Genetic and biochemical interactions involving tricarboxylic acid cycle (TCA) function using a collection of mutants defective in all TCA cycle genes

The eight enzymes of the tricarboxylic acid (TCA) cycle are encoded by at least 15 different nuclear genes in Saccharomyces cerevisiae. We have constructed a set of yeast strains defective in these genes as part of a comprehensive analysis of the interactions among the TCA cycle proteins. The 15 major TCA cycle genes can be sorted into five phenotypic categories on the basis of their growth on nonfermentable carbon sources. We have previously reported a novel phenotype associated with mutants defective in the IDH2 gene encoding the Idh2p subunit of the NAD+-dependent isocitrate dehydrogenase (NAD-IDH). Null and nonsense idh2 mutants grow poorly on glycerol, but growth can be enhanced by extragenic mutations, termed glycerol suppressors, in the CIT1 gene encoding the TCA cycle citrate synthase and in other genes of oxidative metabolism. The TCA cycle mutant collection was utilized to search for other genes that can suppress idh2 mutants and to identify TCA cycle genes that display a similar suppressible growth phenotype on glycerol. Mutations in 7 TCA cycle genes were capable of functioning as suppressors for growth of idh2 mutants on glycerol. The only other TCA cycle gene to display the glycerol-suppressor-accumulation phenotype was IDH1, which encodes the companion Idh1p subunit of NAD-IDH. These results provide genetic evidence that NAD-IDH plays a unique role in TCA cycle function.     

The Effects of Direct-fed Microbial Supplementation,as an Alternative to Antibiotics,on Growth Performance,Intestinal Immune Status,and Epithelial Barrier Gene Expression in Broiler Chickens

The objective of this study was to investigate the effects of Bacillus subtilis-based probiotic supplementation in broiler chicken diets on growth performance, feed efficiency, intestinal cytokine, and tight junction (TJ) protein mRNA expression. Zero-day-old broiler chicks (n = 140) were randomly assigned to one of five dietary treatments: basal diet (CON); basal diet supplemented with either antibiotic bacitracin methylene disalicylate (BMD); or probiotics, namely, B. subtilis strain 1781 (PB1), a combination of B. subtilis strain 1104 + strain 747 (PB2), or B. subtilis strain 1781 + strain 747 (PB3). Body weight and feed intake were measured at 14 days of age, and the feed conversion ratio (FCR) was calculated. At 14 days of age, ileal samples were collected and used for intestinal cytokine, TJ protein, and mucin gene expression analysis using qRT-PCR. The chickens supplemented with antibiotic (BMD) and B. subtilis strain 1781 alone (PB1) had significantly higher body weights compared to controls of the same age. Dietary supplementation with antibiotic (BMD) or probiotics (PB1, PB2, PB3) significantly improved the feed efficiency as evidenced by decreased FCR compared to controls. No differences were observed in the expression of IL1β, IL17F, IFNγ, and MUC2 gene among the different treatment groups. However, elevated expression of IL6 (BMD, PB1, PB2), IL8 (PB2), and TNFSF15 (PB1, PB2, PB3) compared to controls was observed in the ileum. IL2 and IL10 expression was upregulated in chicks in the PB2 and PB3 groups, and IL4 was elevated in the PB1 group. IL13 was elevated in all probiotic-fed groups (PB1, PB2, PB3). Probiotic supplementation was also shown to significantly increase the expression of TJ proteins JAM2, ZO1 (PB2, PB3), and occludin (PB1, PB2). Taken together, B. subtilis supplementation altered intestinal immune activity and influenced gut barrier integrity through increased tight junction gene expression.     

A database of 389 medicinal plants for diabetes

Medicinal plants used to treat hypoglycemic and hyperglycemic conditions are of considerable interest to ethno-botanical community as they are recognized to contain valuable medicinal properties in different parts of the plant. The active principles of many plant species with desired properties are isolated to cure ailments such as diabetes type-1 and type-2, respectively. Here, we describe DiaMedBase, a database containing information of medicinal plants for diabetes. AVAILABILITY: http://www.progenebio.in/DMP/DMP.htm.     

静磁场对单株人体体表正常菌生长影响的研究

本文通过40mT和120mT两种静磁场作用下表皮葡萄球菌生长过程的研究,发现试验所选强度静磁场加速了表皮葡萄球菌在对数生长期的生长速率,而在进入稳定生长期后其生长速率反而低于对照组,但就整个生长周期而言,静磁场作用下表皮葡萄球菌的总量大于对照组,表明了试验所选静磁场对表皮葡萄球菌生长有一定促进作用.     

Racial admixture and its impact on BMI and blood pressure in African and Mexican Americans

Admixed populations such as African Americans and Hispanic Americans present both challenges and opportunities in genetic epidemiologic research. Because of variation in admixture levels among individuals, case-control association studies may be subject to stratification bias. On the other hand, admixed populations also present special opportunities both for examining the role of genetic and environmental factors for observed racial/ethnic differences, and for possibly mapping alleles that contribute to such differences. Here we examined the distribution and relationship of individual admixture (IA) estimates with BMI and three measures of blood pressure in two admixed populations in the NHLBI Family Blood Pressure Program (FBPP): African Americans and Mexican Americans. For the African Americans, we observed modest but significant differences in average African IA among four recruitment sites. We observed a slight excess of African IA among hypertensives compared to normotensives, and a positive (non-significant) regression of African IA on blood pressure in untreated participants. Within Mexican Americans, we found no difference in average IA between hypertensives and normotensives, but a positive (marginally significant) regression of African IA on diastolic blood pressure. We also observed a significant positive regression of Caucasian IA (and negative regression of Native American IA) on BMI. Our results are suggestive of genetic differences between Africans and non-Africans that influence blood pressure, but such effects are likely to be modest compared to environmental ones. Excess obesity among Native Americans compared to whites is not consistent with a simple genetic explanation.     

A triple-drug nanotherapy to target breast cancer cells,cancer stem cells,and tumor vasculature

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, accounting for the majority of breast cancer-related death. Due to the lack of specific therapeutic targets, chemotherapeutic agents (e.g., paclitaxel) remain the mainstay of systemic treatment, but enrich a subpopulation of cells with tumor-initiating capacity and stem-like characteristics called cancer stem cells (CSCs); thus development of a new and effective strategy for TNBC treatment is an unmet medical need. Cancer nanomedicine has transformed the landscape of cancer drug development, allowing for a high therapeutic index. In this study, we developed a new therapy by co-encapsulating clinically approved drugs, such as paclitaxel, verteporfin, and combretastatin (CA4) in polymer-lipid hybrid nanoparticles (NPs) made of FDA-approved biomaterials. Verteporfin is a drug used in the treatment of macular degeneration and has recently been found to inhibit the Hippo/YAP (Yes-associated protein) pathway, which is known to promote the progression of breast cancer and the development of CSCs. CA4 is a vascular disrupting agent and has been tested in phase II/III of clinical trials. We found that our new three drug-NP not only effectively inhibited TNBC cell viability and cell migration, but also significantly diminished paclitaxel-induced and/or CA4-induced CSC enrichment in TNBC cells, partially through inhibiting the upregulated Hippo/YAP signaling. Combination of verteporfin and CA4 was also more effective in suppressing angiogenesis in an in vivo zebrafish model than single drug alone. The efficacy and application potential of our triple drug-NPs were further assessed by using clinically relevant patient-derived xenograft (PDX) models. Triple drug-NP effectively inhibited the viability of PDX organotypic slide cultures ex vivo and stopped the growth of PDX tumors in vivo. This study developed an approach capable of simultaneously inhibiting bulk cancer cells, CSCs, and angiogenesis.Subject terms: Breast cancer, Cancer stem cells