The translatome of neuronal cell bodies, dendrites,and axons

To form synaptic connections and store information, neurons continuously remodel their proteomes. The impressive length of dendrites and axons imposes logistical challenges to maintain synaptic proteins at locations remote from the transcription source (the nucleus). The discovery of thousands of messenger RNAs (mRNAs) near synapses suggested that neurons overcome distance and gain autonomy by producing proteins locally. It is not generally known, however, if, how, and when localized mRNAs are translated into protein. To investigate the translational landscape in neuronal subregions, we performed simultaneous RNA sequencing (RNA-seq) and ribosome sequencing (Ribo-seq) from microdissected rodent brain slices to identify and quantify the transcriptome and translatome in cell bodies (somata) as well as dendrites and axons (neuropil). Thousands of transcripts were differentially translated between somatic and synaptic regions, with many scaffold and signaling molecules displaying increased translation levels in the neuropil. Most translational changes between compartments could be accounted for by differences in RNA abundance. Pervasive translational regulation was observed in both somata and neuropil influenced by specific mRNA features (e.g., untranslated region [UTR] length, RNA-binding protein [RBP] motifs, and upstream open reading frames [uORFs]). For over 800 mRNAs, the dominant source of translation was the neuropil. We constructed a searchable and interactive database for exploring mRNA transcripts and their translation levels in the somata and neuropil [MPI Brain Research, The mRNA translation landscape in the synaptic neuropil. https://public.brain.mpg.de/dashapps/localseq/ Accessed 5 October 2021]. Overall, our findings emphasize the substantial contribution of local translation to maintaining synaptic protein levels and indicate that on-site translational control is an important mechanism to control synaptic strength

In vivo extracellular recordings of thalamic and cortical visual responses reveal V1 connectivity rules

The brain’s connectome provides the scaffold for canonical neural computations. However, a comparison of connectivity studies in the mouse primary visual cortex (V1) reveals that the average number and strength of connections between specific neuron types can vary. Can variability in V1 connectivity measurements coexist with canonical neural computations? We developed a theory-driven approach to deduce V1 network connectivity from visual responses in mouse V1 and visual thalamus (dLGN). Our method revealed that the same recorded visual responses were captured by multiple connectivity configurations. Remarkably, the magnitude and selectivity of connectivity weights followed a specific order across most of the inferred connectivity configurations. We argue that this order stems from the specific shapes of the recorded contrast response functions and contrast invariance of orientation tuning. Remarkably, despite variability across connectivity studies, connectivity weights computed from individual published connectivity reports followed the order we identified with our method, suggesting that the relations between the weights, rather than their magnitudes, represent a connectivity motif supporting canonical V1 computations

Advancing brain barriers RNA sequencing: guidelines from experimental design to publication

Background: RNA sequencing (RNA-Seq) in its varied forms has become an indispensable tool for analyzing differential gene expression and thus characterization of specific tissues. Aiming to understand the brain barriers genetic signature, RNA seq has also been introduced in brain barriers research. This has led to availability of both, bulk and single-cell RNA-Seq datasets over the last few years. If appropriately performed, the RNA-Seq studies provide powerful datasets that allow for significant deepening of knowledge on the molecular mechanisms that establish the brain barriers. However, RNA-Seq studies comprise complex workflows that require to consider many options and variables before, during and after the proper sequencing process.Main body: In the current manuscript, we build on the interdisciplinary experience of the European PhD Training Network BtRAIN (https://www.btrain-2020.eu/) where bioinformaticians and brain barriers researchers collaborated to analyze and establish RNA-Seq datasets on vertebrate brain barriers. The obstacles BtRAIN has identified in this process have been integrated into the present manuscript. It provides guidelines along the entire workflow of brain barriers RNA-Seq studies starting from the overall experimental design to interpretation of results. Focusing on the vertebrate endothelial blood–brain barrier (BBB) and epithelial blood-cerebrospinal-fluid barrier (BCSFB) of the choroid plexus, we provide a step-by-step description of the workflow, highlighting the decisions to be made at each step of the workflow and explaining the strengths and weaknesses of individual choices made. Finally, we propose recommendations for accurate data interpretation and on the information to be included into a publication to ensure appropriate accessibility of the data and reproducibility of the observations by the scientific community.Conclusion: Next generation transcriptomic profiling of the brain barriers provides a novel resource for understanding the development, function and pathology of these barrier cells, which is essential for understanding CNS homeostasis and disease. Continuous advancement and sophistication of RNA-Seq will require interdisciplinary approaches between brain barrier researchers and bioinformaticians as successfully performed in BtRAIN. The present guidelines are built on the BtRAIN interdisciplinary experience and aim to facilitate collaboration of brain barriers researchers with bioinformaticians to advance RNA-Seq study design in the brain barriers community

Right-wing populism in central Europe: Hungarian case (Fidesz, Jobbik)

© 2020, Universidad del Zulia. All rights reserved. The migration crisis of 2015 in Europe had a huge impact on the political field of the European Union. The migration crisis has caused an increase in xenophobia in countries receiving migrants, while at the same time giving a powerful impetus to the revival of nationalism. The Visegrád group countries – the Czech Republic, Slovakia, Poland and Hungary – took a particularly harsh position on migration flows and the EU migration regulations. Among these countries, Hungary stands out for its consistent political position, which is resistant to criticism from outside, including from the structures of official Brussels

EXPERIENCE WITH SURGICAL TREATMENT IN PATIENTS WITH LYMPHOPROLIFERATIVE LESION IN THE BRAIN AND SKULL VAULT BONES

The problem of lymphoproliferative lesions of the central nervous system (CNS) is urgent in both patients with immunodeficiency states and those without background systemic pathology in spite of the fact that the statistics vary greatly in these two categories. Despite a wide range of noninvasive diagnostic procedures, it is impossible to obtain a significant confirmation of primary lymphoproliferative CNS lesion in patients with no background systemic manifestations of the disease. Stereotactic biopsy, followed by combination chemo- and radiotherapy in accordance with the existing protocols, is a well-known procedure to treat suspected primary CNS lymphoma. This paper describes 4 cases of primary CNS and skull bone lymphomas in patients operated on for skull bone granuloma (in one case) or rapid progression of focal and global cerebral neurological deficit (in 3 cases). A postoperative histological analysis using the currently available methods revealed lymphoproliferative lesions; in this connection the patients continued treatment by oncologists

Evolution of pallium, hippocampus and cortical cell types revealed by single-cell transcriptomics in reptiles

Computations in the mammalian cortex are carried out by glutamatergic and GABAergic neurons forming specialized circuits and areas. Here we asked how these neurons and areas evolved in amniotes. We built a gene expression altas of the pallium of two reptilian species using large-scale single-cell mRNA sequencing. The transcriptomic signature of glutamatergic neurons in reptilian cortex suggests that mammalian neocortical layers are made of new cell types generated by diversification of ancestral gene regulatory programs. By contrast, the diversity of reptilian cortical GABAergic neurons indicates that the interneuron classes known in mammals already existed in the common ancestor of all amniotes