Patterns of brain growth in one FGFR2 mouse model for Apert Syndrome

Apert syndrome is a disorder associated with craniosynostosis resulting from one of two mutations in Fibroblast Growth Factor Receptor 2 (FGFR2). Individuals with Apert syndrome demonstrate brain dysmorphology, often associated with cognitive deficits. In this study, micro magnetic resonance images of the brain of FGFR2+/P253R mice and their wildtype littermates were acquired at two ages, P0 (newborn) and P2 (two days old). Fifteen landmarks on the brain surface were collected to compare growth patterns in the morphological phenotypes of the brain."Work supported by NIDCR R01 DE018500

Stakeholder perspectives on ecosystem-based management of the Antarctic krill fishery

Information about stakeholder aspirations is a fundamental requirement for ecosystem-based management, but the detail is often elusive, and debates may focus on simplistic opposing positions. This is exemplified by the Antarctic krill fishery, which, despite a current operational catch limit equivalent to just 1% of the estimated biomass and actual annual catches much lower than this, is the subject of a high-profile debate framed around ambiguous concepts such as sustainability. Q methodology was applied to explore the detailed views of representatives of three stakeholder sectors (the fishing industry, conservation-focused non-governmental organisations (NGOs), and scientists from seven countries involved in research on the krill-based ecosystem). The analysis distinguished two clear groupings, one of which included the views of all NGO participants while the other included the views of fishing industry participants and a subset of the scientists. Key differences between the groups included the priority given to different management measures, and to continued commercial fishing. However, the results also revealed considerable overlap between viewpoints. Both groups prioritised the maintenance of ecosystem health and recognised the importance of defining management objectives. Also, neither group prioritised a decrease in catch limits. This suggests that most participants in the study agree that management should improve but do not perceive a major problem in the ecosystem's ability to support current catch levels. Cooperation to identify shared management objectives based on stakeholder aspirations for the ecosystem might enhance progress, whereas polarised discussions about preferred management measures or ambiguous concepts are likely to impede progress

The Sex and Race Specific Relationship between Anthropometry and Body Fat Composition Determined from Computed Tomography: Evidence from the Multi-Ethnic Study of Atherosclerosis.

BackgroundFew studies have investigated the relationship of anthropometric measurements with computed tomography (CT) body fat composition, and even fewer determined if these relationships differ by sex and race.MethodsCT scans from 1,851 participants in the population based Multi-Ethnic Study of Atherosclerosis were assessed for visceral and subcutaneous fat areas by semi-automated segmentation of body compartments. Regression models were used to investigate relationships for anthropometry with visceral and subcutaneous fat separately by sex and race/ethnicity.ResultsParticipants were 50% female, 41% Caucasian, 13% Asian, 21% African American, and 25% Hispanic. For visceral fat, the positive relationship with weight (p = 0.028), waist circumference (p<0.001), waist to hip ratio (p<0.001), and waist to height ratio (p = 0.05) differed by sex, with a steeper slope for men. That is, across the range of these anthropometric measures the rise in visceral fat is faster for men than for women. Additionally, there were differences by race/ethnicity in the relationship with height (p<0.001), weight (p<0.001), waist circumference (p<0.001), hip circumference (p = 0.006), and waist to hip ratio (p = 0.001) with the Hispanic group having shallower slopes. For subcutaneous fat, interaction by sex was found for all anthropometric indices at p<0.05, but not for race/ethnicity.ConclusionThe relationship between anthropometry and underlying adiposity differs by sex and race/ethnicity. When anthropometry is used as a proxy for visceral fat in research, sex-specific models should be used

Obesity Accelerates Acute Promyelocytic Leukemia in Mice and Reduces Sex Differences in Latency and Penetrance

Objective: Obesity has emerged as a prominent risk factor for multiple serious disease states, including a variety of cancers, and is increasingly recognized as a primary contributor to preventable cancer risk. However, few studies of leukemia have been conducted in animal models of obesity. This study sought to characterize the impact of obesity, diet, and sex in a murine model of acute promyelocytic leukemia (APL). Methods: Male and female C57BL/6J.mCG+/PR mice, genetically predisposed to sporadic APL development, and C57BL/6J (wild type) mice were placed on either a high-fat diet (HFD) or a low-fat diet (LFD) for up to 500 days. Results: Relative to LFD-fed mice, HFD-fed animals displayed increased disease penetrance and shortened disease latency as indicated by accelerated disease onset. In addition, a diet-responsive sex difference in APL penetrance and incidence was identified, with LFD-fed male animals displaying increased penetrance and shortened latency relative to female counterparts. In contrast, both HFD-fed male and female mice displayed 100% disease penetrance and insignificant differences in disease latency, indicating that the sexual dimorphism was reduced through HFD feeding. Conclusions: Obesity and obesogenic diet promote the development of APL in vivo, reducing sexual dimorphisms in disease latency and penetrance

Dysthymia characteristics of heavy alcohol use in depressed adolescents

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30990/1/0000665.pd

Diagnosis and Assessment of Depression and Suicidality Using the NIMH Diagnostic Interview Schedule for Children (DISC-2.3)

The Diagnostic Interview Schedule for Children (DISC-2.3) was studied in a sample of 265 adolescent inpatients to determine type and concurrent validity of depressive symptoms and depressive disorder diagnoses for different DISC-2.3 informants (parent, adolescent, both). The Children's Depression Rating Scale — Revised, Reynolds Adolescent Depression Scale (RADS), Suicide Ideation Questionnaire — Junior, Spectrum of Suicide Behavior Scale, and clinical consensus diagnoses were used to assess concurrent validity. Results indicated that (1) parents, compared to adolescents, reported a higher prevalence of all depressive symptoms with the exception of weight change; (2) DISC-2.3 depressive and suicidality symptoms were related positively to independent validating criteria for all informant conditions, suggesting good concurrent validity; (3) the DISC-2.3 both informant condition correctly identified the most depressive disorders; and (4) the parent, but not the adolescent, DISC-2.3 Informant condition contributed to the prediction of clinical consensus diagnoses of depression after taking into account RADS scores.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44585/1/10802_2004_Article_424863.pd

Methods and Models of the Hanford Internal Dosimetry Program, PNNL-MA-860

The Hanford Internal Dosimetry Program (HIDP) provides internal dosimetry support services for operations at the Hanford Site. The HIDP is staffed and managed by the Radiation and Health Technology group, within the Pacific Northwest National Laboratory (PNNL). Operations supported by the HIDP include research and development, the decontamination and decommissioning of facilities formerly used to produce and purify plutonium, and waste management activities. Radioelements of particular interest are plutonium, uranium, americium, tritium, and the fission and activation product radionuclides 137Cs, 90Sr, and 60Co. This manual describes the technical basis for the design of the routine bioassay monitoring program and for assessment of internal dose. The purposes of the manual are as follows: • Provide assurance that the HIDP derives from a sound technical base. • Promote the consistency and continuity of routine program activities. • Provide a historical record. • Serve as a technical reference for radiation protection personnel. • Aid in identifying and planning for future needs

Activation of p38 MAPK pathway in the skull abnormalities of Apert syndrome Fgfr2+P253R mice

<p>Abstract</p> <p>Background</p> <p>Apert syndrome is characterized by craniosynostosis and limb abnormalities and is primarily caused by FGFR2 +/P253R and +/S252W mutations. The former mutation is present in approximately one third whereas the latter mutation is present in two-thirds of the patients with this condition. We previously reported an inbred transgenic mouse model with the Fgfr2 +/S252W mutation on the C57BL/6J background for Apert syndrome. Here we present a mouse model for the Fgfr2+/P253R mutation.</p> <p>Results</p> <p>We generated inbred <it>Fgfr2</it>^{+/<it>P253R </it>}mice on the same C56BL/6J genetic background and analyzed their skeletal abnormalities. 3D micro-CT scans of the skulls of the <it>Fgfr2</it>^{+/<it>P253R </it>}mice revealed that the skull length was shortened with the length of the anterior cranial base significantly shorter than that of the <it>Fgfr2</it>^{+/<it>S252W </it>}mice at P0. The <it>Fgfr2</it>^{+/<it>P253R </it>}mice presented with synostosis of the coronal suture and proximate fronts with disorganized cellularity in sagittal and lambdoid sutures. Abnormal osteogenesis and proliferation were observed at the developing coronal suture and long bones of the <it>Fgfr2</it>^{+/<it>P253R </it>}mice as in the <it>Fgfr2</it>^{+/<it>S252W </it>}mice. Activation of mitogen-activated protein kinases (MAPK) was observed in the <it>Fgfr2</it>^{+/<it>P253R </it>}neurocranium with an increase in phosphorylated p38 as well as ERK1/2, whereas phosphorylated AKT and PKCα were not obviously changed as compared to those of wild-type controls. There were localized phenotypic and molecular variations among individual embryos with different mutations and among those with the same mutation.</p> <p>Conclusions</p> <p>Our <it>in vivo </it>studies demonstrated that the Fgfr2 +/P253R mutation resulted in mice with cranial features that resemble those of the <it>Fgfr2</it>^{+/<it>S252W </it>}mice and human Apert syndrome. Activated p38 in addition to the ERK1/2 signaling pathways may mediate the mutant neurocranial phenotype. Though Apert syndrome is traditionally thought to be a consistent phenotype, our results suggest localized and regional variations in the phenotypes that characterize Apert syndrome.</p

Item response theory detects differential item functioning between healthy and ill children in QoL measures

To demonstrate the value of item response theory (IRT) and differential item functioning (DIF) methods in examining a health-related quality of life (HRQOL) measure in children and adolescents

Functional and epigenetic phenotypes of humans and mice with DNMT3A Overgrowth Syndrome

Germline mutations in the DNMT3A gene can cause an overgrowth syndrome associated with behavioural and hematopoietic phenotypes. Here the authors describe a mouse model of this syndrome that recapitulates many of these features, including conserved alterations in DNA methylation in the blood cells of both species