The Role of Disordered Ribosomal Protein Extensions in the Early Steps of Eubacterial 50 S Ribosomal Subunit Assembly

Although during the past decade research has shown the functional importance of disorder in proteins, many of the structural and dynamics properties of intrinsically unstructured proteins (IUPs) remain to be elucidated. This review is focused on the role of the extensions of the ribosomal proteins in the early steps of the assembly of the eubacterial 50 S subunit. The recent crystallographic structures of the ribosomal particles have revealed the picture of a complex assembly pathway that condenses the rRNA and the ribosomal proteins into active ribosomes. However, little is know about the molecular mechanisms of this process. It is thought that the long basic r-protein extensions that penetrate deeply into the subunit cores play a key role through disorder-order transitions and/or co-folding mechanisms. A current view is that such structural transitions may facilitate the proper rRNA folding. In this paper, the structures of the proteins L3, L4, L13, L20, L22 and L24 that have been experimentally found to be essential for the first steps of ribosome assembly have been compared. On the basis of their structural and dynamics properties, three categories of extensions have been identified. Each of them seems to play a distinct function. Among them, only the coil-helix transition that occurs in a phylogenetically conserved cluster of basic residues of the L20 extension appears to be strictly required for the large subunit assembly in eubacteria. The role of α helix-coil transitions in 23 S RNA folding is discussed in the light of the calcium binding protein calmodulin that shares many structural and dynamics properties with L20

Genome-wide association study identifies the first germline genetic variant associated with Erdheim Chester disease

[Objective] Erdheim-Chester disease (ECD) is rare histiocytosis with a wide range of clinical manifestations. Somatic mutations are key to the pathogenesis of the disease; however, the relationship between germline genetic variants and ECD has not been examined so far. The present study aims to explore the inherited genetic component of ECD by performing the first genome-wide association study.[Methods] After quality controls, a cohort of 255 ECD patients and 7,471 healthy donors was included in this study. Afterwards, a logistic regression followed by in silico functional annotation was performed.[Results] A signal at the 18q12.3 genomic region was identified as a new susceptibility locus for ECD (p-value=2.75x10-11; OR=2.09). This association was annotated to the SETBP1 gene, which is involved in clonal haematopoiesis. Functional annotation of this region and of the identified suggestive signals revealed additional genes that could be potentially involved in the pathogenesis of the disease.[Conclusion] Overall, this work demonstrates that germline genetic variants can impact on the development of ECD and suggests new pathways with a potential pathogenic role.This work was supported by the project “Genome-wide and epigenome-wide association study in patients with Erdheim-Chester Disease”, funded by by Histio UK, and supported in part by the Intramural Research Program of the National Human Genome Research Institute and Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) (RD21/0002/0039). M.A.H. is a recipient of a Miguel Servet fellows hip (CP21/00132) from Instituto de Salud Carlos III. L.O.F. was supported by a Juan de la Cierva Incorporación fellowship (IJC2019-040746-I) funded by MCIN/AEI/10.13039/501100011033.Peer reviewe

Neurexin-1 and Frontal Lobe White Matter: An Overlapping Intermediate Phenotype for Schizophrenia and Autism Spectrum Disorders

Background: Structural variation in the neurexin-1 (NRXN1) gene increases risk for both autism spectrum disorders (ASD) and schizophrenia. However, the manner in which NRXN1 gene variation may be related to brain morphology to confer risk for ASD or schizophrenia is unknown. Method/Principal Findings: 53 healthy individuals between 18–59 years of age were genotyped at 11 single nucleotide polymorphisms of the NRXN1 gene. All subjects received structural MRI scans, which were processed to determine cortical gray and white matter lobar volumes, and volumes of striatal and thalamic structures. Each subject’s sensorimotor function was also assessed. The general linear model was used to calculate the influence of genetic variation on neural and cognitive phenotypes. Finally, in silico analysis was conducted to assess potential functional relevance of any polymorphisms associated with brain measures. A polymorphism located in the 39 untranslated region of NRXN1 significantly influenced white matter volumes in whole brain and frontal lobes after correcting for total brain volume, age and multiple comparisons. Follow-up in silico analysis revealed that this SNP is a putative microRNA binding site that may be of functional significance in regulating NRXN1 expression. This variant also influenced sensorimotor performance, a neurocognitive function impaired in both ASD and schizophrenia. Conclusions: Our findings demonstrate that the NRXN1 gene, a vulnerability gene for SCZ and ASD, influences brai

Food, Nutrition and Agrobiodiversity Under Global Climate Change

Available evidence and predictions suggest overall negative effects on agricultural production as a result of climate change, especially when more food is required by a growing population. Information on the effects of global warming on pests and pathogens affecting agricultural crops is limited, though crop–pest models could offer means to predict changes in pest dynamics, and help design sound plant health management practices. Host-plant resistance should continue to receive high priority as global warming may favor emergence of new pest epidemics. There is increased risk, due to climate change, to food and feed contaminated by mycotoxin-producing fungi. Mycotoxin biosynthesis gene-specific microarray is being used to identify food-born fungi and associated mycotoxins, and investigate the influence of environmental parameters and their interactions for control of mycotoxin in food crops. Some crop wild relatives are threatened plant species and efforts should be made for their in situ conservation to ensure evolution of new variants, which may contribute to addressing new challenges to agricultural production. There should be more emphasis on germplasm enhancement to develop intermediate products with specific characteristics to support plant breeding. Abiotic stress response is routinely dissected to component physiological traits. Use of transgene(s) has led to the development of transgenic events, which could provide enhanced adaptation to abiotic stresses that are exacerbated by climate change. Global warming is also associated with declining nutritional quality of food crops. Micronutrient-dense cultivars have been released in selected areas of the developing world, while various nutritionally enhanced lines are in the release pipeline. The high-throughput phenomic platforms are allowing researchers to accurately measure plant growth and development, analyze nutritional traits, and assess response to stresses on large sets of individuals. Analogs for tomorrow’s agriculture offer a virtual natural laboratory to innovate and test technological options to develop climate resilience production systems. Increased use of agrobiodiversity is crucial to coping with adverse impacts of global warming on food and feed production and quality. No one solution will suffice to adapt to climate change and its variability. Suits of technological innovations, including climate-resilient crop cultivars, will be needed to feed 9 billion people who will be living in the Earth by the middle of the twenty-first century

Metachondromatosis: Clinical and radiological diagnosis and differential diagnosis

The clinical case of a 9-year-old patient derived from Orthopedics to the Institute of Genetics at Universidad Nacional de Colombia due to a longstanding medical history of multiple bony outgrowths that required surgical management without etiologic diagnosis is presented in this paper. A possible diagnosis of metachondromatosis is suggested based on the clinical course, the family history, and the findings of the biopsy and regular growth parameters. On the other hand, differential diagnoses were compared taking into account the most common enchondromatosis type, based on data obtained during physical examination, radiological signs and other variables. This comparison was grounded on the review of existing literature on this type of entities