酪氨酸激酶受体EphA5及其配体ephrin-A5在小鼠脊髓发育过程中的表达

目的研究两个Eph家族分子,EphA5受体及其配体ephrin—A5,在脊髓发育过程中的表达方式。方法β-半乳糖苷酶基因敲入小鼠和配体亲和探针分析受体的表达,两种不同的亲和探针分析配体的表达,基因敲除小鼠作为对照。结果在发育过程中,EphA5表达于脊髓腹侧,而ephrin—A5表达于脊髓背侧。结论EphA5和ephrin—A5在多个脊髓发育阶段都有表达,他们可能在脊髓背腹侧组织结构的建立过程中发挥重要作用。     

End-group effects on the properties of PEG-co-PGA hydrogels

A series of resorbable poly(ethylene glycol)-co-poly(glycolic acid) (PEG-co-PGA, 4KG5) macromonomers have been synthesized with the chemistries from three different photopolymerizable end-groups (acrylates, methacrylates and urethane methacrylates). The aim of the study is to examine the effects of the chemistry of the cross-linker group on the properties of photocross-linked hydrogels. 4KG5 hydrogels were prepared by photopolymerization with high vinyl group conversion as confirmed by ¹H nuclear magnetic resonance spectrometry using a 1D diffusion-ordered spectrometry pulse sequence. Our study reveals that the nature of end-groups in a moderately amphiphilic polymer can adjust the distribution and size of the micellar configuration in water, leading to changes in the macroscopic structure of hydrogels. By varying the chemistry of the cross-linker group (diacrylates (DA), dimethacrylates (DM) and urethane dimethacrylates (UDM)), we determined that the hydrophobicity of a single core polymer consisting of poly(glycolic acid) could be fine-tuned, leading to significant variations in the mechanical, swelling and degradation properties of the gels. In addition, the effects of cross-linker chemistry on cytotoxicity and proliferation were examined. Cytotoxicity assays showed that the three types of hydrogels (4KG5 DA, DM and UDM) were biocompatible and the introduction of RGD ligand enhanced cell adhesion. However, differences in gel properties and stability differentially affected the spreading and proliferation of myoblast C2C12 cells.     

Suicidal ideation and behaviors among youths in juvenile detention

OBJECTIVE: To examine suicidal ideation, suicide attempts, lethality of suicide attempts, and the relationship between psychiatric disorder and recent attempts in newly detained juveniles. METHOD: The sample included 1,829 juveniles, ages 10 to 18 years, sampled after intake to a detention center in Chicago. Interviewers administered the Diagnostic Interview Schedule for Children to assess for thoughts of death, suicidal ideation, suicide plans, lifetime suicide attempts, number of attempts, age at first attempt, attempts within the past 6 months, method of suicide attempts, and psychiatric disorder. RESULTS: More than one third of juvenile detainees and nearly half of females had felt hopeless or thought about death in the 6 months before detention. Approximately 1 in 10 (10.3%, 95% confidence interval: 7.7%-12.8%) juvenile detainees had thought about committing suicide in the past 6 months, and 1 in 10 (11.0%, 95% confidence interval: 8.3%-13.7%) had ever attempted suicide. Recent suicide attempts were most prevalent in females and youths with major depression and generalized anxiety disorder. CONCLUSIONS: Fewer than half of detainees with recent thoughts of suicide had told anyone about their ideation. Identifying youths at risk for suicide, especially those suffering from depressive and anxiety disorders, is a crucial step in preventing suicide.     

PARC and CUL7 form atypical cullin RING ligase complexes

CUL7 and the p53-associated, PARkin-like cytoplasmic protein (PARC) were previously reported to form homodimers and heterodimers, the first demonstration of cullin dimerization. Although a CUL7-based SKP1/CUL1/F-box (SCF)-like complex has been observed, little is known about the existence of a PARC-based SCF-like complex and how PARC interacts with CUL7-based complexes. To further characterize PARC-containing complexes, we examined the ability of PARC to form an SCF-like complex. PARC binds RBX1 and is covalently modified by NEDD8, defining PARC as a true cullin. However, PARC fails to bind SKP1 or F-box proteins, including the CUL7-associated FBXW8. To examine the assembly of PARC- and CUL7-containing complexes, tandem affinity purification followed by multidimensional protein identification technology were used. Multidimensional protein identification technology analysis revealed that the CUL7 interaction with FBXW8 was mutually exclusive of CUL7 binding to PARC or p53. Notably, although heterodimers of CUL7 and PARC bind p53, p53 is not required for the dimerization of CUL7 and PARC. The observed physical separation of FBXW8 and PARC is supported functionally by the generation of Parc-/-, Fbxw8-/- mice, which do not show exacerbation of the Fbxw8-/- phenotype. Finally, all of the PARC and CUL7 subcomplexes examined exhibit E3 ubiquitin ligase activity in vitro. Together, these findings indicate that the intricate assembly of PARC- and CUL7-containing complexes is highly regulated, and multiple subcomplexes may exhibit ubiquitin ligase activity.     

Parental psychopathology and migraine headaches among adolescent girls

Migraine headaches and depression often co-occur within individuals, and both syndromes run in families. However, knowledge about how these disorders relate across generations, as well as how migraine relates to other forms of psychopathology, is sparse. This study examined risk for migraine among female adolescent offspring of parents with different types of psychopathology. The sample was drawn from the Minnesota Twin Family Study, a community-based study of adolescents and their families ( n  = 674, 17-year-old female adolescents and their biological parents). Diagnoses of maternal, paternal and offspring major depression, antisocial behaviour, alcohol dependence and drug dependence were based on structured interviews. Migraine headaches in each family member were assessed via interviews with the mother. Parental depression, antisocial behaviour and drug dependence were associated with offspring migraine. These associations mostly remained significant even when parental migraine and the corresponding type of psychopathology in offspring were adjusted for. In contrast, there were no significant associations between parental psychopathology and offspring stomach problems, indicating that these associations did not extend to all offspring somatic symptoms. These results emphasize the need to look at antisocial behaviour and substance-related problems when examining associations between migraine and psychopathology, and indicate that more research on inter-generational links between migraine and psychopathology is needed.     

Absence of cytomegalovirus-resistance mutations after valganciclovir prophylaxis, in a prospective multicenter study of solid-organ transplant recipients

We investigated the emergence of cytomegalovirus (CMV) ganciclovir-resistance mutations in 301 high-risk solid-organ transplant (SOT) recipients after oral prophylaxis, for 100 days, with either valganciclovir or ganciclovir. For patients treated with ganciclovir, the incidence of CMV UL97 mutations was 1.9% (2/103) at the end of prophylaxis and 6.1% (2/33) for patients with suspected CMV disease up to 1 year after transplantation. No resistance mutations were detected in samples from valganciclovir-treated patients. Dual polymerase (UL54) and UL97 resistance mutations were not seen. Valganciclovir was associated with negligible risk of resistance and thus constitutes a useful alternative to ganciclovir prophylaxis for CMV in high-risk SOT recipients.