bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial proline catabolism activates Ras1/cAMP/PKA-induced filamentation inCandida albicans
Authors: Silao Fitz Gerald S. , Ward Meliza , Ryman Kicki , Wallström Axel , Brindefalk Björn , Udekwu Klas , Ljungdahl Per O. 
Published: July 2018

AbstractAmino acids are among the earliest identified inducers of yeast-to-hyphal transitions inCandida albicans, an opportunistic fungal pathogen of humans. Here, we show that the morphogenic amino acids arginine, ornithine and proline are internalized and metabolized in mitochondria via aPUT1- andPUT2-dependent pathway that results in enhanced ATP production. Elevated ATP levels correlate with Ras1/cAMP/PKA pathway activation and Efg1-induced gene expression. The magnitude of amino acid-induced filamentation is linked to glucose availability; high levels of glucose repress mitochondrial function thereby dampening filamentation. Furthermore, arginine-induced morphogenesis occurs more rapidly and independently of Dur1,2-catalyzed urea degradation, indicating that mitochondrial-generated ATP, not CO2, is the primary morphogenic signal derived from arginine metabolism. The important role of the SPS-sensor of extracellular amino acids in morphogenesis is the consequence of induced amino acid permease gene expression, i.e., SPS-sensor activation enhances the capacity of cells to take up morphogenic amino acids, a requisite for their catabolism.C. albicanscells engulfed by murine macrophages filament, resulting in macrophage lysis. Phagocytosedput1-/-andput2-/- cells do not filament and do not lyse macrophages, consistent with a critical role of mitochondrial proline metabolism in virulence.
Rationally derived inhibitors of hepatitis C virus (HCV) p7 channel activity reveal prospect for bimodal antiviral therapy
Authors: Shaw Joseph , Gosein Rajendra , Kalita Monoj Mon , Foster Toshana L. , Kankanala Jayakanth , Mahato D. Ram , Scott Claire , King Barnabas J. , Brown Emma , Bentham Matthew J. , Wetherill Laura , Bloy Abigail , Samson Adel , Harris Mark , Mankouri Jamel , Rowlands David , Macdonald Andrew , Tarr Alexander W. , Fischer Wolfgang B. , Foster Richard , Griffin Stephen 
Published: July 2018

AbstractSince the 1960s, a single class of agent has been licensed targeting virus-encoded ion channels, or “viroporins”, contrasting the success of channel blocking drugs in other areas of medicine. Although resistance arose to these prototypic adamantane inhibitors of the influenza A virus (IAV) M2 proton channel, a growing number of clinically and economically important viruses are now recognised to encode essential viroporins providing potential targets for modern drug discovery.We describe the first rationally designed viroporin inhibitor with a comprehensive structure-activity relationship (SAR). This step-change in understanding not only revealed a second biological function for the p7 viroporin from hepatitis C virus (HCV) during virus entry, but also enabled the synthesis of a labelled tool compound that retained biological activity. Hence, p7 inhibitors (p7i) represent a unique class of HCV antiviral targeting both the spread and establishment of infection, as well as a precedent for future viroporin-targeted drug discovery.
mRNA compartmentalisation spatially orients tissue morphogenesis
Authors: Costa Guilherme , Bradbury Joshua , Tarannum Nawseen , Herbert Shane P. 
Published: July 2018

ABSTRACTPolarised targeting of diverse mRNAs to motile cellular protrusions is a hallmark of cell migration1–3. Although a widespread phenomenon, definitive functions for endogenous targeted mRNAs and their relevance to modulation of in-vivo tissue dynamics remain elusive. Here, using single-molecule analysis, endogenous gene-edited mRNAs and zebrafish in-vivo live-cell imaging, we report that mRNA polarisation acts as a molecular compass that orients motile cell polarity and spatially directs tissue movement. Clustering of protrusion-derived RNAseq datasets defined a core 192 bp localisation element underpinning precise mRNA targeting to incipient sites of filopodia formation at cell protrusions. Such targeting of the small GTPase, RAB13, generated tight spatial coupling of mRNA localisation, translation and protein activity, achieving precise subcellular compartmentalisation of RAB13 protein function to create a polarised domain of filopodia extension. Consequently, genomic excision of this localisation element and specific perturbation of endogenous RAB13 targeting – but not translation – depolarised filopodial dynamics in motile endothelial cells and induced miss-patterning of nascent blood vessels in-vivo. Hence, mRNA polarisation, not expression, is the primary spatial determinant of the site of RAB13 action, preventing ectopic functionality at inappropriate subcellular loci and orienting tissue morphogenesis. Considering the unexpected spatial diversity of other polarised mRNA clusters we identified, mRNA-mediated compartmentalisation of protein function at distinct subcellular sites likely coordinates broad aspects of in-vivo tissue behaviour.
Gene-Based Analysis in HRC Imputed Genome Wide Association Data Identifies Three Novel Genes For Alzheimer’s Disease
Authors: Baker Emily , Sims Rebecca , Leonenko Ganna , Frizzati Aura , Harwood Janet , Grozeva Detelina ,   GERAD/PERADES,   IGAP consortia, Morgan Kevin , Passmore Peter , Holmes Clive , Powell John , Brayne Carol , Gill Michael , Mead Simon , Heun Reiner , Bossù Paola , Spalletta Gianfranco , Goate Alison , Cruchaga Carlos , van Duijn Cornelia , Maier Wolfgang , Ramirez Alfredo , Jones Lesley , Hardy John , Ivanov Dobril , Hill Matthew , Holmans Peter , Allen Nicholas , Morgan Paul , Williams Julie , Escott-Price Valentina ,   GERAD Consortium,   ADGC Consortium,   CHARGE Consortium,   EADI Consortium
Published: July 2018

AbstractA novel POLARIS gene-based analysis approach was employed to compute gene-based polygenic risk score (PRS) for all individuals in the latest HRC imputed GERAD (N cases=3,332 and N controls=9,832) data using the International Genomics of Alzheimer’s Project summary statistics (N cases=13,676 and N controls=27,322, excluding GERAD subjects) to identify the SNPs and weight their risk alleles for the PRS score. SNPs were assigned to known, protein coding genes using GENCODE (v19). SNPs are assigned using both 1) no window around the gene and 2) a window of 35kb upstream and 10kb downstream to include transcriptional regulatory elements. The overall association of a gene is determined using a logistic regression model, adjusting for population covariates.Three novel gene-wide significant genes were determined from the POLARIS gene-based analysis using a gene window; PPARGC1A, RORA and ZNF423. The ZNF423 gene resides in an Alzheimer’s disease (AD)-specific protein network which also includes other AD-related genes. The PPARGC1A gene has been linked to energy metabolism and the generation of amyloid beta plaques and the RORA has strong links with genes which are differentially expressed in the hippocampus. We also demonstrate no enrichment for genes in either loss of function intolerant or conserved noncoding sequence regions.
Fast Optical Sectioning for Widefield Fluorescence Mesoscopy with the Mesolens based on HiLo Microscopy
Authors: Schniete Jan , Franssen Aimee , Dempster John , Bushell Trevor , Amos William Bradshaw , McConnell Gail 
Published: July 2018

ABSTRACTWe present here a fast optical sectioning method for optical mesoscopy based on HiLo microscopy, which makes possible imaging of specimens of up to 4.4 mm × 3 mm × 3 mm in volume in under 17 hours (estimated for a z-stack comprising 1000 images excluding computation time) with subcellular resolution throughout. Widefield epifluorescence imaging is performed with the Mesolens using a high pixel-number camera capable of sensor-shifting to generate a 259.5 Megapixel image, and we have developed custom software to perform HiLo processing of the very large datasets. Using this method, we obtain comparable sectioning strength to confocal laser scanning microscopy (CLSM), with sections as thin as 6.8±0.2 μm and raw acquisition speed of 1 minute per slice which is up to 30 times faster than CLSM on the full field of view (FOV) of the Mesolens of 4.4 mm with lateral resolution of 0.7 μm and axial resolution of 7 μm. We have applied this HiLo mesoscopy method to image fixed and fluorescently stained hippocampal neuronal specimens and a 5-day old zebrafish larva.
Heat-stress triggers MAPK crosstalk to turn on the hyper-osmotic response pathway
Authors: Dunayevich Paula , Baltanás Rodrigo , Clemente José , Couto Alicia , Sapochnik Daiana , Colman-Lerner Alejandro 
Published: July 2018

AbstractCells make decisions based on a combination of external and internal signals. In yeast, the high osmolarity response (HOG) is a mitogen-activated protein kinase (MAPK) pathway that responds to a variety of stimuli, and it is central to the general stress response. Here we studied the effect of heat-stress (HS) on HOG. Using live-cell reporters and genetics, we show that HS promotes Hog1 phosphorylation and gene expression, exclusively via the Sln1 phosphorelay branch, and that the strength of the activation is larger in yeast adapted to high external osmolarity. HS stimulation of HOG is indirect. First, we found that it depends on the operation of a second MAPK pathway, the cell-wall integrity (CWI), a well-known mediator of HS. Second, we show that HS causes glycerol loss via the channel Fps1, and that strictly requires the CWI MAPK Slt2. Third, blocking glycerol efflux also blocks HOG activation, strongly suggesting that it is the resulting loss of turgor by the loss of the accompanying water what causes HOG stimulation. Thus, taken together, our findings highlight a central role for Fps1, and the metabolism of glycerol, in the communication between the yeast MAPK pathways, essential for survival and reproduction in changing environments.
ReaDDy 2: Fast and flexible software framework for interacting-particle reaction dynamics
Authors: Hoffmann Moritz , Fröhner Christoph , Noé Frank 
Published: July 2018

AbstractInteracting-particle reaction dynamics (iPRD) combines the simulation of dynamical trajectories of interacting particles as in molecular dynamics (MD) simulations with reaction kinetics, in which particles appear, disappear, or change their type and interactions based on a set of reaction rules. This combination facilitates the simulation of reaction kinetics in crowded environments, involving complex molecular geometries such as polymers, and employing complex reaction mechanisms such as breaking and fusion of polymers. iPRD simulations are ideal to simulate the detailed spatiotemporal reaction mechanism in complex and dense environments, such as in signalling processes at cellular membranes, or in nano- to microscale chemical reactors. Here we introduce the iPRD software ReaDDy 2, which provides a Python interface in which the simulation environment, particle interactions and reaction rules can be conveniently defined and the simulation can be run, stored and analyzed. A C++ interface is available to enable deeper and more flexible interactions with the framework. The main computational work of ReaDDy 2 is done in hardware-specific simulation kernels. While the version introduced here provides single- and multi-threading CPU kernels, the architecture is ready to implement GPU and multi-node kernels. We demonstrate the efficiency and validity of ReaDDy 2 using several benchmark examples. ReaDDy 2 is available at the https://readdy.github.io/ website.
Contrasting patterns of divergence at the regulatory and sequence level in EuropeanDaphnia galeatanatural populations
Authors: Ravindran Suda Parimala , Herrmann Maike , Cordellier Mathilde 
Published: July 2018

ABSTRACTUnderstanding the genetic basis of local adaptation has long been a focus of evolutionary biology. Recently there has been increased interest in deciphering the evolutionary role ofDaphnia’s plasticity and the molecular mechanisms of local adaptation. Using transcriptome data, we assessed the differences in gene expression profiles and sequences in four EuropeanDaphnia galeatapopulations. In total, ~33% of 32,903 transcripts were differentially expressed between populations. Among 10,280 differentially expressed transcripts, 5,209 transcripts deviated from neutral expectations and their population-specific expression pattern is likely the result of local adaptation processes. Furthermore, a SNP analysis allowed inferring population structure and distribution of genetic variation. The population divergence at the sequence-level was comparatively higher than the gene expression level by several orders of magnitude and consistent with strong founder effects and lack of gene flow between populations. Using sequence information, the candidate transcripts were annotated using a comparative genomics approach. Thus, we identified candidate transcriptomic regions for local adaptation in a key species of aquatic ecosystems in the absence of any laboratory induced stressor.
Protein Structural Biology Using Cell-Free Platform from Wheat Germ
Authors: Novikova Irina V. , Sharma Noopur , Moser Trevor , Sontag Ryan , Liu Yan , Collazo Michael J. , Cascio Duilio , Shokuhfar Tolou , Hellmann Hanjo , Knoblauch Michael , Evans James E. 
Published: July 2018

AbstractOne of the biggest bottlenecks for structural analysis of proteins remains the creation of high yield and high purity samples of the target protein. Cell-free protein synthesis technologies are powerful and customizable platforms for obtaining functional proteins of interest in short timeframes while avoiding potential toxicity issues and permitting high-throughput screening. These methods have benefited many areas of genomic and proteomics research, therapeutics, vaccine development and protein chip constructions. In this work, we demonstrate a versatile and multistage eukaryotic wheat-germ cell-free protein expression pipeline to generate functional proteins of different sizes from multiple host organism and DNA source origins. We also developed a robust purification procedure, which can produce highly-pure (>98%) proteins with no specialized equipment required and minimal time invested. This pipeline successfully produced and analyzed proteins in all three major geometry formats used for structural biology including single particle analysis, and both two-dimensional and three-dimensional protein crystallography. The flexibility of the wheat germ system in combination with the multiscale pipeline described here provides a new workflow for rapid generation of samples for structural characterization that may not be amenable to other recombinant approaches.
Influence of inlet boundary conditions in computations of turbulent jet flames
Authors: Lewandowski Michał T. , Płuszka Paweł , Pozorski Jacek 
Published: July 2018

Purpose
This paper aims to assess the sensitivity of numerical simulation results of turbulent reactive flow to the formulation of inlet boundary conditions. The analysis concerns the profiles of the mean velocity the turbulence kinetic energy k and its dissipation rate ϵ. It is intended to provide guidance to the determination of inlet conditions when only global flow data are available. This situation can be met both in simple laboratory experiments and in industrial full-scale applications, when measurements are either incomplete or infeasible, resulting in lack of detailed inlet data.

Design/methodology/approach
Two turbulence–chemistry interaction models were studied: eddy dissipation concept and partially stirred reactor. Three different velocity profiles and related turbulence statistics were applied to present feasible scenarios and their consequences. Simulations with the most appropriate inlet data were accompanied with profiles of turbulent quantities obtained with a proposed method. This method was contrasted to other approaches popular in the literature: the pre-inlet pipe and the separate cold flow simulations of a burner. The methodology was validated on two laboratory-scale jet flames: Delft Jet-in-Hot-Coflow and Sandia CHN B. The simulations were carried out with open source code OpenFOAM.

Findings
The proposed relations for turbulence kinetic energy and its dissipation rate at the inlet are found to provide results comparable to those obtained with the use of experimental data as inlet boundary conditions. Moreover, from a certain location downstream the jet, weakly dependent on the Reynolds number, the influence of inlet conditions on flow statistics was found to be negligible.

Originality/value
This work reveals the consequences of the use of rather crude assumptions made for inlet boundary conditions. Proposed formulas for the profiles for k and epsilon are attractive alternatives to other approaches aiming to determine the inlet boundary conditions for turbulent jet flows.
The influence of information technology strategy and management support to the internal business process, competitive advantage, financial and non-financial performance of the company
Authors: Astuti Endang , Suhadak  , Rahayu Sri Mangesti , Wilopo  
Published: July 2018

Purpose
The purpose of this paper is to conduct a research to analyze and to explain the influence of information technology strategy (ITS) and management support (MS) on internal business processes (IBPs), competitive advantage (CA) and financial performance (FP) and non-financial performance (NFP) of a company.

Design/methodology/approach
This study uses a quantitative approach and is included in an explanatory research. This study belongs to the category of perceptive research, and the unit of analysis is an individual (Singarimbun and dan Effendi, 1989). The study population is Carrefour executives/managers. The unit of analysis in this study is an individual who is a Carrefour manager and who becomes the sample. This study is conducted throughout the Carrefour chains in Indonesia. Method of data analysis uses descriptive analysis and inferential statistic, using partial least square.

Findings
This study found that ITS has no significant effect on FP, but it has a significant effect on NFP. It also found that MS has a significant effect on IBP CA and FP and NFP. This study found that IBPs have no significant effect on FP but have a significant effect on NFP and CA. CA has no significant effect on FP, but it has a significant effect on NFP. Further, NFP has a significant effect on FP.

Originality/value
This research is important to understand comprehensively the relationship between information technology and IBPs, CA and company performance. The difference between this study and previous studies is that this study examines the relationship between MS and IBP to CA, NFP and corporate FP.
Using news to predict Chinese medicinal material price index movements
Authors: Yu Miao , Guo Chonghui 
Published: July 2018

Purpose
The purpose of this paper is to propose an approach for predicting the movements of Chinese medicinal material price indexes using news based on text mining.

Design/methodology/approach
A research framework and three major methods, namely, domain dictionary construction, market convergence time calculation and dimensionality reduction integrating semantic analysis, are proposed for the approach. The proposed approach is applied in practice for predicting the price index movements of the top ten Chinese medicinal materials that receive the greatest media attention.

Findings
A set of experiments performed herein show that a predictive relationship exists between the news and the commodity market and that each of the three major methods improves the forecasting performance.

Research limitations/implications
Because the field of Chinese medicinal materials lacks a corpus that can be used for sentiment analysis, the accuracy of a trained automatic sentiment classifier is lower than obtained by a manual method, which can cause the calculated convergence result to be inaccurate, thus affecting the final prediction model. The manual method of having people label news decreases the proposed method’s aspects of being intelligent and automatic.

Practical implications
Using the method proposed herein to predict the trends in Chinese medicinal materials prices helps farmers arrange a reasonable planting plan to pursue their best interests.

Social implications
The method proposed herein to predict the trends in the prices of Chinese medicinal materials is conducive to the government arranging planned drug availabilities in order to avoid disasters in which herbs are looted.

Originality/value
The produced prediction result is meaningful in supporting farmers and investors to make better decisions in growing and trading Chinese medicinal material, which leads to financial returns on investments and the avoidance of severe losses.
Financial health and management practices: a multi-year cross country analysis of PLCs
Authors: Hasan Md Shamimul , Omar Normah , Hassan ABM Rashedul 
Published: July 2018

Purpose
The purpose of this study is to examine the relationship between financial strength or condition and managerial practices in preparing financial statements of public limited companies. The objectives of this study are threefold – to measure the financial strength, to measure integrity index and to examine the relationship between management practices and financial strength.

Design/methodology/approach
Financial ratios, Altman’s Z-Score, integrity index, ranking approach and chi-square test are used to achieve the objectives. A multi-year cross-country analysis is done by considering sample of seven Asian countries, namely, Malaysia, Singapore, Thailand, Indonesia, Hong Kong, China and Japan.

Findings
The study catches the relationship between management practices and financial strength across sample countries. Management practices is one of the responsible factors for this relationship. They use discretionary power in preparing financial statements to control the trading results. The principles of accounting do not support the alteration of financial data to look the company better on paper. The cost of financial statement fraud is higher than other occupational fraud.

Research limitations/implications
This study does not cover factors other than management practices and further study could be conducted to look for the other reasons that may also responsible for the deviations.

Practical implications
Conflict of interest between shareholders and board of directors is not a new phenomenon. Auditing system is introduced to minimize this conflict of interest, but they failed to uphold their position in reality. Management also needs to prove their integrity in financial statements. Ethical consideration is the highest priority.

Social implications
Stakeholders, especially regulators, professional bodies and academics, should concentrate on the issue on ‘how to reduce the manipulation in financial statements’ to create a safe investments avenue for the nation.

Originality/value
This study provides empirical evidences regarding the influence of management practices on financial statements and financial strength of listed companies across countries. The culture, attitudes, beliefs, perceptions, etc., are different from country to country. The aim is to contribute empirical evidence about the relationship between management practices and financial health in different settings. This study is first of its kind.