bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human inbreeding has decreased in time through the Holocene
Authors: Ceballos Francisco C. , Gürün Kanat , Altınışık N. Ezgi , Gemici Hasan Can , Karamurat Cansu , Koptekin Dilek , Vural Kıvılcım Başak , Sürer Elif , Erdal Yılmaz Selim , Götherström Anders , Özer Füsun , Atakuman Çiğdem , Somel Mehmet 
Published: September 2020

SummaryThe history of human inbreeding is controversial. The development of sedentary agricultural societies may have had opposite influences on inbreeding levels. On the one hand, agriculture and food surplus may have diminished inbreeding by increasing population sizes and lowering endogamy, i.e. inbreeding due to population isolation. On the other hand, increased sedentism, as well as the advent of private property may have promoted inbreeding through the emergence of consanguineous marriage customs or via ethnic and caste endogamy. The net impact is unknown, and to date, no systematic study on the temporal frequency of inbreeding in human societies has been conducted. Here we present a new approach for reliable estimation of runs of homozygosity (ROH) in genomes with ≥3x mean coverage across >1 million SNPs, and apply this to 440 ancient Eurasian genomes from the last 15,000 years. We show that the frequency of inbreeding, as measured by ROH, has decreased over time. The strongest effect is associated with the Neolithic transition, but the trend has since continued, indicating a population size effect on inbreeding prevalence. We further show that most inbreeding in our historical sample can be attributed to endogamy, although singular cases of high consanguinity can also be found in the archaeogenomic record.HighlightsA study of 440 ancient genomes shows inbreeding decreased over time.The decrease appears linked with population size increase due to farming.Extreme consanguineous matings did occur among farmers, but rarely.
Integrating identification and quantification uncertainty for differential protein abundance analysis with Triqler
Authors: The Matthew , Käll Lukas 
Published: September 2020

AbstractProtein quantification for shotgun proteomics is a complicated process where errors can be introduced in each of the steps. Triqler is a Python package that estimates and integrates errors of the different parts of the label-free protein quantification pipeline into a single Bayesian model. Specifically, it weighs the quantitative values by the confidence we have in the correctness of the corresponding PSM. Furthermore, it treats missing values in a way that reflects their uncertainty relative to observed values. Finally, it combines these error estimates in a single differential abundance FDR that not only reflects the errors and uncertainties in quantification but also in identification. In this tutorial, we show how to (1) generate input data for Triqler from quantification packages such as MaxQuant and Quandenser, (2) run Triqler and what the different options are, (3) interpret the results, (4) investigate the posterior distributions of a protein of interest in detail and (5) verify that the hyperparameter estimations are sensible.
Dual-view oblique plane microscopy (dOPM)
Authors: Sparks Hugh , Dent Lucas , Bakal Chris , Behrens Axel , Salbreux Guillaume , Dunsby Chris 
Published: September 2020

AbstractWe present a new folded dual-view oblique plane microscopy (OPM) technique termed dOPM that enables two orthogonal views of the sample to be obtained by translating a pair of tilted mirrors in refocussing space. Using a water immersion 40× 1.15 NA primary objective, deconvolved image volumes of 200 nm beads were measured to have full width at half maxima (FWHM) of 0.35±0.04 μm and 0.39±0.02 μm laterally and 0.81±0.07 μm axially. The laterally integrated z-sectioning value was 1.33±0.45 μm using light-sheet FWHM in the frames of the two views of 4.99±0.58 μm and 4.89±0.63 μm. To qualitatively demonstrate that the system can reduce shadow artefacts while providing a more isotropic resolution, a multi-cellular spheroid approximately 100 μm in diameter was imaged.
Reduced long-lasting insecticidal net efficacy and pyrethroid insecticide resistance are associated with over-expression ofCYP6P4, CYP6P3andCYP6Z1in populations ofAnopheles coluzziifrom South-East Côte d’Ivoire
Authors: Meiwald Anne , Clark Emma , Kristan Mojca , Edi Constant , Jeffries Claire L. , Pelloquin Bethanie , Irish Seth R. , Walker Thomas , Messenger Louisa A. 
Published: September 2020

AbstractBackgroundResistance to major public health insecticides in Côte d’Ivoire has intensified and now threatens the long-term effectiveness of malaria vector control interventions.MethodsThis study evaluated the bioefficacy of conventional and next-generation long-lasting insecticidal nets (LLINs), determined resistance profiles, and characterized molecular and metabolic mechanisms in wildAnopheles coluzziifrom South-East Côte d’Ivoire in 2019.ResultsPhenotypic resistance was intense: more than 25% of mosquitoes survived exposure to ten times the doses of pyrethroids required to kill susceptible populations. Similarly, 24-hour mortality to deltamethrin-only LLINs was very low and not significantly different to an untreated net. Sub-lethal pyrethroid exposure did not induce significant delayed vector mortality 72 hours later. In contrast, LLINs containing the synergist piperonyl butoxide (PBO), or new insecticides, clothianidin and chlorfenapyr, were highly toxic toAn. coluzzii. Pyrethroid-susceptibleAn. coluzziiwere significantly more likely to be infected with malaria, compared to those that survived insecticidal exposure. Pyrethroid resistance was associated with significant over-expression ofCYP6P4, CPY6Z1andCYP6P3.ConclusionsStudy findings raise concerns regarding the operational failure of standard LLINs and support the urgent deployment of vector control interventions incorporating PBO, chlorfenapyr or clothianidin in areas of high resistance intensity in Côte d’Ivoire.
Functional genomic screens identify human host factors for SARS-CoV-2 and common cold coronaviruses
Authors: Wang Ruofan , Simoneau Camille R. , Kulsuptrakul Jessie , Bouhaddou Mehdi , Travisano Katherine , Hayashi Jennifer M. , Carlson-Stevermer Jared , Oki Jennifer , Holden Kevin , Krogan Nevan J. , Ott Melanie , Puschnik Andreas S. 
Published: September 2020

AbstractTheCoronaviridaeare a family of viruses that causes disease in humans ranging from mild respiratory infection to potentially lethal acute respiratory distress syndrome. Finding host factors that are common to multiple coronaviruses could facilitate the development of therapies to combat current and future coronavirus pandemics. Here, we conducted parallel genome-wide CRISPR screens in cells infected by SARS-CoV-2 as well as two seasonally circulating common cold coronaviruses, OC43 and 229E. This approach correctly identified the distinct viral entry factors ACE2 (for SARS-CoV-2), aminopeptidase N (for 229E) and glycosaminoglycans (for OC43). Additionally, we discovered phosphatidylinositol phosphate biosynthesis and cholesterol homeostasis as critical host pathways supporting infection by all three coronaviruses. By contrast, the lysosomal protein TMEM106B appeared unique to SARS-CoV-2 infection. Pharmacological inhibition of phosphatidylinositol phosphate biosynthesis and cholesterol homeostasis reduced replication of all three coronaviruses. These findings offer important insights for the understanding of the coronavirus life cycle as well as the potential development of host-directed therapies.
Pathway Analysis within Multiple Human Ancestries Reveals Novel Signals for Epistasis in Complex Traits
Authors: Turchin Michael C. , Darnell Gregory , Crawford Lorin , Ramachandran Sohini 
Published: September 2020

AbstractGenome-wide association (GWA) studies have identified thousands of significant genetic associations in humans across a number of complex traits. However, the majority of these studies focus on linear additive relationships between genotypic and phenotypic variation. Epistasis, or non-additive genetic interactions, has been identified as a major driver of both complex trait architecture and evolution in multiple model organisms; yet, this same phenomenon is not considered to be a significant factor underlying human complex traits. There are two possible reasons for this assumption. First, most large GWA studies are conducted solely with European cohorts; therefore, our understanding of broad-sense heritability for many complex traits is limited to just one ancestry group. Second, current epistasis mapping methods commonly identify significant genetic interactions by exhaustively searching across all possible pairs of SNPs. In these frameworks, estimated epistatic effects size are often small and power can be low due to the multiple testing burden. Here, we present a case study that uses a novel region-based mapping approach to analyze sets of variants for the presence of epistatic effects across six diverse subgroups within the UK Biobank. We refer to this method as the “MArginal ePIstasis Test for Regions” or MAPIT-R. Even with limited sample sizes, we find a total of 245 pathways within the KEGG and REACTOME databases that are significantly enriched for epistatic effects in height and body mass index (BMI), with 67% of these pathways being detected within individuals of African ancestry. As a secondary analysis, we introduce a novel region-based “leave-one-out” approach to localize pathway-level epistatic signals to specific interacting genes in BMI. Overall, our results indicate that non-European ancestry populations may be better suited for the discovery of non-additive genetic variation in human complex traits — further underscoring the need for publicly available, biobank-sized datasets of diverse groups of individuals.
TAEL 2.0: An Improved Optogenetic Expression System for Zebrafish
Authors: LaBelle Jesselynn , Ramos-Martinez Adela , Shen Kyle , Motta-Mena Laura B. , Gardner Kevin H. , Materna Stefan C. , Woo Stephanie 
Published: September 2020

AbstractInducible gene expression systems are valuable tools for studying biological processes. We previously developed an optogenetic gene expression system called TAEL that is optimized for use in zebrafish. When illuminated with blue light, TAEL transcription factors dimerize and activate gene expression downstream of the TAEL-responsive C120 promoter. By using light as the inducing agent, the TAEL/C120 system overcomes limitations of traditional inducible expression systems by enabling fine spatial and temporal regulation of gene expression. Here, we describe ongoing efforts to improve the TAEL/C120 system. We made modifications to both the TAEL transcriptional activator and the C120 regulatory element, collectively referred to as TAEL 2.0. We demonstrate that TAEL 2.0 consistently induces higher levels of reporter gene expression and at a faster rate, but with comparable background and toxicity as the original TAEL system. With these improvements, we were able to create functional stable transgenic lines to express the TAEL 2.0 transcription factor either ubiquitously or with a tissue-specific promoter. We demonstrate that the ubiquitous line in particular can be used to induce expression at late embryonic and larval stages, addressing a major deficiency of the original TAEL system. This improved optogenetic expression system will be a broadly useful resource for the zebrafish community.
The impact of the fragile health system on the implementation of health policies in Yemen
Authors: Hussein Taha , Dureab Fekri , Al-Waziza Raof , Noman Hanan , Hennig Lisa , Jahn Albrecht 
Published: September 2020

AbstractBackgroundThe on-going humanitarian crisis in Yemen is one of the worst in the world, with more than14 million people in acute need. The conflict in Yemen deteriorated the country’s already fragile health system and lead to the collapse of more than half of the health facilities. Health system fragmentation is also a problem in Yemen, which is complicated by the existence of two health ministries with different strategies. The aim of this study is to evaluate the effect of health system fragmentation on the implementation of health policies in Yemen across the global agendas of Universal Health Coverage (UHC), Health Security (GHS) and Health Promotion (HP) in the context of WHO’s priorities achieving universal health coverage, addressing health emergencies and promoting healthier populations.MethodsThe study is qualitative research using key informant in-depth interviews and documents analysis.ResultsThere are many health stakeholders in Yemen, including the public, private, and NGO sectors - each with different priorities and interests, which did not always align with national policies and strategies. The WHO and Ministry of Public Health and Population (MoPHP) are the main supporters to implement all policies related to the UHC, GHS and HP agendas. Interestingly, initiatives initially pursuing a health security approach to control the cholera epidemic realigned with the UHC concept and moved from an initial focus on health security, to propose a minimum health service package, a classical UHC intervention. Overall, Universal Health Coverage is the most adapted agenda, health security agendas were highly disrupted due to conflicts and health staffs were caught unprepared for emerging outbreaks. The health promotion agenda was largely ignored.ConclusionRestoring peace, building on synergies between the three health agendas through joint planning between the MoPHP and other health actors are highly recommended.
Hybridisation capture allows DNA damage analysis of ancient marine eukaryotes
Authors: Armbrecht L. , Hallegraeff G. , Bolch C.J.S. , Woodward C. , Cooper A. 
Published: September 2020

AbstractMarine sedimentary ancient DNA (sedaDNA) is increasingly used to study past ocean ecosystems, however, studies have been severely limited by the very low amounts of DNA preserved in the subseafloor, and the lack of bioinformatic tools to authenticatesedaDNA in metagenomic data. We applied a hybridisation capture ‘baits’ technique to target marine eukaryotesedaDNA (specifically, phytoplankton, ‘Phytobaits1’; and harmful algal bloom taxa, ‘HABbaits1’), which resulted in up to 4- and 9-fold increases, respectively, in the relative abundance of eukaryotes compared to shotgun sequencing. We further used the new bioinformatic tool ‘HOPS’ to authenticate thesedaDNA component, establishing a new proxy to assesssedaDNA authenticity, the Ancient: Default (A:D) sequences ratio, here positively correlated with subseafloor depth, and generated the first-ever DNA damage profiles of a key phytoplankton, the ubiquitous coccolithophoreEmiliania huxleyi.Our study opens new options for the detailed investigation of marine eukaryotes and their evolution over geological timescales.
Homing Choices of Breast Cancer Cells Revealed by Tissue Specific Invasion and Extravasation Lab-on-a-chip Platforms
Authors: Firatligil-Yildirir Burcu , Bati-Ayaz Gizem , Tahmaz Ismail , Bilgen Muge , Pesen-Okvur Devrim , Yalcin-Ozuysal Ozden 
Published: September 2020

AbstractMetastasis is one of the major obstacles for breast cancer patients. Limitations of current models demand the development of novel platforms to predict metastatic potential and homing choices of cancer cells. Here, two novel Lab-on-a-chip (LOC) platforms, invasion/chemotaxis (IC-chip) and extravasation (EX-chip), are presented for the quantitative assessment of invasion and extravasation, towards specific tissues. On IC-chip, invasive MDA-MB-231, but not non-invasive MCF-7 breast cancer cells invaded lung and liver microenvironments. Lung-specific but not bone-specific MDA-MB-231 clones efficiently invaded lung microenvironment, stressing ability of IC-chip to demonstrate differentin vivometastatic behaviors. On EX-chip, MDA-MB-231 cells extravasated more into the lung microenvironment compared to the liver and breast highlighting the potency of the platform to mimicin vivohoming choices. Overall, this study presents IC-chip and EX-chip that can determine tissue-specific invasion and extravasation potentials of cancer cells providing the groundwork for novel diagnostic tools to predict metastasis risk.
First 3D-Structural Data of Full-length Rod-Outer-Segment Guanylyl Cyclase 1 in Bovine Retina by Cross-linking/Mass Spectrometry
Authors: Rehkamp Anne , Tänzler Dirk , Tüting Christian , Kastritis Panagiotis L. , Iacobucci Claudio , Ihling Christian H. , Kipping Marc , Koch Karl-Wilhelm , Sinz Andrea 
Published: September 2020

AbstractThe rod-outer-segment guanylyl cyclase 1 (ROS-GC1) is a key transmembrane protein for retinal phototransduction. Mutations of ROS-GC1 correlate with different retinal diseases that often lead to blindness. No structural data are available for ROS-GC1 so far. We performed a 3D-structural analysis of native ROS-GC1 from bovine retina by cross-linking/mass spectrometry (XL-MS) and computational modeling. Absolute quantification and activity measurements of native ROS-GC1 were performed by MS-based assays directly in bovine retina samples. Our data present the first 3D-structural analysis of active, full-length ROS-GC1 in bovine retina. We propose a novel domain organization for the intracellular domain ROS-GC1. Our XL-MS data reveal that the α-helical domain connecting the kinase homology and catalytic domains can acquire different conformations. Also, the XL-MS data of native ROS-GC1 in bovine retina agree with a dimeric architecture. Our integrated approach can serve as a blueprint for conducting 3D-structural studies of membrane proteins in their native environment.
hcga: Highly Comparative Graph Analysis for network phenotyping
Authors: Peach Robert L. , Arnaudon Alexis , Schmidt Julia A. , Palasciano Henry A. , Bernier Nathan R. , Jelfs Kim , Yaliraki Sophia , Barahona Mauricio 
Published: September 2020

AbstractNetworks are widely used as mathematical models of complex systems across many scientific disciplines, not only in biology and medicine but also in the social sciences, physics, computing and engineering. Decades of work have produced a vast corpus of research characterising the topological, combinatorial, statistical and spectral properties of graphs. Each graph property can be thought of as a feature that captures important (and some times overlapping) characteristics of a network. In the analysis of real-world graphs, it is crucial to integrate systematically a large number of diverse graph features in order to characterise and classify networks, as well as to aid network-based scientific discovery. In this paper, we introduce HCGA, a framework for highly comparative analysis of graph data sets that computes several thousands of graph features from any given network. HCGA also offers a suite of statistical learning and data analysis tools for automated identification and selection of important and interpretable features underpinning the characterisation of graph data sets. We show that HCGA outperforms other methodologies on supervised classification tasks on benchmark data sets whilst retaining the interpretability of network features. We also illustrate how HCGA can be used for network-based discovery through two examples where data is naturally represented as graphs: the clustering of a data set of images of neuronal morphologies, and a regression problem to predict charge transfer in organic semiconductors based on their structure. HCGA is an open platform that can be expanded to include further graph properties and statistical learning tools to allow researchers to leverage the wide breadth of graph-theoretical research to quantitatively analyse and draw insights from network data.
Mitochondrial alternative oxidase contributes to successful tardigrade anhydrobiosis
Authors: Wojciechowska Daria , Karachitos Andonis , Roszkowska Milena , Rzeźniczak Wiktor , Sobkowiak Robert , Kaczmarek Łukasz , Kosicki Jakub , Kmita Hanna 
Published: September 2020

ABSTRACTAnhydrobiosis can be described as an adaptation to lack of water. This adaptation provides some organisms including tardigrades with a set of capabilities allowing them to survive extreme conditions that even do not exist on Earth. However, the underlying cellular mechanisms are still not explained. Available data assumes important contribution of mitochondrial proteins. Since mitochondrial alternative oxidase (AOX) described as a drought response element has recently been proposed for various invertebrates including tardigrades, we have decided to check if AOX is involved in successful anhydrobiosis of tardigrades.Milnesium inceptumwas used as a model for the study. We confirmed functionality ofM. inceptumAOX and estimated its activity contribution to anhydrobiosis of different duration. We observed that AOX activity was particularly important forM. inceptumrevival after longer-term anhydrobiosis but did not affect rehydration stage. The results may contribute to explanation and then application of anhydrobiosis underlying mechanisms.
Douglas fir and Norway spruce admixtures to beech forests along in Northern Germany – Are soil nutrient conditions affected?
Authors: Foltran Estela Covre , Ammer Christian , Lamersdorf Norbert 
Published: September 2020

AbstractThe establishment of mixed forest stands can be seen as an option to improve soil nutrient conditions and to protect forest ecosystems from various impacts of climate change. Our study analyzed groups of pure mature European beech (Fagus sylvatica; B), Douglas fir (Pseudotsuga menziesii; D) and Norway spruce (Picea abies; S) stands as well as mixtures of beech with either Douglas fir (DB) or spruce (SB), i.e. 5 forest stands per site along Northern Germany with two regionally clearly differing sites conditions (i.e., 3 loess-influenced, loamy sites in the Solling region, southern Lower Saxony and 4 sandy lowland sites further north). In order to determine possible influences of the tree species and their mixtures on soil properties, the organic layer and the mineral topsoil were first chemically characterized for all 35 plots down to a depth of 30 cm (pH, C, N, P, CEC, exchangeable nutrient cation contents and stocks, base saturation-BS). Our results indicated, independent of sites condition, that pure S stands showed the lowest pH and BS, meanwhile B the highest BS. The impact of D varied depending on site condition. On sandy soils, pure D showed higher pH and BS than under pure S, while on loamy soils the pH under D and B was lower than under S. Regarding cations stocks under sandy soils conditions, S stands and its admixture SB depleted soil Ca and Mg stocks more than pure D and B. In contrast, under loamy soil conditions B showed depleted (lowest) soil exchangeable Ca and Mg stocks more than under S stands. Soil exchangeable K under mixed stands were among the highest compared to pure stands, independent of the site condition. Thus, mixed species stands generally decreased soil base cation depletion compared to pure conifer stands. Admixtures of Douglas-fir (DB) seem to lead to smaller changes in pH, CEC and BS than those of Norway spruce, this effect become more important at sandy soil sites. Therefore, forest management may consider mixtures of European beech and Douglas fir as a reasonable management option without apprehending negative effects on soil chemistry.