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Farm households in the UNESCO World Heritage site Sundarbans face serious problems, including increased soil salinity, frequent extreme weather events, seawater intrusion and flood damage, all of which cause distress to the livelihoods of the farm families. Policymakers commonly acknowledge livestock as a crucial resource for mitigating economic losses caused by crop failures due to extreme weather events. Despite Sundarbans' vulnerability to extreme weather events, smallholder farmers' livelihoods vary across the region. Identifying spatial livelihood variations aids in targeted strategies to address climate extremes. We chose the highest cow- and buffalo-populated blocks among the 19 blocks in the Sundarbans to assess variations in livelihood dimensions, including nutritional, economic, social and infrastructural security. We used dummy variable regression models to examine the differences in livelihood security dimensions among households living in different locations. The study found that Namkhana had the highest livelihood security score among the blocks studied, while Gosaba had the lowest score because it's in a remote area with limited infrastructure. The study found a significant difference in the overall livelihood security score among the blocks we examined, indicating the need for a location-specific, cluster-based approach for the overall development of the Sundarbans. The study can shape a policy framework for socio-economic development in the Indian Sundarbans through its findings on location-specific livelihood security. For securing smallholder farmers' livelihoods in the vulnerable Sundarbans region, policymakers must give priority to improving infrastructure, viz., roads, marketing facilities and animal healthcare centers.
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Agricultura , Gado , Humanos , Feminino , Bovinos , Animais , Fazendas , Agricultura/métodos , Fazendeiros , ClimaRESUMO
BACKGROUND: Raw areca nut (RAN) consumption induces oral, esophageal and gastric cancers, which are significantly associated with the overexpression of pituitary tumor transforming gene 1/securin and chromosomal instability (CIN). An association of Securin/PTTG1 upregulation and gastric cancer in human was also demonstrated earlier. Since the molecular mechanism underlying securin upregulation remains unclear, this study intended to investigate the association of securin upregulation with the Rb-E2F1 circuit and epigenetic histone (H3) modification patterns both globally and in the promoter region of the securin gene. METHODS: Six groups of mice were used, and in the treated group, each mouse consumed 1 mg of RAN extract with lime per day ad libitum in the drinking water for 60 days, after which the dose was increased by 1 mg every 60 days. Histopathological evaluation of stomach tissues was performed and securin expression was analysed by immunoblotting as well as by immunohistochemistry. ChIP-qPCR assays were performed to evaluate the recruitment of different histone modifications in the core promoter region of securin gene as well as its upstream and downstream regions. RESULTS: All mice developed gastric cancer with securin overexpression after 300 days of feeding. Immunohistochemistry data revealed hyperphosphorylation of Rb and upregulation of E2F1 in the RAN-treated samples. Increased trimethylation of H3 lysine 4 and acetylation of H3 lysine 9 and 18 both globally and in the promoter region of the securin gene were observed by increasing the levels of lysine-N-methyltransferase 2A, lysine-acetyltransferase, EP-300 and PCAF after RAN treatment. ChIP-qPCR data revealed that the quantity of DNA fragments retrieved from the immunoprecipitated samples was maximum in the -83 to -192 region than further upstream and the downstream of the promoter for H3K4Me3, H3K9ac, H3K18ac and H3K9me3. CONCLUSIONS: RAN-mediated pRb-inactivation induced securin upregulation, a putative E2F1 target, by inducing misregulation in chromatin remodeling in its promoter region, which led to transcriptional activation and subsequent development of chromosomal instability. Therefore, present results have led to the hypothesis that RAN-induced changes in the epigenetic landscape, securin overexpression and subsequent elevation of chromosomal instability is probably byproducts of inactivation of the pRb pathway.
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Research over the years revealed that precocious anaphase, securin overexpression, and genome instability in both target and nontarget cells are significantly associated with the increased risk of areca nut (AN) and lime-induced oral, esophageal, and gastric cancers. Further, hyperphosphorylation of Rb and histone H3 epigenetic modifications both globally and in the promoter region of the securin gene were demonstrated after AN + lime exposure. This study aims whether the extract of raw AN + lime relaxes chromatin structure which further facilitates the histone H3 epigenetic modifications during the initial phase of carcinogenesis. Three groups of mice (10 in each group) were used. The treated group consumed 1 mg/day/mice of AN extract with lime ad libitum in the drinking water for 60 days. The dose was increased by 1 mg every 60 days. Isolated nuclei were digested with DNaseI and 2 kb and below DNA was eluted from the agarose gel, purified and PCR amplified by using securin and GAPDH primers. Securin and E2F1 expression, pRb phosphorylation, and histone epigenetic modifications were analyzed by immunohistochemistry. The number of DNA fragments within 2 kb in size after DNaseI treatment was higher significantly in AN + lime exposed tissue samples than in the untreated one. The PCR result showed that the number of fragments bearing securin gene promoter and GAPDH gene was significantly higher in AN + lime exposed DNaseI-treated samples. Immunohistochemistry data revealed increased Rb hyperphosphorylation, upregulation of E2F1, and securin in the AN + lime-treated samples. Increased trimethylation of histone H3 lysine 4 and acetylation of H3 lysine 9 and 18 were observed globally in the treated samples. Therefore, the results of this study have led to the hypothesis that AN + lime exposure relaxes the chromatin, changes the epigenetic landscape, and deregulates the Rb-E2F1 circuit which might be involved in the upregulation of securin and some other proto-oncogenes that might play an important role in the initial phases of AN + lime mediated carcinogenesis.
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Cromatina , Nozes , Extratos Vegetais , Animais , Camundongos , Acetilação , Areca/química , Carcinogênese , Cromatina/genética , Histonas/genética , Histonas/metabolismo , Lisina/genética , Nozes/química , Extratos Vegetais/farmacologia , Securina/genética , Securina/metabolismoRESUMO
The virus bacteriophage T4, from the family Myoviridae, employs an intriguing contractile injection machine to inject its genome into the bacterium Escherichia coli Although the atomic structure of phage T4 is largely understood, the dynamics of its injection machinery remains unknown. This study contributes a system-level model describing the nonlinear dynamics of the phage T4 injection machinery interacting with a host cell. The model employs a continuum representation of the contractile sheath using elastic constants inferred from atomistic molecular-dynamics (MD) simulations. Importantly, the sheath model is coupled to component models representing the remaining structures of the virus and the host cell. The resulting system-level model captures virus-cell interactions as well as competing energetic mechanisms that release and dissipate energy during the injection process. Simulations reveal the dynamical pathway of the injection process as a "contraction wave" that propagates along the sheath, the energy that powers the injection machinery, the forces responsible for piercing the host cell membrane, and the energy dissipation that controls the timescale of the injection process. These results from the model compare favorably with the available (but limited) experimental measurements.
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Bacteriófago T4 , Internalização do Vírus , Bacteriófago T4/química , Bacteriófago T4/metabolismo , Bacteriófago T4/fisiologia , Escherichia coli/virologia , Modelos Biológicos , Simulação de Dinâmica MolecularRESUMO
Potentilla fulgens is a medicinal plant in North-East India whose root is reported to have anti-diabetic, anticarcinogenic and antioxidant properties. The potential of hydro-alcoholic extract of P. fulgens root (PRE) for providing protection to mammalian cells exposed to ionising radiation was investigated in this study. The methanolic extract of PRE shows an enhanced radical scavenging ability in a concentration dependent manner. PRE-pre-treatment to stimulated human blood lymphocytes (HBLs) reduced the frequency of deletion and exchange aberrations induced by X-irradiation. Similar protection of chromosome aberrations was also observed in mouse bone marrow cells (BMCs) where mice were given PRE extract (1 mg extract/day/mice) ad libitum in the drinking water for 45 days before whole-body X-irradiation. Of the various extracts prepared by partitioning of the methanol extract, the ethyl-acetate (EA) fraction was found to possess better antioxidant, radical scavenging and DNA-damage reduction activities. PRE-pre-treatment also reduced the radiation-induced cell-cycle delay effectively in HBL. In HEK-293 cells, PRE reduced radiation-induced G2-block in cell kinetics. Interestingly, PRE-treatment alone increased the concentration of endogenous glutathione (GSH) in mouse BMC and in stimulated HBL along with the elevated expression of γ-glutamyl-cysteine synthetase heavy/catalytic subunit, a key determinant of GSH synthesis. Studies on expression of two DNA-repair genes revealed that there was a marked increase in the expression of GADD45 and H2AX genes after X-irradiation in stimulated HBL, and such expression was reduced significantly if PRE-treatment was given prior to radiation. The present findings show the ability of PRE to reduce radiation-induced DNA damages probably by free radical scavenging whereas modulation of expression of DNA-repair genes' and endogenous GSH-increment emerge as effective strategies. The present study is the first report on the selected medicinal plant species that suggests it to be a potential natural radioprotector when used as root extract or its EA fraction for mitigating radiation toxicity.
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Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Dano ao DNA/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Extratos Vegetais/farmacologia , Acetatos/química , Animais , Antioxidantes/farmacologia , Proteínas de Ciclo Celular/metabolismo , Células Cultivadas , Glutationa/metabolismo , Células HEK293 , Histonas/metabolismo , Humanos , Masculino , Camundongos , Raízes de Plantas/química , Plantas Medicinais/química , Potentilla/química , Radiação IonizanteRESUMO
15-Lipoxygenase (15-LOX) belongs to the family of nonheme iron containing enzymes that catalyzes the peroxidation of polyunsaturated fatty acids (PUFAs) to generate eicosanoids that play an important role in signaling pathways. The role of 15-LOX has been demonstrated in atherosclerosis as well as other inflammatory diseases. In the present study, drug-like compounds were first screened from a set of anti-inflammatory phytochemicals based on Lipinski's rule of five (ROF) and in silico toxicity filters. Two lead compounds-quinine (QUIN) and rutaecarpine (RUT) were shortlisted by analyzing molecular interactions and binding energies of the filtered compounds with the target using molecular docking. Molecular dynamics simulation studies indicate stable trajectories of apo_15-LOX and docked complexes (15-LOX_QUIN and 15-LOX_RUT). In vitro 15-LOX inhibition studies shows that both QUIN and RUT have lower inhibitory concentration (IC50 ) value than the control (quercetin). Both QUIN and RUT exhibit moderate antioxidant activities. The cell viability study of these compounds suggests no significant toxicity in HEK-293 cell lines. Further, QUIN and RUT both did not show any inhibition against selected Gram-positive and Gram-negative bacterial species. Thus, based on our present findings, rutaecarpine and quinine may be suggested as promising 15-LOX inhibitor for the prevention of the atherosclerosis development.
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Alcaloides Indólicos/química , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos/química , Quinazolinas/química , Araquidonato 15-Lipoxigenase , Ciclo-Oxigenase 2/efeitos dos fármacos , Células HEK293 , Humanos , Alcaloides Indólicos/uso terapêutico , Inflamação/genética , Inflamação/patologia , Inibidores de Lipoxigenase , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Neoplasias/genética , Neoplasias/patologia , Compostos Fitoquímicos/uso terapêutico , Quinazolinas/uso terapêutico , Quinina/química , Quinina/farmacologia , Relação Estrutura-AtividadeRESUMO
Bacteriophage T4 infects the bacterial host (Escherichia coli) using an efficient genomic delivery machine that is driven by elastic energy stored in a contractile tail sheath. Although the atomic structure of T4 is largely known, the dynamics of its fascinating injection machinery is not understood. This article contributes, to our knowledge, the first predictions of the energetics and dynamics of the T4 injection machinery using a novel dynamic model. The model employs an atomistic (molecular dynamics) representation of a fraction of the sheath structure to generate a continuum model of the entire sheath that also couples to a model of the viral capsid and tail tube. The resulting model of the entire injection machine reveals estimates for the energetics, timescale, and pathway of the T4 injection process as well as the force available for cell rupture. It also reveals the large and highly nonlinear conformational changes of the sheath whose elastic energy drives the injection process.
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Bacteriófago T4/metabolismo , Bacteriófago T4/ultraestrutura , Simulação de Dinâmica Molecular , Bacteriófago T4/química , Capsídeo/química , Capsídeo/metabolismo , Capsídeo/ultraestrutura , Elasticidade , Escherichia coli/metabolismo , Escherichia coli/virologia , Hidrodinâmica , Cinética , Dinâmica não Linear , Rotação , Ligação Viral , Integração Viral/fisiologia , Internalização do VírusRESUMO
Research over the years has generated enough evidence to implicate areca nut, as a carcinogen in humans. Besides oral, significant rise in the incidence of cancers of the oesophagus, liver and stomach was seen among areca nut chewers. Early diagnosis seems key to understand the initial processes of carcinogenesis which is highly curable. In North-East India, betel quid contains raw areca nut (RAN), lime and small portion of betel leaf without any other constituents. This study was not intended to isolate any active ingredients from the RAN and to look its action. The present objective is to validate the screening of precocious anaphase and analysis of expression of Securin and p53 in non-target cells like human peripheral blood lymphocytes (PBLs) and mouse bone marrow cells (BMCs) as early indicative parameters of RAN + lime-induced cancers. A total of 35 mice were examined at different time points for following ad libitum administration of RAN extract in drinking water with lime. Peripheral blood was collected from 32 human donors of which, 24 were RAN + lime heavy chewers. Expression of genes was assessed by immunoblotting and/or by immunohistochemistry. Histological preparation of stomach tissue of mice revealed that RAN + lime induced stomach cancer. A gradual increase in the frequency of precocious anaphases and aneuploid cells was observed in both RAN + lime-treated mouse BMC and human PBL of RAN heavy chewers. Levels of p53 and Securin were increased in these cells during early days of RAN + lime exposure. The level of Securin was significantly higher in human tumour samples than their adjacent normal counterpart. The expression of Securin was increased significantly in RAN + lime-administered mice as well as in stomach tumour. Present study revealed that precocious anaphase and expression of p53 and Securin in non-target cells are significantly associated with an increased risk of RAN-induced cancer and thus these parameters can be of early diagnostic value.
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Areca/química , Biomarcadores Tumorais/genética , Carcinógenos/toxicidade , Extratos Vegetais/toxicidade , Securina/genética , Proteína Supressora de Tumor p53/genética , Anáfase/efeitos dos fármacos , Animais , Biomarcadores Tumorais/metabolismo , Carcinogênese/efeitos dos fármacos , Células Cultivadas , Detecção Precoce de Câncer , Feminino , Expressão Gênica , Instabilidade Genômica , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/patologia , Masculino , CamundongosRESUMO
A range of methods are presented to calculate a solute's hydration shell from computer simulations of dilute solutions of monatomic ions and noble gas atoms. The methods are designed to be parameter-free and instantaneous so as to make them more general, accurate, and consequently applicable to disordered systems. One method is a modified nearest-neighbor method, another considers solute-water Lennard-Jones overlap followed by hydrogen-bond rearrangement, while three methods compare various combinations of water-solute and water-water forces. The methods are tested on a series of monatomic ions and solutes and compared with the values from cutoffs in the radial distribution function, the nearest-neighbor distribution functions, and the strongest-acceptor hydrogen bond definition for anions. The Lennard-Jones overlap method and one of the force-comparison methods are found to give a hydration shell for cations which is in reasonable agreement with that using a cutoff in the radial distribution function. Further modifications would be required, though, to make them capture the neighboring water molecules of noble-gas solutes if these weakly interacting molecules are considered to constitute the hydration shell.
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Gases Nobres/química , Água/análise , Água/química , Ligação de Hidrogênio , Simulação de Dinâmica MolecularRESUMO
INTRODUCTION: Potentilla fulgens is a commonly used folk medicine by natives of northeast India, Nepal and Bhutan and is rich in polyphenolic and triterpene constituents. OBJECTIVE: To identify chemomarkers in the roots of P. fulgens by an interplay of (13)C-NMR, matrix-assisted laser desorption/ionisation with time-of-flight (MALDI/TOF) MS, electrospray ionisation (ESI) MS/MS and HPLC/UV. MATERIAL AND METHODS: The (13)C-NMR spectrum of crude methanolic extract was recorded in deuterated dimethyl sulphoxide. For MALDI/TOF/MS analysis, 2,5-dihydroxybenzoic acid was used as the matrix. For determination of chemical constituents, two independent simple isocratic HPLC/UV methods for monomeric/oligomeric flavanols and triterpene acids were developed and validated. RESULTS: The (13)C-NMR spectrum of the methanolic extract indicated the presence of B-type oligomeric polyphenolics containing mainly epicatechin/catechin (epicat/cat) and epiafzelechin/afzelechin (epiafz/afz) as the monomeric units. Several isobaric monomeric and oligomeric flavanols and triterpenoids were tentatively identified by MALDI/TOF/MS and ESI/MS/MS. Fourteen compounds (four monomeric and five dimeric flavanols and five triterpene acids) were isolated using repeated column chromatography and semi-preparative HPLC, and were quantitated using HPLC/UV. CONCLUSION: It is evident from these analyses that roots of P. fulgens contain flavans, including oligomeric flavanols, as major constituents followed by triterpene acids. The methods described can be applied to other Potentilla species to identify their constituents.
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Flavanonas/isolamento & purificação , Extratos Vegetais/química , Raízes de Plantas/química , Potentilla/química , Triterpenos/isolamento & purificação , Cromatografia Líquida de Alta Pressão/métodos , Flavanonas/química , Gentisatos , Espectroscopia de Ressonância Magnética/métodos , Medicina Tradicional do Leste Asiático , Extratos Vegetais/isolamento & purificação , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Espectrometria de Massas em Tandem/métodos , Triterpenos/químicaRESUMO
Liver toxicity due to iron overload leads to oxidative damage of proteins, lipids and nucleic acids which in turn manifests several human diseases. Here, we evaluated the improving effect of Clerodendrum colebrookianum leaf on iron overload induced liver injury along with in vitro iron chelation and the protection of Fenton reaction induced DNA damage was conducted. Iron overload was induced by intraperitoneal administration of iron-dextran into mice. Post oral administration of different doses of the extract (50, 100 and 200 mg/kg body weight) showed significant decrease in different biochemical markers such as liver iron, serum ferritin and serum enzyme levels, along with decreased lipid peroxidation, protein oxidation and collagen content. In addition, the extract effectively enhanced the antioxidant enzyme levels and also exhibited the potential activity of the reductive release of ferritin iron. The protective effect of C. colebrookianum extract on injured liver was furthermore supported by the histopathological studies that showed improvement histologically. In conclusion, the present results demonstrated the hepatoprotective efficiency of C. colebrookianum leaf in iron overloaded mice, and hence, a potential iron chelating drug for iron overload diseases.
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Clerodendrum/química , Sobrecarga de Ferro/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Animais , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/patologia , Humanos , Ferro/toxicidade , Sobrecarga de Ferro/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Extratos Vegetais/química , Folhas de Planta/químicaRESUMO
The effect of dietary inorganic and organic chromium (Cr) on body morphometry, carcass traits, and nutrient composition, including different minerals and fatty acids in meat and internal organs of Black Bengal goats, was studied. Thirty weaned Black Bengal kids of 3-5 months (5.40 ± 0.34 kg body weight) were assigned randomly into five groups and fed additional Cr for 150 days. The experimental diets comprised a basal diet supplemented with Cr at the rate of 0 (control; without Cr supplementation), 1.0 and 1.5 mg/kg of inorganic Cr (Cr(III)-chloride), and 1.0 and 1.5 mg/kg of organic Cr (Cr-yeast). The body morphometry such as body length, heart girth, paunch girth, loin width, leg circumference, and the carcass traits, namely, slaughter body weight, dressing percentage, hind quarter and forequarter weight, and rib eye area of goats, were not significantly (P < 0.05) changed due to inorganic and organic Cr supplementation. However, organic Cr supplementation (1.0 and 1.5 mg/kg) resulted in a reduction of breast and back fat thickness (P < 0.05) compared with the control group. The weights of internal organs including liver, lungs, spleen, kidney, testes, and heart and their weights as a percentage of slaughter weight were similar (P > 0.05) among different experimental groups. Dry matter, ether extract, and total ash concentrations of muscle and internal organs of Cr-supplemented groups were not affected (P > 0.05) by Cr supplementation. However, crude protein contents in the liver, muscle, kidney, and lungs were greater (P < 0.05) in the organic Cr groups than in the control and inorganic Cr groups. In meat (longissimus dorsi muscle), total saturated fatty acid concentration was lower (P < 0.05; 59.4% versus 55.7%) and the unsaturated fatty acid concentration was greater (P < 0.05; 40.6% versus 44.3%) including palmitoleic acid, heptadecenoic acid, elaidic acid, and arachidonic acid in the organic or inorganic Cr-supplemented groups than in the basal diet group. In conclusion, dietary supplementation of organic Cr in Black Bengal goats has no influence on the carcass traits, but may improve the meat quality with greater protein content, lean, and healthier fatty acids for human consumption.
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Cromo , Cabras , Animais , Humanos , Cromo/farmacologia , Cromo/metabolismo , Cabras/metabolismo , Suplementos Nutricionais , Dieta/veterinária , Ácidos Graxos/metabolismo , Músculos/metabolismo , Nutrientes , Proteínas , Peso Corporal , Composição Corporal , Carne/análise , Ração Animal/análiseRESUMO
The present study was conducted to evaluate the effect of feeding conch shell (Turbinella pyrum) powder (either fresh or calcined) as a marine organic source of calcium (Ca) supplemented in the diet of crossbred calves on voluntary intake, growth performance, and blood biochemistry in growing crossbred Jersey calves. A growth trial of 90 days was conducted on 15 Jersey crossbred female calves (Av. weight, 70.68 ± 2.90 kg; Av. age, 197.73 ± 12.40 days), equally divided into three groups of 5 animals each, i.e., control (T0), treatment 1 (T1), and treatment 2 (T2). All animals were fed total mixed ration (TMR) prepared with a concentrate mixture, chaffed paddy straw, and green fodder at the ratio of 40:30:30 on DM basis. Calves under the control group were fed with TMR containing a standard mineral mixture having dicalcium phosphate (DCP) as a Ca source. Calves under T1 group were supplemented with TMR containing fresh conch shell powder (FCSP), and T2 calves were fed with TMR containing conch shell calcined powder (CSCP) as Ca source. We observed 11.66% increase (p < 0.01) in Ca concentration in CSCP compared to FCSP. The concentration of minerals like Mg, Co, Mn, and Fe was enhanced in CSCP compared to the FCSP. However, the calcination process of fresh conch shell powder (FCSP) reduced the concentration of Cu, and Zn. The Ca/P ratio was estimated as 2.11, 2.06, and 2.10 in T0, T1, and T2 diets, which could be considered ideal for calf ration. Calves under T1, and T2 groups consumed significantly (p < 0.001) greater amounts (g/kg W0.75) of DM and CP compared to T0. However, increased voluntary intake did not translate into increased body weight gain (kg), and feed conversion ratio (kg DMI/kg gain) in T1 and T2 groups in comparison to T0. We observed similar blood glucose, urea, alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine transaminase (ALT) concentration among the three treatments. Ca, and P levels in blood plasma were also identical among the three groups. The digestibility of Ca was increased significantly (p = 0.01) in FCSP (T1)- and CSCP (T2)-treated calves compared to control (T0) calves. Similarly, T1 and T2 enhanced P digestibility compared to T0. This first report with short-term experimentation depicted some promising scope for the use of locally available conch shell powder (fresh or calcined form) as a potential source of Ca for feeding to livestock, because these new sources of Ca did not affect intake, digestibility of Ca and P, growth performance, blood chemistry, and liver enzymes negatively in weaned crossbred calves.
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BACKGROUND: There are strong indications for a causal association between areca-nut consumption and cancers. In Meghalaya, India, the variety of areca-nut is used as raw and unprocessed form whose chemical composition and pharmacological actions have been reported. Yet we know little on the initial pathway involved in areca-nut associated carcinogenesis since it is difficult to assess its effects on genetic alterations without interference of other compounding factors. Therefore, present study was undertaken in mice to verify the ability of raw areca-nut (RAN) to induce cancer and to monitor the expression of certain genes involved in carcinogenesis. This study was not intended to isolate any active ingredients from the RAN and to look its action. METHODS: Three groups of mice (n = 25 in each) were taken and used at different time-points for different experimental analysis. The other three groups of mice (n = 15 in each) were considered for tumor induction studies. In each set, two groups were administered RAN-extract ad libitum in drinking water with or without lime. The expression of certain genes was assessed by conventional RT-PCR and immunoblotting. The mice were given the whole RAN-extract with and without lime in order to mimic the human consumption style of RAN. RESULTS: Histological preparation of stomach tissue revealed that RAN induced stomach cancer. A gradual increase in the frequency of precocious anaphase and aneuploid cells was observed in the bone marrow cells with a greater increment following RAN + lime administeration. Levels of p53, Bax, Securin and p65 in esophageal and stomach cells were elevated during early days of RAN exposure while those of different mitotic checkpoint proteins were downregulated. Apoptotic cell death was detected in non-cancerous stomach cells but not in tumor cells which showed overexpression of Bax and absence of PARP. CONCLUSION: Present study suggested (a) RAN induces stomach cancer, however, presence of lime promoted higher cell transformation and thereby developed cancer earlier, (b) perturbations in components of the chromosome segregation machinery could be involved in the initial process of carcinogenicity and (c) the importance of precocious anaphase as a screening marker for identification of mitotic checkpoint defects during early days.
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Areca/toxicidade , Instabilidade Cromossômica/efeitos dos fármacos , Genes cdc/efeitos dos fármacos , Extratos Vegetais/toxicidade , Neoplasias Gástricas/etiologia , Animais , Instabilidade Cromossômica/genética , Citometria de Fluxo , Genes cdc/genética , Immunoblotting , Camundongos , Nozes/toxicidade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Gástricas/genética , Transcriptoma/efeitos dos fármacos , Transcriptoma/genéticaRESUMO
We have performed constrained molecular dynamics simulations of magnesium chloride in water-ethanol mixtures. From the potentials of mean force (PMFs) of the Mg(2+)-Cl(-) ion pair, we notice that, as the mole fraction of ethanol increases, the depths of the minima of the contact ion pair (CIP) and solvent assisted ion pair (SAIP) increase, but the depth of the CIP minimum increases more in comparison to the SAIP minimum. This shows that ion pairing becomes more favorable with an increase in the mole fraction of ethanol. Significant differences in the PMFs between the Mg(2+) and the Cl(-) ion (depending upon whether the second Cl(-) ion is present in the first coordination shell of the Mg(2+) ion or not) seem to have been reported for the first time in this work. The local mole fraction of water molecules in the first solvation shell of ions is generally greater than in the bulk. The diffusional behavior of solvent molecules in solvation shells of the ion-pair indicates that the ions as well as the first solvation shells of the ions diffuse at much slower rates. Also, the diffusion constant of bulk water in the mixtures is greatly reduced compared to the pure solvent value.
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Etanol/química , Cloreto de Magnésio/química , Solventes/química , Água/química , Difusão , Conformação Molecular , Simulação de Dinâmica MolecularRESUMO
The present study was performed to evaluate the influence of dietary inorganic and organic chromium (Cr) supplementation on blood biochemical constituents and mineral concentrations as well as the changes in the mineral composition of internal organs of Black Bengal goats. Thirty Black Bengal kids of 3 to 5 months (5.40 ± 0.34 kg body weight) were allocated randomly to five treatment groups. The five groups were control (without added Cr in a basal diet), 1.0, 1.5 mg/kg of inorganic Cr, 1.0, and 1.5 mg/kg of organic Cr added per kilogram of feed dry matter. The duration of the experiment was 150 days during which the changes in the blood biochemical and mineral concentrations at 0, 30, 60, and 150 days were evaluated. At the end of the trial, mineral composition in the muscle, skin, and internal organs (liver, lungs, kidney, heart, spleen, and testis) were analyzed. Any blood variables were not affected at or before 60 days of Cr supplementation. Both inorganic and organic Cr supplementation lowered (P < 0.05) concentrations of blood glucose, cortisol, non-esterified fatty acids, and ß-hydroxybutyric acid after 60 days of Cr supplementation. Organic Cr-supplemented groups exhibited higher (P < 0.05) blood insulin concentration and neutrophil activity compared to the control. Supplementation of Cr in either form had no substantial effect (P > 0.05) on the blood hemoglobin, total leukocyte count, total protein, albumin, globulin, immunoglobulin G, total antioxidant capacity, and liver enzymes (aminotransferases) concentration, and also blood minerals (zinc, iron, and manganese) concentration. Blood Cr and copper concentrations were increased (P < 0.05) due to both organic and inorganic Cr supplementation. Minerals (calcium, phosphorus, magnesium, iron, zinc, copper, and manganese) concentrations of internal organs of Cr-supplemented groups were mostly not affected (P > 0.05) by Cr supplementation. However, the concentrations of Cr and copper in blood and Cr in all internal organs, skin, and muscle of organic Cr-supplemented groups were higher (P < 0.05) than in those fed the basal diet. In conclusion, dietary inorganic and organic Cr supplementation, especially the organic form, after long term supplementation (> 60 days) could be beneficial in regulating blood glucose and fat metabolism and the immune status of Black Bengal goats.
RESUMO
NorthEast India, with its unique geographic location in the midst of the Himalayas and Bay of Bengal, has served as a passage for the movement of modern humans across the Indian subcontinent and East/Southeast Asia. In this study we look into the population genetics of a unique population called the Khasi, speaking a language (also known as the Khasi language) belonging to the Austroasiatic language family and residing amidst the Tibeto-Burman speakers as an isolated population. The Khasi language belongs to one of the three major broad classifications or phyla of the Austroasiatic language and the speakers of the three sub-groups are separated from each other by large geographical distances. The Khasi speakers are separated from their nearest Austroasiatic language-speaking sub-groups: the "Mundari" sub-family from East and peninsular India and the "Mon-Khmers" in Mainland Southeast Asia. We found the Khasi population to be genetically distinct from other Austroasiatic speakers, i.e. Mundaris and Mon-Khmers, but relatively similar to the geographically proximal Tibeto Burmans. The possible reasons for this genetic-linguistic discordance lie in the admixture history of different migration events that originated from East Asia and proceeded possibly towards Southeast Asia. We found at least two distinct migration events from East Asia. While the ancestors of today's Tibeto-Burman speakers were affected by both, the ancestors of Khasis were insulated from the second migration event. Correlating the linguistic similarity of Tibeto-Burman and Sino-Tibetan languages of today's East Asians, we infer that the second wave of migration resulted in a linguistic transition while the Khasis could preserve their linguistic identity.
RESUMO
Of paramphistomid trematodes, three species viz., Homalogaster paloniae, Calicophoron calicophorum and Orthocoelium streptocoelium are commonly prevalent in bovine hosts in Northeast India. The aim of the present study was to genetically characterise these species using rDNA second internal transcribed spacer (ITS2) so as to supplement the morphological criteria substantiated by molecular findings. The annotated ITS2 region from H. paloniae, C. calicophorum and O. streptocoelium were found to be 289 bp, 288 bp and 288 bp long, respectively. On comparison, the Indian isolates of the three species were observed to have a maximum identity of 99% with each of their respective counterparts from Japan. The secondary structure models were inferred using minimum free energy modelling algorithms. The paramphistomes displayed the typical four helix ITS2 secondary structure and differed from each other due to minor nucleotide differences. The consensus ITS2 secondary structure model revealed the presence of conservative motifs GACGAGGGUG and GCGGUAGAGUC in helix III. Monophyly is well supported for a clade consisting of the Japanese and Indian paramphistomes with significant bootstrap values.
Assuntos
DNA de Helmintos/química , DNA de Helmintos/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Gado/parasitologia , Paramphistomatidae/genética , Paramphistomatidae/isolamento & purificação , Animais , Bovinos , Índia , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Paramphistomatidae/classificação , Filogenia , Análise de Sequência de DNA , Homologia de Sequência do Ácido NucleicoRESUMO
BACKGROUND AND AIM: Alpha-tocopherol supplementation influences milk yield, milk quality, and udder health of dairy cows, which needs to be investigated for Jersey crossbred cows at hot-humid climate. Therefore, the present study was framed with an objective to study the effect of pre and postpartum Alpha-tocopherol supplementation on milk yield, milk quality, and udder health status of Jersey crossbred cows at tropical climate. MATERIALS AND METHODS: For this study, 19 similar parity, body condition score, and production level dairy animals were separated randomly into three groups, namely, Control, T1 and T2. Control group (no supplementation) was compared with two treatment groups, namely, T1 and T2. Supplementation of Alpha-tocopherol was done in concentrate fed to the animals (at 1 g/cow/day) 30 days prepartum to 30 days postpartum in T1 and 30 days prepartum to 60 days postpartum in T2 groups. Observations were taken for different parameters up to 5 months of lactation. RESULTS: Statistically analyzed data revealed that overall significantly (p<0.01) more milk production was found in T2, followed by T1 than the control group. Overall significantly (p<0.01) lower somatic cell counts and modified California mastitis tests were recorded in T2, followed by T1 than the control group. Overall significantly (p<0.01), better milk quality in terms of methylene blue reduction test was found in T2, followed by T1 than control groups. Differences in the milk composition of all three groups were non-significant (p>0.05). CONCLUSION: Supplementation of Alpha-tocopherol during prepartum to initial lactation period may enhance milk yield, milk quality, and udder health status of Jersey crossbred cows at the tropical lower Gangetic region.
RESUMO
The Glutathione S-transferases (GSTs) protects cellular DNA against oxidative damage. The role of GSTP1 polymorphism (A313G; Ile105Val) as a susceptibility factor in oral cancer was evaluated in a hospital-based case-control study in North-East India, because the habit of chewing raw areca-nut (RAN) with/without tobacco is common in this region. Genetic polymorphism was investigated by genotyping 445 cases and 444 controls. Individuals with the GSTP1 AA-genotype showed association with the oral cancer (OR = 3.1, 95% CI = 2.4-4.2, p = 0.0002). Even after adjusting for age, sex and habit the AA-genotype is found to be significantly associated with oral cancer (OR = 2.4, 95% CI = 1.7-3.2, p = 0.0001). A protein-protein docking analysis demonstrated that in the GG-genotype the binding geometry between c-Jun Kinase and GSTP1 was disrupted. It was validated by immunohistochemistry in human samples, showing lower c-Jun-phosphorylation and down-regulation of pro-apoptotic genes in normal oral epithelial cells with the AA-genotype. In silico docking revealed that AA-genotype weakly detoxifies the RAN/tobacco metabolites. In addition, experiments revealed a higher level of 8-Oxo-2'-deoxyguanosine induction in tumor samples with the AA-genotype. Thus, habit of using RAN/tobacco and GSTP1 AA-genotype together play a significant role in predisposition to oral cancer risk by showing higher DNA-lesions and lower c-Jun phosphorylation that may inhibit apoptosis.