bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucose clearance and uptake is increased in the SOD1G93Amouse model of amyotrophic lateral sclerosis through an insulin-independent mechanism
Authors: McDonald Tanya S. , Kumar Vinod , Fung Jenny N. , Woodruff Trent M. , Lee John D. 
Published: August 2020

AbstractMetabolic disturbances are associated with the progression of the neurodegenerative disorder, amyotrophic lateral sclerosis (ALS), however the molecular events that drive energy imbalances in ALS are not completely understood. In this study we aimed to elucidate deficits in energy homeostasis in the SOD1G93Amouse model of ALS. We identified that SOD1G93Amice at mid-symptomatic disease stage have increased oxygen consumption and faster exogenous glucose uptake, despite presenting with normal insulin tolerance. Fasting glucose homeostasis was also disturbed, along with increased liver glycogen stores, despite elevated circulating glucagon, suggesting that glucagon signalling is impaired. Metabolic gene expression profiling of livers indicated that glucose cannot be utilised efficiently in SOD1G93Amice. Overall, we demonstrate that glucose homeostasis and uptake are altered in SOD1G93Amice, which is linked to an increase in insulin-independent glucose uptake and a disturbance in glucagon sensitivity, suggesting glucagon secretion and signalling could be potential therapeutic targets for ALS.
scGNN: a novel graph neural network framework for single-cell RNA-Seq analyses
Authors: Wang Juexin , Ma Anjun , Chang Yuzhou , Gong Jianting , Jiang Yuexu , Fu Hongjun , Wang Cankun , Qi Ren , Ma Qin , Xu Dong 
Published: August 2020

ABSTRACTSingle-cell RNA-sequencing (scRNA-Seq) is widely used to reveal the heterogeneity and dynamics of tissues, organisms, and complex diseases, but its analyses still suffer from multiple grand challenges, including the sequencing sparsity and complex differential patterns in gene expression. We introduce the scGNN (single-cell graph neural network) to provide a hypothesis-free deep learning framework for scRNA-Seq analyses. This framework formulates and aggregates cell-cell relationships with graph neural networks and models heterogeneous gene expression patterns using a left-truncated mixture Gaussian model. scGNN integrates three iterative multi-modal autoencoders and outperforms existing tools for gene imputation and cell clustering on four benchmark scRNA-Seq datasets. In an Alzheimer’s disease study with 13,214 single nuclei from postmortem brain tissues, scGNN successfully illustrated disease-related neural development and the differential mechanism. scGNN provides an effective representation of gene expression and cell-cell relationships. It is also a novel and powerful framework that can be applied to scRNA-Seq analyses.
Severity Assessment and Progression Prediction of COVID-19 Patients based on the LesionEncoder Framework and Chest CT
Authors: Feng You-Zhen , Liu Sidong , Cheng Zhong-Yuan , Quiroz Juan C. , Rezazadegan Dana , Chen Ping-Kang , Lin Qi-Ting , Qian Long , Liu Xiao-Fang , Berkovsky Shlomo , Coiera Enrico , Song Lei , Qiu Xiao-Ming , Cai Xiang-Ran 
Published: August 2020

AbstractAutomatic severity assessment and progression prediction can facilitate admission, triage, and referral of COVID-19 patients. This study aims to explore the potential use of lung lesion features in the management of COVID-19, based on the assumption that lesion features may carry important diagnostic and prognostic information for quantifying infection severity and forecasting disease progression.A novel LesionEncoder framework is proposed to detect lesions in chest CT scans and to encode lesion features for automatic severity assessment and progression prediction. The LesionEncoder framework consists of a U-Net module for detecting lesions and extracting features from individual CT slices, and a recurrent neural network (RNN) module for learning the relationship between feature vectors and collectively classifying the sequence of feature vectors.Chest CT scans of two cohorts of COVID-19 patients from two hospitals in China were used for training and testing the proposed framework. When applied to assessing severity, this framework outperformed baseline methods achieving a sensitivity of 0.818, specificity of 0.952, accuracy of 0.940, and AUC of 0.903. It also outperformed the other tested methods in disease progression prediction with a sensitivity of 0.667, specificity of 0.838, accuracy of 0.829, and AUC of 0.736. The LesionEncoder framework demonstrates a strong potential for clinical application in current COVID-19 management, particularly in automatic severity assessment of COVID-19 patients. This framework also has a potential for other lesion-focused medical image analyses.
Altitude as a protective factor from COVID-19
Authors: Thomson Timothy M. , Casas Fresia , Guerrero Harold Andre , Figueroa-Mujíca Rómulo , Villafuerte Francisco C. , Machicado Claudia 
Published: August 2020

AbstractThe COVID-19 pandemic had a delayed onset in South America compared to Asia (outside of China), Europe or North America. In spite of the presumed time advantage for the implementation of preventive measures to help contain its spread, the pandemic in that region followed growth rates that paralleled, and currently exceed, those observed several weeks before in Europe. Indeed, in early August 2020, many countries in South and Central America presented among the highest rates in the world of COVID-19 confirmed cases and deaths per million inhabitants. Here, we have taken an ecological approach to describe the current state of the pandemic in Peru and its dynamics. Our analysis supports a protective effect of altitude from COVID-19 incidence and mortality. Further, we provide circumstantial evidence that internal migration through a specific land route is a significant factor progressively overriding the protection from COVID-19 afforded by high altitude. Finally, we show that protection by altitude is independent of poverty indexes and is inversely correlated with the prevalence in the population of risk factors associated with severe COVID-19, including hypertension and hypercholesterolemia. We discuss long-term multisystemic adaptive traits to hypobaric hypoxia as possible mechanisms that may explain the observed protective effect of high altitude from death due to COVID-19.
COVID-19 Case Mortality Rates Continue to Decline in Florida
Authors: Harris Jeffrey E. 
Published: August 2020

AbstractWe studied COVID-19 case mortality in Florida among four successive cohorts of persons at least 50 years of age, each of whom we followed for 28 to 48 days from date of diagnosis. The cohorts were separated by date of diagnosis into four nonoverlapping intervals: March 29 - April 18; April 29 - May 19; May 21 - June 10; and June 14 - July 4, 2020. Case mortality rates declined consistently and significantly over the course of the four intervals: 57% among those aged 50-59 years; 62% among those aged 60-69 years; 52% among those aged 70-79 years; and 34% among those aged 80 or more years. These findings were consistent with progressive improvements in the medical care of COVID-19 patients. We further studied case mortality by hospitalization status. The case mortality rate among hospitalized patients aged 60-69 years fell significantly from the first to the third interval. During the fourth interval, an apparent rise in mortality among hospitalized patients in the same age group was mirrored by a significant decline in mortality among those not hospitalized. These findings were consistent with the out-of-hospital treatment of some patients who would have previously been hospitalized.This study relies exclusively on publicly available, aggregate health data that contain no individual identifiers. The author has no competing interests and no funding sources to declare. This article represents to the sole opinion of its author and does not necessarily represent the opinions of the Massachusetts Institute of Technology, the National Bureau of Economic Research, Eisner Health, or any other organization.
The effect of wildSaccharomyceson composition and aroma of the Sauvignon blanc
Authors: Mendes Sandra D. C. , Arcari Stefany Grützmann , Ramirez-Castrillon Mauricio , Werner Simone Silmara , Valente Patricia 
Published: August 2020

ABSTRACTSaccharomycesstrains isolated from vineyards in Southern Brazil were used as starter in micro-fermentations of Sauvignon Blanc juice (SB) to study the ability to produce different aromatic profiles. The molecular characterization allowed to differentiate the isolates from vineyards 06 CE, 11CE, 33CE, 01PP, 12M, 13PP, 26PP, 28AD, 41PP from the reference strain (2048SC) used in wine production. Under the same conditions tested, each strain belonging to the genusSaccharomycesproduced metabolites in different concentration and combination, significantly influencing the aroma of the SB must. Volatile compounds such as octanoic acid, diethyl succinate and ethyl lactate were associated with the strains 26PP, 41PP, 01PP and 12M, while the strains 33CE, 28AD, 13PP and 06 CE were associated with the production of ethyl acetate, 1-hexanol, highlighting 06CE for production of 1-hexanol (592.87 ± 17.46 µg/L). In addition, the olfactory activity value (OAV> 1) allowed the evaluation of the range of participation of each compound in the final SB fermented. Finally, the selected wild strains are promising to improve the regional character of the wine.
Extensive Phenomenological Overlap between Induced and Naturally-Occurring Synaesthetic Experiences
Authors: Schwartzman David. J. , Oblak Ales , Rothen Nicolas , Bor Daniel , Seth Anil. K. 
Published: August 2020

AbstractGrapheme-colour synaesthesia (GCS) is defined by additional perceptual experiences, which are automatically and consistently triggered by specific inducing stimuli. The associative nature of GCS has motivated attempts to induce synaesthesia by means of associative learning. Two recent studies have shown that extensive associative training can generate not only behavioural (consistency and automaticity) and neurophysiological markers of GCS, but also synaesthesia-like phenomenology [1,2]. However, these studies provided only superficial descriptions regarding the training-related changes in subjective experience: they did not directly assess how closely induced synaesthetic experiences mirror those found in natural GCS. Here we report an extended qualitative analysis of the transcripts of the semi-structured interviews obtained following the completion of the associative training protocol used by [2]. In addition, we performed a comparable analysis of responses to an interview with a new population of natural occurring grapheme-colour synaesthetes (NOS), allowing us to directly compare the phenomenological dimensions of induced and naturally occurring synaesthetic experience. Our results provide an extensive addition to the description of the phenomenology of NOS experience, revealing a high degree of heterogeneity both within and across all experiential categories. Capitalising on this unique level of detail, we identified a number of shared experiential categories between NOS and induced synaesthesia-like (ISL) groups, including:stability of experience, location of colour experience, shape of co-occurring colour experience, relative strength of colour experience and automaticity of colour experience. Only the automaticity of colour experience differed significantly between the two groups: NOS experience was reported as being mostly automatic, whereas induced ISL were mostly described as being ‘wilful’. We observed three additional experiential categories relating to the automaticity of synaesthetic experience within the NOS group:contextually varied experience, semi-automatic experienceandreflective association, which suggests that, as with other experiential categories, the automaticity of synaesthetic experience is also highly heterogeneous. Our results provide new evidence that that intensive training of letter-colour associations can alter conscious perceptual experiences in non-synaesthetes, and that such alterations produce synaesthesia-like phenomenology which substantially resembles similarities to natural grapheme-colour synaesthesia.
Genomics of a killifish from the Seychelles islands supports transoceanic island colonization and reveals relaxed selection of developmental genes
Authors: Cui Rongfeng , Tyers Alexandra M , Malubhoy Zahabiya Juzar , Wisotsky Sadie , Valdesalici Stefano , Henriette Elvina , Pond Sergei L Kosakovsky , Valenzano Dario Riccardo 
Published: August 2020

AbstractHow freshwater fish colonize remote islands remains an evolutionary puzzle. Tectonic drift and trans-oceanic dispersal models have been proposed as possible alternative mechanisms. Integrating dating of known tectonic events with population genetics and experimental test of salinity tolerance in the Seychelles islands golden panchax (Pachypanchax playfairii), we found support for trans-oceanic dispersal being the most likely scenario. At the macroevolutionary scale, the non-annual killifish golden panchax shows stronger genome-wide purifying selection compared to annual killifishes from continental Africa. Reconstructing past demographies in isolated golden panchax populations provides support for decline in effective population size, which could have allowed slightly deleterious mutations to segregate in the population. Unlike annual killifishes, where relaxed selection preferentially targets aging-related genes, relaxation of purifying selection in golden panchax affects genes involved in developmental processes, including fgf10.
Induction of core symptoms of autism spectrum disorders by in vivo CRISPR/Cas9-based gene editing in the brain of adolescent rhesus monkeys
Authors: Wu Shi-Hao , Li Xiao , Qin Dong-Dong , Zhang Lin-Heng , Cheng Tian-Lin , Chen Zhi-Fang , Nie Bin-Bin , Ren Xiao-Feng , Wu Jing , Wang Wen-Chao , Hu Ying-Zhou , Gu Yilin , Lv Long-Bao , Yin Yong , Hu Xin-Tian , Qiu Zi-Long 
Published: August 2020

AbstractAlthough CRISPR/Cas9-mediated gene editing is widely applied to mimic human disorders, whether acute manipulation of disease-causing genes in the brain leads to behavioral abnormalities in non-human primates remains to be determined. Here we induced genetic mutations in MECP2, a critical gene linked to Rett syndrome (RTT) and autism spectrum disorders (ASDs), in the hippocampus (DG and CA1–4) of adolescent rhesus monkeys (Macaca mulatta) in vivo via adeno-associated virus (AAV)-delivered Staphylococcus aureus Cas9 with sgRNAs targeting MECP2. In comparison to monkeys injected with AAV-SaCas9 alone (n = 4), numerous autistic-like behavioral abnormalities were identified in the AAV-SaCas9-sgMECP2-injected monkeys (n = 7), including social interaction deficits, abnormal sleep patterns, insensitivity to aversive stimuli, abnormal hand motions and defective social reward behaviors. Furthermore, some aspects of ASDs and RTT, such as stereotypic behaviors, did not appear in the MECP2 gene-edited monkeys, suggesting that different brain areas likely contribute to distinct ASD symptoms. This study showed that acute manipulation of disease-causing genes via in vivo gene editing directly led to behavioral changes in adolescent primates, paving the way for the rapid generation of genetically engineered non-human primate models for neurobiological studies and therapeutic development.
The ESCRT protein CHMP5 restricts bone formation by controlling endolysosome-mitochondrion-mediated cell senescence
Authors: Zhang Fan , Wang Yuan , Zhang Luyang , Wang Chunjie , Chen Deping , Liu Haibo , Xu Ren , Haynes Cole M. , Shim Jae-Hyuck , Ge Xianpeng 
Published: August 2020

AbstractThe dysfunction of the cellular endolysosomal pathway, such as in lysosomal storage diseases, can cause severe musculoskeletal disorders. However, how endolysosomal dysfunction causes musculoskeletal abnormalities remains poorly understood, limiting therapeutic options. Here, we report that CHMP5, a member of the endosomal sorting complex required for transport (ESCRT)-III protein family, is essential to maintain the endolysosomal pathway and regulate bone formation in osteogenic lineage cells. Genetic ablation ofChmp5in mouse osteogenic cells increases bone formation in vivo and in vitro. Mechanistically,Chmp5deletion causes endolysosomal dysfunction by decreasing the VPS4A protein, and CHMP5 overexpression is sufficient to increase the VPS4A protein. Subsequently, endolysosomal dysfunction disturbs mitochondrial functions and increases mitochondrial ROS, ultimately resulting in skeletal cell senescence. Senescent skeletal cells cause abnormal bone formation by combining cell-autonomous and paracrine actions. Importantly, elimination of senescent cells using senolytic drugs can alleviate musculoskeletal abnormalities inChmp5conditional knockout mice. Therefore, our results show that cell senescence represents an underpinning mechanism and a therapeutic target for musculoskeletal disorders caused by the aberrant endolysosomal pathway. These results also uncover the function and mechanism of CHMP5 in the regulation of cell senescence by affecting the endolysosomal-mitochondrial pathway.
Sex identification in embryos and adults of Darwin’s finches
Authors: Dobreva Mariya P. , Lynton-Jenkins Joshua G. , Chaves Jaime A. , Tokita Masayoshi , Bonneaud Camille , Abzhanov Arkhat 
Published: August 2020

AbstractDarwin’s finches, endemic to the Galapagos and Cocos islands, are an iconic example of adaptive radiation and evolution under natural selection. Comparative genetic studies using embryos of Darwin’s finches have shed light on the possible evolutionary processes underlying the speciation of this clade. Molecular identification of the sex of embryonic samples is important for such studies, where this information often cannot be inferred otherwise. We tested a fast and simple chicken embryo protocol for extraction of genomic DNA on Darwin’s finch embryos. In addition, we suggest modifications to two of the previously reported PCR primer sets forCHD1, a gene used for sexing in adult passerine birds. The sex of all 29 tested embryos of six species of Darwin’s finches was determined successfully by PCR, using both primer sets. Hatchlings/nestlings and fledglings are also impossible to distinguish visually. This includes juveniles of sexually dimorphic species which are yet to moult in adult-like plumage and beak colouration. Furthermore, four species of Darwin’s finches are monomorphic, males and females looking alike. Therefore, sex assessment in the field can be a source of error, especially with respect to juveniles and mature monomorphic birds outside of the mating season. We caught 567 juveniles and adults belonging to six species of Darwin’s finches and only 44% had unambiguous sex-specific morphology. We sexed 363 birds by PCR, including individuals sexed based on marginal sex specific morphological traits (N=278) and birds which were impossible to classify in the field (N=39). For birds with marginal sex specific traits, PCR results revealed a 13% sexing error rate. This demonstrates that PCR based sexing can improve field studies on Darwin’s finches, especially when individuals with unclear sex-related morphology are involved. The protocols used here provide an easy and reliable way to sex Darwin’s finches throughout ontogeny, from embryos to adults.
Areca catechu-(Betel-nut)-induced whole transcriptome changes associated with diabetes, obesity and metabolic syndrome in a human monocyte cell line
Authors: Cardoso Shirleny , Ogunkolade B. William , Lowe Rob , Savage Emanuel , Mein Charles A , Boucher Barbara J , Hitman Graham A 
Published: August 2020

AbstractBetel-nut consumption is the fourth most common addictive habit globally and there is good evidence to link it with obesity, type 2 diabetes and the metabolic syndrome. We adopted a genome-wide transcriptomic approach in a human monocyte cell line incubated with arecoline and its nitrosated products to identify gene expression changes relevant to obesity, type 2 diabetes and the metabolic syndrome. The THP1 monocyte cell line was incubated separately with arecoline and 3-methylnitrosaminopropionaldehyde (MNPA) in triplicate for 24 hours and pooled cDNA indexed paired-end libraries were sequenced (Illumina NextSeq 500). After incubation with arecoline and MNPA, 15 and 39 genes respectively had significant changes in their expression (q<0.05, log fold change 1.5). Eighteen of those genes have reported associations with type 2 diabetes and obesity in humans; of these genes there was strong evidence to implicateCLEC10A,MAPK8IP1,NEGR1,NQ01andINHBE. In summary, these pilot studies have identified a large number of genes whose expression was changed significantly in human TPH1 cells following incubation with arecoline or with 3-methylnitrosaminopropionaldehyde. These findings suggest that further investigation of these genes in betel-quid chewers with obesity and/or type 2 diabetes is warranted.
Mutational Survivorship Bias: The case of PNKP
Authors: Bermudez-Guzman Luis , Jimenez-Huezo Gabriel , Arguedas Andrés , Leal Alejandro 
Published: August 2020

AbstractThe molecular function of a protein relies on its structure. Understanding how mutations alter structure and function in multi-domain proteins, is key to elucidate how a pathological phenotype is generated. However, one may fall into the logical bias of assessing protein damage only based on the mutations that are viable (survivorship bias), which can lead to partial conclusions. This is the case of PNKP, an important nuclear and mitochondrial DNA repair enzyme with kinase and phosphatase function. Most mutations in PNKP are confined to the kinase domain, leading to a pathological spectrum of three apparently distinct clinical entities. Since proteins and domains may have a different tolerance to disease causing mutations, we evaluated whether mutations in PNKP are under survivorship bias. Even when all mutations in the kinase domain are deleterious, we found a mayor mutation tolerability landscape in terms of survival. Instead, the phosphatase domain is less tolerant due to its low mutation rates, higher degree of sequence conservation, lower dN/dS ratios, and more disease-propensity hotspots. Thus, in multi-domain proteins, we propose the term “Wald’s domain” for those who are not apparently more associated with disease, but that are less resistant to mutations in terms of survival. Together, our results support previous experimental evidence that demonstrated that the phosphatase domain is functionally more necessary and relevant for DNA repair, especially in the context of the development of the central nervous system. Thus, this bias should be taken into account when analyzing the mutational landscape in protein structure, function, and finally in disease.