Longitudinal changes in acylated versus unacylated ghrelin levels may be involved in the underlying mechanisms of the switch in nutritional phases in Prader-Willi syndrome

Introduction: Prader-Willi syndrome (PWS) is characterized by a switch from failure to thrive to excessive weight gain and hyperphagia in early childhood. An elevated, more unfavorable ratio between acylated and unacylated ghrelin (AG/UAG ratio) might play a role in the underlying mechanisms of this switch. We aimed to assess the evolution of the appetite-regulating hormones acylated ghrelin (AG) and unacylated ghrelin (UAG) and the AG/UAG ratio and their association with the change in eating behavior in children with PWS, compared to healthy age-matched controls. Methods: A longitudinal study was conducted in 134 children with PWS and 157 healthy controls, from the Netherlands, France, and Belgium. Levels of AG and UAG and the AG/UAG ratio were measured and nutritional phases as reported for PWS were scored. Results: The AG/UAG ratio was lower in the first years of life in PWS than in controls and started to increase from the age of 3 years, resulting in a high-normal AG/UAG ratio compared to controls. The AG levels remained stable during the different nutritional phases (p = 0.114), while the UAG levels decreased from 290 pg/mL in phase 1a to 137 pg/mL in phase 2b (p < 0.001). The AG/UAG ratio increased significantly from 0.81 in phase 2a to 1.24 in phase 2b (p = 0.012). Conclusions: The change from failure to thrive to excessive weight gain and hyperphagia in infants and children with PWS coincides with an increase in AG/UAG ratio. The increase in AG/UAG ratio occurred during phase 2a, thus before the onset of hyperphagia

Sensitivity of the Atlantic meridional overturning circulation to South Atlantic freshwater anomalies

The sensitivity of the Atlantic Meridional Overturning Circulation (AMOC) to changes in basin integrated net evaporation is highly dependent on the zonal salinity contrast at the southern border of the Atlantic. Biases in the freshwater budget strongly affect the stability of the AMOC in numerical models. The impact of these biases is investigated, by adding local anomaly patterns in the South Atlantic to the freshwater fluxes at the surface. These anomalies impact the freshwater and salt transport by the different components of the ocean circulation, in particular the basin-scale salt-advection feedback, completely changing the response of the AMOC to arbitrary perturbations. It is found that an appropriate dipole anomaly pattern at the southern border of the Atlantic Ocean can collapse the AMOC entirely even without a further hosing. The results suggest a new view on the stability of the AMOC, controlled by processes in the South Atlantic. <br/

Serious, Minor, and Non-Delinquents in Early Adolescence: The Impact of Cumulative Risk and Promotive Factors. The TRAILS Study

This study uses a social-ecological approach to the development of delinquency. The authors emphasize that a balance between eliminating risk and enhancing protection across domains is essential in reducing problems and promoting competence. The cumulative risk and promotive effects of temperament, family and school factors in preadolescence were examined on different groups of delinquents (based on self-report) in early adolescence. Data from the first two waves of the TRAILS study (N = 2,230) were used. The results provide evidence for a compensatory model that assumes main effects of risk and promotive factors on problem behavior. Accumulation of risks in preadolescence promoted being a serious delinquent in early adolescence, with the strongest effects for temperament. Accumulation of promotive effects decreased being a delinquent and supported being a non-delinquent. Furthermore, evidence is found for a counter-balancing effect of cumulative promotive and risk factors. Exposure to more promotive domains in the relative absence of risk domains decreased the percentage of serious delinquents. Our results did not support a protective model. Implications for prevention and intervention are discussed

Effect of the Size of Clods Contained Covering Soil on the Seedling Emergence of Rice Plant Sown under Upland Field Condition

水稲農林23号を用いて, 覆土の土塊の大きさが, 乾田に深播き(覆土7cm)された個体の出芽ならびに幼苗諸器官の長さに及ぼす影響について, 覆土が3cmの場合と比較しながら検討した。乾田に播種された種子が大きい土塊で覆土されると, 覆土が3cmの場合には鞘葉の伸長が抑制される。しかし, 不完全葉はほとんどの個体で3cm以上に伸長する。また大土塊の間隙が小土塊で充足された場合は, 鞘葉および不完全葉ともに, 大土塊だけの場合よりも長くなる。その結果, すべての区の出芽率は, 播種後12日目には90%以上に達する。覆土が7cmの場合には, 覆土の土塊が大きくても, 鞘葉および不完全葉は覆土が3cmの場合よりも著しく長くなる。その結果, 第1本葉が不完全葉から抽出する位置が高められる。しかし, 鞘葉および不完全葉の伸長のみによっては出芽することはできず, 出芽するためには, 第2節間および第1本葉が伸長しなければならない。覆土の土塊が大きい場合には, 第2節間の伸長が抑制される。と同時に, 出芽までの間に幼芽の伸長を妨げる土塊の数も多くなるので, 出芽率は著しく低下する。しかし, 大土塊の間隙が小さい土塊によって充足されると, 第2節間が著しく長くなり, 第1本葉をおしあげる。その結果, 出芽率は単一土塊の場合に比べて著しく高まる。以上の結果と土壌中への光の侵入量との関係について, 若干考察した。 / This experiment was carried out to clarify the effects of size of clods in covering soil on the emergence and the elongation of rice seedling sown under upland field condition in pot (10cm×10cm×12cm) culture. Variety used was Norin No. 23. Seeds were covered with 3cm and 7cm depth of soil. In the case of 3cm in depth of seeding, if seeds were covered with larger clods, the elongation of coleoptile was inhibited, but the profile elongated longer than 3cm. When gaps between larger clods were filled with smaller clods, the length of coleoptile and profile became longer. Consequently, the emergence percentage of all plots reached more than 90% the 12th day after seeding. In the case of 7cm in depth of seeding, if seeds were covered with larger clods, coleoptile or profile elongated to 3 to 4cm in length, but the elongation of second internode was inhibited. As a result, the emergence percentage decreased significantly. When gaps between larger clods were filled with smaller clods, however, the length of second internode increased and first leaf was pushed up through the soil by second internode. Consequently, the emergence percentage increased significantly

Cognitive ability, parental socioeconomic position and internalising and externalising problems in adolescence: Findings from two European cohort studies

We investigated whether cognitive ability (CA) may be a moderator of the relationship of parental socioeconomic position (SEP) with internalising and externalising problems in adolescents. We used data from two longitudinal cohort studies; the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Tracking Adolescents’ Individual Lives Survey (TRAILS). Indicators of SEP were mother’s education and household income. CA was estimated with IQ scores, derived from the Wechsler Intelligence Scale for Children. Internalising and externalising problems were measured with the Strengths and Difficulties Questionnaire in ALSPAC and with the Child Behavior Checklist in TRAILS. Logistic regression analyses were used to estimate the relative index of inequality (RII) for each outcome; the RII provides the odds ratio comparing the most to least deprived for each measure of SEP. In fully adjusted models an association of mother’s education with externalising problems was observed [ALSPAC RII 1.42 (95%CI: 1.01–1.99); TRAILS RII 2.21 (95%CI: 1.37–3.54)], and of household income with internalising and externalising problems [pooled ALSPAC & TRAILS internalising RII 1.30 (95%CI: 0.99–1.71); pooled ALSPAC & TRAILS externalising RII 1.38 (95%CI: 1.03–1.84)]. No consistent associations were observed between mother’s education and internalising problems. Results of stratified analyses and interaction-terms showed no evidence that CA moderated the association of SEP with internalising or externalising problems

Cohort differences in 3-year adaptation to health problems among Dutch middle-aged, 1992–1995 and 2002–2005

Midlife is a period during which ageing-related health problems first emerge. In view of increasing life expectancy, it is of great importance that people in midlife adapt to possible health problems, to be able to lead productive and engaged lives as long as possible. It may be expected that given the better circumstances in which more recent cohorts grew up, they are better equipped to adapt to health problems than earlier cohorts. This study addresses the question if the way people in midlife adapt to health problems is or is not improving in the Netherlands. The study is based on the nationally representative 1992–1993 and 2002–2003 cohorts of the Longitudinal Aging Study Amsterdam (ages 55–64 years), with follow-up cycles in 1995–1996 (n = 811) and 2005–2006 (n = 829), respectively. Mastery is considered as a measure of adaptation, and 3-year change in mastery is compared in subjects without and with health problems at baseline. A rise was observed in the prevalence of diabetes, chronic lung disease, arthritis, subthreshold depression, and disability. Subjects without health problems in the recent cohort had better mastery than their counterparts in the early cohort. Regardless of cohort membership, mastery declined over 3 years for those with subthreshold depression, mild disability, chronic lung disease, and stroke. In the recent cohort only, mastery declined for those with cognitive impairment, but improved for those with heart disease. These findings do not support the expectation that recent cohorts are better equipped to deal with health problems for conditions other than heart disease

Non-Linear Elasticity of Extracellular Matrices Enables Contractile Cells to Communicate Local Position and Orientation

Most tissue cells grown in sparse cultures on linearly elastic substrates typically display a small, round phenotype on soft substrates and become increasingly spread as the modulus of the substrate increases until their spread area reaches a maximum value. As cell density increases, individual cells retain the same stiffness-dependent differences unless they are very close or in molecular contact. On nonlinear strain-stiffening fibrin gels, the same cell types become maximally spread even when the low strain elastic modulus would predict a round morphology, and cells are influenced by the presence of neighbors hundreds of microns away. Time lapse microscopy reveals that fibroblasts and human mesenchymal stem cells on fibrin deform the substrate by several microns up to five cell lengths away from their plasma membrane through a force limited mechanism. Atomic force microscopy and rheology confirm that these strains locally and globally stiffen the gel, depending on cell density, and this effect leads to long distance cell-cell communication and alignment. Thus cells are acutely responsive to the nonlinear elasticity of their substrates and can manipulate this rheological property to induce patterning

Small-Animal PET Imaging of Amyloid-Beta Plaques with [11C]PiB and Its Multi-Modal Validation in an APP/PS1 Mouse Model of Alzheimer's Disease

In vivo imaging and quantification of amyloid-β plaque (Aβ) burden in small-animal models of Alzheimer's disease (AD) is a valuable tool for translational research such as developing specific imaging markers and monitoring new therapy approaches. Methodological constraints such as image resolution of positron emission tomography (PET) and lack of suitable AD models have limited the feasibility of PET in mice. In this study, we evaluated a feasible protocol for PET imaging of Aβ in mouse brain with [11C]PiB and specific activities commonly used in human studies. In vivo mouse brain MRI for anatomical reference was acquired with a clinical 1.5 T system. A recently characterized APP/PS1 mouse was employed to measure Aβ at different disease stages in homozygous and hemizygous animals. We performed multi-modal cross-validations for the PET results with ex vivo and in vitro methodologies, including regional brain biodistribution, multi-label digital autoradiography, protein quantification with ELISA, fluorescence microscopy, semi-automated histological quantification and radioligand binding assays. Specific [11C]PiB uptake in individual brain regions with Aβ deposition was demonstrated and validated in all animals of the study cohort including homozygous AD animals as young as nine months. Corresponding to the extent of Aβ pathology, old homozygous AD animals (21 months) showed the highest uptake followed by old hemizygous (23 months) and young homozygous mice (9 months). In all AD age groups the cerebellum was shown to be suitable as an intracerebral reference region. PET results were cross-validated and consistent with all applied ex vivo and in vitro methodologies. The results confirm that the experimental setup for non-invasive [11C]PiB imaging of Aβ in the APP/PS1 mice provides a feasible, reproducible and robust protocol for small-animal Aβ imaging. It allows longitudinal imaging studies with follow-up periods of approximately one and a half years and provides a foundation for translational Alzheimer neuroimaging in transgenic mice

Inflammatory Rheumatic Disorders and Bone

Inflammatory joint diseases such as rheumatoid arthritis, as well as other rheumatic conditions, such as systemic lupus erythematosus (SLE) and ankylosing spondylitis, comprise a heterogeneous group of joint disorders that are all associated with extra-articular side effects, including bone loss and fractures. The concept of osteoimmunology is based on growing insights into the links between the immune system and bone. The pathogenesis of osteoporosis in these patients is multifactorial. We have, more or less as an example, described this extensively for patients with SLE. High disease activity (inflammation) and immobility are common factors that substantially increase fracture risk in these patients, on top of the background fracture risk based on, among other factors, age, body mass index, and gender. Although no fracture reduction has been shown in intervention studies in patients with inflammatory rheumatic diseases, we present treatment options that might be useful for clinicians who are treating these patients