bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular characterization of pathogenic African trypanosomes in biting flies and camels in surra-endemic areas outside the tsetse fly belt in Kenya
Authors: Getahun Merid N. , Villinger Jandouwe , Bargul Joel L. , Orone Abel , Ngiela John , Ahuya Peter O. , Muema Jackson M. , Saini Rajinder K. , Torto Baldwyn , Masiga Daniel K. 
Published: June 2020

AbstractBackgroundAfrican animal trypanosomosis is becoming prevalent beyond its traditionally defined geographical boundaries and is a threat to animals beyond the tsetse belts in and outside Africa. However, knowledge of infections with clinically important trypanosome species and their diversity among field-collected hematophagous biting flies and domestic animals is limited mainly to tsetse and their mammalian hosts in tsetse-infested areas. This study aimed to examine the presence of trypanosomes in both biting flies and domestic animals outside the tsetse belt in northern Kenya, potential mechanical vector species, and their host-feeding profiles.MethodsWe screened for pathogenic African trypanosomes in blood samples from domestic animals and field-trapped flies by microscopy and sequencing of internal transcribed spacer (ITS1) gene PCR products. We sequenced kinetoplast maxicircle genes to confirmTrypanosoma bruceidetection and the RoTat 1.2 and kinetoplast minicircle genes to differentiate type-A and type-BTrypanosoma evansi, respectively. Further, we identified the hosts that field-trapped flies fed on by PCR-HRM and sequencing of 16S rRNA genes.ResultsHippobosca camelina,Stomoxys calcitrans, Tabanusspp., andPangonia rueppelliiare potential vectors of trypanosomes outside the tsetse belt in Marsabit County, northern Kenya. We identifiedTrypanosoma spp., includingTrypanosoma vivax,T. evansi,T. brucei, andT. congolensein these biting flies as well as in camels (Camelus dromedarius). Trypanosomes detected varied from single up to three trypanosome species inH. camelinaand camels in areas where no tsetse flies were trapped. Similar trypanosomes were detected inGlossina pallidipescollected from a tsetse-infested area in Shimba Hills, coastal Kenya, showing the wide geographic distribution of trypanosomes. Furthermore, we show that these biting flies acquired blood meals from camels, cattle, goats, and sheep. Phylogenetic analysis revealed diverseTrypanosomaspp. associated with variations in virulence and epidemiology in camels, which suggests that camel trypanosomosis may be due to mixed trypanosome infections rather than only surra (T. evansi), as previously thought.
On the secondary waves of the pandemic launched in Iran and other countries
Authors: Kovriguine D. , Nikitenkova S. 
Published: June 2020

AbstractIn the last decade of April 2020, the second epidemic wave began in Iran. If judging by the dynamics of total cases, the birth of this second wave coincides practically with the maximum growth rate of the primary epidemic started in Iran from the very beginning of 2020. Today, the secondary epidemic wave almost doubles the peak of the primary. The new epidemic wave grows rapidly and unpredictably. Also, we admit that the secondary epidemic waves are already getting started in other countries.
Comparison of Care Utilization and Medical Institutional Death among Older Adults by Home Care Facility Type: A Retrospective Cohort Study in Fukuoka, Japan
Authors: Kim Sung-A , Babazono Akira , Jamal Aziz , Li Yunfei , Liu Ning 
Published: June 2020

AbstractObjectivesWe compared the care services use and medical institutional deaths among older adults across four home care facility types.DesignThis was a retrospective cohort study.SettingWe used administrative claims data from April 2014 to March 2017.ParticipantsWe included 18,347 residents of Fukuoka Prefecture, Japan, who received home care during the period, and aged ≥75 years with certified care needs of at least level 3. Participants were categorized based on home care facility use (i.e., general clinics, Home Care Support Clinics/Hospitals (HCSCs), enhanced HCSCs with beds, and enhanced HCSCs without beds).Primary and secondary outcome measuresWe used generalized linear regression models to estimate care utilization and the incidence of medical institutional death, as well as the potential influence of sex, age, care needs level, and Charlson comorbidity index as risk factors.ResultsThe results of generalized linear models showed the inpatient days were 53.3, 67.4, 63.9, and 72.6 for users of enhanced HCSCs with beds, enhanced HCSCs without beds, HCSCs, and general clinics, respectively. Correspondingly, the numbers of home care days were 64.0, 51.6, 57.9, and 28.4. Our multivariable logistic regression model estimated medical institutional death rate among participants who died during the study period (n = 9919) was 2.32 times higher (P<0.001) for general clinic users than enhanced HCSCs with beds users (relative risks=1.69, P<0.001).ConclusionsParticipants who used enhanced HCSCs with beds had a relatively low inpatient utilization, medical institutional deaths, and a high utilization of home care and home-based end-of-life care. Findings suggest enhanced HCSCs with beds could reduce hospitalization days and medical institutional deaths. Our study warrants further investigations of home care as part of community-based integrated care.Trial registrationThis study was approved by the Kyushu University Institutional Review Board for Clinical Research (Approval No. 20209).Strengths and limitations of this studyThis was a retrospective cohort study including data on 18,347 individuals.This study was designed to suggest the kind of healthcare system that will be needed in the future in aging societies by examining the associations of the type of home care provision system with end-of-life care and place of death for older adults.We calculated the number of years that participants lived during the study period and estimated the annual utilization rates per person-year of observation.This study was conducted using data only on residents of Fukuoka Prefecture in Japan, which limits the generalizability of our findingsThere were no clinical data for individual participants because this study focused on the types of healthcare facilities that provide home care.
Modelling the impact of lockdown easing measures on cumulative COVID-19 cases and deaths in England
Authors: Ziauddeen H , Subramaniam N , Gurdasani D 
Published: June 2020

AbstractBackgroundAs countries begin to ease the lockdown measures instituted to control the COVID-19 pandemic, there is a risk of a resurgence of the pandemic, and early reports of this are already emerging from some countries. Unlike many other countries, the UK started easing lockdown in England when levels of community transmission were still high, and this could have a major impact on case numbers and deaths. However thus far, the likely impacts of easing restrictions at this point in the pandemic have not been quantified. Using a Bayesian model, we assessed the potential impacts of successive lockdown easing measures in England, focussing on scenarios where the reproductive number (R) remains ≤1 in line with the UK government’s stated aim.MethodsWe developed a Bayesian model to infer incident cases and R in England, from incident death data from the Office of National Statistics. We then used this to forecast excess cases and deaths in multiple plausible scenarios in which R increases at one or more time points, compared to a baseline scenario where R remains unchanged by the easing of lockdown.FindingsThe model inferred an R of 0.752 on the 13th May when England first started easing lockdown. In the most conservative scenario where R increases to 0.80 as lockdown was eased further on 1st June and then remained constant, the model predicts an excess 257 (95% 108-492) deaths and 26,447 (95% CI 11,105-50,549) cumulative cases over 90 days. In the scenario with maximal increases in R (but staying ≤1) with successive easing of lockdown, the model predicts 3,174 (95% 1,334-6,060) excess cumulative deaths and 421,310 (95% 177,012-804,811) excess cases.ResultsWhen levels of transmission are high, even small changes in R with easing of lockdown can have significant impacts on expected cases and deaths, even if R remains ≤1. This will have a major impact on population health, tracing systems and health care services in England.. Following an elimination strategy rather than one of maintenance of R below 1 would substantially mitigate the impact of the COVID-19 epidemic within England. This study provides urgently needed information for developing public health policy for the next stages of the pandemic.
Tracking the contribution of inductive bias to individualized internal models
Authors: Török Balázs , Nagy Dávid G. , Kiss Mariann M. , Janacsek Karolina , Németh Dezső , Orbán Gergő 
Published: June 2020

AbstractInternal models capture the regularities of the environment and are central to understanding how humans adapt to environmental statistics. In general, the correct internal model is unknown to observers, instead approximate and transient ones are recruited. However, experimenters assume an ideal observer model, which captures stimulus structure but ignores the diverging hypotheses that humans form during learning. We combine non-parametric Bayesian methods and probabilistic programming to infer rich and dynamic individualised internal models from response times in an implicit visuomotor sequence learning task. We identify two contributors to the internal model: the ideal observer model and a Markov model capturing only immediate temporal dependencies between observations. Individual learning curves revealed internal models initially dominated by the Markov model, which was later traded-off with the ideal observer model. Thus, our results reveal a structured inductive bias that varies across individuals both in strength and persistence but is consistent in overall structure.
Docking studies in targeting proteins involved in cardiovascular disorders using phytocompounds fromTerminalia arjuna
Authors: Kumar Vikas , Sharma Nitin , Sourirajan Anuradha , Khosla Prem Kumar , Dev Kamal 
Published: June 2020

AbstractTerminalia arjuna(Roxb.) Wight and Arnot (T. arjuna) commonly known as Arjuna has been known for its cardiotonic nature in heart failure, ischemic, cardiomyopathy, atherosclerosis, myocardium necrosis and also has been used in the treatment of different human disorders such as blood diseases, anaemia and viral diseases. Our focus has been on phytochemicals which do not exhibit any cytotoxicity and have significant cardioprotective activity. Since Protein-Ligand interactions play a key role in structure-based drug design, therefore with the help of molecular docking, we screened 19 phytochemicals present inT. arjunaand investigated their binding affinity against different cardiovascular target proteins. The three-dimensional (3D) structure of target cardiovascular proteins were retrieved from Protein Data Bank, and docked with 3D Pubchem structures of 19 phytochemicals using Autodock vina. Molecular docking and drug-likeness studies were made using ADMET properties while Lipinski’s rule of five was performed for the phytochemicals to evaluate their cardio protective activity. Among all selected phytocompounds, arjunic acid, arjungenin, and terminic acid were found to fulfill all ADMET rules, drug likeness, and are less toxic in nature. Our studies, therefore revealed that these three phytochemicals fromT. arjunacan be used as promising candidates for developing broad spectrum drugs against cardiovascular diseases.
PP1 promotes cyclin B destruction and the metaphase-anaphase transition by dephosphorylating CDC20
Authors: Bancroft James , Holder James , Geraghty Zoë , Alfonso-Pérez Tatiana , Murphy Daniel , Barr Francis A. , Gruneberg Ulrike 
Published: June 2020

AbstractUbiquitin-dependent proteolysis of cyclin B and securin initiates sister chromatid segregation and anaphase. The anaphase promoting complex/cyclosome (APC/C) and its co-activator CDC20 form the main ubiquitin E3 ligase for these proteins. APC/CCDC20is regulated by CDK1-cyclin B and counteracting PP1 and PP2A family phosphatases through modulation of both activating and inhibitory phosphorylations. Here we report that PP1 promotes cyclin B destruction at the onset of anaphase by removing specific inhibitory phosphorylation in the N-terminus of CDC20. Depletion or chemical inhibition of PP1 stabilises cyclin B and results in a pronounced delay at the metaphase-to-anaphase transition after chromosome alignment. This requirement for PP1 is lost in cells expressing CDK1-phosphorylation defective CDC206Amutants. These CDC206Acells show a normal spindle checkpoint response, but once all chromosomes have aligned rapidly degrade cyclin B and enter into anaphase in the absence of PP1 activity. PP1 therefore facilitates the metaphase-to-anaphase by promoting APC/CCDC20-dependent destruction of cyclin B in human cells.
Tumor to normal single cell mRNA comparisons reveal a pan-neuroblastoma cancer cell
Authors: Kildisiute Gerda , Kholosy Waleed M. , Young Matthew D. , Roberts Kenny , Elmentaite Rasa , van Hooff Sander R. , Khabirova Eleonora , Piapi Alice , Thevanesan Christine , Blanco Eva Bugallo , Burke Christina , Mamanova Lira , Lijnzaad Philip , Margaritis Thanasis , Holstege Frank C.P. , Tas Michelle L. , Wijnen Marc H.W.A. , van Noesel Max M. , del Valle Ignacio , Barone Giuseppe , van der Linden Reinier , Duncan Catriona , Anderson John , Achermann John C. , Haniffa Muzlifah , Teichmann Sarah A. , Rampling Dyanne , Sebire Neil J. , He Xiaoling , de Krijger Ronald R. , Barker Roger A. , Meyer Kerstin B. , Bayraktar Omer , Straathof Karin , Molenaar Jan J. , Behjati Sam 
Published: June 2020

AbstractNeuroblastoma is an embryonal childhood cancer that arises from aberrant development of the neural crest, mostly within the fetal adrenal medulla. It is not established what developmental processes neuroblastoma cancer cells represent. Here, we sought to reveal the phenotype of neuroblastoma cancer cells by comparing cancer (n=16,591) with fetal adrenal single cell transcriptomes (n=57,972). Our principal finding was that the neuroblastoma cancer cell resembled fetal sympathoblasts, but no other fetal adrenal cell type. The sympathoblastic state was a universal feature of neuroblastoma cells, transcending cell cluster diversity, individual patients and clinical phenotypes. We substantiated our findings in 652 neuroblastoma bulk transcriptomes and by integrating canonical features of the neuroblastoma genome with transcriptional signals. Overall, our observations indicate that there exists a pan-neuroblastoma cancer cell state which may be an attractive target for novel therapeutic avenues.
Comparison of real-time quantitative Polymerase Chain Reaction (PCR) and digital droplet PCR for quantification of hormone membrane receptorFSHR, GPERandLHCGRtranscripts in human primary granulosa lutein cells
Authors: Sperduti Samantha , Anzivino Claudia , Villani Maria Teresa , De Feo Gaetano , Simoni Manuela , Casarini Livio 
Published: June 2020

AbstractBackgroundQuantitative real time polymerase chain reaction (qPCR) and droplet digital PCR (ddPCR) are methods used for gene expression analysis in several contexts, including reproductive endocrinology.ObjectivesHerein, we compared qPCR and ddPCR technologies for gene expression analysis of hormone membrane receptor-encoding genes, such as follicle-stimulating hormone (FSHR), G protein-coupled estrogen (GPER)and choriogonadotropin receptors (LHCGR), as well as the commonly usedRPS7housekeeping gene, in order to identify the most reliable method to be applied for gene expression analysis in the context of human reproduction.MethodsTotal RNA was extracted from human primary granulosa cells of donor patients undergoing assisted reproduction and used for gene expression analysis by qPCR and ddPCR, after finding the optimal annealing temperature.ResultsBoth techniques provided results reflecting the low number ofFSHRandGPERtranscripts, although ddPCR detected also unspecific transcripts in usingRPS7primers and quantified the low-expressed genes with major accuracy, thanks to its higher reaction efficiency. The absoluteFSHRandGPERtranscript number was also determined by ddPCR, resulting in 50- to 170-fold lower amount thanLHCGRtranscripts.ConclusionThese results suggest that ddPCR is the candidate technology for analysis of genes with relatively low expression levels and provides useful insights for characterizing hormone receptor expression levels in the context of reproductive endocrinology.
Fusion Speed of Biomolecular Condensates
Authors: Ghosh Archishman , Zhou Huan-Xiang 
Published: June 2020

AbstractBiomolecular condensates formed through phase separation have a tendency to fuse. The speed with which fusion occurs is a direct indicator of condensate liquidity, which is key to both cellular functions and diseases. Using a dual-trap optical tweezers setup, we found the fusion speeds of four types of condensates to differ by two orders of magnitude. The order of fusion speed correlates with the fluorescence of Thioflavin T, which in turn reflects the macromolecular packing density inside condensates. Unstructured protein or polymer chains pack loosely and readily rearrange, leading to fast fusion. In contrast, structured protein domains pack more closely and have to break extensive contacts before rearrangement, corresponding to slower fusion. This molecular interpretation for disparate fusion speeds portends a unified understanding of the underlying physicochemical determinants.Entry for the Table of ContentsThe tendency of biomolecular condensates to fuse is key to cellular function and diseases. Using optical tweezers, fluorescence microscopy, and theoretical modeling, Ghosh and Zhou have begun to unravel the molecular origin for disparate fusion speeds among different biomolecular condensates. They found that fusion speed is dictated by macromolecular packing density inside condensates, which can be reported by ThT fluorescence.
Phase response analyses support a relaxation oscillator model of locomotor rhythm generation inCaenorhabditis elegans
Authors: Ji Hongfei , Fouad Anthony D. , Teng Shelly , Liu Alice , Alvarez-Illera Pilar , Yao Bowen , Li Zihao , Fang-Yen Christopher 
Published: June 2020

AbstractNeural circuits coordinate with muscles and sensory feedback to generate motor behaviors appropriate to an animal’s environment. InC. elegans, the mechanisms by which the motor circuit generates undulations and modulates them based on the environment are largely unclear. We quantitatively analyzedC. eleganslocomotion during free movement and during transient optogenetic muscle inhibition. Undulatory movements were highly asymmetrical with respect to the duration of bending and unbending during each cycle. Phase response curves induced by brief optogenetic inhibition of head muscles showed gradual increases and rapid decreases as a function of phase at which the perturbation was applied. A relaxation oscillator model based on proprioceptive thresholds that switch the active muscle moment was developed and is shown to quantitatively agree with data from free movement, phase responses, and previous results for gait adaptation to mechanical loadings. Our results suggest a neuromuscular mechanism underlyingC. elegansmotor pattern generation within a compact circuit.
Puromycin reactivity does not accurately localize translation at the subcellular level
Authors: Enam Syed Usman , Zinshteyn Boris , Goldman Daniel H. , Cassani Madeline , Livingston Nathan M. , Seydoux Geraldine , Green Rachel 
Published: June 2020

AbstractPuromycin is a tyrosyl-tRNA mimic that blocks translation by labeling and releasing elongating polypeptide chains from translating ribosomes. Puromycin has been used in molecular biology research for decades as a translation inhibitor. The development of puromycin antibodies and derivatized puromycin analogs has enabled the quantification of active translation in bulk and single-cell assays. More recently,in vivopuromycylation assays have become popular tools for localizing translating ribosomes in cells. These assays often use elongation inhibitors to purportedly inhibit the release of puromycin-labeled nascent peptides from ribosomes. Here, usingin vitroandin vivoexperiments, we demonstrate that, even in the presence of elongation inhibitors, puromycylated peptides are released and diffuse away from ribosomes. Puromycylation assays reveal subcellular sites, such as nuclei, where puromycylated peptides accumulate post-release and which do not necessarily coincide with sites of active translation. Our findings urge caution when interpreting puromycylation assays in thein vivocontext.
It’s all relative: population estimates enhance kin recognition in the guppy
Authors: Daniel Mitchel J. 
Published: June 2020

AbstractKin recognition plays a fundamental role in social evolution, enabling active inbreeding avoidance, nepotism, and promoting cooperative social organization. Many organisms recognize kin based on phenotypic similarity – a process called phenotype matching – by comparing information associated with their own phenotype against the phenotypes of conspecifics. However, recent theory demonstrates that to accurately judge phenotypic similarity (and hence, relatedness), individuals require estimates of the population’s distribution of phenotypes as a “frame of reference.” Here, I use the Trinidadian guppy (Poecilia reticulata) to provide the first empirical test of this population estimation theory. I varied the phenotypic distributions of the groups in which focal individuals developed and found that, as adults, their patterns of inbreeding avoidance and nepotistic intrasexual competition differed as predicted by population estimation theory. Individuals reared with conspecifics more similar to themselves treated novel conspecifics as less closely related, suggesting a shifted population estimate. Individuals reared with more phenotypically variable conspecifics exhibited less extreme kin discrimination, suggesting a broader population estimate. These results provide experimental evidence that population estimates inform phenotype matching, and are acquired plastically through social experience. By calibrating phenotype matching to the population distribution of phenotypes, population estimation enhances kin recognition, increasing opportunities for the evolution of inbreeding avoidance and nepotism.
Nanopore sequencing from liquid biopsy: analysis of copy number variations from cell-free DNA of lung cancer patients
Authors: Martignano Filippo , Crucitta Stefania , Mingrino Alessandra , Semeraro Roberto , Del Re Marzia , Petrini Iacopo , Magi Alberto , Conticello Silvestro G. 
Published: June 2020

ABSTRACTAlterations in the genetic content, such as Copy Number Variations (CNVs) is one of the hallmarks of cancer and their detection is used to recognize tumoral DNA. Analysis of cell-free DNA from plasma is a powerful tool for non-invasive disease monitoring in cancer patients. Here we exploit third generation sequencing (Nanopore) to obtain a CNVs profile of tumoral DNA from plasma, where cancer-related chromosomal alterations are readily identifiable.Compared to Illumina sequencing -the only available alternative- Nanopore sequencing represents a viable approach to characterize the molecular phenotype, both for its ease of use, costs and rapid turnaround (6 hours).