bluuebunny/crossref_metadata_2025_split huggingface dataset:
An integrative variant analysis suite for whole exome next-generation sequencing data
Authors: Challis Danny , Yu Jin , Evani Uday S , Jackson Andrew R , Paithankar Sameer , Coarfa Cristian , Milosavljevic Aleksandar , Gibbs Richard A , Yu Fuli 
Published: January 2012

Abstract

Background
Whole exome capture sequencing allows researchers to cost-effectively sequence the coding regions of the genome. Although the exome capture sequencing methods have become routine and well established, there is currently a lack of tools specialized for variant calling in this type of data.

Results
Using statistical models trained on validated whole-exome capture sequencing data, the Atlas2 Suite is an integrative variant analysis pipeline optimized for variant discovery on all three of the widely used next generation sequencing platforms (SOLiD, Illumina, and Roche 454). The suite employs logistic regression models in conjunction with user-adjustable cutoffs to accurately separate true SNPs and INDELs from sequencing and mapping errors with high sensitivity (96.7%).

Conclusion
We have implemented the Atlas2 Suite and applied it to 92 whole exome samples from the 1000 Genomes Project. The Atlas2 Suite is available for download at http://sourceforge.net/projects/atlas2/. In addition to a command line version, the suite has been integrated into the Genboree Workbench, allowing biomedical scientists with minimal informatics expertise to remotely call, view, and further analyze variants through a simple web interface. The existing genomic databases displayed via the Genboree browser also streamline the process from variant discovery to functional genomics analysis, resulting in an off-the-shelf toolkit for the broader community.
COPD exacerbations in general practice: variability in oral prednisolone courses
Authors: de Vries Marianne , Berendsen Annette J , Bosveld Henk EP , Kerstjens Huib AM , van der Molen Thys 
Published: January 2012

Abstract

Background
The use of oral corticosteroids as treatment of COPD exacerbations in primary care is well established and evidence-based. However, the most appropriate dosage regimen has not been determined and remains controversial. Corticosteroid therapy is associated with a number of undesirable side effects, including hyperglycaemias, so differences in prescribing might be relevant. This study examines the differences between GPs in dosage and duration of prednisolone treatment in patients with a COPD exacerbation. It also investigates the number of general practitioners (GPs) who adjust their treatment according to the presence of diabetic co-morbidity.

Methods
Cross-sectional study among 219 GPs and 25 GPs in training, located in the Northern part of the Netherlands.

Results
The response rate was 69%. Nearly every GP prescribed a continuous dose of prednisolone 30 mg per day. Among GPs there were substantial differences in treatment duration. GPs prescribed courses of five, seven, ten, or fourteen days. A course of seven days was most common. The duration of treatment depended on exacerbation and disease severity. A course of five days was especially prescribed in case of a less severe exacerbation. In a more severe exacerbation duration of seven to fourteen days was more common. Hardly any GP adjusted treatment to the presence of diabetic co-morbidity.

Conclusion
Under normal conditions GPs prescribe prednisolone quite uniformly, within the range of the current Dutch guidelines. There is insufficient guidance regarding how to adjust corticosteroid treatment to exacerbation severity, disease severity and the presence of diabetic co-morbidity. Under these circumstances, there is a substantial variation in treatment duration.
LPS induced inflammatory responses in human peripheral blood mononuclear cells is mediated through NOX4 and Giα dependent PI-3kinase signalling
Authors: Ngkelo Anta , Meja Koremu , Yeadon Mike , Adcock Ian , Kirkham Paul A 
Published: January 2012

Abstract
COPD is a disease of innate immunity and bacterial infections are a dominant cause of exacerbations in the later stages resulting in poor health and high mortality. The pathogen-associated molecular pattern (PAMP) lipopolysaccharide (LPS) is sensed by immune cells through activation of the toll-like receptor 4 (TLR4). This leads to the activation of NADPH oxidase (NOX) and NF-κB which together drive COPD inflammation. In this study we show in human PBMCs that LPS stimulated proinflammatory cytokine release (CXCL8 and IL6) was inhibited by approximately 50% by the broad specificity phosphatidylinositol 3-kinase (PI3K) inhibitor, wortmannin. Our results also demonstrate that activation of PI3K following LPS stimulation is mediated by a NOX4 dependent mechanism releasing endogenous H2O2, as the NOX4 inhibitor apocynin blocked LPS induced AKT phosphorylation. Moreover, LPS-induced PI3K activation was inhibited by the anti-oxidant N-acetylcysteine in a concentration dependent manner (IC50 ~100 μM). In addition, our data demonstrated that inhibition of small G proteins, by pre-treatment with pertussis toxin, inhibited LPS-induced AKT phosphorylation. Furthermore, the G-protein inhibitors pertussis toxin and mastoparan both inhibited LPS-induced CXCL8 and IL-6 release by approximately 50%. Together, these data indicate there is a mechanism in human PBMCs where TLR4 activation by LPS leads to ROS generation through NOX4 and activation of the PI3K pathway. This effect is apparently mediated through small G proteins facilitating the release of pro-inflammatory cytokines.
SYBR Green-based Real-Time PCR targeting kinetoplast DNA can be used to discriminate between the main etiologic agents of Brazilian cutaneous and visceral leishmaniases
Authors: Pita-Pereira Daniela , Lins Rachel , Oliveira Marcia P , Lima Rosimar B , Pereira Bernardo AS , Moreira Otacilio C , Brazil Reginaldo P , Britto Constança 
Published: January 2012

Abstract

Background
Leishmaniases control has been hampered by the unavailability of rapid detection methods and the lack of suitable therapeutic and prophylactic measures. Accurate diagnosis, which can distinguish between Leishmania isolates, is essential for conducting appropriate prognosis, therapy and epidemiology. Molecular methods are currently being employed to detect Leishmania infection and categorize the parasites up to genus, complex or species level. Real-time PCR offers several advantages over traditional PCR, including faster processing time, higher sensitivity and decreased contamination risk.

Results
A SYBR Green real-time PCR targeting the conserved region of kinetoplast DNA minicircles was able to differentiate between Leishmania subgenera. A panel of reference strains representing subgenera Leishmania and Viannia was evaluated by the derivative dissociation curve analyses of the amplified fragment. Distinct values for the average melting temperature were observed, being 78.95°C ± 0.01 and 77.36°C ± 0.02 for Leishmania and Viannia, respectively (p < 0.05). Using the Neighbor-Joining method and Kimura 2-parameters, the alignment of 12 sequences from the amplified conserved minicircles segment grouped together L. (V.) braziliensis and L. (V.) shawii with a bootstrap value of 100%; while for L. (L.) infantum and L. (L.) amazonensis, two groups were formed with bootstrap values of 100% and 62%, respectively. The lower dissociation temperature observed for the subgenus Viannia amplicons could be due to a lower proportion of guanine/cytosine sites (43.6%) when compared to species from subgenus Leishmania (average of 48.4%). The method was validated with 30 clinical specimens from visceral or cutaneous leishmaniases patients living in Brazil and also with DNA samples from naturally infected Lutzomyia spp. captured in two Brazilian localities.

Conclusions
For all tested samples, a characteristic amplicon melting profile was evidenced for each Leishmania subgenus, corroborating the data from reference strains. Therefore, the analysis of thermal dissociation curves targeting the conserved kinetoplast DNA minicircles region is able to provide a rapid and reliable method to identify the main etiologic agents of cutaneous and visceral leishmaniases in endemic regions of Brazil.
Determination of SGK1 mRNA in non-small cell lung cancer samples underlines high expression in squamous cell carcinomas
Authors: Abbruzzese Claudia , Mattarocci Stefano , Pizzuti Laura , Mileo Anna M , Visca Paolo , Antoniani Barbara , Alessandrini Gabriele , Facciolo Francesco , Amato Rosario , D'Antona Lucia , Rinaldi Massimo , Felsani Armando , Perrotti Nicola , Paggi Marco G 
Published: January 2012

Abstract

Background
Lung cancer represents the most frequent cause of death for cancer. In non-small cell lung cancer (NSCLC), which accounts for the vast majority of this disease, only early detection and treatment, when possible, may significantly affect patient's prognosis. An important role in NSCLC malignancy is attributed to the signal transduction pathways involving PI3Kinase, with consequent activation of the AKT family factors. The serum and glucocorticoid kinase (SGK) factors, which share high structural and functional homologies with the AKT factors, are a family of ubiquitously expressed serine/threonine kinases under the control of cellular stress and hormones. SGK1 is the most represented SGK member.

Methods
By means of immunohistochemistry and quantitative real-time PCR, we determined SGK1 protein and mRNA expression in a cohort of 66 formalin-fixed, paraffin-embedded NSCLC surgical samples. All samples belonged to patients with a well-documented clinical history.

Results
mRNA expression was significantly higher in squamous cell carcinomas, and correlated with several clinical prognostic indicators, being elevated in high-grade tumors and in tumors with bigger size and worse clinical stage. No correlation was found between SGK1 protein expression and these clinical parameters.

Conclusions
This explorative analysis of SGK1 expression in NSCLC samples highlights the potential role of this factor in NSCLC patients' prognosis. Moreover, the higher expression in the squamous cell carcinoma subtype opens new therapeutic possibilities in this NSCLC subtype by designing specific kinase inhibitors.
Intellectual disability and other neuropsychiatric outcomes in high-risk children of mothers with schizophrenia, bipolar disorder and unipolar major depression
Authors: Morgan Vera A. , Croft Maxine L. , Valuri Giulietta M. , Zubrick Stephen R. , Bower Carol , McNeil Thomas F. , Jablensky Assen V. 
Published: January 2012

BackgroundRecent evidence points to partially shared genetics of neuropsychiatric disorders.AimsWe examined risk of intellectual disability and other neuropsychiatric outcomes in 3174 children of mothers with schizophrenia, bipolar disorder or unipolar major depression compared with 3129 children of unaffected mothers.MethodWe used record linkage across Western Australian population-based registers. The contribution of obstetric factors to risk of intellectual disability was assessed.ResultsChildren were at significantly increased risk of intellectual disability with odds ratios (ORs) of 3.2 (95% CI 1.8–5.7), 3.1 (95% CI 1.9–4.9) and 2.9 (95% CI 1.8–4.7) in the maternal schizophrenia, bipolar disorder and unipolar depression groups respectively. Multivariate analysis suggests familial and obstetric factors may contribute independently to the risk. Although summated labour/delivery complications (OR = 1.4, 95% CI 1.0–2.0) just failed to reach significance, neonatal encephalopathy (OR = 7.7, 95% CI 3.0–20.2) and fetal distress (OR = 1.8, 95% CI 1.1–2.7) were independent significant predictors. Rates of rare syndromes in children of mothers with mental disorder were well above population rates. Risk of pervasive developmental disorders, including autism, was significantly elevated for children of mothers with bipolar disorder. Risk of epilepsy was doubled for children of mothers with unipolar depression.ConclusionsOur findings provide epidemiological support for clustering of neuropsychiatric disorders. Further larger epidemiological studies are warranted.
Treatment-resistant and insufficiently treated depression and all-cause mortality following myocardial infarction
Authors: Scherrer Jeffrey F. , Chrusciel Timothy , Garfield Lauren D. , Freedland Kenneth E. , Carney Robert M. , Hauptman Paul J. , Bucholz Kathleen K. , Owen Richard , Lustman Patrick J. 
Published: January 2012

BackgroundDepression is a known risk factor for mortality after an acute myocardial infarction. Patients with treatment-responsive depression may have a better prognosis than those with treatment-resistant depression.AimsWe sought to determine whether mortality following acute myocardial infarction was associated with treatment-resistant depression.MethodFollow-up began after myocardial infarction and continued until death or censorship. Depression was counted as present if diagnosed any time during the study period. Treatment for depression was defined as receipt of 12 or more weeks of continuous antidepressant therapy at a therapeutic dose during follow-up. Treatment-resistant depression was defined as use of two or more antidepressants plus augmentation therapy, receipt of electroconvulsive therapy or use of monoamine oxidase inhibitors. Mean duration of follow-up was 39 months.ResultsDuring follow-up of 4037 patients with major depressive disorder who had had a myocardial infarction, 6.9% of those with insufficiently treated depression, 2.4% of those with treated depression and 5.0% of those with treatment-resistant depression died. A multivariable survival model that adjusted for sociodemographics, anxiety disorders, beta-blocker use, mortality risk factors and health service utilisation indicated that compared with treated patients, insufficiently treated patients were 3.04 (95% CI 2.12–4.35) times more likely and patients with treatment-resistant depression were 1.71 (95% CI 1.05–2.79) times more likely to die.ConclusionsAll-cause mortality following an acute myocardial infarction is greatest in patients with depression who are insufficiently treated and is a risk in patients with treatment-resistant depression. However, the risk of mortality associated with treatment-resistant depression is partly explained by comorbid disorders. Further studies are warranted to determine whether changes in depression independently predict all-cause mortality.
The effect of near‐bed turbulence on sperm dilution and fertilization success of broadcast‐spawning bivalves
Authors: Quinn Noel P. , Ackerman Josef D. 
Published: January 2012

Lay AbstractMany marine and some freshwater bottom‐dwelling (benthic) invertebrates broadcast their gametes into the water column where fertilization occurs. The relatively slow swimming speed and rapid dilution of sperm by water currents is thought to limit fertilization, even though species that reproduce this way can be extremely successful. We examined how water velocity and bottom roughness affected the fertilization success of zebra and quagga mussels (Dreissena polymorpha and D. bugensis) in a laboratory flow chamber and in Lake Erie. Our results demonstrate that velocity gradients dilute the concentration of sperm to levels that can lead to sperm limitation. We also found that the strength and pattern of the turbulence in the water flow near the bottom had a strong effect on fertilization. Bottom roughness that led to the ejection of fluid away from the bottom—such as what occurs downstream of a patch of mussels—contributed to higher fertilization success than bottom roughness that led to skimming flows or sweeps of flow toward the bed. Bottom roughness needs to be considered in biological and other transport processes occurring near the bottom.Biologically, dreissenid mussels are the first freshwater benthic organisms that have been shown to be sperm limited. Ecologically, the presence of their shells in the flow chamber and on the lakebed in Lake Erie created sufficient roughness to affect fertilization success. In other words, the mussels had changed the physical environment in a way that favored their reproduction. This new observation helps to explain why dreissenid mussels are successful invaders of freshwater ecosystems.
The mysterious cognitive abilities of bees: why models of visual processing need to consider experience and individual differences in animal performance
Authors: Dyer Adrian G. 
Published: January 2012

SummaryVision is one of the most important modalities for the remote perception of biologically important stimuli. Insects like honeybees and bumblebees use their colour and spatial vision to solve tasks, such as navigation, or to recognise rewarding flowers during foraging. Bee vision is one of the most intensively studied animal visual systems, and several models have been developed to describe its function. These models have largely assumed that bee vision is determined by mechanistic hard-wired circuits, with little or no consideration for behavioural plasticity or cognitive factors. However, recent work on both bee colour vision and spatial vision suggests that cognitive factors are indeed a very significant factor in determining what a bee sees. Individual bumblebees trade-off speed for accuracy, and will decide on which criteria to prioritise depending upon contextual information. With continued visual experience, honeybees can learn to use non-elemental processing, including configural mechanisms and rule learning, and can access top-down information to enhance learning of sophisticated, novel visual tasks. Honeybees can learn delayed-matching-to-sample tasks and the rules governing this decision making, and even transfer learned rules between different sensory modalities. Finally, bees can learn complex categorisation tasks and display numerical processing abilities for numbers up to and including four. Taken together, this evidence suggests that bees do have a capacity for sophisticated visual behaviours that fit a definition for cognition, and thus simple elemental models of bee vision need to take account of how a variety of factors may influence the type of results one may gain from animal behaviour experiments.
Long-term memory and response generalization in mushroom body extrinsic neurons in the honeybee Apis mellifera
Authors: Haehnel Melanie , Menzel Randolf 
Published: January 2012

SUMMARY
Honeybees learn to associate an odor with sucrose reward under conditions that allow the monitoring of neural activity by imaging Ca2+ transients in morphologically identified neurons. Here we report such recordings from mushroom body extrinsic neurons – which belong to a recurrent tract connecting the output of the mushroom body with its input, potentially providing inhibitory feedback – and other extrinsic neurons. The neurons' responses to the learned odor and two novel control odors were measured 24 h after learning. We found that calcium responses to the learned odor and an odor that was strongly generalized with it were enhanced compared with responses to a weakly generalized control. Thus, the physiological responses measured in these extrinsic neurons accurately reflect what is observed in behavior. We conclude that the recorded recurrent neurons feed information back to the mushroom body about the features of learned odor stimuli. Other extrinsic neurons may signal information about learned odors to different brain regions.
Independence of net water flux from paracellular permeability in the intestine ofFundulus heteroclitus, a euryhaline teleost
Authors: Wood Chris M. , Grosell Martin 
Published: January 2012

SUMMARYParacellular permeability and absorptive water flux across the intestine of the euryhaline killifish were investigated using in vitro gut sac preparations from seawater- and freshwater-acclimated animals. The permeability of polyethylene glycol (PEG), a well-established paracellular probe, was measured using trace amounts of radiolabelled oligomers of three different molecular sizes (PEG-400, PEG-900 and PEG-4000) at various times after satiation feeding. All three PEG molecules were absorbed, with permeability declining as a linear function of increasing hydrodynamic radius. Response patterns were similar in seawater and freshwater preparations, though water absorption and PEG-900 permeability were greater in the latter. Despite up to 4-fold variations in absorptive water flux associated with feeding and fasting (highest at 1–3 h, lowest at 12–24 h and intermediate at 1–2 weeks post-feeding), there were no changes in PEG permeability for any size oligomer. When PEG permeability was measured in the opposite direction (i.e. serosal to mucosal) from net water flux, it was again unchanged. HgCl2 (10–3 mol l–1), a putative blocker of aquaporins, eliminated absorptive water flux yet increased PEG-4000 permeability by 6- to 8-fold in both freshwater and seawater preparations. Experimentally raising the serosal osmolality by addition of 300 mmol l–1 mannitol increased the absorptive water flux rate 10-fold, but did not alter PEG permeability. Under these conditions, HgCl2 reduced absorptive water flux by 60% and again increased PEG permeability by 6- to 8-fold in both freshwater and seawater preparations. Clearly, there was no influence of solvent drag on PEG movement. The putative paracellular blocker 2,4,6-triaminopyrimidine (TAP, 20 mmol l–1) had no effect on net water flux or PEG permeability. We conclude that PEG and water move by separate pathways; absorptive water transport probably occurs via a transcellular route in the intestine of Fundulus heteroclitus.
Wake structures behind a swimming robotic lamprey with a passively flexible tail
Authors: Leftwich Megan C. , Tytell Eric D. , Cohen Avis H. , Smits Alexander J. 
Published: January 2012

SUMMARY
A robotic lamprey, based on the silver lamprey, Ichthyomyzon unicuspis, was used to investigate the influence of passive tail flexibility on the wake structure and thrust production during anguilliform swimming. A programmable microcomputer actuated 11 servomotors that produce a traveling wave along the length of the lamprey body. The waveform was based on kinematic studies of living lamprey, and the shape of the tail was taken from a computer tomography scan of the silver lamprey. The tail was constructed of flexible PVC gel, and nylon inserts were used to change its degree of flexibility. Particle image velocimetry measurements using three different levels of passive flexibility show that the large-scale structure of the wake is dominated by the formation of two pairs of vortices per shedding cycle, as seen in the case of a tail that flexed actively according to a pre-defined kinematic pattern, and did not bend in response to fluid forces. When the tail is passively flexible, however, the large structures are composed of a number of smaller vortices, and the wake loses coherence as the degree of flexibility increases. Momentum balance calculations indicate that, at a given tailbeat frequency, increasing the tail flexibility yields less net force, but changing the cycle frequency to match the resonant frequency of the tail increases the force production.