The novel cis-encoded antisense RNA AsrC positively regulates the expression of rpoE-rseABC operon and thus enhances the motility of Salmonella enterica serovar typhi

Bacterial noncoding RNAs are essential in many cellular processes, including response to environmental stress, and virulence. Deep sequencing analysis of the Salmonella enterica serovar Typhi (S. Typhi) transcriptome revealed a novel antisense RNA transcribed in cis on the strand complementary to rseC, an activator gene of sigma factor RpoE. In this study, expression of this antisense RNA was confirmed in S. Typhi by Northern hybridization. Rapid amplification of cDNA ends and sequence analysis identified an 893 bp sequence from the antisense RNA coding region that covered all of the rseC coding region in the reverse direction of transcription. This sequence of RNA was named as AsrC. After overexpression of AsrC with recombinantant plasmid in S. Typhi, the bacterial motility was increased obviously. To explore the mechanism of AsrC function, regulation of rseC and rpoE expression by AsrC was investigated. We found that AsrC increased the levels of rseC mRNA and protein. The expression of rpoE was also increased in S. Typhi after overexpression of AsrC, which was dependent on rseC. Thus, we propose that AsrC increased RseC level and indirectly activating RpoE which can initiate fliA expression and promote the motility of S. Typhi

Activation of relaxin family receptor 1 from different mammalian species by relaxin peptide and small-molecule agonist ML290

Relaxin peptide (RLN), which signals through the relaxin family peptide 1 (RXFP1) GPCR receptor, has shown therapeutic effects in an acute heart failure clinical trial. We have identified a small-molecule agonist of human RXFP1, ML290; however, it does not activate the mouse receptor. To find a suitable animal model for ML290 testing and to gain mechanistic insights into the interaction of various ligands with RXFP1, we have cloned rhesus macaque, pig, rabbit, and guinea pig RXFP1s and analyzed their activation by RLN and ML290. HEK293T cells expressing macaque or pig RXFP1 responded to relaxin and ML290 treatment as measured by an increase of cAMP production. Guinea pig RXFP1 responded to relaxin but had very low response to ML290 treatment only at highest concentrations used. The rabbit RXFP1 amino acid sequence was the most divergent, with a number of unique substitutions within the ectodomain and the seven-transmembrane domain (7TM). Two splice variants of rabbit RXFP1 derived through alternative splicing of the fourth exon were identified. In contrast to the other species, rabbit RXFP1s were activated by ML290, but not with human, pig, mouse, or rabbit RLNs. Using FLAG-tagged constructs, we have shown that both rabbit RXFP1 variants are expressed on the cell surface. No binding of human Eu-labeled RLN to rabbit RXFP1 was detected, suggesting that in this species, RXFP1 might be non-functional. We used chimeric rabbit–human and guinea pig–human constructs to identify regions important for RLN or ML290 receptor activation. Chimeras with the human ectodomain and rabbit 7TM domain were activated by RLN, whereas substitution of part of the guinea pig 7TM domain with the human sequence only partially restored ML290 activation, confirming the allosteric mode of action for the two ligands. Our data demonstrate that macaque and pig models can be used for ML290 testing

Visuospatial characteristics of an elderly Chinese population: results from the WAIS-R Block Design Test

Visuospatial deficits have long been recognized as a potential predictor of dementia, with visuospatial ability decline having been found to accelerate in later stages of dementia. We, therefore, believe that the visuospatial performance of patients with mild cognitive impairment (MCI) and dementia (Dem) might change with varying visuospatial task difficulties. This study administered the WAIS-R Block Design Test (BDT) to determine whether visuospatial ability can help discriminate between MCI patients from Dem patients and normal controls (NC). Results showed that the BDT could contribute to the discrimination between MCI and Dem. Specifically, simple BDT task scores could best distinguish MCI from Dem patients, while difficult BDT task scores could contribute to discriminating between MCI and NC. Given the potential clinical value of the BDT in the diagnosis of Dem and MCI, normative data stratified by age and education for the Chinese elderly population are presented for use in research and clinical settings

Sex-related differences of lipid metabolism induced by triptolide: The possible role of the LXRα/SREBP-1 signaling pathway

Triptolide, a diterpenoid isolated from the plant Tripterygium Hook. f., exerts a unique bioactive spectrum of anti-inflammatory and anticancer activities. However, triptolide’s clinical applications are limited due to its severe toxicities.Fatty liver toxicity occurs in response to triptolide, and this toxic response significantly differs between males and females. This report investigated the pathogenesis underlying the sex-related differences in the dyslipidosis induced by triptolide in rats. Wistar rats were administered 0, 150, 300 or 450 μg triptolide/kg/day by gavage for 28 days. Ultrastructural examination revealed that more lipid droplets were present in female triptolide-treated rats than in male triptolide-treated rats. Furthermore, liver triglyceride, total bile acid and free fatty acid levels were significantly increased in female rats in the 300 and 450 μg/kg dose groups. The expression of liver X receptor α (LXRα) and its target genes, cholesterol 7α-hydroxylase (CYP7A1) and Sterol regulatory element-binding transcription factor 1(SREBP-1), increased following triptolide treatment in both male and female rats; however, the female rats were more sensitive to triptolide than the male rats. In addition, the expression of acetyl-CoA carboxylase 1(ACC1), a target gene of SREBP-1, increased in the female rats treated with 450 μg triptolide/kg/day, and ACC1 expression contributed to the sex-related differences in the triptolide-induced dysfunction of lipid metabolism. Our results demonstrate that the sex-related differences in LXR/SREBP-1-mediated regulation of gene expression in rats are responsible for the sex-related differences in lipid metabolism induced by triptolide, which likely underlie the sex-related differences in triptolide hepatotoxicity. This study will be important for predicting sex-related effects on the pharmacokinetics and toxicity of triptolide and for improving its safety

Spatial variations of prokaryotic communities in surface water from India Ocean to Chinese marginal seas and their underlining environmental determinants

To illustrate the biogeographic patterns of prokaryotic communities in surface sea water, 24 samples were systematically collected across a large distance from Indian Ocean to Chinese marginal seas, with an average distance of 453 km between two adjacent stations. A total of 841,364 quality reads was produced by the high throughput DNA sequencing of the 16S rRNA genes. Phylogenetic analysis showed that Proteobacteria were predominant in all samples, with Alphaproteobacteria and Gammaproteobacteria being the two most abundant components. Cyanobacteria represented the second largest fraction of the total quality reads, and mainly included Prochlorococcus and Synechococcus. The semi-closed marginal seas, including South China Sea (SCS) and nearby regions, exhibited a transition in community composition between oceanic and coastal seas, based on the distribution patterns of Prochlorococcus and Synechococcus as well as a non-metric multidimensional scaling (NMDS) analysis. Distinct clusters of prokaryotes from coastal and open seas, and from different water masses in Indian Ocean were obtained by Bray-Curtis dissimilarity analysis at the OTU level, revealing a clear spatial heterogeneity. The major environmental factors correlated with the community variation in this broad scale were identified as salinity, temperature and geographic distance. Community comparison among regions shows that anthropogenic contamination is another dominant factor in shaping the biogeographic patterns of the microorganisms. These results suggest that environmental factors involved in complex interactions between land and sea act synergistically in driving spatial variations in coastal areas

Advancements in the Underlying Pathogenesis of Schizophrenia: Implications of DNA Methylation in Glial Cells

Schizophrenia (SZ）is a chronic and severe mental illness for which currently there is no cure. At present, the exact molecular mechanism involved in the underlying pathogenesis of SZ is unknown. The disease is thought to be caused by a combination of genetic, biological, psychological, and environmental factors. Recent studies have shown that epigenetic regulation is involved in SZ pathology. Specifically, DNA methylation, one of the earliest found epigenetic modifications, has been extensively linked to modulation of neuronal function, leading to psychiatric disorders such as SZ. However, increasing evidence indicates that glial cells, especially dysfunctional oligodendrocytes undergo DNA methylation changes that contribute to the pathogenesis of SZ. This review primarily focuses on DNA methylation involved in glial dysfunctions in SZ. Clarifying this mechanism may lead to the development of new therapeutic interventional strategies for the treatment of SZ and other illnesses by correcting abnormal methylation in glial cells

The evolutionarily conserved E3 ubiquitin ligase AtCHIP contributes to plant immunity

Plants possess a sophisticated immune system to recognize and respond to microbial threats in their environment. The level of immune signaling must be tightly regulated so that immune responses can be quickly activated in the presence of pathogens, while avoiding autoimmunity. HSP90s, along with their diverse array of co-chaperones, forms chaperone complexes that have been shown to play both positive and negative roles in regulating the accumulation of immune receptors and regulators. In this study, we examined the role of AtCHIP, an evolutionarily conserved E3 ligase that was known to interact with chaperones including HSP90s in multicellular organisms including fruit fly, C. elegans, plants and human. Atchip knockout mutants display enhanced disease susceptibility to a virulent oomycete pathogen, and overexpression of AtCHIP causes enhanced disease resistance at low temperature. Although CHIP was reported to target HSP90 for ubiquitination and degradation, accumulation of HSP90.3 was not affected in Atchip plants. In addition, protein accumulation of nucleotide-binding, leucine-rich repeat domain immune receptor (NLR) SNC1 is not altered in Atchip mutant. Thus, while AtCHIP plays a role in immunity, it does not seem to regulate the turnover of HSP90 or SNC1. Further investigation is needed in order to determine the exact mechanism behind AtCHIP’s role in regulating plant immune responses

Expression of Agrobacterium homolog genes encoding T-complex recruiting protein under virulence induction conditions

Proteins encoded by three Agrobacterial genes atu5117, atu4860 and atu4856 are highly homologous to each other in amino acid sequence. All three proteins are able to bind VirD2 and named as VBP1, VBP2 and VBP3 (VirD2-binding protein) respectively. VBP is involved in the T-DNA transfer by recruiting the T-complex to T4SS and defined as T-complex recruiting protein. To know whether these three homologous genes are expressed differently under virulence induction conditions, we tested the effects of virulence induction conditions, including varied pH, temperature and acetosyringone concentration, on the expressions of three VBP-encoding genes. Our data showed that atu5117 and atu4856 maintained constant expression under the tested induction conditions, whereas the expression of atu4860 was affected by the culture conditions. The culture conditions favorable to the expression of atu4860 differ from the reported induction conditions for other virulence proteins. Especially, pH value was a crucial factor for the expression of atu4860. Moreover, the deletion of atu5117 affected the expression of atu4860. These results suggest that the mechanisms regulating the expression of these three homologous genes are different from the virulence induction mechanism and that VBP homologs are presumably involved in other biological processes in addition to T-complex recruitment

Effect of the gall wasp Leptocybe invasa on hydraulic architecture in Eucalyptus camaldulensis plants

The gall wasp, Leptocybe invasa (Hymenoptera; Eulophidae), is a devastating pest of eucalypt plantations in the Middle East, the Mediterranean basin, Africa, India, South-East Asia, and China. Heavy galling causes the leaves to warp and in extreme cases it may stunt the growth of the trees of Eucalyptus camaldulensis. However, the physiological mechanisms underlying how L. invasa inhibits the growth of plants of E. camaldulensis are unclear. Because the growth rate of plants is mainly dependent on photosynthesis that is largely correlated with hydraulic architecture, we speculate that galling of L. invasa depresses hydraulic conductance of stem and leaf. In the present study, we examined the effects of L. invasa galling on hydraulic architecture and photosynthetic parameters in E. camaldulensis plants. We found that galling of L. invasa significantly decreased stem hydraulic conductance (Kstem), midday leaf water potential (md), minor vein density (MVD), and stomatal density (SD). Furthermore, the stomatal conductance (gs), chlorophyll content, CO2 assimilation rate (An) and photosynthetic electron flow were reduced in infected plants. Therefore, the galling of L. invasa not only declined the water supply from stem to leaves, but also restricted water transport within leaf. As a result, galled plants of E. camaldulensis reduced leaf number, leaf area, SD and gs to balance water supply and transpirational demand. Furthermore, galled plants had lower leaf nitrogen content, leading to decreases in chlorophyll content, CO2 assimilation rate and photosynthetic electron flow. These results indicate that the change in hydraulic architecture is responsible for the inhibition of growth rate in galled plants

Significance of interleukin-33 and its related cytokines in patients with breast cancers

Interleukin-33 (IL-33) is a recently identified cytokine, an important member of the IL-1 family. IL-33 binds to its receptor ST2 to induce type 2 cytokines and exert both pro-inflammatory and protective functions in host defense and disease. Murine breast carcinoma models suggest disruption of ST2 signaling may enhance the anti-tumor immune response, suggesting IL-33 impedes anti-tumor immunity. However, the role of IL-33 in patients with breast cancers is not elucidated. We detected the expression of IL-33 in tumor tissue, and IL-33 and its related cytokines in serum from breast cancer patients. Using Luminex and immunohistochemistry methods, we found that serum levels of IL-33 were nearly 2-fold higher in patients with breast cancers, compared to patients with benign breast diseases. In cancer tissues, expression of IL-33 was higher than matched normal breast tissues from the same patients, and was also associated with a well-differentiated phenotype, HER2 overexpression, more lymph nodes involvement, and a family history of malignant carcinoma. These results suggest that IL-33 may play an important role in the progress of breast cancers and may be a useful biomarker for predicting the progress and metastasis of breast cancers