ProHap enables human proteomic database generation accounting for population diversity.

Amid the advances in genomics, the availability of large reference panels of human haplotypes is key to account for human diversity within and across populations. However, mass spectrometry-based proteomics does not benefit from this information. To address this gap, we introduce ProHap, a Python-based tool that constructs protein sequence databases from phased genotypes of reference panels.

Management, health, and veterinary care of donkeys in Switzerland: A cross-sectional study.

Limited information currently exists concerning donkey husbandry and health in Switzerland. Within the framework of this study, Swiss donkey owners, veterinarians, and official veterinary offices were surveyed online to obtain information on current husbandry and feeding practices, health care, and status of Swiss donkeys and to clarify the need for further education in this area. A total of 705 owners with 1463 donkeys, 141 veterinarians, and 19 official veterinary offices were included in the study.

Protective effect of TCR-mediated MAIT cell activation during experimental autoimmune encephalomyelitis.

Mucosal-associated invariant T (MAIT) cells express semi-invariant T cell receptors (TCR) for recognizing bacterial and yeast antigens derived from riboflavin metabolites presented on the non-polymorphic MHC class I-related protein 1 (MR1). Neuroinflammation in multiple sclerosis (MS) is likely initiated by autoreactive T cells and perpetuated by infiltration of additional immune cells, but the precise role of MAIT cells in MS pathogenesis remains unknown. Here, we use experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, and find an accumulation of MAIT cells in the inflamed central nervous system (CNS) enriched for MAIT17 (RORγt) and MAIT1/17 (T-betRORγt) subsets with inflammatory and protective features.

The NR4A2/VGF pathway fuels inflammation-induced neurodegeneration via promoting neuronal glycolysis.

A disturbed balance between excitation and inhibition (E/I balance) is increasingly recognized as a key driver of neurodegeneration in multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system. To understand how chronic hyperexcitability contributes to neuronal loss in MS, we transcriptionally profiled neurons from mice lacking inhibitory metabotropic glutamate signaling with shifted E/I balance and increased vulnerability to inflammation-induced neurodegeneration. This revealed a prominent induction of the nuclear receptor NR4A2 in neurons.