bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal lineages from 10-11thcentury commoner cemeteries of the Carpathian Basin
Authors: Maár Kitti , Varga Gergely I. B. , Kovács Bence , Schütz Oszkár , Maróti Zoltán , Kalmár Tibor , Nyerki Emil , Nagy István , Latinovics Dóra , Tihanyi Balázs , Marcsik Antónia , Pálfi György , Bernert Zsolt , Gallina Zsolt , Varga Sándor , Költő László , Raskó István , Török Tibor , Neparáczki Endre 
Published: January 2021

AbstractBackgroundNomadic groups of conquering Hungarians played a predominant role in Hungarian prehistory, but genetic data are available only from the immigrant elite strata. Most of the 10-11th century remains in the Carpathian Basin belong to common people, whose origin and relation to the immigrant elite has been widely debated.MethodsMitogenome sequences were determined from 202 individuals with Next Generation Sequencing combined with hybridization capture. Median Joining networks were used for phylogenetic analysis. The commoner population was compared to 87 ancient Eurasian populations with sequence based (Fst) and haplogroup based population genetic methods.ResultsHaplogroup composition of the commoner population markedly differs from the elite and in contrast to the elite, commoners cluster with European populations. Besides, detectable sub-haplogroup sharing indicates admixture between the elite and commoners.ConclusionsMajority of the 10-11thcentury commoners most likely represent local populations of the Carpathian Basin, which admixed with the eastern immigrant groups including conquering Hungarians.
An active finite viscoelastic model for gastric smooth muscle contraction
Authors: Panda Satish Kumar , Buist Martin Lindsay 
Published: January 2021

AbstractA coupled electromechanical model to describe the transduction process of cellular electrical activity into mechanical deformation has been presented. The model consolidates a biophysical smooth muscle cell model, a biophysical actin-myosin interaction model, a sliding filament model and a viscoelastic constitutive model to construct an active finite viscoelastic model. The key input to this model is an electrical pulse which then estimates the resulting stress and deformation in the cell. The proposed model was used to recreate experimental observations performed on canine and porcine gastric tissue strips. In all cases, the simulation results were well matched with the experimental data (R2>0.9).
Resource selection by the Endangered Arabian tahr: identifying critical habitats for conservation and climate change adaptation
Authors: Ross S , Rawahi H. , Jahdhami M.H. 
Published: January 2021

AbstractThe Arabian tahr is an Endangered mountain ungulate endemic to the Hajar Mountains of Arabia. The Arabian tahr population is in decline and threats to tahr habitat are intensifying, in addition new potential challenges from climate change are emerging. Fundamental to future conservation planning is understanding tahr habitat selection patterns, so we can prioritise habitat protection, and understand how habitat may be used to provide thermal refuge and allow adaptation to climate change impacts. We used GPS collars and resource selection functions to characterise Arabian tahr habitat preferences in Wadi Sareen Nature Reserve, Oman. We found tahr habitat selection was dependent on scale, sex and season. Vegetation resources were only selected at the smallest scales of selection and avoided at other scales. Habitat providing low heat load and thermal refuge were intensely selected at small and medium scales, by both sexes and in both seasons, suggesting the importance of thermal refuges in facilitating thermoregulation. Higher elevations, steep slopes and rugged habitats were selected across all scales tested here, and in previous landscape-scale studies, indicating the fundamental importance of these habitats in supporting Arabian tahr populations. Our results identified critical habitats required to sustain Arabian tahr, and demonstrated the importance of thermal refuges to species living in the hot climates such as the Arabian Peninsula. Given the accessibility of habitat layers, and ease in which the identified habitats can be mapped using a geographical information system, understanding the habitat selection of tahr and other species is a crucial step to increasing conservation management capacity of threatened species. Given our uncertainty of how to conserve wildlife under future climate change, understanding the availability and distribution of wildlife habitat is an important baseline from where we can plan, connect and preserve the resources necessary for wildlife conservation.
Multiple Mutualist Effects generate synergistic selection and strengthen fitness alignment in a tripartite interaction between legumes, rhizobia, and mycorrhizal fungi
Authors: Afkhami Michelle E. , Friesen Maren L. , Stinchcombe John R. 
Published: January 2021

AbstractNearly all organisms interact with multiple mutualists, and complementarity within these complex interactions can result in synergistic fitness effects. However, it remains largely untested how multiple mutualists impact eco-evolutionary dynamics. We tested how multiple microbial mutualists-- N-fixing bacteria and mycorrrhizal fungi-- affected selection and heritability in their shared host plant (Medicago truncatula), as well as fitness alignment between partners. Our results demonstrate for the first time that multispecies mutualisms synergistically affect selection and heritability of host traits and enhance fitness alignment between mutualists. Specifically, we found that multiple mutualists doubled the strength of selection on a plant architectural trait, resulted in 2-3-fold higher heritability of reproductive success, and more than doubled the strength of fitness alignment between N-fixing bacteria and plants. Taken together, these findings show that synergism generated by multiple mutualisms extends to key components of microevolutionary change, and emphasizes the importance of multiple mutualist effects in understanding evolutionary trajectories.
Paths to annihilation: Genetic and demographic consequences of range contraction patterns
Authors: Rogan Jordan , Parker Mickey Ray , Hancock Zachary B. , Earl Alexis D. , Buchholtz Erin K. , Chyn Kristina , Martina Jason , Fitzgerald Lee A. 
Published: January 2021

ABSTRACTSpecies range contractions are important contributors to biological annihilation, yet typically do not receive the same attention as extinctions. Range contractions can lead to marked impacts on populations but are often only characterized by measurements of reduced extent. For effective conservation efforts, it is critical to recognize that not all range contractions are the same. We propose four distinct patterns of range contraction:shrinkage,amputation,hollow, andfragmentation. We tested their impact on populations of a generic generalist species using forward-time simulations. Results showed that all four patterns differentially reduced population abundance (declines of 60-80%) and significantly increased average relatedness, with differing patterns in nucleotide diversity (π) declines relative to the contraction pattern. The fragmentation pattern resulted in the strongest effects on post-contraction genetic diversity and structure. Defining and quantifying range contraction patterns and their consequences for the planet’s biodiversity provides necessary information to combat biological annihilation in the Anthropocene.
PRESENILIN 1mutations causing early-onset familial Alzheimer’s disease or familial acne inversa differ in their effects on genes facilitating energy metabolism and signal transduction
Authors: Barthelson Karissa , Dong Yang , Newman Morgan , Lardelli Michael 
Published: January 2021

ABSTRACTBackgroundThe most common cause of early-onset familial Alzheimer’s disease (EOfAD) is mutations inPRESENILIN 1(PSEN1) allowing production of mRNAs encoding full-length, but mutant, proteins. In contrast, a single known frameshift mutation inPSEN1causes familial acne inversa (fAI) without EOfAD. The molecular consequences of heterozygosity for these mutation types, and how they cause completely different diseases, remains largely unexplored.ObjectiveTo analyse brain transcriptomes of young adult zebrafish to identify similarities and differences in the effects of heterozygosity forpsen1mutations causing EOfAD or fAI.MethodsRNA sequencing was performed on mRNA isolated from the brains of a single family of 6-month-old zebrafish siblings either wild type or possessing a single, heterozygous EOfAD-like or fAI-like mutation in their endogenouspsen1gene.ResultsBoth mutations downregulate genes encoding ribosomal subunits, and upregulate genes involved in inflammation. Genes involved in energy metabolism appeared significantly affected only by the EOfAD-like mutation, while genes involved in Notch, Wnt and neurotrophin signalling pathways appeared significantly affected only by the fAI-like mutation. However, investigation of direct transcriptional targets of Notch signalling revealed possible increases in γ-secretase activity due to heterozygosity for eitherpsen1mutation. Transcriptional adaptation due to the fAI-like frameshift mutation was evident.ConclusionWe observed both similar and contrasting effects on brain transcriptomes of the heterozygous EOfAD-like and fAI-like mutations. The contrasting effects may illuminate how these mutation types cause distinct diseases.
Dermal macrophages set pain sensitivity by modulating tissue NGF levels through SNX25–Nrf2 signaling
Authors: Tanaka Tatsuhide , Okuda Hiroaki , Terada Yuki , Shinjo Takeaki , Banja Mitsuko , Nishimura Kazuya , Isonishi Ayami , Furue Hidemasa , Takemura Shoko , Tatsumi Kouko , Wanaka Akio 
Published: January 2021

AbstractCrosstalk between peripheral neurons and immune cells plays important roles in pain sensation. We identifiedsorting nexin 25(Snx25) as a pain-modulating gene in a transgenic mouse line with reduced pain behavior.Snx25conditional-KO (cKO) in monocyte/macrophage-lineage cells but not in the peripheral sensory neurons reduced pain responses in both normal and neuropathic conditions. Cross transplantation experiments of bone marrows between cKO and wild type (WT) mice revealed that cKO macrophages caused dull phenotype in WT mice and WT macrophages in turn increased pain behavior in cKO mice. SNX25 in dermal macrophages enhances NGF (one of the key factors in pain sensation) production by inhibiting ubiquitin-mediated degradation of Nrf2, a transcription factor that activatesNgfmRNA synthesis. We conclude that dermal macrophages set pain sensitivity by producing and secreting NGF into the dermis in addition to their host defense functions.
A mean-field approach for modeling the propagation of perturbations in biochemical reaction networks
Authors: Przedborski Michelle , Sharon David , Chan Steven , Kohandel Mohammad 
Published: January 2021

AbstractOften, the time evolution of a biochemical reaction network is crucial for determining the effects of combining multiple pharmaceuticals. Here we illustrate a mathematical framework for modeling the dominant temporal behaviour of a complicated molecular pathway or biochemical reaction network in response to an arbitrary perturbation, such as resulting from the administration of a therapeutic agent. The method enables the determination of the temporal evolution of a target protein as the perturbation propagates through its regulatory network. The mathematical approach is particularly useful when the experimental data that is available for characterizing or parameterizing the regulatory network is limited or incomplete. To illustrate the method, we consider the examples of the regulatory networks for the target proteins c-Myc and Chop, which play an important role in venetoclax resistance in acute myeloid leukemia. First we show how the networks that regulate each target protein can be reduced to a mean-field model by identifying the distinct effects that groups of proteins in the regulatory network have on the target protein. Then we show how limited proteinlevel data can be used to further simplify the mean-field model to pinpoint the dominant effects of the network perturbation on the target protein. This enables a further reduction in the number of parameters in the model. The result is an ordinary differential equation model that captures the temporal evolution of the expression of a target protein when one or more proteins in its regulatory network have been perturbed. Finally, we show how the dominant effects predicted by the mathematical model agree with RNA sequencing data for the regulatory proteins comprising the molecular network, despite the model not having a priori knowledge of this data. Thus, while the approach gives a simplified model for the expression of the target protein, it allows for the interpretation of the effects of the perturbation on the regulatory network itself. This method can be easily extended to sets of target proteins to model components of a larger systems biology model, and provides an approach for partially integrating RNA sequencing data and protein expression data. Moreover, it is a general approach that can be used to study drug effects on specific protein(s) in any disease or condition.
PilB fromStreptococcus sanguinisis a bimodular type IV pilin with a direct role in adhesion
Authors: Raynaud Claire , Sheppard Devon , Berry Jamie-Lee , Gurung Ishwori , Pelicic Vladimir 
Published: January 2021

ABSTRACTType IV pili (T4P) are functionally versatile filamentous nanomachines, nearly ubiquitous in prokaryotes. They are predominantly polymers of one major pilin, but also contain minor pilins whose functions are often poorly defined, and likely to be diverse. Here, we show that the minor pilin PilB from the T4P ofS. sanguinisdisplays an unusual bimodular 3D structure, with a bulky von Willebrand factor A-like (vWA) module “grafted” onto a small pilin module via a short unstructured loop. Structural modelling suggests that PilB is only compatible with a localisation at the tip of T4P. By performing a detailed functional analysis, we found that (i) the vWA module contains a canonical metal ion-dependent adhesion site (MIDAS), preferentially binding Mg2+and Mn2+, (ii) abolishing metal-binding has no impact on the structure of PilB or piliation, (iii) metal-binding is important forS. sanguinisT4P-mediated twitching motility and adhesion to eukaryotic cells, and (iv) the vWA module shows an intrinsic binding ability to several host proteins. These findings reveal an elegant, yet simple, evolutionary tinkering strategy to increase T4P functional versatility, by grafting an adhesive module onto a pilin for presentation by the filaments. This strategy appears to have been extensively used by bacteria, in which modular pilins are widespread and exhibit an astonishing variety of architectures.
Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model
Authors: Joaquín Cáceres C. , Cardenas-Garcia Stivalis , Carnaccini Silvia , Seibert Brittany , Rajao Daniela S. , Wang Jun , Perez Daniel R. 
Published: January 2021

ABSTRACTThe COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the defining global health emergency of this century. GC-376 is a Mproinhibitor with antiviral activity against SARS-CoV-2in vitro. Using the K18-hACE2 mouse model, thein vivoantiviral efficacy of GC-376 against SARS-CoV-2 was evaluated. GC-376 treatment was not toxic in K18-hACE2 mice and produced milder tissue lesions, reduced viral loads, fewer presence of viral antigen, and reduced inflammation in comparison to vehicle-treated controls, most notably in the brain in mice challenged with a low virus dose. Although GC-376 was not sufficient to improve neither clinical symptoms nor survival, it did show a positive effect against SARS-CoV-2in vivo. This study supports the notion that the K18-hACE2 mouse model is suitable to study antiviral therapies against SARS-CoV-2, and GC-376 represents a promising lead candidate for further development to treat SARS-CoV-2 infection.
Hospital‐physician integration and Medicare’s site‐based outpatient payments
Authors: Post Brady , Norton Edward C. , Hollenbeck Brent , Buchmueller Thomas , Ryan Andrew M. 
Published: January 2021

AbstractObjectiveTo determine the relationship between Medicare's site‐based outpatient billing policy and hospital‐physician integration.Data sourcesNational Medicare claims data from 2010 to 2016.Study DesignFor each physician‐year, we calculated the disparity between Medicare reimbursement under hospital ownership and under physician ownership. Using logistic regression analysis, we estimated the relationship between these payment differences and hospital‐physician integration, adjusting for region, market concentration, and time fixed effects. We measured integration status using claims data and legal tax names.Data CollectionThe study included integrated and non‐integrated physicians who billed Medicare between January 1, 2010, and December 31, 2016 (n = 2 137 245 physician‐year observations).Principal FindingsMedicare reimbursement for physician services would have been $114 000 higher per physician per year if a physician were integrated compared to being non‐integrated. Primary care physicians faced a 78% increase, medical specialists 74%, and surgeons 224%. These payment differences exhibited a modest positive relationship to hospital‐physician vertical integration. An increase in this outpatient payment differential equivalent to moving from the 25th to 75th percentile was associated with a 0.20 percentage point increase in the probability of integrating with a hospital (95% CI: 0.0.10‐0.30). This effect was slightly larger among primary care physicians (0.27, 95% CI: 0.18 to 0.35) and medical specialists (0.26, 95% CI: 0.05 to 0.48), while not significantly different from zero among surgeons (−0.02; 95% CI: −0.27 to 0.22).ConclusionsThe payment differences between outpatient settings were large and grew over time. Even routine annual outpatient payment updates from Medicare may prompt some hospital‐physician vertical integration, particularly among primary care physicians and medical specialists.
Forensic analysis of anabolic steroids tablets composition using attenuated total reflection Fourier transform infrared microspectroscopy (µATR‐FTIR) mapping
Authors: Lemos Vanessa Ferreira , Ortiz Rafael Scorsatto , Limberger Renata Pereira 
Published: January 2021

AbstractThe use of falsified and unregistered drugs is a worldwide public health problem. Because these global market products usually do not follow the Good Manufacturing Practices required by health legislation, its composition may be completely different from the original or may contain relevant concentrations of impurities and toxic contaminants. Since anabolic steroids are among the main irregular therapeutic classes seized in Brazil, here we propose a new methodology for analyzing these products, in tablets form, using Attenuated Total Reflection Fourier Transform Infrared Microspectroscopy (µATR‐FTIR) mapping. Spectra were acquired from solid tablets by attenuated total reflection, through point mapping methodology. In data processing, a characteristic absorption band for each Active Pharmaceutical Ingredient (API) was integrated and plotted to create its distribution map. This technique was applied in an unprecedented way for the forensic analysis of anabolic steroids and proved to be effective in distinguishing falsified products based on the detection of their APIs. It was possible to detect APIs in 26 out of 30 samples, five of which were classified as falsified only through µATR‐FTIR analysis. We were able to create distribution maps of the detected substances associating the microspectroscopic results with characteristic band integration method, which can be used to detect substances and to study samples’ homogeneity. We concluded that this methodology is promising for the analysis of anabolic steroid tablets, and can be used in a complementary way with techniques already consolidated in forensic laboratory routine for a better classification of questioned samples between authentic and falsified ones.
Identification of small proline‐rich protein 1B (SPRR1B) as a prognostically predictive biomarker for lung adenocarcinoma by integrative bioinformatic analysis
Authors: Zhang Zihe , Shi Ruifeng , Xu Songlin , Li Yongwen , Zhang Hongbing , Liu Minghui , Zhu Guangsheng , Chen Chen , Pan Zhenhua , Liu Hongyu , Chen Jun 
Published: January 2021

AbstractBackgroundWith the ongoing development of targeted therapy and immunotherapy in recent years, the overall five‐year survival rate of NSCLC patients has not improved, and the search for novel diagnostic and prognostic markers for lung adenocarcinoma continues.MethodsLung adenocarcinoma (LUAD) gene expression data and relevant clinical information were obtained from the TCGA. Hub genes were identified with weighted gene co‐expression network analysis (WGCNA) and protein–protein interaction network (PPI). Survival analyses were also performed using GEPIA. The 536 LUAD patients were divided into two groups according to the SPRR1B expression level and analyzed by gene set enrichment analysis (GSEA) and verified by immunoblotting. The effects of SPRR1B on cell proliferation and cell metastasis and apoptosis were evaluated by 5‐ethynyl‐2′‐deoxyuridine (EdU) staining, colony formation assay, transwell migration and invasion assay, and flow cytometry, respectively.ResultsA total of 2269 DEGs were analyzed by WGCNA and five hub genes (CCK, FETUB, PCSK9, SPRR1B, and SPRR2D) were identified. Among them, SPRR1B was selected as one of the most significant prognostic genes in LUAD. SPRR1B was found to be highly expressed in lung adenocarcinoma cells compared with that in normal bronchial epithelial cells. In addition, silencing of SPRR1B could inhibit the cell proliferation, invasion, and migration of lung adenocarcinoma cells, but induced cell apoptosis and G2/M phase arrest in vitro. The result of GSEA and immunoblotting revealed that SPRR1B activated the MAPK signaling pathway involved in the proliferation and metastasis of lung cancer.ConclusionsOur findings demonstrate that SPRR1B may function as a prognosis predictor in lung adenocarcinoma.