miR-17∼92 exerts stage-specific effects in adult V-SVZ neural stem cell lineages

Neural stem cells (NSCs) in the adult ventricular-subventricular zone (V-SVZ) generate neurons and glia throughout life. MicroRNAs are important post-transcriptional regulators frequently acting in a context-dependent manner. Here, microRNA profiling defines cohorts of miRNAs in quiescent and activated NSCs, with miR-17∼92 highly upregulated in activated NSCs and transit amplifying cells (TACs) versus quiescent NSCs. Conditional miR-17∼92 deletion in the adult V-SVZ results in stage-specific effects. In NSCs, it reduces proliferation in vitro and in vivo, whereas in TACs, it selectively shifts neurogenic OLIG2; -; DLX2; +; toward oligodendrogenic OLIG2; +; DLX2; -; TACs, due to de-repression of an oligodendrogenic program, leading to increased oligodendrogenesis in vivo. This differential regulation of TAC subpopulations highlights the importance of TAC heterogeneity. Finally, in the NSC lineage for intraventricular oligodendrocyte progenitors, miR-17∼92 deletion decreases proliferation and maturation. Together, these findings reveal multiple stage-specific functions of the miR-17∼92 cluster within different adult V-SVZ lineages

Superaging correlation function and ergodicity breaking for Brownian motion in logarithmic potentials

We consider an overdamped Brownian particle moving in a confining asymptotically logarithmic potential, which supports a normalized Boltzmann equilibrium density. We derive analytical expressions for the two-time correlation function and the fluctuations of the time-averaged position of the particle for large but finite times. We characterize the occurrence of aging and nonergodic behavior as a function of the depth of the potential, and support our predictions with extensive Langevin simulations. While the Boltzmann measure is used to obtain stationary correlation functions, we show how the non-normalizable infinite covariant density is related to the super-aging behavior.Comment: 16 pages, 6 figure

Spatially fractional-order viscoelasticity, non-locality and a new kind of anisotropy

Spatial non-locality of space-fractional viscoelastic equations of motion is studied. Relaxation effects are accounted for by replacing second-order time derivatives by lower-order fractional derivatives and their generalizations. It is shown that space-fractional equations of motion of an order strictly less than 2 allow for a new kind anisotropy, associated with angular dependence of non-local interactions between stress and strain at different material points. Constitutive equations of such viscoelastic media are determined. Explicit fundamental solutions of the Cauchy problem are constructed for some cases isotropic and anisotropic non-locality

Fractional diffusion modeling of ion channel gating

An anomalous diffusion model for ion channel gating is put forward. This scheme is able to describe non-exponential, power-law like distributions of residence time intervals in several types of ion channels. Our method presents a generalization of the discrete diffusion model by Millhauser, Salpeter and Oswald [Proc. Natl. Acad. Sci. USA 85, 1503 (1988)] to the case of a continuous, anomalous slow conformational diffusion. The corresponding generalization is derived from a continuous time random walk composed of nearest neighbor jumps which in the scaling limit results in a fractional diffusion equation. The studied model contains three parameters only: the mean residence time, a characteristic time of conformational diffusion, and the index of subdiffusion. A tractable analytical expression for the characteristic function of the residence time distribution is obtained. In the limiting case of normal diffusion, our prior findings [Proc. Natl. Acad. Sci. USA 99, 3552 (2002)] are reproduced. Depending on the chosen parameters, the fractional diffusion model exhibits a very rich behavior of the residence time distribution with different characteristic time-regimes. Moreover, the corresponding autocorrelation function of conductance fluctuations displays nontrivial features. Our theoretical model is in good agreement with experimental data for large conductance potassium ion channels

Lattice Kinetics of Diffusion-Limited Coalescence and Annihilation with Sources

We study the 1D kinetics of diffusion-limited coalescence and annihilation with back reactions and different kinds of particle input. By considering the changes in occupation and parity of a given interval, we derive sets of hierarchical equations from which exact expressions for the lattice coverage and the particle concentration can be obtained. We compare the mean-field approximation and the continuum approximation to the exact solutions and we discuss their regime of validity.Comment: 24 pages and 3 eps figures, Revtex, accepted for publication in J. Phys.

Analysis of Fourier transform valuation formulas and applications

The aim of this article is to provide a systematic analysis of the conditions such that Fourier transform valuation formulas are valid in a general framework; i.e. when the option has an arbitrary payoff function and depends on the path of the asset price process. An interplay between the conditions on the payoff function and the process arises naturally. We also extend these results to the multi-dimensional case, and discuss the calculation of Greeks by Fourier transform methods. As an application, we price options on the minimum of two assets in L\'evy and stochastic volatility models.Comment: 26 pages, 3 figures, to appear in Appl. Math. Financ

Prospective Identification and Purification of Quiescent Adult Neural Stem Cells from Their In Vivo Niche

SummaryAdult neurogenic niches harbor quiescent neural stem cells; however, their in vivo identity has been elusive. Here, we prospectively isolate GFAP+CD133+ (quiescent neural stem cells [qNSCs]) and GFAP+CD133+EGFR+ (activated neural stem cells [aNSCs]) from the adult ventricular-subventricular zone. aNSCs are rapidly cycling, highly neurogenic in vivo, and enriched in colony-forming cells in vitro. In contrast, qNSCs are largely dormant in vivo, generate olfactory bulb interneurons with slower kinetics, and only rarely form colonies in vitro. Moreover, qNSCs are Nestin negative, a marker widely used for neural stem cells. Upon activation, qNSCs upregulate Nestin and EGFR and become highly proliferative. Notably, qNSCs and aNSCs can interconvert in vitro. Transcriptome analysis reveals that qNSCs share features with quiescent stem cells from other organs. Finally, small-molecule screening identified the GPCR ligands, S1P and PGD2, as factors that actively maintain the quiescent state of qNSCs

The influence of the Great Recession on perinatal health—an ecological study on the trend changes and regional differences in Portugal

Background: Few studies examine the relationship between socioeconomic factors and trends in mortality in high-income European countries. Due to the lack of regional-level data, most recent studies on social inequality in Portugal do not investigate regional differences. This study analyses time trends and regional disparities in the evolution of perinatal mortality (PMR) and infant mortality (IMR) associated with demographic and socioeconomic indicators following Portugal's 2008 economic and financial crisis. Methods: Associations were assessed using generalised linear models. A Poisson joinpoint regression model was applied to identify relevant PMR and IMR changes between 2000 and 2018. Country regional disparities were analysed using Mixed Effect Multilevel models. Findings: IMR and PMR significantly decreased in the pre-crisis period but not in the post-crisis period. The significant differences between regions in IMR and PMR in 2000 were followed by a different evolution of regional IMR after 2008. PMR and IMR were not significantly associated with socioeconomic indicators. A significant positive association with maternal age at first birth was identified. Interpretation: Results confirm the influence of the crisis on PMR and IMR trends in Portugal, taking into account recurring associations between macroeconomic cycles, variations in mortality trends, macroeconomic volatility, and stagnation of IMR and PMR. Regional inequalities confirm the internal variability of the crisis influence and persistent spatial inequalities affecting IMR patterns. Funding: FCT, under the Institute of Public Health of the University of Porto (ISPUP)– EPIUnit ( UIDB/04750/2020) and ITR ( LA/P/0064/2020), Maastricht University's external PhD programme under the Care and Public Health Research Institute ( CAPHRI), and the RECAP preterm project (grant agreement no 733280). © 2023 The Author(s)FCT, under the Institute of Public Health of the University of Porto (ISPUP)–EPIUnit (UIDB/04750/2020) and ITR (LA/P/0064/2020), Maastricht University's external PhD programme under the Care and Public Health Research Institute (CAPHRI), and the RECAP preterm project (grant agreement no 733280)

Understanding participation in European cohort studies of preterm children: The views of parents, healthcare professionals and researchers

Background: Retention of participants in cohort studies is a major challenge. A better understanding of all elements involved in participation and attrition phenomena in particular settings is needed to develop effective retention strategies. The study aimed to achieve an in-depth understanding of participant retention in longitudinal cohorts focusing on participants’ and researcher’s perspectives, across three diverse socio-geographic and cultural settings. Methods: This study used a triangulation of multi-situated methods to collect data on cohort studies of children born with less than 32 weeks of gestation in Denmark, Italy and Portugal. It included focus groups and individual semi-driven interviewing with involved key actors (i.e. parents, staff, healthcare professionals, researchers) and a collaborative visual methodology. A purposive sample of 48 key actors (n = 13 in Denmark; n = 13 in Italy; n = 22 in Portugal) was collected. A triangulation of phenomenological thematic analysis with discourse analysis was applied. Cross-contextual and context-specific situational elements involved in participation and attrition phenomena in these child cohorts were identified at various levels and stages. Results: Main findings included: situational challenges affecting potential and range of possibilities for implementation strategies (geopolitical environment, societal changes, research funding models); situational elements related to particular strategies acting as deterrents (postal questionnaires) and facilitators (multiple flexible strategies, reminders, regular interaction); main motivations to enrol and participate (altruism/solidarity and gratitude/sense of duty to reciprocate); main motivational deterrents to participate to follow-up waves (lack of bonding, insufficient feedback); entanglement of clinical and research follow-up as facilitator and deterrent. Conclusions: The multi-situated approach used, addressing the interplay of the lived experience of individuals, was of most value to understand participation variability under different implemented strategies in-context. Cross-contextual and context-specific situational elements that have been influential factors towards participation and attrition in the cohorts were identified.info:eu-repo/semantics/publishedVersio

Randomly Crosslinked Macromolecular Systems: Vulcanisation Transition to and Properties of the Amorphous Solid State

As Charles Goodyear discovered in 1839, when he first vulcanised rubber, a macromolecular liquid is transformed into a solid when a sufficient density of permanent crosslinks is introduced at random. At this continuous equi- librium phase transition, the liquid state, in which all macromolecules are delocalised, is transformed into a solid state, in which a nonzero fraction of macromolecules have spontaneously become localised. This solid state is a most unusual one: localisation occurs about mean positions that are distributed homogeneously and randomly, and to an extent that varies randomly from monomer to monomer. Thus, the solid state emerging at the vulcanisation transition is an equilibrium amorphous solid state: it is properly viewed as a solid state that bears the same relationship to the liquid and crystalline states as the spin glass state of certain magnetic systems bears to the paramagnetic and ferromagnetic states, in the sense that, like the spin glass state, it is diagnosed by a subtle order parameter. In this review we give a detailed exposition of a theoretical approach to the physical properties of systems of randomly, permanently crosslinked macromolecules. Our primary focus is on the equilibrium properties of such systems, especially in the regime of Goodyear's vulcanisation transition.Comment: Review Article, REVTEX, 58 pages, 3 PostScript figure