bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spirometric indices in primary ciliary dyskinesia: systematic review and meta-analysis
Authors: Halbeisen Florian S. , Jose Anu , de Jong Carmen , Nyilas Sylvia , Latzin Philipp , Kuehni Claudia E. , Goutaki Myrofora 
Published: December 2018

AbstractPrimary ciliary dyskinesia (PCD) is a genetic, heterogeneous disease caused by dysfunction of cilia. Evidence is sparse and reports of lung function of PCD patients ranges from normal to severe impairment. This systematic review and meta-analysis of studies of lung function of PCD patients examines the spirometric indices of PCD patients and differences by age group and sex.We searched PubMed, Embase, and Scopus for studies that described lung function in ≥10 patients with PCD. We performed meta-analyses and metaregression to explain heterogeneity. We included 24 studies, ranging from 13-158 patients per study. The most commonly reported spirometric indices were forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) presented as mean and standard deviation of percent of predicted values. We found considerable heterogeneity for both parameters (I2range 94-96%). The heterogeneity remained when we stratified the analysis by age; however, FEV1 in adult patients was lower. Even after taking into account explanatory factors, the largest part of the between-studies variance remained unexplained. Heterogeneity could be explained by genetic differences between study populations, methodological factors related to the variability of study inclusion criteria, or details on the performance and evaluation of lung function measurements that we could not account for. Prospective studies therefore need to use standardised protocols and international reference values. These results underline the possibility of distinct PCD phenotypes as in other chronic respiratory diseases. Detailed characterisation of these phenotypes and related genotypes is needed in order to better understand the natural history of PCD.
Comparing the functional structure of neural networks from representational similarity analysis with those from functional connectivity and univariate analyses
Authors: Pillet Ineke , de Beeck Hans Op , Masson Haemy Lee 
Published: December 2018

AbstractThe invention of representational similarity analysis (RSA, following multi-voxel pattern analysis (MVPA)) has allowed cognitive neuroscientists to identify the representational structure of multiple brain regions, moving beyond functional localization. By comparing these structures, cognitive neuroscientists can characterize how brain areas form functional networks. Univariate analysis (UNIVAR) and functional connectivity analysis (FCA) are two other popular methods to identify the functional structure of brain networks. Despite their popularity, few studies have examined the relationship between the structure of the networks from RSA with those from UNIVAR and FCA. Thus, the aim of the current study is to examine the similarities between neural networks derived from RSA with those from UNIVAR and FCA to explore how these methods relate to each other. We analyzed the data of a previously published study with the three methods and compared the results by performing (partial) correlation and multiple regression analysis. Our findings reveal that neural networks resulting from RSA, UNIVAR, and FCA methods are highly similar to each other even after ruling out the effect of anatomical proximity between the network nodes. Nevertheless, the neural network from each method shows idiosyncratic structure that cannot be explained by any of the other methods. Thus, we conclude that the RSA, UNIVAR and FCA methods provide similar but not identical information on how brain regions are organized in functional networks.
Surrogate R-spondins for tissue-specific potentiation of Wnt signaling
Authors: Luca Vincent C. , Miao Yi , Li Xingnan , Hollander Michael J. , Kuo Calvin J. , Garcia K. Christopher 
Published: December 2018

ABSTRACTSecreted R-spondin1-4 proteins (RSPO1-4) orchestrate stem cell renewal and tissue homeostasis by potentiating Wnt/β-catenin signaling. RSPOs induce the turnover of negative Wnt regulators RNF43 and ZNRF3 through a process that requires RSPO interactions with either Leucine-rich repeat containing G-protein coupled receptors (LGRs) or heparin sulfate proteoglycans (HSPGs). Here, we describe the engineering of ‘surrogate RSPOs’ that function independently of LGRs and HSPGs to enhance Wnt signaling on cell types expressing a target surface marker. These bispecific proteins were generated by fusing an RNF43- or ZNRF3-specific single chain antibody variable fragment (scFv) to the immune cytokine IL-2. Surrogate RSPOs mimic the function of natural RSPOs by crosslinking the extracellular domain (ECD) of RNF43 or ZNRF3 to the ECD of the IL-2 receptor CD25, which sequesters the complex and results in highly selective amplification of Wnt signaling on CD25+ cells. Furthermore, surrogate RSPOs were able substitute for wild type RSPO in a colon organoid growth assay when intestinal stem cells were transduced to express CD25. Our results provide proof-of-concept for a technology that may be adapted for use on a broad range of cell- or tissue-types and will open new avenues for the development of Wnt-based therapeutics for regenerative medicine.
Dark aerobic sulfide oxidation by anoxygenic phototrophs in anoxic waters
Authors: Berg Jasmine S. , Pjevac Petra , Sommer Tobias , Buckner Caroline R.T. , Philippi Miriam , Hach Philipp F. , Liebeke Manuel , Holtappels Moritz , Danza Francesco , Tonolla Mauro , Sengupta Anupam , Schubert Carsten J. , Milucka Jana , Kuypers Marcel M.M. 
Published: December 2018

SUMMARYAnoxygenic phototrophic sulfide oxidation by green and purple sulfur bacteria (PSB) plays a key role in sulfide removal from anoxic shallow sediments and stratified waters. Although some PSB can also oxidize sulfide with nitrate and oxygen, little is known about the prevalence of this chemolithotrophic lifestyle in the environment. In this study, we investigated the role of these phototrophs in light-independent sulfide removal in the chemocline of Lake Cadagno. Our temporally resolved, high-resolution chemical profiles indicated that dark sulfide oxidation was coupled to high oxygen consumption rates of ~9 μM O2·h−1. Single-cell analyses of lake water incubated with13CO2in the dark revealed thatChr. okeniiwas to a large extent responsible for aerobic sulfide oxidation and it accounted for up to 40 % of total dark carbon fixation. The genome ofChr. okeniireconstructed from the Lake Cadagno metagenome confirms its capacity for microaerophilic growth and provides further insights into its metabolic capabilities. Moreover, our genomic and single-cell data indicated that other PSB grow microaerobically in these apparently anoxic waters. Altogether, our observations suggest that aerobic respiration may not only play an underappreciated role in anoxic environments, but also that organisms typically considered strict anaerobes may be involved.ORIGINALITY-SIGNIFICANCE STATEMENTThis study reveals that dark aerobic sulfide oxidation within an anoxic layer dominated by anoxygenic phototrophic bacteria in the stratified water column of Lake Cadagno is to a large extent carried out by the anoxygenic phototrophic bacteriumChromatium okenii. Our findings imply that aerobic metabolisms may be more prevalent in anoxic zones than previously thought. We also present an environmental metagenome-assembled genome ofChr. okeniiwhich is the first genome sequence for the genusChromatiumand reveals new interesting physiological features of this environmentally relevant organism, including its capacity for aerobic respiration.
Podoplanin interaction with caveolin-1 promotes tumour cell migration and invasion
Authors: Pedro Luisa , Shields Jacqueline D. 
Published: December 2018

AbstractPodoplanin, a highly O-glycosylated type-1 transmembrane glycoprotein, found in lymphatic endothelial cells, podocytes, alveolar epithelial cells and lymph node fibroblasts is also expressed by tumour cells, and is correlated with more aggressive disease. Despite numerous studies documenting podoplanin expression, the mechanisms underlying its tumour-promoting functions remain unclear. Using a murine melanoma cell line that endogenously expresses podoplanin, we demonstrate interactions with proteins necessary for cytoskeleton reorganization, adhesion and matrix degradation, and endocytosis/receptor recycling but also identify a novel interaction with caveolin-1. We generated a panel of podoplanin and caveolin-1 variants to determine the molecular interactions and functional consequences of these interactions. Complementaryin vitroandin vivosystems confirmed the existence of a functional cooperation in which surface expression of both full length, signalling competent podoplanin and caveolin-1 are necessary to induce directional migration and invasion, which is executed via PAK1 and ERK1 pathways. Our findings establish that podoplanin signalling mediates the invasive properties of melanoma cells in a caveolin-1 dependent manner.Summary StatementThis manuscript describes a new interaction and functional cooperation between podoplanin and caveolin1 that drives tumour cell invasion into surrounding tissues.
Galaxy-Kubernetes integration: scaling bioinformatics workflows in the cloud
Authors: Moreno Pablo , Pireddu Luca , Roger Pierrick , Goonasekera Nuwan , Afgan Enis , van den Beek Marius , He Sijin , Larsson Anders , Schober Daniel , Ruttkies Christoph , Johnson David , Rocca-Serra Philippe , Weber Ralf JM , Gruening Björn , Salek Reza M , Kale Namrata , Perez-Riverol Yasset , Papatheodorou Irene , Spjuth Ola , Neumann Steffen 
Published: December 2018

SummaryMaking reproducible, auditable and scalable data-processing analysis workflows is an important challenge in the field of bioinformatics. Recently, software containers and cloud computing introduced a novel solution to address these challenges. They simplify software installation, management and reproducibility by packaging tools and their dependencies. In this work we implemented a cloud provider agnostic and scalable container orchestration setup for the popular Galaxy workflow environment. This solution enables Galaxy to run on and offload jobs to most cloud providers (e.g. Amazon Web Services, Google Cloud or OpenStack, among others) through the Kubernetes container orchestrator.AvailabilityAll code has been contributed to the Galaxy Project and is available (since Galaxy 17.05) at https://github.com/galaxyproject/ in the galaxy and galaxy-kubernetes repositories. https://public.phenomenal-h2020.eu/ is an example deployment.Suppl. InformationSupplementary Files are available online.Contactpmoreno@ebi.ac.uk, European Molecular Biology Laboratory, EMBL-EBI, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK, Tel: +44-1223-494267, Fax: +44-1223-484696.
Parent and offspring genotypes influence gene expression in early life
Authors: Newhouse Daniel J. , Barcelo-Serra Margarida , Tuttle Elaina M. , Gonser Rusty A. , Balakrishnan Christopher N. 
Published: December 2018

AbstractParents can have profound effects on offspring fitness. Little, however, is known about the mechanisms through which parental care variation influences offspring physiology in natural systems. White-throated sparrows Zonotrichia albicollis (WTSPs) exist in two genetic morphs, tan and white, controlled by a large polymorphic supergene. Morphs mate disassortatively, resulting in two pair types: tan male x white female (TxW) pairs, which provide biparental care and white male x tan female (WxT) pairs, which provide female-biased care. To investigate the effects of parental care variation, we performed RNA-seq on WTSP nestlings sampled from nests of both pair types. Pair type had the largest effect on nestling gene expression, with 881 genes differentially expressed (DE) and seven correlated gene co-expression modules. The DE genes and modules up-regulated in nests with female-biased parental care primarily function in metabolism and stress-related pathways resulting from the overrepresentation of stress response and proteolysis genes. These results show that parental genotypes, a proxy for parental care in this system, alter nestling physiology and highlight avenues of further research investigating the ultimate implications of alternative parental care strategies. Nestlings also exhibited morph-specific gene expression, driven by innate immunity genes and co-expression of genes located in the supergene. Remarkably, we identified the same regulatory hub genes in these blood-derived expression networks as were previously identified in WTSP brains (EPM2A, BPNT1, TAF5L). These hub genes were located within the supergene, highlighting the importance of this gene complex in structuring regulatory networks across diverse tissues.
Human labour pain is influenced by the voltage-gated potassium channel KV6.4 subunit
Authors: Lee Michael C. , Nahorski Michael S. , Hockley James R.F. , Lu Van B. , Ison Gillian , Pattison Luke A. , Callejo Gerard , Stouffer Kaitlin , Fletcher Emily , Brown Christopher , Drissi Ichrak , Wheeler Daniel , Ernfors Patrik , Menon David , Reimann Frank , St John Smith Ewan , Woods C. Geoffrey 
Published: December 2018

AbstractWe sought genetic effects on labour pain by studying healthy women who did not request analgesia during their first delivery. Extensive sensory and psychometric testing were normal in these women, except for significantly higher cuff-pressure pain. We found an excess of heterozygotes carrying the rare allele of SNP rs140124801 in KCNG4. The rare variant KV6.4-Met419 exerts a dominant negative effect and cannot modulate the voltage-dependence of KV2.1 inactivation because it fails to traffic to the plasma membrane. In vivo, we observed Kcng4 (KV6.4) expression in 40% of retrograde labelled mouse uterine sensory neurones, all of which expressed KV2.1, and over 90% expressed nociceptor genes Trpv1 and Scn10a. In neurones overexpressing KV6.4-Met419, the voltage-dependence of inactivation for KV2.1 is more depolarised compared to neurones overexpressing KV6.4. Finally, KV6.4-Met419 overexpressing neurones have a higher action potential threshold. We conclude KV6.4 can influence human labour pain by modulating the excitability of uterine nociceptors.
Functional connectomics of affective and psychotic pathology
Authors: Baker Justin T. , Dillon Daniel G. , Patrick Lauren M. , Roffman Joshua L. , Brady Roscoe O. , Pizzagalli Diego A. , Öngür Dost , Holmes Avram J. 
Published: December 2018

ABSTRACTConverging evidence indicates that groups of patients with nominally distinct psychiatric diagnoses are not separated by sharp or discontinuous neurobiological boundaries. In healthy populations, individual differences in behavior are reflected in variability across the collective set of functional brain connections (functional connectome). These data suggest that the spectra of transdiagnostic symptom profiles observed in psychiatric patients may map onto detectable patterns of network function. To examine the manner through which neurobiological variation might underlie clinical presentation we obtained functional magnetic resonance imaging (fMRI) data from over 1,000 individuals, including 210 diagnosed with a primary psychotic disorder or affective psychosis (bipolar disorder with psychosis and schizophrenia or schizoaffective disorder), 192 presenting with a primary affective disorder without psychosis (unipolar depression, bipolar disorder without psychosis), and 608 demographically and data-quality matched healthy comparison participants recruited through a large-scale study of brain imaging and genetics. Here, we examine variation in functional connectomes across psychiatric diagnoses, finding striking evidence for disease connectomic “fingerprints” that are commonly disrupted across distinct forms of pathology and appear to scale as a function of illness severity. Conversely, other properties of network connectivity were preferentially disrupted in patients with psychotic illness, but not patients without psychotic symptoms. This work allows us to establish key biological and clinical features of the functional connectomes of severe mental disease.SIGNIFICANCE STATEMENTHistorically, most research on the biological origins of psychiatric illness has focused on individual diagnostic categories, studied in isolation. Mounting evidence suggests nominally distinct psychiatric diagnoses are not separated by clear neurobiological boundaries. Here, we derive functional connectomic signatures in over 1,000 individuals including patients presenting with specific categories of impairment (psychosis), clinical diagnoses, or severity of illness as reflected in treatment seeking. Our analyses revealed features of connectome functioning that are commonly disrupted across distinct forms of pathology, scaling with clinical severity. Conversely, other aspects of network connectivity were preferentially disrupted in patients with psychotic illness, but not patients without psychotic symptoms. These data have important implications for the establishment of functional connectome fingerprints of severe mental disease.
Bacteria boost mammalian host NAD metabolism by engaging the deamidated biosynthesis pathway
Authors: Shats Igor , Liu Juan , Williams Jason G. , Deterding Leesa J. , Lim Chaemin , Lee Ethan , Fan Wei , Sokolsky Marina , Kabanov Alexander V. , Locasale Jason W. , Li Xiaoling 
Published: December 2018

AbstractNicotinamide adenine dinucleotide (NAD), a cofactor for hundreds of metabolic reactions in all cell types, plays an essential role in diverse cellular processes including metabolism, DNA repair, and aging1. NAD metabolism is critical to maintain cellular homeostasis in response to the environment, and disruption of this homeostasis is associated with decreased cellular NAD levels in aging2. Conversely, elevated NAD synthesis is required to sustain the increased metabolic rate of cancer cells3,4. Consequently, therapeutic strategies aimed to both upregulate NAD (i.e. NAD-boosting nutriceuticals) or downregulate NAD (inhibitors of key NAD synthesis enzymes) are being actively investigated5–10. However, how this essential metabolic pathway is impacted by the environment remains unclear. Here, we report an unexpected trans-kingdom cooperation between bacteria and mammalian cells wherein bacteria contribute to host NAD biosynthesis. Bacteria confer cancer cells with the resistance to inhibitors of NAMPT, the rate limiting enzyme in the main vertebrate NAD salvage pathway. Mechanistically, a microbial nicotinamidase (PncA) that converts nicotinamide to nicotinic acid, a key precursor in the alternative deamidated NAD salvage pathway, is necessary and sufficient for this protective effect. This bacteria-enabled resistance mechanism that allows the mammalian host to bypass the drug-induced metabolic block represents a novel paradigm in drug resistance. This host-microbe metabolic interaction also enables bacteria to dramatically enhance the NAD-boosting efficiency of nicotinamide supplementationin vitroandin vivo, demonstrating a crucial role of microbes, gut microbiota in particular, in organismal NAD metabolism.
A novel humanized mouse model to study the function of human cutaneous memory T cells in vivo in human skin
Authors: Klicznik Maria M. , Benedetti Ariane , Gail Laura M. , Varkhande Suraj R. , Holly Raimund , Laimer Martin , Stoecklinger Angelika , Sir Andreas , Reitsamer Roland , Neuper Theresa , Horejs-Hoeck Jutta , Rosenblum Michael D. , Campbell Daniel J. , Murauer Eva M. , Gratz Iris K. 
Published: December 2018

AbstractHuman skin contains a population of memory T cells that support tissue homeostasis and provide protective immunity. The study of human memory T cells is often restricted to in vitro studies and to human PBMC serving as primary cell source. Because the tisse environment impacts the phenotype and function of memory T cells, it is crucial to study these cells within their tissue. Here we utilized immunodeficient NOD-scid IL2rγnull (NSG) mice that carried in vivo-generated engineered human skin (ES). ES were generated from human keratinocytes and fibroblasts and is initially devoid of skin-resident immune cells. Upon adoptive transfer of human PBMC this reductionist system allowed to study human T cell recruitment from a circulating pool of T cells into non-inflamed human skin in vivo. Circulating human memory T cells preferentially infiltrated ES and showed diverse functional profiles of T cells found in fresh human skin. The chemokine and cytokine microenvironment of ES closely resembled that of non-inflamed human skin. Upon entering the ES T cells assumed a resident memory T cell-like phenotype in the absence of infection, and a proportion of these cutaneous T cells can be locally activated upon injection of monocyte derived dendritic cells (moDCs) that presented Candida albicans. Interestingly, we found that CD69+ memory T cells produced higher levels of effector cytokines in response to Candida albicans, compared to CD69- T cells. Overall, this model has broad utility in many areas of human skin immunology research, including the study of immune-mediated skin diseases.
Long memory or structural break? Empirical evidences from index volatility in stock market
Authors: Luo Yi , Huang Yirong 
Published: December 2018

PurposeThe purpose of this paper is to explore whether stock index volatility series exhibit real long memory.Design/methodology/approachThe authors employ sequential procedure to test structural break in volatility series, and use DFA and 2ELW to estimate long memory parameter for the whole samples and subsamples, and further apply adaptive FIGARCH (AFIGARCH) to describe long memory and structural break.FindingsThe empirical results show that stock index volatility series are characterized by long memory and structural break, and therefore it is appropriate to use AFIGARCH to model stock index volatility process.Originality/valueThis study empirically investigates the properties of long memory and structural break in stock index volatility series. The conclusion has a certain reference value for understanding the properties of long memory and structural break in volatility series for academic researchers, market participants and policy makers, and for modeling and forecasting future volatility, testing market efficiency, pricing financial assets, constructing quantitative investment strategy and measuring market risk.