ADP-ribosylation factor-related protein 1 (ARFRP1) plays a specific role in Golgi function controlling recruitment of GRIP domain proteins and ARL1 to the trans-Golgi. Deletion of the mouse Arfrp1 ...gene causes embryonic lethality during early gastrulation, because epiblast cells detach from the ectodermal cell layer and do not differentiate to mesodermal tissue. Here we show that in Arfrp1-/- embryos E-cadherin is mistargeted to intracellular compartments, whereas in control embryos it is present at the cell surface of trophectodermal and ectodermal cells. In enterocytes of intestine-specific Arfrp1 null mutants (Arfrp1vil-/-), E-cadherin is associated with intracellular membranes, partially colocalizing with the cis-Golgi marker GM130 or with punctae close to the cell surface. In contrast, in control enterocytes E-cadherin is exclusively located in the lateral membranes. In addition, ARL1 is dislocated from Golgi membranes to the cytosol of Arfrp1vil-/- enterocytes. Depletion of endogenous ARFRP1 by RNA interference leads to a dislocation of E-cadherin from the cell surface in HeLa cells and to a reduced cell aggregation in Ltk-Ecad cells. ARFRP1 was coimmunoprecipitated in a complex with E-cadherin, α-catenin, β-catenin, γ-catenin, and p120ctn from lysates of Madin-Darby canine kidney cells stably expressing myc-ARFRP1. These data indicate that knock-out of Arfrp1 disrupts the trafficking of E-cadherin through the Golgi and suggest an essential role of the GTPase in trans-Golgi network function.
This paper presents numerical analysis of the discrete fundamental solution of the discrete Laplace operator on a rectangular lattice. Additionally, to provide estimates in interior and exterior ...domains, two different regularisations of the discrete fundamental solution are considered. Estimates for the absolute difference and lp‐estimates are constructed for both regularisations. Thus, this work extends the classical results in the discrete potential theory to the case of a rectangular lattice and serves as a basis for future convergence analysis of the method of discrete potentials on rectangular lattices.
Der demografische Wandel befördert Fachkräfteengpässe und den Bedarf an medizinischen Leistungen. Eine Möglichkeit für Krankenhäuser, einen Wettbewerbsvorteil zu erlangen, bietet eine ...diversitätsspezifische Unternehmensrepräsentation. Im Mittelpunkt der Mixed-Methods-Analyse steht die Fragestellung: Wie stellen sächsische Krankenhäuser Diversität und Inklusion – im Kontext der Personalgewinnung – auf der Unternehmenswebseite dar? Theoretische Grundlage der Querschnittserhebung bildet das Modell der vier Dimensionen von Diversität. Mithilfe der qualitativen Inhaltsanalyse (inhaltliche Strukturierung) werden die Internetpräsenzen der Einrichtungen analysiert. Durch die multiple Regression werden Zusammenhänge in Bezug auf die Krankenhausgröße sowie die Einwohnerzahl des Landkreises/der kreisfreien Stadt untersucht. Im Hinblick auf die Ergebnisse beziehen sich die inhaltlichen Aspekte vorwiegend auf die organisationale (v.a. Funktionen, Arbeitsinhalte) und die äußere Dimension mit den Schwerpunkten Ausbildungsmöglichkeiten und Elternschaft der Beschäftigten. In Bezug auf den Stellenwert wird eine Spannweite von fünf bis 131 kodierten Segmenten je Webseite dargestellt. Es besteht ein signifikanter Zusammenhang zwischen höherer Bettenzahl der Einrichtung sowie steigender Summe von Paraphrasen. Zusammenfassend kann gesagt werden, dass diversitätsspezifische Inhalte auf Webseiten zur Steigerung eines Employer Branding beitragen können. Die Maßnahmen sollten sich insbesondere am Learning-and-Effectiveness-Paradigma orientieren.
Demographic change fosters shortages of skilled workers and the need for medical services. One way for hospitals to gain a competitive advantage is through diversity-specific corporate presentation. The mixed-methods analysis focuses on the question: How do Saxon hospitals present diversity and inclusion – in the context of personnel recruitment – on the corporate website? The theoretical basis of the cross-sectional data is the model of the four layers of diversity. With the help of qualitative content analysis (content structuring), the internet presences of the institutions are analyzed. The multiple regression analyses correlations in relation to the size of the hospital and the number of inhabitants in the district or city. The results shows that the content aspects predominantly relate to the organizational (above all functions, work content) and the external dimension with the focus on training opportunities and parenthood of employees. In terms of importance, a range of five to 131 coded segments per website is presented. There is a significant correlation between the higher number of beds in the facility and the increasing sum of coded segments on the websites. In summary, it can be said that diversity-specific content on websites can help to increase an employer branding. The measures should be oriented in particular to the learning-and-effectiveness paradigm.
A Discrete Theorem of Goursat Hommel, Angela
Advances in applied Clifford algebras,
12/2014, Letnik:
24, Številka:
4
Journal Article
Recenzirano
In order to describe stress and displacement fields in the neightborhood of singularities in fracture mechanics the so-called theory of complex stress function based on Kolosov and Muskhelishvili can ...be used. The relation between linear elasticity and complex function theory is based on the Theorem of Goursat. In this paper a discrete version of the Theorem is proved.
Aims/hypothesis
Islet transplantation is used therapeutically in a minority of patients with type 1 diabetes. Successful outcomes are hampered by early islet beta cell loss. The adjuvant ...co-transplantation of mesenchymal stromal cells (MSCs) has the promise to improve islet transplant outcome.
Methods
We used a syngeneic marginal islet mass transplantation model in a mouse model of diabetes. Mice received islets or islets plus 250,000 MSCs. Kidney subcapsule, intra-hepatic and intra-ocular islet transplantation sites were used. Apoptosis, vascularisation, beta cell proliferation, MSC differentiation and laminin levels were determined by immunohistochemical analysis and image quantification post-transplant.
Results
Glucose homeostasis after the transplantation of syngeneic islets was improved by the co-transplantation of MSCs together with islets under the kidney capsule (
p
= 0.01) and by intravenous infusion of MSCs after intra-hepatic islet transplantation (
p
= 0.05). MSC co-transplantation resulted in reduced islet apoptosis, with reduced numbers of islet cells positive for cleaved caspase 3 being observed 14 days post-transplant. In kidney subcapsule, but not in intra-ocular islet transplant models, we observed increased re-vascularisation rates, but not increased blood vessel density in and around islets co-transplanted with MSCs compared with islets that were transplanted alone. Co-transplantation of MSCs did not increase beta cell proliferation, extracellular matrix protein laminin production or alpha cell numbers, and there was negligible MSC transdifferentiation into beta cells.
Conclusions/interpretation
Co-transplantation of MSCs may lead to improved islet function and survival in the early post-transplantation period in humans receiving islet transplantation.
Aims/hypothesis
The aim of this study was to determine whether BMI in early childhood was affected by the COVID-19 pandemic and containment measures, and whether it was associated with the risk for ...islet autoimmunity.
Methods
Between February 2018 and May 2023, data on BMI and islet autoimmunity were collected from 1050 children enrolled in the Primary Oral Insulin Trial, aged from 4.0 months to 5.5 years of age. The start of the COVID-19 pandemic was defined as 18 March 2020, and a stringency index was used to assess the stringency of containment measures. Islet autoimmunity was defined as either the development of persistent confirmed multiple islet autoantibodies, or the development of one or more islet autoantibodies and type 1 diabetes. Multivariate linear mixed-effect, linear and logistic regression methods were applied to assess the effect of the COVID-19 pandemic and the stringency index on early-childhood BMI measurements (BMI as a time-varying variable, BMI at 9 months of age and overweight risk at 9 months of age), and Cox proportional hazard models were used to assess the effect of BMI measurements on islet autoimmunity risk.
Results
The COVID-19 pandemic was associated with increased time-varying BMI (
β
= 0.39; 95% CI 0.30, 0.47) and overweight risk at 9 months (
β
= 0.44; 95% CI 0.03, 0.84). During the COVID-19 pandemic, a higher stringency index was positively associated with time-varying BMI (
β
= 0.02; 95% CI 0.00, 0.04 per 10 units increase), BMI at 9 months (
β
= 0.13; 95% CI 0.01, 0.25) and overweight risk at 9 months (
β
= 0.23; 95% CI 0.03, 0.43). A higher age-corrected BMI and overweight risk at 9 months were associated with increased risk for developing islet autoimmunity up to 5.5 years of age (HR 1.16; 95% CI 1.01, 1.32 and HR 1.68, 95% CI 1.00, 2.82, respectively).
Conclusions/interpretation
Early-childhood BMI increased during the COVID-19 pandemic, and was influenced by the level of restrictions during the pandemic. Controlling for the COVID-19 pandemic, elevated BMI during early childhood was associated with increased risk for childhood islet autoimmunity in children with genetic susceptibility to type 1 diabetes.
Graphical Abstract
Display omitted
Intrahepatic transplantation of allogeneic pancreatic islets offers a promising therapy for type 1 diabetes. However, long-term insulin independency is often not achieved due to ...severe islet loss shortly after transplantation. To improve islet survival and function, extrahepatic biomaterial-assisted transplantation of pancreatic islets to alternative sites has been suggested. Herein, we present macroporous, star-shaped poly(ethylene glycol) (starPEG)-heparin cryogel scaffolds, covalently modified with adhesion peptides, for the housing of pancreatic islets in three-dimensional (3D) co-culture with adherent mesenchymal stromal cells (MSC) as accessory cells. The implantable biohybrid scaffolds provide efficient transport properties, mechanical protection, and a supportive extracellular environment as a desirable niche for the islets. MSC colonized the cryogel scaffolds and produced extracellular matrix proteins that are important components of the natural islet microenvironment known to facilitate matrix-cell interactions and to prevent cellular stress. Islets survived the seeding procedure into the cryogel scaffolds and secreted insulin after glucose stimulation in vitro. In a rodent model, intact islets and MSC could be visualized within the scaffolds seven days after subcutaneous transplantation. Overall, this demonstrates the potential of customized macroporous starPEG-heparin cryogel scaffolds in combination with MSC to serve as a multifunctional islet supportive carrier for transplantation applications.
Diabetes results in the insufficient production of insulin by the pancreatic β-cells in the islets of Langerhans. Transplantation of pancreatic islets offers valuable options for treating the disease; however, many transplanted islets often do not survive the transplantation or die shortly thereafter. Co-transplanted, supporting cells and biomaterials can be instrumental for improving islet survival, function and protection from the immune system. In the present study, islet supportive hydrogel sponges were explored for the co-transplantation of islets and mesenchymal stromal cells. Survival and continued function of the supported islets were demonstrated in vitro. The in vivo feasibility of the approach was shown by transplantation in a mouse model.
Abstract Objectives To determine the impact of the COVID-19 pandemic on the incidence rates of infection and islet autoimmunity in children at risk for type 1 diabetes. Methods 1050 children aged 4 ...to 7 months with an elevated genetic risk for type 1 diabetes were recruited from Germany, Poland, Sweden, Belgium and the UK. Reported infection episodes and islet autoantibody development were monitored until age 40 months from February 2018 to February 2023. Results The overall infection rate was 311 (95% Confidence Interval CI, 304–318) per 100 person years. Infection rates differed by age, country, family history of type 1 diabetes, and period relative to the pandemic. Total infection rates were 321 per 100 person-years (95% CI 304–338) in the pre-pandemic period (until February 2020), 160 (95% CI 148–173) per 100 person-years in the first pandemic year (March 2020—February 2021; P < 0.001) and 337 (95% CI 315–363) per 100 person-years in subsequent years. Similar trends were observed for respiratory and gastrointestinal infections. Islet autoantibody incidence rates were 1.6 (95% CI 1.0–2.4) per 100 person-years in the pre-pandemic period, 1.2 (95% CI 0.8–1.9) per 100 person-years in the first pandemic year ( P = 0.46), and 3.4 (95% CI 2.3–4.8) per 100 person-years in subsequent years ( P = 0.005 vs. pre-pandemic year; P < 0.001 vs. first pandemic year). Conclusions The COVID-19 pandemic was associated with significantly altered infection patterns. Islet autoantibody incidence rates increased two-fold when infection rates returned to pre-pandemic levels.
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