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The nonsense-mediated mRNA decay (NMD) pathway functions to degrade both abnormal and wild-type mRNAs. NMD is essential for viability in most organisms, but the molecular basis for this requirement is unknown. Here we show that a single, conserved NMD target, the mRNA coding for the stress response factor growth arrest and DNA-damage inducible 45 (GADD45) can account for lethality in Drosophila lacking core NMD genes. Moreover, depletion of Gadd45 in mammalian cells rescues the cell survival defects associated with NMD knockdown. Our findings demonstrate that degradation of Gadd45 mRNA is the essential NMD function and, surprisingly, that the surveillance of abnormal mRNAs by this pathway is not necessarily required for viability. Messenger RNA (mRNA) molecules act as the templates from which proteins are made, and so control the amount of protein in a cell. Having too much of certain proteins can harm cells. Additionally, some mRNAs contain errors, and so can create faulty proteins that may also harm the cell. Cells have therefore developed ways to destroy excess or error-ridden mRNAs to avoid a deadly build up of proteins. One such quality control mechanism is called nonsense-mediated decay (NMD). This mechanism is so important that cells that cannot perform nonsense-mediated decay die, although it is not clear exactly what kills the cells. Now, Nelson et al. have found that fruit flies whose cells are unable to perform nonsense-mediated decay die because a harmful protein called Gadd45 builds up in the cells. In normal cells, nonsense-mediated decay destroys the mRNA that relays the instructions for making Gadd45, which keeps the amount of the Gadd45 protein in the cell low. Further experiments show that removing Gadd45 from cells that lack nonsense-mediated decay saves the flies. Removing Gadd45 from human and mouse cells that are unable to perform nonsense-mediated decay also allows these cells to survive. These findings imply that the only nonsense-mediated decay function needed for cells to live is the destruction of Gadd45 mRNA. This further implies that most faulty and normal mRNAs that are normally destroyed by nonsense-mediated decay do not cause the cells to die when nonsense-mediated decay is lost. Learning that creating faulty proteins when nonsense-mediated decay is lost is not necessarily harmful to cells opens new possibilities to treating numerous genetic diseases. In some diseases, cells can only produce faulty forms of a particular protein. Nonsense-mediated decay normally destroys all of these mutant proteins, but it may sometimes be better to have faulty versions of a protein than to have none of it. Safely getting rid of nonsense-mediated decay by also eliminating Gadd45 from cells may therefore be a treatment strategy worth exploring.

The unfolded protein response (UPR) is a collection of pathways that maintains the protein secretory pathway during the many physiological and pathological conditions that cause stress in the endoplasmic reticulum (ER). The UPR is mediated in part by Ire1, an ER transmembrane kinase and endoribonuclease that is activated when misfolded proteins accumulate in the ER. Ire1's nuclease initiates the cytosolic splicing of the mRNA encoding X-box binding protein (Xbp1), a potent transcription factor that then upregulates genes responsible for restoring ER function. This same nuclease is responsible for the degradation of many other mRNAs that are localized to the ER, through Regulated Ire1 Dependent Decay (RIDD). Here we show that Smt3, a homolog of small ubiquitin-like modifier (sumo), is a non-canonical RIDD target in Drosophila S2 cells. Unlike other RIDD targets, the sumo transcript does not stably associate with the ER membrane, but instead relies on an Xbp1-like stem loop and a second UPR mediator, Perk, for its degradation during stress.

Evidence has accumulated that confirms the success of a positive youth development (PYD) approach. Importantly, a positive development approach is just that—an approach. It is not a particular program or curriculum but a set of practices designed to achieve one or more positive outcomes. As such, PYD practices can be added onto other programs to make positive outcomes more likely. For example, a tutoring program can work hard to hire and train staff to work with students in a trusting, respectful relationship. Camp counselors can be encouraged to build rapport and positive bonds among the campers.

Parent-teen discussions about sexual and reproductive health (SRH) are associated with delayed sex and higher contraceptive use among teens. Using the National Survey of Family Growth, we conducted bivariate and multivariate analyses of different types of parent-teen SRH discussions among two cohorts of teens. We describe differences in patterns for males and females by race/ethnicity and nativity, and test for racial/ethnic interactions within each cohort. Analyses found that the prevalence of parent-teen discussions about SRH increased across cohorts. For males and females, there were increases in parent-teen discussions about condoms, and for males only, there were increases in any SRH discussions and discussions about contraception and STIs. Based on interactions, parent-teen discussions and STI discussions increased most for Hispanic females, and among Hispanics, increased most for the foreign-born. These data indicate increases in different types of parent-teen SRH discussions, particularly for males and foreign-born teens overall, and for Hispanic teen females regarding condom use. Future research should examine what factors are driving these changes, including changes in the structure of U.S. Hispanic communities and expansion of evidence-based teen pregnancy prevention programs.

Children who are nurtured, protected, and supported in the first years of life tend to have better individual outcomes and are more likely to grow to become healthy, productive adults. Child well-being varies across states, yet the field lacks a comprehensive review of infant and toddler indicators measured at the state-level. This paper reviews indicators of well-being from the prenatal period to three years that meet certain a priori criteria. Most of the child-level indicators identified were in the physical health domain; relatively fewer indicators were found in the early cognition and language or social-emotional-behavioral domains. While some states are making progress toward developing integrated early childhood data systems, more work is needed to provide robust data on infant and toddler development. These results highlight the need to develop a broader range of indicators of infant and toddler well-being and improve measurement sources to better inform policies and programs advancing population health.

Objective This study examined the associations between household food security (access to sufficient, safe, and nutritious food) during infancy and attachment and mental proficiency in toddlerhood. Methods Data from a longitudinal nationally representative sample of infants and toddlers ( n  = 8944) from the Early Childhood Longitudinal Study—9-month (2001–2002) and 24-month (2003–2004) surveys were used. Structural equation modeling was used to examine the direct and indirect associations between food insecurity at 9 months, and attachment and mental proficiency at 24 months. Results Food insecurity worked indirectly through depression and parenting practices to influence security of attachment and mental proficiency in toddlerhood. Conclusions Social policies that address the adequacy and predictability of food supplies in families with infants have the potential to affect parental depression and parenting behavior, and thereby attachment and cognitive development at very early ages.

Context: Few studies with nationally representative longitudinal data have examined whether and how family religiosity is associated with adolescent sexual and contraceptive behavior. Methods: Data from the 1997 National Longitudinal Survey of Youth were used to examine associations between a multidimensional measure of family religiosity assessed during early adolescence and reproductive health outcomes (sexual activity, number of partners and consistent contraceptive use) at age 17. Pathways through which family religiosity is associated with these outcomes were identified using structural equation models. Results: Family religiosity was negatively associated with adolescent sexual activity, both directly (beta, -0.14) and indirectly (-0.02). The indirect association was mediated by family cohesion (as reflected in parental monitoring among the entire sample and among males, and in parent-teenager relationship quality and family routine activities among females) and negative peer behaviors. Greater family religiosity was indirectly associated with having fewer sexual partners (-0.03) and with using contraceptives consistently (0.02); these relationships were mediated through later age at first sex, more positive peer environments and higher levels of parental monitoring and awareness. However, among sexually active males (but not females), family religiosity was directly and negatively associated with contraceptive consistency (-0.11). CONCLUSION: Cohesive family environments and positive peer networks contribute to reduced levels of risky sexual behavior among adolescents from religious families. Parents who monitor their children's activities and peer environments, engage their families in regular activities and foster strong parent-child relationships can help reduce risky sexual behavior, regardless of family religiosity. Parental involvement in prevention programs may help reduce rates of teenage pregnancy and STDs.

Photosynthetic organisms regulate their responses to many diverse stimuli in an effort to balance light harvesting with utilizable light energy for carbon fixation and growth (source–sink regulation). This balance is critical to prevent the formation of reactive oxygen species that can lead to cell death. However, investigating the molecular mechanisms that underlie the regulation of photosynthesis in cyanobacteria using ensemble-based measurements remains a challenge due to population heterogeneity. Here, to address this problem, we used long-term quantitative time-lapse fluorescence microscopy, transmission electron microscopy, mathematical modelling and genetic manipulation to visualize and analyse the growth and subcellular dynamics of individual wild-type and mutant cyanobacterial cells over multiple generations. We reveal that mechanical confinement of actively growing Synechococcus sp. PCC 7002 cells leads to the physical disassociation of phycobilisomes and energetic decoupling from the photosynthetic reaction centres. We suggest that the mechanical regulation of photosynthesis is a critical failsafe that prevents cell expansion when light and nutrients are plentiful, but when space is limiting. These results imply that cyanobacteria must convert a fraction of the available light energy into mechanical energy to overcome frictional forces in the environment, providing insight into the regulation of photosynthesis and how microorganisms navigate their physical environment. Using single-cell imaging of the cyanobacterium Synechococcus , the authors show that confinement or mechanical perturbations result in altered photosynthetic activity.

Data from the 2007 National Survey of Children’s Health are used to develop an index of positive child well-being that has several innovative and important characteristics. It distinguishes child well-being from contexts of child development; it is built with rich micro-data (rather than population-level macro-data) to create unique measures of well-being for individual children; and it focuses on positive, rather than negative, aspects of development. These data can be aggregated to provide a perspective on the proportions of children in the population who are doing well on all, some, or no developmental domains. Based on child development theory and research, the index is constructed within a framework of four conceptually distinct developmental domains, each of which is comprised of three sub-domains. The index distinguishes among children in predicted directions, by poverty level and parental education. White children tend to do better than Hispanic or black children in all domains, though neither minority subgroup is consistently better or worse off than the other subgroup. Girls score slightly higher than boys on the index. About three in four children score positively on three or four domains. The index provides a composite, multidimensional view of positive child well-being that can be useful to researchers and policy analysts, and which addresses some weaknesses of other similar indices.

Using data from the Early Childhood Longitudinal Study-Birth Cohort, 9-month resident father surveys (N=6,816), this paper examines the association between male pregnancy intentions, prenatal behaviors, and postbirth father involvement. Findings indicate that prenatal behaviors are associated with five domains of father involvement. Men who did not want the pregnancy are less likely to exhibit paternal warmth following the birth, whereas men who wanted the pregnancy sooner than it occurred are more likely to exhibit nurturing behaviors. The influence of fathers' pregnancy intentions and prenatal behaviors on postbirth involvement is for the most part not dependent on child gender. Findings suggest that prenatal programs that encourage fathers to actively participate in the pregnancy may be beneficial to later child well-being.