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Biology subjects

Tanner, S.

Publications and source records attributed to Tanner, S..

9 recordsLinked to original sources

Forest fragmentation, anthropogenic land use, and climate shape sand fly community composition in central Panama.

Background: American cutaneous leishmaniasis (ACL) is endemic in central Panama, where rapid land use change is transforming tropical landscapes and potentially altering the ecology of sand fly vectors. Although researchers have widely studied environmental determinants of individual vector species, community-level responses of sand fly assemblages to landscape modification remain poorly understood. We evaluated how landscape composition, fragmentation, climate, and topography influence sand fly community structure in a rural landscape of central Panama. Methodology/Principal Findings: We combined metacommunity analyses with joint species distribution models (JSDMs) to quantify species-specific and community-level responses to climatic variables, land-cover composition, and forest configuration. We collected 1,692 individuals representing 30 species, including nine anthropportunist taxa of epidemiological importance. Sand fly assemblages had strong nestedness, low species turnover, and predominantly positive residual associations. Several anthropportunist sand fly species occurred across heterogeneous landscapes, although their responses to environmental conditions differed among taxa. Land-cover composition, forest fragmentation metrics, and elevation together explained about half of the variance in species occurrence and abundance, with the remainder attributed to climate and spatial, temporal, and community-level random effects. Grassland cover contributed most strongly to sand fly occurrence and abundance, whereas artificial surfaces consistently reduced both metrics. Fragmentation effects varied by species: edge density often increased occurrence and abundance, whereas more forest patches generally suppressed populations. Increased precipitation broadly enhanced occurrence and abundance, whereas higher temperatures negatively affected several taxa. Conclusions/significance: Landscape heterogeneity predictably structures sand fly communities, and different forms of anthropogenic disturbance exert non-uniform effects on vector assemblages. The nested organization of these assemblages and the co-occurrence of several anthropophilic species suggest that multiple potential vector species may be present across heterogeneous landscapes. These findings highlight the need for landscape-informed surveillance and control strategies that prioritize grassland-forest interfaces and other disturbed ecotones where sand fly species of epidemiological importance frequently co-occur.

ecology↗

A rapid, sensitive, and quantitative high plex biomarker digital detection platform enabled by Hypercoding

Low-cost, multiplexed, and automated assays are needed to make omic technologies more broadly accessible in clinical, research, and commercial settings. We present Hypercoding, a scalable technology for detection and quantitation of multi-omic targets. Drawing from data reliability methods in the telecommunications field, Hypercoding uses fluorescent signals from hybridization with an error-correcting code to enable detection of high-plexity targets from biological samples, such as human DNA. In the presence of the target, a linear DNA construct is circularized, immobilized, and amplified to enable single-molecule detection of a target via rapid readout cycles within a 96-well plate. We demonstrate capability for >10,000 code plexity and accurate (98.7%) genotyping of 209 pharmacogenomic variants. Furthermore, we show computation of copy number variation with whole chromosome and sub-gene resolution, as well as quantitation of target abundance down to 10 fM sensitivity with a dynamic range of up to 10 logs.

genomics↗

Mechanisms and Safety of Ultrasound Phacoemulsification

ObjectiveA comprehensive technical and biomedical analysis of ultrasound-induced effects during phacoemulsification cataract surgery (PCS) and an assessment of the potential risks associated with ultrasound emulsification MethodsModeling ultrasound wave propagation and intensities using the finite element method (FEM). Cavitation onset was experimentally validated in a pressure chamber observed with a high-speed camera. The thermal effects of ultrasound energy were estimated through established physical and thermal models and confirmed in a cuvette setup using thermistor probes. ResultsAt the distal end of the PCS tip, the ultrasound wave intensity reached 0.2 W/mm2, resulting in ocular tissue displacements in the anterior chamber below 2 {micro}m. The temperature rise in the anterior chamber was less than 0.2 {degrees}C/s. Both observations indicate negligible mechanical and thermal risk to ocular tissues. High-speed imaging confirmed cavitation confined to the tip region. Emulsification efficacy was maintained even under conditions that suppressed cavitation, including elevated ambient pressures and cavitation-inhibiting fluids. Results indicate that mechanical fragmentation by tip oscillation ("jackhammer effect") is the only relevant emulsification mechanism, while cavitation plays a negligible role. Acoustic streaming was observed during ultrasound excitation without phaco sleeve. During phacoemulsification, the sleeve suppressed acoustic streaming into the anterior chamber. ConclusionsThe findings validate the safety of ultrasound-based PCS and confirm that tissue fragmentation is primarily driven by the oscillating tips direct action.

bioengineering↗

Gene model for the ortholog of DENR in Drosophila simulans

Gene model for the ortholog of Density regulated protein (DENR) in the May 2017 (Princeton ASM75419v2/DsimGB2) Genome Assembly (GenBank Accession: GCA_000754195.3) of Drosophila simulans. This ortholog was characterized as part of a developing dataset to study the evolution of the Insulin/insulin-like growth factor signaling pathway (IIS) across the genus Drosophila using the Genomics Education Partnership gene annotation protocol for Course-based Undergraduate Research Experiences.

genomics↗

Gene model for the ortholog of Ilp5 in Drosophila erecta

Gene model for the ortholog of Insulin-like peptide 5 (Ilp5) in the Dere_CAF1 Genome Assembly (GenBank Accession: GCA_000005135.1) of Drosophila erecta. This ortholog was characterized as part of a developing dataset to study the evolution of the insulin/insulin-like growth factor signaling pathway across the genus Drosophila using the Genomics Education Partnership gene annotation protocol for Course-based Undergraduate Research Experiences.

genomics↗

Prenatal Environmental Determinants of Aromatase Brain-Promoter Methylation in Cord Blood: Chemical, Airborne, Pharmacological, and Nutritional Factors

Aromatase, an enzyme encoded by the gene CYP19A1, plays central roles in neurodevelopment. In the brain, its function is to convert androgens into neuroestrogens, ensuring balanced hormonal signalling. Both animal experiments and human studies have shown that, in males, disruption of aromatase, either genetically or epigenetically, can increase symptoms of autism. Prenatal exposure to bisphenol A (BPA), a common plastic chemical, can increase levels of DNA methylation--a key epigenetic modification--at the brain-specific CYP19A1 promoter, P1.f, reducing CYP19A1 expression. However, the extent to which other neurodevelopmentally relevant environmental exposures influence P1.f methylation remains unclear. Here, in the Barwon Infant Study (BIS) birth cohort (N = 906), we analysed the association between 25 prenatal exposures (from five classes previously linked to neurodevelopmental outcomes: manufactured chemicals, air pollution, and pharmacological, nutrition and sunlight-related factors) and methylation of the CYP19A1 P1.f promoter using Weighted Quantile Sum (WQS) regression. We found that the WQS mixture index, a weighted combination of the prenatal exposures, was positively associated with higher P1.f methylation (Adjusted Mean Difference (AMD) = 0.712 (95% CI 0.11, 1.315), p = 0.021), indicating reduced brain aromatase activity. Prenatal exposures with the strongest contribution to the mixture effect included bisphenols (including BPA), reduced sunlight, household mould, phthalates, low folate intake, and air pollution. These findings highlight epigenetic modification of the aromatase gene as a biologically plausible, convergent mechanism through which multiple environmental risk factors for autism may exert effects.

genomics↗

Prenatal DEHP plastic chemical exposure increases the likelihood of child autism and ADHD symptoms through epigenetic programming

Increasing evidence implicates prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP), a common endocrine-disrupting plastic chemical, in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). However, the underlying mechanisms are poorly understood. Here we examined whether cord blood DNA methylation, a key epigenetic marker, mediates the association between prenatal DEHP exposure and ASD/ADHD symptoms in 847 children enrolled in the Barwon Infant Study. ASD and ADHD are complex phenotypes characterised by differences at the gene regulatory network and neuronal circuit level, where heterogeneous genetic and environmental risk factors converge. Accordingly, we employed a data-driven computational strategy that helped elucidate broader functional epigenetic signatures of ASD and ADHD elicited by DEHP exposure. This included (1) a methylation profile score for DEHP exposure (MPSDEHP), and (2) an analysis of co-methylated gene networks. Causal mediation analysis demonstrated that both MPSDEHP and a DEHP-associated network of co-methylated genes mediated the effect of DEHP exposure on increased ASD and ADHD symptoms at ages 2 and 4 years (proportion of effect mediated ranged from 0.21 to 0.80). The co-methylation network was enriched for neural cell-type markers, ASD risk genes (including FOXP1, SHANK2, and PLXNB1), and targets of endocrine receptors previously linked to DEHP (including targets of the estrogen receptor ER and the glucocorticoid receptor GR), providing biological plausibility. We validated key results in independent blood (n=66) and postmortem brain (n=40) DNA methylation datasets. These findings provide mechanistic evidence linking DEHP to ASD and ADHD symptoms and reinforce growing concerns regarding the risks of prenatal exposure.\n\nSignificanceExposure to endocrine-disrupting plastic chemicals has been linked to adverse neurodevelopment, but the underlying biological mechanisms remain unclear. We demonstrate that prenatal exposure to di-(2-ethylhexyl) phthalate (DEHP), a common plasticizer, increases autism and ADHD symptoms through alterations in DNA methylation, a key epigenetic regulator of gene activity. Using birth cohort data, we identify epigenetic signatures of prenatal DEHP exposure, including alterations in an endocrine-related co-methylation network enriched for neural cell-type markers and known autism-associated genes. These signatures mediate the effects of DEHP on autism and ADHD symptoms and are also associated with autism in external blood and postmortem-brain datasets, providing independent validation. This causal evidence further underscores concerns regarding the consequences of prenatal plastic-chemical exposure on the developing brain.

neuroscience↗

A framework for evaluating edited cell libraries created by massively parallel genome engineering

Genome engineering methodologies are transforming biological research and discovery. Approaches based on CRISPR technology have been broadly adopted and there is growing interest in the generation of massively parallel edited cell libraries. Comparing the libraries generated by these varying approaches is challenging and researchers lack a common framework for defining and assessing the characteristics of these libraries. Here we describe a framework for evaluating massively parallel libraries of edited genomes based on established methods for sampling complex populations. We define specific attributes and metrics that are informative for describing a complex cell library and provide examples for estimating these values. We also connect this analysis to generic phenotyping approaches, using either pooled (typically via a selection assay) or isolate (often referred to as screening) phenotyping approaches. We approach this from the context of creating massively parallel, precisely edited libraries with one edit per cell, though the approach holds for other types of modifications, including libraries containing multiple edits per cell (combinatorial editing). This framework is a critical component for evaluating and comparing new technologies as well as understanding how a massively parallel edited cell library will perform in a given phenotyping approach.

genomics↗

Copy number variants in clinical WGS: deployment and interpretation for rare and undiagnosed disease

PurposeCurrent diagnostic testing for genetic disorders involves serial use of specialized assays spanning multiple technologies. In principle, whole genome sequencing (WGS) has the potential to detect all genomic mutation types on a single platform and workflow. Here we sought to evaluate copy number variant (CNV) calling as part of a clinically accredited WGS test.\n\nMethodsUsing a depth-based copy number caller we performed analytical validation of CNV calling on a reference panel of 17 samples, compared the sensitivity of WGS-based variants to those from a clinical microarray, and set a bound on precision using orthogonal technologies. We developed a protocol for family-based analysis, annotation, filtering, visualization of WGS based CNV calls, and deployed this across a clinical cohort of 79 rare and undiagnosed cases.\n\nResultsWe found that CNV calls from WGS are at least as sensitive as those from microarrays, while only creating a modest increase in the number of variants interpreted (~10 CNVs per case). We identified clinically significant CNVs in 15% of the first 79 cases analyzed. This pipeline also enabled identification of cases of uniparental disomy (UPD) and a 50% mosaic trisomy 14. Directed analysis of some CNVs enabled break-point level resolution of genomic rearrangements and phasing of de-novo CNVs.\n\nConclusionRobust identification of CNVs by WGS is possible within a clinical testing environment, and further developments will bring improvements in resolution of smaller and more complex CNVs.

genomics↗