Stem Cell-Based Approaches for the Treatment of Diabetes

The incidence of diabetes and the associated debilitating complications are increasing at an alarming rate worldwide. Current therapies for type 1 diabetes focus primarily on administration of exogenous insulin to help restore glucose homeostasis. However, such treatment rarely prevents the long-term complications of this serious metabolic disorder, including neuropathy, nephropathy, retinopathy, and cardiovascular disease. Whole pancreas or islet transplantations have enjoyed limited success in some individuals, but these approaches are hampered by the shortage of suitable donors and the burden of lifelong immunosuppression. Here, we review current approaches to differentiate nonislet cell types towards an islet-cell phenotype which may be used for larger-scale cell replacement strategies. In particular, the differentiation protocols used to direct embryonic stem cells, progenitor cells of both endocrine and nonendocrine origin, and induced pluripotent stem cells towards an islet-cell phenotype are discussed

Elevating zero dimensional global scaling predictions to self-consistent theory-based simulations

We have developed an innovative workflow, STEP-0D, within the OMFIT integrated modelling framework. Through systematic validation against the International Tokamak Physics Activity (ITPA) global H-mode confinement database, we demonstrated that STEP-0D, on average, predicts the energy confinement time with a mean relative error (MRE) of less than 19%. Moreover, this workflow showed promising potential in predicting plasmas for proposed fusion reactors such as ARC, EU-DEMO, and CFETR, indicating moderate H-factors between 0.9 and 1.2. STEP-0D allows theory-based prediction of tokamak scenarios, beginning with zero-dimensional (0D) quantities. The workflow initiates with the PRO-create module, generating physically consistent plasma profiles and equilibrium using the same 0D quantities as the IPB98(y,2) confinement scaling. This sets the starting point for the STEP (Stability, Transport, Equilibrium, and Pedestal) module, which further iterates between theory-based physics models of equilibrium, core transport, and pedestal to yield a self-consistent solution. Given these attributes, STEP-0D not only improves the accuracy of predicting plasma performance but also provides a path towards a novel fusion power plant (FPP) design workflow. When integrated with engineering and costing models within an optimization, this new approach could eliminate the iterative reconciliation between plasma models of varying fidelity. This potential for a more efficient design process underpins STEP-0D's significant contribution to future fusion power plant development.Comment: 12 pages, 13 figures, accepted by Physics of Plasmas 202

Comparing eDNA metabarcoding and conventional pelagic netting to inform biodiversity monitoring in deep ocean environments

The performance of environmental DNA (eDNA) metabarcoding has rarely been evaluated against conventional sampling methods in deep ocean mesopelagic environments. We assessed the biodiversity patterns generated with eDNA and two co-located conventional methods, oblique midwater trawls and vertical multinets, to compare regional and sample-level diversity. We then assessed the concordance of ecological patterns across water column habitats and evaluated how DNA markers and the level of sampling effort influenced the inferred community. We found eDNA metabarcoding characterized regional diversity well, detecting more taxa while identifying similar ecological patterns as conventional samples. Within sampling locations, eDNA metabarcoding rarely detected taxa across more than one replicate. While more taxa were found in eDNA than oblique midwater trawls within sample stations, fewer were found compared to vertical multinets. Our simulations show greater eDNA sampling effort would improve concordance with conventional methods. We also observed that using taxonomic data from multiple markers generated ecological patterns most similar to those observed with conventional methods. Patterns observed with Exact Sequence Variants were more stable across markers suggesting they are more powerful for detecting change. eDNA metabarcoding is a valuable tool for identifying and monitoring biological hotspots but some methodological adjustments are recommended for deep ocean environments

Skeletal muscle delimited myopathy and verapamil toxicity in SUR2 mutant mouse models of AIMS

ABCC9-related intellectual disability and myopathy syndrome (AIMS) arises from loss-of-function (LoF) mutations in the ABCC9 gene, which encodes the SUR2 subunit of ATP-sensitive potassium (

Examining increased flexibility in assessment formats

There have been calls in the literature for changes to assessment practices in higher education, to increase flexibility and give learners more control over the assessment process (Boud and Falchikov 2006; Nicol and MacFarlane-Dick 2006; Taras 2002). This article explores the possibilities of allowing student choice in the format used to present their work, as a starting point for changing assessment, based on recent studies and current examples of flexible assessment practice in Higher Education. The benefits of this flexible assessment format approach are highlighted, along with a discussion of classic assessment considerations such as validity, reliability and marking concerns. The role of technology in facilitating assessment method choice is considered, in terms of new opportunities for providing student choice in the way they evidence their learning and present their work. Considerations for implementing flexible assessment choices into the curriculum are presented, along with a call that further research into such practice is needed to develop a comprehensive set of practical recommendations and best practice for implementation of flexible assessment choice into the curriculum. The article should be of interest to curriculum developers and academics considering implementing changes to the assessment process to increase student ownership and control

Complex consequences of Cantu syndrome SUR2 variant R1154Q in genetically modified mice

Cantu syndrome (CS) is caused by gain-of-function (GOF) mutations in pore-forming (Kir6.1, KCNJ8) and accessory (SUR2, ABCC9) ATP-sensitive potassium (KATP) channel subunits, the most common mutations being SUR2[R1154Q] and SUR2[R1154W], carried by approximately 30% of patients. We used CRISPR/Cas9 genome engineering to introduce the equivalent of the human SUR2[R1154Q] mutation into the mouse ABCC9 gene. Along with minimal CS disease features, R1154Q cardiomyocytes and vascular smooth muscle showed much lower KATP current density and pinacidil activation than WT cells. Almost complete loss of SUR2-dependent protein and KATP in homozygous R1154Q ventricles revealed underlying diazoxide-sensitive SUR1-dependent KATP channel activity. Surprisingly, sequencing of SUR2 cDNA revealed 2 distinct transcripts, one encoding full-length SUR2 protein; and the other with an in-frame deletion of 93 bases (corresponding to 31 amino acids encoded by exon 28) that was present in approximately 40% and approximately 90% of transcripts from hetero- and homozygous R1154Q tissues, respectively. Recombinant expression of SUR2A protein lacking exon 28 resulted in nonfunctional channels. CS tissue from SUR2[R1154Q] mice and human induced pluripotent stem cell-derived (hiPSC-derived) cardiomyocytes showed only full-length SUR2 transcripts, although further studies will be required in order to fully test whether SUR2[R1154Q] or other CS mutations might result in aberrant splicing and variable expressivity of disease features in human CS