Challenges for brain repair: insights from adult neurogenesis in birds and mammals

Adult neurogenesis is a widespread phenomenon occurring in many species, including humans. The functional and therapeutic implications of this form of brain plasticity are now beginning to be realized. Comparative approaches to adult neurogenesis will yield important clues about brain repair. Here, we compare adult neurogenesis in birds and mammals. We review recent studies on the glial identity of stem cells that generate new neurons, the different modes of migration used by the newly generated neurons to reach their destinations, and how these systems respond to experimentally induced cell death. We integrate these findings to address how comparative analysis at the molecular level might be used for brain repair

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

Decoherence in an exactly solvable qubit model with initial qubit-environment correlations

We study a model of dephasing (decoherence) in a two-state quantum system (qubit) coupled to a bath of harmonic oscillators. An exact analytic solution for the reduced dynamics of a two-state system in this model has been obtained previously for factorizing initial states of the combined system. We show that the model admits exact solutions for a large class of correlated initial states which are typical in the theory of quantum measurements. We derive exact expressions for the off-diagonal elements of the qubit density matrix, which hold for an arbitrary strength of coupling between the qubit and the bath. The influence of initial correlations on decoherence is considered for different bath spectral densities. Time behavior of the qubit entropy in the decoherence process is discussed.Comment: 10 pages, 5 figure

A fluorescent perilipin 2 knock-in mouse model visualizes lipid droplets in the developing and adult brain

Lipid droplets (LDs) are dynamic lipid storage organelles. They are tightly linked to metabolism and can exert protective functions, making them important players in health and disease. Most LD studies in vivo rely on staining methods, providing only a snapshot. We therefore developed a LD-reporter mouse by endogenously labelling the LD coat protein perilipin 2 (PLIN2) with tdTomato, enabling staining-free fluorescent LD visualisation in living and fixed tissues and cells. Here we validate this model under standard and high-fat diet conditions and demonstrate that LDs are present in various cells in the healthy brain, including neurons, astrocytes, ependymal cells, neural stem/progenitor cells and microglia. Furthermore, we show that LDs are abundant during brain development and can be visualized using live-imaging of embryonic slices. Taken together, our tdTom-Plin2 mouse serves as a novel tool to study LDs and their dynamics under both physiological and diseased conditions in all tissues expressing Plin2

Improving Understanding of Participation and Attrition Phenomena in European Cohort Studies : Protocol for a Multi-Situated Qualitative Study

Background: Cohort studies represent a strong methodology for increasing one's understanding of human life-course development and etiological mechanisms. Retention of participants, especially during long follow-up periods, is, however, a major challenge. A better understanding of the motives for participation and attrition in cohort studies in diverse sociogeographic and cultural settings is needed, as this information is most useful in developing effective retention strategies. Objective: This study aims to improve our understanding of participation and attrition phenomena in a European cohort study of very preterm/very-low-birth-weight (VPT/VLBW) infants from various sociogeographic and cultural settings to better understand variability and ultimately contribute to developing novel and more "in-context" strategies to improve retention. Methods: This study uses a triangulation of multisituated methods to collect data on various cohorts in the Research on European Children and Adults Born Preterm (RECAP) network, which include focus group discussions, individual semidriven interviews, and a collaborative, reflexive visual methodology (participant-generated VideoStories) with relevant key actors involved with these cohort studies such as adult participants, parents (caregivers), cohort staff, health care professionals, and academic researchers. The methodological strategy aims to provide a shared flexible framework of various qualitatively driven methods to collect data on VPT/VLBW adult and child cohorts, from which research partners may choose and combine those most pertinent to apply in their own specific contexts. Data from all sources and sites will be submitted to a triangulation of phenomenological thematic analysis with discourse analysis. Results: As of January 2020, in this study, we enrolled 92 participants variously involved with child and adult RECAP partnering cohorts from six countries. Multisite enrollment and data collection are expected to be completed in all seven study settings by June 2020. Findings will be reported in future publications. Conclusions: Qualitative research methods are a useful complement for enriching and illuminating quantitative results. We expect that opting for a multisituated study approach addressing the interplay of the lived experience of individuals in both researcher and researched stances of particular cohort study settings will contribute to filling some gaps in the understanding of participation variability and effectiveness of different implemented strategies in context. Moreover, health research subjects have traditionally been positioned as passive objects of study rather than active participants, even though they have the greatest stake in improving health care policies and practices. Including collaborative methods allows us to counteract the "top-down" model by handing over some research control to the very people who are providing the data on which research findings will be based while also acknowledging the value of their involvement.Peer reviewe

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

Swimming suppresses correlations in dilute suspensions of pusher microorganisms

Active matter exhibits various forms of non-equilibrium states in the absence of external forcing, including macroscopic steady-state currents. Such states are often too complex to be modelled from first principles and our understanding of their physics relies heavily on minimal models. These have mostly been studied in the case of "dry" active matter, where particle dynamics are dominated by friction with their surroundings. Significantly less is known about systems with long-range hydrodynamic interactions that belong to "wet" active matter. Dilute suspensions of motile bacteria, modelled as self-propelled dipolar particles interacting solely through long-ranged hydrodynamic fields, are arguably the most studied example from this class of active systems. Their phenomenology is well-established: at sufficiently high density of bacteria, there appear large-scale vortices and jets comprising many individual organisms, forming a chaotic state commonly known as bacterial turbulence. As revealed by computer simulations, below the onset of collective motion, the suspension exhibits very strong correlations between individual microswimmers stemming from the long-ranged nature of dipolar fields. Here we demonstrate that this phenomenology is captured by the minimal model of microswimmers. We develop a kinetic theory that goes beyond the commonly used mean-field assumption, and explicitly takes into account such correlations. Notably, these can be computed exactly within our theory. We calculate the fluid velocity variance, spatial and temporal correlation functions, the fluid velocity spectrum, and the enhanced diffusivity of tracer particles. We find that correlations are suppressed by particle self-propulsion, although the mean-field behaviour is not restored even in the limit of very fast swimming.Comment: 23 pages, 9 figure