A Modeling Study on the Operational Stability of a Variable Speed Direct Expansion Air Conditioning System

The instability in a refrigeration system, conventionally known as hunting, is the phenomena of the oscillation of certain system operational parameters such as the degree of refrigerant superheat (DS), refrigerant mass flow rate and evaporating pressure. Hunting has been noticed in not only the refrigeration systems controlled by thermostatic expansion valves (TEVs), but also those controlled by electronic expansion valves (EEVs), and hence attracted a lot of research interest. However, no previous studies on the impacts of both the operational parameters of an EEV and the simultaneous variation of compressor and supply fan speed in a variable speed (VS) direct expansion (DX) air conditioning (A/C) system may be identified. Â This paper reports on a modeling study on the operational stability of a VS DX A/C system. An existing detailed, physical based dynamic model for a VS DX A/C system has been further developed by adding equations for both the temperature sensor in an EEV and the air side of the evaporator. Using this further developed model, a modeling study on the stability of a VS DX A/C system based on the classical minimal-stable-signal (MSS) theory has been carried out. The effects of the dynamics of the temperature sensor, Proportional-Integral (PI) control settings of the EEV and variable speed operation of both compressor and supply fan on the operational stability of the VS DX A/C system have been investigated. The modelling results demonstrated that increasing the time constant of the temperature sensor would help mitigating the system instability, and increasing the compressor speed or decreasing the supply fan speed would lead to the movement of a mixture-vapor transition point towards evaporator exit, leading to potential instability of the VS DX A/C system.

Co-methylated Genes in Different Adipose Depots of Pig are Associated with Metabolic, Inflammatory and Immune Processes

It is well established that the metabolic risk factors of obesity and its comorbidities are more attributed to adipose tissue distribution rather than total adipose mass. Since emerging evidence suggests that epigenetic regulation plays an important role in the aetiology of obesity, we conducted a genome-wide methylation analysis on eight different adipose depots of three pig breeds living within comparable environments but displaying distinct fat level using methylated DNA immunoprecipitation sequencing. We aimed to investigate the systematic association between anatomical location-specific DNA methylation status of different adipose depots and obesity-related phenotypes. We show here that compared to subcutaneous adipose tissues which primarily modulate metabolic indicators, visceral adipose tissues and intermuscular adipose tissue, which are the metabolic risk factors of obesity, are primarily associated with impaired inflammatory and immune responses. This study presents epigenetic evidence for functionally relevant methylation differences between different adipose depots

Marked methylation changes in intestinal genes during the perinatal period of preterm neonates

BACKGROUND: The serious feeding- and microbiota-associated intestinal disease, necrotizing enterocolitis (NEC), occurs mainly in infants born prematurely (5-10% of all newborns) and most frequently after formula-feeding. We hypothesized that changes in gene methylation is involved in the prenatal maturation of the intestine and its response to the first days of formula feeding, potentially leading to NEC in preterm pigs used as models for preterm infants. RESULTS: Reduced Representation Bisulfite Sequencing (RRBS) was used to assess if changes in intestinal DNA methylation are associated with formula-induced NEC outbreak and advancing age from 10 days before birth to 4 days after birth. Selected key genes with differentially methylated gene regions (DMRs) between groups were further validated by HiSeq-based bisulfite sequencing PCR and RT-qPCR to assess methylation and expression levels. Consistent with the maturation of many intestinal functions in the perinatal period, methylation level of most genes decreased with advancing pre- and postnatal age. The highest number of DMRs was identified between the newborn and 4 d-old preterm pigs. There were few intestinal DMR differences between unaffected pigs and pigs with initial evidence of NEC. In the 4 d-old formula-fed preterm pigs, four genes associated with intestinal metabolism (CYP2W1, GPR146, TOP1MT, CEND1) showed significant hyper-methylation in their promoter CGIs, and thus, down-regulated transcription. Methylation-driven down-regulation of such genes may predispose the immature intestine to later metabolic dysfunctions and severe NEC lesions. CONCLUSIONS: Pre- and postnatal changes in intestinal DNA methylation may contribute to high NEC sensitivity in preterm neonates. Optimizing gene methylation changes via environmental stimuli (e.g. diet, nutrition, gut microbiota), may help to make immature newborn infants more resistant to gut dysfunctions, both short and long term. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2164-15-716) contains supplementary material, which is available to authorized users

DNA methylation changes at infertility genes in newborn twins conceived by in vitro fertilisation

Background: The association of in vitro fertilisation (IVF) and DNA methylation has been studied predominantly at regulatory regions of imprinted genes and at just thousands of the ~28 million CpG sites in the human genome.Methods: We investigated the links between IVF and DNA methylation patterns in whole cord blood cells (n = 98) and cord blood mononuclear cells (n = 82) from newborn twins using genome-wide methylated DNA immunoprecipitation coupled with deep sequencing.Results: At a false discovery rate (FDR) of 5%, we identified one significant whole blood DNA methylation change linked to conception via IVF, which was located ~3 kb upstream of TNP1, a gene previously linked to male infertility. The 46 most strongly associated signals (FDR of 25%) included a second region in a gene also previously linked to infertility, C9orf3, suggesting that our findings may in part capture the effect of parental subfertility. Using twin modelling, we observed that individual-specific environmental factors appear to be the main overall contributors of methylation variability at the FDR 25% IVF-associated differentially methylated regions, although evidence for methylation heritability was also obtained at several of these regions. We replicated previous findings of differential methylation associated with IVF at the H19/IGF2 region in cord blood mononuclear cells, and we validated the signal at C9orf3 in monozygotic twins. We also explored the impact of intracytoplasmic sperm injection on the FDR 25% signals for potential effects specific to male or female infertility factors.Conclusions: To our knowledge, this is the most comprehensive study of DNA methylation profiles at birth and IVF conception to date, and our results show evidence for epigenetic modifications that may in part reflect parental subfertility

Complex I assembly function and fatty acid oxidation enzyme activity of ACAD9 both contribute to disease severity in ACAD9 deficiency

Acyl-CoA dehydrogenase 9 (ACAD9) is an assembly factor for mitochondrial respiratory chain Complex I (CI), and ACAD9 mutations are recognized as a frequent cause of CI deficiency. ACAD9 also retains enzyme ACAD activity for long-chain fatty acids in vitro, but the biological relevance of this function remains controversial partly because of the tissue specificity of ACAD9 expression: high in liver and neurons and minimal in skin fibroblasts. In this study, we hypothesized that this enzymatic ACAD activity is required for full fatty acid oxidation capacity in cells expressing high levels of ACAD9 and that loss of this function is important in determining phenotype in ACAD9-deficient patients. First, we confirmed that HEK293 cells express ACAD9 abundantly. Then, we showed that ACAD9 knockout in HEK293 cells affected long-chain fatty acid oxidation along with Cl, both of which were rescued by wild type ACAD9. Further, we evaluated whether the loss of ACAD9 enzymatic fatty acid oxidation affects clinical severity in patients with ACAD9 mutations. The effects on ACAD activity of 16 ACAD9 mutations identified in 24 patients were evaluated using a prokaryotic expression system. We showed that there was a significant inverse correlation between residual enzyme ACAD activity and phenotypic severity of ACAD9-deficient patients. These results provide evidence that in cells where it is strongly expressed, ACAD9 plays a physiological role in fatty acid oxidation, which contributes to the severity of the phenotype in ACAD9-deficient patients. Accordingly, treatment of ACAD9 patients should aim at counteracting both CI and fatty acid oxidation dysfunction

An atlas of DNA methylomes in porcine adipose and muscle tissues

It is evident that epigenetic factors, especially DNA methylation, have essential roles in obesity development. Here, using pig as a model, we investigate the systematic association between DNA methylation and obesity. We sample eight variant adipose and two distinct skeletal muscle tissues from three pig breeds living within comparable environments but displaying distinct fat level. We generate 1,381 Gb of sequence data from 180 methylated DNA immunoprecipitation libraries, and provide a genome-wide DNA methylation map as well as a gene expression map for adipose and muscle studies. The analysis shows global similarity and difference among breeds, sexes and anatomic locations, and identifies the differentially methylated regions. The differentially methylated regions in promoters are highly associated with obesity development via expression repression of both known obesity-related genes and novel genes. This comprehensive map provides a solid basis for exploring epigenetic mechanisms of adipose deposition and muscle growth

第831回千葉医学会例会・第15回千葉大学放射線医学教室例会

Figure S2. All a-DMRs within (1) genomic location. Top: a-DMRs (purple), gene, DHS clusters, transcription factor ChIP-seq, ChromHMM segmentation, combined segmentation and conservation; and (2) scatterplot: x-axis = Age, y-axis = Normalised methylation. (PDF 34909 kb

Association of thyroid-stimulating hormone and lipid levels with suicide attempts among adolescents with major depressive disorder in China

ObjectivesEvidence suggested that thyroid-stimulating hormone (TSH) and lipid levels were associated with major depressive disorder (MDD). However, its role in suicide attempts in adolescents with MDD was unclear. This investigation was to probe into the relationship between TSH, lipid levels, and attempted suicide in adolescents with MDD.MethodsA total of 179 adolescents with MDD were included from January 2021 to January 2022. Socio-demographic data and clinical data were obtained through self-made questionnaires. TSH and lipid levels were analyzed by a recognized laboratory. The Epidemiological Studies Depression Scale (CES-D) was used to assess the severity of depression. Questions about whether there was a behavior of suicide attempts were completed through conversation interviews.ResultsResults showed that the CES-D total score, TSH, and low-density lipoprotein cholesterol (LDL-C) of suicide attempters were significantly higher than those of non-suicide attempters. Ordinary family relationships were more likely to attempt suicide than good family relationships. The CES-D total score, ordinary family relationships, TSH and LDL-C were still significant in binary logistic regression, with an adjusted odds ratio (OR) of 1.04, 3.42, 5.14, and 1.76, respectively. The area under the receiver operating characteristic (ROC) curve showed that the area under the ROC curve (AUC) ranged from 0.60 to 0.74.ConclusionSuicide attempts are common among adolescents with MDD and were associated with CES-D total score, ordinary family relationships, TSH, and LDL-C. Given the association between suicide attempts and TSH and LDL-C, the dynamic changes in TSH and LDL-C levels should be detected regularly

Coronavirus Papain-like Proteases Negatively Regulate Antiviral Innate Immune Response through Disruption of STING-Mediated Signaling

Viruses have evolved elaborate mechanisms to evade or inactivate the complex system of sensors and signaling molecules that make up the host innate immune response. Here we show that human coronavirus (HCoV) NL63 and severe acute respiratory syndrome (SARS) CoV papain-like proteases (PLP) antagonize innate immune signaling mediated by STING (stimulator of interferon genes, also known as MITA/ERIS/MYPS). STING resides in the endoplasmic reticulum and upon activation, forms dimers which assemble with MAVS, TBK-1 and IKKε, leading to IRF-3 activation and subsequent induction of interferon (IFN). We found that expression of the membrane anchored PLP domain from human HCoV-NL63 (PLP2-TM) or SARS-CoV (PLpro-TM) inhibits STING-mediated activation of IRF-3 nuclear translocation and induction of IRF-3 dependent promoters. Both catalytically active and inactive forms of CoV PLPs co-immunoprecipitated with STING, and viral replicase proteins co-localize with STING in HCoV-NL63-infected cells. Ectopic expression of catalytically active PLP2-TM blocks STING dimer formation and negatively regulates assembly of STING-MAVS-TBK1/IKKε complexes required for activation of IRF-3. STING dimerization was also substantially reduced in cells infected with SARS-CoV. Furthermore, the level of ubiquitinated forms of STING, RIG-I, TBK1 and IRF-3 are reduced in cells expressing wild type or catalytic mutants of PLP2-TM, likely contributing to disruption of signaling required for IFN induction. These results describe a new mechanism used by CoVs in which CoV PLPs negatively regulate antiviral defenses by disrupting the STING-mediated IFN induction