bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using null models to compare bacterial and microeukaryotic metacommunity assembly under shifting environmental conditions
Authors: Vass Máté , Székely Anna J. , Lindström Eva S. , Langenheder Silke 
Published: September 2019

AbstractTemporal variations in microbial metacommunity structure and assembly processes in response to shifts in environmental conditions are poorly understood. Hence, we conducted a temporal field study by sampling rock pools in four-day intervals during a 5-week period that included strong changes in environmental conditions due to intensive rain. We characterized bacterial and microeukaryote communities by 16S and 18S rRNA gene sequencing, respectively. Using a suite of null-model approaches to assess dynamics in community assembly, we found that strong changes in environmental conditions induced small but significant temporal changes in assembly processes and triggered different responses in bacterial and microeukaryotic metacommunities, promoting distinct selection processes. Incidence-based approaches showed that the assemblies of both communities were mainly governed by stochastic processes. In contrast, abundance-based methods indicated the dominance of historical contingency and unmeasured factors in case of bacteria and microeukaryotes, respectively, which we distinguished from dispersal-related processes using additional tests. Taken together, our study highlights that community assembly processes are not static, and the relative importance of different assembly processes can vary under different conditions and between different microbial groups.
Single-cell atlas of the first intra-mammalian developmental stage of the human parasite Schistosoma mansoni
Authors: Diaz Soria Carmen Lidia , Lee Jayhun , Chong Tracy , Coghlan Avril , Tracey Alan , Young Matthew D , Andrews Tallulah , Hall Christopher , Ng Bee Ling , Rawlinson Kate , Doyle Stephen R. , Leonard Steven , Lu Zhigang , Bennett Hayley M , Rinaldi Gabriel , Newmark Phillip A. , Berriman Matthew 
Published: September 2019

AbstractOver 250 million people suffer from schistosomiasis, a tropical disease caused by parasitic flatworms known as schistosomes. Humans become infected by free-swimming, water-borne larvae, which penetrate the skin. The earliest intra-mammalian stage, called the schistosomulum, undergoes a series of developmental transitions. These changes are critical for the parasite to adapt to its new environment as it navigates through host tissues to reach its niche, where it will grow to reproductive maturity. Unravelling the mechanisms that drive intra-mammalian development requires knowledge of the spatial organisation and transcriptional dynamics of different cell types that comprise the schistomulum body. To fill these important knowledge gaps, we performed single-cell RNA sequencing on two-day old schistosomula of Schistosoma mansoni. We identified likely gene expression profiles for muscle, nervous system, tegument, parenchymal/primordial gut cells, and stem cells. In addition, we validated cell markers for all these clusters by in situ hybridisation in schistosomula and adult parasites. Taken together, this study provides a comprehensive cell-type atlas for the early intra-mammalian stage of this devastating metazoan parasite.
Using a residency index to estimate the economic value of saltmarsh provisioning services for commercially important fish species
Authors: McCormick Hannah A. , Salguero-Gómez Roberto , Mills Morena , Davis Katrina 
Published: September 2019

ABSTRACTEvery year, 100 hectares of saltmarsh in the United Kingdom are lost due to sea level rise. The remaining areas are threatened by land conversion, agricultural activities, and climate change. There are important economic consequences to saltmarsh loss, as saltmarsh provides valuable ecosystem services including flood protection, carbon sequestration, and nursery habitat for commercially fished species. Quantifying the economic value of these ecosystem services can help target policies for saltmarsh restoration, or ‘managed realignment’, of new saltmarsh areas. In this study, we quantify the economic value of saltmarsh as a habitat for commercially fished species by developing a residency index. The residency index weights the relative importance of saltmarsh along a species’ lifecycle by explicitly incorporating the target species’ life histories and the estimated proportion of time it spends in saltmarsh at juvenile and adult life stages. Using this index, we estimate the value of saltmarsh to UK commercial fisheries landings. We find that UK saltmarsh contributes annually between 16.7% and 18.2% of total UK commercial landings for European seabass (Dicentrarchus labrax), European plaice (Pleuronectes platessa), and Common sole (Solea solea). Our findings highlight the importance of saltmarsh protection and restoration. Furthermore, our approach provides a general framework that integrates population ecology methods and economic analyses to assess the value of saltmarsh and other coastal habitats for fisheries worldwide.
Integrated clonal analysis reveals circulating tumor DNA in urine and plasma of glioma patients
Authors: Mouliere Florent , Heider Katrin , Smith Christopher G. , Su Jing , Thompson Mareike , Morris James , Wan Jonathan C.M. , Chandrananda Dineika , Hadfield James , Grezlak Marta , Hudecova Irena , Cooper Wendy , Gale Davina , Eldridge Matt , Watts Colin , Brindle Kevin , Rosenfeld Nitzan , Mair Richard 
Published: September 2019

AbstractGlioma-derived cell-free tumor DNA is challenging to detect using standard liquid biopsy techniques as its levels in body fluids are very low, similar to those in patients with early stage carcinomas. By sequencing cell-free DNA across thousands of clonal and private mutations identified individually in each patient’s tumor we detected tumor-derived DNA in plasma (10/12, 83%) and urine samples (8/11, 72%) from the majority (7/8, 87.5%) of glioma patients tested.One Sentence SummaryCirculating tumor DNA can be detected in the majority of plasma and urine samples from primary brain tumor patients using sequencing guided by mutations detected in multi-region tumor biopsies.
High-sensitivity monitoring of ctDNA by patient-specific sequencing panels and integration of variant reads
Authors: Wan Jonathan C. M. , Heider Katrin , Gale Davina , Murphy Suzanne , Fisher Eyal , Morris James , Mouliere Florent , Chandrananda Dineika , Marshall Andrea , Gill Andrew B. , Chan Pui Ying , Barker Emily , Young Gemma , Cooper Wendy N. , Hudecova Irena , Marass Francesco , Bignell Graham R. , Alifrangis Constantine , Middleton Mark R. , Gallagher Ferdia A. , Parkinson Christine , Durrani Amer , McDermott Ultan , Smith Christopher G. , Massie Charles , Corrie Pippa G. , Rosenfeld Nitzan 
Published: September 2019

AbstractCirculating tumor-derived DNA (ctDNA) can be used to monitor cancer dynamics noninvasively. Patients with small tumors have few copies of ctDNA in plasma, resulting in limited sensitivity to detect low-volume or residual disease. We show that sampling limitations can be overcome and sensitivity for ctDNA detection can be improved by massively parallel sequencing when hundreds to thousands of mutations are identified by tumor genotyping. We describe the INtegration of VAriant Reads (INVAR) analysis pipeline, which combines patient-specific mutation lists with both custom error-suppression methods and signal enrichment based on biological features of ctDNA. In this framework, the sensitivity can be estimated independently for each sample based on the number of informative reads, which is the product of the number of mutations analyzed and the average depth of unique sequencing reads. We applied INVAR to deep sequencing data generated by custom hybrid-capture panels, and showed that when ~106 informative reads were obtained INVAR allowed detection of tumor-derived DNA fractions to parts per million (ppm). In serial samples from patients with advanced melanoma on treatment, we detected ctDNA when imaging confirmed tumor volume of ~1cm3. In patients with resected early-stage melanoma, ctDNA was detected in 40% of patients who later relapsed, with higher rates of detection when more informative reads were obtained. We further demonstrated that INVAR can be generalized and allows improved detection of ctDNA from whole-exome and low-depth whole-genome sequencing data.
Does body position before and during blood sampling influence the athlete biological passport variables?
Authors: Tiffany Astolfi , Olaf Schumacher Yorck , von Roten Fabienne Crettaz , Martial Saugy , Raphael Faiss 
Published: September 2019

AbstractThe Athlete’s Biological Passport (ABP) is a tool for the indirect detection of blood doping. Current guidelines from the World Anti-Doping Agency (WADA) require a delay of 2 hours after any physical exercise and to be seated for 10 minutes prior to any blood sampling to obtain a valid measurement. Since body position prior to and during phlebotomy may influence the outcome, this study compared blood biomarker variations with changes in body position during blood sample collection. Ten successive venous blood samples from 38 subjects of 3 groups (elite cyclists, apnea divers and controls) in three situations (seated, after a 50 m walk, and supine) were collected and analyzed via flow cytometry. While reticulocytes percentage was unchanged in all conditions, haemoglobin concentration and hematocrit were stable after at least 10 min in a seated position. Due to shifts in plasma volume, the measures were significantly higher after changing posture for a short walk, but readjusted to previous levels after only 5 min. Supine position caused generally lower values after 10-30 min. The results support the current guidelines and additionally provide evidence to adjust the waiting time for blood sampling after short changes in posture.
Identification and quantification of meat product ingredients by whole-genome metagenomics (All-Food-Seq)
Authors: Hellmann Sören Lukas , Ripp Fabian , Bikar Sven-Ernö , Schmidt Bertil , Köppel René , Hankeln Thomas 
Published: September 2019

AbstractComplex food matrices bear the risk of intentional or accidental admixture of non-declared species. Moreover, declared components can be present in false proportions, since expensive taxa might be exchanged for cheaper ones. We have previously reported that PCR-free metagenomic sequencing of total DNA extracted from sausage samples combined with bioinformatic analysis (termed All-Food-Seq, AFS), can be a valuable screening tool to identify the taxon composition of food ingredients. Here we illustrate this principle by analysing regional Doner kebap samples, which revealed unexpected and unlabelled poultry and plant components in three of five cases. In addition, we systematically apply AFS to a broad set of reference meat material of known composition (i.e. reference sausages) to evaluate quantification accuracy and potential limitations. We include a detailed analysis of the effect of different food matrices and the possibility of false-positive sequence read assignment to closely related species, and we compare AFS quantification results to quantitative real-time PCR (qPCR) and droplet digital PCR (ddPCR). AFS emerges as a potent PCR-free screening tool, which can detect multiple target species of different kingdoms of life within a single assay. Mathematical calibration accounting for pronounced matrix effects can significantly improves AFS quantification accuracy. In comparison, AFS performs better than classical qPCR, and is on par with ddPCR.
Massive analysis of 64’628 bacterial genomes to decipher a water reservoir and origin of mobile colistin resistance (mcr) gene variants: is there another role for this family of enzymes?
Authors: Khedher Mariem Ben , Baron Sophie Alexandra , Riziki Toilhata , Ruimy Raymond , Diene Seydina M. , Rolain Jean-Marc 
Published: September 2019

AbstractSince 2015, new worrying colistin resistance mechanism, mediated by mcr-1 gene has been reported worldwide along with eight newly described variants (mcr-2 to mcr-9) but their source(s) and reservoir(s) remain largely unexplored. Here, we conducted a massive bioinformatic analysis of 64’628 downloaded bacterial genomes to investigate the reservoir and origin of these mcr variants. We identified a total of 6’651 significant positive hits (aa sequence coverage > 90 % and similarity >50%) with the nine MCR variants from these genomes that include 39 bacterial genera and more than 1050 species. Although these variants could be identified in bacteria from human and animal sources, we found plenty MCR variants in unsuspected bacteria from environmental origin, especially from water sources. The ubiquitous presence of mcr variants in bacteria from water likely suggests another role in the biosphere of these enzymes as an unknown defense system against natural antimicrobial peptides and/or bacteriophage predation.
When two cells are better than one: specialized stellate cells provide a privileged route for uniquely rapid water flux inDrosophilarenal tubule
Authors: Cabrero Pablo , Terhzaz Selim , Dornan Anthony J. , Ghimire Saurav , Holmes Heather L. , Turin Daniel R. , Romero Michael F. , Davies Shireen A. , Dow Julian A. T. 
Published: September 2019

AbstractInsects are highly successful, in part through an excellent ability to osmoregulate. The renal (Malpighian) tubules can secrete fluid faster on a per-cell basis than any other epithelium, but the route for these remarkable water fluxes has not been established. InDrosophila melanogaster, we show that 4 members of the Major Intrinsic Protein family are expressed at very high level in the fly renal tissue; the aquaporins Drip and Prip, and the aquaglyceroporins Eglp2 and Eglp4. As predicted from their structure and by their transport function by expressing these proteins inXenopusoocytes, Drip, Prip and Eglp2 show significant and specific water permeability, whereas Eglp2 and Eglp4 show very high permeability to glycerol and urea. Knockdowns of any of these genes impacts tubule performance resulting in impaired hormone-induced fluid secretion. TheDrosophilatubule has two main secretory cell types: active cation-transporting principal cells with the aquaglyceroporins localize to opposite plasma membranes and small stellate cells, the site of the chloride shunt conductance, with these aquaporins localising to opposite plasma membranes. This suggests a model in which cations are pumped by the principal cells, causing chloride to follow through the stellate cells in order to balance the charge. As a consequence, osmotically obliged water follows through the stellate cells. Consistent with this model, fluorescently labelled dextran, anin vivomarker of membrane water permeability, is trapped in the basal infoldings of the stellate cells after kinin diuretic peptide stimulation, confirming that these cells provide the major route for transepithelial water flux. The spatial segregation of these components of epithelial water transport may help to explain the unique success of the higher insects.Significance statementThe tiny insect renal (Malpighian) tubule can transport fluid at unparalleled speed, suggesting unique specialisations. Here we show that strategic allocation of Major Intrinsic Proteins (MIPs) to specific cells within the polarized tubule allow the separation of metabolically intense active cation transport from chloride and water conductance. This body plan is general to at least many higher insects, providing a clue to the unique success of the class Insecta.
Hippocampal place cells encode local surface texture boundaries
Authors: Wang Chia-Hsuan , Monaco Joseph D. , Knierim James J. 
Published: September 2019

SummaryThe cognitive map is often assumed to be a Euclidean map that isometrically represents the real world (i.e. the Euclidean distance between any two locations in the physical world should be preserved on the cognitive map). However, accumulating evidence suggests that environmental boundaries can distort the mental representations of a physical space. For example, the distance between two locations can be remembered as longer than the true physical distance if the locations are separated by a boundary. While this overestimation is observed under different experimental conditions, even when the boundary is formed by flat surface cues, its physiological basis is not well understood. We examined the neural representation of flat surface cue boundaries, and of the space segregated by these boundaries, by recording place cell activity from dorsal CA1 and CA3 while rats foraged on a circular track or square platform with inhomogeneous surface textures. About 40% of the place field edges concentrated near the surface cue boundaries on the circular track (significantly above the chance level 33%). Similarly, the place field edges were more prevalent near the boundaries on the platforms than expected by chance. In both 1-dimensional and 2-dimensional environments, the population vectors of place cell activity changed more abruptly with distance between locations that crossed cue boundaries than between locations within a bounded region. These results show that the locations of surface boundaries were evident as enhanced decorrelations of the neural representations of locations to either side of the boundaries. This enhancement might underlie the cognitive phenomenon of overestimation of distances across boundaries.
Gene activation and repression by the glucocorticoid receptor are mediated by sequestering Ep300 and two modes of chromatin binding
Authors: Portuguez Avital Sarusi , Grbesa Ivana , Tal Moran , Deitch Rachel , Raz Dana , Weismann Ran , Schwartz Michal , Loza Olga , Sung Myong-Hee , Kaplan Tommy , Hakim Ofir 
Published: September 2019

ABSTRACTThe transcription factor glucocorticoid receptor (GR) is a key mediator of stress response and a broad range of physiological processes. How can GR rapidly activate the expression of some genes while repress others, remains an open question due to the challenge to associate GR binding sites (GBSs) to their distant gene targets. Mapping the full 3D scope of GR-responsive promoters using high-resolution 4C-seq unravelled spatial separation between chromatin interaction networks of GR-activated and repressed genes. Analysing GR binding sites and other regulatory loci in their functional 3D context revealed that GR sequesters the co-activator Ep300 from active non-GBS enhancers in both activated and repressed gene compartments. While this is sufficient for rapid gene repression, gene activation is countered by productive recruitment of Ep300 to GBS. Importantly, in GR-activated compartments Klf4 binding at non-GBS regulatory elements cluster in 3D with GBS and antagonizes GR activation. In addition, we revealed ROR and Rev-erb transcription factors as novel co-regulators for GR-mediated gene expression.
p53-induced apoptosis is specified by a translation program regulated by PCBP2 and DHX30
Authors: Rizzotto Dario , Zaccara Sara , Rossi Annalisa , Galbraith Matthew D. , Andrysik Zdenek , Pandey Ahwan , Sullivan Kelly D. , Quattrone Alessandro , Espinosa Joaquín M. , Dassi Erik , Inga Alberto 
Published: September 2019

ABSTRACTActivation of p53 by the small molecule Nutlin can result in a combination of cell cycle arrest and apoptosis. The relative strength of these events is difficult to predict by classical gene expression analysis, leaving uncertainty as to the therapeutic benefits of Nutlin. Here, we report a new translational control mechanism shaping p53-dependent apoptosis. Using polysome profiling, we establish Nutlin-induced apoptosis to be associated with the enhanced translation of mRNAs carrying multiple copies of a newly identified 3’UTR CG-rich motif mediating p53-dependent death (CGPD-motif). We identified PCBP2 and DHX30 as CGPD-motif interactors. We found that in cells undergoing persistent cell cycle arrest in response to Nutlin, CGPD-motif mRNAs are repressed by the PCBP2-dependent binding of DHX30 to the motif. Thus, upon DHX30 depletion in these cells, the translation of CGPD-motif mRNAs is increased, and the response to Nutlin shifts towards apoptosis. Instead, DHX30 inducible overexpression in SJSA1 cells, that undergo Nutlin-induced apoptosis, leads to decreased translation of CGPD-motif mRNAs. Overall, this work establishes the role of PCBP2-DHX30 in controlling the translation of CGPD-motif mRNAs and thus provide a new mechanism to modulate the induction of p53-dependent apoptosis.
Ndc80/Nuf2-like protein KKIP1 connects a stable kinetoplastid outer kinetochore complex to the inner kinetochore and responds to metaphase tension
Authors: Brusini Lorenzo , D’Archivio Simon , McDonald Jennifer , Wickstead Bill 
Published: September 2019

AbstractKinetochores perform an essential role in eukaryotes, coupling chromosomes to the mitotic spindle. In model organisms they are composed of a centromere-proximal inner kinetochore and an outer kinetochore network that binds to microtubules. In spite of its universal function, the composition of kinetochores in extant eukaryotes can differ greatly, and understanding how these different systems evolved and now function are important questions in cell biology. In trypanosomes and other Kinetoplastida, the kinetochores are extremely divergent, with most components showing no detectable similarity to proteins in other systems. They may also be very different functionally, potentially binding to the spindle directly via the inner kinetochore protein KKT4. However, we do not know the extent of the trypanosome kinetochore and proteins interacting with a highly divergent Ndc80/Nuf2-like protein, KKIP1, suggest the existence of more centromere-distal complexes. Here we use quantitative proteomics from multiple start-points to define a stable 9-protein kinetoplastid outer kinetochore (KOK) complex. Two of these core components were recruited from other nuclear processes, exemplifying the role of moonlighting proteins in kinetochore evolution. The complex is physically and biochemically distinct from KKT proteins, but KKIP1 links the inner and outer sets, with its C-terminus very close to the centromere and N-terminus at the outer kinetochore. Moreover, trypanosome kinetochores exhibit intra-kinetochore movement during metaphase, primarily by elongation of KKIP1, consistent with pulling at the outer kinetochores. Together, these data suggest that the KOK complex, KKIP5 and N-terminus of KKIP1 likely constitute the extent of the trypanosome outer kinetochore and that this assembly binds to the spindle with sufficient strength to stretch the kinetochore.