bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermosensitivity of the voltage-dependent activation of calcium homeostasis modulator 1 (calhm1) ion channel
Authors: Jeon Young Keul , Choi Si Won , Kwon Jae Won , Woo Joohan , Choi Seong Woo , Kim Sang Jeong , Kim Sung Joon 
Published: October 2020

AbstractCalcium homeostasis modulator 1 (calhm1) proteins form an outwardly rectifying nonselective ion channel having exceedingly slow kinetics and low sensitivity to voltage that is shifted by lowering extracellular Ca2+([Ca2+]e). Here we found that physiological temperature dramatically facilitates the voltage-dependent activation of the calhm1 current (Icalhm1); increased amplitude (Q10, 7-15) and fastened speed of activation. Also, the leftward shift of the half-activation voltage (V1/2) was similary observed in the normal and lower [Ca2+]e. Since calhm1 is highly expressed in the brain and taste cells, the thermosensitivity should be considered in their electrophysiology.
HIV-1 gp120 impairs spatial memory through CREB
Authors: Shrestha Jenny , Santerre Maryline , Allen Charles NS , Arjona Sterling P , Mukerjee Ruma , Park Jin , Bagashev Asen , Wang Ying , Kaul Marcus , Chin Jeannie , Sawaya Bassel E 
Published: October 2020

SUMMARYHIV-associated neurocognitive disorders (HAND) remains an unsolved problem in the clinical management of HIV-1 carriers, because existing anti-retroviral therapy while suppressing viral replication, do not prevent neurocognitive impairment (e.g. spatial memory loss). HIV-1 gp120 protein has been proposed to contribute to HAND because it is shed by infected cells and the use of antibodies revealed its presence in cerebrospinal fluid (CSF) even in the combinatory antiretroviral therapy (cART) era. The cyclic AMP response element-binding protein (CREB) has long been known to be a star player in memory. CREB exerts its effect partially through regulating the genes for peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α and brain-derived neurotrophic factor (BDNF). CREB, PGC-1α, and BDNF levels are low in the brains of patients with neurodegenerative diseases and a dearth of either protein is associated with cognitive decline. We have obtained data showing that gp120 contributes to neurodegeneration by altering CREB phosphorylation on serine residue 133 thus disrupting mitochondrial movement and synaptic plasticity leading to spatial memory loss. Inhibition of CREB function was also associated with a decrease of ATP levels and lower mitochondrial DNA copy numbers. Our data was validatedin vitro(primary mouse neurons and neuronal cell line, SH-SY5Y) andin vivo(gp120-tg mice and mice injected with gp120). The negative effect of gp120 was alleviated in cells and animals in the presence of Rolipram. Hence, we conclude that HIV-1 gp120 protein contributes to spatial memory impairment via inhibition of CREB protein activity.
selfRL: Two-Level Self-Supervised Transformer Representation Learning for Link Prediction of Heterogeneous Biomedical Networks
Authors: Wang Xiaoqi , Yang Yaning , Liao Xiangke , Li Lenli , Li Fei , Peng Shaoliang 
Published: October 2020

AbstractPredicting potential links in heterogeneous biomedical networks (HBNs) can greatly benefit various important biomedical problem. However, the self-supervised representation learning for link prediction in HBNs has been slightly explored in previous researches. Therefore, this study proposes a two-level self-supervised representation learning, namely selfRL, for link prediction in heterogeneous biomedical networks. The meta path detection-based self-supervised learning task is proposed to learn representation vectors that can capture the global-level structure and semantic feature in HBNs. The vertex entity mask-based self-supervised learning mechanism is designed to enhance local association of vertices. Finally, the representations from two tasks are concatenated to generate high-quality representation vectors. The results of link prediction on six datasets show selfRL outperforms 25 state-of-the-art methods. In particular, selfRL reveals great performance with results close to 1 in terms of AUC and AUPR on the NeoDTI-net dataset. In addition, the PubMed publications demonstrate that nine out of ten drugs screened by selfRL can inhibit the cytokine storm in COVID-19 patients. In summary, selfRL provides a general frame-work that develops self-supervised learning tasks with unlabeled data to obtain promising representations for improving link prediction.
eDNA metabarcoding outperforms traditional fisheries sampling and reveals fine-scale heterogeneity in a temperate freshwater lake
Authors: Gehri Rebecca R , Larson Wesley A. , Gruenthal Kristen , Sard Nicholas , Shi Yue 
Published: October 2020

AbstractUnderstanding biodiversity in aquatic systems is critical to ecological research and conservation efforts, but accurately measuring species richness using traditional methods can be challenging. Environmental DNA (eDNA) metabarcoding, which uses high-throughput sequencing and universal primers to amplify DNA from multiple species present in an environmental sample, has shown great promise for augmenting results from traditional sampling to characterize fish communities in aquatic systems. Few studies, however, have compared exhaustive traditional sampling with eDNA metabarcoding of corresponding water samples at a small spatial scale. We intensively sampled Boardman Lake (137 ha) in Michigan, USA from May to June in 2019 using gill and fyke nets and paired each net set with lake water samples collected in triplicate. We analyzed water samples using eDNA metabarcoding with 12S and 16S fish-specific primers and compared estimates of fish diversity among methods. In total, we set 60 nets and analyzed 180 1 L lake water samples. We captured a total of 12 fish species in our traditional gear and detected 40 taxa in the eDNA water samples, which included all the species observed in nets. The 12S and 16S assays detected a comparable number of taxa, but taxonomic resolution varied between the two genes. In our traditional gear, there was a clear difference in the species selectivity between the two net types, and there were several species commonly detected in the eDNA samples that were not captured in nets. Finally, we detected spatial heterogeneity in fish community composition across relatively small scales in Boardman Lake with eDNA metabarcoding, but not with traditional sampling. Our results demonstrated that eDNA metabarcoding was substantially more efficient than traditional gear for estimating community composition, highlighting the utility of eDNA metabarcoding for assessing species diversity and informing management and conservation.
Multivariate Meta-Analysis of Differential Principal Components underlying Human Primed and Naive-like Pluripotent States
Authors: Johnson Kory R. , Mallon Barbara S. , Fann Yang C. , Chen Kevin G. 
Published: October 2020

ABSTRACTThe ground or naive pluripotent state of human pluripotent stem cells (hPSCs), which was initially established in mouse embryonic stem cells (mESCs), is an emerging and tentative concept. To verify this important concept in hPSCs, we performed a multivariate meta-analysis of major hPSC datasets via the combined analytic powers of percentile normalization, principal component analysis (PCA),t-distributed stochastic neighbor embedding (t-SNE), and SC3 consensus clustering. This vigorous bioinformatics approach has significantly improved the predictive values of the current meta-analysis. Accordingly, we were able to reveal various similarities between some naive-like hPSCs (NLPs) and their human and mousein vitrocounterparts. Moreover, we also showed numerous fundamental inconsistencies between diverse naive-like states, which are likely attributed to interlaboratory protocol differences. Collectively, our meta-analysis failed to provide global transcriptomic markers that support a bona fide human naive pluripotent state, rather suggesting the existence of altered pluripotent states under current naive-like growth protocols.
An organ-based multi-level model for glucose homeostasis: organ distributions, timing, and impact of blood flow
Authors: Herrgårdh Tilda , Li Hao , Nyman Elin , Cedersund Gunnar 
Published: October 2020

AbstractGlucose homeostasis is the tight control of glucose in the blood. This complex control is important and not yet sufficiently understood, due to its malfunction in serious diseases like diabetes. Due to the involvement of numerous organs and sub-systems, each with their own intra-cellular control, we have developed a multi-level mathematical model, for glucose homeostasis, which integrates a variety of data. Over the last 10 years, this model has been used to insert new insights from the intra-cellular level into the larger whole-body perspective. However, the original cell-organ-body translation has during these years never been updated, despite several critical shortcomings, which also have not been resolved by other modelling efforts. For this reason, we here present an updated multi-level model. This model provides a more accurate sub-division of how much glucose is being taken up by the different organs. Unlike the original model, we now also account for the different dynamics seen in the different organs. The new model also incorporates the central impact of blood flow on insulin-stimulated glucose uptake. Each new improvement is clear upon visual inspection, and they are also supported by statistical tests. The final multi-level model describes >300 data points in >40 time-series and dose-response curves, resulting from a large variety of perturbations, describing both intra-cellular processes, organ fluxes, and whole-body meal responses. We hope that this model will serve as an improved basis for future data integration, useful for research and drug developments within diabetes.
Collagen fibre-mediated mechanical damage increases calcification of bovine pericardium for use in bioprosthetic heart valves
Authors: Whelan Alix , Williams Elizabeth , Fitzpatrick Emma , Murphy Bruce , Gunning Paul S. , O’Reilly David , Lally Caitríona 
Published: October 2020

AbstractIn cases of aortic stenosis, bioprosthetic heart valves (BHVs), with leaflets made from glutaraldehyde fixed bovine pericardium (GLBP), are often implanted to replace the native diseased valve. Widespread use of these devices, however, is restricted due to inadequate long-term durability owing specifically to premature leaflet failure. Mechanical fatigue damage and calcification remain the primary leaflet failure modes, where glutaraldehyde treatment is known to accelerate calcification. The literature in this area is limited, with some studies suggesting mechanical damage increases calcification and others that they are independent degenerative mechanisms. In this study, specimens which were non-destructively pre-sorted according to collagen fibre architecture and then uniaxially cyclically loaded until failure or 1 million cycles, were placed in anin-vitrocalcification solution. Measurements of percentage volume calcification demonstrated that the weakest specimen group (those with fibres aligned perpendicular to the load) had statistically significantly higher volumes of calcification when compared to those with a high fatigue life. Moreover, SEM imaging revealed that ruptured and damaged fibres presented binding sites for calcium to attach; resulting in more than 4 times the volume of calcification in fractured samples when compared to those which did not fail by fatigue. To the authors’ knowledge, this study quantifies for the first time, that mechanical damage drives calcification in commercial-grade GLBP and that this calcification varies spatially according to localised levels of damage. These findings illustrate that not only is calcification potential in GLBP exacerbated by fatigue damage, but that both failure phenomena are underpinned by the unloaded collagen fibre organisation. Consequently, controlling for GLBP collagen fibre architecture in leaflets could minimise the progression of these prevalent primary failure modes in patient BHVs.
The 55K SNP-Based Exploration of QTL for Spikelet Number Per Spike in a Tetraploid Wheat (Triticum turgidumL.) Population: Chinese Landrace ‘Ailanmai’ × Wild Emmer
Authors: Mo Ziqiang , Zhu Jing , Wei Jiatai , Zhou Jieguang , Xu Qiang , Tang Huaping , Mu Yang , Deng Mei , Jiang Qiantao , Liu Yaxi , Chen Guoyue , Wang Jirui , Qi Pengfei , Li Wei , Wei Yuming , Zheng Youliang , Lan Xiujin , Ma Jian 
Published: October 2020

AbstractThe spikelet number per spike (SNS) is a primary factor determining wheat yield. Common wheat breeding reduces the genetic diversity among elite germplasm resources, leading to a detrimental effect on future wheat production. It is, therefore, necessary to explore new genetic resources for SNS to increase wheat yield. A tetraploid landrace ‘Ailanmai’ × wild emmer wheat recombinant inbred line (RIL) population was used to construct a genetic map using the wheat 55K single nucleotide polymorphism (SNP) array. The linkage map containing 1150 bin markers with a total genetic distance of 2411.8 cM was obtained. Based on phenotypic data from eight environments and best linear unbiased prediction (BLUP) values, five quantitative trait loci (QTL) for SNS were identified, explaining 6.71-29.40% of the phenotypic variation. Two of them,QSns.sau-AM-2B.3andQSns.sau-AM-3B.2, were detected as the major and novel QTL. Their effects were further validated in two additional F2populations using tightly linked Kompetitive Allele-Specific PCR (KASP) markers. Potential candidate genes within the physical intervals of corresponding QTL were predicted to participate in inflorescence development and spikelet formation. Genetic associations between SNS and other agronomic traits were also detected and analyzed. This study demonstrates the feasibility of wheat 55K SNP array developed for common wheat in genetic mapping of tetraploid population and shows the potential application of wheat related species in wheat improvement programs.
EVQuant; high-throughput quantification and characterization of extracellular vesicle (sub)populations
Authors: Hartjes T.A. , Slotman J.A. , Vredenbregt M.S. , Dits N. , Van der Meel R. , Duijvesz D. , Kulkarni J.A. , French P.J. , Van Cappellen W.A. , Schiffelers R.M. , Houtsmuller A.B. , Jenster G.W. , Van Royen M.E. 
Published: October 2020

AbstractExtracellular vesicles (EVs) reflect the cell of origin in terms of nucleic acids and protein content. They are found in biofluids and represent an ideal liquid biopsy biomarker source for many diseases. Unfortunately, clinical implementation is limited by available technologies for EV analysis. We have developed a simple, robust and sensitive microscopy-based high-throughput assay (EVQuant) to overcome these limitations and allow widespread use in the EV community. The EVQuant assay can detect individual immobilized EVs as small as 35 nm and determine their concentration in biofluids without extensive EV isolation or purification procedures. It can also identify specific EV subpopulations based on combinations of biomarkers and is used here to identify prostate-derived urinary EVs as CD9-/CD63+. Moreover, characterization of individual EVs allows analysis of their size distribution. The ability to identify, quantify and characterize EV (sub-)populations in high-throughput substantially extents the applicability of the EVQuant assay over most current EV quantification assays.
A comparison of cognitive-motor integration performance and resting state functional brain network connectivity in female athletes suggests intact motor network and visuomotor skill in those with a concussion history
Authors: Pierias Alanna E , Gorbet Diana E , Wojtowicz Magdalena , Prieur Andrea , Sergio Lauren 
Published: October 2020

AbstractStructural neural changes following concussion are often not captured by standard imaging techniques. However, there is growing evidence that damage to white matter tracts and change in functional network connectivity may be observed following concussive injury. We investigated behavioural performance on a cognitive-motor integration (CMI) task in conjunction with alterations in resting state functional connectivity (rs-FC) in brain networks in a population of 30 female varsity athletes, with 16 having a previous history of concussion. Behavioural performance on accuracy, timing, and trajectory measures of a CMI task were assessed between the concussion history group and the control group. Rs-FC within the nodes of the Default Mode Network (DMN), Dorsal Attention Network (DAN), the Frontoparietal Network, and the Anterior Cerebellar Lobule Network, was assessed against performance scores on accuracy, timing, and trajectory measures. Main findings indicate no difference in behavioural performance between those with concussion history and those without, in contrast to previous findings in a group of primarily male varsity athletes. In addition, no difference in rs-FC was noted in correlation with behavioural performance scores on either accuracy, timing, or trajectory. These findings may suggest sex-related differences in performance on a CMI task, and a resiliency in both functional network connectivity and visuomotor skilled performance in varsity female athletes.
Assessment of two DNA extraction kits for profiling poultry respiratory microbiota from multiple sample types
Authors: Abundo Michael E.C. , Ngunjiri John M. , Taylor Kara J.M. , Ji Hana , Ghorbani Amir , Mahesh KC , Weber Bonnie P. , Johnson Timothy J. , Lee Chang-Won 
Published: October 2020

AbstractCharacterization of poultry microbiota is becoming increasingly important due to the growing need for microbiome-based interventions to improve poultry health and production performance. However, the lack of standardized protocols for sampling, sample processing, DNA extraction, sequencing, and bioinformatic analysis can hinder data comparison between studies. Here, we investigated how the DNA extraction process affects microbial community compositions and diversity metrics in different chicken respiratory sample types including choanal and tracheal swabs, nasal cavity and tracheal washes, and lower respiratory lavage. We did a side-by-side comparison of the performances of Qiagen DNeasy blood and tissue (BT) and ZymoBIOMICS DNA Miniprep (ZB) kits. In general, samples extracted with the BT kit yielded higher concentrations of total DNA while those extracted with the ZB kit contained higher numbers of bacterial 16S rRNA gene copies per unit volume. Therefore, the samples were normalized to equal amounts of 16S rRNA gene copies prior to sequencing. For each sample type, all predominant taxa detected in samples extracted with one kit were present in replicate samples extracted with the other kit and did not show significant differences at the class level. Furthermore, between-kit differences in alpha and beta diversity metrics were statistically indistinguishable. Therefore, both kits perform similarly with regard to 16S rRNA gene-based poultry microbiome analysis.
Clustering and erratic movement patterns of syringe-injected versus mosquito-inoculated malaria sporozoites underlie decreased infectivity
Authors: de Korne C.M. , Winkel B.M.F. , van Oosterom M.N. , Chevalley-Maurel S. , Houwing H.M. , Sijtsma J.C. , Baalbergen E. , Franke-Fayard B.M.D. , van Leeuwen F.W.B. , Roestenberg M. 
Published: October 2020

ABSTRACTLive attenuated malaria sporozoites are promising vaccine candidates, however, their efficacy critically depends on their capability to reach and infect the host liver. Administration via mosquito inoculation is by far the most potent method for inducing immunity, but highly unpractical. Here, we observed that intradermal syringe-injectedPlasmodium bergheisporozoites (syrSPZ) were three-fold less efficient in migrating to and infecting mouse liver compared to mosquito-inoculated sporozoites (msqSPZ). This was related to a clustered dermal distribution (2-fold decreased median distance betweensyrSPZ vsmsqSPZ) and, more importantly, a 1.4-fold significantly slower and more erratic movement pattern. These erratic movement patterns were likely caused by alteration of dermal tissue morphology (>15 μm intercellular gaps) due to injection pressure and may critically decrease sporozoite infectivity. These results suggest that novel microvolume-based administration technologies hold promise for replicating the success of mosquito-inoculated live attenuated sporozoite vaccines.
The genetic and linguistic structures of Abyssinians and their neighbor reveal the historical demographic dynamics and environmental adaptation in the African Horn region
Authors: Sertse Demissew , Mersha Tesfaye B. , Habtewold Jemaneh Z. 
Published: October 2020

AbstractThe African Horn region that includes the Abyssinian is one of the areas in the world that harbor high human genetic diversity manifesting past intermingling of people of different origins attributed to its geographic immediacy to the middle east and being historical trade and religio-cultural hub. Here, we performed a genetic structure analysis of linguistically differentiated populations of Ethiopia, South Sudan, and Somali. To get insight into the genetic landscape of the horn of Africa against the rest of the world, we leverage HapMap SNPs data from Utah residents with Northern and Western European ancestry (CEU), Maasai (MKK), and Yoruba (YRI) and analyzed for genetic admixture and diversity. The genetic and linguistic affiliations mismatch for most Cushitic and Semitic language speakers. The gradients of genetic variations among the different sub-populations within the region show gene-flow directions and past mass population movements. Ethiopians that predominately inhabited the central and northern Ethiopia harbored ~10-15% of CEU admixture. The African horn ancestral line contributed a total of ~20%, 5%, and 2% to MKK, YRI, and CEU, respectively. MKK showed a high genetic diversity comparable to the Ethiopian Cushitic, Semitic, and North Omotic language speakers. Allelic distribution frequencies among the populations at some outlier loci may also provide insight into the adaptations to critical environmental factors such as Malaria.
High-resolution mapping of the neutralizing and binding specificities of polyclonal rabbit serum elicited by HIV Env trimer immunization
Authors: Dingens Adam S. , Pratap Payal , Malone Keara , Hilton Sarah K. , Ketas Thomas , Cottrell Christopher A. , Overbaugh Julie , Moore John P. , Klasse P.J. , Ward Andrew B. , Bloom Jesse D. 
Published: October 2020

AbstractMapping the epitope specificities of polyclonal serum is critical to rational vaccine design. However, most high-resolution mapping approaches involve isolating and characterizing individual monoclonal antibodies, which incompletely defines the full polyclonal response. Here we use two complementary approaches to directly map the specificities of the neutralizing and binding antibodies of polyclonal anti-HIV-1 sera from rabbits immunized with BG505 Env SOSIP trimers. To map the neutralizing specificity, we used mutational antigenic profiling to determine how all amino-acid mutations in Env affected viral neutralization. To map the binding specificity, we used electron microscopy polyclonal epitope mapping (EMPEM) to directly visualize the Fabs in serum bound to Env trimers. Mutational antigenic profiling showed that the dominant neutralizing specificities were the C3/V5 and/or 241/289 glycan hole epitopes, which were generally only a subset of the more diverse binding specificities mapped with EMPEM. Additional differences between binding and neutralization reflected antigenicity differences between virus and soluble Env trimer. Further, mutational antigenic profiling was able to refine epitope specificity in residue-level detail directly from sera, revealing subtle differences across rabbits. Together, mutational antigenic profiling and EMPEM allow for a holistic view of the binding and neutralizing specificity of polyclonal sera and could be used to finely evaluate and guide vaccine design.