PSAT1 prompted cell proliferation and inhibited cell apoptosis in multiple myeloma through regulating PI3K/AKT pathway

Purpose: To identify the biological function of phosphoserine aminotransferase 1 (PSAT1) in regulating cell proliferation and apoptosis in multiple myeloma (MM).Methods: The mRNA and protein levels of PSAT1 were determined using quantitative real-time polymerase chain reaction (PCR) and western blotting, respectively. Cell proliferation was measured using CCK-8 assay.Results: PSAT1 mRNA and protein expression levels were significantly increased in MM cell lines when compared to control cells. Moreover,  downregulation of PSAT1 inhibited MM cell proliferation and induced cell apoptosis, whereas overexpression of PSAT1 promoted MM cell  proliferation and suppressed cell apoptosis. Further analysis demonstrated that the underlying mechanism was via regulation of PI3K/AKT pathway.Conclusion: The results identified a novel role for PSAT1 in the progression of MM, which may provide a therapeutic and a new anticancer target for the therapy of MM. Keywords: Multiple myeloma, PSAT1, Cell proliferation, PI3K/AKT pathwa

Oxidative damage from repeated tissue isolation for subculturing causes degeneration in Volvariella volvacea

The fungal fruiting body is the organized mycelium. Tissue isolation and mycelium succession are common methods of fungal species purification and rejuvenation in the production of edible mushrooms. However, repeated succession increases strain degeneration. In this study, we examined the effect of repeated tissue isolation from Volvariella volvacea fruitbodies on the occurrence of degeneration. The results showed that less than four times in succession improved production capacity, however, after 12 successions, the traits indicating strain degeneration were apparent. For instance, the density of aerophytic hyphae, hyphal growth rate and hyphal biomass were gradually reduced, while the hyphae branching was increased. Also, other degenerative traits such as prolonged production cycles and decreased biological efficiency became evident. In particular, after 19 successions, the strain degeneration became so severe no fruiting bodies were produces anymore. Meanwhile, with the increase in successions, the antioxidant enzyme activity decreased, reactive oxygen species (ROS) increased, the number of nuclei decreased, and the mitochondrial membrane potential decreased along with morphological changes in the mitochondria. This study showed that repeated tissue isolation increased oxidative damage in the succession strain due to the accumulation of ROS, causing cellular senescence, in turn, degeneration in V. volvacea strain

An AT-hook gene is required for palea formation and floral organ number control in rice

AbstractGrasses have highly specialized flowers and their outer floral organ identity remains unclear. In this study, we identified and characterized rice mutants that specifically disrupted the development of palea, one of the outer whorl floral organs. The depressed palea1 (dp1) mutants show a primary defect in the main structure of palea, implying that palea is a fusion between the main structure and marginal tissues on both sides. The sterile lemma at the palea side is occasionally elongated in dp1 mutants. In addition, we found a floral organ number increase in dp1 mutants at low penetration. Both the sterile lemma elongation and the floral organ number increase phenotype are enhanced by the mutation of an independent gene SMALL DEGENERATIVE PALEA1 (SDP1), whose single mutation causes reduced palea size. E function and presumable A function floral homeotic genes were found suppressed in the dp1–2 mutant. We identified the DP1 gene by map-based cloning and found it encodes a nuclear-localized AT-hook DNA binding protein, suggesting a grass-specific role of chromatin architecture modification in flower development. The DP1 enhancer SDP1 was also positional cloned, and was found identical to the recently reported RETARDED PALEA1 (REP1) gene encoding a TCP family transcription factor. We further found that SDP1/REP1 is downstreamly regulated by DP1

Distinguishing Emission-Associated Ambient Air PM2.5 Concentrations and Meteorological Factor-Induced Fluctuations

Although PM2.5 (particulate matter with aerodynamic diameters less than 2.5 μm) in the air originates from emissions, its concentrations are often affected by confounding meteorological effects. Therefore, direct comparisons of PM2.5 concentrations made across two periods, which are commonly used by environmental protection administrations to measure the effectiveness of mitigation efforts, can be misleading. Here, we developed a two-step method to distinguish the significance of emissions and meteorological factors and assess the effectiveness of emission mitigation efforts. We modeled ambient PM2.5 concentrations from 1980 to 2014 based on three conditional scenarios: realistic conditions, fixed emissions, and fixed meteorology. The differences found between the model outputs were analyzed to quantify the relative contributions of emissions and meteorological factors. Emission-related gridded PM2.5 concentrations excluding the meteorological effects were predicted using multivariate regression models, whereas meteorological confounding effects on PM2.5 fluctuations were characterized by probabilistic functions. When the regression models and probabilistic functions were combined, fluctuations in the PM2.5 concentrations induced by emissions and meteorological factors were quantified for all model grid cells and regions. The method was then applied to assess the historical and future trends of PM2.5 concentrations and potential fluctuations on global, national, and city scales. The proposed method may thus be used to assess the effectiveness of mitigation actions

Effects of reducing dietary crude protein and whole grain feeding on performance and amino acid metabolism in broiler chickens offered wheat-based diets

A total of 336 off-sex, male Ross 308 chicks were offered seven dietary treatments from 7 to 35 days post-hatch; each treatment was offered to eight replicate cages with six birds per cage. Three wheat-based diets were formulated to declining crude protein (CP) levels of 215, 190 and 165 g/kg but with a constant energy density (12.70 MJ/kg), electrolyte balance (250 mEq/kg) and digestible lysine level (11.00 g/kg). In a 2 × 3 factorial arrangement birds were offered either 215 or 165 g/kg CP diets to which 0%, 12.5% and 25.0% whole gain was incorporated post-pelleting. In addition, a ground grain, 190 g/kg CP diet served as a seventh treatment. The assessed parameters included growth performance, relative gizzard, pancreas and abdominal fat-pad weights, nutrient utilisation, concentrations of free amino acid in portal (anterior mesenteric vein) and systemic (brachial vein) plasma and apparent jejunal and ileal amino acid digestibility coefficients and disappearance rates. The CP reduction from 215 to 165 g/kg compromised FCR by 5.99% (1.576 versus 1.487; P

Expression of the Androgen Receptor and its Correlation with Molecular Subtypes in 980 Chinese Breast Cancer Patients

Background Recent studies have shown that androgen displays an inhibitory effect on breast cancer cell lines that express androgen receptor (AR) but not estrogen receptor (ER) and progesterone receptor (PR). We have previously reported that approximately 1/3 of ER negative high grade invasive ductal carcinomas express AR. Thus, AR can serve as a potential therapeutic target for this group of patients. Aim Here we investigated AR expression patterns in 980 consecutive breast carcinomas. Results We found that (1) AR was expressed more frequently (77%) than ER (61%) and PR (60%) in breast carcinomas; (2) AR expression was associated with ER and PR expression ( P < 0.0001), small tumor size ( P = 0.0324) and lower Ki-67 expression ( P = 0.0013); (3) AR expression was found in 65% of ER negative tumors; (4) AR expression was associated with PR and Ki-67 in ER negative tumors, but not in ER positive tumors; (5) AR expression was higher in ER positive subtypes (Luminal A, Luminal B and Luminal HER2 subtypes, 80%-86%) and lower in ER negative subtypes [HER2, triple negative (TN), and TN EFGR positive subtypes; 52%-66%], with over 50% of TN tumors expressing AR. Conclusion More breast carcinomas express AR than ER and PR, including significant numbers of ER negative and TN tumors, for which AR could serve as a potential therapeutic target

Different molecular characteristics and antimicrobial resistance profiles of Clostridium difficile in the Asia-Pacific region

Molecular epidemiology of Clostridium difficile infection (CDI) has been extensively studied in North America and Europe; however, limited data on CDI are available in the Asia-Pacific region. A multicentre retrospective study was conducted in this region. C. difficile isolates were subjected to multilocus sequence typing (ST) and antimicrobial susceptibility testing. Totally, 394 isolates were collected from Hangzhou, Hong Kong, China; Busan, South Korea; Fukuoka, Japan; Singapore; Perth, Sydney, Australia; New York, the United States. C. difficile isolates included 337 toxin A-positive/B-positive/binary toxin-negative (A+B+CDT-), 48 A-B+CDT-, and nine A+B+CDT+. Distribution of dominant STs varied geographically with ST17 in Fukuoka (18.6%), Busan (56.0%), ST2 in Sydney (20.4%), Perth (25.8%). The antimicrobial resistance patterns were significantly different among the eight sites (χ2 = 325.64, p \u3c 0.001). Five major clonal complexes correlated with unique antimicrobial resistances. Healthcare-associated (HA) CDI was mainly from older patients with more frequent antimicrobial use and higher A-B+ positive rates. Higher resistance to gatifloxacin, tetracycline, and erythromycin were observed in HA-CDI patients (χ2 = 4.76-7.89, p = 0.005-0.029). In conclusion, multiple C. difficile genotypes with varied antimicrobial resistance patterns have been circulating in the Asia-Pacific region. A-B+ isolates from older patients with prior antimicrobial use were correlated with HA-CDI

The association of the vanin-1 N131S variant with blood pressure is mediated by endoplasmic reticulum-associated degradation and loss of function

High blood pressure (BP) is the most common cardiovascular risk factor worldwide and a major contributor to heart disease and stroke. We previously discovered a BP-associated missense SNP (single nucleotide polymorphism)-rs2272996-in the gene encoding vanin-1, a glycosylphosphatidylinositol (GPI)-anchored membrane pantetheinase. In the present study, we first replicated the association of rs2272996 and BP traits with a total sample size of nearly 30,000 individuals from the Continental Origins and Genetic Epidemiology Network (COGENT) of African Americans (P=0.01). This association was further validated using patient plasma samples; we observed that the N131S mutation is associated with significantly lower plasma vanin-1 protein levels. We observed that the N131S vanin-1 is subjected to rapid endoplasmic reticulum-associated degradation (ERAD) as the underlying mechanism for its reduction. Using HEK293 cells stably expressing vanin-1 variants, we showed that N131S vanin-1 was degraded significantly faster than wild type (WT) vanin-1. Consequently, there were only minimal quantities of variant vanin-1 present on the plasma membrane and greatly reduced pantetheinase activity. Application of MG-132, a proteasome inhibitor, resulted in accumulation of ubiquitinated variant protein. A further experiment demonstrated that atenolol and diltiazem, two current drugs for treating hypertension, reduce the vanin-1 protein level. Our study provides strong biological evidence for the association of the identified SNP with BP and suggests that vanin-1 misfolding and degradation are the underlying molecular mechanism

KOBAS 2.0: a web server for annotation and identification of enriched pathways and diseases

High-throughput experimental technologies often identify dozens to hundreds of genes related to, or changed in, a biological or pathological process. From these genes one wants to identify biological pathways that may be involved and diseases that may be implicated. Here, we report a web server, KOBAS 2.0, which annotates an input set of genes with putative pathways and disease relationships based on mapping to genes with known annotations. It allows for both ID mapping and cross-species sequence similarity mapping. It then performs statistical tests to identify statistically significantly enriched pathways and diseases. KOBAS 2.0 incorporates knowledge across 1327 species from 5 pathway databases (KEGG PATHWAY, PID, BioCyc, Reactome and Panther) and 5 human disease databases (OMIM, KEGG DISEASE, FunDO, GAD and NHGRI GWAS Catalog). KOBAS 2.0 can be accessed at http://kobas.cbi.pku.edu.cn