Structure of the ATP synthase from Mycobacterium smegmatis provides targets for treating tuberculosis.

The structure has been determined by electron cryomicroscopy of the adenosine triphosphate (ATP) synthase from Mycobacterium smegmatis This analysis confirms features in a prior description of the structure of the enzyme, but it also describes other highly significant attributes not recognized before that are crucial for understanding the mechanism and regulation of the mycobacterial enzyme. First, we resolved not only the three main states in the catalytic cycle described before but also eight substates that portray structural and mechanistic changes occurring during a 360° catalytic cycle. Second, a mechanism of auto-inhibition of ATP hydrolysis involves not only the engagement of the C-terminal region of an α-subunit in a loop in the γ-subunit, as proposed before, but also a "fail-safe" mechanism involving the b'-subunit in the peripheral stalk that enhances engagement. A third unreported characteristic is that the fused bδ-subunit contains a duplicated domain in its N-terminal region where the two copies of the domain participate in similar modes of attachment of the two of three N-terminal regions of the α-subunits. The auto-inhibitory plus the associated "fail-safe" mechanisms and the modes of attachment of the α-subunits provide targets for development of innovative antitubercular drugs. The structure also provides support for an observation made in the bovine ATP synthase that the transmembrane proton-motive force that provides the energy to drive the rotary mechanism is delivered directly and tangentially to the rotor via a Grotthuss water chain in a polar L-shaped tunnel

Interprofessional Team Collaboration for Routine and Emergent Mental Health Concerns Among Collegiate Student-Athletes: A Case Series from the Association for Athletic Training Education Research Network

Collegiate student-athletes experience an increasing number of mental health concerns. To help address these concerns and provide high-quality health care for student-athletes, institutions of higher education are being encouraged to create interprofessional health care teams that are specifically dedicated to managing mental health. We interviewed 3 interprofessional health care teams who collaborate to manage routine and emergency mental health conditions in collegiate student-athletes. Teams represented all 3 National Collegiate Athletics Association (NCAA) divisions and included athletic trainers, clinical psychologists, psychiatrists, dietitians and nutritionists, social workers, nurses, and physician assistants (associates). The interprofessional teams indicated that the existing NCAA recommendations helped to solidify members and roles of the mental health care team; however, they all believed their teams would benefit from more counselors and psychiatrists. Teams had different mechanisms for referral and accessing mental health resources on their campuses, which may make on-the-job training for new members of the team an organizational necessity

Use of Evidence-Based Practice Among Athletic Training Educators, Clinicians, and Students, Part 1: Perceived Importance, Knowledge, and Confidence

Context: Although evidence-based practice (EBP) has become more prevalent, athletic trainers\u27 perceptions of importance and knowledge of these concepts and their confidence in EBP are largely unknown. Objective: To assess perceived importance and knowledge of and confidence in EBP concepts in athletic trainers in various roles and with different degree levels. Design: Cross-sectional study. Setting: Online survey instrument. Patients or Other Participants: The survey was sent to 6702 athletic training educators, clinicians, and postprofessional students. A total of 1209 completed the survey, for a response rate of 18.04%. Main Outcome Measure(s): Demographic information and perceived importance and knowledge of and confidence in the steps of EBP were obtained. One-way analysis of variance, a Kruskal-Wallis test, and an independent-samples t test were used to determine differences in scores among the demographic variables. Results: Athletic trainers demonstrated low knowledge scores (64.2% ± 1.29%) and mild to moderate confidence (2.71 ± 0.55 out of 4.0). They valued EBP as moderately to extremely important (3.49 ± 0.41 out of 4.0). Perceived importance scores differed among roles (clinicians unaffiliated with an education program scored lower than postprofessional educators, P = .001) and highest educational degree attained (athletic trainers with terminal degrees scored higher than those with bachelor\u27s or master\u27s degrees, P \u3c .001). Postprofessional athletic training students demonstrated the highest total EBP knowledge scores (4.65 ± 0.91), whereas clinicians demonstrated the lowest scores (3.62 ± 1.35). Individuals with terminal degrees had higher (P \u3c .001) total knowledge scores (4.31 ± 1.24) than those with bachelor\u27s (3.78 ± 1.2) or master\u27s degrees (3.76 ± 1.35). Postprofessional educators demonstrated greater confidence in knowledge scores (3.36 ± 0.40 out of 4.0) than did those in all other athletic training roles (P \u3c .001). Conclusions: Overall knowledge of the basic EBP steps remained low across the various athletic trainers\u27 roles. The higher level of importance indicated that athletic trainers valued EBP, but this value was not reflected in the knowledge of EBP concepts. Individuals with a terminal degree possessed higher knowledge scores than those with other educational preparations; however, EBP knowledge needs to increase across all demographics of the profession

Pericytes contribute to airway remodeling in a mouse model of chronic allergic asthma

Myofibroblast accumulation, subepithelial fibrosis, and vascular remodeling are complicating features of chronic asthma, but the mechanisms are not clear. Platelet-derived growth factors (PDGFs) regulate the fate and function of various mesenchymal cells and have been implicated as mediators of lung fibrosis. However, it is not known whether PDGF-BB signaling via PDGFRβ, which is critical for the recruitment of pericytes to blood vessels, plays a role in airway remodeling in chronic asthma. In the present study, we used a selective PDGFRβ inhibitor (CP-673451) to investigate the role of PDGFRβ signaling in the development of airway remodeling and lung dysfunction in an established mouse model of house dust mite-induced chronic allergic asthma. Unexpectedly, we found that pharmacological inhibition of PDGFRβ signaling in the context of chronic aeroallergen exposure led to exacerbated lung dysfunction and airway smooth muscle thickening. Further studies revealed that the inflammatory response to aeroallergen challenge in mice was associated with decreased PDGF-BB expression and the loss of pericytes from the airway microvasculature. In parallel, cells positive for pericyte markers accumulated in the subepithelial region of chronically inflamed airways. This process was exacerbated in animals treated with CP-673451. The results indicate that perturbed PDGF-BB/PDGFRβ signaling and pericyte accumulation in the airway wall may contribute to airway remodeling in chronic allergic asthma

The effect of oncoplastic reduction on the incidence of post-operative lymphedema in breast cancer patients undergoing lumpectomy

Purpose: In breast cancer patients with macromastia, breast conservation surgery (BCS) followed by radiation therapy (RT) may be associated with a different complication profile than those without macromastia. Oncoplastic reduction mammoplasty (ORM) aims to reduce breast volume while excising the tumor bed and its margins. Since breast volume was found to be a risk factor for chronic breast lymphedema, this study was performed to determine the impact of ORM on chronic breast lymphedema as well as other complications compared to BCS without ORM. Material & Methods: We performed a retrospective chart review on patients who underwent lumpectomy with RT from 2014 to 2018. Chronic breast lymphedema (CBL) was defined as swelling that persisted \u3e1 year post-RT. Breast volumes (BV) were determined by contoured breast volumes or, if unavailable, estimated by the 95% isodose volumes from the RT treatment planning system. Univariate analysis was used to evaluate patient factors and treatment outcomes in women with BV ≥1300 cc compared to-Evaluate factors associated with ≥1 complication. Identify factors associated with the development of CBL. Results: The total population included 1173 patients: -1122 (95.7%) underwent BCS alone without ORM -51 (4.3%) underwent ORM -733 (62.5%) had a BVcc -440 (37.5%) had BV ≥1300 cc Multivariate regression analysis demonstrated that compared to patients with BV \u3c 1300 cc, patients with BV ≥1300 cc had: -Higher BMI (OR=1.200, P\u3c0.001) -Increased risk of CBL (OR=2.127, P=0.024) -Decreased risk of grade 2 radiation dermatitis (OR=0.457, P=0.002) Conclusion: Our data demonstrates that patients with breast volumes ≥1300 cc were two times more likely to develop CBL. Although patients with ORM had an increased risk for surgical site complications, the ORM procedure may have mitigated their risk for CBL. ORM should be considered at the time of BCS in women with macromastia to reduce their future risk of CBL as there is no cure for this disease.https://scholarlycommons.henryford.com/sarcd2021/1008/thumbnail.jp

StraboSpot data system for structural geology

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.StraboSpot is a geologic data system that allows researchers to digitally collect, store, and share both field and laboratory data. StraboSpot is based on how geologists actually work to collect field data; although initially developed for the structural geology research community, the approach is easily extensible to other disciplines. The data system uses two main concepts to organize data: spots and tags. A spot is any observation that characterizes a specific area, a concept applicable at any spatial scale from regional to microscopic. Spots are related in a purely spatial manner, and consequently, one spot can enclose multiple other spots that themselves contain other spots. In contrast, tags provide conceptual grouping of spots, allowing linkages between spots that are independent of their spatial position. The StraboSpot data system uses a graph database, rather than a relational database approach, to increase flexibility and to track geologically complex relationships. StraboSpot operates on two different platform types: (1) a fieldbased application that runs on iOS and Android mobile devices, which can function in either Internet-connected or disconnected environments; and (2) a web application that runs only in Internet-connected settings. We are presently engaged in incorporating microstructural data into StraboSpot, as well as expanding to include additional field-based (sedimentology, petrology) and lab-based (experimental rock deformation) data. The StraboSpot database will be linked to other existing and future databases in order to provide integration with other digital efforts in the geological sciences and allow researchers to do types of science that were not possible without easy access to digital data

Characterization of cleavage events in the multifunctional cilium adhesin Mhp684 (P146) reveals a mechanism by which mycoplasma hyopneumoniae regulates surface topography

Mycoplasma hyopneumoniae causes enormous economic losses to swine production worldwide by colonizing the ciliated epithelium in the porcine respiratory tract, resulting in widespread damage to the mucociliary escalator, prolonged inflammation, reduced weight gain, and secondary infections. Protein Mhp684 (P146) comprises 1,317 amino acids, and while the N-terminal 400 residues display significant sequence identity to the archetype cilium adhesin P97, the remainder of the molecule is novel and displays unusual motifs. Proteome analysis shows that P146 preprotein is endogenously cleaved into three major fragments identified here as P50P146, P40P146, and P85P146 that reside on the cell surface. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) identified a semitryptic peptide that delineated a major cleavage site in Mhp684. Cleavage occurred at the phenylalanine residue within sequence 672ATEF2QQ677, consistent with a cleavage motif resembling S/T-X-F2XD/E recently identified in Mhp683 and other P97/P102 family members. Biotinylated surface proteins recovered by avidin chromatography and separated by two-dimensional gel electrophoresis (2-D GE) showed that more-extensive endoproteolytic cleavage of P146 occurs. Recombinant fragments F1P146-F3P146 that mimic P50P146, P40P146, and P85P146 were constructed and shown to bind porcine epithelial cilia and biotinylated heparin with physiologically relevant affinity. Recombinant versions of F3P146 generated from M. hyopneumoniae strain J and 232 sequences strongly bind porcine plasminogen, and the removal of their respective C-terminal lysine and arginine residues significantly reduces this interaction. These data reveal that P146 is an extensively processed, multifunctional adhesin of M. hyopneumoniae. Extensive cleavage coupled with variable cleavage efficiency provides a mechanism by which M. hyopneumoniae regulates protein topography

Dietary species richness as a measure of food biodiversity and nutritional quality of diets

Biodiversity is key for human and environmental health. Available dietary and ecological indicators are not designed to assess the intricate relationship between food biodiversity and diet quality. We applied biodiversity indicators to dietary intake data from and assessed associations with diet quality of women and young children. Data from 24-hour diet recalls (55% in the wet season) of n = 6,226 participants (34% women) in rural areas from seven lowand middle-income countries were analyzed. Mean adequacies of vitamin A, vitamin C, folate, calcium, iron, and zinc and diet diversity score (DDS) were used to assess diet quality. Associations of biodiversity indicators with nutrient adequacy were quantified using multilevel models, receiver operating characteristic curves, and test sensitivity and specificity. A total of 234 different species were consumed, of which < 30% were consumed in more than one country. Nine specieswere consumed in all countries and provided, on average, 61% of total energy intake and a significant contribution of micronutrients in the wet season. Compared with Simpson's index of diversity and functional diversity, species richness (SR) showed stronger associations and better diagnostic properties with micronutrient adequacy. For every additional species consumed, dietary nutrient adequacy increased by 0.03 (P < 0.001). Diets with higher nutrient adequacy were mostly obtained when both SR and DDS were maximal. Adding SR to the minimum cutoff for minimum diet diversity improved the ability to detect diets with higher micronutrient adequacy in women but not in children. Dietary SR is recommended as the most appropriate measure of food biodiversity in diets

An Investigation of Abstract Construal on Impression Formation: A Multi-Lab Replication of McCarthy and Skowronski (2011)

Perceivers often view individuals described as “warm” to be generally positive and individuals described as “cold” to be generally negative. Consistent with the tenets of Construal Level Theory, McCarthy and Skowronski (2011) demonstrated this difference was larger among perceivers who were instructed the information was psychologically distant rather than psychologically near; however, those results have never been subjected to replication attempts. To test the replicability of those results, we closely replicated the methods of McCarthy and Skowronski (2011) Study 1b at eight separate data collection sites and pooled the results into a random-effects meta-analysis. Within the replication attempts, the overall effect was not significantly different from zero (d = 0.10, 95% CI [–0.01, 0.22]) and an equivalence test confirmed this effect was smaller than our smallest effect size of interest. However, when the original study was incorporated into the meta-analysis, the overall effect was significantly different from zero in the theoretically-consistent direction (d = 0.13, 95% CI [0.02, 0.24]). The weight of the overall evidence suggests the traits “warm” and “cold” are more influential among participants who were presented with information that was psychologically distant; however, this effect is small. Future research should try to identify more potent moderators, which would make the effect more affordable to detect