Capillary contact points determine beta cell polarity, control secretion and are disrupted in the db/db mouse model of diabetes.

Aims/hypothesis: Almost all beta cells contact one capillary and insulin granule fusion is targeted to this region. However, there are reports of beta cells contacting more than one capillary. We therefore set out to determine the proportion of beta cells with multiple contacts and the impact of this on cell structure and function.

Erratum: Proteomic pathways to metabolic disease and type 2 diabetes in the pancreatic islet.

[This corrects the article DOI: 10.1016/j.isci.

Motivations and perceived harms and benefits of online communication about self-harm: An interview study with young people.

Background: Self-harm behaviour is prevalent among young people and online communication about self-harm is frequent. These online communications are associated with potential harms and potential benefits. To date, few studies have explored the motivations and mechanisms involved in youth online communication about self-harm.

Glucose-Dependent Insulin Secretion from β Cell Spheroids Is Enhanced by Embedding into Softer Alginate Hydrogels Functionalised with RGD Peptide.

Type 1 diabetes results from the loss of pancreatic β cells, reduced insulin secretion and dysregulated blood glucose levels. Replacement of these lost β cells with stem cell-derived β cells, and protecting these cells within macro-device implants is a promising approach to restore glucose homeostasis. However, to achieve this goal of restoration of glucose balance requires work to optimise β cell function within implants.

Applied Geophysics for Managed Aquifer Recharge.

Increasing water stress and decreasing supplies caused by growth and climate variability have expanded demand for managed aquifer recharge (MAR) projects to provide water supply resilience. Some of the most important factors in determining the performance of a MAR project include site selection, subsurface hydrogeologic characteristics and associated properties of the storage zone. Costs for invasive subsurface investigations to address these factors have slowly increased over the past two decades, with drilling costs increasing dramatically by as much as 30% or more since COVID-19 hit, a result of supply chain issues, steel prices, and manpower challenges.

Local activation of focal adhesion kinase orchestrates the positioning of presynaptic scaffold proteins and Ca signalling to control glucose-dependent insulin secretion.

A developing understanding suggests that spatial compartmentalisation in pancreatic β cells is critical in controlling insulin secretion. To investigate the mechanisms, we have developed live-cell subcellular imaging methods using the mouse organotypic pancreatic slice. We demonstrate that the organotypic pancreatic slice, when compared with isolated islets, preserves intact β-cell structure, and enhances glucose-dependent Ca responses and insulin secretion.

Presynaptic-like mechanisms and the control of insulin secretion in pancreatic β-cells.

Exocytotic release of hormones from endocrine cells must encompass mechanisms that direct the hormone into the blood stream. Increasing evidence indicates an intimate link between pancreatic β-cells and the capillary bed of islets of Langerhans in both mouse and human. Integrins are exclusively activated at the region where β-cells contact extracellular matrix proteins that surround the islet capillaries; furthermore, insulin granule exocytosis is targeted to this same region, therefore delivering hormone directly into the blood stream.

Case Report: Hypoglycemia Due to a Novel Activating Glucokinase Variant in an Adult - a Molecular Approach.

We present a case of an obese 22-year-old man with activating variant who had neonatal hypoglycemia, re-emerging with hypoglycemia later in life. We investigated him for asymptomatic hypoglycemia with a family history of hypoglycemia. Genetic testing yielded a novel missense class 3 variant that was subsequently found in his mother, sister and nephew and reclassified as a class 4 likely pathogenic variant.

Good practice recommendations for information provision for those involved in reproductive donation.

Study Question: What information and support should be offered to donors, intended parents and donor-conceived people, in general and in consideration of the availability of direct-to-consumer genetic testing and matching services?

Summary Answer: For donors, intended parents and donor-conceived offspring, recommendations are made that cover information needs and informed consent, psychosocial implications and disclosure.

What Is Known Already: Trends indicate that the use of donor-assisted conception is growing and guidance is needed to help these recipients/intended parents, the donors and offspring, navigate the rapidly changing environment in which donor-assisted conception takes place.

Study Design Size Duration: A working group (WG) collaborated on writing recommendations based, where available, on evidence collected from a literature search and expert opinion.

When ART fails: figures, experiences, interventions and a plea for the 'plan B'.

Infertility is perceived by many of those affected by it as one of the most stressful episodes in life. Assisted reproduction can help only some of the people with a desire for children to experience the birth of a biological child. Most people who remain involuntarily childless eventually come to terms with the situation; their psychological well-being is not lastingly affected.

Insulin-Binding Peptide Probes Provide a Novel Strategy for Pancreatic β-Cell Imaging.

Type 1 diabetes develops in childhood and adolescence, with peak incidence in the early teenage years. There is an urgent need for an accurate method to detect insulin-producing β-cells in patients that is not affected by alterations in β-cell function. As part of our research program to design specific probes to measure β-cell mass, we recently developed a novel insulin-binding peptide probe (IBPP) for the detection of β-cells in vivo.

Proteomic pathways to metabolic disease and type 2 diabetes in the pancreatic islet.

Pancreatic islets are essential for maintaining physiological blood glucose levels, and declining islet function is a hallmark of type 2 diabetes. We employ mass spectrometry-based proteomics to systematically analyze islets from 9 genetic or diet-induced mouse models representing a broad cross-section of metabolic health. Quantifying the islet proteome to a depth of >11,500 proteins, this study represents the most detailed analysis of mouse islet proteins to date.

Psychosomatically Oriented Diagnostics and Therapy for Fertility Disorders. Guideline of the DGPFG (S2k-Level, AWMF Registry Number 016/003, December 2019).

The purpose of this official guideline published and coordinated by the German Society for Psychosomatic Gynecology and Obstetrics [Deutsche Gesellschaft für Psychosomatische Frauenheilkunde und Geburtshilfe (DGPFG)] is to provide a consensus-based overview of psychosomatically oriented diagnostic procedures and treatments for fertility disorders by evaluating the relevant literature. This S2k guideline was developed using a structured consensus process which included representative members of various professions; the guideline was commissioned by the DGPFG and is based on the 2014 version of the guideline. The guideline provides recommendations on psychosomatically oriented diagnostic procedures and treatments for fertility disorders.

Machine Learning Algorithms, Applied to Intact Islets of Langerhans, Demonstrate Significantly Enhanced Insulin Staining at the Capillary Interface of Human Pancreatic β Cells.

Pancreatic β cells secrete the hormone insulin into the bloodstream and are critical in the control of blood glucose concentrations. β cells are clustered in the micro-organs of the islets of Langerhans, which have a rich capillary network. Recent work has highlighted the intimate spatial connections between β cells and these capillaries, which lead to the targeting of insulin secretion to the region where the β cells contact the capillary basement membrane.

The Role of Vascular Cells in Pancreatic Beta-Cell Function.

Insulin-producing β-cells constitute the majority of the cells in the pancreatic islets. Dysfunction of these cells is a key factor in the loss of glucose regulation that characterizes type 2 diabetes. The regulation of many of the functions of β-cells relies on their close interaction with the intra-islet microvasculature, comprised of endothelial cells and pericytes.

How Category Selection Impacts Inference Reliability: Inheritance Inference From an Ecological Perspective.

This article presents results from a simulation-based study of inheritance inference, that is, inference from the typicality of a property among a "base" class to its typicality among a subclass of the class. The study aims to ascertain which kinds of inheritance inferences are reliable, with attention to the dependence of their reliability upon the type of environment in which inferences are made. For example, the study addresses whether inheritance inference is reliable in the case of "exceptional subclasses" (i.

Structural and functional polarisation of human pancreatic beta cells in islets from organ donors with and without type 2 diabetes.

Aims/hypothesis: We hypothesised that human beta cells are structurally and functional polarised with respect to the islet capillaries. We set out to test this using confocal microscopy to map the 3D spatial arrangement of key proteins and live-cell imaging to determine the distribution of insulin granule fusion around the cells.

Methods: Human pancreas samples were rapidly fixed and processed using the pancreatic slice technique, which maintains islet structure and architecture.

Bioactivation of Encapsulation Membranes Reduces Fibrosis and Enhances Cell Survival.

Encapsulation devices are an emerging barrier technology designed to prevent the immunorejection of replacement cells in regenerative therapies for intractable diseases. However, traditional polymers used in current devices are poor substrates for cell attachment and induce fibrosis upon implantation, impacting long-term therapeutic cell viability. Bioactivation of polymer surfaces improves local host responses to materials, and here we make the first step toward demonstrating the utility of this approach to improve cell survival within encapsulation implants.

Enhanced structure and function of human pluripotent stem cell-derived beta-cells cultured on extracellular matrix.

The differentiation of human stem cells into insulin secreting beta-like cells holds great promise to treat diabetes. Current protocols drive stem cells through stages of directed differentiation and maturation and produce cells that secrete insulin in response to glucose. Further refinements are now needed to faithfully phenocopy the responses of normal beta cells.