ATRT-SHH comprises three molecular subgroups with characteristic clinical and histopathological features and prognostic significance.

Atypical teratoid/rhabdoid tumor (ATRT) is an aggressive central nervous system tumor characterized by loss of SMARCB1/INI1 protein expression and comprises three distinct molecular groups, ATRT-TYR, ATRT-MYC and ATRT-SHH. ATRT-SHH represents the largest molecular group and is heterogeneous with regard to age, tumor location and epigenetic profile. We, therefore, aimed to investigate if heterogeneity within ATRT-SHH might also have biological and clinical importance. Consensus clustering of DNA methylation profiles and confirmatory t-SNE analysis of 65 ATRT-SHH yielded three robust molecular subgroups, i.e., SHH-1A, SHH-1B and SHH-2. These subgroups differed by median age of onset (SHH-1A: 18 months, SHH-1B: 107 months, SHH-2: 13 months) and tumor location (SHH-1A: 88% supratentorial; SHH-1B: 85% supratentorial; SHH-2: 93% infratentorial, often extending to the pineal region). Subgroups showed comparable SMARCB1 mutational profiles, but pathogenic/likely pathogenic SMARCB1 germline variants were over-represented in SHH-2 (63%) as compared to SHH-1A (20%) and SHH-1B (0%). Protein expression of proneural marker ASCL1 (enriched in SHH-1B) and glial markers OLIG2 and GFAP (absent in SHH-2) as well as global mRNA expression patterns differed, but all subgroups were characterized by overexpression of SHH as well as Notch pathway members. In a Drosophila model, knockdown of Snr1 (the fly homologue of SMARCB1) in hedgehog activated cells not only altered hedgehog signaling, but also caused aberrant Notch signaling and formation of tumor-like structures. Finally, on survival analysis, molecular subgroup and age of onset (but not ASCL1 staining status) were independently associated with overall survival, older patients (> 3 years) harboring SHH-1B experiencing relatively favorable outcome. In conclusion, ATRT-SHH comprises three subgroups characterized by SHH and Notch pathway activation, but divergent molecular and clinical features. Our data suggest that molecular subgrouping of ATRT-SHH has prognostic relevance and might aid to stratify patients within future clinical trials.

Morphometry of human musculus gluteus maximus in foetal period.

BACKGROUND: Magnus gluteal muscle (musculus gluteus maximus) belongs to the group of lower limb girdle muscles. It is one of the biggest muscles in human organism and is located mostly superficially in gluteal region. Literature provides discussion concerning its role in movement such as walking, running and climbing as well as plastic surgery in reconstructive operations of trochanter. Magnus gluteal muscle plays an important role in orthopaedic surgery. OBJECTIVES: The goal of the study was to analyse the human magnus gluteal muscle in the foetal period. MATERIAL AND METHODS: The analysis was carried out on 154 muscles originating from human foetuses (including 30 females - 39%) belonging to the collection of Normal Anatomy Dept. of Wroclaw Medical University. The body length was assessed with the use of vertex-tuberal (v-tub) length and it was included in the range 107-205 mm, which corresponds with the period 17-30 weeks of foetal life. The survey incorporated the following methods: anthropological, preparational and image acquisition which was acquired with the use of high-resolution digital camera. In order to take computer measurements, the following systems were exploited: Image J and Scion for Windows. Statistical analysis was carried out with the use of STATISTICA package v. 9 (t-Student test). RESULTS: The magnus gluteal muscle was analysed in respect to sexual dimorphism and symmetry. On the basis of elicited parameters, the model of muscle increase in foetal period was defined. The following measurements were taken: v-tub, vertex-plantare (v-pl), body mass, muscle particular sides lengths and distance between corresponding measurement points. In every muscle, the lengths of four sections forming the circumference as well as the area were measured. CONCLUSIONS: No difference was observed in foetal magnus gluteal muscle sexual dimorphism or symmetry (p > 0.05). The correlation diagram was used to calculate the muscle weekly increase in foetal period. The results suggest that lesions and pathologies in the region of magnus gluteal muscle are acquired in post foetal period.

Impaired autonomic regulation of resistance arteries in mice with low vascular endothelial growth factor or upon vascular endothelial growth factor trap delivery.

BACKGROUND: Control of peripheral resistance arteries by autonomic nerves is essential for the regulation of blood flow. The signals responsible for the maintenance of vascular neuroeffector mechanisms in the adult, however, remain largely unknown. METHODS AND RESULTS: Here, we report that VEGF( partial differential/ partial differential) mice with low vascular endothelial growth factor (VEGF) levels suffer defects in the regulation of resistance arteries. These defects are due to dysfunction and structural remodeling of the neuroeffector junction, the equivalent of a synapse between autonomic nerve endings and vascular smooth muscle cells, and to an impaired contractile smooth muscle cell phenotype. Notably, short-term delivery of a VEGF inhibitor to healthy mice also resulted in functional and structural defects of neuroeffector junctions. CONCLUSIONS: These findings uncover a novel role for VEGF in the maintenance of arterial neuroeffector function and may help us better understand how VEGF inhibitors cause vascular regulation defects in cancer patients.

Ultrastructural characteristics of circadian pacemaker neurones, immunoreactive to an antibody against a pigment-dispersing hormone in the fly's brain.

Neurones immunoreactive to an antibody against a pigment-dispersing hormone (PDH-ir) are considered to be pacemaker cells in the neuronal circadian system of flies. We investigated the ultrastructure of PDH-ir varicosities, possible releasing sites of the PDH-like peptide, in the distal medulla of the optic lobe and in the dorsal protocerebrum of the two fly species Drosophila melanogaster and Musca domestica. In both species PDH-ir varicosities show accumulation of dense core vesicles (DCVs). PDH-like peptide is localized in the DCVs as shown by post-embedding immuno-electron microscopy. Localization of PDH-like peptide in DCVs and normally lacking synaptic specializations at PDH-ir varicosities in the medulla are interpreted as a non-synaptic paracrine release of peptide.