Microbiota links to neural dynamics supporting threat processing

There is growing recognition that the composition of the gut microbiota influences behaviour, including responses to threat. The cognitive‐interoceptive appraisal of threat‐related stimuli relies on dynamic neural computations between the anterior insular (AIC) and the dorsal anterior cingulate (dACC) cortices. If, to what extent, and how microbial consortia influence the activity of this cortical threat processing circuitry is unclear. We addressed this question by combining a threat processing task, neuroimaging, 16S rRNA profiling and computational modelling in healthy participants. Results showed interactions between high‐level ecological indices with threat‐related AIC‐dACC neural dynamics. At finer taxonomic resolutions, the abundance of Ruminococcus was differentially linked to connectivity between, and activity within the AIC and dACC during threat updating. Functional inference analysis provides a strong rationale to motivate future investigations of microbiota‐derived metabolites in the observed relationship with threat‐related brain processes.     

Evaluation of the bioequivalence and food effect on the bioavailability of CC-486 (oral azacitidine) tablets in adult patients with cancer

Cancer Chemotherapy and Pharmacology - CC-486 is an oral formulation of azacitidine that allows for extended dosing schedules to prolong azacitidine exposure to malignant cells and maximize...     

A benzothiazole-based new fluorogenic chemosensor for the detection of CN− and its real-time application in environmental water samples and living cells

Since the cyanide ion is used in a wide range of industries and is harmful to both human health and the environment, a number of research efforts are dedicated to creating fluorescence sensors for the detection of cyanide (CN⁻). Herein, for the fluorescence detection of CN⁻, a new highly selective and sensitive sensor 2-(3-(benzo[d]thiazol-2-yl)-4-hydroxybenzylidene)-1H-indene-1,3(2H)-dione (BID) was created by conjugating a benzothiazole moiety with 1H-indene-1,3(2H)-dione. The donor and acceptor components of this hybrid receptor were covalently connected through a double bond. The nucleophilic addition of a cyanide anion to the BID inhibits the intramolecular charge transfer (ICT) transition, resulting in spectral and colour alterations in the receptor. When the solvent polarity was increased from n-hexane to methanol, this molecule exhibited a bathochromic shift in the emission wavelength (610 to 632 nm), suggesting the presence of a solvatochromic action. The sensor BID has shown strong specificity towards CN⁻ by interrupting its internal charge transfer (ICT), resulting in a significant change in the UV-vis spectrum and a notable blue shift in the fluorescence emission spectrum. The cyanide anion (CN⁻) is responsible for the optical alterations observed by BID, as opposed to the other anions examined. The detection limit was 5.97 nM, significantly less than the WHO''s permitted amount of CN⁻ in drinking water. The experimental findings indicate that BID''s fluorescence response to CN⁻ is pH insensitive throughout a wide pH range of 6.0 to 12.0. The interaction mechanism between the BID and CN⁻ ions has been studied by HRMS, ¹H-NMR titration experiments, FT-IR, and DFT, which confirmed the nucleophilic addition of CN⁻ on vinylidene and subsequent disturbance of ICT. Additionally, we demonstrated the real-time detection application of CN⁻ in environmental water samples and live-cell imaging.

Since the cyanide ion is used in a wide range of industries and is harmful to both human health and the environment, a number of research efforts are dedicated to creating fluorescence sensors for the detection of cyanide (CN⁻).     

Delineating developmental and metabolic pathways in vivo by expression profiling using the RIKEN set of 18,816 full-length enriched mouse cDNA arrays

We have systematically characterized gene expression patterns in 49 adult and embryonic mouse tissues by using cDNA microarrays with 18,816 mouse cDNAs. Cluster analysis defined sets of genes that were expressed ubiquitously or in similar groups of tissues such as digestive organs and muscle. Clustering of expression profiles was observed in embryonic brain, postnatal cerebellum, and adult olfactory bulb, reflecting similarities in neurogenesis and remodeling. Finally, clustering genes coding for known enzymes into 78 metabolic pathways revealed a surprising coordination of expression within each pathway among different tissues. On the other hand, a more detailed examination of glycolysis revealed tissue-specific differences in profiles of key regulatory enzymes. Thus, by surveying global gene expression by using microarrays with a large number of elements, we provide insights into the commonality and diversity of pathways responsible for the development and maintenance of the mammalian body plan.