Analysis of scanning force microscopy images of protein-induced DNA bending using simulations

Bending of DNA is a feature essential to the function of many DNA-binding proteins. Bending angles can be estimated with a variety of techniques, but most directly from images obtained using scanning force microscopy (SFM). Direct measurement of the bending angle using a tangent method often produces angles that deviate significantly from values obtained using other techniques. Here, we describe the application of SFM in combination with simulations of DNA as a means to estimate protein-induced bending angles in a reliable and unbiased fashion. In this manner, we were able to obtain accurate estimates for the bending angles induced by nuclear factor I, octamer-binding transcription factor 1, the human XPC-Rad23B complex

Papermaking at Hayle Mill

65 pages, 1 unnumbered leaf of plates : illustrations, samples, 1 folded map. Includes a book, Papermaking at Hayle Mill, 1808-1987 by Maureen Green; a map, The Loose Valley, 1856 with the mills on Loose Stream; Mill photographs; Sample papers; and 12 proof sheets for the book; all issued in a box. Printed in black, red, and blue. Contents printed inside the box: Hayle Mill book -- Loose Valley map -- Mill photographs -- Sample papers. Printed on Finale, the last paper made at Hayle Mill. ... The portrait of Samuel Green was prepared and printed on Epson Archival paper by Ellen Dorn Levitt who also scanned the watermarks and maps preparing them, with Claire Van Vliet, for platemaking. Much of the letterpress printing used polymer plates from Boxcar Press ... and was printed by Andrew Miller-Brown. ... the photographs were scanned by Ellen Dorn Levitt from old prints in the Hayle Mill Archive and cleaned up in Photoshop. They were printed by Emily Corrow on a Xerox Docucolor 240 copier in Hammermill 100lb archival cover copy paper --Colophon of book. Exposed stitch binding. Two color fabric covering on clamshell box, title printed on paper, mounted on box spine. Gift of the Museum on behalf of the original donor, Ruth Fine. Curated title for Fleet Library Special Collections exhibition By Hand: Women & Books Exhibit fall, 2021.https://digitalcommons.risd.edu/specialcollections_books_printmaking/1003/thumbnail.jp

HSF2BP Interacts with a Conserved Domain of BRCA2 and Is Required for Mouse Spermatogenesis

The tumor suppressor BRCA2 is essential for homologous recombination (HR), replication fork stability, and DNA interstrand crosslink repair in vertebrates. We identify HSF2BP, a protein previously described as testis specific and not characterized functionally, as an interactor of BRCA2 in mouse embryonic stem cells, where the 2 proteins form a constitutive complex. HSF2BP is transcribed in all cultured human cancer cell lines tested and elevated in some tumor samples. Inactivation of the mouse Hsf2bp gene results in male infertility due to a severe HR defect during spermatogenesis. The BRCA2-HSF2BP interaction is highly evolutionarily conserved and maps to armadillo repeats in HSF2BP and a 68-amino acid region between the BRC repeats and the DNA binding domain of human BRCA2 (Gly2270-Thr2337) encoded by exons 12 and 13. This region of BRCA2 does not harbor known cancer-associated missense mutations and may be involved in the reproductive rather than the tumor-suppressing function of BRCA2. BRCA2 is a key homologous recombination mediator in vertebrates. Brandsma et al. show that it directly interacts with a testis-expressed protein, HSF2BP, and that male mice deficient for HSF2BP are infertile due to a meiotic recombination defect. They also find that HSF2BP contributes to DNA repair in mouse embryonic stem cells

Denudation of the continental shelf between Britain and France at the glacial-interglacial timescale

The erosional morphology preserved at the sea bed in the eastern English Channel dominantly records denudation of the continental shelf by fluvial processes over multiple glacial-interglacial sea-level cycles rather than by catastrophic flooding through the Straits of Dover during the mid-Quaternary. Here, through the integration of multibeam bathymetry and shallow sub-bottom 2D seismic reflection profiles calibrated with vibrocore records, the first stratigraphic model of erosion and deposition on the eastern English Channel continental shelf is presented. Published Optical Stimulated Luminescence (OSL) and C ages were used to chronometrically constrain the stratigraphy and allow correlation of the continental shelf record with major climatic/sea-level periods. Five major erosion surfaces overlain by discrete sediment packages have been identified. The continental shelf in the eastern English Channel preserves a record of processes operating from Marine Isotope Stage (MIS) 6 to MIS 1. Planar and channelised erosion surfaces were formed by fluvial incision during lowstands or relative sea-level fall. The depth and lateral extent of incision was partly conditioned by underlying geology (rock type and tectonic structure), climatic conditions and changes in water and sediment discharge coupled to ice sheet dynamics and the drainage configuration of major rivers in Northwest Europe. Evidence for major erosion during or prior to MIS 6 is preserved. Fluvial sediments of MIS 2 age were identified within the Northern Palaeovalley, providing insights into the scale of erosion by normal fluvial regimes. Seismic and sedimentary facies indicate that deposition predominantly occurred during transgression when accommodation was created in palaeovalleys to allow discrete sediment bodies to form. Sediment reworking over multiple sea-level cycles (Saalian-Eemian-early Weichselian) by fluvial, coastal and marine processes created a multi-lateral, multi-storey succession of palaeovalley-fills that are preserved as a strath terrace. The data presented here reveal a composite erosional and depositional record that has undergone a high degree of reworking over multiple sea-level cycles leading to the preferential preservation of sediments associated with the most recent glacial-interglacial period

Geyserite in Hot-Spring Siliceous Sinter: Window on Earth’s Hottest Terrestrial (Paleo)environment and its Extreme Life

International audienceSiliceous hot-spring deposits, or sinters, typically form in active, terrestrial (on land), volcanic terrains where magmatically heated waters circulating through the shallow crust emerge at the Earth's surface as silica-charged geothermal fluids. Geyserites are sinters affiliated with the highest temperature (~ 75–100 °C), natural geothermal fluid emissions, comprising localized, lithologically distinctive, hydrothermal silica precipitates that develop around geysers, spouters and spring-vents. They demarcate the position of hot-fluid upflow zones useful for geothermal energy and epithermal mineral prospecting. Near-vent areas also are “extreme environment” settings for the growth of microbial biofilms at near-boiling temperatures. Microbial biosignatures (e.g., characteristic silicified microbial textures, carbon isotopes, genetic material, lipid biomarkers) may be extracted from modern geyserite. However, because of strong taphonomic filtering and subsequent diagenesis, fossils in geyserite are very rare in the pre-Quaternary sinter record which, in and of itself, is patchy in time and space back to about 400 Ma. Only a few old examples are known, such as geyserite reported from the Devonian Drummond Basin (Australia), Devonian Rhynie cherts (Scotland), and a new example described herein from the spectacularly well-preserved, Late Jurassic (150 Ma), Yellowstone-style geothermal landscapes of Patagonia, Argentina. There, geyserite is associated with fossil vent-mounds and silicified hydrothermal breccias of the Claudia sinter, which is geologically related to the world-class Cerro Vanguardia gold/silver deposit of the Deseado Massif, a part of the Chon Aike siliceous large igneous province. Tubular, filament-like micro-inclusions from Claudia were studied using integrated petrographic and laser micro-Raman analysis, the results of which suggest a biological origin. The putative fossils are enclosed within nodular geyserite, a texture typical of subaerial near-vent conditions. Overall, this worldwide review of geyserite confirms its significance as a mineralizing geological archive reflecting the nature of Earth's highest temperature, habitable terrestrial sedimentary environment. Hot-spring depositional settings also may serve as analogs for early Earth paleoenvironments because of their elevated temperature of formation, rapid mineralization by silica, and morphologically comparable carbonaceous material sourced from prokaryotes adapted to life at high temperatures

Crystal Structure and Functional Analysis of the SARS-Coronavirus RNA Cap 2′-O-Methyltransferase nsp10/nsp16 Complex

Cellular and viral S-adenosylmethionine-dependent methyltransferases are involved in many regulated processes such as metabolism, detoxification, signal transduction, chromatin remodeling, nucleic acid processing, and mRNA capping. The Severe Acute Respiratory Syndrome coronavirus nsp16 protein is a S-adenosylmethionine-dependent (nucleoside-2′-O)-methyltransferase only active in the presence of its activating partner nsp10. We report the nsp10/nsp16 complex structure at 2.0 Å resolution, which shows nsp10 bound to nsp16 through a ∼930 Å2 surface area in nsp10. Functional assays identify key residues involved in nsp10/nsp16 association, and in RNA binding or catalysis, the latter likely through a SN2-like mechanism. We present two other crystal structures, the inhibitor Sinefungin bound in the S-adenosylmethionine binding pocket and the tighter complex nsp10(Y96F)/nsp16, providing the first structural insight into the regulation of RNA capping enzymes in (+)RNA viruses

Panta Rhei benchmark dataset: socio-hydrological data of paired events of floods and droughts

As the adverse impacts of hydrological extremes increase in many regions of the world, a better understanding of the drivers of changes in risk and impacts is essential for effective flood and drought risk management and climate adaptation. However, there is currently a lack of comprehensive, empirical data about the processes, interactions and feedbacks in complex human-water systems leading to flood and drought impacts. Here we present a benchmark dataset containing socio-hydrological data of paired events, i.e., two floods or two droughts that occurred in the same area. The 45 paired events occurred in 42 different study areas and cover a wide range of socio-economic and hydro-climatic conditions. The dataset is unique in covering both floods and droughts, in the number of cases assessed, and in the quantity of socio-hydrological data. The benchmark dataset comprises: 1) detailed review style reports about the events and key processes between the two events of a pair; 2) the key data table containing variables that assess the indicators which characterise management shortcomings, hazard, exposure, vulnerability and impacts of all events; 3) a table of the indicators-of-change that indicate the differences between the first and second event of a pair. The advantages of the dataset are that it enables comparative analyses across all the paired events based on the indicators-of-change and allows for detailed context- and location-specific assessments based on the extensive data and reports of the individual study areas. The dataset can be used by the scientific community for exploratory data analyses e.g. focused on causal links between risk management, changes in hazard, exposure and vulnerability and flood or drought impacts. The data can also be used for the development, calibration and validation of socio-hydrological models. The dataset is available to the public through the GFZ Data Services (Kreibich et al. 2023, link for review: https://dataservices.gfz-potsdam.de/panmetaworks/review/923c14519deb04f83815ce108b48dd2581d57b90ce069bec9c948361028b8c85/).</p

Extending in vitro digestion models to specific human populations: Perspectives, practical tools and bio-relevant information

[EN] Background In vitro digestion models show great promise in facilitating the rationale design of foods. This paper provides a look into the current state of the art and outlines possible future paths for developments of digestion models recreating the diverse physiological conditions of specific groups of the human population. Scope and approach Based on a collective effort of experts, this paper outlines considerations and parameters needed for development of new in vitro digestion models, e.g. gastric pH, enzymatic activities, gastric emptying rate and more. These and other parameters are detrimental to the adequate development of in vitro models that enable deeper insight into matters of food luminal breakdown as well as nutrient and nutraceutical bioaccessibility. Subsequently, we present an overview of some new and emerging in vitro digestion models mirroring the gastro-intestinal conditions of infants, the elderly and patients of cystic fibrosis or gastric bypass surgery. Key findings and conclusions This paper calls for synchronization, harmonization and validation of potential developments in in vitro digestion models that would greatly facilitate manufacturing of foods tailored or even personalized, to a certain extent, to various strata of the human population.Shani-Levi, C.; Alvito, P.; Andrés Grau, AM.; Assunção, R.; Barbera, R.; Blanquet-Diot, S.; Bourlieu, C.... (2017). Extending in vitro digestion models to specific human populations: Perspectives, practical tools and bio-relevant information. Trends in Food Science & Technology. 60:52-63. https://doi.org/10.1016/j.tifs.2016.10.017S52636

Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci

To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with similar to 2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 x 10(-9)) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p <2.4 x 10(-6)). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 x 10(-7)) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 x 10(-15)). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 x 10(-8)). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups