Molecular evolution of Cide family proteins: Novel domain formation in early vertebrates and the subsequent divergence

<p>Abstract</p> <p>Background</p> <p>Cide family proteins including Cidea, Cideb and Cidec/Fsp27, contain an N-terminal CIDE-N domain that shares sequence similarity to the N-terminal CAD domain (NCD) of DNA fragmentation factors Dffa/Dff45/ICAD and Dffb/Dff40/CAD, and a unique C-terminal CIDE-C domain. We have previously shown that Cide proteins are newly emerged regulators closely associated with the development of metabolic diseases such as obesity, diabetes and liver steatosis. They modulate many metabolic processes such as lipolysis, thermogenesis and TAG storage in brown adipose tissue (BAT) and white adipose tissue (WAT), as well as fatty acid oxidation and lipogenesis in the liver.</p> <p>Results</p> <p>To understand the evolutionary process of Cide proteins and provide insight into the role of Cide proteins as potential metabolic regulators in various species, we searched various databases and performed comparative genomic analysis to study the sequence conservation, genomic structure, and phylogenetic tree of the CIDE-N and CIDE-C domains of Cide proteins. As a result, we identified signature sequences for the N-terminal region of Dffa, Dffb and Cide proteins and CIDE-C domain of Cide proteins, and observed that sequences homologous to CIDE-N domain displays a wide phylogenetic distribution in species ranging from lower organisms such as hydra (<it>Hydra vulgaris</it>) and sea anemone (<it>Nematostella vectensis</it>) to mammals, whereas the CIDE-C domain exists only in vertebrates. Further analysis of their genomic structures showed that although evolution of the ancestral CIDE-N domain had undergone different intron insertions to various positions in the domain among invertebrates, the genomic structure of <it>Cide </it>family in vertebrates is stable with conserved intron phase.</p> <p>Conclusion</p> <p>Based on our analysis, we speculate that in early vertebrates CIDE-N domain was evolved from the duplication of NCD of Dffa. The CIDE-N domain somehow acquired the CIDE-C domain that was formed around the same time, subsequently generating the Cide protein. Subsequent duplication and evolution have led to the formation of different Cide family proteins that play unique roles in the control of metabolic pathways in different tissues.</p

Regulation of gene expression by FSP27 in white and brown adipose tissue

<p>Abstract</p> <p>Background</p> <p>Brown and white adipose tissues (BAT and WAT) play critical roles in controlling energy homeostasis and in the development of obesity and diabetes. The mouse Fat-Specific protein 27 (FSP27), a member of the cell death-inducing DFF45-like effector (CIDE) family, is expressed in both BAT and WAT and is associated with lipid droplets. Over-expression of FSP27 promotes lipid storage, whereas <it>FSP27 </it>deficient mice have improved insulin sensitivity and are resistant to diet-induced obesity. In addition, <it>FSP27</it>-deficient white adipocytes have reduced lipid storage, smaller lipid droplets, increased mitochondrial activity and a higher expression of several BAT-selective genes. To elucidate the molecular mechanism by which FSP27 controls lipid storage and gene expression in WAT and BAT, we systematically analyzed the gene expression profile of <it>FSP27-</it>deficient WAT by microarray analysis and compared the expression levels of a specific set of genes in WAT and BAT by semi-quantitative real-time PCR analysis.</p> <p>Results</p> <p>BAT-selective genes were significantly up-regulated, whereas WAT-selective genes were down-regulated in the WAT of <it>FSP27-</it>deficient mice. The expression of the BAT-selective genes was also dramatically up-regulated in the WAT of <it>leptin/FSP27 </it>double deficient mice. In addition, the expression levels of genes involved in multiple metabolic pathways, including oxidative phosphorylation, the TCA cycle, fatty acid synthesis and fatty acid oxidation, were increased in the <it>FSP27-</it>deficient WAT. In contrast, the expression levels for genes involved in extracellular matrix remodeling, the classic complement pathway and TGF-β signaling were down-regulated in the <it>FSP27-</it>deficient WAT. Most importantly, the expression levels of regulatory factors that determine BAT identity, such as CEBPα/β, PRDM16 and major components of the cAMP pathway, were markedly up-regulated in the WAT of <it>FSP27-</it>deficient mice. The expression levels of these regulatory factors were also up-regulated in <it>leptin/FSP27 </it>double deficient mice. Interestingly, distinct gene expression profiles were observed in the BAT of <it>FSP27-</it>deficient mice. Taken together, these data suggest that the WAT of <it>FSP27-</it>deficient mice have a gene expression profile similar to that of BAT.</p> <p>Conclusions</p> <p>FSP27 acts as a molecular determinant that controls gene expression for a diversity of metabolic and signaling pathways and, in particular, the expression of regulatory factors, including CEBPα/β, PRDM16 and components of the cAMP signaling pathway, that control the identity of WAT and BAT.</p

Complete genome analysis of bacteriochlorophyll acontaining Roseicitreum antarcticum ZS2-28T reveals its adaptation to Antarctic intertidal environment

Aerobic anoxygenic phototrophic bacteria (AAPB) are photoheterotrophic prokaryotes able to use both light and dissolved organic matter as energy sources. Roseicitreum antarcticum ZS2-28T was isolated from intertidal sediment in the Larsemann Hills, Princess Elizabeth Land, Antarctica, and was able to produce bacteriochlorophyll a. It is the type strain of the sole species within the genus Roseicitreum. The complete genome sequence of the bacterium was determined using Illumina HiSeq X and PacBio RSII systems. The genome of R. antarcticum ZS2-28T was 4253095 bp and consisted of one chromosome and four plasmids. A number of genes related to the bacteriochlorophyll a production, photosynthetic reaction, cold adaptation, salt adaptation, ultra-violet resistance and DNA damage repairing were found in the genome. In addition to genomic islands and type IV secretion systems, genes related to gene transfer agents were detected in the genome of R. antarcticum ZS2-28T, suggesting that this bacterium can adapt to its environment by acquiring exogenous nucleic acids. The annotated complete genome sequence provides genetic insights into the environmental adaptation and ecological function of R. antarcticum ZS2-28T in Antarctic coastal area

Measuring pollutant emissions of cattle breeding and its spatial-temporal variation in China

The rapid development of animal husbandry has resulted in serious pollution issues in the livestock and poultry breeding industry, increasing the cost of environmental management. This issue is particularly prominent in China due to its rapid economic development, significant domestic consumption, and aggressive carbon neutrality targets. This study analyses pollution emissions and spatial-temporal variation in China's cattle breeding industry. Using an emission coefficient method and panel data of 31 Chinese provinces/municipalities between 2002 and 2017, we measure the total volume of pollutant emissions from China's cattle breeding industry and five major pollutants: chemical oxygen demand, total nitrogen, total phosphorus, copper, and zinc. We also analyse the dynamic variation of the spatial distribution. The results show that both the total emissions volume and emissions of the five major pollutants have decreased to different extents, among which chemical oxygen demand has decreased the fastest. Spatial divergence is strengthened as the heavy pollution areas have moved from the southeast to the northwest of the country. This study contributes to current research by its focus on the cattle breading industry and by our improvements to the pollutant emission measurement method

Preliminary genome analysis of psychrotolerant marine bacterium Pseudoalteromonas sp. BSw20308 reveals its potential applications

The genus Pseudoalteromonas is ubiquitous in the marine environment and can synthesize a wide range of extracellular compounds. Psychrotolerant Pseudoalteromonas sp. BSw20308 was isolated from the Chukchi Sea, a marginal sea of the Arctic Ocean. It produces a number of extracellular enzymes that can degrade polysaccharides and proteins. The BSw20308 genome was sequenced to 38.1-fold coverage, and the sequences were assembled into 146 contigs (≥500 bp). In total, 4 172 open reading frames (ORFs) with an average gene length of 987 bp were detected. At least 86 ORFs were predicted by sequence analysis to encode a variety of catalytic modules involved in the degradation of polysaccharides, proteins, and lipids. In addition, 36 ORFs were predicted to encode catalytic modules involved in the degradation of organic pollutants and halogenated compounds, and in the production of bioactive compounds. The draft genome sequence of BSw20308 provides new information about the ecological function and adaptation of the genus Pseudoalteromonas in Arctic marine environments, and also indicates its potential applications in the biotechnology industries (e.g., enzymology, and pollutant degradation)

Of Natural Killer cells and Hepatitis C Virus

Natural Killer (NK) cells are important effector cells in Hepatitis C Virus (HCV) infection, a virus that chronically infects around 2.5% of the world population and is a major cause of liver disease and hepatocellular carcinoma. The exact mechanisms, however, through which NK cells are activated in response to HCV remain elusive. Using the well-established HCV replicon cell-culture model we show that after co- culture of HCV replicon-carrying hepatocytes with peripheral blood mononuclear cells (PBMCs), NK cells increase expression of the high-affinity IL-2 receptor chain CD25, proliferate rapidly and produce IFN-gamma. Activation of NK cells was dependent on IL-2, most likely produced by T cells and on cell-cell contact mediated signals from monocytes. Monocytes from replicon-carrying co-cultures showed increased expression of OX40L, a member of the tumor necrosis factor family and concurrently its receptor OX40 was increased on NK cells. Blocking of OX40L in those co-cultures, as well as depletion of CD14+ monocytes abrogated the virus-induced activation and effector functions of NK cells. Together, our data reveals a novel mechanism of monocyte mediated NK cell activation against virus-infected cells involving the OX40/OX40L axis with potential relevance for therapeutic intervention by e.g. agonistic antibodies against OX40, which are already tested in cancer therapy

Up-Regulation of Mitochondrial Activity and Acquirement of Brown Adipose Tissue-Like Property in the White Adipose Tissue of Fsp27 Deficient Mice

Fsp27, a member of the Cide family proteins, was shown to localize to lipid droplet and promote lipid storage in adipocytes. We aimed to understand the biological role of Fsp27 in regulating adipose tissue differentiation, insulin sensitivity and energy balance. Fsp27−/− mice and Fsp27/lep double deficient mice were generated and we examined the adiposity, whole body metabolism, BAT and WAT morphology, insulin sensitivity, mitochondrial activity, and gene expression changes in these mouse strains. Furthermore, we isolated mouse embryonic fibroblasts (MEFs) from wildtype and Fsp27−/− mice, followed by their differentiation into adipocytes in vitro. We found that Fsp27 is expressed in both brown adipose tissue (BAT) and white adipose tissue (WAT) and its levels were significantly elevated in the WAT and liver of leptin-deficient ob/ob mice. Fsp27−/− mice had increased energy expenditure, lower levels of plasma triglycerides and free fatty acids. Furthermore, Fsp27−/− and Fsp27/lep double-deficient mice are resistant to diet-induced obesity and display increased insulin sensitivity. Moreover, white adipocytes in Fsp27−/− mice have reduced triglycerides accumulation and smaller lipid droplets, while levels of mitochondrial proteins, mitochondrial size and activity are dramatically increased. We further demonstrated that BAT-specific genes and key metabolic controlling factors such as FoxC2, PPAR and PGC1α were all markedly upregulated. In contrast, factors inhibiting BAT differentiation such as Rb, p107 and RIP140 were down-regulated in the WAT of Fsp27−/− mice. Remarkably, Fsp27−/− MEFs differentiated in vitro show many brown adipocyte characteristics in the presence of the thyroid hormone triiodothyronine (T3). Our data thus suggest that Fsp27 acts as a novel regulator in vivo to control WAT identity, mitochondrial activity and insulin sensitivity

Improved strategy for post-traumatic hydrocephalus following decompressive craniectomy: Experience of a single center

BackgroundPatients with head trauma may develop hydrocephalus after decompressive craniectomy. Many studies have referred one-stage cranioplasty (CP) and ventriculoperitoneal shunt (VPS) was applied to treat cranial defect with post-traumatic hydrocephalus (PTH), but the safety and efficiency of the procedure remain controversial.MethodsThis is a retrospective cohort study including 70 patients of PTH following decompressive craniectomy who underwent simultaneous (50) and separated (20) procedures of cranioplasty and VPS from March 2014 to March 2021 at the authors’ institution with at least 30 days of follow-up. Patient characteristics, clinical findings, and complications were collected and analyzed.ResultsFifty patients with PTH underwent improved simultaneous procedures and 20 patients underwent staged surgeries. Among the cases, the overall complication rate was 22.86%. Complications suffered by patients who underwent one-stage procedure of CP and VPS did not differ significantly, compared with patients in the group of staged procedures (22% vs. 25%, p = 0.763). The significant difference was not observed in the two groups, regarding the complications of subdural/epidural fluid collection (4%/6% vs. 0/2%, p = 1.000/1.000), epidural hemorrhage (6% vs. 4%, p = 0.942), dysfunction of shunting system (0 vs. 2%, p = 0.286), postoperative seizure (8% vs. 4%, p = 1.000), and reoperation case (0 vs. 2%, p = 0.286). No case of subdural hemorrhage, incision/intracranial/abdominal infection, shunting system dysfunction, or reoperation was observed in the group of simultaneous procedure. Complications including subdural/epidural fluid collection, subdural hemorrhage, and incision/intracranial infection were not shown in the case series of the staged procedure group.ConclusionThe improved simultaneous procedure of cranioplasty and VPS is effective and safe to treat cranial defect and post-traumatic hydrocephalus with low risk of complications