Search bioRxiv⌕ Search

Biology subjects

Neves, A.

Publications and source records attributed to Neves, A..

5 recordsLinked to original sources

Community needs for FAIR pathogen data

BackgroundDatasets related to infectious diseases are essential for public health decision-making, yet their reuse remains limited by persistent barriers to data sharing and integration. Achieving data that are Findable, Accessible, Interoperable, and Reusable (FAIR) is widely recognized as essential for accelerating scientific discovery and enabling coordinated responses to emerging threats, but the needs of the global pathogen data community have not been systematically characterized. AimThis study, conducted by the Pathogen Data Network (PDN), aims to identify infrastructural and educational priorities among stakeholders working with infectious disease-related data in order to guide community-responsive support for data sharing and interoperability. MethodsA cross-sectional stakeholder survey was disseminated to a well-defined expert population within PDN networks and via open professional channels. A total of 136 responses from researchers, healthcare professionals, bioinformaticians, and educators were analyzed descriptively to identify prioritized barriers, training needs, and preferred support mechanisms. ResultsRespondents consistently identified structural constraints as the primary impediments to effective data use, including limited funding (74%), data-aggregation challenges (68%), and a shortage of skilled personnel (52%). Respondents identified bioinformatics for infectious disease research (68%) as the highest priority for training, followed by guidance on using the integrated pathogen data and tools portal provided by the PDN, the Pathogens Portal (51%). The Pathogens Portal was also ranked as the most essential PDN resource (72%). Preferred training formats included virtual short courses (68%) and webinars (66%). Notably, while researchers emphasized technical subjects like machine learning, educators prioritized foundational case studies. ConclusionThese findings provide an evidence-based diagnostic of community needs and suggest that barriers to FAIR pathogen data are predominantly systemic rather than purely technological. The survey framework and openly available dataset offer a reusable template for assessing needs in other communities and regions. By aligning training, infrastructure development, and outreach with empirically identified priorities, organizations supporting infectious disease research can strengthen the interoperability and reuse of data and establish a benchmark for future community-driven improvements.

scientific communication and education↗

Pulsed stimulated Brillouin microscopy enables high-sensitivity mechanical imaging of live and fragile biological specimens

Brillouin microscopy is an emerging optical elastography technique capable of assessing mechanical properties of biological samples in a 3D, all-optical and hence non-contact fashion. The typically weak Brillouin scattering signal can be substantially enhanced via a stimulated photon-phonon process, which improves the signal-to-background ratio (SBR) as well as provides higher spectral resolution. However, current implementations of stimulated Brillouin spectroscopy (SBS) require high pump powers, which prohibit applications in many areas of biology, especially when studying photosensitive samples, or when live-imaging in 3D and/or over extended time periods. Here, we present a pulsed SBS scheme that takes full advantage of the non-linearity of the pump-probe interaction in SBS. In particular, we show that through quasi-pulsing and diligent optimization of signal detection parameters, the required pump laser power can be decreased ~20-fold without affecting the signal levels or spectral precision. Moreover, we devise a custom analysis approach that facilitates the analysis of complex, multi-peaked Brillouin spectra in order to harness the high spectral resolution of SBS for the specific identification of biomechanical components inside the point-spread function of the microscope. We then demonstrate the low-phototoxicity and high-specificity of our pulsed SBS approach by imaging sensitive single cells, zebrafish larvae, and mouse embryos as well as adult C. elegans with sub-cellular detail. Furthermore, our method permits observing the mechanics of organoids and C. elegans embryos over time. We expect that the substantially lower photo-burden and improved SBR of pulsed SBS will facilitate studying biomechanics in 3D at high spatio-temporal resolution in living biological specimens in a non-invasive manner, opening up exciting new possibilities for the field of mechanobiology.

bioengineering↗

MusMorph, a database of standardized mouse morphology data for morphometric meta-analyses

Complex morphological traits are the product of many genes with transient or lasting developmental effects that interact in anatomical context. Mouse models are a key resource for disentangling such effects, because they offer myriad tools for manipulating the genome in a controlled environment. Unfortunately, phenotypic data are often obtained using laboratory-specific protocols, resulting in self-contained datasets that are difficult to relate to one another for larger scale analyses. To enable meta-analyses of morphological variation, particularly in the craniofacial complex and brain, we created MusMorph, a database of standardized mouse morphology data spanning numerous genotypes and developmental stages, including E10.5, E11.5, E14.5, E15.5, E18.5, and adulthood. To standardize data collection, we implemented an atlas-based phenotyping pipeline that combines techniques from image registration, deep learning, and morphometrics. Alongside stage-specific atlases, we provide aligned micro-computed tomography images, dense anatomical landmarks, and segmentations (if available) for each specimen (N=10,056). Our workflow is open-source to encourage transparency and reproducible data collection. The MusMorph data and scripts are available on FaceBase (www.facebase.org, doi.org/10.25550/3-HXMC) and GitHub (https://github.com/jaydevine/MusMorph).

genetics↗

The Microbial Metabolite 4-Cresol Improves Glucose Homeostasis and Enhances β-Cell Function

Gut microbiota changes are associated with increased risk of Type 2 diabetes (T2D) and obesity. Through serum metabolome profiling in patients with cardiometabolic disease (CMD) we identified significant inverse correlation between the microbial metabolite 4-cresol and T2D. Chronic administration of non toxic dose of 4-cresol in two complementary preclinical models of CMD reduced adiposity, glucose intolerance and liver triglycerides, and enhanced insulin secretion in vivo, which may be explained by markedly increased pancreas weight, augmented islet density and size, and enhanced vascularisation suggesting activated islet neogenesis. Incubation of isolated islets with 4-cresol enhanced insulin secretion, insulin content and cell proliferation. In both CMD models 4-cresol treatment in vivo was associated with altered expression of SIRT1 and the kinase DYRK1A, which may contribute to mediate its biological effects. Our findings identify 4-cresol as an effective regulator of {beta}-cell function and T2D endophenotypes, which opens therapeutic perspectives in syndromes of insulin deficiency.

physiology↗

Distinct gene-selective roles for a network of core promoter factors in Drosophila neural stem cell identity.

The transcriptional mechanisms that allow neural stem cells (NSC) to balance self-renewal with differentiation are not well understood. Employing an in vivo RNAi screen we identify here NSC-TAFs, a subset of nine TATA-binding protein associated factors (TAFs), as NSC identity genes in Drosophila. We found that depletion of NSC-TAFs results in decreased NSC clone size, reduced proliferation, defective cell polarity and increased hypersensitivity to cell cycle perturbation, without affecting NSC survival. Integrated gene expression and genomic binding analyses revealed that NSC-TAFs function with both TBP and TRF2, and that NSC-TAF-TBP and NSC-TAF-TRF2 shared target genes encode different subsets of transcription factors and RNA-binding proteins with established or emerging roles in NSC identity and brain development. Taken together, our results demonstrate that core promoter factors are selectively required for NSC identity in vivo by promoting cell cycle progression and NSC cell polarity as well as by restraining premature differentiation. Because pathogenic variants in a subset of TAFs have all been linked to human neurological disorders, this work may stimulate and inform future animal models of TAF-linked neurological disorders.\n\nAuthor summaryThe brains of many animal species are built with brain stem cells. Having too many brain stem cells can lead to brain tumors whereas too few can lead to birth defects such as microcephaly. A number of next generation sequencing studies have implicated proteins referred to as TATA-box-binding protein associated factors (TAFs) in human neurological disorders including microcephaly, but prior to this study, their function in brain development was unknown. Here we use brain stem cells, known as neural stem cells (NSCs), from the fruit fly Drosophila melanogaster as a model system to decipher how TAFs control brain stem cell identity. By combining genetics and low-input genomics, we show that TAFs directly control NSC cell division and cell polarity but do not appear to be required for NSC survival. We further show that TAFs accomplish these functions by associating either with their canonical partner TBP (TATA-binding protein) or the related protein TRF2. In summary, our study reveals unexpected and gene-selective functions of a unique subset of TAFs and their binding partners, which could inform future studies that seek to model human neurological disorders associated with TAFs.

developmental biology↗