bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell cycle dynamics of chromosomal organisation at single-cell resolution
Authors: Nagano Takashi , Lubling Yaniv , Varnai Csilla , Dudley Carmel , Leung Wing , Baran Yael , Mandelson-Cohen Netta , Wingett Steven , Fraser Peter , Tanay Amos 
Published: December 2016

SummaryChromosomes in proliferating metazoan cells undergo dramatic structural metamorphoses every cell cycle, alternating between a highly condensed mitotic structure facilitating chromosome segregation, and a decondensed interphase structure accommodating transcription, gene silencing and DNA replication. These cyclical structural transformations have been evident under the microscope for over a century, but their molecular-level analysis is still lacking. Here we use single-cell Hi-C to study chromosome conformations in thousands of individual cells, and discover a continuum ofcis-interaction profiles that finely position individual cells along the cell cycle. We show that chromosomal compartments, topological domains (TADs), contact insulation and long-range loops, all defined by ensemble Hi-C maps, are governed by distinct cell cycle dynamics. In particular, DNA replication correlates with build-up of compartments and reduction in TAD insulation, while loops are generally stable from G1 through S and G2. Analysing whole genome 3D structural models using haploid cell data, we discover a radial architecture of chromosomal compartments with distinct epigenomic signatures. Our single-cell data creates an essential new paradigm for the re-interpretation of chromosome conformation maps through the prism of the cell cycle.
A computational method for detection of structural variants using Deviant Reads and read pair Orientation: DevRO
Authors: Sayyab Shumaila , Rafati Nima , Carneiro Miguel , Garreau Hervé , Andersson Göran , Andersson Leif , Johan Rubin Carl 
Published: December 2016

AbstractBackgroundNext generation sequencing (NGS) technology has made it possible to perform high-resolution screens for structural variants. Computational methods for detection of structural variants utilize paired-end mapping information, depth of coverage, split reads, or some combination of such data. The available methods are particularly designed to detect structural variants in single genomes or multiple genomes in a pairwise manner. The aim of this study was to develop a bioinformatics pipeline for detection of large structural variants using multiple pooled populations.ResultsHere we describe the method “DevRO”, developed to enable identification of structural variants using short insert paired-ends and long-range mate-pairs. DevRO uses paired-end mapping information from both types of libraries for identification of inversions, deletions and duplications followed by read depth information to screen for copy number variants. DevRO can detect structural variants in multiple populations without the need for pairwise comparisons. It uses a combined approach based on (i) paired-end mapping and (ii) depth of coverage that gives power to the study as compared to traditional methods that are based on either of these. DevRO is also designed to detect deletions in the reference assembly, which is an added functionality as compared to available methods.ConclusionWe report a bioinformatics pipeline “DevRO” for detection of structural variants using paired-end mapping and depth of coverage methods tested on sequencing reads from multiple pooled rabbit populations. This method is useful when large numbers of populations have been re-sequenced as compared to traditional methods that can detect structural variants in a pairwise manner.
Single-channel in-Ear-EEG detects the focus of auditory attention to concurrent tone streams and mixed speech
Authors: Fiedler Lorenz , Wöstmann Malte , Graversen Carina , Brandmeyer Alex , Lunner Thomas , Obleser Jonas 
Published: December 2016

AbstractObjectiveConventional, multi-channel scalp electroencephalography (EEG) allows the identification of the attended speaker in concurrent-listening (“cocktail party”) scenarios. This implies that EEG might provide valuable information to complement hearing aids with some form of EEG and to install a level of neuro-feedback.ApproachTo investigate whether a listener’s attentional focus can be detected from single-channel hearing-aid-compatible EEG configurations, we recorded EEG from three electrodes inside the ear canal (“in-Ear-EEG”) and additionally from 64 electrodes on the scalp. In two different, concurrent listening tasks, participants (n = 7) were fitted with individualized in-Ear-EEG pieces and were either asked to attend to one of two dichotically-presented, concurrent tone streams or to one of two diotically-presented, concurrent audiobooks. A forward encoding model was trained to predict the EEG response at single EEG channels.Main resultsEach individual participants’ attentional focus could be detected from single-channel EEG response recorded from short-distance configurations consisting only of a single in-Ear-EEG electrode and an adjacent scalp-EEG electrode. The differences in neural responses to attended and ignored stimuli were consistent in morphology (i.e., polarity and latency of components) across subjects.SignificanceIn sum, our findings show that the EEG response from a single-channel, hearing-aid-compatible configuration provides valuable information to identify a listener’s focus of attention.
Dynamically controlled light delivery over large brain volumes through tapered optical fibers
Authors: Pisanello Ferruccio , Mandelbaum Gil , Pisanello Marco , Oldenburg Ian A. , Sileo Leonardo , Markowitz Jeffrey E. , Peterson Ralph E. , Della Patria Andrea , Haynes Trevor M. , Emara Mohamed S. , Spagnolo Barbara , Datta Sandeep R. , Sabatini Bernardo L. , De Vittorio Massimo 
Published: December 2016

ABSTRACTOptogenetics promises spatiotemporal precise control of neural processes using light. However, the spatial extent of illumination within the brain is difficult to control and cannot be adjusted using standard fiber optics. We demonstrate that optical fibers with tapered tips can be used to illuminate either large brain volumes or dynamically selectable subregions. Remotely adjusting the light input angle to the fiber varies the light-emitting portion of the taper over several millimeters without movement of the implant. We use this mode to activate dorsal versus ventral striatum of individual mice and reveal different effects of each manipulation on motor behavior. Conversely injecting light over the full numerical aperture of the fiber results in light emission from the entire taper surface, achieving broader and more efficient optogenetic activation of neurons when compared to the standard flat-faced fiber stimulation. Thus, tapered fibers permit focal or broad illumination that can be precisely and dynamically matched to experimental needs.
Model-based branching point detection in single-cell data by K-Branches clustering
Authors: Chlis Nikolaos K. , Wolf F. Alexander , Theis Fabian J. 
Published: December 2016

MotivationThe identification of heterogeneities in cell populations by utilizing single-cell technologies such as single-cell RNA-Seq, enables inference of cellular development and lineage trees. Several methods have been proposed for such inference from high-dimensional single-cell data. They typically assign each cell to a branch in a differentiation trajectory. However, they commonly assume specific geometries such as tree-like developmental hierarchies and lack statistically sound methods to decide on the number of branching events.ResultsWe present K-Branches, a solution to the above problem by locally fitting half-lines to single-cell data, introducing a clustering algorithm similar to K-Means. These halflines are proxies for branches in the differentiation trajectory of cells. We propose a modified version of the GAP statistic for model selection, in order to decide on the number of lines that best describe the data locally. In this manner, we identify the location and number of subgroups of cells that are associated with branching events and full differentiation, respectively. We evaluate the performance of our method on single-cell RNA-Seq data describing the differentiation of myeloid progenitors during hematopoiesis, single-cell qPCR data of mouse blastocyst development and artificial data.AvailabilityAn R implementation of K-Branches is freely available athttps://github.com/theislab/kbranchesContactfabian.theis@helmholtz-muenchen.de
Development of Narrow Spectrum ATP-competitive Kinase Inhibitors as Probes for BIKE and AAK1
Authors: Couñago Rafael M. , Axtman Alison D. , Capuzzi Stephen J. , Azevedo Hátylas , Drewry David H. , Elkins Jonathan M. , Gileadi Opher , Guimarães Cristiano R. W. , Mascarello Alessandra , Serafim Ricardo A. M. , Wells Carrow I. , Willson Timothy M. , Zuercher William J. 
Published: December 2016

ABSTRACTUnderstanding the structural determinants of inhibitor selectivity would facilitate the design and preparation of kinase probes. We describe a pair of matched compounds differing only by one degree of saturation but showing dramatic differential activities at select kinases. We utilized x-ray crystallography and computational analysis to rationalize the basis of the differential activity.
Estimation of a growth factor for achieve scalability in ad hoc networks
Authors: Ospina Juan Pablo , Ortiz Triviño Jorge Eduardo 
Published: December 2016

<p>Given the fact that the ad hoc networks with flat architectures are not scalable, this study focuses on determining the conditions to guarantee the scalability in a hierarchical architecture based on the resources availability in the different layers of the network. A model based on the truncated geometric distribution that allows to characterize the available resources in an ad hoc network was proposed. Starting by this characterization, the concept of growth factor j was introduced as a constant value that represents the appropriate relationship among the available resources in two successive layers of the network to ensure scalability. Simulation scenarios were explored to develop the estimation process of the growth factor j in ad hoc networks of two and three-layer hierarchical architectures in the software ns-3. The results showed that the growth of resources between layers in an ad hoc network can be expressed through a linear model. Also, a relation was found between the estimated value of j and the golden ratio as a way to inspire the design of artificial system based on the attributes that can be found in nature. </p>
China and the South China Sea “Lawfare”
Authors: HSIAO ANNE HSIU-AN 
Published: December 2016

The strategic values of the South China Sea had long been recognized. More recently, the South China Sea has once again become an international flashpoint, as disputes take place in the context of a rising and perceived more assertive People’s Republic of China (China) vis-à-vis a relatively declining US that seeks to retain its influence and interests in East Asia. This paper tries to illustrate the growing strategic role of international law in the geopolitics of the South China Sea at play — a subject matter that has so far been less explored — and to assess how the intensified legal maneuvers, or “lawfare” between China on the one hand, and other South China Sea claimants as well as the US on the other, reflect China’s attitude toward the South China Sea dispute and may impact upon the peace and security in the region. It concludes that the “lawfare” since 2009, especially the South China Sea arbitration proceedings initiated by the Philippines, may have not only increased the uncertainties of China’s behavior and China–US relations, but also made the situations in both East and South China seas more complicated. Moreover, China’s responses in the “lawfare” also suggest that China has become more “rule-of-law oriented” as well as hegemonic. The dual images of China raise some uncertainty as to how the South China Sea disputes might eventually be resolved.
The influence of volcanic rocks on the characterization of Rosebank Field – new insights from ocean-bottom seismic data and geological analogues integrated through interpretation and modelling
Authors: Poppitt S. , Duncan L. J. , Preu B. , Fazzari F. , Archer J. 
Published: December 2016

Abstract
During Late Paleocene–Early Eocene times, the modern Rosebank structure was located at the juxtaposition of the easterly advancing Flett volcanic system and the northerly prograding Flett delta. As a result, the Rosebank reservoir sandstones are interstratified with volcanic and volcaniclastic rocks, offering challenges for reservoir imaging, depth prediction and reservoir characterization. These challenges have driven the application of Ocean Bottom Node (OBN) seismic technology. OBN data have yielded improved velocity models for depth conversion, better reservoir definition and key insights to aid the modelling of sand distribution from seismic attributes. Spectral decomposition of the OBN seismic data has facilitated the extraction of distinct volcanic subunits, whilst spectral enhancement has enabled visualization of complex stacking patterns within individual igneous layers. To complement the seismic analysis, detailed geological analogue studies have been undertaken in volcanic provinces such as the Palaeogene volcanic district of SE Greenland and the Columbia River Flood Basalt Province, USA. No single outcrop provides a definitive analogy to Rosebank, but each offers insights that provide an important link to understanding and managing the main subsurface uncertainties associated with field development. Integration of these multiple workflows have improved the reservoir characterization and provided the foundation for the optimization of the field development plan.
Critical role of microbiota within cecal crypts on the regenerative capacity of the intestinal epithelium following surgical stress
Authors: Zaborin Alexander , Krezalek Monika , Hyoju Sanjiv , Defazio Jennifer R. , Setia Namrata , Belogortseva Natalia , Bindokas Vytautas P. , Guo Qiti , Zaborina Olga , Alverdy John C. 
Published: December 2016

Cecal crypts represent a unique niche that are normally occupied by the commensal microbiota. Due to their density and close proximity to stem cells, microbiota within cecal crypts may modulate epithelial regeneration. Here we demonstrate that surgical stress, a process that invariably involves a short period of starvation, antibiotic exposure, and tissue injury, results in cecal crypt evacuation of their microbiota. Crypts devoid of their microbiota display pathophysiological features characterized by abnormal stem cell activation as judged by leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) staining, expansion of the proliferative zone toward the tips of the crypts, and an increase in apoptosis. In addition, crypts devoid of their microbiota display loss of their regenerative capacity as assessed by their ability to form organoids ex vivo. When a four-member human pathogen community isolated from the stool of a critically ill patient is introduced into the cecum of mice with empty crypts, crypts become occupied by the pathogens and further disruption of crypt homeostasis is observed. Fecal microbiota transplantation restores the cecal crypts’ microbiota, normalizes homeostasis within crypts, and reestablishes crypt regenerative capacity. Taken together, these findings define an emerging role for the microbiota within cecal crypts to maintain epithelial cell homeostasis in a manner that may enhance recovery in response to the physiological stress imposed by the process of surgery. NEW & NOTEWORTHY This study provides novel insight into the process by which surgical injury places the intestinal epithelium at risk for colonization by pathogenic microbes and impairment of its regenerative capacity via loss of its microbiota. We show that fecal transplant restores crypt homeostasis in association with repopulation of the microbiota within cecal crypts.
Kvβ1.1 (AKR6A8) senses pyridine nucleotide changes in the mouse heart and modulates cardiac electrical activity
Authors: Tur Jared , Chapalamadugu Kalyan C. , Katnik Christopher , Cuevas Javier , Bhatnagar Aruni , Tipparaju Srinivas M. 
Published: December 2016

The present study investigates the physiological role of Kvβ1 subunit for sensing pyridine nucleotide (NADH/NAD+) changes in the heart. We used Kvβ1.1 knockout (KO) or wild-type (WT) mice and established that Kvβ1.1 preferentially binds with Kv4.2 and senses the pyridine nucleotide changes in the heart. The cellular action potential duration (APD) obtained from WT cardiomyocytes showed longer APDs with lactate perfusion, which increases intracellular NADH levels, while the APDs remained unaltered in the Kvβ1.1 KO. Ex vivo monophasic action potentials showed a similar response, in which the APDs were prolonged in WT mouse hearts with lactate perfusion; however, the Kvβ1.1 KO mouse hearts did not show APD changes upon lactate perfusion. COS-7 cells coexpressing Kv4.2 and Kvβ1.1 were used for whole cell patch-clamp recordings to evaluate changes caused by NADH (lactate). These data reveal that Kvβ1.1 is required in the mediated inactivation of Kv4.2 currents, when NADH (lactate) levels are increased. In vivo, isoproterenol infusion led to increased NADH in the heart along with QTc prolongation in wild-type mice; regardless of the approach, our data show that Kvβ1.1 recognizes NADH changes and modulates Kv4.2 currents affecting AP and QTc durations. Overall, this study uses multiple levels of investigation, including the heterologous overexpression system, cardiomyocyte, ex vivo, and ECG, and clearly depicts that Kvβ1.1 is an obligatory sensor of NADH/NAD changes in vivo, with a physiological role in the heart. NEW & NOTEWORTHY Cardiac electrical activity is mediated by ion channels, and Kv4.2 plays a significant role, along with its binding partner, the Kvβ1.1 subunit. In the present study, we identify Kvβ1.1 as a sensor of pyridine nucleotide changes and as a modulator of Kv4.2 gating, action potential duration, and ECG in the mouse heart.
Differential effects of Mas receptor deficiency on cardiac function and blood pressure in obese male and female mice
Authors: Wang Yu , Shoemaker Robin , Powell David , Su Wen , Thatcher Sean , Cassis Lisa 
Published: December 2016

Angiotensin-(1–7) [ANG-(1–7)] acts at Mas receptors (MasR) to oppose effects of angiotensin II (ANG II). Previous studies demonstrated that protection of female mice from obesity-induced hypertension was associated with increased systemic ANG-(1–7), whereas male obese hypertensive mice exhibited increased systemic ANG II. We hypothesized that MasR deficiency ( MasR−/−) augments obesity-induced hypertension in males and abolishes protection of females. Male and female wild-type ( MasR+/+) and MasR−/− mice were fed a low-fat (LF) or high-fat (HF) diet for 16 wk. MasR deficiency had no effect on obesity. At baseline, male and female MasR−/− mice had reduced ejection fraction (EF) and fractional shortening than MasR+/+ mice. Male, but not female, HF-fed MasR+/+ mice had increased systolic and diastolic (DBP) blood pressures compared with LF-fed controls. In HF-fed females, MasR deficiency increased DBP compared with LF-fed controls. In contrast, male HF-fed MasR−/− mice had lower DBP than MasR+/+ mice. We quantified cardiac function after 1 mo of HF feeding in males of each genotype. HF-fed MasR−/− mice had higher left ventricular (LV) wall thickness than MasR+/+ mice. Moreover, MasR+/+, but not MasR−/−, mice displayed reductions in EF from HF feeding that were reversed by ANG-(1–7) infusion. LV fibrosis was reduced in HF-fed MasR+/+ but not MasR−/− ANG-(1–7)-infused mice. These results demonstrate that MasR deficiency promotes obesity-induced hypertension in females. In males, HF feeding reduced cardiac function, which was restored by ANG-(1–7) in MasR+/+ but not MasR−/− mice. MasR agonists may be effective therapies for obesity-associated cardiovascular conditions. NEW & NOTEWORTHY MasR deficiency abolishes protection of female mice from obesity-induced hypertension. Male MasR-deficient obese mice have reduced blood pressure and declines in cardiac function. ANG-(1–7) infusion restores obesity-induced cardiac dysfunction of wild-type, but not MasR-deficient, male mice. MasR agonists may be cardioprotective in obese males and females.
Heat induces interleukin-6 in skeletal muscle cells via TRPV1/PKC/CREB pathways
Authors: Obi Syotaro , Nakajima Toshiaki , Hasegawa Takaaki , Kikuchi Hironobu , Oguri Gaku , Takahashi Masao , Nakamura Fumitaka , Yamasoba Tatsuya , Sakuma Masashi , Toyoda Shigeru , Tei Chuwa , Inoue Teruo 
Published: December 2016

Interleukin-6 (IL-6) is released from skeletal muscle cells and induced by exercise, heat, catecholamine, glucose, lipopolysaccharide, reactive oxygen species, and inflammation. However, the mechanism that induces release of IL-6 from skeletal muscle cells remains unknown. Thermosensitive transient receptor potential (TRP) proteins such as TRPV1–4 play vital roles in cellular functions. In this study we hypothesized that TRPV1 senses heat, transmits a signal into the nucleus, and produces IL-6. The purpose of the present study is to investigate the underlying mechanisms whereby skeletal muscle cells sense and respond to heat. When mouse myoblast cells were exposed to 37–42°C for 2 h, mRNA expression of IL-6 increased in a temperature-dependent manner. Heat also increased IL-6 secretion in myoblast cells. A fura 2 fluorescence dual-wavelength excitation method showed that heat increased intracellular calcium flux in a temperature-dependent manner. Intracellular calcium flux and IL-6 mRNA expression were increased by the TRPV1 agonists capsaicin and N-arachidonoyldopamine and decreased by the TRPV1 antagonists AMG9810 and SB366791 and siRNA-mediated knockdown of TRPV1. TRPV2, 3, and 4 agonists did not change intracellular calcium flux. Western blotting with inhibitors demonstrated that heat increased phosphorylation levels of TRPV1, followed by PKC and cAMP response element-binding protein (CREB). PKC inhibitors, Gö6983 and staurosporine, CREB inhibitors, curcumin and naphthol AS-E, and knockdown of CREB suppressed the heat-induced increases in IL-6. These results indicate that heat increases IL-6 in skeletal muscle cells through the TRPV1, PKC, and CREB signal transduction pathway.NEW & NOTEWORTHY Heat increases the release of interleukin-6 (IL-6) from skeletal muscle cells. IL-6 has been shown to serve immune responses and metabolic functions in muscle. It can be anti-inflammatory as well as proinflammatory. However, the mechanism that induces release of IL-6 from skeletal muscle cells remains unknown. Here we show that heat increases IL-6 in skeletal muscle cells through the transient receptor potential vannilloid 1, PKC, and cAMP response element-binding protein signal transduction pathway.