bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Synthetic, Host-defense Peptide Protects Against Organ Injury/Dysfunction in a Rat Model of Severe Hemorrhagic Shock
Authors: Yamada Noriaki , Martin Lukas B. , Zechendorf Elisabeth , Purvis Gareth S. D. , Chiazza Fausto , Varrone Barbara , Collino Massimo , Shepherd Joanna , Heinbockel Lena , Gutsmann Thomas , Correa Wilmar , Brandenburg Klaus , Marx Gernot , Schuerholz Tobias , Brohi Karim , Thiemermann Christoph 
Published: March 2017

Objective:
To evaluate (1) levels of the host-defense/antimicrobial peptide LL-37 in patients with trauma and hemorrhagic shock (HS) and (2) the effects of a synthetic host-defense peptide; Pep19-4LF on multiple organ failure (MOF) associated with HS.

Background:
HS is a common cause of death in severely injured patients. There is no specific therapy that reduces HS-associated MOF.

Methods:
(1) LL-37 was measured in 47 trauma/HS patients admitted to an urban major trauma center. (2) Male Wistar rats were submitted to HS (90 min, target mean arterial pressure: 27–32 mm Hg) or sham operation. Rats were treated with Pep19-4LF [66 (n = 8) or 333 μg/kg · h (n = 8)] or vehicle (n = 12) for 4 hours following resuscitation.

Results:
Plasma LL-37 was 12-fold higher in patients with trauma/HS compared to healthy volunteers. HS rats treated with Pep19-4LF (high dose) had a higher mean arterial pressure at the end of the 4-hour resuscitation period (79 ± 4 vs 54 ± 5 mm Hg) and less renal dysfunction, liver injury, and lung inflammation than HS rats treated with vehicle. Pep19-4LF enhanced (kidney/liver) the phosphorylation of (1) protein kinase B and (2) endothelial nitric oxide synthase. Pep19-4LF attenuated the HS-induced (1) translocation of p65 from cytosol to nucleus, (2) phosphorylation of IκB kinase on Ser176/180, and (3) phosphorylation of IκBα on Ser32/36 resulting in inhibition of nuclear factor kappa B and formation of proinflammatory cytokines. Pep19-4LF prevented the release of tumor necrosis factor alpha caused by heparan sulfate in human mononuclear cells by binding to this damage-associated molecular pattern.

Conclusions:
Trauma-associated HS results in release of LL-37. The synthetic host-defense/antimicrobial peptide Pep19-4LF attenuates the organ injury/dysfunction associated with HS.
Is It Time to Reconsider Postoperative Epidural Analgesia in Patients Undergoing Elective Ventral Hernia Repair?
Authors: Prabhu Ajita S. , Krpata David M. , Perez Arielle , Phillips Sharon , Huang Li-Ching , Haskins Ivy N. , Rosenblatt Steven , Poulose Benjamin K. , Rosen Michael J. 
Published: March 2017

Objective:
We aimed to evaluate the association of epidural analgesia (EA) with hospital length of stay (LOS), wound morbidity, postoperative complications, and patient-reported outcomes in patients undergoing ventral hernia repair (VHR).

Background:
EA has been shown to reduce LOS in certain surgical populations. The LOS benefit in VHR is unclear.

Methods:
Patients having VHR performed in the Americas Hernia Society Quality Collaborative (AHSQC) were separated into 2 comparable groups matched on several confounding factors using a propensity score algorithm: one group received postoperative EA, and the other did not. The groups were then evaluated for hospital LOS, 30-day wound morbidity, other complications, and 30-day patient-reported outcomes using pain and hernia-specific quality-of-life instruments.

Results:
A 1:1 match was achieved and the final analysis included 763 patients receiving EA and 763 not receiving EA. The EA group had an increased LOS (5.49 vs 4.90 days; P < 0.05). The rate of wound events was similar between the groups. There was an increased risk of having any postoperative complication associated with having EA (26% vs 21%; P < 0.05). Pain intensity-scaled scores were significantly higher (worse) in the EA group versus the non-EA group (47.6 vs 44.0; P = 0.04).

Conclusions:
The LOS benefit of EA noted for other operations may not apply to patients undergoing VHR. Further study is necessary to determine the beneficial role of invasive pain management procedures in this group of patients with an extremely common disease state.
Effects of Intraoperative Fluid Management on Postoperative Outcomes
Authors: Shin Christina H. , Long Dustin R. , McLean Duncan , Grabitz Stephanie D. , Ladha Karim , Timm Fanny P. , Thevathasan Tharusan , Pieretti Alberto , Ferrone Cristina , Hoeft Andreas , Scheeren Thomas W. L. , Thompson Boyd Taylor , Kurth Tobias , Eikermann Matthias 
Published: March 2017

Objective:
Evaluate the dose-response relationship between intraoperative fluid administration and postoperative outcomes in a large cohort of surgical patients.

Background:
Healthy humans may live in a state of fluid responsiveness without the need for fluid supplementation. Goal-directed protocols driven by such measures are limited in their ability to define the optimal fluid state during surgery.

Methods:
This analysis of data on file included 92,094 adult patients undergoing noncardiac surgery with endotracheal intubation between 2007 and 2014 at an academic tertiary care hospital and two affiliated community hospitals. The primary exposure variable was total intraoperative volume of crystalloid and colloid administered. The primary outcome was 30-day survival. Secondary outcomes were respiratory complications within three postoperative days (pulmonary edema, reintubation, pneumonia, or respiratory failure) and acute kidney injury. Exploratory outcomes were postoperative length of stay and total cost of care. Our models were adjusted for patient-, procedure-, and anesthesia-related factors.

Results:
A U-shaped association was observed between the volume of fluid administered intraoperatively and 30-day mortality, costs, and postoperative length of stay. Liberal fluid volumes (highest quintile of fluid administration practice) were significantly associated with respiratory complications whereas both liberal and restrictive (lowest quintile) volumes were significantly associated with acute kidney injury. Moderately restrictive volumes (second quintile) were consistently associated with optimal postoperative outcomes and were characterized by volumes approximately 40% less than traditional textbook estimates: infusion rates of approximately 6–7 mL/kg/hr or 1 L of fluid for a 3-hour case.

Conclusions:
Intraoperative fluid dosing at the liberal and restrictive margins of observed practice is associated with increased morbidity, mortality, cost, and length of stay.
The Most Informative Neural Code Accounts For Population Heterogeneity
Authors: Zavitz Elizabeth , Price Nicholas SC 
Published: March 2017

AbstractPerception is produced by ‘reading out’ the representation of a sensory stimulus contained in the firing rates of a population of neurons. To examine experimentally how populations code information, a common approach is to decode a linearly-weighted sum of the neurons’ firing rates. This approach is popular because of its biological validity: weights in a computational decoder are analogous to synaptic strengths. For neurons recorded in vivo, weights are highly variable when derived through machine learning methods, but it is unclear what neuronal properties explain this variability, and how the variability affects decoding performance. To address this, we recorded from neurons in the middle temporal area (MT) of anesthetized marmosets (Callithrix jacchus) viewing stimuli comprising a sheet of dots that moved coherently in one of twelve different directions. We found that high gain and direction selectivity both predicted that a neuron would be weighted more highly in an optimised decoding model. Although learned weights differed markedly from weights chosen according to apriorirules based on a neuron’s tuning profile, decoding performance was only marginally better for the learned weights. In the models with apriorirules, selectivity is the best predictor of weighting, and defining weights according to a neuron’s preferred direction and selectivity improves decoding performance to very near the maximum level possible, as defined by the learned weights.New & NoteworthyWe examined which aspects of a neuron’s tuning account for its contribution to sensory coding. Strongly direction-selective neurons were weighted most highly by machine learning algorithms trained to discriminate motion direction. Models witha prioridefined decoding weights demonstrate that the learned weighting scheme causally improved direction representation by a neuronal population. Optimising decoders (using machine learning) lead to only marginally better performance than decoders based purely on a neuron’s preferred direction and selectivity.
Dynamical networks: finding, measuring, and tracking neural population activity using network science
Authors: Humphries Mark D. 
Published: March 2017

ABSTRACTSystems neuroscience is in a head-long rush to record from as many neurons at the same time as possible. As the brain computes and codes using neuron populations, it is hoped these data will uncover the fundamentals of neural computation. But with hundreds, thousands, or more simultaneously recorded neurons comes the inescapable problems of visualising, describing, and quantifying their interactions. Here I argue that network science provides a set of scalable, analytical tools that already solve these problems. By treating neurons as nodes and their interactions as links, a single network can visualise and describe an arbitrarily large recording. I show that with this description we can quantify the effects of manipulating a neural circuit, track changes in population dynamics over time, and quantitatively define theoretical concepts of neural populations such as cell assemblies. Using network science as a core part of analysing population recordings will thus provide both qualitative and quantitative advances to our understanding of neural computation.
Psychiatric Genomics: An Update and an Agenda
Authors: Sullivan Patrick F , Agrawal Arpana , Bulik Cynthia M , Andreassen Ole A , Børglum Anders D , Breen Gerome , Cichon Sven , Edenberg Howard J , Faraone Stephen V , Gelernter Joel , Mathews Carol A , Nievergelt Caroline M , Smoller Jordan , O’Donovan Michael C ,   for the Psychiatric Genomics Consortium
Published: March 2017

AbstractThe Psychiatric Genomics Consortium (PGC) is the largest consortium in the history of psychiatry. In the past decade, this global effort has delivered a rapidly increasing flow of new knowledge about the fundamental basis of common psychiatric disorders, particularly given its dedication to rapid progress and open science. The PGC has recently commenced a program of research designed to deliver “actionable” findings - genomic results that (a) reveal the fundamental biology, (b) inform clinical practice, and (c) deliver new therapeutic targets. This is the central idea of the PGC: to convert the family history risk factor into biologically, clinically, and therapeutically meaningful insights. The emerging findings suggest that we are entering into a phase of accelerated translation of genetic discoveries to impact psychiatric practice within a precision medicine framework.CollaboratorsPGC Coordinating Committee: Mark Daly, Michael Gill, John Kelsoe, Karestan Koenen, Douglas Levinson, Cathryn Lewis, Ben Neale, Danielle Posthuma, Jonathan Sebat, and Pamela Sklar.
Quantitative evaluation of two-photon calcium imaging modalities for high-speed volumetric calcium imaging in scattering brain tissue
Authors: Weisenburger Siegfried , Prevedel Robert , Vaziri Alipasha 
Published: March 2017

AbstractConsiderable efforts are currently being devoted to enhance the speed, spatial resolution and the size of the 3D sample volumes in which calcium imaging methods can capture neuronal network activity in different model systems. In the mammalian brain, tissue scattering severely limits the use of parallel acquisition techniques such as wide-field imaging and, as a consequence, methods based on two-photon point-scanning (2PM) have become the method of choice. However, 2PM faces severe restrictions due to technical limitations such as scan speed, laser power, and those related to the fluorescent probes, calling for conceptually new approaches to enhance the performance of two-photon calcium imaging schemes. Here we provide a detailed quantitative evaluation and comparison of different excitation/detection modalities from the perspective of detecting neuronal activity that are based on different point-spread functions (PSF), laser repetition rates and sampling strategies. We demonstrate the conditions for which imaging speed and signal-to-noise ratio are optimized for a given average power. Our results are based on numerical simulations which are informed by experimentally measured parameters and show that volumetric field of view and acquisition speed can be considerably improved compared to traditional 2PM schemes by a holistic optimization approach.
Synthetic analysis of natural variants yields insights into the evolution and function of auxin signaling F-box proteins inArabidopsis thaliana
Authors: Wright R. Clay , Zahler Mollye L. , Gerben Stacey R. , Nemhauser Jennifer L. 
Published: March 2017

ABSTRACTThe evolution of complex body plans in land plants has been paralleled by gene duplication and divergence within nuclear auxin-signaling networks. A deep mechanistic understanding of auxin signaling proteins therefore may allow rational engineering of novel plant architectures. Towards that end, we analyzed natural variation in the auxin receptor F-box family of wild accessions of the reference plantArabidopsis thalianaand used this information to populate a structure/function map. We employed a synthetic assay to identify natural hypermorphic F-box variants, and then assayed auxin-associated phenotypes in accessions expressing these variants. To more directly measure the impact of the strongest variant in our synthetic assay on auxin sensitivity, we generated transgenic plants expressing this allele. Together, our findings link evolved sequence variation to altered molecular performance and auxin sensitivity. This approach demonstrates the potential for combining synthetic biology approaches with quantitative phenotypes to harness the wealth of available sequence information and guide future engineering efforts of diverse signaling pathways.
Modeling signaling-dependent pluripotent cell states with boolean logic can predict cell fate transitions
Authors: Yachie-Kinoshita Ayako , Onishi Kento , Ostblom Joel , Posfai Eszter , Rossant Janet , Zandstra Peter W. 
Published: March 2017

Pluripotent stem cells (PSCs) exist in multiple stable states, each with specific cellular properties and molecular signatures. The process by which pluripotency is either maintained or destabilized to initiate specific developmental programs is poorly understood. We have developed a model to predict stabilized PSC gene regulatory network (GRN) states in response to combinations of input signals. While previous attempts to model PSC fate have been limited to static cell compositions, our approach enables simulations of dynamic heterogeneity by combining an Asynchronous Boolean Simulation (ABS) strategy with simulated single cell fate transitions using Strongly Connected Components (SCCs). This computational framework was applied to a reverse-engineered and curated core GRN for mouse embryonic stem cells (mESCs) to simulate responses to LIF, Wnt/β-catenin, FGF/ERK, BMP4, and Activin A/Nodal pathway activation. For these input signals, our simulations exhibit strong predictive power for gene expression patterns, cell population composition, and nodes controlling cell fate transitions. The model predictions extend into early PSC differentiation, demonstrating, for example, that a Cdx2-high/Oct4-low state can be efficiently and robustly generated from mESCs residing in a naïve and signal-receptive state sustained by combinations of signaling activators and inhibitors.One Sentence SummaryPredictive control of pluripotent stem cell fate transitions
Gut microbiota analysis in rats with methamphetamine-induced conditioned place preference
Authors: Ning Tingting , Gong Xiaokang , Xie Lingling , Baomiao MA 
Published: March 2017

ABSTRACTMethamphetamine abuse is a major public health crisis. Because accumulating evidence supports the hypothesis that the gut microbiota plays an important role in central nervous system (CNS) function, and research on the roles of the microbiome in CNS disorders holds conceivable promise for developing novel therapeutic avenues for treating CNS disorders, we sought to determine whether administration of methamphetamine leads to alterations in the intestinal microbiota. In this study, the gut microbiota profiles of rats with methamphetamine-induced conditioned place preference (CPP) were analysed through 16S rRNA gene sequencing. The faecal microbial diversity was slightly higher in the METH CPP group. The propionate-producing genusPhascolarctobacteriumwas attenuated in the METH CPP group, and the familyRuminococcaceaewas elevated in the METH CPP group. Short chain fatty acid analysis revealed that the concentrations of propionate were decreased in the faecal matter of METH-administered rats. These findings provide direct evidence that administration of METH causes gut dysbiosis, enable a better understanding of the function of gut microbiota in the process of drug abuse, and provide a new paradigm for addiction treatment.
The Sentieon Genomics Tools - A fast and accurate solution to variant calling from next-generation sequence data
Authors: Freed Donald , Aldana Rafael , Weber Jessica A. , Edwards Jeremy S. 
Published: March 2017

AbstractIn the past six years worldwide capacity for human genome sequencing has grown by more than five orders of magnitude, with costs falling by nearly two orders of magnitude over the same period [1], [2]. The rapid expansion in the production of next-generation sequence data and the use of these data in a wide range of new applications has created a need for improved computational tools for data processing. The Sentieon Genomics tools provide an optimized reimplementation of the most accurate pipelines for calling variants from next-generation sequence data, resulting in more than a 10-fold increase in processing speed while providing identical results to best practices pipelines. Here we demonstrate the consistency and improved performance of Sentieon’s tools relative to BWA, GATK, MuTect, and MuTect2 through analysis of publicly available human exome, low-coverage genome, and high-depth genome sequence data.
Widespread paleopolyploidy, gene tree conflict, and recalcitrant relationships among the carnivorous Caryophyllales
Authors: Walker Joseph F. , Yang Ya , Moore Michael J. , Mikenas Jessica , Timoneda Alfonso , Brockington Samuel F. , Smith Stephen A. 
Published: March 2017

ABSTRACTThe carnivorous members of the large, hyperdiverse Caryophyllales (e.g. Venus flytrap, sundews andNepenthespitcher plants) represent perhaps the oldest and most diverse lineage of carnivorous plants. However, despite numerous studies seeking to elucidate their evolutionary relationships, the early-diverging relationships remain unresolved.To explore the utility of phylogenomic data sets for resolving relationships among the carnivorous Caryophyllales, we sequenced ten transcriptomes, including all the carnivorous genera except those in the rare West African liana family (Dioncophyllaceae). We used a variety of methods to infer the species tree, examine gene tree conflict and infer paleopolyploidy events.Phylogenomic analyses support the monophyly of the carnivorous Caryophyllales, with an origin of 68-83 mya. In contrast to previous analyses recover the remaining non-core Caryophyllales as non-monophyletic, although there are multiple reasons this result may be spurious and node supporting this relationship contains a significant amount gene tree discordance. We present evidence that the clade contains at least seven independent paleopolyploidy events, previously debated nodes from the literature have high levels of gene tree conflict, and taxon sampling influences topology even in a phylogenomic data set.Our data demonstrate the importance of carefully considering gene tree conflict and taxon sampling in phylogenomic analyses. Moreover, they provide a remarkable example of the propensity for paleopolyploidy in angiosperms, with at least seven such events in a clade of less than 2500 species.
Neurons define non-myelinated axon segments by the regulation of galectin-4-containing axon membrane domains
Authors: Díez-Revuelta Natalia , Higuero Alonso M. , Velasco Silvia , Peñas-de-la-Iglesia María , Gabius Hans-Joachim , Abad-Rodríguez José 
Published: March 2017

AbstractThe mechanism underlying selective myelination of axons versus dendrites or neuronal somata relies on the expression of somatodendritic membrane myelination inhibitors (i.e. JAM2). However, axons still present long unmyelinated segments proposed to contribute to axonal plasticity and higher order brain functions. Why these segments remain unmyelinated is still an unresolved issue. The bifunctional lectin galectin-4 (Gal-4) organizes the transport of axon glycoproteins by binding to N-acetyllactosamine (LacNac) termini of N-glycans. We have shown that Gal-4 is sorted to segmental domains (G4Ds) along the axon surface, reminiscent of these long unmyelinated axon segments in cortical neurons. We report here that oligodendrocytes (OLGs) do not deposit myelin on Gal-4 covered surfaces or myelinate axonal G4Ds. In addition, Gal-4 interacts and co-localizes in G4Ds with contactin-1, a marker of non-myelinated nodes of Ranvier. Neither Gal-4 expression nor G4D dimensions are affected by myelin extracts or myelinating OLGs, but are reduced with neuron maturation. As in vitro, Gal-4 is consistently segregated from myelinated structures in the brain. Our data shape the novel concept that neurons establish and regulate axon membrane domains expressing Gal-4, the first inhibitor of myelination identified in axons, whose boundaries delineate myelination-incompetent axon segments along neuron development.
Analyzing contentious relationships and outlier genes in phylogenomics
Authors: Walker Joseph F. , Brown Joseph W. , Smith Stephen A. 
Published: March 2017

ABSTRACTRecent studies have demonstrated that conflict is common among gene trees in phylogenomic studies, and that less than one percent of genes may ultimately drive species tree inference in supermatrix analyses. Here, we examined two datasets where supermatrix and coalescent-based species trees conflict. We identified two highly influential “outlier” genes in each dataset. When removed from each dataset, the inferred supermatrix trees matched the topologies obtained from coalescent analyses. We also demonstrate that, while the outlier genes in the vertebrate dataset have been shown in a previous study to be the result of errors in orthology detection, the outlier genes from a plant dataset did not exhibit any obvious systematic error and therefore may be the result of some biological process yet to be determined. While topological comparisons among a small set of alternate topologies can be helpful in discovering outlier genes, they can be limited in several ways, such as assuming all genes share the same topology. Coalescent species tree methods relax this assumption but do not explicitly facilitate the examination of specific edges. Coalescent methods often also assume that conflict is the result of incomplete lineage sorting (ILS). Here we explored a framework that allows for quickly examining alternative edges and support for large phylogenomic datasets that does not assume a single topology for all genes. For both datasets, these analyses provided detailed results confirming the support for coalescent-based topologies. This framework suggests that we can improve our understanding of the underlying signal in phylogenomic datasets by asking more targeted edge-based questions.