scholarly journals Neurosteroid Biosynthesis and Action in the Purkinje Cell

2009 ◽  
Vol 2 ◽  
pp. JEN.S2290 ◽  
Author(s):  
Kazuyoshi Tsutsui
Keyword(s):  
Purkinje Cell ◽  
De Novo ◽  
Current Knowledge ◽  
Neuronal Circuit ◽  
Vertebrate Brain ◽  
Neonatal Life ◽  
Cerebellar Neuron ◽  
Brain Data ◽  
Circuit Formation ◽  
Biological Actions

It is now clearly established that steroids can be synthesized de novo by the vertebrate brain. Such steroids are called neurosteroids. To understand neurosteroid action in the brain, data on the regio- and temporal-specific synthesis of neurosteroids are needed. In the middle 1990s, the Purkinje cell, an important cerebellar neuron, was identified as a major site for neurosteroid formation in vertebrates. This discovery has allowed deeper insights into neuronal neurosteroidogenesis and biological actions of neurosteroids have become clear by the studies using the Purkinje cell as an excellent cellular model, which is known to play an important role in memory and learning processes. From the past 10 years of research on mammals, we now know that the Purkinje cell actively synthesizes progesterone and estradiol de novo from cholesterol during neonatal life, when cerebellar neuronal circuit formation occurs. Both progesterone and estradiol promote dendritic growth, spinogenesis, and synaptogenesis via each cognate nuclear receptor in the developing Purkinje cell. Such neurosteroid actions that may be mediated by neurotrophic factors contribute to the formation of cerebellar neuronal circuit during neonatal life. Allopregnanolone, a progesterone metabolite, is also synthesized in the cerebellum and acts on Purkinje cell survival in the neonate. The aim of this review is to summarize the current knowledge regarding the biosynthesis and biological actions of neurosteroids in the Purkinje cell during development.

scholarly journals The L1-dependant and Pol III transcribed Alu retrotransposon, from its discovery to innate immunity

2021 ◽  
Vol 48 (3) ◽  
pp. 2775-2789
Author(s):  
Ludwig Stenz
Keyword(s):  
Human Genome ◽  
Viral Infections ◽  
De Novo ◽  
Current Knowledge ◽  
Innate Immune ◽  
De Novo Mutation ◽  
Neuronal Diversity ◽  
Alu Sequences ◽  
Pol Iii ◽  
The Brain

AbstractThe 300 bp dimeric repeats digestible by AluI were discovered in 1979. Since then, Alu were involved in the most fundamental epigenetic mechanisms, namely reprogramming, pluripotency, imprinting and mosaicism. These Alu encode a family of retrotransposons transcribed by the RNA Pol III machinery, notably when the cytosines that constitute their sequences are de-methylated. Then, Alu hijack the functions of ORF2 encoded by another transposons named L1 during reverse transcription and integration into new sites. That mechanism functions as a complex genetic parasite able to copy-paste Alu sequences. Doing that, Alu have modified even the size of the human genome, as well as of other primate genomes, during 65 million years of co-evolution. Actually, one germline retro-transposition still occurs each 20 births. Thus, Alu continue to modify our human genome nowadays and were implicated in de novo mutation causing diseases including deletions, duplications and rearrangements. Most recently, retrotransposons were found to trigger neuronal diversity by inducing mosaicism in the brain. Finally, boosted during viral infections, Alu clearly interact with the innate immune system. The purpose of that review is to give a condensed overview of all these major findings that concern the fascinating physiology of Alu from their discovery up to the current knowledge.

From the discovery to molecular understanding of cellular iron-sulfur protein biogenesis

2020 ◽  
Vol 401 (6-7) ◽  
pp. 855-876 ◽  
Author(s):  
Roland Lill
Keyword(s):  
De Novo ◽  
Current Knowledge ◽  
Protein Stabilization ◽  
S Protein ◽  
Cellular Iron ◽  
Iron Sulfur ◽  
Protein Biogenesis ◽  
Sulfur Protein ◽  
Initial Discovery ◽  
S Proteins

AbstractProtein cofactors often are the business ends of proteins, and are either synthesized inside cells or are taken up from the nutrition. A cofactor that strictly needs to be synthesized by cells is the iron-sulfur (Fe/S) cluster. This evolutionary ancient compound performs numerous biochemical functions including electron transfer, catalysis, sulfur mobilization, regulation and protein stabilization. Since the discovery of eukaryotic Fe/S protein biogenesis two decades ago, more than 30 biogenesis factors have been identified in mitochondria and cytosol. They support the synthesis, trafficking and target-specific insertion of Fe/S clusters. In this review, I first summarize what led to the initial discovery of Fe/S protein biogenesis in yeast. I then discuss the function and localization of Fe/S proteins in (non-green) eukaryotes. The major part of the review provides a detailed synopsis of the three major steps of mitochondrial Fe/S protein biogenesis, i.e. the de novo synthesis of a [2Fe-2S] cluster on a scaffold protein, the Hsp70 chaperone-mediated transfer of the cluster and integration into [2Fe-2S] recipient apoproteins, and the reductive fusion of [2Fe-2S] to [4Fe-4S] clusters and their subsequent assembly into target apoproteins. Finally, I summarize the current knowledge of the mechanisms underlying the maturation of cytosolic and nuclear Fe/S proteins.

scholarly journals Long-term follow-up until early adulthood in autosomal dominant, complex SPG30 with a novel KIF1A variant: a case report

2019 ◽  
Vol 45 (1) ◽  
Author(s):  
Carlotta Spagnoli ◽  
Susanna Rizzi ◽  
Grazia Gabriella Salerno ◽  
Daniele Frattini ◽  
Carlo Fusco
Keyword(s):  
Autosomal Dominant ◽  
De Novo ◽  
Current Knowledge ◽  
Brain Mri ◽  
Early Adulthood ◽  
Cerebellar Atrophy ◽  
Mild Intellectual Disability ◽  
Long Term Follow Up

Abstract Background Pathogenic variants in KIF1A (kinesin family member 1A) gene have been associated with hereditary spastic paraplegia (HSP) type 30 (SPG30), encopassing autosomal dominant and recessive, pure and complicated forms. Case presentation We report the long-term follow-up of a 19 years-old boy first evaluated at 18 months of age because of toe walking and unstable gait with frequent falls. He developed speech delay, mild intellectual disability, a slowly progressive pyramidal syndrome, microcephaly, bilateral optic subatrophy and a sensory axonal polyneuropathy. Brain MRI showed cerebellar atrophy, stable along serial evaluations (last performed at 18 years of age). Targeted NGS sequencing disclosed the de novo c.914C > T missense, likely pathogenic variant on KIF1A gene. Conclusions We report on a previously unpublished de novo heterozygous likely pathogenic KIF1A variant associated with slowly progressive complicated SPG30 and stable cerebellar atrophy on long-term follow-up, adding to current knowledge on this HSP subtype.

scholarly journals Targeting Multiple-Myeloma-Induced Immune Dysfunction to Improve Immunotherapy Outcomes

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Sergio Rutella ◽  
Franco Locatelli
Keyword(s):  
Multiple Myeloma ◽  
De Novo ◽  
Current Knowledge ◽  
Cell Immunity ◽  
Benign Monoclonal Gammopathy ◽  
Molecular Determinants ◽  
Clinical Responses ◽  
Cause Of Failure ◽  
Immune Defects ◽  
Cell Malignancy

Multiple myeloma (MM) is a plasma cell malignancy associated with high levels of monoclonal (M) protein in the blood and/or serum. MM can occurde novoor evolve from benign monoclonal gammopathy of undetermined significance (MGUS). Current translational research into MM focuses on the development of combination therapies directed against molecularly defined targets and that are aimed at achieving durable clinical responses. MM cells have a unique ability to evade immunosurveillance through several mechanisms including, among others, expansion of regulatory T cells (Treg), reduced T-cell cytotoxic activity and responsiveness to IL-2, defects in B-cell immunity, and induction of dendritic cell (DC) dysfunction. Immune defects could be a major cause of failure of the recent immunotherapy trials in MM. This article summarizes our current knowledge on the molecular determinants of immune evasion in patients with MM and highlights how these pathways can be targeted to improve patients’ clinical outcome.

scholarly journals Genetic and Genomic Resources to Study Natural Variation in Brassica rapa

2020 ◽  
Author(s):  
Ping Lou ◽  
Scott Woody ◽  
Kathleen Greenham ◽  
Robert VanBuren ◽  
Marivi Colle ◽  
...  
Keyword(s):  
Brassica Rapa ◽  
Natural Variation ◽  
De Novo ◽  
Coat Color ◽  
Current Knowledge ◽  
Genomic Structure ◽  
Close Relative ◽  
Structure Variation ◽  
Genomic Resources ◽  
Ril Population

ABSTRACTThe globally important crop Brassica rapa, a close relative of Arabidopsis, is an excellent system for modeling our current knowledge of plant growth on a morphologically diverse crop. The long history of B. rapa domestication across Asia and Europe provides a unique collection of locally adapted varieties that span large climatic regions with various abiotic and biotic stress tolerance traits. This diverse gene pool provides a rich source of targets with the potential for manipulation towards the enhancement of productivity of crops both within and outside the Brassicaceae. To expand the genetic resources available to study natural variation in B. rapa, we constructed an Advanced Intercross Recombinant Inbred (AI-RIL) population using B. rapa subsp. trilocularis (Yellow Sarson) R500 and the B. rapa subsp. parachinensis (Cai Xin) variety L58. Our current understanding of genomic structure variation across crops suggests that a single reference genome is insufficient for capturing the genetic diversity within a species. To complement this AI-RIL population and current and future B. rapa genomic resources, we generated a de novo genome assembly of the B. rapa subsp. trilocularis (Yellow Sarson) variety R500, the maternal parent of the AI-RIL population. The genetic map for the R500 x L58 population generated using this de novo genome was used to map QTL for seed coat color and revealed the improved mapping resolution afforded by this new assembly.

Pathophysiology of intestinal metaplasia of the stomach: emphasis on CDX2 regulation

2010 ◽  
Vol 38 (2) ◽  
pp. 358-363 ◽  
Author(s):  
Rita Barros ◽  
Vânia Camilo ◽  
Bruno Pereira ◽  
Jean-Noel Freund ◽  
Leonor David ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Intestinal Metaplasia ◽  
De Novo ◽  
Current Knowledge ◽  
Regulatory Mechanisms ◽  
Cancer Development ◽  
Molecular Pathways ◽  
Neoplastic Lesion ◽  
Increased Risk

IM (intestinal metaplasia) of the stomach is a pre-neoplastic lesion that usually follows Helicobacter pylori infection and that confers increased risk for gastric cancer development. After setting the role played by CDX2 (Caudal-type homeobox 2) in the establishment of gastric IM, it became of foremost importance to unravel the regulatory mechanisms behind its de novo expression in the stomach. In the present paper, we review the basic pathology of gastric IM as well as the current knowledge on molecular pathways involved in CDX2 regulation in the gastric context.

An Emerging Role for Chloroplasts in Disease and Defense

2021 ◽  
Vol 59 (1) ◽  
pp. 423-445
Author(s):  
Pradeep Kachroo ◽  
Tessa M. Burch-Smith ◽  
Murray Grant
Keyword(s):  
Immune Responses ◽  
De Novo ◽  
Current Knowledge ◽  
Reactive Oxygen ◽  
Host Immunity ◽  
Retrograde Signaling ◽  
Oxygen Species ◽  
Nitrogen Species ◽  
De Novo Synthesis ◽  
Key Players

Chloroplasts are key players in plant immune signaling, contributing to not only de novo synthesis of defensive phytohormones but also the generation of reactive oxygen and nitrogen species following activation of pattern recognition receptors or resistance (R) proteins. The local hypersensitive response (HR) elicited by R proteins is underpinned by chloroplast-generated reactive oxygen species. HR-induced lipid peroxidation generates important chloroplast-derived signaling lipids essential to the establishment of systemic immunity. As a consequence of this pivotal role in immunity, pathogens deploy effector complements that directly or indirectly target chloroplasts to attenuate chloroplast immunity (CI). Our review summarizes the current knowledge of CI signaling and highlights common pathogen chloroplast targets and virulence strategies. We address emerging insights into chloroplast retrograde signaling in immune responses and gaps in our knowledge, including the importance of understanding chloroplast heterogeneity and chloroplast involvement in intraorganellular interactions in host immunity.

scholarly journals Cholesterol homeostasis in the vertebrate retina: Biology and pathobiology

2020 ◽  
pp. jlr.TR120000979 ◽  
Author(s):  
Sriganesh Ramachandra Rao ◽  
Steven J. Fliesler
Keyword(s):  
De Novo ◽  
Current Knowledge ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Neural Retina ◽  
Cholesterol Homeostasis ◽  
Sterol Synthesis ◽  
Topic Area ◽  
Sterol Transport ◽  
Age Related

Cholesterol is a quantitatively and biologically significant constituent of all mammalian cell membrane, including those that comprise the retina. Retinal cholesterol homeostasis entails the interplay between de novo synthesis, uptake, intra-retinal sterol transport, metabolism and efflux. Defects in these complex processes are associated with several congenital and age-related disorders of the visual system. Herein, we provide an overview of the following topics: a) cholesterol synthesis in the neural retina; b) lipoprotein uptake and intraretinal sterol transport in the neural retina and the retinal pigment epithelium (RPE); c) cholesterol efflux from the neural retina and the RPE; and d) biology and pathobiology of defects in sterol synthesis and sterol oxidation in the neural retina and the RPE. We focus, in particular, on studies involving animal models of monogenic disorders pertinent to the above topics, as well as in vitro models using biochemical, metabolic, and omic approaches. We also identify current knowledge gaps as well as opportunities in the field that beg further research in this topic area.

scholarly journals Cardiovascular and Metabolic Consequences of Liver Transplantation: A Review

Medicina ◽  
2019 ◽  
Vol 55 (8) ◽  
pp. 489
Author(s):  
Plotogea ◽  
Ilie ◽  
Sandru ◽  
Chiotoroiu ◽  
Bratu ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Liver Transplantation ◽  
De Novo ◽  
Current Knowledge ◽  
Morbidity And Mortality ◽  
High Morbidity ◽  
Term Survival ◽  
The Metabolic Syndrome ◽  
Acute Liver Disease

Liver transplantation (LT) is considered the curative treatment option for selected patients who suffer from end-stage or acute liver disease or hepatic malignancy (primary). After LT, patients should be carefully monitored for complications that may appear, partially due to immunosuppressive therapy, but not entirely. Cardiovascular diseases are frequently encountered in patients with LT, being responsible for high morbidity and mortality. Patients with underlying cardiovascular and metabolic pathologies are prone to complications after the transplant, but these complications can also appear de novo, mostly associated with immunosuppressants. Metabolic syndrome, defined by obesity, hypertension, dyslipidemia, and hyperglycemia, is diagnosed among LT recipients and is aggravated after LT, influencing the long-term survival. In this review, our purpose was to summarize the current knowledge regarding cardiovascular (CV) diseases and the metabolic syndrome associated with LT and to assess their impact on short and long-term morbidity and mortality.

scholarly journals GTP metabolic reprogramming by IMPDH2: unlocking cancer cells’ fuelling mechanism

2020 ◽  
Vol 168 (4) ◽  
pp. 319-328 ◽  
Author(s):  
Satoshi Kofuji ◽  
Atsuo T Sasaki
Keyword(s):  
De Novo ◽  
Current Knowledge ◽  
Metabolic Reprogramming ◽  
Inosine Monophosphate Dehydrogenase ◽  
Metabolic Demand ◽  
Adaptive Mechanisms ◽  
Key Aspects ◽  
Polymerase I ◽  
Rate Limiting

Abstract Growing cells increase multiple biosynthetic processes in response to the high metabolic demands needed to sustain proliferation. The even higher metabolic requirements in the setting of cancer provoke proportionately greater biosynthesis. Underappreciated key aspects of this increased metabolic demand are guanine nucleotides and adaptive mechanisms to regulate their concentration. Using the malignant brain tumour, glioblastoma, as a model, we have demonstrated that one of the rate-limiting enzymes for guanosine triphosphate (GTP) synthesis, inosine monophosphate dehydrogenase-2 (IMPDH2), is increased and IMPDH2 expression is necessary for the activation of de novo GTP biosynthesis. Moreover, increased IMPDH2 enhances RNA polymerase I and III transcription directly linking GTP metabolism to both anabolic capacity as well as nucleolar enlargement historically observed as associated with cancer. In this review, we will review in detail the basis of these new discoveries and, more generally, summarize the current knowledge on the role of GTP metabolism in cancer.

Sign in / Sign up

Export Citation Format

Share Document