Urinary tract infections trigger synucleinopathy via the innate immune response.

Symptoms in the urogenital organs are common in multiple system atrophy (MSA), also in the years preceding the MSA diagnosis. It is unknown how MSA is triggered and these observations in prodromal MSA led us to hypothesize that synucleinopathy could be triggered by infection of the genitourinary tract causing ɑ-synuclein (ɑSyn) to aggregate in peripheral nerves innervating these organs. As a first proof that peripheral infections could act as a trigger in MSA, this study focused on lower urinary tract infections (UTIs), given the relevance and high frequency of UTIs in prodromal MSA, although other types of infection might also be important triggers of MSA. We performed an epidemiological nested-case control study in the Danish population showing that UTIs are associated with future diagnosis of MSA several years after infection and that it impacts risk in both men and women. Bacterial infection of the urinary bladder triggers synucleinopathy in mice and we propose a novel role of ɑSyn in the innate immune system response to bacteria. Urinary tract infection with uropathogenic E. coli results in the de novo aggregation of ɑSyn during neutrophil infiltration. During the infection, ɑSyn is released extracellularly from neutrophils as part of their extracellular traps. Injection of MSA aggregates into the urinary bladder leads to motor deficits and propagation of ɑSyn pathology to the central nervous system in mice overexpressing oligodendroglial ɑSyn. Repeated UTIs lead to progressive development of synucleinopathy with oligodendroglial involvement in vivo. Our results link bacterial infections with synucleinopathy and show that a host response to environmental triggers can result in ɑSyn pathology that bears semblance to MSA.

The Arc of Generational Care: A Case Series Considering Grandparent Roles and Care Needs in Pediatric Palliative Care.

Children receiving palliative care services are held within the context of a family and often within multiple-generational arms. The purpose of this case series paper is to recognize grandparents' roles in their family system from a personal, cultural, and anthropological perspective; to explore emotions and experiences as applies to grandparents of children receiving palliative care; and to provide tangible insight into caring well for families across the generational arc.

Compliance with parents' rules: between-person and within-person predictions.

The current study focused on the childhood to adolescence transition and sought to determine why some children are more compliant than others as well as why children comply more often with some of their parents' rules than with others. Indices of parents' agency and children's agency were tested as predictors of compliance. Parent-based decision-making and parents' responses to expressed disagreement served as indices of parents' agency while children's beliefs regarding the legitimacy of parents' rules and felt obligation to obey rules served as indices of children's agency. Parent-child dyads (n = 218; 51% female, 49% European American, 47% African American) were interviewed during the summers following the children's 5th (M adolescent age = 11.9 years) and 6th grade school years. Children who felt that their parents' rules were more legitimate were more compliant overall than were children who felt that the rules were less legitimate. Children compiled more with rules governing topics perceived to be legitimately regulated by parents, when parents made more decisions regarding the topic and when parents responded to disagreement by standing strong. Results were generally consistent across parents' and children's reports of compliance and across cross-sectional and longitudinal analyses. At the transition from childhood to adolescence, only children's agency explained why some children are more compliant than others, but parents' and children's agency helped to explain why children complied with some rules more than others.

Brief report: improving the validity of assessments of adolescents' feelings of privacy invasion.

Studies of privacy invasion have relied on measures that combine items assessing adolescents' feelings of privacy invasion with items assessing parents' monitoring behaviors. Removing items assessing parents' monitoring behaviors may improve the validity of assessments of privacy invasion. Data were collected from 163 adolescents (M age 13 years, 5 months; 47% female; 50% European American, non-Hispanic, 46% African American) and their mothers. A model specifying separate factors for privacy invasion and monitoring behavior fit adolescent-reported and parent-reported data significantly better than a single factor model. Although privacy invasion and monitoring behavior were positively associated, privacy invasion and monitoring behavior correlations were significantly different from one another across all ten variables reported by adolescents and across eight of the nine variables reported by mothers. The pattern of results strongly supports a recommendation for researchers to exclude items assessing monitoring behaviors to provide a more valid assessment of privacy invasion.

Genomic insulators: connecting properties to mechanism.

Insulators are regulatory elements that establish independent domains of transcriptional activity within eukaryotic genomes. Insulators possess two properties: an anti-enhancer activity that blocks enhancer-promoter communication, and an anti-silencer activity that prevents the spread of repressive chromatin. Some insulators are composite elements with separable activities, while others employ a single mechanism to confer both properties. Recent studies focus on elucidating the molecular mechanisms of insulator function. Emerging themes support connections between insulators, transcriptional activators and topological chromosomal domains. Understanding these processes will provide insights into prevention of inappropriate regulatory interactions, knowledge that can be applied to gene therapies.

Identification of genomic sites that bind the Drosophila suppressor of Hairy-wing insulator protein.

Eukaryotic genomes are divided into independent transcriptional domains by DNA elements known as insulators. The gypsy insulator, a 350-bp element isolated from the Drosophila gypsy retrovirus, contains twelve degenerate binding sites for the Suppressor of Hairy-wing [Su(Hw)] protein. Su(Hw) associates with over 500 non-gypsy genomic sites, the functions of which are largely unknown. Using a bioinformatics approach, we identified 37 putative Su(Hw) insulators (pSIs) that represent regions containing clustered matches to the gypsy insulator Su(Hw) consensus binding sequence. The majority of these pSIs contain fewer than four Su(Hw) binding sites, with only seven showing in vivo Su(Hw) association, as demonstrated by chromatin immunoprecipitation. To understand the properties of the pSIs, these elements were tested for enhancer-blocking capabilities using a transgene assay system. In a complementary set of experiments, effects of the pSIs on transcriptional regulation of genes at the natural genomic location were determined. Our data suggest that pSIs have complex genomic functions and, in some cases, establish insulators. These studies provide the first direct evidence that the Su(Hw) protein contributes to the regulation of gene expression in the Drosophila genome through the establishment of endogenous insulators.

Studies of the role of the Drosophila scs and scs' insulators in defining boundaries of a chromosome puff.

Insulators are DNA elements that establish independent transcriptional domains within eukaryotic genomes. The Drosophila scs and scs' insulators localize near the borders of a structural domain in the polytene chromosomes, known as a puff, produced by transcription of the 87A heat shock protein (hsp) genes. It has been suggested that scs and scs' are boundary elements that delimit this decondensed chromatin domain, reflecting the mechanism by which these sequences act to constrain regulatory interactions. This model was tested using transposons that carried a yellow gene to assess enhancer blocking and an hsp70-lacZ gene to examine the structure of a heat shock puff in the presence and absence of insulators. We found that although scs and scs' blocked enhancer function, these sequences did not prevent the spread of decondensation resulting from hsp70-lacZ transcription. Further analysis of the endogenous 87A locus demonstrated that scs and scs' reside within, not at, the borders of the puff. Taken together, our studies suggest that scs and scs' are not boundary elements that block the propagation of an altered chromatin state associated with puff formation. We propose that these insulators may have a direct role in limiting regulatory interactions in the gene-dense 87A region.

Family support programs and adolescent mental health: review of evidence.

Family support programs aim to improve parent wellbeing and parenting as well as adolescent mental and behavioral health by addressing the needs of parents of adolescents experiencing or at risk for mental health problems. Family support programs can be part of the treatment for adolescents diagnosed with mental or behavioral health problems, or family support programs can be delivered as prevention programs designed to prevent the onset or escalation of mental or behavioral health problems. This review discusses the rationale for family support programs and describes the range of services provided by family support programs. The primary focus of the review is on evaluating the effectiveness of family support programs as treatments or prevention efforts delivered by clinicians or peers. Two main themes emerged from the review. First, family support programs that included more forms of support evidenced higher levels of effectiveness than family support programs that provided fewer forms of support. Discussion of this theme focuses on individual differences in client needs and program adaptions that may facilitate meeting diverse needs. Second, family support prevention programs appear to be most effective when serving individuals more in need of mental and behavioral health services. Discussion of this theme focuses on the intensity versus breadth of the services provided in prevention programs. More rigorous evaluations of family support programs are needed, especially for peer-delivered family support treatments.

Information management strategies in early adolescence: developmental change in use and transactional associations with psychological adjustment.

Adolescents use various strategies to manage their parents' access to information. This study tested developmental change in strategy use, longitudinal associations between disclosing and concealing strategies, and longitudinal associations linking disclosing and concealing strategies with antisocial behavior and depressive symptoms. Self-report data (n = 218; 49% female; 49% European American, 47% African American) following Grades 5 (M age = 11 years, 11 months), 6, and 7 show that the use of disclosing strategies (e.g., telling all, telling if asked) following misbehavior declined while use of concealing strategies (e.g., omitting details, keeping secrets, lying) increased over time. Longitudinal links between strategies suggest a transactional process wherein infrequent disclosing is a gateway to concealment but concealment also predicts subsequent rank-order reductions in disclosure. Infrequent disclosing was associated with more subsequent antisocial behavior and depressive symptoms, whereas more antisocial behavior was associated with more subsequent concealment. Although absolute declines in disclosure and increases in concealment are normative, individual differences show that adolescents reporting low levels of disclosure, rather than high levels of concealment, appear to experience the most adjustment problems.

Biology of Habrobracon gelechiae (Hymenoptera: Braconidae), as a parasitoid of the obliquebanded leafroller (Lepidoptera: Tortricidae).

Habrobracon gelechiae Ashmead (Hymenoptera: Braconidae) was studied as a parasitoid of the obliquebanded leafroller, Choristoneura rosaceana (Harris) (Lepidoptera: Tortricidae) in California pistachio (Pistacia vera L.) orchards. Ovipositional behavior, adult longevity and fecundity, and the effects of temperature on developmental time and survival were determined. Habrobracon gelechiae develops as a gregarious, ectoparasitic idiobiont on late-instar C. rosaceana larvae. At 25°C, adult female wasps survived longer when provided honey and water (35.4 ± 4.9 d) or honey, water, and host larvae (34.4 ± 2.4 d) than when provided water (8.9 ± 1.1 d) or no food (5.9 ± 0.8 d). Over the adult lifespan, females parasitized 20.6 ± 2.1 hosts and deposited 228.8 ± 24.6 eggs. The intrinsic rate of increase was 0.24, the mean generation time was 18.15 d, and the double time 2.88 d. At constant temperatures, H. gelechiae successfully developed (egg to adult) from 15 to 35 °C. The developmental rate was fit to a nonlinear model, providing estimates of the parasitoid's lower (10.5 °C), upper (36.0 °C), and optimal (33.3 °C) development temperatures. Based on a linear model, 155 degree days were estimated for egg to adult eclosion. Temperature-dependent nonlinear model of survival showed similar shape with the model of development rate. The wasp developed under two diurnal temperature regimes, with 31.0 ± 13.3% survival at low (4-15 °C) and 63.0 ± 11.4% survival at high (15-35 °C) temperature regimes. The results are discussed with respect to H. gelechiae potential as a parasitoid of C. rosaceana in California's San Joaquin Valley.

Individual differences in early adolescents' beliefs in the legitimacy of parental authority.

Adolescents differ in the extent to which they believe that parents have legitimate authority to impose rules restricting adolescents' behavior. The purpose of the current study was to test predictors of individual differences in legitimacy beliefs during the middle school years. Annually, during the summers following Grades 5, 6, and 7, early adolescents (n = 218; 51% female, 47% African American, 73% in 2-parent homes) reported their beliefs regarding the legitimacy of parents' rules that restrict and monitor adolescents' free time activities. Cross-lagged analyses revealed that legitimacy beliefs were bidirectionally associated with independent decision making, psychological control, antisocial peer involvement, and resistance to control. Legitimacy beliefs declined more rapidly during the middle school years for boys than for girls and for adolescents who were older relative to their classmates. More independent decision making in Grades 5 and 6 predicted larger than expected declines in legitimacy beliefs in Grades 6 and 7. In sum, legitimacy beliefs weaken developmentally, and weaker legitimacy beliefs relative to same-grade peers are anteceded by premature autonomous experiences, psychological control, and adolescent attributes.

A test of insulator interactions in Drosophila.

Insulators are a class of elements that define independent domains of gene function. The Drosophila gypsy insulator is proposed to establish regulatory isolation by forming loop domains that constrain interactions between transcriptional control elements. This supposition is based upon the observation that insertion of a single gypsy insulator between an enhancer and promoter blocks enhancer function, while insertion of two gypsy insulators promotes enhancer bypass and activation of transcription. To investigate this model, we determined whether non-gypsy insulators interacted with each other and with the gypsy insulator. Pairs of scs or scs' insulators blocked enhancer function. Further, an intervening scs insulator did not block gypsy insulator interactions. Taken together, these data suggest that not all Drosophila insulators interact, with this property restricted to some insulators, such as gypsy. Three gypsy insulators inserted between an enhancer and promoter blocked enhancer function, indicating that gypsy insulator interactions may be restricted to pairs. Our studies imply that formation of loop domains may represent one of many mechanisms used by insulators to impart regulatory isolation.

An endogenous suppressor of hairy-wing insulator separates regulatory domains in Drosophila.

Insulators define independent domains of gene function throughout the genome. The Drosophila gypsy insulator was isolated from the gypsy retrotransposon as a region that contains a cluster of binding sites for the Suppressor of Hairy-wing [Su(Hw)] protein. To study the effects of the gypsy insulator on gene expression within a single genomic domain, targeted gene replacement was used to exchange the endogenous yellow gene, located at cytological location 1A, with a set of gypsy-modified yellow genes. Replaced yellow genes carried a gypsy insulator positioned between the yellow promoter and either the upstream or the downstream tissue-specific enhancers. Whereas the gypsy insulator blocked the function of the upstream enhancers at the endogenous location, the downstream enhancers were not blocked. Investigation of the 1A region revealed two clustered Su(Hw)-binding sites downstream of the yellow gene, named 1A-2, that bind Su(Hw) in vivo and possess enhancer blocking function. We propose that interaction between 1A-2 and the gypsy insulator permits activation of yellow expression by enhancers in the neighboring achaete-scute complex, causing an apparent absence of the block of the downstream yellow enhancers. Based on these data, we suggest that 1A-2 is an endogenous Su(Hw) insulator that separates regulatory domains within the Drosophila genome.