Tumorigenesis of rat mammary epithelial cells by N-nitroso-N-methylurea in anin vitro system: Characterization of the microtumors

Summary Chemical carcinogenesis is a lengthy process that involves the rather loosely defined stages of initiation, promotion, and progression. Several model systems of mammary carcinogenesis have been designed to elucidate the mechanisms of chemical carcinogenesis. Most of these systems have included animal models. While organ specific chemical carcinogenesis can be initiated in these systems, the subsequent stages of promotion and progression are difficult to study in detail. Investigations onin vitro carcinogenesis have shown transformation of mammalian cells in culture; the transformational event, however, is difficult to discern within the monolayer culture. We have recently reported the development of anin vitro carcinogenesis system that allows both the initiation as well as the progression of mammary cells in a collagen gel matrix culture system. The cells transformed by a chemical carcinogen develop into discernible microtumors with the three dimensions of a collagen gel culture. Isolation of these microtumors from the collagen gel an subsequent culture in monolayer has produced cells capable of colony formation in soft agar. The present study further characterizes these microtumors originatedin vitro by analysis of cell growth kinetics versus parallel control cells. In addition, flow cytometric and cytogenetic studies have been performed to investigate the chromosomal stability of these cells. It was also observed that the microtumors, producedin vitro from mammary epithelial cells of an inbred strain of rats, show the ability to form tumors upon transplantation into the fat pad of syngeneic hosts.     

Social entrainment in the old frugivorous bats, Rousettusleschenaulti from the Lonar crater

Onset and end of activity of the old frugivorous bats Rousettus leschenaulti, roosting in a temple ruin of the Lonar crater were observed at 10-day intervals for one year. The old bats emerged about 4 h after and returned about 4 h before the young bats. Onset of activity of the old bats was entrained by the loud vocalization of the early emerging young conspecifics at dusk. The old bats free-ran when the young conspecifics were evicted from the roost but re-entrained when they were re-introduced. Socially isolated old bats in the laboratory also free-ran in the scotophase of LD 12:12 cycles until the onset of activity coincided with lights-off which resulted in a delayed phase shift. After the exposure to light, the sequence of events repeated all over again. Ecological implications of this social entrainment are discussed.     

Epidemiology of soil transmitted helminths and risk analysis of hookworm infections in the community: Results from the DeWorm3 Trial in southern India

Since 2015, India has coordinated the largest school-based deworming program globally, targeting soil-transmitted helminths (STH) in ~250 million children aged 1 to 19 years twice yearly. Despite substantial progress in reduction of morbidity associated with STH, reinfection rates in endemic communities remain high. We conducted a community based parasitological survey in Tamil Nadu as part of the DeWorm3 Project—a cluster-randomised trial evaluating the feasibility of interrupting STH transmission at three geographically distinct sites in Africa and Asia—allowing the estimation of STH prevalence and analysis of associated factors. In India, following a comprehensive census, enumerating 140,932 individuals in 36,536 households along with geospatial mapping of households, an age-stratified sample of individuals was recruited into a longitudinal monitoring cohort (December 2017-February 2018) to be followed for five years. At enrolment, a total of 6089 consenting individuals across 40 study clusters provided a single adequate stool sample for analysis using the Kato-Katz method, as well as answering a questionnaire covering individual and household level factors. The unweighted STH prevalence was 17.0% (95% confidence interval [95%CI]: 16.0–17.9%), increasing to 21.4% when weighted by age and cluster size. Hookworm was the predominant species, with a weighted infection prevalence of 21.0%, the majority of which (92.9%) were light intensity infections. Factors associated with hookworm infection were modelled using mixed-effects multilevel logistic regression for presence of infection and mixed-effects negative binomial regression for intensity. The prevalence of both Ascaris lumbricoides and Trichuris trichiura infections were rare (<1%) and risk factors were therefore not assessed. Increasing age (multivariable odds ratio [mOR] 21.4, 95%CI: 12.3–37.2, p<0.001 for adult age-groups versus pre-school children) and higher vegetation were associated with an increased odds of hookworm infection, whereas recent deworming (mOR 0.3, 95%CI: 0.2–0.5, p<0.001) and belonging to households with higher socioeconomic status (mOR 0.3, 95%CI: 0.2–0.5, p<0.001) and higher education level of the household head (mOR 0.4, 95%CI: 0.3–0.6, p<0.001) were associated with lower odds of hookworm infection in the multilevel model. The same factors were associated with intensity of infection, with the use of improved sanitation facilities also correlated to lower infection intensities (multivariable infection intensity ratio [mIIR] 0.6, 95%CI: 0.4–0.9, p<0.016). Our findings suggest that a community-based approach is required to address the high hookworm burden in adults in this setting. Socioeconomic, education and sanitation improvements alongside mass drug administration would likely accelerate the drive to elimination in these communities.Trial Registration: {"type":"clinical-trial","attrs":{"text":"NCT03014167","term_id":"NCT03014167"}}NCT03014167.     

Potential of isoquercitrin as antisickling agent: a multi-spectroscopic,thermophoresis and molecular modeling approach

Abstract

Sickle cell disease is an inherited disease caused by point mutation in hemoglobin (β-globin gene). Under oxygen saturation, sickle hemoglobin form polymers, leading to rigid erythrocytes. The transition of the blood vessels is altered and initiated by the adhesion of erythrocytes, neutrophils and endothelial cells. Sickle Hemoglobin (HbS) polymerization is a major cause in red blood cells (RBC), promoting sickling and destruction of RBCs. Isoquercitrin, a medicinal bioactive compound found in various medicinal plants, has multiple health benefits. The present study examines the potential of isoquercitrin as an anti-sickle agent, showing a significant decrease in the rate of polymerization as well as sickling of RBCs. Isoquercitrin-induced graded alteration in absorbance and fluorescence of HbS, confirmed their interaction. A negative value of ΔG° strongly suggests that it is a spontaneous exothermic reaction induced by entropy. Negative ΔH° and positive ΔS° predicted that hydrogen and hydrophobic binding forces interfered with a hydrophobic microenvironment of β6Val leading to polymerization inhibition of HbS. HbS-Isoquercitrin complex exhibits helical structural changes leading to destabilization of the HbS polymer as confirmed by CD spectroscopy. MST and DSC results indicate greater changes in thermophoretic mobility and thermal stability of sickle hemoglobin in the presence of isoquercitrin, respectively. These findings were also supported by molecular simulation studies using DOCK6 and GROMACS. Hence, we can conclude that isoquercitrin interacts with HbS through hydrogen bonding, which leads to polymerization inhibition. Consequently, isoquercitrin could potentially be used as a medication for the treatment of sickle cell disease.

Communicated by Ramaswamy H. Sarma     

PRpnp,a novel dual activity PNP family protein improves plant vigour and confers multiple stress tolerance in Citrus aurantifolia

Under field conditions, plants are often simultaneously exposed to several abiotic and biotic stresses resulting in significant reductions in growth and yield; thus, developing a multi-stress tolerant variety is imperative. Previously, we reported the neofunctionalization of a novel PNP family protein, Putranjiva roxburghii purine nucleoside phosphorylase (PRpnp) to trypsin inhibitor to cater to the needs of plant defence. However, to date, no study has revealed the potential role and mechanism of either member of this protein group in plant defence. Here, we overexpressed PRpnp in Citrus aurantifolia which showed nuclear-cytoplasmic localization, where it functions in maintaining the intracellular purine reservoir. Overexpression of PRpnp significantly enhanced tolerance to salt, oxidative stress, alkaline pH, drought and two pests, Papilio demoleus and Scirtothrips citri in transgenic plants. Global gene expression studies revealed that PRpnp overexpression up-regulated differentially expressed genes (DEGs) related to ABA- and JA-biosynthesis and signalling, plant defence, growth and development. LC–MS/MS analysis validated higher endogenous ABA and JA accumulation in transgenic plants. Taken together, our results suggest that PRpnp functions by enhancing the endogenous ABA and JA, which interact synergistically and it also inhibits trypsin proteases in the insect gut. Also, like other purine salvage genes, PRpnp also regulates CK metabolism and increases the levels of CK-free bases in transgenic Mexican lime. We also suggest that PRpnp can be used as a potential candidate to develop new varieties with improved plant vigour and enhanced multiple stress resistance.     

Molecular analyses of methanogen diversity associated with cattle dung

Methanogen communities were characterized in cattle dung of different ages by using a culture-independent approach. Community structures were determined by the phylogenetic analyses of methyl-coenzyme M reductase A (mcrA) clones of fresh, 8-month-old, and 24-month-old-dry dung samples. The clones in the mcrA libraries of fresh and 8-month old dung samples were identified as belonging to Methanomicrobiales, Methanobacteriales, and Methanosarcinales. However, clones in the library of 24-month-old dung were not affiliated to Methanomicrobiales. Anaerobic digestion of 2-month-old dung produced only 15% less methane compared to fresh dung which indicated the possibility of using dry dung to fuel the biogas plants in areas where unavailability of fresh dung hinders their continuous functioning. Our results first time showed the presence of viable methanogens in dry cattle dung stored for prolonged periods of time.     

Interaction of fishes with pathogenic micro-organisms and application of phages for their control: a review

The present condition of aquacultural industry is influenced by the economical losses due to various aquacultural diseases causing fish mortality. The present review provides benchmark information related to application of bacteriophages in aquacultural industries over available traditional treatment procedures like antibiotics and chemotherapy. The traditional methods are mostly less advantageous due to development of resistance, non-specific targeting of bacteria including intestinal microflora, etc. In short here we discuss the interaction between fish, bacteria and their phages in order to have an alternate treatment method for the pathogens responsible for aquacultural diseases.     

Pathogenic LMNA variants disrupt cardiac lamina-chromatin interactions and de-repress alternative fate genes

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Host Plant Use by the Invasive Halyomorpha halys (St?l) on Woody Ornamental Trees and Shrubs

The brown marmorated stink bug, Halyomorpha halys (Stål) (Hemiptera: Pentatomidae) is an invasive plant-feeding insect native to eastern Asia. This herbivore is highly polyphagous, feeding on and damaging diverse plants, including field crops, vegetables, tree fruits, and ornamentals. Woody ornamental plants provide early- and late-season resources for adults emerging from and returning to overwintering sites, as well as feeding and breeding sites for H. halys throughout the growing season. In this study, we quantify the use of diverse plants by H. halys in two commercial nurseries in Maryland, recording data on the abundance of egg masses, early and late instar nymphs, and adults over a three-year study period. Our specific goals were to provide a quantitative comparison of the use of diverse plant species and cultivated varieties, identify non-hosts that could be used to create landscapes refractory to H. halys, and determine whether the use of plants varied across life stages of H. halys or the taxonomic status of plants. We found broad use of diverse plants in this study, identifying 88 host plants used by all life stages of H. halys. We also highlight the 43 plant taxa that did not support any life stage of H. halys and are thus classified as non-hosts. Interestingly, some of these plants were congeners of highly-used plants, underscoring high intrageneric and intraspecific variation in the use of plants by this polyphagous herbivore. We discuss how the selective planting of non-hosts, especially gymnosperms, may aid in reducing the agricultural and nuisance pest status of this invasive insect.