Recruitment kinetics of DNA repair proteins Mdc1 and Rad52 but not 53BP1 depend on damage complexity.

The recruitment kinetics of double-strand break (DSB) signaling and repair proteins Mdc1, 53BP1 and Rad52 into radiation-induced foci was studied by live-cell fluorescence microscopy after ion microirradiation. To investigate the influence of damage density and complexity on recruitment kinetics, which cannot be done by UV laser irradiation used in former studies, we utilized 43 MeV carbon ions with high linear energy transfer per ion (LET = 370 keV/µm) to create a large fraction of clustered DSBs, thus forming complex DNA damage, and 20 MeV protons with low LET (LET = 2.6 keV/µm) to create mainly isolated DSBs. Kinetics for all three proteins was characterized by a time lag period T(0) after irradiation, during which no foci are formed. Subsequently, the proteins accumulate into foci with characteristic mean recruitment times τ(1). Mdc1 accumulates faster (T(0) = 17 ± 2 s, τ(1) = 98 ± 11 s) than 53BP1 (T(0) = 77 ± 7 s, τ(1) = 310 ± 60 s) after high LET irradiation. However, recruitment of Mdc1 slows down (T(0) = 73 ± 16 s, τ(1) = 1050 ± 270 s) after low LET irradiation. The recruitment kinetics of Rad52 is slower than that of Mdc1, but exhibits the same dependence on LET. In contrast, the mean recruitment time τ(1) of 53BP1 remains almost constant when varying LET. Comparison to literature data on Mdc1 recruitment after UV laser irradiation shows that this rather resembles recruitment after high than low LET ionizing radiation. So this work shows that damage quality has a large influence on repair processes and has to be considered when comparing different studies

A summary of water-quality and salt marsh monitoring, Humboldt Bay, California

This report summarizes data-collection activities associated with the U.S. Geological Survey Humboldt Bay Water-Quality and Salt Marsh Monitoring Project. This work was undertaken to gain a comprehensive understanding ofwater-quality conditions, salt marsh accretion processes, marsh-edge erosion, and soil-carbon storage in Humboldt Bay, California. Multiparameter sondes recorded water temperature, specific conductance, and turbidity at a 15-minute timestep at two U.S. Geological Survey water-quality stations: Mad River Slough near Arcata, California (U.S. Geological Survey station 405219124085601) and (2) Hookton Slough near Loleta, California (U.S. Geological Survey station 404038124131801). At each station, discrete water samples were collected to develop surrogate regression models that were used to compute a continuous time seriesof suspended-sediment concentration from continuously measured turbidity. Data loggers recorded water depth at a 6-minute timestep in the primary tidal channels (Mad River Slough and Hookton Slough) in two adjacent marshes (Mad River marsh and Hookton marsh). The marsh monitoring network included five study marshes. Three marshes (Mad River, Manila, and Jacoby) are in the northern embayment of Humboldt Bay and two marshes (White and Hookton) are in the southern embayment. Surface deposition and elevation change were measured using deep rod surface elevation tables and feldspar marker horizons. Sediment characteristics and soil-carbon storage were measured using a total of 10 shallow cores, distributed across 5 study marshes, collected using an Eijkelkamp peat sampler. Rates of marsh edge erosion (2010–19) were quantified in four marshes (Mad River, Manila, Jacoby, and White) by estimating changes in the areal extent of the vegetated marsh plain using repeat aerial imagery and light detection and ranging (LiDAR)-derived elevation data. During the monitoring period (2016–19), the mean suspended-sediment concentration computed for Hookton Slough (50±20 milligrams per liter [mg/L]) was higher than Mad River Slough (18±7 mg/L). Uncertainty in mean suspended-sediment concentration values is reported using a 90-percent confidence interval. Across the five study marshes, elevation change (+1.8±0.6 millimeters per year[mm/yr]) and surface deposition (+2.5±0.5 mm/yr) were lower than published values of local sea-level rise (4.9±0.8 mm/yr), and mean carbon density was 0.029±0.005 grams of carbon per cubic centimeter. From 2010 to 2019, marsh edge erosion and soil carbon loss were greatest in low-elevation marshes with the marsh edge characterized by a gentle transition from mudflat to vegetated marsh (herein, ramped edge morphology) and larger wind-wave exposure. Jacoby Creek marsh experienced the greatest edge erosion. In total, marsh edge erosion was responsible for 62.3 metric tons of estuarine soil carbon storage loss across four study marshes. Salt marshes are an important component of coastal carbon, which is frequently referred to as “blue carbon.” The monitoring data presented in this report provide fundamental information needed to manage blue carbon stocks, assess marsh vulnerability, inform sea-level rise adaptation planning, and build coastal resiliency to climate change

A prioritization protocol for coastal wetland restoration on Molokaʻi, Hawaiʻi

Hawaiian coastal wetlands provide important habitat for federally endangered waterbirds and socio-cultural resources for Native Hawaiians. Currently, Hawaiian coastal wetlands are degraded by development, sedimentation, and invasive species and, thus, require restoration. Little is known about their original structure and function due to the large-scale alteration of the lowland landscape since European contact. Here, we used 1) rapid field assessments of hydrology, vegetation, soils, and birds, 2) a comprehensive analysis of endangered bird habitat value, 3) site spatial characteristics, 4) sea-level rise projections for 2050 and 2100 and wetland migration potential, and 5) preferences of the Native Hawaiian community in a GIS site suitability analysis to prioritize restoration of coastal wetlands on the island of Molokaʻi. The site suitability analysis is the first, to our knowledge, to incorporate community preferences, habitat criteria for endangered waterbirds, and sea-level rise into prioritizing wetland sites for restoration. The rapid assessments showed that groundwater is a ubiquitous water source for coastal wetlands. A groundwater-fed, freshwater herbaceous peatland or “coastal fen” not previously described in Hawaiʻi was found adjacent to the coastline at a site being used to grow taro, a staple crop for Native Hawaiians. In traditional ecological knowledge, such a groundwater-fed, agro-ecological system is referred to as a loʻipūnāwai (spring pond). Overall, 39 plant species were found at the 12 sites; 26 of these were wetland species and 11 were native. Soil texture in the wetlands ranged from loamy sands to silt and silty clays and the mean % organic carbon content was 10.93% ± 12.24 (sd). In total, 79 federally endangered waterbirds, 13 Hawaiian coots (‘alae keʻokeʻo; Fulica alai) and 66 Hawaiian stilts (aeʻo; Himantopus mexicanus knudseni), were counted during the rapid field assessments. The site suitability analysis consistently ranked three sites the highest, Kaupapaloʻi o Kaʻamola, Kakahaiʻa National Wildlife Refuge, and ʻŌhiʻapilo Pond, under three different weighting approaches. Site prioritization represents both an actionable plan for coastal wetland restoration and an alternative protocol for restoration decision-making in places such as Hawaiʻi where no pristine “reference” sites exist for comparison

Treatment Motivations and Expectations in Patients with Actinic Keratosis: A German-Wide Multicenter, Cross-Sectional Trial

Patient-centered motives and expectations of the treatment of actinic keratoses (AK) have received little attention until now. Hence, we aimed to profile and cluster treatment motivations and expectations among patients with AK in a nationwide multicenter, cross-sectional study including patients from 14 German skin cancer centers. Patients were asked to complete a self-administered questionnaire. Treatment motives and expectations towards AK management were measured on a visual analogue scale from 1–10. Specific patient profiles were investigated with subgroup and correlation analysis. Overall, 403 patients were included. The highest motivation values were obtained for the items “avoid transition to invasive squamous cell carcinoma” (mean ± standard deviation; 8.98 ± 1.46), “AK are considered precancerous lesions” (8.72 ± 1.34) and “treating physician recommends treatment” (8.10 ± 2.37; p < 0.0001). The highest expectation values were observed for the items “effective lesion clearance” (8.36 ± 1.99), “safety” (8.20 ± 2.03) and “treatment-related costs are covered by health insurance” (8.00 ± 2.41; p < 0.0001). Patients aged ≥77 years and those with ≥7 lesions were identified at high risk of not undergoing any treatment due to intrinsic and extrinsic motivation deficits. Heat mapping of correlation analysis revealed four clusters with distinct motivation and expectation profiles. This study provides a patient-based heuristic tool for a personalized treatment decision in patients with AK

Evolutionary origins of hepatitis A virus in small mammals

The origins of human hepatitis A virus (HAV) are unknown. We conducted a targeted search for HAV-related viruses in small mammals sampled globally and discovered highly diversified viruses in bats, rodents, hedgehogs, and shrews. We demonstrate that these viruses share unique biological features with HAV, including structural, genomic, antigenic, and pathogenic properties. We found evidence of major shifts of HAV-related viruses between mammalian hosts in the past, suggesting both an origin of this viral genus in small mammals and a zoonotic origin of human HAV. Our data show that risk assessments for emerging viruses can benefit greatly from the analysis of viral infection patterns that evolved within animal reservoirs

Evolutionary origins of hepatitis A virus in small mammals

Hepatitis A virus (HAV) is an ancient and ubiquitous human pathogen recovered previously only from primates. The sole species of the genus Hepatovirus, existing in both enveloped and nonenveloped forms, and with a capsid structure intermediate between that of insect viruses and mammalian picornaviruses, HAV is enigmatic in its origins. We conducted a targeted search for hepatoviruses in 15,987 specimens collected from 209 small mammal species globally and discovered highly diversified viruses in bats, rodents, hedgehogs, and shrews, which by pairwise sequence distance comprise 13 novel Hepatovirus species. Near-complete genomes from nine of these species show conservation of unique hepatovirus features, including predicted internal ribosome entry site structure, a truncated VP4 capsid protein lacking N-terminal myristoylation, a carboxyl-terminal pX extension of VP1, VP2 late domains involved in membrane envelopment, and a cis-acting replication element within the 3Dpol sequence. Antibodies in some bat sera immunoprecipitated and neutralized human HAV, suggesting conservation of critical antigenic determinants. Limited phylogenetic cosegregation among hepatoviruses and their hosts and recombination patterns are indicative of major hepatovirus host shifts in the past. Ancestral state reconstructions suggest a Hepatovirus origin in small insectivorous mammals and a rodent origin of human HAV. Patterns of infection in small mammals mimicked those of human HAV in hepatotropism, fecal shedding, acute nature, and extinction of the virus in a closed host population. The evolutionary conservation of hepatovirus structure and pathogenesis provide novel insight into the origins of HAV and highlight the utility of analyzing animal reservoirs for risk assessment of emerging viruses

DNA methylome analysis in Burkitt and follicular lymphomas identifies differentially methylated regions linked to somatic mutation and transcriptional control

Although Burkitt lymphomas and follicular lymphomas both have features of germinal center B cells, they are biologically and clinically quite distinct. Here we performed whole-genome bisulfite, genome and transcriptome sequencing in 13 IG-MYC translocation-positive Burkitt lymphoma, nine BCL2 translocation-positive follicular lymphoma and four normal germinal center B cell samples. Comparison of Burkitt and follicular lymphoma samples showed differential methylation of intragenic regions that strongly correlated with expression of associated genes, for example, genes active in germinal center dark-zone and light-zone B cells. Integrative pathway analyses of regions differentially methylated in Burkitt and follicular lymphomas implicated DNA methylation as cooperating with somatic mutation of sphingosine phosphate signaling, as well as the TCF3-ID3 and SWI/SNF complexes, in a large fraction of Burkitt lymphomas. Taken together, our results demonstrate a tight connection between somatic mutation, DNA methylation and transcriptional control in key B cell pathways deregulated differentially in Burkitt lymphoma and other germinal center B cell lymphomas