bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-Frequency Horizontal Semicircular Canal Function in Certain Menière’s Disease
Authors: Jerin Claudia , Maxwell Rebecca , Gürkov Robert 
Published: May 2018

Objectives:
To characterize video head impulse testing (vHIT) in definitive Menière’s disease and to investigate the relationship between vHIT results and other audiovestibular function tests.

Design:
Fifty-four patients with certain Menière’s disease, that is, patients with clinically definite Menière’s disease and endolymphatic hydrops visualized by locally enhanced inner ear MR imaging, were recruited for this study. All patients underwent vHIT. The vestibular-ocular reflex gain at 60 ms and refixation saccades were the outcome parameters measured. Saccades were characterized by determining the saccade frequency, their mean latency, and their mean velocity.

Results:
Seven of 54 patients had bilateral normal vHITs. Clearly pathologically vHITs with decreased gain and refixation saccades were observed in further seven patients. The majority of patients exhibited vHITs with refixation saccades but normal gain. Saccades mostly occurred bilaterally. There was no correlation between vHIT gain or saccades and caloric irrigation, cervical vestibular evoked myogenic potential or audiometry for Menière’s ears. Furthermore, vHIT gain or saccades correlated neither with age nor with the duration of the disease.

Conclusions:
Pathological low vHIT gain values are rarely observed in patients with certain Menière’s disease, while refixation saccades occur very frequently. In the majority of patients, saccades occur bilaterally. In Menière’s disease, in contrast to vestibular neuritis, there is no compensatory decrease of saccade latency over time.
Preperitoneal or Subcutaneous Wound Catheters as Alternative for Epidural Analgesia in Abdominal Surgery
Authors: Mungroop Timothy H. , Bond Marinde J. , Lirk Philipp , Busch Olivier R. , Hollmann Markus W. , Veelo Denise P. , Besselink Marc G. 
Published: May 2018

Objective:
To assess whether the location of wound catheters (ie, preperitoneal vs. subcutaneous) impacts outcomes, when compared with alternatives such as epidural analgesia.

Background:
Continuous wound infiltration is an alternative for epidural analgesia in abdominal surgery but studies have shown conflicting results. This difference could be explained by different efficacy of preperitoneal versus subcutaneous placement of the infiltrative catheters.

Methods:
A systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines until April 3, 2017. Primary endpoints were pain scores in rest and when moving at 24 hours postoperatively. Secondary endpoints included postoperative pain scores at 12 and 48 hours, functional recovery, pain treatment-related complications, and patient satisfaction.

Results:
After screening 2283 studies, 29 randomized controlled trials (RCTs) with 2059 patients were included. Methodological quality of these RCTs ranged from moderate to high. In the one direct comparison (60 patients), preperitoneal catheters led to better pain control than subcutaneous catheters. Superiority of preperitoneal compared with subcutaneous placement was confirmed indirectly in placebo-controlled RCTs. Preperitoneal wound catheters provided comparable pain control compared with active controls, such as epidural analgesia. Recovery parameters, opioid consumption, incidence of hypotension, and patient satisfaction seemed to be in favor of preperitoneal wound catheters compared with active alternatives, as well as placebo.

Conclusion:
Continuous wound infiltration with preperitoneal wound catheters is an effective pain modality in abdominal surgery. Pain control is as effective as epidural analgesia, but could be favored based upon recovery parameters and patient satisfaction.
Analyzing Enzyme Kinetic Data Using the Powerful Statistical Capabilities of R
Authors: Huitema Carly , Horsman Geoff 
Published: May 2018

AbstractWe describe a powerful tool for enzymologists to use for typical non-linear fitting of common equations in enzyme kinetics using the statistical program R. Enzyme kinetics is a powerful tool for understanding enzyme catalysis, regulation, and inhibition but tools to perform the analysis have limitations. Software to perform the necessary nonlinear analysis may be proprietary, expensive or difficult to use, especially for a beginner. The statistical program R is ideally suited to analyzing enzyme kinetic data; it is free in two respects: there is no cost and there is freedom to distribute and modify. It is also robust, powerful and widely used in other fields of biology. In this paper we introduce the program R to enzymologists who want to analyze their data but are unfamiliar with R or similar command line statistical analysis programs. Data are inputted and examples of different non-linear models are fitted. Results are extracted and plots are generated to assist judging the goodness of fit. The instructions will allow users to create their own modifications to adapt the protocol to their own experiments. Because of the use of scripts, a method can be modified and used to analyze different datasets in less than one hour.
The genetic prehistory of the Greater Caucasus
Authors: Wang Chuan-Chao , Reinhold Sabine , Kalmykov Alexey , Wissgott Antje , Brandt Guido , Jeong Choongwon , Cheronet Olivia , Ferry Matthew , Harney Eadaoin , Keating Denise , Mallick Swapan , Rohland Nadin , Stewardson Kristin , Kantorovich Anatoly R. , Maslov Vladimir E. , Petrenko Vladimira G. , Erlikh Vladimir R. , Atabiev Biaslan Ch. , Magomedov Rabadan G. , Kohl Philipp L. , Alt Kurt W. , Pichler Sandra L. , Gerling Claudia , Meller Harald , Vardanyan Benik , Yeganyan Larisa , Rezepkin Alexey D. , Mariaschk Dirk , Berezina Natalia , Gresky Julia , Fuchs Katharina , Knipper Corina , Schiffels Stephan , Balanovska Elena , Balanovsky Oleg , Mathieson Iain , Higham Thomas , Berezin Yakov B. , Buzhilova Alexandra , Trifonov Viktor , Pinhasi Ron , Belinskiy Andrej B. , Reich David , Hansen Svend , Krause Johannes , Haak Wolfgang 
Published: May 2018

AbstractArchaeogenetic studies have described the formation of Eurasian ‘steppe ancestry’ as a mixture of Eastern and Caucasus hunter-gatherers. However, it remains unclear when and where this ancestry arose and whether it was related to a horizon of cultural innovations in the 4thmillennium BCE that subsequently facilitated the advance of pastoral societies likely linked to the dispersal of Indo-European languages. To address this, we generated genome-wide SNP data from 45 prehistoric individuals along a 3000-year temporal transect in the North Caucasus. We observe a genetic separation between the groups of the Caucasus and those of the adjacent steppe. The Caucasus groups are genetically similar to contemporaneous populations south of it, suggesting that – unlike today – the Caucasus acted as a bridge rather than an insurmountable barrier to human movement. The steppe groups from Yamnaya and subsequent pastoralist cultures show evidence for previously undetected farmer-related ancestry from different contact zones, while Steppe Maykop individuals harbour additional Upper Palaeolithic Siberian and Native American related ancestry.
Disproportionate feedback interactions govern cell-type specific proliferation in mammalian cells
Authors: Sengupta Dola , Kompella Vijay Phanindra Srikanth , Kar Sandip 
Published: May 2018

AbstractIn mammalian cells, the critical decision to maintain quiescence over proliferation commitment in and around the G1-S transition depends on more than one intertwined feedback interaction, and is highly cell-type dependent. However, the precise role played by these individual feedback regulations, in order to generate such diverse nature of proliferation commitment, is still poorly understood. Herein, we propose a generic mathematical model of G1-S transition in mammalian cells that not only reconciles distinct single cell experimental observations in a cell-type specific manner, but also makes experimentally testable non-intuitive predictions. Intriguingly, The model analysis reveals that the feedback motifs responsible for the G1-S transition act in a disparate fashion to organize the cell-type specific proliferation response in different mammalian cells. The proposed model, in principle, can be effectively tuned to explore proliferation dynamics in a cell-type specific way to gain crucial insights about novel therapeutic intervention to prevent unwanted cellular proliferation.
Supercharging enables organized assembly of synthetic biomolecules
Authors: Simon Anna J. , Ramasubramani Vyas , Glaser Jens , Pothukuchy Arti , Gerberich Jillian , Leggere Janelle , Morrow Barrett R. , Golihar Jimmy , Jung Cheulhee , Glotzer Sharon C. , Taylor David W. , Ellington Andrew D. 
Published: May 2018

AbstractThere are few methods for the assembly of defined protein oligomers and higher order structures that could serve as novel biomaterials. Using fluorescent proteins as a model system, we have engineered novel oligomerization states by combining oppositely supercharged variants. A well-defined, highly symmetrical 16-mer (two stacked, circular octamers) can be formed from alternating charged proteins; higher order structures then form in a hierarchical fashion from this discrete protomer. During SUpercharged PRotein Assembly (SuPrA), electrostatic attraction between oppositely charged variants drives interaction, while shape and patchy physicochemical interactions lead to spatial organization along specific interfaces, ultimately resulting in protein assemblies never before seen in nature.
Prefrontal co-expression of schizophrenia risk genes is associated with treatment response in patients
Authors: Pergola Giulio , Di Carlo Pasquale , Jaffe Andrew E. , Papalino Marco , Chen Qiang , Hyde Thomas M. , Kleinman Joel E. , Shin Joo Heon , Rampino Antonio , Blasi Giuseppe , Weinberger Daniel R. , Bertolino Alessandro 
Published: May 2018

AbstractGene co-expression networks are relevant to functional and clinical translation of schizophrenia (SCZ) risk genes. We hypothesized that SCZ risk genes may converge into coexpression pathways which may be associated with gene regulation mechanisms and with response to treatment in patients with SCZ. We identified gene co-expression networks in two prefrontal cortexpost-mortemRNA sequencing datasets (total N=688) and replicated them in four more datasets (total N=227). We identified and replicated (all p-values<.001) a single module enriched for SCZ risk loci (13 risk genes in 10 loci).In silicoscreening of potential regulators of the SCZ risk module via bioinformatic analyses identified two transcription factors and three miRNAs associated with the risk module. To translatepost-morteminformation into clinical phenotypes, we identified polymorphisms predicting co-expression and combined them to obtain an index approximating module co-expression (Polygenic Co-expression Index: PCI). The PCI-co-expression association was successfully replicated in two independent brain transcriptome datasets (total N=131; all p-values<.05). Finally, we tested the association between the PCI and short-term treatment response in two independent samples of patients with SCZ treated with olanzapine (total N=167). The PCI was associated with treatment response in the positive symptom domain in both clinical cohorts (all p-values<.05).In summary, our findings in a large sample of humanpost-mortemprefrontal cortex show that coexpression of a set of genes enriched for schizophrenia risk genes is relevant to treatment response. This co-expression pathway may be co-regulated by transcription factors and miRNA associated with it.
Construction and analysis of mRNA, miRNA, lncRNA, and TF regulatory networks reveal the key genes in prostate cancer
Authors: Li Su-Liang , Ye Yun , Wang Sheng-Yu 
Published: May 2018

AbstractPurpose: Prostate cancer (PCa) causes a common male urinary system malignant tumour, and the molecular mechanisms of PCa remain poorly understood. This study aims to investigate the underlying molecular mechanisms of PCa with bioinformatics.Methods: Original gene expression profiles were obtained from the GSE64318 and GSE46602 datasets in the Gene Expression Omnibus (GEO). We conducted differential screens of the expression of genes (DEGs) between two groups using the R software limma package. The interactions between the differentially expressed miRNAs, mRNAs and lncRNAs were predicted and merged with the target genes. Co-expression of the miRNAs, lncRNAs and mRNAs were selected to construct the mRNA-miRNA and-lncRNA interaction networks. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for the DEGs. The protein-protein interaction (PPI) networks were constructed, and the transcription factors were annotated. The expression of hub genes in the TCGA datasets was verified to improve the reliability of our analysis.Results: The results demonstrated that 60 miRNAs, 1578 mRNAs and 61 lncRNAs were differentially expressed in PCa. The mRNA-miRNA-lncRNA networks were composed of 5 miRNA nodes, 13 lncRNA nodes, and 45 mRNA nodes. The DEGs were mainly enriched in the nuclei and cytoplasm and were involved in the regulation of transcription, related to sequence-specific DNA binding, and participated in the regulation of the PI3K-Akt signalling pathway. These pathways are related to cancer and focal adhesion signalling pathways. Furthermore, we found that 5 miRNAs, 6 lncRNAs, 6 mRNAs and 2 TFs play important regulatory roles in the interaction network. The expression levels of EGFR, VEGFA, PIK3R1, DLG4, TGFBR1 and KIT were significantly different between PCa and normal prostate tissue.Conclusion: Based on the current study, large-scale effects of interrelated mRNAs, miRNAs, lncRNAs, and TFs were revealed and a model for predicting the mechanism of PCa was provided. This study provides new insight for the exploration of the molecular mechanisms of PCa and valuable clues for further research.
Transient Overexpression of VEGF-A in Adipose Tissue Promotes Energy Expenditure via Activation of the Sympathetic Nervous System
Authors: Zhao Yueshui , Li Xin , Yanga Li , Eckel-Mahan Kristin , Tong Qingchun , Gu Xue , Kolonin Mikhail G. , Kai Sun 
Published: May 2018

AbstractAdipose-derived VEGF-A stimulates functional blood vessel formation in obese fat pads which in turn facilitates healthy expansion of the adipose tissue. However, the detailed mechanism(s) governing the process remains largely unknown. Here, we investigated the role of sympathetic nervous system activation in the process. To this end, we induced overexpression of VEGF-A in an adipose-specific doxycycline (Dox)-inducible transgenic mouse model for a short period of time during high fat-diet (HFD) feeding. We found that local overexpression of VEGF-A in adipose tissue stimulated lipolysis and browning rapidly after Dox induction. Immunofluorescent staining against tyrosine hydroxylase (TH) indicated higher levels of sympathetic innervation in adipose tissue of transgenic mice. In response to the increased norepinephrine (NE) level, expression of β3-andrenoceptor was significantly upregulated and the downstream protein kinase A (PKA) pathway was activated, as indicated by the enhanced phosphorylation of the whole PKA substrates, in particular the hormone sensitive lipase (HSL) in adipocytes. As the result, the adipose tissue exhibited increased lipolysis, browning, and energy expenditure. Importantly, all these effects were abolished upon the treatment with β3-adrenoceptor antagonist SR59230A. Collectively, these results demonstrate that transient overexpressed VEGF-A activates sympathetic nervous system which hence promotes lipolysis and browning in adipose tissue.
Data-driven modeling of cholinergic modulation of neural microcircuits: bridging neurons, synapses, and network states
Authors: Ramaswamy Srikanth , Markram Henry 
Published: May 2018

1AbstractNeuromodulators, such as acetylcholine (ACh), control information processing in neural microcircuits by regulating neuronal and synaptic physiology. Computational models and simulations enable predictions on the potential role of ACh in reconfiguring network states. As a prelude into investigating how the cellular and synaptic effects of ACh collectively influence emergent network dynamics, we developed a data-driven framework incorporating phenomenological models of the anatomy and physiology of cholinergic modulation of the neocortex. The first-draft models were integrated into a biologically detailed tissue model of neocortical microcircuitry to predict how ACh affects different types of neurons and synapses, and consequently alters global network states. Preliminary simulations not only corroborate the long-standing notion that ACh desynchronizes network activity, but also reveal a potentially finegrained control over a spectrum of neocortical states. We show that low levels of ACh, such as those during sleep, drive microcircuit activity into slow oscillations and network synchrony, whereas high ACh concentrations, such as those during wakefulness, govern fast oscillations and network asynchrony. In addition, network states modulated by ACh levels shape spike-time cross-correlations across distinct neuronal populations in strikingly different ways. These effects are likely due to the differential regulation of neurons and synapses caused by increasing levels of ACh that enhances cellular excitability by increasing neuronal activity and decreases the efficacy of local synaptic transmission by altering neurotransmitter release probability. We conclude by discussing future directions to refine the biological accuracy of the framework, which will extend its utility and foster the development of hypotheses to investigate the role of neuromodulation in neural information processing.
A computational model to understand mouse iron physiology and diseases
Authors: Parmar Jignesh H. , Mendes Pedro 
Published: May 2018

AbstractIt is well known that iron is an essential element for life but is toxic when in excess or in certain forms. Accordingly there are many diseases that result directly from either lack or excess of iron. Iron has also been associated with a wide range of other diseases and may have an important role in aging. Yet many molecular and physiological aspects of iron regulation have only been discovered recently and others are still awaiting elucidation. In the last 18 years, after the discovery of the hormone hepcidin, many details of iron regulation have become better understood and a clearer picture is starting to emerge, at least in qualitative terms. However there is still no good quantitative and dynamic description of iron absorption, distribution, storage and mobilization that agrees with the wide array of phenotypes presented in several iron-related diseases. The present work addresses this issue by developing a mathematical model of iron distribution in mice that was calibrated with existing ferrokinetic data and subsequently validated against data from a series of iron disorders, such as hemochromatosis, β-thalassemia, atransferrinemia and anemia of inflammation. To adequately fit the ferrokinetic data required including the following mechanisms: a) the role of transferrin in deliving iron to tissues, b) the induction of hepcidin by high levels of transferrin-bound iron, c) the ferroportin-dependent hepcidin-regulated iron export from tissues, d) the erythropoietin regulation of erythropoiesis, and e) direct NTBI uptake by the liver. The utility of such a model to simulate disease interventions was demonstrated by using it to investigate the outcome of different schedules of transferrin treatment in β-thalassemia. The present model is a successful step towards a comprehensive mathematical model of iron physiology incorporating cellular and organ level details.
Acetylcholine inhibits platelet activation and regulates hemostasis
Authors: Bennett John A. , Ture Sara K. , Schmidt Rachel A. , Mastrangelo Michael A. , Cameron Scott J. , Terry Lara E. , Yule David I. , Morrell Craig N. , Lowenstein Charles J. 
Published: May 2018

AbstractPlatelets are key mediators of thrombosis. Many agonists of platelet activation are known, but there are fewer identified endogenous inhibitors of platelets, such as prostacyclin and nitric oxide (NO). Acetylcholinesterase inhibitors such as donepezil can cause bleeding in patients, but the underlying mechanisms are not well understood. We hypothesized that acetylcholine is an endogenous inhibitor of platelets.We measured the effect of acetylcholine or analogues of acetylcholine upon human platelet activation ex vivo. We characterized expression of components of the acetylcholine signaling pathway in human platelets. We tested the effect of a subunit of the acetylcholine receptor, CHRNA7, on acetylcholine signaling in platelets. Acetylcholine and analogues of acetylcholine inhibited platelet activation, as measured by P-selectin translocation and GPIIbIIIA conformational changes. Conversely, we found that antagonists of the acetylcholine receptor such as pancuronium enhance platelet activation. Furthermore, drugs inhibiting acetylcholinesterase such as donepezil also inhibit platelet activation, suggesting that platelets release acetylcholine. We found that NO mediates acetylcholine inhibition of platelets. Human platelets express members of the acetylcholine signaling pathway includingCHRNA2, CHRNA7, CHRNB1, andACHE. Platelets from mice lackingChrna7are hyperactive when stimulated by thrombin and resistant to inhibition by acetylcholine. Furthermore, acetylcholinesterase inhibitors prolonged bleeding in wild-type mice. Knockout mice lackingChrna7subunits of the acetylcholine receptor display prolonged bleeding as well.Our data suggest that acetylcholine is an endogenous inhibitor of platelet activation. The cholinergic system may be a novel target for anti-thrombotic therapies.
Decoding Selective Attention to Context Memory: An Aging Study
Authors: Powell Patrick S. , Strunk Jonathan , James Taylor , Polyn Sean M. , Duarte Audrey 
Published: May 2018

AbstractEmerging evidence has suggested that the tendency for older adults to bind too much contextual information during encoding (i.e., hyper-binding) may contribute to poorer memory for relevant contextual information during retrieval. While these findings are consistent with theories of age-related declines in selective attention and inhibitory control, the degree to which older adults are able to selectively attend to relevant contextual information during encoding is unknown. To better understand the neural dynamics associated with selective attention during encoding, the current study applied multivariate pattern analyses (MVPA) to oscillatory EEG in order to track moment-to-moment shifts of attention between relevant and irrelevant contextual information during encoding. Young and older adults studied pictures of objects in the presence of two contextual features: a color and a scene, and their attention was directed to the object’s relationship with one of those contexts (i.e., target context). Results showed that patterns of oscillatory power successfully predicted whether selective attention was directed to a scene or color, across age groups. Individual differences in overall classification performance were associated with individual differences in target context memory accuracy during retrieval. However, changes in classification performance within a trial, suggestive of fluctuations in selective attention, predicted individual differences in hyper-binding. To the best of our knowledge, this is the first study to use MPVA techniques to decode attention during episodic encoding and the impact of attentional shifts toward distracting information on age-related context memory impairments and hyper-binding. These results are consistent with the as-of-yet unsubstantiated theory that age-related declines in context memory may be attributable to poorer selective attention and/or greater inhibitory deficits in older adults.