bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virus-derived variation in diverse human genomes
Authors: Kojima Shohei , Kamada Anselmo Jiro , Parrish Nicholas F. 
Published: November 2020

AbstractAcquisition of genetic material from viruses by their hosts can generate inter-host structural genome variation. We developed computational tools enabling us to study virus-derived structural variants (SVs) in population-scale whole genome sequencing (WGS) datasets and applied them to 3,332 humans. Although SVs had already been cataloged in these subjects, we found previously-overlooked virus-derived SVs. We detected somatic SVs present in the sequenced lymphoblastoid cell lines (LCLs) derived from squirrel monkey retrovirus (SMRV), human immunodeficiency virus 1 (HIV-1), and human T lymphotropic virus (HTLV-1); these variants are attributable to infection of LCLs or their progenitor cells and may impact gene expression results and the biosafety of experiments using these cells. In addition, we detected new heritable SVs derived from human herpesvirus 6 (HHV-6) and human endogenous retrovirus-K (HERV-K). We report the first solo-DR HHV-6 that likely to reflects rearrangement of a known full-length endogenous HHV-6. We used linkage disequilibrium between single nucleotide variants (SNVs) and variants in reads that align to HERV-K, which often cannot be mapped uniquely using conventional short-read sequencing analysis methods, to locate previously-unknown polymorphic HERV-K loci. Some of these loci are tightly linked to trait-associated SNVs, some are in complex genome regions inaccessible to prior methods, and some contain novel HERV-K haplotypes likely derived from gene conversion from an unknown source or introgression. These tools and results broaden our perspective on the coevolution between viruses and humans, including ongoing virus-to-human gene transfer contributing to genetic variation between humans.
Chromosomal neighbourhoods allowidentification of organ specific changesin gene expression
Authors: Roy Rishi Das , Hallikas Outi , Christensen Mona M. , Renvoisé Elodie , Jernvall Jukka 
Published: November 2020

ABSTRACTAlthough most genes share their chromosomal neighbourhood with other genes, distribution of genes has not been explored in the context of individual organ development; the common focus of developmental biology studies. Because developmental processes are often associated with initially subtle changes in gene expression, here we explored whether neighbouring genes are informative in the identification of differentially expressed genes. First, we quantified the chromosomal neighbourhood patterns of genes having related functional roles in the mammalian genome. Although the majority of protein coding genes have at least five neighbours within 1 Mb window around each gene, very few of these neighbours regulate development of the same organ. Analyses of transcriptomes of developing mouse molar teeth revealed that whereas expression of genes regulating tooth development changes, their neighbouring genes show no marked changes, irrespective of their level of expression. Finally, we test whether inclusion of gene neighbourhood in the analyses of differential expression could provide additional benefits. For the analyses, we developed an algorithm, called DELocal that identifies differentially expressed genes by comparing their expression changes to changes in adjacent genes in their chromosomal regions. Our results show that DELocal removes detection bias towards large changes in expression, thereby allowing identification of even subtle changes in development. Future studies, including the detection of differential expression, may benefit from, and further characterize the significance of gene-gene neighbour relationships.Author SummaryDevelopment of organs is typically associated with small and hard to detect changes in gene expression. Here we examined how often genes regulating specific organs are neighbours to each other in the genome, and whether this gene neighbourhood helps in the detection of changes in gene expression. We found that genes regulating individual organ development are very rarely close to each other in the mouse and human genomes. We built an algorithm, called DELocal, to detect changes in gene expression that incorporates information about neighbouring genes. Using transcriptomes of developing mouse molar teeth containing gene expression profiles of thousands of genes, we show how genes regulating tooth development are ranked high by DELocal even if their expression level changes are subtle. We propose that developmental biology studies can benefit from gene neighbourhood analyses in the detection of differential expression and identification of organ specific genes.
Quantitative dSTORM super-resolution microscopy localizes Aurora kinase A/AURKA in the mitochondrial matrix
Authors: Durel Béatrice , Kervrann Charles , Bertolin Giulia 
Published: November 2020

AbstractMitochondria are dynamic organelles playing essential metabolic and signaling functions in cells. Their ultrastructure has largely been investigated with electron microscopy (EM) techniques, which provided a wide range of information on how mitochondria acquire a tissue-specific shape, how they change during development, and how they are altered in disease conditions. However, quantifying protein-protein proximities using EM is extremely challenging. Super-resolution microscopy techniques as direct stochastic optical reconstruction microscopy (dSTORM) now provide a fluorescent-based alternative to EM with a higher quantitative throughput. Recently, super-resolution microscopy approaches including dSTORM led to valuable advances in our knowledge of mitochondrial ultrastructure, and in linking it with new insights in organelle functions. Nevertheless, dSTORM is currently used to image integral mitochondrial proteins only, and there is little or no information on proteins transiently present at this compartment. The cancer-related Aurora kinase A/AURKA is a protein localized at various subcellular locations, including mitochondria. After performing dSTORM, we here use the Geo-coPositioning System (GcoPS) image analysis method to quantify the degree of colocalization of AURKA with compartment-specific mitochondrial markers. We show that two-color dSTORM provides sufficient spatial resolution to visualize AURKA in the mitochondrial matrix. We conclude by demonstrating that optimizing fixation procedures is a key step to follow AURKA in the matrix. In this light, we show that a methanol-based fixation leads to a better detection of the matrix pool of AURKA than an aldehyde-based fixation. Our results indicate that dSTORM coupled to GcoPS colocalization analysis is a suitable approach to explore the compartmentalization of non-integral mitochondrial proteins as AURKA, in a qualitative and quantitative manner. This method also opens up the possibility of analyzing the proximity between AURKA and its multiple mitochondrial partners with exquisite spatial resolution, thereby allowing novel insights into the mitochondrial functions controlled by AURKA.
The effects of different frequencies of rhythmic acoustic stimulation on gait kinematics and trunk sway in healthy elderly population
Authors: Minino Roberta , Lopez Emahnuel Troisi , Sorrentino Pierpaolo , Rucco Rosaria , Lardone Anna , Pesoli Matteo , Tafuri Domenico , Mandolesi Laura , Sorrentino Giuseppe , Liparoti Marianna 
Published: November 2020

ABSTRACTThe use of rhythmic acoustic stimulation (RAS) in improving gait and balance in healthy elderly subjects has been widely investigated. However, methodologies and results are often controversial. In this study, we hypothesize that both the kinematic features of gait and stability, depend on the frequency at which RAS is administered. Our aim was to observe, through 3D Gait Analysis, the effect of different types of RAS (at a fixed frequency or based on the average cadence of each subject) on both gait spatio-temporal parameters and stability. The latter was estimated through an innovative measure, the trunk displacement index (TDI) that we have recently implemented. We observed that the low frequencies RAS led to a general slowdown of gait, which did not provide any clear benefit and produced harmful effects on stability when the frequency became too low compared to the individual natural frequency. On the contrary, the high frequencies of RAS showed a slight acceleration of gait, accompanied by better stability (as documented by a lower TDI value), regardless of the type of RAS. Finally, the RAS equal to the individual natural cadence also produced an increase in stability.
Bayesian optimization of multivariate genomic prediction models based on secondary traits for improved accuracy gains and phenotyping costs
Authors: Hamazaki Kosuke , Iwata Hiroyoshi 
Published: November 2020

AbstractKey messageWe propose a novel approach to the Bayesian optimization of multi-variate genomic prediction models based on secondary traits to improve accuracy gains and phenotyping costs via efficient Pareto frontier estimation.Multivariate genomic prediction based on secondary traits, such as data from various omics technologies including high-throughput phenotyping (e.g., unmanned aerial vehicle-based remote sensing), has attracted much attention because it offers improved accuracy gains compared with genomic prediction based only on marker genotypes. Although there is a trade-off between accuracy gains and phenotyping costs of secondary traits, no attempt has been made to optimize these trade-offs. In this study, we propose a novel approach to optimize multivariate genomic prediction models for secondary traits measurable at early growth stages for improved accuracy gains and phenotyping costs. The proposed approach employs Bayesian optimization for efficient Pareto frontier estimation, representing the maximum accuracy at a given cost. The proposed approach successfully estimated the optimal secondary trait combinations across a range of costs while providing genomic predictions for only about 20% of all possible combinations. The simulation results reflecting the characteristics of each scenario of the simulated target traits showed that the obtained optimal combinations were reasonable. Analysis of real-time target trait data showed that the proposed multivariate genomic prediction model had significantly superior accuracy compared to the univariate genomic prediction model.
Modeling the frequency and number of persons to test to detect and control COVID-19 outbreaks in congregate settings
Authors: Paul Prabasaj , Mosites Emily , Laws Rebecca L. , Scobie Heather , Slayton Rachel B. , Clarke Kristie E. N. 
Published: November 2020

AbstractBackgroundCongregate settings are at risk for coronavirus disease 2019 (COVID-19) outbreaks. Diagnostic testing can be used as a tool in these settings to identify outbreaks and to control transmission.MethodsWe used transmission modeling to estimate the minimum number of persons to test and the optimal frequency to detect small outbreaks of COVID-19 in a congregate facility. We also estimated the frequency of testing needed to interrupt transmission within a facility.ResultsThe number of people to test and frequency of testing needed depended on turnaround time, facility size, and test characteristics. Parameters are calculated for a variety of scenarios. In a facility of 100 people, 26 randomly selected individuals would need to be tested at least every 6 days to identify a true underlying prevalence of at least 5%, with test sensitivity of 85%, and greater than 95% outbreak detection sensitivity. Disease transmission could be interrupted with universal, facility-wide testing with rapid turnaround every three days.ConclusionsTesting a subset of individuals in congregate settings can improve early detection of small outbreaks of COVID-19. Frequent universal diagnostic testing can be used to interrupt transmission within a facility, but its efficacy is reliant on rapid turnaround of results for isolation of infected individuals.
Interaction of Amphiphilic Lipoarabinomannan with Host Carrier Lipoproteins in Tuberculosis Patients: Implications for Blood-based Diagnostics
Authors: Jakhar Shailja , Sakamuri Ramamurthy , Vu Dung , Dighe Priya , Stromberg Loreen R. , Lilley Laura , Hengartner Nicolas , Swanson Basil I. , Moreau Emmanuel , Dorman Susan E. , Mukundan Harshini 
Published: November 2020

AbstractLipoarabinomannan (LAM), an amphiphilic lipoglycan of theMycobacterium tuberculosiscell wall, is a diagnostic target for tuberculosis. Previous work from our laboratory and others suggests that LAM is associated with host serum lipoproteins, which may in turn have implications for diagnostic assays. Our team has developed two serum assays for amphiphile detection: lipoprotein capture and membrane insertion. The lipoprotein capture assay relies on capture of the host lipoproteins, exploiting the biological association of host lipoprotein with microbial amphiphilic biomarkers to “concentrate” LAM. In contrast, the membrane insertion assay is independent of the association between pathogen amphiphiles and host lipoprotein association, and directly captures LAM based on its thermodynamic propensity for association with a supported lipid membrane, which forms the functional surface of an optical biosensor. In this manuscript, we explored the use of these assays for the detection of LAM in sera from adults whose tuberculosis status had been well-characterized using conventional microbiological tests, and endemic controls. Using the lipoprotein capture assay, LAM signal/noise ratios were >1.0 in 29/35 (83%) individuals with culture-confirmed active tuberculosis, 8/13 (62%) individuals with tuberculosis symptoms but no positive culture forM. tuberculosis, and 0/6 (0%) symptom-free endemic controls. To evaluate serum LAM levels without bias associated with potential differences in circulating host lipoprotein concentrations between individuals, we subsequently processed available samples to liberate LAM from associated host lipoprotein assemblies followed by direct detection of the pathogen biomarker using the membrane insertion approach. Using the membrane insertion assay, signal/noise for detection of serum LAM was greater than that observed using the lipoprotein capture method for culture-confirmed TB patients (6/6), yet remained negative for controls (2/2). Taken together, these results suggest that detection of serum LAM is a promising TB diagnostic approach. Further work is required to optimize assay performance and to decipher the implications of LAM/host lipoprotein associations for diagnostic assay performance and TB pathogenesis.
Could TDX-1 explain the changes observed in endocrine pancreas due to chronic cola drink consumption in rats? A global point of view
Authors: Cao Gabriel , González Julián , Fragola Juan P. Ortiz , Muller Angélica , Tumarkin Mariano , Moriondo Marisa , Azzato Francisco , Blanco Manuel Vazquez , Milei José 
Published: November 2020

AbstractIn previous studies, we reported evidence showing that chronic cola consumption in rats impairs pancreatic metabolism of insulin and glucagon and produces some alterations typically observed in the metabolic syndrome (i.e, hyperglycemia, and hypertriglyceridemia) with an increase in oxidative stress. Of note, no apoptosis nor proliferation of islet cells could be demonstrated. In the present study, 36 male Wistar rats were divided in three groups to freely drink regular cola, light cola, or water (controls). We assessed the impact of the three different beverages in glucose tolerance, lipid levels, creatinine levels and immunohistochemical changes addressed for the expression of insulin, glucagon, PDX-1 and NGN3 in islet cells, to evaluate the possible participation of PDX-1 in the changes observed in α and β cells after 6 months of treatment. On the other hand, we assessed by stereological methods, the mean volume of islets (Vi) and three important variables, the fractional β-cell area, the cross-sectional area of alpha (A α-cell) and beta cells (A β-cell), and the number of β and α cell per body weight.Cola drinking caused impaired glucose tolerance as well as fasting hyperglycemia and increase of insulin immunolabeling. Immunohistochemical expression for PDX-1 was significantly high in regular cola consumption group compared to control. In this case, we observed cytoplasmatic and nuclear localization. Likewise, a mild but significant decrease of Vi was detected after 6 months of cola drink consumption compared with control group. Also, we observed a significant decrease of fractional β cell area compared with control rats. Accordingly, a reduced mean value of islet α and β cell number per body weight compared to control was detected. Interestingly, consumption of light cola increased the Vi compared to control. In line with this, a decreased cross-sectional area of β-cells was observed after chronic consumption of both, regular and light cola, compared to controls. On the other hand, NGN3 was negative in all three groups. Our results support for the first time, the idea that TDX-1 plays a key role in the dynamics of the pancreatic islets after chronic consumption of sweetened beverages. The loss of islets cells might be attributed to autophagy, favored by the local metabolic conditions.
Genetically controlled mtDNA editing prevents ROS damage by arresting oxidative phosphorylation
Authors: Stenberg Simon , Li Jing , Gjuvsland Arne B. , Persson Karl , Demitz-Helin Erik , Peña Carles Gonzalez , Yue Jia-Xing , Gilchrist Ciaran , Ärengård Timmy , Ghiaci Payam , Larsson-Berglund Lisa , Zackrisson Martin , Höög Johanna L. , Molin Mikael , Liti Gianni , Omholt Stig W. , Warringer Jonas 
Published: November 2020

AbstractDeletion of mitochondrial DNA in eukaryotes is mainly attributed to rare accidental events associated with mitochondrial replication or repair of double-strand breaks. We report the discovery that yeast cells arrest harmful intramitochondrial superoxide production by shutting down respiration through genetically controlled deletion of mitochondrial oxidative phosphorylation genes. We show that the regulatory circuitry underlying this editing critically involves the antioxidant enzyme superoxide dismutase 2 and two-way mitochondrial-nuclear communication. While mitochondrial DNA homeostasis is rapidly restored after cessation of a short-term superoxide stress, long-term stress causes maladaptive persistence of the deletion process, leading to complete annihilation of the cellular pool of intact mitochondrial genomes and irrevocable loss of respiratory ability. Our results may therefore be of etiological as well as therapeutic importance with regard to age-related mitochondrial impairment and disease.One-Sentence SummaryGenetically controlled editing of mitochondrial DNA is an integral part of the yeast’s defenses against oxidative damage.
Agreement Test Between The Six Minutes Walking Test And Four Meter Gait Speed
Authors: Nusdwinuringtyas Nury , Fransiska Tresia , Sunarjo Peggy , Triangto Kevin , Dahlan Sopiyudin 
Published: November 2020

Background/ObjectiveIn the field of Physical Medicine and Rehabilitation, it is essential to measure individual functional capacity, which could be evaluated through walking tests. Aside from the commonly used six minutes walking test (6MWT), four meter gait speed (4MGS) are widely used for its practicality. This study aimed to assess the agreement between 4 MGS and the 6MWT in Indonesian healthy adults.MethodsThis agreement analysis study had recruited 61 healthy and sedentary Indonesians aged 18 until 50 years old, and they were instructed to perform three tests, namely 6MWT and 4MGS with six meters and eight meters track. These gait speed were then compared to assess validity.ResultsMean gait speed results for males in 6MWT is 1.602 m/s, whereas 4MGS in six meter track is 2.114 m/s and similarly 2.108 m/s in the eight meter track. Females on the other hand, achieved 1.462 m/s for 6MWT, 1.908 m/s and 1.986 m/s for 4MGS in six and eight meter simultaneously. Bland Altman Agreement test between the 6MWT and 4MGS shows scatter dots with close limit of agreement, thus showing a good agreement between the 6MWT and 4 MGS with both tracks.DiscussionBoth track length of 4 MGS were in a good agreement with 6MWT for functional capacity assessment.ConclusionsIn response to the COVID-19 pandemic era, shorter track of 4MGS (six meters) can be feasibly utilized. It is evident that shorter duration and track will boost the tests practicality in assessing functional capacity for both inpatient and outpatient settings.
Effects of Na+channel isoforms and lipid membrane environment on temperature tolerance of cardiac Na+current in zebrafish (Danio rerio) and rainbow trout (Oncorhynchus mykiss)
Authors: Haverinen Jaakko , Dzhumaniiazova Irina , Abramochkin Denis V. , Hassinen Minna , Vornanen Matti 
Published: November 2020

ABSTRACTHeat tolerance of heart rate in fish is suggested to be limited by impaired electrical excitation of the ventricle due to the antagonistic effects of high temperature on Na+(INa) and K+(IK1) ion currents (INais depressed at high temperatures while IK1is resistant to them). To examine the role of Na+channel proteins and the lipid matrix of the channels in heat tolerance of INa, we compared temperature-dependencies of zebrafish (Danio rerio) and rainbow trout (Oncorhynchus mykiss) ventricular INa, and INagenerated by the cloned zebrafish and rainbow trout NaV1.4 and NaV1.5 Na+channels in HEK cells. Whole-cell patch clamp recordings showed that zebrafish ventricular INahas better heat tolerance and slower inactivation kinetics than rainbow trout ventricular INa. In contrast, heat tolerance and inactivation kinetics of zebrafish and rainbow trout NaV1.4 channels are similar when expressed in the identical plasma membrane lipid matrix of HEK cells. The same applies to NaV1.5 channels. Thermal adaptation of the ventricular INais largely achieved by differential expression of Na+channel alpha subunits: zebrafish which tolerate well high temperatures mainly express the slower NaV1.5 isoform, while rainbow trout which prefer cold waters mainly express the faster NaV1.4 isoform. Differences in elasticity (stiffness) of the lipid bilayer may be also involved in thermal adaptation of INa. These findings suggest that both the protein component and its lipid bilayer matrix are involved in thermal adaptation of the voltage-gated Na+channels and therefore in heart rate regulation under thermal stress in fish.
Fecundity determines the outcome of founding queen associations in ants
Authors: Teggers Eva-Maria , Deegener Falk , Libbrecht Romain 
Published: November 2020

AbstractAnimal cooperation evolved because of its benefits to the cooperators. Pleometrosis in ants - the cooperation of queens to found a colony - benefits colony growth, but also incurs costs for some of the cooperators because only one queen usually survives the association. While several traits are associated with queen survival, they tend to be confounded and it is unclear which factor specifically determines the outcome of pleometrosis. In this study, we used the antLasius nigerto monitor offspring production in colonies founded by one or two queens. Then, we experimentally paired queens that differed in fecundity but not in size, andvice versa, to disentangle the effect of these factors on queen survival. Finally, we investigated how fecundity and size differed between queens depending on whether they were chosen as pleometrotic partners. Our results indicate that pleometrosis increased and accelerated worker production via a nutritional boost to the larvae. The most fecund queens more frequently survived the associations, even when controlling for size and worker parentage, and queens selected as pleometrotic partners were less fecund. Our results are consistent with fecundity being central to the onset and outcome of pleometrosis, a typical case of cooperation among unrelated animals.