Biology subjects

Stewart, K.

Publications and source records attributed to Stewart, K..

At least 19 recordsLinked to original sources

bioRxiv2026

Function-driven geometry directs human pilosebaceous unit development

Single-cell technologies have generated cell censuses of tissues, however, how tissue geometry reflects functional needs remains poorly characterized. The human pilosebaceous unit offers a tractable model, a prenatally-formed complex mini-organ combining hair and sebum production with a stem cell reservoir. Using histomorphology, spatial transcriptomics, and single-cell multiomics on the same human prenatal scalp skin samples (8-19 post-conception weeks), integrated and analyzed using machine learning approaches, we built a spatiotemporal map of pilosebaceous unit development. We demonstrate that epithelial-mesenchymal interactions coordinate cellular fate and organogenesis, using an in vitro hair-bearing skin organoid model to validate this tissue-patterning. In addition, we show sebaceous gland developmental programmes are overcome during tumor formation. Our large-scale multi-modal analysis provides a unique framework for understanding form and function of tissues with applications in tissue engineering and pathology.

developmental biology↗

bioRxiv2025

Population-level temporal decoding and dynamical structure in frontostriatal circuits during decision making

Perceptual decisions unfold over time, requiring neural circuits to evaluate sensory evidence, track elapsed time, and commit to an action. To investigate how these computations are distributed across corticostriatal circuits, we recorded large-scale neural population activity using Neuropixels probes in the rat frontal orienting field (FOF) and anterior dorsal striatum (ADS) during a free-response auditory change detection task. Both regions exhibited structured, highly dynamic population activity during task performance. Using single-trial population decoding, we found that both FOF and ADS robustly encoded retrospective time from stimulus onset and prospective time preceding the decision report. Using a new approach to analyze temporal encoding to identify the dynamical structure supporting decoding, we found that time encoding could be decomposed into two primary dynamical motifs: monotonic ramp-like trajectories and transient bump-like trajectories. While these modes were similarly expressed during early evidence evaluation, FOF exhibited more pronounced decision-aligned changes near the time of the decision report, possibly reflecting a state transition at commitment. Population geometry analyses further revealed stable low-dimensional subspaces during evidence evaluation that transitioned at decision commitment, with significantly larger subspace changes in FOF than ADS. Together, these results reveal a common dynamical framework during evidence evaluation across corticostriatal circuits, while identifying a selective reorganization of FOF dynamics associated with decision commitment.

neuroscience↗

bioRxiv2025

A functional Red List Index for monitoring trends in functional diversity

Functional diversity supports ecosystem function and resilience but is in decline due to ongoing extinctions. Despite this, no functional diversity metrics are included in the set of indicators adopted by governments to measure progress towards the Global Biodiversity Framework. Monitoring changes in functional diversity is essential to understand differences between taxonomic and functional diversity trends. The Red List Index (RLI) is a widely used metric in conservation policy, and tracks trends in aggregate extinction risk across sets of species over time. We present a functional Red List Index (fRLI), which weights species by their morphological uniqueness at either local or global scales, to indicate the risk that future extinctions could pose to functional diversity. We applied the fRLI on birds and found higher aggregate extinction risk for both local and global fRLI compared with the standard RLI. Species with higher local uniqueness were more likely to be at higher risk of extinction while we found no difference for globally unique species. Globally or locally unique species were not more likely to show escalation in extinction risk between 1988 and 2024 than less unique species; however, locally unique birds had a lower proportion of their resident range covered by site-based conservation measures, leaving them vulnerable to future decline. The fRLI provides a tool to monitor the impact of extinction risk on functional diversity and could be applied to other taxonomic groups with comprehensive or representative coverage of Red List assessments and trait data.

ecology↗

bioRxiv2025

An aqueous watercress extract with topical anti-inflammatory properties in inflamed human skin

Watercress (Nasturtium officinale) is a species of the Brassicaceae plant family, with a biochemical composition which suggests potential uses in anti-inflammatory skincare applications. Watercress has a high content of both anti-inflammatory compounds (e.g., polyphenols) and compounds which upregulate the Nrf2-mediated antioxidant gene response (e.g., isothiocyanates) in human tissues. We have developed a process to manufacture an aqueous watercress extract that contains isothiocyanates and flavonoid-type polyphenols, some of which are known anti-inflammatory compounds. We partially characterized the chemical composition of our extract (LC-QTOF-MS), and we demonstrated in a cultured full-thickness human skin model, that the extract was non-cytotoxic and non-irritant, as monitored by cell viability and IL1 concentrations, respectively. In human trials, in vivo, we showed by visual clinical scoring of inflammation that the extract had anti-inflammatory properties. The anti-inflammatory properties of the aqueous watercress extract may provide a treatment for inflammatory skin diseases such as eczema.

biochemistry↗

bioRxiv2025

Time-adaptive modulation of evidence evaluation in rat posterior parietal cortex

A crucial component of successful decision making is determining the optimal timescale over which to evaluate evidence. For example, when detecting transient changes in the environment, it is best to focus evaluation on the current evidence as opposed to older evidence. However, it is unclear how this adjustment in timescale is achieved in the brain in terms of how the neurons that process evidence adjust their dynamics. To address this question, we used Neuropixel probes to record spiking activity from neurons in the posterior parietal cortex (PPC) of rats performing a free-response auditory change detection task in which subjects evaluate sensory evidence over short timescales to determine when a change occurs in a noisy sensory stream. Consistent with longer timescale temporal integration tasks, we found that PPC neurons modulated their activity by the strength of evidence leading to decisions, were selective for the rats choices, and had opposing populations of neurons that were positively versus negatively modulated by evidence. However, in contrast to temporal integration tasks, responses of neurons to individual pulses of evidence were transient, such that the effect of the evidence on activity tapered off over a timescale corresponding to the subjects behavioral timescale of evidence evaluation. Intriguingly, PPC also exhibited "gain changes" in the influence of evidence as a function of decision time that were consistent with changes in behavioral urgency. In addition, reversible inactivation revealed an important role for PPC in this auditory change detection, such that PPC inactivation altered choice behavior and the timescale over which rats evaluated evidence. Together, our results suggest important contributions of PPC to free-response decisions that involve adjusting timescales of evidence evaluation.

neuroscience↗

bioRxiv2025

A breath of fresh air: comparative evaluation of passive versus active airborne eDNA sampling strategies

Terrestrial biodiversitys rapid decline demands expansion of high-resolution biomonitoring to support science-based policy. Environmental DNA (eDNA) analysis has proven effective in aquatic systems but remains underexplored for terrestrial habitats, partly due to point-source sampling bias and difficulty in upscaling. Air has emerged as a promising substrate yet most studies use active samplers which tend to be expensive, bulky, and require power. We used a newly developed, inexpensive, reusable, and easy-to-use passive airborne eDNA sampler (Nutshell eDNA sampler) to capture eDNA suspended in air across time (6 to 96 hours) within Rotterdam Zoo, the Netherlands. Its performance was compared to two commonly-used active airborne eDNA samplers for vertebrate diversity detection. In total, 88 species were detected, including 24 zoo residents. The Nutshell eDNA sampler was the most effec-tive at detecting zoo residents, surpassing active samplers in species richness within 48 hours and continuing to accumulate new species beyond 96 hours, including detections of both patchy and singleton signals. It also detected the furthest species signal (515 m). Zoo airborne eDNA further demonstrated a positive correlation to species total biomass, suggest-ing larger vertebrates release proportionately more DNA into the air. Our findings indicate that for long, unsupervised biomonitoring, passive airborne eDNA sampling presents a prom-ising approach for assessing vertebrate communities and putatively reduces detection noise in stochastic air eDNA signals. While deeper investigations into airborne eDNA sampling strategies are needed, passive methods can offer a much needed logistically flexible, low-maintenance approach compared to short-burst collection strategies employed by many ac-tive samplers.

ecology↗

bioRxiv2025

Threat reduction must be coupled with targeted recovery programmes to conserve global bird diversity

Biodiversity is undergoing severe declines while threats to natural populations continue to escalate worldwide. Ambitious international commitments have been made to preserve biodiversity, with the goal of preventing extinctions and maintaining ecosystem resilience, yet the efficacy of large-scale protection remains unclear. Here we use a trait-based approach to show that global actions - such as the immediate abatement of all threats across at least half of species ranges for [~]10,000 bird species - will only prevent half of projected species extinctions and functional diversity loss attributable to current and future threats in the next 100 years. Nonetheless, targeted recovery programmes prioritizing protection of the 100 most functionally unique threatened birds could avoid 68% of projected functional diversity loss. Actions targeting habitat loss and degradation will prevent the greatest number of species extinctions and proportion of functional diversity loss relative to other drivers of extinction, whereas control of hunting and collection and disturbance and accidental mortality would save fewer species but disproportionately boost functional richness. These findings show that conservation of avian diversity requires action partitioned across all drivers of decline, and highlights the importance of understanding and mitigating the ecological impacts of species extinctions predicted to occur even under optimistic levels of conservation action.

ecology↗

bioRxiv2024

Renal arterial dysfunction, impaired pressure natriuresis and salt-sensitivity in a mouse model of Cushing syndrome

BackgroundCushing Syndrome arises from endogenous overproduction of ACTH by a tumour or is acquired through chronic exposure to glucocorticoid medication. Hypertension is a major complication, increasing cardiovascular risk, but underlying mechanisms are not clearly defined. MethodsWe infused male C57BL/6J mice with ACTH or vehicle for 14-21 days, inducing cardinal features of Cushing Syndrome. The renal pressure natriuresis response was measured under anesthesia and ex vivo artery function assessed by myography. ResultsACTH infusion blunted the natriuretic and diuretic responses to incremental increases in blood pressure. Renal hemodynamics did not change with blood pressure in controls, but renal autoregulation was impaired in ACTH mice. The ex vivo contractile response of the renal artery to phenylephrine was diminished in Cushing Syndrome mice, as was endothelium-dependent and endothelium-independent relaxation. On 0.3% sodium diet, there was no evidence of sodium retention in ACTH-treated mice but the diurnal rhythm of sodium excretion was abnormal and mice had non-dipping BP. The Cushing Syndrome model also displayed enhanced salt preference and amplified salt-sensitive blood pressure. ConclusionCushing Syndrome induces a cluster of phenotypes impacting sodium homeostasis and blood pressure regulation. Hypertension, salt-sensitivity and non-dipping blood pressure are important cardiovascular risk factors, and, beyond Cushing Syndrome, our findings are relevant to obesity and the metabolic syndrome, in which tissue glucocorticoid homeostasis is abnormal.

physiology↗

bioRxiv2024

Variation in spatial population structure in the Anopheles gambiae species complex

Anopheles gambiae, Anopheles coluzzii, and Anopheles arabiensis are three of the most widespread vectors of malaria parasites, with geographical ranges stretching across wide swaths of Africa. Understanding the population structure of these closely related species, including the extent to which populations are connected by gene flow, is essential for understanding how vector control implemented in one location might indirectly affect vector populations in other locations. Here, we assessed the population structure of each species based on a combined data set of publicly available and newly processed whole-genome sequences. The data set included single nucleotide polymorphisms from whole genomes of 2,410 individual mosquitoes sampled from 128 locations across 19 African countries. We found that A. gambiae sampled from several countries in West and Central Africa showed low genetic differentiation from each other according to principal components analysis (PCA) and ADMIXTURE modeling. Using Estimated Effective Migration Surfaces (EEMS), we showed that this low genetic differentiation indicates high effective migration rates for A. gambiae across this region. Outside of this region, we found eight groups of sampling locations from Central, East, and Southern Africa for which A. gambiae showed higher genetic differentiation, and lower effective migration rates, between each other and the West/Central Africa group. These results indicate that the barriers to and corridors for migration between populations of A. gambiae differ across the geographical range of this malaria vector species. Using the same methods, we found higher genetic differentiation and lower migration rates between populations of A. coluzzii in West and Central Africa than for A. gambiae in the same region. In contrast, we found lower genetic differentiation and higher migration rates between populations of A. arabiensis in Tanzania, compared to A. gambiae in the same region. These differences between A. gambiae, A. coluzzii, and A. arabiensis indicate that migration barriers and corridors may vary, even between very closely related species. Overall, our results demonstrate that migration rates vary both within and between species of Anopheles mosquitoes, presumably based on species-specific responses to the ecological or environmental conditions that may impede or facilitate migration, and the geographical patterns of these conditions across the landscape. Together with previous findings, this study provides robust evidence that migration rates between populations of malaria vectors depend on the ecological context, which should be considered when planning surveillance of vector populations, monitoring for insecticide resistance, and evaluating interventions.

ecology↗

bioRxiv2024

Carbonyl Reductase 1: a novel regulator of blood pressure in Down Syndrome

BackgroundApproximately one in every 800 children is born with the severe aneuploid condition of Down Syndrome (DS), a trisomy of chromosome 21. Low blood pressure (hypotension) is a common condition associated with DS and can have a significant impact on exercise tolerance and quality of life. Little is known about the factors driving this hypotensive phenotype and therefore therapeutic interventions are limited. Carbonyl reductase 1 (CBR1) is an enzyme contributing to the metabolism of prostaglandins, glucocorticoids, reactive oxygen species and neurotransmitters, encoded by a gene (CBR1) positioned on chromosome 21 with potential to impact blood pressure. MethodsUtilising genetically modified mice and telemetric blood pressure measurement, we tested the hypothesis that CBR1 influences blood pressure and that its overexpression contributes to hypotension in DS. ResultsIn a mouse model of DS (Ts65Dn), which exhibit hypotension, CBR1 activity was increased and pharmacological inhibition of CBR1 increased blood pressure. Mice heterozygous null for Cbr1 had reduced CBR1 enzyme activity and elevated blood pressure. Further experiments indicate that the underlying mechanisms include alterations in sympathetic tone and prostaglandin metabolism. ConclusionsWe conclude that CBR1 activity contributes to blood pressure homeostasis and inhibition of CBR1 may present a novel therapeutic opportunity to correct symptomatic hypotension in DS.

physiology↗

bioRxiv2023

An unconventional mechanism of IL-1β secretion that requires Type I IFN in lupus monocytes

Systemic Lupus Erythematosus (SLE) is characterized by autoreactive B cell activation, upregulation of Type I Interferon (IFN) and widespread inflammation. Mitochondrial nucleic acids (NAs) are increasingly recognized as triggers of IFN1. Thus, defective removal of mitochondria from mature red blood cells (Mito+ RBCs), a feature of SLE, contributes to IFN production by myeloid cells2. Here we identify blood monocytes (Mo) that have internalized RBCs and co-express IFN-stimulated genes (ISGs) and interleukin-1{beta} (IL-1{beta}) in SLE patients with active disease. We show that ISG expression requires the interaction between Mito+ RBC-derived mitochondrial DNA (mtDNA) and cGAS, while IL-1{beta} production entails Mito+ RBC-derived mitochondrial RNA (mtRNA) triggering of RIG-I-like receptors (RLRs). This leads to the cytosolic release of Mo-derived mtDNA that activates the NLRP3 inflammasome. Importantly, IL-1{beta} release depends on the IFN-inducible myxovirus resistant protein 1 (MxA), which enables the translocation of this cytokine into a trans-Golgi network (TGN)-mediated unconventional secretory pathway. Our study highlights a novel and synergistic pathway involving IFN and the NLRP3 inflammasome in SLE.

immunology↗

bioRxiv2022

Trait diversity metrics can perform well with highly incomplete datasets

O_LICharacterizing changes in trait diversity at large spatial scales provides insight into the impact of human activity on ecosystem structure and function. However, the approach is often based on trait datasets that are incomplete and unrepresentative, with uncertain impacts on trait diversity estimates. C_LIO_LITo address this knowledge gap, we simulated random and biased removal of data from a near complete avian trait dataset (9579 species) and assessed whether trait diversity metrics were robust to data incompleteness with and without using imputation to fill data gaps. Specifically, we compared two commonly used metrics each calculated with two methods: trait richness (calculated with convex hulls and trait probabilities densities) and trait divergence (calculated with distance-based Rao and trait probability densities). C_LIO_LIWithout imputation, estimates of global avian trait diversity (richness and divergence) were robust when 30-70% of species had missing data for four out of 11 continuous traits, depending on severity of bias and the method used. However, when missing traits were imputed based on present morphological trait data and phylogeny, trait diversity metrics consistently remained representative of the true value, even when 70% of species were missing data for four out of 11 traits and data were not missing at random (biased with respect to body mass). Trait probability densities and distance-based Rao were particularly robust to missingness and bias when combined with imputation, with convex hull-based trait richness being less reliable. C_LIO_LIExpanding global morphometric datasets to represent more taxa and traits, and to quantify intraspecific variation, remains a priority. In the meantime, our results show that widely used methods can successfully quantify large-scale trait diversity even when data are missing for two-thirds of species, so long as missing traits are estimated using imputation. C_LI

ecology↗

bioRxiv2022

Guided construction of single cell reference for human and mouse lung

Accurate cell type identification is a key and rate-limiting step in single cell data analysis. Single cell references with comprehensive cell types, reproducible and functional validated cell identities, and common nomenclatures are much needed by the research community to optimize automated cell type annotation and facilitate data integration, sharing, and collaboration. In the present study, we developed a novel computational pipeline to utilize the LungMAP CellCards as a dictionary to consolidate single-cell transcriptomic datasets of 104 human lungs and 17 mouse lung samples and constructed "LungMAP CellRef" and "LungMAP CellRef Seed" for both normal human and mouse lungs. "CellRef Seed" has an equivalent prediction power and produces consistent cell annotation as does "CellRef" but improves computational efficiency and simplifies its utilization for fast automated cell type annotation and online visualization. This atlas set incorporates 48 human and 40 mouse well-defined lung cell types catalogued from diverse anatomic locations and developmental time points. Using independent datasets, we demonstrated the utility of our CellRefs for automated cell type annotation analysis of both normal and disease lungs. User-friendly web interfaces were developed to support easy access and maximal utilization of the LungMAP CellRefs. LungMAP CellRefs are freely available to the pulmonary research community through fast interactive web interfaces to facilitate hypothesis generation, research discovery, and identification of cell type alterations in disease conditions.

bioinformatics↗

bioRxiv2022

Differential sensory and immune gene evolution in sea turtles with contrasting demographic and life histories

Sea turtles represent an ancient lineage of marine vertebrates that evolved from terrestrial ancestors over 100 MYA, yet the genomic basis of the unique physiological and ecological traits enabling these species to thrive in diverse marine habitats remains largely unknown. Additionally, many populations have drastically declined due to anthropogenic activities over the past two centuries, and their recovery is a high global conservation priority. We generated and analyzed high-quality reference genomes for the leatherback (Dermochelys coriacea) and green (Chelonia mydas) turtles, representing the two extant sea turtle families. These genomes are highly syntenic and homologous, but localized regions of non-collinearity were associated with higher copy numbers of immune, zinc-finger, and olfactory receptor (OR) genes in green turtles, with ORs related to waterborne odorants greatly expanded in green turtles. Our findings suggest that divergent evolution of these key gene families may underlie immunological and sensory adaptations assisting navigation, occupancy of neritic versus pelagic environments, and diet specialization. Reduced collinearity was especially prevalent in microchromosomes, with greater gene content, heterozygosity, and genetic distances between species, supporting their critical role in vertebrate evolutionary adaptation. Finally, diversity and demographic histories starkly contrasted between species, indicating that leatherback turtles have had a low yet stable effective population size, exhibit extremely low diversity compared to other reptiles, and harbor a higher genetic load compared to green turtles, reinforcing concern over their persistence under future climate scenarios. These genomes provide invaluable resources for advancing our understanding of evolution and conservation best practices in an imperiled vertebrate lineage. Statement of significanceSea turtle populations have undergone recent global declines. We analyzed de novo assembled genomes for both extant sea turtle families through the Vertebrate Genomes Project to inform their conservation and evolutionary biology. These highly conserved genomes were differentiated by localized gene-rich regions of divergence, particularly within microchromosomes, suggesting that these genomic elements play key functional roles in the evolution of sea turtles and possibly other vertebrates. We further demonstrate that dissimilar evolutionary histories impact standing genomic diversity and genetic load, and are critical to consider when using these metrics to assess adaptive potential and extinction risk. Our results also demonstrate how reference genome quality impacts inferences of comparative and conservation genomics analyses that need to be considered in their application.

genomics↗

bioRxiv2021

Skin stem cells orchestrate de novo generation of extrathymic regulatory T cells to establish a temporary protective niche during wound healing

Adult stem cells reside in various tissues to govern homeostasis and repair damage. During wound healing, these stem cells must be mobilized to enter the center of the injury where they are exposed to many inflammatory immune cells infiltrating the wounded tissue. While these immune cells are indispensable for preventing infections and clearing dead cells, they can also create a harsh inflammatory environment which could potentially damage the stem cells and prevent their self-renewal and differentiation. Here, using a model of cutaneous wound healing in which hair follicle stem cells (HFSCs) repair the wound, we show that, upon migrating into the wound, skin stem cells acquire a strong immune modulatory capacity which allows them to sculpt a temporary immune suppressive niche for self-protection. We reveal that the HFSCs in the wound bed orchestrate extrathymic differentiation of regulatory T (Treg) cells by providing co-stimulation to the woundinfiltrating CD4 effector T cells. In this way, Treg cells can be generated de novo in close proximity to and can intimately protect HFSCs from the collateral damage inflicted by inflammatory neutrophils. This study uncovered a striking inflammatory adaptation capacity unique to adult tissue stem cells which allows them to shape their own immune suppressive niche during wound repair.

immunology↗

bioRxiv2020

Kidney single-cell atlas reveals myeloid heterogeneity in progression and regression of kidney disease.

The kidney has a limited capacity to repair following injury, however, the endogenous reparative pathways are not well understood. Here we employ integrated droplet- and plate-based scRNA-seq in the murine reversible unilateral ureteric obstruction model to dissect the transcriptomic landscape at the single cell level during renal injury and resolution of fibrosis. We generate a comprehensive catalogue of the changes induced during injury and repair, revealing significant myeloid cell heterogeneity, which would not have been identifiable by conventional flow cytometry. We identify new markers for the myeloid populations within the kidney as well as identification of novel subsets including an Arg1+ monocyte population specific to early injury and a Mmp12+ macrophage subset exclusive to repair. Finally, using paired blood exchange to track circulating immune cells, we confirm that monocytes are recruited to the kidney early after injury and are the source of Ccr2+ macrophages that accumulate in late injury. Our data demonstrate the utility of complementary technologies to identify novel myeloid subtypes that may represent therapeutic targets to inhibit progression or promote regression of kidney disease.

immunology↗

bioRxiv2020

The need to harmonize insecticide resistance testing: methodology, intensity concentrations and molecular mechanisms evaluated in Aedes aegypti populations in Central America and Hispaniola

BackgroundThe Zika AIRS Project, a USAID-funded initiative worked across the Latin America and Caribbean regions from 2016 to 2019, as an emergency to contain the spread of the Zika virus. All entomological records in the target countries showed wide distribution and high abundance of Aedes aegypti populations, however the susceptibility profiles of these insects to insecticides commonly employed by vector control campaigns were in most cases incomplete or inexistent. In close collaboration with the Ministries of Health of individual countries, Zika-AIRS teams conducted insecticide susceptibility testing of an array of insecticides in A. aegypti populations of each country. Procedures applied met the standard international protocols instructed by the World Health Organization and Centers for Disease Control and Prevention. Methodology and main findingsThe insecticides tested were selected under categories such as pyrethroids, organophosphates and carbamate. Results showed A. aegypti populations displaying high and widely distributed resistance to all pyrethroids across countries, tolerance to organophosphates and full susceptibility to a carbamate. Key inconsistencies between testing methods are presented and discussed. Additionally, four kdr mutations were analyzed to detect molecular mechanisms of insecticide resistance. The screening for kdr mutations suggested the widespread nature of V1016I mutation, linked to pyrethroid resistance in A. aegypti populations distributed and sampled in the above mentioned regions. Conclusions and perspectivesThis multi-country study contributes with updated information to the public health decision-makers across Central America and the Caribbean. This study provided training and established technical networks for more effective and sustainable insecticide surveillance programs. Most but not all records of insecticide resistance in A. aegypti were consistent between methodologies, thus inconsistent issues are discussed here to call for further improvement in procedures and convey more practical guidelines for surveillance teams in countries where Aedes-borne diseases are endemic. Author summaryAt the forefront of the fight against arboviruses transmission is the insecticide-based vector control. All countries in the Latin American and Caribbean region invest valuable resources from their limited budget to acquire and implement insecticide-based tools, with non-existent or weak insecticide resistance monitoring programs. Hence, the USAID-funded Zika AIRS Project (ZAP) collaborated with the Ministries of Health of multiple countries to update the profile of susceptibility to insecticides in Aedes aegypti populations. We found widespread resistance to pyrethroid and organophosphate insecticides, which account to almost 100% of the products available to control adult mosquitoes. As we used both of World Health Organization and Centers for Disease Control and Prevention standard methods, we found many similarities and some inconsistencies in the susceptibility profiles obtained for the very same vector populations. Additionally, we obtained insight on potential molecular mechanisms of resistance across the countries, finding the kdr mutation V1016I possibly involved in loss of susceptibility. This study is the biggest cross-country update of insecticide resistance for Aedes aegypti in years, and it should be used as evidence for improving the selection of insecticides in these countries and a call for further support to maintain insecticide resistance monitoring programs.

ecology↗

bioRxiv2019

Lipidome profiles of postnatal day 2 vaginal swabs reflect fat composition of gilts postnatal diet

We hypothesized that postnatal development of the vagina is impacted by early nutritional environment. Our objective was to determine if lipid profiles of vaginal swabs were different between gilts suckled by sow or fed milk replacer the first 48 h postpartum, with and without a lard-based fat supplement. Gilts (>1.3 kg) were selected at birth across 8 litters and assigned to treatments: colostrum suckled (S, n=8); S plus fat supplement (SF, n=5); bottle-fed milk replacer (B, n=8); or B plus fat supplement (BF, n=7). At 48 h postnatal, vaginal swabs were taken with a cytology brush, immersed in ultrapure water to burst cells, and lipids extracted for analysis using multiple reaction monitoring (MRM)-profiling. Lipids extracted from serum collected at 48 h from gilts and milk collected from sows at 24 h were also analyzed with MRM-profiling. Receiver operating characteristic curve analysis found 18 lipids highly distinguished [area-under-the-curve (AUC) > 0.9] between S and B gilts, including phosphatidylethanolamine with 34 carbon and four unsaturations in the fatty acyl residues [PE(34:4)]. Twelve lipids from vaginal swabs highly correlated (r > 0.6; p < 0.01) with nutrition source. Lipids more abundant in milk replacer drove association. For example, mean intensity of PE (34:4) was 149-fold higher in milk replacer than colostrum, with 1.6- and 2.12-fold higher levels in serum and vaginal swab samples (p < 0.001), respectively, of B versus S gilts. Findings support that vaginal swabs can be used to noninvasively study effects of perinatal nutrition on tissue composition.\n\nSummary sentenceVaginal swab lipidome profiles at 48 h reflect the fat composition of neonatal diet during first two days postnatal.

developmental biology↗