Search

Type 1 interferon (IFN-I) response is the first line of host defense against invading viruses. In the absence of definite mouse models, the role of IFN-I in SARS-CoV-2 infections remained to be perplexing. Here, we developed two mouse models, one with constitutively high IFN-I response (hACE2;Irgm1−/−) and the other with dampened IFN-I response (hACE2;Ifnar1−/−) to comprehend the role of IFN-I response during SARS-CoV-2 invasion. We found that hACE2;Irgm1−/−mice were resistant to lethal SARS-CoV-2 infection with substantially reduced cytokine storm and immunopathology. In striking contrast, a severe SARS-CoV-2 infection along with immune cells infiltration, inflammatory response, and enhanced pathology was observed in the lungs of hACE2;Ifnar1−/−mice. Additionally, hACE2;Ifnar1−/−mice were highly susceptible to SARS-CoV-2 neuroinvasion in the brain accompanied by immune cell infiltration, microglia/astrocytes activation, cytokine response, and demyelination of neurons. The hACE2;Irgm1−/−Ifnar1−/−double knockout mice or hACE2;Irgm1−/−mice treated with STING or RIPK2 pharmacological inhibitors displayed loss of the protective phenotypes observed in hACE2;Irgm1−/−mice suggesting that heightened IFN-I response accounts for the observed immunity. Taken together, we explicitly demonstrate that IFN-I protects from lethal SARS-CoV-2 infection, andIrgm1(IRGM) could be an excellent therapeutic target.GRAPHICAL ABSTRACT

Mitochondrial fitness is governed by mitochondrial quality control pathways comprising mitochondrial dynamics and mitochondrial-selective autophagy (mitophagy). Disruption of these processes has been implicated in many human diseases, including viral infections. Here, we report a comprehensive analysis of the effect of dengue infection on host mitochondrial homeostasis and its significance in dengue disease pathogenesis. Despite severe mitochondrial stress and injury, we observed that the pathways of mitochondrial quality control and mitochondrial biogenesis are paradoxically downregulated in dengue-infected human liver cells. This leads to the disruption of mitochondrial homeostasis and the onset of cellular injury and necrotic death in the infected cells. Interestingly, dengue promotes global autophagy but selectively disrupts mitochondrial-selective autophagy (mitophagy). Dengue downregulates the expression of PINK1 and Parkin, the two major proteins involved in tagging the damaged mitochondria for elimination through mitophagy. Mitophagy flux assays also suggest that Parkin-independent pathways of mitophagy are also inactive during dengue infection. Dengue infection also disrupts mitochondrial biogenesis by downregulating the master regulators PPARγ and PGC1α. Dengue-infected cells release mitochondrial damage-associated molecular patterns (mtDAMPs) such as mitochondrial DNA into the cytosol and extracellular milieu. Furthermore, the challenge of naive immune cells with culture supernatants from dengue-infected liver cells was sufficient to trigger proinflammatory signaling. In correlation with our

We model a sustainable supply chain with simultaneous consideration of greening and Corporate Social Responsibility by supplier and buyer and analyze it for four different decision alternatives. In the first two cases, a single supply chain agent looks after both greening and social responsibility, in the other two cases, one agent takes one of the responsibilities. We compared these four cases by considering both full information and asymmetric information about the buyer's marginal production cost. Using the supplier Stackelberg game, we obtained the optimal values of decision variables under both information scenarios. The supplier negotiates with the buyer using the wholesale price contract or the linear two-part tariff contract. The second one is the dominating choice. For this contract the value of information is also higher for all decision alternatives. We have revealed the conditions under which the supplier would be benefited by choosing the greening effort and where the buyer would be benefited by taking up social responsibility. Further, we have designed a cut-off policy and found that the supplier and buyer can trade without conflicts only at a high level of consumer sensitivity towards greening and social responsiveness. This result suggests that if sustainability is left completely on consumer pressure, then the supplier and the buyer may not incorporate sustainability in the supply chain practices. We could specify those consumer sensitivity levels under which there must be government regulations to derive sustainability.

Emergence of SARS-CoV-2 as a serious pandemic has altered the global socioeconomic dynamics. The wide prevalence, high death counts and rapid emergence of new variants urge for establishment of research infrastructure to facilitate rapid development of efficient therapeutic modalities and preventive measures. In agreement with this, five SARS-CoV2 strains (ILS01, ILS02, ILS03, ILS15 and ILS24) of four different clades (19A, 19B, 20A and 20B) were isolated from patient swab samples collected during the 1st COVID-19 wave in Odisha, India. The viral isolates were adapted to in-vitro cultures and further characterized to identify strain specific variations in viral growth characteristics. All the five isolates showed substantial amount of virus induced CPE however ILS03 belonging to 20A clade displayed highest level of CPE. Time kinetics experiment revealed spike protein expression was evident after 16th hours post infection in all five isolates. ILS03 induced around 90% of cytotoxicity. Further, the susceptibility of various cell lines (human hepatoma cell line (Huh-7), CaCo2 cell line, HEK-293T cells, Vero, Vero-E6, BHK-21, THP-1 cell line and RAW 264.7 cells) were assessed. Surprisingly, it was found that the human monocyte cells THP-1 and murine macrophage cell line RAW 264.7 were permissive to all the SARS-CoV-2 isolates. The neutralization susceptibility of viral isolates to vaccine-induced antibodies was determined using sera from individuals vaccinated in the Government run vaccine drive in India. The micro-neutralization assay suggested that both Covaxin and Covishield vaccines were equally effective (100% neutralization) against all of the isolates. The whole genome sequencing of culture adapted viral isolates and viral genome from patient oropharyngeal swab sample suggested that repetitive passaging of SARS-CoV2 virus in Vero-E6 cells did not lead to emergence of many mutations during the adaptation in cell culture. Phylogenetic analyses revealed that the five isolates clustered to respective clades. The major goal was to isolate and adapt SARS-CoV-2 viruses in in-vitro cell culture with minimal modification to facilitate research activities involved in understanding the molecular virology, host-virus interactions, application of these strains for drug discovery and animal challenge models development which eventually will contribute towards the development of effective and reliable therapeutics.

The Dengue virus (DENV) and Chikungunya virus (CHIKV) are the arboviruses that pose a threat to global public health. Coinfection and antibody-dependent enhancement are major areas of concern during DENV and CHIKV infections, which can alter the clinical severity. Acute hepatic illness is a common manifestation and major sign of disease severity upon infection with either dengue or chikungunya. Hence, in this study, we characterized the coexistence and interaction between both the viruses in human hepatic (Huh7) cells during the coinfection/superinfection scenario. We observed that prior presence of or subsequent superinfection with DENV enhanced CHIKV replication. However, prior CHIKV infection negatively affected DENV. In comparison to monoinfection, coinfection with both DENV and CHIKV resulted in lower infectivity as compared to monoinfections with modest suppression of CHIKV but dramatic suppression of DENV replication. Subsequent investigations revealed that subneutralizing levels of DENV or CHIKV anti-sera can respectively promote the ADE of CHIKV or DENV infection in FcγRII bearing human myelogenous leukemia cell line K562. Our observations suggest that CHIKV has a fitness advantage over DENV in hepatic cells and prior DENV infection may enhance CHIKV disease severity if the patient subsequently contracts CHIKV. This study highlights the natural possibility of dengue–chikungunya coinfection and their subsequent modulation in human hepatic cells. These observations have important implications in regions where both viruses are prevalent and calls for proper management of DENV-CHIKV coinfected patients.

Syrian golden hamsters (Mesocricetus auratus) infected by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) manifests lung pathology. In this study, efforts were made to check the infectivity of a local SARS‐CoV‐2 isolate in a self‐limiting and non‐lethal hamster model and evaluate the differential expression of lung proteins during acute infection and convalescence. The findings of this study confirm the infectivity of this isolate in vivo. Analysis of clinical parameters and tissue samples show the pathophysiological manifestation of SARS‐CoV‐2 infection similar to that reported earlier in COVID‐19 patients and hamsters infected with other isolates. However, diffuse alveolar damage (DAD), a common histopathological feature of human COVID‐19 was only occasionally noticed. The lung‐associated pathological changes were very prominent on the 4th day post‐infection (dpi), mostly resolved by 14 dpi. Here, we carried out the quantitative proteomic analysis of the lung tissues from SARS‐CoV‐2‐infected hamsters on day 4 and day 14 post‐infection. This resulted in the identification of 1585 proteins of which 68 proteins were significantly altered between both the infected groups. Pathway analysis revealed complement and coagulation cascade, platelet activation, ferroptosis, and focal adhesion as the top enriched pathways. In addition, we also identified altered expression of two pulmonary surfactant‐associated proteins (Sftpd and Sftpb), known for their protective role in lung function. Together, these findings will aid in understanding the mechanism(s) involved in SARS‐CoV‐2 pathogenesis and progression of the disease.

In this letter, a new configuration of a compact low-profile tapered antenna array has been proposed to reduce the first sidelobe level (FSLL) in two orthogonal planes using a small number of nonidentical rectangular microstrip antenna elements. The tapering coefficients corresponding to cosine-square distributions over a pedestal have been used to realize amplitude tapering in two orthogonal planes of an array for suppressed sidelobe levels. The FSLL of −17.5 dB in the E plane and −15.0 dB in the H plane is practically achieved. The simulated results are verified experimentally, which are in agreement.

Nanotechnology has gained increasing attention in the modern world. It deals with submicroscopic materials referred to as nanoparticles (NPs) of size ranging between 1–100 nm. The primary objective of nanotechnology is to modify the size and structure of NPs for their improved utility. Numerous approaches have been established for the synthesis of NPs including chemical, physical, photochemical, and biological methods. Methodologies based on physical and chemical strategies have their own limitations, such as the use of toxic substances, toxic by-product formation, and high energy requirement. The biological route for Ns synthesis has proven to be more efficient in being cost-effective and eco-friendly. The bio-derived method overcomes the limitations of physical and chemical approaches and is a greener route as well as the base for novel research applications. Over the past several years, plants, algae, and microorganisms including fungi, bacteria, and viruses already have served as nanofactories in the synthesis of NPs. Biologically synthesized NPs have shown enormous applications in the clinical field, and throughout biofuel industries. Nanotechnology also has played an important role in biofuel industries via numerous renewal energy productions. It also has been demonstrated successfully to deal with issues related to climate change.

COVID-19 that emerged as a global pandemic is caused by SARS-CoV-2 virus. The virus genome analysis during disease spread reveals about its evolution and transmission. We did whole genome sequencing of 225 clinical strains from the state of Odisha in eastern India using ARTIC protocol-based amplicon sequencing. Phylogenetic analysis identified the presence of all five reported clades 19A, 19B, 20A, 20B and 20C in the population. The analyses revealed two major routes for the introduction of the disease in India i.e. Europe and South-east Asia followed by local transmission. Interestingly, 19B clade was found to be much more prevalent in our sequenced genomes (17%) as compared to other genomes reported so far from India. The haplogroup analysis for clades showed evolution of 19A and 19B in parallel whereas the 20B and 20C appeared to evolve from 20A. Majority of the 19A and 19B clades were present in cases that migrated from Gujarat state in India suggesting it to be one of the major initial points of disease transmission in India during month of March and April. We found that with the time 20A and 20B clades evolved drastically that originated from central Europe. At the same time, it has been observed that 20A and 20B clades depicted selection of four common mutations i.e. 241 C>T (5’UTR), P323L in RdRP, F942F in NSP3 and D614G in the spike protein. We found an increase in the concordance of G614 mutation evolution with the viral load in clinical samples as evident from decreased Ct value of spike and Orf1ab gene in qPCR. Molecular modelling and docking analysis identified that D614G mutation enhanced interaction of spike with TMPRSS2 protease, which could impact the shedding of S1 domain and infectivity of the virus in host cells.

Fiber-optic gyroscope comes under the category of optical gyroscopes which works on the principle of Sagnac effect. This paper provides a crux of fiber-optic gyroscope and its working principle. Fiber-optic gyroscopes work on the principle of the Sagnac effect. In Sagnac effect, the light beam is split into two separate beams. These beams then propagate in opposite directions with respect to each other. When the setup is stationary, the beams travel in same path and reach the output without any delay, if the setup is rotating, then one beam travels less distance than the other beam, and at output these beams arrive at different time and undergo interference to produce a fringe pattern which is sensitive to the phase difference between the beams. Fiber-optic gyroscope works on the similar basis, with a difference that the beams are made to travel within an optical fiber. These beams are obtained by passing light through a coupler and launched into the fiber using a collimator. Fiber-optic gyroscope is majorly used in military and aeronautical-based applications.

It is essential to simplify the feed network in tapered antenna arrays to reduce its cost and complexity. Aperiodic arrays represent an interesting solution for sharp beam forming, simplification of feed network, and improvement of first side lobe level (FSLL). In this paper, a complete analysis based on variation of distances between elements based on standard aperture distribution coefficients for side lobe reduction is proposed. The procedure relies on varying the locations of the array elements to realize tapering for reduction in interference of wireless communication systems.

A design technique of an antenna array with amplitude distribution/tapering to suppress the first side lobe level by exploiting the property of the rectangular microstrip antenna (RMSA) is proposed. Non-identical antenna array elements have been designed using the RMSAs by varying their width and hence the gain (keeping the length and hence the frequency same) to obtain the amplitude distribution for a desired first side lobe level. This eliminates the need of a complicated feed network with unequal power division to realize amplitude tapering. The conceptualized design is verified for a number of corporate-fed arrays and an analysis is carried out to give design guidelines with respect to the number of elements in the array. A symmetric corporate-fed 8-element antenna array with a cosine-square over pedestal amplitude distribution, operating at 1.8 GHz, has been designed and fabricated to validate the proposed concept. There is a reasonable agreement between simulated and measured results.

Highly pathogenic avian influenza (HPAI) H5N1 viruses are a threat to poultry in Asia, Europe, Africa and North America. Here, we report isolation and characterization of H5N1 viruses isolated from ducks and turkeys in Kerala, Chandigarh and Uttar Pradesh, India between November 2014 and March 2015. Genetic and phylogenetic analyses of haemagglutinin gene identified that the virus belonged to a new clade 2.3.2.1c which has not been detected earlier in Indian poultry. The virus possessed molecular signature for high pathogenicity to chickens, which was corroborated by intravenous pathogenicity index of 2.96. The virus was a reassortant which derives its PB2 gene from H9N2 virus isolated in China during 2007-2013. However, the neuraminidase and internal genes are of H5N1 subtype. Phylogenetic and network analysis revealed that after detection in China in 2013/2014, the virus moved to Europe, West Africa and other Asian countries including India. The analyses further indicated multiple introductions of H5N1 virus in Indian poultry and internal spread in Kerala. One of the outbreaks in ducks in Kerala is linked to the H5N1 virus isolated from wild birds in Dubai suggesting movement of virus probably through migration of wild birds. However, the outbreaks in ducks in Chandigarh and Uttar Pradesh were from an unknown source in Asia which also contributed gene pools to the outbreaks in Europe and West Africa. The widespread incidence of the novel H5N1 HPAI is similar to the spread of clade 2.2 ("Qinghai-like") virus in 2005, and should be monitored to avoid threat to animal and public health.

The main feature of an antenna array is its ability to form and scan the shaped main beam by using the amplitude and phase inputs as the controlling parameters at element level. In this paper, a comprehensive analysis of various parameters of a uniformly spaced linear array with respect to a number of elements for different amplitude distribution/window functions has been presented. There is a general assumption that any given window function will realize the expected parameters of the array even for a small number of array elements. A systematic study has been done to bring out very clearly the minimum number of elements that is required to realize antenna performance for a particular amplitude distribution. Effect of number of elements to obtain the desired first side lobe level and efficiency is presented. Contributions have been made to discuss the effects on directivity, gain, and beamwidth of the linear array.

Series fed arrays with feed at the centre element have been used as a natural tapered array for first sidelobe level (FSLL) reduction. The fact that all elements of the series fed arrays do not receive equal power has been used to realize natural tapering in these arrays. An analysis with respect to number of elements and size of the elements for the series fed arrays used is clearly brought about.

The width of the Rectangular Microstrip Antenna (RMSA) is varied to change its gain and hence the aperture distribution of the series fed array in the E plane. In series fed antenna arrays, the aperture distribution (amplitude tapering) is realized by keeping the width of the central RMSA maximum and reducing the width of other elements as per the desired tapering. To realize uniform aperture distribution for centrally fed linear array, width of the RMSA has been varied in the reverse manner in comparison to the conventional tapering method to effectively realize uniform linear tapered array. An analysis with respect to number of elements and sharpness of tapering is presented and reduction of First Side Lobe Level (FSLL) is obtained. Simulated and experimental results are in good agreement.

The recent reports of human infection due to H6 subtype avian influenza viruses (AIV), which are prevalent in terrestrial poultry, indicate evolution of the virus to a possible pandemic strain. Here, we report antigenic and genetic characterization of two H6N2 viruses isolated from apparently healthy domestic ducks in Kerala and Assam, India during 2014 and 2015, respectively. Hemagglutination inhibition assay revealed antigenic divergence between the two isolates, which was corroborated by amino acid differences at 55 positions (15.98%) between their hemagglutinin (HA) 1.The sequence analyses indicated that both the viruses are avian origin with avian receptor specificity, low pathogenic to poultry and sensitive to oseltamivir. However, Kerala14 had V27I mutation marker for amantadine resistance in M2. The Assam15 virus had an additional N-linked glycosylation on HA2 (position 557) compared to Kerala14 virus. Phylogenetic analysis of the HA gene revealed that both the viruses belonged to distinct lineages (Eurasian and Asia II). Phylogeny of neuraminidase and internal gene segments revealed that both the viruses are novel reassortants and are genetically distinct with different gene constellations. The results suggest independent introductions of the two H6N2 viruses into India and migratory wild birds in the Central Asian flyway might be the source of H6N2 viruses in ducks in India. Therefore, continued AIV surveillance in poultry and wild birds is essential for early detection of emergence of novel strains with pandemic potential and control of their spread.

An antenna array with modified compact feed has been designed with non-identical elements using cosine square amplitude distribution with the purpose of reducing the first side lobe level. The proposed feed network uses an overall area of 25.47% less than that of a similar array with conventional corporate feed network. Experimental results of this six element array validate the theoretical parameters.

We read with interest the paper by Ter Haar et al describing 187 patients with undefined autoinflammatory syndromes, some of whom had variants of unknown significance (VOUS) in the known genes.1 Patients with genetic mutations had a higher frequency of family history of similar disorder, suggesting that these variants may have some role to play. We report a 4-year-old girl who presented with familial cold autoinflammatory syndrome-2 (FCAS2) phenotype and a novel mutation in leucine-rich repeat (LRR) domain of the nucleotide oligomerization domain (NOD)-like receptor protein 12 (NLRP12).2 3 This child had episodic fever each lasting a fortnight and occurring once or twice a month. It was associated with recurrent, watery, non-infective diarrhoea since birth. Stools were occasionally admixed with blood. Colonoscopy was normal but biopsy showed cryptitis. She had several infections in childhood: one probable meningitis, one pneumonia and two episodes of subcutaneous abscesses. She …

Thermodynamic protonotion constants of N-ortho xylyl thiovioluric acid [NOXTVA], N-para xylyl thiovioluric acid [NPXTVA], N- meta xylyl thiovioluric acid [NMXTVA] and N-a-naphtyl thiovioluric acid [NANTVA] and thermodynamic formation constants of the complexes of Cu (ll), Co(ll), Ni (ll), Pb (ll) and Zn (ll) with these compounds have been determined at three different temperatures in 80% v/v water dioxane mixture by potentiometric measurements. The thermodynamic functions corresponding to stepwise complexation processes have been calculated at 300C. The stepwise complexation is found to be predominantly as enthalpy driven process.

The present study evaluates the effects of chitooligosaccharides (COS) for the management of alloxan induced diabetes in mice. For the management of the carbohydrate metabolism in diabetes by the COS, the amount of glucose in blood along with quantification of glycogen in liver were measured and noted a significant recovery in respect to diabetic control group. As hyperlipidemia and oxidative stress are the disorders of diabetes so, we have also assessed the serum levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDLc), very low density lipoprotein cholesterol (VLDLc) and high density lipoprotein cholesterol (HDLc). For the recovery of oxidative stress the SOD MDA catalase in liver and GOT and GPT activities in serum were measured. The COS results a significant recovery in the levels of above mentioned biosensors of lipid profile when treated to experimentally induce diabetic mice. The effect of COS at the dose of 10mg/kg body weight was found to be a potent agent for diabetes and complication associated with this disease. The COS has no toxic effect in general which has been focused here by the monitoring of COS dose in normal healthy mice. The results of this study enlighted that the COS has antidiabetic, antihyperlipidemic and antioxidative activities.