546G>T allowed the development of an antisense oligonucleotide that promoted canonical GAA pre-mRNA splicing and elevated GAA enzymatic activity. Our results indicate that this extended generic splicing assay allows the detection of aberrant splicing in cases of mRNA degradation to enable functional analysis of unknown splicing variants and the development of targeted treatment options.Crop diversity underpins food security and adaptation to climate change. Concerted conservation efforts are needed to maintain and make this diversity available to plant scientists, breeders and farmers. Here we present the story of the rescue and reconstitution of the unique seed collection held in the international genebank of International Center for Agricultural Research in the Dry Areas (ICARDA) in Syria. Being among the first depositors to the Svalbard Global Seed Vault, ICARDA managed to safety duplicate more than 80% of its collection before the last staff had to leave the genebank in 2014 because of the war. Based on the safety duplicates, ICARDA since 2015 have rebuilt their collections and resumed distribution of seeds to users internationally from their new premises in Morocco and Lebanon. We describe the multifaceted and layered structure of the global system for the conservation and use of crop diversity that enabled this successful outcome. Genebanks do not work alone but in an increasingly strengthened and experienced multilateral system of governance, science, financial support and collaboration. This system underpins efforts to build sustainable and socially equitable agri-food systems.Fibrosis is a common pathological feature of chronic disease. Deletion of the NF-κB subunit c-Rel limits fibrosis in multiple organs, although the mechanistic nature of this protection is unresolved. Using cell-specific gene-targeting manipulations in mice undergoing liver damage, we elucidate a critical role for c-Rel in controlling metabolic changes required for inflammatory and fibrogenic activities of hepatocytes and macrophages and identify Pfkfb3 as the key downstream metabolic mediator of this response. Independent deletions of Rel in hepatocytes or macrophages suppressed liver fibrosis induced by carbon tetrachloride, while combined deletion had an additive anti-fibrogenic effect. In transforming growth factor-β1-induced hepatocytes, c-Rel regulates expression of a pro-fibrogenic secretome comprising inflammatory molecules and connective tissue growth factor, the latter promoting collagen secretion from HMs. Macrophages lacking c-Rel fail to polarize to M1 or M2 states, explaining reduced fibrosis in RelΔLysM mice. Pharmacological inhibition of c-Rel attenuated multi-organ fibrosis in both murine and human fibrosis. In conclusion, activation of c-Rel/Pfkfb3 in damaged tissue instigates a paracrine signalling network among epithelial, myeloid and mesenchymal cells to stimulate fibrogenesis. Targeting the c-Rel-Pfkfb3 axis has potential for therapeutic applications in fibrotic disease.Microporous annealed particle (MAP) scaffolds are flowable, in situ crosslinked, microporous scaffolds composed of microgel building blocks and were previously shown to accelerate wound healing. To promote more extensive tissue ingrowth before scaffold degradation, we aimed to slow MAP degradation by switching the chirality of the crosslinking peptides from L- to D-amino acids. Unexpectedly, despite showing the predicted slower enzymatic degradation in vitro, D-peptide crosslinked MAP hydrogel (D-MAP) hastened material degradation in vivo and imparted significant tissue regeneration to healed cutaneous wounds, including increased tensile strength and hair neogenesis. MAP scaffolds recruit IL-33 type 2 myeloid cells, which is amplified in the presence of D-peptides. Remarkably, D-MAP elicited significant antigen-specific immunity against the D-chiral peptides, and an intact adaptive immune system was required for the hydrogel-induced skin regeneration. buy SNX-5422 These findings demonstrate that the generation of an adaptive immune response from a biomaterial is sufficient to induce cutaneous regenerative healing despite faster scaffold degradation.Mitochondrial DNA (mtDNA) mutations are the major cause of mitochondrial diseases. Cells harboring disease-related mtDNA mutations exhibit various phenotypic abnormalities, such as reduced respiration and elevated lactic acid production. Induced pluripotent stem cell (iPSC) lines derived from patients with mitochondrial disease, with high proportions of mutated mtDNA, exhibit defects in maturation into neurons or cardiomyocytes. In this study, we have discovered a small-molecule compound, which we name tryptolinamide (TLAM), that activates mitochondrial respiration in cybrids generated from patient-derived mitochondria and fibroblasts from patient-derived iPSCs. We found that TLAM inhibits phosphofructokinase-1 (PFK1), which in turn activates AMPK-mediated fatty-acid oxidation to promote oxidative phosphorylation, and redirects carbon flow from glycolysis toward the pentose phosphate pathway to reinforce anti-oxidative potential. Finally, we found that TLAM rescued the defect in neuronal differentiation of iPSCs carrying a high ratio of mutant mtDNA, suggesting that PFK1 represents a potential therapeutic target for mitochondrial diseases.The global burden of diabetes has resulted in an increase in the prevalence of diabetic retinopathy (DR), a microvascular complication of diabetes. Lifelong repetitive screening for DR is essential for early detection and timely management to prevent visual impairment due to the silent sight-threatening disorder. Colour fundus photography (CFP) is helpful for documentation of the retinopathy as well as for counselling the patient. CFP has established roles in DR screening, detection, progression and monitoring of treatment response. DR screening programmes use validated mydriatic or non-mydriatic fundus cameras for retinal imaging and trained image graders identify referable DR. Smartphone-based fundus cameras and handheld fundus cameras that are cost-effective, portable and easy to handle in remote places are gaining popularity in recent years. The images captured with these low-cost devices can be immediately sent to trained ophthalmologists for grading of DR. Recent increase in numbers of telemedicine programmes based on imaging with digital fundus cameras and remote interpretation has facilitated larger population coverage of DR screening and timely referral of those with sight-threatening DR to ophthalmologists.