Redefining high risk multiple myeloma with an APOBEC/Inflammation-based classifier.

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Mutational impact of APOBEC3A and APOBEC3B in a human cell line and comparisons to breast cancer.

A prominent source of mutation in cancer is single-stranded DNA cytosine deamination by cellular APOBEC3 enzymes, which results in signature C-to-T and C-to-G mutations in TCA and TCT motifs. Although multiple enzymes have been implicated, reports conflict and it is unclear which protein(s) are responsible. Here we report the development of a selectable system to quantify genome mutation and demonstrate its utility by comparing the mutagenic activities of three leading candidates-APOBEC3A, APOBEC3B, and APOBEC3H.

APOBEC3B regulates R-loops and promotes transcription-associated mutagenesis in cancer.

The single-stranded DNA cytosine-to-uracil deaminase APOBEC3B is an antiviral protein implicated in cancer. However, its substrates in cells are not fully delineated. Here APOBEC3B proteomics reveal interactions with a surprising number of R-loop factors.

Forces on and in the cell walls of living plants.

Environmental influences and differential growth subject plants to mechanical forces. Forces on the whole plant resolve into tensile forces on its primary cell walls and both tensile and compression forces on the secondary cell wall layers of woody tissues. Forces on cell walls are further resolved into forces on cellulose microfibrils and the noncellulosic polymers between them.

Primary mucosal melanomas of the head and neck are characterised by overexpression of the DNA mutating enzyme APOBEC3B.

Aims: Primary head/neck mucosal melanomas (MMs) are rare and exhibit aggressive biologic behaviour and elevated mutational loads. The molecular mechanisms responsible for high genomic instability observed in head/neck MMs remain elusive. The DNA cytosine deaminase APOBEC3B (A3B) constitutes a major endogenous source of mutation in human cancer.

Drying of virus-containing particles: modelling effects of droplet origin and composition.

Background And Purpose: Virus-containing aerosol droplets emitted by breathing, speech or coughing dry rapidly to equilibrium with ambient relative humidity (RH), increasing in solute concentration with effects on virus survival and decreasing in diameter with effects on sedimentation and respiratory uptake. The aim of this paper is to model the effect of ionic and macromolecular solutes on droplet drying and solute concentration.

Methods: Deliquescence-efflorescence concepts and Kohler theory were used to simulate the evolution of solute concentrations and water activity in respiratory droplets, starting from efflorescence data on mixed NaCl/KCl aerosols and osmotic pressure data on respiratory macromolecules.

Nanostructural deformation of high-stiffness spruce wood under tension.

Conifer wood is an exceptionally stiff and strong material when its cellulose microfibrils are well aligned. However, it is not well understood how the polymer components cellulose, hemicelluloses and lignin co-operate to resist tensile stress in wood. From X-ray scattering, neutron scattering and spectroscopic data, collected under tension and processed by novel methods, the ordered, disordered and hemicellulose-coated cellulose components comprising each microfibril were shown to stretch together and demonstrated concerted, viscous stress relaxation facilitated by water.

Aerosol Transmission of SARS-CoV-2: Physical Principles and Implications.

Evidence has emerged that SARS-CoV-2, the coronavirus that causes COVID-19, can be transmitted airborne in aerosol particles as well as in larger droplets or by surface deposits. This minireview outlines the underlying aerosol science, making links to aerosol research in other disciplines. SARS-CoV-2 is emitted in aerosol form during normal breathing by both asymptomatic and symptomatic people, remaining viable with a half-life of up to about an hour during which air movement can carry it considerable distances, although it simultaneously disperses.

Characterization of the mechanism by which the RB/E2F pathway controls expression of the cancer genomic DNA deaminase APOBEC3B.

APOBEC3B (A3B)-catalyzed DNA cytosine deamination contributes to the overall mutational landscape in breast cancer. Molecular mechanisms responsible for upregulation in cancer are poorly understood. Here we show that a single E2F cis-element mediates repression in normal cells and that expression is activated by its mutational disruption in a reporter construct or the endogenous gene.

APOBEC3A catalyzes mutation and drives carcinogenesis in vivo.

The APOBEC3 family of antiviral DNA cytosine deaminases is implicated as the second largest source of mutation in cancer. This mutational process may be a causal driver or inconsequential passenger to the overall tumor phenotype. We show that human APOBEC3A expression in murine colon and liver tissues increases tumorigenesis.

The DNA Cytosine Deaminase APOBEC3B is a Molecular Determinant of Platinum Responsiveness in Clear Cell Ovarian Cancer.

Purpose: Clear cell ovarian carcinoma (CCOC) is an aggressive disease that often demonstrates resistance to standard chemotherapies. Approximately 25% of patients with CCOC show a strong APOBEC mutation signature. Here, we determine which APOBEC3 enzymes are expressed in CCOC, establish clinical correlates, and identify a new biomarker for detection and intervention.

HIV-1 Vif Triggers Cell Cycle Arrest by Degrading Cellular PPP2R5 Phospho-regulators.

HIV-1 Vif hijacks a cellular ubiquitin ligase complex to degrade antiviral APOBEC3 enzymes and PP2A phosphatase regulators (PPP2R5A-E). APOBEC3 counteraction is essential for viral pathogenesis. However, Vif also functions through an unknown mechanism to induce G2 cell cycle arrest.

The deaminase APOBEC3B triggers the death of cells lacking uracil DNA glycosylase.

Human cells express up to 9 active DNA cytosine deaminases with functions in adaptive and innate immunity. Many cancers manifest an APOBEC mutation signature and APOBEC3B (A3B) is likely the main enzyme responsible. Although significant numbers of APOBEC signature mutations accumulate in tumor genomes, the majority of APOBEC-catalyzed uracil lesions are probably counteracted in an error-free manner by the uracil base excision repair pathway.

A Conserved Mechanism of APOBEC3 Relocalization by Herpesviral Ribonucleotide Reductase Large Subunits.

An integral part of the antiviral innate immune response is the APOBEC3 family of single-stranded DNA cytosine deaminases, which inhibits virus replication through deamination-dependent and -independent activities. Viruses have evolved mechanisms to counteract these enzymes, such as HIV-1 Vif-mediated formation of a ubiquitin ligase to degrade virus-restrictive APOBEC3 enzymes. A new example is Epstein-Barr virus (EBV) ribonucleotide reductase (RNR)-mediated inhibition of cellular APOBEC3B (A3B).

HIV-1 restriction by endogenous APOBEC3G in the myeloid cell line THP-1.

HIV-1 replication in CD4-positive T lymphocytes requires counteraction of multiple different innate antiviral mechanisms. Macrophage cells are also thought to provide a reservoir for HIV-1 replication but less is known in this cell type about virus restriction and counteraction mechanisms. Many studies have combined to demonstrate roles for APOBEC3D, APOBEC3F, APOBEC3G and APOBEC3H in HIV-1 restriction and mutation in CD4-positive T lymphocytes, whereas the APOBEC enzymes involved in HIV-1 restriction in macrophages have yet to be delineated fully.

Evolution of rotavirus C in humans and several domestic animal species.

Rotavirus C (RVC) causes enteric disease in multiple species, including humans, swine, bovines, and canines. To date, the evolutionary relationships of RVC populations circulating in different host species are poorly understood, owing to the low availability of genetic sequence data. To address this gap, we sequenced 45 RVC complete genomes from swine samples collected in the United States and Mexico.

Polyomavirus T Antigen Induces Expression Using an LXCXE-Dependent and TP53-Independent Mechanism.

APOBEC3B is a single-stranded DNA cytosine deaminase with beneficial innate antiviral functions. However, misregulated APOBEC3B can also be detrimental by inflicting APOBEC signature C-to-T and C-to-G mutations in genomic DNA of multiple cancer types. Polyomavirus and papillomavirus oncoproteins induce APOBEC3B overexpression, perhaps to their own benefit, but little is known about the cellular mechanisms hijacked by these viruses to do so.

Epstein-Barr virus BORF2 inhibits cellular APOBEC3B to preserve viral genome integrity.

The apolipoprotein B messenger RNA editing enzyme, catalytic polypeptide-like (APOBEC) family of single-stranded DNA (ssDNA) cytosine deaminases provides innate immunity against virus and transposon replication. A well-studied mechanism is APOBEC3G restriction of human immunodeficiency virus type 1, which is counteracted by a virus-encoded degradation mechanism. Accordingly, most work has focused on retroviruses with obligate ssDNA replication intermediates and it is unclear whether large double-stranded DNA (dsDNA) viruses may be similarly susceptible to restriction.

Mutation Signatures Including APOBEC in Cancer Cell Lines.

Background: Multiple endogenous and exogenous sources of DNA damage contribute to the overall mutation burden in cancer, with distinct and overlapping combinations contributing to each cancer type. Many mutation sources result in characteristic mutation signatures, which can be deduced from tumor genomic DNA sequences. Examples include spontaneous hydrolytic deamination of methyl-cytosine bases in CG motifs (AGEING signature) and C-to-T and C-to-G mutations in 5'-TC(A/T) motifs (APOBEC signature).

Structure of native cellulose microfibrils, the starting point for nanocellulose manufacture.

There is an emerging consensus that higher plants synthesize cellulose microfibrils that initially comprise 18 chains. However, the mean number of chains per microfibril is usually greater than 18, sometimes much greater. Microfibrils from woody tissues of conifers, grasses and dicotyledonous plants, and from organs like cotton hairs, all differ in detailed structure and mean diameter.

Genotypic and epitope characteristics of group A porcine rotavirus strains circulating in Canada.

Surveillance of Rotavirus A (RVA) infections in North America swine populations are limited and not performed over a significant time period to properly assess the diversity of RVA strains in swine. The VP7 (G) and VP4 (P) genes of 32 Canadian RVA strains, circulating between 2009 and 2015 were sequenced, identifying the G3P[13], G5P[7], G9P[7], G9[13], and G9[19] genotype combinations. The Canadian RVA strains were compared to the RVA strains present in the swine ProSystems RCE rotavirus vaccine.

Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular diseases.

Background: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death and disability worldwide, yet ASCVD risk factor control and secondary prevention rates remain low. A fixed-dose combination of blood pressure- and cholesterol-lowering and antiplatelet treatments into a single pill, or polypill, has been proposed as one strategy to reduce the global burden of ASCVD.

Objectives: To determine the effect of fixed-dose combination therapy on all-cause mortality, fatal and non-fatal ASCVD events, and adverse events.

Complete Genome Sequence of Porcine Epidemic Diarrhea Virus Strain COL/Cundinamarca/2014 from Colombia.

Porcine epidemic diarrhea virus (PEDV) has been found throughout Europe and Asia, and has emerged in North and South America. A whole genome sequence was obtained from a paraffin-embedded tissue sample from the Instituto Colombiano Agropecuario (ICA), Colombia through Next Generation Sequencing techniques to further understand the evolution of PEDV.

Hydrogen-Bonding Network and OH Stretch Vibration of Cellulose: Comparison of Computational Modeling with Polarized IR and SFG Spectra.

Hydrogen bonds play critical roles in noncovalent directional interactions determining the crystal structure of cellulose. Although diffraction studies accurately determined the coordinates of carbon and oxygen atoms in crystalline cellulose, the structural information on hydrogen atoms involved in hydrogen-bonding is still elusive. This could be complemented by vibrational spectroscopy; but the assignment of the OH stretch peaks has been controversial.