Criterios de calidad y evaluación: un instrumento de medición para el área de la lengua alemana

La Xarxa Universitària sobre Responsabilitat Social és una xarxa de més de 40 universitats d'Alemanya i Àustria establerta el 2009 que volen fer realitat i ampliar la seva responsabilitat social promovent sistemàticament la participació a la societat civil d'estudiants, professors i altres membres universitaris, vinculant-ho amb la seva missió educativa per influir activament en la societat i contribuir a la transferència mútua de coneixements. L'aprenentatge servei (ApS) és una manera de fer-ho. El 2018, un taller va iniciar una discussió entre representants del món acadèmic i de la societat civil. El focus era analitzar els criteris de qualitat de l’ApS. El grup va plantejar deu criteris diferents que proporcionen un marc de referència per a les diferents manifestacions de l’ApS a la comunitat. A partir d'aquests criteris, es van desenvolupar procediments i instruments adequats per oferir als actors orientació i suggeriments per a la implementació i avaluació dels projectes d’ApS.The University Network on Social Responsibility is a network of more than 40 universities in Germany and Austria established in 2009 that want to realise and expand their social responsibility by systematically promoting the civil society engagement of students, teachers, and other members of higher education, linking this with their educational mission and thus actively influencing society and contributing to the mutual transfer of knowledge. This can be done through the teaching-learning format of service learning (SL). In 2018, a workshop initiated a discussion between representatives of academia and civil society. The focus was the aspect of quality of SL. The group came up with ten different criteria which provide a frame of reference for the different manifestations of SL in the community. Based on these criteria, suitable procedures and instruments were developed to provide SL actors with orientation and suggestions for the implementation and evaluation of SL projects.La Red Universitaria sobre Responsabilidad Social es una red de más de 40 universidades en Alemania y Austria, establecida en 2009, que desean realizar y expandir su responsabilidad social promoviendo sistemáticamente la participación de la sociedad civil de estudiantes, docentes y otros miembros universitarios, vinculando con su misión educativa para influir activamente en la sociedad y contribuir a la transferencia mutua de conocimientos. Ello se puede hacer a través del aprendizaje-servicio (ApS). En 2018, un taller inició un debate entre representantes de la academia y la sociedad civil. El foco fue los aspectos de calidad del ApS. El grupo ideó diez criterios diferentes que proporcionan un marco de referencia para las diferentes manifestaciones de ApS en la comunidad. Con base en estos criterios, se desarrollaron procedimientos e instrumentos adecuados para proporcionar a los actores orientación y sugerencias para la implementación y evaluación de proyectos de ApS

Lack of APLP1 leads to subtle alterations in neuronal morphology but does not affect learning and memory

The amyloid precursor protein APP plays a crucial role in Alzheimer pathogenesis. Its physiological functions, however, are only beginning to be unraveled. APP belongs to a small gene family, including besides APP the closely related amyloid precursor-like proteins APLP1 and APLP2, that all constitute synaptic adhesion proteins. While APP and APLP2 are ubiquitously expressed, APLP1 is specific for the nervous system. Previous genetic studies, including combined knockouts of several family members, pointed towards a unique role for APLP1, as only APP/APLP1 double knockouts were viable. We now examined brain and neuronal morphology in APLP1 single knockout (KO) animals, that have to date not been studied in detail. Here, we report that APLP1-KO mice show normal spine density in hippocampal CA1 pyramidal cells and subtle alterations in dendritic complexity. Extracellular field recordings revealed normal basal synaptic transmission and no alterations in synaptic plasticity (LTP). Further, behavioral studies revealed in APLP1-KO mice a small deficit in motor function and reduced diurnal locomotor activity, while learning and memory were not affected by the loss of APLP1. In summary, our study indicates that APP family members serve both distinct and overlapping functions that need to be considered for therapeutic treatments of Alzheimer's disease

Regulatory feedback cycle of the insulin-degrading enzyme and the amyloid precursor protein intracellular domain: Implications for Alzheimer's disease

One of the major pathological hallmarks of Alzheimer´s disease (AD) is an accumulation of amyloid-β (Aβ) in brain tissue leading to formation of toxic oligomers and senile plaques. Under physiological conditions, a tightly balanced equilibrium between Aβ-production and -degradation is necessary to prevent pathological Aβ-accumulation. Here, we investigate the molecular mechanism how insulin-degrading enzyme (IDE), one of the major Aβ-degrading enzymes, is regulated and how amyloid precursor protein (APP) processing and Aβ-degradation is linked in a regulatory cycle to achieve this balance. In absence of Aβ-production caused by APP or Presenilin deficiency, IDE-mediated Aβ-degradation was decreased, accompanied by a decreased IDE activity, protein level, and expression. Similar results were obtained in cells only expressing a truncated APP, lacking the APP intracellular domain (AICD) suggesting that AICD promotes IDE expression. In return, APP overexpression mediated an increased IDE expression, comparable results were obtained with cells overexpressing C50, a truncated APP representing AICD. Beside these genetic approaches, also AICD peptide incubation and pharmacological inhibition of the γ-secretase preventing AICD production regulated IDE expression and promoter activity. By utilizing CRISPR/Cas9 APP and Presenilin knockout SH-SY5Y cells results were confirmed in a second cell line in addition to mouse embryonic fibroblasts. In vivo, IDE expression was decreased in mouse brains devoid of APP or AICD, which was in line with a significant correlation of APP expression level and IDE expression in human postmortem AD brains. Our results show a tight link between Aβ-production and Aβ-degradation forming a regulatory cycle in which AICD promotes Aβ-degradation via IDE and IDE itself limits its own production by degrading AICD

Fat Mass and Obesity-Associated Gene (FTO) in Eating Disorders: Evidence for Association of the rs9939609 Obesity Risk Allele with Bulimia nervosa and Anorexia nervosa

Objective: The common single nucleotide polymorphism (SNP) rs9939609 in the fat mass and obesity-associated gene (FTO) is associated with obesity. As genetic variants associated with weight regulation might also be implicated in the etiology of eating disorders, we evaluated whether SNP rs9939609 is associated with bulimia nervosa (BN) and anorexia nervosa (AN). Methods: Association of rs9939609 with BN and AN was assessed in 689 patients with AN, 477 patients with BN, 984 healthy non-population-based controls, and 3,951 population-based controls (KORA-S4). Based on the familial and premorbid occurrence of obesity in patients with BN, we hypothesized an association of the obesity risk A-allele with BN. Results: In accordance with our hypothesis, we observed evidence for association of the rs9939609 A-allele with BN when compared to the non-population-based controls (unadjusted odds ratio (OR) = 1.142, one-sided 95% confidence interval (CI) 1.001-infinity; one-sided p = 0.049) and a trend in the population-based controls (OR = 1.124, one-sided 95% CI 0.932-infinity; one-sided p = 0.056). Interestingly, compared to both control groups, we further detected a nominal association of the rs9939609 A-allele to AN (OR = 1.181, 95% CI 1.027-1.359, two-sided p = 0.020 or OR = 1.673, 95% CI 1.101-2.541, two-sided p = 0.015,). Conclusion: Our data suggest that the obesity-predisposing FTO allele might be relevant in both AN and BN. Copyright (C) 2012 S. Karger GmbH, Freibur

A recent gibbon ape leukemia virus germline integration in a rodent from New Guinea

Germline colonization by retroviruses results in the formation of endogenous retroviruses (ERVs). Most colonization’s occurred millions of years ago. However, in the Australo-Papuan region (Australia and New Guinea), several recent germline colonization events have been discovered . The Wallace Line separates much of Southeast Asia from the Australo-Papuan region restricting faunal and pathogen dispersion. West of the Wallace Line, gibbon ape leukemia viruses (GALVs) have been isolated from captive gibbons. Two microbat species from China appear to have been infected naturally. East of Wallace’s Line, the woolly monkey virus (a GALV) and the closely related koala retrovirus (KoRV) have been detected in eutherians and marsupials in the Australo-Papuan region, often vertically transmitted. The detected vertically transmitted GALV-like viruses in Australo-Papuan fauna compared to sporadic horizontal transmission in Southeast Asia and China suggest the GALV-KoRV clade originates in the former region and further models of early-stage genome colonization may be found. We screened 278 samples, seven bat and one rodent family endemic to the Australo-Papuan region and bat and rodent species found on both sides of the Wallace Line. We identified two rodents ( Melomys ) from Australia and Papua New Guinea and no bat species harboring GALV-like retroviruses. Melomys leucogaster from New Guinea harbored a genomically complete replication-competent retrovirus with a shared integration site among individuals. The integration was only present in some individuals of the species indicating this retrovirus is at the earliest stages of germline colonization of the Melomys genome, providing a new small wild mammal model of early-stage genome colonization

Exploiting the 2-Amino-1,3,4-thiadiazole Scaffold To Inhibit <i>Trypanosoma brucei </i>Pteridine Reductase in Support of Early-Stage Drug Discovery

Pteridine reductase-1 (PTR1) is a promising drug target for the treatment of trypanosomiasis. We investigated the potential of a previously identified class of thiadiazole inhibitors of Leishmania major PTR1 for activity against Trypanosoma brucei (Tb). We solved crystal structures of several TbPTR1-inhibitor complexes to guide the structure-based design of new thiadiazole derivatives. Subsequent synthesis and enzyme- and cell-based assays confirm new, mid-micromolar inhibitors of TbPTR1 with low toxicity. In particular, compound 4m, a biphenyl-thiadiazole-2,5-diamine with IC50 = 16 μM, was able to potentiate the antitrypanosomal activity of the dihydrofolate reductase inhibitor methotrexate (MTX) with a 4.1-fold decrease of the EC50 value. In addition, the antiparasitic activity of the combination of 4m and MTX was reversed by addition of folic acid. By adopting an efficient hit discovery platform, we demonstrate, using the 2-amino-1,3,4-thiadiazole scaffold, how a promising tool for the development of anti-T. brucei agents can be obtained

Insight into the proteome of the hyperthermophilic Crenarchaeon Ignicoccus hospitalis: the major cytosolic and membrane proteins

Ignicoccus hospitalis, a hyperthermophilic, chemolithoautotrophic Crenarchaeon, is the host of Nanoarchaeum equitans. Together, they form an intimate association, the first among Archaea. Membranes are of fundamental importance for the interaction of I. hospitalis and N. equitans, as they harbour the proteins necessary for the transport of macromolecules like lipids, amino acids, and cofactors between these organisms. Here, we investigated the protein inventory of I. hospitalis cells, and were able to identify 20 proteins in total. Experimental evidence and predictions let us conclude that 11 are soluble cytosolic proteins, eight membrane or membrane-associated proteins, and a single one extracellular. The quantitatively dominating proteins in the cytoplasm (peroxiredoxin; thermosome) antagonize oxidative and temperature stress which I. hospitalis cells are exposed to at optimal growth conditions. Three abundant membrane protein complexes are found: the major protein of the outer membrane, which might protect the cell against the hostile environment, forms oligomeric complexes with pores of unknown selectivity; two other complexes of the cytoplasmic membrane, the hydrogenase and the ATP synthase, play a key role in energy production and conversion