bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of accelerated metabolomic and epigenetic ageing in a UK cohort
Authors: Robinson Oliver , Hyam Marc Chadeau , Karaman Ibrahim , Pinto Rui Climaco , Fiorito Giovanni , Gao He , Heard Andy , Jarvelin Marjo-Riitta , Lewis Mathew , Pazoki Raha , Polidoro Silvia , Tzoulaki Ioanna , Wielscher Matthias , Elliott Paul , Vineis Paolo 
Published: September 2018

AbstractMarkers of biological ageing have potential utility in primary care and public health. We developed an elastic net regression model of age based on untargeted metabolic profiling across multiple platforms, including nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry in urine and serum (almost 100,000 features assayed), within a large sample (N=2,239) from the UK occupational Airwave cohort. We investigated the determinants of accelerated ageing, including genetic, lifestyle and psychological risk factors for premature mortality. The metabolomic age model was well correlated with chronological age (r=0.85 in independent test set). Increased metabolomic age acceleration (mAA) was associated (p<0.0025) with overweight/obesity and depression and nominally associated (p<0.05) with high alcohol use and low income. DNA methylation age acceleration (N=1,102) was nominally associated (p<0.05) with high alcohol use, anxiety and post-traumatic stress disorder, but not correlated with mAA. Biological age acceleration may present an important mechanism linking psycho-social stress to age-related disease.
Assessing Disease Experience across the Life Span for Individuals with Osteogenesis Imperfecta: Challenges and Opportunities for Patient-Reported Outcomes (PROs) Measurement
Authors: Tosi Laura L. , Floor Marianne K. , Dollar Christina M. , Gillies Austin P. ,   Members of the Brittle Bone Disease Consortium, Hart Tracy S. , Cuthbertson David , Sutton V. Reid , Krischer Jeffrey P. 
Published: September 2018

ABSTRACTBackgroundPatient reported outcome (PRO) information is crucial for establishing better patient-provider communication, improving shared decision making between clinicians and patients, and assessing patient responses to therapeutic interventions and increasing satisfaction with care. We used the Brittle Bones Disease Consortium (BBDC) Contact Registry for People with OI, managed by the Rare Disease Clinical Research Network (RDCRN) to (1) to evaluate the construct validity of the Patient-Reported Outcome Measurement Information System®(PROMIS®) to record important components of the disease experience among individuals with OI; and (2) explore the feasibility of using a registry to recruit individuals with OI to report on health status. Our long-term goal is to enhance communication of health and disease management findings back to the OI community, especially those who do not have access to major OI clinical centers.ResultsWe demonstrated the construct validity of PROMIS instruments in OI. Our results confirm that the scores from most domains differ significantly from the general US population: individuals with OI have worse symptom burden and functioning. We found no excessive floor or ceiling effects. Our study demonstrates that the BBDC Contact Registry can be used to recruit participants for online health status surveys. However, there are numerous challenges that must be addressed: lack of self-knowledge of OI type, under-representation of men, limited ethnic diversity, and imperfect questionnaire completion rates.ConclusionOur pilot study demonstrated the feasibility of using a contact registry to recruit respondents from the OI community and to obtain analyzable PROMIS data regarding disease experience. Because the results differ from the general population and avoid excessive floor and ceiling effects, PROMIS instruments can be used to assess response to therapeutic interventions in individuals with OI. Future directions will include (1) development and validation of an OI-specific patient-based classification system that aggregates persons with similar clinical characteristics and risks for complications to identify treatment needs; and (2) integrating these PRO tools into routine patient care and research studies.
Spatio-temporal modelling ofLeishmania infantuminfection among domestic dogs: a simulation study and sensitivity analysis applied to rural Brazil
Authors: Buckingham-Jeffery Elizabeth , Hill Edward M. , Datta Samik , Dilger Erin , Courtenay Orin 
Published: September 2018

AbstractBackgroundThe parasiteLeishmania infantumcauses zoonotic visceral leishmaniasis (VL), a potentially fatal vector-borne disease of canids and humans. Zoonotic VL poses a significant risk to public health, with regions of Latin America being particularly afflicted by the disease.Leishmania infantumparasites are transmitted between hosts during blood feeding by infected female phlebotomine sand flies. With a principal reservoir host ofL. infantumbeing domestic dogs, limiting prevalence in this reservoir may result in a reduced risk of infection for the human population. To this end, a primary focus of research efforts has been to understand disease transmission dynamics among dogs. One way this can be achieved is through the use of mathematical models.MethodsWe have developed a stochastic, spatial, individual-based mechanistic model ofL. infantumtransmission in domestic dogs. The model framework was applied to a rural Brazilian village setting with parameter values informed by fieldwork and laboratory data. To ensure household and sand fly populations were realistic, we statistically fit distributions for these entities to existing survey data. To identify the model parameters of highest importance, we performed a stochastic parameter sensitivity analysis of the prevalence of infection among dogs to the model parameters.ResultsWe computed parametric distributions for the number of humans and animals per household and a non-parametric temporal profile for sand fly abundance. The stochastic parameter sensitivity analysis determined prevalence ofL. infantuminfection in dogs to be most strongly affected by the sand fly associated parameters and the proportion of immigrant dogs already infected withL. infantumparasites.ConclusionsEstablishing the model parameters with the highest sensitivity of averageL. infantuminfection prevalence in dogs to their variation helps motivate future data collection efforts focusing on these elements. Moreover, the proposed mechanistic modelling framework provides a foundation that can be expanded to explore spatial patterns of zoonotic VL in humans and to assess spatially targeted interventions.
Predictive model in the presence of missing data: the centroid criterion for variable selection
Authors: Gaudart Jean , Adalian Pascal , Leonetti George 
Published: September 2018

AbstractIntroductionIn many studies, covariates are not always fully observed because of missing data process. Usually, subjects with missing data are excluded from the analysis but the number of covariates can be greater than the size of the sample when the number of removed subjects is high. Subjective selection or imputation procedures are used but this leads to biased or powerless models.The aim of our study was to develop a method based on the selection of the nearest covariate to the centroid of a homogeneous cluster of covariates. We applied this method to a forensic medicine data set to estimate the age of aborted fetuses.AnalysisMethodsWe measured 46 biometric covariates on 50 aborted fetuses. But the covariates were complete for only 18 fetuses.First, to obtain homogeneous clusters of covariates we used a hierarchical cluster analysis.Second, for each obtained cluster we selected the nearest covariate to the centroid of the cluster, maximizing the sum of correlations (the centroid criterion).Third, with the covariate selected this way, the sample size was sufficient to compute a classical linear regression model.We have shown the almost sure convergence of the centroid criterion and simulations were performed to build its empirical distribution.We compared our method to a subjective deletion method, two simple imputation methods and to the multiple imputation method.ResultsThe hierarchical cluster analysis built 2 clusters of covariates and 6 remaining covariates. After the selection of the nearest covariate to the centroid of each cluster, we computed a stepwise linear regression model. The model was adequate (R2=90.02%) and the cross-validation showed low prediction errors (2.23 10−3).The empirical distribution of the criterion provided empirical mean (31.91) and median (32.07) close to the theoretical value (32.03).The comparisons showed that deletion and simple imputation methods provided models of inferior quality than the multiple imputation method and the centroid method.ConclusionWhen the number of continuous covariates is greater than the sample size because of missing process, the usual procedures are biased. Our selection procedure based on the centroid criterion is a valid alternative to compose a set of predictors.
Human Migration and the Spread of the Nematode ParasiteWuchereria bancrofti
Authors: Small Scott T. , Labbé Frédéric , Coulibaly Yaya I. , Nutman Thomas B. , King Christopher L. , Serre David , Zimmerman Peter A. 
Published: September 2018

AbstractThe human disease lymphatic filariasis causes the debilitating effects of elephantiasis and hydrocele. Lymphatic filariasis currently affects the lives of 90 million people in 52 countries. There are three nematodes that cause lymphatic filariasis,Brugia malayi, B. timori, andWuchereria bancrofti, but 90% of all cases of lymphatic filariasis are caused solely byW. bancrofti. Here we use population genomics to identify the geographic origin ofW. bancroftiand reconstruct its spread. Previous genomic sequencing efforts have suffered from difficulties in obtaining Wb DNA. We used selective whole genome amplification to enrichW. bancroftiDNA from infected blood samples and were able to analyze 47 whole genomes ofW. bancroftifrom endemic locations in Haiti, Mali, Kenya, and Papua New Guinea. Our results are consistent with a Southeast Asia or East Asia origin forW. bancroftispread around the globe by infecting migrating populations of humans. Austronesians probably introducedW. ban-croftito Madagascar where later migrations moved it to continental Africa. From Africa,W. bancroftispread to the New World during the transatlantic slave trade. The greater genetic diversity ofW. bancroftipopulations from Haiti are also consistent with genetic admixture from multiple source populations. Genome scans for locally adapted haplotypes identified genes associated with human immune suppression and insecticide sensitivity. Locally adapted haplotypes may provide a foundation to understand the distribution ofW. bancrofticompared to that of other filarial nematodes and how populations may differ in response to eradication efforts.
Recruit symbiosis establishment and Symbiodiniceae composition influenced by adult corals and reef sediment
Authors: Ali A , Kriefall N , Emery LE , Kenkel CD , Matz MV , Davies SW 
Published: September 2018

ABSTRACTFor most reef-building corals, the establishment of symbiosis occurs via horizontal transmission, where juvenile coral recruits acquire their algal symbionts (family Symbiodiniaceae) from their surrounding environment post-settlement. This transmission strategy allows corals to interact with a diverse array of symbionts, potentially facilitating adaptation to the newly settled environment. We exposed aposymbiotic Pseudodiploria strigosa recruits from the Flower Garden Banks to natal reef sediment (C-S+), symbiotic adult coral fragments (C+S-), sediment and coral fragments (C+S+), or seawater controls (C-S-) and quantified rates of symbiont uptake and Symbiodiniaceae community composition within each recruit using metabarcoding of the ITS2 locus. The most rapid uptake was observed in C+S+ treatments and this combination also led to the highest symbiont alpha diversity in recruits. While C-S+ treatments exhibited the next highest uptake rate, only one individual recruit successfully established symbiosis in the C+S-treatment, suggesting that sediment both serves as a direct symbiont source for coral recruits and promotes (or, potentially, mediates) transmission from adult coral colonies. In turn, presence of adult corals facilitated uptake from the sediment, perhaps via chemical signaling. Taken together, our results reinforce the key role of sediment in algal symbiont uptake by P. strigosa recruits and suggest that sediment plays a necessary, but perhaps not sufficient, role in the life cycle of the algal Symbiodinaceae symbionts.
Distinct nanoscale calcium channel and synaptic vesicle topographies contribute to the diversity of synaptic function
Authors: Rebola Nelson , Reva Maria , Kirizs Tekla , Szoboszlay Miklos , Moneron Gael , Nusser Zoltan , DiGregorio David A. 
Published: September 2018

SUMMARYThe nanoscale topographical arrangement of voltage-gated calcium channels (VGCC) and synaptic vesicles (SVs) determines synaptic strength and plasticity, but whether distinct spatial distributions underpin diversity of synaptic function is unknown. We performed single bouton Ca2+imaging, Ca2+chelator competition, immunogold electron microscopic (EM) localization of VGCCs and the active zone (AZ) protein Munc13-1, at two cerebellar synapses. Unexpectedly, we found that weak synapses exhibited 3-fold more VGCCs than strong synapses, while the coupling distance was 5-fold longer. Reaction-diffusion modelling could explain both functional and structural data with two strikingly different nanotopographical motifs: strong synapses are composed of SVs that are tightly coupled (∼10 nm) to VGCC clusters, whereas at weak synapses VGCCs were excluded from the vicinity (∼50 nm) of docked vesicles. The distinct VGCC-SV topographical motifs also confer differential sensitivity to neuromodulation. Thus VGCC-SV arrangements are not canonical across CNS synapses and their diversity could underlie functional heterogeneity.
The geography of malaria elimination in Bangladesh: combining data layers to estimate the spatial spread of parasites
Authors: Chang Hsiao-Han , Wesolowski Amy , Sinha Ipsita , Jacob Christopher G , Mahmud Ayesha , Uddin Didar , Zaman Sazid Ibna , Hossain Md Amir , Faiz M Abul , Ghose Aniruddha , Sayeed Abdullah Abu , Rahman M Ridwanur , Islam Akramul , Karim Mohammad Jahirul , Rezwan M Kamar , Shamsuzzaman Abul Khair Mohammad , Jhora Sanya Tahmina , Aktaruzzaman M M , Miotto Olivo , Engø-Monsen Kenth , Kwiatkowski Dominic , Maude Richard J , Buckee Caroline O 
Published: September 2018

AbstractMalaria control programs face difficult resource allocation decisions. Of particular concern for countries aiming for malaria elimination, the regular movement of individuals to and from endemic areas undermines local interventions by reintroducing infections and sustaining local transmission. Quantifying this movement of malaria parasites around a country has become a priority for national control programs, but remains methodologically challenging, particularly in areas with highly mobile populations. Here, we combined multiple data sources to measure the geographical spread of malaria parasites, including epidemiological surveillance data, travel surveys, parasite genetic data, and anonymized mobile phone data. We collected parasite genetic barcodes and travel surveys from 2,090 patients residing in 176 unions in southeast Bangladesh. We developed a genetic mixing index to quantify the likelihood of samples being local or imported. We then inferred the direction and intensity of parasite flow between locations using an epidemiological model, and estimated the proportion of imported cases assuming mobility patterns parameterized using the travel survey and mobile phone calling data. Our results show that each data source provided related but different information about the patterns of geographic spread of parasites. We identify a consistent north/south separation of the Chittagong Hill Tracts region in Bangladesh, and found that in addition to imported infections from forested regions, frequent mixing also occurs in low transmission but highly populated areas in the southwest. Thus, unlike risk maps generated from incidence alone, our maps provide evidence that elimination programs must address ongoing movement of parasites around the lower transmission areas in the southwest.
Characteristics of a SAR11 strain grown in batch and continuous culture
Authors: Grant Scott R. , Church Matthew J. , Ferrón Sara , Laws Edward A. , Rappé Michael S. 
Published: September 2018

AbstractIn this study, a strain of SAR11 subgroup IIIa (termed HIMB114) isolated from the tropical Pacific Ocean was grown in seawater-based batch and continuous culture in order to quantify cellular features and metabolism relevant to SAR11 ecology. We report the first direct measurements of cellular elemental quotas for nitrogen (N) and phosphorus (P) for SAR11: 1.4 ± 0.9 fg N and 0.44 ± 0.01 fg P, respectively, that were consistent with the small size of HIMB114 cells (average volume of 0.09 µm3). However, the mean carbon (C) cellular quota of 50 ± 47 fg C was anomalously high, but variable. Rates of phosphate (PO43-) uptake measured from both batch and continuous cultures were exceptionally slow: in chemostats growing at 0.3 d−1, HIMB114 took up 1.1 ± 0.3 amol P cell−1d−1, suggesting that <30% of the cellular P requirement of HIMB114 was met by PO43-assimilation. The mean rate of leucine incorporation, a measure of bacterial production, during late log phase growth of batch HIMB114 cultures was 0.042 ± 0.02 amol Leu cell−1h−1. While only weakly correlated with changes in specific growth rates, the onset of stationary phase resulted in decreases in cell-specific leucine incorporation that were proportional to changes in growth rate. Rates of cellular production, respiratory oxygen consumption, and changes in total organic C concentrations constrained cellular growth efficiencies to 13 ± 4%. Hence, despite the small, streamlined genome and diminutively sized cells, SAR11 strain HIMB114 appears to grow at efficiencies similar to naturally occurring bacterioplankton communities.ImportanceWhile SAR11 bacteria contribute a significant fraction to the total picoplankton biomass in the ocean and likely are major players in organic C and nutrient cycling, the cellular characteristics and metabolic features of most lineages have either been only hypothesized from genomes or otherwise not measured in controlled laboratory experimentation. The dearth of data on even the most basic characteristics for what is arguably the most abundant heterotroph in seawater has limited the specific consideration of SAR11 in ocean ecosystem modeling efforts. In this study, we provide measures of cellular P, N, C, aerobic respiration and bacterial production for a SAR11 strain growing in natural seawater media that can be used to directly relate these features of SAR11 to biogeochemical cycling in the oceans. Through the development of a chemostat system to measure nutrient uptake during steady-state growth, we have also documented inorganic P uptake rates that allude to the importance of organic phosphorous to meet cellular P demands, even in the presence of non-limiting PO43-concentrations.
Genotyping by low-coverage whole-genome sequencing in intercross pedigrees from outbred founders: a cost efficient approach
Authors: Zan Yanjun , Payen Thibaut , Lillie Mette , Honaker Christa F. , Siegel Paul B. , Carlborg Örjan 
Published: September 2018

ABSTRACTBackgroundExperimental intercrosses between outbred founder populations are powerful resources for mapping loci contributing to complex traits (Quantitative Trait Loci or QTL). Here, we present an approach and accompanying software for high-resolution genotype imputation in such populations using whole-genome high coverage sequence data on founder individuals (∼30×) and low coverage sequence data on intercross individuals (∼0.4×). The method is illustrated in a large F2pedigree between lines of chickens that have been divergently selected for 40 generations for the same trait (body weight at 8 weeks of age).ResultsDescribed is how hundreds of individuals were whole-genome sequenced in a cost- and time-efficient manner using aTn5-based library preparation protocol optimized for this application. In total, 7.6M markers segregated in this pedigree and 10.0 to 13.7% were informative for imputing the founder line genotypes within the F0-F2families. The genotypes imputed from low coverage sequence data were consistent with the founder line genotypes estimated using SNP and microsatellite markers both at individual imputed sites (92%) and across the genome of individual chickens (93%). The resolution of the recombination breakpoints was high with 50% being resolved within <10kb.ConclusionsA method for genotype imputation from low-coverage whole-genome sequencing in outbred intercrosses is described and evaluated. By applying it to an outbred chicken F2cross it is illustrated that it provides high quality, high-resolution genotypes in a time and cost efficient manner.
Expression of TorsinA in a heterologous yeast system reveals interactions with conserved lumenal domains of LINC and nuclear pore complexes
Authors: Chalfant Madeleine , Barber Karl W. , Borah Sapan , Thaller David , Lusk C. Patrick 
Published: September 2018

ABSTRACTDYT1 dystonia is caused by an in-frame deletion of a glutamic acid codon in the gene encoding the AAA+ ATPase TorsinA. TorsinA localizes within the lumen of the nuclear envelope/ER and binds to a membrane-spanning co-factor, LAP1 or LULL1, to form an ATPase; the substrate(s) of TorsinA remain ill defined. Here we use budding yeast, which lack Torsins, to interrogate TorsinA function. We show that TorsinA accumulates at nuclear envelope embedded spindle pole bodies (SPBs) in a way that requires its oligomerization and the conserved SUN-domain protein, Mps3. TorsinA is released from SPBs upon expression of LAP1 and stabilized by LAP1 mutants incapable of stimulating TorsinA ATPase activity, suggesting the recapitulation of a TorsinA-substrate cycle. While the expression of TorsinA or TorsinA-ΔE impacts the fitness of strains expressingmps3alleles, a genetic interaction with a conserved component of the nuclear pore complex, Pom152, is specific for TorsinA. This specificity is mirrored by a physical interaction between Pom152 and TorsinA, but not TorsinA-ΔE. These data suggest that TorsinA-nucleoporin interactions would be abrogated by TorsinA-ΔE, providing new experimental avenues to interrogate the molecular basis behind nuclear envelope herniations seen in cells lacking TorsinA function.