Structural and functional insights into the enzymatic plasticity of the SARS-CoV-2 NiRAN domain.

The enzymatic activity of the SARS-CoV-2 nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain is essential for viral propagation, with three distinct activities associated with modification of the nsp9 N terminus, NMPylation, RNAylation, and deRNAylation/capping via a GDP-polyribonucleotidyltransferase reaction. The latter two activities comprise an unconventional mechanism for initiating viral RNA 5' cap formation, while the role of NMPylation is unclear. The structural mechanisms for these diverse enzymatic activities have not been properly delineated.

Structural and functional insights into the enzymatic plasticity of the SARS-CoV-2 NiRAN Domain.

The enzymatic activity of the SARS-CoV-2 nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain is essential for viral propagation, with three distinct activities associated with modification of the nsp9 N-terminus, NMPylation, RNAylation, and deRNAylation/capping via a GDP-polyribonucleotidyltransferase reaction. The latter two activities comprise an unconventional mechanism for initiating viral RNA 5'-cap formation, while the role of NMPylation is unclear. The structural mechanisms for these diverse enzymatic activities have not been properly delineated.

Structural basis of dual activation of cell division by the actinobacterial transcription factors WhiA and WhiB.

Studies of transcriptional initiation in different bacterial clades reveal diverse molecular mechanisms regulating this first step in gene expression. The WhiA and WhiB factors are both required to express cell division genes in Actinobacteria and are essential in notable pathogens such as . The WhiA/B regulons and binding sites have been elucidated in (), where they coordinate to activate sporulation septation.

Longitudinal change of reticular pseudodrusen area in ultrawide-field imaging.

This study aimed to investigate the longitudinal change in the reticular pseudodrusen (RPD) area in the fundus and its association with late age-related macular degeneration (AMD). 91 RPD eyes (55 patients; age 67.9 ± 7.

Chromosome Damage in Relation to Recent Radiation Exposure and Radiation Quality in Nuclear Power Plant Workers.

Ionizing radiation is a well-known carcinogen that causes genomic instability. However, the biological and carcinogenetic effects of occupational radiation exposure at low doses have not been extensively studied. The aim of this study was to assess chromosomal instability in power plant workers exposed to occupational radiation at low doses in South Korea.

Metabolites with SARS-CoV-2 Inhibitory Activity Identified from Human Microbiome Commensals.

The COVID-19 pandemic has highlighted the need to identify additional antiviral small molecules to complement existing therapies. Although increasing evidence suggests that metabolites produced by the human microbiome have diverse biological activities, their antiviral properties remain poorly explored. Using a cell-based SARS-CoV-2 infection assay, we screened culture broth extracts from a collection of phylogenetically diverse human-associated bacteria for the production of small molecules with antiviral activity.

Photoenzymatic Synthesis of α-Tertiary Amines by Engineered Flavin-Dependent "Ene"-Reductases.

α-Tertiary amines are a common motif in pharmaceutically important molecules but are challenging to prepare using asymmetric catalysis. Here, we demonstrate engineered flavin-dependent 'ene'-reductases (EREDs) can catalyze radical additions into oximes to prepare this motif. Two different EREDs were evolved into competent catalysts for this transformation with high levels of stereoselectivity.

EN-FACE IMAGING OF ATYPICAL EPIRETINAL TISSUE IN LAMELLAR MACULAR HOLE.

Purpose: To elucidate the significance of en-face optical coherence tomography imaging of atypical epiretinal tissue (AET) in the lamellar macular hole (LMH).

Methods: This study involved 29 eyes of 29 patients who underwent surgical treatment for LMH with AET. Best-corrected visual acuity, metamorphopsia assessment (M-score), and optical coherence tomography were evaluated before and 6 months after surgery.

Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex.

Backtracking, the reverse motion of the transcriptase enzyme on the nucleic acid template, is a universal regulatory feature of transcription in cellular organisms but its role in viruses is not established. Here we present evidence that backtracking extends into the viral realm, where backtracking by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-dependent RNA polymerase (RdRp) may aid viral transcription and replication. Structures of SARS-CoV-2 RdRp bound to the essential nsp13 helicase and RNA suggested the helicase facilitates backtracking.

Structural basis for backtracking by the SARS-CoV-2 replication-transcription complex.

Backtracking, the reverse motion of the transcriptase enzyme on the nucleic acid template, is a universal regulatory feature of transcription in cellular organisms but its role in viruses is not established. Here we present evidence that backtracking extends into the viral realm, where backtracking by the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) may aid viral transcription and replication. Structures of SARS-CoV-2 RdRp bound to the essential nsp13 helicase and RNA suggested the helicase facilitates backtracking.

Medial Epicanthoplasty: What Works and What Does Not.

Blepharoplasty is the most frequently performed cosmetic surgical procedure in Asia. The epicanthal fold, which is common in Asians, is characterized by a curved skin fold that partially hides the caruncle and lacrimal lake. The epicanthal fold may cause weakening of the esthetic appearance after blepharoplasty.

Controlled Segmentation of Metal Nanowire Array by Block Copolymer Lithography and Reversible Ion Loading.

Spatial arrangement of 1D nanomaterials may offer enormous opportunities for advanced electronics and photonics. Moreover, morphological complexity and chemical diversity in the nanoscale components may lead to unique properties that are hardly anticipated in randomly distributed homogeneous nanostructures. Here, controlled chemical segmentation of metal nanowire arrays using block copolymer lithography and subsequent reversible metal ion loading are demonstrated.

Highly tunable refractive index visible-light metasurface from block copolymer self-assembly.

The refractive index of natural transparent materials is limited to 2-3 throughout the visible wavelength range. Wider controllability of the refractive index is desired for novel optical applications such as nanoimaging and integrated photonics. We report that metamaterials consisting of period and symmetry-tunable self-assembled nanopatterns can provide a controllable refractive index medium for a broad wavelength range, including the visible region.

Mitochondrial ATP synthase activity is impaired by suppressed O-GlcNAcylation in Alzheimer's disease.

Glycosylation with O-linked β-N-acetylglucosamine (O-GlcNAc) is one of the protein glycosylations affecting various intracellular events. However, the role of O-GlcNAcylation in neurodegenerative diseases such as Alzheimer's disease (AD) is poorly understood. Mitochondrial adenosine 5'-triphosphate (ATP) synthase is a multiprotein complex that synthesizes ATP from ADP and Pi.

Direct Observation of a Carbon Filament in Water-Resistant Organic Memory.

The memory for the Internet of Things (IoT) requires versatile characteristics such as flexibility, wearability, and stability in outdoor environments. Resistive random access memory (RRAM) to harness a simple structure and organic material with good flexibility can be an attractive candidate for IoT memory. However, its solution-oriented process and unclear switching mechanism are critical problems.

Directed self-assembly of cylinder-forming diblock copolymers on sparse chemical patterns.

Using both theory and experiment, we investigate the possibility of creating perfectly ordered block copolymer nanostructures on sparsely patterned substrates. Our study focuses on scrutinizing the appropriate pattern conditions to avoid undesired morphologies or defects when depositing cylinder-forming AB diblock copolymer thin films on the substrates which are mostly neutral with periodic stripe regions preferring the minority domain. By systematically exploring the parameter space using self-consistent field theory (SCFT), the optimal conditions for target phases are determined, and the effects of the chemical pattern period and the block copolymer film thickness on the target phase stability are also studied.

A bivalent conjugate vaccine containing PspA families 1 and 2 has the potential to protect against a wide range of Streptococcus pneumoniae strains and Salmonella Typhi.

Previously we showed that conjugation of pneumococcal surface protein A (PspA) to Vi capsular polysaccharide from Salmonella Typhi enhanced the anti-PspA response without the need to add adjuvant. In the current study conjugates consisting of the α helical regions of PspA families 1 or 2 bound to Vi were used to vaccinate mice to test their ability to protect against a lethal intravenous challenge of a range of various strains of Streptococcus pneumoniae. Conjugate vaccine containing PspA family 1 provided good protection from PspA family 1 challenge strains but offered very little protection against PspA family 2 challenge strains.

Protection of mice against pandemic H1N1 influenza virus challenge after immunization with baculovirus-expressed stabilizing peptide fusion hemagglutinin protein.

Current influenza vaccines are produced in embryonated chicken eggs. However, egg-based vaccines have various problems. To address these problems, recombinant protein vaccines have been developed as new vaccine candidates.

Radiation-induced changes in DNA methylation and their relationship to chromosome aberrations in nuclear power plant workers.

Purpose: We investigated the association between occupational radiation exposure and DNA methylation changes in nuclear power plant workers. We also evaluated whether radiation- induced DNA methylation alterations are associated with chromosome aberrations.

Materials And Methods: The study population included 170 radiation-exposed workers and 30 controls.

Nanodomain swelling block copolymer lithography for morphology tunable metal nanopatterning.

Ordered metal nanopatterns are crucial requirements for electronics, magnetics, catalysts, photonics, and so on. Despite considerable progress in the synthetic route to metal nanostructures, highly ordered metal nanopatterning over a large-area is still challenging. Nanodomain swelling block copolymer lithography is presented as a general route to the systematic morphology tuning of metal nanopatterns from amphiphilic diblock copolymer self-assembly.

Cyto-/genotoxic effects of the ethanol extract of Chan Su, a traditional Chinese medicine, in human cancer cell lines.

Ethnopharmacological Relevance: Chan Su, an ethanolic extract from skin and parotid venom glands of the Bufo bufo gargarizans Cantor, is widely used as a traditional Chinese medicine for cancer therapy. Although the anti-cancer properties of Chan Su have been investigated, no information exists regarding whether Chan Su has genotoxic effects in cancer cells. The aim of the present study was to examine the cyto-/genotoxic effect of Chan Su in human breast carcinoma (MCF-7 cells), human lung carcinoma (A-549 cells), human T cell leukemia (Jurkat T cells), and normal human lymphocytes.

Enhanced cytotoxic and genotoxic effects of gadolinium following ELF-EMF irradiation in human lymphocytes.

There are many studies of Gd nephrotoxicity and neurotoxicity, whereas research on cyto- and genotoxicity in normal human lymphocytes is scarce. It is important to investigate the effect of extremely low-frequency electromagnetic fields (ELF-EMF) on Gd toxicity, as patients are co-exposed to Gd and ELF-EMF generated by MRI scanners. We investigated the cytotoxicity and genotoixcity of Gd and the possible enhancing effect of ELF-EMF on Gd toxicity in cultured human lymphocytes by performing a micronuclei (MN) assay, trypan blue dye exclusion, single cell gel electrophoresis, and apoptosis analyses using flow cytometry.

Selective Effects of Curcumin on CdSe/ZnS Quantum-dot-induced Phototoxicity Using UVA Irradiation in Normal Human Lymphocytes and Leukemia Cells.

Quantum dots (QDs) have received considerable attention due to their potential role in photosensitization during photodynamic therapy. Although QDS are attractive nanomaterials due to their novel and unique physicochemical properties, concerns about their toxicity remain. We suggest a combination strategy, CdSe/ZnS QDs together with curcumin, a natural yellow pigment from turmeric, to reduce QD-induced cytotoxicity.

Cytotoxicity and genotoxicity induced by photothermal effects of colloidal gold nanorods.

Gold nanorods (Au NRs) that absorb near-infrared (NIR) light have great potential in the field of nanomedicine. Photothermal therapy (PTT), a very attractive cancer therapy in nanomedicine, combines nanomaterials and light. The aim of this study was to elucidate the molecular mechanism involved in Au NR-mediated cytotoxic, genotoxic, and other biological responses, in the presence or absence of NIR irradiation.