Investigating the Molecular Basis of Adult Neurogenesis: Single-Cell Multi-Omics Unveils DNA Methylation as a Key Regulator of Astrocyte Stemness

The ventricular-subventricular zone (vSVZ) of adult mammalian brains harbors specialized astrocytes, called adult neural stem cells (NSCs), which are capable of generating both neurons and glial cells. In contrast, common parenchymal astrocytes perform a wide range of structural, metabolic, homeostatic and neurosupportive functions. Despite these distinct functions, studies employing immunostaining and single-cell RNA-sequencing have demonstrated that NSCs and astrocytes largely express the same set of genes, which raises the question how stem cell function is molecularly encoded. To address this question, I analyzed a single-cell triple-omic data set that contains information on gene expression, chromatin accessibility and DNA methylation for hundreds of cells of the adult NSC lineage, as well as common parenchymal astrocytes. To enable this analysis, I developed "scbs", a Python software for the analysis of single-cell methylation data. I devised and implemented two major improvements over the current state of the art analysis workflow: First, instead of segmenting the genome into fixed intervals, I devised an approach to scan the entire genome for informative regions called variably methylated regions (VMRs). Second, instead of simply averaging methylation values within these tiles, I devised a more robust measure of DNA methylation. By making use of these new methods, I demonstrated that adult NSCs possess a unique DNA methylation profile that is not found in common parenchymal astrocytes. This NSC methylome is characterized by hypomethylation of genes required for neurogenesis. I propose that this feature contributes to the neurogenic capabilities of NSCs by enabling the transcriptional activation of these genes. In contrast, common parenchymal astrocytes are locked in their current astrocyte fate by DNA methylation. To test this hypothesis, I analyzed single-cell multi-omic data from mice that were subjected to ischemia, as ischemia is known to induce a neurogenic response in common parenchymal astrocytes and NSCs. My analysis suggests that this gain of neurogenic capabilities is accompanied by gain of an NSC methylome, which supports the idea that a specific DNA methylome is required for stem cell function. Overall, my results demonstrate that DNA methylation is dynamic even in adult tissues and not just in embryonic development, and furthermore unveils DNA methylation as a crucial factor that constrains or enables alternative cellular fates

Nonlinearity-induced photonic topological insulator

The hallmark feature of topological insulators renders edge transport virtually impervious to scattering at defects and lattice disorder. In our work, we experimentally demonstrate a topological system, using a photonic platform, in which the very existence of the topological phase is brought about by nonlinearity. Whereas in the linear regime, the lattice structure remains topologically trivial, light beams launched above a certain power threshold drive the system into its transient topological regime, and thereby define a nonlinear unidirectional channel along its edge. Our work studies topological properties of matter in the nonlinear regime, and may pave the way towards compact devices that harness topological features in an on-demand fashion

Orthorhombic versus monoclinic symmetry of the charge-ordered state of NaV2O5

High-resolution X-ray diffraction data show that the low-temperature superstructure of alpha-NaV2O5 has an F-centered orthorhombic 2a x 2b x 4c superlattice. A structure model is proposed, that is characterized by layers with zigzag charge order on all ladders and stacking disorder, such that the averaged structure has space group Fmm2. This model is in accordance with both X-ray scattering and NMR data. Variations in the stacking order and disorder offer an explanation for the recently observed devils staircase of the superlattice period along c.Comment: REVTEX, 4 pages including 2 figures, shortened, submitted to PR

Clinical characteristics of subsequent histologically confirmed meningiomas in long-term childhood cancer survivors:A Dutch LATER study

Background: Meningiomas are the most frequent brain tumours occurring after pediatric cranial radiotherapy (CrRT). Data on course of disease, to inform clinical management of meningiomas, are sparse. This study reports the clinical characteristics of histologically confirmed meningiomas in childhood cancer survivors (CCS) in the Netherlands.& nbsp; Methods: In total, 6015 CCS from the Dutch Long-Term Effects After Childhood Cancer (LATER) cohort were eligible, including 1551 with prior CrRT. These CCS were diagnosed with cancer ag

Hemimetabolous genomes reveal molecular basis of termite eusociality

Around 150 million years ago, eusocial termites evolved from within the cockroaches, 50 million years before eusocial Hymenoptera, such as bees and ants, appeared. Here, we report the 2-Gb genome of the German cockroach, Blattella germanica, and the 1.3-Gb genome of the drywood termite Cryptotermes secundus. We show evolutionary signatures of termite eusociality by comparing the genomes and transcriptomes of three termites and the cockroach against the background of 16 other eusocial and non-eusocial insects. Dramatic adaptive changes in genes underlying the production and perception of pheromones confirm the importance of chemical communication in the termites. These are accompanied by major changes in gene regulation and the molecular evolution of caste determination. Many of these results parallel molecular mechanisms of eusocial evolution in Hymenoptera. However, the specific solutions are remarkably different, thus revealing a striking case of convergence in one of the major evolutionary transitions in biological complexity

USPOREDNA RAČUNOVODSTVENA STRUKTURNA ANALIZA FINANCUSKIH IZVJEŠTAJA U DJELATNOSTI "HOTELI I RESTORANI" U CILJU EFIKASNIJEG UPRAVLJANJA

Djelatnost "Hoteli i restorani" sastoji se od nekoliko poddjelatnosti od kojih je najznačajnija "Hoteli". U radu se utvrđuju strukturni odnosi između pojedinih poddjelatnosti i financijsko stanje i profitabilnost poslovanja na razini djelatnosti i poddjelatnosti. Financijsko je stanje kod većina poddjelatnosti uneravnoteženo, što znači da nije uspostavljena ni dugoročna ni kratkoročna uravnoteženost. Profitabilnost pojedinih poddjelatnosti u razmatranom razdoblju je negativna. Sve to upućuje na zaključak da je stanje u djelatnosti "Hoteli i restorani" teško što podrazumijeva hitnu intervenciju na makro i na mikro području. Računovodstvena analiza je temelj na osnovu kojeg je moguće donijeti adekvatne odluke

Altered energy partitioning across terrestrial ecosystems in the European drought year 2018

Drought and heat events, such as the 2018 European drought, interact with the exchange of energy between the land surface and the atmosphere, potentially affecting albedo, sensible and latent heat fluxes, as well as CO(2)exchange. Each of these quantities may aggravate or mitigate the drought, heat, their side effects on productivity, water scarcity and global warming. We used measurements of 56 eddy covariance sites across Europe to examine the response of fluxes to extreme drought prevailing most of the year 2018 and how the response differed across various ecosystem types (forests, grasslands, croplands and peatlands). Each component of the surface radiation and energy balance observed in 2018 was compared to available data per site during a reference period 2004-2017. Based on anomalies in precipitation and reference evapotranspiration, we classified 46 sites as drought affected. These received on average 9% more solar radiation and released 32% more sensible heat to the atmosphere compared to the mean of the reference period. In general, drought decreased net CO(2)uptake by 17.8%, but did not significantly change net evapotranspiration. The response of these fluxes differed characteristically between ecosystems; in particular, the general increase in the evaporative index was strongest in peatlands and weakest in croplands. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'

Mobility in a Globalised World 2014

The term mobility has different meanings in the following science disciplines. In economics, mobility is the ability of an individual or a group to improve their economic status in relation to income and wealth within their lifetime or between generations. In information systems and computer science, mobility is used for the concept of mobile computing, in which a computer is transported by a person during normal use. Logistics creates by the design of logistics networks the infrastructure for the mobility of people and goods. Electric mobility is one of today’s solutions from engineering perspective to reduce the need of energy resources and environmental impact. Moreover, for urban planning, mobility is the crunch question about how to optimise the different needs for mobility and how to link different transportation systems. In this publication we collected the ideas of practitioners, researchers, and government officials regarding the different modes of mobility in a globalised world, focusing on both domestic and international issues