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Pancreatic cancer (PC) is a major gastrointestinal cancer in terms of worldwide incidence and mortality. Despite advances in diagnostic and treatment modalities, the mortality of PC is still a serious concern in both sexes. Immune therapy using inhibitors of immune checkpoints, especially inhibitors of programmed cell death protein 1/programmed cell death ligand-1(PD-1/PD-L1), offer huge benefits to cancer patients. This review describes an up-to-date information on the role of PD-1 and PD-L1 in the development of immune tolerance in PC alongside the current clinical trials and the known outcomes citing the available literature. We also included the details on PD-1/PD-L1-mediated signalling in maintenance of PC stem cells and metastasis. We reviewed the critical information on safety, tolerance, and efficacy of clinically important regimens of PD-1/PD-L1 blocking agents and targeted therapeutics. This review elucidates the underlying mechanisms of PD-1/PD-L1 alliance in tolerance of the immune system, maintenance of stem cells, and metastasis promotion as well as design regimens with high safety and excellent tolerability and efficacy for management of PC in advanced stages.

Humans usually contract dengue by being bitten by arthropods, and more than 3.6 billion people are at risk per year. Although studies are conducted to screen and trace out the possible pathophysiology of the virus, an adequate receptor-based study has not been completed. Understanding how the dengue virus (DV) engraves its landing sites requires identification of such cellular receptors. In many model studies, heparan sulfate (HS) has been reported to act as a DV receptor under various conditions. However, the physiological relevance of these findings remains uncertain. Therefore, it is still unclear whether HS is used by viral strains or not, and if at all used by clinical or non-cell culture-adapted strains of DV. The present review aims to identify relevant experimental evidences that confirm the possible interaction between envelope protein and HS chains. We collected data from a series of studies to conclude the interactive role.

This research was aimed at investigating the physicochemical, thermal, and mechanical properties of newly identified cellulosic fiber extracted from the bark of Erythrina variegata (EV) tree. The c...

The present experiment was carried out during Kharif, 2016-2017 at College of Horticulture, Dr. Y.S.R. Horticultural University, Venkataramannagudem to assess the impact of mutagens on mutagenicity like Mutation frequency on M1 population basis, Mutagenic effectiveness, Mutagenic efficiency and Frequency of albino, xantha and chlorina mutants in turmeric. The experiment was laid out in factorial randomized block design and replicated thrice under open field conditions. Rhizomes are treated with gamma rays (25 Gy and 50 Gy) and EMS (250 ppm, 500 ppm and 1000 ppm) along with control. Maximum mutagenic frequency, effectiveness and efficiency was observed in25 Gy, 250 ppm EMS and combination of 25 Gy + 250 ppm EMS and minimum was recorded in 50 Gy gamma rays, 1000 ppm EMS and combination both 50 Gy + 500 ppm EMS and 50 Gy + 1000 ppm EMS .

Epitranscriptomics involves functionally relevant biochemical modifications of RNA taking place at the transcriptome level without a change in the sequence of ribonucleotides. Several types of modifications that affect the processing and function of differentRNA types have been reported. Methylation at N 6 of Adenosine called m6 A is one such modification, quite widespread in occurrence and reported in snRNAs, lncRNAs , circRNAs, rRNAs, miRNAs , and most abundantly, in mRNAs. The significant implications of m 6A in various types of cancers are being widely recognized. Here, we give a brief about the enzymes that install the m6A modification (= m6A writers), that remove it (= m6A erasers) and certain RNA binding proteins (= m6A readers) which affect the fate of the m6A-containing RNA by recruiting various proteins. We also discuss the relevance of m6A in ncRNAs in various cancer types, followed by a discussion on the role of m6 A of mRNA and ncRNA in lung cancer.

Large-scale plantations of pine species were done in the bare hills of the Middle Mountain region of Nepal during the early 1980s. There is a growing concern on the sustainability of the planted pine forests in the country due to the presence of invasive alien plant species (IAPS). Invasive alien plant species are considered as one of the drivers of forest degradation and deforestation. Ageratina adenophora is one of the problematic IAPS found in the planted pine forests throughout the country. In this study, we employed different treatments to control the invasion of A. adenophora in the planted pine (Pinus patula) forest. The research design included four different treatments, viz., (i) control, (ii) stem felling, (iii) floor clearance, and (iv) stem felling cum floor clearance in one block (Block I), which was replicated in another block (Block II). The data were collected using circular sample plots with 2m radius. The ANOVA and TukeyHSD Tests were applied during the analysis process so as to determine the effects of treatments on invasion of A. adenophora. The "floor clearance treatment" was found to be significantly effective to reduce the presence of A. adenophora in the planted pine forest. On the contrary, the "opening of forest cover treatment" was found to be conducive to this invasive species to invade the area. The "stem felling cum floor clearance treatment" could be an effective strategy to control invasion of A. adenophora in planted forest, but as it demands a high cost, it is likely to be appropriate for small forest areas where promotion of regeneration is of high priority.

This study was carried out at Goat Research Station, Bandipur, Tanahun, Nepal to evaluate the different factors affecting the growth performance of pure Boer goat since its arrival on 2015. A total of 225 kids of Boer goat born from 218 kidding does recorded between 2015 and 2019 were used for analysis of birth weight, weaning weight, eight month weight and yearling weight in response to sex and type of birth. The overall least square means for birth weight is 3.246 ± 0.056 kg, weaning weight is 17.86 ± 0.105 kg, eight month weight is 28.66 ± 0.2.6 kg and yearling weight is 45.10 ± 0.218 kg. The least square means across sex for birth weight, weaning weight, eight month weight and yearling weight were 3.368 ± 0.090 kg, 18.42 ± 0.226 kg, 31.69 ± 0.415 kg and 49.29 ± 0.707 kg for male and 3.136 ± 0.068 kg, 17.43 ±0.150 kg, 26.35 ± 0.378 kg and 42.18 ± 0.778 kg for female respectively. Sex and type of birth have significant effect on birth weight and weaning weight, while for eight month weight and yearling weight, sex have significant effect but no significant effect on type of birth. In conclusion, the overall growth performance of Boer goat in Goat Research Station was to the expectation and may increase on improvement of management and environmental effects. Bang. J. Anim. Sci. 2020. 49 (2): 166-169

Background: Physical parameters like pH and temperature play a major role in the design of an industrial enzymatic process. Enzyme stability and activity are greatly influenced by these parameters; hence optimization and control of these parameters becomes a key point in determining the economic feasibility of the process. Objective: This study was taken up with the objective to optimize physical parameters for maximum stability and activity of xylose reductase from D. nepalensis NCYC 3413 through separate and simultaneous optimization studies and comparison thereof. Method: Effects of pH and temperature on the activity and stability of xylose reductase from Debaryomyces nepalensis NCYC 3413 were investigated by enzyme assays and independent variables were optimised using surface response methodology. Enzyme activity and stability were optimised separately and concurrently to decipher the appropriate conditions. Results: Optimized conditions of pH and temperature for xylose reductase activity were determined to be 7.1 and 27 ℃ respectively, with predicted responses of specific activity (72.3 U/mg) and half-life time (566 min). The experimental values (specific activity 50.2 U/mg, half-life time 818 min) were on par with predicted values indicating the significance of the model. Conclusion: Simultaneous optimization of xylose reductase activity and stability using statistical methods is effective as compared to optimisation of the parameters separately.

Background: Global emergence of carbapenem-resistant Klebsiella pneumoniae is a major public health concern. Phage therapy – application of lytic phage to kill pathogenic bacteria – is considered as one of the promising alternatives to tackle this antibiotic crisis in recent days. This study aimed to isolate, characterize and evaluate therapeutic efficacy of a novel K. pneumoniae phage in mouse model.Methods: A novel lytic bacteriophage (phage) Kp_Pokalde_002 was isolated against carbapenem-resistant K. pneumoniae (Kp56) and characterized. Safety parameters of the phage were evaluated by bioinformatic analysis of its genome. A lethal dose (~1×107 CFU/mouse) of Kp56 was determined and administrated in the mice. The infected mice were treated with phage Kp_Pokalde_002 at a multiplicity of infection (MOI) 1.0 (~1×107 PFU/mouse) via both oral and intraperitoneal (IP) routes.Results: Isolated phage comprised an icosahedral capsid with a short tail. Based on genome analysis, the phage was strictly lytic belonging the Podoviridae family (T7-like viruses) and free from any virulent and antibiotic-resistant genes. The phage was stable up to 60 °C for 30 minutes and effective between pH 4 to 11 (optimum pH 9). The phage exhibited a short latent period (20 minutes) with burst size of 121 phage particles per infected cell. The infected mice were rescued with the phage therapy via both oral and IP route. Significant reduction of bacterial load (3-7 log10 CFU/ml) in the blood and lung was observed in the treatment group.Conclusions: We provide an evidence of successful phage therapy against carbapenem-resistant K. pneumoniae infected mouse model using locally isolated lytic phage.Keywords: Bacteriophage; klebsiella pneumonia; phage therapy

There is increasing evidence that some functionally related, co-expressed genes cluster within eukaryotic genomes. We present a novel pipeline that delineates such eukaryotic gene clusters. Using this tool for bread wheat, we uncovered 44 clusters of genes that are responsive to the fungal pathogen Fusarium graminearum. As expected, these Fusarium-responsive gene clusters (FRGCs) included metabolic gene clusters, many of which are associated with disease resistance, but hitherto not described for wheat. However, the majority of the FRGCs are non-metabolic, many of which contain clusters of paralogues, including those implicated in plant disease responses, such as glutathione transferases, MAP kinases, and germin-like proteins. 20 of the FRGCs encode nonhomologous, non-metabolic genes (including defence-related genes). One of these clusters includes the characterised Fusarium resistance orphan gene, TaFROG. Eight of the FRGCs map within 6 FHB resistance loci. One small QTL on chromosome 7D (4.7 Mb) encodes eight Fusarium-responsive genes, five of which are within a FRGC. This study provides a new tool to identify genomic regions enriched in genes responsive to specific traits of interest and applied herein it highlighted gene families, genetic loci and biological pathways of importance in the response of wheat to disease.

This study was carried out to determine the prevalence, intensity and management systems associated with tick infestation in sheep and goats from Bui and Donga-Mantung Divisions. A total of 704 animals consisting of 342 males and 362 females (463 adults and 241 young (kids/lambs) were physically examined for tick infestation, of which 383 were goats and 321 sheep aged 5 months to 7 years. Of the 704 animals examined, 651 were found positive with one or more ticks giving an overall prevalence of 92.5%. The highest prevalence was recorded in sheep (99.4%) while 86.7% was recorded in goats. There was a significant difference (p

Breast cancer (BC) is the most common cancer in women. Globally, the incidence of BC surpassed lung cancer for the first time in 2020, and it is highly heterogeneous. The tumor microenvironment (TME) of BC consists of blood vessels, fibroblasts, signaling molecules, immune cells, and extracellular matrix. Numerous studies have provided considerable evidence regarding the association between the circadian rhythm (CR) and human diseases. The CR induces remodeling of the TME cells and their components by disturbing the cellular metabolism, altering gene expression, and aberrantly activating signaling pathways. In this review we present the recent updates on the CR genes and their molecular mechanisms and signaling pathways. In addition, we present the mutations and single nucleotide polymorphisms in the CR genes and the CR pathways in BC biology and the management of the CR in patients with BC. The association between the CR and the TME in BC is also explored.

Novel scaffolds of stilbene were identified as inhibitors of Mycobacterium tuberculosis by targeting the nucleoid-associated protein, HU, using molecular docking. Based on the proposed combinatorial libraries I to VI, structures I and III had significantly greater docking binding energy that was comparable to that of the reference ligand, protein HU, from Mycobacterium tuberculosis. Using these docking results, 18 compounds were synthesized, characterized and evaluated for in vitro antitubercular (anti-TB) efficacy in the Mycobacterium tuberculosis strain, H37Rv. The in vitro screening results indicated a significant positive correlation between the docking binding efficacy (r2 > 0.5) and clogp. Compounds 3f, 3d and 4f were ranked as top scoring ligands that interacted with amino acids ARG 53, ARG 55, PRO 81, PHE 79, and LYS 13, where the –NO2 or –Cl substitution at the para position of the 3-phenyl ring was essential for interacting of the HU protein. The hydrogen bonding with ARG 55 and LYS 13 of these compounds was similar to that with the reference ligand that inhibits the HUMtb protein. Compounds 3d, 3f, and 4f were evaluated as active leads, with MIC90 values of 21.3, 23.2 and 44.1 μM, respectively. The above mentioned compounds were also evaluated for antibacterial and antifungal efficacy in a panel of selected bacteria and fungi. Compound 3d had efficacy (MIC90: 6.82 μM) in S. aureus and E. coli. Compound 3f was also efficacious in E. coli and A. Niger, with an MIC90 value of 7.42 μM for both microorganisms. The fluoro-phenyl derivatives, 3i and 4i, were efficacious in C. albicans (MIC90 values of 8.2 and 7.8 μM, respectively) and A. niger (MIC90 values of 4.1 and 3.1 μM, respectively). Our results suggest that substitutions at the para position of 3-phenyl acryl derivatives with –NO2 and –Cl significantly affected the binding interactions with the HUMtb protein in the docking studies. Furthermore these compounds had antitubercular and antimicrobial efficacy. The substituted phenyl acrylic acid and hydrazides could be inhibitors of the HUMtb protein of Mycobacterium tuberculosis.

Among three races of Colletotrichum orbiculare, which cause anthracnose of cucurbits, screening for race 2 resistance was studied under greenhouse conditions at various inoculum concentrations, and plants were rated on different days postinoculation (DPI). The objectives of this study were optimizing inoculum concentration and phenotyping DPI for seedling resistance. Five inoculum concentrations were compared (2.5 × 104, 5 × 104, 1 × 105, 2.5 × 105, and 5 × 105conidial spores/ml). Four watermelon genotypes (‘Black Diamond’, ‘Charleston Gray 133’, PI 543210, and PI 189225) and two cucumber genotypes (‘Marketer’ and ‘H19 Little Leaf’) were evaluated. Disease was recorded on the percentage of cotyledon area lesion, severity of hypocotyl lesion (SHL), severity of petiole lesion (SPL), and percentage of leaf area lesion (PLL), as well as a disease index (INDX) from 5 to 14 DPI. There was a significant difference among genotypes and inoculum concentrations. The resistant PI 189225 was significantly different (P < 0.05) from the highly susceptible PI 543210. Inoculum 1 × 105spores/ml was at par with 5 × 105and 2.5 × 105but significantly different from 5 × 104and 2.5 × 104for AUDPS PLL, AUDPS INDX, AUDPS SPL, and AUDPS SHL. Inoculum at 1 × 105spores/ml was optimal to differentiate germplasm. A genotype plus genotype-by-environment biplot showed that PLL was a representative rating. A single PLL rating on 9 DPI would optimize resources for screening a large set of germplasm for anthracnose resistance in a watermelon breeding program.

Myelination is one of the most important aspect of membrane remodeling, hence it is very much essential to understand the factors that can aid in remyelination once the myelin layer gets reduced or is lost due to several physiological factors. Studies have shown that the activities taking place within the nervous system itself can aid in remyelination. The current study is based on understanding the role action potential play in aiding in remyelination of the nerve fiber which would not only help in regaining the strength of the signal and also for the faster propagation of the impulse thus addressing several neurological issues arising due to myelin degradation. The idea is to develop an appropriate mathematical model to study the effects of the action potential in remyelination which will be computationally viable and to understand its role in neuronal growth. The findings of this study suggest that variation in the rate at which the membrane potential changes can have a significant impact on neuronal growth and therefore the issues arising out of myelin degradation such as multiple scheloris could be addressed.

Oncogenic KRAS mutations and inactivation of the APC tumor suppressor co-occur in colorectal cancer (CRC). Despite efforts to target mutant KRAS directly, most therapeutic approaches focus on downstream pathways, albeit with limited efficacy. Moreover, mutant KRAS alters the basal metabolism of cancer cells, increasing glutamine utilization to support proliferation. We show that concomitant mutation of Apc and Kras in the mouse intestinal epithelium profoundly rewires metabolism, increasing glutamine consumption. Furthermore, SLC7A5, a glutamine antiporter, is critical for colorectal tumorigenesis in models of both early- and late-stage metastatic disease. Mechanistically, SLC7A5 maintains intracellular amino acid levels following KRAS activation through transcriptional and metabolic reprogramming. This supports the increased demand for bulk protein synthesis that underpins the enhanced proliferation of KRAS-mutant cells. Moreover, targeting protein synthesis, via inhibition of the mTORC1 regulator, together with Slc7a5 deletion abrogates the growth of established Kras-mutant tumors. Together, these data suggest SLC7A5 as an attractive target for therapy-resistant KRAS-mutant CRC.

The main viral protease (Mpro) of SARS-CoV-2 is a nucleophilic cysteine hydrolase and a current target for anti-viral chemotherapy. We describe a high-throughput solid phase extraction coupled to mass spectrometry Mpro assay. The results reveal some β-lactams, including penicillin esters, are active site reacting Mpro inhibitors, thus highlighting the potential of acylating agents for Mpro inhibition.

Pulmonary disease due to Mycobacterium abscessus (Mab) has become an increasing cause of health concern, particularly among individuals infected with nontuberculous mycobacteria. Since Mab is intrinsically resistant to many antibiotics, it is very challenging to treat patients with symptomatic disease. In this case series, we report four patients with symptomatic pulmonary Mab who had prior history of antituberculosis treatment intake and declared cured at the end of treatment. The current episode was confirmed to be due to Mab infection by molecular and clinical diagnosis and received species specific-antibiotics therapy. All were periodically monitored for the sputum smear and culture conversions throughout the treatment period. The clinical course was variable though all received similar antibiotic regimen and showed varied treatment outcomes. The time of diagnosis and the treatment outcome indicate that a better understanding of host-pathogen interactions is essential for the successful treatment of pulmonary Mab infection.

A series of new C3 heterocyclic-substituted ciprofloxacin derivatives were prepared from ciprofloxacin acid hydrazide as possible chimeric molecules. They were evaluated for their possible in vitro antibacterial (agar cup/bore diffusion method) and antitubercular (Lowenstein-Jensen (LJ) slant method) activities. The results indicated that all the test compounds are highly effective against all the bacterial strains and have shown excellent anti-tubercular activity against normal, multidrug resistant and extensively drug resistant strains of Mycobacterium tuberculosis. They were found to be more potent antibacterial and antitubercular agents than the standard, ciprofloxacin. The minimum inhibitory concentration (MIC)'s of all the compounds against M. tuberculosis were found to be 0.0625 µg/mL as compared to ciprofloxacin (MIC = 2 to > 8 µg/mL). Molecular docking studies were performed by using AUTODOCK 4.2 on the new ciprofloxacin derivatives at the active site of crystal structure of fluoroquinolones target enzyme Mtb DNA gyrase GyrA N-terminal domain (PDB ID: 3ILW) and also on the active site of crystal structure of chosen heterocyclics target enzyme enoyl-acyl carrier protein (ACP) reductase enzyme (PDB ID: 4TZK). Interestingly, almost all the compounds have shown relatively greater binding affinity at both the active sites than ciprofloxacin. Compound 6 exhibited the highest affinity for 3ILW and 4TZK.

Animals are susceptible to heat stress under tropical environmental conditions. Exposure of growing male and female animals to severe heat stress during summer adversely affects their growth and re...

Background and Aims: Among the various biomarkers, high sensitivity C-Reactive Protein (hs-CRP) has been widely studied and is easy to use in the prognostication of patients with acute ST elevation myocardial infarction (STEMI). This study aimed to associate serum level of hs-CRP with in-hospital mortality in patients presented with acute STEMI. Methods: This was a hospital-based prospective observational study conducted in Shahid Gangalal National Heart Centre among patients presented to the emergency department with chest pain of less than 24 hours duration, who were diagnosed subsequently to have STEMI. Patients who had known chronic inflammatory diseases, septic foci and chest pain of over 24 hours were excluded from the study. Blood sample for Hs-CRP was sent from the emergency department and was measured with Finecare TM FIA system; Model number: FS-112. The study was conducted from April 2019 to March 2020. Patient outcomes were stratified as per the four groups of serum level of hs-CRP and among them the relationship between mortality and hs-CRP level was tested with chi-square test. The p-value across the groups was again tested for inter-group significance using the Bonferroni adjusted significance level. Results: 140 patients (112 males and 28 females) with mean age of 58.1±14.86 years were enrolled in the study. There was no increased in-hospital mortality in acute STEMI patients who had serum level of hs-CRP below 3 mg/l. In-hospital mortality showed an increasing trend above this level but it reached statistical significance beyond 10 mg/l only. Thirty five percent of our patients of acute STEMI were found to have serum level of hs-CRP above this threshold. The total in-hospital mortality was 13 (9.28%). Conclusion: The increased serum level of hs-CRP was associated with increased in-hospital mortality in patients with acute STEMI.

Background: Medicinal plants and their products are gaining global popularity due to their several health benefits. However, the biological activities of the vast majority of medicinal plant species have not been explored yet. In this study, we evaluated the enzyme inhibitory potential of six medicinal plant species involved in digestion, skin-related problems, and neurological problems. Methods: The 80% methanol extracts of leaves of six locally available plants from the Bagmati province of Nepal were analyzed for their flavonoids content, phenolics content, antioxidant activity, and enzymes inhibitory potential. Antioxidant activity was analyzed by the DPPH assay. Alpha-amylase inhibition was carried out by the DNSA method. Lipase, tyrosinase, elastase, acetylcholinesterase, and butyrylcholinesterase inhibitions were analyzed by using p-NPB, L-DOPA, AAAPVN, acetylthiocholine, and butyrylthiocholine as a respective substrate. Results: Among the analyzed plants species, Artocarpus heterophyllus displayed highest α-amylase (IC50=6.28 ± 0.01 μg/mL), lipase (IC50= 475.14 ± 3.17 μg/mL), elastase (IC50= 72.75 ± 3.41 μg/mL) and acetylcholinesterase (IC50= 68.66 ± 1.71 μg/mL) inhibition, whereas, Actinidia deliciosa displayed highest tyrosinase inhibition (IC50=139.87 ± 0.72 μg/mL) and butyrylcholinesterase inhibition (IC50= 18.32 ± 0.44 μg/mL). Furthermore, Jasminum humile showed no inhibitory tendencies against elastase and Lygodium japonicum showed no inhibition towards lipase and elastase at the given concentration range. Conclusions: Our study revealed that A. deliciosa and A. heterophyllus are the potential source of α- amylase, lipase, elastase, acetylcholinesterase, and butyrylcholinesterase inhibitors. Based on our findings, we concluded that the analyzed plant species are of great scientific interest to the pharmaceutical, cosmetics, and food industries.

The epidemic outbreak of Corona-virus emerged in the capital of Hubei province of China in December 2019 has engulfed almost all the sections of the society across globe irrespective of age, sex, race, religion, and color. The exposure of Covid-19 has increased the risk of numerous problems like stress, disorder, unemployment, poverty and other numerous challenges. This paper talks about the socio-psychological implications pertaining to the spread of coronavirus and how it has caused deaths in lakhs and how developing cum developed countries alike have imposed lockdowns, curfews, restrictions on public movements, markets, workplace, constructions, and transport and instructed people to maintain social distance which has adversely affected the daily life of common masses; particularly the daily wage earners who have no other alternative to feed their respective family thereby putting them in a state of dilemma. Many health experts have given a warning that if the disease is not controlled, it will take a heavy toll on the global level. The paper discusses about the Covid-19 has created anxiety, stress, strain, confusion, trauma, mental health problems, violence against women, children and encourage the risks of suicidal behavior. It also talks about the effects of Covid-19 on the marginalized and poor sections of the society such as migrant workers, street vendors and daily wage labours and how keeping social distance, avoiding gathering, staying at home, avoid travelling, keeping away from doing daily routine work activities etc. are some of the important challenges faced by common masses.

Introduction: Neonatal sepsis is a major cause of neonatal morbidity and mortality worldwide, especially in developing countries like Nepal. Antibiotic resistance among microorganisms poses new challenges in the treatment of neonatal sepsis. The present study is conducted with the objectives of determining clinico-bacteriological profile and antibiotic susceptibility among isolated bacteria in a neonatal intensive care unit. Methods: A descriptive cross-sectional study was conducted from January 1, 2017, to December 31, 2019, in the neonatal intensive care unit of a tertiary care hospital after obtaining ethical clearance from Institutional Review Committee (Reference Number: 2020-064). The sample size was calculated and 77 neonates with culture-proven sepsis were included in the study. The antibiotic susceptibility tests of the isolates were done by Kirby-Bauer disc diffusion method. Data entry was done in Statistical Packages for the Social Sciences version 20. Results: Of the 841 specimens (blood, cerebrospinal fluid, urine, tracheal aspirate and pus) processed for culture, bacteria were isolated in 84 (10.0%) specimens. Among the 84, gram-negative bacilli were the predominant isolates 76 (90.5%); of which Acinetobacter baumannii was the most common 27 (32.1%). Both the Gram-negative and the Gram-positive bacteria showed high resistance to Penicillin and Cephalosporins. Gram-negative bacteria showed maximum sensitivity to Colistin, Carbapenems, Tigecycline and Fluoroquinolones. Gram-positive bacteria showed maximum susceptibility to Amikacin, Vancomycin and Carbapenems. Conclusions: Judicious use of antibiotics based on the updated knowledge of prevalent organisms in the local hospital setting and their antibiotic sensitivity pattern is of utmost importance for the effective treatment of neonatal sepsis.

This study was carried out to record the avifaunal diversity of the riverine habitats along the Godavari River in Papikonda National Park, during a short survey conducted from 2017 to 2018. A total of 63 bird species belonging to 25 families were recorded during the survey. The study resulted in the recording of eight globally threatened avian species including the Endangered Black-bellied Tern Sterna acuticauda, and seven Near Threatened species, viz.: Painted Stork Mycteria leucocephala, Black-headed Ibis Threskiornis melanocephalus, Great Thick Knee Esacus recurvirostris, River Lapwing Vanellus duvaucelli, Malabar Pied Hornbill Anthracoceros coronatus, Grey-headed Fish Eagle Haliaeetus ichthyaetus, and Oriental Darter Anhinga melanogaster. Species including Black-bellied Tern Sterna acuticauda, Grey-headed Fish Eagle Haliaeetus ichthyaetus, Indian Eagle-owl Bubo bengalensis, and Black Eagle Ictinaetus malaiensis were recorded for the first time along the riverine habitats of Papikonda National Park. Sand mining of the riverbed and discharge of effluents into the Godavari River has already negatively impacted the associated habitats and avifaunal diversity.

The release of soft red winter wheat (Triticum aestivum, L.) germplasm lines VA11DH‐P46xTrib‐28 (Reg. no. GP‐1048, PI 691656), VA11DH‐P46xTrib‐99 (Reg. no. GP‐1049, PI 691657), and VA11DH‐P46xTrib‐103 (Reg. no. GP‐1050, PI 691658) is intended to provide breeders with genetic material having exceptional milling and baking quality performance. The quantitative nature of milling and baking performance makes improvement and early generation selection difficult. Marker assisted and genomic selection breeding schemes can be improved by introducing breeding material with superior end‐use quality and use of known predictive DNA markers. These three lines have acceptable agronomic performance with grain yields (4605–5733 kg ha−1) similar to or higher than those of Pioneer ‘26R46’ (4568 kg ha−1). The lines have exceptional milling and baking performance with mean flour yields (733–736 g kg−1), softness equivalence (550–573 g kg−1), flour protein (89–94 g kg−1), solvent retention capacity for lactic acid (1162–1189 g kg−1) and sodium carbonate (672–697 g kg−1), and cookie diameters (19.1–19.5 cm) that are better than or similar to (p < .05) those of Pioneer 26R46 (721 g kg−1, 531 g kg−1, 93 g kg−1, 1221 g kg−1, 703 g kg−1, and 18.9 cm). Public domain – authored by a U.S. government employee

Epithelial cells that contain a large number of mitochondrial DNA (mtDNA) are shed in host feces. Recently, researchers have developed mtDNA markers targeting mtDNA of specific hosts and applied them to microbial source tracking (MST) for different environmental waters. This review describes the performance, persistence in environmental waters, and correlations of host-specific mtDNA markers with fecal indicators and bacterial MST markers to assess their usefulness in MST. Furthermore, concentrations are summarized for human- and animal-specific mtDNA markers in fecal sources and water that have been reported previously. For accurate identification of pollution sources, the use of host-specific mtDNA markers in combination with other MST markers in a toolbox approach is highly recommended.

The present study aims to explore the thermochemical conversion feasibility of an unexplored weed biomass, Tithonia diversifolia. In this investigation, the predictive ability of response surface model (RSM) and artificial neural network (ANN) models for bio-oil yield from pyrolysis of Tithonia Diversifolia was carried out in a fixed bed reactor. The influence of process parameters which included temperature (375–675 °C), heating rate (10–50 °C/min), nitrogen flow rate (50–250 mL/min), and particle size ( 1 mm) on bio-oil yield was investigated by central composite design (CCD) of RSM and feedforward backpropagation neural network with different topology. Based on statistical value for coefficient of determination (R2), mean average error (MAE), root mean square error (RMSE), standard error of prediction (SEP), and absolute average deviation (AAD), it was found that the ANN was more efficient than the RSM model for predicting bio-oil yield. The bio-oil obtained was analyzed for different physical and chemical properties which revealed that the bio-oil can be used as renewable fuel and chemicals.

Glioma-associated oncogene homolog 1 (GLI1) is reported as an amplified gene in human glioblastoma cells. It is a krupple like transcription factor, belonging to the zinc finger family. The basic function of GLI1 is normal neural development at various stages of human. The GLI1 gene was first mapped on the chromosome sub-bands 12q13.3-14.1. Further, single nucleotide polymorphism is mostly observed in translating a region of 5’ and 3’- UTR of GLI1 gene in addition to two post-transcriptional splice variants, GLIΔN and tGLI. Additionally, it also regulates a plethora of gene which mediates crucial cellular processes like proliferation, differentiation, oncogenesis, EMT, and metastasis. It also regulates tumor tolerance, chemoresistance, and radioresistance. Aberrant expression of GLI1 predicts the poor survival of breast cancer patients. GLI1 is an essential mediator of the SHH signaling pathway regulating self-renewal of stem cells, angiogenesis, and expression of FOXS1, CYR61. GLI1 mediated HH pathway can induce apoptosis. Hence, GLI1 can be a future diagnostic, prognostic marker, and as well as a potent target of therapeutics in breast cancer.

Deletion of the pfhrp2 gene in Plasmodium falciparum can lead to false-negative rapid diagnostic test (RDT) results, constituting a major challenge for evidence-based malaria treatment. Here we analyzed the whole genome sequences of 138 P. falciparum clinical samples collected from the China-Myanmar boarder for pfhrp2 and pfhrp3 gene deletions. We found pfhrp2 and pfhrp3 deletions in 9.4% and 3.6% of samples, respectively, with no samples harboring deletions of both genes. The pfhrp2 deletions showed 2 distinct breakpoints, representing 2 different chromosomal deletion events. A phylogenetic analysis performed using genome-wide single-nucleotide polymorphisms revealed that the 2 pfhrp2 breakpoint groups as well as all the pfhrp3-negative parasites formed separate clades, suggesting they might have resulted from clonal expansion of pfhrp2- and pfhrp3-negative parasites. These findings highlight the need for urgent surveys to determine the prevalence of pfhrp2-negative parasites causing false-negative RDT results and a plan for switching of RDTs pending the survey results.

Colon cancer (CC) is a major global health challenge. Diet, microbiome, obesity, and family history are some of the etiological factors that contribute to the occurrence of CC. Recent investigations have established a strong correlation between colonic microbiota composition and CC. The microbiota protects or damages colonic cells, depending on the type of metabolites and their mechanism of action. Microbiota dysbiosis enhances CC-cell proliferation and promotes metastasis. The microbiota modulates CC progression by epigenetic modifications mediated through either microbial metabolites or structural component interactions with host colon epithelial cells. In addition, gut homeostasis correlates with modulation of host inflammatory and immune responses. This review highlights the microbiome conundrum in tumor growth and metastasis, epigenetic regulation, tumor microenvironment maintenance, microbiome-derived reactive oxygen species in tumor progression, and microbiome-derived metabolites in CC prevention. Understanding the microbiome conundrum in CC development and progression will aid in developing a diet-based therapeutic strategy for colon tumorigenesis management.

Synthetic transmembrane ion transport systems are emerging as new tools for anticancer therapy. Here, a series of 2-hydroxy-N1,N3-diarylisophthalamide-based fluorescent ion channel-forming compounds are reported. Ion transport studies across large unilamellar vesicles confirmed that the compound with two 3,5-bis(trifluoromethyl)phenyl arms is the most efficient transporter among the series and it facilitates M+/Cl− symport. The compound formed supramolecular ion channels with a single-channel conductance of 100 ± 2 pS, a diameter of 5.06 ± 0.16 Å and a permeability ratio, PCl−/PK+, of 8.29 ± 1. The molecular dynamics simulations of the proposed M2.11 channel (i.e. 11 coaxial layers of a dimeric rosette) with K+ and Cl− in the preequilibrated POPC lipid bilayer with water molecules illustrated various aspects of channel formation and ion permeation. Cell viability assay with the designed compounds indicated that cell death is being induced by the individual compounds which follow the order of their ion transport activity and chloride and cations play roles in cell death. The inherent fluorescence of the most active transporter was helpful to monitor its permeation in cells by confocal microscopy. The apoptosis-inducing activity upon perturbation of intracellular ionic homeostasis was established by monitoring mitochondrial membrane depolarization, generation of reactive oxygen species, cytochrome c release, activation of the caspase 9 pathway, and finally the uptake of the propidium iodide dye in the treated MCF7 cells., We report a 2-hydroxy-N1,N3-diarylisophthalamide-based self-assembled channel that cotransports M+/Cl− and induces apoptotic cell death.

Honey bees are important pollinators and are essential in agriculture; as such they get exposed to a wide range of pesticides while foraging in contaminated fields or during the spray of chemical on crops. It is therefore important to know the toxicity and evaluate the impacts of bees’ exposure to these molecules. Acetamiprid and cypermethrin are two pesticides widely used in Cameroon and other countries. The objective of this study was to determine the toxicity of acetamiprid and cypermethrin on the native subspecies of Apis mellifera L. in agricultural areas in Adamaoua-Cameroon and to evaluate the impact on honeybee foragers exposed to lethal and sublethal doses of these two insecticides. The results obtained in laboratory conditions show that acetamiprid and cypermethrin are toxic to A. mellifera. The symptoms of neurotoxicity and first mortality appear 15 min after the ingestion of the high concentrations and about 30 to 45 min after the inoculation of the pesticides through contact route and the mortality increases with the concentration and time. The LC50 of acetamiprid obtained after 24 h are respectively 5.26 ng/μl for the topical application and 4.70 μg/μl by the oral route. At the same time, the LC50 of cypermethrin are respectively 2.27 ng/μl for topical application and 2.68 ng/μl for oral toxicity. For a sustainable agriculture and beekeeping, it is, therefore, important to establish quality measures on these insecticides in the ecosystem and to set up a phyto-pharmacovigilance and awareness system to the population.

Autophagy is a self-destructive process that occurs in the cells during abnormal conditions like protein aggregation due to misfolding, nutrient deprivation, damage to vital cell organelles, pathogenic infections, and during cancer. Typically, autophagy plays a key role in the renovation of new cells by balancing the equilibrium between cell death and cell renewal. Dysregulation of autophagy has a profound effect on protein turnover, mitochondrial homeostasis, clearance of damaged organelles, and cellular metabolism, which lead to neurodegenerative, metabolic, and proliferative diseases. Despite its antitumorigenic role, autophagy can promote cell proliferation by enhancing chemotherapeutic resistance in liver cancer. In the present review, we provide a comprehensive overview and discussion on the role of autophagy in the drug-resistant mechanisms of liver cancer.

The trillions of microbes that colonize and live around us govern the health of both plants and animals through a cascade of direct and indirect mechanisms. Understanding of this enormous and largely untapped microbial diversity has been the focus of microbial research from the past few decades or so. Amidst the advancements in sequencing technologies, significant progress has been made to taxonomically and functionally catalogue these microbes and also to establish their exact role in the health and disease state. In comparison to the human microbiome, plants are also surrounded by a vast diversity of microbes that form complex ecological communities that affect plant growth and health through collective metabolic activities and interactions. This plant microbiome has a substantial influence on human health and environment via its passage through the nasal route and digestive tract and is responsible for changing our gut microbiome. This review primarily focused on the advances and challenges in microbiome research at the interface of plant and human, and role of microbiome at different compartments of the body’s ecosystems along with their correlation to health and diseases. This review also highlighted the potential therapies in modulating the gut microbiota and technologies for studying the microbiome.

Background: One of the main cause of thyroid disease is autoimmune thyroid disease and anti thyroid peroxidase (TPO) antibodies is a major marker of the condition. There are very few studies in the country regarding the etiology of thyroid disorders and hence this study is being conducted for it. Methods: This is retrospective cross sectional study from 28 January 2019 to 29 July 2019 done at National Academy of Medical Sciences, Bir Hospital, Kathmandu. The laboratory serum sample data of all Anti TPO antibody results from patients seeking treatment at the instituition were analyzed for age and gender variation. Anti TPO antibody titre of equal or more than 34 IU/ml was considered as positive. Results: Out of 768 samples analysed for study, 79.9% were of women and 20.1 % were of men. A total of 205 (26.7%) were positive for anti TPO antibodies of which 83.4% were women and 16.6% were men . Women had more patients with anti TPO antibodies positive as compared men (27.9 vs 21.1%). Mean Anti TPO titre were also more in women as compared to men (61.01 vs 48.20 IU/ml). Conclusions: About one fourth of the patients had siginificant titers of anti TPO antibodies suggestive of thyroid autoimmunity. Both prevalence of positive anti TPO antibody titres and the mean anti TPO antibody titre values were more in women as compared to men. Further well designed larger community studies are required.

Supplementation of concentrate feed during late pregnancy of doe is an approach to improve milk yield and kid performance after kidding. The experiment was conducted to find out appropriate level and duration of supplementation to the pregnant doe. The data of the experiment were analyzed applying Completely Randomized Design (CRD) with factorial arrangements with three replications. First factor used in the experiment was the duration of concentrate feeding (15 days, 30 days, 45 days and 60 days) and second was amount of concentrate supplemented (2.00%, 1.75%, 1.50% and 1.25% of their body weight). Birth weight, weaning weight, milk yield and kid mortality in different groups were recorded. Birth weight and weaning weight were found higher in 60 days supplemented group i.e. 2.3±0.23 kg and 10.94±0.41 kg, respectively. Both birth weight and weaning weight were also found higher with 2 percent concentrate feeding group than others i.e. 2.1±0.23 kg and 9.64±0.42 kg, respectively. Milk yield recorded for fourth week shows that higher milk yields were found in 2 percent concentrate supplemented group with 60 days time period. The result showed that by increasing the level of concentrate during late gestation period of does increased the birth weight, weaning weight of kids and increased milk yield of does. So the higher level of concentrate supplementation is required during 45 to 60 days of late gestation in does. Bang. J. Anim. Sci. 2019. 48 (1): 23-28

Continuous discharge of enteric viruses through treated wastewater is a potential threat to the environment and humans. This study aimed to investigate the occurrence and reduction of enteric viruses at two wastewater treatment plants (WWTPs) in the Kathmandu Valley, Nepal. Twenty-two samples (from the influent samples and effluent samples, n = 11 each) were collected at two WWTPs (WWTP A and WWTP B, installing oxidation ditch and non-aerated lagoon systems, respectively) between April and August 2018. Human adenoviruses, JC and BK polyomaviruses, Aichi virus 1, enteroviruses, noroviruses of genogroup I (NoVs-GI), group A rotaviruses, and human cosavirus, along with plant viruses (pepper mild mottle and tobacco mosaic viruses), were detected using quantitative PCR. The most prevalent enteric virus was NoVs-GI (100%), followed by human adenoviruses (95%), and enteroviruses and JC polyomaviruses (91%). Log10 reduction values of all tested viruses were found to be lower than those of fecal indicator bacteria. Both WWTPs were less efficient for the reduction of pathogens (p

An experiment was conducted at Gokuleshwor, Baitadi to evaluate the management practices of Lipaphiserysimi (Kalt.) during Rabi season in 2017/18.Field experiment was laid out in a randomized complete block design (RCBD) with 5 treatments and 3 replications. The treatments were:1) jholmol @250 ml/litre of water2) 2) Altineem @2.5ml/litre of water 3) Cow urine @250 ml/litre of water 4) Mustard cake @25kg/ha and 5) untreated (control). Each plot consists of 2m*2m (4m2). Field experiment showed that the highest reduction of Lipaphiserysimi (Kalt.) was achieved in jholmol followed by altineem but these two treatments were statistically at per during almost all the spray times. Thus, jholmol might be the best option in eco-friendly management of Lipaphiserysimi (Kalt).

Bovine tropical theileriosis (BTT) is a haemoprotozoan tick-borne disease that implicates huge losses to livestock in terms of considerable mortality and morbidity in tropical and subtropical regions of the globe. Currently available diagnostic methods have less specificity and sensitivity towards the detection of Theileria species. Therefore, an attempt was made to diagnose Theileria annulata by targeting a multi-copy gene, viz. mitochondrially encoded cytochrome b (MT-CYB) gene via polymerase chain reaction (PCR) in different agro-zones of India. 129 cattle blood samples were collected from major livestock rearing regions of India and processed for both molecular and microscopic techniques. Screening of Giemsa-stained thin blood smears was able to detect 14 samples (10.85%) as positive for T. annulata. However, the MT-CYB gene-based PCR assay detected 107 samples (82.94%) positive for T. annulata out of 129 samples. Furthermore, the MT-CYB gene-based PCR assay was standardized in terms of its sensitivity and specificity. Specificity of PCR assay was evaluated against other common haemoprotozoan parasites of tropical countries viz. Babesia bigemina, Anaplasma marginale and Trypanosoma evansi. The multi-copy MT-CYB gene-based PCR assay provided an optimum level of sensitivity (up to the level of 10 femtogram) and high specificity. Haematological examination (Hb, PCV and TLC) of 113 samples revealed significantly (p

Background: Identification of candidate reference genes for real time PCR study is a preliminary requirement to normalize experimental data and thus, deduce a reliable conclusion. Complex tissues like mouse mammary gland constitutes various cell types which makes it difficult to identify reference gene constantly expressing under different experimental conditions. Methods: In this study we have identified suitable reference genes for 4T1 tumor cell line derived from mouse mammary tumor cells. We have studied four genes namely Gapdh, Actb, Prdx1 and Ctbp1 for their expression stability in CPV2.NS1 post transfected 4T1 cells by Best Keeper. Result: By our study, three reference genes i.e. Prdx1, Gapdh and Ctbp1 were found to be quite correlated with the BestKeeper index, but by considering all three criteria of selection by BestKeeper algorithm, Prdx1 showed minimum standard deviation and coefficient of variation and was found to be ranked at first position by BestKeeper which suggests Prdx1 to be considered as better internal control gene among all other reference genes taken in our study for qPCR based experiments in 4T1 mouse mammary tumor cell line transfected with CPV2.NS1

Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSC) provide a powerful model system to uncover fundamental mechanisms that control cellular identity during mammalian development. Histone methylation governs gene expression programs that play a key role in the regulation of the balance between self-renewal and differentiation of ESCs. Lysine-specific demethylase 1 (LSD1, also known as KDM1A), the first identified histone lysine demethylase, demethylates H3K4me1/2 and H3K9me1/2 at target loci in a context-dependent manner. Moreover, it has also been shown to demethylate non-histone substrates playing a central role in the regulation of numerous cellular processes. In this review, we summarize current knowledge about LSD1 and the molecular mechanism by which LSD1 influences the stem cells state, including the regulatory circuitry underlying self-renewal and pluripotency.

Acholeplasma (A.) laidlawii is an opportunistic pathogen with the ability to disseminate resistance determinants to antibiotics, however, its resistance to macrolides has been less studied. The aim of the present study was to characterize the mechanisms responsible for the resistance to macrolides, tiamulin and lincomycin found in a strain of A. laidlawii isolated from a pig with pneumonia. MICs of erythromycin, 15- and 16-membered macrolides, tiamulin and lincomycin were determined by microdilution method with and without reserpine, an inhibitor of ABC efflux pumps and regions of the genome were sequenced. Reserpine only decreased lincomycin MIC but it did not change the MICs of macrolides and tiamulin. The analysis of the DNA sequence of 23S rRNA showed nucleotide substitutions at eight different positions, although none of them were at positions previously related to macrolide resistance. Five mutations were found in the L22 protein, one of them at the stop codon. In addition, two mutations were found in the amino acid sequence of L4. The combination of multiple mutations in the ribosomal proteins L22 and L4 together with substitutions in 23S rRNA DNA sequence was associated with the resistance to macrolides, the pleuromutilin and lincomycin in the studied A. laidlawii strain.