bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interneuron-specific plasticity at parvalbumin and somatostatin inhibitory synapses onto CA1 pyramidal neurons shapes hippocampal output
Authors: Udakis Matt , Pedrosa Victor , Chamberlain Sophie E.L. , Clopath Claudia , Mellor Jack R 
Published: September 2019

SummaryThe formation and maintenance of spatial representations within hippocampal cell assemblies is strongly dictated by patterns of inhibition from diverse interneuron populations. Although it is known that inhibitory synaptic strength is malleable, induction of long-term plasticity at distinct inhibitory synapses and its regulation of hippocampal network activity is not well understood. Here, we show that inhibitory synapses from parvalbumin and somatostatin expressing interneurons undergo long-term depression and potentiation respectively (PV-iLTD and SST-iLTP) during physiological activity patterns. Both forms of plasticity rely on T-type calcium channel activation to confer synapse specificity but otherwise employ distinct mechanisms. Since parvalbumin and somatostatin interneurons preferentially target perisomatic and distal dendritic regions respectively of CA1 pyramidal cells, PV-iLTD and SST-iLTP coordinate a reprioritisation of excitatory inputs from entorhinal cortex and CA3. Furthermore, circuit-level modelling reveals that PV-iLTD and SST-iLTP cooperate to stabilise place cells while facilitating representation of multiple unique environments within the hippocampal network.
A viral ring nuclease anti-CRISPR subverts type III CRISPR immunity
Authors: Athukoralage Januka S , McMahon Stephen , Zhang Changyi , Grüschow Sabine , Graham Shirley , Krupovic Mart , Whitaker Rachel J , Gloster Tracey , White Malcolm F 
Published: September 2019

ABSTRACTThe CRISPR system provides adaptive immunity against mobile genetic elements in bacteria and archaea. On detection of viral RNA, type III CRISPR systems generate a cyclic oligoadenylate (cOA) second messenger1–3, activating defence enzymes and sculpting a powerful antiviral response that can drive viruses to extinction4,5. Cyclic nucleotides are increasingly implicated as playing an important role in host-pathogen interactions6,7. Here, we identify a widespread new family of viral anti-CRISPR (Acr) enzymes that rapidly degrade cyclic tetra-adenylate (cA4). The viral ring nuclease (AcrIII-1) is the first Acr described for type III CRISPR systems and is widely distributed in archaeal and bacterial viruses, and proviruses. The enzyme uses a novel fold to bind cA4specifically and utilizes a conserved active site to rapidly cleave the signalling molecule, allowing viruses to neutralise the type III CRISPR defence system. The AcrIII-1 family has a broad host range as it targets cA4signalling molecules rather than specific CRISPR effector proteins. This study highlights the crucial role of cyclic nucleotide signalling in the conflict between viruses and their hosts.
CNVmap: a method and software to detect and map copy number variants from segregation data
Authors: Falque Matthieu , Jebreen Kamel , Paux Etienne , Knaak Carsten , Mezmouk Sofiane , Martin Olivier C. 
Published: September 2019

AbstractSingle nucleotide polymorphisms (SNPs) are widely used for detecting quantitative trait loci or for searching for causal variants of diseases. Nevertheless,structuralvariations such as copy-number variants (CNVs) represent a large part of natural genetic diversity and contribute significantly to trait variation. Over the past decade, numerous methods and softwares have been developed to detect CNVs. Such approaches are based on exploiting sequencing data or SNP arrays, but they bypass a wealth of information such as genotyping data from segregating populations, producede.g.for QTL mapping. Here we propose an original method to both detect andgenetically mapCNVs using mapping panels. Specifically, we exploit the apparent heterozygous state of duplicated loci: peaks in appropriately defined genome-wide allelic profiles provide highly specific signatures that identify the nature and position of the CNVs. Our original method and software can detect and map automatically up to 33 different predefined types of CNVs based on segregation data only. We validate this approach on simulated and experimental bi-parental mapping panels in two maize and one wheat populations. Most of the events found correspond to having just one extra copy in one of the parental lines but the corresponding allelic value can be that of either parent. We also find cases with two or more additional copies, especially in wheat where these copies locate to homeologues. More generally, our computational tool can be used to give additional value, at no cost, to many datasets produced over the past decade from genetic mapping panels.
Bacterial genes outnumber archaeal genes in eukaryotic genomes
Authors: Brückner Julia , Martin William F. 
Published: September 2019

AbstractThe origin of eukaryotes is one of evolution’s most important transitions, yet it is still poorly understood. Evidence for how it occurred should be preserved in eukaryotic genomes. Based on phylogenetic trees from ribosomal RNA and ribosomal proteins, eukaryotes are typically depicted as branching together with or within archaea. This ribosomal affiliation is widely interpreted as evidence for an archaeal origin of eukaryotes. However, the extent to which the archaeal ancestry of genes for the cytosolic ribosomes of eukaryotic cells is representative for the rest of the eukaryotic genome is unknown. Here we have clustered 19,050,992 protein sequences from 5,443 bacteria and 212 archaea with 3,420,731 protein sequences from 150 eukaryotes spanning six eukaryotic supergroups to identify genes that link eukaryotes exclusively to bacteria and archaea respectively. By downsampling the bacterial sample we obtain estimates for the bacterial and archaeal proportions of genes among 150 eukaryotic genomes. Eukaryotic genomes possess a bacterial majority of genes. On average, eukaryotic genes are 56% bacterial in origin. The majority drops to 53% in eukaryotes that never possessed plastids, and increases to 61% in photosynthetic eukaryotic lineages, where the cyanobacterial ancestor of plastids contributed additional genes to the eukaryotic genome, reaching 67% in higher plants. Intracellular parasites, which undergo reductive evolution in adaptation to the nutrient rich environment of the cells that they infect, relinquish bacterial genes for metabolic processes. In the current sample, this process of adaptive gene loss is most pronounced in the human parasite Encephalitozoon intestinalis with 86% archaeal and 14% bacterial derived genes. The most bacterial eukaryote genome sampled is rice, with 67% bacterial and 33% archaeal genes. The functional dichotomy, initially described for yeast, of archaeal genes being involved in genetic information processing and bacterial genes being involved in metabolic processes is conserved across all eukaryotic supergroups.
Resegmentation is an ancestral feature of the gnathostome vertebral skeleton
Authors: Criswell Katharine E. , Gillis J. Andrew 
Published: September 2019

AbstractThe vertebral skeleton is a defining feature of vertebrate animals. However, the mode of vertebral segmentation varies considerably between major lineages. In tetrapods, adjacent somite halves recombine to form a single vertebra through the process of “resegmentation”. However, in teleost fishes, there is considerable mixing between cells of the anterior and posterior somite halves, without clear resegmentation. To determine whether resegmentation is a tetrapod novelty, or an ancestral feature of jawed vertebrates, we tested the relationship between somites and vertebrae in a cartilaginous fish, the skate (Leucoraja erinacea). Using cell lineage tracing, we show that skate trunk vertebrae arise through tetrapod-like resegmentation, with anterior and posterior halves of each vertebra deriving from adjacent somites. We further show that tail vertebrae also arise through resegmentation, despite a duplication of the number of vertebrae per body segment. These findings resolve axial resegmentation as an ancestral feature of the jawed vertebrate body plan.
Thalamocortical network connectivity controls spatiotemporal dynamics of cortical and thalamic traveling waves
Authors: Bhattacharya Sayak , Le Cauchois Matthieu B. , Iglesias Pablo A. , Chen Zhe S. 
Published: September 2019

AbstractPropagation of neural activity in spatially structured neuronal networks has been observed in awake, anesthetized and sleeping brains. However, it remains unclear how traveling waves are coordinated temporally across recurrently connected brain structures, and how network connectivity affects spatiotemporal neural activity. Here we develop a computational model of a two-dimensional thalamocortical network that enables us to investigate traveling wave characteristics in space-time. We show that thalamocortical and intracortical network connectivity, excitation/inhibition balance, thalamocortical/corticothalamic delay can independently or jointly change the spatiotemporal patterns (radial, planar and rotating waves) and characteristics (speed, direction and frequency) of cortical and thalamic traveling waves. Simulations of our model further predict that increased thalamic inhibition induces slower cortical wave frequency, and enhanced cortical excitation increases cortical wave speed and oscillation frequencies. Overall, the model study provides not only theoretical insight into the basis for spatiotemporal wave patterns, but also experimental predictions that potentially control these dynamics.Author SummaryCognition or sensorimotor control requires the coordination of neural activity across widespread brain circuits. Propagating waves of oscillatory neural activities have been observed at both macroscopic and mesoscopic levels, with various frequencies, spatial coverage, and modalities. However, a complete understanding how thalamocortical traveling waves are originated and temporally coordinated in the thalamus and cortex are still unclear. Furthermore, it remains unknown how the network connectivity, excitation/inhibition balance, thalamocortical or corticothalamic delay determine the spatiotemporal wave patterns and characteristics of cortical and thalamic traveling waves. Here we develop a computational model of a two-dimensional thalamocortical network to investigate the thalamic and neocortical traveling wave characteristics in space-time, which allows us to quantitatively assess the impact of thalamocortical network properties on the formation and maintenance of complex traveling wave patterns. Our computational model provides strong theoretical insight into the basis of spatiotemporal wave propagation, as well as experimental predictions that control these wave dynamics.
Chikungunya virus infection impairs osteogenic differentiation of bone marrow-derived mesenchymal stem cells
Authors: Roy Enakshi , Shi Wen , Duan Bin , Reid St Patrick 
Published: September 2019

AbstractChikungunya virus (CHIKV) is a positive-sense, single-stranded RNA virus, belonging to the genus alphavirus in the familyTogaviridae. The virus is spread by theAedesspecies (sp.) mosquitoes in tropical and subtropical regions of the world. CHIKV causes Chikungunya fever (CHIKF), where the acute stage of infection is characterized by high fever, headache, rash, and polyarthralgia. In 30-40% of cases, patients develop a chronic stage with debilitating joint pain persisting for months to years imposing a burden on the population in terms of disability adjusted life years (DALY). Presently, no vaccines or treatment options are available for this infection. Prior investigations reveal that CHIKV infection is associated with bone pathology; however, the molecular mechanism underlying CHIKV-induced bone pathology remains poorly defined. Studies show that disruption of osteogenic differentiation and function of bone marrow-derived mesenchymal stem cells (BMMSCs) can lead to bone pathologies. However, to date pathogenesis of CHIKV infection in this context has not been studied. In the current study, we investigated the susceptibility of BMMSCs to CHIKV and studied the effect of infection on BMMSCs-derived osteogenic cells. To our knowledge, for the first time we report that CHIKV can productively infect BMMSCs. We observed a decrease in the intracellular and extracellular alkaline phosphatase (ALP) activity and reduction in calcium phosphate deposition in infected cells compared to mock-infected control. Thus, we conclude that CHIKV infects BMMSCs and disrupts function of osteogenic cells.ImportanceAlthough studies have shown association of bone pathology and CHIKV infection, the pathogenesis of infection causing altered bone homeostasis is not fully understood. Here, we demonstrate for the first time that BMMSCs are susceptible to CHIKV infection. Furthermore, we observe that infection causes disruption in the function of BMMSC- derived osteogenic cells. Impaired function of these osteogenic cells will likely lead to a disruption in bone homeostasis and in part, provides a mechanism for the observed bone pathology associated with CHIKV pathogenesis.
Ser/Thr kinase Trc controls neurite outgrowth inDrosophilaby modulating microtubule-microtubule sliding
Authors: Norkett Rosalind , del Castillo Urko , Lu Wen , Gelfand Vladimir I. 
Published: September 2019

AbstractCorrect neuronal development requires tailored neurite outgrowth. Neurite outgrowth is driven by microtubule sliding – the transport of microtubules along each other. We have recently demonstrated that a “mitotic” kinesin-6 (Pavarotti inDrosophila) effectively inhibits microtubule-sliding and neurite outgrowth. However, mechanisms of Pavarotti regulation in interphase cells and specifically in neurite outgrowth are unknown. Here, we use a combination of live imaging and biochemical methods to show that the inhibition of microtubule sliding by Pavarotti is controlled by phosphorylation. We identify the Ser/Thr NDR kinase Tricornered (Trc) as a Pavarotti-dependent regulator of microtubule sliding in neurons. Further, we show that Trc-mediated phosphorylation of Pavarotti promotes its interaction with 14-3-3 proteins. 14-3-3 binding is necessary for Pavarotti to interact with microtubules and inhibit sliding. Thus, we propose a pathway by which microtubule sliding can be up or down regulated in neurons to control neurite outgrowth, and establish parallels between microtubule sliding in mitosis and post-mitotic neurons.
Rapid accumulation of mutations in growing mycelia of a hypervariable fungus Schizophyllum commune
Authors: Bezmenova Aleksandra V. , Zvyagina Elena A. , Fedotova Anna V. , Kasianov Artem S. , Neretina Tatiana V. , Penin Aleksey A. , Bazykin Georgii A. , Kondrashov Alexey S. 
Published: September 2019

AbstractThe number of mutations that occur per nucleotide per generation varies between species by several orders of magnitude. In multicellular eukaryotes, the per generation mutation rate depends both on the per cell division mutation rate and on the number of germline cell divisions per generation. In a range of species, from fungi to humans, the number of germline cell divisions is lower than that of somatic cells, reducing the mutation burden on the offspring. The basidiomycete Schizophyllum commune has the highest level of genetic polymorphism known among eukaryotes. In a previous study, it was also found to have a high per generation mutation rate, probably contributing to its high polymorphism. However, this rate has been measured only in a breeding experiment on Petri dishes, and it is unclear how this result translates to natural populations. Here, we used an experimental design that measures the rate of accumulation of de novo mutations in a linearly growing mycelium. We show that S. commune accumulates mutations at a uniform rate of 1.4·10−7 substitutions per nucleotide per meter of growth, which is 3 orders of magnitude higher than the corresponding rates in the oak Quercus robur and the fungus Armillaria gallica. This figure is consistent with the estimate obtained before, and suggests the lack of a dedicated germline in this system. If so, even a low per cell division mutation rate can translate into a very high per generation mutation rate when the number of cell divisions between consecutive meioses is large.
A roadmap for BIM adoption and implementation in developing countries: the Pakistan case
Authors: Girginkaya Akdag Suzan , Maqsood Uzair 
Published: September 2019

Purpose
Digital media is reshaping architectural design by introducing new tools, methods and workflows. Among various AEC tools, Building Information Modeling (BIM) has gained popularity due to its collaboration platform enabling cross-disciplinary teamwork during whole life cycle of buildings. BIM has further transformed culture and processes associated with design, construction and operation of buildings, hence triggering new building regulations in developed countries. However, in developing countries, BIM implementation is facing several barriers, such as lack of investment in technology and training, hesitation in quitting traditional tools and practices, etc. The purpose of this paper is to highlight potentials of BIM for developing countries, which are in need of more sustainable policies for enhancing their economic and environmental performances.

Design/methodology/approach
Throughout the text, a literature review on BIM including its dimensions and benefits, impacts on architectural design and adoption in global and local contexts is provided. In case study, surveys and structured interviews are conducted with BIM user and non-BIM user architects throughout Pakistan. Beyond 2D/3D modeling, the use of BIM applications for sustainable design process such as scheduling (4D), cost estimation (5D), performance analysis and facilities management (6D) is investigated.

Findings
Using analytical tools of an online surveying tool and SPSS statistical software, barriers and motivations for BIM implementation in Pakistan are determined. Strategies for further BIM adoption and implementation via “education and training institutions” and “supporting organizations and institutions” are defined.

Originality/value
As a developing country, Pakistan shall be moving the barriers for the spread of BIM technology. Recent research covered the entire AEC sector (Masood et al., 2014; Sohu et al., 2017; Ali et al., 2018), yet this paper focuses specifically on architectural design and practice field. In order to find out experiences and expectations about BIM technology in the architecture sector, professionals are surveyed and four chief architects are interviewed. How far have Pakistani architects adopted BIM? For which project types and scales is BIM more serviceable for them? Which BIM applications are they implementing to overcome the limitations in their professional practice? In Pakistan, where sustainability, in terms of scheduling, cost estimation, performance analysis and facilities management, is an indispensible measure for local practices, has implementation of BIM technology achieved sustainability in architectural design process? What are the motivations of Pakistani architects for becoming BIM users in future?
Sociocultural factors as determinants of female entrepreneurs’ business strategies
Authors: Cullen Ufi 
Published: September 2019

PurposeThis paper aims to contribute to the understanding of the impact of social institutions, and, in particular, of national culture, on business success, further considering how these institutions influence entrepreneurial decisions around partnership structure and networking strategies, for instance. It additionally examines how the female entrepreneur finds her way around these institutions to help her business succeed, evaluating whether this success is a culture-independent phenomenon that can be achieved through using similar, potentially advantageous strategies regardless of national context or whether adjustments are required before entering a foreign market.Design/methodology/approachThe data were collected through a survey study from 240 established female entrepreneurs with 120 from each country. Two existing surveys were used to create the questions. The target sample group was comprised of successful female businesses within northwest England and western Turkey. These regions were selected due to their convenience and accessibility. Only successful businesses or, in other words, established entrepreneurs were accepted to this study. The business success criteria were: age of business (>5 years); stability or growth recorded on profitability; sales volume; and number of employees within the last financial year.FindingsThe findings showed significant differences between the two groups of established female entrepreneurs in their demographic characteristics, networking pattern, work pattern, business structure and perceived impediments at different stages of business venturing. The findings assert that the cultural dimensions of power distance and individualism have the most significant impact upon the established female entrepreneurs’ business strategies.Originality/valueTo date, limited studies have examined the country-specific factors, which may account for variance in women entrepreneurs’ behaviour and subsequent outcomes. This study attempts to close this gap through taking a closer look at the country-specific sociocultural factors creating differences in established female entrepreneurs’ business strategies within the context of Turkey and the UK. Should any female business strategy have become successful in one country, then policymakers and women support organisations can work on developing ways for benchmarking. Moreover, this study aims to guide female entrepreneurs to develop feasible international market entry strategies to ensure survival in today’s global market.
Partnership working across sectors: a multi-professional perspective
Authors: El-Farargy Nancy 
Published: September 2019

Purpose
The Public Bodies (Joint Working) (Scotland) Act 2014 set the framework for the integration of adult health and social care services. Teams, organisations and sectors are now required to work in partnership and interdependently to deliver shared outcomes for the people they serve. The purpose of this paper is to explore any features, practices and behaviours that could influence effective partnership working across sectors.

Design/methodology/approach
A questionnaire was designed and distributed to a range of stakeholders working in health, social care and the third sector. With reference to the changing health and social care reform agenda, the aims of the survey were to gather views, experiences and perceptions of working across sectors, and any workforce development needs.

Findings
The majority of respondents were from the NHS (80.3 per cent, 118/147), and experiences were largely drawn from those working with the third sector. The utility of working with the third sector was positively highlighted; however, there were limited opportunities to fully engage. Whilst formal education and training was welcomed, workforce development needs were mostly related to fostering relationships and building mutual trust.

Originality/value
This paper highlights views, perceptions, enablers and barriers to integrated care in Scotland. Whilst the Scottish integration landscape is currently not fully fledged, insights into prevailing attitudes towards integrated care, by a cohort of the Scottish health and care workforce, are offered. In particular, reflections by the NHS workforce to working with third sector services are discussed.