B Cell apoptosis in the central nervous system in experimental autoimmune Encephalomyelitis: Roles of B Cell CD95, CD95L and Bcl-2 expression

The role and fate of B cells in the central nervous system (CNS) in experimental autoimmune encephalomyelitis (EAE) are unknown. Using enzyme-linked immunospot assays we now show that B cells reactive to myelin basic protein (MBP) accumulate in the CNS of Lewis rats with acute EAE induced by immunization with MBP and adjuvants. We also report that B cells are eliminated from the CNS by apoptosis during spontaneous recovery from this disease. Apoptotic B cells were identified by flow cytometry of inflammatory cells extracted from the spinal cord and by histological sections of the spinal cord using light and electron microscopic immunocytochemistry. B cell apoptosis occurred preferentially in the CNS rather than in the peripheral lymphoid organs and was maximal just prior to the onset of spontaneous clinical recovery. Three colour flow cytometry indicated that B cells expressing CD95 (Fas) or CD95 ligand (CD95L) were highly vulnerable to apoptosis, whereas B cells expressing Bcl-2 were relatively protected from apoptosis. We propose that B cells are eliminated from the CNS by the interaction of CD95L and CD95 on the same B cell and that this contributes to the spontaneous resolution of CNS inflammation and clinical recovery in acute EAE

The effect of maternal undernutrition on the rat placental transcriptome: protein restriction up-regulates cholesterol transport

Fetal exposure to a maternal low protein diet during rat pregnancy is associated with hypertension, renal dysfunction and metabolic disturbance in adult life. These effects are present when dietary manipulations target only the first half of pregnancy. It was hypothesised that early gestation protein restriction would impact upon placental gene expression and that this may give clues to the mechanism which links maternal diet to later consequences. Pregnant rats were fed control or a low protein diet from conception to day 13 gestation. Placentas were collected and RNA Sequencing performed using the Illumina platform. Protein restriction down-regulated 67 genes and up-regulated 24 genes in the placenta. Ingenuity pathway analysis showed significant enrichment in pathways related to cholesterol and lipoprotein transport and metabolism, including atherosclerosis signalling, clathrin-mediated endocytosis, LXR/RXR and FXR/RXR activation. Genes at the centre of these processes included the apolipoproteins ApoB, ApoA2 and ApoC2, microsomal triglyceride transfer protein (Mttp), the clathrin-endocytosis receptor cubilin, the transcription factor retinol binding protein 4 (Rbp4) and transerythrin (Ttr; a retinol and thyroid hormone transporter). Real-time PCR measurements largely confirmed the findings of RNASeq and indicated that the impact of protein restriction was often striking (cubilin up-regulated 32-fold, apoC2 up-regulated 17.6-fold). The findings show that gene expression in specific pathways is modulated by maternal protein restriction in the day-13 rat placenta. Changes in cholesterol transport may contribute to altered tissue development in the fetus and hence programme risk of disease in later life

Recent progress in genetics of aging, senescence and longevity: focusing on cancer-related genes

It is widely believed that aging results from the accumulation of molecular damage, including damage of DNA and mitochondria and accumulation of molecular garbage both inside and outside of the cell. Recently, this paradigm is being replaced by the “hyperfunction theory�, which postulates that aging is caused by activation of signal transduction pathways such as TOR (Target of Rapamycin). These pathways consist of different enzymes, mostly kinases, but also phosphatases, deacetylases, GTPases, and some other molecules that cause overactivation of normal cellular functions. Overactivation of these sensory signal transduction pathways can cause cellular senescence, age-related diseases, including cancer, and shorten life span. Here we review some of the numerous very recent publications on the role of signal transduction molecules in aging and age-related diseases. As was emphasized by the author of the “hyperfunction model�, many (or actually all) of them also play roles in cancer. So these “participants� in pro-aging signaling pathways are actually very well acquainted to cancer researchers. A cancer-related journal such as Oncotarget is the perfect place for publication of such experimental studies, reviews and perspectives, as it can bridge the gap between cancer and aging researchers

Gut microbiota functions: metabolism of nutrients and other food components

The diverse microbial community that inhabits the human gut has an extensive metabolic repertoire that is distinct from, but complements the activity of mammalian enzymes in the liver and gut mucosa and includes functions essential for host digestion. As such, the gut microbiota is a key factor in shaping the biochemical profile of the diet and, therefore, its impact on host health and disease. The important role that the gut microbiota appears to play in human metabolism and health has stimulated research into the identification of specific microorganisms involved in different processes, and the elucidation of metabolic pathways, particularly those associated with metabolism of dietary components and some host-generated substances. In the first part of the review, we discuss the main gut microorganisms, particularly bacteria, and microbial pathways associated with the metabolism of dietary carbohydrates (to short chain fatty acids and gases), proteins, plant polyphenols, bile acids, and vitamins. The second part of the review focuses on the methodologies, existing and novel, that can be employed to explore gut microbial pathways of metabolism. These include mathematical models, omics techniques, isolated microbes, and enzyme assays