Optogenetic acidification of synaptic vesicles and lysosomes

Acidification is required for the function of many intracellular organelles, but methods to acutely manipulate their intraluminal pH have not been available. Here we present a targeting strategy to selectively express the light-driven proton pump Arch3 on synaptic vesicles. Our new tool, pHoenix, can functionally replace endogenous proton pumps, enabling optogenetic control of vesicular acidification and neurotransmitter accumulation. Under physiological conditions, glutamatergic vesicles are nearly full, as additional vesicle acidification with pHoenix only slightly increased the quantal size. By contrast, we found that incompletely filled vesicles exhibited a lower release probability than full vesicles, suggesting preferential exocytosis of vesicles with high transmitter content. Our subcellular targeting approach can be transferred to other organelles, as demonstrated for a pHoenix variant that allows light-activated acidification of lysosomes

In Vivo Methods for the Assessment of Topical Drug Bioavailability

This paper reviews some current methods for the in vivo assessment of local cutaneous bioavailability in humans after topical drug application. After an introduction discussing the importance of local drug bioavailability assessment and the limitations of model-based predictions, the focus turns to the relevance of experimental studies. The available techniques are then reviewed in detail, with particular emphasis on the tape stripping and microdialysis methodologies. Other less developed techniques, including the skin biopsy, suction blister, follicle removal and confocal Raman spectroscopy techniques are also described

Biological Earth observation with animal sensors.

Space-based tracking technology using low-cost miniature tags is now delivering data on fine-scale animal movement at near-global scale. Linked with remotely sensed environmental data, this offers a biological lens on habitat integrity and connectivity for conservation and human health; a global network of animal sentinels of environmen-tal change

Perceived and observed biases within scientific communities: a case study in movement ecology

Who conducts biological research, where they do it and how results are disseminated vary among geographies and identities. Identifying and documenting these forms of bias by research communities is a critical step towards addressing them. We documented perceived and observed biases in movement ecology, a rapidly expanding sub-discipline of biology, which is strongly underpinned by fieldwork and technology use. We surveyed attendees before an international conference to assess a baseline within-discipline perceived bias (uninformed perceived bias). We analysed geographic patterns in Movement Ecology articles, finding discrepancies between the country of the authors’ affiliation and study site location, related to national economics. We analysed race-gender identities of USA biology researchers (the closest to our sub-discipline with data available), finding that they differed from national demographics. Finally, we discussed the quantitatively observed bias at the conference, to assess within-discipline perceived bias informed with observational data (informed perceived bias). Although the survey indicated most conference participants as bias-aware, conversations only covered a subset of biases. We discuss potential causes of bias (parachute-science, fieldwork accessibility), solutions and the need to evaluate mitigatory action effectiveness. Undertaking data-driven analysis of bias within sub-disciplines can help identify specific barriers and move towards the inclusion of a greater diversity of participants in the scientific process

Current developments in antibiotic discovery: Global microbial diversity as a source for evolutionary optimized anti-bacterials: Global microbial diversity as a source for evolutionary optimized anti-bacterials

In light of the pending antibiotic resistance crisis, we need to go back to nature and search for novel anti-bacterial compounds