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关键词： Halophyte   Domestication   Crop   DNA methylation   Transposable element   Gene expression  

摘要： Key message Puccinellia tenuiflora was domesticated for two years by growing it under non-saline conditions, providing epigenetic and biochemical insights into the initial domestication of extreme halophytes. Some halophytes have economic value as crop species. The domestication of halophytes may offer hope in solving the problem of soil salinization. We domesticated a wild halophyte, Puccinellia tenuiflora, for two years by growing it under non-saline conditions in a greenhouse and used re-sequencing, genome-wide DNA methylation, biochemical, and transcriptome analyses to uncover the mechanisms underlying alterations in the halophyte's tolerance to saline following domestication. Our results showed that non-saline domestication altered the methylation status for a number of genes and transposable elements, resulting in a much higher frequency of hypomethylation than hypermethylation. These modifications to DNA methylation were observed in many critical salinity-tolerance genes, particularly their promoter regions or transcriptional start sites. Twenty-nine potassium channel genes were hypomethylated and three were hypermethylated, suggesting that the DNA methylation status of potassium channel genes was influenced by domestication. The accelerated uptake of potassium is a major salinity tolerance characteristic of P. tenuiflora. We propose that modifications to the DNA methylation of potassium channel genes may be associated with the development of salinity tolerance in this species. By assessing whether non-saline domestication could change the salinity tolerance of P. tenuiflora, we demonstrated that non-saline domesticated plants are less tolerant to saline, which may be attributable to altered sucrose metabolism. DNA methylation and transposable elements may, therefore, be integrated into an environment-sensitive molecular engine that promotes the rapid domestication of P. tenuiflora to enable its use as a crop plant.

关键词： URIDA   Iron   TMPRSS6   SNPs  

摘要： In current study, we discuss clinical oral iron refractoriness cases and highlight need for a classification system to define TMPRSS6 gene variants. Out of 231 cases of microcytic hypochromic anemia screened (Sept 2019-Dec 2020), 17 cases (7.35%) with unexplained iron refractoriness (URIDA) phenotype were enrolled after ruling out secondary causes and compliance related issues. 11 (65%) had absent/negligible response (0-0.4 g/dl Hb rise) while 6 (35%) partial (0.5-0.9 g/dl Hb rise) response to initial iron trial at 4-8 weeks. Of these 17 cases, inappropriate hepcidin levels (normal-high) were noted in 11/15 (73%) tested. TSAT/Hepcidin ratio was low in 13/15 (87%). Genetic analysis of TMPRSS6 gene by NGS revealed variations in 15/17 (88%) cases. 10/15 cases with variations harbored a common splice site INDEL that was noted to be pathogenic SNP (MAF-0.19) on casecontrol association study in combination with other known missense SNPs with an odds ratio of 6.38 and relative risk 2.66 (p- < 0.01).

关键词： Myceliophthora thermophila   Endoxylanase   Production   Purification   Poultry feed   Nutrition  

摘要： Endoxylanase production from M. thermophila BJTLRMDU3 using rice straw was enhanced to 2.53-fold after optimization in solid state fermentation (SSF). Endoxylanase was purified to homogeneity employing ammonium sulfate precipitation followed by gel filtration chromatography and had a molecular mass of similar to 25 kDa estimated by SDS-PAGE. Optimal endoxy- lanase activity was recorded at pH 5.0 and 60 degrees C. Purified enzyme showed complete tolerance to n-hexane, but activity was slightly inhibited by other organic solvents. Among surfactants, Tweens (20, 60, and 80) and Triton X 100 slightly enhanced the enzyme activity. The V-max and K-m values for purified endoxylanase were 6.29 mu mol/min/mg protein and 5.4 mg/ml, respectively. Endoxylanase released 79.08 and 42.95% higher reducing sugars and soluble proteins, respectively, which control after 48 h at 60 degrees C from poultry feed. Synergistic effect of endoxylanase (100 U/g) and phytase (15 U/g) on poultry feed released higher amount of reducing sugars (58.58 mg/feed), soluble proteins (42.48 mg/g feed), and inorganic phosphate (28.34 mg/feed) in contrast to control having 23.55, 16.98, and 10.46 mg/feed of reducing sugars, soluble proteins, and inorganic phosphate, respectively, at 60 degrees C supplemented with endoxylanase only.

关键词： Biological control   Mosquito   Entomopathogens   Immunosuppressive   Phagocytosis   Hemocytes  

摘要： In order to increase the virulence of two commonly used entomopathogens namely Beauveria bassiana and Metarhizium anisopliae for effective mosquito control programs, we developed new combined formulation by the use of immunosuppressive concentration of imidacloprid. Exposure of sublethal concentration (LC10 1.34 ppb) of imidacloprid to second instar larvae for 92 h that differently modulated the larval biochemical markers by decreasing the total protein (20.65% reduction), acetylcholinesterase (35.74% reduction) and increases the beta-carboxylesterase (26.59% increase) and acid phosphatase (30.69% increase) levels while no significant difference was noticed in alkaline phosphatase of C. quinquefasciatus. Further we demonstrated that the imidacloprid exposure brings about reduction in phenoloxidase level (39.48% decrease) and nitric oxide production (37.64% decrease) in larval homogenate over control. The reduction in viability of hemocytes (15.37% decrease) and phagocytic activity of hemocytes (32.18% decrease) was noticed in imidacloprid treatment. Moreover in laboratory condition, exposure of 1 x 107 spores/ml of B. bassiana (984) and M. anisopliae (6060) alone for 92 h cumulative toxicity assay exhibited larval mortality of 36.47% and 47.64% respectively against C. quinquefasciatus. However in the synergistic experimental studies with LC10 of imidacloprid and 1 x 107 spores/ml of B. bassiana or M. anisopliae to the larvae for 92 h cumulative assay brought 60% and 50.59% more insecticidal activity than the respective entomopathogens alone. The substantial increase of larvicidal activity noticed in the synergistic test conditions against larvae of C. quinquefasciatus revealed that the inclusion of sublethal concentration was proved to be useful for effective larval control.

关键词： Black tea   Human saliva   Flow rate   Total protein content   Thiol   alpha-Amylase  

摘要： Saliva is firstly interacted with food or drink during ingestion. Alteration of salivary biochemistry by black tea consumption is unclear and rarely discussed in literature. The current work highlighted the immediate and delayed effect of black tea drinking on the change of several salivary parameters, including flow rate, alpha-amylase and catalase activity, malondialdehyde, thiol, nitric oxide, hydrogen peroxide and total protein content. Twelve healthy subjects aged between 22 and 31 years old were recruited in the study. The saliva was collected before, after and 30 min after black tea consumption. The black tea intake generally caused an increase of salivary flow rate, total protein content, catalase, H2O2 and MDA but reduction in thiol and nitric oxide for majority of the subjects. Principal component analysis showed that the salivary flow rate, production rate of total protein content, nitric oxide, thiol and malondialdehyde of saliva were primarily significant for black tea consumption.

关键词： Leishmania donovani   Pentose phosphate pathway   6-phosphogluconate dehydrogenase   Enzyme kinetics   Antibiotics   Structural insights  

摘要： 6-phosphogluconate dehydrogenase (6PGDH) participates in pentose phosphate pathway of glucose metabolism by catalyzing oxidative decarboxylation of 6-phsophogluconate (6PG) and its absence has been lethal for several eukaryotes. Despite being a validated drug target in many organisms like Plasmodium, the enzyme has not been explored in leishmanial parasites. In the present study, 6PGDH of Leishmania donovani (Ld6PGDH) is cloned and purified followed by its characterization using biochemical and structural approaches. Ld6PGDH lacks the glycine-serine-rich sequence at its C-terminal that is present in other eukaryotes including humans. Leishmanial 6PGDH possesses more affinity for substrate (6PG) and cofactor (NADP) in comparison to that of human. The enzymatic activity is inhibited by gentamicin and cefuroxime through competitive mode with functioning more potently towards leishmanial 6PGDH than its human counterpart. CD analysis has shown higher alpha-helical content in the secondary structure of Ld6PGDH, while fluorescence studies revealed that tryptophan residues are not completely accessible to solvent environment. The three-dimensional structure was generated through homology modelling and docked with substrate and cofactor. The docking studies demonstrated two separate binding pockets for 6PG and NADP with higher affinity for the cofactor binding, and Asn105 is interacting with substrate as well as the cofactor. Additionally, MD simulation has shown complexes of Ld6PGDH with 6PG and NADP to be more stable than its apo form. Altogether, the present study might provide the foundation to investigate this enzyme as potential target against leishmaniasis.

关键词： Premature infants   Late-onset sepsis   Bronchopulmonary dysplasia  

摘要： Studies in preterm infants have shown an association between late-onset sepsis (LOS) and the development of bronchopulmonary dysplasia (BPD). It is unknown whether clinical or biochemical characteristics during sepsis modulate the risk for BPD. This single-center retrospective cohort study included all patients with a gestational age < 30 weeks, born between 2009 and 2015, in whom empiric antimicrobial treatment was initiated > 72 h after birth and continued for at least 5 days, independent on microbiological results. The association between clinical and biochemical characteristics of LOS and the development of BPD in survivors were assessed with multivariate logistic regression analysis adjusted for early-onset sepsis, small for gestational age, and gestational age. Of the 756 admitted infants, 256 infants (mean GA: 27.0 weeks;birthweight: 924 grams) had at least one LOS episode, of whom 79 (30.9%) developed BPD. Analyses showed that only the need for and duration of mechanical ventilation during LOS were independently associated with an increased risk for BPD (adjusted OR 2.62, 95% CI 1.38, 4.96, p value 0.003, and OR 1.004, 95% CI 1.00, 1.007, p value 0.045, respectively). Conclusion: During a LOS, the need for and duration of mechanical ventilation are independently associated with the risk of developing BPD in preterm infants. What is Known: Premature infants diagnosed with a late-onset sepsis are at higher risk of developing bronchopulmonary dysplasia This association is mainly shown in infants with a positive blood culture What is New: This study investigates the clinical and biochemical characteristics of late-onset sepsis and the development of bronchopulmonary dysplasia The need for mechanical ventilation and duration of mechanical ventilation during late-onset sepsis are associated with an increased risk of developing bronchopulmonary dysplasia.

关键词： Anabaena sphaerica   Zinc toxicity   Oxidative stress   Ultrastructure   Photosynthesis  

摘要： The current study describes the mechanisms of zinc toxicity in the cyanobacterium Anabaena sphaerica after eight days treatment with 10 mg L-1 ZnCl2. The application of zinc not only showed elevated accumulation of the metal inside the cells but also exhibited devastating impacts on the cell numbers, morphology, and ultrastructure of A. sphaerica. The effects of zinc on the pigments contents, oxygen evolution rate, F-v/F-m, electron transport rate, and carbohydrate content were also evaluated in A. sphaerica. Moreover, zinc adversely affected nutrient uptake and the cellular energy budget in the test cyanobacterium which in turn hampered heterocyst development and nitrogen fixation. Alongside, the cyanobacterium experienced zinc-mediated non-competitive inhibition of glutamine synthetase activity, curtailed synthesis of amino acids and proteins. Furthermore, drastically reduced total lipid and increased unsaturated lipid contents were also the prominent characteristics of zinc stressed A. sphaerica. Most importantly, zinc stress caused severe damages to the protein, lipid, and DNA by triggering hydrogen peroxide generation and accumulation of oxidized glutathione. Therefore, excess zinc is highly toxic to the cyanobacterium A. sphaerica, and the mechanisms of its toxicity followed a cascade of events including oxidative stress mediated geopardisation of growth and ultrastructure, metabolic derangements, and macromolecular damages.

关键词： Anthracyclines   Chemotherapy   Acute cardiotoxicity   Electrocardiogram (ECG)   Nutraceuticals   Antioxidants  

摘要： Doxorubicin (DOX) is a potent anti-cancer antibiotic that was widely used for treatment of various cancers. It produces free radicals which result in extreme dose-limiting cardiotoxicity. This study investigated the cardioprotective potential of chia seed oil, an active polyphenolic nutraceutical against doxorubicin-induced cardiotoxicity in Wistar rats. Twenty-four female Wistar rats were divided into four groups (n = 6) which consist of normal control, DOX control, test-A and test-B group. Animals were prophylactically treated with two different doses of test drug, i.e. chia seed oil 2.5 ml/kg/day and 5 ml/kg/day in test-A and test-B groups orally for 7 days. Doxorubicin (25 mg/kg;single dose) was administered intraperitoneally to DOX control, Test-A and Test-B animals on the seventh day to induce cardiotoxicity. ECG analysis was done before and after treatment. Besides ECG, CK, CK-MB, LDH, AST, MDA and GSH were analyzed. DOX had significantly altered ECG, CK, CK-MB, LDH, AST, MDA and GSH. Pre-treatment with chia seed oil significantly alleviated DOX-induced ECG changes and also guarded against DOX-induced rise of serum CK, CK-MB and AST levels. Chia seed oil alleviated histopathological alteration in DOX-treated rats. It also significantly inhibited DOX-induced GSH depletion and elevation of MDA. The present study revealed that chia seed oil exerts cardioprotection against doxorubicin-induced cardiotoxicity in female Wistar rats. Our study opens the perspective to clinical studies to precisely consider chia seed oil as a potential chemoprotectant nutraceutical in the combination chemotherapy with doxorubicin to limit its cardiotoxicity.