Miracle-dz/UniFAR-FTUs huggingface dataset:
Mucosal gene expression in response to SARS-CoV-2 is associated with early viral load

Little is known about the relationships between symptomatic early-time SARS-CoV-2 viral load and upper airway mucosal gene expression and immune response. To examine the association of symptomatic SARS-CoV-2 early viral load with upper airway mucosal gene expression, we profiled the host mucosal transcriptome from nasopharyngeal swab samples from 68 adults with symptomatic, mild-to-moderate COVID-19. We measured SARS-CoV-2 viral load using qRT-PCR. We then examined the association of SARS-CoV-2 viral load with upper airway mucosal immune response. We detected SARS-CoV-2 in all samples and recovered >80% of the genome from 85% of the samples from symptomatic COVID-19 adults. The respiratory virome was dominated by SARS-CoV-2, with limited co-detection of common respiratory viruses i.e., only the human Rhinovirus (HRV) being identified in 6% of the samples. We observed a significant positive correlation between SARS-CoV-2 viral load and interferon signaling (OAS2, OAS3, IFIT1, UPS18, ISG15, ISG20, IFITM1, and OASL), chemokine signaling (CXCL10 and CXCL11), and adaptive immune system (IFITM1, CD300E, and SIGLEC1) genes in symptomatic, mild-to-moderate COVID-19 adults, when adjusted for age, sex and race. Interestingly, the expression levels of most of these genes plateaued at a CT value of ~25. Overall, our data shows that early nasal mucosal immune response to SARS-CoV-2 infection is viral load dependent, which potentially could modify COVID-19 outcomes. AUTHOR SUMMARY Several prior studies have shown that SARS-CoV-2 viral load can predict the likelihood of disease spread and severity. A higher detectable SARS-CoV-2 plasma viral load was associated with worse respiratory disease severity. However, the relationship between SARS-CoV-2 viral load and airway mucosal gene expression and immune response remains elusive. We profiled the nasal mucosal transcriptome from nasal samples collected from adults infected with SARS-CoV-2 during Spring 2020 with mild-to-moderate symptoms using a comprehensive metatranscriptomics method. We observed a positive correlation between SARS-CoV-2 viral load with interferon signaling, chemokine signaling, and adaptive immune system in adults with COVID-19. Our data suggest that early nasal mucosal immune response to SARS-CoV-2 infection was viral load-dependent and may modify COVID-19 outcomes.
The UbiB family member Cqd1 forms a novel membrane contact site in mitochondria

Mitochondria are essential organelles of eukaryotic cells that are characterized by their unique and complex membrane system. They are confined from the cytosol by an envelope consisting of two membranes. Signals, metabolites, proteins and lipids have to be transferred across these membranes via proteinaceous contact sites to keep mitochondria functional. In the present study we identified a novel mitochondrial contact site that is formed by the inner membrane protein Cqd1 and the outer membrane proteins Por1 and Om14. Similar to the mitochondrial porin, Por1, Cqd1 is highly conserved, suggesting that this complex is conserved in form and function from yeast to human. Cqd1 is a member of the UbiB protein kinase-like family (also called aarF domain containing kinases). It was recently shown that Cqd1 in cooperation with Cqd2 controls the cellular distribution of coenzyme Q by a yet unknown mechanism. Our data suggest that Cqd1 in addition is involved in the homeostasis of phospholipids and contributes to the maintenance of mitochondrial morphology and architecture. Summary statement Here, we show that the conserved mitochondrial inner membrane protein Cqd1 interacts with the outer membrane proteins Por1 and Om14. Additionally, we provide evidence that Cqd1 is important for maintaining mitochondrial homeostasis.
FBXW7 triggers degradation of WDR5 to prevent mitotic slippage

During prolonged mitotic arrest induced by anti-microtubule drugs, cell fate decision is determined by two alternative pathways, one leading to cell death, the other inducing premature escape from mitosis by mitotic slippage. FBWX7, a member of the F-box family of proteins and substrate-targeting subunit of the SCF (SKP1-CUL1-F-Box) E3 ubiquitin ligase complex promotes mitotic cell death and prevents mitotic slippage. In this study, we report that WDR5, a component of the mixed lineage leukemia (MLL) complex of Histone 3 Lysine 4 (H3K4) methyltransferases is a substrate of FBXW7. WDR5 binds to FBXW7 in vivo and in vitro and its ubiquitin-mediated proteasomal degradation is mediated by FBXW7. Furthermore, we find that WDR5 depletion counteracts FBXW7 loss-of-function by reducing mitotic slippage and polyploidization. Our data elucidate a new mechanism in mitotic cell fate regulation which might contribute to prevent chemotherapy resistance in patients after anti-microtubule drug treatment.
Myosin-dependent partitioning of junctional Prickle2 toward the anterior vertex during planar polarization of Xenopus neuroectoderm

Planar cell polarity (PCP) of tissues is established by mutually exclusive partitioning of transmembrane proteins Frizzled and Vangl with their respective binding partners, Dishevelled and Prickle. While the amplification and maintenance of this pattern have been well studied, it remains unclear how the anterior-biased protein localization is initiated. Moreover, PCP protein complexes are located at adherens junctions and their polarization requires the activity of non-muscle myosin II (NMII), but how NMII contributes to PCP is not fully understood. Here we analyze time-lapse images of mNeonGreen-tagged Prickle2 (Pk2) in mid-gastrula stage Xenopus presumptive neuroectoderm and demonstrate that Pk2 puncta move along bicellular apical junctions in a biased manner toward the anterior vertex, where the Vangl-Pk complexes are normally enriched. In addition, length changes of bicellular junction segments flanking each Pk2 punctum are often different from each other, and appear more dynamic near the vertices, suggesting that Pk2 movement is driven by intrinsic junction heterogeneity. Reducing NMII activity eliminates the anterior movement, and surprisingly, increases the motility of Pk2 punta. By assessing the correlation between Pk2 movement and the relative positioning of each Pk2 punctum along apical junctions, we uncovered that NMII activity is required for the anterior Pk2 movement by maintaining the elongation of posterior junction segment while inhibiting Pk2 movement toward both vertices flanking the junctions. Our findings provide the first evidence of biased partitioning of junctional PCP proteins toward the anterior vertex and support the hypothesis that NMII activity facilitates Pk2 polarization not via a direct transport but by regulating intrinsic dynamics of the bicellular junction.
JNK Signalling Regulates Self-Renewal of Proliferative Urine-Derived Renal Progenitor Cells via Inhibition of Ferroptosis

With a global increase in chronic kidney disease patients, alternatives to dialysis and organ transplantation are needed. Stem cell-based therapies could be one possibility to treat chronic kidney disease. Here, we used multipotent urine-derived renal progenitor cells (UdRPCs) to study nephrogenesis. UdRPCs treated with the JNK inhibitor-AEG3482, displayed decreased proliferation and downregulated transcription of cell cycle-associated genes as well as the kidney progenitor markers -SIX2, CITED1, and SALL1. In addition, levels of activated SMAD2/3, which is associated with the maintenance of self-renewal in UdRPCs, were decreased. JNK inhibition resulted in less efficient oxidative phosphorylation and more lipid peroxidation via ferroptosis-an iron-dependent non-apoptotic cell death pathway linked to various forms of kidney disease. Our study reveals the importance of JNK signalling in maintaining self-renewal as well as protection against ferroptosis in SIX2-positive UdRPCs. We propose that UdRPCs can be used for modelling ferroptosis-induced kidney diseases.
Reprogramming of fish somatic cells for nuclear transfer is primed by Xenopus egg extract

Somatic cell reprogramming in vitro prior to nuclear transfer is one strategy expected to improve clone survival during development. In this study, we investigated the reprogramming extent of fish fin somatic cells after in vitro exposure to Xenopus egg extract and subsequent culture. Using a cDNA microarray approach, we observed drastic changes in the gene expression profile of the treated cells. Several actors of the TGFβ and Wnt/β-catenin signaling pathways, as well as some mesenchymal markers, were inhibited in treated cells, while several epithelial markers were upregulated. This was associated with morphological changes of the cells in culture, suggesting that egg extract drove somatic cells towards a mesenchymal-epithelial transition (MET), the hallmark of somatic reprogramming in induced pluripotent stem cells (iPSCs). However, treated cells were also characterized by a strong decrease in de novo lipid biosynthesis metabolism, the lack of re-expression of pou2 and nanog pluripotency markers, and absence of DNA methylation remodeling of their promoter region. In all, this study showed that Xenopus egg extract treatment initiated an in vitro reprogramming of fin somatic cells in culture. Although not thorough, the induced changes have primed the somatic chromatin for a better embryonic reprogramming upon nuclear transfer.
Plasma proteome perturbation for CMV DNAemia in kidney transplantation

Background Cytomegalovirus (CMV) infection, either de novo or as reactivation after allotransplantation and chronic immunosuppression, is recognized to cause detrimental alloimmune effects, inclusive of higher susceptibility to graft rejection and substantive impact on chronic graft injury and reduced transplant survival. To obtain further insights into the evolution and pathogenesis of CMV infection in an immunocompromised host we evaluated changes in the circulating host proteome serially, before and after transplantation, and during and after CMV DNA replication (DNAemia), as measured by quantitative polymerase chain reaction (QPCR). Methods LC-MS-based proteomics was conducted on 168 serially banked plasma samples, from 62 propensity score-matched kidney transplant recipients. Patients were stratified by CMV replication status into 31 with CMV DNAemia and 31 without CMV DNAemia. Patients had blood samples drawn at protocol times of 3- and 12-months post-transplant. Additionally, blood samples were also drawn before and 1 week and 1 month after detection of CMV DNAemia. Plasma proteins were analyzed using an LCMS 8060 triple quadrupole mass spectrometer. Further, public transcriptomic data on time matched PBMCs samples from the same patients was utilized to evaluate integrative pathways. Data analysis was conducted using R and Limma. Results Samples were segregated based on their proteomic profiles with respect to their CMV Dnaemia status. A subset of 17 plasma proteins was observed to predict the onset of CMV at 3 months post-transplant enriching platelet degranulation (FDR, 4.83E-06), acute inflammatory response (FDR, 0.0018), blood coagulation (FDR, 0.0018) pathways. An increase in many immune complex proteins were observed at CMV infection. Prior to DNAemia the plasma proteome showed changes in the anti-inflammatory adipokine vaspin (SERPINA12), copper binding protein ceruloplasmin (CP), complement activation (FDR=0.03), and proteins enriched in the humoral (FDR=0.01) and innate immune responses (FDR=0.01). Conclusion Plasma proteomic and transcriptional perturbations impacting humoral and innate immune pathways are observed during CMV infection and provide biomarkers for CMV disease prediction and resolution. Further studies to understand the clinical impact of these pathways can help in the formulation of different types and duration of anti-viral therapies for management of CMV infection in the immunocompromised host.
Development of molecular markers of the Kunitz trypsin inhibitor mutant alleles generated by CRISPR/Cas9-mediated mutagenesis in soybean

The digestibility of soybean meal can be severely impacted by trypsin inhibitor (TI), one of the most abundant anti-nutritional factors present in soybean seeds. TI can restrain the function of trypsin, a critical enzyme that breaks down proteins in the digestive tract. Soybean accessions with low TI content have been identified. However, it is challenging to breed the low TI trait into elite cultivars due to a lack of molecular markers associated with low TI traits. We identified Kunitz trypsin inhibitor 1 (KTI1, Glyma01g095000) and KTI3 (Glyma08g341500) as two seed-specific TI genes. Mutant kti1 and kti3 alleles carrying small deletions or insertions within the gene open reading frames were created in the soybean cultivar Glycine max cv. Williams 82 (WM82) using the CRISPR/Cas9-mediated genome editing approach. The KTI content and TI activity both remarkably reduced in kti1/3 mutants compared to the WM82 seeds. There was no significant difference in terms of plant growth or maturity days of kti1/3 transgenic and WM82 plants in greenhouse condition. We further identified a T1 line, #5-26, that carried double homozygous kti1/3 mutant alleles, but not the Cas9 transgene. Based on the sequences of kti1/3 mutant alleles in #5-26, we developed markers to co-select for these mutant alleles by using a gel-electrophoresis-free method. The kti1/3 mutant soybean line and associated selection markers will assist in accelerating the introduction of low TI trait into elite soybean cultivars in the future.
Dynamics of bacterial recombination in the human gut microbiome

Horizontal gene transfer is a ubiquitous force in microbial evolution. Previous studies have shown that the human gut is a hot spot for gene transfer between species, but the more subtle exchange of variation within species – collectively known as recombination – remains poorly characterized in this ecosystem. Here, we show how the genetic structure of the human gut microbiome provides a unique opportunity to measure individual recombination events from sequenced fecal samples, enabling quantitative comparisons of recombination across a diverse range of species that inhabit a common environment. By analyzing a large collection of recent recombination events in the core genomes of 29 gut commensals, we uncovered systematic heterogeneities in the rates and lengths of transferred segments, which are difficult to explain by existing models of ecological isolation or homology-dependent recombination rates. We also find that natural selection plays a role in facilitating the spread of genetic variants onto different strain backgrounds, both within individual hosts and across the broader global population. These results shed light on the dynamics of in situ recombination, which place important constraints on the adaptability of gut microbial communities.
Effect of reduced genomic representation on using runs of homozygosity for inbreeding characterization

Runs of homozygosity (ROHs) are proxy for genomic Identical-by-Descent segments and are increasingly used to measure individual inbreeding. ROHs analyses are mostly carried out on SNPs-arrays and whole-genome-sequencing data. Softwares recurrently used for their detection usually assume that genomic positions which have not been genotyped are non-variant. This might be true for whole-genome-sequencing data, but not for reduced genomic representations and can lead to spurious ROHs detection. We simulated the outputs of whole-genome-sequencing, two SNP-arrays and RAD-sequencing for three populations with different sizes. We compare the results of ROHs calling with two softwares: PLINK and RZooRoH. We demonstrate that to obtain meaningful estimates of inbreeding coefficients, RZooRoH requires fraction of genome seven times smaller compared to PLINK. When the SNP density is above 20 SNPs/Mb for PLINK and 3 SNPs/Mb for RZooRoH, ranks of ROHs-based inbreeding coefficients are conserved among individuals. With reduced genomic representations, ROHs distributions are consistently biased towards an underestimation of the total numbers of small and an overestimation of the total numbers of large ROHs, except for RZooRoH and high-density SNPs-arrays. We conclude that both ROHs-based inbreeding coefficients and ROHs distributions exact quantification are highly dependent on the fraction of genome sequenced and should thus be treated with caution. However, relative inbreeding estimates, such as comparison between individuals or populations, are reliable with reduced genomic representations providing that the fraction of genome sequenced is large enough. Consequently, we advise researchers working with reduced genomic data to use SNPs-independent measures or model-based ROHs calling methods for inbreeding estimations.
Human-sloth bear conflict in Nepal – case study from an unprotected Churia forest

Human-sloth bear conflict is common throughout most areas where sloth bears coexist with humans. Though similar reports are available from different parts of Nepal’s lowlands, comprehensive studies that can inform human safety and conflict mitigation are highly lacking. We used data from questionnaire-based interviews with conflict-affected people and witnesses to provide detailed information about human-sloth bear conflict (1990-2021) in the Trijuga forest, an important but unprotected area for sloth bear conservation in Nepal. The data were analyzed using descriptive statistics, chi-square tests, and regression analysis. For the time period, 66 conflict incidents involving 69 human individuals were recorded, with an annual average of 2.06 (SD = 1.48) incidents and 1.80 (SD = 1.32) attacks. The attacks injured 59 people with a fatality rate of 8.47% among those that were injured. Conflicts primarily impacted people from minority ethnic groups and mostly affected men. Victims were generally of working age group (25 – 55), engaged in farming, and frequented the forest regularly for resources. Conflicts typically occurred between 0900 and 1500, inside forests, and in places of poor land cover visibility. Poor visibility was also a significant positive determinant of bear attacks on humans. Despite statistically insignificant variation in conflicts across seasons or months, they tended to be more prevalent during the monsoon and post-monsoon seasons. Victims of bear attacks frequently had serious injuries, especially to the head and neck area of the body. Serious injuries were more likely to occur to lone individuals than to people who were in groups of two or more. Taking into account sloth bear ecology and the socio-demographic profile of the conflict victims, we discuss measures that can promote coexistence between humans and sloth bears in light of the findings.
Rapid bilevel optimization to concurrently solve musculoskeletal scaling, marker registration, and inverse kinematic problems for human motion reconstruction

Creating large-scale public datasets of human motion biomechanics could unlock data-driven breakthroughs in our understanding of human motion, neuromuscular diseases, and assistive devices. However, the manual effort currently required to process motion capture data is costly and limits the collection and sharing of large-scale biomechanical datasets. We present a method to automate and standardize motion capture data processing: bilevel optimization that is able to scale the body segments of a musculoskeletal model, register the locations of optical markers placed on an experimental subject to the markers on a musculoskeletal model, and compute body segment kinematics given trajectories of experimental markers during a motion. The optimization requires less than five minutes of computation to process a subject’s motion capture data, compared with about one day of manual work for a human expert. On a sample of 34 trials of experimental data, the root-mean-square marker reconstruction error (RMSE) was 1.38 cm, approximately 40% lower than the 2.58 cm achieved manually by 3 experts. Optimization solutions reconstructed known joint angle trajectories from four diverse motion trials of synthetic data to an average of 0.79 degrees RMSE. We have published an open source cloud service at AddBiomechanics.org to process experimental motion capture data, which is available at no cost and asks that users agree to share processed and de-identified data with the community. Reducing the barriers to processing and sharing high-quality human motion biomechanics data will enable more people to engage in state-of-the-art biomechanical analysis in their work, do so at lower cost, and share larger and more accurate datasets. Author summary Creating large-scale public datasets of human motion could unlock data-driven breakthroughs in our understanding of neuromuscular diseases, assistive devices, and human motion more broadly. The manual effort currently required to process these motion datasets is costly and limits the collection and sharing of large-scale datasets. Our cloud-based software tool, called AddBiomechanics, uses state-of-the-art optimization techniques to automatically scale the body segments of a musculoskeletal model to match the subject of interest, and then compute body segment kinematics during a motion. The optimization requires less than five minutes of computation to process a subject’s motion capture data, compared with about one day of manual work for a human expert. The accuracy of the approach in quantifying the body segment kinematics is as good or better than the results achieved manually by experts. Reducing the barriers to processing and sharing high-quality human motion biomechanics data will enable more people to engage in state-of-the-art biomechanical analysis, do so at lower cost, and share larger and more accurate datasets.
Interspecific territoriality has facilitated recent increases in the breeding habitat overlap of North American passerines

As species’ ranges shift in response to human-induced global changes, species interactions are expected to play a large role in shaping the resultant range dynamics and, subsequently, the composition of modified species assemblages. Most research on the impact of species interactions on range dynamics focuses on the effects of trophic interactions and exploitative competition for resources, but an emerging body of work shows that interspecific competition for territories and mates also affects species range shifts. As such, it is paramount to build a strong understanding of how these forms of behavioural interference between species impact landscape-scale patterns. Here, we examine recent (1997-2019) range dynamics of North American passerines to test the hypothesis that behavioural interference impacts the ease with which species move across landscapes. Over this 22-year period, we found that fine-scale spatial overlap between species (syntopy) increased more for species pairs that engage in interspecific territoriality than for those that do not. We found no evidence, however, for an effect of reproductive interference (hybridisation) on syntopy, and no effect of either type of interference on range-wide overlap (sympatry). Examining the net effects of species interactions on continent-scale range shifts may require species occurrence data spanning longer time periods than are currently available for North American passerines, but our results show that interspecific territoriality has had an overall stabilising influence on species coexistence over the past two decades.