Carp edema virus in ornamental fish farming in India: A potential threat to koi carps but not to co-cultured Indian major carp or goldfish

254-262Koi sleepy disease caused by carp edema virus (CEV) of pox virus is a potential carp killer and poses a constant threat to co-cultured fish. Only limited studies are available on its occurrence from the eastern part of India. Here, we report a large-scale mortality of koi carps (Cyprinuscarpio koi)in ornamental fish farm of Choudwar, Cuttack, Odisha. The fish showed clinical signs of ulcers on body, patchy haemorrhages, massive necrosis of gills, and observed sleeping at the bottom of tanks before death. However, the goldfish maintained in the same tanks did not show any clinical signs or mortality. We noticed Trichodina infestation in the gills of affected animals and secondary bacterium Aeromonashydrophila in kidney tissue. The gills, liver and kidneys of koi carp were found positive for carp edema virus (CEV) (Poxviridae) in PCR followed by sequencing and blast search, and phylogenetic analysis. The damages to the gills and kidney along with the presence of intracytoplasmic eosinophilic inclusions in gill epithelial cells upon histopathology suggested viral association. Experimental challenge with CEV failed to reproduce the disease in Indian major carp and goldfish, the commonly co-cultured fish species with koi carp, though, the disease was reproduced in koi carp. To our best knowledge, it is the first report of CEV infection from the farm of the eastern part of the country. Another mortality incidence in ornamental shop retailer in the same locality also revealed the presence of CEV in koi carp and pointed possibly towards its wide spread. Observations from this study suggest the need for CEV disease surveillance in the country

Carp edema virus in ornamental fish farming in India: A potential threat to koi carps but not to co-cultured Indian major carp or goldfish

254-262Koi sleepy disease caused by carp edema virus (CEV) of pox virus is a potential carp killer and poses a constant threat to co-cultured fish. Only limited studies are available on its occurrence from the eastern part of India. Here, we report a large-scale mortality of koi carps (Cyprinuscarpio koi)in ornamental fish farm of Choudwar, Cuttack, Odisha. The fish showed clinical signs of ulcers on body, patchy haemorrhages, massive necrosis of gills, and observed sleeping at the bottom of tanks before death. However, the goldfish maintained in the same tanks did not show any clinical signs or mortality. We noticed Trichodina infestation in the gills of affected animals and secondary bacterium Aeromonashydrophila in kidney tissue. The gills, liver and kidneys of koi carp were found positive for carp edema virus (CEV) (Poxviridae) in PCR followed by sequencing and blast search, and phylogenetic analysis. The damages to the gills and kidney along with the presence of intracytoplasmic eosinophilic inclusions in gill epithelial cells upon histopathology suggested viral association. Experimental challenge with CEV failed to reproduce the disease in Indian major carp and goldfish, the commonly co-cultured fish species with koi carp, though, the disease was reproduced in koi carp. To our best knowledge, it is the first report of CEV infection from the farm of the eastern part of the country. Another mortality incidence in ornamental shop retailer in the same locality also revealed the presence of CEV in koi carp and pointed possibly towards its wide spread. Observations from this study suggest the need for CEV disease surveillance in the country

Semi-analytical approach-based studies of the squeeze film lubrication between rough porous annular discs: Rabinowitsch fluid model

In recent years, there has been much interest in the effects of porosity and surface roughness (SR) or geometric irregularities between two moving plates under hydrodynamic lubrication. Porous bearings are used extensively in wide range of equipment, including computers, office equipment, home appliances, electric motors, and vehicles. In light of the importance of the aforementioned applications, we explored how SR and porous materials affect annular discs under the condition of a squeeze film. A five-point Gauss quadrature integral formula has been used to examine the characteristics of annular discs and a small perturbation method has been used to discretise the governing Rabinowitsch fluid flow (RFF) equations. The impact of nonlinear parameters on the behaviour of porosity and SR have been visualised in terms of film pressure (FP), load carrying capacity (LCC), and squeeze response time (SRT) of annular discs. Under the conditions of pseudoplastic and dilatant fluids, the effects of SR and porous materials between annular discs have been estimated in the form of the film pressure, LCC, and SRT and are presented in this manuscript as tables and graphs. According to the findings, the performance of an annular disc is significantly affected by porous material and radial roughness patterns. In addition, when RFF is carried through a rough surface and porous media, the performance is found to improve for dilatant fluids but suffer for pseudoplastic fluids

Leishmaniasis: Plants as a source of antileishmanial agents

Leishmania infection causes a group of tropical diseases and has remained neglected for decades. It spreads by sandfly vector and is one of the most fatal protozoan diseases after malaria. Leishmaniases are a group of diseases caused by the infection of different Leishmania species and display clinically different forms like “Visceral leishmaniasis” (VL), “mucocutaneous leishmaniasis” and “cutaneous leishmaniasis” (CL). Approximately one billion people living in an endemic area are at high risk. Three hundred thousand cases of VL are reported annually and around twenty thousand people die every year, proving it as one of the most lethal forms of leishmaniasis. Until now, no effective vaccine could be made. There is an increase in drug resistance in the case of conventional drugs. New synthetic drugs are either too costly or have side effects. Requirements of new drugs are of utmost importance to control this situation. Plants provide a source of unlimited chemical diversity, which can be screened for antileishmanial activities. Moreover, their low cost and less or no side effects make them idle candidates in the search of new antileishmanial drugs

Reliability Analysis of Radiation Tolerant Low Voltage CCCII Circuit For Space Applications

In this paper, the impact of radiation on the MOS devices is investigated on recently reported programmablesecond generation Current Controlled Conveyor (CCCII) wherein some updates are suggested to take Hot Carrier Injection, Bias Temperature Instability, and Time Dependent Dielectric Breakdown into account. As radiation is yet another important factor that causes change in threshold voltage, the transistors which are amenable to larger threshold shift and may lead to functional failure are identified first. Subsequently, three possibilities; uses of all thin oxide devices, all thick oxide devices, and mixed devices are being investigate and it is found that while using mixed devices, the circuit becomes functional at lower voltage without any effective increase in leakage current. Architecture is updated to enhance the performance of circuits under time-based ageing and radiation environment. The major challenge is to control dynamic leakage and radiative noise due to imposed radiation. All simulations are carried out using 28nm CMOS technology models in Cadence Virtuoso environment using ±1.0V supply voltage and results have been verified with post layout netlist. Proposed circuit can function at low voltage with the reduced degradation for 8 years at 25 °C consumes less area as compared to the existing CCCII circuit with 0.008 FIT value

Platelet protective efficacy of 3,4,5 trisubstituted isoxazole analogue by inhibiting ROS-mediated apoptosis and platelet aggregation

Thrombocytopenia is a major hematological concern in oxidative stress-associated pathologies and chronic clinical disorders, where premature platelet destruction severely affects the normal functioning of thrombosis and hemostasis. In addition, frequent exposure of platelets to chemical entities and therapeutic drugs immensely contributes in the development of thrombocytopenia leading to huge platelet loss, which might be fatal sometimes. Till date, there are only few platelet protective molecules known to combat thrombocytopenia. Hence, small molecule therapeutics are extremely in need to relieve the burden on limited treatment strategies of thrombocytopenia. In this study, we have synthesized a series of novel 3,4,5 trisubstituted isoxazole derivatives, among which compound 4a [4-methoxy-N'-(5-methyl-3-phenylisoxazole-4-carbonyl) benzenesulfonohydrazide] was found to significantly ameliorate the oxidative stress-induced platelet apoptosis by restoring various apoptotic markers such as ROS content, cytosolic Ca(2+) levels, eIF2-α phosphorylation, mitochondrial membrane depolarization, cytochrome c release, caspase activation, PS externalization, and cytotoxicity markers. Additionally, compound 4a dose dependently inhibits collagen-induced platelet aggregation. Hence, compound 4a can be considered as a prospective molecule in the treatment regime of platelet activation and apoptosis and other clinical conditions of thrombocytopenia. Further studies might ensure the use of compound 4a as a supplementary therapeutic agent to treat, thrombosis and CVD-associated complications. Over all, the study reveals a platelet protective efficacy of novel isoxazole derivative 4a with a potential to combat oxidative stress-induced platelet apoptosis

The Unusual Monomer Recognition of Guanine-Containing Mixed Sequence DNA by a Dithiophene Heterocyclic Diamidine

DB1255 is a symmetrical diamidinophenyl-dithiophene that exhibits cellular activity by binding to DNA and inhibiting binding of ERG, an ETS family transcription factor that is commonly overexpressed or translocated in leukemia and prostate cancer [Nhili, R., Peixoto, P., Depauw, S., Flajollet, S., Dezitter, X., Munde, M. M., Ismail, M. A., Kumar, A., Farahat, A. A., Stephens, C. E., Duterque-Coquillaud, M., Wilson, W. D., Boykin, D. W., and David-Cordonnier, M. H. (2013) Nucleic Acids Res. 41, 125−138]. Because transcription factor inhibition is complex but is an attractive area for anticancer and antiparasitic drug development, we have evaluated the DNA interactions of additional derivatives of DB1255 to gain an improved understanding of the biophysical chemistry of complex function and inhibition. DNase I footprinting, biosensor surface plasmon resonance, and circular dichroism experiments show that DB1255 has an unusual and strong monomer binding mode in minor groove sites that contain a single GC base pair flanked by AT base pairs, for example, 5′-ATGAT-3′. Closely related derivatives, such as compounds with the thiophene replaced with furan or selenophane, bind very weakly to GC-containing sequences and do not have biological activity. DB1255 is selective for the ATGAT site; however, a similar sequence, 5′-ATGAC-3′, binds DB1255 more weakly and does not produce a footprint. Molecular docking studies show that the two thiophene sulfur atoms form strong, bifurcated hydrogen bond-type interactions with the G-N-H sequence that extends into the minor groove while the amidines form hydrogen bonds to the flanking AT base pairs. The central dithiophene unit of DB1255 thus forms an excellent, but unexpected, single-GC base pair recognition module in a monomer minor groove complex

Targeting the DNA-binding activity of the human ERG transcription factor using new heterocyclic dithiophene diamidines

Direct modulation of gene expression by targeting oncogenic transcription factors is a new area of research for cancer treatment. ERG, an ETS-family transcription factor, is commonly over-expressed or translocated in leukaemia and prostate carcinoma. In this work, we selected the di-(thiophene-phenylamidine) compound DB1255 as an ERG/DNA binding inhibitor using a screening test of synthetic inhibitors of the ERG/DNA interaction followed by electrophoretic mobility shift assays (EMSA) validation. Spectrometry, footprint and biosensor-surface plasmon resonance analyses of the DB1255/DNA interaction evidenced sequence selectivity and groove binding as dimer. Additional EMSA evidenced the precise DNA-binding sequence required for optimal DB1255/DNA binding and thus for an efficient ERG/DNA complex inhibition. We further highlighted the structure activity relationshipsfrom comparison with derivatives. In cellulo luciferase assay confirmed this modulation both with the constructed optimal sequences and the Osteopontin promoter known to be regulated by ERG and which ERG-binding site was protected from DNaseI digestion on binding of DB1255. These data showed for the first time the ERG/DNA complex modulation, both in vitro and in cells, by a heterocyclic diamidine that specifically targets a portion of the ERG DNA recognition site