bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hippo signaling suppresses tumor cell metastasis via a Yki-Src42A positive feedback loop
Authors: Ding Yan , Wang Guiping , Zhan Meixiao , Sun Xiaohan , Deng Yanran , Zhao Yunhe , Liu Bin , Liu Qingxin , Wu Shian , Zhou Zizhang 
Published: December 2021

AbstractMetastasis is an important cause of death from malignant tumors. It is of great significance to explore the molecular mechanism of metastasis for the development of anti-cancer drugs. Here, we find that the Hippo pathway hampers tumor cell metastasis in vivo. Silence of hpo or its downstream wts promotes tumor cell migration in a Yki-dependent manner. Furthermore, we identify that inhibition of the Hippo pathway promotes tumor cell migration through transcriptional activating src42A, a Drosophila homolog of the SRC oncogene. Yki activates src42A transcription through direct binding its intron region. Intriguingly, Src42A further increases Yki transcriptional activity to form a positive feedback loop. Finally, we show that SRC is also a target of YAP and important for YAP to promote the migration of human hepatocellular carcinoma cells. Together, our findings uncover a conserved Yki/YAP-Src42A/SRC positive feedback loop promoting tumor cell migration and provide SRC as a potential therapeutic target for YAP-driven metastatic tumors.
Modeling serological testing to inform relaxation of social distancing for COVID-19 control
Authors: Kraay Alicia N. M. , Nelson Kristin N. , Zhao Conan Y. , Demory David , Weitz Joshua S. , Lopman Benjamin A. 
Published: December 2021

AbstractSerological testing remains a passive component of the public health response to the COVID-19 pandemic. Using a transmission model, we examine how serological testing could have enabled seropositive individuals to increase their relative levels of social interaction while offsetting transmission risks. We simulate widespread serological testing in New York City, South Florida, and Washington Puget Sound and assume seropositive individuals partially restore their social contacts. Compared to no intervention, our model suggests that widespread serological testing starting in late 2020 would have averted approximately 3300 deaths in New York City, 1400 deaths in South Florida and 11,000 deaths in Washington State by June 2021. In all sites, serological testing blunted subsequent waves of transmission. Findings demonstrate the potential benefit of widespread serological testing, had it been implemented in the pre-vaccine era, and remain relevant now amid the potential for emergence of new variants.
Individual differences in information-seeking
Authors: Kelly Christopher. A. , Sharot Tali 
Published: December 2021

AbstractVast amounts of personalized information are now available to individuals. A vital research challenge is to establish how people decide what information they wish to obtain. Here, over five studies examining information-seeking in different domains we show that information-seeking is associated with three diverse motives. Specifically, we find that participants assess whether information is useful in directing action, how it will make them feel, and whether it relates to concepts they think of often. We demonstrate that participants integrate these assessments into a calculation of the value of information that explains information seeking or its avoidance. Different individuals assign different weights to these three factors when seeking information. Using a longitudinal approach, we find that the relative weights assigned to these information-seeking motives within an individual show stability over time, and are related to mental health as assessed using a battery of psychopathology questionnaires.
Higher order genetic interactions switch cancer genes from two-hit to one-hit drivers
Authors: Park Solip , Supek Fran , Lehner Ben 
Published: December 2021

AbstractThe classic two-hit model posits that both alleles of a tumor suppressor gene (TSG) must be inactivated to cause cancer. In contrast, for some oncogenes and haploinsufficient TSGs, a single genetic alteration can suffice to increase tumor fitness. Here, by quantifying the interactions between mutations and copy number alterations (CNAs) across 10,000 tumors, we show that many cancer genes actually switch between acting as one-hit or two-hit drivers. Third order genetic interactions identify the causes of some of these switches in dominance and dosage sensitivity as mutations in other genes in the same biological pathway. The correct genetic model for a gene thus depends on the other mutations in a genome, with a second hit in the same gene or an alteration in a different gene in the same pathway sometimes representing alternative evolutionary paths to cancer.
Water sources aggregate parasites with increasing effects in more arid conditions
Authors: Titcomb Georgia , Mantas John Naisikie , Hulke Jenna , Rodriguez Ivan , Branch Douglas , Young Hillary 
Published: December 2021

AbstractShifts in landscape heterogeneity and climate can influence animal movement in ways that profoundly alter disease transmission. Water sources that are foci of animal activity have great potential to promote disease transmission, but it is unknown how this varies across a range of hosts and climatic contexts. For fecal-oral parasites, water resources can aggregate many different hosts in small areas, concentrate infectious material, and function as disease hotspots. This may be exacerbated where water is scarce and for species requiring frequent water access. Working in an East African savanna, we show via experimental and observational methods that water sources increase the density of wild and domestic herbivore feces and thus, the concentration of fecal-oral parasites in the environment, by up to two orders of magnitude. We show that this effect is amplified in drier areas and drier periods, creating dynamic and heterogeneous disease landscapes across space and time. We also show that herbivore grazing behaviors that expose them to fecal-oral parasites often increase at water sources relative to background sites, increasing potential parasite transmission at these hotspots. Critically, this effect varies by herbivore species, with strongest effects for two animals of concern for conservation and development: elephants and cattle.
Time-restricted feeding induces Lactobacillus- and Akkermansia-specific functional changes in the rat fecal microbiota
Authors: Palomba Antonio , Tanca Alessandro , Abbondio Marcello , Sau Rosangela , Serra Monica , Marongiu Fabio , Fraumene Cristina , Pagnozzi Daniela , Laconi Ezio , Uzzau Sergio 
Published: December 2021

AbstractDiet is a key factor influencing gut microbiota (GM) composition and functions, which in turn affect host health. Among dietary regimens, time-restricted (TR) feeding has been associated to numerous health benefits. The impact of TR feeding on the GM composition has been mostly explored by means of metagenomic sequencing. To date, however, little is known about the modulation of GM functions by this dietary regimen. Here, we analyzed the effects of TR feeding on GM functions by evaluating protein expression changes in a rat model through a metaproteomic approach. We observed that TR feeding has a relevant impact on GM functions, specifically leading to an increased abundance of several enzymes involved in carbohydrate and protein metabolism and expressed byLactobacillusspp. andAkkermansia muciniphila. Taken together, these results contribute to deepening our knowledge about the key relationship between diet, GM, and health.
Degenerate topological line surface phonons in quasi-1D double helix crystal SnIP
Authors: Peng Bo , Murakami Shuichi , Monserrat Bartomeu , Zhang Tiantian 
Published: December 2021

AbstractDegenerate points/lines in the band structures of crystals have become a staple of the growing number of topological materials. The bulk-boundary correspondence provides a relation between bulk topology and surface states. While line degeneracies of bulk excitations have been extensively characterised, line degeneracies of surface states are not well understood. We show that SnIP, a quasi-one-dimensional van der Waals material with a double helix crystal structure, exhibits topological nodal rings/lines in both the bulk phonon modes and their corresponding surface states. Using a combination of first-principles calculations, symmetry-based indicator theories and Zak phase analysis, we find that two neighbouring bulk nodal rings form doubly degenerate lines in their drumhead-like surface states, which are protected by the combination of time-reversal symmetry $${{{\mathcal{T}}}}$$
T
and glide mirror symmetry $${\bar{M}}_{y}$$

M

¯

y

. Our results indicate that surface degeneracies can be generically protected by symmetries such as $${{{\mathcal{T}}}}{\bar{M}}_{y}$$

T

M

¯

y

, and phonons provide an ideal platform to explore such degeneracies.
Most myopathic lamin variants aggregate: a functional genomics approach for assessing variants of uncertain significance
Authors: Anderson Corey L. , Langer Emma R. , Routes Timothy C. , McWilliams Seamus F. , Bereslavskyy Igor , Kamp Timothy J. , Eckhardt Lee L. 
Published: December 2021

AbstractHundreds of LMNA variants have been associated with several distinct disease phenotypes. However, genotype–phenotype relationships remain largely undefined and the impact for most variants remains unknown. We performed a functional analysis for 178 variants across five structural domains using two different overexpression models. We found that lamin A aggregation is a major determinant for skeletal and cardiac laminopathies. An in vitro solubility assay shows that aggregation-prone variants in the immunoglobulin-like domain correlate with domain destabilization. Finally, we demonstrate that myopathic-associated LMNA variants show aggregation patterns in induced pluripotent stem cell derived-cardiomyocytes (iPSC-CMs) in contrast to non-myopathic LMNA variants. Our data-driven approach (1) reveals that striated muscle laminopathies are predominantly protein misfolding diseases, (2) demonstrates an iPSC-CM experimental platform for characterizing laminopathic variants in human cardiomyocytes, and (3) supports a functional assay to aid in assessing pathogenicity for myopathic variants of uncertain significance.
Mesenchymal stromal cells mitigate liver damage after extended resection in the pig by modulating thrombospondin-1/TGF-β
Authors: Nickel Sandra , Vlaic Sebastian , Christ Madlen , Schubert Kristin , Henschler Reinhard , Tautenhahn Franziska , Burger Caroline , Kühne Hagen , Erler Silvio , Roth Andreas , Wild Christiane , Brach Janine , Hammad Seddik , Gittel Claudia , Baunack Manja , Lange Undine , Broschewitz Johannes , Stock Peggy , Metelmann Isabella , Bartels Michael , Pietsch Uta-Carolin , Krämer Sebastian , Eichfeld Uwe , von Bergen Martin , Dooley Steven , Tautenhahn Hans-Michael , Christ Bruno 
Published: December 2021

AbstractPost-surgery liver failure is a serious complication for patients after extended partial hepatectomies (ePHx). Previously, we demonstrated in the pig model that transplantation of mesenchymal stromal cells (MSC) improved circulatory maintenance and supported multi-organ functions after 70% liver resection. Mechanisms behind the beneficial MSC effects remained unknown. Here we performed 70% liver resection in pigs with and without MSC treatment, and animals were monitored for 24 h post surgery. Gene expression profiles were determined in the lung and liver. Bioinformatics analysis predicted organ-independent MSC targets, importantly a role for thrombospondin-1 linked to transforming growth factor-β (TGF-β) and downstream signaling towards providing epithelial plasticity and epithelial-mesenchymal transition (EMT). This prediction was supported histologically and mechanistically, the latter with primary hepatocyte cell cultures. MSC attenuated the surgery-induced increase of tissue damage, of thrombospondin-1 and TGF-β, as well as of epithelial plasticity in both the liver and lung. This suggests that MSC ameliorated surgery-induced hepatocellular stress and EMT, thus supporting epithelial integrity and facilitating regeneration. MSC-derived soluble factor(s) did not directly interfere with intracellular TGF-β signaling, but inhibited thrombospondin-1 secretion from thrombocytes and non-parenchymal liver cells, therewith obviously reducing the availability of active TGF-β.
Water sources and kidney function: investigating chronic kidney disease of unknown etiology in a prospective study
Authors: Vlahos Penny , Schensul Stephen L. , Anand Shuchi , Shipley Emma , Diyabalanage Saranga , Hu Chaoran , Ha Toan , Staniec Allison , Haider Lalarukh , Schensul Jean J. , Hewavitharane Pasan , Silva Tudor , Chandrajith Rohana , Nanayakkara Nishantha 
Published: December 2021

AbstractA chronic Kidney Disease of unknown etiology (CKDu) has emerged with disproportionately high prevalence across dry lowland agricultural communities globally. Here we present the results of a prospective cohort of 293 patients with CKDu in the endemic region of Wilgamuwa, Sri Lanka, in whom we measured baseline kidney function and undertook quarterly follow up over 2 years. Well water was the primary historic drinking water source in the region, although a majority (68%) of participants reported switching to reverse osmosis water during study follow ups. Participants who reported ever drinking from well water had estimated glomerular filtration rates −6.7 (SD: 2.8) ml/min/1.73 m2 lower than participants who did not drink from well water historically (p = 0.0184) during the study period. Geospatial analysis identifies a cluster within the region where CKDu progression is significantly higher than the surrounding area. Samples of household wells (n = 262) indicated 68% had detectable agrochemical compounds with concentration above global water quality standards. It is expected that the detected contaminants compounds are indicators of poor water quality and that there is likely additional agrochemical exposure including commercial additives that may contribute to CKDu onset and/or progression. Thus, our study finds that well water exposure during a person’s lifetime in this region is associated with kidney function decline and identifies and quantifies putative nephrotoxic agrochemicals above safe drinking water concentrations in these wells.
Insights into the changes in the proteome of Alzheimer disease elucidated by a meta-analysis
Authors: Haytural Hazal , Benfeitas Rui , Schedin-Weiss Sophia , Bereczki Erika , Rezeli Melinda , Unwin Richard D. , Wang Xusheng , Dammer Eric B. , Johnson Erik C. B. , Seyfried Nicholas T. , Winblad Bengt , Tijms Betty M. , Visser Pieter Jelle , Frykman Susanne , Tjernberg Lars O. 
Published: December 2021

AbstractMass spectrometry (MS)-based proteomics is a powerful tool to explore pathogenic changes of a disease in an unbiased manner and has been used extensively in Alzheimer disease (AD) research. Here, by performing a meta-analysis of high-quality proteomic studies, we address which pathological changes are observed consistently and therefore most likely are of great importance for AD pathogenesis. We retrieved datasets, comprising a total of 21,588 distinct proteins identified across 857 postmortem human samples, from ten studies using labeled or label-free MS approaches. Our meta-analysis findings showed significant alterations of 757 and 1,195 proteins in AD in the labeled and label-free datasets, respectively. Only 33 proteins, some of which were associated with synaptic signaling, had the same directional change across the individual studies. However, despite alterations in individual proteins being different between the labeled and the label-free datasets, several pathways related to synaptic signaling, oxidative phosphorylation, immune response and extracellular matrix were commonly dysregulated in AD. These pathways represent robust changes in the human AD brain and warrant further investigation.
ProMetIS, deep phenotyping of mouse models by combined proteomics and metabolomics analysis
Authors: Imbert Alyssa , Rompais Magali , Selloum Mohammed , Castelli Florence , Mouton-Barbosa Emmanuelle , Brandolini-Bunlon Marion , Chu-Van Emeline , Joly Charlotte , Hirschler Aurélie , Roger Pierrick , Burger Thomas , Leblanc Sophie , Sorg Tania , Ouzia Sadia , Vandenbrouck Yves , Médigue Claudine , Junot Christophe , Ferro Myriam , Pujos-Guillot Estelle , de Peredo Anne Gonzalez , Fenaille François , Carapito Christine , Herault Yann , Thévenot Etienne A. 
Published: December 2021

AbstractGenes are pleiotropic and getting a better knowledge of their function requires a comprehensive characterization of their mutants. Here, we generated multi-level data combining phenomic, proteomic and metabolomic acquisitions from plasma and liver tissues of two C57BL/6 N mouse models lacking the Lat (linker for activation of T cells) and the Mx2 (MX dynamin-like GTPase 2) genes, respectively. Our dataset consists of 9 assays (1 preclinical, 2 proteomics and 6 metabolomics) generated with a fully non-targeted and standardized approach. The data and processing code are publicly available in the ProMetIS R package to ensure accessibility, interoperability, and reusability. The dataset thus provides unique molecular information about the physiological role of the Lat and Mx2 genes. Furthermore, the protocols described herein can be easily extended to a larger number of individuals and tissues. Finally, this resource will be of great interest to develop new bioinformatic and biostatistic methods for multi-omics data integration.
Meteorological and social conditions contribute to infectious diarrhea in China
Authors: Yang Xiang , Xiong Weifeng , Huang Tianyao , He Juan 
Published: December 2021

AbstractInfectious diarrhea in China showed a significant pattern. Many researchers have tried to reveal the drivers, yet usually only meteorological factors were taken into consideration. Furthermore, the diarrheal data they analyzed were incomplete and the algorithms they exploited were inefficient of adapting realistic relationships. Here, we investigate the impacts of meteorological and social factors on the number of infectious diarrhea cases in China. A machine learning algorithm called the Random Forest is utilized. Our results demonstrate that nearly half of infectious diarrhea occurred among children under 5 years old. Generally speaking, increasing temperature or relative humidity leads to increased cases of infectious diarrhea in China. Nevertheless, people from different age groups or different regions own different sensitivities to meteorological factors. The weight of feces that are harmfully treated could be a possible reason for infectious diarrhea of the elderly as well as children under 5 years old. These findings indicate that infectious diarrhea prevention for children under 5 years old remains a primary task in China. Personalized prevention countermeasures ought to be provided to different age groups and different regions. It is essential to bring the weight of feces that are harmfully treated to the forefront when considering infectious diarrhea prevention.
Local delivery of hydrogel encapsulated vascular endothelial growth factor for the prevention of medication-related osteonecrosis of the jaw
Authors: Sharma Dileep , Hamlet Stephen , Vaquette Cedryck , Petcu Eugen Bogdan , Ramamurthy Poornima , Ivanovski Saso 
Published: December 2021

AbstractThe anti-angiogenic effects of bisphosphonates have been hypothesized as one of the major etiologic factors in the development of medication-related osteonecrosis of the jaw (MRONJ), a severe debilitating condition with limited treatment options. This study evaluated the potential of a gelatine-hyaluronic acid hydrogel loaded with the angiogenic growth factor, vascular endothelial growth factor (VEGF), as a local delivery system to aid in maintaining vascularization in a bisphosphonate-treated (Zoledronic Acid) rodent maxillary extraction defect. Healing was assessed four weeks after implantation of the VEGF-hydrogel into extraction sockets. Gross examination and histological assessment showed that total osteonecrosis and inflammatory infiltrate was significantly reduced in the presence of VEGF. Also, total vascularity and specifically neovascularization, was significantly improved in animals that received VEGF hydrogel. Gene expression of vascular, inflammatory and bone specific markers within the defect area were also significantly altered in the presence of VEGF. Furthermore, plasma cytokine levels were assessed to determine the systemic effect of locally delivered VEGF and showed similar outcomes. In conclusion, the use of locally delivered VEGF within healing extraction sockets assists bone healing and prevents MRONJ via a pro-angiogenic and immunomodulatory mechanism.
Identification of climate induced optimal rice yield and vulnerable districts rankings of the Punjab, Pakistan
Authors: Janjua Azhar Ali , Aslam Muhammad , Sultana Naheed , Batool Zia 
Published: December 2021

AbstractThe study attracted to insinuate the inhabitant anomalies of the crop yield in the districts of the Punjab where climate variation, inputs utilization, and district exponents are indispensable factors. Impact evaluation of sowing and harvesting dates for rice yield has been analyzed. Suitable sowing and harvesting dates and potential districts for the crop are proposed. Data consisting of 13,617 observations of more than 90 factors encompassing valuable dimensions of the growth of the crops collected through comprehensive surveys conducted by the Agriculture Department of Punjab are formulated to incorporate in this study. The results establish the significant negative repercussions of climate variability while the impacts vary in the districts. The crop yield deteriorates considerably by delaying the sowing and harvesting times. Districts climate-induced vulnerability ranking revealed Layyah, Jhelum, Mianwali, Khanewal and Chinniot, the most vulnerable while Kasur, Gujrat, Mandi Bhauddin, Nankana Sahib and Hafizabad, the least vulnerable districts. Spatial mapping explains the geographical pattern of vulnerabilities and yield/monetary losses. The study ranks districts using climate-induced yield and monetary loss (222.30 thousand metric tons of rice which are equal to 27.79 billion PKR climatic losses in single rice season) and recommends: the formation of district policy to abate the adverse climate impact, utilization of suitable climate variation by adhering proper sowing and harvesting times, setting the prioritized districts facing climate-induced losses for urgent attention and preferable districts for rice crop.