The COVID‐19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) presents a great threat to human health. The interplay between the virus and host plays a crucial role in ...successful virus replication and transmission. Understanding host–virus interactions are essential for the development of new COVID‐19 treatment strategies. Here, we show that SARS‐CoV‐2 infection triggers redistribution of cyclin D1 and cyclin D3 from the nucleus to the cytoplasm, followed by proteasomal degradation. No changes to other cyclins or cyclin‐dependent kinases were observed. Further, cyclin D depletion was independent of SARS‐CoV‐2‐mediated cell cycle arrest in the early S phase or S/G2/M phase. Cyclin D3 knockdown by small‐interfering RNA specifically enhanced progeny virus titres in supernatants. Finally, cyclin D3 co‐immunoprecipitated with SARS‐CoV‐2 envelope (E) and membrane (M) proteins. We propose that cyclin D3 impairs the efficient incorporation of envelope protein into virions during assembly and is depleted during SARS‐CoV‐2 infection to restore efficient assembly and release of newly produced virions.
Synopsis
Many viruses, including coronaviruses, manipulate cell cycle progression through cyclin‐CDKs complexes. Surprisingly, cyclin D3 degradation induced by SARS‐CoV‐2 promotes infection not via cell cycle arrest but by relieving cyclin interference with virion assembly.
Productive SARS‐CoV‐2 infection induces cell cycle arrest and depletes cyclin D from infected cells.
Cell cycle arrest induced by SARS‐CoV‐2 is not dependent on cyclin D degradation.
Cyclin D3 knockdown enhances SARS‐CoV‐2 infection.
Cyclin D3 associates with envelope (E) and membrane (M) proteins of SARS‐CoV‐2 and impairs efficient envelope protein incorporation into virions.
Efficient assembly and release of newly produced SARS‐CoV‐2 virions depends on virus‐induced redistribution and degradation of host cell D‐type cyclins.
Efficient assembly and release of newly‐produced SARS‐CoV‐2 virions depends on virus‐induced redistribution and degradation of host cell D‐type cyclins.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This review article compiles the characteristics of resin based dental composites and an effort is made to point out their future perspectives. Recent research studies along with few earlier articles ...were studied to compile the synthesis schemes of commonly used monomers, their characteristics in terms of their physical, mechanical and polymerization process with selectivity towards the input parameters of polymerization process. This review covers surface modification processes of various filler particles using silanes, wear behaviour, antimicrobial behaviour along with its testing procedures to develop the fundamental knowledge of various characteristics of resin based composites. In the end of this review, possible areas of further interests are pointed out on the basis of literature review on resin based dental materials.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Immunotherapeutic manipulation of the antitumor immune response offers an attractive strategy to target genomic instability in cancer. A subset of tumor-specific somatic mutations can be translated ...into immunogenic and HLA-bound epitopes called neoantigens, which can induce the activation of helper and cytotoxic T lymphocytes. However, cancer immunoediting and immunosuppressive mechanisms often allow tumors to evade immune recognition. Recent evidence also suggests that the tumor neoantigen landscape extends beyond epitopes originating from nonsynonymous single-nucleotide variants in the coding exome. Here we review emerging approaches for identifying, prioritizing, and immunologically targeting personalized neoantigens using polyvalent cancer vaccines and T-cell receptor gene therapy. SIGNIFICANCE: Several major challenges currently impede the clinical efficacy of neoantigen-directed immunotherapy, such as the relative infrequency of immunogenic neoantigens, suboptimal potency and priming of
tumor-specific T cells, and tumor cell-intrinsic and -extrinsic mechanisms of immune evasion. A deeper understanding of these biological barriers could help facilitate the development of effective and durable immunotherapy for any type of cancer, including immunologically "cold" tumors that are otherwise therapeutically resistant.
Coal is the major fossil fuel used for power generation in India. For producing more and more coal, mining activities are increasing day by day. Coal mining activities lead to environmental changes ...to a large extent such as degradation in quality of air, water, soil, changes in landform, land use/land cover and vegetation distribution. Environmental Impact Assessment (EIA) is therefore important to study the nature and impact of mining activities on the environment. The present study includes a review of the environmental impact studies done on various specific aspects in India, which involve methodologies of field-site investigation, laboratory analysis and satellite data processing. The study could be broadly divided into two parts. Firstly, taking Jharia coal-field as a case study, the parameters/criteria affecting the environment have been identified. The parameters that are the most affected due to mining are air, water, soil, agricultural land, vegetation and, topography. Later, Analytical Hierarchy Process (AHP) has been used for prioritizing of these parameters/criteria to carry out EIA in Jharia coal-field. Upon analysis, air has been found to be the most affected followed by water, soil, vegetation, agricultural land and topography. Moreover, the alternatives for each parameter/criterion have also been prioritized. The proposed methodology will help in deriving relationships based on field, laboratory and satellite data analysis. Once these relationships are derived, steps could be taken by policy makers for modification of the existing mine policies and incorporating the new measures in future mine planning so as to reduce the impact of coal mining on the environment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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•Lignin is an underutilized profuse macromolecule; generated 1–2 x105 tons annually.•Comparative analysis of bio-chemical lignin valorization strategies was evaluated.•Progress ...insights of various lignin based promising applications were provided.•Cutting-edge synthetic and metabolic engineering strategies were investigated.•Critical analysis of life cycle, techno-economics & societal impacts were outlined.
The pulp and biorefining industries produce their waste as lignin, which is one of the most abundant renewable resources. So far, lignin has been remained severely underutilized and generally burnt in a boiler as a low-value fuel. To demonstrate lignin's potential as a value-added product, we will review market opportunities for lignin related applications by utilizing the thermo-chemical/biological depolymerization strategies (with or without catalysts) and their comparative evaluation. The application of lignin and its derived aromatics in various sectors such as cement industry, bitumen modifier, energy materials, agriculture, nanocomposite, biomedical, H2 source, biosensor and bioimaging have been summarized. This comprehensive review article also highlights the technical, economic, environmental, and socio-economic variable that affect the market value of lignin-derived by-products. The review shows the importance of lignin, and its derived products are a platform for future bioeconomy and sustainability.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
High-throughput genomic technologies have revealed a remarkably complex portrait of intratumor heterogeneity in cancer and have shown that tumors evolve through a reiterative process of genetic ...diversification and clonal selection. This discovery has challenged the classical paradigm of clonal dominance and brought attention to subclonal tumor cell populations that contribute to the cancer phenotype. Dynamic evolutionary models may explain how these populations grow within the ecosystem of tissues, including linear, branching, neutral, and punctuated patterns. Recent evidence in breast cancer favors branching and punctuated evolution driven by genome instability as well as nongenetic sources of heterogeneity, such as epigenetic variation, hierarchal tumor cell organization, and subclonal cell-cell interactions. Resolution of the full mutational landscape of tumors could help reconstruct their phylogenetic trees and trace the subclonal origins of therapeutic resistance, relapsed disease, and distant metastases, the major causes of cancer-related mortality. Real-time assessment of the tumor subclonal architecture, however, remains limited by the high rate of errors produced by most genome-wide sequencing methods as well as the practical difficulties associated with serial tumor genotyping in patients. This review focuses on novel approaches to mitigate these challenges using bulk tumor, liquid biopsies, single-cell analysis, and deep sequencing techniques. The origins of intratumor heterogeneity and the clinical, diagnostic, and therapeutic consequences in breast cancer are also explored.
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We present 5-year results from CheckMate 227 Part 1, in which nivolumab plus ipilimumab improved overall survival (OS) versus chemotherapy in patients with metastatic non-small-cell lung cancer, ...regardless of tumor programmed death ligand 1 (PD-L1) status.
Adults with stage IV/recurrent non-small-cell lung cancer without
mutations or
alterations and with tumor PD-L1 ≥ 1% or < 1% (n = 1739) were randomly assigned. Patients with tumor PD-L1 ≥ 1% were randomly assigned to first-line nivolumab plus ipilimumab, nivolumab alone, or chemotherapy. Patients with tumor PD-L1 < 1% were randomly assigned to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy. End points included exploratory 5-year results for efficacy, safety, and quality of life.
At a minimum follow-up of 61.3 months, 5-year OS rates were 24% versus 14% for nivolumab plus ipilimumab versus chemotherapy (PD-L1 ≥ 1%) and 19% versus 7% (PD-L1 < 1%). The median duration of response was 24.5 versus 6.7 months (PD-L1 ≥ 1%) and 19.4 versus 4.8 months (PD-L1 < 1%). Among patients surviving 5 years, 66% (PD-L1 ≥ 1%) and 64% (PD-L1 < 1%) were off nivolumab plus ipilimumab without initiating subsequent systemic anticancer treatment by the 5-year time point. Survival benefit continued after nivolumab plus ipilimumab discontinuation because of treatment-related adverse events, with a 5-year OS rate of 39% (combined PD-L1 ≥ 1% and < 1% populations). Quality of life in 5-year survivors treated with nivolumab plus ipilimumab was similar to that in the general US population through the 5-year follow-up. No new safety signals were observed.
With all patients off immunotherapy treatment for ≥ 3 years, nivolumab plus ipilimumab increased 5-year survivorship versus chemotherapy, including long-term, durable clinical benefit regardless of tumor PD-L1 expression. These data support nivolumab plus ipilimumab as an effective first-line treatment for patients with metastatic non-small-cell lung cancer.
Lignin is produced as a byproduct in cellulosic biorefinery as well in pulp and paper industries and has the potential for the synthesis of a variety of phenolics chemicals, biodegradable polymers, ...and high value-added chemicals surrogate to conventional petro-based fuels. Therefore, in this critical review, we emphasize the possible scenario for lignin isolation, transformation into value addition chemicals/materials for the economic viability of current biorefineries. Additionally, this review covers the chemical structure of lignocellulosic biomass/lignin, worldwide availability of lignin and describe various thermochemical (homogeneous/heterogeneous base/acid-catalyzed depolymerization, oxidative, hydrogenolysis etc.) and biotechnological developments for the production of bio-based low molecular weight phenolics, i.e. polyhydroxyalkanoates, vanillin, adipic acid, lipids etc. Besides, some functional chemicals applications, lignin-formaldehyde ion exchange resin, electrochemical and production of few targeted chemicals are also elaborated. Finally, we examine the challenges, opportunities and prospects way forward related to lignin valorization.
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•2G Lignin as a bio-based biorefineries platform for highly advanced products preparation.•Thermocatalytic and biotechnological approaches were emphasized for lignin value addition.•Thermo catalytic approach is an effective process for lignin valorization in bulk scale.•In biological valorization, adipic acid production is promising towards scale-up.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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