REGULATION OF THE BROAD-SPECTRUM DISEASE RESISTANCE PROTEIN RPW8.2 BY PHOSPHORYLATION AND 14-3-3 IN ARABIDOPSIS

Ascomycete powdery mildew (PM) fungi belonging to the order of Erysiphales cause diseases on more than 10,000 plant species including economically important staple food crops and numerous horticultural plants. The Arabidopsis protein RPW8.2 confers broad-spectrum resistance against all infectious powdery mildew pathogens. RPW8.2 is unique among characterized plant R proteins in that it activates broad-spectrum resistance to PM fungi, and the protein is specifically targeted to the extra-haustorium membrane (EHM). However, how RPW8.2 is regulated to exert haustorium-targeted defenses remains poorly characterized. To understand how RPW8.2 is regulated, I first performed a thorough site-specific mutagenesis of potential serine or threonine residues in RPW8.2 and identified two residues, threonine at 64 and serine at 138 to be critical for RPW8.2’s function. While the T64A mutation makes RPW8.2 auto-active, the S138A mutation abolishes RPW8.2’s ability to activate cell death and defense, with S138A being dominant over T64A. This suggests that RPW8.2 is negatively and positively regulated by (de)phosphorylation at T64 and S138, respectively. One candidate phosphatase and two kinases were genetically and biochemically tested for a potential role in (de)phosphorylation of RPW8.2. I also investigated how an RPW8.2-interacting protein 14-3-3λ regulates RPW8.2’s function. To this end, I developed a novel, divalent 14-3-3-sequestering protein named RYC to circumvent likely functional redundancy among different 14-3-3 isoforms. Our results demonstrate that RYC can effectively sequester multiple 14-3-3 isoforms from plants and human. When expressed in guard cells of Arabidopsis, RYC sequestered 14-3-3s away from H+-ATPases, thereby inducing stomatal closure, which in turn increased drought tolerance of transgenic Arabidopsis. When expressed in powdery-mildew-invaded cells, RYC abrogated RPW8.2-mediared resistance to powdery mildew, yet did not grossly affect its EHM-specific localization, suggesting that the C-terminus of RPW8.2 may exert a self-inhibition function which can be relieved when 14-3-3λ binds to the C-terminus during fungal infection. Taken together, our results lead to a better understanding of the molecular mechanisms regulating RPW8.2

Options for basing Dietary Reference Intakes (DRIs) on chronic disease endpoints: report from a joint US-/Canadian-sponsored working group.

Dietary Reference Intakes (DRIs) are used in Canada and the United States in planning and assessing diets of apparently healthy individuals and population groups. The approaches used to establish DRIs on the basis of classical nutrient deficiencies and/or toxicities have worked well. However, it has proved to be more challenging to base DRI values on chronic disease endpoints; deviations from the traditional framework were often required, and in some cases, DRI values were not established for intakes that affected chronic disease outcomes despite evidence that supported a relation. The increasing proportions of elderly citizens, the growing prevalence of chronic diseases, and the persistently high prevalence of overweight and obesity, which predispose to chronic disease, highlight the importance of understanding the impact of nutrition on chronic disease prevention and control. A multidisciplinary working group sponsored by the Canadian and US government DRI steering committees met from November 2014 to April 2016 to identify options for addressing key scientific challenges encountered in the use of chronic disease endpoints to establish reference values. The working group focused on 3 key questions: 1) What are the important evidentiary challenges for selecting and using chronic disease endpoints in future DRI reviews, 2) what intake-response models can future DRI committees consider when using chronic disease endpoints, and 3) what are the arguments for and against continuing to include chronic disease endpoints in future DRI reviews? This report outlines the range of options identified by the working group for answering these key questions, as well as the strengths and weaknesses of each option

TBS (Trabecular Bone Score) Expands Understanding of Spaceflight Effects on the Lumbar Spine of Long Duration Astronauts

Background: Bone loss due to long-duration spaceflight has been characterized by both DXA and QCT serial scans. It is unclear if these spaceflight-induced changes in bone mineral density and structure result in increased fracture incidence. NASA astronauts currently fly on 5-6-month missions on the International Space Station (ISS) and at least one 12-month mission is planned. While NASA has measured areal BMD (by DXA) and volumetric BMD (by QCT), and has estimated hip strength (by finite element models of QCT data, no method has yet been used to examine bone microarchitecture from lumbar spine (LS). DXA scans are routinely performed pre- and post-flight on all ISS astronauts to follow BMD changes associated with space flight. Trabecular Bone Score (TBS) is a relatively new method that measures grey-scale-level texture information extracted from lumbar spine DXA images and correlates with 3D parameters of bone micro-architecture. We evaluated the ability of LS TBS to discriminate changes in astronauts who have flown on ISS missions and to determine if TBS can provide additional information compared to DXA. Methods: LS (L1-4) DXA scans from 51 astronauts (mean age, 47 +/- 4) were divided into 3 groups based on the exercise regimes performed while onboard the ISS. Pre-ARED (exercise using a load-limited resistive exercise device, <300lb), ARED (exercise with a high-load resistive exercise device, up to 600lb) and a Bisphos group (ARED exercise and a 70-mg alendronate tablet once a week before and during flight, starting 17 days before launch). DXA scans were performed and analyzed on a Hologic Discovery W using the same technician for the pre- and postflight scans. LSC for the LS in our laboratory is 0.025 g/cm2. TBS was performed at the Mercy Hospital, Cincinnati, Ohio on a similar Hologic computer. TBS precision was calculated from 16 comparable test subjects (0.0XX g/cm2). Data were preliminary analyzed using a paired, 2-tailed t-test for the difference between pre- and postflight means

The Impact of Patient and Provider Education on Statin Therapy Initiation and Adherence in Type II Diabetics

Purpose/Background Type 2 diabetes mellitus (T2DM) is a common, chronic disease that increases the risk of coronary artery disease and stroke fourfold, which makes protecting cardiac function a priority. The American Diabetes Association (ADA) and American Heart Association (AHA) recommend the prescription of statins to reduce cardiovascular complications. Unfortunately, provider and patient adherence to this recommendation is poor.This study aimed to determine if shared-decision making and patient follow-up within a 6 month period of being newly diagnosed with T2D has an effect on the initiation rate of statin therapy. Methods In this retrospective study we requested data from the University of Tennessee Family Medicine clinic on newly diagnosed diabetic patients from December 2021 to December 2023 that met criteria (40 years or older, eligible for statin therapy, new diagnosis of T2D, had at least one follow-up appointment within the last 2 years). Information requested included the patient’s sex, age, baseline HbA1C, referral date, and whether or not statin therapy was initiated within 6 months of diagnosis. The data was then analyzed for descriptive statistics using Intellectus statistical analysis software. Results Twenty-nine patients (8 male, 21 female) met inclusion criteria. The mean age of the participants was 52.8 years (female mean age: 54.9 years; male mean age: 47.5 years), and the mean baseline HgA1C was 9.16%. Of the 29 patients included in the study, 100% of them had statin therapy initiated within 6 months of diagnosis. Implications for Nursing Practice The results of this study are reassuring that patient follow up within 6 months of a new T2D diagnosis is key in initiating current statin therapy guidelines. These findings reinforce the essential role of nurse practitioners in the management of T2D and associated cardiovascular risk, highlighting the importance of patient education, regular monitoring, and collaborative care

Deep Underground Science and Engineering Laboratory - Preliminary Design Report

The DUSEL Project has produced the Preliminary Design of the Deep Underground Science and Engineering Laboratory (DUSEL) at the rehabilitated former Homestake mine in South Dakota. The Facility design calls for, on the surface, two new buildings - one a visitor and education center, the other an experiment assembly hall - and multiple repurposed existing buildings. To support underground research activities, the design includes two laboratory modules and additional spaces at a level 4,850 feet underground for physics, biology, engineering, and Earth science experiments. On the same level, the design includes a Department of Energy-shepherded Large Cavity supporting the Long Baseline Neutrino Experiment. At the 7,400-feet level, the design incorporates one laboratory module and additional spaces for physics and Earth science efforts. With input from some 25 science and engineering collaborations, the Project has designed critical experimental space and infrastructure needs, including space for a suite of multidisciplinary experiments in a laboratory whose projected life span is at least 30 years. From these experiments, a critical suite of experiments is outlined, whose construction will be funded along with the facility. The Facility design permits expansion and evolution, as may be driven by future science requirements, and enables participation by other agencies. The design leverages South Dakota's substantial investment in facility infrastructure, risk retirement, and operation of its Sanford Laboratory at Homestake. The Project is planning education and outreach programs, and has initiated efforts to establish regional partnerships with underserved populations - regional American Indian and rural populations

Comparative genome analyses reveal sequence features reflecting distinct modes of host-adaptation between dicot and monocot powdery mildew

Powdery mildew (PM) is one of the most important and widespread plant diseases caused by biotrophic fungi. Notably, while monocot (grass) PM fungi exhibit high-level of host-specialization, many dicot PM fungi display a broad host range. To understand such distinct modes of host-adaptation, we sequenced the genomes of four dicot PM biotypes belonging to Golovinomyces cichoracearum or Oidium neolycopersici. We compared genomes of the four dicot PM together with those of Blumeria graminis f.sp. hordei (both DH14 and RACE1 isolates), B. graminis f.sp. tritici, and Erysiphe necator infectious on barley, wheat and grapevine, respectively. We found that despite having a similar gene number (6620–6961), the PM genomes vary from 120 to 222 Mb in size. This high-level of genome size variation is indicative of highly differential transposon activities in the PM genomes. While the total number of genes in any given PM genome is only about half of that in the genomes of closely related ascomycete fungi, most (~ 93%) of the ascomycete core genes (ACGs) can be found in the PM genomes. Yet, 186 ACGs were found absent in at least two of the eight PM genomes, of which 35 are missing in some dicot PM biotypes, but present in the three monocot PM genomes, indicating remarkable, independent and perhaps ongoing gene loss in different PM lineages. Consistent with this, we found that only 4192 (3819 singleton) genes are shared by all the eight PM genomes, the remaining genes are lineage- or biotype-specific. Strikingly, whereas the three monocot PM genomes possess up to 661 genes encoding candidate secreted effector proteins (CSEPs) with families containing up to 38 members, all the five dicot PM fungi have only 116–175 genes encoding CSEPs with limited gene amplification. Compared to monocot (grass) PM fungi, dicot PM fungi have a much smaller effectorome. This is consistent with their contrasting modes of host-adaption: while the monocot PM fungi show a high-level of host specialization, which may reflect an advanced host-pathogen arms race, the dicot PM fungi tend to practice polyphagy, which might have lessened selective pressure for escalating an with a particular host.Wu, Y., Ma, X., Pan, Z. et al. Comparative genome analyses reveal sequence features reflecting distinct modes of host-adaptation between dicot and monocot powdery mildew. BMC Genomics 19, 705 (2018)

The Association Between Depressive Symptoms and Accumulation of Stress Among Black Men in the Health and Retirement Study

Background and Objectives: Among the multiple factors posited to drive the health inequities that black men experience, the fundamental role of stress in the production of poor health is a key component. Allostatic load (AL) is considered to be a byproduct of stressors related to cumulative disadvantage. Exposure to chronic stress is associated with poorer mental health including depressive symptoms. Few studies have investigated how AL contributes to depressive symptoms among black men. The purpose of the cross-sectional study was to examine the association between AL and depressive symptoms among middle- to old age black men. Research Design and Methods: This project used the 2010 and 2012 wave of the Health and Retirement Study enhanced face-to-face interview that included a biomarker assessment and psychosocial questionnaire. Depressive symptoms, assessed by the endorsement of 3 or more symptoms on the Center for Epidemiological Studies—Depression 8-item scale, was the outcome variable. The main independent variable, AL, score was calculated by summing the number values that were in the high range for that particular biomarker value scores ranging from 0 to 7. black men whose AL score was 3 or greater were considered to be in the high AL group. Modified Poisson regression was used to estimate prevalence ratios (PRs) and corresponding 95% confidence intervals (CIs). Results: There was a larger proportion of black men in the high AL group who reported depressive symptoms (30.0% vs.20.0%) compared with black men in the low AL group. After adjusting for age, education, income, drinking, and smoking status, the prevalence of reporting 3 or more depressive symptoms was statistically significant among black men in the high AL group (PR = 1.61 [95% CI: 1.20–2.17]) than black men in the low AL group. Discussion and Implications: Exposure to chronic stress is related to reporting 3 or more depressive symptoms among black men after controlling for potential confounders. Improving the social and economic conditions for which black men work, play, and pray is key to reducing stress, thereby potentially leading to the reporting of fewer depressive symptoms

An analysis of dormancy, ABA responsiveness, after-ripening and pre-harvest sprouting in hexaploid wheat (Triticum aestivum L.) caryopses

Embryo and caryopsis dormancy, abscisic acid (ABA) responsiveness, after-ripening (AR), and the disorder pre-harvest sprouting (PHS) were investigated in six genetically related wheat varieties previously characterized as resistant, intermediate, or susceptible to PHS. Timing of caryopsis AR differed between varieties; AR occurred before harvest ripeness in the most PHS-susceptible, whereas AR was slowest in the most PHS-resistant. Whole caryopses of all varieties showed little ABA-responsiveness during AR; PHS-susceptible varieties were responsive at the beginning of the AR period whereas PHS-resistant showed some responsiveness throughout. Isolated embryos showed relatively little dormancy during grain-filling and most varieties exhibited a window of decreased ABA-responsiveness around the period of maximum dry matter accumulation (physiological maturity). Susceptibility to PHS was assessed by overhead misting of either isolated ears or whole plants during AR; varieties were clearly distinguished using both methods. These analyses allowed an investigation of the interactions between the different components of seed development, compartments, and environment for the six varieties. There was no direct relationship between speed of caryopsis AR and embryo dormancy or ABA-responsiveness during seed maturation. However, the velocity of AR of a variety was closely associated with the degree of susceptibility to PHS during AR suggesting that these characters are developmentally linked. Investigation of genetic components of AR may therefore aid breeding approaches to reduce susceptibility to PHS

Does Random Treatment Assignment Cause Harm to Research Participants?

BACKGROUND: Some argue that by precluding individualized treatment, randomized clinical trials (RCTs) provide substandard medical care, while others claim that participation in clinical research is associated with improved patient outcomes. However, there are few data to assess the impact of random treatment assignment on RCT participants. We therefore performed a systematic review to quantify the differences in health outcomes between randomized trial participants and eligible non-participants. METHODS AND FINDINGS: Studies were identified by searching Medline, the Web of Science citation database, and manuscript references. Studies were eligible if they documented baseline characteristics and clinical outcomes of RCT participants and eligible non-participants, and allowed non-participants access to the same interventions available to trial participants. Primary study outcomes according to patient group (randomized trial participants versus eligible non-participants) were extracted from all eligible manuscripts. For 22 of the 25 studies (88%) meeting eligibility criteria, there were no significant differences in clinical outcomes between patients who received random assignment of treatment (RCT participants) and those who received individualized treatment assignment (eligible non-participants). In addition, there was no relation between random treatment assignment and clinical outcome in 15 of the 17 studies (88%) in which randomized and nonrandomized patients had similar health status at baseline. CONCLUSIONS: These findings suggest that randomized treatment assignment as part of a clinical trial does not harm research participants

A sociological dilemma: race, segregation, and US sociology

US sociology has been historically segregated in that, at least until the 1960s, there were two distinct institutionally organized traditions of sociological thought – one black and one white. For the most part, however, dominant historiographies have been silent on that segregation and, at best, reproduce it when addressing the US sociological tradition. This is evident in the rarity with which scholars such as WEB Du Bois, E Franklin Frazier, Oliver Cromwell Cox, or other ‘African American Pioneers of Sociology’, as Saint-Arnaud calls them, are presented as core sociological voices within histories of the discipline. This article addresses the absence of African American sociologists from the US sociological canon and, further, discusses the implications of this absence for our understanding of core sociological concepts. With regard to the latter, the article focuses in particular on the debates around equality and emancipation and discusses the ways in which our understanding of these concepts could be extended by taking into account the work of African American sociologists and their different interpretations of core themes