Natural incidence of egg parasitoids of Edessa meditabunda (F.) (Hemiptera: Pentatomidae) on Crotalaria spectabilis in Campo Novo do Parecis, MT, Brazil

Egg parasitoids of the stink bug Edessa meditabunda (F) were studied on rattlepod Crotalaria spectabilis used in soybean crop rotation in Campo Novo do Parecis, Mato Grosso state, central western Brazil. Seven species of parasitoids were found: two Encyrtidae, one Eurytomidae, and four Platygastridae. The occurrence of Trissolcus euchisti (Ashmead) and Trissolcus elimatus Johnson (Platygastridae) on eggs of E. meditabunda is recorded for the first time. Moreover, this is the first record of T. elimatus and T. euchisti from Brazil.     

Synthesis and evaluation of the antiproliferative activity of novel isoindolo[2,1-a]quinoxaline and indolo[1,2-a]quinoxaline derivatives

A novel series of isoindolo[2,1-a]quinoxaline and indolo[1,2-a]quinoxaline derivatives was synthesized and evaluated in vitro against various human cancer cell lines for antiproliferative activity. These new compounds displayed activity against leukemia and breast cancer cell lines in the 3- to 18-μM concentration range.     

Efficient, non-toxic hybrid PPV-PAMAM dendrimer as a gene carrier for neuronal cells

A novel hybrid dendrimer (TRANSGEDEN) that combines a conjugated rigid polyphenylenevinylene (PPV) core with flexible polyamidoamine (PAMAM) branches at the surface was synthesized and characterized. The potential of this material as a nonviral gene delivery system was also examined, and it was observed that dendriplexes formed by TRANSGEDEN and small interfering ribonucleic acids (siRNAs) can be incorporated into >90% of neuronal cells without any toxicity up to a dendrimer concentration of 3 μM. TRANSGEDEN was used to deliver a specific siRNA to rat cerebellar granular neurons (CGNs) to knock down the cofilin-1 protein. Cofilin-1 removal partially protects CGNs from N-methyl D-aspartate (NMDA)-mediated neuronal death.     

Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy

The aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (lcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA), and anti-topoisomerase I (ATA). Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32×10⁻¹², OR = 0.75). Also, rs12540874 in GRB10 gene (P = 1.27 × 10⁻⁶, OR = 1.15) and rs11047102 in SOX5 gene (P = 1.39×10⁻⁷, OR = 1.36) showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79×10⁻⁶¹, OR = 2.48), in the HLA-DPA1/B1 loci with ATA (P = 4.57×10⁻⁷⁶, OR = 8.84), and in NOTCH4 with ACA P = 8.84×10⁻²¹, OR = 0.55) and ATA (P = 1.14×10⁻⁸, OR = 0.54). We have identified three new non-HLA genes (IRF8, GRB10, and SOX5) associated with SSc clinical and auto-antibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc.     

Optimization of respiratory chain enzymatic assays in muscle for the diagnosis of mitochondrial disorders

The diagnosis of mitochondrial disorders is difficult due to clinical and genetic heterogeneity. Measurements of mitochondrial respiratory chain (RC) enzyme activities are essential for both clinical diagnoses and many basic research questions. Current protocols for RC analysis are not standardized, and so are prone to inter-laboratory variability, and also to biochemical interferences that lead to analytical discrepancies. Moreover, knowledge of the analytical performances of these assays, which is essential to draw meaningful conclusions from the results, is lacking. To understand this variability and to propose possible solutions, we systematically investigated the effect of different homogenization protocols and chemical conditions on RC assays using muscle homogenates. We developed optimized protocols and a novel complex III method with improved sensitivity, precision, and linearity. These methods can be reliably performed on minute muscle samples with a single-wavelength spectrophotometer. Moreover, we measured the variability of the proposed homogenization protocol and we provide a systematic evaluation of each assay's specificity, precision, and linearity. These data will be useful for quality control in both clinical and research laboratories.     

The spindle assembly checkpoint: perspectives in tumorigenesis and cancer therapy

Loss or gain of chromosomes, a condition known as aneuploidy, is a common feature of tumor cells and has therefore been proposed as the driving force for tumorigenesis. Such chromosomal instability can arise during mitosis as a result of mis-segregation of the duplicated sister chromatids to the two daughter cells. In normal cells, missegregation is usually prevented by the spindle assembly checkpoint (SAC), a sophisticated surveillance mechanism that inhibits mitotic exit until all chromosomes have successfully achieved bipolar attachment to spindle microtubules. Complete abrogation of SAC activity is lethal to normal as well as to tumor cells, as a consequence of massive chromosome mis-segregation. Importantly, many human aneuploid tumor cells exhibit a weakened SAC activity that allows them to tolerate gains or losses of a small number of chromosomes; and interfering with this SAC residual activity may constitute a suitable strategy to kill cancer cells. This review focuses on the potential link between SAC and tumorigenesis, and the therapeutic strategy to target the SAC for cancer treatment.     

Linking biological activity with herbal constituents by systems biology-based approaches: effects of Panax ginseng in type 2 diabetic Goto-Kakizaki rats

Although a number of animal experiments and clinical trials have investigated the effects of ginseng roots on diabetes, the relationship between their therapeutic effects on diabetes and the quality and the growth age of this herb have not yet been reported. This study systematically investigated the effects of 3- to 6-year-old ginseng roots on glycemic and plasma lipid control in a rat model of type 2 diabetes. Six groups of male Goto-Kakizaki (GK) rats received either metformin, 3- to 6-year-old ginseng roots, or no treatment. The treatments were administered twice daily for 9 weeks. A combined approach was used that involved applying liquid chromatography-mass spectrometry-based lipidomics, measuring biochemical parameters and profiling the components of ginseng roots of different ages. Compared to the untreated controls, treatment with 4- and 6-year-old ginseng roots significantly improved glucose disposal, and 5-year-old ginseng treatment significantly increased high density lipoprotein cholesterol. Treatment with 6-year-old ginseng significantly decreased total plasma triacylglyceride (TG) and very-low-density lipoprotein cholesterol and improved plasma glycated hemoglobin (HbA1c). In addition, treatment with 4- to 6-year-old ginseng influenced plasma lipidomics in diabetic GK rats by reducing TG lipid species. Metformin significantly reduced fasting blood glucose by 41% and reduced HbA1c by 11%, but showed no effects on the plasma lipid parameters. The present study demonstrates that ginseng roots show growth age-dependent therapeutic effects on hyperlipidemia and hyperglycemia in diabetic GK rats. These age-dependent effects may be linked with the variation in both the ratios and concentrations of specific bioactive ginsenosides in ginseng roots of different growth ages. This study introduced novel systems biology-based approaches for linking biological activities with potential active components in herbal mixtures.