During CNS development, interneuron precursors have to migrate extensively before they integrate in specific microcircuits. Known regulators of neuronal motility include classical neurotransmitters, yet the mechanisms that assure interneuron dispersal and interneuron/projection neuron matching during histogenesis remain largely elusive. We combined time-lapse video microscopy and electrophysiological analysis of the nascent cerebellum of transgenic Pax2-EGFP mice to address this issue. We found that cerebellar interneuronal precursors regularly show spontaneous postsynaptic currents, indicative of synaptic innervation, well before settling in the molecular layer. In keeping with the sensitivity of these cells to neurotransmitters, ablation of synaptic communication by blocking vesicular release in acute slices of developing cerebella slows migration. Significantly, abrogation of exocytosis primarily impedes the directional persistence of migratory interneuronal precursors. These results establish an unprecedented function of the early synaptic innervation of migrating neuronal precursors and demonstrate a role for synapses in the regulation of migration and pathfinding.

The varicella zoster virus (VZV) causes the childhood disease commonly known as chickenpox and can later in life reactivate as herpes zoster. The adaptive immune system is known to play an important role in suppressing VZV reactivation. A central aspect of this system is the presentation of VZV-derived peptides by the major histocompatibility complex (MHC) proteins. Here, we investigate if key VZV proteins have evolved their amino acid sequence to avoid presentation by MHC based on predictive models of MHC-peptide affinity. This study shows that the immediate-early proteins of all characterized VZV strains are profoundly depleted for high-affinity MHC-I-restricted epitopes. The same depletion can be found in its closest animal analog, the simian varicella virus. Further orthology analysis towards other herpes viruses suggests that the protein amino acid frequency is one of the primary drivers of targeted epitope depletion.

Background. The current catheters and fibres used for endovenous laser and radiofrequency ablation of varicose veins have a radial energy emission. This gives an opportunity to treat veins of a large diameter which was previously considered to be challenging. The majority of studies categorise veins of more than 1 cm in diameter as large (Chaar C.I., et al. 2011; Florescu C., et al. 2014). Many patients have saphenous veins 1e2 cm in diameter, which can be occluded in almost 100% of cases. Treating veins more than 2 cm in diameter with tumescent anaesthesia may be associated with formation of a "blind pocket". This means that a part of the vein does not have appropriate contact with the fibre. This can be one of the reasons for recanalisation. The aim of this study was to investigate the results of endovenous laser ablation (EVLA) of saphenous veins larger than 2 cm in diameter. Methods. This was a prospective non-comparative study that included 231 patients who underwent 261 EVLA of the great saphenous vein (GSV) between November 2014 and June 2019. EVLA was performed using 1470 nm laser, radial fibres, and an automatic pull back device. All procedures were performed under tumescent anaesthesia. The average diameter of the veins at the saphenofemoral junction was 24 AE 6 mm (range 21e43 mm). EVLA was administered at the average power of 8e10 W. The linear endovenous energy density in dilated segments was 83e147 J/cm. The follow up period was 178 AE 67 days (range 61e540 days). Duplex ultrasound was performed on days one and seven, and months two and six after the treatment. Results. Two hundred and thirty (88%) veins were occluded the day after EVLA. In 31 (12%) cases there were non-occluded segments of dilated parts of the saphenous vein on the day after the procedure. These segments were found to be occluded in 21 of 31 patients at seven days. In 11 (4%) cases, ultrasound guided foam sclerotherapy (UGFS) was performed. Short stumps of GSV (19 AE 6 mm) were found in 12 (5%) patients at six month follow up, with no reflux in these stumps. Recanalisation of a long segment of the GSV with reflux was found in two (0.8%) cases, which was treated by EVLA and UGFS. Conclusion. EVLA using radial fibres is effective for a GSV more than 2 cm with a 99% occlusion rate in the early follow up period.

The relationship between neurological damage and cardiovascular disease is often observed. This type of damage is both a cause and an effect of cardiovascular disease. Mitochondria are the key organelles of the cell and are primarily subject to oxidative stress. Mitochondrial dysfunctions are involved in the etiology of various diseases. A decrease in the efficiency of the heart muscle can lead to impaired blood flow and decreased oxygen supply to the brain. Astaxanthin (AST), a marine-derived xanthophyll carotenoid, has multiple functions and its effects have been shown in both experimental and clinical studies. We investigated the effects of AST on the functional state of brain mitochondria in rats after heart failure. Isoproterenol (ISO) was used to cause heart failure. In the present study, we found that ISO impaired the functional state of rat brain mitochondria (RBM), while the administration of AST resulted in an improvement in mitochondrial efficiency. The respiratory control index (RCI) in RBM decreased with the use of ISO, while AST administration led to an increase in this parameter. Ca2+ retention capacity (CRC) decreased in RBM isolated from rat brain after ISO injection, and AST enhanced CRC in RBM after heart failure. The study of changes in the content of regulatory proteins such as adenine nucleotide translocase 1 and 2 (ANT1/2), voltage dependent anion channel (VDAC), and cyclophilin D (CyP-D) of mitochondrial permeability transition pore (mPTP) showed that ISO reduced their level, while AST restored the content of these proteins almost to the control value. In general, AST improves the functional state of mitochondria and can be considered as a prophylactic drug in various therapeutic approaches.

No abstract