Transforming Growth Factor-β, Macrophage Colony-Stimulating Factor and C-Reactive Protein Levels Correlate with CD14highCD16+ Monocyte Induction and Activation in Trauma Patients

Severe injury remains a leading cause of death and morbidity in patients under 40, with the number of annual trauma-related deaths approaching 160,000 in the United States. Patients who survive the initial trauma and post-traumatic resuscitation are at risk for immune dysregulation, which contributes to late mortality and accounts for approximately 20% of deaths after traumatic injury. This post-traumatic immunosuppressed state has been attributed to over-expression of anti-inflammatory mediators in an effort to restore host homeostasis. We measured a panel of monocyte markers and cytokines in 50 severely injured trauma patients for 3 days following admission. We made the novel observation that the subpopulation of monocytes expressing high levels of CD14 and CD16 was expanded in the majority of patients. These cells also expressed CD163 consistent with differentiation into alternatively activated macrophages with potential regulatory or wound-healing activity. We examined factors in trauma plasma that may contribute to the generation and activation of these cells. The percentage of CD14^highCD16⁺ monocytes after trauma correlated strongly with plasma C-reactive protein (CRP) transforming growth factor-β (TGF-β), and macrophage colony-stimulating factor (M-CSF) levels. We demonstrate a role for TGF-β and M-CSF, but not CRP in generating these cells using monocytes from healthy volunteers incubated with plasma from trauma patients. CD16 is a receptor for CRP and IgG, and we showed that monocytes differentiated to the CD14^highCD16⁺ phenotype produced anti-inflammatory cytokines in response to acute phase concentrations of CRP. The role of these cells in immunosuppression following trauma is an area of ongoing investigation.     

Predictive functional profiling using marker gene sequences and community diversity analyses of microbes in full-scale anaerobic sludge digesters

Anaerobic digestion (AD) is widely used in treating the sewage sludge, as it can reduce the amount of sludge, eliminate pathogens and produce biofuel. To enhance the operational performance and stability of anaerobic bioreactors, operational and conventional chemical data from full-scale sludge anaerobic digesters were collected over a 2-year period and summarized, and the microbial community diversity of the sludge sample was investigated at various stages of the AD process. For the purpose of distinguishing between the functional and community diversity of the microbes, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) software was used to impute the prevalence of 16S rDNA marker gene sequences in the difference in various sludge samples. Meanwhile, a taxa analysis was also carried out to investigate the different sludge samples. The microbial community diversity analysis of one AD sludge sample showed that the most dominant bacterial genera were Saccharicrinis, Syntrophus, Anaerotruncus and Thermanaerothrix. Among archaea, acetoclastic Methanosaeta represented 56.0 %, and hydrogenotrophic Methanospirillum, Methanoculleus, Methanothermus and Methanolinea accounted for 41.3 % of all methanogens. The taxa, genetic and functional prediction analyses of the feedstock and AD sludge samples suggested great community diversity differences between them. The taxa of bacteria in two AD sludge samples were considerably different, but the abundances of the functional KEGG pathways took on similar levels. The numbers of identified pathogens were significantly lower in the digested sludge than in the feedstock, but the PICRUSt results showed the difference in “human diseases” abundances in the level-1 pathway between the two sludge samples was small.     

Epigenetic regulation of autophagy by the methyltransferase EZH2 through an MTOR-dependent pathway

Macroautophagy is an evolutionarily conserved cellular process involved in the clearance of proteins and organelles. Although the autophagy regulation machinery has been widely studied, the key epigenetic control of autophagy process still remains unknown. Here we report that the methyltransferase EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) epigenetically represses several negative regulators of the MTOR (mechanistic target of rapamycin [serine/threonine kinase]) pathway, such as TSC2, RHOA, DEPTOR, FKBP11, RGS16 and GPI. EZH2 was recruited to these genes promoters via MTA2 (metastasis associated 1 family, member 2), a component of the nucleosome remodeling and histone deacetylase (NuRD) complex. MTA2 was identified as a new chromatin binding protein whose association with chromatin facilitated the subsequent recruitment of EZH2 to silenced targeted genes, especially TSC2. Downregulation of TSC2 (tuberous sclerosis 2) by EZH2 elicited MTOR activation, which in turn modulated subsequent MTOR pathway-related events, including inhibition of autophagy. In human colorectal carcinoma (CRC) tissues, the expression of MTA2 and EZH2 correlated negatively with expression of TSC2, which reveals a novel link among epigenetic regulation, the MTOR pathway, autophagy induction, and tumorigenesis.     

Overexpression of Camellia sinensis H1 histone gene confers abiotic stress tolerance in transgenic tobacco

Key message

Overexpression of CsHis in tobacco promoted chromatin condensation, but did not affect the phenotype. It also conferred tolerance to low-temperature, high-salinity, ABA, drought and oxidative stress in transgenic tobacco.

Abstract

H1 histone, as a major structural protein of higher-order chromatin, is associated with stress responses in plants. Here, we describe the functions of the Camellia sinensis H1 Histone gene (CsHis) to illustrate its roles in plant responses to stresses. Subcellular localization and prokaryotic expression assays showed that the CsHis protein is localized in the nucleus, and its molecular size is approximately 22.5 kD. The expression levels of CsHis in C. sinensis leaves under various conditions were investigated by qRT-PCR, and the results indicated that CsHis was strongly induced by various abiotic stresses such as low-temperature, high-salinity, ABA, drought and oxidative stress. Overexpression of CsHis in tobacco (Nicotiana tabacum) promoted chromatin condensation, while there were almost no changes in the growth and development of transgenic tobacco plants. Phylogenetic analysis showed that CsHis belongs to the H1C and H1D variants of H1 histones, which are stress-induced variants and not the key variants required for growth and development. Stress tolerance analysis indicated that the transgenic tobacco plants exhibited higher tolerance than the WT plants upon exposure to various abiotic stresses; the transgenic plants displayed reduced wilting and senescence and exhibited greater net photosynthetic rate (Pn), stomatal conductance (Gs) and maximal photochemical efficiency (Fv/Fm) values. All the above results suggest that CsHis is a stress-induced gene and that its overexpression improves the tolerance to various abiotic stresses in the transgenic tobacco plants, possibly through the maintenance of photosynthetic efficiency.     

Prevalence and Predictors of Somatic Symptoms among Child and Adolescents with Probable Posttraumatic Stress Disorder: A Cross-Sectional Study Conducted in 21 Primary and Secondary Schools after an Earthquake

Purpose

To explore the prevalence rates and predictors of somatic symptoms among child and adolescent survivors with probable posttraumatic stress disorder (PTSD) after an earthquake.

Methods

A total of 3053 students from 21 primary and secondary schools in Baoxing County were administered the Patient Health Questionnaire-13 (PHQ-13), a short version of PHQ-15 without the two items about sexuality and menstruation, the Children''s Revised Impact of Event Scale (CRIES), and the self-made Earthquake-Related Experience Questionnaire 3 months after the Lushan earthquake.

Results

Among child and adolescent survivors, the prevalence rates of all somatic symptoms were higher in the probable PTSD group compared with the controls. The most frequent somatic symptoms were trouble sleeping (83.2%), feeling tired or having low energy (74.4%), stomach pain (63.2%), dizziness (58.1%), and headache (57.7%) in the probable PTSD group. Older age, having lost family members, having witnessed someone get seriously injured, and having witnessed someone get buried were predictors for somatic symptoms among child and adolescent survivors with probable PTSD.

Conclusions

Somatic symptoms among child and adolescent earthquake survivors with probable PTSD in schools were common, and predictors of these somatic symptoms were identified. These findings may help those providing psychological health programs to find the child and adolescent students with probable PTSD who are at high risk of somatic symptoms in schools after an earthquake in China.     

Optimal Aspect Ratio and Excitation Spectral Region of LSPR Sensors Using Individual Au Dimmeric Nanoplates

Plasmonics - Both the excitation wavelength and aspect ratio AR are key parameters controlling the refractive index sensitivity performances of plasmonic sensors of individual Au nanoplate dimmers....     

Identification of blapsins A and B as potent small-molecule 14-3-3 inhibitors from the insect Blaps japanensis

In this study, we report three novel naturally occurring compounds, blapsins A (1) and B (2), and blapsamide (3) from the ethanol extract of the stink beetle, Blaps japanensis. The structures of these compounds were determined using spectroscopic methods. Compound 3 is a phenolic compound bearing a formamido group in the structure. Functional studies revealed that compounds 1 and 2 potently inhibited 14-3-3 protein-protein interactions (PPIs) with IC(50) values of 9.2 and 10.0 μM as determined by an ELISA assay, and 2.0 and 2.5 μM in an FP assay, respectively. These compounds represent the first example of natural small-molecule 14-3-3 inhibitors.     

Cell origins and diagnostic accuracy of interleukin 27 in pleural effusions

The objective of the present study was to investigate the presence of interleukin (IL)-27 in pleural effusions and to evaluate the diagnostic significance of pleural IL-27. The concentrations of IL-27 were determined in pleural fluids and sera from 68 patients with tuberculous pleural effusion, 63 malignant pleural effusion, 22 infectious pleural effusion, and 21 transudative pleural effusion. Flow cytometry was used to identify which pleural cell types expressed IL-27. It was found that the concentrations of pleural IL-27 in tuberculous group were significantly higher than those in malignant, infectious, and transudative groups, respectively. Pleural CD4(+) T cells, CD8(+) T cells, NK cells, NKT cells, B cells, monocytes, macrophages, and mesothelial cells might be the cell sources for IL-27. IL-27 levels could be used for diagnostic purpose for tuberculous pleural effusion, with the cut off value of 1,007 ng/L, IL-27 had a sensitivity of 92.7% and specificity of 99.1% for differential diagnosing tuberculous pleural effusion from non-tuberculous pleural effusions. Therefore, compared to non-tuberculous pleural effusions, IL-27 appeared to be increased in tuberculous pleural effusion. IL-27 in pleural fluid is a sensitive and specific biomarker for the differential diagnosing tuberculous pleural effusion from pleural effusions with the other causes.     

Endogenous generation of sulfur dioxide in rat tissues

While sulfur dioxide (SO₂) has been previously known for its toxicological effects, it is now known to be produced endogenously in mammals from sulfur-containing amino acid l-cysteine. l-cysteine is catalyzed by cysteine dioxygenase (CDO) to l-cysteinesulfinate, which converts to β-sulfinylpyruvate through transamination by aspartate aminotransferase (AAT), and finally spontaneously decomposes to pyruvate and SO₂. The present study explored endogenous SO₂ production, and AAT and CDO distribution in different rat tissue. SO₂ content was highest in stomach, followed by tissues in the right ventricle, left ventricle, cerebral gray matter, pancreas, lung, cerebral white matter, renal medulla, spleen, renal cortex and liver. AAT activity and AAT1 mRNA expression were highest in the left ventricle, while AAT1 protein expression was highest in the right ventricle. AAT2 and CDO mRNA expressions were both highest in liver tissue. AAT2 protein expression was highest in the renal medulla, but CDO protein expression was highest in liver tissue. In all tissues, AAT1 and AAT2 were mainly distributed in the cytoplasm rather than the nucleus. These observed differences among tissues endogenously generating SO₂ and associated enzymes are important in implicating the discovery of SO₂ as a novel endogenous signaling molecule.