bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different bottom trawl fisheries have a differential impact on the status of the North Sea seafloor habitats
Authors: Rijnsdorp A D , Hiddink J G , van Denderen P D , Hintzen N T , Eigaard O R , Valanko S , Bastardie F , Bolam S G , Boulcott P , Egekvist J , Garcia C , van Hoey G , Jonsson P , Laffargue P , Nielsen J R , Piet G J , Sköld M , van Kooten T 
Published: March 2020

AbstractFisheries using bottom trawls are the most widespread source of anthropogenic physical disturbance to seafloor habitats. To mitigate such disturbances, the development of fisheries-, conservation-, and ecosystem-based management strategies requires the assessment of the impact of bottom trawling on the state of benthic biota. We explore a quantitative and mechanistic framework to assess trawling impact. Pressure and impact indicators that provide a continuous pressure–response curve are estimated at a spatial resolution of 1 × 1 min latitude and longitude (∼2 km2) using three methods: L1 estimates the proportion of the community with a life span exceeding the time interval between trawling events; L2 estimates the decrease in median longevity in response to trawling; and population dynamic (PD) estimates the decrease in biomass in response to trawling and the recovery time. Although impact scores are correlated, PD has the best performance over a broad range of trawling intensities. Using the framework in a trawling impact assessment of ten métiers in the North Sea shows that muddy habitats are impacted the most and coarse habitats are impacted the least. Otter trawling for crustaceans has the highest impact, followed by otter trawling for demersal fish and beam trawling for flatfish and flyshooting. Beam trawling for brown shrimps, otter trawling for industrial fish, and dredging for molluscs have the lowest impact. Trawling is highly aggregated in core fishing grounds where the status of the seafloor is low but the catch per unit of effort (CPUE) per unit of impact is high, in contrast to peripheral grounds, where CPUE per unit of impact is low.
Patient characteristics associated with objective measures of digital health tool use in the United States: A literature review
Authors: Nouri Sarah S , Adler-Milstein Julia , Thao Crishyashi , Acharya Prasad , Barr-Walker Jill , Sarkar Urmimala , Lyles Courtney 
Published: March 2020

Abstract

Objective
The study sought to determine which patient characteristics are associated with the use of patient-facing digital health tools in the United States.

Materials and Methods
We conducted a literature review of studies of patient-facing digital health tools that objectively evaluated use (eg, system/platform data representing frequency of use) by patient characteristics (eg, age, race or ethnicity, income, digital literacy). We included any type of patient-facing digital health tool except patient portals. We reran results using the subset of studies identified as having robust methodology to detect differences in patient characteristics.

Results
We included 29 studies; 13 had robust methodology. Most studies examined smartphone apps and text messaging programs for chronic disease management and evaluated only 1-3 patient characteristics, primarily age and gender. Overall, the majority of studies found no association between patient characteristics and use. Among the subset with robust methodology, white race and poor health status appeared to be associated with higher use.

Discussion
Given the substantial investment in digital health tools, it is surprising how little is known about the types of patients who use them. Strategies that engage diverse populations in digital health tool use appear to be needed.

Conclusion
Few studies evaluate objective measures of digital health tool use by patient characteristics, and those that do include a narrow range of characteristics. Evidence suggests that resources and need drive use.
GenomegaMap: Within-Species Genome-Wide dN/dS Estimation from over 10,000 Genomes
Authors: Wilson Daniel J ,   The CRyPTIC Consortium, Crook Derrick W , Peto Timothy E A , Walker A Sarah , Hoosdally Sarah J , Gibertoni Cruz Ana L , Carter Joshua , Grazian Clara , Earle Sarah G , Kouchaki Samaneh , Lachapelle Alexander , Yang Yang , Clifton David A , Fowler Philip W , Iqbal Zamin , Hunt Martin , Knaggs Jeffrey , Smith E Grace , Rathod Priti , Jarrett Lisa , Matias Daniela , Cirillo Daniela M , Borroni Emanuele , Battaglia Simone , Ghodousi Arash , Spitaleri Andrea , Cabibbe Andrea , Tahseen Sabira , Nilgiriwala Kayzad , Shah Sanchi , Rodrigues Camilla , Kambli Priti , Surve Utkarsha , Khot Rukhsar , Niemann Stefan , Kohl Thomas A , Merker Matthias , Hoffmann Harald , Todt Katharina , Plesnik Sara , Ismail Nazir , Omar Shaheed Vally , Joseph Lavania , Thwaites Guy , Thuong Thuong Nguyen Thuy , Ngoc Nhung Hoang , Srinivasan Vijay , Walker Timothy M , Moore David , Coronel Jorge , Solano Walter , Gao George F , He Guangxue , Zhao Yanlin , Liu Chunfa , Ma Aijing , Zhu Baoli , Laurenson Ian , Claxton Pauline , Koch Anastasia , Wilkinson Robert , Lalvani Ajit , Posey James , Gardy Jennifer , Werngren Jim , Paton Nicholas , Jou Ruwen , Wu Mei-Hua , Lin Wan-Hsuan , Ferrazoli Lucilaine , de Oliveira Rosangela Siqueira , Arandjelovic Irena , Chaiprasert Angkana , Comas Iñaki , Roig Calle Jaime , Drobniewski Francis A , Farhat Maha R , Gao Qian , Hee Rick Ong Twee , Sintchenko Vitali , Supply Philip , van Soolingen Dick 
Published: March 2020

AbstractThe dN/dS ratio provides evidence of adaptation or functional constraint in protein-coding genes by quantifying the relative excess or deficit of amino acid-replacing versus silent nucleotide variation. Inexpensive sequencing promises a better understanding of parameters, such as dN/dS, but analyzing very large data sets poses a major statistical challenge. Here, I introduce genomegaMap for estimating within-species genome-wide variation in dN/dS, and I apply it to 3,979 genes across 10,209 tuberculosis genomes to characterize the selection pressures shaping this global pathogen. GenomegaMap is a phylogeny-free method that addresses two major problems with existing approaches: 1) It is fast no matter how large the sample size and 2) it is robust to recombination, which causes phylogenetic methods to report artefactual signals of adaptation. GenomegaMap uses population genetics theory to approximate the distribution of allele frequencies under general, parent-dependent mutation models. Coalescent simulations show that substitution parameters are well estimated even when genomegaMap’s simplifying assumption of independence among sites is violated. I demonstrate the ability of genomegaMap to detect genuine signatures of selection at antimicrobial resistance-conferring substitutions in Mycobacterium tuberculosis and describe a novel signature of selection in the cold-shock DEAD-box protein A gene deaD/csdA. The genomegaMap approach helps accelerate the exploitation of big data for gaining new insights into evolution within species.
Abnormal Cullin1 neddylation-mediated p21 accumulation participates in the pathogenesis of recurrent spontaneous abortion by regulating trophoblast cell proliferation and differentiation
Authors: Sun Xiaohe , Tong Xiaomei , Hao Yanqing , Li Chao , Zhang Yinli , Pan Yibin , Dai Yongdong , Liu Liu , Zhang Tai , Zhang Songying 
Published: March 2020

Abstract
The study explores the role of neddylation in early trophoblast development and its alteration during the pathogenesis of recurrent spontaneous abortion (RSA). Immunofluorescence and western blot were conducted to evaluate the expression pattern of NEDD8 protein in the first-trimester placentas of healthy control and RSA patients. Neddylated-cullins, especially neddylated-cullin1, were downregulated and their substrate, p21, was accumulated in RSA samples. NEDD8 cytoplasmic recruitment was observed in extravillous trophoblast (EVT) progenitors of RSA placentas. Consistent with the results of clinical samples, neddylation inhibition using MLN4924 in trophoblast cell lines caused obvious p21 accumulation and free NEDD8 cytoplasmic recruitment. Further in vitro study demonstrated neddylation inhibition attenuated proliferation of Jeg-3 cells via p21 accumulation. Moreover, when trophoblast stem (TS) cells derived from first-trimester placentas were cultured for differentiation analyses. MLN4924 impaired the differentiation of TS cells towards EVTs by downregulating HLA-G and GATA3. p21 knockdown could partly rescue MLN4924-suppressed HLA-G and GATA3 expression. In conclusion, cullin1 neddylation-mediated p21 degradation is required for trophoblast proliferation and can affect trophoblast plasticity by affecting HLA-G and GATA3 expression. The results provide insights into the pathological mechanism of RSA and the biological regulation of trophoblast development.
SingleCellSignalR: inference of intercellular networks from single-cell transcriptomics
Authors: Cabello-Aguilar Simon , Alame Mélissa , Kon-Sun-Tack Fabien , Fau Caroline , Lacroix Matthieu , Colinge Jacques 
Published: March 2020

AbstractSingle-cell transcriptomics offers unprecedented opportunities to infer the ligand–receptor (LR) interactions underlying cellular networks. We introduce a new, curated LR database and a novel regularized score to perform such inferences. For the first time, we try to assess the confidence in predicted LR interactions and show that our regularized score outperforms other scoring schemes while controlling false positives. SingleCellSignalR is implemented as an open-access R package accessible to entry-level users and available from https://github.com/SCA-IRCM. Analysis results come in a variety of tabular and graphical formats. For instance, we provide a unique network view integrating all the intercellular interactions, and a function relating receptors to expressed intracellular pathways. A detailed comparison of related tools is conducted. Among various examples, we demonstrate SingleCellSignalR on mouse epidermis data and discover an oriented communication structure from external to basal layers.
Timing of organ initiation is crucial for robust organ size
Authors: Zhu Mingyuan , Chen Weiwei , Mirabet Vincent , Hong Lilan , Bovio Simone , Strauss Soeren , Schwarz Erich M. , Tsugawa Satoru , Wang Zhou , Smith Richard S. , Li Chun-Biu , Hamant Olivier , Boudaoud Arezki , Roeder Adrienne H. K. 
Published: March 2020

Abstract:Organs precisely regulate their size and shape to ensure proper function1–6. The contribution of organ initiation timing to final organ size and shape is often masked by compensatory adjustments to growth later in development7–9. Here we show that DEVELOPMENT RELATED MYB-LIKE1 (DRMY1) is required for both proper organ initiation timing and growth leading to robust sepal size inArabidopsis.Within eachdrmy1flower, the initiation of some sepals is variably delayed. Late-initiating sepals indrmy1mutants remain smaller throughout development resulting in variability in sepal size. DRMY1 focuses the spatiotemporal signaling patterns of the plant hormones auxin and cytokinin, which jointly control the timing of sepal initiation. Contrary to expectation, our findings demonstrate that timing of organ initiation contributes to robust organ size throughout development.
Mathematically Modeling Inflammation as a Promoter of Tumour Growth
Authors: Wilkie Kathleen P. , Aktar Farjana 
Published: March 2020

AbstractInflammation is now known to play a significant role in tumour growth and progression. It is also difficult to adequately quantify systemic inflammation and the resulting localized effects in cancer. Here we use experimental data to infer the possible contributions of inflammation in a mouse model of cancer. The model is validated by predicting tumour growth under anti-inflammatory treatments, and combination cancer therapies are explored. We then extend the model to consider simultaneous tumour implants at two distinct sites, which experimentally was shown to result in one large and one small tumour. We use this model to examine the role inflammation may play in the growth rate separation. Finally, we use this predictive two-tumour model to explore implications of inflammation on metastases, surgical removal of the primary, and adjuvant anti-inflammatory treatments. This work suggests that improved tumour control can be obtained by targeting both the cancer and host, through anti-inflammatory treatments, including reduced metastatic burden post-surgical removal of primary tumours.
Massive rhizobial genomic variations associated with partner quality inLotus–Mesorhizobiumsymbiosis
Authors: Bamba Masaru , Aoki Seishiro , Kajita Tadashi , Setoguchi Hiroaki , Watano Yasuyuki , Sato Shusei , Tsuchimatsu Takashi 
Published: March 2020

ABSTRACTIn diverse mutualistic relationships, genetic variations in impact on the growth of interacting partners—variations in partner quality—are common, despite the theoretical prediction that selection favoring high-quality partners should eliminate such variations. Here, we investigated how variations in partner quality could be maintained in the nitrogen-fixing mutualism betweenLotus japonicusandMesorhizobiumbacteria. We reconstructedde novoassembled full-genome sequences from nine rhizobial symbionts, finding massive variations in the core genome and the contrastingly similar symbiotic islands, indicating recent horizontal gene transfer (HGT) of the symbiosis islands into diverseMesorhizobiumlineages. A cross-inoculation experiment using nine sequenced rhizobial symbionts and 15L. japonicusaccessions revealed extensive quality variations represented by plant growth phenotypes, including genotype-by-genotype interactions. Quality variations were not associated with the presence/absence variations of known symbiosis-related genes in the symbiosis island, but rather, showed significant correlations with the core genome variations, supported by SNP- and kinship matrix-based association analyses. These findings highlight the novel role of HGT of symbiosis islands, which indirectly supply mutations of core genomes intoL. japonicus-associated bacteria, thereby contributing to the maintenance of variations in partner quality.
Identification of Conserved Evolutionary Trajectories in Tumors
Authors: Hodzic Ermin , Shrestha Raunak , Malikic Salem , Collins Colin C. , Litchfield Kevin , Turajlic Samra , Sahinalp S. Cenk 
Published: March 2020

AbstractMotivationAs multi-region, time-series, and single cell sequencing data become more widely available, it is becoming clear that certain tumors share evolutionary characteristics with others. In the last few years, several computational methods have been developed with the goal of inferring the subclonal composition and evolutionary history of tumors from tumor biopsy sequencing data. However, the phylogenetic trees that they report differ significantly between tumors (even those with similar characteristics).ResultsIn this paper, we present a novel combinatorial optimization method, CONETT, for detection of recurrent tumor evolution trajectories. Our method constructs a consensus tree of conserved evolutionary trajectories based on the information about temporal order of alteration events in a set of tumors. We apply our method to previously published datasets of 100 clear-cell renal cell carcinoma and 99 non-small-cell lung cancer patients and identify both conserved trajectories that were reported in the original studies, as well as new trajectories.AvailabilityCONETT is implemented in C++ and available athttps://github.com/ehodzic/CONETT.
Systemic mutational rescue inEscherichia colielicited by a valency dependent, high affinity protein DNA interaction
Authors: Hurd P.J. , Al-Swailem A. M. , Bin Dukhyil A.A.A. , Sheikh Q.I. , Al-Ghanim A. A. , Alfageih L. , Matin M. , Lu Yueh Ting , Abdalgelel A. , Florence J. , Al-Shemirti Mohammed , Al Harbi S. , Brown P.E. , Hornby D.P. 
Published: March 2020

AbstractThe controlled formation of sequence specific DNA protein complexes is a fundamental feature of most genetic transactions. Studies of the impact of point mutations on the function of individual components, such as repressors, remains a key aspect of many Systems and Synthetic Biology research programmes. One of the most dramatic systemic consequences of a point mutation is exhibited by the monomeric DNA methyltransferases M.HhaI and M.EcoRII, where substitution of a single, catalytic cysteine by either glycine or alanine, creates a lethal gain of function phenotype.In vivoexpression of these point mutants promotes the deposition of high affinity nucleoprotein complexes that arrest replicationin vivo, causing cell death. Interestingly, it appears that a systemic response to expression of these mutant enzymes is dramatically enhanced when they are expressed as synthetic dimers. A previously unreported form of “mutational rescue” appears to be triggered as a result of networked crosslinking of host cell DNA resulting from an increased valency of nucleoprotein complex formation. This finding may have significance for developing molecular interventions for the controlled regulation of genome function and for the development of novel antimicrobial and anticancer strategies.
Prion Protein Folding Mechanism Revealed by Pulling Force Studies
Authors: Kriegler Theresa , Lang Sven , Notari Luigi , Hessa Tara 
Published: March 2020

AbstractThe mammalian prion protein (PrP) engages with the ribosome-Sec61 translocation channel complex to generate different topological variants that are either physiological, or involved in neurodegenerative diseases. Here, we describe cotranslational folding and translocation mechanisms of PrP coupled to a Xbp1-based arrest peptide (AP) as folding sensor, to measure forces acting on PrP nascent chain. Our data reveal two main pulling events followed by a minor third one exerted on the nascent chains during their translocation.Using those force landscapes, we show that a specific sequence within an intrinsically disordered region, containing a polybasic and glycine-proline rich residues, modulates the second pulling event by interacting with TRAP complex. This work also delineates the sequence of events involved in generation of PrP toxic transmembrane topologies during its synthesis. Our results shed new insight into the folding of such topological complex protein, where marginal pulling by the signal sequence, together with the downstream sequence in the mature domain, primarily drives an overall inefficient translocation resulting in the nascent chain to adopt other topologies.
A Systematic Protein Turnover Map for Decoding Protein Degradation
Authors: Christiano R. , Kabatnik S. , Mejhert N. , Farese R.V. , Walther T.C. 
Published: March 2020

Protein degradation is mediated by an expansive and complex network of protein modification and degradation enzymes. Matching degradation enzymes with their targets and determining globally which proteins are degraded by the proteasome or lysosome/vacuole has been a major challenge. Further, an integrated view of protein degradation for cellular pathways has been lacking. Here we present a novel analytical platform that combines systematic gene deletions with quantitative measures of protein turnover to deconvolve protein degradation pathways forS. cerevisiae. The resulting turnover map (T-MAP) reveals target candidates of nearly all E2 and E3 ubiquitin ligases and identifies the primary degradation routes for most proteins. We further mined this T-MAP to identify new substrates of ER-associated Degradation (ERAD) involved in sterol biosynthesis and to uncover novel regulatory nodes for sphingolipid biosynthesis. The T-MAP approach should be broadly applicable to the study of other cellular processes and systems, including mammalian systems.One Sentence SummaryA systematic, global map of protein turnover for a large set of yeast mutants reveals scope and specificity of degradation pathways and identifies novel regulatory nodes for lipid metabolism.
Spontaneous Cell Fusions as a Mechanism of Parasexual Recombination in Tumor Cell Populations
Authors: Miroshnychenko Daria , Baratchart Etienne , Ferrall-Fairbanks Meghan C. , Vander Velde Robert , Laurie Mark A , Bui Marilyn M. , Tan Aik Choon , Altrock Philipp M. , Basanta David , Marusyk Andriy 
Published: March 2020

ABSTRACTInitiation and progression of cancers reflect the underlying process of somatic evolution, which follows a Darwinian logic,i.e., diversification of heritable phenotypes provides a substrate for natural selection, resulting in the outgrowth of the most fit subpopulations. Although somatic evolution can tap into multiple sources of diversification, it is assumed to lack access to (para)sexual recombination – a key diversification mechanism throughout all strata of life. Based on observations of spontaneous fusions involving cancer cells, reported genetic instability of polypoid cells, and precedence of fusion-mediated parasexual recombination in fungi, we asked whether cell fusions could serve as a source of parasexual recombination in cancer cell populations. Using differentially labelled tumor cells, we found evidence of low-frequency, spontaneous cell fusions between carcinoma cells in multiple cell line models of breast cancer bothin vitroandin vivo. While some hybrids remained polyploid, many displayed partial ploidy reduction, generating diverse progeny with heterogeneous inheritance of parental alleles, indicative of partial recombination. Hybrid cells also displayed elevated levels of phenotypic plasticity, which may further amplify the impact of cell fusions on the diversification of phenotypic traits. Using mathematical modeling, we demonstrated that the observed rates of spontaneous somatic cell fusions may enable populations of tumor cells to amplify clonal heterogeneity, thus facilitating the exploration of larger areas of the adaptive landscape, relative to strictly asexual populations, which may substantially accelerate a tumor’s ability to adapt to new selective pressures.
Information outreach interventions to promote the information access, use and exchange in the rural areas of Pakistan
Authors: Naeem Salman Bin , Bhatti Rubina , Ahmad Khurshid 
Published: March 2020

PurposeThis study is a part of the doctoral dissertation that proposes concrete measures to improve health-care information outreach program for rural health-care professionals in primary and secondary health care in Punjab, Pakistan. This study aims to report on the barriers to accessing and using online health-care information from rural settings of the Punjab province of Pakistan.Design/methodology/approachA cross-sectional survey was conducted in primary and secondary health-care settings in the Punjab province of Pakistan. The study’s population consisted of the rural primary care physicians (PCPs), who were geographically dispersed across 2,873 different remote health-care settings across Punjab. These practice settings included 2,455 basic health units, 293 rural health centers, 89 tehsil headquarter hospitals and 36 district headquarter hospitals.FindingsLimited internet access, non-availability of required equipment and lack of training facilities were identified as the main barriers. PCPs’ gender, previous enrollment in post-graduation programs and type of health-care facility were significant factors in the perceived barriers related to both “non-availability of required equipment” and “inadequate training facilities on the use of information resources”.Practical implicationsThe findings of the study hold some important practical implications for different stakeholders. This study identifies and addresses the barriers to accessing and using health-care information for PCPs in rural settings. The success of the health-care information outreach program in Punjab, Pakistan, should rely on the eradication of these barriers.Originality/valueTo the best of the authors’ knowledge, this is the first large-scale study in Pakistan that assesses the barriers and proposes ways to overcome these barriers to effectively access and use health-care information.