bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistent alterations in plasma lipid profiles prior to introduction of gluten in the diet associate with progression to celiac disease
Authors: Sen Partho , Carlsson Cecilia , Virtanen Suvi M. , Simell Satu , Hyöty Heikki , Ilonen Jorma , Toppari Jorma , Veijola Riitta , Hyötyläinen Tuulia , Knip Mikael , Orešič Matej 
Published: September 2018

ABSTRACTBackground and AimsCeliac disease (CD) is a chronic enteropathy characterized by an autoimmune reaction in the small intestine in genetically-susceptible individuals. Gluten is the required environmental trigger of clinical CD, but the underlying causes of the autoimmune reaction remain unknown. Herein, we apply lipidomics to elucidate the early events preceding clinical CD in a prospective study of children observed from birth until diagnosis of CD and subsequent introduction of a gluten-free diet.MethodsMass spectrometry–based lipidomics profiling was applied to a longitudinal series of 233 plasma samples from the Type 1 Diabetes Prediction and Prevention (DIPP) study, spanning the period between birth and the introduction of a gluten–free diet following CD diagnosis (n=23 CD progressors, n=23 controls matched for gender, HLA risk, period of birth, and age).Results23 children progressed to CD at a mean age of 4.8 years. They showed increased amounts of triacylglycerols (TGs) of low carbon number and double bond count and a decreased level of phosphatidylcholines by 3 months of age as compared to controls. These differences were exacerbated with age but were not observed at birth. No significant differences were observed in essential (dietary) TGs such as those containing polyunsaturated fatty acids.ConclusionOur findings suggest that abnormal lipid metabolism associated with development of clinical CD may occur prior to the introduction of gluten to the diet. Moreover, our data suggest that the specific TGs found elevated in CD progressors may be due to a host response to compromised intake of essential lipids in the small intestine, requiring de novo lipogenesis.
A fuzzy-registration approach to track cell divisions in time-lapse fluorescence microscopy
Authors: Amarteifio Saoirse , Fallesen Todd , Pruessner Gunnar , Sena Giovanni 
Published: September 2018

AbstractBackgroundParticle-tracking in 3D is an indispensable computational tool to extract critical information on dynamical processes from raw time-lapse imaging. This is particularly true with in vivo time-lapse fluorescence imaging in cell and developmental biology, where complex dynamics are observed at high temporal resolution. Common tracking algorithms used with time-lapse data in fluorescence microscopy typically assume a continuous signal where background, recognisable keypoints and independently moving objects of interest are permanently visible. Under these conditions, simple registration and identity management algorithms can track the objects of interest over time. In contrast, here we consider the case of transient signals and objects whose movements are constrained within a tissue, where standard algorithms fail to provide robust tracking.ResultsTo optimize 3D tracking in these conditions, we propose the merging of registration and tracking tasks into a fuzzy registration algorithm to solve the identity management problem. We describe the design and application of such an algorithm, illustrated in the domain of plant biology, and make it available as an open-source software implementation. The algorithm is tested on mitotic events in 4D data-sets obtained with light-sheet fluorescence microscopy on growing Arabidopsis thaliana roots expressing CYCB::GFP. We validate the method by comparing the algorithm performance against both surrogate data and manual tracking.ConclusionThis method fills a gap in existing tracking techniques, following mitotic events in challenging data-sets using transient fluorescent markers in unregistered images.
Initial Sequencing and Characterization of Gastrointestinal and Oral Microbiota in Urban Pakistani Adults Reveals Abnormally High Levels of Potentially Starch Metabolizing Bacteria in the General Population
Authors: Batool Maria , Ali Syed Baqir , Jaan Ali , Khalid Kehkishan , Ali Syeda Aba , Kamal Kainat , Raja Afraz Ahmed , Gul Farzana , Pedroso Inti , Apte Zachary , Nasir Arshan 
Published: September 2018

ABSTRACTWe describe the characterization of the gastrointestinal tract (gut) and oral microbiota (bacteria) in 32 urban Pakistani adults representing seven major geographies and six ethnicities in the country. Study participants were between ages 18 and 40, had body mass index between 18 and 25 Kg/m2, and were early-career students or professionals belonging to 25 major cities of the country. These individuals donated a total of 61 samples (32 gut and 29 oral) that were subjected to 16S ribosomal RNA (rRNA) gene sequencing. Microbiome composition of Pakistani individuals was compared against the uBiome database of selected individuals who self-reported to be in excellent health. Using the crude measure of percentage overlap or similarity between the gut microbiota profile of Pakistani and uBiome dataset as proxy for health, our sequencing indicated that the Pakistani gut microbiota was moderately healthy relative to the uBiome dataset and Pakistani women appeared healthier relative to men. The Pakistani gut microbiome seemed susceptible to obesity and weight gain, levels of probiotics was very high likely due to the popularity of milk-based and fermented foods in the Pakistani diet, and bacteria that metabolize starch and carbohydrates (typically seen in the gut microbiota of honey bee) were abnormally enriched in the gut of Pakistani men. Our investigations reveal serious issues with the dietary habits and lifestyle of Pakistani individuals of consuming food enriched in high carbohydrates and fats, overcooked in oil and spices, following a sedentary lifestyle, little or no daily intake of fresh fruits, over-consumption of antibiotics from a very early age, and health and hygiene standards that do not meet international standards. Our sequencing is the first step towards generating a country-wide understanding of the impact of the local diet and lifestyle on Pakistani gut microbiota and can help understand its overall association with health and wellness.
Surface sediment samples from early age of seafloor exploration can provide a late 19th century baseline of the marine environment
Authors: Rillo Marina C. , Kucera Michal , Ezard Thomas H. G. , Giles Miller C. 
Published: September 2018

ABSTRACTOcean-floor sediment samples collected up to 150 years ago represent an important historical archive to benchmark global changes in the seafloor environment, such as species’ range shifts and invasions and pollution trends. Such benchmarking requires that the historical sediment samples represent the state of the environment at or shortly before the time of collection. However, early oceanographic expeditions sampled the ocean floor using devices like the sounding tube or a dredge, which potentially disturb the sediment surface and recover a mix of Holocene (surface) and deeper, Pleistocene sediments. Here we use climate-sensitive microfossils as a fast biometric method to assess if historical seafloor samples contain a mixture of modern and glacial sediments. Our assessment is based on comparing the composition of planktonic foraminifera (PF) assemblages in historical samples with Holocene and Last Glacial Maximum (LGM) global reference datasets. We show that eight out of the nine historical samples contain PF assemblages more similar to the Holocene than to the LGM PF assemblages, but the comparisons are only significant when there is a high local species’ temporal turnover (from the LGM to the Holocene). When analysing temporal turnover globally, we show that upwelling and temperate regions had greatest species turnover, which are areas where our methodology would be most diagnostic. Our results suggest that sediment samples from historical collections can provide a baseline of the state of marine ecosystems in the late 19th century, and thus be used to assess ocean global change trends.
Genetic hubs: a phylogeographer’s widget for pinpointing of ancestral populations
Authors: Ondřej Mikula 
Published: September 2018

AbstractStatistical phylogeography benefits from the development of increasingly realistic models of spatially structured genetic variation. Their fitting, however, is computationally demanding and requires population and/or genomic sampling that is not available for many species of interest. ‘Genetic hubs’ is a method that can be used for exploratory analyses of various kinds of genetic data, including those as typical in mitochondrial phylogeography, i.e. many small samples of single locus genotypes scattered throughout the species distributional range. ‘Genetic hubs’ allows to quantify and visualize gradients of genetic variation with the aim to pinpoint possible origin of expansion. It estimates local genetic variability as an accessibility of all genetic variation from the site in question and it allows to take dissimilarity of genotypes into account. The method represents fast and versatile tool that can be used whenever history of range expansion is assumed to shape the observed distribution of genetic variation and it is useful especially for preliminary analyses whose purpose is to provide sound basis for formulation of testable hypotheses and design of follow-up studies.
WFD ecological status indicator shows poor correlation with flow parameters in a large Alpine catchment
Authors: Larsen Stefano , Bruno Maria Cristina , Zolezzi Guido 
Published: September 2018

SummarySince the implementation of the Water Framework Directive, the ecological status of European running waters has been evaluated using a set of harmonised ecological indicators that should guide conservation and restoration actions. Among these, the restoration of the natural flow regime (ecological flows) is considered indispensable for the achievement of the good ecological status, and yet the sensitivity of the current biological indicators to hydrologic parameters remains understudied. The Italian Star_ICMi well represents other similar WFD indicators; it is a macroinvertebrate-based multimetric index officially adopted to assess the ecological status of running waters at the national level. Recent legislation has also included the Star_ICMi as one of the indicators used to assess and prescribe ecological flows in river reaches regulated by water abstraction. However, the relationship between river hydrology and the Star_ICMi index is so far virtually unknown. Using data from the Trentino - Alto Adige Alpine region, we first assessed the relationship between the Star_ICMi and synthetic descriptors of the physico-chemical (LIMeco) and morphological (MQI) status of respectively 280 and 184 river reaches. Then, we examined the relation between the Star_ICMi and a set of ecologically-relevant hydrologic parameters derived from discharge time-series measured at 21 hydrometric stations, representing both natural and regulated river reaches. Although the Star_ICMi showed significant and linear relationships with the physico-chemical character and, slightly, with the morphological quality of the reaches, its response to flow parameters appeared weak or non-existent when examined with linear models. Mixed quantile regressions allowed the identification of flow parameters that represented limiting factors for macroinvertebrate communities and the associated Star_ICMi scores. In particular, the index showed ‘negative floors’ where lower values were observed in reaches with large temporal variation in flow magnitude as well as frequent low and high flow events. The modelled quantiles also tracked the transition of the index from acceptable to unacceptable conditions.The results suggest that while the central tendency of the Star_ICMi index is not strongly influenced by river flow character, some key flow parameters represent limiting factors that allow the index to reach its lowest values, eventually ‘pushing’ the site towards unacceptable ecological conditions. The identification of limiting flow parameters can aid the setting of hydrologic thresholds over which ecological impairment is likely to occur. Overall, however, results imply caution is needed in using biological indicator like the Star_ICMi for the quantitative assessment and design of ecological flows.
Assessment of a highly multiplexed RNA sequencing platform and comparison to existing high-throughput gene expression profiling techniques
Authors: Reed Eric , Moses Elizabeth , Xiao Xiaohui , Liu Gang , Campbell Joshua , Perdomo Catalina , Monti Stefano 
Published: September 2018

AbstractThe need to reduce per sample cost of RNA-seq profiling for scalable data generation has led to the emergence of highly multiplexed RNA-seq. These technologies utilize barcoding of cDNA sequences in order to combine samples into single sequencing lane to be separated during data processing. In this study, we report the performance of one such technique denoted as sparse full length sequencing (SFL), a ribosomal RNA depletion-based RNA sequencing approach that allows for the simultaneous sequencing of 96 samples and higher. We offer comparisons to well established single-sample techniques, including: full coverage Poly-A capture RNA-seq and microarray, as well as another low-cost highly multiplexed technique known as 3’ digital gene expression (3’DGE). Data was generated for a set of exposure experiments on immortalized human lung epithelial (AALE) cells in a two-by-two study design, in which samples received both genetic and chemical perturbations of known oncogenes/tumor suppressors and lung carcinogens. SFL demonstrated improved performance over 3’DGE in terms of coverage, power to detect differential gene expression, and biological recapitulation of patterns of differential gene expression from in vivo lung cancer mutation signatures.
Cutting tree branches to pick OTUs: a novel method of provisional species delimitation
Authors: Ondřej Mikula 
Published: September 2018

AbstractDelimitation of species is crucial in all studies of biodiversity, its geographic patterns and evolutionary dynamics as well as in the corresponding conservation applications. In practice, operational taxonomic units (OTUs) are often used as provisional surrogates of the species, whose evidence-based and robust delimitation requires too extensive data and complex analyses. The novel method for this provisional species delimitation is suggested, which uses any phylogenetic tree with meaningful branch lengths as an input and delimits OTUs on it by identification of branches whose removal significantly changes structure of the tree. Such branches are considered to reflect interspecific differentiation that is assumed generally more erratic than intraspecific branching. It is called branch-cutting method as it evaluates structural importance of the branch by its cutting (shrinking to zero length) and inspecting impact of this operation on the average pairwise distances between tree tips. Tree tips can be also constrained to be either conspecific or heterospecific which allows the method to achieve more robust and informed delimitations and to focus on particular phylogenetic scale. Usefulness of the method is demonstrated on four empirical examples and comparison with similar methods is performed.
MMseqs2 desktop and local web server app for fast, interactive sequence searches
Authors: Mirdita Milot , Steinegger Martin , Söding Johannes 
Published: September 2018

SummaryThe MMseqs2 desktop and web server app facilitates interactive sequence searches through custom protein sequence and profile databases on personal workstations. By eliminating MMseqs2’s runtime overhead, we reduced response times to a few seconds at sensitivities close to BLAST.Availability and implementationThe app is easy to install for non-experts. Source code, prebuilt desktop app packages for Windows, macOS and Linux, Docker images for the web server application, and a demo web server are available at https://search.mmseqs.com.Contactmartin.steinegger@mpibpc.mpg.de or soeding@mpibpc.mpg.de
Evolution of cation binding in the active sites of P-loop nucleoside triphosphatases
Authors: Shalaeva Daria N. , Cherepanov Dmitry A. , Galperin Michael Y. , Mulkidjanian Armen Y. 
Published: September 2018

AbstractThe activity of cellular nucleoside triphosphatases (NTPases) must be tightly controlled to prevent spontaneous ATP hydrolysis leading to cell death. While most P-loop NTPases require activation by arginine or lysine fingers, some of the apparently ancestral ones are, instead, activated by potassium ions, but not by sodium ions. We combined comparative structure analysis of P-loop NTPases of various classes with molecular dynamics (MD) simulations of Mg-ATP complexes in water and in the presence of potassium, sodium, or ammonium ions. In all analyzed structures, the conserved P-loop motif keeps the triphosphate chains of enzyme-bound NTPs in an extended, catalytically prone conformation, similar to that attained by ATP in water in the presence of potassium or ammonium ions bound between alpha- and gamma-phosphate groups. The smaller sodium ions could not reach both alpha- and gamma-phosphates of a protein-bound extended phosphate chain and therefore are unable to activate most potassium-dependent P-loop NTPases.
Cryo-EM structures reveal bilayer remodeling during Ca2+ activation of a TMEM16 scramblase
Authors: Falzone Maria E. , Rheinberger Jan , Lee Byoung-Cheol , Peyear Thasin , Sasset Linda , Raczkowski Ashleigh , Eng Edward , Lorenzo Annarita Di , Andersen Olaf S. , Nimigean Crina M. , Accardi Alessio 
Published: September 2018

AbstractThe lipid distribution of plasma membranes of eukaryotic cells is asymmetric and phospholipid scramblases disrupt this asymmetry by mediating the rapid nonselective transport of lipids down their concentration gradients. As a result, phosphatidylserine is exposed to the outer leaflet of membrane, an important step in extracellular signaling networks controlling processes such as apoptosis, blood coagulation, membrane fusion and repair. Several members of the TMEM16 family have been identified as Ca2+-activated scramblases but the mechanisms underlying their Ca2+-dependent gating and their effects on the surrounding lipid bilayer remain poorly understood. Here we describe three high-resolution cryo-electron microscopy structures of a fungal scramblase from Aspergillus fumigatus, afTMEM16, reconstituted in lipid nanodiscs, revealing large Ca2+-dependent conformational changes of the protein as well as significant, function dependent membrane reorganization.
Functional retinal imaging using adaptive optics swept-source OCT at 1.6MHz
Authors: Azimipour Mehdi , Migacz Justin V. , Zawadzki Robert J. , Werner John S. , Jonnal Ravi S. 
Published: September 2018

AbstractObjective optical assessment of photoreceptor function may permit earlier diagnosis of retinal disease than current methods such as perimetry, electrophysiology, and clinical imaging. In this work, we describe an adaptive optics (AO) optical coherence tomography (OCT) system designed to measure functional responses of single cones to visible stimuli. The OCT subsystem consisted of a raster-scanning Fourier-domain mode-locked laser that acquires A-scans at 1.64MHz with a center wavelength of 1063nm, and an AO subsystem providing diffraction-limited imaging. Analysis of serial volumetric images revealed phase changes of cone photoreceptors consistent with outer segment elongation and proportional to stimulus intensity, as well as other morphological changes in the outer segment and retinal pigment epithelium.
Bidirectional Control of Coronary Vascular Resistance by Eicosanoids via a Novel GPCR
Authors: Alkayed Nabil J. , Cao Zhiping , Qian Zu Yuan , Nagarajan Shanthi , Liu Xuehong , Nelson Jonathan , Xie Fuchun , Li Bingbing , Fan Wei , Liu Lijuan , Grafe Marjorie R. , Xiao Xiangshu , Barnes Anthony P. , Kaul Sanjiv 
Published: September 2018

AbstractArachidonic acid metabolites epoxyeicosatrienoates (EETs) and hydroxyeicosatetraenoates (HETEs) are important regulators of myocardial blood flow and coronary vascular resistance (CVR), but their mechanisms of action are not fully understood. We identified G protein-coupled receptor 39 (GPR39)as a microvascular smooth muscle cell (mVSMC) receptor antagonistically regulated by two endogenous eicosanoids: 15-HETE, which stimulates GPR39 to increase mVSMC intracellular calcium and augment microvascular CVR, and 14,15-EET, which inhibits these actions. Furthermore, zinc ion acts as an allosteric modulator of GPR39 to potentiate the efficacy of the two ligands. Our findings will have a major impact on understanding the roles of eicosanoids in cardiovascular physiology and disease, and provide an opportunity for the development of novel GPR39-targeting therapies for cardiovascular disease.One Sentence SummaryGPR39 is a microvascular smooth muscle cell receptor regulated by two vasoactive eicosanoids with opposing actions.
Genomic sequence capture of haemosporidian parasites: Methods and prospects for enhanced study of host-parasite evolution
Authors: Barrow Lisa N. , Allen Julie M. , Huang Xi , Bensch Staffan , Witt Christopher C. 
Published: September 2018

AbstractAvian malaria and related haemosporidians (Plasmodium, [Para]Haemoproteus, and Leucocytoozoon) represent an exciting multi-host, multi-parasite system in ecology and evolution. Global research in this field accelerated after 1) the publication in 2000 of PCR protocols to sequence a haemosporidian mitochondrial (mtDNA) barcode, and 2) the development in 2009 of an open-access database to document the geographic and host ranges of parasite mtDNA haplotypes. Isolating haemosporidian nuclear DNA from bird hosts, however, has been technically challenging, slowing the transition to genomic-scale sequencing techniques. We extend a recently-developed sequence capture method to obtain hundreds of haemosporidian nuclear loci from wild bird samples, which typically have low levels of infection, or parasitemia. We tested 51 infected birds from Peru and New Mexico and evaluated locus recovery in light of variation in parasitemia, divergence from reference sequences, and pooling strategies. Our method was successful for samples with parasitemia as low as ∼0.03% (3 of 10,000 blood cells infected) and mtDNA divergence as high as 15.9% (one Leucocytozoon sample), and using the most cost-effective pooling strategy tested. Phylogenetic relationships estimated with >300 nuclear loci were well resolved, providing substantial improvement over the mtDNA barcode. We provide protocols for sample preparation and sequence capture including custom probe kit sequences, and describe our bioinformatics pipeline using aTRAM 2.0, PHYLUCE, and custom Perl and Python scripts. This approach can be applied to the tens of thousands of avian samples that have already been screened for haemosporidians, and greatly improve our understanding of parasite speciation, biogeography, and evolutionary dynamics.