IDENTIFICATION OF LEAD COMPOUNDS WITH COBRA VENOM DETOXIFICATION ACTIVITY IN ANDROGRAPHIS PANICULATA (BURM. F.) NEES THROUGH IN SILICO METHOD

Objective: To validate the cobra venom detoxification activity in Andrographis paniculata and identification of lead molecules.Methods: The structures of phytochemicals were procured from databases or created by ChemSketch and CORINA. Of the14 cobra venom proteins selected as receptor molecules, the 3D structures of phospholipase A2 and cobrotoxin were retrieved from protein data bank and serine protease, L-amino acid oxidase and acetylcholinesterase were modelled. The structures of remaining nine proteins were retrieved from SWISSMODEL repository. The active sites of the receptor molecules were detected by Q-site Finder and Pocket Finder. Docking was carried out by AutoDock 4.2. To avoid error in lead identification, top ranked five hit molecules obtained in AutoDock were again docked by iGEMDOCK, FireDock and HEX server. The results were analyzed following Dempster-Shafer theory. The molecular property and biological activity of the lead molecules were predicted by molinspiration.Results: Docking results in AutoDock revealed that the plant having phytochemicals for detoxifying all venom proteins but only one potential hit molecule against each of the following proteins viz., cobramin A, cobramin B, long neurotoxin 1, long neurotoxin 2, long neurotoxin 3, long neurotoxin 4 and long neurotoxin 5 and several hit molecules (6-12) were obtained against phospholipase A2, cobrotoxin, cytotoxin 3, acetylcholinesterase, L-aminoacid oxidase, proteolase and serine protease. Therefore, in latter case lead molecules were identified through Dempster-Shafer theory. The theoretical prediction of drug likeliness and bioactivity of the molecules highlighted the plant as the best source of anti-cobra venom drug.Conclusion: The results substantiated its traditional use and further investigation on biological system is essential for evolving novel drug.Keywords: Andrographis paniculata, Cobra, Docking, Venom, Protein, Neurotoxin, Snake bit

Proteinuria in early detection of human leptospirosis

Background: Leptospirosis is an infectious disease caused by spirochetes bacteria Leptospira spp. and is reported from all over the world. As the clinical signs and symptoms of Leptospirosis often are nonspecific and the disease is early mistaken for other major infectious febrile illness, laboratory test to confirm the clinical diagnosis thus is essential for optimal treatment and patient management.Methods: Serum and urine samples were collected from patients clinically suspected cases of Leptospirosis. Preparations of urine concentrate by precipitation and centrifugation.Results: It was interesting to note that immunoglobulins are present in the urine protein concentrate of patients with Leptospirosis on the day of admission in the hospital, with urine albumin reports either positive or negative. By ELISA test it was noted that antibodies present in urine and serum were of both IgM and IgG class against the Leptospiral antigens from three pathogenic serovars and one non-pathogenicserovars. In the immunospot test which was done and compared with standard ELISA test for serum antibodies using same antigen showed that antibodies present in urine protein concentrate, which was collected on the day of admission when patients come with suspecting symptoms of Leptospirosis.Conclusions: Proteinuria is the most frequent abnormality noted in all patients at some stage of illness. This is the first report on the presence of immunoglobulins in urine samples, which were found to be of IgM and IgG classes. These findings are of significant diagnostic potential as a simple immune-spot test can be done for detecting anti-leptospiral antibodies in urine samples of suspected cases. The present attempt was aimed at developing an immunospot test, a simple and rapid diagnostic test to detect Leptospirosis using urine samples of clinically suspected patients of the infection at the earliest. It was found to be in good correlation with standard ELISA method which is being used to detect serum antibodies in Leptospira infected patients using the same antigen

EFFICACY TESTING OF ‘SOFT’ PESTICIDES FOR THE MANAGEMENT OF CABBAGE BUTTERFLY (PIERIS BRASSICAE NEPALENSIS DOUBLEDAY) IN SALYAN, NEPAL

Hit-or-miss use of chemical pesticides and benightedness on the long-term impacts of hard pesticides on plants, soil, human health, and environments in conjunction with the resurgence of cabbage butterfly are the major impediments to the production of cabbage across the globe. This study, thus, was executed to disinter the effective soft pesticides which can keep the Pieris brassicae nepalensis well below the economic injury level, minimize their resurgence or even eradicate them so as to surge the production and productivity of cabbage in Salyan district, Nepal from April to July 2022. The experiment was set down in one factorial randomized complete block design with soft pesticides: Neemix @5ml/l, Cow urine solution@ 1:10, Botanical extract fermented with cow urine (BEFCU)@1:5, Emamectin benzoate @2gm/l, Spinosad @0.3ml/l, Cypermethrin@2ml/l, and Control, were used as treatments and each treatment were replicated thrice. Mean larval population, percentage of infested leaves, average hole per infested leaves, head diameter, height, and yield of cabbage were the parameters that were documented during the entire experimental period. Spraying of soft pesticides unraveled significant sway in larval mortality as well as diminution in the damage. Zenithal reduction in the cabbage butterfly population was recorded on the application of Spinosad (80%) followed by Cypermethrin (71.29%), Emamectin benzoate (71.25%), and Neemix (67.22%). Similarly, the nadir percentage of damage on leaves was documented on the application of Spinosad and Cypermethrin followed by Emamection benzoate. Maximum head diameter (16.10 cm) and yield (23.44 Mt/ha) were obtained when cabbage was sprayed with Spinosad followed by Cypermethrin whereas minimum head diameter (13.37 cm) and yield (13.76 Mt/ha) was recorded with the control. Spinosad and Cypermethrin, thus, are superior soft pesticides for the management of cabbage butterfly relative to other treatments in Salyan district. Farmers, therefore, are suggested to exploit Spinosad and Cypermethrin for the control and management of cabbage butterfly in an attempt to boost the production and productivity of cabbage

Behavioral Phenotypes Associated with MPTP Induction of Partial Lesions in Common Marmosets (\u3cem\u3eCallithrix jacchus\u3c/em\u3e)

Parkinson’s disease is a chronic neurodegenerative disorder with the core motor features of resting tremor, bradykinesia, rigidity, and postural instability. Non-motor symptoms also occur, and include cognitive dysfunction, mood disorders, anosmia (loss of smell), and REM sleep disturbances. As the development of medications and other therapies for treatment of non-motor symptoms is ongoing, it is essential to have animal models that aid in understanding the neural changes underlying non-motor PD symptoms and serve as a testing ground for potential therapeutics. We investigated several non-motor symptoms in 10 adult male marmosets using the MPTP model, with both the full (n = 5) and partial (n = 5) MPTP dosing regimens. Baseline data in numerous domains were collected prior to dosing; assessments in these same domains occurred post-dosing for 12 weeks. Marmosets given the partial MPTP dose (designed to mimic the early stages of the disease) differed significantly from marmosets given the full MPTP dose in several ways, including behavior, olfactory discrimination, cognitive performance, and social responses. Importantly, while spontaneous recovery of PD motor symptoms has been previously reported in studies of MPTP monkeys and cats, we did not observe recovery of any non-motor symptoms. This suggests that the neurochemical mechanisms behind the non-motor symptoms of PD, which appear years before the onset of symptoms, are independent of the striatal dopaminergic transmission. We demonstrate the value of assessing a broad range of behavioral change to detect non-motor impairment, anosmia, and differences in socially appropriate responses, in the marmoset MPTP model of early PD

Effect of paddy straw plus nonforage fiber sources based complete rations with different levels of neutral detergent fiber on hemato-biochemical and mineral profile of lactating dairy cows

Aim: This study was conducted to assess the effect of feeding paddy straw plus nonforage fiber sources based complete rations with different levels of neutral detergent fiber (NDF) on hemato-biochemical and mineral parameters of lactating dairy cows. Materials and Methods: The study was conducted for 6 months in 18 lactating dairy cows, divided into three groups of six each, by feeding them on paddy straw plus nonforage fiber sources based complete rations containing different levels of NDF, in two phases of 3 months (90 days) each, being the early and mid lactation phases, respectively. Three isonitrogenous and isocaloric complete rations, T1, T2 and T3 with 25%, 30% and 35% NDF, respectively, were fed to the experimental animals. Blood samples were collected at the beginning and the end of each of the two phases to estimate the different hematological, plasma protein, and mineral parameters to know the overall health status of the animals and standard methods were followed to analyze the samples. Results: There was no significant difference (p>0.05) in various hematological parameters such as hemoglobin, glucose, and blood urea nitrogen (BUN) in blood; plasma protein parameters such as total protein, albumin, globulin and albumin: globulin ratio and mineral parameters such as plasma calcium and phosphorus levels at the beginning and end of Phase I (1st day and 90th day) and Phase II (91st day and 180th day) as well as between the three dietary treatments, with all the values being in the normal range for lactating dairy cows. Even though nonsignificant (p>0.05), the BUN values of animals fed on ration T1, both at the beginning and end of Phase I, were higher than that of animals fed on rations T2 and T3 because the diet T1 with lowest NDF and the highest soluble carbohydrate content underwent rapid fermentation in the rumen, produced more energy, which was utilized by the rumen microbes to degrade the protein in the feed to ammonia, the excess ammonia being transported to the liver and excreted through the blood resulting in a higher BUN content. Conclusion: Feeding of paddy straw plus nonforage fiber sources based complete rations with different levels of NDF had no effect on hemato-biochemical and mineral profile as well as overall health status of lactating dairy cows. However, the higher, BUN values found in cows fed on diet T1 with 25% NDF as compared to those fed on T2 and T3 with 30% and 35% NDF, respectively, indicate more wastage of protein in T1 as compared to T2 and T3, in early lactation

Current status of viral diseases affecting black pepper and cardamom

Black pepper and cardamom are the important spice crops grown in India and other countries. Viruses are one of the major yield limiting factors in both these spice crops. Viral diseases spread at a faster rate in these spices, as they are vegetatively propagated. Lack of sensitive detection methods has led to the widespread distribution of viral diseases in all black pepper and cardamom growing regions. The viruses infecting these two spice crops have now been identified; characterized and sensitive diagnostics have been developed. Integration of various approaches like use of resistant varieties, virus-free planting materials, vector control and cultural methods are required for the management of viral diseases. Rejuvenation of viral disease affected black pepper plantations through proper soil and plant health management were proved to be successful. The present review deals with characterization, diagnosis and management of viral diseases affecting black pepper and cardamom

Structures of FOX-4 cephamycinase in complex with transition-state analog inhibitors

Boronic acid transition-state analog inhibitors (BATSIs) are partners with β-lactam antibiotics for the treatment of complex bacterial infections. Herein, microbiological, biochemical, and structural findings on four BATSIs with the FOX-4 cephamycinase, a class C β-lactamase that rapidly hydrolyzes cefoxitin, are revealed. FOX-4 is an extended-spectrum class C cephalosporinase that demonstrates conformational flexibility when complexed with certain ligands. Like other β-lactamases of this class, studies on FOX-4 reveal important insights into structure–activity relationships. We show that SM23, a BATSI, shows both remarkable flexibility and affinity, binding similarly to other β-lactamases, yet retaining an IC50 value < 0.1 μM. Our analyses open up new opportunities for the design of novel transition-state analogs of class C enzymes

Bone Marrow-Derived Microglia-Based Neurturin Delivery Protects Against Dopaminergic Neurodegeneration in a Mouse Model of Parkinson\u27s Disease

Although neurotrophic factors have long been recognized as potent agents for protecting against neuronal degeneration, clinical success in treating Parkinson\u27s disease and other neurodegenerative disorders has been hindered by difficulties in delivery of trophic factors across the blood brain barrier (BBB). Bone marrow hematopoietic stem cell-based gene therapy is emerging as a promising tool for overcoming drug delivery problems, as myeloid cells can cross the BBB and are recruited in large numbers to sites of neurodegeneration, where they become activated microglia that can secrete trophic factors. We tested the efficacy of bone marrow-derived microglial delivery of neurturin (NTN) in protecting dopaminergic neurons against neurotoxin-induced death in mice. Bone marrow cells were transduced ex vivo with lentivirus expressing the NTN gene driven by a synthetic macrophage-specific promoter. Infected bone marrow cells were then collected and transplanted into recipient animals. Eight weeks after transplantation, the mice were injected with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropuridine (MPTP) for seven days to induce dopaminergic neurodegeneration. Microglia-mediated NTN delivery dramatically ameliorated MPTP-induced degeneration of tyrosine hydroxylase (TH)-positive neurons of the substantia nigra and their terminals in the striatum. Microglia-mediated NTN delivery also induced significant recovery of synaptic marker staining in the striatum of MPTP-treated animals. Functionally, NTN treatment restored MPTP-induced decline in general activity, rearing behavior, and food intake. Thus, bone marrow-derived microglia can serve as cellular vehicles for sustained delivery of neurotrophic factors capable of mitigating dopaminergic injury

Brilliant Photoluminescence and Triboluminescence from Ternary Complexes of Dy-III and Tb-III with 3-Phenyl-4-propanoy1-5-isoxazolonate and a Bidentate Phosphine Oxide Coligand

Three new lanthanide heterocyclic beta-diketonate complexes [Dy(PPI)(3)(EtOH)(2)] (1), [Dy(PPI)(3)(DPEPO)] (2), and [Tb(PPI)(3)(DPEPO)] (3) [where HPPI = 3-pheny1-4-propanoyl-5-isoxazolone and DPEPO = bis(2(diphenylphosphino)phenyl)ether oxide] have been synthesized and fully characterized. Single-crystal X-ray diffraction analyses reveal that these complexes are mononuclear and that the central Ln(III) ion is coordinated to eight oxygen atoms that are provided by three bidentate beta-diketonate ligands and ethanol or bidentate DPEPO in a distorted square antiprismatic geometry. These complexes have high molar absorption coefficients (up to 3 X 10(4) M-1 cm(-1) at 285 nm) and display strong visible and, for Dy-III, NIR luminescence upon irradiation at the ligand-centered band in the range 250-350 nm. The emission quantum yields and the luminescence lifetimes at room temperature are 3 +/- 0.5% and 15 +/- 1 us for 1, 12 +/- 2% and 33 +/- 1 mu s for 2, and 42 +/- 6% and 795 +/- 1 mu s for 3. Moreover, the crystals of 2 and 3 exhibit brilliant triboluminescence, visible in daylight