The Importance of REST for Development and Function of Beta Cells.

Beta cells are defined by the genes they express, many of which are specific to this cell type, and ensure a specific set of functions. Beta cells are also defined by a set of genes they should not express (in order to function properly), and these genes have been called forbidden genes. Among these, the transcriptional repressor RE-1 Silencing Transcription factor (REST) is expressed in most cells of the body, excluding most populations of neurons, as well as pancreatic beta and alpha cells. In the cell types where it is expressed, REST represses the expression of hundreds of genes that are crucial for both neuronal and pancreatic endocrine function, through the recruitment of multiple transcriptional and epigenetic co-regulators. REST targets include genes encoding transcription factors, proteins involved in exocytosis, synaptic transmission or ion channeling, and non-coding RNAs. REST is expressed in the progenitors of both neurons and beta cells during development, but it is down-regulated as the cells differentiate. Although REST mutations and deregulation have yet to be connected to diabetes in humans, REST activation during both development and in adult beta cells leads to diabetes in mice

Concise reviews: in vitro-produced pancreas organogenesis models in three dimensions: self-organization from few stem cells or progenitors.

Three-dimensional models of organ biogenesis have recently flourished. They promote a balance between stem/progenitor cell expansion and differentiation without the constraints of flat tissue culture vessels, allowing for autonomous self-organization of cells. Such models allow the formation of miniature organs in a dish and are emerging for the pancreas, starting from embryonic progenitors and adult cells. This review focuses on the currently available systems and how these allow new types of questions to be addressed. We discuss the expected advancements including their potential to study human pancreas development and function as well as to develop diabetes models and therapeutic cells

In vivo imaging of murine endocrine islets of Langerhans with extended-focus optical coherence microscopy

Aims/hypothesis: Structural and functional imaging of the islets of Langerhans and the insulin-secreting beta cells represents a significant challenge and a long-lasting objective in diabetes research. In vivo microscopy offers a valuable insight into beta cell function but has severe limitations regarding sample labelling, imaging speed and depth, and was primarily performed on isolated islets lacking native innervations and vascularisation. This article introduces extended-focus optical coherence microscopy (xfOCM) to image murine pancreatic islets in their natural environment in situ, i.e. in vivo and in a label-free condition. Methods: Ex vivo measurements on excised pancreases were performed and validated by standard immunohistochemistry to investigate the structures that can be observed with xfOCM. The influence of streptozotocin on the signature of the islets was investigated in a second step. Finally, xfOCM was applied to make measurements of the murine pancreas in situ and in vivo. Results: xfOCM circumvents the fundamental physical limit that trades lateral resolution for depth of field, and achieves fast volumetric imaging with high resolution in all three dimensions. It allows label-free visualisation of pancreatic lobules, ducts, blood vessels and individual islets of Langerhans ex vivo and in vivo, and detects streptozotocin-induced islet destruction. Conclusions/interpretation: Our results demonstrate the potential value of xfOCM in high-resolution in vivo studies to assess islet structure and function in animal models of diabetes, aiming towards its use in longitudinal studies of diabetes progression and islet transplant

Attempts to eradicate two Pelargonium viruses (PFBV and PLPV) by meristem culture and shoot-tip cryotherapy

Attempts to eradicate the Pelargonium flower break virus (PFBV) and Pelargonium line pattern virus (PLPV) by meristem culture and apex “droplet-vitrification” cryopreservation was carried out using 5 different cultivars. A simple meristem culture did not permit to eliminate PFBV and only 15% of Pelargonium x hortorum ‘Stellar Artic’ plants regenerated from meristems was PLPV-ELISA-negative. Plants regenerated from cryopreserved apices were tested by DAS-ELISA after a 3-month growing period. Viruses were not detected in 25 and 50% of the tested plants for PFBV and PLPV respectively. Immunolocalisations were carried out for virus localisation in apices from greenhouse plants (control) and vitroplants regenerated after meristem culture or cryopreservation. Immunolocalisations realised on control explants excised from DAS-ELISA positive plants showed that PFBV and PLPV were present in the apices, even in the meristematic dome. However, viral particles were more numerous in the cells of the basal zone than in the more meristematic ones. Immunolocalisations realised on apices from the DAS-ELISA negative cryoregenerated plants showed the viruses were still present. Our results firstly demonstrated that PFBV and PLPV are even present inside meristematic cells and secondly that cryopreservation could decrease their amount in Pelargonium plants but without eliminating them totally. More knowledge on virus behaviour during cryopreservation processes could optimize the management of genetic resources using this conservation method

Cell Cycle-Dependent Differentiation Dynamics Balances Growth and Endocrine Differentiation in the Pancreas

Organogenesis relies on the spatiotemporal balancing of differentiation and proliferation driven by an expanding pool of progenitor cells. In the mouse pancreas, lineage tracing at the population level has shown that the expanding pancreas progenitors can initially give rise to all endocrine, ductal, and acinar cells but become bipotent by embryonic day 13.5, giving rise to endocrine cells and ductal cells. However, the dynamics of individual progenitors balancing self-renewal and lineage-specific differentiation has never been described. Using three-dimensional live imaging and in vivo clonal analysis, we reveal the contribution of individual cells to the global behaviour and demonstrate three modes of progenitor divisions: symmetric renewing, symmetric endocrinogenic, and asymmetric generating a progenitor and an endocrine progenitor. Quantitative analysis shows that the endocrine differentiation process is consistent with a simple model of cell cycle-dependent stochastic priming of progenitors to endocrine fate. The findings provide insights to define control parameters to optimize the generation of β-cells in vitro

Language for Specific Purposes Testing: A Historical Review

Language for specific purposes (LSP) has a long history in the language testing literature. An outgrowth of the communicative language movement of the 1970s, LSP testing arose out of the practical need to assess individuals’ abilities to perform specific tasks in academic and professional settings. This historical review traces the evolution of LSP testing in the language testing literature, focusing specifically on theory and research in two key areas: (a) authenticity and (b) the interaction between language knowledge and background knowledge. The review then turns to how Douglas (2000), in the most comprehensive treatment of LSP testing to date, incorporates insights from these two lines of work into his conceptualization. Throughout the review, tensions and debates emerging from the literature are discussed. The final section addresses the uncertain future of LSP in the language testing landscape

Language for Specific Purposes Testing: A Historical Review

Language for specific purposes (LSP) has a long history in the language testing literature. An outgrowth of the communicative language movement of the 1970s, LSP testing arose out of the practical need to assess individuals’ abilities to perform specific tasks in academic and professional settings. This historical review traces the evolution of LSP testing in the language testing literature, focusing specifically on theory and research in two key areas: (a) authenticity and (b) the interaction between language knowledge and background knowledge. The review then turns to how Douglas (2000), in the most comprehensive treatment of LSP testing to date, incorporates insights from these two lines of work into his conceptualization. Throughout the review, tensions and debates emerging from the literature are discussed. The final section addresses the uncertain future of LSP in the language testing landscape

A herbarium of roses in early 19th century at the crossroad between botany and horticulture: interwoven networks, entangled curiosities

This article focuses on the herbarium created in the early 19th century by André Dupont (1742-1817), a French rose-grower. This herbarium is uncommon because the author took many liberties with the botanical standards of the time in the selection of plants, the names, the classifications, the organization of the plates, and the content of handwritten notes on the labels, among others. Adopting a historiographical approach to collections as encounters between networks rooted in disparate or neighboring cultures, the article argues that the significance of such a disconcerting object is enhanced by its contextualization in both the status of the author and the history of the plants it contains. It demonstrates that Dupont’s herbarium of roses expresses a form of curiosity, inspired by botanical practice but oriented towards a special kind of gardening, that of connoisseurs. It reflects a way of thinking and paying attention, with a concern for plant cultivation and preservation that is representative of a new insight into the diversity of roses in the early 19th century

A Multilevel Framework for Recruiting and Supporting Graduate Students from Culturally Diverse Backgrounds in School Psychology Programs

The lack of cultural diversity among practitioners and trainers in the field of school psychology has been recognized as a longstanding problem. In particular, individuals from racial, ethnic, and linguistic minority and international backgrounds often encounter a range of barriers to pursuing graduate study in school psychology. Given the urgent need to increase diversity among school psychologists, faculty and institutions must take proactive measures to deconstruct these barriers and to support the success of all students. This article outlines a multilevel framework for recruiting and supporting graduate students from culturally diverse backgrounds in school psychology programs. Within this framework, research-based strategies are presented at the primary, secondary, and tertiary levels of support. Moreover, considerations for assessing program and student outcomes are discussed, and applications to school psychology programs internationally are considered