| 1. |
- Fonseca, Luis Vazquez, et al.
(author)
-
Mutations in COQ8B (ADCK4) found in patients with steroid-resistant nephrotic syndrome alter COQ8B function
- 2018
-
In: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 39:3, s. 406-414
-
Journal article (peer-reviewed)abstract
- Mutations in COQ8B cause steroid-resistant nephrotic syndrome with variable neurological involvement. In yeast, COQ8 encodes a protein required for coenzyme Q (CoQ) biosynthesis, whose precise role is not clear. Humans harbor two paralog genes: COQ8A and COQ8B (previously termed ADCK3 and ADCK4). We have found that COQ8B is a mitochondrial matrix protein peripherally associated with the inner membrane. COQ8B can complement a Delta COQ8 yeast strain when its mitochondrial targeting sequence (MTS) is replaced by a yeast MTS. This model was employed to validate COQ8B mutations, and to establish genotype-phenotype correlations. All mutations affected respiratory growth, but there was no correlation between mutation type and the severity of the phenotype. In fact, contrary to the case of COQ2, where residual CoQ biosynthesis correlates with clinical severity, patients harboring hypomorphic COQ8B alleles did not display a different phenotype compared with those with null mutations. These data also suggest that the system is redundant, and that other proteins (probably COQ8A) may partially compensate for the absence of COQ8B. Finally, a COQ8B polymorphism, present in 50% of the European population (NM_024876.3:c.521A > G, p.His174Arg), affects stability of the protein and could represent a risk factor for secondary CoQ deficiencies or for other complex traits.
|
|
| 2. |
- Hoencamp, Claire, et al.
(author)
-
3D genomics across the tree of life reveals condensin II as a determinant of architecture type
- 2021
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 372:6545, s. 984-989
-
Journal article (peer-reviewed)abstract
- We investigated genome folding across the eukaryotic tree of life. We find two types of three-dimensional (3D) genome architectures at the chromosome scale. Each type appears and disappears repeatedly during eukaryotic evolution. The type of genome architecture that an organism exhibits correlates with the absence of condensin II subunits. Moreover, condensin II depletion converts the architecture of the human genome to a state resembling that seen in organisms such as fungi or mosquitoes. In this state, centromeres cluster together at nucleoli, and heterochromatin domains merge. We propose a physical model in which lengthwise compaction of chromosomes by condensin II during mitosis determines chromosome-scale genome architecture, with effects that are retained during the subsequent interphase. This mechanism likely has been conserved since the last common ancestor of all eukaryotes.
|
|
| 3. |
- Meyer, Kristina, et al.
(author)
-
Are global and specific interindividual differences in cortical thickness associated with facets of cognitive abilities, including face cognition?
- 2019
-
In: Royal Society Open Science. - : The Royal Society. - 2054-5703. ; 6:7
-
Journal article (peer-reviewed)abstract
- Face cognition (FC) is a specific ability that cannot be fully explained by general cognitive functions. Cortical thickness (CT) is a neural correlate of performance and learning. In this registered report, we used data from the Human Connectome Project (HCP) to investigate the relationship between CT in the core brain network of FC and performance on a psychometric task battery, including tasks with facial content. Using structural equation modelling (SEM), we tested the existence of face-specific interindividual differences at behavioural and neural levels. The measurement models include general and face-specific factors of performance and CT. There was no face-specificity in CT in functionally localized areas. In post hoc analyses, we compared the preregistered, small regions of interest (ROIs) to larger, non-individualized ROIs and identified a face-specific CT factor when large ROIs were considered. We show that this was probably due to low reliability of CT in the functional localization (intra-class correlation coefficients (ICC) between 0.72 and 0.85). Furthermore, general cognitive ability, but not face-specific performance, could be predicted by latent factors of CT with a small effect size. In conclusion, for the core brain network of FC, we provide exploratory evidence (in need of cross-validation) that areas of the cortex sharing a functional purpose did also share morphological properties as measured by CT.
|
|
| 4. |
- Pearce, Kim F., et al.
(author)
-
Regulation of advanced therapy medicinal products in Europe and the role of academia
- 2014
-
In: Cytotherapy. - : Elsevier BV. - 1477-2566 .- 1465-3249. ; 16:3, s. 289-297
-
Research review (peer-reviewed)abstract
- Background aims. Advanced therapy medicinal products (ATMP) are gene therapy, somatic cell therapy or tissue-engineered products regulated under (EC) No. 1394/2007 to ensure their free movement within the European Union while guaranteeing the highest level of health protection for patients. Academic good manufacturing practice (GMP) centers are major contributors in the development of ATMPs and this study assessed the impact of regulations on them. Methods. European academic and non-industrial facilities (n = 747) were contacted, and a representative sample of 50 replied to a detailed questionnaire. Experienced centres were further selected in every Member State (MS) for semi-structured interviews. Indicators of ATMP production and development success were statistically assessed, and opinions about directive implementation were documented. Results. Facilities experienced in manufacturing cell therapy transplant products are the most successful in developing ATMPs. New centres lacking this background struggle to enter the field, and there remains a shortage of facilities in academia participating in translational research. This is compounded by heterogeneous implementation of the regulations across MS. Conclusions. GMP facilities successfully developing ATMPs are present in all MS. However, the implementation of regulations is heterogeneous between MS, with substantial differences in the definition of ATMPs and in the approved manufacturing environment. The cost of GMP compliance is underestimated by research funding bodies. This is detrimental to development of new ATMPs and commercialization of any that are successful in early clinical trials. Academic GMP practitioners should strengthen their political visibility and contribute to the development of functional and effective European Union legislation in this field.
|
|
| 5. |
- Schmiedek, Florian, et al.
(author)
-
Complex Span Versus Updating Tasks of Working Memory: The Gap Is Not That Deep
- 2009
-
In: Journal of Experimental Psychology: Learning, Memory, and Cognition. - : American Psychological Association (APA). - 0278-7393 .- 1939-1285. ; 35:4, s. 1089-1096
-
Journal article (peer-reviewed)abstract
- How to best measure working memory capacity is an issue of ongoing debate. Besides established complex span tasks, which combine short-term memory demands with generally unrelated secondary tasks, there exists a set of paradigms characterized by continuous and simultaneous updating of several items in working memory, such as the n-back, memory updating, or alpha span tasks. With a latent variable analysis (N = 96) based on content-heterogeneous operationalizations of both task families, the authors found a latent correlation between a complex span factor and an updating factor that was not statistically different from unity (r = .96). Moreover, both factors predicted fluid intelligence (reasoning) equally well. The authors conclude that updating tasks measure working memory equally well as complex span tasks. Processes involved in building, maintaining, and updating arbitrary bindings may constitute the common working memory ability underlying performance on reasoning, complex span, and updating tasks.
|
|
| 6. |
- Tagliaferri, Luca, et al.
(author)
-
ENT COBRA ONTOLOGY : the covariates classification system proposed by the Head & Neck and Skin GEC-ESTRO Working Group for interdisciplinary standardized data collection in head and neck patient cohorts treated with interventional radiotherapy (brachytherapy)
- 2018
-
In: Journal of Contemporary Brachytherapy. - : Termedia Publishing. - 1689-832X .- 2081-2841. ; 10:3, s. 260-266
-
Research review (peer-reviewed)abstract
- Purpose: Clinical data collecting is expensive in terms of time and human resources. Data can be collected in different ways; therefore, performing multicentric research based on previously stored data is often difficult. The primary objective of the ENT COBRA (COnsortium for BRachytherapy data Analysis) ontology is to define a specific terminological system to standardized data collection for head and neck (H&N) cancer patients treated with interventional radiotherapy.Material and methods: ENT-COBRA is a consortium for standardized data collection for H&N patients treated with interventional radiotherapy. It is linked to H&N and Skin GEC-ESTRO Working Group and includes 11 centers from 6 countries. Its ontology was firstly defined by a multicentric working group, then evaluated by the consortium followed by a multi-professional technical commission involving a mathematician, an engineer, a physician with experience in data storage, a programmer, and a software expert.Results: Two hundred and forty variables were defined on 13 input forms. There are 3 levels, each offering a specific type of analysis: 1. Registry level (epidemiology analysis); 2. Procedures level (standard oncology analysis); 3. Research level (radiomics analysis). The ontology was approved by the consortium and technical commission; an ad-hoc software architecture ("broker") remaps the data present in already existing storage systems of the various centers according to the shared terminology system. The first data sharing was successfully performed using COBRA software and the ENT COBRA Ontology, automatically collecting data directly from 3 different hospital databases (Lubeck, Navarra, and Rome) in November 2017.Conclusions: The COBRA Ontology is a good response to the multi-dimensional criticalities of data collection, retrieval, and usability. It allows to create a software for large multicentric databases with implementation of specific remapping functions wherever necessary. This approach is well-received by all involved parties, primarily because it does not change a single center's storing technologies, procedures, and habits.
|
|
