Biology subjects

Mendes, J.

Publications and source records attributed to Mendes, J..

4 recordsLinked to original sources

bioRxiv2026

A randomized trial of grant writing coaching groups: Qualitative interviews revealing key elements of intervention efficacy

Background Training in grant proposal writing is an essential component of professional development for academic scientists in the biomedical and behavioral sciences. Despite the expansion of inter- and intra-institutional grant writing coaching groups as an approach to honing these skills, specific features that enhance or limit coaching group effectiveness have not been rigorously studied. Methods Qualitative inerviews were conducted with a subset of early-career investigators (n=204 and coaches (n=36) engaged in a national, U.S. based, group-randomized trial of grant writing coaching groups to test the effects of two variables on submission and funding of national-level proposals: (1) coaching duration (regular/extended dose) and (2) mode of engaging a scientific advisor (someone with content-aligned expertise) in the coaching process. This report focuses on interviews conducted upon completion of the regular coaching dose - 5 months of biweekly, group-based coaching sessions to support active proposal writing. Interviews were designed to identify which coaching group elements were perceived to be the most critical. Transcribed interviews were analyzed using deductive (participants) or open (coaches) coding to identify themes. Results Triangulation of results from participant and coach interviews showed strong concordance that coaches, peers, and scientific advisors all played key roles in supporting intervention efficacy. Sufficient alignment of scientific fields and/or methodologies among group members was important, although breadth of perspectives was also valued. Other critical group features were skilled and well-organized coaches, detailed feedback, peer-to-peer support (technical and psychosocial), and clear expectations for group functioning. Factors attenuating impact included variation in participants' engagement and "readiness to write," within-group mismatches of expertise or grant mechanisms, and limited research support at some participants' home institutions. Conclusion This study identified key elements of successful grant writing coaching groups and potential barriers to their effectiveness, while yielding insights about tailoring this approach for individuals at different stages of proposal development.

scientific communication and education↗

bioRxiv2026

Sexual conflict, directional sexual selection and phenotypic plasticity jointly drive the evolution of extreme phenotypic variation

How broad phenotypic variation is maintained in natural populations in the face of selection is a central question in evolutionary biology. We address this question in the water strider Microvelia longipes, where males exhibit striking variation in rear leg length used in male-male contests for dominance. Using reaction norm experiments on inbred lines, we demonstrate that phenotypic plasticity contributes to expanding phenotypic variation, but requires high genetic variation to generate the broad range of trait expression observed in natural populations. Experimental evolution favouring trait exaggeration revealed that directional sexual selection not only fails to erode variation of male rear leg length, but rather amplifies it beyond the natural distribution. Additionally, male-limited selection in favour of dominance generated substantial fecundity costs in females, underscoring the role of sexual conflict driven by females in constraining exaggerated secondary sexual traits in males. Our findings show that sexually antagonistic selection and directional sexual selection jointly generate high genetic variation, which phenotypic plasticity inflates into broad phenotypic distribution of male weapon size. This provides an empirical explanation for the high variability of male exaggerated weapons in nature.

evolutionary biology↗

bioRxiv2025

Promoter-proximal gatekeepers restrict pleiotropic enhancer inputs to achieve tissue specificity

The spatiotemporal expression of developmental genes is regulated by the interplay of two key regulatory elements: core promoters, generally assumed to support only basal transcription, and enhancers, which enable their tissue- and stage-specific activation. Here, we show that spatiotemporal specificity can also be encoded within the core promoter. Using the Drosophila twist E3 enhancer as a model, we found that E3 is pleiotropic and activates four functionally unrelated genes. Despite receiving the same enhancer input, each target gene displays distinct and non-overlapping expression patterns. We demonstrate that the selective activation of each target gene is encoded within their promoter regions. Core promoters act as "gatekeepers" that restrict enhancer input into precise tissue- and stage-specific transcription, while proximal-promoter elements facilitate enhancer responsiveness. We propose that promoters function as active interpreters rather than passive recipients of enhancer signals, providing a critical but under-appreciated layer of regulatory specificity within complex gene expression programs.

genetics↗

bioRxiv2024

Disconnection Between Microvascular Damage and Neurodegeneration in Early Diabetic Retinopathy

AimDiabetic retinopathy (DR) is a common complication of diabetes mellitus and can result in vision loss. Early clinically diagnosed signs of DR are linked to vascular damage, impacting on the neural retina typically at later stages. However, vascular changes and potential effects on neural cells before clinical diagnosis of DR are less understood. MethodsTo learn more about the earliest stages of DR we studied postmortem retina from diabetic donors who did not have clinical DR. Histological phenotyping and quantitative analysis were carried out on retina from 14 donors (3 controls, 10 diabetics, and 1 DR case) to examine capillary loss in the deeper vascular plexus (DVP) and the superficial vascular plexus (SVP) of the retinal vasculature and to study effects on the neural retina. ResultThe advanced DR case exhibited profound vascular and neural damage as expected, whereas none of the ten randomly selected diabetic donors had any DR signs that would have been diagnosed clinically. Within that group, two showed very minor capillary dropout in the SVP, whilst in the remaining diabetic cases the SVP was indistinguishable from the controls. In contrast, over half of the diabetic retinas showed capillary dropout in the DVP and increased capillary diameter. Furthermore, a pan retinal loss of inner nuclear layer cells was observed in those diabetics with capillary dropout compared to the controls (p<0.05), but there was no local spatial correlation between neural cell loss and capillary dropout. ConclusionsOur study has established a novel histological biomarker for diabetes related tissue damage at the earliest stages of DR in human postmortem retina, which appears to be common in people with diabetes before DR can be clinically diagnosed. Furthermore, the spatial mismatch between local capillary dropout and the diffuse neural loss in the INL suggests that at this very early stage of DR, microvascular loss may not causally be directly connected to neurodegeneration and that diabetes may affect the two readouts independently. RESEARCH IN CONTEXTWhat is already known about this subject? O_LIEarly DR is currently clinically defined by visible microvascular changes. C_LIO_LITests of retinal function in people with diabetes imply neuroretinal impairments in early DR. C_LIO_LIClinical imaging in people with diabetes suggests reduced perfusion in the deep retinal vasculature plexus. C_LI What is the key question? (one bullet point only; formatted as a question) O_LIHow does retinal microvascular damage relate to neuronal damage? C_LI What are the new findings? O_LIWe have developed a sensitive histological biomarker for microvascular damage in postmortem retinal tissue. C_LIO_LIEarly vascular changes in the deeper plexus occur in diabetes even in the absence of manifest DR. C_LIO_LINeurodegenerative changes are distributed throughout the retina in diabetes and do not spatially correlate with microvascular nonperfusion. C_LI How might this impact on clinical practice in the foreseeable future? O_LIDeeper plexus perfusion can be a useful early biomarker to assess DR. C_LI

pathology↗