The vascular gene Apold1 is dispensable for normal development but controls angiogenesis under pathological conditions.

The molecular mechanisms of angiogenesis have been intensely studied, but many genes that control endothelial behavior and fate still need to be described. Here, we characterize the role of Apold1 (Apolipoprotein L domain containing 1) in angiogenesis in vivo and in vitro. Single-cell analyses reveal that - across tissues - the expression of Apold1 is restricted to the vasculature and that Apold1 expression in endothelial cells (ECs) is highly sensitive to environmental factors. Using Apold1-/- mice, we find that Apold1 is dispensable for development and does not affect postnatal retinal angiogenesis nor alters the vascular network in adult brain and muscle. However, when exposed to ischemic conditions following photothrombotic stroke as well as femoral artery ligation, Apold1-/- mice display dramatic impairments in recovery and revascularization. We also find that human tumor endothelial cells express strikingly higher levels of Apold1 and that Apold1 deletion in mice stunts the growth of subcutaneous B16 melanoma tumors, which have smaller and poorly perfused vessels. Mechanistically, Apold1 is activated in ECs upon growth factor stimulation as well as in hypoxia, and Apold1 intrinsically controls EC proliferation but not migration. Our data demonstrate that Apold1 is a key regulator of angiogenesis in pathological settings, whereas it does not affect developmental angiogenesis, thus making it a promising candidate for clinical investigation.

Effects of Early Life Stress on Bone Homeostasis in Mice and Humans.

Bone pathology is frequent in stressed individuals. A comprehensive examination of mechanisms linking life stress, depression and disturbed bone homeostasis is missing. In this translational study, mice exposed to early life stress (MSUS) were examined for bone microarchitecture (µCT), metabolism (qPCR/ELISA), and neuronal stress mediator expression (qPCR) and compared with a sample of depressive patients with or without early life stress by analyzing bone mineral density (BMD) (DXA) and metabolic changes in serum (osteocalcin, PINP, CTX-I). MSUS mice showed a significant decrease in NGF, NPYR1, VIPR1 and TACR1 expression, higher innervation density in bone, and increased serum levels of CTX-I, suggesting a milieu in favor of catabolic bone turnover. MSUS mice had a significantly lower body weight compared to control mice, and this caused minor effects on bone microarchitecture. Depressive patients with experiences of childhood neglect also showed a catabolic pattern. A significant reduction in BMD was observed in depressive patients with childhood abuse and stressful life events during childhood. Therefore, future studies on prevention and treatment strategies for both mental and bone disease should consider early life stress as a risk factor for bone pathologies.

Hippocampal gene expression induced by cold swim stress depends on sex and handling.

Stress-related disorders such as PTSD and depression are more prevalent in women than men. One reason for such discordance may be that brain regions involved in stress responses are more sensitive to stress in females. Here, we compared the effects of acute stress on gene transcription in the hippocampus of female and male mice, and also examined the involvement of two key stress-related hormones, corticosterone and corticotropin releasing hormone (Crh). Using quantitative reverse transcription polymerase chain reaction (RT-qPCR), we measured gene expression of Fos, Per1 and Sgk1 45 min after exposure to brief cold swim stress. Stress induced a stronger increase in Fos and Per1 expression in females than males. The handling control procedure increased Fos in both sexes, but occluded the effects of stress in males. Further, handling increased Per1 only in males. Sgk1 was insensitive to handling, and increased in response to stress similarly in males and females. The transcriptional changes observed after swim stress were not mimicked by corticosterone injections, and the stress-induced increase in Fos, Per1 and Sgk1 could neither be prevented by pharmacologically blocking glucocorticoid receptor (GR) nor by blocking Crh receptor 1 (Crhr1) before stress exposure. Finally, we demonstrate that the effects are stressor-specific, as the expression of target genes could not be increased by brief restraint stress in either sex. In summary, we find strong effects of acute swim stress on hippocampal gene expression, complex interactions between handling and sex, and a remarkably unique response pattern for each gene. Overall, females respond to a cold swim challenge with stronger hippocampal gene transcription than males, independent of two classic mediators of the stress response, corticosterone and Crh. These findings may have important implications for understanding the higher vulnerability of women to certain stress-related neuropsychiatric diseases.

[Surgical treatment of tumors of the central region of brain in children: analysis of own material and review of the literature]. / Leczenie operacyjne nowotworów obszaru srodkowego mózgu u dzieci--analiza materialu wlasnego i przeglad pismiennictwa.

UNLABELLED: AIM OF THIS PAPER: Is to present our results of surgical treatment of central region tumors in children and to determine prognostic factors for patients' survival. METHOD: Retrospective analysis of medical records, radiographies and histopathological specimens of patients treated at the Dept. of Neurosurgery with the diagnosis of central region tumor and review of questionnaires mailed to the patients' parents. The statistical analysis was performed using the "Statistica.pl" software. MATERIAL: From January 1980 to March 2003, 114 such children were treated (mean age--8.05 years, mean follow-up time--38.4 months). In the subgroup of benign tumors (n=70), 70% of children are still alive 21.4% are dead and no data are available for the remaining 8.5% (mean survival time--23 months). In the subgroup of malignant tumors (n=12), 33.3% of patients are still alive and 66.6% are dead (mean survival time--14.2 months). In the group treated surgically (total or partial resection) (n=35), 71.4% of children are still alive, 17.1% are dead and no data are available in 11.4% of cases (mean survival time--24 months). In the group of children who underwent palliative procedures only (n=47), 59.5% are still alive, 27% are dead and no data are available for the remaining 12.7% (mean survival time--18.3 months). The statistical analysis revealed highly significant differences in the survival of children dependent on the tumor grade (p=0.00059) and the extent of resection (p=0.00825). CONCLUSIONS: Tumors of the central region of brain in children are highly heterogenous, so in every case the histological diagnosis should be obtained. Prognostic factors are the degree of histologic malignancy and the extent of surgical resection. In every case surgical resection should be considered.