Repurposing of glatiramer acetate to treat cardiac ischemia in rodent models.

Myocardial injury may ultimately lead to adverse ventricular remodeling and development of heart failure (HF), which is a major cause of morbidity and mortality worldwide. Given the slow pace and substantial costs of developing new therapeutics, drug repurposing is an attractive alternative. Studies of many organs, including the heart, highlight the importance of the immune system in modulating injury and repair outcomes.

Conventional type 1 dendritic cells are essential for the development of primary biliary cholangitis.

Background & Aims: Primary biliary cholangitis (PBC) is a progressive-cholestatic autoimmune liver disease. Dendritic cells (DC) are professional antigen-presenting cells and their prominent presence around damaged bile ducts of PBC patients are documented. cDC1 is a rare subset of DC known for its cross-presentation abilities and interleukin 12 production.

Large-scale proteomics analysis of five brain regions from Parkinson's disease patients with a GBA1 mutation.

Despite being the second most common neurodegenerative disorder, little is known about Parkinson's disease (PD) pathogenesis. A number of genetic factors predispose towards PD, among them mutations in GBA1, which encodes the lysosomal enzyme acid-β-glucosidase. We now perform non-targeted, mass spectrometry based quantitative proteomics on five brain regions from PD patients with a GBA1 mutation (PD-GBA) and compare to age- and sex-matched idiopathic PD patients (IPD) and controls.

Proteomics analysis of the brain from a Gaucher disease mouse identifies pathological pathways including a possible role for transglutaminase 1.

Gaucher disease (GD) is a lysosomal storage disorder (LSD) caused by the defective activity of acid β-glucosidase (GCase) which results from mutations in GBA1. Neurological forms of GD (nGD) can be generated in mice by intra-peritoneal injection of conduritol B-epoxide (CBE) which irreversibly inhibits GCase. Using this approach, a number of pathological pathways have been identified in mouse brain by RNAseq.

Differential gene expression in the calvarial and cortical bone of juvenile female mice.

Introduction: Both the calvarial and the cortical bones develop through intramembranous ossification, yet they have very different structures and functions. The calvaria enables the rapid while protected growth of the brain, whereas the cortical bone takes part in locomotion. Both types of bones undergo extensive modeling during embryonic and post-natal growth, while bone remodeling is the most dominant process in adults.

Genomic structural plasticity of rodent-associated Bartonella in nature.

Rodent-associated Bartonella species have shown a remarkable genetic diversity and pathogenic potential. To further explore the extent of the natural intraspecific genomic variation and its potential role as an evolutionary driver, we focused on a single genetically diverse Bartonella species, Bartonella krasnovii, which circulates among gerbils and their associated fleas. Twenty genomes from 16 different B.

β-sitosterol reduces anxiety and synergizes with established anxiolytic drugs in mice.

Anxiety and stress-related conditions represent a significant health burden in modern society. Unfortunately, most anxiolytic drugs are prone to side effects, limiting their long-term usage. Here, we employ a bioinformatics screen to identify drugs for repurposing as anxiolytics.

Dasatinib response in acute myeloid leukemia is correlated with FLT3/ITD, PTPN11 mutations and a unique gene expression signature.

Novel targeted therapies demonstrate improved survival in specific subgroups (defined by genetic variants) of acute myeloid leukemia (AML) patients, validating the paradigm of molecularly targeted therapy. However, identifying correlations between AML molecular attributes and effective therapies is challenging. Recent advances in high-throughput in vitro drug sensitivity screening applied to primary AML blasts were used to uncover such correlations; however, these methods cannot predict the response of leukemic stem cells (LSCs).

sp. nov. and sp. nov., two novel species closely related to the zoonotic , isolated from black rats and wild desert rodent-fleas.

The genus (Family: ; Order: Class: Alphaproteobacteria) comprises facultative intracellular Gram-negative, haemotropic, slow-growing, vector-borne bacteria. Wild rodents and their fleas harbor a great diversity of species and strains of the genus , including several zoonotic ones. This genetic diversity coupled with a fastidious nature of the organism results in a taxonomic challenge that has led to a massive collection of uncharacterized strains.

Heterochronic regulation of lung development the Lin28-Let-7 pathway.

The heterochronic gene Lin28 regulates diverse developmental processes. It was shown previously that global Lin28A overexpression during mouse embryogenesis results in perinatal lethality. However, the reason for this early lethality has not been elucidated.

Illuminating spatial A-to-I RNA editing signatures within the brain.

Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by ADAR enzymes, is a ubiquitous mechanism that generates transcriptomic diversity. This process is particularly important for proper neuronal function; however, little is known about how RNA editing is dynamically regulated between the many functionally distinct neuronal populations of the brain. Here, we present a spatial RNA editing map in the brain and show that different neuronal populations possess distinct RNA editing signatures.

The Toll Pathway in the Central Nervous System of Flies and Mammals.

Toll receptors, first identified to regulate embryogenesis and immune responses in the adult fly and subsequently defined as the principal sensors of infection in mammals, are increasingly appreciated for their impact on the homeostasis of the central as well as the peripheral nervous systems. Whereas in the context of immunity, the fly Toll and the mammalian TLR pathways have been researched in parallel, the expression pattern and functionality have largely been researched disparately. Herein, we provide data on the expression pattern of the Toll homologues, signaling components, and downstream effectors in ten different cell populations of the adult fly central nervous system (CNS).

Culturing CTLs under Hypoxic Conditions Enhances Their Cytolysis and Improves Their Anti-tumor Function.

Cytotoxic T lymphocytes (CTLs) used in immunotherapy are typically cultured under atmospheric O pressure but encounter hypoxic conditions inside tumors. Activating CTLs under hypoxic conditions has been shown to improve their cytotoxicity in vitro, but the mechanism employed and the implications for immunotherapy remain unknown. We activated and cultured OT-I CD8 T cells at either 1% or 20% O.

Regulatory module involving FGF13, miR-504, and p53 regulates ribosomal biogenesis and supports cancer cell survival.

The microRNA miR-504 targets TP53 mRNA encoding the p53 tumor suppressor. miR-504 resides within the fibroblast growth factor 13 (FGF13) gene, which is overexpressed in various cancers. We report that the FGF13 locus, comprising FGF13 and miR-504, is transcriptionally repressed by p53, defining an additional negative feedback loop in the p53 network.

MS1-based label-free proteomics using a quadrupole orbitrap mass spectrometer.

Presented is a data set for benchmarking MS1-based label-free quantitative proteomics using a quadrupole orbitrap mass spectrometer. Escherichia coli digest was spiked into a HeLa digest in four different concentrations, simulating protein expression differences in a background of an unchanged complex proteome. The data set provides a unique opportunity to evaluate the proteomic platform (instrumentation and software) in its ability to perform MS1-intensity-based label-free quantification.