bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signal, bias, and the role of transcriptome assembly quality in phylogenomic inference
Authors: Spillane Jennifer L , LaPolice Troy M , MacManes Matthew D , Plachetzki David C 
Published: July 2020

AbstractThe empirical details of whole transcriptome sequencing and assembly have been thoroughly evaluated, but few studies have addressed how user-defined aspects of the assembly process may influence performance in phylogenomic analyses. Errors in transcriptome assembly could affect ortholog prediction, alignment quality, and phylogenetic signal. Here we investigate the impacts of transcriptome assembly quality in phylogenomic studies by constructing phylogenomic data matrices from alternative transcriptome assemblies representing high-quality and intentionally low-quality assembly outcomes. We leveraged a well-resolved topology for craniates to apply a topological constraint to our analyses, providing a way to quantify phylogenetic signal. Craniates are amply represented in publicly available raw RNA-seq repositories, allowing us to control for transcriptome tissue type as well. By studying the performance of phylogenomic datasets derived from these alternative high- and low-quality inputs in a controlled experiment, we show that high-quality transcriptomes produce richer phylogenomic datasets with partitions that have lower alignment ambiguity, less compositional bias, and stronger phylogenetic signal than low-quality transcriptome assemblies. Our findings demonstrate the importance of transcriptome assembly in phylogenomic analyses and suggest that a portion of the uncertainty observed in phylogenomic studies could be alleviated at the assembly stage.
Co-expression of Mitochondrial Genes and ACE2 in Cornea Involved in COVID-19 Infection
Authors: Yuan Jian , Fan Dandan , Xue Zhengbo , Qu Jia , Su Jianzhong 
Published: July 2020

AbstractThe Coronavirus disease 2019 (COVID-19) pandemic severely challenges public health and necessitates the need for increasing our understanding of COVID-19 pathogenesis, especially host factors facilitating virus infection and propagation. Here, the co-expression network was constructed by mapping the well-known ACE2, TMPRSS2 and host susceptibility genes implicated in COVID-19 GWAS onto a cornea, retinal pigment epithelium and lung. We found a significant co-expression module of these genes in the cornea, revealing that cornea is potential extra-respiratory entry portal of SARS-CoV-2. Strikingly, both co-expression and interaction networks show a significant enrichment in mitochondrial function, which are the hub of cellular oxidative homeostasis, inflammation and innate immune response. We identified a corneal mitochondrial susceptibility module (CMSM) of 14 mitochondrial genes by integrating ACE2 co-expression cluster and SARS-CoV-2 interactome. Gene ECSIT, as a cytosolic adaptor protein involved in inflammatory responses, exhibits the strongest correlation with ACE2 in CMSM, which has shown to be an important risk factor for SARS-CoV-2 infection and prognosis. Our co-expression and protein interaction network analysis uncover that the mitochondrial function related genes in cornea contribute to the dissection of COVID-19 susceptibility and potential therapeutic interventions.
Wireless AI-Powered IoT Sensors for Laboratory Mice Behavior Recognition
Authors: Chen Meng , Liu Yifan , Tam John Chung , Chan Ho-yin , Li Xinyue , Chan Chishing , Li Wen J. 
Published: July 2020

AbstractAccording to the U.S. Department of Agriculture in 2018, there are more than 100 million animals used in research, education, and testing per year. Of the laboratory animals used for research, 95 percent are mice and rats as reported by the Foundation for Biomedical Research (FBR). We present here our work in developing wireless Artificial Intelligent (AI)-powered IoT Sensors (AIIS) for laboratory mice motion recognition utilizing embedded micro-inertial measurement units (uIMUs). Based on the AIIS, we have demonstrated a small-animal motion tracking and recognition system that could recognize 5 common behaviors of mice in cages with accuracy of ~76.23%. The key advantage of this AIIS-based system is to enable high throughput behavioral monitoring of multiple to a large group of laboratory animals, in contrast to traditional video tracking systems that usually track only single or a few animals at a time. The system collects motion data (i.e., three axes linear accelerations and three axes angular velocities) from the IoT sensors attached to different mice, and classifies these data into different behaviors using machine learning algorithms. One of the challenging problems for data analysis is that the distribution of behavior samples is extremely imbalanced. Behaviors such assleepingandwalkingdominate the entire sample set from different mice. However, machine learning algorithms often require a balanced sample set to achieve optimal performance. Thus, several methods are proposed to solve the imbalanced sample problem. Data processing methods for data segmentation, feature extraction, feature selection, imbalanced learning, and machine learning are explored to process motion data includingsleeping, walking, rearing, digging, shaking, grooming, drinking and scratching. For example, by tuning the parameters of a machine-learning algorithm (i.e., Support Vector Machine (SVM)), the average accuracy of classifying five behaviors (i.e., sleeping, walking, rearing, digging and shaking) is 48.07% before solving the imbalance sample issue. To address this problem, an iteration of sample and feature selection is applied to improve the SVM performance. A combination of oversampling and undersampling is used to handle imbalanced classes, and feature selection provides the optimal number of features. The accuracy increases from 48.07% to 76.23% when the optimized combination is used. We further obtained an average accuracy of 86.46% by removingshaking, which is proved to have a negative effect on the overall performance, out of these five behaviors. Furthermore, we were able to classify less frequent behaviors includingrearing, digging, grooming, drinkingandscratchingat an average accuracy of 96.35%.
Single-cell landscape of immunological responses in COVID-19 patients
Authors: Zhang Ji-Yuan , Wang Xiang-Ming , Xing Xudong , Xu Zhe , Zhang Chao , Song Jin-Wen , Fan Xing , Xia Peng , Fu Jun-Liang , Wang Si-Yu , Xu Ruo-Nan , Dai Xiao-Peng , Shi Lei , Huang Lei , Jiang Tian-Jun , Shi Ming , Zhang Yuxia , Zumla Alimuddin , Maeurer Markus , Bai Fan , Wang Fu-Sheng 
Published: July 2020

AbstractIn COVID-19 caused by SARS-CoV-2 infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of five healthy donors and 13 COVID-19 patients including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in COVID-19 patients showed a strong interferon-alpha response, and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4+Effector-GNLY (Granulysin), CD8+Effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during the disease progression.
A hacked kitchen scale-based system for quantification of grip strength in rodents
Authors: Homolak Jan , Virag Davor , Kodvanj Ivan , Matak Ivica , Perhoc Ana Babic , Knezovic Ana , Barilar Jelena Osmanovic , Trkulja Vladimir , Salkovic-Petrisic Melita 
Published: July 2020

AbstractAssessment of neuromuscular function is critical for understanding pathophysiological changes related to motor system dysfunction in many rodent disease models. Among methods used for quantification of grip performance in rodents, gauge-based grip strength meters provide the most reliable results, however, such instruments are unaffordable by many laboratories. Here we demonstrate how to build a rodent grip strength apparatus from scratch using a digital kitchen scale, an empty cage, and a microcontroller, with both hardware and software being completely open-source to enable maximal modularity and flexibility of the instrument in concordance with the principles of open-source bioinstrumentation. Furthermore, we test the griPASTA system for assessment of increased muscular rigidity in the proof-of-concept experiment in the rat model of Parkinson’s disease induced by intrastriatal administration of 6-hydroxydopamine (6-OHDA). Finally, the importance of bioinstrumental customization is demonstrated by utilizing griPASTA for assessment of trial speed from initial-to-maximal deflection time segments and controlling for its potential confounding effects on the grip strength.Significance StatementNeuromuscular function analyzed by grip strength performance tests is an integral part of motor system neuroscience and neurotoxicology. Strain gauge-based grip strength meters provide the most reliable results, however, commercial solutions are unaffordable by many. Consequently, cheap semi-quantitative tests are often used at the expense of precision and reliability. We propose griPASTA – a simple and robust open-source grip strength platform made from an ordinary kitchen scale. griPASTA could improve the quality and reproducibility of grip strength experiments by enabling researchers to obtain quantitative grip strength data in high resolution using a highly customizable platform.
Macroscopic cortical dynamics: Spatially uncorrelated but temporally coherent rich-club organisations in source-space resting-state EEG
Authors: Mehrkanoon Steve 
Published: July 2020

AbstractSynchronous oscillations of neuronal populations support resting-state cortical activity. Recent studies indicate that resting-state functional connectivity is not static, but exhibits complex dynamics. The mechanisms underlying the complex dynamics of cortical activity have not been well characterised. Here, we directly apply singular value decomposition (SVD) in source-reconstructed electroencephalography (EEG) in order to characterise the dynamics of spatiotemporal patterns of resting-state functional connectivity. We found that changes in resting-state functional connectivity were associated with distinct complex topological features, “Rich-Club organisation”, of the default mode network, salience network, and motor network. Rich-club topology of the salience network revealed greater functional connectivity between ventrolateral prefrontal cortex and anterior insula, whereas Rich-club topologies of the default mode networks revealed bilateral functional connectivity between fronto-parietal and posterior cortices. Spectral analysis of the dynamics underlying Rich-club organisations of these source-space network patterns revealed that resting-state cortical activity exhibit distinct dynamical regimes whose intrinsic expressions contain fast oscillations in the alpha-beta band and with the envelope-signal in the timescale of < 0.1 Hz. Our findings thus demonstrated that multivariate eigen-decomposition of source-reconstructed EEG is a reliable computational technique to explore how dynamics of spatiotemporal features of the resting-state cortical activity occur that oscillate at distinct frequencies.
Comparing DNA Extraction and 16s Amplification Methods for Plant-Associated Bacterial Communities
Authors: Giangacomo Cecelia , Mohseni Mohsen , Kovar Lynsey , Wallace Jason G. 
Published: July 2020

AbstractPlant-associated microbes play important roles in global ecology and agriculture. The most common method to profile these microbial communities is amplicon sequencing of the bacterial 16s rRNA gene. Both the DNA extraction and PCR amplification steps of this process are subject to bias, especially since the latter requires some way to exclude DNA from plant organelles, which would otherwise dominate the sample. We compared several common DNA extraction kits and 16s rRNA amplification protocols to determine the relative biases of each and to make recommendations for plant microbial researchers. For DNA extraction, we found that, as expected, kits optimized for soil were the best for soil, though each still included a distinct “fingerprint” of its own biases. Plant samples were less clear, with different species having different “best” options. For 16s amplification, we find that using peptide nucleic acid (PNA) clamps provides the least taxonomic distortion, while chloroplast-discriminating primers are easy and inexpensive but present significant bias in the results. We do not recommend blocking oligos, as they involved a more complex protocol and showed significant taxonomic bias in the results. Further methods development will hopefully result in protocols that are even more reliable and less biased.
Spectrum of pathogenic variants and multiple founder effects in amelogenesis imperfecta associated withMMP20
Authors: Nikolopoulos Georgios , Smith Claire E. L. , Poulter James A. , Murillo Gina , Silva Sandra , Brown Catriona J. , Day Peter F. , Soldani Francesca , Al-Bahlani Suhaila , Harris Sarah A. , O’Connell Mary J. , Inglehearn Chris F. , Mighell Alan J. 
Published: July 2020

AbstractAmelogenesis imperfecta (AI) describes a heterogeneous group of developmental enamel defects that typically have Mendelian inheritance. Exome sequencing of ten families with recessive hypomaturation AI revealed 4 novel and 1 known variants in the matrix metallopeptidase 20 (MMP20) gene that were predicted to be pathogenic.MMP20encodes a protease that cleaves the developing extracellular enamel matrix and is necessary for normal enamel crystal growth during amelogenesis. New homozygous missense changes were shared between four families of Pakistani heritage (c.625G>C; p.(E209Q)) and two of Omani origin (c.710C>A; p.(S237Y)). In two families of UK origin and one from Costa Rica, affected individuals were homozygous for the previously reported c.954-2A>T; p.(I319Ffs*19) variant. For each of these variants, microsatellite haplotypes appeared to exclude a recent founder effect, but elements of haplotype were conserved, suggesting more distant founding ancestors. New compound heterozygous changes were identified in one family of European heritage; c.809_811+12delACGgtaagattattainsCCAG; p.(?) and c.1122A>C; p.(Q374H). All four new variants are within the zinc dependant peptidase domain. This report further elucidates the mutation spectrum ofMMP20and the probable impact on protein function, confirms a consistent hypomaturation phenotype and shows that mutations inMMP20are a common cause of autosomal recessive AI in some communities.Data AvailabilityThe data that support the findings of this study are openly available in ClinVar athttps://www.ncbi.nlm.nih.gov/clinvar/, accession numbers: SCV001338799 - SCV001338802 and in the AI Leiden Open Variation Database (LOVD) athttp://dna2.leeds.ac.uk/LOVD/with reference numbers: 0000000313 – 0000000317.
Characterization of a novel amastin-like surface protein (ALSP) ofLeishmania donovani, a probable lipase
Authors: Biswas Bapi , Laha Bhakti , Sengupta Pratyay , Das Koushik , Ghosh Monidipa 
Published: July 2020

ABSTRACTIn the current study, a novel putative protein ofLeishmania donovani, amastin-like surface protein (ALSP) has been characterized. The gene was cloned in a bacterial system and the protein was overexpressed. A polyclonal antibody was developed against the protein, which detected a 10 kDa band in theL. donovaniamastigote. ALSP mRNA was detected inL. donovaniamastigote, which was not expressed in the promastigote. ALSP mRNA was not expressed in either morphological forms ofLeishmania major. MALDI-TOF confirmed the molecular weight of ALSP as 10 kDa. I-TASSER predicted the function of ALSP as a lipase, which was confirmed by preliminaryin-vitroexperiments using amastigotes ofL. donovani. ALSP has GAS amino acid sequences, which might act as the active site for its lipase activity. The selective expression of ALSP in amastigotes probably makes it important in virulence mechanisms such as survival in the phagolysosome and modulation of its membrane and other metabolic functions, necessary for parasite survival in the human host. ALSP can act as a peptide vaccine target and maybe detected in the peripheral blood or urine as a molecular biomarker of active disease in visceral leishmaniasis.
The essential role of Dnmt1 in gametogenesis in the large milkweed bug Oncopeltus fasciatus
Authors: Washington Joshua T. , Cavender Katelyn R. , Amukamara Ashley U. , McKinney Elizabeth C. , Schmitz Robert J. , Moore Patricia J. 
Published: July 2020

AbstractGiven the importance of DNA methylation in protection of the genome against transposable elements and transcriptional regulation in other taxonomic groups, the diversity in both levels and patterns of DNA methylation in the insects raises questions about its function and evolution. We show that the maintenance DNA methyltransferase, DNMT1, affects meiosis and is essential to fertility in milkweed bugs, Oncopeltus fasciatus, while DNA methylation is not required in somatic cells. Our results support the hypothesis that Dnmt1 is required for the transition of germ cells to gametes in O. fasciatus and that this function is conserved in male and female gametogenesis. They further suggest that DNMT1 has a function independent of DNA methylation in germ cells. Our results raise the question of how a gene so critical in fitness across multiple insect species can have diverged widely across the insect tree of life.
Host transcriptional responses and SARS-CoV-2 isolates from the nasopharyngeal samples of Bangladeshi COVID-19 patients
Authors: Islam Abul Bashar Mir Md. Khademul , Khan Md. Abdullah-Al-Kamran , Ahmed Rasel , Hossain Md. Sabbir , Kabir Shah Md. Tamim , Islam Md. Shahidul , Siddiki A.M.A.M. Zonaed 
Published: July 2020

AbstractAs the COVID-19 pandemic progresses, fatality and cases of new infections are also increasing at an alarming rate. SARS-CoV-2 follows a highly variable course and it is becoming more evident that individual’s immune system has a decisive influence on the progression of the disease. However, the detailed underlying molecular mechanisms of the SARS-CoV-2 mediate disease pathogenesis are largely unknown. Only a few host transcriptional responses in COVID-19 have been reported so far from the Western world, but no such data has been generated from the South-Asian region yet to correlate the conjectured lower fatality around this part of the globe. In this context, we aimed to perform the transcriptomic profiling of the COVID-19 patients from Bangladesh along with the reporting of the SARS-CoV-2 isolates from these patients. Moreover, we performed a comparative analysis to demonstrate how differently the various SARS-CoV-2 infection systems are responding to the viral pathogen. We detected a unique missense mutation at 10329 position of ORF1ab gene, annotated to 3C like proteinase, which is found in 75% of our analyzed isolates; but is very rare globally. Upon the functional enrichment analyses of differentially modulated genes, we detected a similar host induced response reported earlier; this response was mainly mediated by the innate immune system, interferon stimulation, and upregulated cytokine expression etc. in the Bangladeshi patients. Surprisingly, we did not perceive the induction of apoptotic signaling, phagosome formation, antigen presentation and production, hypoxia response within these nasopharyngeal samples. Furthermore, while comparing with the other SARS-CoV-2 infection systems, we spotted that lung cells trigger the more versatile immune and cytokine signaling which was several folds higher compared to our reported nasopharyngeal samples. We also observed that lung cells did not expressACE2in a very high amount as suspected, however, the nasopharyngeal cells are found overexpressingACE2. But the amount ofDPP4expression within the nasal samples was significantly lower compared to the other cell types. Surprisingly, we observed that lung cells express a very high amount of integrins compared to the nasopharyngeal samples, which might suggest the putative reasons for an increased amount of viral infections in the lungs. From the network analysis, we got clues on the probable viral modulation for the overexpression of these integrins. Our data will provide valuable insights in developing potential studies to elucidate the roles of ethnicity effect on the viral pathogenesis, and incorporation of further data will enrich the search of an effective therapeutics.
A psychometric platform to collect somatosensory sensations for neuroprosthetic use
Authors: Valle Giacomo , Iberite Francesco , Strauss Ivo , D’Anna Edoardo , Granata Giuseppe , Stieglitz Thomas , Raspopovic Stanisa , Petrini Francesco M. , Rossini Paolo M. , Micera Silvestro 
Published: July 2020

AbstractSomatosensory neuroprostheses exploit invasive and non-invasive feedback technologies to restore sensorimotor functions lost to disease or trauma. These devices use electrical stimulation to communicate sensory information to the brain. A sensation characterization procedure is thus necessary to determine the appropriate stimulation parameters and to establish a clear personalized map of the sensations that can be restored. Several questionnaires have been described in the literature to collect the quality, type, location and intensity of the evoked sensations, but there is still no standard psychometric platform. Here we propose a new psychometric system containing previously validated questionnaires on evoked sensations, which can be applied to any kind of somatosensory neuroprosthesis. The platform collects stimulation parameters used to elicit sensations; records subjects’ percepts in terms of sensation location, type, quality, perceptual threshold, and intensity. It further collects data using standardized assessment questionnaires and scales, performs measurements over time, and collects phantom limb pain syndrome data. The psychometric platform is user-friendly and provides clinicians with all the information needed to assess the sensory feedback. The psychometric platform was validated with three trans-radial amputees. They platform was used to assess intraneural sensory feedback provided through implanted peripheral nerve interfaces. The proposed platform could act as a new standardized assessment toolbox to homogenize the reporting of results obtained with different technologies in the field of somatosensory neuroprosthetics.