Biology subjects

Malhotra, R.

Publications and source records attributed to Malhotra, R..

At least 19 recordsLinked to original sources

bioRxiv2026

Biomechanical effects of load-carrying in adolescent idiopathic scoliosis: a subject-specific musculoskeletal modelling study

Load carrying is a common activity during adolescence, yet its biomechanical consequences for the structurally asymmetric spine in adolescent idiopathic scoliosis (AIS) remain poorly understood. This study investigated how load magnitude, carrying height, and side of application influence spinal loading and paraspinal muscle forces in AIS. A subject-specific musculoskeletal model of a 16-year-old female with a 59{degrees} right-convex thoracic curve was used to simulate bilateral and unilateral load carrying at the hand, chest, and above-shoulder levels, with loads corresponding to 5%, 10%, and 15% of body weight. Intervertebral compressive and lateral forces and erector spinae (ES) and multifidus (MF) muscle forces were evaluated. Spinal loading increased progressively with load magnitude and carrying height. At 15% body weight, compressive forces at the curve apex increased from 511-566 N at hand level to 721-831 N above the shoulder. Unilateral carrying produced distinct side-dependent responses: convex-side carrying generated greater compressive forces, whereas concave-side carrying generated greater lateral forces, which were concentrated around the curve apex. Paraspinal muscles also exhibited muscle-specific responses. ES forces primarily reflected the imposed external asymmetry, with unilateral carrying eliciting predominantly contralateral recruitment, whereas MF maintained a characteristic convex-side dominance concentrated around the curve apex. These findings demonstrate that load carrying in AIS produces a coupled biomechanical response governed by both the external loading configuration and the pre-existing structural asymmetry of the spine, highlighting the importance of considering loading direction and muscular adaptation alongside load magnitude when evaluating everyday carrying activities in AIS.

bioengineering↗

bioRxiv2026

Influence of trunk posture on spinal loading and paraspinal muscle forces in adolescent idiopathic scoliosis: a subject-specific musculoskeletal modelling study

Adolescent idiopathic scoliosis (AIS) alters spinal geometry and may influence the biomechanical response of the spine during functional postures. However, posture-dependent changes in spinal loading and paraspinal muscle forces in AIS remain poorly understood. This study investigated the effects of trunk posture on intervertebral loading and paraspinal muscle forces using a subject-specific musculoskeletal model of an adolescent with AIS. The spinal deformity was reconstructed from biplanar radiographs and incorporated into a full-body musculoskeletal model. Flexion, extension, lateral bending, and axial rotation were simulated at three incremental magnitudes, with motion distributed across the thoracolumbar spine. Intervertebral compressive and lateral forces around the curve apex and forces in the erector spinae (ES) and multifidus (MF) muscles were evaluated. Trunk flexion produced the greatest compressive loading, reaching 337 N at the curve apex and 372 N two levels below the apex at 30{degrees} flexion. Lateral bending produced pronounced direction-dependent loading: concave-side bending increased lateral forces, whereas convex-side bending increased compressive forces. Axial rotation produced similar but smaller direction-dependent changes. Paraspinal muscle forces were consistently asymmetric, with concave-side dominance of the ES and convex-side dominance of the MF. Flexion and convex-sided movements generally produced greater muscle imbalance, while increasing posture magnitude amplified spinal loading and muscle forces. These findings demonstrate that trunk posture, movement direction, and magnitude substantially influence the biomechanical environment of the scoliotic spine and should be considered when evaluating spinal mechanics in AIS.

bioengineering↗

bioRxiv2026

An ncBAF-ETS2 Chromatin-Remodelling Axis Drives Vascular Smooth Muscle Cell Osteogenic Reprogramming in Vascular Calcification

Introduction: Vascular calcification is a detrimental ageing-related pathology that is markedly accelerated in metabolic disorders. It is driven by osteogenic differentiation of vascular smooth muscle cells (VSMCs), however epigenetic regulatory pathways activated early in this transition remain poorly defined. Methods: An in vitro calcification model was developed using primary human aortic VSMCs cultured with or without mineral stress. Epigenetic changes were assessed using targeted PCR arrays and CUT&RUN sequencing. Key findings were validated in vivo using single-cell sequencing datasets from human large arteries and spatial transcriptomic analysis in atherosclerotic carotid plaques. Transcriptomic and CUT&RUN analyses identified gene targets altered by epigenetic remodelling, and molecular tools were applied to study effects on metabolism, inflammation, apoptosis, and calcification. Results: During early calcification in response to mineral stress, SWI/SNF chromatin remodelling complexes shift toward ncBAF enrichment in pre-osteogenic VSMCs. ncBAF complexes activated transcriptional programs involved in inflammation, apoptosis, and glycolysis-all hallmarks of calcifying VSMCs. The transcription factor ETS2 was identified as a novel component of ncBAF complexes. Disruption of ncBAF or ETS2 impaired osteogenic differentiation and calcification. Notably, ETS2 expression was regulated by ncBAF, forming a positive feedback loop that reinforced VSMC phenotypic switching. Co-activation of ETS2 and ncBAF and the resulting transcriptional shifts were confirmed in human arterial single-cell datasets, with osteogenic/inflammatory clusters showing NFkB and RUNX2 activation. Spatial transcriptomics further suggested that a macrophage-rich microenvironment may promote the differentiation of smooth muscle cells toward an overt osteogenic/inflammatory phenotype. Immunohistochemistry showed that ETS2 levels correlated with calcification severity in human vessels supporting the potential clinical relevance of ETS2. Conclusions: Our findings identify a novel epigenetic mechanism in vascular calcification, where ncBAF and ETS2 cooperate to drive VSMC phenotypic switching. This ncBAF-ETS2 axis represents a potential therapeutic target to modulate VSMC plasticity and intervene early in the progression of cardiovascular calcification.

cell biology↗

bioRxiv2025

A Novel FNDC1-NAMPT-NAD axis is Implicated in Small and Large-vessel Arterial Disease and Drives Vascular Calcification

Vascular calcification represents a convergent pathological feature of diverse cardiovascular diseases, yet the upstream molecular programs orchestrating this process remain poorly defined. Here, we uncover fibronectin type III domain-containing 1 (FNDC1) as a previously unrecognized regulator of vascular calcification across both microvascular and macrovascular beds. Integrative transcriptomic profiling of human calciphylaxis lesions and atherosclerotic coronaries identified FNDC1 as one of the most significantly upregulated genes. In primary human vascular smooth muscle cells, FNDC1 drove osteogenic phenotype switch and vascular calcification through activation of PI3K/AKT signaling and metabolic reprogramming. Mechanistically, FNDC1 directly binds to nicotinamide phosphoribosyltransferase (NAMPT) resulting in elevated intracellular NAD levels, thus coupling vascular signaling to control of NAD biosynthesis. In murine models, genetic deletion of Fndc1 or pharmacologic inhibition of NAMPT suppressed arterial calcification and prolonged survival. Clinically, circulating FNDC1 levels were elevated in patients with both calciphylaxis and coronary artery disease and independently predicted cardiovascular risk in 42,687 UK Biobank participants. Together, these findings establish FNDC1 as a central mediator of vascular pathology and highlight the FNDC1- NAMPT-NAD+ axis as a promising target for therapeutic intervention.

cell biology↗

bioRxiv2024

In vivo Treatment of a Severe Vascular Disease via a Bespoke CRISPR-Cas9 Base Editor

Genetic vascular disorders are prevalent diseases that have diverse etiologies and few treatment options. Pathogenic missense mutations in the alpha actin isotype 2 gene (ACTA2) primarily affect smooth muscle cell (SMC) function and cause multisystemic smooth muscle dysfunction syndrome (MSMDS), a genetic vasculopathy that is associated with stroke, aortic dissection, and death in childhood. Here, we explored genome editing to correct the most common MSMDS-causative mutation ACTA2 R179H. In a first-in-kind approach, we performed mutation-specific protein engineering to develop a bespoke CRISPR-Cas9 enzyme with enhanced on-target activity against the R179H sequence. To directly correct the R179H mutation, we screened dozens of configurations of base editors (comprised of Cas9 enzymes, deaminases, and gRNAs) to develop a highly precise corrective A-to-G edit with minimal deleterious bystander editing that is otherwise prevalent when using wild-type SpCas9 base editors. We then created a murine model of MSMDS that exhibits phenotypes consistent with human patients, including vasculopathy and premature death, to explore the in vivo therapeutic potential of this base editing strategy. Delivery of the customized base editor via an engineered SMC-tropic adeno-associated virus (AAV-PR) vector substantially prolonged survival and rescued systemic phenotypes across the lifespan of MSMDS mice, including in the vasculature, aorta, and brain. Together, our optimization of a customized base editor highlights how bespoke CRISPR-Cas enzymes can enhance on-target correction while minimizing bystander edits, culminating in a precise editing approach that may enable a long-lasting treatment for patients with MSMDS.

bioengineering↗

bioRxiv2024

CINner: modeling and simulation of chromosomal instability in cancer at single-cell resolution

Cancer development is characterized by chromosomal instability, manifesting in frequent occurrences of different genomic alteration mechanisms ranging in extent and impact. Mathematical modeling can help evaluate the role of each mutational process during tumor progression, however existing frameworks can only capture certain aspects of chromosomal instability (CIN). We present CINner, a mathematical framework for modeling genomic diversity and selection during tumor evolution. The main advantage of CINner is its flexibility to incorporate many genomic events that directly impact cellular fitness, from driver gene mutations to copy number alterations (CNAs), including focal amplifications and deletions, missegregations and whole-genome duplication (WGD). We apply CINner to find chromosome-arm selection parameters that drive tumorigenesis in the absence of WGD in chromosomally stable cancer types. We found that the selection parameters predict WGD prevalence among different chromosomally unstable tumors, hinting that the selective advantage of WGD cells hinges on their tolerance for aneuploidy and escape from nullisomy. Direct application of CINner to model the WGD proportion and fraction of genome altered (FGA) further uncovers the increase in CNA probabilities associated with WGD in each cancer type. CINner can also be utilized to study chromosomally stable cancer types, by applying a selection model based on driver gene mutations and focal amplifications or deletions. Finally, we used CINner to analyze the impact of CNA probabilities, chromosome selection parameters, tumor growth dynamics and population size on cancer fitness and heterogeneity. We expect that CINner will provide a powerful modeling tool for the oncology community to quantify the impact of newly uncovered genomic alteration mechanisms on shaping tumor progression and adaptation.

genomics↗

bioRxiv2022

Single-cell multi-omics reveals dynamics of purifying selection of pathogenic mitochondrial DNA across human immune cells

Cells experience intrinsic and extrinsic pressures that affect their proclivity to expand and persist in vivo. In congenital disorders caused by loss-of-function mutations in mitochondrial DNA (mtDNA), metabolic vulnerabilities may result in cell-type specific phenotypes and depletion of pathogenic alleles, contributing to purifying selection. However, the impact of pathogenic mtDNA mutations on the cellular hematopoietic landscape is not well understood. Here, we establish a multi-omics approach to quantify deletions in mtDNA alongside cell state features in single cells derived from Pearson syndrome patients. We resolve the interdependence between pathogenic mtDNA and lineage, including purifying selection against deletions in effector/memory CD8 T-cell populations and recent thymic emigrants and dynamics in other hematopoietic populations. Our mapping of lineage-specific purifying selection dynamics in primary cells from patients carrying pathogenic heteroplasmy provides a new perspective on recurrent clinical phenotypes in mitochondrial disorders, including cancer and infection, with potential broader relevance to age-related immune dysfunction.

genetics↗

bioRxiv2022

Integrative single-cell meta-analysis reveals disease-relevant vascular cell states and markers in human atherosclerosis

Coronary artery disease (CAD) and atherosclerosis are characterized by plaque formation in the arteries wall. CAD progression involves complex interactions and phenotypic plasticity within and between distinct vascular and immune cell lineages. Single-cell RNA-seq (scRNA-seq) studies have highlighted lineage-specific transcriptomic signatures, but the reported cell phenotypes in humans remain controversial. Here, we meta-analyzed four scRNA-seq datasets, creating the first map of human cell diversity in atherosclerosis. We generated an atlas of 118,578 high-quality cells, characterized cell-type diversity and provided insights into smooth muscle cell (SMC) phenotypic modulation, transcription factor activity and cell-cell communication. We integrated genome-wide association study (GWAS) data and uncovered a critical role for modulated SMC phenotypes in CAD and coronary calcification. Finally, we identified candidate markers of fibromyocyte and fibrochondrogenic human SMCs (LTBP1 and CRTAC1) that may serve as proxies of atherosclerosis progression. Altogether, we created a unified cellular map of atherosclerosis informing cell state-specific mechanistic and translational studies of cardiovascular diseases.

genomics↗

bioRxiv2022

FHL5 controls vascular disease-associated gene programs in smooth muscle cells

BackgroundGenome-wide association studies (GWAS) have identified hundreds of loci associated with common vascular diseases such as coronary artery disease (CAD), myocardial infarction (MI), and hypertension. However, the lack of mechanistic insights for a majority of these loci limits translation of these findings into the clinic. Among these loci with unknown functions is UFL1-FHL5 (chr6q16.1), a locus that reached genome-wide significance in a recent CAD/MI GWAS meta-analysis. In addition to CAD/MI, UFL1-FHL5 is also implicated to coronary calcium, intracranial aneurysm, and migraine risk, consistent with the widespread pleiotropy observed among other GWAS loci. MethodsWe apply a multimodal approach leveraging statistical fine-mapping, epigenomic profiling, and imaging of human coronary artery tissues to implicate Four-and-a-half LIM domain 5 (FHL5) as the top candidate causal gene. We unravel the molecular mechanisms of the cross-phenotype genetic associations through in vitro functional analyses and epigenomic profiling experiments. ResultsWe prioritized FHL5 as the top candidate causal gene at the UFL1-FHL5 locus through eQTL colocalization methods. FHL5 gene expression was enriched in the SMC and pericyte population in human artery tissues with coexpression network analyses supporting a functional role in regulating SMC contraction. Unexpectedly, under procalcifying conditions, FHL5 overexpression promoted vascular calcification and dysregulated processes related to extracellular matrix organization and calcium handling. Lastly, by mapping FHL5 binding sites and inferring FHL5 target gene function using artery tissue gene regulatory network analyses, we highlight regulatory interactions between FHL5 and downstream CAD/MI loci, such as FOXL1 and FN1 that have roles in vascular remodeling. ConclusionTaken together, these studies provide mechanistic insights into the pleiotropic genetic associations of UFL1-FHL5. We show that FHL5 mediates vascular disease risk through transcriptional regulation of downstream vascular remodeling loci. These trans-acting mechanisms may account for a portion of the heritable risk for complex vascular diseases.

genomics↗

bioRxiv2022

Effects of larval and adult crowding on fitness components in Drosophila populations adapted to larval crowding experienced under different combinations of food amount and egg number

Since the realization in the 1970s that simple discrete-time population growth models can show complex unstable dynamics of population size, many explanations were proposed for the evolution of enhanced population stability. The most plausible of these was density-dependent selection, suggested to favour greater stability due to r-K trade-offs. However, the first experiment aimed at testing this prediction revealed that Drosophila melanogaster populations adapted to larval crowding did not evolve greater constancy stability than their ancestral controls. A subsequent study showed that D. ananassae populations adapted to larval crowding had evolved greater constancy and persistence than ancestral controls. These D. ananassae populations had experienced chronic larval crowding in conditions of very low amounts of food, whereas the earlier studied D. melanogaster populations had experienced chronic larval crowding at fairly high food amounts. Further theoretical work also suggested that populations adapting to crowding could evolve greater stability even in the absence of r-K trade-offs. Most recently, studies in our laboratory showed that two sets of crowding adapted D. melanogaster populations, derived from a common ancestral lineage, which differed in the food amounts at which they experienced larval crowding, evolved different patterns of constancy and persistence stability. These two sets of populations also differed in the traits, e.g. larval feeding rate, that evolved as they became more competitive. Here, we examine the response of key fitness components to larval and adult densities in these two sets of populations, to see whether differences in their stability attributes can be explained by variation in how their life-histories respond to crowding at different life stages. Of all traits examined, only pre-adult survivorship responded differently to larval density across the two sets of populations. The populations that adapted to larval crowding at low food amounts showed reduced sensitivity of pre-adult survivorship to larval density, compared to those that adapted to larval crowding at high food amounts. We discuss our results in the context of different ways in which density-dependent selection may facilitate the evolution of greater constancy or persistence, depending on the ecological details of how crowding was experienced.

evolutionary biology↗

bioRxiv2022

Anatomical structures, cell types, and biomarkers of the healthy human blood vasculature

More than 150 scientists from 17 consortia are collaborating on an international project to build a Human Reference Atlas, which maps all 37 trillion cells in the healthy adult human body. The initial release of this atlas provided hierarchical lists of the anatomical structures, cell types, and biomarkers in 11 organs. Here, we describe the methods we used as part of this initiative to build the first open, computer-readable, and comprehensive database of the adult human blood vasculature, called the Human Reference Atlas-Vasculature Common Coordinate Framework (HRA-VCCF). It includes 961 vessels and their branching connections, 10 cell types, and 10 biomarkers. With this paper we are releasing additional details on vessel types and subtypes, branching sequence, anastomoses, portal systems, microvasculature, functional tissue units, mappings to regions vessels supply or drain, and links to 3D reference objects. Future versions will add variants, geometric properties of vessels, and connections to the lymph vasculature; and, it will iteratively expand and improve the database as additional experimental data become available through the participating consortia.

cell biology↗

bioRxiv2021

Redox regulation of PTPN22 affects the severity of T cell dependent autoimmune inflammation

Chronic autoimmune diseases are associated with mutations in PTPN22, a modifier of T cell receptor signaling. As with all protein tyrosine phosphatases the activity of PTPN22 is redox regulated, but if or how such regulation can modulate inflammatory pathways in vivo is not known. To determine this, we created a mouse with a cysteine-to-serine mutation at position 129 in PTPN22 (C129S), a residue proposed to alter the redox regulatory properties of PTPN22 by forming a disulfide with the catalytic C227 residue. The C129S mutant mouse showed a stronger T cell-dependent inflammatory response and development of T cell dependent autoimmune arthritis due to enhanced TCR signaling and activation of T cells, an effect neutralized by a mutation in Ncf1, a component of the NOX2 complex. Activity assays with purified proteins suggest that the functional results can be explained by an increased sensitivity to oxidation of the C129S mutated PTPN22 protein. We also observed that the disulfide of native PTPN22 can be directly reduced by the thioredoxin system, while the C129S mutant lacking this disulfide was less amenable to reductive reactivation. In conclusion, we show that PTPN22 functionally interacts with Ncf1 and is regulated by oxidation via the non-catalytic C129 residue and oxidation-prone PTPN22 leads to increased severity in the development of T cell-dependent autoimmunity. Significance statementA hitherto unstudied aspect of PTPN22 biology is its regulation by cell redox states. Here we created a mouse model where PTPN22 was mutated to respond differentially to redox levels in vivo and found that PTPN22 function is regulated by reactive oxygen species and that redox regulation of PTPN22 impacts T-cell-dependent autoimmune inflammation.

immunology↗

bioRxiv2021

Anatomical Structures, Cell Types, and Biomarkers Tables Plus 3D Reference Organs in Support of a Human Reference Atlas

1.This paper reviews efforts across 16 international consortia to construct human anatomical structures, cell types, and biomarkers (ASCT+B) tables and three-dimensional reference organs in support of a Human Reference Atlas. We detail the ontological descriptions and spatial three-dimensional anatomical representations together with user interfaces that support the registration and exploration of human tissue data. Four use cases are presented to demonstrate the utility of ASCT+B tables for advancing biomedical research and improving health.

cell biology↗

bioRxiv2021

Dysfunctional vascular smooth muscle cells mediate early and late-stage neuroinflammation and Tau hyperphosphorylation

Despite the emerging evidence implying early vascular contributions to neurogenerative syndromes, the role of vascular smooth muscle cells (VSMCs) in the pathogenesis of Alzheimers disease is still not well understood. Herein, we show that VSMCs in brains of AD patients and the animal model of the disease, are deficient in multiple VSMC-contractile markers which correlated with Tau accumulation in brain arterioles. Ex vivo and in vitro experiments demonstrated that VSMCs undergo dramatic phenotypic transitions under AD-like conditions, adopting pro-inflammatory and synthetic phenotypes. Notably, these changes coincided with Tau hyperphosphorylation at residues Y18, T205 and S262. We also observed that loss of VSMC markers occurred in an age-dependent manner, and that expression of Sm22 and -Sma proteins were inversely correlated with CD68 and Tau accumulation in brain arterioles of 3xTg-AD mice. Together, these findings further support the contribution of VSMCs in AD pathogenesis, and nominate VSMCs as potential novel therapeutic target in AD. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=160 SRC="FIGDIR/small/439741v1_ufig1.gif" ALT="Figure 1"> View larger version (87K): org.highwire.dtl.DTLVardef@8b1648org.highwire.dtl.DTLVardef@163dc88org.highwire.dtl.DTLVardef@123677borg.highwire.dtl.DTLVardef@15eed09_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

The evolutionary history of a gammaretrovirus currently colonizing the mule deer genome is marked by extensive recombination

All vertebrate genomes have been colonized by retroviruses along their evolutionary trajectory. While endogenous retroviruses (ERVs) can contribute important physiological functions to contemporary hosts, such benefits are attributed to long-term co-evolution of ERV and host because germline infections are rare and expansion is slow, because the host effectively silences them. The genomes of several outbred species including mule deer (Odocoileus hemionus) are currently being colonized by ERVs, which provides an opportunity to study ERV dynamics at a time when few are fixed. Because we have locus-specific data on the distribution of cervid endogenous retrovirus (CrERV) in populations of mule deer, in this study we determine the molecular evolutionary processes acting on CrERV at each locus in the context of phylogenetic origin, genome location, and population prevalence. A mule deer genome was de novo assembled from short and long insert mate pair reads and CrERV sequence generated at each locus. CrERV composition and diversity have recently measurably increased by horizontal acquisition of a new retrovirus lineage. This new lineage has further expanded CrERV burden and CrERV genomic diversity by activating and recombining with existing CrERV. Resulting inter-lineage recombinants endogenized and subsequently retrotransposed. CrERV loci are significantly closer to genes than expected if integration were random and gene proximity might explain the recent expansion by retrotransposition of one recombinant CrERV lineage. Thus, in mule deer, retroviral colonization is a dynamic period in the molecular evolution of CrERV that also provides a burst of genomic diversity to the host population.

genomics↗

bioRxiv2020

Patch characteristics and domestic dogs differentially affect carnivore space use in fragmented landscapes in Southern Chile

In an increasingly anthropogenic world, native species face multiple interacting threats. Habitat fragmentation and domestic dogs are two such perturbations threatening terrestrial mammals globally. Here, we implemented a camera trap survey in the fragmented central valley/Andean foothills transition of the Los Lagos Region in Southern Chile to evaluate space use of native carnivores in a landscape comprised of patches of native forest amidst a matrix of pastureland. Using an occupancy modeling framework to account for imperfect detection, we examined the impacts of dogs and landscape metrics of fragmentation on three mesocarnivores - the foxes culpeo (Lycalopex culpaeus) and chilla (Lycalopex griseus) and the wild cat guina (Leopardus guigna). Factors driving occupancy differed for each of the native species, while detection rates for both canid species increased with dog occupancy. We found that a small (12%) simulated increase in dog occupancy negatively impacted the spatial use of the culpeo. Habitat loss and fragmentation were positive drivers for the chilla and the dog, and indirectly impacted the culpeo through the domestic dog. The guina did not respond to fragmentation and other habitat covariates or dog occupancy. Instead, all native carnivore species temporally partitioned diel activity with dogs. We highlight that the effects of dogs or fragmentation are not ubiquitous across the carnivore guild with varied tolerance. However, future conditions of increased fragmentation and habitat loss will likely increase the potential contact between domestic dogs and native carnivores.

ecology↗

bioRxiv2020

Structural and functional analysis of female sex hormones against SARS-Cov2 cell entry

Emerging evidence suggests that males are more susceptible to severe infection by the SARS-CoV-2 virus than females. A variety of mechanisms may underlie the observed gender-related disparities including differences in sex hormones. However, the precise mechanisms by which female sex hormones may provide protection against SARS-CoV-2 infectivity remains unknown. Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor. We further observed that glycosylation of the ACE2 receptor enhances SARS-CoV-2 infectivity. Importantly estrogens can disrupt glycan-glycan interactions and glycan-protein interactions between the human ACE2 and the SARS-CoV2 thereby blocking its entry into cells. In a mouse model, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein. These results shed light on a putative mechanism whereby female sex hormones may provide protection from developing severe infection and could inform the development of future therapies against COVID-19.

cell biology↗

bioRxiv2020

Michigan ZoomIN: validating crowd-sourcing to identify mammals from camera surveys

Camera trap studies have become a popular medium to assess many ecological phenomena including population dynamics, patterns of biodiversity, and monitoring of endangered species. In conjunction with the benefit to scientists, camera traps present an unprecedented opportunity to involve the public in scientific research via image classifications. However, this engagement strategy comes with a myriad of complications. Volunteers vary in their familiarity with wildlife, and thus, the accuracy of user-derived classifications may be biased by the commonness or popularity of species and user-experience. From an extensive multi-site camera trap study across Michigan U.S.A, images were compiled and identified through a public science platform called Michigan ZoomIN. We aggregated responses from 15 independent users per image using multiple consensus methods to assess accuracy by comparing to species identification completed by wildlife experts. We also evaluated how different factors including consensus algorithms, study area, wildlife species, user support, and camera type influenced the accuracy of user-derived classifications. Overall accuracy of user-derived classification was 97%; although, several canid (e.g., Canis lupus, Vulpes vulpes) and mustelid (e.g., Neovison vison) species were repeatedly difficult to identify by users and had lower accuracy. When validating user-derived classification, we found that study area, consensus method, and user support best explained accuracy. To continue to overcome stigma associated with data from untrained participants, we demonstrated their value by showing the accuracy from volunteers was comparable to experts when classifying North American mammals. Our hierarchical workflow that integrated multiple consensus methods lead to more image classifications without extensive training and even when the expertise of the volunteer was unknown. Ultimately, adopting such an approach can harness broader participation, expedite future camera trap data synthesis, and improve allocation of resources by scholars to enhance performance of public participants and increase accuracy of user-derived data.

ecology↗