bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional Network Analysis on Brains Reveals a Potential Regulatory Role of PPP1R3F in Autism Spectrum Disorders
Authors: Torshizi Abolfazl Doostparast , Duan Jubao , Wang Kai 
Published: May 2018

AbstractObjectiveThis study aims at identifying master regulators of transcriptional networks in autism spectrum disorders (ASDs).ResultsWith two sets of independent RNA-Seq data generated on cerebellum from patients with ASDs and control subjects (N=39 and 45 for set 1, N=24 and 38 for set 2, respectively), we carried out a network deconvolution of transcriptomic data, followed by virtual protein activity analysis. We identified PPP1R3F (Protein Phosphatase 1 Regulatory Subunit 3F) as a master regulator affecting a large body of downstream genes that are associated with the disease phenotype. Pathway enrichment analysis on the identified targets of PPP1R3F in both datasets indicated alteration of endocytosis pathway. This exploratory analysis is limited by sample size, but it illustrates a successful application of network deconvolution approaches in the analysis of brain gene expression data and generates a hypotheses that may be further validated by large-scale studies in the future.
Graded and bidirectional control of real-time reach kinematics by the cerebellum
Authors: Becker Matthew I. , Person Abigail L. 
Published: May 2018

AbstractThe rules governing the relationship between cerebellar output and movement production remain unknown despite the well-recognized importance of the cerebellum in motor learning and precision. In this study, we investigated how cerebellar output sculpts reach behavior in mice by manipulating neural activity in the anterior interposed nucleus (IntA) in closed-loop with ongoing behavior. Optogenetic modulation of cerebellar output revealed monotonically graded and bidirectional control of real-time reach velocity by IntA. Furthermore, kinematic effects were relatively context invariant, suggesting that cerebellar output summates with ongoing motor commands generated elsewhere throughout the reaching movement. These results characterize the relationship between cerebellar output modulation and reach behavior as a bidirectional and scalable kinematic command signal. Our findings illustrate how learned, predictive coding in the cerebellar cortex could be actuated through the cerebellar nuclei to contribute in real time to purposive motor control.
Integrated Molecular Profiling Studies to Characterize the Cellular Origins of High-Grade Serous Ovarian Cancer
Authors: Lawrenson Kate , Fonseca Marcos A.S. , Segato Felipe , Lee Janet M. , Corona Rosario I. , Seo Ji-Heui , Coetzee Simon , Lin Yvonne G. , Pejovic Tanja , Mhawech-Fauceglia Paulette , Drapkin Ronny , Karlan Beth Y. , Hazelett Dennis J. , Freedman Matthew L. , Gayther Simon A. , Noushmehr Houtan 
Published: May 2018

AbstractHistorically, high-grade serous ovarian cancers (HGSOCs) were thought to arise from ovarian surface epithelial cells (OSECs) but recent data implicate fallopian tube secretory epithelial cells (FTSECs) as the major precursor. We performed transcriptomic and epigenomic profiling to characterize molecular similarities between OSECs, FTSECs and HGSOCs. Transcriptomic signatures of FTSECs were preserved in most HGSOCs reinforcing FTSECs as the predominant cell-of-origin; though an OSEC-like signature was associated with increased chemosensitivity (Padj= 0.03) and was enriched in proliferative-type tumors, suggesting a dualistic model for HGSOC origins. More super-enhancers (SEs) were shared between FTSECs and HGSOCs than between OSECS and HGSOCs (P< 2.2 × 10−16). SOX18, ELF3 and EHF transcription factors (TFs) coincided with HGSOC SEs and represent putative novel drivers of tumor development. Our integrative analyses support a predominantly fallopian origin for HGSOCs and indicate tumorigenesis may be driven by different TFs according to cell-of-origin.
Partitioning protein ParP directly links chemotaxis to biofilm dispersal in Pseudomonas aeruginosa
Authors: Reinhardt Jesse M. , Bardy Sonia L. 
Published: May 2018

AbstractThe recent characterization of partitioning proteins in the localization of chemotaxis signal transduction systems was proposed to have broad implications for polarly-flagellated non-enterobacteriaceae gamma-proteobacteria. These studies showed that the loss of either partitioning protein resulted in equivalent reductions in swimming motility and chemotaxis protein localization and inheritance. However, the role of these chemotaxis partitioning proteins outside of Vibrio spp. remains untested. Our studies on the chemotaxis partitioning proteins in Pseudomonas aeruginosa revealed an unexpected role for the partitioning protein ParP. While the P. aeruginosa ParC and ParP homologs are needed for wild type swimming motility, the loss of ParP results in a greater swimming defect compared to the parC mutant. Our studies revealed that the Par-like proteins directly interact with each other and the chemotaxis system, and ParP interacts with DipA. Deletion of dipA results in a similar defect in swimming motility as the parP mutant. ParP has an interdependence for polar cluster formation, but not localization, with both CheA and DipA, and CheA cluster formation is partially dependent on ParP. Due to the direct interactions and interdependence of cluster formation of ParP and DipA, and the similar phenotypes of the parP and dipA mutants, further investigation into the role of ParP in biofilm dispersion is warranted.ImportanceImpaired chemotaxis protein cluster formation or inheritance reduces chemotaxis which can have an impact on of the virulence of a bacterium. In some gamma-proteobacteria there are systems in place to ensure that chemotaxis proteins, like chromosomes and plasmids, are localized for optimal chemotaxis and that daughter cells inherit their own clusters for use after cell division. Par-like proteins have been implicated in the partitioning and localization of chemotaxis proteins and the chemotactic ability of Vibrio spp. and Rhodobacter sphaeroides [1–3]. We propose that Par-like proteins can do more than localize chemotaxis proteins to the poles of the cells. In P. aeruginosa, they bring together other key proteins involved in regulating flagellar-based motility, and we propose they function as a critical link between biofilm dispersal and motility.
Susceptibility to Neutralization by Broadly Neutralizing Antibodies Correlates with Infected Cell Binding for a Panel of Clade B HIV Reactivated from Latent Reservoirs
Authors: Ren Yanqin , Korom Maria , Truong Ronald , Chan Dora , Huang Szu-han , Kovacs Colin C. , Benko Erika , Safrit Jeffrey T. , Lee John , Garbán Hermes , Apps Richard , Goldstein Harris , Lynch Rebecca M. , Jones R.Brad 
Published: May 2018

AbstractEfforts to HIV cure are obstructed by reservoirs of latently infected CD4+T-cells that can re-establish viremia. Broadly neutralizing HIV-specific antibodies (bNAbs), defined by unusually high neutralization breadths against globally diverse viruses, may contribute to the elimination of these reservoirs by binding to reactivated cells, targeting them for immune clearance. However, the relationship between neutralization of reservoir isolates and binding to corresponding infected primary CD4+T-cells has not been determined. Thus, the extent to which neutralization breadths and potencies can be used to infer the corresponding parameters of infected-cell binding is currently unknown. We assessed the breadths and potencies of bNAbs against 36 viruses reactivated from peripheral blood CD4+T-cells of ARV-treated HIV-infected individuals, using paired neutralization and infected-cell binding assays. Single antibody breadths ranged from 0–64% for neutralization (IC80≤10μg/ml) and 0–89% for binding, with two-antibody combinations reaching 0-83% and 50-100%, respectively. Infected-cell binding correlated with virus neutralization for 10 out of 14 antibodies (e.g. 3BNC117, r=0.87, p<0.0001). Heterogeneity was observed, however, with a lack of significant correlations for 2G12, CAP256.VRC26.25, 2F5, and 4E10. Our results provide guidance on the selection of bNAbs for interventional cure studies; both by providing a direct assessment of intra-and inter-individual variability in neutralization and infected cell binding in a novel cohort, and by defining the relationships between these parameters for a panel of bNAbs.ImportanceAlthough anti-retroviral therapies have improved the lives of people who are living with HIV, they do not cure infection. Efforts are being directed towards harnessing the immune system to eliminate the virus that persists, potentially resulting in virus-free remission without medication. HIV-specific antibodies hold promise for such therapies owing to their abilities to both prevent the infection of new cells (neutralization), and also to direct the killing of infected cells. We isolated 36 HIV strains from individuals whose virus was suppressed by medication, and tested 14 different antibodies for neutralization of these viruses and for binding to cells infected with the same viruses (critical for engaging natural killer cells). For both neutralization and infected-cell binding, we observed variation both between individuals, and amongst different viruses within an individual. For most antibodies, neutralization activity correlated with infected cell binding. These data provide guidance on the selection of antibodies for clinical trials.
Characterisation of Antibody Interactions with the G Protein of Vesicular Stomatitis Virus Indiana Strain and Other Vesiculovirus G Proteins
Authors: Munis Altar M , Tijani Maha , Hassall Mark , Mattiuzzo Giada , Collins Mary K , Takeuchi Yasuhiro 
Published: May 2018

ABSTRACTVesicular stomatitis virus Indiana strain G protein (VSVind.G) is the most commonly used envelope glycoprotein to pseudotype lentiviral vectors (LV) for experimental and clinical applications. Recently, G proteins derived from other vesiculoviruses (VesG), for example Cocal virus, have been proposed as alternative LV envelopes with possible advantages compared to VSVind.G. Well-characterised antibodies that recognise VesG will be useful for vesiculovirus research, development of G protein-containing advanced therapy medicinal products (ATMPs), and deployment of VSVind-based vaccine vectors. Here we show that one commercially available monoclonal antibody, 8G5F11, binds to and neutralises G proteins from three strains of VSV as well as Cocal, and Maraba viruses, whereas the other commercially available monoclonal anti-VSVind.G antibody, IE9F9, binds to and neutralises only VSVind.G. Using a combination of G protein chimeras and site-directed mutations, we mapped the binding epitopes of IE9F9 and 8G5F11 on VSVind.G. IE9F9 binds close to the receptor binding site and competes with soluble low-density lipoprotein receptor (LDLR) for binding to VSVind.G, explaining its mechanism of neutralisation. In contrast, 8G5F11 binds close to a region known to undergo conformational changes when the G protein moves to its post-fusion structure, and we propose that 8G5F11 cross-neutralises VesGs by inhibiting this.IMPORTANCEVSVind.G is currently regarded as the gold-standard envelope to pseudotype lentiviral vectors. However, recently other G proteins derived from vesiculoviruses have been proposed as alternative envelopes. Here, we investigated two anti-VSVind.G monoclonal antibodies for their ability to cross-react with other vesiculovirus G proteins, and identified the epitopes they recognise, and explored the mechanisms behind their neutralisation activity. Understanding how cross-neutralising antibodies interact with other G proteins may be of interest in the context of host-pathogen interaction and co-evolution as well as providing the opportunity to modify the G proteins and improve G protein-containing medicinal products and vaccine vectors.
The Gut Microbiome of the Eastern Spruce Budworm Does Not Influence Larval Growth or Survival
Authors: Schwarz Melbert T. , Kneeshaw Daniel , Kembel Steven W. 
Published: May 2018

ABSTRACTMicrobial communities have been shown to play an important role for host health in mammals, especially humans. It is thought that microbes could play an equally important role in other animal hosts such as insects. A growing body of evidence seems to support this, however most of the research effort in understanding host-microbe interactions in insects has been focused on a few well-studied groups such as bees, cockroaches and termites. We studied the effects of the gut-associated microbial community on the growth and survival of the eastern spruce budworm Choristoneura fumiferana, an economically important lepidopteran forest pest in eastern Canada and the northeastern United States. Contrary to our expectations, the gut microbial community of spruce budworm larvae does not appear to influence host growth or survival. Our results agree with the hypothesis that lepidopteran larvae lack resident microbial communities and are not nutritionally dependent on bacterial symbionts.
Mapping DNA sequence to transcription factor binding energy in vivo
Authors: Barnes Stephanie L. , Belliveau Nathan M. , Ireland William T. , Kinney Justin B. , Phillips Rob 
Published: May 2018

AbstractDespite the central importance of transcriptional regulation in systems biology, it has proven difficult to determine the regulatory mechanisms of individual genes, let alone entire gene networks. It is particularly difficult to analyze a promoter sequence and identify the locations, regulatory roles, and energetic properties of binding sites for transcription factors and RNA polymerase. In this work, we present a strategy for interpreting transcriptional regulatory sequences using in vivo methods (i.e. the massively parallel reporter assay Sort-Seq) to formulate quantitative models that map a transcription factor binding site’s DNA sequence to transcription factor-DNA binding energy. We use these models to predict the binding energies of transcription factor binding sites to within 1 kBT of their measured values. We further explore how such a sequence-energy mapping relates to the mechanisms of trancriptional regulation in various promoter contexts. Specifically, we show that our models can be used to design specific induction responses, analyze the effects of amino acid mutations on DNA sequence preference, and determine how regulatory context affects a transcription factor’s sequence specificity.
Cryo-EM structure of the volume-regulated anion channel LRRC8
Authors: Kasuya Go , Nakane Takanori , Yokoyama Takeshi , Jia Yanyan , Inoue Masato , Watanabe Kengo , Nakamura Ryoki , Nishizawa Tomohiro , Kusakizako Tsukasa , Tsutsumi Akihisa , Yanagisawa Haruaki , Dohmae Naoshi , Hattori Motoyuki , Ichijo Hidenori , Yan Zhiqiang , Kikkawa Masahide , Shirouzu Mikako , Ishitani Ryuichiro , Nureki Osamu 
Published: May 2018

AbstractMaintenance of cell volume against osmotic change is crucial for proper cell functions, such as cell proliferation and migration. The leucine-rich repeat-containing 8 (LRRC8) proteins are anion selective channels, and were recently identified as pore components of the volume-regulated anion channels (VRACs), which extrude anions to decrease the cell volume upon cell-swelling. Here, we present the human LRRC8A structure, determined by a single-particle cryo-electron microscopy analysis. The sea anemone-like structure represents a trimer of dimers assembly, rather than a symmetrical hexameric assembly. The four-spanning transmembrane region has a gap junction channel-like membrane topology, while the LRR region containing 15 leucine-rich repeats forms a long twisted arc. The channel pore is along the central axis and constricted on the extracellular side, where the highly conserved polar and charged residues at the tip of the extracellular helix contribute to the anion and other osmolyte permeability. Comparing the two structural populations facilitated the identification of both compact and relaxed conformations, suggesting that the LRR region is flexible and mobile with rigid-body motions, which might be implicated in structural transitions upon pore opening. Overall, our structure provides a framework for understanding the molecular mechanisms of this unique class of ion channels.
A Cell Cycle Switch Dictates Organ Repair and Tissue Growth Responses in TheDrosophilaHindgut
Authors: Cohen Erez , Allen Scott R , Sawyer Jessica K , Fox Donald T 
Published: May 2018

ABSTRACTPloidy-increasing cell cycles drive tissue growth in many developing organs. Such cycles, including endocycles, are increasingly appreciated to drive tissue growth following injury or activated growth signaling in mature organs. In these organs, the regulation and distinct roles of different cell cycles remains unclear. Here, we uncover a programmed switch between cell cycles in theDrosophilahindgut pylorus. Using an acute injury model, we identify mitosis as the response in larval pyloric cells, whereas endocycles occur in adult pyloric cells. By developing a novel genetic method, DEMISE (Dual-Expression-Method-for-Induced-Site-specific-Eradication), we show the cell cycle regulator Fizzy-related dictates the decision between mitosis and endocycles. After injury, both cycles accurately restore tissue mass and genome content. However, in response to sustained growth signaling, only endocycles preserve epithelial architecture. Our data reveal distinct cell cycle programming in response to similar stimuli in mature vs. developmental states and reveal a tissue-protective role of endocycles.
Effectiveness of Demand creation promotions and demand creation personnel in creating demand for Voluntary Medical Male Circumcision in Chitungwiza district, Zimbabwe in 2016
Authors: Matikiti Taurai , Juru Tsitsi P , Gombe Notion , Nsubuga Peter , Tshimanga Mufuta 
Published: May 2018

AbstractZimbabwe is one of the 14 countries in eastern and southern Africa that have adopted Voluntary Medical Male Circumcision (VMMC) as an HIV prevention intervention in response to WHO’s recommendation for countries with generalised high HIV epidemics and low VMMC prevalence. However, since 2013 when VMMC was scalled up in Zimbabwe, there was a general low uptake of the VMMC programme particularly on the target age group 20-29 years which has an immediate reduction in the HIV burden. The failure of VMMC uptake in the priority age group prompted the need to analyse the effectiveness of demand creation promotions and personnel used in creating demand for VMMC in Chitungwiza district, Zimbabwe. We employed judgmental sampling, a non-probability sampling technique where we interviewed VMMC clients (n=50) and service providers (n=10) using self administered questions, and community mobilisers (n=10) and demand creation teams (n=3) using face-to-face interviews based on their experience, knowledge and professional judgment. We also randomly analysed client records in the form of 50 Client Intake Forms (CIF) books. We found out that Community mobilisers and Demand creation officers were effective in mobilising clients in the age group 10-15 years and 16-30 years respectively. The use of clinicians (nurses) was also found to be useful in creating demand for VMMC. We also found out that intensifying campaigns during school holidays, the use of tent-based/caravan campaigns and the door to door campaigns were most effective strategies under demand creation promotions. We concluded that there is need to increase demand creation officers and qualified community mobilisers. To regulary train and motivate current community mobilisers as well as increasing the use of clinicians(nurses) in demand creation. We recommended the need to increase the number of mobile caravans and intensifying on the door to door campaigns in the district.
How HR practice, work engagement and job crafting influence employee performance
Authors: Guan Xiaoyu , Frenkel Stephen 
Published: May 2018

PurposeScholars have adopted different theoretical perspectives to explain the influence of HR practice on employee outcomes. However, few studies have investigated the role of human resource (HR) practice in fostering higher in-role and extra-role employee performance by encouraging employee participation in job design, a process referred to as job crafting. Drawing on human resource management (HRM) process theory and the job crafting literature, this study aims to examine how work engagement and job crafting mediate the relationship between employee perceptions of HR practice and employee performance.Design/methodology/approachThe authors use survey on a sample of 455 employees working in five Chinese manufacturing firms to test their theoretical model.FindingsThis study finds that where management maintains a strong HR system, employees are more likely to be engaged in their work and participate in job crafting. In addition, job crafting on its own, and work engagement and job crafting together, are shown to mediate the HRM–performance relationship.Research limitations/implicationsIn a Chinese context, line managers (including supervisors) are both important implementers of HR policy and vary in their adoption of particular roles. Yet our research did not consider the role of these persons in facilitating work engagement or job crafting. Future studies could usefully explore how these managers vary in their attitudes towards job crafting and the roles they play in encouraging this important activity.Practical implicationsOne important implication is that strong HR system with distinctive, consistent and consensus HR practices should be used by managers to motivate employees to encourage work engagement and job crafting behaviours.Originality/valueThis study enriches the theoretical framework to explain the underlying mechanism between HRM and employee performance from job crafting perspective.
Transformation of public distribution system in Chhattisgarh: Dr Raman Singh’s leadership
Authors: Shubham Shubham , Mittal Shashank , Sengupta Atri 
Published: May 2018

Subject area
Organizational behavior, Organizational leadership, Organizational transformation.

Study level/applicability
First year management students in the course Organizational Behavior (OB). Final year management students in the elective course on leadership and change management. Middle level managers who are working in industry, in the management development program related to change leadership and change management.

Case overview
This case deals with the transformation of the public distribution system (PDS) under the leadership of Dr Raman Singh. The PDS system was an inefficient system and the food grain supply intended for the poor was diverted by intermediaries before reaching the intended beneficiaries. Having experiences in central government ministries as a cabinet minister, Dr Raman Singh decided to transform the PDS. The challenges faced were primarily from that of the reticent bureaucracy and dealing with them requires patience and the skills of a transformational and motivational leader which Dr Raman Singh possessed.

Expected learning outcomes
This case intends to develop understanding of various dimensions related to transformational and motivational styles of leadership. Further, it intends to develop understanding of crucial institutional and organizational changes and how leaders bring about these changes in sync with technological and process changes.

Supplementary materials
Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code
CSS: 6: Human Resource Management.