bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interspecific introgression reveals a role of male genital morphology during the evolution of reproductive isolation inDrosophila
Authors: Frazee Stephen R. , Harper Angelica R. , Afkhami Mehrnaz , Wood Michelle L. , McCrory John C. , Masly John P. 
Published: June 2020

AbstractRapid divergence in genital structures among nascent species has been posited to be an early-evolving cause of reproductive isolation, although evidence supporting this idea as a widespread phenomenon remains mixed. Using a collection of interspecific introgression lines between twoDrosophilaspecies that diverged ∼240,000 years ago, we tested the hypothesis that even modest divergence in genital morphology can result in substantial fitness losses. We studied the reproductive consequences of variation in the male epandrial posterior lobes betweenDrosophila mauritianaandD. sechelliaand found that divergence in posterior lobe morphology has significant fitness costs on several pre-fertilization and post-copulatory reproductive measures. Males with divergent posterior lobe morphology also significantly reduced the life span of their mates. Interestingly, one of the consequences of genital divergence was decreased oviposition and fertilization, which suggests that a sensory bias for posterior lobe morphology could exist in females, and thus posterior lobe morphology may be the target of cryptic female choice in these species. Our results provide evidence that divergence in genitalia can in fact give rise to substantial reproductive isolation early during species divergence, and they also reveal novel reproductive functions of the external male genitalia inDrosophila.
Ultrasensitive single-cell proteomics workflow identifies >1000 protein groups per mammalian cell
Authors: Cong Yongzheng , Motamedchaboki Khatereh , Misal Santosh A. , Liang Yiran , Guise Amanda J. , Truong Thy , Huguet Romain , Plowey Edward D. , Zhu Ying , Lopez-Ferrer Daniel , Kelly Ryan T. 
Published: June 2020

AbstractWe report on the combination of nanodroplet sample preparation, ultra-low-flow nanoLC, high-field asymmetric ion mobility spectrometry (FAIMS), and the latest-generation Orbitrap Eclipse Tribrid mass spectrometer for greatly improved single-cell proteome profiling. FAIMS effectively filtered out singly charged ions for more effective MS analysis of multiply charged peptides, resulting in an average of 1056 protein groups identified from single HeLa cells without MS1-level feature matching. This is 2.3 times more identifications than without FAIMS and a far greater level of proteome coverage for single mammalian cells than has been previously reported for a label-free study. Differential analysis of single microdissected motor neurons and interneurons from human spinal tissue indicated a similar level of proteome coverage, and the two subpopulations of cells were readily differentiated based on single-cell label-free quantification.
Precision combination therapies based on recurrent oncogenic co-alterations
Authors: Li Xubin , Dowling Elisabeth K. , Yan Gonghong , Bozorgui Behnaz , Imarinad Parisa , Elnaggar Jacob H. , Luna Augustin , Menter David G. , Kopetz Scott , Sander Chris , Korkut Anil 
Published: June 2020

AbstractCancer cells depend on multiple driver alterations whose oncogenic effects can be suppressed by drug combinations. Discovery of effective combination therapies is challenging due to the complexity of the biomolecular landscape of drug responses. Here, we developed the method REFLECT (REcurrent Features Leveraged for Combination Therapies), which integrates machine learning and cancer informatics algorithms. The method maps recurrent co-alteration signatures from multi-omic data across patient cohorts to combination therapies. Using the REFLECT framework, we generated a precision therapy resource matching 2,201 drug combinations to co-alteration signatures across 201 cohorts stratified from 10,392 patients and 33 cancer types. We validated that REFLECT-predicted combinations introduce significantly higher therapeutic benefit through analysis of independent data from comprehensive drug screens. In patient cohorts with immunotherapy response markers, HER2 activation and DNA repair aberrations, we identified therapeutically actionable co-alteration signatures shared across patient sub-cohorts. REFLECT provides a framework to design combination therapies tailored to patient cohorts in data-driven clinical trials.
Siamese cat tyrosinase has enhanced proteasome degradation and increased cellular aggregation
Authors: Niesman Ingrid R. 
Published: June 2020

AbstractSiamese cats are a notable example of a temperature-sensitive partial albinism phenotype. The signature color-pointing pattern is the result of an amino acid substitution – G302R – in the cysteine-rich domain of feline tyrosinase. The precise mechanism for the loss of tyrosinase enzyme activity due to this mutation is unknown.ObjectiveWe have used a cellular biology approach to begin unravel relationships between feline coloration, behavior and increased risk for feline cognitive dysfunction syndrome. GFP-fusion constructs of wild type domestic short hair tyrosinase and Siamese (G302R) tyrosinase generated to study cellular trafficking, degradation and the propensity for cellular aggregation.Data DescriptionC-terminal GFP G302R expression has reduced Golgi localization, increased cytosolic fractions with reduced calnexin co-localization. N-terminal GFP constructs were retained in the ER, with little to no Golgi associated forms. C-terminal and N-terminal GFP G302R TYR is observed to have increased high molecular weight aggregation following proteasome inhibition.
Selective Vulnerability of Senescent Glioblastoma Cells to Bcl-XL Inhibition
Authors: Rahman Masum , Olson Ian , Mansour Moustafa , Carlstrom Lucas P. , Sutiwisesak Rujapope , Saber Rehan , Rajani Karishma , Warrington Arthur E , Howard Adam , Schroeder Mark , Chen Sisi , Decker Paul A. , Sananikone Eliot F. , Zhu Yi , Parney Ian F. , Burma Sandeep , Brown Desmond , Rodriguez Moses , Sarkaria Jann N. , Kirkland James , Burns Terry C. 
Published: June 2020

AbstractDespite decades of research and numerous basic science advances, there have only marginal gains in improving glioblastoma multiforme survival. Therefore, new ideas and approaches for treating this aggressive disease are essential to drive progress forward. Conventional therapies, such as radiation and Temozolomide (TMZ), function to cause oxidative stress and DNA damage yielding a senescent-like state of replicative arrest in susceptible cells. However, increasing evidence demonstrates malignant cells can escape senescence leading to tumor recurrence. Ablation of non-replicating senescent tumor cells after radiation and chemotherapy may be an avenue to reduce the rates of tumor recurrence. Senolytic agents have been developed that selectively target senescent cells, but it remains unknown whether senolytics might be utilized against senescent-like glioma cells. We employed radiation or TMZ to induce a functionally senescent state in human glioblastoma cells. Viable cells that survive these treatments were then utilized to screen candidate senolytic drugs, to identify those selectively effective at ablating senescent-like cells over naïve non-tumor and proliferative cells. Among 10 candidate senolytic drugs evaluated, only Bcl-XL inhibitors demonstrated reproducible senolytic activity in radiated or TMZ-treated glioma across the majority of GBM cell lines evaluated. Conversely, Bcl-2 inhibitors and other established senolytic drugs failed to show any consistent senolytic activity. In agreement with these data, Bcl-XL knockdown selectively reduced the viability of senescent-like GBM cells, whereas knockdown of Bcl-2 or Bcl-W yielded no senolytic effect. These findings demonstrate the potential to harness radiation-induced biology to ablate latent surviving cells and highlight Bcl-XL dependency as a potential vulnerability of surviving GBM cells after exposure to radiation or TMZ.
pHLARE: A Genetically Encoded Ratiometric Lysosome pH Biosensor
Authors: Webb Bradley A. , Cook Jessica , Wittmann Torsten , Barber Diane L. 
Published: June 2020

AbstractMany lysosome functions are determined by a lumenal pH of ~5.0, including the activity of resident acid-activated hydrolases. Lysosome pH (pHlys) is increased in neurodegenerative disorders and predicted to be decreased in cancers, making it a potential target for therapeutics to limit the progression of these diseases. Accurately measuring pHlys, however, is limited by currently used dyes that accumulate in multiple intracellular compartments and cannot be propagated in clonal cells for longitudinal studies orin vivodeterminations. To resolve this limitation, we developed a genetically encoded ratiometric pHlys biosensor, pHLARE (pH LysosomalActivityREporter), which localizes predominantly in lysosomes, has a dynamic range of pH 4.0 to 6.5, and can be stably expressed in cells. Using pHLARE we show decreased pHlys with inhibiting activity of the mammalian target of rapamycin complex 1 (mTORC1), in breast and pancreatic cancer cells compared with tissue-matched untransformed cells, and with the activated oncogene H-RasV12. pHLARE is a new tool to accurately measure pHlys, for improved understanding of lysosome dynamics that could be a promising therapeutic target.Summary StatementMost lysosome functions require a low lumenal pH, which is dysregulated in many human diseases. We report a new genetically biosensor to accurately measure lysosome pH dynamics, which we use to show decreased lysosome pH in cancer cell lines.
Mercury methylation by metabolically versatile and cosmopolitan marine bacteria
Authors: Lin Heyu , Ascher David B. , Myung Yoochan , Lamborg Carl H. , Hallam Steven J. , Gionfriddo Caitlin M. , Holt Kathryn E. , Moreau John W. 
Published: June 2020

AbstractMicrobes transform aqueous mercury (Hg) into methylmercury (MeHg), a potent neurotoxin in terrestrial and marine food webs. This process requires the gene pairhgcAB, which encodes for proteins that actuate Hg methylation, and has been well described for anoxic environments. However, recent studies report potential MeHg formation in suboxic seawater, although the microorganisms involved remain poorly understood. In this study, we conducted large-scale multi-omic analyses to search for putative microbial Hg methylators along defined redox gradients in Saanich Inlet (SI), British Columbia, a model natural ecosystem with previously measured Hg and MeHg concentration profiles. Analysis of gene expression profiles along the redoxcline identified several putative Hg methylating microbial groups, includingCalditrichaeota, SAR324 andMarinimicrobia, with the last by far the most active based onhgctranscription levels.Marinimicrobia hgcgenes were identified from multiple publicly available marine metagenomes, consistent with a potential key role in marine Hg methylation. Computational homology modelling predicted thatMarinimicrobiaHgcAB proteins contain the highly conserved structures required for functional Hg methylation. Furthermore, a number of terminal oxidases from aerobic respiratory chains were associated with several SI putative novel Hg methylators. Our findings thus reveal potential novel marine Hg-methylating microorganisms with a greater oxygen tolerance and broader habitat range than previously recognised.
An emerging role ofPrevotella histicolaon estrogen-deficiency induced bone loss through the gut microbiota-bone axis
Authors: Wang Zhongxiang , Chen Kai , Wu Congcong , Chen Junhao , Pan Hao , Liu Yangbo , Wu Peng , Yuan Jiandong , Lang Junzhe , Du Juanjuan , Xu Jiake , Jin Keke , Chen Lei 
Published: June 2020

AbstractGut microbiota (GM)-bone axis has emerged as a crucial mediator in the maintenance of bone homeostasis. Estrogen-deficiency induced bone loss is closely associated with an altered GM. However, the underlying mechanisms remain not fully understood. To this end, feces samples collected from the postmenopausal patients with osteoporosis (PMO) and with normal bone mass (PMN) were examined by 16s rRNA gene sequencing. We found that GM in PMO group was featured by a significant decreased proportion of genusPrevotellain comparison with that in the PMN group. Next,Prevotella histicola(P.histicola), a typical specie ofPrevotella, was orally given to the mice following the ovariectomy (OVX) procedure and it significantly prevented OVX induced bone loss. Mechanistically, the protective effects ofP.histicolaon bone mass were found to be associated with the inhibition of osteoclastic resorption by attenuating osteoclastogenic cytokines expression and ameliorating gut permeability. Thus,P.histicolamay prevent estrogen-deficiency induced bone loss through the GM-bone axis.
Peripheral blood immune status at clinical onset correlates with severity of Coronavirus Disease 2019
Authors: Santoro Nathalie , Cignetti Alessandro , Tenace Valerio , Casonato Ines Clotilde , Cosseddu Domenico , Vizzini Margherita , De Rosa Giovanni , Geuna Massimo 
Published: June 2020

AbstractThe Coronavirus Disease 2019 (COVID-19) pandemic is a global threat to healthcare systems, requiring hospitalization in sub intensive and intensive care for respiratory syndrome in 25-30% of patients and accounting for a lethality up to 15%.In this retrospective study the clinical characteristics of 215 COVID-19 patients were correlated with the peripheral blood immune status.Different groups of COVID-19 patients may be identified on the basis of clinical behavior and a strong correlation between groups and age and comorbidities as well as with the immune profile is demonstrated. A lower age correlates with a lower severity of the disease differentiating between patients who may be quarantined at home and those requiring hospitalization. An older age (>82 years) together with a higher number of comorbidities is associated to a very severe prognosis. The absolute number of CD3+, CD4+, CD8+ T lymphocytes was progressively decreasing according to the severity of the disease and a CD3+ and CD8+ threshold indicating very severe cases is suggested.
Prevention of COVID-19 in Ghana: Compliance audit of selected transportation stations in the Greater Accra region of Ghana
Authors: Bonful Harriet Affran , Addo-Lartey Adolphina , Aheto Justice MK , Ganle John Kuumouri , Sarfo Bismark , Aryeetey Richmond 
Published: June 2020

AbstractGlobally, as little evidence exists on transmission patterns of COVID-19, recommendations to prevent infection include appropriate and frequent handwashing plus physical and social distancing. We conducted an exploratory observational study to assess compliance with these recommendations in selected transportation stations in Ghana. A one-hour audit of 45 public transport stations in the Greater Accra region was carried out between 27th and 29th March 2020. Using an adapted World Health Organization (WHO) hand hygiene assessment scale, the availability and use of handwashing facilities, social distancing, and ongoing public education on COVID-19 prevention measures were assessed, weighted and scored to determine the level of compliance of stations. Compliance with recommendations was categorized as “inadequate” “basic”, “intermediate” and “advanced” based on the overall score. The majority (80%) of stations in Accra have at least one Veronica Bucket with flowing water and soap but the number of washing places at each station is not adequate. Only a small minority (18%) of stations were communicating the need to wash hands frequently and appropriately, and to practice social/physical distancing while at the station. In most stations (95%), hand washing practice was either not observed or only infrequently. Almost all stations (93%) did not have alcohol-based hand sanitizers for public use, while social distancing was rarely (only 2%) practiced. In over 90% of the stations, face masks were either not worn or only worn by a few passengers. Compliance with COVID-19 prevention measures was inadequate in 13 stations, basic in 16 stations, intermediate in 7 stations, and advanced in 9 stations. Compliance with COVID-19 prevention measures in public transportation stations in the Greater Accra region remains a challenge. Awareness creation should aim to elevate COVID-19 risk perception of transportation operators and clients. Transport operators and stations need support and guidance to enforce hand washing and social distancing.
A Fractal Viewpoint to COVID-19 Infection
Authors: Sotolongo-Costa Oscar , Weberszpil José , Sotolongo-Grau Oscar 
Published: June 2020

AbstractOne of the central tools to control the COVID-19 pandemics is the knowledge of its spreading dynamics. Here we develop a fractal model capable of describe this dynamics, in term of daily new cases, and provide quantitative criteria for some predictions. We propose a fractal dynamical model using conformed derivative and fractal time scale. A Burr-XII shaped solution of the fractal-like equation is obtained. The model is tested using data from several countries, showing that a single function is able to describe very different shapes of the outbreak. The diverse behavior of the outbreak on those countries is presented and discussed. Moreover, a criterion to determine the existence of the pandemic peak and a expression to find the time to reach herd immunity are also obtained.
Monitoring life expectancy levels during the COVID-19 pandemic: Example of the unequal impact in Spanish regions
Authors: Trias-Llimós Sergi , Riffe Tim , Bilal Usama 
Published: June 2020

AbstractBackgroundTo provide an interpretable summary of the impact on mortality of the COVID-19 pandemic we estimate weekly and annual life expectancies at birth in Spain and its regions.MethodsWe used daily death count data from the Spanish MoMo, and death counts from 2018, and population on 1 July, 2019 by region (CCAA), age groups, and sex from the Spanish National Statistics Institute. We estimated weekly and annual (2019 and 2020*, the shifted annual calendar period up to June 14th 2020) life expectancies at birth as well as their differences with respect to 2019.ResultsWeekly life expectancies at birth in Spain were lower in weeks 11-20, 2020 compared to the same weeks in 2019. This drop in weekly life expectancy was especially strong in weeks 13 and 14 (March 23rd to April 5th), with national declines ranging between 6.1 and 7.6 years and maximum regional weekly declines of up to 15 years in Madrid. Annual life expectancy differences between 2019 and 2020 also reflected an overall drop in annual life expectancy of 0.8 years for both men and women. These drops ranged between 0 years in several regions (e.g. Canary and Balearic Islands) to 2.7 years among men in Madrid.ConclusionsLife expectancy is an easy to interpret measure for understanding the heterogeneity of mortality patterns across Spanish regions. Weekly and annual life expectancy are sensitive useful indicators for understanding disparities and communicating the gravity of the situation because differences are expressed in intuitive year units.Key messages-Weekly and annual updated life expectancy are valuable indicators of the health impacts of the pandemic in populations.-The impact of the COVID-19 pandemic in Spain has been severe and highly heterogeneous, with weekly life expectancy falls of up to 15 years in Madrid, and with annual life expectancy falls ranging between 0 and 2.7 years.-Our results for Spain provide important insights into the magnitude of the pandemic in mortality levels across regions and are easy to interpret and compare.
Solar UV–B/A Radiation is Highly Effective in Inactivating SARS-CoV-2
Authors: Nicastro Fabrizio , Sironi Giorgia , Antonello Elio , Bianco Andrea , Biasin Mara , Brucato John R. , Ermolli Ilaria , Pareschi Giovanni , Salvati Marta , Tozzi Paolo , Trabattoni Daria , Clerici Mario 
Published: June 2020

AbstractSolar UV-C photons do not reach Earth’s surface, but are known to be endowed with germicidal properties that are also effective on viruses. The effect of softer UV-B and UV-A photons, which copiously reach the Earth’s surface, on viruses are instead little studied, particularly on single-stranded RNA viruses.Here we combine our measurements of the action spectrum of Covid-19 in response to UV light, Solar irradiation measurements on Earth during the SARS-CoV-2 pandemics, worldwide recorded Covid-19 mortality data and our “Solar-Pump” diffusive model of epidemics to show that (a) UV-B/A photons have a powerful virucidal effect on the single-stranded RNA virus Covid-19 and that (b) the Solar radiation that reaches temperate regions of the Earth at noon during summers, is sufficient to inactivate 63% of virions in open-space concentrations (1.5×103 TCID50/mL, higher than typical aerosol) in less than 2 minutes.We conclude that the characteristic seasonality imprint displayed world-wide by the SARS-Cov-2 mortality time-series throughout the diffusion of the outbreak (with temperate regions showing clear seasonal trends and equatorial regions suffering, on average, a systematically lower mortality), might have been efficiently set by the different intensity of UV-B/A Solar radiation hitting different Earth’s locations at different times of the year.Our results suggest that Solar UV-B/A play an important role in planning strategies of confinement of the epidemics, which should be worked out and set up during spring/summer months and fully implemented during low-solar-irradiation periods.
Prevalence and risk factors associated with Anxiety Symptoms and Disorders Among Chronic Kidney Disease patients – A Systematic Review and Meta-analysis of studies
Authors: Huang Caleb Weihao , Wee Poh Hui , Low Lian Leng , Koong Ying Leng Agnes , Htay Htay , Fan Qiao , Foo Wai Yin Marjorie , Seng Jun Jie Benjamin 
Published: June 2020

AbstractBackgroundAnxiety is associated with poor health outcomes among chronic kidney disease (CKD) patients. This review summarizes the prevalence and risk factors associated with anxiety symptoms and disorders among CKD patients.MethodsArticles evaluating the prevalence and risk factors associated with anxiety symptoms and disorders among CKD patients, as diagnosed via DSM 4th or 5th edition criteria, clinical interviews or validated questionnaires, were searched in Medline®, Embase®, PsychINFO® and CINAHL®. Using random-effects meta-analyses, prevalence of anxiety was estimated. A narrative review on the risk factors associated with anxiety was presented.ResultsFrom 4941 articles, 61 studies were included. Pooled prevalence of anxiety disorders (9 studies, n=1071) among CKD patients across studies was 18.9% while that of anxiety symptoms (52 studies, n=10,739) was 42.8%. Across continents, prevalence of anxiety symptoms was highest in Europe and Asia. Between pre-dialysis and dialysis patients, prevalence of anxiety symptoms was statistically comparable at 30.5% and 42.1% respectively. Most commonly studied risk factors associated with anxiety were female gender, increased age, concomitant depression, and increased comorbidities.ConclusionGiven the high prevalence of anxiety disorders and symptoms, there is a need for developing clinical guidelines on anxiety screening among CKD patients, facilitating early identification of at-risk patients.