Stage-Specific Timing of the microRNA Regulation of \u3cem\u3elin-28\u3c/em\u3e by the Heterochronic Gene \u3cem\u3elin-14\u3c/em\u3e in \u3cem\u3eCaenorhabditis elegans\u3c/em\u3e

In normal development, the order and synchrony of diverse developmental events must be explicitly controlled. In the nematode Caenorhabditis elegans, the timing of larval events is regulated by hierarchy of proteins and microRNAs (miRNAs) known as the heterochronic pathway. These regulators are organized in feedforward and feedback interactions to form a robust mechanism for specifying the timing and execution of cell fates at successive stages. One member of this pathway is the RNA binding protein LIN-28, which promotes pluripotency and cell fate decisions in successive stages. Two genetic circuits control LIN-28 abundance: it is negatively regulated by the miRNA lin-4, and positively regulated by the transcription factor LIN-14 through a mechanism that was previously unknown. In this report, we used animals that lack lin-4 to elucidate LIN-14’s activity in this circuit. We demonstrate that three let-7 family miRNAs—miR-48, miR-84, and miR-241—inhibit lin-28 expression. Furthermore, we show genetically that these miRNAs act between lin-14 and lin-28, and that they comprise the pathway by which lin-14 positively regulates lin-28. We also show that the lin-4 family member mir-237, also regulates early cell fates. Finally, we show that the expression of these miRNAs is directly inhibited by lin-14 activity, making them the first known targets of lin-14 that act in the heterochronic pathway

Concomitant Adolescent Vaccination in the U.S., 2007–2012

Concomitant (same-day) delivery of two or more vaccines to adolescents is effective, safe, and efficient. Increasing concomitant vaccination could improve coverage for recommended adolescent vaccines, but little is known about who receives vaccines concomitantly

Impact of maternal and paternal preconception health on birth outcomes using prospective couples’ data in Add Health

Retrospective studies of preconception health have demonstrated that parents’ health conditions and behaviors can impact a newborn’s birth outcomes and, subsequently, future health status. This study sought to examine the impact of preconception health, measured prospectively, among both mothers and fathers, on two important birth outcomes: birthweight and gestational age

School Entry Requirements and Coverage of Nontargeted Adolescent Vaccines

Low human papillomavirus (HPV) vaccination coverage is an urgent public health problem requiring action. To identify policy remedies to suboptimal HPV vaccination, we assessed the relationship between states’ school entry requirements and adolescent vaccination

Summer Peaks in Uptake of Human Papillomavirus and Other Adolescent Vaccines in the United States

BACKGROUND: Seasonality in human papillomavirus (HPV) vaccination could have a large impact on national cancer prevention efforts. We hypothesized that uptake of HPV vaccine and other adolescent vaccines in the United States would be highest in the summer. METHODS: Data came from health care provider-verified vaccination records for 70,144 adolescents (ages 13-17 years) from the 2008 to 2012 versions of the National Immunization Survey-Teen. Using the Edwards method for testing annual trends, we examined seasonal patterns in the uptake of HPV and other recommended adolescent vaccines [tetanus, diphtheria, and pertussis (Tdap) booster and meningococcal vaccine]. HPV vaccine initiation (receipt of the first of the three-dose series) data were for female adolescents. RESULTS: Uptake for HPV and other adolescent vaccines peaked in the summer across years and states (all P < 0.001). Uptake was five times as frequent at the peak as at the trough for HPV vaccine, and HPV vaccine initiation was highest in June, July, and August (percent of doses delivered in these months: 38.7%). The same pattern existed for Tdap booster and meningococcal vaccine. Concomitant (same-day) vaccination of HPV vaccine with other adolescent vaccines also demonstrated summer peaks each year nationally (all P < 0.001). CONCLUSION: Uptake of adolescent vaccines increased dramatically in summer months. These summer peaks are an important opportunity for interventions focused on concomitant vaccination. IMPACT: The potential cancer prevention impact of HPV vaccination programs could be increased, for example, by delivering messages about concomitant vaccination during the summer, when adolescents and their parents might be most open to them

Simian immunodeficiency virus (SIV) envelope quasispecies transmission and evolution in infant rhesus macaques after oral challenge with uncloned SIVmac251: increased diversity is associated with neutralizing antibodies and improved survival in previously immunized animals

BACKGROUND: Oral infection of infant macaques with simian immunodeficiency virus (SIV) is a useful animal model to test interventions to reduce postnatal HIV transmission via breast-feeding. We previously demonstrated that immunization of infant rhesus macaques with either modified vaccinia virus Ankara (MVA) expressing SIV Gag, Pol and Env, or live-attenuated SIVmac1A11 resulted in lower viremia and longer survival compared to unimmunized controls after oral challenge with virulent SIVmac251 (Van Rompay et al., J. Virology 77:179–190, 2003). Here we evaluate the impact of these vaccines on oral transmission and evolution of SIV envelope variants. RESULTS: Limiting dilution analysis of SIV RNA followed by heteroduplex mobility assays of the V1–V2 envelope (env) region revealed two major env variants in the uncloned SIVmac251 inoculum. Plasma sampled from all infants 1 week after challenge contained heterogeneous SIV env populations including one or both of the most common env variants in the virus inoculum; no consistent differences in patterns of env variants were found between vaccinated and unvaccinated infants. However, SIV env variant populations diverged in most vaccinated monkeys 3 to 5 months after challenge, in association with the development of neutralizing antibodies. CONCLUSIONS: These patterns of viral envelope diversity, immune responses and disease course in SIV-infected infant macaques are similar to observations in HIV-infected children, and underscore the relevance of this pediatric animal model. The results also support the concept that neonatal immunization with HIV vaccines might modulate disease progression in infants infected with HIV by breast-feeding

How to Launch an Interdisciplinary Leadership Program

Building a doctoral program in leadership is never an easy task, and building an interdisciplinary doctoral program is even more difficult. Yet, it is the interdisciplinary approach that differentiates typical leadership programs from others and offers learners an integrated view of leadership theories and practices. This special report presents an example of designing and implementing an interdisciplinary doctoral program that promotes social justice leadership. Drawing from firsthand experiences of program faculty, staff, and administration, we share lessons learned and the logic behind adopting an interdisciplinary approach for those creating programs that seeks to promote social justice. We found that by allowing students and faculty to convene together, rather than disperse into separate, isolated academic disciplines, emerging scholar-practitioners are encouraged to engage in realistic, professional practice investigation and problem-solving techniques. Through this experience, we also found that conscious coursework design involves integrating multiple, often quite divergent, disciplines into a core set of courses. Additionally, we learned that unifying students through a common mission permits distinctive discussions, including personal reflection and ethical decision-making opportunities among the concepts, constructs, and knowledge that extend beyond disciplinary lines (Cherney et al., 2012). We also found that cultivating a diverse student body and faculty base requires everyone to work strategically within the program, recognizing the call for coherence and consistency across disciplinary lines. Finally, we discovered that developing a dissertation in practice allows students to implement an evidence-based solution within their professional practice setting as their pinnacle doctorate work (Herr & Anderson, 2014; Olson & Clark, 2009). We conclude this paper by reiterating our finding that leadership programs that promote social justice are enhanced by adopting an interdisciplinary approach as this allows for the creation of a program that challenges students to learn at a more complex level, faculty to integrate disciplines, and programs to promote socially just ideals. We discuss implications for other schools seeking to develop an interdisciplinary doctoral leadership program

Correlates of Human Papillomavirus Vaccine Coverage: A State-Level Analysis

We tested the hypothesis that states with higher rates of cancers associated with human papillomavirus (HPV) would have lower HPV vaccine coverage

HPV vaccine for teen boys: Dyadic analysis of parents' and sons' beliefs and willingness

Parents and adolescents often decide together whether the child should receive human papillomavirus (HPV) vaccine. However, few studies have investigated the dyadic nature of beliefs that affect this process

Parents' Support for School-Entry Requirements for Human Papillomavirus Vaccination: A National Study

The number of states proposing school-entry requirements for human papillomavirus (HPV) vaccination has increased over the last decade. However, data are currently limited regarding parents' support of such laws. We sought to obtain the first national estimates of parents' support of HPV vaccination school-entry requirements