Disruption of Murine mp29/Syf2/Ntc31 Gene Results in Embryonic Lethality with Aberrant Checkpoint Response

Human p29 is a putative component of spliceosomes, but its role in pre-mRNA is elusive. By siRNA knockdown and stable overexpression, we demonstrated that human p29 is involved in DNA damage response and Fanconi anemia pathway in cultured cells. In this study, we generated p29 knockout mice (mp29GT/GT) using the mp29 gene trap embryonic stem cells to study the role of mp29 in DNA damage response in vivo. Interruption of mp29 at both alleles resulted in embryonic lethality. Embryonic abnormality occurred as early as E6.5 in mp29GT/GT mice accompanied with decreased mRNA levels of α-tubulin and Chk1. The reduction of α-tubulin and Chk1 mRNAs is likely due to an impaired post-transcriptional event. An aberrant G2/M checkpoint was found in mp29 gene trap embryos when exposed to aphidicolin and UV light. This embryonic lethality was rescued by crossing with mp29 transgenic mice. Additionally, the knockdown of zfp29 in zebrafish resulted in embryonic death at 72 hours of development postfertilization (hpf). A lower level of acetylated α-tubulin was also observed in zfp29 morphants. Together, these results illustrate an indispensable role of mp29 in DNA checkpoint response during embryonic development

Is relatively young age within a school year a risk factor for mental health problems and poor school performance? A population-based cross-sectional study of adolescents in Oslo, Norway

BACKGROUND: Several studies have shown that children who are relatively young within a school year are at greater risk for poorer school performance compared with their older peers. One study also reported that relative age within a school year is an independent risk factor for emotional and behavioral problems. The objective of this study was to test the hypothesis that relatively younger adolescents in the multiethnic population of Oslo have poorer school performance and more mental health problems than their relatively older classmates within the same school year. METHODS: This population-based cross-sectional study included all 10(th)-grade pupils enrolled in 2000 and 2001 in the city of Oslo. The participation rate was 88%. Of the 6,752 pupils in the study sample, 25% had a non-Norwegian background. Mental health problems were quantified using the abbreviated versions of Symptom Check List-25 (SCL-10) and the Strength and Difficulties Questionnaire (SDQ). Information on school performances and mental health problems were self-reported. We controlled for confounding factors including parental educational level, social support, gender, and ethnicity. RESULTS: The youngest one-third of pupils had significantly lower average school grades than the middle one-third and oldest one-third of their classmates (p < 0.001). Of the mental health problems identified in the questionnaires, the groups differed only on peer problems; the youngest one-third reported significantly more problems than the middle and oldest groups (p < 0.05). Age within a school year and gender showed significant interactions with total SDQ score, SDQ peer problems score, SDQ pro social score, and SCL-10 score. After stratifying for gender, the peer problem scores differed significantly between age groups only among boys. The SCL-10 score was significant, but only in girls and in the opposite direction to that expected, with the oldest pupils having significantly higher scores than the other two groups (p < 0.05). CONCLUSION: In adolescents from a multicultural city in Norway, relative age within a school year significantly influenced academic performance. In contrast to data from Great Britain, relative age within a school year was not an important risk factor for mental health problems in adolescents in Oslo

MR imaging of therapy-induced changes of bone marrow

MR imaging of bone marrow infiltration by hematologic malignancies provides non-invasive assays of bone marrow cellularity and vascularity to supplement the information provided by bone marrow biopsies. This article will review the MR imaging findings of bone marrow infiltration by hematologic malignancies with special focus on treatment effects. MR imaging findings of the bone marrow after radiation therapy and chemotherapy will be described. In addition, changes in bone marrow microcirculation and metabolism after anti-angiogenesis treatment will be reviewed. Finally, new specific imaging techniques for the depiction of regulatory events that control blood vessel growth and cell proliferation will be discussed. Future developments are directed to yield comprehensive information about bone marrow structure, function and microenvironment

Tamoxifen and raloxifene modulate gap junction coupling during early phases of retinoic acid-dependent neuronal differentiation of NTera2/D1 cells

Gap junctions (GJ) represent a cellular communication system known to influence neuronal differentiation and survival. To assess a putative role of this system for neural effects of tamoxifen (TAM) and raloxifene (RAL), we used the human teratocarcinoma cell line NTera2/D1, retinoic acid (RA)-dependent neuronal differentiation of which is regulated by gap junctions formed of connexin43 (Cx43). As demonstrated by Western blot analysis, concentrations above 1 µmol/l for TAM, and 0.1 µmol/l for RAL lead to a temporary time- and concentration-dependent increase in Cx43 immunoreactivity, which reached a peak for TAM after 1 day and for RAL after 2 days. Immunocytochemical stainings revealed the increase in Cx43 immunoreactivity to result from an accumulation in intracellular compartments such as the Golgi apparatus or lysosomes. In addition, TAM and RAL were able to prevent the RA-dependent decrease of Cx43 immunoreactivity in NTera2/D1 cells, normally observed during neuronal differentiation. This suggested a suppression of neuronal differentiation to result from these substances. According to this, treatment of NTera2/D1 cells with 10 µmol/l TAM or RAL during weeks 1 and 2 of a 6 weeks RA-driven differentiation schedule impaired, whereas treatment during weeks 5 and 6 did not impair, neuronal differentiation of these cells. Modulation of GJ coupling between NTera2/D1 cells by TAM and RAL seems therefore to perturb early neuronal differentiation, whereas differentiated neurons in the mature brain seem to be not affected. These effects could be of importance for actions of TAM and RAL on early embryonic steps of nervous system formation

What do parents think about parental participation in school-based interventions on energy balance-related behaviours? a qualitative study in 4 countries

<p>Abstract</p> <p>Background</p> <p>Overweight and obesity in youth has increased dramatically. Therefore, overweight prevention initiatives should start early in life and target modifiable energy balance-related behaviours. Parental participation is often advocated as important for school-based interventions, however, getting parents involved in school-based interventions appears to be challenging based on earlier intervention experiences. The purpose of this study was to get insight into the determinants of and perspectives on parental participation in school-interventions on energy balance-related behaviours (physical activity, healthy eating, sedentary behaviours) in parents of ten- to twelve-year olds in order to develop an effective parental module for school-based interventions concerning energy balance-related behaviours.</p> <p>Methods</p> <p>Four countries (Belgium, Hungary, Norway and Spain) conducted the focus group research based on a standardised protocol and a semi-structured questioning route. A variation in parental socio-economic status (SES) and parental school involvement was taken into account when recruiting the parents. The audio taped interviews were transcribed, and a qualitative content analysis of the transcripts was conducted in each country.</p> <p>Results</p> <p>Seventeen focus group interviews were conducted with a total of 92 parents (12 men, 80 women). Physical activity was considered to be a joint responsibility of school and parents, nutrition as parent's responsibility but supported by the school, and prevention of sedentary behaviours as parent's sole responsibility. Parents proposed interactive and practical activities together with their child as the best way to involve them such as cooking, food tasting, nutrition workshops, walking or cycling tours, sport initiations together with their child. Activities should be cheap, on a convenient moment, focused on their children and not on themselves, not tutoring, not theoretical, and school-or home-based.</p> <p>Conclusions</p> <p>Parents want to be involved in activities related to energy balance-related behaviours if this implies 'doing things together' with their child at school or at home.</p

Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections.

The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.This work was supported by the Biotechnology and Biological Sciences Research Council and by the Wellcome Trust.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.ppat.100514

Epithelial to mesenchymal transition and breast cancer

Epithelial-mesenchymal plasticity in breast carcinoma encompasses the phenotypic spectrum whereby epithelial carcinoma cells within a primary tumor acquire mesenchymal features and re-epithelialize to form a cohesive secondary mass at a metastatic site. Such plasticity has implications in progression of breast carcinoma to metastasis, and will likely influence response to therapy. The transcriptional and epigenetic regulation of molecular and cellular processes that underlie breast cancer and result in characteristic changes in cell behavior can be monitored using an increasing array of marker proteins. Amongst these markers exists the potential for emergent prognostic, predictive and therapeutic targeting