Regulation of cell cycle and differentiation markers by pathogenic, non-pathogenic and opportunistic skin bacteria.

Skin is the first line of defense against the physical, chemical and the biological environment. It is an ideal organ for studying molecular responses to biological infections through a variety of skin cells that specialize in immune responses. Comparative analysis of skin response to pathogenic, non-pathogenic, and commensal bacteria would help in the identification of disease specific pathways for drug targets.

Association of TNF-α polymorphisms (-857, -863 and -1031), TNF-α serum level and lipid profile with acne vulgaris.

Background: Acne is an inflammatory condition principally affected by genetic and dietary factors. Investigation into functional polymorphisms of TNF-α gene and their association with acne vulgaris will be helpful in exploring genetic influence on skin immune mediated inflammatory events. In the present study, we analyzed association of TNF-α gene polymorphisms, its expression levels and lipid profiles in a large cohort of acne patients and controls.

On the climate benefit of a coal-to-gas shift in Germany's electric power sector.

Methane emissions along the natural gas supply chain are critical for the climate benefit achievable by fuel switching from coal to natural gas in the electric power sector. For Germany, one of the world's largest primary energy consumers, with a coal and natural gas share in the power sector of 35% and 13%, respectively, we conducted fleet-conversion modelling for reference year 2018, taking domestic and export country specific greenhouse gas (GHG)-emissions in the natural gas and coal supply chains into account. Methane leakage rates below 4.

Understanding the geobiology of the terminal Ediacaran Khatyspyt Lagerstätte (Arctic Siberia, Russia).

The Khatyspyt Lagerstätte (~544 Ma, Russia) provides a valuable window into late Ediacaran Avalon-type ecosystems with rangeomorphs, arboreomorphs, and mega-algae. Here, we tackle the geobiology of this Lagerstätte by the combined analysis of paleontological features, sedimentary facies, and lipid biomarkers. The Khatyspyt Formation was deposited in carbonate ramp environments.

Recent magmatism drives hydrocarbon generation in north-east Java, Indonesia.

Conventional studies of petroleum basins associate oil generation with the gradual burial of organic-rich sediments. These classical models rely on the interplay between pressure, temperature, and the time required for organic matter transformation to oil and gas. These processes usually occur over geological timescales, but may be accelerated by rapid reactions when carbon-rich sediments are exposed to migrating magmatic fluids.

Skinomics, transcriptional profiling approaches to molecular and structural biology of epidermis.

Skinomics is a field of bioinformatics applied specifically to skin biology and, by extension, to dermatology. Skinomics has been expanding into extensive genome-wide association studies, eg, of psoriasis, proteomics, lipidomics, metabolomics, metagenomics, and the studies of the microbiome. Here, the current state of the field of transcriptomics is reviewed, including the studies of the gene expression in human skin under several healthy and disease conditions.

The taphonomic fate of isorenieratene in Lower Jurassic shales-controlled by iron?

Fossil derivatives of isorenieratene, an accessory pigment in brown-colored green sulfur bacteria, are often used as tracers for photic zone anoxia through Earth's history, but their diagenetic behavior is still incompletely understood. Here, we assess the preservation of isorenieratene derivatives in organic-rich shales (1.5-8.

Cardiac fibroblast transcriptome analyses support a role for interferogenic, profibrotic, and inflammatory genes in anti-SSA/Ro-associated congenital heart block.

The signature lesion of SSA/Ro autoantibody-associated congenital heart block (CHB) is fibrosis and a macrophage infiltrate, supporting an experimental focus on cues influencing the fibroblast component. The transcriptomes of human fetal cardiac fibroblasts were analyzed using two complementary approaches. Cardiac injury conditions were simulated in vitro by incubating human fetal cardiac fibroblasts with supernatants from macrophages transfected with the SSA/Ro-associated noncoding Y ssRNA.

Embryonic AP1 Transcription Factor Deficiency Causes a Collodion Baby-Like Phenotype.

AP1 transcription factors are important controllers of gene expression in the epidermis, and altered AP1 factor function can perturb keratinocyte proliferation and differentiation. However, our understanding of how AP1 signaling changes may underlie or exacerbate skin disease is limited. We have shown that inhibiting AP1 factor function in suprabasal adult epidermis leads to reduced filaggrin levels and to a phenotype that resembles the genetic disorder ichthyosis vulgaris.

A bioengineered living cell construct activates an acute wound healing response in venous leg ulcers.

Chronic nonhealing venous leg ulcers (VLUs) are widespread and debilitating, with high morbidity and associated costs; about $15 billion is spent annually on the care of VLUs in the United States. Despite this, there is a paucity of treatments for VLUs because of the lack of pathophysiologic insight into ulcer development as well as the lack of knowledge regarding biologic actions of existing VLU-targeted therapies. The bioengineered bilayered living cellular construct (BLCC) skin substitute is a U.

Meta-Analysis of Transcriptional Responses to Mastitis-Causing Escherichia coli.

Bovine mastitis is a widespread disease in dairy cows, and is often caused by bacterial mammary gland infection. Mastitis causes reduced milk production and leads to excessive use of antibiotics. We present meta-analysis of transcriptional profiles of bovine mastitis from 10 studies and 307 microarrays, allowing identification of much larger sets of affected genes than any individual study.

Resistin gene polymorphisms are associated with acne and serum lipid levels, providing a potential nexus between lipid metabolism and inflammation.

Acne vu lgaris is a multifactorial inflammatory skin disease causing social stigma and psychological effect on patients. We hypothesized that the genes that can affect both lipid metabolism and inflammation may be central for acne formation and present targets for treatment. Pro-inflammatory adipokine resistin, one such likely target, activates NFkB and JNK pathways inducing TLR-2, IL-1, IL-6, and TNFα genes.

The homeoprotein DLX3 and tumor suppressor p53 co-regulate cell cycle progression and squamous tumor growth.

Epidermal homeostasis depends on the coordinated control of keratinocyte cell cycle. Differentiation and the alteration of this balance can result in neoplastic development. Here we report on a novel DLX3-dependent network that constrains epidermal hyperplasia and squamous tumorigenesis.

Targeting downstream transcription factors and epigenetic modifications following Toll-like receptor 7/8 ligation to forestall tissue injury in anti-Ro60 associated heart block.

Based on the consistent demonstration of fibrosis of the atrioventricular node surrounded by macrophages and multinucleated giant cells in anti-Ro antibody exposed fetuses dying with heart block, this study focuses on macrophage signaling stimulated by ssRNA associated with the Ro60 protein and the impact of antagonizing innate cell drivers such as TLR7/8. Transcriptome and epigenetic modifications which affect transcription factors, NF-κB and STAT1, were selected to evaluate the phenotype of macrophages in which TLR7/8 was ligated following treatment with either anti-Ro60/Ro60/hY3 RNA immune complexes or transfection with hY3. Based on microarray, TNF and IL6 were among the most highly upregulated genes in both stimulated conditions, each of which was significantly inhibited by preincubation with hydroxychloroquine (HCQ).

C35 Hopanoid Side Chain Biosynthesis: Reduction of Ribosylhopane into Bacteriohopanetetrol by a Cell-Free System Derived from Methylobacterium organophilum.

The major bacterial triterpenoids of the hopane series each consist of a C30 triterpene hopane moiety and an additional nonterpene C5 side chain derived from D-ribose and linked through its C-5 carbon atom to the hopane side chain. Bacteriohopanetetrol and aminobacteriohopanetriol are the most common representatives of this natural product series, adenosylhopane and ribosylhopane being putative precursors. Deuterium-labelled ribosylhopane was obtained by hemisynthesis and converted into deuterium-labelled bacteriohopanetetrol in the presence of NADPH, thus giving evidence of this as yet unknown precursor-to-product relationship in the bacterial hopanoid metabolic pathway.

Transcriptional changes associated with resistance to inhibitors of epidermal growth factor receptor revealed using metaanalysis.

Background: EGFR is important in maintaining metabolic homeostasis in healthy cells, but in tumors it activates downstream signaling pathways, causing proliferation, angiogenesis, invasion and metastasis. Consequently, EGFR is targeted in cancers using reversible, irreversible or antibody inhibitors. Unfortunately, tumors develop inhibitor resistance by mutations or overexpressing EGFR, or its ligand, or activating secondary, EGFR-independent pathways.

Keratinocyte p38δ loss inhibits Ras-induced tumor formation, while systemic p38δ loss enhances skin inflammation in the early phase of chemical carcinogenesis in mouse skin.

p38δ expression and/or activity are increased in human cutaneous malignancies, including invasive squamous cell carcinoma (SCC) and head and neck SCC, but the role of p38δ in cutaneous carcinogenesis has not been well-defined. We have reported that mice with germline loss of p38δ exhibited a reduced susceptibility to skin tumor development compared with wild-type mice in the two-stage 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) chemical skin carcinogenesis model. Here, we report that p38δ gene ablation inhibited the growth of tumors generated from v-ras(Ha) -transformed keratinocytes in skin orthografts to nude mice, indicating that keratinocyte-intrinsic p38δ is required for Ras-induced tumorigenesis.

Structural and biochemical changes underlying a keratoderma-like phenotype in mice lacking suprabasal AP1 transcription factor function.

Epidermal keratinocyte differentiation on the body surface is a carefully choreographed process that leads to assembly of a barrier that is essential for life. Perturbation of keratinocyte differentiation leads to disease. Activator protein 1 (AP1) transcription factors are key controllers of this process.

Differential transcriptional effects of EGFR inhibitors.

EGF and its receptor EGFR serve as a paradigm for signaling in cell, molecular and tumor biology. EGFR inhibitors, drugs targeting the intracellular kinase activity and antibodies targeting the extracellular ligand binding, are used to treat breast, lung, colon and other cancers. Nominally affecting the same target, inhibitors have different effects, suggesting that use of inhibitor combinations may provide beneficial in cancer treatment.

The isotopic biosignatures of photo- vs. thiotrophic bivalves: are they preserved in fossil shells?

Symbiont-bearing and non-symbiotic marine bivalves were used as model organisms to establish biosignatures for the detection of distinctive symbioses in ancient bivalves. For this purpose, the isotopic composition of lipids (δ13C) and bulk organic shell matrix (δ13C, δ34S, δ15N) from shells of several thiotrophic, phototrophic, or non-symbiotic bivalves were compared (phototrophic: Fragum fragum, Fragum unedo, Tridacna maxima; thiotrophic: Codakia tigerina, Fimbria fimbriata, Anodontia sp.; non-symbiotic: Tapes dorsatus, Vasticardium vertebratum, Scutarcopagia sp.

Keratinocyte detachment-differentiation connection revisited, or anoikis-pityriasi nexus redux.

Epidermis, a continuously self-renewing and differentiating organ, produces a protective stratum corneum that shields us from external chemical, physical and microbial threats. Epidermal differentiation is a multi-step process regulated by influences, some unknown, others insufficiently explored. Detachment of keratinocytes from the basement membrane is one such pro-differentiation stimulus.

Cutaneous microbiome studies in the times of affordable sequencing.

Background: Skin is our first line of defense against pathogenic microorganisms and the intimate contact between the epidermis and microbes has been well known.

Purposes: Microbes that cause infection are associated with inflammatory dermatoses and exacerbate wound healing. It is therefore of vital importance to understand the intricacies of skin-microbiota interactions.

Delayed skin wound repair in proline-rich protein tyrosine kinase 2 knockout mice.

Proline-rich protein tyrosine kinase 2 (Pyk2) is a member of the focal adhesion kinase family. We used Pyk2 knockout (Pyk2-KO) mice to study the role of Pyk2 in cutaneous wound repair. We report that the rate of wound closure was delayed in Pyk2-KO compared with control mice.

Analysis and meta-analysis of transcriptional profiling in human epidermis.

Because of its accessibility, skin has been among the first organs analyzed using DNA microarrays; psoriasis, melanomas, carcinomas, chronic wounds, and responses of epidermal keratinocytes in culture have been intensely investigated. Skin has everything: stem cells, differentiation, signaling, inflammation, hereditary diseases, etc. Here we provide step-by-step instructions for bioinformatics analysis of transcriptional profiling of skin.