Structural analysis of the P132L disease mutation in caveolin-1 reveals its role in the assembly of oligomeric complexes.

Caveolin-1 (CAV1) is a membrane-sculpting protein that oligomerizes to generate flask-shaped invaginations of the plasma membrane known as caveolae. Mutations in CAV1 have been linked to multiple diseases in humans. Such mutations often interfere with oligomerization and the intracellular trafficking processes required for successful caveolae assembly, but the molecular mechanisms underlying these defects have not been structurally explained. Here, we investigate how a disease-associated mutation in one of the most highly conserved residues in CAV1, P132L, affects CAV1 structure and oligomerization. We show that P132 is positioned at a major site of protomer-protomer interactions within the CAV1 complex, providing a structural explanation for why the mutant protein fails to homo-oligomerize correctly. Using a combination of computational, structural, biochemical, and cell biological approaches, we find that despite its homo-oligomerization defects P132L is capable of forming mixed hetero-oligomeric complexes with WT CAV1 and that these complexes can be incorporated into caveolae. These findings provide insights into the fundamental mechanisms that control the formation of homo- and hetero-oligomers of caveolins that are essential for caveolae biogenesis, as well as how these processes are disrupted in human disease.

Feeding Appropriate Nutrients during the Adult Stage to Promote the Growth and Development of Carposina sasakii Offspring.

Nutrients consumed during the adult stage are a key factor affecting the growth, development, and reproduction of insect offspring and thus could play an important role in insect population research. However, there is absence of conclusive evidence regarding the direct effects of parental (F0) nutritional status on offspring (F1) fitness in insects. Carposina sasakii Matsumura is a serious, widespread fruit-boring pest that negatively impacts orchards and the agricultural economy across East Asia. In this study, life history data of F1 directly descended from F0C. sasakii fed with seven different nutrients (water as control, 5 g·L-1 honey solution, 10 g·L-1 honey solution, 5 g·L-1 sucrose solution, 10 g·L-1 sucrose solution, 15 g·L-1 sucrose solution, and 20 g·L-1 sucrose solution) were collected under laboratory conditions. The growth and development indices, age-stage specific survival rate, age-stage specific fecundity, age-stage specific life expectancy, age-stage specific reproductive value, and population parameters of these offspring were analyzed according to the age-stage, two-sex life table theory. The results showed that the nutritional status of F0 differentially affects the growth, development, and reproduction of F1. The F1 offspring of F0 adult C. sasakii fed with 10 g·L-1 sucrose had significantly higher life table parameters than those of other treatments (intrinsic rate of increase, r = 0.0615 ± 0.0076; finite rate of increase, λ = 1.0634 ± 0.0081; net reproductive rate, R0 = 12.61 ± 3.57); thus, 10 g·L-1 sucrose was more suitable for raising C. sasakii in the laboratory than other treatments. This study not only provides clear evidence for the implications of altering F0 nutritional conditions on the fitness of F1 in insects, but also lays the foundation for the implementation of feeding technologies within the context of a well-conceived laboratory rearing strategy for C. sasakii.

LGBTQI+ representation in pre-licensure nursing textbooks: A qualitative descriptive analysis.

BACKGROUND: To improve health equity, nursing curricula should include content specific to the needs of marginalized and underserved communities, such as lesbian, gay, bisexual, transgender, queer, and intersex groups (LGBTQI+). Harmful and absent academic discussions of LGBTQI+ patients lead to provider discomfort and inadequacy in treating this patient population. Nursing schools are well-positioned to increase comfort with LGBTQI+ content as part of pre-licensure curricula. This article presents a systematic evaluation of LGBTQI+ content in nursing pre-licensure textbooks and the nature and quality of the representations. METHODS: A qualitative descriptive analysis of LGBTQI+ content from 14 nursing-specific textbooks required by a pre-licensure degree program at the Johns Hopkins School of Nursing was conducted by a student-led team with faculty oversight. A priori and iterative search terms were used to identify and extract text segments that referenced LGBTQI+ content in each textbook. An iterative codebook was developed, codes were applied, and analysis of the information and context in which the terms were presented was performed. RESULTS: The research team observed gaps and notable patterns in distribution of LGBTQI+ terms and health content areas across the textbooks reviewed. The majority of LGBTQI+ search terms were identified in the following health content areas: social determinants of health, sexual/reproductive health, pediatric sexual & gender diversity, intersectionality, and infectious disease. Based on qualitative descriptive analyses, the data were organized into the following categories: a) Language; b) Medicalization; c) Vague, Incomplete, or Lacking Specificity; and d) Comprehensive Approach. CONCLUSION: Findings highlight the need for increased academic exposure for pre-licensure nursing students regarding the care of LGBTQI+ patients. Thoughtful inclusion of LGBTQI+ content may better foster the delivery of evidence-based care for this patient population. These findings underscore the need for improved nursing curricula to support nurses in delivering affirming care for LGBTQI+ populations.

Development and psychometric properties of the tool for assessing LGBTQI+ health training (TALHT) in pre-licensure nursing curricula.

BACKGROUND: There is a lack of comprehensive lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI+) content in pre-licensure nursing curricula. LGBTQI+ people commonly experience mistreatment from nurses and healthcare providers due to a lack of knowledge or personal biases. To date, few instruments exist to guide LGBTQI+-specific curricular improvement. OBJECTIVES/DESIGN/SETTING/PARTICIPANT/METHODS: Johns Hopkins School of Nursing LGBTQI+ Health Initiative and Emory University School of Nursing developed the Tool for Assessing LGBTQI+ Health Training (TALHT) to assist in evaluating gaps and redundancies in LGBTQI+ health content within pre-licensure nursing curricula. Face and content validity were evaluated among experts in LGBTQI+ health, curricular development, nursing education, and measure development (N = 22). The TALHT was modified based on expert feedback and a pilot with pre-licensure faculty (N = 13) to evaluate utility and acceptability of the refined measure. RESULTS: Face and content validity evaluation of the 60-item iteration of the TALHT showed that the majority of items were consistently relevant among external expert reviewers. However, the clarity and readability of items were lacking. We triangulated the quantitative and qualitative data from experts to adapt and reduce the number of items in the TALHT to 20 items. Pilot testing of the revised 20-item measure found that utility and acceptability of the tool were rated highly among pre-licensure faculty. CONCLUSION: The validation of the TALHT comes at a time when this type of instrument is clearly needed. The Future of Nursing 2020-2030 report calls for nursing education to incorporate competencies in caring for diverse populations to promote health equity. The Essentials: Core Competencies for Professional Nursing Education calls for a transition to operationalization of competency-based nursing education. The TALHT provides faculty and programs with a valid and reliable means to operationalize implementation of those competencies as they pertain to LGBTQI+ health.

U.S. medical school admissions and enrollment practices: status of LGBTQ inclusivity.

CONTEXT: The failure to collect information on lesbian, gay, bisexual, transgender, and queer (LGBTQ) identity in healthcare and medical education is a part of a systemic problem that limits academic medical institutions' ability to address LGBTQ health disparities. OBJECTIVES: To determine whether accurate sexual and gender minority (SGM) demographic data is being consistently collected for all US medical schools during admissions and enrollment, and whether differences exist between collection practices at osteopathic and allopathic schools. METHODS: Secure, confidential electronic were sent via email in July 2019 to 180 osteopathic (n=42) and allopathic (n=138) medical schools identified through the American Association of Colleges of Osteopathic Medicine Student Guide to Osteopathic Medical Colleges database and the American Association of Medical Colleges Medical School Admissions Requirements database. The nine question survey remained open through October 2019 and queried for; (1) the ability of students to self report SGM status during admissions and enrollment; and (2) availability of SGM specific resources and support services for students. Chi square analysis and the test for equality of proportions were performed. RESULTS: Seventy five of 180 (41.7%) programs responded to the survey; 74 provided at least partial data. Of the 75 respondent schools, 55 (73.3%) allowed applicants to self report a gender identity other than male or female, with 49 (87.5%) of those being allopathic schools compared with 6 (31.6%) osteopathic schools. Similarly, 15 (20.0%) allowed applicants to report sexual orientation, with 14 (25.5%) of those being allopathic schools compared with one (5.3%) osteopathic school. Fifty four of 74 (73.0%) programs allowed matriculants to self report a gender identity other than male or female; 11 of 74 (14.7%) allowed matriculants to report sexual orientation. CONCLUSIONS: Demographics collection practices among American medical education programs that responded to our survey indicated that they undervalued sexual orientation and gender identity, with osteopathic programs being less likely than allopathic programs to report inclusive best practices in several areas. American medical education programs, and their supervising bodies, must update their practices with respect to the collection of sexual orientation and gender identity demographics as part of a holistic effort to address SGM health disparities.

Density-Dependent Demography and Mass-Rearing of Carposina sasakii (Lepidoptera: Carposinidae) Incorporating Life Table Variability.

Carposina sasakii Matsumura is one of the most destructive fruit-boring pests of pome and stone fruit trees in eastern Asia. Because larvae complete their development inside a single fruit, larval density per fruit is a critical factor in their survival, development, and fecundity. The effect of larval density was examined to determine the ideal density for devising an economic and sustainable mass-rearing system for harvesting of C. sasakii. Mass production of insects of the same age of a specific stage is not only important in biological control, but also in pheromone extraction, culturing of entomopathogenic nematodes and fungi, etc. Life history data for six larval densities (1-5, 6-10, 11-15, 16-20, 21-30, and 31-40 larvae/apple) were collected at 25.5 ± 0.5°C, 75.0 ± 5.0% RH, and a photoperiod of 15:9 (L: D) h. Data were analyzed using the age-stage, two-sex life table. The results showed that the highest preadult survival rate (42.00%), fecundity (104.70 eggs), and population parameters (intrinsic rate of increase r = 0.0718 d-1, net reproductive rate R0 = 23.03 eggs, and finite rate of increase λ = 1.0744 d-1) were observed at a density of 1-5 larvae/apple. However, when the rearing costs and production rate were considered, the density of 16-20 larvae/apple was the most economical for mass-rearing C. sasakii in order to achieve a daily harvest rate of 1,000 pupae (from 273 apples per day). To ensure the sustainability of the mass-rearing system, we included the life table variability in the harvesting strategy.

Morphological differences of the reproductive system could be used to predict the optimum Grapholita molesta (Busck) control period.

The oriental fruit moth (OFM), Grapholita molesta (Busck), is one of the dominant fruit-boring pests worldwide. In order to conduct integrated control of OFM effectively, it is important to predict the optimum control period. OFM populations have been monitored either by the number of trapped male moths exposed to sex pheromones or by the number of trapped male and female moths using food traps in orchards. The mating status and development stage of the trapped moths have not been characterized. The present paper studies the anatomical morphology of the OFM reproductive system at different development periods. The results revealed that OFM ovarian development can be divided into six stages. The average daily fecundity of OFM had an excellent positive correlation (r = 0.86) with the percentages of OFM in the egg maturation & oviposition stage, which could be used as an indicator in field population prediction work. There were obvious differences in the morphology of the corpus bursa and the heavy muscular area of the ductus ejaculatorius simplex before and after mating, and these differences could be used to increase the accuracy in predicting the optimum OFM control period.

Blood type, ABO genetic variants, and ovarian cancer survival.

OBJECTIVE: Blood type A and the A1 allele have been associated with increased ovarian cancer risk. With only two small studies published to date, evidence for an association between ABO blood type and ovarian cancer survival is limited. METHODS: We conducted a retrospective cohort study of Tumor Registry confirmed ovarian cancer cases from the Vanderbilt University Medical Center with blood type from linked laboratory reports and ABO variants from linked Illumina Exome BeadChip data. Associations with overall survival (OS) were quantified by hazard ratios (HR) and confidence intervals (CI) from proportional hazards regression models; covariates included age, race, stage, grade, histologic subtype, and year of diagnosis. RESULTS: ABO phenotype (N = 694) and/or genotype (N = 154) data were available for 713 predominantly Caucasian (89.3%) cases. In multivariable models, blood type A had significantly better OS compared to either O (HR: 0.75, 95% CI: 0.60-0.93) or all non-A (HR: 0.77, 95% CI: 0.63-0.94) cases. Similarly, missense rs1053878 minor allele carriers (A2) had better OS (HR: 0.50, 95% CI: 0.25-0.99). Among Caucasians, this phenotype association was strengthened, but the genotype association was attenuated; instead, four variants sharing moderate linkage disequilibrium with the O variant were associated with better OS (HR: 0.62, 95% CI: 0.39-0.99) in unadjusted models. CONCLUSIONS: Blood type A was significantly associated with longer ovarian cancer survival in the largest such study to date. This finding was supported by genetic analysis, which implicated the A2 allele, although O related variants also had suggestive associations. Further research on ABO and ovarian cancer survival is warranted.