Understanding speciation requires the identification of traits that cause reproductive isolation. This remains a major challenge since it is difficult to determine which of the many divergent traits actually caused speciation. To overcome this difficulty, we studied the sexual cue traits and behaviors associated with rapid speciation between EA and WN sympatric behavioral races of Drosophila athabasca that diverged only 16,000-20,000 years ago. First, we found that sexual isolation was essentially complete and driven primarily by divergent female mating preferences. To determine the target of female mate choice, we found that, unlike cuticular hydrocarbons (CHCs), male courtship song is highly divergent between EA and WN in both allopatry and sympatry and is not affected by latitudinal variation. We then used pheromone rub-off experiments to show no effect of CHCs on divergent female mate choice. In contrast, both male song differences and male mating success in hybrids exhibited a large X-effect and playback song experiments confirmed that male courtship song is indeed the target of sexual isolation. These results show that a single secondary sexual trait is a major driver of speciation and suggest that we may be overestimating the number of traits involved in speciation when we study older taxa.

BackgroundThe Mobile Insulin Titration Intervention (MITI) program helps patients with type 2 diabetes find their correct basal insulin dose without in-person care. Requiring only basic cell phone technology (text messages and phone calls), MITI is highly accessible to patients receiving care in safety-net settings. MITI was shown in a randomized controlled trial (RCT) to be efficacious at a New York City (NYC) safety-net clinic where patients often have challenges coming for in-person care. In 2016, MITI was implemented as usual care at Bellevue Hospital (the site of the original RCT) and at Gouverneur Health (a second NYC safety-net clinic) under 2 different staffing models.ObjectiveThis implementation study examined MITI’s transition into real-world settings. To understand MITI’s flexibility, generalizability, and acceptability among patients and providers, we evaluated whether MITI continued to produce positive outcomes in expanded underserved populations, outside of an RCT setting.MethodsPatients enrolled in MITI received weekday text messages asking for their fasting blood glucose (FBG) values and a weekly titration call. The goal was for patients to reach their optimal insulin dose (OID), defined either as the dose of once-daily basal insulin required to achieve either an FBG of 80-130 mg/dL (4.4-7.2 mmol/L) or as the reaching of the maximum dose of 50 units. After 12 weeks, if OID was not reached, the patients were asked to return to the clinic for in-person care and titration. MITI program outcomes, clinical outcomes, process outcomes, and patient satisfaction were assessed.ResultsMITI was successful at both sites, each with a different staffing model. Providers referred 170 patients to the program—129 of whom (75.9%, 129/170) were eligible. Of these, 113 (87.6%, 113/129) enrolled. Moreover, 84.1% (95/113) of patients reached their OID, and they did so in an average of 24 days. Clinical outcomes show that mean FBG levels fell from 209 mg/dL (11.6 mmol/L) to 141 mg/dL (7.8 mmol/L), P<.001. HbA1c levels fell from 11.4% (101 mmol/mol) to 10.0% (86 mmol/mol), P<.001. Process outcomes show that 90.1% of MITI’s text message prompts received a response, nurses connected with patients 81.9% of weeks to provide titration instructions, and 85% of attending physicians made at least one referral to the MITI program. Satisfaction surveys showed that most patients felt comfortable sharing information over text and felt the texts reminded them to take their insulin, check their sugar, and make healthy food choices.ConclusionsThis implementation study showed MITI to have continued success after transitioning from an RCT program into real-world settings. MITI showed itself to be flexible and generalizable as it easily fits into a second site staffed by general medical clinic–registered nurses and remained acceptable to patients and staff who had high levels of engagement with the program.

Amino-terminal (Nt-) acetylation (NTA) is a common protein modification, affecting 80% of cytosolic proteins in humans. The human essential gene, NAA10, encodes for the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex, also including the accessory protein, NAA15. The full spectrum of human genetic variation in this pathway is currently unknown. Here we reveal the genetic landscape of variation in NAA10 and NAA15 in humans. Through a genotype-first approach, one clinician interviewed the parents of 56 individuals with NAA10 variants and 19 individuals with NAA15 variants, which were added to all known cases (N = 106 for NAA10 and N = 66 for NAA15). Although there is clinical overlap between the two syndromes, functional assessment demonstrates that the overall level of functioning for the probands with NAA10 variants is significantly lower than the probands with NAA15 variants. The phenotypic spectrum includes variable levels of intellectual disability, delayed milestones, autism spectrum disorder, craniofacial dysmorphology, cardiac anomalies, seizures, and visual abnormalities (including cortical visual impairment and microphthalmia). One female with the p.Arg83Cys variant and one female with an NAA15 frameshift variant both have microphthalmia. The frameshift variants located toward the C-terminal end of NAA10 have much less impact on overall functioning, whereas the females with the p.Arg83Cys missense in NAA10 have substantial impairment. The overall data are consistent with a phenotypic spectrum for these alleles, involving multiple organ systems, thus revealing the widespread effect of alterations of the NTA pathway in humans.

Background A lack of educational continuity creates disorienting friction at the onset of residency. Few programs have harnessed the benefits of coaching, which can facilitate self-directed learning, competency development, and professional identity formation, to help ease this transition. Objective To describe the process of training faculty Bridge Coaches for the Transition to Residency Advantage (TRA) program for interns. Methods Nineteen graduate faculty educators participated in a coaching training course with formative skills assessment as part of a faculty development program starting in January 2020. Surveys (n = 15; 79%) and a focus group (n = 7; 37%) were conducted to explore the perceived impact of the training course on coaching skills, perceptions of coaching, and further program needs during the pilot year of the TRA program. Results Faculty had strong skills around establishing trust, authentic listening, and supporting goal-setting. They required more practice around guiding self-discovery and following a coachee-led agenda. Faculty found the training course to be helpful for developing coaching skills. Faculty embraced their new roles as coaches and appreciated having a community of practice with other coaches. Suggestions for improvement included more opportunities to practice and receive feedback on skills and additional structures to further support TRA program encounters with coaches. Conclusions The faculty development program was feasible and had good acceptance among participants. Faculty were well-suited to serve as coaches and valued the coaching mindset. Adequate skills reinforcement and program structure were identified as needs to facilitate a coaching program in graduate medical education.

NAA10 encodes for the enzyme NAA10, which is the catalytic subunit in the N-terminal acetyltransferase A (NatA) complex. N-alpha-acetylation is one of the most common co-translational protein modifications in humans and is essential for normal cell function. The auxiliary and regulatory subunits of the NatA complex are NAA15 and Huntington-interacting protein (HYPK), respectively. Through a genotype-first approach with primarily exome sequencing, one clinician identified and interviewed the parents of 56 individuals with NAA10 variants and 19 individuals with NAA15 variants. Clinical features of affected individuals include variable levels of intellectual disability, delayed speech and motor milestones and autism spectrum disorder, which are usually more severe in individuals with NAA10 variants compared to those with NAA15 variants. Additionally, some individuals present with mild craniofacial dysmorphology, congenital cardiac anomalies and seizures. The majority of individuals with NAA10 variants present with visual abnormalities, which often include astigmatism, myopia, strabismus, amblyopia, and/or cortical visual impairment. Further, there are a subset of individuals who have exotropia/esotropia, microphthalmia, blindness, and/or have abnormalities to the optic disc or nerve. In individuals with NAA15 variants, visual abnormalities were present in a small subset with strabismus, amblyopia, astigmatism, and other visual impairment, with many individuals affected by this syndrome wearing eyeglasses. We discovered a female (Individual 23) with the common p.Arg83Cys variant, yet she is the only female published to date who was born with microphthalmia, along with stigmatism in her left eye, myopia and possible cortical visual impairment. We report another male with microphthalmia with a frameshift p.Thr152Argfs*6 variant in NAA10. Vineland-3 functional assessment demonstrates that the overall level of functioning for the probands with NAA15 variants was significantly higher than the probands with NAA10 variants. When the results for NAA10 are separated by sex, inheritance pattern, and variant type, it is clear that the frameshift variants located toward the C-terminal end of NAA10 have much less impact on overall functioning. The females with the p.Arg83Cys missense in NAA10 have a similar level of impairment to the females with other missense changes in NAA10. The overall data are consistent with a phenotypic spectrum for these alleles involving multiple organ systems, including visual development, and as such we suggest that the condition involving NAA10 should be interchangeably referred to as Ogden syndrome and/or NAA10-related neurodevelopmental syndrome, and the condition involving NAA15 should be referred to as NAA15-related neurodevelopmental syndrome.