Hin-mediated DNA knotting and recombining promote replicon dysfunction and mutation

<p>Abstract</p> <p>Background</p> <p>The genetic code imposes a dilemma for cells. The DNA must be long enough to encode for the complexity of an organism, yet thin and flexible enough to fit within the cell. The combination of these properties greatly favors DNA collisions, which can knot and drive recombination of the DNA. Despite the well-accepted propensity of cellular DNA to collide and react with itself, it has not been established what the physiological consequences are.</p> <p>Results</p> <p>Here we analyze the effects of recombined and knotted plasmids in <it>E. coli </it>using the Hin site-specific recombination system. We show that Hin-mediated DNA knotting and recombination (i) promote replicon loss by blocking DNA replication; (ii) block gene transcription; and (iii) cause genetic rearrangements at a rate three to four orders of magnitude higher than the rate for an unknotted, unrecombined plasmid.</p> <p>Conclusion</p> <p>These results show that DNA reactivity leading to recombined and knotted DNA is potentially toxic and may help drive genetic evolution.</p

Differential respiratory health effects from the 2008 northern California wildfires: A spatiotemporal approach

AbstractWe investigated health effects associated with fine particulate matter during a long-lived, large wildfire complex in northern California in the summer of 2008. We estimated exposure to PM2.5 for each day using an exposure prediction model created through data-adaptive machine learning methods from a large set of spatiotemporal data sets. We then used Poisson generalized estimating equations to calculate the effect of exposure to 24-hour average PM2.5 on cardiovascular and respiratory hospitalizations and ED visits. We further assessed effect modification by sex, age, and area-level socioeconomic status (SES). We observed a linear increase in risk for asthma hospitalizations (RR=1.07, 95% CI=(1.05, 1.10) per 5µg/m3 increase) and asthma ED visits (RR=1.06, 95% CI=(1.05, 1.07) per 5µg/m3 increase) with increasing PM2.5 during the wildfires. ED visits for chronic obstructive pulmonary disease (COPD) were associated with PM2.5 during the fires (RR=1.02 (95% CI=(1.01, 1.04) per 5µg/m3 increase) and this effect was significantly different from that found before the fires but not after. We did not find consistent effects of wildfire smoke on other health outcomes. The effect of PM2.5 during the wildfire period was more pronounced in women compared to men and in adults, ages 20–64, compared to children and adults 65 or older. We also found some effect modification by area-level median income for respiratory ED visits during the wildfires, with the highest effects observed in the ZIP codes with the lowest median income. Using a novel spatiotemporal exposure model, we found some evidence of differential susceptibility to exposure to wildfire smoke

Identifying Grasp and Pinch Patterns in Ceramic Interventions: Video Analysis of Adults Completing Ceramic Activities

Background: Occupation-based interventions are effective in hand rehabilitation. The purpose of this study was to identify the grasp and pinch patterns used during specific ceramic activities for rehabilitative interventions. Method: A convenience sample of 59 videos with 38 subjects were taken of adults without hand dysfunction completing various ceramic activities. Elementary Grasp Actions (EGA’s) were analyzed to identify the different grasps and pinch patterns. Results: The EGA’s occurred 279 times across 12 ceramics activities. The EGA’s with the highest frequencies include nonprehensile, pinch, and lateral pinch. Nonprehensile was the most frequently used grasp used by the left hand. The EGA’s with the most prolonged durations were nonprehensile, special pinch, and oblique. The mean frequency and duration of each grasp and pinch pattern for specific ceramic activities are presented. Conclusion: Therapists can use the results of this study to help individuals with hand dysfunction through specific ceramic activity interventions

Impoundment increases methane emissions in Phragmites‐invaded coastal wetlands

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Sanders‐DeMott, R., Eagle, M., Kroeger, K., Wang, F., Brooks, T., Suttles, J., Nick, S., Mann, A., & Tang, J. Impoundment increases methane emissions in Phragmites‐invaded coastal wetlands. Global Change Biology, 28(15), (2022): 4539– 4557. https://doi.org/10.1111/gcb.16217.Saline tidal wetlands are important sites of carbon sequestration and produce negligible methane (CH4) emissions due to regular inundation with sulfate-rich seawater. Yet, widespread management of coastal hydrology has restricted tidal exchange in vast areas of coastal wetlands. These ecosystems often undergo impoundment and freshening, which in turn cause vegetation shifts like invasion by Phragmites, that affect ecosystem carbon balance. Understanding controls and scaling of carbon exchange in these understudied ecosystems is critical for informing climate consequences of blue carbon restoration and/or management interventions. Here, we (1) examine how carbon fluxes vary across a salinity gradient (4–25 psu) in impounded and natural, tidally unrestricted Phragmites wetlands using static chambers and (2) probe drivers of carbon fluxes within an impounded coastal wetland using eddy covariance at the Herring River in Wellfleet, MA, United States. Freshening across the salinity gradient led to a 50-fold increase in CH4 emissions, but effects on carbon dioxide (CO2) were less pronounced with uptake generally enhanced in the fresher, impounded sites. The impounded wetland experienced little variation in water-table depth or salinity during the growing season and was a strong CO2 sink of −352 g CO2-C m−2 year−1 offset by CH4 emission of 11.4 g CH4-C m−2 year−1. Growing season CH4 flux was driven primarily by temperature. Methane flux exhibited a diurnal cycle with a night-time minimum that was not reflected in opaque chamber measurements. Therefore, we suggest accounting for the diurnal cycle of CH4 in Phragmites, for example by applying a scaling factor developed here of ~0.6 to mid-day chamber measurements. Taken together, these results suggest that although freshened, impounded wetlands can be strong carbon sinks, enhanced CH4 emission with freshening reduces net radiative balance. Restoration of tidal flow to impounded ecosystems could limit CH4 production and enhance their climate regulating benefits.This project was supported by USGS-NPS Natural Resources Preservation Program #2021-07, U.S. Geological Survey Coastal & Marine Hazards and Resources Program and the USGS Land Change Science Program's LandCarbon program, and NOAA National Estuarine Research Reserve Science Collaborative NA14NOS4190145. R Sanders-DeMott was supported by a USGS Mendenhall Fellowship and partnership with Restore America's Estuaries

LIF-dependent survival of embryonic stem cells is regulated by a novel palmitoylated Gab1 signalling protein.

The cytokine leukaemia inhibitory factor (LIF) promotes self-renewal of mouse embryonic stem cells (ESCs) through activation of the transcription factor Stat3. However, the contribution of other ancillary pathways stimulated by LIF in ESCs, such as the MAPK and PI3K pathways, is less well understood. We show here that naive-type mouse ESCs express high levels of a novel effector of the MAPK and PI3K pathways. This effector is an isoform of the Gab1 (Grb2-associated binder protein 1) adaptor protein that lacks the N-terminal pleckstrin homology (PH) membrane-binding domain. Although not essential for rapid unrestricted growth of ESCs under optimal conditions, the novel Gab1 variant (Gab1β) is required for LIF-mediated cell survival under conditions of limited nutrient availability. This enhanced survival is absolutely dependent upon a latent palmitoylation site that targets Gab1β directly to ESC membranes. These results show that constitutive association of Gab1 with membranes through a novel mechanism promotes LIF-dependent survival of murine ESCs in nutrient-poor conditions

Evaluation of a Heat Vulnerability Index on Abnormally Hot Days: An Environmental Public Health Tracking Study

Background: Extreme hot weather conditions have been associated with increased morbidity and mortality, but risks are not evenly distributed throughout the population. Previously, a heat vulnerability index (HVI) was created to geographically locate populations with increased vulnerability to heat in metropolitan areas throughout the United States

College student sleep quality and mental and physical health are associated with food insecurity in a multi-campus study

Objective: To assess the relationship between food insecurity, sleep quality, and days with mental and physical health issues among college students. Design: An online survey was administered. Food insecurity was assessed using the ten-item Adult Food Security Survey Module. Sleep was measured using the nineteen-item Pittsburgh Sleep Quality Index (PSQI). Mental health and physical health were measured using three items from the Healthy Days Core Module. Multivariate logistic regression was conducted to assess the relationship between food insecurity, sleep quality, and days with poor mental and physical health. Setting: Twenty-two higher education institutions. Participants: College students (n 17 686) enrolled at one of twenty-two participating universities. Results: Compared with food-secure students, those classified as food insecure (43·4 %) had higher PSQI scores indicating poorer sleep quality (P \u3c 0·0001) and reported more days with poor mental (P \u3c 0·0001) and physical (P \u3c 0·0001) health as well as days when mental and physical health prevented them from completing daily activities (P \u3c 0·0001). Food-insecure students had higher adjusted odds of having poor sleep quality (adjusted OR (AOR): 1·13; 95 % CI 1·12, 1·14), days with poor physical health (AOR: 1·01; 95 % CI 1·01, 1·02), days with poor mental health (AOR: 1·03; 95 % CI 1·02, 1·03) and days when poor mental or physical health prevented them from completing daily activities (AOR: 1·03; 95 % CI 1·02, 1·04). Conclusions: College students report high food insecurity which is associated with poor mental and physical health, and sleep quality. Multi-level policy changes and campus wellness programmes are needed to prevent food insecurity and improve student health-related outcomes

Short-Term Effects of Air Pollution on Wheeze in Asthmatic Children in Fresno, California

BACKGROUND: Although studies have demonstrated that air pollution is associated with exacerbation of asthma symptoms in children with asthma, little is known about the susceptibility of subgroups, particularly those with atopy. OBJECTIVE: This study was designed to evaluate our a priori hypothesis that identifiable subgroups of asthmatic children are more likely to wheeze with exposure to ambient air pollution. METHODS: A cohort of 315 children with asthma, 6-11 years of age, was recruited for longitudinal follow-up in Fresno, California (USA). During the baseline visit, children were administered a respiratory symptom questionnaire and allergen skin-prick test. Three times a year, participants completed 14-day panels during which they answered symptom questions twice daily. Ambient air quality data from a central monitoring station were used to assign exposures to the following pollutants: particulate matter &lt;= 2.5 mu m in aerodynamic diameter, particulate matter between 2.5 and 10 mu m in aerodynamic diameter (PM(10-2.5)), elemental carbon, nitrogen dioxide (NO(2)), nitrate, and O(3). RESULTS: For the group as a whole, wheeze was significantly associated with short-term exposures to NO(2) [odds ratio (OR) = 1.10 for 8.7-ppb increase; 95% confidence interval (CI), 1.02-1.20] and PM(10-2.5) (OR = 1.11 for 14.7-mu g/m(3) increase; 95% CI, 1.01-1.22). The association with wheeze was stronger for these two pollutants in children who were skin-test positive to cat or common fungi and in boys with mild intermittent asthma. CONCLUSION: A pollutant associated with traffic emissions, NO(2), and a pollutant with bioactive constituents, PM(10-2.5), were associated with increased risk of wheeze in asthmatic children living in Fresno, California. Children with atopy to cat or common fungi and boys with mild intermittent asthma were the subgroups for which we observed the largest associations

Bioactive Hydrogel Substrates: Probing Leukocyte Receptor–Ligand Interactions in Parallel Plate Flow Chamber Studies

The binding of activated integrins on the surface of leukocytes facilitates the adhesion of leukocytes to vascular endothelium during inflammation. Interactions between selectins and their ligands mediate rolling, and are believed to play an important role in leukocyte adhesion, though the minimal recognition motif required for physiologic interactions is not known. We have developed a novel system using poly(ethylene glycol) (PEG) hydrogels modified with either integrin-binding peptide sequences or the selectin ligand sialyl Lewis X (SLe(X)) within a parallel plate flow chamber to examine the dynamics of leukocyte adhesion to specific ligands. The adhesive peptide sequences arginine–glycine–aspartic acid–serine (RGDS) and leucine–aspartic acid–valine (LDV) as well as sialyl Lewis X were bound to the surface of photopolymerized PEG diacrylate hydrogels. Leukocytes perfused over these gels in a parallel plate flow chamber at physiological shear rates demonstrate both rolling and firm adhesion, depending on the identity and concentration of ligand bound to the hydrogel substrate. This new system provides a unique polymer-based model for the study of interactions between leukocytes and endothelium as well as a platform to develop improved scaffolds for cardiovascular tissue engineering