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The particular Single-Cell Sequencing: A stunning Light Perfect around the Dark Corner involving Cancer.
ATO reduces levels of viral SUMO-E2A protein, while increasing SUMO-PML, suggesting that ATO interferes with SUMOylation of proteins crucial for HAdV replication. It is concluded that ATO targets cellular processes key to HAdV replication and is relevant for the development of antiviral intervention strategies. © 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.Hypoxia inducible factors (HIFs) are the key transcription factors that allow cancer cells to survive hypoxia. HIF's stability is mainly controlled by von Hippel-Lindau (pVHL)-mediated ubiquitylation. Unlike sporadic clear-cell renal carcinomas, VHL mutation is rarely observed in hepatocellular carcinoma (HCC) and the regulatory mechanisms of pVHL-HIF signaling remain elusive. Here, it is shown that deubiquitylase ovarian tumor domain-containing 6B (OTUD6B) suppresses HCC metastasis through inhibiting the HIF activity. OTUD6B directly interacts with pVHL, decreases its ubiquitylation and proteasomal degradation to reduce HIF-1α accumulation in HCC cells under hypoxia. Cyclosporine A in vivo Surprisingly, OTUD6B limits the ubiquitylation of pVHL independent of its deubiquitylase activity. OTUD6B couples pVHL and elongin B/C to form more CBCVHL ligase complex, which protects pVHL from proteasomal degradation. Depletion of OTUD6B results in the dissociation of CBCVHL complex and the degradation of pVHL by Trp Asp repeat and suppressors of cytokine signaling box-containing protein 1 (WSB1). In human HCC tissues, the protein level of OTUD6B is positively correlated with pVHL, but negatively with HIF-1α and vascular endothelial growth factor. Low expression of OTUD6B predicts poor patient survival. Furthermore, OTUD6B gene is a direct transcriptional target of HIF-1α and upregulated upon hypoxia. These results indicate a previously unrecognized feedback loop consisting of OTUD6B, pVHL, and HIF-1α, and provide insights into the targeted hypoxic microenvironment for HCC therapy. © 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.The cell nucleus is constantly subjected to externally applied forces. During metazoan evolution, the nucleus has been optimized to allow physical deformability while protecting the genome under load. Aberrant nucleus mechanics can alter cell migration across narrow spaces in cancer metastasis and immune response and disrupt nucleus mechanosensitivity. Uncovering the mechanical roles of lamins and chromatin is imperative for understanding the implications of physiological forces on cells and nuclei. Lamin-knockout and -rescue fibroblasts and probed nucleus response to physiologically relevant stresses are generated. A minimal viscoelastic model is presented that captures dynamic resistance across different cell types, lamin composition, phosphorylation states, and chromatin condensation. The model is conserved at low and high loading and is validated by micropipette aspiration and nanoindentation rheology. A time scale emerges that separates between dominantly elastic and dominantly viscous regimes. While lamin-A and lamin-B1 contribute to nucleus stiffness, viscosity is specified mostly by lamin-A. Elastic and viscous association of lamin-B1 and lamin-A is supported by transcriptional and proteomic profiling analyses. Chromatin decondensation quantified by electron microscopy softens the nucleus unless lamin-A is expressed. A mechanical framework is provided for assessing nucleus response to applied forces in health and disease. © 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.RNA sequencing has greatly facilitated gene expression studies but is weak in studying temporal RNA dynamics; this issue can be addressed by analyzing nascent RNAs. A famous method for nascent RNA analysis is metabolic labeling with noncanonic nucleoside followed by affinity purification, however, purification processes can always introduce biases into data analysis. Here, a chemical method for nascent RNA sequencing that avoids affinity purification based on acrylonitrile-mediated uridine-to-cytidine (U-to-C) conversion (AMUC-seq) via 4-thiouridine (s4U) cyanoethylation is presented. This method converts s4U base-pairing with guanine through the nucleophilic addition of s4U to acrylonitrile. The high reaction efficiency permits AMUC-seq directly and efficiently to recover nascent RNA information from total RNAs. AMUC-seq is validated by being used to detect mRNA half-lives and investigating the direct gene targets of a G-quadruplex stabilizer, which can be regarded as potential anticancer drug, in human cells. Thousands of direct gene targets of this drug are verified (these genes are significantly enriched in cancer such as SRC and HRAS). AMUC-seq also confirms G-quadruplex stabilization that impacts RNA polyadenylation. These results show AMUC-seq is qualified for the study of temporal RNA dynamics, and it can be a promising strategy to study the therapeutic mechanism of transcription-modulating drugs. © 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.Surface plasmon polaritons (SPPs) are viable candidates for integration into on-chip nano-circuitry that allow access to high data bandwidths and low energy consumption. Metal-insulator-metal tunneling junctions (MIM-TJs) have recently been shown to excite and detect SPPs electrically; however, experimentally measured efficiencies and outcoupling mechanisms are not fully understood. It is shown that the MIM-TJ cavity SPP mode (MIM-SPP) can outcouple via three pathways to i) photons via scattering of MIM-SPP at the MIM-TJ interfaces, ii) SPPs at the metal-dielectric interfaces (bound-SPPs) by mode coupling through the electrodes, and iii) photons and bound-SPP modes by mode coupling at the MIM-TJ edges. It is also shown that, for Al-AlO x -Cr-Au MIM-TJs on glass, the MIM-SPP mode outcouples efficiently to bound-SPPs through either electrode (pathway 2); this outcoupling pathway can be selectively turned on and off by changing the respective electrode thickness. Outcoupling at the MIM-TJ edges (pathway 3) is efficient and sensitive to the edge topography, whereas most light emission originates from roughness-induced scattering of the MIM-SPP mode (pathway 1). Using an arbitrary roughness profile, it is demonstrated that various roughness facets can raise MIM-SPP outcoupling efficiencies to 0.62%. These results pave the way for understanding the topographical parameters needed to develop CMOS-compatible plasmonic circuitry elements. © 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.The emergence of the strain of coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and its impact on global health have made imperative the development of effective and safe vaccines for this lethal strain. link2 SARS-CoV-2 now adds to the list of coronavirus diseases that have threatened global health, along with the SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) coronaviruses that emerged in 2002/2003 and 2012, respectively. link3 As of April 2020, no vaccine is commercially available for these coronavirus strains. Nevertheless, the knowledge obtained from the vaccine development efforts for MERS and SARS can be of high value for COVID-19 (coronavirus disease 2019). Here, we review the past and ongoing vaccine development efforts for clinically relevant coronavirus strains with the intention that this information helps in the development of effective and safe vaccines for COVID-19. In addition, information from naturally exposed individuals and animal models to coronavirus strains is described for the same purpose of helping into the development of effective vaccines against COVID-19. © The Author(s) 2020.The implementation of nano/microelectronic devices requires efficient strategies for the realization of supramolecular structures with desired function and supported on appropriate substrates. This article illustrates a strategy based on the synthesis of thiophene oligomers having the same "sulfur-overrich" quaterthiophene inner core (non bonding interactional algorithm) and different terminal groups. Nano/microfibers are formed on surfaces having a morphology independent of the nature of the deposition substrate and displaying a wide tuning of properties that make the fibers optoelectronically suitable for application in devices. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.DNA-templated self-assembly represents a rich and growing subset of supramolecular chemistry where functional self-assemblies are programmed in a versatile manner using nucleic acids as readily-available and readily-tunable templates. In this review, we summarize the different DNA recognition modes and the basic supramolecular interactions at play in this context. We discuss the recent results that report the DNA-templated self-assembly of small molecules into complex yet precise nanoarrays, going from 1D to 3D architectures. Finally, we show their emerging functions as photonic/electronic nanowires, sensors, gene delivery vectors, and supramolecular catalysts, and their growing applications in a wide range of area from materials to biological sciences. © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.Heavy metal (HM) pollution in aquatic ecosystems has an adverse effect on both aquatic life forms as well as terrestrial living beings, including humans. Since HMs are recalcitrant, they accumulate in the environment and are subsequently biomagnified through the food chain. Conventional physical and chemical methods used to remove the HMs from aquatic habitats are usually expensive, slow, non-environment friendly, and mostly inefficient. On the contrary, phytoremediation and microbe-assisted remediation technologies have attracted immense attention in recent years and offer a better solution to the problem. These newly emerged remediation technologies are eco-friendly, efficient and cost-effective. Both phytoremediation and microbe-assisted remediation technologies adopt different mechanisms for HM bioremediation in aquatic ecosystems. Recent advancement of molecular tools has contributed significantly to better understand the mechanisms of metal adsorption, translocation, sequestration, and tolerance in plants and microbes. Albeit immense possibilities to use such bioremediation as a successful environmental clean-up technology, it is yet to be successfully implemented in the field conditions. This review article comprehensively discusses HM accumulation in Indian aquatic environments. Furthermore, it describes the effect of HMs accumulation in the aquatic environment and the role of phytoremediation as well as microbe-assisted remediation in mitigation of the HM toxicity. Finally, the review concludes with a note on the challenges, opportunities and future directions for bioremediation in the aquatic ecosystems. © King Abdulaziz City for Science and Technology 2020.In the present study, the effect of elevated CO2 on growth, physiology, yield and proteome was studied on two maize (Zea mays L.) varieties grown under Free-air CO2 enrichment. Growth in high CO2 (530 ppm) did not affect either photosynthesis or pigment contents in both varieties. Reduced MDA content, antioxidant and antioxidative enzymes levels were observed in both varieties in response to high CO2. PEHM-5 accumulated more biomass than SMH-3031 under eCO2. PEHM-5 also had more seed starch and total soluble sugar than SMH-3031. However, SMH-3031 had increased number of seed per cob than PEHM-5. Interestingly, thousand seed weight was significantly increased in PEHM-5 only, while it was decreased in SMH-3031 under eCO2. We observed increased seed size in PEHM-5, while the size of the SMH-3031 seeds remained unaltered. Leaf proteomics revealed more abundance of proteins related to Calvin cycle, protein synthesis assembly and degradation, defense and redox homeostasis in PEHM-5 that contributed to better growth and yield in elevated CO2.
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