a thrombosed SFA endograft between November 2001 and December 2011. Of these, 46 (58%) were treated with thrombolysis (n=40, 87%) or thrombectomy (n=6, 13%) and form the study group (33 men; median age 66.8 years, range 30-80). Median time from stent-graft insertion to thrombosis was 3 months (range 0-53). Thrombolysis was successful in 38 (95%) patients over a mean 24 hours (range 3-48); one patient had failed lysis and another died during lytic treatment. Thrombectomy was successful in all 6 patients. Thrombosis without a causal lesion was significantly more common in occlusions that presented <30 days after insertion (p=0.01). Over a median follow-up of 14 months (range 1-69), reinterventions were performed for restenosis in 12 patients and reocclusion in 14 patients, all within 18 months after thrombolytic treatment. More than a third of patients (16/45) had definitive failures (2/6 from the thrombectomy group); 4 were treated conservatively (no/minor symptoms) and 12 had bypass grafts. Three (7%) patients eventually required a major amputation. The primary, assisted primary, and secondary patency rates of thrombolysis at 6 months were 56%, 56%, and 68%, respectively. Secondary patency for the entire cohort was 58% at 1 year. Thrombolysis and thrombectomy of thrombosed endografts in the SFA is effective and safe. Patency rates after treatment are moderate, but prolonged secondary patency can be achieved.


Synergistic Engineering of Conduction Band, Conductivity, and Interface of Bilayered Electron Transport Layers with Scalable TiO2 and SnO2 Nanoparticles for High-Efficiency Stable Perovskite Solar Cells.
A simple, synergistic engineering of the conduction band (CB), conductivity, and interface of TiO2-based bilayered electron transport layers (ETLs) via scalable TiO2 and SnO2 nanoparticles processed at low temperature (≤ 100 °C) for regular planar perovskite solar cells (PSCs) was developed. The bottom layer (Lt-TiO2:SnO2 nanocomposite film) was prepared by spin coating from the ethanol suspension of small ground TiO2 nanoparticles with big ground SnO2 nanoparticles as the additive. The top C-SnO2 layer (spin-coated from the concentrated commercial SnO2 nanoparticles (C-SnO2 NPs, 20 wt %, 7 nm in size suspended in H2O)) can be regarded as an interlayer between Lt-TiO2:SnO2 and perovskite (Psk) absorbers. Bilayered Lt-TiO2:SnO2/C-SnO2 ETLs are dense films with a cascade CB, good conductivity, facile electron extraction/transport ability, and a highly hydrophilic surface for depositing high-quality Psk films. Regular planar PSCs based on Lt-TiO2:SnO2/C-SnO2 ETLs combined with a (FAI)0.90(PbI2)0.94(MABr)0.10(PbBr2)0.10 absorber and a spiro-OMeTAD hole transporter achieved the highest power conversion efficiency of 22.04% with a negligible current hysteresis. The champion cell lost less than 3% of the initial efficiency under continuous room lighting (1000 lux) for 1000 h (lost 10% after 2184 h) without encapsulation under an inert atmosphere. Four related low-temperature-processed ETLs (Lt-TiO2/C-SnO2, Lt-C-SnO2, Lt-TiO2:SnO2, and Lt-TiO2) were fabricated using the same metal oxide nanoparticle suspensions and studied simultaneously to reveal the function of each metal oxide in the bilayered Lt-TiO2:SnO2/C-SnO2 ETLs. In the bottom Lt-TiO2:SnO2 layer, small TiO2 nanoparticles were needed for making a dense film, and highly conducting big SnO2 nanoparticles are used to increase the conductivity of ETLs and a handy electron transport path for reducing the charge accumulation and series resistance of the cell. A top C-SnO2 layer (regarded as an interlayer between Psk and Lt-TiO2:SnO2) was used to extract/transport electrons facilely, to form a bilayered ETL with a cascade CB, and to create a hydrophilic surface to deposit high-quality Psk films to enhance the photovoltaic performance of the PSCs. This study provides a blueprint for designing good-performance ETLs for high-efficiency, stable regular planar PSCs using various sized nanoparticles prepared in a very simple and low-cost way.


Dephosphorylation of the mannose-6-phosphate recognition marker is localized in later compartments of the endocytic route. Identification of purple acid phosphatase (uteroferrin) as the candidate phosphatase.
The mannose-6-phosphate (Man6P) recognition marker in lysosomal proteins is known to be dephosphorylated after the delivery of lysosomal proteins to the endosome/lysosome compartment. The rate of Man6P recognition marker inactivation depends on the cell type and lysosomal protein. In the present study we show that in BHK 21 cells, which rapidly dephosphorylate lysosomal proteins, the recognition marker is stable in the endosomal compartment, to which lysosomal enzymes such as arylsulfatase A are delivered during endocytosis at 20 degrees C. Dephosphorylation depends on the transfer of internalized lysosomal enzymes from the 20 degrees C compartment to later compartments, most likely lysosomes. This transfer is sensitive to NH4C1 and nocodazole. In vitro experiments identified purple acid phosphatase (uteroferrin) as a candidate for the lysosomal phosphatase catalyzing in vivo the dephosphorylation of Man6P recognition marker.


Laparoscopic splenectomy for immune thrombocytopenic purpura.
To evaluate laparoscopic splenectomy as a treatment of immune thrombocytopenic purpura (ITP). Retrospective review of 18 patients followed up from 1 to 30 months. Referral center using community hospital. Consecutive series of patients undergoing laparoscopic splenectomy for ITP. Laparoscopic splenectomy. Surgical and hematologic results. Eighteen patients underwent laparoscopic splenectomy for ITP. All procedures were completed laparoscopically. There was no perioperative mortality. Pancreatitis developed in 1 patient (6%); 17 (94%) of 18 patients responded to splenectomy. The mean platelet count increased from 29 x 10(9) to 461 x 10(9)/L after laparoscopic splenectomy and stabilized at 327 x 10(9)/L (mean follow-up period, 15 months). Mean (+/- SEM) operative blood loss was 214 +/- 52 mL, necessitating no transfusions. Mean hospital stay was 2 days (range, 1-7 days). Most patients tolerated a liquid diet the day of the operation and a solid diet the next day. Parenteral narcotic usage averaged 12.3 morphine equivalent units, and 6 patients (33%) required no parenteral analgesia. An accessory spleen was identified in 1 patient (6%). Mean (+/- SEM) operative time was 130 +/- 8 minutes and was significantly less in the second half of our experience (117 vs 144 minutes, P = .04). Laparoscopic splenectomy is safe and effective for the management of ITP and allows rapid recovery. With increasing experience, operative times decrease. Laparoscopic splenectomy should be the treatment of choice for patients with ITP who require splenectomy.


High allele frequency of the p.Q258X mutation and identification of a novel mis-splicing mutation in the STAR gene in Korean patients with congenital lipoid adrenal hyperplasia.
Steroidogenic acute regulatory (STAR) protein plays a crucial role in steroidogenesis, and mutations in the STAR gene cause congenital lipoid adrenal hyperplasia (CLAH). This study investigated the STAR mutation spectrum and functionally analyzed a novel STAR mutation in Korean patients with CLAH. Mutation analysis of STAR was carried out in 25 unrelated Korean CLAH patients. A region of STAR comprising exons 4-7 was cloned from human genomic DNA into an expression vector, followed by site-directed mutagenesis and transient expression in COS7 cells. The splicing pattern was analyzed by in vitro transcription, and each transcript was functionally characterized by measuring pregnenolone production in COS7 cells cotransfected with the cholesterol side chain cleavage system. Mutation p.Q258X was identified in 46 of 50 alleles (92%); mutation c.653C>T was detected in two alleles (4%); and mutations p.R182H and c.745-6_810del were found in one allele (2%). Reverse transcriptase-PCR products amplified from a patient heterozygous for compound c.653C>T and c.745-6_810del mutation revealed multiple alternatively spliced mRNAs. In vitro expression analysis of a minigene consisting of exons 4-7 containing the c.653C>T yielded two transcripts in which exon 6 or exons 5 and 6 were skipped. The encoded proteins exhibited defective pregnenolone-producing ability. The c.745-6_810del mutation led to full and partial intron retention. p.Q258X is the most common STAR mutation in Korea. A previously reported c.653C>T variant was found to cause aberrant splicing at the mRNA level, resulting in perturbation of STAR function. The c.745-6_810del mutation also resulted in aberrant splicing.


[Forensic phenotyping: How far along?]
The prediction of a person's aspect from analysis of an anonymous DNA sample has made significant progress in the last decade. Pigmentation (eyes, hair and, more recently, skin colour) can now be determined with good accuracy; face shape is still not amenable to prediction (except, in general lines, from ancestry). Age can apparently also be determined from methylation profiles. Police forces are, understandably, very interested in this technology, with a tendency to over-estimate its accuracy. Legislation varies greatly, with some nations opting for complete prohibition (Germany) and others allowing wide application of the approach (United Kingdom).


Biosynthesis and bioproduction of coenzyme Q10 by yeasts and other organisms.
CoQ (coenzyme Q), an isoprenylated benzoquinone, is a well-known component of the electron-transfer system in eukaryotes. The main role of CoQ is to transfer electrons from NADH dehydrogenase and succinate dehydrogenase to CoQ:cytochrome c reductase in the respiratory chain. However, recent evidence indicates that an involvement in respiration is not the only role of CoQ. The second apparent role of CoQ is its anti-oxidation property, and other novel roles for CoQ, such as in disulfide-bond formation, sulfide oxidation and pyrimidine metabolism, have been reported. CoQ10, having ten isoprene units in the isoprenoid side chain, has been used as a medicine and is now commercially popular as a food supplement. Two yeast species, namely the budding yeast Saccharomyces cerevisiae, which produces CoQ6, and the fission yeast Schizosaccharomyces pombe, which produces CoQ10, are the main subjects of the present minireview because they have greatly contributed to our basic knowledge of CoQ biosynthesis among eukaryotes. The biosynthetic pathway that converts p-hydroxybenzoate into CoQ consists of eight steps in yeasts. The five enzymes involved in the biosynthetic pathway have been identified in both yeasts, yet the functions of three proteins were still not known. Analyses of the biosynthetic pathway in yeasts also contribute to the understanding of human genetic diseases related to CoQ deficiency. In the present minireview I focus on the biochemical and commercial aspects of CoQ in yeasts and in other organisms for comparison.


Manipulating meso-scale solvent structure from Pd nanoparticle deposits in deep eutectic solvents.
Deep Eutectic Solvents (DESs) are complex solutions that present unique challenges compared to traditional solvents. Unlike most aqueous electrolytes and ionic liquids, DESs have delicate hydrogen bond networks that are responsible for their highly sensitive compositional dependence on the melting point. Prior work has demonstrated a unique nanoscale structure both experimentally and theoretically that brings both challenges and opportunities to their adoption in traditional electrochemical processes. In this study, we use in situ sample-rotated ultra-small angle x-ray scattering to resolve the near-interface solvent structure after electrodepositing Pd nanoparticles onto a glassy carbon electrode in choline chloride:urea and choline chloride:ethylene glycol DESs. Our results indicate that a hierarchical solvent structure can be observed on the meso-scale in the choline chloride:urea and choline chloride:ethylene glycol systems. Importantly, this extended solvent structure increases between -0.3 V and -0.5 V (vs Ag/AgCl) and remains high until -0.9 V (vs Ag/AgCl). Experimentally, the nature of this structure is more pronounced in the ethylene glycol system, as evidenced by both the x-ray scattering and the electrochemical impedance spectroscopy. Molecular dynamics simulations and dipolar orientation analysis reveal that chloride delocalization near the Pd interface and long-range interactions between the choline and each hydrogen bond donor (HBD) are very different and qualitatively consistent with the experimental data. These results show how the long-range solvent-deposit interactions can be tuned by changing the HBD in the DES and the applied potential.


Mapping tertiary interactions in protein folding reactions: a novel mass spectrometry- and chemical synthesis-based approach.
A novel mass spectrometry- and chemical synthesis-based approach for studying protein folding reactions is described, and its initial application to study the folding/unfolding reaction of a homo-hexameric enzyme 4-oxalocrotonate (4OT) is reported. This new approach involves the application of total chemical synthesis to prepare protein analogues that contain a photoreactive amino acid site-specifically incorporated into their primary amino acid sequence. To this end, a photoreactive amino acid-containing analogue of 4OT in which Pro-1 was replaced with p-benzoyl-l-phenylalanine (Bpa) was prepared. This analogue can be used to map structurally specific protein-protein interactions in 4OT's native folded state. These photocrosslinking studies and peptide mapping results with (PlBpa)4OT indicate that this construct is potentially useful for probing the structural properties of equilibrium and kinetic intermediates in 4OT's folding reaction.


Fast and efficient QTL mapper for thousands of molecular phenotypes.
In order to discover quantitative trait loci, multi-dimensional genomic datasets combining DNA-seq and ChiP-/RNA-seq require methods that rapidly correlate tens of thousands of molecular phenotypes with millions of genetic variants while appropriately controlling for multiple testing. We have developed FastQTL, a method that implements a popular cis-QTL mapping strategy in a user- and cluster-friendly tool. FastQTL also proposes an efficient permutation procedure to control for multiple testing. The outcome of permutations is modeled using beta distributions trained from a few permutations and from which adjusted P-values can be estimated at any level of significance with little computational cost. The Geuvadis & GTEx pilot datasets can be now easily analyzed an order of magnitude faster than previous approaches. Source code, binaries and comprehensive documentation of FastQTL are freely available to download at http://fastqtl.sourceforge.net/ firstname.lastname@example.com or email@example.com Supplementary data are available at Bioinformatics online.


Relation of extent of extracranial carotid artery atherosclerosis as measured by B-mode ultrasound to the extent of coronary atherosclerosis.
The extent of carotid artery atherosclerosis as measured by B-mode ultrasound has been shown to be strongly and independently correlated with the presence or absence of coronary atherosclerotic disease (CAD), but no studies to date have used carotid B-mode ultrasound to compare the extent of atherosclerotic disease in the two arterial circulations. We used data from a registry of patients undergoing cardiac catheterization and B-mode ultrasound of the carotid arteries to compare the extent of CAD (number of major coronary vessels with 50% or greater stenosis as judged by a consensus interpretation) with the extent of extracranial carotid atherosclerosis. Four hundred thirty-four patients (234 men, 200 women) greater than 40 years of age were stratified by gender and then divided into quartiles on the basis of a B-mode score that was derived by summing arterial wall thickness at nine sites in the left and nine sites in the right carotid arteries. Evaluation of extent of CAD for the four B-mode quartiles showed that men in the lowest B-mode quartile were over six times more likely to have normal coronary arteries than three- to four-vessel CAD, while men in the highest B-mode quartile were over 10 times more likely to have three- to four-vessel CAD than normal coronary arteries. The findings were similar for women but not as dramatic. Gender-specific discriminant function models using traditional risk factors alone or in combination with B-mode score were developed to predict the extent of CAD.(ABSTRACT TRUNCATED AT 250 WORDS)


Hypofractionated stereotactic radiation therapy: an effective therapy for recurrent high-grade gliomas.
Salvage options for recurrent high-grade gliomas (HGGs) are limited by cumulative toxicity and limited efficacy despite advances in chemotherapeutic and radiotherapeutic techniques. Previous studies have reported encouraging survival results and favorable toxicity with fractionated stereotactic radiotherapy, and small studies have shown similar benefit using a shortened course of hypofractionated stereotactic radiation therapy (H-SRT). We sought to determine the efficacy and toxicity profile of H-SRT alone or in addition to repeat craniotomy or concomitant chemotherapy. Between 1994 and 2008, 147 patients with recurrent HGG were treated with H-SRT (median dose, 35 Gy in 3.5-Gy fractions). Cox regression models were used to analyze survival outcomes. Variables included age, surgery before H-SRT, time to first recurrence, reirradiation dose, inclusion of chemotherapy with H-SRT, and gross tumor volume (GTV). Younger age (P = .001), smaller GTV (P = .025), and shorter time between diagnosis and recurrence (P = .034) were associated with improvement in survival from H-SRT. Doses of radiation > or = 35 Gy approached significance (P = .07). There was no significant benefit of surgical resection or chemotherapy in this population when analysis was controlled for other prognostic factors. H-SRT was well tolerated and resulted in a median survival time of 11 months after H-SRT, independent of re-operation or concomitant chemotherapy. Patients who experienced recurrence within 6 months after initial treatment had an excellent response and should not be disqualified from H-SRT. This is the largest series to examine the efficacy and tolerability of H-SRT in recurrent HGG.


Dichotomy in the NRT gene families of dicots and grass species.
A large proportion of the nitrate (NO(3)(-)) acquired by plants from soil is actively transported via members of the NRT families of NO(3)(-) transporters. In Arabidopsis, the NRT1 family has eight functionally characterised members and predominantly comprises low-affinity transporters; the NRT2 family contains seven members which appear to be high-affinity transporters; and there are two NRT3 (NAR2) family members which are known to participate in high-affinity transport. A modified reciprocal best hit (RBH) approach was used to identify putative orthologues of the Arabidopsis NRT genes in the four fully sequenced grass genomes (maize, rice, sorghum, Brachypodium). We also included the poplar genome in our analysis to establish whether differences between Arabidopsis and the grasses may be generally applicable to monocots and dicots. Our analysis reveals fundamental differences between Arabidopsis and the grass species in the gene number and family structure of all three families of NRT transporters. All grass species possessed additional NRT1.1 orthologues and appear to lack NRT1.6/NRT1.7 orthologues. There is significant separation in the NRT2 phylogenetic tree between NRT2 genes from dicots and grass species. This indicates that determination of function of NRT2 genes in grass species will not be possible in cereals based simply on sequence homology to functionally characterised Arabidopsis NRT2 genes and that proper functional analysis will be required. Arabidopsis has a unique NRT3.2 gene which may be a fusion of the NRT3.1 and NRT3.2 genes present in all other species examined here. This work provides a framework for future analysis of NO(3)(-) transporters and NO(3)(-) transport in grass crop species.


Oxidative Stress as the Main Target in Diabetic Retinopathy Pathophysiology.
Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus (DM) causing vision impairment even at young ages. There are numerous mechanisms involved in its development such as inflammation and cellular degeneration leading to endothelial and neural damage. These mechanisms are interlinked thus worsening the diabetic retinopathy outcome. In this review, we propose oxidative stress as the focus point of this complication onset.


Extraskeletal Ewing's sarcoma: a case report and review of the literature.
Case report. To report on the diagnosis and current treatment of a rare tumor about the cervical spine. Extraskeletal Ewing's sarcoma (EES) is rare and has not been previously described about the cervical spine. We present a case of a 24-year-old man with a large mass in the posterior triangle of the neck extending through the vertebral foramens of the cervical vertebrae. This was identified as an extraskeletal Ewing's sarcoma. Traditional treatment paradigms have been associated with a poor prognosis. Since the recommendations of the Intergroup Rhabdomyosarcoma Study II study of multimodal chemotherapy and radiotherapy, this tumor has a significantly better prognosis. Surgical debulking of the tumor was necessary to relieve cord compression. Histologic analysis was used to confirm both magnetic resonance imaging and computed tomography diagnosis. A chemoradiation therapy program was commenced in accordance with Intergroup Rhabdomyosarcoma Study II recommendations. Computed tomography and magnetic resonance imaging demonstrated a large lobulated mass extending through the exit foramens of C2/C3 and C3/C4. The mass was entirely extraskeletal and extradural. Histologic examination of the excised mass showed microscopy consistent with extraskeletal Ewing's sarcoma. After surgical debulking and chemoradiation, the patient made a complete recovery. A review of the literature confirms that extraskeletal Ewing's sarcoma is a rare tumor and particularly so in the region of the cervical spine. Early diagnosis and surgical debulking combined with current multimodality chemoradiation programs can produce a favorable outcome.


[Thromboembolic disease and congenital venous abnormalities].
A pulmonary embolus and a bilateral thrombosis of the internal carotid artery caused the sudden death of two young adults with a congenital venous abnormality. The study of 49 patients suffering from a Klippel-Trenaunay syndrome showed that 11 out of 49 patients, or 22.5 p. cent had thrombosis problems: namely 7 pulmonary emboli and 8 deep thrombophlebitis. Phlebography did not permit to discover any specific anatomical abnormality. 5 out of 11 patients presented avalvular and dilated deep veins. 6 out of 11 presented angioma of the pelvis. In the group of patients with Klippel-Trenaunay who never presented a deep venous thrombosis, the same signs are noted in one third of the cases. It is possible that coagulation insufficiency may explain the high number of thrombophlebitis. However, an extended analysis of 11 patients did not permit to discover any abnormality. But, subsequently, a study of the fibrinolytic activity demonstrated a normal fibrinogen level, while the fibrinopeptide A level was markedly elevated in each case, with an abnormal thrombin activity.


Fear-avoidance beliefs, catastrophizing, and distress: a longitudinal subgroup analysis on patients with musculoskeletal pain.
The aim of the present study was to describe fear-avoidance beliefs, catastrophizing, and emotional distress among musculoskeletal pain patients in primary healthcare and to explore the relationship of psychological risk profiles for pain, function, and sick leave from baseline through 1-year and 3-year follow-ups. Ratings from 110 musculoskeletal pain patients were collected and cluster analysis was used to identify subgroups with similar patterns on fear-avoidance beliefs, catastrophizing, and emotional distress. The clusters were examined cross-sectionally and prospectively on sick leave, function, and pain. Five distinct profiles were found: "low scores cluster," "high score cluster," "fear-avoidance beliefs and catastrophizing cluster," "distress only cluster," and "medium catastrophizing cluster." The "low scores cluster" and "distress only cluster" had the most favorable scores on outcome variables. The analysis of common developmental pathways showed considerable stability over time. Reorganization of clusters in a psychological "high risk cluster" and a "low risk cluster" showed significant differences at 1-year and 3-year follow-ups in functional ability as well as in decreased sick leave. There were no significant differences between the groups on average pain ratings at the 2 measure points. Distinct profiles of catastrophizing, fear-avoidance beliefs, and emotional distress were extracted and meaningfully related to future sick leave and dysfunction outcomes. The structures of the profiles were essentially stable and became more accentuated across a 3-year period. The results underscore the need to address psychological aspects as fear-avoidance beliefs, catastrophizing, and emotional distress in the management of patients with musculoskeletal pain and may open the path for a better tailored treatment approach for this patient group.


Studies of anticipation in bipolar affective disorder.
Anticipation refers to the increase in disease severity or decrease in age of onset in successive generations. The concept evolved from the theories and dogma of degeneration that were pervasive in psychiatry and medicine in the late 19th century and into the early 20th century. The term was set aside with the criticism of geneticist Lionel Penrose, who argued that anticipation was the result of ascertainment biases. The renewed interest in anticipation followed the identification of its molecular genetic basis in the form of unstable trinucleotide repeats. Subsequently, several diseases have been studied clinically for the presence of anticipation. Although anticipation has been identified in many diseases, including bipolar disorder, only diseases showing a pattern of progressive neurodegeneration have been associated with unstable trinucleotide repeats. This review summarizes the research on anticipation in bipolar disorder and other secular trends in the patterns of the illness such as the cohort effect. The changing nature of bipolar disorder is likely to be a result of combined influences from several genes, some of which are likely to be in a state of flux, as well as environmental or cultural forces that converge to give the clinical picture of anticipation.


Nomenclature for factors of the dog major histocompatibility system (DLA), 1998. First report of the ISAG DLA Nomenclature Committee. International Society for Animals Genetics.
A Nomenclature Committee for factors of the dog major histocompatibility system or dog leukocyte antigen (DLA) has been convened under the auspices of the International Society for Animal Genetics (ISAG) to define a sequence-based nomenclature for the genes of the DLA system. The remit of this committee includes: i) assignment of gene names; ii) rules for naming alleles; iii) assignment of names to published alleles; iv) assignment of names to new alleles; and v) rules for acceptance of new alleles.


Pulmonary fibrosis: searching for model answers.
Substantial challenges remain in our understanding of fibrotic lung diseases. Nowhere is this more true than in the elucidation and verification of the pathogenetic basis upon which they develop. Scientific progress, most recently in the field of experimental therapy, has relied closely on interpreting data derived from animal modeling. Such models are used to identify the cellular interactions and molecular pathways involved in lung tissue repair and fibrosis. Over the coming years, the significance of new discoveries will continue to be evaluated using the in vivo analysis of animal models substituting for patients with actual pulmonary fibrosis. The commonest strategy to induce experimental pulmonary fibrosis is by directly administering a profibrotic agent to either wild-type animals or those that bear a specific genetic modification. The creation of new models has been greatly enhanced by the availability of stem cell lines and methods for introducing genetic mutations into these cells. Despite an increasing choice of models, there are still good reasons to continue adapting and using one of its earliest examples, the bleomycin model, in post-genomic pulmonary fibrosis research. A brief review of the exacting requirements of such research will place the strengths of this particular model in perspective.


Similarities and differences in the glycosylation mechanisms in prokaryotes and eukaryotes.
Recent years have witnessed a rapid growth in the number and diversity of prokaryotic proteins shown to carry N- and/or O-glycans, with protein glycosylation now considered as fundamental to the biology of these organisms as it is in eukaryotic systems. This article overviews the major glycosylation pathways that are known to exist in eukarya, bacteria and archaea. These are (i) oligosaccharyltransferase (OST)-mediated N-glycosylation which is abundant in eukarya and archaea, but is restricted to a limited range of bacteria; (ii) stepwise cytoplasmic N-glycosylation that has so far only been confirmed in the bacterial domain; (iii) OST-mediated O-glycosylation which appears to be characteristic of bacteria; and (iv) stepwise O-glycosylation which is common in eukarya and bacteria. A key aim of the review is to integrate information from the three domains of life in order to highlight commonalities in glycosylation processes. We show how the OST-mediated N- and O-glycosylation pathways share cytoplasmic assembly of lipid-linked oligosaccharides, flipping across the ER/periplasmic/cytoplasmic membranes, and transferring "en bloc" to the protein acceptor. Moreover these hallmarks are mirrored in lipopolysaccharide biosynthesis. Like in eukaryotes, stepwise O-glycosylation occurs on diverse bacterial proteins including flagellins, adhesins, autotransporters and lipoproteins, with O-glycosylation chain extension often coupled with secretory mechanisms.


Insulin-like growth factor-I in Helicobacter pylori gastritis and response to eradication using bismuth based triple therapy.
To measure insulin-like growth factor-I (IGF-I) concentrations in the presence and absence of Helicobacter pylori infection and in response to eradication of the organism. An enzyme linked immunosorbent assay was used to measure gastric and fasting serum concentrations of IGF-I in 17 patients with and 11 without H pylori infection. Repeat assessments were performed in the infected patients six weeks after they received a two week course of bismuth chelate, metronidazole, and amoxycillin. IGF-I was detected at very low concentrations in gastric juice and in mucosal incubates. The median serum IGF-I concentration was 88 micrograms/l in the patients infected with H pylori compared with 90 micrograms/l in the non-infected controls; IGF-I concentrations dropped to 77 micrograms/l following eradication therapy (p = 0.014). The similarity in baseline IGF-I concentrations in the presence and absence of H pylori suggests that their subsequent drop after treatment is more likely to be due to the treatment.


Nutritional status at diagnosis in children with cancer. 2. An assessment by arm anthropometry.
Assessment of nutritional status in children with cancer is important but measures based on weight can be problematic at diagnosis, especially in those with advanced disease. Likewise, dual energy x-ray absorptiometry may be confounded by other radiological procedures and is not commonly available in low-income countries where most children with cancer live. Arm anthropometry is not subject to these constraints. In a study sample of 99 Canadian patients with cancer at diagnosis, mid-upper arm circumference correlated well with lean body mass as measured by dual energy x-ray absorptiometry but triceps skin fold thickness was a poor predictor of fat mass. Arm anthropometry can be a useful tool for the measurement of nutritional status in children with cancer. However, further studies, particularly in low-income countries and in children with solid tumors at diagnosis, are required to determine the full extent of its utility.


[The method of estimation of endothelium functional condition in patients with essential arterial hypertension in combination with diabetes mellitus type 2].
The method of estimation of endothelium-dependent vasodilatation (EDVD) of the brachial artery has been elaborated to the patients with essential arterial hypertension stage II in combination with diabetes mellitus type 2 using the method of multivariate regression analysis as an alternative to the reactive hyperemia test using high-resolution ultrasound. The method allows estimating of EDVD of the brachial artery on the basis of five traditional parameters of ultrasound diagnostics without special equipment. This simplifies the diagnosis, significantly reduces its duration and might have widespread use in the primary diagnosis.


[State of taste sensitivity to table salt in male workers with high blood pressure and in normotensive ones].
The article covers data on studies of sensitivity to common salt in machinery construction workers of Moscow suburb, to reveal individuals prone to arterial hypertension. Increased threshold of sensitivity to common salt was seen in 52.6% of the workers observed by occupational therapists as having arterial hypertension, among the normotensive workers the increased threshold was seen only in 18%. Being noninvasive and simple, the method detecting sensitivity to common salt, that obtained data in examination of workers exposed to occupational hazards and having increased or normal blood pressure, is recommended as a screening tool to identify workers prone to arterial hypertension. The workers with increased threshold of sensitivity to common salt are advised to reduce salt in diet.


Establishment of a modified QuEChERS extraction and liquid chromatography-tandem mass spectrometry method for multiple pesticide residues followed by determination of the residue levels and exposure assessment in livestock urine.
The establishment of an analytical method for pesticide residues in livestock urine can realize the real-time monitoring of pesticide pollution in livestock breeding. In this study, a novel method was developed for the determination of 106 pesticide residues in livestock urine based on a modified QuEChERS extraction and liquid chromatography-tandem mass spectrometry. Acetonitrile was used to extract target analytes through acidic and alkaline switching of the sample environment. The purification effect of captiva EMR-Lipid on samples was investigated. Three kinds of materials, C18, polar enhanced polymer (PEP), N-propylethylenediamine (PSA), were selected from 20 kinds of materials as adsorbents for QuEChERS. A mass analysis was carried out using simultaneous scanning in both positive and negative ion mode and multiple reaction monitoring mode. All analytes showed good linearity, with correlation coefficients (R2) greater than 0.9923; their limits of quantification were 0.02-1.95 ng/mL. The average recoveries at low, medium, and high spiked levels were in the range of 70.1 %-117.3 %, with intra-day precision ranging from 3.4 % to 16.9 % and inter-day precision ranging from 4.0 % to 19.3 %. The established analytical method was used to analyze the pesticide residue in swine urine and bovine urine collected from farms in Yining, Xinjiang, China. A total of 8 pesticides were detected, and the residue ranged from less than the limit of quantitation to 22.4 ng/mL. The top three pesticides with the highest detection frequency were clothianidin, thiamethoxam, and dinotefuran. The exposure assessment based on the monitored pesticide residue concentration levels showed that the detected pesticides could pose little risk to cattle and pigs.


Modifications to rat lens major intrinsic protein in selenite-induced cataract.
To identify modifications to rat lens major intrinsic protein (MIP) isolated from selenite-induced cataract and to determine whether m-calpain (EC 18.104.22.168) is responsible for cleavage of MIP during cataractogenesis. Cataracts were induced in rats by a single injection of sodium selenite. Control and cataract lenses were harvested on day 16 and dissected into cortical and nuclear regions. Membranes were washed with urea buffer followed by NaOH. The protein was reduced/alkylated, delipidated, and cleaved with cyanogen bromide (CNBr). Cleavage products were fractionated by high-performance liquid chromatography (HPLC), and peptides were characterized by mass spectrometry and tandem mass spectrometry. MIP cleavage by m-calpain was carried out by incubation with purified enzyme, and peptides released from the membrane were analyzed by Edman sequencing. The intact C terminus, observed in the control nuclear and cataractous cortical membranes, was not observed in the cataractous nuclear membranes. Mass spectrometric analysis revealed heterogeneous cleavage of the C terminus of MIP in control and cataract nuclear regions. The major site of cleavage was between residues 238 and 239, corresponding to the major site of in vitro cleavage by m-calpain. However, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometric analysis indicated that in vivo proteolysis during cataract formation also included sites closer to the C terminus not produced by m-calpain in vitro. Evidence for heterogeneous N-terminal cleavage was also observed at low levels with no differences between control and cataractous lenses. The major site of phosphorylation was determined to be at serine 235. Specific sites of MIP N- and C-terminal cleavage in selenite-induced cataractous lenses were identified. The heterogeneous cleavage pattern observed suggests that m-calpain is not the sole enzyme involved in MIP C-terminal processing in rat lens nuclei.


Development and Characterization of Metformin Loaded Pectin Nanoparticles for T2 Diabetes Mellitus.
The present investigation was aimed to formulate and evaluate Metformin loaded pectin (PCM) nanoparticles (NPs) for sustained action for management of Type 2 Diabetes Mellitus (T2DM). The nanoparticles were formulated by ionic gelation technique. The nano-formulations were subjected for the analyses of entrapment efficiency and drug release stud for 12h. The optimized formulation examined various in vitro characterizations such as particle size, zeta potential, surface morphology and FTIR studies. The in vitro heamocomptability, protein binding stability and glucose uptake studies were performed with nanoparticles. The PCMNP-4 showed drug entrapment efficiency, 68 ± 4.2 % and demonstrated favourable in vitro prolonged release characteristics. The mean particles diameter of optimized formulation was 482.7 nm and 0.270 poly dispersity index (PI), had spherical shape and zeta potential of (+38.85 mV). In addition, the nanoparticles were reasonably stable in the presence of excess bovine serum albumin, which suggested that the nanoparticles may also be stable in the blood stream. The percentage of haemolysis induced by Metformin and placebo PCNPs were less than 5%. The results indicated that the PCMNPs are hemocompatible and therefore, safe for oral administration. The glucose uptake was increased 1.5 fold in RBCs and L6 skeleton muscle cell line compared with Metformin. Hence, the designed nanoparticle system could possibly be advantageous in terms of prolonged release, to achieve reduced dose frequency and improve patient compliance.


ATP and UTP responses of cultured rat aortic smooth muscle cells revisited: dominance of P2Y2 receptors.
1. It has previously been shown that ATP and UTP stimulate P2Y receptors in vascular smooth muscle cells (VSMCs), but the nature of these receptors, in particular the contribution of P2Y2 and P2Y4 subtypes, has not been firmly established. Here we undertake a further pharmacological analysis of [3H]inositol polyphosphate responses to nucleotides in cultured rat VSMCs. 2. ATP generated a response that was partial compared to UTP, as reported earlier. 3. In the presence of a creatine phosphokinase (CPK) system for regenerating nucleoside triphosphates, the response to ATP was increased, the response to UTP was unchanged, and the difference between UTP and ATP concentration-response curves disappeared. Chromatographic analysis showed that ATP was degraded slightly faster than UTP. 4. The response to UDP was always smaller than that to UTP, but with a shallow slope and a high potency component. In the presence of hexokinase (which prevents the accumulation of ATP/UTP from ADP/UDP), the maximum response to UDP was reduced and the high-potency component of the curve was retained. By contrast, the response to ADP was weaker throughout in the presence of hexokinase. 5. ATP gamma S was an effective agonist with a similar EC50 to UTP, but with a lower maximum. ITP was a weak agonist compared with UTP. 6. Suramin was an effective antagonist of the response to UTP (pA2=4.48), but not when ATP was the agonist. However, suramin was an effective antagonist (pA2=4.45) when stimulation with ATP was in the presence of the CPK regenerating system. 7. Taken together with the results of others, these findings indicate that the response of cultured rat VSMCs to UTP and to ATP is predominantly at the P2Y2 receptor, and that there is also a response to UDP at the P2Y6 receptor.


What contributes to depression in Parkinson's disease?
Depression is a common problem in patients with Parkinson's disease, but its mechanism is poorly understood. It is thought that neurochemical changes contribute to its occurrence, but it is unclear why some patients develop depression and others do not. Using a community-based sample of patients with Parkinson's disease, we investigated the contributions of impairment, disability and handicap to depression in Parkinson's disease. Ninety-seven patients seen in a population-based study on the prevalence of Parkinson's disease completed the Beck Depression Inventory (BDI). Clinical and historical information on symptoms and complications of Parkinson's disease were obtained from the patients by a neurologist. In addition, clinician and patient ratings of disability on the Schwab and England scale were obtained and a quality of life questionnaire was completed. Moderate to severe depression (BDI > or = 18) was reported by 19.6% of the patients. Higher depression scores were associated with advancing disease severity, recent self-reported deterioration, higher akinesia scores, a mini-mental score of < 25 and occurrence of falls. Disability as rated by the neurologist accounted for 34% of the variance of depression scores. Self-reported impairment of cognitive function and the feeling of stigmatization accounted for > 50% of the variance of depression scores. Depression in patients with Parkinson's disease is associated with advancing disease severity, recent disease deterioration and occurrence of falls. Regression analysis suggests that depression in Parkinson's disease is more strongly influenced by the patients' perceptions of handicap than by actual disability. The treatment of depression should therefore be targeted independently of treatment of the motor symptoms of Parkinson's disease, and consider the patients' own perception of their disease.


Work, telework, and mental health during COVID-19.
This review addresses the impact of the COVID-19 pandemic on workers' mental health, in particular, teleworking conditions. Our analysis is based on documents from several international organizations and specialized scientific publications. The retrieved information reveals that the pandemic has had a significant effect on the mental health of frontline workers and employees who had to migrate to a virtual environment without prior warning. However, a positive aspect is reflected in the development of several remote mental health care devices implemented to protect vulnerable population, frontline workers, and the general population. Finally, this paper underscores the importance of developing public policies for protecting workers' mental health.


Identification and characterization of uvrA, a DNA repair gene of Deinococcus radiodurans.
Deinococcus radiodurans is extraordinarily resistant to DNA damage, because of its unusually efficient DNA repair processes. The mtcA+ and mtcB+ genes of D. radiodurans, both implicated in excision repair, have been cloned and sequenced, showing that they are a single gene, highly homologous to the uvrA+ genes of other bacteria. The Escherichia coli uvrA+ gene was expressed in mtcA and mtcB strains, and it produced a high degree of complementation of the repair defect in these strains, suggesting that the UvrA protein of D. radiodurans is necessary but not sufficient to produce extreme DNA damage resistance. Upstream of the uvrA+ gene are two large open reading frames, both of which are directionally divergent from the uvrA+ gene. Evidence is presented that the proximal of these open reading frames may be irrB+.


Associations between obsessive-compulsive classes and pathological gambling in a national cohort of male twins.
Because of shared characteristics, pathological gambling (PG) has been variously conceptualized as an obsessive-compulsive (OC) spectrum disorder or as an addictive disorder. Prior community-based studies have not systematically determined the association between PG and OC features and whether common genetic factors contribute to both conditions. To examine the association and genetic correlation between PG and OC features. We performed a latent class analysis (LCA) of OC features, cross-sectional tests of association, and classic twin genetic analysis using results of telephone interviews conducted from March 2002 through November 2003. Participants included 1675 male twin pairs from the Vietnam Era Twin Registry, aged 45 to 60 years. Ten OC features were queried and used to derive OC classes identified via LCA. The best-fitting LCA model identified the following 4 OC classes: unaffected (class 1), ritual/symmetry compulsions (class 2), germ/contamination obsessions (class 3), and severe OC (class 4). All PG symptoms were more common in class 4 OC and 6 of 10 PG symptoms were significantly more common in class 4 OC (P < .01). Participants in the severe class were most likely to have 4 or more DSM-IV or DSM-5 PG diagnostic criteria (odds ratio, 3.8 [95% CI, 1.8-8.2]). The genetic correlation between phenotypes was 0.44 (95% CI, 0.16-0.75). The association between OC features and diagnostic criteria for PG highlights a role of obsessions and compulsivity in PG, and the lifetime co-occurrence of these disorders results in part from common genetic variance. Phenotypic and genetic overlap between OC features and PG add to our understanding of the most appropriate classification of PG and offers insights for treatment development.


Cloning and characterization of an aminoglycoside 6'-N-acetyltransferase gene from Citrobacter freundii which confers an altered resistance profile.
A novel gene encoding a 6'-N-aminoglycoside acetyltransferase, aac(6')-In, has been cloned and sequenced from Citrobacter freundii 13996-19, a clinical isolate from Venezuela. This gene mediates resistance to amikacin, 2'-N-ethylnetilmicin, isepamicin, kanamycin, netilmicin, and tobramycin. The aac(6')-In gene is 573 nucleotides in length and encodes a putative protein of 190 amino acids. AAC(6')-In is most closely related to AAC(6')-Im and AAC(6')-Ie, demonstrating 64.4% and 62.3% similarity, respectively, at the protein level, suggesting these proteins share a common ancestor. The aac(6')-In flanking sequences demonstrated homology to integron- and transposon-related elements which are often found associated with resistance determinants. Hybridization studies performed with an intragenic probe specific for aac(6')-In indicate that this gene is prevalent within Venezuela but has not been observed outside of the country. Furthermore, the aac(6)-In gene was found in 10 different species of gram-negative bacteria.


Direct and indirect effect of the COVID-19 pandemic on patients with cardiomyopathy.
(1) To evaluate the prevalence and hospitalisation rate of COVID-19 infections among patients with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM) in the Royal Brompton and Harefield Hospital Cardiovascular Research Centre (RBHH CRC) Biobank. (2) To evaluate the indirect impact of the pandemic on patients with cardiomyopathy through the Heart Hive COVID-19 study. (3) To assess the impact of the pandemic on national cardiomyopathy-related hospital admissions. (1) 1236 patients (703 DCM, 533 HCM) in the RBHH CRC Biobank were assessed for COVID-19 infections and hospitalisations; (2) 207 subjects (131 cardiomyopathy, 76 without heart disease) in the Heart Hive COVID-19 study completed online surveys evaluating physical health, psychological well-being, and behavioural adaptations during the pandemic and (3) 11 447 cardiomyopathy-related hospital admissions across National Health Service (NHS) England were studied from NHS Digital Hospital Episode Statistics over 2019-2020. A comparable proportion of patients with cardiomyopathy in the RBHH CRC Biobank had tested positive for COVID-19 compared with the UK population (1.1% vs 1.6%, p=0.14), but a higher proportion of those infected were hospitalised (53.8% vs 16.5%, p=0.002). In the Heart Hive COVID-19 study, more patients with cardiomyopathy felt their physical health had deteriorated due to the pandemic than subjects without heart disease (32.3% vs 13.2%, p=0.004) despite only 4.6% of the cardiomyopathy cohort reporting COVID-19 symptoms. A 17.9% year-on-year reduction in national cardiomyopathy-related hospital admissions was observed in 2020. Patients with cardiomyopathy had similar reported rates of testing positive for COVID-19 to the background population, but those with test-proven infection were hospitalised more frequently. Deterioration in physical health amongst patients could not be explained by COVID-19 symptoms, inferring a significant contribution of the indirect consequences of the pandemic. NCT04468256.


Energy Regulation in Inflammatory Sarcopenia by the Purinergic System.
The purinergic system has a dual role: the maintenance of energy balance and signaling within cells. Adenosine and adenosine triphosphate (ATP) are essential for maintaining these functions. Sarcopenia is characterized by alterations in the control of energy and signaling in favor of catabolic pathways. This review details the association between the purinergic system and muscle and adipose tissue homeostasis, discussing recent findings in the involvement of purinergic receptors in muscle wasting and advances in the use of the purinergic system as a novel therapeutic target in the management of sarcopenia.


Multiple supra-aortic stenting for Takayasu arteritis: extensive revascularization and two-year follow-up.
A patient with Takayasu arteritis with multiple supra-aortic lesions underwent successful treatment with two-staged stent implantation. Stenotic bilateral common carotid, innominate, and left subclavian arteries were dilated, and no restenosis was observed during the follow-up period of 2 years despite recurrent inflammation. Stenting for supra-aortic vessels in cases of Takayasu arteritis has rarely been reported, and to our knowledge, this is the first report of multiple stent placement for all the supra-aortic branches involved.