The Optic Nerve at Stake: Update on Environmental Factors Modulating Expression of Leber's Hereditary Optic Neuropathy.

Optic neuropathies are characterized by the degeneration of the optic nerves and represent a considerable individual and societal burden. Notably, Leber's hereditary optic neuropathy (LHON) is a devastating vision disease caused by mitochondrial gene mutations that hinder oxidative phosphorylation and increase oxidative stress, leading to the loss of retinal ganglion neurons and axons. Loss of vision is rapid and severe, predominantly in young adults.

Message in a Scaffold: Natural Biomaterials for Three-Dimensional (3D) Bioprinting of Human Brain Organoids.

Brain organoids are invaluable tools for pathophysiological studies or drug screening, but there are still challenges to overcome in making them more reproducible and relevant. Recent advances in three-dimensional (3D) bioprinting of human neural organoids is an emerging approach that may overcome the limitations of self-organized organoids. It requires the development of optimal hydrogels, and a wealth of research has improved our knowledge about biomaterials both in terms of their intrinsic properties and their relevance on 3D culture of brain cells and tissue.

PPAR Gamma and Viral Infections of the Brain.

Peroxisome Proliferator-Activated Receptor gamma (PPARγ) is a master regulator of metabolism, adipogenesis, inflammation and cell cycle, and it has been extensively studied in the brain in relation to inflammation or neurodegeneration. Little is known however about its role in viral infections of the brain parenchyma, although they represent the most frequent cause of encephalitis and are a major threat for the developing brain. Specific to viral infections is the ability to subvert signaling pathways of the host cell to ensure virus replication and spreading, as deleterious as the consequences may be for the host.

Bacteria-derived long chain fatty acid exhibits anti-inflammatory properties in colitis.

Objective: Data from clinical research suggest that certain probiotic bacterial strains have the potential to modulate colonic inflammation. Nonetheless, these data differ between studies due to the probiotic bacterial strains used and the poor knowledge of their mechanisms of action.

Design: By mass-spectrometry, we identified and quantified free long chain fatty acids (LCFAs) in probiotics and assessed the effect of one of them in mouse colitis.

Correction: Comprehensive Analysis of Human Cytomegalovirus MicroRNA Expression during Lytic and Quiescent Infection.

[This corrects the article DOI: 10.1371/journal.pone.

Peroxisome proliferator-activated receptor γ (PPARγ) activation: A key determinant of neuropathogeny during congenital infection by cytomegalovirus.

Congenital infection by human cytomegalovirus (HCMV) might result in permanent neurological sequelae, including sensorineural deafness, cerebral palsies or devastating neurodevelopmental abnormalities. We recently disclosed that Peroxisome Proliferator-Activated Receptor gamma (PPARγ), a transcription factor of the nuclear receptor superfamily, is a key determinant of HCMV pathogenesis in developing brain. Using neural stem cells from human embryonic stem cells, we showed that HCMV infection strongly increases levels and activity of PPARγ in NSCs.

PPARγ Is Activated during Congenital Cytomegalovirus Infection and Inhibits Neuronogenesis from Human Neural Stem Cells.

Congenital infection by human cytomegalovirus (HCMV) is a leading cause of permanent sequelae of the central nervous system, including sensorineural deafness, cerebral palsies or devastating neurodevelopmental abnormalities (0.1% of all births). To gain insight on the impact of HCMV on neuronal development, we used both neural stem cells from human embryonic stem cells (NSC) and brain sections from infected fetuses and investigated the outcomes of infection on Peroxisome Proliferator-Activated Receptor gamma (PPARγ), a transcription factor critical in the developing brain.

Cytomegalovirus Infection Triggers the Secretion of the PPARγ Agonists 15-Hydroxyeicosatetraenoic Acid (15-HETE) and 13-Hydroxyoctadecadienoic Acid (13-HODE) in Human Cytotrophoblasts and Placental Cultures.

Introduction: Congenital infection by human cytomegalovirus (HCMV) is a leading cause of congenital abnormalities of the central nervous system. Placenta infection by HCMV allows for viral spread to fetus and may result in intrauterine growth restriction, preeclampsia-like symptoms, or miscarriages. We previously reported that HCMV activates peroxisome proliferator-activated receptor gamma (PPARγ) for its own replication in cytotrophoblasts.

Human Cytomegalovirus Infection Dysregulates the Localization and Stability of NICD1 and Jag1 in Neural Progenitor Cells.

Unlabelled: Human cytomegalovirus (HCMV) infection of the developing fetus frequently results in major neural developmental damage. In previous studies, HCMV was shown to downregulate neural progenitor/stem cell (NPC) markers and induce abnormal differentiation. As Notch signaling plays a vital role in the maintenance of stem cell status and is a switch that governs NPC differentiation, the effect of HCMV infection on the Notch signaling pathway in NPCs was investigated.

MicroRNA miR-21 attenuates human cytomegalovirus replication in neural cells by targeting Cdc25a.

Unlabelled: Congenital human cytomegalovirus (HCMV) infection is a leading cause of birth defects, primarily manifesting as neurological disorders. HCMV infection alters expression of cellular microRNAs (miRs) and induces cell cycle arrest, which in turn modifies the cellular environment to favor virus replication. Previous observations found that HCMV infection reduces miR-21 expression in neural progenitor/stem cells (NPCs).

Comprehensive analysis of human cytomegalovirus microRNA expression during lytic and quiescent infection.

Background: Human cytomegalovirus (HCMV) encodes microRNAs (miRNAs) that function as post-transcriptional regulators of gene expression during lytic infection in permissive cells. Some miRNAs have been shown to suppress virus replication, which could help HCMV to establish or maintain latent infection. However, HCMV miRNA expression has not been comprehensively examined and compared using cell culture systems representing permissive (lytic) and semi-permissive vs.

A new amyloidosis caused by fibrillar aggregates of mutated corneodesmosin.

Heterozygous nonsense mutations in the CDSN gene encoding corneodesmosin (CDSN), an adhesive protein expressed in cornified epithelia and hair follicles, cause hypotrichosis simplex of the scalp (HSS), a nonsyndromic form of alopecia. Truncated mutants of CDSN ((mut)CDSN), which bear the N-terminal adhesive Gly/Ser-rich domain (GS domain) of the protein, abnormally accumulate as amorphous deposits at the periphery of hair follicles and in the papillary dermis of the patient skin. Here, we present evidence that the (mut)CDSN deposits display an affinity for amyloidophilic dyes, namely Congo red and thioflavin T.

Transcriptional regulation of peptidylarginine deiminase expression in human keratinocytes.

Peptidylarginine deiminase (PAD, EC 3.5.3.

Long-range enhancer differentially regulated by c-Jun and JunD controls peptidylarginine deiminase-3 gene in keratinocytes.

Long-range cis elements are critical regulators of transcription, particularly for clustered paralogous genes. Such are the five PADI genes in 1p35-36 encoding peptidylarginine deiminases, which catalyze deimination, a Ca2+-dependent post-translational modification. Deimination has been implicated in the pathophysiology of severe human diseases such as multiple sclerosis and rheumatoid arthritis.

Long-range enhancer associated with chromatin looping allows AP-1 regulation of the peptidylarginine deiminase 3 gene in differentiated keratinocyte.

Transcription control at a distance is a critical mechanism, particularly for contiguous genes. The peptidylarginine deiminases (PADs) catalyse the conversion of protein-bound arginine into citrulline (deimination), a critical reaction in the pathophysiology of multiple sclerosis, Alzheimer's disease and rheumatoid arthritis, and in the metabolism of the major epidermal barrier protein filaggrin, a strong predisposing factor for atopic dermatitis. PADs are encoded by 5 clustered PADI genes (1p35-6).

Update on peptidylarginine deiminases and deimination in skin physiology and severe human diseases.

Deimination (or citrullination) is a recently described post-translational modification, but its consequences are not yet well understood. It is catalysed by peptidylarginine deiminases (PADs). These enzymes transform arginyl residues involved in a peptidyl link into citrullyl residues in a calcium-dependent manner.

Crucial roles of MZF1 and Sp1 in the transcriptional regulation of the peptidylarginine deiminase type I gene (PADI1) in human keratinocytes.

Peptidylarginine deiminases (PADs) catalyze the conversion of protein-bound arginine residues into citrulline residues in a calcium-dependent manner. The PAD1 gene (PADI1) is expressed in a few tissues, including the epidermis, where the protein is detected with a higher level in the more differentiated keratinocytes. Using quantitative reverse transcription-PCR experiments, we show that PADI1 mRNAs are more abundant in keratinocytes cultured with 1.

Peptidylarginine deiminases and deimination in biology and pathology: relevance to skin homeostasis.

Deimination corresponds to the transformation of arginine residues within a peptide sequence into citrulline residues. Catalyzed by peptidylarginine deiminases, it decreases the net positive charge of proteins, alters intra and intermolecular ionic interactions and probably the folding of target proteins. Deimination has recently been implicated in several physiological and pathological processes.

NF-Y and Sp1/Sp3 are involved in the transcriptional regulation of the peptidylarginine deiminase type III gene (PADI3) in human keratinocytes.

Human peptidylarginine deiminase type III gene (PADI3) encodes a crucial post-translational modification enzyme that converts protein-bound arginine residues into citrulline residues. Its expression is restricted to a few cell types, including keratinocytes in the granular layer of the epidermis and in the inner root sheath of hair follicles. In these cells, the enzyme is involved in terminal processing of intermediate filament-binding proteins such as filaggrin and trichohyalin.

The peptidylarginine deiminases expressed in human epidermis differ in their substrate specificities and subcellular locations.

Deimination, a post-translational modification catalyzed by peptidylarginine deiminases (PADs), appears as a crucial Ca(2+)-dependent event in the last steps of epidermal differentiation. In normal human epidermis, where the deiminated proteins are filaggrin and keratins, PAD1, 2 and 3 are expressed but their relative role is unknown. The three PADs, produced as active recombinant forms, showed distinct synthetic-substrate specificities, various efficiencies to deiminate filaggrin and particular calcium and pH sensitivities.

Regulation of the expression of peptidylarginine deiminase type II gene (PADI2) in human keratinocytes involves Sp1 and Sp3 transcription factors.

Peptidylarginine deiminases (PAD) convert protein-bound arginine residues into citrulline residues in a Ca(2+) ion-dependent manner. Among the five isoforms (PAD1, 2, 3, 4, and 6) existing in rodents and humans, PAD2 is the most widely expressed in both species, tissues, and organs. In order to study the mechanisms regulating the expression of the human PAD2 gene, PADI2, we characterized its promoter region using transfected human keratinocytes.

Peptidylarginine deiminase isoforms 1-3 are expressed in the epidermis and involved in the deimination of K1 and filaggrin.

Post-translational conversion of arginine to citrulline residues is catalyzed by peptidylarginine deiminases (PAD). Although the existence of five isoforms of PAD has been reported in rodents and humans, their tissue distribution, substrate specificity, and physiological function have yet to be explored. In the epidermis, deimination of filaggrin and keratins is involved in maintaining hydration of the stratum corneum (SC), and hence the cutaneous barrier function.

Comparative analysis of the mouse and human peptidylarginine deiminase gene clusters reveals highly conserved non-coding segments and a new human gene, PADI6.

Peptidylarginine deiminases (PADs) convert arginine residues in proteins into citrullines. They are suspected to be involved in multiple sclerosis and rheumatoid arthritis pathophysiology, and they play a role in epidermis homeostasis and possibly in regulation of gene expression through histone modification. In humans, four isoforms encoded by the genes PADI1-4 are known so far.

Netherton syndrome: disease expression and spectrum of SPINK5 mutations in 21 families.

Netherton syndrome is a severe autosomal recessive skin disorder characterized by congenital erythroderma, a specific hair-shaft abnormality, and atopic manifestations with high IgE levels. Recently, we identified SPINK5, which encodes the serine protease inhibitor Kazal-type 5 protein (LEKTI), as the defective gene in Netherton syndrome. Here we describe the intron-exon organization of the gene and characterize the SPINK5 mutations in patients from 21 families of different geographic origin, using denaturing high performance liquid chromatography and direct sequencing.