Find research datasets worth reusing

opencc-zeroJun 2022View details →

Associated data for: Disease and weather induce rapid shifts in a rangeland ecosystem mediated by a keystone species (Cynomys ludovicianus)

Habitat loss and changing climate have direct impacts on native species but can also interact with disease pathogens to influence wildlife communities. In the North American Great Plains, black-tailed prairie dogs (Cynomys ludovicianus) are a keystone species that create important grassland habitat for numerous species and serve as prey for predators, but lethal control driven by agricultural conflict has severely reduced their abundance. Novel disease dynamics caused by epizootic plague (Yersinia pestis) within prairie dog colonies have further reduced prairie dog abundances, in turn destabilizing associated wildlife communities. We capitalized on a natural experiment — collecting data on prairie dog distributions, vegetation structure, avian abundance, and mesocarnivore and ungulate occupancy before (2015–2017) and after (2018–2019) a plague event in northeastern Wyoming, USA. Plague decimated black-tailed prairie dog populations in what was then the largest extant colony complex, reducing colony cover in the focal area from over 10,000 ha to less than 50 ha. We documented dramatic declines in mesocarnivore occupancy and raptor abundance post-plague, with probability of occupancy or abundance approaching zero in species that rely on prairie dogs for a high proportion of their diet (e.g., ferruginous hawk [Buteo regalis], American badger [Taxidea taxus], and swift fox [Vulpes velox]). Following the plague outbreak, abnormally high precipitation in 2018 hastened vegetation recovery from prairie dog disturbance on colonies where constant herbivory had formerly maintained shortgrass structure necessary for certain colony-associates. As a result, we observed large shifts in avian communities on former prairie dog colonies, including near-disappearance of mountain plovers (Charadrius montanus) and increases in mid-grass associated songbirds (e.g., lark bunting [Calamospiza melanocorys]). Our research highlights how precipitation can interact with disease-induced loss of a keystone species to induce drastic and rapid shifts in wildlife communities. Although grassland taxa co-evolved with high spatiotemporal variation, fragmentation of remaining North American rangelands paired with higher-than-historical variability in climate and disease dynamics are likely to destabilize these systems in the future.

opencc-by-4.0Jun 2022View details →

Multimodal single cell analysis of the paediatric lower airway reveals novel immune cell phenotypes in early life health and disease

RDS files of SingleCellExperiment objects containing raw single cell RNA-seq count data required to replicate the analyses presented at: <a href="https://oshlacklab.com/paed-cf-cite-seq/">https://oshlacklab.com/paed-cf-cite-seq/</a> and described in the pre-print titled: "Multimodal single cell analysis of the paediatric lower airway reveals novel immune cell phenotypes in early life health and disease". Instructions for how to incorporate the raw data into the analysis can be found at: <a href="https://oshlacklab.com/paed-cf-cite-seq/gettingStarted.html">https://oshlacklab.com/paed-cf-cite-seq/gettingStarted.html</a> and the complete analysis code and additional data files can be cloned/downloaded from: <a href="https://github.com/Oshlack/paed-cf-cite-seq">https://github.com/Oshlack/paed-cf-cite-seq</a>.

opencc-zeroJun 2022View details →

Parkinson's disease-associated, sex-specific changes in DNA methylation at PARK7 (DJ-1), ATXN1, SLC17A6, NR4A2, and PTPRN2 in cortical neurons

Evidence for epigenetic regulation playing a role in Parkinson's disease (PD) is growing, particularly for DNA methylation. Approximately 90% of PD cases are due to a complex interaction between age, genes, and environmental factors, and epigenetic marks are thought to mediate the relationship between aging, genetics, the environment, and disease risk. To date, there are a small number of published genome-wide studies of DNA methylation in PD, but none accounted for cell-type or sex in their analyses. Given the heterogeneity of bulk brain tissue samples and known sex differences in PD risk, progression, and severity, these are critical variables to account for. In this first genome-wide analysis of DNA methylation in an enriched neuronal population from PD post-mortem parietal cortex, we report sex-specific PD-associated methylation changes in PARK7 (DJ-1), SLC17A6 (VGLUT2), PTPRN2 (IA-2β), NR4A2 (NURR1), and other genes involved in developmental pathways, neurotransmitter packaging and release, and axon and neuron projection guidance.

opencc-by-4.0Jun 2022View details →

Source Data files for: Primary cilia and SHH signaling impairments in human and mouse models of Parkinson's disease

Parkinson’s disease (PD) as a progressive neurodegenerative disorder arises from multiple genetic and environmental factors. However, underlying pathological mechanisms remain poorly understood. Using multiplexed single-cell transcriptomics, we analyze human neural precursor cells (hNPCs) from sporadic PD (sPD) patients. Alterations in gene expression appear in pathways related to primary cilia (PC). Accordingly, in these hiPSC-derived hNPCs and neurons, we observe a shortening of PC. Additionally, we detect a shortening of PC in PINK1-deficient human cellular and mouse models of familial PD. Furthermore, in sPD models, the shortening of PC is accompanied by an increased SHH signal transduction. Inhibition of this pathway rescues the alterations in PC morphology and mitochondrial dysfunction. Thus, increased SHH activity due to ciliary dysfunction is needed for the development of pathoetiological phenotypes observed in sPD, like mitochondrial dysfunction. In sum, altered PC function is part of early PD pathoetiology and inhibiting the overactive SHH signaling is a potential neuroprotective therapy.

DYRK1a inhibitor mediated rescue of Drosophila models of Alzheimer's disease-Down Syndrome phenotypes

Alzheimer's disease (AD) is the most common neurodegenerative disease which is becoming increasingly prevalent due to ageing populations resulting in huge social, economic, and health costs to the community. Despite the pathological processing of genes such as Amyloid Precursor Protein (APP) into Amyloid-b and Microtubule Associated Protein Tau (MAPT) gene, into hyperphosphorylated Tau tangles being known for decades, there remains no treatments to halt disease progression. One population with increased risk of AD are people with Down syndrome (DS), who have a 90% lifetime incidence of AD, due to trisomy of human chromosome 21 (HSA21) resulting in three copies of APP and other AD-associated genes, such as DYRK1A (Dual specificity tyrosine-phosphorylation-regulated kinase 1A) overexpression. This suggests that blocking DYRK1A might have therapeutic potential. However, it is still not clear to what extent DYRK1A overexpression by itself leads to AD-like phenotypes and how these compare to Tau and Amyloid-b mediated pathology. Likewise, it is still not known how effective a DYRK1A antagonist may be at preventing or improving any Tau, Amyloid-b and DYRK1a mediated phenotype. To address these outstanding questions, we characterised Drosophila models with targeted overexpression of human Tau, human Amyloid-b or the fly orthologue of DYRK1A, called minibrain (mnb). We found targeted overexpression of these AD-associated genes caused degeneration of photoreceptor neurons, shortened lifespan, as well as causing loss of locomotor performance, sleep, and memory. Treatment with the experimental DYRK1A inhibitor PST-001 decreased pathological phosphorylation of human Tau (at serine (S) 262). PST-001 reduced degeneration caused by human Tau, Amyloid-b or mnb lengthening lifespan as well as improving locomotion, sleep and memory loss caused by expression of these AD and DS genes. This demonstrated PST-001 effectiveness as a potential new therapeutic targeting AD and DS pathology.

Data from: Protecting great apes from disease: compliance with measures to reduce anthroponotic disease transmission

Based on an international sample of past (N=420) and potential future visitors (N=569) to wild great ape tourism sites in Africa, we used an online questionnaire to characterise visitors' practices, assess expectations (e.g., about proximity to great apes) and identify key factors related to potential compliance with disease mitigation measures. This was implemented adapting a framework from health literature (the Health Belief Model; HBM), particularly focused on reducing COVID-19 transmission at an early stage of the pandemic.

opencc-zeroJul 2023View details →

Long-read-based draft genome sequence of Indian black gram IPU-94-1 'Uttara': Insights into disease resistance and seed storage protein genes

Black gram [Vigna mungo (L.) Hepper var. mung<a>o</a>] [LAV1] is a warm-season legume highly prized for its protein content along with significant folate and iron proportions. To expedite the genetic enhancement of black gram, a high-quality draft genome from the center of origin of the crop is indispensable. Here, we established a draft genome sequence of an Indian black gram cultivar, 'Uttara' (IPU 94-1), known for its high resistance to mungbean yellow mosaic virus. Pacific Biosciences of California, Inc. (PacBio) single-molecule real-time (SMRT) and Illumina sequencing assembled a draft reference-guided assembly with a cumulative size of ~454.4 Mb, of which, 444.4 Mb was anchored on 11 pseudomolecules corresponding to 11 chromosomes. Uttara assembly denotes features of a high-quality draft genome illustrated through high N50 value (42.88 Mb), gene completeness (benchmarking universal single-copy ortholog [BUSCO] score 94.17%), and low levels of ambiguous nucleotides (N) percent (0.0005%). Gene discovery using transcript evidence predicted 28,881 protein-coding genes, from which, ~95% were functionally annotated. A global survey of genes associated with disease resistance revealed 119 nucleotide binding site–leucine rich repeat (NBS-LRR) proteins, while 23 genes encoding seed storage proteins (SSPs) were discovered in black gram. A large set of microsatellite loci were discovered for marker development in the crop. Our draft genome of an Indian black gram provides the foundational genomic resources for the improvement of important agronomic traits and ultimately will help in accelerating black gram breeding programs.

The first records of Sea Star Wasting Disease in Crossaster papposus in Europe

Sea Star Wasting Disease (SSWD) refers to a suite of gross pathological signs observed in Asteroidea species. It presents to varying degrees as abnormal posture, epidermal ulceration, arm autotomy and eversion of viscera. We report observations of SSWD in the sunstar Crossaster papposus, the first observations of its kind in Europe. While the exact cause of SSWD remains unknown, studies have proposed pathogenic and environmental-stress pathways for disease outbreaks. Although the present observations do not support a precise aetiology, the presence of SSWD in a keystone predator may have wide reaching ecological and management implications.

Floral traits mediate pollinator disease transmission

Plants modulate multitrophic ecological interactions, and variation in plant traits can affect these interactions. Pollinators are exposed to pathogens at flowers and acquire or transmit pathogens at different rates on different plant species, but the traits mediating those interactions are almost entirely unknown. We experimentally manipulated five plant traits that span scales including flower, inflorescence, and plant, to determine their effects on pathogen transmission between foraging bees. Specifically, we manipulated two morphological traits (corolla lip length and flower orientation within an inflorescence) and three resource distribution traits (inflorescence nectar, plant patch nectar and plant aggregation) in tents to test how plant traits affect bee pathogen transmission. We also quantified foraging behavior and fecal deposition patterns as potential mechanisms driving differences in transmission, and assessed trait manipulation consequences for bee reproduction. We found that pathogen transmission was reduced when we trimmed the corolla lip, evenly dispersed nectar distribution within an inflorescence, or aggregated plants in space. Some traits also affected bee reproduction; tents with trimmed corollas had more larval production than control tents, and tents with evenly distributed nectar across plant patches had more larval production than tents with clumped resources. Thus, some trait manipulations both reduced transmission and increased bee microcolony reproduction, although our design does not allow us to discern whether these are related or separate effects. Taken together, our results demonstrate causal effects of several floral traits on pathogen transmission and pollinator reproduction, indicating the importance of intraspecific plant trait variation for pollinator health and population dynamics.

Impact of disease characteristics and knowledge on public risk perception of Zoonoses

Zoonoses represent a global public health threat. Understanding lay perceptions of risk associated with these diseases can better inform proportionate policy interventions that mitigate their current and future impacts. While individual zoonoses (e.g. Bovine Spongiform Encephalopathy) have received scientific and public attention, we know little about how multiple zoonotic diseases vary relative to each other in lay risk perceptions. To this end, we examined public perceptions of eleven zoonoses across twelve qualitative attributes of risk among the UK public (n = 727, volunteer sample), using an online survey. We found that attribute ratings were predominantly explained via two basic dimensions of risk related to public knowledge and dread. We also show that, despite participants reporting low familiarity with most of the diseases presented, zoonoses were perceived as essentially avoidable. These findings imply that infection is viewed as dependent upon actions under personal control which has significant implications for policy development.

Data from: Comparative host-pathogen associations of Snake Fungal Disease in sympatric species of water snakes (Nerodia)

The ascomycete fungus Ophidiomyces ophiodiicola (Oo) is the causative agent of ophidiomycosis (Snake Fungal Disease), which has been detected globally. However, surveillance efforts in the central U.S., specifically Texas, have been minimal. The threatened and rare Brazos water snake (Nerodia harteri harteri) is one of the most range restricted snakes in the U.S. and is sympatric with two wide-ranging congeners, N. erythrogaster transversa and N. rhombifer, in north central Texas; thus, providing an opportunity to test comparative host-pathogen associations in this system. To accomplish this, we surveyed a portion of the Brazos river drainage (~400 river km) over 29 months and tested 150 Nerodia individuals for the presence of Oo via quantitative PCR and recorded any potential signs of Oo infection. We found Oo was distributed across the entire range of N. h. harteri, Oo prevalence was 46% overall, and there was a significant association between Oo occurrence and signs of infection in our sample. Models indicated adults had a higher probability of Oo infection than juveniles and subadults, and adult N. h. harteri had a higher probability of infection than adult N. rhombifer but not higher than adult N. e. transversa. High Oo prevalence estimates (94.4%) in adult N. h. harteri has implications for their conservation and management owing to their patchy distribution, comparatively low genetic diversity, and threats from anthropogenic habitat modification.

opencc-zeroDec 2022View details →

Data from: Avian disease surveillance on the island of San Cristóbal, Galápagos.

Endemic island species face unprecedented threats, with many populations in decline or at risk of extinction. One important threat is the introduction of novel and potentially devastating diseases, made more pressing due to accelerating global connectivity, urban development, and climatic changes. In the Galápagos archipelago two important wildlife diseases: avian pox (Avipoxvirus spp.) and avian malaria (Plasmodium spp. and related Haemosporidia) challenge endemic species. San Cristóbal island has seen a paucity of disease surveillance in avian populations, despite the island's connectedness to the continent and the wider archipelago. To survey prevalence and better understand the dynamics of these two diseases on San Cristóbal, we captured 1,207 birds of 11 species on the island between 2016 and 2020. Study sites included urban and rural lowland localities as well as rural highland sites in 2019. Of 995 blood samples screened for avian haemosporidia none tested positive for infection. In contrast, evidence of past and active pox infection was observed in 97 birds and identified as strains Gal1 and Gal2. Active pox prevalence differed significantly with contemporary climatic conditions, being highest during El Niño events (~11% in 2016 and in 2019 versus <1% in the La Niña year of 2018). Pox prevalence was also higher at urban sites than rural (11% to 4%, in 2019) and prevalence varied between host species, ranging from 12% in Medium Ground Finches (Geospiza fortis) to 4% in Yellow Warblers (Setophaga petechial aureola). In the most common infected species (Small Ground Finch: Geospiza fuliginosa), birds recovered from pox had significantly longer wings, which may suggest a selective cost to infection. These results illustrate the threat future climate changes and urbanization may present in influencing disease dynamics in the Galápagos, while also highlighting unknowns regarding species-specific susceptibilities to avian pox and the transmission dynamics facilitating outbreaks within these iconic species.

Predicting spatio-temporal population patterns of Borrelia burgdorferi, the Lyme disease pathogen

The causative bacterium of Lyme disease, Borrelia burgdorferi, expanded from an undetected human pathogen into the etiologic agent of the most common vector-borne disease in the United States over the last several decades. Systematic field collections of the tick vector reveal increases in the geographic range and population size of B. burgdorferi that coincided with increases in human Lyme disease incidence across New York State. Here we investigate the impact of environmental features on the population dynamics of B. burgdorferi. Analytical models developed using field collections of nearly 19,000 nymphal Ixodes scapularis and spatially- and temporally-explicit environmental features accurately explained the variation of B. burgdorferi population sizes across space and time. Importantly, the model identified environmental features that can be used to predict the biogeographical patterns of B. burgdorferi-infected ticks into future years and in previously unsampled areas. Forecasting the distribution and abundance of a pathogen at fine geographic scales offers a powerful strategy to mitigate a serious public health threat.

opencc-by-4.0Aug 2022View details →

Raw output data from ColabFold modelling for the paper 'Interaction of C21ORF2 with a domain of NEK1 mutated in human diseases is vital for NEK1 function in human cells'

Raw output data from ColabFold modelling for the paper 'Interaction of C21ORF2 with a domain of NEK1 mutated in human diseases is vital for NEK1 function in human cells' File descriptions: NEK11160endC21ORF2_amber_2e60f_relaxed_rank_1_model_1_fixed.pdb ColabFold output PDB file - Rank 1 model NEK11160endC21ORF2_amber_2e60f_relaxed_rank_2_model_2_fixed.pdb ColabFold output PDB file - Rank 2 model NEK11160endC21ORF2_amber_2e60f_relaxed_rank_3_model_4_fixed.pdb ColabFold output PDB file - Rank 3 model NEK11160endC21ORF2_amber_2e60f_relaxed_rank_4_model_3_fixed.pdb ColabFold output PDB file - Rank 4 model NEK11160endC21ORF2_amber_2e60f_relaxed_rank_5_model_5_fixed.pdb ColabFold output PDB file - Rank 5 model NEK11160endC21ORF2_amber_2e60f_coverage.png ColabFold output chart - MSA sequence coverage NEK11160endC21ORF2_amber_2e60f_PAE.png ColabFold output chart - PAE for each model NEK11160endC21ORF2_amber_2e60f_plddt.png ColabFold output chart - predicted IDDT per position Supplementary Excel file 1 List of residues predicted to be involved in intermolecular interactions, and the type of interaction (based on PDB files for each models, generated using BIOVIA Discovery Studio 2021)

Safety of ChAdOx1 nCoV-19 vaccination in patients with end-stage renal disease on hemodialysis

This dataset was the minimal dataset of the research article entitle 'Safety of ChAdOx1 nCoV-19 vaccination in patients with end-stage renal disease on hemodialysis'. The study aims to investigate the localized and systemic adverse effects (AEs) within 30-days after the first dose of ChAdOx1 nCoV19 (Oxford-AstraZeneca) vaccination in end-stage renal disease (ESRD) patients receiving hemodialysis (HD). The first dataset is the raw data for logistic regression analyses examining the risk factors in association with AEs, another dataset contains the second- and the seventh- day incidences of various AEs depicted in bar graphs. It comprises variables recording the status of patient-reported local and systemic AEs in questionnaire on the second and seventh days after vaccination as well as patients' baseline demographic and clinical characteristics.

PAM-altering SNP-based allele-specific CRISPR-Cas9 therapeutic strategies for Huntington's disease

Huntington's disease (HD) is caused by an expanded CAG repeat in huntingtin (HTT). Since HD is dominant, and loss of HTT leads to neurological abnormalities, safe therapeutic strategies require selective inactivation of mutant HTT. Previously, we proposed a concept of CRISPR-Cas9 using mutant-specific PAM sites generated by SNPs to selectively inactivate mutant HTT. Aiming at revealing suitable targets for clinical development, we analyzed the largest HD genotype dataset to reveal target PAM-altering SNPs (PAS) and subsequently evaluated their allele specificities. The gRNAs based on the PAM sites generated by rs2857935, rs16843804, and rs16843836 showed high levels of allele specificity in patient-derived cells. Simultaneous use of two gRNAs based on rs2857935-rs16843804 or rs2857935-rs16843836 produced selective genomic deletions in mutant HTT and prevented the transcription of mutant HTT mRNA without impacting the expression of normal counterpart or re-integration of the excised fragment elsewhere in the genome. RNAseq and off-target analysis confirmed high levels of allele specificity and the lack of recurrent off-targeting. Approximately 60% of HD subjects are eligible for mutant-specific CRISPR-Cas9 strategies of targeting one of these 3 PAS in conjunction with one non-allele-specific site, supporting high applicability of PAS-based allele-specific CRISPR approaches in the HD patient population.

The c-Abl inhibitor IkT-148009 therapeutically suppresses neurodegeneration in models of heritable and sporadic Parkinson's Disease

Parkinson's Disease (PD) is the second most prevalent neurodegenerative disease of the central nervous system, with an estimated 5,000,000 cases worldwide. PD pathology is characterized by the accumulation of misfolded a-synuclein, which is thought to play a critical role in the etiopathogenesis of the disease. Animal models of PD suggest that activation of the Abelson Tyrosine Kinase, or c-Abl, plays an essential role in the initiation and progression of a-synuclein pathology and initiates processes leading to the degeneration of dopaminergic and non-dopaminergic neurons. Given the essential role of c-Abl in the disease, a proprietary c-Abl inhibitor library was developed to identify potent, orally bioavailable c-Abl inhibitors capable of crossing the blood-brain barrier based on pre-defined characteristics, leading to the discovery of IkT-148009. IkT-148009 is a selective, potent, brain-penetrant c-Abl inhibitor with a favorable toxicology profile that was analyzed for therapeutic potential in animal models of slowly progressive, a-synuclein-dependent disease. In models of both inherited and sporadic Parkinson's disease in the mouse, IkT-148009 suppressed c-Abl activation to baseline and substantially protected neurons from degeneration when administered therapeutically by once daily oral gavage beginning four weeks after disease initiation. Recovery of normal behavioral function in diseased mice occurred within 8 weeks of initiating treatment and occurred concomitantly with a substantial reduction of a-synuclein pathology in the brain. These disease-modifying outcomes in mice suggest IkT-148009 has the potential to be a disease-modifying therapy in human disease.

Complete allele-specific silencing of the gain-of-function mutation of Huntington's disease

Dominant gain-of-function mechanism in Huntington's disease (HD) suggests selective inactivation of mutant HTT produces the biggest therapeutic benefit. Here, we developed a complete allele-specific CRISPR/Cas9 strategy to permanently silence mutant HTT through nonsense-mediated decay (NMD), capitalizing on an exonic PAM (protospacer adjacent motif)-Altering SNP (PAS). Comprehensive sequence/haplotype analysis identified PAS-generated NGG PAM sites on exons of common HTT haplotypes in HD patients, revealing a single clinically meaningful PAS-based mutant-specific NMD-CRISPR/Cas9 strategy. The alternative allele of rs363099 eliminates NGG PAM site on the most frequent normal HTT haplotype in HD, permitting mutant HTT-specific CRISPR/Cas9 therapeutics in ~20% of HD patients with European ancestry. Our rs363099-based CRISPR/Cas9 showed perfect allele specificity and good targeting efficiencies in cells derived from HD patients. Dramatically reduced mutant HTT mRNA and complete loss of mutant HTT protein indicate that our allele-specific CRISPR/Cas9 strategy completely inactivates mutant HTT through NMD. RNAseq analysis also supported high levels of on-target gene specificity because no other genes except HTT were altered in clonal lines developed through our NMD-CRISPR/Cas9 strategy. Together, our data demonstrating significant target population, selective inactivation of mutant HTT, good targeting efficiency, and lack of recurrent off-targeting establish its therapeutic value of novel rs363099-based mutant HTT-specific NMD-CRISPR/Cas9 strategy in HD.

opencc-by-4.0Dec 2022View details →

How extreme drought events , introduced species, and disease interact to impact influence threatened amphibian populations

Long term dataset of amphibian breeding in the Bay Area of California. We used this  7-y dataset (2013–2019) on amphibian breeding activity that encompassed a recent extreme drought event to assess 1) how breeding activities of these taxa differed during and after drought conditions and 2) the additive and interactive relationships of drought, chytrid fungal infection (Bd), and invasive species with the presence and abundance of larval amphibians.