bluuebunny/crossref_metadata_2025_split huggingface dataset:
Murine germinal center B cells require functional Fms-like tyrosine kinase 3 signaling for IgG1 class-switch recombination
Authors: Svensson Mattias N. D. , Andersson Karin M. E. , Wasén Caroline , Erlandsson Malin C. , Nurkkala-Karlsson Merja , Jonsson Ing-Marie , Brisslert Mikael , Bemark Mats , Bokarewa Maria I. 
Published: November 2015

SignificanceThe protein kinase fms-like tyrosine kinase 3 receptor (Flt3) has an important role during early B-cell development. Recent reports have shown that Flt3 is reexpressed on peripheral B cells during activation, however the function for Flt3 during B-cell activation is poorly understood. The present study describes a role for Flt3 during B-cell activation and antibody production. We show that Flt3 is reexpressed on activated germinal center B cells and that lack of functional Flt3 signaling in peripheral B cells results in a specific deficiency in production of the antibody subclass IgG1. Mechanistic studies indicate that Flt3 synergizes with the IL-4 receptor to promote proper activation of Stat6 and class switch to IgG1. This study provides evidence for a previously unknown function for Flt3 during peripheral B-cell activation.
Stress dynamically regulates behavior and glutamatergic gene expression in hippocampus by opening a window of epigenetic plasticity
Authors: Nasca Carla , Zelli Danielle , Bigio Benedetta , Piccinin Sonia , Scaccianoce Sergio , Nisticò Robert , McEwen Bruce S. 
Published: November 2015

Significance
Chronic stress alters the hippocampal responses to familiar and novel stressors, behaviorally, physiologically, and epigenetically. In the aftermath of chronic stress in WT mice and in mice with a BDNF loss-of-function allele without any applied stress, there is a window of plasticity that allows familiar and novel experiences to alter anxiety- and depressive-like behaviors, reflected also in electrophysiological changes in the dentate gyrus (DG) in vitro. A consistent biomarker of mood-related behaviors in DG is reduced type 2 metabotropic glutamate (mGlu2), which regulates the release of glutamate. Within this window, familiar stress rapidly and epigenetically up-regulates mGlu2 by a P300-driven histone H3 lysine 27 acetylation and improves mood behaviors. This transient epigenetic plasticity may be useful for treatment of stress-related disorders where dysregulaton of glutamate is involved.
Enhancing potency of siRNA targeting fusion genes by optimization outside of target sequence
Authors: Gavrilov Kseniya , Seo Young-Eun , Tietjen Gregory T. , Cui Jiajia , Cheng Christopher J. , Saltzman W. Mark 
Published: November 2015

Significance
Potency is a key parameter in development of siRNAs for clinical use. However, current design and optimization approaches are concentrated on determining best target sequences within the entire mRNA sequence of interest. This methodology falls short when the available region of the target mRNA becomes restricted, as when targeting the junction site of a fusion oncogene. Here we demonstrate alternative optimization strategies for further improving silencing performance when the targetable region of the mRNA is confined. We apply this approach for siRNA against fusion genes BCR-ABL and TMPRSS2-ERG. We further demonstrate the importance of concurrent development of siRNA design and delivery strategies for more effective siRNA therapeutics and draw attention to the implications of target protein half-life and nonspecific vehicle toxicity.
Responsiveness of G protein-coupled odorant receptors is partially attributed to the activation mechanism
Authors: Yu Yiqun , de March Claire A. , Ni Mengjue J. , Adipietro Kaylin A. , Golebiowski Jérôme , Matsunami Hiroaki , Ma Minghong 
Published: November 2015

Significance
Mammalian odorant receptors (ORs) comprise the largest family of G protein-coupled receptors, which are frequent drug targets. While many ORs respond specifically to select odorants, recent studies have identified a small number of ORs that respond to a large set of diverse odorants. Up to date, little is known about the molecular and structural features that shape the OR response properties. Our study reveals that broadly responsive ORs show elevated basal activity, suggesting a lower activation barrier. Surprisingly, a single amino acid mutation is sufficient to confer high basal activity and broad responsiveness to an OR, which originally shows weak responses to few odorants.
Architecture of the human XPC DNA repair and stem cell coactivator complex
Authors: Zhang Elisa T. , He Yuan , Grob Patricia , Fong Yick W. , Nogales Eva , Tjian Robert 
Published: November 2015

Significance
Embryonic or pluripotent stem cells are unique in their ability to self-renew in culture and to generate all lineages of an adult organism, making them valuable tools for modeling early developmental processes and for developing regenerative medicine technologies. An important factor in controlling the expression of pluripotency genes is the Xeroderma pigmentosum complementation group C (XPC) DNA repair complex. This study presents, to our knowledge, the first complete structures of different XPC complexes by electron microscopy to establish an important framework for a molecular understanding of XPC’s two primary functions. In conjunction with our biochemical findings, we synthesize a model of how XPC performs both its evolutionarily conserved DNA repair function and its evolutionarily nonconserved transcription function.
Reversed-phase liquid chromatographic analysis of hydrophobic interaction between proanthocyanidins and a C8-alkyl compound in aqueous solution
Authors: Yanagida Akio , Takeshige Shinya , Shibusawa Yoichi 
Published: November 2015

Abstract
Structural and physicochemical properties of oligomeric flavan-3-ols (proanthocyanidins) in aqueous solution were investigated by spectrometric and reversed-phase (RP) HPLC analyses. Circular dichroism and fluorescence spectra of (–)-epicatechin (EC) oligomers linked through C-4 to C-8 interflavan bonds showed that EC oligomers larger than dimers formed a stable secondary structure in water. These EC oligomers are water-soluble hydrophilic compounds, whereas the oligomers were strongly retained by a C8-alkyl stationary phase under conventional RP-HPLC conditions. In a further C8-HPLC study, the hydrophobic interaction between EC oligomers and 1-octanesulfonic acid sodium salt (OSA Na) added to the mobile phase was quantitatively evaluated based on the relationship between the logarithm of the retention factor of the solute and the OSA Na concentration in the mobile phase. The strength values of the hydrophobic interaction of EC oligomers larger than dimers were the highest of 22 tested polyphenolic standards.
Towards a framework for the quantitative assessment of trawling impact on the seabed and benthic ecosystem
Authors: Rijnsdorp A. D. , Bastardie F. , Bolam S. G. , Buhl-Mortensen L. , Eigaard O. R. , Hamon K. G. , Hiddink J. G. , Hintzen N. T. , Ivanović A. , Kenny A. , Laffargue P. , Nielsen J. R. , O'Neill F. G. , Piet G. J. , Polet H. , Sala A. , Smith C. , van Denderen P. D. , van Kooten T. , Zengin M. 
Published: November 2015

AbstractA framework to assess the impact of mobile fishing gear on the seabed and benthic ecosystem is presented. The framework that can be used at regional and local scales provides indicators for both trawling pressure and ecological impact. It builds on high-resolution maps of trawling intensity and considers the physical effects of trawl gears on the seabed, on marine taxa, and on the functioning of the benthic ecosystem. Within the framework, a reductionist approach is applied that breaks down a fishing gear into its components, and a number of biological traits are chosen to determine either the vulnerability of the benthos to the impact of that gear component, or to provide a proxy for their ecological role. The approach considers gear elements, such as otter boards, twin trawl clump, and groundrope, and sweeps that herd the fish. The physical impact of these elements on the seabed, comprising scraping of the seabed, sediment mobilization, and penetration, is a function of the mass, size, and speed of the individual component. The impact of the elements on the benthic community is quantified using a biological-trait approach that considers the vulnerability of the benthic community to trawl impact (e.g. sediment position, morphology), the recovery rate (e.g. longevity, maturation age, reproductive characteristics, dispersal), and their ecological role. The framework is explored to compare the indicators for pressure and ecological impact of bottom trawling in three main seabed habitat types in the North Sea. Preliminary results show that the Sublittoral mud (EUNIS A5.3) is affected the most due to the combined effect of intensive fishing and large proportions of long-lived taxa.
Dexmedetomidine versus Propofol Sedation Reduces Delirium after Cardiac Surgery
Authors: Djaiani George , Silverton Natalie , Fedorko Ludwik , Carroll Jo , Styra Rima , Rao Vivek , Katznelson Rita 
Published: November 2015

AbstractAbstract
When compared with propofol, dexmedetomidine sedation reduced incidence, delayed onset, and shortened duration of postoperative delirium in elderly patients after cardiac surgery.

Background
Postoperative delirium (POD) is a serious complication after cardiac surgery. Use of dexmedetomidine to prevent delirium is controversial. The authors hypothesized that dexmedetomidine sedation after cardiac surgery would reduce the incidence of POD.

Methods
After institutional ethics review board approval, and informed consent, a single-blinded, prospective, randomized controlled trial was conducted in patients 60 yr or older undergoing cardiac surgery. Patients with a history of serious mental illness, delirium, and severe dementia were excluded. Upon admission to intensive care unit (ICU), patients received either dexmedetomidine (0.4 μg/kg bolus followed by 0.2 to 0.7 μg kg−1 h−1 infusion) or propofol (25 to 50 μg kg−1 min−1 infusion) according to a computer-generated randomization code in blocks of four. Assessment of delirium was performed with confusion assessment method for ICU or confusion assessment method after discharge from ICU at 12-h intervals during the 5 postoperative days. Primary outcome was the incidence of POD.

Results
POD was present in 16 of 91 (17.5%) and 29 of 92 (31.5%) patients in dexmedetomidine and propofol groups, respectively (odds ratio, 0.46; 95% CI, 0.23 to 0.92; P = 0.028). Median onset of POD was on postoperative day 2 (1 to 4 days) versus 1 (1 to 4 days), P = 0.027, and duration of POD 2 days (1 to 4 days) versus 3 days (1 to 5 days), P = 0.04, in dexmedetomidine and propofol groups, respectively.

Conclusions
When compared with propofol, dexmedetomidine sedation reduced incidence, delayed onset, and shortened duration of POD in elderly patients after cardiac surgery. The absolute risk reduction for POD was 14%, with a number needed to treat of 7.1.
Combined Mitral and Tricuspid Valve Surgery Performed via a Right Minithoracotomy Approach
Authors: Mihos Christos G. , Pineda Andrés M. , Davila Hector , Larrauri-Reyes Maiteder C. , Santana Orlando 
Published: November 2015

Objective Combined mitral and tricuspid valve surgery is associated with an increased perioperative morbidity and mortality. We evaluated the outcomes of a less invasive right minithoracotomy approach in patients undergoing primary or reoperative double-valve surgery. Methods We retrospectively evaluated 132 consecutive patients with mitral and tricuspid valve disease who underwent double-valve surgery via a right minithoracotomy at our institution between January 2009 and April 2014. Results The cohort included 81 female (61%) and 51 male (39%) patients, with a mean ± SD age of 67 ± 13 years. The mean ± SD preoperative left ventricular ejection fraction, mitral regurgitation grade, and creatinine were 53% ± 12%, 3.8 ± 0.6, and 1.26 ± 1.17, respectively. The patients underwent primary (88%) or reoperative (12%) mitral and tricuspid valve surgery, which consisted of 88 mitral repairs (67%), 44 mitral replacements (33%), 131 tricuspid repairs (99%), and 1 tricuspid replacement (1%). Postoperatively, there were 6 cases of acute kidney injury (5%), 6 reoperations for bleeding (5%), 4 cerebrovascular accidents (3%), and 12 cases of atrial fibrillation (9%). The median intensive care unit length of stay and total hospital lengths of stay were 61 hours (interquartile range, 43–112 hours) and 8 days (interquartile range, 6–13 days), respectively. The in-hospital mortality was 4%. Actuarial survival at 1 and 5 years was 93% and 88%, respectively. Conclusions In patients undergoing primary or reoperative mitral and tricuspid valve surgery, a right minithoracotomy approach is associated with a low perioperative morbidity and good midterm survival.
Minimally Invasive Mitral Valve Surgery in Truly High-Risk Patients: Are We Pushing the Boundaries? An Observational Study
Authors: Moscarelli Marco , Margaryan Rafik , Cerillo Alfredo , Kallushi Enkel , Farneti Pierandrea , Solinas Marco 
Published: November 2015

Objective This study aimed to assess in a retrospective series of truly high-risk patients who underwent minimally invasive mitral valve surgery: (1) postoperative and long-term results and (2) logistic EuroSCORE and EuroSCORE II discrimination power. Methods Between 2003 and 2013, we reviewed in our institution patients who underwent minimally invasive mitral valve surgery with or without tricuspid valve repair via right minithoracotomy with logistic EuroSCORE of 20 or higher. Results Among a total number of 1604, 88 patients were identified. Median logistic and EuroSCORE II was 27.29 (interquartile range, 15.3) and 12.7% (11.3%), respectively. Mean (SD) age was 71.9 (8.4) years; 42 were female (47.7%); 60 patients (68.1%) underwent previous sternotomy. Mitral valve was replaced in 59 (67%) and repaired in 29 (32.9%) patients; tricuspid valve repair was performed in 23 patients (26.1%). Median cardiopulmonary bypass and cross-clamp times were 157 minutes (interquartile range, 131–187 minutes) and 83 minutes (81–116 minutes), respectively; conversion to sternotomy and reopening for bleeding was necessary in 4 (4.5%) and 3 (3.4%) patients; permanent and transient neurological injuries were reported in 6 (6.8%) and 3 (3.4%) patients; acute kidney injury was reported in 13 patients (14.7%); 15 patients (17%) had pulmonary complications. Ten patients died while in the hospital (11.2%). Survival at 6 years was 78% (95% confidence interval, 69–88). Conclusions In this series of truly high-risk patients, minimally invasive mitral surgery was associated with acceptable early mortality and morbidity as well as long-term outcomes; both logistic and EuroSCORE II showed suboptimal discrimination power.
Simulated Prosthesis Overlay for Patient-Specific Planning of Transcatheter Aortic Valve Implantation Procedures
Authors: Sündermann Simon H. , Gessat Michael , Maier Willibald , Kempfert Jörg , Frauenfelder Thomas , Nguyen Thi D. L. , Maisano Francesco , Falk Volkmar 
Published: November 2015

Objective We tested the hypothesis that simulated three-dimensional prosthesis overlay procedure planning may support valve selection in transcatheter aortic valve implantation (TAVI) procedures. Methods Preoperative multidimensional computed tomography (MDCT) data sets from 81 consecutive TAVI patients were included in the study. A planning tool was developed, which semiautomatically creates a three-dimensional model of the aortic root from these data. Three-dimensional templates of the commonly used TAVI implants are spatially registered with the patient data and presented as graphic overlay. Fourteen physicians used the tool to perform retrospective planning of TAVI procedures. Results of prosthesis sizing were compared with the prosthesis size used in the actually performed procedure, and the patients were accordingly divided into three groups: those with equal size (concordance with retrospective planning), oversizing (retrospective planning of a smaller prosthesis), and undersizing (retrospective planning of a larger prosthesis). Results In the oversizing group, 85% of the patients had new pacemaker implantation. In the undersizing group, in 66%, at least mild paravalvular leakage was observed (greater than grade 1 in one third of the cases). In 46% of the patients in the equal-size group, neither of these complications was observed. Conclusions Three-dimensional prosthesis overlay in MDCT-derived patient data for patient-specific planning of TAVI procedures is feasible. It may improve valve selection compared with two-dimensional MDCT planning and thus yield better outcomes.
Kaiju: Fast and sensitive taxonomic classification for metagenomics
Authors: Menzel Peter , Lee Ng Kim , Krogh Anders 
Published: November 2015

AbstractThe constantly decreasing cost and increasing out-put of current sequencing technologies enable large scale metagenomic studies of microbial communities from diverse habitats. Therefore, fast and accurate methods for taxonomic classification are needed, which can operate on increasingly larger datasets and reference databases. Recently, several fast metagenomic classifiers have been developed, which are based on comparison of genomick-mers. However, nucleotide comparison using a fixedk-mer length often lacks the sensitivity to overcome the evolutionary distance between sampled species and genomes in the reference database. Here, we present the novel metagenome classifierKaijufor fast assignment of reads to taxa. Kaiju finds maximum exact matches on the protein-level using the Borrows-Wheeler transform, and can optionally allow amino acid substitutions in the search using a greedy heuristic. We show in a genome exclusion study that Kaiju can classify more reads with higher sensitivity and similar precision compared to fastk-mer based classifiers, especially in genera that are underrepresented in reference databases. We also demonstrate that Kaiju classifies more than twice as many reads in ten real metagenomes compared to programs based on genomick-mers. Kaiju can process up to millions of reads per minute, and its memory footprint is below 6 GB of RAM, allowing the analysis on a standard PC. The program is available under the GPL3 license at:http://bioinformatics-centre.github.io/kaiju
Strong Selection is Necessary for Evolution of Blindness in Cave Dwellers
Authors: Cartwright Reed A. , Schwartz Rachel S. , Merry Alexandra L. , Howell Megan M. 
Published: November 2015

AbstractBlindness has evolved repeatedly in cave-dwelling organisms, and investigating the loss of sight in cave dwellers presents an opportunity to understand the operation of fundamental evolutionary processes, including drift, selection, mutation, and migration. The observation of blind organisms has prompted many hypotheses for their blindness, including both accumulation of neutral, loss-of-function mutations and adaptation to darkness. Here we model the evolution of blindness in caves. This model captures the interaction of three forces: (1) selection favoring alleles causing blindness, (2) immigration of sightedness alleles from a surface population, and (3) loss-of-function mutations creating blindness alleles. We investigated the dynamics of this model and determined selection-strength thresholds that result in blindness evolving in caves despite immigration of sightedness alleles from the surface. Our results indicate that strong selection is required for the evolution of blindness in cave-dwelling organisms, which is consistent with recent work suggesting a high metabolic cost of eye development.
Learning structure in gene expression data using deep architectures, with an application to gene clustering
Authors: Gupta Aman , Wang Haohan , Ganapathiraju Madhavi 
Published: November 2015

AbstractGenes play a central role in all biological processes. DNA microarray technology has made it possible to study the expression behavior of thousands of genes in one go. Often, gene expression data is used to generate features for supervised and unsupervised learning tasks. At the same time, advances in the field of deep learning have made available a plethora of architectures. In this paper, we use deep architectures pre-trained in an unsupervised manner using denoising autoencoders as a preprocessing step for a popular unsupervised learning task. Denoising autoencoders (DA) can be used to learn a compact representation of input, and have been used to generate features for further supervised learning tasks. We propose that our deep architectures can be treated as empirical versions of Deep Belief Networks (DBNs). We use our deep architectures to regenerate gene expression time series data for two different data sets. We test our hypothesis on two popular datasets for the unsupervised learning task of clustering and find promising improvements in performance.
The Genetic Equidistance Phenomenon at the Proteomic Level
Authors: Luo Denghui , Huang Shi 
Published: November 2015

AbstractThe field of molecular evolution started with the alignment of a few protein sequences in the early 1960s. Among the first results found, the genetic equidistance result has turned out to be the most unexpected. It directly inspired the ad hoc universal molecular clock hypothesis that in turn inspired the neutral theory. Unfortunately, however, what is only a maximum distance phenomenon was mistakenly transformed into a mutation rate phenomenon and became known as such. Previous work studied a small set of selected proteins. We have performed proteome wide studies of 7 different sets of proteomes involving a total of 15 species. All 7 sets showed that within each set of 3 species the least complex species is approximately equidistant in average proteome wide identity to the two more complex ones. Thus, the genetic equidis-tance result is a universal phenomenon of maximum distance. There is a reality of constant albeit stepwise or discontinuous increase in complexity during evolution, the rate of which is what the original molecular clock hypothesis is really about. These results provide additional lines of evidence for the recently proposed maximum genetic diversity (MGD) hypothesis.Availability and implementationThe source code repository is publicly available athttps://github.com/Sephiroth1st/EquidistanceScriptContacthuangshi@sklmg.edu.cnSupplementary informationSupplementary data are available online.