Playing hide and seek: tumor cells in control of MHC class I antigen presentation

MHC class I (MHC-I) molecules present a blueprint of the intracellular proteome to T cells allowing them to control infection or malignant transformation. As a response, pathogens and tumor cells often downmodulate MHC-I mediated antigen presentation to escape from immune surveillance. Although the fundamental rules of antigen presentation are known in detail, the players in this system are not saturated and new modules of regulation have recently been uncovered. Here, we update the understanding of antigen presentation by MHC-I molecules and how this can be exploited by tumors to prevent exposure of the intracellular proteome. This knowledge can provide new ways to improve immune responses against tumors and pathogens.Chemical Immunolog

Using knowledge: the dilemmas of 'bridging research and policy'

The 'knowledge agenda' has become a central part of development discourse. This paper addresses one aspect of this discourse - the use of policy research in the social sciences - and the dilemmas that have been encountered by both development agencies and researchers in communicating and making use of that research. Development agencies as well as NGOs have initiated work to evaluate and document the effectiveness of research partnerships, knowledge capacity building and (social) science policy impact. As a multilateral initiative, the Global Development Network (GDN), and especially its 'Bridging Research and Policy' project, provides a vehicle to address issues related to research impact. Twelve perspectives on improving research and policy linkages are outlined to reveal that how the problem is defined shapes policy responses. Taken together, these explanations provide a multifaceted picture of the research-policy nexus indicating that there are many possible routes to 'bridging' research and policy. These diverse perspectives will be categorised into three broad categories of explanation: (i) supply-side; (ii) demand-led; and (iii) policy currents. However, knowledge is part of the solution to many development problems but not of itself a panacea

Expanding the clinical spectrum of 3-phosphoglycerate dehydrogenase deficiency

3-Phosphoglycerate dehydrogenase (3-PGDH) deficiency is considered to be a rare cause of congenital microcephaly, infantile onset of intractable seizures and severe psychomotor retardation. Here, we report for the first time a very mild form of genetically confirmed 3-PGDH deficiency in two siblings with juvenile onset of absence seizures and mild developmental delay. Amino acid analysis showed serine values in CSF and plasma identical to what is observed in the severe infantile form. Both patients responded favourably to relatively low dosages of serine supplementation with cessation of seizures, normalisation of their EEG abnormalities and improvement of well-being and behaviour. These cases illustrate that 3-PGDH deficiency can present with mild symptoms and should be considered as a treatable disorder in the differential diagnosis of mild developmental delay and seizures. Synopsis: we present a novel mild phenotype in patients with 3-PGDH deficiency

QRiH: Towards a fitting system for humanities research evaluation .

Merit, Expertise and Measuremen

Mutations in the urocanase gene UROC1 are associated with urocanic aciduria

[EN] Urocanase is an enzyme in the histidine pathway encoded by the UROC1 gene. This report describes the first putative mutations, p. L70P and p.R450C, in the coding region of the UROC1 gene in a girl with urocanic aciduria presenting with mental retardation and intermittent ataxia. Computed (in silico) predictions, protein expression studies and enzyme activity assays suggest that none of the mutations can produce a fully functional enzyme. The p. L70P substitution, which probably implies the disruption of an alpha-helix in the N-terminus, would alter its properties and therefore, its function. The p.R450C change would render impossible any interaction between urocanase and its substrate and would loss its enzyme activity. Consequently, these studies suggest that both mutations could alter the correct activity of urocanase, which would explain the clinical and biochemical findings described in this patient.We are grateful to the patient for her kind collaboration. We are indebted to Dr C Marco-Marín for the in silico structural studies. CIBERER is an initiative of the Instituto de Salud Carlos III. This work was supported by grants from the Fondo de Investigación Sanitaria (PI051318 and PI070548).Espinós-Armero, CÁ.; Pineda, M.; Martínez-Rubio, D.; Aída Ormazabal; María Antonia Vilaseca; Leo J. M. Spaapen; Palau, F.... (2009). Mutations in the urocanase gene UROC1 are associated with urocanic aciduria. Journal of Medical Genetics. 46(6):407-411. https://doi.org/10.1136/jmg.2008.06063240741146

Who benefits from HEIs engagement? An analysis of priority stakeholders and activity profiles of HEIs in the United Kingdom

It has been suggested that higher education institutions (HEIs) may develop different activity profiles (including research, teaching and socio-economic engagement) in their attempt to maximise the fit between institutional resources and strategic opportunities; the latter include strategies of engagement with different groups of external stakeholders. Understanding the extent to which HEIs’ resources and activity profiles are aligned with their strategic prioritisation of stakeholder groups, allows us to better understand the different ways in which HEIs drive socioeconomic development. Using non-parametric techniques – qualitative and quantitative ordinal multidimensional scaling – applied to data on the universe of HEIs in the United Kingdom, we show that HEIs with different institutional resources and undertaking different sets of activities prioritise their engagement with different stakeholder groups. We also confirm the complex associations between HEIs’ institutional resources, activity profiles and stakeholder prioritisation strategies, which lock HEIs into configurations that are difficult to change

Leveraging open innovation to improve society: past achievements and future trajectories

Open innovation (OI) is an approach which describes a purposive attempt to draw together knowledge from different contributors to develop and exploit innovation. It has become clear that OI directly benefits organisations' economic performance and resilience, but researchers, practitioners, and policy makers became also convinced that OI might be the way forward to tackle the world’s most pressing societal challenges, representing unresolved Grand Challenges, which can only be weathered by diverse sets of collaborative partners that join forces. Although anecdotal evidence points at how OI practices can be employed to achieve societal impact not only in private firms but also in public organisations, very little understanding exists -beyond anecdotal- to link OI to societal impact. This special issue has the ambition to start the discussion and establish a framework as the stepping stone to tackle this complex research gap

Identification of a conserved transcriptional activator-repressor module controlling the expression of genes involved in tannic acid degradation and gallic acid utilization in aspergillus niger

Microbial Biotechnolog