The first genetic landscape of inherited retinal dystrophies in Portuguese patients identifies recurrent homozygous mutations as a frequent cause of pathogenesis.

Inherited retinal diseases (IRDs) are a group of ocular conditions characterized by an elevated genetic and clinical heterogeneity. They are transmitted almost invariantly as monogenic traits. However, with more than 280 disease genes identified so far, association of clinical phenotypes with genotypes can be very challenging, and molecular diagnosis is essential for genetic counseling and correct management of the disease. In addition, the prevalence and the assortment of IRD mutations are often population-specific. In this work, we examined 230 families from Portugal, with individuals suffering from a variety of IRD diagnostic classes (270 subjects in total). Overall, we identified 157 unique mutations (34 previously unreported) in 57 distinct genes, with a diagnostic rate of 76%. The IRD mutational landscape was, to some extent, different from those reported in other European populations, including Spanish cohorts. For instance, the EYS gene appeared to be the most frequently mutated, with a prevalence of 10% among all IRD cases. This was, in part, due to the presence of a recurrent and seemingly founder mutation involving the deletion of exons 13 and 14 of this gene. Moreover, our analysis highlighted that as many as 51% of our cases had mutations in a homozygous state. To our knowledge, this is the first study assessing a cross-sectional genotype-phenotype landscape of IRDs in Portugal. Our data reveal a rather unique distribution of mutations, possibly shaped by a small number of rare ancestral events that have now become prevalent alleles in patients

CropPol: a dynamic, open and global database on crop pollination

Seventy five percent of the world's food crops benefit from insect pollination. Hence, there has been increased interest in how global change drivers impact this critical ecosystem service. Because standardized data on crop pollination are rarely available, we are limited in our capacity to understand the variation in pollination benefits to crop yield, as well as to anticipate changes in this service, develop predictions, and inform management actions. Here, we present CropPol, a dynamic, open and global database on crop pollination. It contains measurements recorded from 202 crop studies, covering 3,394 field observations, 2,552 yield measurements (i.e. berry weight, number of fruits and kg per hectare, among others), and 47,752 insect records from 48 commercial crops distributed around the globe. CropPol comprises 32 of the 87 leading global crops and commodities that are pollinator dependent. Malus domestica is the most represented crop (32 studies), followed by Brassica napus (22 studies), Vaccinium corymbosum (13 studies), and Citrullus lanatus (12 studies). The most abundant pollinator guilds recorded are honey bees (34.22% counts), bumblebees (19.19%), flies other than Syrphidae and Bombyliidae (13.18%), other wild bees (13.13%), beetles (10.97%), Syrphidae (4.87%), and Bombyliidae (0.05%). Locations comprise 34 countries distributed among Europe (76 studies), Northern America (60), Latin America and the Caribbean (29), Asia (20), Oceania (10), and Africa (7). Sampling spans three decades and is concentrated on 2001-05 (21 studies), 2006-10 (40), 2011-15 (88), and 2016-20 (50). This is the most comprehensive open global data set on measurements of crop flower visitors, crop pollinators and pollination to date, and we encourage researchers to add more datasets to this database in the future. This data set is released for non-commercial use only. Credits should be given to this paper (i.e., proper citation), and the products generated with this database should be shared under the same license terms (CC BY-NC-SA). This article is protected by copyright. All rights reserved

Pollination supply models from a local to global scale

Ecological intensification has been embraced with great interest by the academic sector but is still rarely taken up by farmers because monitoring the state of different ecological functions is not straightforward. Modelling tools can represent a more accessible alternative of measuring ecological functions, which could help promote their use amongst farmers and other decision-makers. In the case of crop pollination, modelling has traditionally followed either a mechanistic or a data-driven approach. Mechanistic models simulate the habitat preferences and foraging behaviour of pollinators, while data-driven models associate georeferenced variables with real observations. Here, we test these two approaches to predict pollination supply and validate these predictions using data from a newly released global dataset on pollinator visitation rates to different crops. We use one of the most extensively used models for the mechanistic approach, while for the data-driven approach, we select from among a comprehensive set of state-of-the-art machine-learning models. Moreover, we explore a mixed approach, where data-derived inputs, rather than expert assessment, inform the mechanistic model. We find that, at a global scale, machine-learning models work best, offering a rank correlation coefficient between predictions and observations of pollinator visitation rates of 0.56. In turn, the mechanistic model works moderately well at a global scale for wild bees other than bumblebees. Biomes characterized by temperate or Mediterranean forests show a better agreement between mechanistic model predictions and observations, probably due to more comprehensive ecological knowledge and therefore better parameterization of input variables for these biomes. This study highlights the challenges of transferring input variables across multiple biomes, as expected given the different composition of species in different biomes. Our results provide clear guidance on which pollination supply models perform best at different spatial scales – the first step towards bridging the stakeholder–academia gap in modelling ecosystem service delivery under ecological intensification

Motor, cognitive, and behavioral difficulties in children and adolescents with neurofibromatosis type 1 (von Recklinghausen disease)

Les données de la littérature concernant les difficultés cognitives et comportementales dans la Neurofibromatose de type 1 (NF1) sont nombreuses avec des résultats parfois contradictoires. Après une revue de la littérature, ce travail de recherche : (i) décrit les difficultés comportementales, cognitives et motrices chez 78 patients atteints de NF1, âgés de 5 à 18 ans, au moyen de questionnaires aux parents (qualité de vie, impact de la maladie, difficultés des parents eux-mêmes, Conners, BRIEF, CBCL), et d'une évaluation de l'efficience intellectuelle et neuropsychologique détaillée ; (ii) analyse les relations entre les aspects cliniques, comportementaux, neuropsychologiques et l'imagerie (présence ou non d'« Objets Brillants Non Identifiés » caractéristiques de la NF1). Les difficultés d'apprentissage, malgré une qualité de vie plutôt bonne et un faible impact de la maladie, les troubles attentionnels et l'anxiété de l'enfant constituaient les principales sources d'inquiétude des parents. Les questionnaires étaient corrélés entre eux, mais ils étaient peu liés aux tests neuropsychologiques. La présence de difficultés cognitives spécifiques, en particulier visuo-spatiales et en motricité fine, a été confirmée. Aucune relation n'a pu être établie entre la neuropsychologie et l'imagerie. Les difficultés neuropsychologiques étaient plus sévères dans les formes familiales que sporadiques.Cognitive and behavioral difficulties are common in children with Neurofibromatosis type 1 (NF1), however findings concerning the specific neuropsychological and behavioral profile as well as the association of these difficulties with clinical manifestations and brain imagery abnormalities are often contradictory. After a literature review, the present study: (i) describes behavioral, cognitive, and motor difficulties in 78 patients with NF1, aged 5 to 18 years, using parental questionnaires (quality of life, impact of illness, parental difficulties, Conners, BRIEF, CBCL), and tests of intellectual efficiency and specific neuropsychological functions; (ii) examines the relationships between clinical, behavioral, neuropsychological and imaging findings (presence or absence of "Unidentified Bright Objects" UBOs, characteristic feature of NF1). Learning disabilities, despite relatively good report of quality of life, attention disorders and child anxiety were the main parental concerns. All parental questionnaires were strongly inter-correlated, and associated with an overall positive or negative parental attitude during the interview with the psychologist. Parental concerns were only weakly related to neuropsychological tests. The presence of specific cognitive difficulties, particularly in visuospatial and fine motor skills, was confirmed. Imaging data were not associated with neuropsychological scores. Cognitive difficulties were more important in familial than sporadic forms

Difficultés motrices, cognitives et comportementales chez les enfants et adolescents atteints de neurofibromatose de type 1 (maladie de von Recklinghausen)

Cognitive and behavioral difficulties are common in children with Neurofibromatosis type 1 (NF1), however findings concerning the specific neuropsychological and behavioral profile as well as the association of these difficulties with clinical manifestations and brain imagery abnormalities are often contradictory. After a literature review, the present study: (i) describes behavioral, cognitive, and motor difficulties in 78 patients with NF1, aged 5 to 18 years, using parental questionnaires (quality of life, impact of illness, parental difficulties, Conners, BRIEF, CBCL), and tests of intellectual efficiency and specific neuropsychological functions; (ii) examines the relationships between clinical, behavioral, neuropsychological and imaging findings (presence or absence of "Unidentified Bright Objects" UBOs, characteristic feature of NF1). Learning disabilities, despite relatively good report of quality of life, attention disorders and child anxiety were the main parental concerns. All parental questionnaires were strongly inter-correlated, and associated with an overall positive or negative parental attitude during the interview with the psychologist. Parental concerns were only weakly related to neuropsychological tests. The presence of specific cognitive difficulties, particularly in visuospatial and fine motor skills, was confirmed. Imaging data were not associated with neuropsychological scores. Cognitive difficulties were more important in familial than sporadic forms.Les données de la littérature concernant les difficultés cognitives et comportementales dans la Neurofibromatose de type 1 (NF1) sont nombreuses avec des résultats parfois contradictoires. Après une revue de la littérature, ce travail de recherche : (i) décrit les difficultés comportementales, cognitives et motrices chez 78 patients atteints de NF1, âgés de 5 à 18 ans, au moyen de questionnaires aux parents (qualité de vie, impact de la maladie, difficultés des parents eux-mêmes, Conners, BRIEF, CBCL), et d'une évaluation de l'efficience intellectuelle et neuropsychologique détaillée ; (ii) analyse les relations entre les aspects cliniques, comportementaux, neuropsychologiques et l'imagerie (présence ou non d'« Objets Brillants Non Identifiés » caractéristiques de la NF1). Les difficultés d'apprentissage, malgré une qualité de vie plutôt bonne et un faible impact de la maladie, les troubles attentionnels et l'anxiété de l'enfant constituaient les principales sources d'inquiétude des parents. Les questionnaires étaient corrélés entre eux, mais ils étaient peu liés aux tests neuropsychologiques. La présence de difficultés cognitives spécifiques, en particulier visuo-spatiales et en motricité fine, a été confirmée. Aucune relation n'a pu être établie entre la neuropsychologie et l'imagerie. Les difficultés neuropsychologiques étaient plus sévères dans les formes familiales que sporadiques

Intellectual functioning in Silver-Russell syndrome First study in adults

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Cognitive Profile of Children With Intracranial Germ Cell Tumor According to Tumor Location

International audiencePurpose: The purpose of this study was to evaluate the long-term cognitive sequelae and to describe the neuropsychological profile of patients with intracranial germ cell tumors according to tumor location (pineal or suprasellar site). Patients and Methods: Forty-five children treated at Gustave Roussy between 1991 and 2010 were assessed with neuropsychological tests to measure IQ, memory, visuospatial, motor, and executive skills at a mean delay of 4.2 years after diagnosis. All patients have received chemotherapy associated with surgery in 17 cases. Thirty-nine patients received, radiotherapy (focal 27, focal plus ventricles 8, craniospinal 4). Twenty-three patients had 2 IQ assessments with a mean delay of 4.1 years between the first and second. Results: Full scale IQ was preserved, with higher verbal IQ than other IQ indexes. Visuospatial, fine-motor, and executive difficulties were present in a significant proportion of patients. Visuospatial and fine-motor deficits were significantly associated with oculomotor difficulties, more present in the pineal than in the suprasellar group. No cognitive decline was observed between the first and the second IQ assessment. Conclusions: Overall cognitive abilities were preserved in children treated for central nervous system germ cell tumor

Intellectual functioning in Silver-Russell syndrome First study in adults

International audienceSilver-Russell syndrome (SRS) is a rare genetic disorder (estimated incidence 1/30,000 to 100,000 live births). So far, only a few studies have focused on the cognitive profile of individuals with SRS, and these were conducted some time ago, concentrated on pediatric cohorts, and included patients who had been diagnosed using a variety of clinical diagnostic systems. There has yet to be any research on the intellectual functioning of adults with SRS. This study sought to establish the intelligence, strengths and weaknesses within intellectual profile of adults with SRS, compared with normative data. Ten individuals with 11p15 epimutation aged 18–39 years completed the Wechsler Adult Intelligence Scale-Fourth Edition. Measures of interest included participants’ intelligence (Full Scale Intelligence Quotient [FSIQ]) and four domains of cognitive functioning: verbal comprehension, perceptual reasoning, working memory and processing speed. Discrepancy scores were calculated, and descriptive statistical and linear correlations were used to investigate factors associated with IQ outcome. Clinical and medical information such as rehabilitation, and perceived difficulties in daily life were collected by interviews and questionnaires. Results showed that the mean FSIQ score was in the average range (M = 95.40, SD = 18.55) and they performed best on verbal comprehension. Frequent daily difficulties were reported by patients and/or their families: learning disabilities and low self-esteem were perceived by 60% of adults. Early intervention and multidisciplinary care from childhood to adulthood are important in SRS for care potential medical, cognitive and psychosocial problems. This is the first study to document the intellectual functioning of adults with SRS

First Structural Insights into alpha-L-Arabinofuranosidases from the Two GH62 Glycoside Hydrolase Subfamilies*

Background: -l-Arabinofuranosidases hydrolyze arabinofuranosyl side chains from xylans. Results: The first crystal structures of two fungal -l-arabinofuranosidases representing two distinct subfamilies from the glycoside hydrolase GH62 family are presented. The examination of these unveils specificity determinants. Conclusion: The structures of complexes with arabinose and cellotriose provide preliminary insight into substrate recognition and catalysis. Significance: This work provides the first structural description members of the GH62 family. -l-Arabinofuranosidases are glycoside hydrolases that specifically hydrolyze non-reducing residues from arabinose-containing polysaccharides. In the case of arabinoxylans, which are the main components of hemicellulose, they are part of microbial xylanolytic systems and are necessary for complete breakdown of arabinoxylans. Glycoside hydrolase family 62 (GH62) is currently a small family of -l-arabinofuranosidases that contains only bacterial and fungal members. Little is known about the GH62 mechanism of action, because only a few members have been biochemically characterized and no three-dimensional structure is available. Here, we present the first crystal structures of two fungal GH62 -l-arabinofuranosidases from the basidiomycete Ustilago maydis (UmAbf62A) and ascomycete Podospora anserina (PaAbf62A). Both enzymes are able to efficiently remove the -l-arabinosyl substituents from arabinoxylan. The overall three-dimensional structure of UmAbf62A and PaAbf62A reveals a five-bladed -propeller fold that confirms their predicted classification into clan GH-F together with GH43 -l-arabinofuranosidases. Crystallographic structures of the complexes with arabinose and cellotriose reveal the important role of subsites +1 and +2 for sugar binding. Intriguingly, we observed that PaAbf62A was inhibited by cello-oligosaccharides and displayed binding affinity to cellulose although no activity was observed on a range of cellulosic substrates. Bioinformatic analyses showed that UmAbf62A and PaAbf62A belong to two distinct subfamilies within the GH62 family. The results presented here provide a framework to better investigate the structure-function relationships within the GH62 family