bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic Physical Disturbance Substantially Alters the Response of Biological Soil Crusts to a Wetting Pulse, as Characterized by Metatranscriptomic Sequencing
Authors: Steven Blaire , Kuske Cheryl R. 
Published: May 2018

AbstractBiological soil crusts (biocrusts) are microbial communities that are a feature of arid surface soils worldwide. In drylands where precipitation is pulsed and ephemeral, the ability of biocrust microbiota to rapidly initiate metabolic activity is critical to their survival. Community gene expression was compared after a short duration (1 hour) wetting pulse in both intact and soils disturbed by chronic foot trampling.Across the metatranscriptomes the majority of transcripts were cyanobacterial in origin, suggesting that cyanobacteria accounted for the bulk of the transcriptionally active cells. Chronic trampling substantially altered the functional profile of the metatranscriptomes, specifically resulting in a significant decrease in transcripts for nitrogen fixation. Soil depth (biocrust and below crust) was a relatively small factor in differentiating the metatranscriptomes, suggesting that the metabolically active bacteria were similar between shallow soil horizons. The dry samples were consistently enriched for hydrogenase genes, indicating that molecular hydrogen may serve as an energy source for the desiccated soil communities. The water pulse was associated with a restructuring of the metatranscriptome, particularly for the biocrusts. Biocrusts increased transcripts for photosynthesis and carbon fixation, suggesting a rapid resuscitation upon wetting. In contrast, the trampled surface soils showed a much smaller response to wetting, indicating that trampling altered the metabolic response of the community. Finally, several biogeochemical cycling genes in carbon and nitrogen cycling were assessed for their change in abundance due to wetting in the biocrusts. Different transcripts encoding the same gene product did not show a consensus response, with some more abundant in dry or wet biocrusts, highlighting the challenges in relating transcript abundance to biogeochemical cycling rates.These observations demonstrate that metatranscriptome sequencing was able to distinguish alterations in the function of arid soil microbial communities at two varying temporal scales, a long-term ecosystems disturbance through foot trampling, and a short term wetting pulse. Thus, community metatranscriptomes have the potential to inform studies on the response and resilience of biocrusts to various environmental perturbations.
Regulated nuclear accumulation of a histone methyltransferase times the onset of heterochromatin formation inC. elegansembryos
Authors: Mutlu Beste , Chen Huei-Mei , Moresco James J. , Orelo Barbara D. , Yang Bing , Gaspar John M. , Keppler-Ross Sabine , Yates John R. , Hall David H. , Maine Eleanor M. , Mango Susan E. 
Published: May 2018

ONE SENTENCE SUMMARYMET-2/SETDB1 and interactors (LIN-65/ATF7IP and ARLE-14/ARL14EP) initiate heterochromatin formation during embryogenesis.ABSTRACTHeterochromatin formation during early embryogenesis is timed precisely, but it has been elusive how this process is regulated. Here we report the discovery of a histone methyltransferase complex whose nuclear accumulation determines the onset of heterochromatin formation inC. elegansembryos. We find that the inception of heterochromatin generation coincides with the nuclear accumulation of the methyltransferase MET-2 (SETDB). The absence of MET-2 results in delayed and disturbed heterochromatin formation, whereas accelerated nuclear localization of the methyltransferase leads to precocious heterochromatin. We identify two factors that bind to and function with MET-2: LIN-65, which resembles ATF7IP, localizes MET-2 into nuclear hubs, and ARLE-14, orthologous to ARL14EP, promotes stable association of MET-2 with chromatin. These data reveal that nuclear accumulation of MET-2 in conjunction with LIN-65 and ARLE-14 regulates timing of heterochromatin domains during embryogenesis.
A novel approach of human geroprotector discovery by targeting the converging subnetworks of aging and age-related diseases
Authors: Yang Jialiang , Zhang Bin , Houten Sander , Schadt Eric , Zhu Jun , Suh Yousin , Tu Zhidong 
Published: May 2018

AbstractA key goal of geroscience research is to discover effective interventions to extend human healthspan, the years of healthy life. Currently, majority of the geroprotectors are found by testing compounds in model organisms; whether these compounds will be effective in humans is largely unknown. Here we present a novel strategy called ANDRU (aging network based drug discovery) to help the discovery of human geroprotectors. Instead of relying on model organisms, this approach is driven by human genomic and pharmacogenomic data. It first identifies human aging subnetworks that putatively function at the interface between aging and age-related diseases; it then screens for pharmacological or genetic interventions that may “reverse” the age-associated transcriptional changes seen in these subnetworks. We applied ANDRU to human adipose and artery tissues. In adipose tissue, PTPN1, a target for diabetes treatment and APOE, a known genetic factor for human longevity and diseases like Alzheimer’s disease, were ranked at the top. For small molecules, conjugated linoleic acid and metformin, a drug commonly used to treat type 2 diabetes, were ranked among the top compounds. In artery tissue, N-methyl-D-aspartate antagonists and curcumin were ranked at the top. In summary, ANDRU represents a promising human data-driven strategy that may speed up the discovery of interventions to extend human healthspan.
Parallel multimodal circuits control an innate foraging behavior
Authors: López-Cruz Alejandro , Pokala Navin , Sordillo Aylesse , Flavell Steven W. , McGrath Patrick T. , Bargmann Cornelia I. 
Published: May 2018

SUMMARYForaging strategies that enable animals to locate food efficiently are composed of highly conserved behavioral states with characteristic features. Here, we identify parallel multimodal circuit modules that control an innate foraging state -- local search behavior -- after food removal in the nematodeCaenorhabditis elegans. Two parallel groups of chemosensory and mechanosensory glutamatergic neurons that detect food-related cues trigger local search by inhibiting separate integrating neurons through a metabotropic glutamate receptor, MGL-1. The chemosensory and mechanosensory modules are separate and redundant, as glutamate release from either can drive the full behavior. Spontaneous activity in the chemosensory module encodes information about the time since the last food encounter and correlates with the foraging behavior. In addition, the ability of the sensory modules to control local search is gated by the internal nutritional state of the animal. This multimodal circuit configuration provides robust control of an innate adaptive behavior.
Attenuation of influenza A virus disease severity by viral co-infection in a mouse model
Authors: Gonzalez Andres J. , Ijezie Emmanuel C. , Balemba Onesmo B. , Miura Tanya A. 
Published: May 2018

AbstractInfluenza viruses and rhinoviruses are responsible for a large number of acute respiratory viral infections in human populations and are detected as co-pathogens within hosts. Clinical and epidemiological studies suggest that co-infection by rhinovirus and influenza virus may reduce disease severity and that they may also interfere with each other’s spread within a host population. To determine how co-infection by these two unrelated respiratory viruses affects pathogenesis, we established a mouse model using a minor serogroup rhinovirus (RV1B) and mouse-adapted influenza A virus (PR8). Infection of mice with RV1B two days before PR8 reduced pathogenesis of mild to moderate, but not severe PR8 infections. Disease attenuation was associated with an early inflammatory response in the lungs and enhanced clearance of PR8. However, co-infection by RV1B did not reduce PR8 viral loads early in infection or inhibit replication of PR8 within respiratory epithelia orin vitro. Inflammation in co-infected mice remained focal, in comparison to diffuse inflammation and damage in the lungs of mice infected by PR8. These findings suggest that RV1B stimulates an early immune response that clears PR8 while limiting excessive pulmonary inflammation. The timing of RV1B co-infection was a critical determinant of protection, suggesting that sufficient time is needed to induce this response. Finally, disease attenuation was not unique to RV1B: co-infection by a murine coronavirus two days before PR8 also reduced disease severity. This model will be critical for understanding the mechanisms responsible for attenuation of influenza disease during co-infection by unrelated respiratory viruses.
Structural Basis for Receptor Recognition by Lujo Virus
Authors: Cohen-Dvashi Hadas , Kilimnik Itay , Diskin Ron 
Published: May 2018

AbstractLujo virus (LUJV) has emerged as a novel and highly fatal human pathogen. Despite its membership among the Arenaviridae, LUJV does not classify with the known Old and New World groups of that viral family. Likewise, LUJV was recently found to use neuropilin-2 (NRP2) as a cellular receptor instead of the canonical α-dystroglycan (α-DG) or transferrin receptor 1 (TfR1) utilized by Old World (OW) and New World (NW) arenaviruses, respectively. The emergence of a deadly new pathogen into human populations using an unprecedented entry route raises many questions regarding the mechanism of cell recognition and the risk that Arenaviruses are further diversifying their infection strategies. To provide the basis for combating LUJV in particular, and to increase our general understanding of the molecular changes that accompany an evolutionary switch to a new receptor for Arenaviruses, we used X-ray crystallography to reveal how the GP1 receptor-binding domain of LUJV (LUJVGP1) recognizes NRP2. Our structural data imply that LUJV is evolutionary closer to OW than to NW arenaviruses. Structural analysis supported by experimental validation further suggests that NRP2 recognition is metal ion dependent and that the complete NRP2 binding is formed in the context of the trimeric spike. Taken together, our data provide the mechanism for the cell attachment step of LUJV, the evolutionary relationship between the GP1 domain of this novel pathogen and other arenaviruses, and indispensable information for combating LUJV.
Cell-associated, Heparin-like Molecules Modulate the Ability of LDL to Regulate PCSK9 Uptake
Authors: Galvan Adri M. , Chorba John S. 
Published: May 2018

AbstractProprotein convertase subtilisin/kexin type 9 (PCSK9) targets the LDL receptor (LDLR) for degradation, increasing plasma LDL and, consequently, cardiovascular risk. Uptake of secreted PCSK9 is required for its predominant effect on the LDLR. LDL itself inhibits this uptake, though the mechanism by which it does so remains unclear. In this study, we investigated the relationship between LDL, the PCSK9:LDLR interaction, and PCSK9 uptake. We show that LDL inhibits binding of PCSK9 to the epidermal growth factor precursor homology domain A (EGF-A) domain of the LDLRin vitromore impressively than it inhibits PCSK9 uptake in cells. Furthermore, a cell-based factor responsive to heparin-targeting treatments can explain this difference, consistent with its identity as a cell surface heparan sulfate proteoglycan (HSPG), a known co-receptor for PCSK9. Furthermore, we show that the entire PCSK9 prodomain, but not truncated variants, rescues PCSK9 uptake in the presence of LDL, suggesting that PCSK9:LDL binding requires the entire prodomain. Additionally, we show that the gain-of-function (GOF) PCSK9 variant S127R has increased affinity for heparin-like molecules such as HSPGs, potentially explaining the biochemical basis for its phenotype. Overall, our findings suggest a model where PCSK9, LDL, and HSPGs all interact to regulate PCSK9 uptake into the hepatocyte.
Evidence for Alternative Complement Cascade Activation in Primary CNS Vasculitis
Authors: Mandel-Brehm Caleigh , Retallack Hanna , Knudsen Giselle M. , Yamana Alex , Hajj-Ali Rula A. , Calabrese Leonard H. , Tihan Tarik , Sample Hannah A. , Zorn Kelsey C. , Gorman Mark P. , Cohen Jennifer Madan , Sreih Antoine G. , Marcus Jacqueline F. , Josephson S. Andrew , Douglas Vanja C. , Gelfand Jeffrey M. , Wilson Michael R. , DeRisi Joseph L. 
Published: May 2018

AbstractThe central nervous system (CNS) has a dedicated network of blood vessels to support the physiological activity of the brain, spinal cord and meninges. Consequently, inflammation of CNS vasculature can have devastating effects on neurological function. A lack of understanding regarding the molecular pathology of CNS vasculitis impedes the development of better diagnostics and effective therapies. Here, we analyze the proteome of cerebrospinal fluid from patients with biopsy-confirmed Primary Angiitis of the Central Nervous System (PACNS) relative to non-inflammatory control patients and patients with Reversible Cerebral Vasoconstrictive Syndrome (RCVS), a syndrome that clinically mimics PACNS in several aspects. In PACNS, we find significant elevation of apolipoproteins, immunoglobulins and complement cascade components. Notably, we find a bias towards activation of the alternative complement pathway with elevated levels of the terminal cascade component, complement C5. Given the recent treatment successes of Anti-Neutrophil Cytoplasmic Antibody (ANCA) vasculitis with the C5 receptor inhibitor, CCX168 (Avacopan), our results suggest that complement C5 inhibitors may also prove useful as therapeutic interventions for PACNS.
CD32+and PD-1+Lymph Node CD4 T Cells Support Persistent HIV-1 Transcription in Treated Aviremic Individuals
Authors: Noto Alessandra , Procopio Francesco A. , Banga Riddhima , Suffiotti Madeleine , Corpataux Jean-Marc , Cavassini Matthias , Fenwick Craig , Gottardo Raphael , Perreau Matthieu , Pantaleo Giuseppe 
Published: May 2018

ABSTRACTA recent study conducted in blood has proposed CD32 as the marker identifying the ‘elusive’ HIV reservoir. We have investigated the distribution of CD32+CD4 T cells in blood and lymph nodes(LNs) of healthy HIV-1 uninfected, viremic untreated and long-term treated HIV-1 infected individuals and their relationship with PD-1+CD4 T cells. The frequency of CD32+CD4 T cells was increased in viremic as compared to treated individuals in LNs and a large proportion(up to 50%) of CD32+cells co-expressed PD-1 and were enriched within T follicular helper cells(Tfh) cells. We next investigated the role of LN CD32+CD4 T cells in the HIV reservoir. Total HIV DNA was enriched in CD32+and PD-1+CD4 T cells as compared to CD32-and PD-1-cells in both viremic and treated individuals but there was no difference between CD32+and PD-1+cells. There was not enrichment of latently infected cells with inducible HIV-1 in CD32+versus PD-1+cells in ART treated individuals. HIV-1 transcription was then analyzed in LN memory CD4 T cell populations sorted on the basis of CD32 and PD-1 expression. CD32+PD-1+CD4 T cells were significantly enriched in cell associated HIV RNA as compared to CD32-PD-1-(average 5.2 fold in treated and 86.6 fold in viremics), to CD32+PD-1-(2.2 fold in treated and 4.3 fold in viremics) and to CD32-PD-1+cell populations(2.2 fold in ART treated and 4.6 fold in viremics). Similar levels of HIV-1 transcription were found in CD32+PD-1-and CD32-PD-1+CD4 T cells. Interestingly, the proportion of CD32+and PD-1+CD4 T cells negatively correlated with CD4 T cell counts and length of therapy while positively correlated with viremia. Therefore, the expression of CD32 identifies, independently of PD-1, a CD4 T cell population with persistent HIV-1 transcription and CD32 and PD-1 co-expression the CD4 T cell population with the highest levels of HIV-1 transcription in both viremic and treated individuals.ImportanceThe existence of long-lived latently infected resting memory CD4 T cells represents a major obstacle to the eradication of HIV infection. Identifying cell markers defining latently infected cells containing replication competent virus is important in order to determine the mechanisms of HIV persistence and to develop novel therapeutic strategies to cure HIV infection. We provide evidence that PD-1 and CD32 may have a complementary role in better defining CD4 T cell populations infected with HIV-1. Furthermore, CD4 T cells co-expressing CD32 and PD-1 identify a CD4 T cell population with high levels of persistent HIV-1 transcription.
A synthesis of mapping experiments reveals extensive genomic structural diversity in theMimulus guttatusspecies complex
Authors: Flagel Lex , Blackman Benjamin K. , Fishman Lila , Monnahan Patrick J. , Sweigart Andrea , Kelly John K. 
Published: May 2018

ABSTRACTUnderstanding genomic structural variation such as inversions and translocations is a key challenge in evolutionary genetics. In this paper, we tackle this challenge by developing a novel statistical approach to comparative genetic mapping. The procedure couples a Hidden Markov Model with a Genetic Algorithm to detect large-scale structural variation using low-level sequencing data from multiple genetic mapping populations. We demonstrate the method using five distinct crosses within the flowering plant genusMimulus. The synthesis of data from these experiments is first used to correct numerous errors (misplaced sequences) in theM. guttatusreference genome. Second, we confirm and/or detect eight large inversions polymorphic within theM. guttatusspecies complex. Finally, we show how this method can be applied in genomic scans to improve the accuracy and resolution of Quantitative Trait Locus (QTL) mapping.AUTHOR SUMMARYGenome sequences have proved to be a critical experimental resource for genetic research in many species. However, in some species there is considerable variation in genomic organization, making a single reference genome sequence inadequate. This variation can cause issues in interpreting genomic signals, such as those coming from trait mapping. We introduce a new statistical method and computational tools that use linkage information to reorganize a single reference genome to 1) repair genome assembly errors, and 2) identify variation between individuals or populations of the same species. Using this method we can create a new genome order that improves upon the reference genome. We apply this method to five crosses among plants in theMimulus guttatusspecies complex. In this system we detect eight large chromosomal inversions and improve the resolution of a trait mapping study. This work highlights the utility of our method, and indicates how others studying diverse species might use them to improve their own research.
Mice deficient in nucleoporin Nup210 develop peripheral T cell alterations
Authors: Nieuwenhuijze Annemarie van , Malengier-Devlies Bert , Cauwe Bénédicte , Humblet-Baron Stephanie , Liston Adrian 
Published: May 2018

AbstractThe nucleopore is an essential structure of the eukaryotic cell, regulating passage between the nucleus and cytoplasm. While individual functions of core nucleopore proteins have been identified, the role of other components, such as Nup210, are poorly defined. Here, through the use of an unbiased ENU mutagenesis screen for mutations effecting the peripheral T cell compartment, we identified a Nup210 mutation in a mouse strain with altered CD4 / CD8 T cell ratios. Through the generation of Nup210 knockout mice we identified Nup210 as having a T cell-intrinsic function in the peripheral homeostasis of T cells. Remarkably, despite the deep evolutionary conservation of this key nucleopore complex member, no other major phenotypes developed, with viable and healthy knockout mice. These results identify Nup210 as an important nucleopore complex component for peripheral T cells, and raise further questions of why this nucleopore component shows deep evolutionary conservation despite seemingly redundant functions in most cell types.
The role of satisfaction and loyalty for insurers
Authors: Ruefenacht Matthias 
Published: May 2018

Purpose
The purpose of this paper is to examine the crucial antecedents of satisfaction and loyalty for the insurance industry and discuss how customer satisfaction and loyalty can be increased.

Design/methodology/approach
A large-scale global survey is conducted among 11,736 insurance customers. To analyze the data, structural equation modeling is used to estimate the influence of the identified antecedents of satisfaction and loyalty.

Findings
The results reveal a positive relationship between satisfaction and attitudinal loyalty for the insurance industry. In addition, the individual cognitive-based dimensions of anticipated regret and product category knowledge significantly affect satisfaction. Furthermore, co-production and trust both positively affect satisfaction and attitudinal loyalty.

Research limitations/implications
This study identifies relevant antecedents of satisfaction and attitudinal loyalty for the emerging literature of insurance marketing. Future studies in this domain should examine the influence of additional dimensions which were not part of the present work, such as perceived price fairness, service quality, and switching costs.

Practical implications
By installing and maintaining efficient two-way communication channels, insurers can decrease customers’ anticipated regret and enhance product category knowledge, which, in turn, can increase customer satisfaction. In addition, frequent and honest communication should be used to build up trust and induce co-production, which positively affect satisfaction and attitudinal loyalty.

Originality/value
This paper identifies crucial antecedents of satisfaction and attitudinal loyalty for insurance companies. This research is timely, as previous works have largely neglected the idiosyncrasies of the insurance sector.
Assessing the moderating effect of Shariah Board on the relationship between financial performance and accounting disclosure
Authors: Ajili Hana , Bouri Abdelfettah 
Published: May 2018

PurposeShariah Board (SB) is considered as a typical corporate governance mechanism for the Islamic banking system. This board takes the responsibilities of assuring the compliance of transactions and operations with Islamic rules and principles. The purpose of this paper is to measure the SB quality and examine its moderating effect on the relationship between financial performance and accounting disclosure quality.Design/methodology/approachThis study used a sample of 90 Islamic banks (IBs) during the period 2010-2014. The accounting disclosure quality and the SB quality were measured using self-developed indices. The moderating effect of the SB on the performance/disclosure relationship was examined using the hierarchical regression analysis.FindingsThe main finding of this study is related to the negative moderating effect of SB quality on the relationship between performance and disclosure. Accordingly, it can be said that the higher the quality of the SB is, the lesser the performance affects the disclosure. This result seems to indicate that at high level of SB quality, even when the performance decreases, the IBs engage in complying with accounting disclosure requirements in order to inform the stakeholders on the real situation of the bank.Research limitations/implicationsThe finding of this study would be of great support to stakeholders and policy makers to make more pressure on IBs to improve the quality of their SB structure and show more compliance with the governance recommendations. As an extension to this study, further research can examine other Islamic governance mechanisms, such as the Internal Shariah Review.Originality/valueTo the authors’ knowledge, there has been a dearth of studies dealing with the empirical examination of the moderating impact of the SB quality on the association between the financial performance and the disclosure quality. Therefore, this study could be considered a tentative contribution to the literature by providing some empirical evidence on the links between these three variables using the moderation regression analysis.