Heterozygous Loss-of-Function SEC61A1 Mutations Cause Autosomal-Dominant Tubulo-Interstitial and Glomerulocystic Kidney Disease with Anemia

Autosomal-dominant tubulo-interstitial kidney disease (ADTKD) encompasses a group of disorders characterized by renal tubular and interstitial abnormalities, leading to slow progressive loss of kidney function requiring dialysis and kidney transplantation. Mutations in UMOD, MUC1, and REN are responsible for many, but not all, cases of ADTKD. We report on two families with ADTKD and congenital anemia accompanied by either intrauterine growth retardation or neutropenia. Ultrasound and kidney biopsy revealed small dysplastic kidneys with cysts and tubular atrophy with secondary glomerular sclerosis, respectively. Exclusion of known ADTKD genes coupled with linkage analysis, whole-exome sequencing, and targeted re-sequencing identified heterozygous missense variants in SEC61A1—c.553A>G (p.Thr185Ala) and c.200T>G (p.Val67Gly)—both affecting functionally important and conserved residues in SEC61. Both transiently expressed SEC6A1A variants are delocalized to the Golgi, a finding confirmed in a renal biopsy from an affected individual. Suppression or CRISPR-mediated deletions of sec61al2 in zebrafish embryos induced convolution defects of the pronephric tubules but not the pronephric ducts, consistent with the tubular atrophy observed in the affected individuals. Human mRNA encoding either of the two pathogenic alleles failed to rescue this phenotype as opposed to a complete rescue by human wild-type mRNA. Taken together, these findings provide a mechanism by which mutations in SEC61A1 lead to an autosomal-dominant syndromic form of progressive chronic kidney disease. We highlight protein translocation defects across the endoplasmic reticulum membrane, the principal role of the SEC61 complex, as a contributory pathogenic mechanism for ADTKD

Towards an ‘educational protocol’ for stimulating critical thinking in higher education

edition: Book of Abstracts EARLI 2019status: publishe

The CRITHINKEDU European Course on critical thinking education for university teachers : from conception to delivery

Within the scope of the CRITHINKEDU project1, this intellectual output (Output 3) reports the experience of conceiving and delivering a European training course on Critical Thinking (CT) education for university teachers. It draws on the proposal of the “European inventory of critical thinking skills and dispositions for the 21st century” and the “Preliminary guidelines for quality in critical thinking education” - both presented in the two previous intellectual outputs of the project (Dominguez, 2018a, 2018b). This report is targeted to each leading partner institution or to any Higher Education (HE) institution which desire to later replicate this training course at the local level, to faculty staff interested in the implementation of CT teaching practices and learning activities in their classroom. Deployments within the CRITHINKEDU project will be carried-out as part of the fourth and following intellectual output (Output 4).European CommissionEACEA, through the ERASMUS+ Programm

First results from the releases of Cinereous Vultures (Aegypius monachus) aiming at re-introducing the species in Bulgaria – the start of the establishment phase 2018–2022

The current work presents the preliminary results of the Cinereous Vulture (Aegypius monachus) releases in the Balkan Mountains in 2018–2022, aiming at the species re-introduction in Bulgaria, where it was listed as locally extinct since 1985. The first imports and releases of Cinereous Vultures in Bulgaria started in 2018. Until mid-2022, 72 individuals were released in the Eastern Balkan Mountains (Kotlenska Planina SPA and Sinite Kamani Nature Park) and Vrachanski Balkan Nature Park. Of them, 63 immatures imported from Spain were released from aviaries and nine juveniles captive-bred in European zoos were released by hacking (fledging from an artificial nest). We compared the success in survival and establishment between the different release sites and methods used to adjust the ongoing technics and tactics and to support knowledge improvement for future similar projects.From the nine Cinereous Vultures released by hacking, the results were as follows: 1.00 fledging success, but only 0.22 survival in the first six months – combined period of acclimation, first migration and the first winter. All survivors from that period reached maturity into the wild, but all emigrated from the release site and settled elsewhere.Of the 63 individuals released by aviaries, 32 individuals were released in the Eastern Balkan Mountains (18 individuals are still alive – 0.56 survival; 14 individuals settled in the area, which accounts for 0.44 of all released birds and 0.78 of the survivors). Thirty-one individuals were released in Vrachanski Balkan Nature Park (23 individuals are still alive – 0.74 survival; 22 individuals settled in the area – 0.71 of all released birds and 0.96 of the survivors). Based only on aviary method comparison, the settling of the individuals in the release area was alike in the two sites. However, the Vrachanski Balkan Nature Park performed better in survival – both in acclimation and establishment periods.While comparing the release methods – hacking and release from the aviary – the following results were observed: the survival rate during acclimation was 0.86. Due to more considerable losses during the first migration and dispersal in the individuals released by hacking, the survival rate of 0.22 was significantly lower compared to 0.73 for the birds released from the aviary. Additionally, in both methods, a similar pattern in the first winter and spring migration dispersal was observed. Although the survival was equal in the released-by-hacking or aviary birds after the first year onwards, it is essential to note that the emigration of the hacked birds from the release site was 1.00. In comparison, the birds released from aviaries largely remained and settled in the release area (> 0.77 of the survivors). The cost of release and related acclimation, settling, dispersal and the first winter was the greatest: 0.12–0.17 per period, or cumulatively, it was about 0.27. Survival increased and stabilised to > 0.90 after the first year in the wild and reached nearly 1.00 after two years in the wild onwards.Two distinct nuclei of the Cinereous Vulture were established along the Balkan Mountains – the Eastern Balkan Mountains with 18–23 individuals and four formed pairs using a territory of about 642.74 km2 – 95% home range and 85.72 km2 – 50% core area with center being the town of Kotel; and Vrachanski Balkan Nature Park with present 23–29 individuals, of which 2–3 pairs formed so far, using a territory of about 1,143.66 km2 – 95% home range and 22.89 km2 – 50% core area with center being the village of Zgorigrad. The species readily accepted breeding in artificial nest platforms built by professional arborists on different tree species – oak, beech, sycamore and pine. The only naturally built nests were on the ground (n = 2) (unsuccessful) and in Scots Pine (n = 1) (successful). In 2021 and 2022, in each of the two sites, the first successful reproductions were recorded, which marked the return of the Cinereous Vulture as breeding species – 28 years after the last occasional record of a single breeding pair in the country and 36 years after it was officially listed as locally extinct in Bulgaria