bluuebunny/crossref_metadata_2025_split huggingface dataset:
GSEA-InContext: Identifying novel and common patterns in expression experiments
Authors: Powers Rani K. , Goodspeed Andrew , Pielke-Lombardo Harrison , Tan Aik-Choon , Costello James C. 
Published: February 2018

AbstractMotivationGene Set Enrichment Analysis (GSEA) is routinely used to analyze and interpret coordinate changes in transcriptomics experiments. For an experiment where less than seven samples per condition are compared, GSEA employs a competitive null hypothesis to test significance. A gene set enrichment score is tested against a null distribution of enrichment scores generated from permuted gene sets, where genes are randomly selected from the input experiment. Looking across a variety of biological conditions, however, genes are not randomly distributed with many showing consistent patterns of up- or down-regulation. As a result, common patterns of positively and negatively enriched gene sets are observed across experiments. Placing a single experiment into the context of a relevant set of background experiments allows us to identify both the common and experiment-specific patterns of gene set enrichment.ResultsWe compiled a compendium of 442 small molecule transcriptomic experiments and used GSEA to characterize common patterns of positively and negatively enriched gene sets. To identify experiment-specific gene set enrichment, we developed the GSEA-InContext method that accounts for gene expression patterns within a user-defined background set of experiments to identify statistically significantly enriched gene sets. We evaluated GSEA-InContext on experiments using small molecules with known targets and show that it successfully prioritizes gene sets that are specific to each experiment, thus providing valuable insights that complement standard GSEA analysis.Availability and ImplementationGSEA-InContext is implemented in Python. Code, the background expression compendium, and results are available at:https://github.com/CostelloLab/GSEA-InContext
Local Cortical Activity of Distant Brain Areas can Phase-Lock to the Respiratory Rhythm in the Freely Behaving Rat
Authors: Rojas-Líbano Daniel , del Solar Jonathan Wimmer , Aguilar Marcelo , Montefusco-Siegmund Rodrigo , Maldonado Pedro E. 
Published: February 2018

ABSTRACTAn important unresolved question about neural processing is the mechanism by which distant brain areas coordinate their activities and relate their local processing to global neural events. A potential candidate for the local-global integration are slow rhythms such as respiration, which is also linked to sensory exploration. In this article, we asked if there are modulations of local cortical processing which are time-locked to (peripheral) sensory-motor exploratory rhythms. We studied rats freely behaving on an elevated platform where they would display exploratory and rest behaviors. Concurrent with behavior, we monitored orofacial sampling rhythms (whisking and sniffing) and local field potentials (LFP) from olfactory bulb, dorsal hippocampus, primary motor cortex, primary somatosensory cortex and primary visual cortex. We defined exploration as simultaneous whisking and sniffing above 5 Hz and found that this activity peaked at about 8 Hz. We considered rest as the absence of whisking and sniffing, and in this case, mean respiration occurred at about 3 Hz. We found a consistent shift across all areas toward these rhythm peaks accompanying behavioral state changes. We also found, across areas, that LFP gamma (70-100 Hz) amplitude could phase-lock to the animal’s respiratory rhythm, a finding indicative of respiration-locked changes in local processing. The respiratory rhythm, although occurring at the same frequencies of hippocampal theta, was not spectrally coherent with it, implying a different oscillator. Our results are consistent with the notion of respiration as a binder or integrator of activity between distant brain regions.
The Rate of Molecular Evolution When Mutation May Not Be Weak
Authors: de Koning A.P. Jason , De Sanctis Bianca D. 
Published: February 2018

AbstractOne of the most fundamental rules of molecular evolution is that the rate of neutral evolution equals the mutation rate and is independent of effective population size. This result lies at the heart of the Neutral Theory, and is the basis for numerous analytic approaches that are widely applied to infer the action of natural selection across the genome and through time, and for dating divergence events using the molecular clock. However, this result was derived under the assumption that evolution is strongly mutation-limited, and it has not been known whether it generalizes across the range of mutation pressures or the spectrum of mutation types observed in natural populations. Validated by both simulations and exact computational analyses, we present a direct and transparent theoretical analysis of the Wright-Fisher model of population genetics, which shows that some of the most important rules of molecular evolution are fundamentally changed by considering recurrent mutation’s full effect. Surprisingly, the rate of the neutral molecular clock is found to have population-size dependence and to not equal the mutation rate in general. This is because, for increasing values of the population mutation rate parameter (θ), the time spent waiting for mutations quickly becomes smaller than the cumulative time mutants spend segregating before a substitution, resulting in a net deceleration compared to classical theory that depends on the population mutation rate. Furthermore, selection exacerbates this effect such that more adaptive alleles experience a greater deceleration than less adaptive alleles, introducing systematic bias in a wide variety of methods for inferring the strength and direction of natural selection from across-species sequence comparisons. Critically, the classical weak mutation approximation performs well only whenθ<0.1, a threshold that many biological populations seem to exceed.
Conbase: a software for unsupervised discovery of clonal somatic mutations in single cells through read phasing
Authors: Hård Joanna , Håkim Ezeddin Al , Kindblom Marie , Björklund Åsa K. , Demirci Ilke , Paterlini Marta , Reu Pedro , Sennblad Bengt , Borgström Erik , Ståhl Patrik L. , Michaelsson Jakob , Mold Jeff E. , Frisén Jonas 
Published: February 2018

AbstractHere we report the development of Conbase, a software application for the identification of somatic mutations in single cell DNA sequencing data with high rates of allelic dropout and at low read depth. Conbase leverages data from multiple samples in a dataset and utilizes read phasing to call somatic single nucleotide variants and to accurately predict genotypes in whole genome amplified single cells in somatic variant loci. We demonstrate the accuracy of Conbase on simulated datasets, in vitro expanded fibroblasts and clonally in vivo expanded lymphocyte populations isolated directly from a healthy human donor.
Evidence for the coupling of substrate recognition with transporter opening in MOP-family flippases
Authors: Sham Lok To , Zheng Sanduo , Kruse Andrew C. , Bernhardt Thomas G. 
Published: February 2018

ABSTRACTBacteria produce a variety of surface-exposed polysaccharides important for cell integrity, biofilm formation, and evasion of the host immune response. Synthesis of these polymers often involves the assembly of monomer oligosaccharide units on the lipid carrier undecaprenyl-phosphate at the inner face of the cytoplasmic membrane. For many polymers, including cell wall peptidoglycan, the lipid-linked precursors must be transported across the membrane by flippases to facilitate polymerization at the membrane surface. Flippase activity for this class of polysaccharides is most often attributed to MOP (Multidrug/Oligosaccharidyllipid/Polysaccharide) family proteins. Little is known about how this ubiquitous class of transporters identifies and translocates its cognate precursor over the many different types of lipid-linked oligosaccharides produced by a given bacterial cell. To investigate the specificity determinants of MOP proteins, we selected for variants of the WzxC flippase involved in Escherichia coli capsule (colanic acid) synthesis that can substitute for the essential MurJ MOP-family protein and promote transport of cell wall peptidoglycan precursors. Variants with substitutions predicted to destabilize the inward-open conformation of WzxC lost substrate specificity and supported both capsule and peptidoglycan synthesis. Our results thus suggest that specific substrate recognition by a MOP transporter normally destabilizes the inward-open state, promoting transition to the outward-open conformation and concomitant substrate translocation. Furthermore, the ability of WzxC variants to suppress MurJ inactivation provides strong support for the designation of MurJ as the flippase for peptidoglycan precursors, the identity of which has been controversial.SIGNIFICANCEFrom cell walls in bacteria to protein glycosylation in eukaryotes, surface exposed polysaccharides are built on polyprenol-phosphate lipid carriers. Monomer units are typically assembled at the cytoplasmic face of the membrane and require translocation to the cell surface for polymerization/assembly. MOP-family proteins are a major class of transporters associated with this flippase activity. Despite their ubiquity and importance for cell surface biology, little is known about their transport mechanism. Here, we investigated substrate recognition by MOP transporters in bacteria. We present evidence that transport proceeds via destabilization of the inward-open state of the transporter by specific substrate binding thereby promoting a transition to the outward-open state and substrate release on the opposite face of the membrane.
Temporally unconstrained decoding reveals consistent but time-varying stages of stimulus processing
Authors: Vidaurre Diego , Myers Nicholas E. , Stokes Mark , Nobre Anna C. , Woolrich Mark W. 
Published: February 2018

AbstractIn this paper, we propose a method to track trial-specific neural dynamics of stimulus processing and decision making with high temporal precision. By applying this novel method to a perceptual template-matching task, we tracked representational brain states associated with the cascade of neural processing, from early sensory areas to higher-order areas that are involved in integration and decision-making. We address a major limitation of the traditional decoding approach: that it relies on consistent timing of these processes over trials. Using a temporally unconstrained decoding analysis approach, we found that the timing of the cognitive processes involved in perceptual judgements can vary considerably over trials. This revealed that the sequence of processing states was consistent for all subjects and trials, even when the timing of these states varied. Furthermore, we found that the specific timing of states on each trial was related to the quality of performance over trials.
Flexible sensorimotor computations through rapid reconfiguration of cortical dynamics
Authors: Remington Evan D. , Narain Devika , Hosseini Eghbal A. , Jazayeri Mehrdad 
Published: February 2018

SummarySensorimotor computations can be flexibly adjusted according to internal states and contextual inputs. The mechanisms supporting this flexibility are not understood. Here, we tested the utility of a dynamical system perspective to approach this problem. In a dynamical system whose state is determined by interactions among neurons, computations can be rapidly and flexibly reconfigured by controlling the system‘s inputs and initial conditions. To investigate whether the brain employs such control strategies, we recorded from the dorsomedial frontal cortex (DMFC) of monkeys trained to measure time intervals and subsequently produce timed motor responses according to multiple context-specific stimulus-response rules. Analysis of the geometry of neural states revealed a control mechanism that relied on the system‘s inputs and initial conditions. A tonic input specified by the behavioral context adjusted firing rates throughout each trial, while the dynamics in the measurement epoch allowed the system to establish initial conditions for the ensuing production epoch. This initial condition in turn set the speed of neural dynamics in the production epoch allowing the animal to aim for the target interval. These results provide evidence that the language of dynamical systems can be used to parsimoniously link brain activity to sensorimotor computations.
Mutation in DsbA signal sequence hampers the SRP mechanism: A new strategy to combat virulence factor
Authors: Durrani Faiza Gul , Gul Roquyya , Mirza Muhammad Usman , Kaderbhai Naheed Nazly , Saleem Mahjabeen , Akhter Muhammad Waheed 
Published: February 2018

AbstractDisulphide bond (Dsb) protein, characterized as an important virulence factor in gram negative bacteria. In this study, amino acid mutations in DsbA signal sequence (ss) and its effect on translocation of recombinant Ovine growth hormone (rOGH) was observed. Eight constructs were designed on the basis of increased hydrophobicity and showed that hydrophobicity and specificity of amino acid plays a crucial role in translocation of rOGH. Two DsbAss with the same hydropathy (1.539), one had alteration at -13 and second at -11 position; alanine (Ala) to isoleucine respectively were designed. The former DsbAss translocated rOGH from membrane to cytoplasmic fraction in E. coli as confirmed by SDS-PAGE, Western blot and molecular modelling analysis. MD simulations and binding free energy calculations evidenced that, altering Ala changed the orientation of signal peptide in the Ffh-M domain binding groove and hampered the process of translocation while change at position -11 pointed it outward. We hypothesize, amino acid and position of mutations in DsbAss can hinder the translocation process of signal recognition particle system, thus affecting the virulence of bacteria.
ATP-dependent force generation and membrane scission by ESCRT-III and Vps4
Authors: Schöneberg Johannes , Yan Shannon , Righini Maurizio , Pavlin Mark Remec , Lee Il-Hyung , Carlson Lars-Anders , Bahrami Amir Houshang , Goldman Daniel H. , Ren Xuefeng , Hummer Gerhard , Bustamante Carlos , Hurley James H. 
Published: February 2018

AbstractThe ESCRTs catalyze reverse-topology scission from the inner face of membrane necks in HIV budding, multivesicular endosome biogenesis, cytokinesis, and other pathways. We encapsulated a minimal ESCRT module consisting of ESCRT-III subunits Snf7, Vps24, and Vps2, and the AAA+ ATPase Vps4 such that membrane nanotubes reflecting the correct topology of scission could be pulled from giant vesicles. Upon ATP release by photo-uncaging, this system was capable of generating forces within the nanotubes in a manner dependent upon Vps4 catalytic activity, Vps4 coupling to the ESCRT-III proteins, and membrane insertion by Snf7. At physiological concentrations, single scission events were observed that correlated with forces of ~6 pN, verifying predictions that ESCRTs are capable of exerting forces on membranes. Imaging of scission with subsecond resolution revealed Snf7 puncta at the sites of membrane cutting, directly verifying longstanding predictions for the ESCRT scission mechanism.One Sentence SummaryESCRT-III and Vps4 were reconstituted from within the interior of nanotubes pulled from giant vesicles, revealing that this machinery couples ATP-dependent force production for membrane scission.
Are female leaders more efficient in family firms than in non-family firms?
Authors: Bjuggren Per-Olof , Nordström Louise , Palmberg Johanna 
Published: February 2018

PurposeThe aim of this study is to investigate whether female leaders are more efficient in family firms than in non-family firms.Design/methodology/approachThis paper uses a unique database of ownership and leadership in private Swedish firms that makes it possible to analyze differences in firm performance due to female leadership in family and non-family firms. The analysis is based on survey data merged with micro-level data on Swedish firms. Only firms with five or more employees are included in the analysis. The sample contains more than 1,000 firms.FindingsThe descriptive statistics show that there are many more male than female corporate leaders. However, the regression analysis indicates that female leadership has a much more positive impact on the performance of family firms than on that for non-family firms, where the effect is ambiguous.Originality/valueComparative studies examining the impact of female leadership on firm-level performance in family and non-family firms are rare, and those that exist are most often either qualitative or focused on large, listed firms. By investigating the role of female directors in family and non-family firms, the study adds to the literature on management, corporate governance and family firms.
When two worlds collide: critical reflection on co-production
Authors: Clayson Amanda , Webb Lucy , Cox Nigel 
Published: February 2018

Purpose
The purpose of this paper is to report the findings from reflexive data collection on the evolving co-production research relationship between the two “worlds” of community and academia: people with lived experience and their community intermediaries and academic researchers. It reports analysis of reflections on experience as the different partners explore and evaluate their own experiences of co-productive research within the context of substance use recovery co-production research.

Design/methodology/approach
The research uses reflexive data from perspectives of an intermediary community partner, academic partners, and community researchers on experiences of a series of co-productive research projects. The aim is to identify thematic features of the co-productive experiences from different positions and through the process of adaptation to a co-productive relationship.

Findings
This paper outlines what has been learnt from the experience of co-production and what has “worked” for community and academic partners; around the nature of co-production, barriers to performance, and its value to participants and the wider recovery research agenda.

Originality/value
This paper reports a unique perspective on a developing methodology in health and social care, contributing to a growing body of knowledge pertaining to experiences of co-production research.
An international telecom acquisition: lost in translation when Ya'alla met Boben Yang
Authors: Swierczek Benjamin Morgan , Swierczek Fredric William 
Published: February 2018

Purpose
This study aims to consider the transition that took place between two major telecom multinational companies (MNCs) during an acquisition in an emerging market, Laos. The differences in the orientation of top management, corporate culture and cultural distance led to the ineffective performance of the acquired telecom company.

Design/methodology/approach
Content analysis is used to identify the key factors in the case. The sources of data are annual reports, past interviews, market reports, and participant observation.

Findings
The ineffective performance of the acquisition was related to the lack of cultural compatibility of the new top management, a corporate culture that emphasized costs over customer satisfaction and the failure to close the cultural gap between the Middle Eastern cultural values and the Lao values.

Research limitations/implications
The data are mostly secondary data with some interviews of key managers. The case study would benefit with more extensive primary data, but the company was reluctant to respond.

Practical implications
The match between the top management leadership style, the complementarity of the new corporate culture with the existing one, and the reduction in the gap in national cultures are all critical in the continuing successful performance of an acquisition. A strategy of localization increasing the competencies of the local managers and professionals and the adaptation of the organization processes and practices to the local context are more effective in achieving positive performance.

Social implications
The change in corporate cultures from the collaborative/customer satisfaction emphasis of Tigo to a competitive/cost culture of Beeline led to a significant conflict with other telecom providers in Laos. This had performance consequences for Beeline and also the telecom sector.

Originality/value
This study is a unique demonstration of what happens in an acquisition of a telecom company in an emerging market. It is an interesting interplay of two major telecom companies with similar strategic choices but very different corporate culture orientations.
Looking to manage change successfully? It is dependent on alignment at every level
Authors: Lyman R. Kendall , Daloisio Tony C. 
Published: February 2018

Purpose
To become a great agent of change, you need to diagnose impediments and create remedies. However, to implement change successfully, you must take an inside-out and outside-in approach and focus on and align individual behavior, the functions of teams, and the organization as a whole.

Design/methodology/approach
The paper draws from 10 years of research and work with individuals, teams, and organizations.

Findings
Accelerating change in an organization requires leaders to define and align those activities that set the organization apart and give it a competitive advantage at the individual, team, and organizational levels.

Originality/value
As change leaders or L&D/OD professionals, this paper helps you recognize the need to develop your capabilities in five key roles: focus, align, engage, lead, and sustain.
Beyond ACT & GPA: self-efficacy as a non-cognitive predictor of academic success
Authors: Tepper Robert J. , Yourstone Steven A. 
Published: February 2018

PurposeThe purpose of this study is to identify significant non-cognitive variables as predictors of student success in an introductory accounting class.Design/methodology/approachNon-cognitive characteristics of the students were obtained by surveying two sections of an introductory accounting class. Survey results were combined with student performance in the class. Regression analysis was applied to determine the significant predictors of academic success.FindingsFindings show that students with similar ACT scores and GPA may outperform others owing to the effect of certain non-cognitive variables pertaining to self-efficacy. These included the individual’s perceived skill level, tendency to become discouraged and expected performance relative to others.Research limitations/implicationsOne research limitation is the lack of a pre- and post-test to measure any interventions. No interventions are part of this research study, but this limitation provides a strong suggestion for future research. Also, larger sample sizes might lead to different results.Practical implicationsCognitive ability is the intellectual capability that enables one to acquire, memorize, recall, combine, compare and use information and conceptual skills in new frameworks (Cronbach, 1984; Jensen, 1998). Standardized tests measure cognitive variables (Sedlacek, 2011). Research demonstrates that cognitive ability alone will not provide the best predictive model of performance (Hall et al., 2006). This study of certain non-cognitive variables improves instructor understanding of student success, increases predictive ability and informs teaching methods and interventions.Originality/valueThis study differs from previous research by adding to and enhancing the currently small and limited body of literature. While other studies have identified largely cognitive factors that relate to success in the introductory accounting course (Phillips, 2015), this study identifies significant non-cognitive variables relating to self-efficacy that can help accounting educators better understand student performance in introductory undergraduate financial accounting courses.