Activation of the cGMP signaling pathway is essential in delaying oocyte aging in diabetes mellitus

Uncontrolled diabetes mellitus (DM) adversely affects oocyte maturation and embryo development via mechanisms that are yet unclear. Nonetheless, DM may cause uncoupling of nitric oxide synthases (NOSs) with reduction in the bioavailability of nitric oxide (NO), which is critical to maintain oocyte viability and prevent aging. The current study investigates the role of NO-mediated signaling related to oocyte aging in diabetic and nondiabetic mice. Age-related alterations in the oocytes, including ooplasmic microtubule dynamics (OMD), cortical granule (CG) status, and zona pellucida (ZP) hardening as well as the integrity of the spindle/chromatin were studied using confocal microscopy. Oocytes obtained from diabetic mice exhibited accelerated aging compared to that from nondiabetic mice. Moreover, oocytes from diabetic animals were exquisitely sensitive to NOS and guanylate cyclase (GC) inhibitors (L-NAME, ODQ), which induced aging and relatively resistant to its delay by the cGMP derivative (8-Br-cGMP). Oocytes from nondiabetic control mice displayed similar sensitivity to L-NAME in older oocytes, although to a significantly lower extent than that of DM (P < 0.04-0.0001). Despite the differences in response between DM and nonDM mice, the activation of cGMP pathway is essential to maintain the integrity of oocytes and delay oocyte aging. These findings not only indicate the role of NO signaling in the prevention of oocyte aging but also suggest enhanced aging and NO insufficiency in oocytes from diabetic mice. A comprehensive model incorporating our current findings with NOS, GC, and G kinase cycles is presented.     

Improved photosynthetic characteristics correlated with enhanced biomass in a heterotic F1 hybrid of maize (Zea mays L.)

Photosynthesis Research - Heterosis is a phenomenon wherein F1 hybrid often displays phenotypic superiority and surpasses its parents in terms of growth and agronomic traits. Investigations on the...     

Pronounced hypoxia in models of murine and human leukemia: high efficacy of hypoxia-activated prodrug PR-104

Recent studies indicate that interactions between leukemia cells and the bone marrow (BM) microenvironment promote leukemia cell survival and confer resistance to anti-leukemic drugs. There is evidence that BM microenvironment contains hypoxic areas that confer survival advantage to hematopoietic cells. In the present study we investigated whether hypoxia in leukemic BM contributes to the protective role of the BM microenvironment. We observed a marked expansion of hypoxic BM areas in immunodeficient mice engrafted with acute lymphoblastic leukemia (ALL) cells. Consistent with this finding, we found that hypoxia promotes chemoresistance in various ALL derived cell lines. These findings suggest to employ hypoxia-activated prodrugs to eliminate leukemia cells within hypoxic niches. Using several xenograft models, we demonstrated that administration of the hypoxia-activated dinitrobenzamide mustard, PR-104 prolonged survival and decreased leukemia burden of immune-deficient mice injected with primary acute lymphoblastic leukemia cells. Together, these findings strongly suggest that targeting hypoxia in leukemic BM is feasible and may significantly improve leukemia therapy.     

Molecular analysis of neutrophil spontaneous apoptosis reveals a strong role for the pro-apoptotic BH3-only protein Noxa

Neutrophils enter the peripheral blood from the bone marrow and die after a short time. Molecular analysis of spontaneous neutrophil apoptosis is difficult as these cells die rapidly and cannot be easily manipulated. We use conditional Hoxb8 expression to generate mouse neutrophils and test the regulation of apoptosis by extensive manipulation of B-cell lymphoma protein 2 (Bcl-2)-family proteins. Spontaneous apoptosis was preceded by downregulation of anti-apoptotic Bcl-2 proteins. Loss of the pro-apoptotic Bcl-2 homology domain (BH3)-only protein Bcl-2-interacting mediator of cell death (Bim) gave some protection, but only neutrophils deficient in both BH3-only proteins, Bim and Noxa, were strongly protected against apoptosis. Function of Noxa was at least in part neutralization of induced myeloid leukemia cell differentiation protein (Mcl-1) in neutrophils and progenitors. Loss of Bim and Noxa preserved neutrophil function in culture, and apoptosis-resistant cells remained in circulation in mice. Apoptosis regulated by Bim- and Noxa-driven loss of Mcl-1 is thus the final step in neutrophil differentiation, required for the termination of neutrophil function and neutrophil-dependent inflammation.     

Oleanane triterpenoids in the prevention and therapy of breast cancer: current evidence and future perspectives

Breast cancer is one of the most frequently diagnosed cancers and major cause of death in women in the world. Emerging evidence underscores the value of dietary and non-dietary phytochemicals, including triterpenoids, in the prevention and treatment of breast cancer. Oleanolic acid, an oleanane-type pentacyclic triterpenoid, is present in a large number of dietary and medicinal plants. Oleanolic acid and its derivatives exhibit several promising pharmacological activities, including antioxidant, anti-inflammatory, hepatoprotective, cardioprotective, antipruritic, spasmolytic, antiallergic, antimicrobial and antiviral effects. Numerous studies indicate that oleanolic acid and other oleanane triterpenoids modulate multiple intracellular signaling pathways and exert chemopreventive and antitumor activities in various in vitro and in vivo model systems. A series of novel synthetic oleanane triterpenoids have been prepared by chemical modifications of oleanolic acid and some of these compounds are considered to be the most potent anti-inflammatory and anticarcinogenic triterpenoids. Accumulating studies provide extensive evidence that synthetic oleanane derivatives inhibit proliferation and induce apoptosis of various cancer cells in vitro and demonstrate cancer preventive or antitumor efficacy in animal models of blood, breast, colon, connective tissue, liver, lung, pancreas, prostate and skin cancer. This review critically examines the potential role of oleanolic acid, oleanane triterpenoids and related synthetic compounds in the chemoprevention and treatment of mammary neoplasia. Both in vitro and in vivo studies on these agents and related molecular mechanisms are presented. Several challenges and future directions of research to translate already available impressive preclinical knowledge to clinical practice of breast cancer prevention and therapy are also presented.     

Taxonomic importance of seed macro‐ and micro‐morphology in Abelmoschus (Malvaceae)

Seed morphology of Abelmoschus is known to be variable, but patterns of variation have never been critically studied. We studied seed macro‐ and micro‐morphological characters, including seed shape/size, seed coat pattern and trichome density/structure in multiple samples to evaluate the taxonomic significance of seed characters. Among the studied characters, seed shape and trichome structure were found to have major taxonomic importance and proved to be valuable characters for separating taxa. Two main seed types were present: seeds with deciduous trichomes and seeds with persistent trichomes. These characters offer significant evidence to the distinctness of certain species (A. esculentus, A. moschatus subsp. moschatus, A. moschatus subsp. tuberosus, A. crinitus and A. angulosus). Further, our results indicate that A. moschatus subsp. tuberosus should be maintained as a separate subspecies while A. manihot subsp. tetraphyllus var. pungens may be merged in A. angulosus. No significant intraspecific variation was observed, except in A. esculentus. We conclude that seed coat sculpturing and seed trichomes do indeed provide stable and diagnostic characters for many morphologically closely related taxa of Abelmoschus and that LM/SEM techniques can be useful in solving systematic problems and management of Abelmoschus genetic resources.     

Quantitative estimation of insect diversity inhabiting Calotropis procera in industrial and nonindustrial areas of West Bengal, India

This paper compares the species richnesses, Bray–Curtis similarities, species diversities, evennesses, and the results of various analyses (multivariate, logarithmic series, and lognormal distribution analyses) of insects from four orders (viz., Hemiptera, Orthoptera, aculeate Hymenoptera, and Coleoptera) inhabiting a medicinal plant, Calotropis procera among eight sites within industrial and nonindustrial zones in the Purba Medinipur district (erstwhile Midnapore), West Bengal, India. Both cluster analysis and principal component analysis indicate an effect of industrialization on the diversity of the four insect orders. The species community at each site exhibits an almost pure lognormal distribution. Bootstrap estimation of species diversity also points to the effect of industrialization. A comparison of the values of x and N/S of the logarithmic series indicates a typical relationship between the species community and its diversity. The number of unique species among the eight study sites is 6 according to jackknife estimation. Beta-diversity analysis of the samples shows the impact of industrialization on the abundances and species richness of the insects. Altogether, 16 types of analytical procedure are applied for this purpose, and their suitabilities for this kind of data set are assessed. Disturbance, probably due to industrial emissions, has changed the compositions and structures of the insect communities out to a distance of at least 6 km from the core industrial area.     

High-Specificity Targeted Functional Profiling in Microbial Communities with ShortBRED

Profiling microbial community function from metagenomic sequencing data remains a computationally challenging problem. Mapping millions of DNA reads from such samples to reference protein databases requires long run-times, and short read lengths can result in spurious hits to unrelated proteins (loss of specificity). We developed ShortBRED (Short, Better Representative Extract Dataset) to address these challenges, facilitating fast, accurate functional profiling of metagenomic samples. ShortBRED consists of two components: (i) a method that reduces reference proteins of interest to short, highly representative amino acid sequences (“markers”) and (ii) a search step that maps reads to these markers to quantify the relative abundance of their associated proteins. After evaluating ShortBRED on synthetic data, we applied it to profile antibiotic resistance protein families in the gut microbiomes of individuals from the United States, China, Malawi, and Venezuela. Our results support antibiotic resistance as a core function in the human gut microbiome, with tetracycline-resistant ribosomal protection proteins and Class A beta-lactamases being the most widely distributed resistance mechanisms worldwide. ShortBRED markers are applicable to other homology-based search tasks, which we demonstrate here by identifying phylogenetic signatures of antibiotic resistance across more than 3,000 microbial isolate genomes. ShortBRED can be applied to profile a wide variety of protein families of interest; the software, source code, and documentation are available for download at http://huttenhower.sph.harvard.edu/shortbred     

Polyacrylamide grafted Agar: Synthesis and applications of conventional and microwave assisted technique

Polyacrylamide grafted Agar (Ag-g-PAM) has been successfully synthesized by conventional method and microwave assisted method. The former method employs ceric ammonium nitrate (CAN) as the free radical initiator while the latter uses the combination of ceric ammonium nitrate (CAN) and microwave irradiation. The synthesized graft copolymers have been characterized by elemental analysis (C, H, N, O and S), FTIR spectroscopy, intrinsic viscosity measurement and scanning electron micrograph (SEM); taking agar as a reference. Flocculation efficacy of synthesized graft copolymers was studied in kaolin suspension and in waste water through 'Jar test' procedure. In the present investigation, we have observed that polyacrylamide grafted agar synthesized by microwave assisted technique shows superior properties than conventional technique. These properties are reported in terms of intrinsic viscosity, flocculation efficacy and pollutant load reduction of waste water.