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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.

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 F0 C. 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.

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. 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. 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. 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.

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.

The peach fruit moth, Carposina sasakii Matsumura, is a significant fruit-boring pest that negatively impacts the East Asian agricultural economy. To aid the development of pest control strategies, peach fruit moths are raised and studied for multiple generations in laboratory. It is important when maintaining a laboratory moth colony to consider the effects of nutrition on the colony’s growth, survival, and reproduction. In this study, adult peach fruit moths (F[sub.0] ) were divided into separate groups, and each group was fed one of seven different nutrient solutions under laboratory conditions. The development and fitness of the moths’ offspring (F[sub.1] ) were then analyzed. The results showed that F[sub.0] adult peach fruit moths fed with 10 grams per liter sucrose had F[sub.1] offspring with significantly higher fitness and reproductive parameters, suggesting that this concentration of sucrose is more suitable for raising laboratory peach fruit moths. Thus, appropriate nutrition during the adult stage of the peach fruit moth’s life cycle could play an important role in the development of future offspring in laboratory studies and in turn influence the future of East Asian agriculture. 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 (F[sub.0] ) nutritional status on offspring (F[sub.1] ) 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 F[sub.1] directly descended from F[sub.0] C. sasakii fed with seven different nutrients (water as control, 5 g·L[sup.−1] honey solution, 10 g·L[sup.−1] honey solution, 5 g·L[sup.−1] sucrose solution, 10 g·L[sup.−1] sucrose solution, 15 g·L[sup.−1] sucrose solution, and 20 g·L[sup.−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 F[sub.0] differentially affects the growth, development, and reproduction of F[sub.1] . The F[sub.1] offspring of F[sub.0] adult C. sasakii fed with 10 g·L[sup.−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, R[sub.0] = 12.61 ± 3.57); thus, 10 g·L[sup.−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 F[sub.0] nutritional conditions on the fitness of F[sub.1] 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.

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.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.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.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.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.

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 breast cancer-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 wild type 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. Competing Interest Statement The authors have declared no competing interest.

ObjectiveGastric cancer is a major gastrointestinal malignancy for which targeted therapies are emerging as treatment options. This study sought to identify the most prevalent molecular targets in gastric cancer and to elucidate systematic patterns of exclusivity and co-occurrence among these targets, through comprehensive genomic analysis of a large panel of gastric cancers.DesignUsing high-resolution single nucleotide polymorphism arrays, copy number alterations were profiled in a panel of 233 gastric cancers (193 primary tumours, 40 cell lines) and 98 primary matched gastric non-malignant samples. For selected alterations, their impact on gene expression and clinical outcome were evaluated.Results22 recurrent focal alterations (13 amplifications and nine deletions) were identified. These included both known targets (FGFR2, ERBB2) and also novel genes in gastric cancer (KLF5, GATA6). Receptor tyrosine kinase (RTK)/RAS alterations were found to be frequent in gastric cancer. This study also demonstrates, for the first time, that these alterations occur in a mutually exclusive fashion, with KRAS gene amplifications highlighting a clinically relevant but previously underappreciated gastric cancer subgroup. FGFR2-amplified gastric cancers were also shown to be sensitive to dovitinib, an orally bioavailable FGFR/VEGFR targeting agent, potentially representing a subtype-specific therapy for FGFR2-amplified gastric cancers.ConclusionThe study demonstrates the existence of five distinct gastric cancer patient subgroups, defined by the signature genomic alterations FGFR2 (9% of tumours), KRAS (9%), EGFR (8%), ERBB2 (7%) and MET (4%). Collectively, these subgroups suggest that at least 37% of gastric cancer patients may be potentially treatable by RTK/RAS directed therapies.

A promising drug target, SETDB1, is a dual methyl-lysine (Kme) reader and methyltransferase implicated in cancer and neurodegenerative disease progression. To help understand the role of the triple Tudor domain (3TD) of SETDB1, its Kme reader, we first identify a low micromolar potency small molecule ligand, UNC6535, which occupies simultaneously both the TD2 and TD3 reader binding sites. Further optimization leads to the discovery of UNC10013, a covalent 3TD ligand targeting Cys385 of SETDB1. UNC10013 is potent with a k inact /K I of 1.0 × 10 6  M −1 s −1 and demonstrates proteome-wide selectivity. In cells, negative allosteric modulation of SETDB1-mediated Akt methylation occurs after treatment with UNC10013. Therefore, UNC10013 is a potent, selective, and cell-active covalent ligand for the 3TD of SETDB1, demonstrating negative allosteric modulator properties and making it a promising tool to study the biological role of SETDB1 in disease progression. Design of cysteine-targeting analogs of a reversible SETDB1 triple Tudor domain (3TD) ligand, UNC6535, led to UNC10013, a potent covalent ligand with high selectivity. UNC10013 demonstrated allosteric inhibition of SETDB1-mediated Akt methylation in cells, a promising approach to SETDB1 therapeutics.

The ability of neural stem cells (NSCs) to switch between quiescent and proliferative states is fundamental for adult neurogenesis and regeneration. Microproteins or short open reading frame (sORF)-encoded peptides (SEPs), are highly abundant yet largely understudied, and their role in brain development remains unclear. Here, we demonstrate that two evolutionarily-conserved microprotein paralogs, Simba1 and Simba2, encoded by sORFs CG15715 and CG18081 , respectively, govern the reactivation of Drosophila quiescent NSCs. Both Simba1 and Simba2 function in NSCs and Blood-Brain-Barrier (BBB) glial cells to promote NSC reactivation. Mechanistically, Simba1 and Simba2 act as transcription factors activating the WNT/Wingless signalling pathway during NSC reactivation. We uncover a critical role of Wg signalling molecules in promoting NSC reactivation and the translocation of Wingless from BBB glia to NSCs. Our findings reveal a role for microproteins Simba1/2 in regulating NSC reactivation through Wg signalling. Moreover, our bioinformatic analysis and luciferase assay suggest that ZNF706, the human ortholog of Simba1/2, is required for WNT signaling activation in human cells. The conserved function of Simba1/2/ZNF706 in activating WNT/Wg signalling in Drosophila and humans suggests that this new regulatory paradigm may be applicable to broader cellular processes and disease conditions. Drosophila Microproteins Simba1/2 act in neural stem cells and blood-brain-barrier glia to promote reactivation of neural stem cells via activating WNT/Wingless signaling, while human ortholog ZNF706 is found to have a conserved role in activating WNT pathway.