Ocrelizumab Impairs the Phenotype and Function of Memory CD8 T Cells: A 1-Year Longitudinal Study in Patients With Multiple Sclerosis.

Background And Objective: Depleting CD20 B cells is the primary mechanism by which ocrelizumab (OCRE) is efficient in persons with multiple sclerosis (pwMS). However, the exact role of OCRE on other immune cell subsets directly or indirectly remains elusive. The purpose of this study is to characterize the dynamics of peripheral immune cells of pwMS on OCRE.

Appropriate Thiamin Pyrophosphate Levels Are Required for Acclimation to Changes in Photoperiod.

Thiamin pyrophosphate (TPP) is the active form of vitamin B and works as an essential cofactor for enzymes in key metabolic pathways, such as the tricarboxylic acid (TCA) cycle and the pentose phosphate pathway. Although its action as a coenzyme has been well documented, the roles of TPP in plant metabolism are still not fully understood. Here, we investigated the functions of TPP in the regulation of the metabolic networks during photoperiod transition using previously described Arabidopsis () riboswitch mutant plants, which accumulate thiamin vitamers.

A pathway for repair of NAD(P)H in plants.

Unwanted enzyme side reactions and spontaneous decomposition of metabolites can lead to a build-up of compounds that compete with natural enzyme substrates and must be dealt with for efficient metabolism. It has recently been realized that there are enzymes that process such compounds, formulating the concept of metabolite repair. NADH and NADPH are vital cellular redox cofactors but can form non-functional hydrates (named NAD(P)HX) spontaneously or enzymatically that compete with enzymes dependent on NAD(P)H, impairing normal enzyme function.

Analysis of Chlamydomonas thiamin metabolism in vivo reveals riboswitch plasticity.

Thiamin (vitamin B1) is an essential micronutrient needed as a cofactor for many central metabolic enzymes. Animals must have thiamin in their diet, whereas bacteria, fungi, and plants can biosynthesize it de novo from the condensation of a thiazole and a pyrimidine moiety. Although the routes to biosynthesize these two heterocycles are not conserved in different organisms, in all cases exogenous thiamin represses expression of one or more of the biosynthetic pathway genes.

Examining strategies to facilitate vitamin B1 biofortification of plants by genetic engineering.

Thiamin (vitamin B1) is made by plants and microorganisms but is an essential micronutrient in the human diet. All organisms require it as a cofactor in its form as thiamin pyrophosphate (TPP) for the activity of key enzymes of central metabolism. In humans, deficiency is widespread particularly in populations where polished rice is a major component of the diet.

Recycling of pyridoxine (vitamin B6) by PUP1 in Arabidopsis.

Vitamin B6 is a cofactor for more than 140 essential enzymatic reactions and was recently proposed as a potent antioxidant, playing a role in the photoprotection of plants. De novo biosynthesis of the vitamin has been described relatively recently and is derived from simple sugar precursors as well as glutamine. In addition, the vitamin can be taken up from exogenous sources in a broad range of organisms, including plants.

Cucumber mosaic virus and its 2b RNA silencing suppressor modify plant-aphid interactions in tobacco.

The cucumber mosaic virus (CMV) 2b protein not only inhibits anti-viral RNA silencing but also quenches transcriptional responses of plant genes to jasmonic acid, a key signalling molecule in defence against insects. This suggested that it might affect interactions between infected plants and aphids, insects that transmit CMV. We found that infection of tobacco with a 2b gene deletion mutant (CMVΔ2b) induced strong resistance to aphids (Myzus persicae) while CMV infection fostered aphid survival.

Accelerated cell death 2 suppresses mitochondrial oxidative bursts and modulates cell death in Arabidopsis.

The Arabidopsis ACCELERATED CELL DEATH 2 (ACD2) protein protects cells from programmed cell death (PCD) caused by endogenous porphyrin-related molecules like red chlorophyll catabolite or exogenous protoporphyrin IX. We previously found that during bacterial infection, ACD2, a chlorophyll breakdown enzyme, localizes to both chloroplasts and mitochondria in leaves. Additionally, acd2 cells show mitochondrial dysfunction.

Identification of novel ligands for thiamine pyrophosphate (TPP) riboswitches.

Riboswitches are regions of mRNA to which a metabolite binds in the absence of proteins, resoulting in alteration of transcription, translation or splicing. The most widespread forms of riboswitches are those responsive to TPP (thiamine pyrophosphate) the active form of vitamin B1, thiamine. TPP-riboswitches have been found in all bacterial genomes examined, and are the only ones found in eukaryotes.

The cell biology of tetrapyrroles: a life and death struggle.

Tetrapyrroles such as chlorophyll and heme are co-factors for essential proteins involved in a wide variety of crucial cellular functions. Nearly 2% of the proteins encoded by the Arabidopsis thaliana genome are thought to bind tetrapyrroles, demonstrating their central role in plant metabolism. Although the enzymes required for tetrapyrrole biosynthesis are well characterized, there are still major questions about the regulation of the pathway, and the transport of tetrapyrroles within cells.

Disruption of two defensive signaling pathways by a viral RNA silencing suppressor.

The Cucumber mosaic virus (CMV) 2b counter-defense protein disrupts plant antiviral mechanisms mediated by RNA silencing and salicylic acid (SA). We used microarrays to investigate defensive gene expression in 2b-transgenic Arabidopsis thaliana plants. Surprisingly, 2b inhibited expression of few SA-regulated genes and, in some instances, enhanced the effect of SA on certain genes.

Tetrapyrrole profiling in Arabidopsis seedlings reveals that retrograde plastid nuclear signaling is not due to Mg-protoporphyrin IX accumulation.

Chloroplast biogenesis involves careful coordination of both plastid and nuclear gene expression, which is achieved in part by retrograde signaling from the chloroplast to the nucleus. This can be demonstrated by the fact that the herbicide, Norflurazon (NF), which causes bleaching of chloroplasts, prevents the light induction of photosynthesis-related genes in the nucleus. It has been proposed that the tetrapyrrole pathway intermediate Mg-protoporphyrin IX acts as the signaling molecule in this pathway and accumulates in the chloroplasts and cytosol of the cell after NF treatment.

Thiamine biosynthesis in algae is regulated by riboswitches.

In bacteria, many genes involved in the biosynthesis of cofactors such as thiamine pyrophosphate (TPP) are regulated by ribo switches, regions in the 5' end of mRNAs to which the cofactor binds, thereby affecting translation and/or transcription. TPP riboswitches have now been identified in fungi, in which they alter mRNA splicing. Here, we show that addition of thiamine to cultures of the model green alga Chlamydomonas reinhardtii alters splicing of transcripts for the THI4 and THIC genes, encoding the first enzymes of the thiazole and pyrimidine branches of thiamine biosynthesis, respectively, concomitant with an increase in intracellular thiamine and TPP levels.

Plants need their vitamins too.

Over recent years, the pathways for the biosynthesis of many vitamins have been elucidated at the molecular level in plants, and several unique features are emerging. One is that the mitochondrion plays an important role in the synthesis of folate (vitamin B9), biotin (B7), pantothenate (B5), ascorbate (C), and possibly thiamin (B1). Second, the production of some of these cofactors is regulated by developmental cues, and perhaps more surprisingly, by environmental signals such as high light and salinity.

High-performance liquid chromatography determination of pipecolic acid after precolumn ninhydrin derivatization using domestic microwave.

A novel procedure to specifically quantify low amounts of pipecolic acid and structurally related compounds in several types of biological materials has been characterized. From crude extracts of various types of biological material, the first step was to clear all low-molecular-weight compounds containing primary amino groups by a treatment of nitrous acid. Using a microwave-assisted reaction, the remaining substances containing secondary amino groups were then derivatized with ninhydrin and made soluble in glacial acetic acid.