Rescue of secretion of a rare-disease associated mis-folded mutant glycoprotein in knock-out mammalian cells.

Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ERlocalised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). The enzyme recognises a mis-folded glycoprotein and flags it for ER retention by reglucosylating one of its N-linked glycans. In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease even if the mutant glycoprotein retains activity ("responsive mutant").

Clamping, bending, and twisting inter-domain motions in the misfold-recognizing portion of UDP-glucose: Glycoprotein glucosyltransferase.

UDP-glucose:glycoprotein glucosyltransferase (UGGT) flags misfolded glycoproteins for ER retention. We report crystal structures of full-length Chaetomium thermophilum UGGT (CtUGGT), two CtUGGT double-cysteine mutants, and its TRXL2 domain truncation (CtUGGT-ΔTRXL2). CtUGGT molecular dynamics (MD) simulations capture extended conformations and reveal clamping, bending, and twisting inter-domain movements.

Tumour Necrosis Factor Alpha-induced Protein 3 Negatively Regulates Cutibacterium acnes-induced Innate Immune Events in Epidermal Keratinocytes.

Human epidermal keratinocytes sense the presence of human skin microbiota through pathogen recognition receptors, such as toll-like receptors, and induce innate immune and inflammatory events. In healthy epidermis there is an absence of inflammation despite the continuous presence of cutaneous microbes, which is evidence of an effective immune regulatory mechanism. The aim of this study was to investigate tumour necrosis factor alpha-induced protein 3 (TNFAIP3), a negative regulator of toll-like receptor and nuclear factor kappa B signalling pathways, and its role in these regulatory events.

Erratum to "Modulation of ERQC and ERAD: A Broad-Spectrum Spanner in the Works of Cancer Cells?".

[This corrects the article DOI: 10.1155/2019/8384913.].

Modulation of ERQC and ERAD: A Broad-Spectrum Spanner in the Works of Cancer Cells?

Endoplasmic reticulum glycoprotein folding quality control (ERQC) and ER-associated degradation (ERAD) preside over cellular glycoprotein secretion and maintain steady glycoproteostasis. When cells turn malignant, cancer cell plasticity is affected and supported either by point mutations, preferential isoform selection, altered expression levels, or shifts to conformational equilibria of a secreted glycoprotein. Such changes are crucial in mediating altered extracellular signalling, metabolic behavior, and adhesion properties of cancer cells.

TNIP1 Regulates -Induced Innate Immune Functions in Epidermal Keratinocytes.

Human skin cells recognize the presence of the skin microbiome through pathogen recognition receptors. Epidermal keratinocytes are known to activate toll-like receptors (TLRs) 2 and 4 in response to the commensal (, formerly known as ) bacterium and subsequently to induce innate immune and inflammatory events. These events may lead to the appearance of macroscopic inflammatory acne lesions in puberty: comedos, papules and, pustules.

Factors shaping the composition of the cutaneous microbiota.

From birth, we are constantly exposed to bacteria, fungi and viruses, some of which are capable of transiently or permanently inhabiting our different body parts as our microbiota. The majority of our microbial interactions occur during and after birth, and several different factors, including age, sex, genetic constitution, environmental conditions and lifestyle, have been suggested to shape the composition of this microbial community. Propionibacterium acnes is one of the most dominant lipophilic microbes of the postadolescent, sebum-rich human skin regions.

Propionic Acid Produced by Propionibacterium acnes Strains Contri-butes to Their Pathogenicity.

Propionibacterium acnes is an important member of the skin microbiome. The bacterium can initiate signalling events and changes in cellular properties in keratinocytes. The aim of this study was to analyse the effect of the bacterium on an immortalized human keratinocyte cell line.

UVB-dependent changes in the expression of fast-responding early genes is modulated by huCOP1 in keratinocytes.

Ultraviolet (UV) B is the most prominent physical carcinogen in the environment leading to the development of various skin cancers. We have previously demonstrated that the human ortholog of the Arabidopsis thaliana constitutive photomorphogenesis 1 (COP1) protein, huCOP1, is expressed in keratinocytes in a UVB-regulated manner and is a negative regulator of p53 as a posttranslational modifier. However, it was not known whether huCOP1 plays a role in mediating the UVB-induced early transcriptional responses of human keratinocytes.

Leptin promotes a proinflammatory lipid profile and induces inflammatory pathways in human SZ95 sebocytes.

Background: Leptin, the adipocyte-secreted hormone that regulates weight, is known to link lipid metabolism with inflammation in various cell types. However, its role in human sebocytes has not yet been investigated.

Objectives: The purpose of this study was to investigate the effects of leptin in human sebaceous gland biology.

Role of the TNFA -308G > A polymorphism in the genetic susceptibility to acne vulgaris in a Sicilian population.

Background: Acne vulgaris is a common and clinically well-characterized skin disease that affects a great proportion of the general population and thus, is a major public health problem. The aim of the present study was to investigate whether TNFA -308 G > A polymorphism might be involved in the pathogenesis of acne in a population from Sicily.

Methods: A total of 74 patients with acne and of 88 healthy control subjects from Catania, Italy were examined in the present study.

Interleukin-1A +4845(G> T) polymorphism is a factor predisposing to acne vulgaris.

Acne vulgaris is a common chronic inflammatory skin disease of multifactorial origin. The aim of this study was to clarify whether known polymorphisms of the interleukin-1A (IL1A) and IL1RN genes play a role in the pathogenesis of acne vulgaris. A positive association was found between the minor T allele of the IL1A +4845(G>T) single nucleotide polymorphism (SNP) and acne, whereas no association was found with respect to any alleles of the variable number of tandem repeats (VNTR) polymorphism of the IL1RN gene.

TNFα gene polymorphisms in the pathogenesis of acne vulgaris.

Inflammation plays an important role in acne pathogenesis, and pro-inflammatory cytokines are key factors in these events. Tumor necrosis factor alpha (TNFα) is a central molecule coded by a gene that shows high level of genetic polymorphisms especially in its promoter region. Single nucleotide polymorphisms (SNPs) of the TNFα gene have been shown to be associated with an increased risk to develop chronic inflammatory diseases.

Prenatal typing of Rh and Kell blood group system antigens: the edge of a watershed.

Knowledge of the molecular basis of the blood group systems has enabled the development of assays for blood group genotyping. At this time, polymerase chain reaction (PCR)-based assays validated on fetal material obtained by invasive means (chorionic villus sampling or amniocentesis) are available for all clinically relevant fetal blood groups, However, only Rh typing (D, C, c, E, and e) and K1 genotyping assays are discussed in this review. Importantly, one must remember that results of genotyping assays will not always be concordant with serological typing.