Other-Sex Friendships in Late Adolescence: Risky Associations for Substance Use and Sexual Debut?

Adolescents’ friendships with other-sex peers serve important developmental functions, but they may also facilitate engagement in problem behavior. This study examines the unique contributions of other-sex friendships and friends’ behavior to alcohol use, smoking, and initiation of sexual intercourse among late adolescent girls and boys. A total of 320 adolescents (53% girls; 33% racial/ethnic minorities) provided sociometric nominations of friendships annually in grades 10–12. Friendship networks were derived using social network analysis in each grade. Adolescents and their friends also reported on their alcohol use, smoking, and sexual debut at each assessment. After controlling for demographics, previous problem behavior, and friends’ behavior, other-sex friendships in 10th grade were associated with initiation of smoking among girls over the following year, and other-sex friendships in 11th grade were linked with lower levels of subsequent alcohol use among boys. Additionally, friends’ smoking and sexual experience in 10th grade predicted the same behaviors for all adolescents over the following year. Other-sex friendships thus appear to serve as a risk context for adolescent girls’ smoking and a protective context for adolescent boys’ drinking. Promoting mixed-gender activities and friendships among older high school students may be helpful in reducing males’ alcohol use, but may need to incorporate additional components to prevent increases in females’ smoking

Multifaceted Regulation of Translational Readthrough by RNA Replication Elements in a Tombusvirus

Translational readthrough of stop codons by ribosomes is a recoding event used by a variety of viruses, including plus-strand RNA tombusviruses. Translation of the viral RNA-dependent RNA polymerase (RdRp) in tombusviruses is mediated using this strategy and we have investigated this process using a variety of in vitro and in vivo approaches. Our results indicate that readthrough generating the RdRp requires a novel long-range RNA-RNA interaction, spanning a distance of ∼3.5 kb, which occurs between a large RNA stem-loop located 3'-proximal to the stop codon and an RNA replication structure termed RIV at the 3'-end of the viral genome. Interestingly, this long-distance RNA-RNA interaction is modulated by mutually-exclusive RNA structures in RIV that represent a type of RNA switch. Moreover, a different long-range RNA-RNA interaction that was previously shown to be necessary for viral RNA replicase assembly was also required for efficient readthrough production of the RdRp. Accordingly, multiple replication-associated RNA elements are involved in modulating the readthrough event in tombusviruses and we propose an integrated mechanistic model to describe how this regulatory network could be advantageous by (i) providing a quality control system for culling truncated viral genomes at an early stage in the replication process, (ii) mediating cis-preferential replication of viral genomes, and (iii) coordinating translational readthrough of the RdRp with viral genome replication. Based on comparative sequence analysis and experimental data, basic elements of this regulatory model extend to other members of Tombusviridae, as well as to viruses outside of this family

Risk factors for pressure sores in adult patients with myelomeningocele – a questionnaire-based study

BACKGROUND: Myelomeningocele (MMC) is a part of a complex neural tube defect and a disorder of the cerebrospinal fluid system. Pressure sores are a frequent complication for patients with MMC. Little is known about the risk factors for pressure sores in adults with MMC. The aim of this study was to investigate an association between the presence of pressure sores and other patient characteristics, in order to develop an improved strategy for the management of sores. METHODS: A structured questionnaire regarding sores, medical condition, function and living factors was designed and sent to the 193 patients with MMC registered in the year 2003 at TRS, a National Centre for Rare Disorders in Norway. RESULTS: Out of 193 total, 87 patients participated and 71 patients (82%) reported sores; 26 (30%) at the time of the interview and 45 (52%) during the last 5 years. Sores were mostly localized on toes and feet and occurred exclusively in regions with reduced or missing sensibility. A significant association was found between sores and memory deficit (p = 0.02), Arnold Chiari malformation (p = 0.02) and a record of previous sores (p = 0.004). Sores were not significantly associated with hydrocephalus, syringomyelia, nutrition, body mass index, smoking, physical activity, employment or living together with other persons. Some patients (18, 21%) reported skin inspection by others and the remainder relied on self-inspection. CONCLUSION: Patients with sensory deficit, memory problems, and Arnold Chiari malformation had a higher risk of having pressure sores. This patient group needs improved skin inspection routines and sore treatment

Regulatory role of CD8(+ )T lymphocytes in bone marrow eosinophilopoiesis

BACKGROUND: There is a growing body of evidence to suggest that CD8(+ )T lymphocytes contribute to local allergen-induced eosinophilic inflammation. Since bone marrow (BM) responses are intricately involved in the induction of airway eosinophilia, we hypothesized that CD8(+ )T lymphocytes, as well as CD4(+ )T lymphocytes, may be involved in this process. METHODS: Several approaches were utilized. Firstly, mice overexpressing interleukin-5 (IL-5) in CD3(+ )T lymphocytes (NJ.1638; CD3(IL-5+ )mice) were bred with gene knockout mice lacking either CD4(+ )T lymphocytes (CD4(-/-)) or CD8(+ )T lymphocytes (CD8(-/-)) to produce CD3(IL-5+ )knockout mice deficient in CD4(+ )T lymphocytes (CD3(IL-5+)/CD4(-/-)) and CD8(+ )T lymphocytes (CD3(IL-5+)/CD8(-/-)), respectively. Secondly, CD3(+), CD4(+ )and CD8(+ )T lymphocytes from naïve CD3(IL-5+ )and C57BL/6 mice were adoptively transferred to immunodeficient SCID-bg mice to determine their effect on BM eosinophilia. Thirdly, CD3(IL-5+), CD3(IL-5+)/CD8(-/- )and CD3(IL-5+)/CD4(-/- )mice were sensitized and allergen challenged. Bone marrow and blood samples were collected in all experiments. RESULTS: The number of BM eosinophils was significantly reduced in CD3(IL-5+)/CD8(-/- )mice compared to CD3(IL-5+ )mice and CD3(IL-5+)/CD4(-/- )mice. Serum IL-5 was significantly higher in CD3(IL-5+)/CD4(-/- )mice compared to CD3(IL-5+ )mice but there was no difference in serum IL-5 between CD3(IL-5+)/CD4(-/- )and CD3(IL-5+)/CD8(-/- )mice. Adoptive transfer of CD8(+), but not CD4(+ )T lymphocytes from naïve CD3(IL-5+ )and C57BL/6 mice restored BM eosinophilia in immunodeficient SCID-bg mice. Additionally, allergen challenged CD3(IL-5+)/CD8(-/- )mice developed lower numbers of BM eosinophils compared to CD3(IL-5+ )mice and CD3(IL-5+)/CD4(-/- )mice. CONCLUSION: This study shows that CD8(+ )T lymphocytes are intricately involved in the regulation of BM eosinophilopoiesis, both in non-sensitized as well as sensitized and allergen challenged mice

Chronic inhibition, self-control and eating behavior: test of a 'resource depletion' model

The current research tested the hypothesis that individuals engaged in long-term efforts to limit food intake (e.g., individuals with high eating restraint) would have reduced capacity to regulate eating when self-control resources are limited. In the current research, body mass index (BMI) was used as a proxy for eating restraint based on the assumption that individuals with high BMI would have elevated levels of chronic eating restraint. A preliminary study (Study 1) aimed to provide evidence for the assumed relationship between eating restraint and BMI. Participants (N = 72) categorized into high or normal-range BMI groups completed the eating restraint scale. Consistent with the hypothesis, results revealed significantly higher scores on the weight fluctuation and concern for dieting subscales of the restraint scale among participants in the high BMI group compared to the normal-range BMI group. The main study (Study 2) aimed to test the hypothesized interactive effect of BMI and diminished self-control resources on eating behavior. Participants (N = 83) classified as having high or normal-range BMI were randomly allocated to receive a challenging counting task that depleted self-control resources (ego-depletion condition) or a non-depleting control task (no depletion condition). Participants then engaged in a second task in which required tasting and rating tempting cookies and candies. Amount of food consumed during the taste-and-rate task constituted the behavioral dependent measure. Regression analyses revealed a significant interaction effect of these variables on amount of food eaten in the taste-and-rate task. Individuals with high BMI had reduced capacity to regulate eating under conditions of self-control resource depletion as predicted. The interactive effects of BMI and self-control resource depletion on eating behavior were independent of trait self-control. Results extend knowledge of the role of self-control in regulating eating behavior and provide support for a limited-resource model of self-control. © 2013 Hagger et al

Tau Reduction Does Not Prevent Motor Deficits in Two Mouse Models of Parkinson's Disease

Many neurodegenerative diseases are increasing in prevalence and cannot be prevented or cured. If they shared common pathogenic mechanisms, treatments targeting such mechanisms might be of benefit in multiple conditions. The tau protein has been implicated in the pathogenesis of diverse neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD). Tau reduction prevents cognitive deficits, behavioral abnormalities and other pathological changes in multiple AD mouse models. Here we examined whether tau reduction also prevents motor deficits and pathological alterations in two mouse models of PD, generated by unilateral striatal injection of 6-hydroxydopamine (6-OHDA) or transgene-mediated neuronal expression of human wildtype α-synuclein. Both models were evaluated on Tau+/+, Tau+/– and Tau–/– backgrounds in a variety of motor tests. Tau reduction did not prevent motor deficits caused by 6-OHDA and slightly worsened one of them. Tau reduction also did not prevent 6-OHDA-induced loss of dopaminergic terminals in the striatum. Similarly, tau reduction did not prevent motor deficits in α-synuclein transgenic mice. Our results suggest that tau has distinct roles in the pathogeneses of AD and PD and that tau reduction may not be of benefit in the latter condition

The gene encoding interleukin-13: a susceptibility locus for asthma and related traits

Asthma is a complex inflammatory disorder controlled by both genetic and environmental influences. Multiple genetic analyses have identified the T helper type 2 (Th2) cytokine gene cluster on chromosome 5q as a susceptibility locus for asthma. Recently, the Th2 cytokine interleukin-13 has been shown to be a critical mediator of the asthma phenotype in murine models. In this commentary we discuss several recent studies that have identified polymorphisms in the gene encoding interleukin-13. The consistent genetic associations of interleukin-13 with asthma and related traits across diverse ethnic populations in these studies provides strong support for the candidacy of this cytokine as a susceptibility locus for asthma and atopy on chromosome 5q31

Tauopathic Changes in the Striatum of A53T α-Synuclein Mutant Mouse Model of Parkinson's Disease

Tauopathic pathways lead to degenerative changes in Alzheimer's disease and there is evidence that they are also involved in the neurodegenerative pathology of Parkinson's disease [PD]. We have examined tauopathic changes in striatum of the α-synuclein (α-Syn) A53T mutant mouse. Elevated levels of α-Syn were observed in striatum of the adult A53T α-Syn mice. This was accompanied by increases in hyperphosphorylated Tau [p-Tau], phosphorylated at Ser202, Ser262 and Ser396/404, which are the same toxic sites also seen in Alzheimer's disease. There was an increase in active p-GSK-3β, hyperphosphorylated at Tyr216, a major and primary kinase known to phosphorylate Tau at multiple sites. The sites of hyperphosphorylation of Tau in the A53T mutant mice were similar to those seen in post-mortem striata from PD patients, attesting to their pathophysiological relevance. Increases in p-Tau were not due to alterations on protein phosphatases in either A53T mice or in human PD, suggesting lack of involvement of these proteins in tauopathy. Extraction of striata with Triton X-100 showed large increases in oligomeric forms of α-Syn suggesting that α-Syn had formed aggregates the mutant mice. In addition, increased levels of p-GSK-3β and pSer396/404 were also found associated with aggregated α-Syn. Differential solubilization to measure protein binding to cytoskeletal proteins demonstrated that p-Tau in the A53T mutant mouse were unbound to cytoskeletal proteins, consistent with dissociation of p-Tau from the microtubules upon hyperphosphorylation. Interestingly, α-Syn remained tightly bound to the cytoskeleton, while p-GSK-3β was seen in the cytoskeleton-free fractions. Immunohistochemical studies showed that α-Syn, pSer396/404 Tau and p-GSK-3β co-localized with one another and was aggregated and accumulated into large inclusion bodies, leading to cell death of Substantia nigral neurons. Together, these data demonstrate an elevated state of tauopathy in striata of the A53T α-Syn mutant mice, suggesting that tauopathy is a common feature of synucleinopathies

Moderation of the Association between Media Exposure and Youth Smoking Onset: Race/Ethnicity, and Parent Smoking

This study of youth smoking onset aims to replicate previously published media moderation effects for race/ethnicity in a national longitudinal multiethnic sample of U.S. adolescents. Previous research has demonstrated that associations between media and smoking during adolescence are greater for Whites than Hispanics or Blacks, and for youth living in non-smoking families. In this study, changes in smoking status over 24 months were assessed among 4,511 baseline never-smokers. The incidence of smoking onset was 14.3% by 24 months with no differences by race/ethnicity. Blacks had higher exposure to movie smoking and overall television viewing compared with Whites and Hispanics. Whites responded to movie smoking regardless of parent smoking but more strongly if their parents were non-smokers. In contrast, Black adolescents showed little behavioral response to any media, regardless of parent smoking. Hispanic adolescents responded only to TV viewing and only when their parents did not smoke. In an analysis assessing the influence of the race of smoking characters on smoking behavior of White and Black adolescents, Whites responded to both White and Black movie character smoking, whereas Blacks responded only to smoking by Black movie characters. Taken as a whole, the findings replicate and extend previous findings, suggesting media factors are more influential among adolescents at low to moderate overall risk for smoking. We draw analogies between these low-moderate risk adolescents and “swing voters” in national elections, suggesting that media effects are more apt to influence an adolescent in the middle of the risk spectrum, compared with his peers at either end of it