Effect of C2-exo unsaturation on the cytotoxicity and DNA-binding reactivity of pyrrolo[2,1-c][1,4]benzodiazepines

A series of novel C2-exo unsaturated pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) has been synthesised via a versatile pro-C2 ketone precursor. C2-exo-unsaturation enhances both DNA-binding reactivity and in vitro cytotoxic potency.     

Prevalence of Prostate Cancer in High Boron-Exposed Population: A Community-Based Study

We investigated the possible relationship between boron exposure and prostate cancer (PCa) for men living and being employed at boron mines in villages with rich boron minerals. Out of 456 men studied, 159 were from villages with rich boron sources and boron levels in drinking water of >1?mg?L(-1) and these men formed the study group, while 63 from villages with rich boron sources and boron levels in drinking water of <1?mg?L(-1) were enrolled into control group?1. A further 234 subjects from other villages with no boron mines were considered as control group?2. Prostate specific antigen (PSA) levels could be obtained from a total of 423 men. Urinary boron concentration as an indicator of boron exposure in 63 subjects, prostatic volumes by transrectal ultrasonography in 39 subjects, and prostatic biopsies in 36 subjects were obtained for study and control groups. The daily boron exposure was calculated according to urinary boron levels. Although there was no significant difference among the groups in terms of total PSA levels, the number of subjects with tPSA ≥2.5 and tPSA ≥10.0?ng?dL(-1) prostatic volumes in men whose prostates were biopsied (p?相似文献   

Mixing of Isaria fumosorosea with enhanced diatomaceous earth and bitterbarkomycin for control of Rhyzopertha dominica

The virulence of Isaria fumosorosea alone and integrated with an enhanced formulation of diatomaceous earth (diatomaceous earth + bitterbarkomycin, DEBBM) was tested against the lesser grain borer Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae) under laboratory conditions on stored wheat. The fungus was applied to wheat grains at various concentrations of 3.60 × 10⁶, 3.60 × 10⁸, and 3.60 × 10¹⁰ conidia/kg alone, or in combination with 15 and 30 ppm of DEBBM. R. dominica was held at 20, 25 and 30°C and two RH regimes (56 and 75%) and mortality was registered after 5, 10 and 15 d. Generally, I. fumosorosea was most effective at 25°C caused the highest mortality of R. dominica at 56% RH. The increase of temperature, concentration and exposure interval increased the insecticidal effect of DEBBM at low RH level. The DE alone suppressed the progeny emergence at higher dose rate as compared I. fumosorosea alone, but their simultaneous use further reduced the progeny production of R. dominica. The integrated use of both tested bio control agents synergized the effect of each other and caused the highest mortality at 25°C and 56% RH. The results clearly demonstrated that I. fumosorosea and new enhanced DEBBM can be integrated to be an effective control measure for R. dominica in stored wheat.     

Anti-MDA5 autoantibodies in juvenile dermatomyositis identify a distinct clinical phenotype: a prospective cohort study

Introduction

The aim of this study was to define the frequency and associated clinical phenotype of anti-MDA5 autoantibodies in a large UK based, predominantly Caucasian, cohort of patients with juvenile dermatomyositis (JDM).

Methods

Serum samples and clinical data were obtained from 285 patients with JDM recruited to the UK Juvenile Dermatomyositis Cohort and Biomarker Study. The presence of anti-MDA5 antibodies was determined by immunoprecipitation and confirmed by ELISA using recombinant MDA5 protein. Results were compared with matched clinical data, muscle biopsies (scored by an experienced paediatric neuropathologist) and chest imaging (reviewed by an experienced paediatric radiologist).

Results

Anti-MDA5 antibodies were identified in 7.4% of JDM patients and were associated with a distinct clinical phenotype including skin ulceration (P = 0.03) oral ulceration (P = 0.01), arthritis (P <0.01) and milder muscle disease both clinically (as determined by Childhood Myositis Assessment Score (P = 0.03)) and histologically (as determined by a lower JDM muscle biopsy score (P <0.01)) than patients who did not have anti-MDA5 antibodies. A greater proportion of children with anti-MDA5 autoantibodies achieved disease inactivity at two years post-diagnosis according to PRINTO criteria (P = 0.02). A total of 4 out of 21 children with anti-MDA5 had interstitial lung disease; none had rapidly progressive interstitial lung disease.

Conclusions

Anti-MDA5 antibodies can be identified in a small but significant proportion of patients with JDM and identify a distinctive clinical sub-group. Screening for anti-MDA5 autoantibodies at diagnosis would be useful to guide further investigation for lung disease, inform on prognosis and potentially confirm the diagnosis, as subtle biopsy changes could otherwise be missed.     

Selenium-Fortified Wheat: Potential of Microbes for Biofortification of Selenium and Other Essential Nutrients

Selenium (Se) is an essential micronutrient for humans and animals, and Se deficiency is a worldwide problem. Plants are a main dietary source of Se for humans and livestock. In this study we investigated the effect of two selenium-tolerant bacterial strains Bacillus cereus-YAP6 and Bacillus licheniformis-YAP7, on the growth and Se uptake by wheat plants. The bacteria-inoculated plants exhibited a significant increase in spike length, shoot length and dry biomass. Inoculated Se-treated plants also showed increased stem Se, S, Ca and Fe concentrations, by up to 375%, 40%, 55%, and 104%, respectively, and increased kernel Se, S, Ca and Fe concentrations by up to 154%, 85%, 60%, and 240%, respectively, compared to un-inoculated Se-treated plants. In conclusion, inoculation with strains YAP6 andYAP7 is a good Se biofortification strategy for wheat. Both strains showed resistance to other toxic elements, i.e., As, Cd, Co, Cr, Cu, Mn and Zn. Optimal growth temperature and pH for both strains were 37°C and pH7, respectively, but both strains can grow very well at different temperatures (28–45°C) and at alkaline pH. Both strains have high Se reduction potential: strains YAP6 and YAP7 converted 92% and 32% of selenite into elemental Se within 48 h, respectively.     

Microbial-enhanced Selenium and Iron Biofortification of Wheat (Triticum aestivum L.) - Applications in Phytoremediation and Biofortification

Selenium (Se) is an essential trace element for humans and other mammals. Most dietary Se is derived from crops. To develop a Se biofortification strategy for wheat, the effect of selenate fertilization and bacterial inoculation on Se uptake and plant growth was investigated. YAM2, a bacterium with 99% similarity to Bacillus pichinotyi, showed many plant growth promoting characteristics. Inoculation with YAM2 enhanced wheat growth, both in the presence and absence of selenate: YAM2-inoculated plants showed significantly higher dry weight, shoot length and spike length compared to un-inoculated plants. Selenate also stimulated wheat growth; Un-inoculated Se-treated plants showed a significantly higher dry weight and shoot length compared to control plants without Se. Bacterial inoculation significantly enhanced Se concentration in wheat kernels (167%) and stems (252%), as well as iron (Fe) levels in kernels (70%) and stems (147%), compared to un-inoculated plants. Inoculated Se-treated plants showed a significant increase in acid phosphatase activity, which may have contributed to the enhanced growth. In conclusion; Inoculation with Bacillus sp. YAM2 is a promising Se biofortification strategy for wheat and potentially other crops.     

Septin-Dependent Assembly of the Exocyst Is Essential for Plant Infection by Magnaporthe oryzae

Magnaporthe oryzae is the causal agent of rice blast disease, the most devastating disease of cultivated rice (Oryza sativa) and a continuing threat to global food security. To cause disease, the fungus elaborates a specialized infection cell called an appressorium, which breaches the cuticle of the rice leaf, allowing the fungus entry to plant tissue. Here, we show that the exocyst complex localizes to the tips of growing hyphae during vegetative growth, ahead of the Spitzenkörper, and is required for polarized exocytosis. However, during infection-related development, the exocyst specifically assembles in the appressorium at the point of plant infection. The exocyst components Sec3, Sec5, Sec6, Sec8, and Sec15, and exocyst complex proteins Exo70 and Exo84 localize specifically in a ring formation at the appressorium pore. Targeted gene deletion, or conditional mutation, of genes encoding exocyst components leads to impaired plant infection. We demonstrate that organization of the exocyst complex at the appressorium pore is a septin-dependent process, which also requires regulated synthesis of reactive oxygen species by the NoxR-dependent Nox2 NADPH oxidase complex. We conclude that septin-mediated assembly of the exocyst is necessary for appressorium repolarization and host cell invasion.     

Foliar Manganese Supply Enhances Crop Productivity,Net Benefits,and Grain Manganese Accumulation in Direct-Seeded and Puddled Transplanted Rice

Journal of Plant Growth Regulation - Manganese (Mn) deficiency in human nutrition is widespread in the rice–wheat cropping system where cereal grains are the staple food. Agronomic...     

Therapeutic Potential of Some Plant Extracts Used in Turkish Traditional Medicine on Streptozocin-Induced Type 1 Diabetes Mellitus in Rats

Diabetes mellitus (DM) is known to impair many physiological functions. Some reports claim that medicinal plants can reduce these alterations caused by DM. The aim of this study was to investigate the therapeutic potential of aqueous-methanol extracts of Urtica dioica, Thymus vulgaris (TV), Myrtus communis (MC), Scolymus hispanicus (SH) and Cinnamomun zeylanicum (CZ) on streptozotocin (STZ)-induced type 1 DM in rats. Diabetes was induced via a single i.p. injection of STZ (65 mg/kg body weight). After 1 week to allow for development of diabetes, each plant extract was administered to diabetic rats separately at a dose of 100 mg/kg body weight daily for 28 days. The results showed that only SH extract significantly (P < 0.05) amended fasting blood glucose level. The lipid profile was ameliorated especially by supplementations of TV, MC and CZ extracts. Almost all plant extract treatments markedly (P < 0.05) increased reduced glutathione content and decreased lipid peroxidation levels of erythrocyte, plasma, retina and lens tissues. They also significantly (P < 0.05) amended erythrocyte catalase activity, levels of marker serum enzymes (except amylase), urea and blood urea nitrogen when compared to diabetic rats treated with nothing. Furthermore, none of the plant extracts counteracted body weight loss of diabetic rats. Our data revealed that the aforementioned plant extracts have remarkable potential to counteract DM-caused alterations, probably through their antioxidant and free radical-defusing effects.