Circadian clock mechanism driving mammalian photoperiodism.

The annual photoperiod cycle provides the critical environmental cue synchronizing rhythms of life in seasonal habitats. In 1936, Bünning proposed a circadian-basis for photoperiodic synchronization. Here, light-dark cycles entrain a circadian rhythm of photosensitivity, and the expression of summer or winter biology depends on whether light coincides with the phase of high photosensitivity. Formal studies support the universality of this so-called coincidence timer, but we lack understanding of the mechanisms involved. Here we show in mammals that coincidence timing takes place in the pars tuberalis of the pituitary, through a melatonin-dependent flip-flop switch between circadian transcriptional activation and repression. Long photoperiods produce short night-time melatonin signals, leading to induction of the circadian transcription factor BMAL2, in turn triggering summer biology through the eyes absent / thyrotrophin (EYA3 / TSH) pathway. Conversely, short photoperiods produce long melatonin signals, inducing circadian repressors including DEC1, in turn suppressing BMAL2 and the EYA3/TSH pathway, triggering winter biology. These actions are associated with progressive genome-wide changes in chromatin state, elaborating the effect of the circadian coincidence timer. Hence, circadian clock interactions with pituitary epigenetic pathways form the basis of the mammalian coincidence timer mechanism. Our results constitute a blueprint for circadian-based seasonal timekeeping in vertebrates

‘Maintaining balance and harmony’: Javanese perceptions of health and cardiovascular disease

Community intervention programmes to reduce cardiovascular disease (CVD) risk factors within urban communities in developing countries are rare. One possible explanation is the difficulty of designing an intervention that corresponds to the local context and culture

Incarceration as a key variable in racial disparities of asthma prevalence

<p>Abstract</p> <p>Background</p> <p>Despite the disproportionate incarceration of minorities in the United States, little data exist investigating how being incarcerated contributes to persistent racial/ethnic disparities in chronic conditions. We hypothesized that incarceration augments disparities in chronic disease.</p> <p>Methods</p> <p>Using data from the New York City Health and Nutrition Examination Study, a community-based survey of 1999 adults, we first estimated the association between having a history of incarceration and the prevalence of asthma, diabetes, hypertension using propensity score matching methods. Propensity scores predictive of incarceration were generated using participant demographics, socioeconomic status, smoking, excessive alcohol and illicit drug use, and intimate partner violence. Among those conditions associated with incarceration, we then performed mediation analysis to explore whether incarceration mediates racial/ethnic disparities within the disease.</p> <p>Results</p> <p>Individuals with a history of incarceration were more likely to have asthma compared to those without (13% vs. 6%, p < 0.05) and not more likely to have diabetes or hypertension, after matching on propensity scores. Statistical mediation analysis revealed that increased rates of incarceration among Blacks partially contribute to the racial disparity in asthma prevalence.</p> <p>Conclusion</p> <p>Having been incarcerated may augment racial disparities in asthma among NYC residents. Eliminating health disparities should include a better understanding of the role of incarceration and criminal justice policies in contributing to these disparities.</p

Predictive value of subclinical autistic traits at age 14–15 months for behavioural and cognitive problems at age 3–5 years

It is unclear whether subclinical autistic traits at very young age are transient or stable, and have clinical relevance. This study investigated the relationship between early subclinical autistic traits and the occurrence of later developmental and behavioural problems as well as problems in cognitive and language functioning. Parents of infants aged 14–15 months from the general population completed the Early Screening of Autistic Traits Questionnaire (ESAT). Three groups of children with high, moderate, and low ESAT-scores (total n = 103) were selected. Follow-up assessments included the CBCL 1½–5 at age 3 years, and the SCQ, the ADI-R, the ADOS-G, a non-verbal intelligence test, and language tests for comprehension and production at age 4–5 years. None of the children met criteria for autism spectrum disorder at follow-up. Children with high ESAT-scores at 14–15 months showed significantly more internalizing and externalizing problems at age 3 years and scored significantly lower on language tests at age 4–5 years than children with moderate or low ESAT-scores. Further, significantly more children with high ESAT-scores (14/26, 53.8%) than with moderate and low ESAT-scores (5/36, 13.9% and 1/41, 2.4%, respectively) were in the high-risk/clinical range on one or more outcome domains (autistic symptoms, behavioural problems, cognitive and language abilities). Subclinical autistic traits at 14–15 months predict later behavioural problems and delays in cognitive and language functioning rather than later ASD-diagnoses. The theoretical implications of the findings lie in the pivotal role of early social and communication skills for the development of self-regulation of emotions and impulses. The practical implications bear on the early recognition of children at risk for behavioural problems and for language and cognitive problems

Enchantment in Business Ethics Research

This article draws attention to the importance of enchantment in business ethics research. Starting from a Weberian understanding of disenchantment, as a force that arises through modernity and scientific rationality, we show how rationalist business ethics research has become disenchanted as a consequence of the normalisation of positivist, quantitative methods of inquiry. Such methods absent the relational and lively nature of business ethics research and detract from the ethical meaning that can be generated through research encounters. To address this issue, we draw on the work of political theorist and philosopher, Jane Bennett, using this to show how interpretive qualitative research creates possibilities for enchantment. We identify three opportunities for reenchanting business ethics research related to: (i) moments of novelty or disruption; (ii) deep, meaningful attachments to things studied; and (iii) possibilities for embodied, affective encounters. In conclusion, we suggest that business ethics research needs to recognise and reorient scholarship towards an appreciation of the ethical value of interpretive, qualitative research as a source of potential enchantment

CCAAT/enhancer binding proteins in normal mammary development and breast cancer

CCAAT/enhancer binding proteins (C/EBPs) are a family of leucine zipper, transcription factors that bind to DNA as homodimers and heterodimers. They regulate cellular proliferation, differentiation and apoptosis in the mammary gland. Multiple protein isoforms, including truncated, dominant negatives, are generated by translation of the C/EBPβ transcript or via proteolytic cleavage of the full-length C/EBPβ protein. Gene deletion of individual C/EBP family members has demonstrated an essential role for C/EBPβ in normal mammary development, while transgenic and overexpression studies provide evidence that the dominant-negative C/EBPβ-liver-enriched inhibitory protein isoform induces proliferation in mammary epithelial cells. Mounting evidence suggests that alterations in the ratio of the C/EBPβ-liver-enriched inhibitory protein isoform and the C/EBPβ-liver-enriched activating protein isoform may play a role in the development of breast cancer. This review will consequently focus on C/EBP actions in normal mammary development and on the emerging data that supports a role in breast cancer

Mechanisms of Risk and Resilience in Military Families: Theoretical and Empirical Basis of a Family-Focused Resilience Enhancement Program

Recent studies have confirmed that repeated wartime deployment of a parent exacts a toll on military children and families and that the quality and functionality of familial relations is linked to force preservation and readiness. As a result, family-centered care has increasingly become a priority across the military health system. FOCUS (Families OverComing Under Stress), a family-centered, resilience-enhancing program developed by a team at UCLA and Harvard Schools of Medicine, is a primary initiative in this movement. In a large-scale implementation project initiated by the Bureau of Navy Medicine, FOCUS has been delivered to thousands of Navy, Marine, Navy Special Warfare, Army, and Air Force families since 2008. This article describes the theoretical and empirical foundation and rationale for FOCUS, which is rooted in a broad conception of family resilience. We review the literature on family resilience, noting that an important next step in building a clinically useful theory of family resilience is to move beyond developing broad “shopping lists” of risk indicators by proposing specific mechanisms of risk and resilience. Based on the literature, we propose five primary risk mechanisms for military families and common negative “chain reaction” pathways through which they undermine the resilience of families contending with wartime deployments and parental injury. In addition, we propose specific mechanisms that mobilize and enhance resilience in military families and that comprise central features of the FOCUS Program. We describe these resilience-enhancing mechanisms in detail, followed by a discussion of the ways in which evaluation data from the program’s first 2 years of operation supports the proposed model and the specified mechanisms of action

Autistic Disorder in Patients with Williams-Beuren Syndrome: A Reconsideration of the Williams-Beuren Syndrome Phenotype

International audienceBackground: Williams-Beuren syndrome (WBS), a rare developmental disorder caused by deletion of contiguous genes at 7q11.23, has been characterized by strengths in socialization (overfriendliness) and communication (excessive talkativeness). WBS has been often considered as the polar opposite behavioral phenotype to autism. Our objective was to better understand the range of phenotypic expression in WBS and the relationship between WBS and autistic disorder. Methodology: The study was conducted on 9 French individuals aged from 4 to 37 years old with autistic disorder associated with WBS. Behavioral assessments were performed using Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) scales. Molecular characterization of the WBS critical region was performed by FISH. Findings: FISH analysis indicated that all 9 patients displayed the common WBS deletion. All 9 patients met ADI-R and ADOS diagnostic criteria for autism, displaying stereotypies and severe impairments in social interaction and communication (including the absence of expressive language). Additionally, patients showed improvement in social communication over time. Conclusions: The results indicate that comorbid autism and WBS is more frequent than expected and suggest that the common WBS deletion can result in a continuum of social communication impairment, ranging from excessive talkativeness and overfriendliness to absence of verbal language and poor social relationships. Appreciation of the possible co-occurrence of WBS and autism challenges the common view that WBS represents the opposite behavioral phenotype of autism, and might lead to improved recognition of WBS in individuals diagnosed with autism