181 research outputs found

    Homologous recombination prevents methylation-induced toxicity in Escherichia coli

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    Methylating agents such as N-methyl-N\u27-nitro-N-nitrosoguanidine (MNNG) and methyl methane sulfonate (MMS) produce a wide variety of N- and O-methylated bases in DNA, some of which can block replication fork progression. Homologous recombination is a mechanism by which chromosome replication can proceed despite the presence of lesions. The two major recombination pathways, RecBCD and RecFOR, which repair double-strand breaks (DSBs) and single-strand gaps respectively, are needed to protect against toxicity with the RecBCD system being more important. We find that recombination-deficient cell lines, such as recBCD recF, and ruvC recG, are as sensitive to the cytotoxic effects of MMS and MNNG as the most base excision repair (BER)-deficient (alkA tag) isogenic mutant strain. Recombination and BER-deficient double mutants (alkA tag recBCD) were more sensitive to MNNG and MMS than the single mutants suggesting that homologous recombination and BER play essential independent roles. Cells deleted for the polA (DNA polymerase I) or priA (primosome) genes are as sensitive to MMS and MNNG as alkA tag bacteria. Our results suggest that the mechanism of cytotoxicity by alkylating agents includes the necessity for homologous recombination to repair DSBs and single-strand gaps produced by DNA replication at blocking lesions or single-strand nicks resulting from AP-endonuclease action

    Salinity stress adaptation in finger millet – a mini review

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    Abiotic stressors like salt and drought are two examples that may harm crop production. Therefore, increasing production and creating stress-tolerant cultivars requires crop innovation in response to these stresses. Whole genome sequence (WGS) data releases are used for crop trait development. Tolerance to abiotic stress cannot be induced through single-gene engineering transformation. Plants like finger millet can be mined for undiscovered genes because they already have the gene in their genomes, but it is dormant. Therefore, abiotic stress-tolerant genes can be expressed in the same plant by RNA sequencing and transcriptomics by creating abiotic stress for agricultural development. New genes can have their profiles refined with the aid of this transcriptome research

    p53 null Fluorescent Yellow Direct Repeat (FYDR) mice have normal levels of homologous recombination

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    The tumor suppressor p53 is a transcription factor whose function is critical for maintaining genomic stability in mammalian cells. In response to DNA damage, p53 initiates a signaling cascade that results in cell cycle arrest, DNA repair or, if the damage is severe, programmed cell death. In addition, p53 interacts with repair proteins involved in homologous recombination. Mitotic homologous recombination (HR) plays an essential role in the repair of double-strand breaks (DSBs) and broken replication forks. Loss of function of either p53 or HR leads to an increased risk of cancer. Given the importance of both p53 and HR in maintaining genomic integrity, we analyzed the effect of p53 on HR in vivo using Fluorescent Yellow Direct Repeat (FYDR) mice as well as with the sister chromatid exchange (SCE) assay. FYDR mice carry a direct repeat substrate in which an HR event can yield a fluorescent phenotype. Here, we show that p53 status does not significantly affect spontaneous HR in adult pancreatic cells in vivo or in primary fibroblasts in vitro when assessed using the FYDR substrate and SCEs. In addition, primary fibroblasts from p53 null mice do not show increased susceptibility to DNA damage-induced HR when challenged with mitomycin C. Taken together, the FYDR assay and SCE analysis indicate that, for some tissues and cell types, p53 status does not greatly impact HR.National Institute of Environmental Health Sciences (ES02109)National Cancer Institute (U.S.) (R33CA112151)National Cancer Institute (U.S.) (R01CA79827)United States. Dept. of Energy (DE-FG01-04ER04-21)National Institute of Environmental Health Sciences (T32 ES007020, NIEHS Training Grant in Environmental Toxicology)National Science Foundation (U.S.) (Fellowship

    Burden of present-on-admission infections and health care-associated infections, by race and ethnicity

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    Background: In the United States incidence of sepsis and pneumonia differ by race, but it is unclear whether this is due to intrinsic factors or health care factors. Methods: We conducted a study of 52,006 patients hospitalized during 2006-2008 at a referral hospital in upper Manhattan. We examined how the prevalence of present-on-admission and health care-associated infection compared between non-Hispanic blacks, Hispanics, and non-Hispanic whites adjusting for sociodemographic factors, admission through the emergency department, and comorbid conditions. Results: Non-Hispanic blacks had 1.59-fold (95% confidence interval [CI], 1.29-1.96) and 1.55-fold (95% CI, 1.35-1.77) risk of community-acquired bloodstream infection and urinary tract infection compared with non-Hispanic whites. Hispanic patients had 1.31-fold (95% CI, 1.15-1.49) risk of presenting with community-acquired urinary tract infection compared with non-Hispanic whites. Controlling for admission through the emergency department, comorbidity, and neighborhood income attenuated the differences in prevalence of infections. Conclusions: We found that health disparities in present-on-admission infections might be largely explained by potential lack of ambulatory care, socioeconomic factors, and comorbidity

    Van der Waals Engineering of Ferromagnetic Semiconductor Heterostructures for Spin and Valleytronics

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    The integration of magnetic material with semiconductors has been fertile ground for fundamental science as well as of great practical interest toward the seamless integration of information processing and storage. Here we create van der Waals heterostructures formed by an ultrathin ferromagnetic semiconductor CrI3 and a monolayer of WSe2. We observe unprecedented control of the spin and valley pseudospin in WSe2, where we detect a large magnetic exchange field of nearly 13 T and rapid switching of the WSe2 valley splitting and polarization via flipping of the CrI3 magnetization. The WSe2 photoluminescence intensity strongly depends on the relative alignment between photo-excited spins in WSe2 and the CrI3 magnetization, due to ultrafast spin-dependent charge hopping across the heterostructure interface. The photoluminescence detection of valley pseudospin provides a simple and sensitive method to probe the intriguing domain dynamics in the ultrathin magnet, as well as the rich spin interactions within the heterostructure.Comment: Supplementary Materials included. To appear in Science Advance

    Electrical Control of 2D Magnetism in Bilayer CrI3

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    The challenge of controlling magnetism using electric fields raises fundamental questions and addresses technological needs such as low-dissipation magnetic memory. The recently reported two-dimensional (2D) magnets provide a new system for studying this problem owing to their unique magnetic properties. For instance, bilayer chromium triiodide (CrI3) behaves as a layered antiferromagnet with a magnetic field-driven metamagnetic transition. Here, we demonstrate electrostatic gate control of magnetism in CrI3 bilayers, probed by magneto-optical Kerr effect (MOKE) microscopy. At fixed magnetic fields near the metamagnetic transition, we realize voltage-controlled switching between antiferromagnetic and ferromagnetic states. At zero magnetic field, we demonstrate a time-reversal pair of layered antiferromagnetic states which exhibit spin-layer locking, leading to a remarkable linear dependence of their MOKE signals on gate voltage with opposite slopes. Our results pave the way for exploring new magnetoelectric phenomena and van der Waals spintronics based on 2D materials.Comment: To appear in Nature Nanotechnolog

    Extensive variation in the intelectin gene family in laboratory and wild mouse strains

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    Intelectins are a family of multimeric secreted proteins that bind microbe-specific glycans. Both genetic and functional studies have suggested that intelectins have an important role in innate immunity and are involved in the etiology of various human diseases, including inflammatory bowel disease. Experiments investigating the role of intelectins in human disease using mouse models are limited by the fact that there is not a clear one-to-one relationship between intelectin genes in humans and mice, and that the number of intelectin genes varies between different mouse strains. In this study we show by gene sequence and gene expression analysis that human intelectin-1 (ITLN1) has multiple orthologues in mice, including a functional homologue Itln1; however, human intelectin-2 has no such orthologue or homologue. We confirm that all sub-strains of the C57 mouse strain have a large deletion resulting in retention of only one intelectin gene, Itln1. The majority of laboratory strains have a full complement of six intelectin genes, except CAST, SPRET, SKIVE, MOLF and PANCEVO strains, which are derived from different mouse species/subspecies and encode different complements of intelectin genes. In wild mice, intelectin deletions are polymorphic in Mus musculus castaneus and Mus musculus domesticus. Further sequence analysis shows that Itln3 and Itln5 are polymorphic pseudogenes due to premature truncating mutations, and that mouse Itln1 has undergone recent adaptive evolution. Taken together, our study shows extensive diversity in intelectin genes in both laboratory and wild-mice, suggesting a pattern of birth-and-death evolution. In addition, our data provide a foundation for further experimental investigation of the role of intelectins in disease
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