Depletion of Mcpip1 in murine myeloid cells results in intestinal dysbiosis followed by allergic inflammation

MCPIP1 (called also Regnase-1) is a negative regulator of inflammation. Knockout of the Zc3h12a gene, encoding Mcpip1 in cells of myeloid origin ($Mcpip1^{MKO}$), has a pathological effect on many organs. The aim of this study was to comprehensively analyze pathological changes in the skin caused by Mcpip1 deficiency in phagocytes with an emphasis on its molecular mechanism associated with microbiome dysbiosis. $Mcpip1^{MKO}$ mice exhibited spontaneous wound formation on the skin. On a molecular level, the Th2-type immune response was predominantly characterized by an increase in Il5 and Il13 transcript levels, as well as eosinophil and mast cell infiltration. Irritation by DNFB led to a more severe skin contact allergy in $Mcpip1^{MKO}$ mice. Allergic reactions on the skin were strongly influenced by gut dysbiosis and enhanced systemic dissemination of bacteria. This process was followed by activation of the C/EBP pathway in peripheral macrophages, leading to local changes in the cytokine microenvironment that promoted the Th2 response. A reduced bacterial load inhibited allergic inflammation, indicating the role of intestinal dysbiosis in the development of skin diseases. Our results clearly show that MCPIP1 in phagocytes is an essential negative regulator that controls the gut-skin axis

The influence of heating on the carbon isotope composition, organic geochemistry and petrology of coal from the Upper Silesian Coal Basin (Poland) : an experimental and field study

The impact of natural intra-deposit heating on the δ13C signature, organic geochemistry, and petrology of coal and coal-bearing rocks characterised by various degrees of coalification and palaeoenvironments in the Upper Silesian Coal Basin, Poland, is elaborated. Reconstruction of palaeofire performed by heating experiments up to 400 ◦C in open and semi-closed systems with different heating regimes confirms the crucial significance of temperature and oxygen access. In open-system heating, released 13C-depleted gases enrich residue coke in 13C compared to raw coal. Petrological examinations did not show the impact of palaeofires on the maceral prop-erties of coal. However, the carried-out experiment caused the formation of devolatilisation pores, rounded edges, cracks, pale rims, as well as higher reflectance and paler colour that was what was expected. Extractable compounds become highly depleted, and low-weight organic compounds nearly absent. Relatively high contents of combustion-formed PAHs are an indicator of open-system heating. In semi-closed systems, the final total isotopic composition was almost unchanged as no components are carried away though changes in petrography and geochemistry occur. Increased extract yields reflect the release of bitumen from closed pores and partial pyrolysis of organic matter. Depletion of lighter n-alkane compounds, total carbon TC and volatiles decrease, and variable values of various alkyl aromatic hydrocarbon ratios are also indicative of semi-closed heating. Coal seams suspected of intra-deposit heating show geochemical and isotopic features similar to semi-closed- rather than open-system heating, and their δ13C signatures and organic geochemistry did not respond strongly during laboratory re-heating

MCPIP1 functions as a safeguard of early embryonic development

Monocyte chemoattractant protein-induced protein 1 (MCPIP1), also called Regnase-1, is an RNase that has been described as a key negative modulator of inflammation. MCPIP1 also controls numerous tumor-related processes, such as proliferation, apoptosis and differentiation. In this study, we utilized a zebrafish model to investigate the role of Mcpip1 during embryogenic development. Our results demonstrated that during embryogenesis, the expression of the zc3h12a gene encoding Mcpip1 undergoes dynamic changes. Its transcript levels gradually increase from the 2-cell stage to the spherical stage and then decrease rapidly. We further found that ectopic overexpression of wild-type Mcpip1 but not the catalytically inactive mutant form resulted in an embryonic lethal phenotype in zebrafish embryos (24 hpf). At the molecular level, transcriptomic profiling revealed extensive changes in the expression of genes encoding proteins important in the endoplasmic reticulum stress response and in protein folding as well as involved in the formation of primary germ layer, mesendoderm and endoderm development, heart morphogenesis and cell migration. Altogether, our results demonstrate that the expression of zc3h12a must be tightly controlled during the first cell divisions of zebrafish embryos and that a rapid decrease in its mRNA expression is an important factor promoting proper embryo development

The Disappearance of Coal Seams Recorded in Associated Gangue Rocks in the SW Part of the Upper Silesian Coal Basin, Poland

Coal seams in the Upper Silesian Coal Basin vanish within the Carboniferous Upper Silesian Sandstone Series and below an unconformity marking the Carboniferous top surface. Changes in the geochemical, mineralogical, petrological and palynological characteristics of gangue rocks associated with the vanished seams record what happened. The observed changes could have been caused by (1) coal-seam paleofire, (2) peat combustion, (3) igneous intrusion, (4) metasomatism and/or (5) weathering. Multifaceted research on samples collected at the Jas-Mos mining area, a part of the operating Jastrz˛ebie-Bzie Coal Mine that are representative of different geological settings in the northern and southern parts of the mining area, point to intra-deposit paleofire as the most plausible reason for the disappearance. Biomarkers enabled recognition of differences in heating duration and oxygen access. Coal seams in the south burned quickly with abundant oxygen supply. Seams in the north pyrolyzed for an extended time under conditions of limited oxygen. Though other methods used proved less sensitive, all confirmed low (100–150 C) paleotemperature heating. Overall, the reason for the local disappearance of the coal seams, making their exploitation difficult and unprofitable, can be assigned to a variety of different processes in a complex overlapping history of variable weathering, heating due to local endogenic fires and, probably, earlier peat combustion

Human BDNF/TrkB variants impair hippocampal synaptogenesis and associate with neurobehavioural abnormalities

Abstract: Brain-derived neurotrophic factor (BDNF) signals through its high affinity receptor Tropomyosin receptor kinase-B (TrkB) to regulate neuronal development, synapse formation and plasticity. In rodents, genetic disruption of Bdnf and TrkB leads to weight gain and a spectrum of neurobehavioural phenotypes. Here, we functionally characterised a de novo missense variant in BDNF and seven rare variants in TrkB identified in a large cohort of people with severe, childhood-onset obesity. In cells, the E183K BDNF variant resulted in impaired processing and secretion of the mature peptide. Multiple variants in the kinase domain and one variant in the extracellular domain of TrkB led to a loss of function through multiple signalling pathways, impaired neurite outgrowth and dominantly inhibited glutamatergic synaptogenesis in hippocampal neurons. BDNF/TrkB variant carriers exhibited learning difficulties, impaired memory, hyperactivity, stereotyped and sometimes, maladaptive behaviours. In conclusion, human loss of function BDNF/TrkB variants that impair hippocampal synaptogenesis may contribute to a spectrum of neurobehavioural disorders

Human BDNF/TrkB variants impair hippocampal synaptogenesis and associate with neurobehavioural abnormalities

Abstract: Brain-derived neurotrophic factor (BDNF) signals through its high affinity receptor Tropomyosin receptor kinase-B (TrkB) to regulate neuronal development, synapse formation and plasticity. In rodents, genetic disruption of Bdnf and TrkB leads to weight gain and a spectrum of neurobehavioural phenotypes. Here, we functionally characterised a de novo missense variant in BDNF and seven rare variants in TrkB identified in a large cohort of people with severe, childhood-onset obesity. In cells, the E183K BDNF variant resulted in impaired processing and secretion of the mature peptide. Multiple variants in the kinase domain and one variant in the extracellular domain of TrkB led to a loss of function through multiple signalling pathways, impaired neurite outgrowth and dominantly inhibited glutamatergic synaptogenesis in hippocampal neurons. BDNF/TrkB variant carriers exhibited learning difficulties, impaired memory, hyperactivity, stereotyped and sometimes, maladaptive behaviours. In conclusion, human loss of function BDNF/TrkB variants that impair hippocampal synaptogenesis may contribute to a spectrum of neurobehavioural disorders

Long Noncoding RNAs in Metabolic Syndrome Related Disorders

Ribonucleic acids (RNAs) are very complex and their all functions have yet to be fully clarified. Noncoding genes (noncoding RNA, sequences, and pseudogenes) comprise 67% of all genes and they are represented by housekeeping noncoding RNAs (transfer RNA (tRNA), ribosomal RNA (rRNA), small nuclear RNA (snRNA), and small nucleolar RNA (snoRNA)) that are engaged in basic cellular processes and by regulatory noncoding RNA (short and long noncoding RNA (ncRNA)) that are important for gene expression/transcript stability. In this review, we summarize data concerning the significance of long noncoding RNAs (lncRNAs) in metabolic syndrome related disorders, focusing on adipose tissue and pancreatic islands

C57BL/6J mice as a polygenic developmental model of diet-induced obesity

Susceptibility to obesity changes during the course of life. We utilized theC57BL/6J (B6) and 129S mouse as a genetic model for variation in diet-induced obesity to define the adiposity phenotypes from birth to maturity at8 weeks-of-age. From birth to 8 weeks-of-age, both male and female 129Smice had significantly higher fat mass and adiposity index than B6 mice,although they were not obese. After 8 weeks-of-age, B6 had greater adiposity/obesity than 129S mice in response to a high fat (HF). We sought to deter-mine the mechanism activating the fat accumulation in B6 mice at 8-weeks-of-age. We used microarray analysis of gene expression during developmentof inguinal fat to show that molecular networks of lipogenesis were maximallyexpressed at 8 weeks-of-age. In addition, the DNA methylation analysis of theSfrp5promoter and binding of acetylated histones toSfrp5andAclypromoterregions showed that major differences in the expression of genes of lipogenesisand chromatin structure occur during development. Differences in lipogenesisnetworks could account for the strain-dependent differences in adiposity upto 8 weeks-of-age; however, changes in the expression of genes in these net-works were not associated with the susceptibility to DIO in B6 male micebeyond 8 weeks-of-age