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Background: Actinomycetes particularly the Streptomyces sp. derived from marine and coastal habitats are regarded as the main source of antibiotics. In the current study, to isolate the antibiotic-producing actinomycetes sediment samples were collected from Manakudy estuary, Kanyakumari District, Tamil Nadu. Results: The isolates were selected based on the antagonistic activity; the highly active isolate was identified as Streptomyces sp. CMSTAAHL-3. The culture media for the antibiotic production was optimized by one variable at a time and confirmed by the zone of inhibition against tested pathogens such as Staphylococcus aureus, Enterococcus faecalis, Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa. Then by altering the four factors starch, urea, MgSO4 and NaCl at five levels, statistical optimization of the media components was explored using Response Surface Methodology-Central Composite Design and found that the predicted antibiotic response was closely correlated with the experimentally one and was confirmed by the zone of inhibition. Conclusions: The Streptomyces sp. CMSTAAHL-3 and its antibiotics may be of great use in the treatment of a variety of pathogens, and the ideal culture medium discovered in this experiment will be helpful for further research involving large-scale fermentation for the effective production of antibiotics.How to cite: Selvaraj JN, Ganapathi U, Vincent SGP, et al. Statistical optimization of media components for antibiotic production in Streptomyces sp. CMSTAAHAL-3. Electron J Biotechnol 2023;64. https://doi.org/10.1016/j.ejbt.2023.03.005.

Primary lymphomas of the central nervous system (PCNSL) are defined as diffuse large B-cell lymphomas (DLBCL) confined to the CNS. Here, the authors complete whole genome sequencing and RNA-seq to characterize 51 PCNSLs, and find common mutations in immune pathways and upregulated TERT expression and find distinct pathway differences between DLBCL and other primary CNS lymphomas.

Introduction: Periodontitis, a chronic inflammatory disease with microbial etiology, is mediated by multiple inflammatory processes and oxidative stress is now well recognized as a part of periodontal pathogenesis. A balance between reactive oxygen species and antioxidants is required to maintain periodontal health. Medicinal herbs with bioactive phytocompounds have rich source of antioxidants and anti-inflammatory compounds. Ormocarpum cochinchinense is a medicinal herb with antioxidants and anti-inflammatory phytocompounds. The phytocompounds activities of the herb are not much explored. This study is focused on the In-vitro antioxidant and anti-inflammatory activities of the ethanolic extract of leaves of O. cochinchinense. To assess the In-vitro antioxidant and In-vitro anti-inflammatory activities of ethanolic extracts of O. cochinchinense. Materials and Methods: The leaves of O. cochinchinense were collected, air dried in the shade, and then powdered in an electric blender. The preparation of ethanolic extract was carried out. In-vitro antioxidant studies using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Nitric Oxide (NO) assays along with anti-inflammatory activity by protein denaturation inhibition and membrane stabilization method were studied. Descriptive statistics were used for continuous variables and expressed in mean and standard deviation. One way ANOVA with post-hoc tukey test or Kruskal–Wallis test, Post-hoc Mann–Whitney U test was used according to the normal distribution of the sample. To compare the individual study group against their standard group, independent t test, and Mann–Whitney U test have been used. P < 0.05 was considered significant. Results: O. cochinchinense had significant antioxidant and anti-inflammatory activities. The ethanolic extract showed dose-dependant activity in all analyses performed (P < 0.05). NO inhibition assay showed 95% of antioxidant activity and 80% of anti-inflammatory activity in the Human Red Blood Cell (HRBC) Membrane Stabilization assay. Conclusions: O. cochinchinense could be used as an adjuvant supplement to conventional therapy in the treatment of chronic inflammatory diseases.

Radiation-induced gliomas (RIGs) have been reported in patients after treatment with cranial irradiation for various primary malignancies but their origin are still unclear. Here, the authors define the genomic, epigenetic and transcriptional landscape of 32 RIGs cases.

Acute Myeloid Leukemia (AML) is a heterogeneous disease with highest mortality compared to other types of leukemia. There is a need to find the gene abnormalities and mechanisms behind them due to their heterogenic nature. The present study is aimed to understand genes, pathways and biomarker proteins influenced by transcriptomic deregulation due to AML. Differentially expressed gene (DEG), protein-protein interaction network, gene ontology, KEGG pathway, variant analysis and secretome analyses were performed using different AML RNAseq datasets. A total of 655 DEGs including 291 up-regulated and 364 down-regulated genes, which were satisfied with a fold change of 1.5 were identified. Top hub genes for AML were identified as TP53, PTPRC and AKT1. This integrative bioinformatics approach revealed the deregulation of T Cell Receptor (TCR) pathway and altered immune response related genes. The survival analysis revealed the associated deregulation of multiple TCR pathway related genes. Variant analysis identified the benign and likely benign nature of many important target genes and markers screened, which were found to have an important role in the progression of AML. DEGs and secretome analysis found out a set of seven molecules represents potential biomarkers for AML. In vitro analytical validation showed overexpression pattern of CD109 and LRP12 in AML cell line and HL-60 cells than the normal human bone marrow-derived stromal cell line HS-5. Here we report first time for CD109 and LRP12 as a possible biomarkers for the diagnostic significance. Amino acid substitutions detected by variant analysis and deregulation of immune checkpoint molecules revealed their role in reducing immune response and inability to fight cancer cells. In conclusion, this study highlights the possibility of new biomarkers for AML and the mechanism of decrease in immune response due to the downregulation of co-stimulatory immune molecules, which needs further clinical validation investigations.

A study was carried out for a period of 90 days during the summer season with the inclusion of chromium propionate and vitamin E with selenium, in the feed to investigate their effect on 24 uniparous lactating Holstein Friesian cows in an early phase of lactation. Cows were randomly assigned to four supplemental doses of 0 (T0); 500 IU/animal/day of vitamin E and 0.3 mg/kg DM of selenium (T1); 0.5 mg/kg DM of chromium propionate (T2) and 0.5 mg/kg DM of chromium propionate, 500 IU/animal/day of vitamin E and 0.3 mg/kg DM of selenium (T3). The mean THI value in the morning was 75.10±0.42 and 80.01±0.64 in the afternoon indicating that the animals were under mild to moderate heat stress. Increase in the DMI was found in the supplemented groups with a significant difference between control and T3 group. Milk yield differed significantly between the control and supplemented groups. The hematological profile did not vary significantly among the groups. Supplementation of chromium along with vitamin E and selenium decreased the cortisol level and glutathione peroxidase activity signigicantly in the T3 group. Chromium supplemented groups (T2 and T3) showed greater increase in mean total protein, albumin concentration and A/G ratio. However, the mean values for thyroid profile, liver enzymes, superoxide dismutase, catalase, globulin, total cholesterol, triglycerides, glucose, urea, creatinine were comparable among the four groups. Statistical analysis revealed that the rectal temperature, respiratory rate, and pulse rate in supplemented groups were significantly reduced. The findings showed that chromium supplementation plays a significant role in alleviating thermal stress and is further more beneficial when supplemented with proven antioxidants vitamin E and selenium.

To study the retaliation performances of various methodologies of sowing by accompanying organic manures on growth, yield, and all other yield attributes of wheat (Triticum aestivum L.) crop. A field experiment was executed during the Rabi season of 2020-21 at the crop research farm of SHUATS, Prayagraj.The experiment was laid out in the most commonly encountered Randomized Block Design (RBD) with three replications of each treatment for all traits. Given this experiment three methods of sowing, i.e. M1 (Broadcasting), M2 (Line sowing), M3 (System of Wheat Intensification) as well as three organic manures i.e. O1 (Farmyard manure 12 t/ha), O2 (Poultry manure 5 t/ha), O3 (Vermicompost 4 t/ha) and two liquid manures Panchagavya 3% and Jeevamrutha 500 l/ha. And the liquid manures were foliar sprayed at 15, 30, and 45 days after sowing (DAS). Results were revealed that the maximum number of tillers (10.53), Dry weight (18.00 g/plant), Effective tillers (10.43), Spike length (11.73 cm), and Grains per spike (58.38) were found to be significantly higher with the application of treatment SWI + Poultry manure (5 t/ha) + Panchagavya 3% FS + Jeevamrutha 500/h FS as compared to the other treatments. Maximum values were ensured with Plant height (78.30 cm), test weight (36.73 g), Grain yield (3.16 t/ha), Straw yield (4.48 t/ha), and harvest index (41.39 %). Hence with the current experiment’s outputs, this study concluded that Line sowing + Poultry manure (5 t/ha) + Panchagavya 3% FS + Jeevamrutha 500 l/ha FS were produced more grains and productivity as compared to other organic treatment combinations.

Abstract Background Pediatric patients with relapsed or refractory disease represent a population with a desperate medical need. The aim of the INFORM (INdividualized Therapy FOr Relapsed Malignancies in Childhood) program is to translate next generation molecular diagnostics into a biomarker driven treatment strategy. The program consists of two major foundations: the INFORM registry providing a molecular screening platform and the INFORM2 series of biomarker driven phase I/II trials. The INFORM2 NivEnt trial aims to determine the recommended phase 2 dose (RP2D) of the combination treatment of nivolumab and entinostat (phase I) and to evaluate activity and safety (phase II). Methods This is an exploratory non-randomized, open-label, multinational and multicenter seamless phase I/II trial in children and adolescents with relapsed / refractory or progressive high-risk solid tumors and CNS tumors. The phase I is divided in 2 age cohorts: 12–21 years and 6–11 years and follows a 3 + 3 design with two dose levels for entinostat (2 mg/m2 and 4 mg/m2 once per week) and fixed dose nivolumab (3 mg/kg every 2 weeks). Patients entering the trial on RP2D can seamlessly enter phase II which consists of a biomarker defined four group basket trial: high mutational load (group A), high PD-L1 mRNA expression (group B), focal MYC(N) amplification (group C), low mutational load and low PD-L1 mRNA expression and no MYC(N) amplification (group D). A Bayesian adaptive design will be used to early stop cohorts that fail to show evidence of activity. The maximum number of patients is 128. Discussion This trial intends to exploit the immune enhancing effects of entinostat on nivolumab using an innovative biomarker driven approach in order to maximize the chance of detecting signs of activity. It prevents exposure to unnecessary risks by applying the Bayesian adaptive design for early stopping for futility. The adaptive biomarker driven design provides an innovative approach accelerating drug development and reducing exposure to investigational treatments in these vulnerable children at the same time. Trial registration ClinicalTrials.gov, NCT03838042 . Registered on 12 February 2019.

Green synthesis of silver nanoparticles (AgNPs) has gained greater interest among chemists and researchers in this current scenario. The present research investigates the larvicidal and anti-proliferation activity of AgNPs derived from Knoxia sumatrensis aqueous leaf extract (K. sumatrensis-ALE) as a potential capping and reducing candidate. The synthesized AgNPs were characterized through-UV-spectra absorption peak at 425 nm. The XRD and FT-IR studied displayed the crystalline nature and presence of functional groups in prepared samples. FE-SEM showed the hexagonal shape of NPs with the size of 7.73 to 32.84 nm. The synthesized AgNPs displayed superior antioxidant and anti-proliferative activity (IC50 53.29 µg/mL) of breast cancer cell line (MCF-7). Additionally, larvicidal activity against mosquito vector Culex quinquefasciatus larvae delivered (LC50-0.40, mg/L, and LC90-15.83) significant mortality rate post treatment with synthesized AgNPs. Overall, the present research illustrates that the synthesized AgNPs have high biological potential and present a perfect contender in the pharmacological and mosquitocidal arena.

The total ionizing dose (TID) and non ionizing energy loss (NIEL) effects of 100 MeV phosphorous (P7+) and 80 MeV nitrogen (N6+) ions on 200 GHz silicon-germanium heterojunction bipolar transistors (SiGe HBTs) were examined in the total dose range from 1 to 100 Mrad(Si). The in-situ I–V characteristics like Gummel characteristics, excess base current (ΔIB), net oxide trapped charge (NOX), current gain (hFE), avalanche multiplication (M − 1), neutral base recombination (NBR) and output characteristics (IC-VCE) were analysed before and after irradiation. The significant degradation in device parameters was observed after 100 MeV P7+ and 80 MeV N6+ ion irradiation. The 100 MeV P7+ ions create more damage in the SiGe HBT structure and in turn degrade the electrical characteristics of SiGe HBTs more when compared to 80 MeV N6+. The SiGe HBTs irradiated up to 100 Mrad of total dose were annealed from 50 °C to 400 °C in different steps for 30 min duration in order to study the recovery of electrical characteristics. The recovery factors (RFs) are employed to analyse the contribution of room temperature and isochronal annealing in total recovery. Keywords: SiGe HBT, Ion irradiation, Gamma irradiation, Current gain degradation, Isochronal annealing, Recovery factors

Background: Periostin, a matricellular protein, is downregulated in chronic inflammatory periodontal disease and is negatively modulated by tumor necrosis factor-α (TNF-α) in human periodontal fibroblast cell culture. The study aimed to estimate the gingival crevicular fluid (GCF) levels of periostin and TNF-α and to discern their relationship in chronic periodontitis (CP) individuals with and without Type II diabetes mellitus (DM). Materials and Methods: A total of 60 participants were divided into three groups, with 20 in each group. Group I – systemically and periodontally healthy, Group II – generalized CP, and Group III – generalized CP with Type II DM. Plaque index, gingival index, sulcular bleeding index, probing depth, and clinical attachment level were recorded. GCF periostin and TNF-α were quantified using the enzyme-linked immunosorbent assay. Results: Intergroup comparison was performed using the one-way ANOVA and Kruskal–Wallis. The relationship between the variables was analyzed using the Pearson's and Kendall's Tau correlation. The GCF periostin levels in Groups I, II, and III was 27.52 ± 2.39 ng/mL, 20.18 ± 1.42 ng/mL, and 16.77 ± 3.29 ng/mL, respectively. The GCF TNF-α levels in Groups I, II, and III was 92.41 ± 19.30 ng/L, 118.53 ± 21.93 ng/L, and 147.67 ± 16.35 ng/L, respectively. Periostin decreased, and TNF-α increased in periodontal disease; moreover, periostin level correlated negatively with all the site-specific clinical parameters whereas TNF-α positively correlated (P < 0.001). Conclusions: TNF-α strongly and negatively downregulates periostin in a chronically inflamed locale leading to compromised integrity of the periodontium.

The evolution and genetic nature of metastatic lesions is not completely characterized. Here the authors perform a comprehensive whole-genome study of colorectal metastases in comparison to matched primary tumors and define a multistage progression model and metastasis-specific changes that, in part, are therapeutically actionable.

Background: Agro-wastes were used for the production of fibrinolytic enzyme in solid-state fermentation. The process parameters were optimized to enhance the production of fibrinolytic enzyme from Bacillus halodurans IND18 by statistical approach. The fibrinolytic enzyme was purified, and the properties were studied. Results: A two-level full factorial design was used to screen the significant factors. The factors such as moisture, pH, and peptone were significantly affected enzyme production and these three factors were selected for further optimization using central composite design. The optimum medium for fibrinolytic enzyme production was wheat bran medium containing 1% peptone and 80% moisture with pH 8.32. Under these optimized conditions, the production of fibrinolytic enzyme was found to be 6851 U/g. The fibrinolytic enzyme was purified by 3.6-fold with 1275 U/mg specific activity. The molecular mass of fibrinolytic enzyme was determined by sodium dodecyl sulphate polyacrylamide gel electrophoresis, and it was observed as 29 kDa. The fibrinolytic enzyme depicted an optimal pH of 9.0 and was stable at a range of pH from 8.0 to 10.0. The optimal temperature was 60°C and was stable up to 50°C. This enzyme activated plasminogen and also degraded the fibrin net of blood clot, which suggested its potential as an effective thrombolytic agent. Conclusions: Wheat bran was found to be an effective substrate for the production of fibrinolytic enzyme. The purified fibrinolytic enzyme degraded fibrin clot. The fibrinolytic enzyme could be useful to make as an effective thrombolytic agent.

Amylase production by Bacillus cereus IND4 was investigated by solid state fermentation (SSF) using cow dung substrate. The SSF conditions were optimized by using one-variable-at-a-time approach and two level full factorial design. Two level full factorial design demonstrated that moisture, pH, fructose, yeast extract and ammonium sulphate have significantly influenced enzyme production (p

Aim: The objective of this study was to investigate the chromosomal profile of indigenous pigs by computing morphometric measurements. Materials and Methods: A cytogenetic study was carried out in 60 indigenous pigs to analyze the chromosomal profile by employing the short term peripheral blood lymphocyte culture technique. Results: The modal chromosome number (2n) in indigenous pigs was found to be 38 and a fundamental number of 64 as in the exotic. First chromosome was the longest pair, and thirteenth pair was the second largest while Y-chromosome was the smallest in the karyotype of the pig. The mean relative length, arm ratio, centromeric indices and morphological indices of chromosomes varied from 1.99±0.01 to 11.23±0.09, 1.04±0.05 to 2.95±0.02, 0.51±0.14 to 0.75±0.09 and 2.08±0.07 to 8.08±0.15%, respectively in indigenous pigs. Sex had no significant effect (p>0.05) on all the morphometric measurements studied. Conclusion: The present study revealed that among autosomes first five pairs were sub metacentric, next two pairs were sub telocentric (6-7), subsequent five pairs were metacentric (8-12) and remaining six pairs were telocentric (13-18), while both allosomes were metacentric. The chromosomal number, morphology and various morphometric measurements of the chromosomes of the indigenous pigs were almost similar to those established breeds reported in the literature.

The aim of the present investigation is to treat the dye house effluent using electro-oxidation and to analyse the result using Taguchi method. L16 orthogonal array was applied as an experimental design to analyse the results and to determine optimum conditions for acid fast red dye removal from aqueous solution. Various operating parameters were selected to study the electro-oxidation for the colour removal of the effluent. The operating parameter such as dye concentration, reaction time, solution pH and current density were studied and the significance of the variables was analysed using Taguchi method. Taguchi method is suitable for the experimental design and for the optimization of process variables for the dye removal.

The effects of high total dose proton irradiation on the reliability of silicon NPN rf power bipolar junction transistor (BJT) were examined by subjecting to 1, 3, and 5 MeV protons in the dose range from 100 Krad to 100 Mrad. The electrical characteristics such as Gummel characteristics (IB, IC-VBE), excess base current (ΔIB = IBpost – IBpre), current gain (hFE), and output characteristics (IC-VCE), built-in potential (Vbi) and the effective doping concentration (Nd) were studied before and after irradiation. SRIM simulation was conducted to understand the range and energy loss of protons in the BJT structure. SRIM and experimental results infer that the proton irradiation at lower energy (1 MeV) was found to degrade the current–voltage(I-V) and capacitance–voltage (C-V) characteristics more severely than higher-energy (3 and 5 MeV) proton irradiation. Thermal annealing on irradiated devices was also conducted to study the parametric recovery of irradiated devices. [ABSTRACT FROM AUTHOR]

Aim: The present study was undertaken to estimate the genetic parameters and to assess the inheritance pattern of egg quality traits in White Leghorns. Materials and Methods: Data on 480 eggs produced by 40 week old pullets of 4 genetic groups were used for studying egg quality traits. Heritabilities and correlations were estimated by full sib correlation method using Mixed Model Least Squares and Maximum Likelihood (LSMLMW) computer program. Results: The egg weight, haugh unit, yolk index, albumen index, yolk weight, albumen weight, shell weight and shell thickness ranged from 50.01 ± 0.48 to 53.89 ± 0.43 g, 65.38 ± 0.92 to 80.98 ± 1.01, 0.341 ± 0.003 to 0.353 ± 0.003, 0.056 ± 0.002 to 0.087 ± 0.002, 14.16 ± 0.13 to 15.58 ± 0.12 g, 30.92 ± 0.39 to 33.18 ± 0.39 g, 4.32 ± 0.05 to 5.12 ± 0.05 g and 0.336 ± 0.003 to 0.376 ± 0.003 mm, respectively. Heritability estimates for egg weight, yolk index, albumen index and albumen weight ranged from low to medium while those of haugh unit, yolk weight, shell weight and shell thickness ranged from low to high. The genetic and phenotypic correlations of egg weight with other egg quality traits except shell quality traits were mostly positive and moderate to high. High positive genetic and phenotypic correlations between haugh unit and other traits were observed. Genetic correlation of yolk weight with albumen weight was positive while that with shell quality traits was mostly negative. Shell weight was positively correlated with shell thickness. Conclusion: Significant genetic group differences were observed for various egg quality traits studied. The heritability estimates for different egg quality traits were low to moderate. The association among egg quality traits was positive in general. [Vet World 2013; 6(5.000): 263-266]

Aim: The main intension of this research work is to develop a feeding system for growing Nellore ram lambs by feeding maize silage based rations supplemented with concentrate and or legume hay at certain levels to investigate the growth rate. Materials and Methods: Experimental animals (Nellore ram lambs) were purchased from local sandy and maize silage was prepared at village by using silos (9''L X 9''W X 8''D) and concentrate mixture was prepared at feed mill located at department by using locally available ingredients. Animals were housed in well ventilated sheds and were dewormed and vaccinated against diseases. Fortnightly body weights were taken by using spring balance and calculated the total weight gain and ADG. The experimental animals were divided into seven groups based on their body weight to contain six in each and were fed intensively for five months with sole maize silage (R-I), silage + concentrate at 0.5 per cent body weight (R-II), silage + concentrate at 1.0 per cent body weight (R-III), silage + concentrate at 1.5 per cent body weight (R-IV), silage + lucerne hay (R-V) and silage + GN haulms (R-VI) and sweet sorghum bagasse based complete diet (R-VII) to study the growth rate. Results: Significantly (P

Introduction: Escherichia coli are the most common uropathogen worldwide accounting for 80% of the Urinary Tract Infections (UTIs). Nosocomial infections caused by Multi-drug resistant Gram negative bacteria expressing Extended Spectrum β Lactamase enzyme, pose a serious therapeutic challenge to clinicians due to limited therapeutic options. Stringent adherence to Hospital Antibiotic Policy in treating Urinary Escherichia coli ESBLs is a borne necessity. Aim: A clinical audit was undertaken in the form of a crosssectional study to evaluate the compliance on appropriate antibiotic prescription and strict adherence to Hospital Antibiotic Policy for therapeutic management of the patients infected with urinary Escherichia coli ESBL producers. Materials and Methods: A cross-sectional medical audit on adherence to treatment of Escherichia coli ESBL producers from in-patients diagnosed to have urinary tract infections for a duration of 7 months was conducted as a prospective study. Clinical data, culture and sensitivity reports of the patient diagnosed with urinary Escherichia coli ESBLs were compared with the treatment chart to ensure strict adherence to hospital antibiotic policy for appropriate therapy by physicians. Data were analysed using IBM SPSS version 20 software. Results: The incidence of uncomplicated cystitis, pyelonephritis and complicated pyelonephritis cases were 65.24% (107 out of 164), 20.7% (34 out of 164) and 14.02% (23 out of 164) respectively. Resistance to individual fluoroquinolones like norfloxacin, ciprofloxacin and ofloxacin were found to be 60%, 59% and 47.5% respectively. As per hospital antibiotic policy, fluoroquinolones were prescribed in only 23% of the patients for the treatment of urinary Escherichia coli ESBLs. Conclusion: Irrational utilization of antibiotics and nonadherence to antibiotic policy could have been the significant risk factors for drug resistance. Optimized antibiotic use, Microbiology laboratory support and periodic antibiotic audit led by effective infection control team would hasten the development of drug resistance.