Endothelial PlexinD1 signaling instructs spinal cord vascularization and motor neuron development

How the vascular and neural compartment cooperate to achieve such a complex and highly specialized structure as the central nervous system is still unclear. Here, we reveal a crosstalk between motor neurons (MNs) and endothelial cells (ECs), necessary for the coordinated development of MNs. By analyzing cell-to-cell interaction profiles of the mouse developing spinal cord, we uncovered semaphorin 3C (Sema3C) and PlexinD1 as a communication axis between MNs and ECs. Using cell-specific knockout mice and in vitro assays, we demonstrate that removal of Sema3C in MNs, or its receptor PlexinD1 in ECs, results in premature and aberrant vascularization of MN columns. Those vascular defects impair MN axon exit from the spinal cord. Impaired PlexinD1 signaling in ECs also causes MN maturation defects at later stages. This study highlights the importance of a timely and spatially controlled communication between MNs and ECs for proper spinal cord development

Greeks of Alexandria: Time, Place and Identity through the visual representations of a community in transition

The thesis, based on anthropological fieldwork conducted in Alexandria (Egypt) from 2011 to 2012, focuses on the Greek Alexandrian community, a socially and territorially bounded urban diaspora entity, which through institutions, spatial arrangements and face-to-face interactions articulates a sense of connection to place through claims regarding a historically continuous socio-spatial connection to both Alexandria (and Egypt) and Greece. The thesis draws on notions of time and space as a framework for discussing the social dynamics of the Greek Alexandrian community in relation to the complex context of social, economic and political transformations it has experienced over the last 60 years. The aim is to explore culturally defined concepts of identity and memory among Greek Alexandrians, particularly in relation to the major social, political and economic events that followed the Egyptian revolution of 1952, causing significant social and spatial transformations within the Greek Alexandrian community. These changes altered prevailing concepts of public and private space and affected the possibilities of successful inter-generational transmission of values and identities. As perceptions and practices explored in the thesis differ, depending on community role – leaders versus members – but also on age, the concept of generation is used to examine the diverse ways in which the past, present and future are variously understood and confronted. Changing notions of Greek Alexandrian identity are explored by focusing not only on the community’s narrative constructs but also on the visual and material objects that members of the community considered to be meaningful. A wide range of ethnographic material was examined, from narratives, texts and interviews, to visual data such as photographs, videos, films, pictures, and material elements such as urban buildings and other spatial arrangements that are recognized as being central to the community. These diverse elements are brought together in the discussion of collaboration with research participants, which resulted in an exhibition on the history of the community. The exhibition became the means through which interactions across the community’s people and places unfolded, diverse narratives and sentiments about the past, the present and the future emerged, and the area in which frictions and tensions revealed themselves

Disruption of stem cell niche-confined R-spondin 3 expression leads to impaired hematopoiesis

Self-renewal and differentiation of stem and progenitor cells are tightly regulated to ensure tissue homeostasis. This regulation is enabled both remotely by systemic circulating cues, such as cytokines and hormones, and locally by various niche-confined factors. R-spondin 3 (RSPO3) is one of the most potent enhancers of Wnt signaling and its expression is usually restricted to the stem cell niche where it provides localized enhancement of Wnt signaling to regulate stem cell expansion and differentiation. Disruption of this niche-confined expression can disturb proper tissue organization and lead to cancers. Here, we investigate the consequences of disrupting the niche restricted expression of RSPO3 in various tissues including the hematopoietic system. We show that normal Rspo3 expression is confined to the perivascular niche in the bone marrow. Induction of increased systemic levels of circulating RSPO3 outside of the niche results in prominent loss of early-B cell progenitors and anemia but surprisingly has no effect on hematopoietic stem cells (HSCs). Using molecular, pharmacological and genetic approaches, we demonstrate that these RSPO3-induced hematopoietic phenotypes are Wnt and RSPO3 dependent and mediated through non-canonical Wnt signaling. Our study highlights a distinct role for a Wnt/RSPO3 signaling axis in the regulation of hematopoiesis, as well as possible challenges related to therapeutic usage of R-spondins for regenerative medicine

Expectations Traps and Monetary Policy with Limited Commitment

We study the existence and uniqueness properties of monetary policy with limited commitment in LQ RE models. We use a New Keynesian model with debt accumulation in the spirit of Leeper (1991) as a 'lab', because this model generates multiple equilibria under pure discretion, and under full commitment there are two distinct determinate regimes. We study how these properties change over the continuum of intermediate cases between commitment and discretion. We find that although multiple equilibria exist for high degrees of precommitment, even a small degree of precommitment selects a unique equilibrium for a wide range of parameters. We discuss the stability properties of policy equilibria which can be used to design an equilibrium selection criterion. We also demonstrate very different welfare implications for different policy equilibria

The Interest Rate - Exchange Rate Nexus: Exchange Rate Regimes and Policy Equilibria

We study a credible Markov-perfect monetary policy in an open New Keynesian economy with incomplete financial markets. We demonstrate the existence of two discretionary equilibria. Following a shock the economy can be stabilised either 'quickly' or 'slow', both dynamic paths satisfy conditions of optimality and time-consistency. The model can help us to understand sudden change of the interest rate and exchange rate volatility in 'tranquil' and 'volatile' regimes even under a fully credible 'soft peg' of the nominal exchange rate in developing countries

Engineering Human Brain Organoids: From Basic Research to Tissue Regeneration

Background: Brain organoids are self-organized from human pluripotent stem cells and developed into various brain region following the developmental process of brain. Brain organoids provide promising approach for studying brain development process and neurological diseases and for tissue regeneration. Methods: In this review, we summarized the development of brain organoids technology, potential applications focusing on disease modeling for regeneration medicine, and multidisciplinary approaches to overcome current limitations of the technology. Results: Generations of brain organoids are categorized into two major classes by depending on the patterning method. In order to guide the differentiation into specific brain region, the extrinsic factors such as growth factors, small molecules, and biomaterials are actively studied. For better modelling of diseases with brain organoids and clinical application for tissue regeneration, improvement of the brain organoid maturation is one of the most important steps. Conclusion: Brain organoids have potential to develop into an innovative platform for pharmacological studies and tissue engineering. However, they are not identical replicas of their in vivo counterpart and there are still a lot of limitations to move forward to clinical applications