Mutations in the guinea pig preproglucagon gene are restricted to a specific portion of the prohormone sequence

AbstractA cDNA clone encoding guinea pig preproglucagon has been isolated from a pancreatic cDNA library. The predicted amino acid sequence of proglucagon is highly conserved in all regions, in comparison to other mammals, except for the C-terminal portion of the 29-residue glucagon region, in which 5 amino acid substitutions have occurred. These changes may serve to offset the reduced receptor-binding potency of the highly mutated insulin in this New World species.GlucagonEvolutionHystricomorphcDNAGlycogenolytic hormon

Renal tissue engineering for regenerative medicine using polymers and hydrogels

Chronic Kidney Disease (CKD) is a growing worldwide problem, leading to end-stage renal disease (ESRD). Current treatments for ESRD include haemodialysis and kidney transplantation, but both are deemed inadequate since haemodialysis does not address all other kidney functions, and there is a shortage of suitable donor organs for transplantation. Research in kidney tissue engineering has been initiated to take a regenerative medicine approach as a potential treatment alternative, either to develop effective cell therapy for reconstruction or engineer a functioning bioartificial kidney. Currently, renal tissue engineering encompasses various materials, mainly polymers and hydrogels, which have been chosen to recreate the sophisticated kidney architecture. It is essential to address the chemical and mechanical aspects of the materials to ensure they can support cell development to restore functionality and feasibility. This paper reviews the types of polymers and hydrogels that have been used in kidney tissue engineering applications, both natural and synthetic, focusing on the processing and formulation used in creating bioactive substrates and how these biomaterials affect the cell biology of the kidney cells used

Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort

Background Individuals with rare kidney diseases account for 5–10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. Methods People aged 0–96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan–Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window). Findings Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9–16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32–0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. Interpretation Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3–5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. Funding RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity

Cytoskeletal protein degradation in brain death donor kidneys associates with adverse posttransplant outcomes

In brain death, cerebral injury contributes to systemic biological dysregulation, causing significant cellular stress in donor kidneys adversely impacting the quality of grafts. Here, we hypothesized that donation after brain death (DBD) kidneys undergo proteolytic processes that may deem grafts susceptible to posttransplant dysfunction. Using mass spectrometry and immunoblotting, we mapped degradation profiles of cytoskeletal proteins in deceased and living donor kidney biopsies. We found that key cytoskeletal proteins in DBD kidneys were proteolytically cleaved, generating peptide fragments, predominantly in grafts with suboptimal posttransplant function. Interestingly, alpha-actinin-4 and talin-1 proteolytic fragments were detected in brain death but not in circulatory death or living donor kidneys with similar donor characteristics. As talin-1 is a specific proteolytic target of calpain-1, we investigated a potential trigger of calpain activation and talin-1 degradation using human ex vivo precision-cut kidney slices and in vitro podocytes. Notably, we showed that activation of calpain-1 by transforming growth factor-beta generated proteolytic fragments of talin-1 that matched the degradation fragments detected in DBD preimplantation kidneys, also causing dysregulation of the actin cytoskeleton in human podocytes; events that were reversed by calpain-1 inhibition. Our data provide initial evidence that brain death donor kidneys are more susceptible to cytoskeletal protein degradation. Correlation to posttransplant outcomes may be established by future studies

An investigation of the library and information requirements of mobile library users in South Ceredigion, Dyfed Final report

SIGLEAvailable from British Library Document Supply Centre- DSC:Q027.4 / BLDSC - British Library Document Supply CentreGBUnited Kingdo