Cadmium and arsenic-induced-stress differentially modulates Arabidopsis root architecture, peroxisome distribution, enzymatic activities and their nitric oxide content

In plant cells, cadmium (Cd) and arsenic (As) exert toxicity mainly by inducing oxidative stress through an imbalance between the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), and their detoxification. Nitric oxide (NO) is a RNS acting as signalling molecule coordinating plant development and stress responses, but also as oxidative stress inducer, depending on its cellular concentration. Peroxisomes are versatile organelles involved in plant metabolism and signalling, with a role in cellular redox balance thanks to their antioxidant enzymes, and their RNS (mainly NO) and ROS. This study analysed Cd or As effects on peroxisomes, and NO production and distribution in the root system, including primary root (PR) and lateral roots (LRs). Arabidopsis thaliana wild-type and transgenic plants enabling peroxisomes to be visualized in vivo, through the expression of the 35S-cyan fluorescent protein fused to the peroxisomal targeting signal1 (PTS1) were used. Peroxisomal enzymatic activities including the antioxidant catalase, the H2O2-generating glycolate oxidase, and the hydroxypyruvate reductase, and root system morphology were also evaluated under Cd/As exposure. Results showed that Cd and As differently modulate these activities, however, catalase activity was inhibited by both. Moreover, Arabidopsis root system was altered, with the pollutants differently affecting PR growth, but similarly enhancing LR formation. Only in the PR apex, and not in LR one, Cd more than As caused significant changes in peroxisome distribution, size, and in peroxisomal NO content. By contrast, neither pollutant caused significant changes in peroxisomes size and peroxisomal NO content in the LR apex

A review on additive manufacturing and materials for catalytic applications: Milestones, key concepts, advances and perspectives

Catalysis, a driving force of the chemical industry is increasingly being influenced by additive manufacturing. The link between them is based on the need to intensify catalytic processes in order to make them more efficient and sustainable. Additive manufacturing can satisfy such a need, generating devices with an advanced design, easy production, and great adaptation, in addition to their catalytic functionality. The exponential growth of examples reported on the application of 3D-printing in catalysis has led to the need to compile and analyse these cases and thus establish, through this review, the most in-depth analysis done to date. The manuscript includes a brief background of the history of additive manufacturing and the classification of the different printing techniques. Subsequently, it identifies the intensification of processes, among other aspects, as the key for understanding the union of additive manufacturing and catalysis. Then, it explores in detail how such a combination occurs, establishing the most comprehensive classification to date between the two large groups of printable devices with catalytic properties. Finally, a series of perspectives are proposed in which the most probable courses of new advances in this field of research are identified.O.H. Laguna agradece a la Universidad de Jaén por el apoyo el contrato postdoctoral a través de la ‘‘Acción 6 del Plan de Apoyo a la Investigación de la Universidad de Jaén (2017-2019).

Systematic identification of phenotypically enriched loci using a patient network of genomic disorders

Background Network medicine is a promising new discipline that combines systems biology approaches and network science to understand the complexity of pathological phenotypes. Given the growing availability of personalized genomic and phenotypic profiles, network models offer a robust integrative framework for the analysis of "omics" data, allowing the characterization of the molecular aetiology of pathological processes underpinning genetic diseases. Methods Here we make use of patient genomic data to exploit different network-based analyses to study genetic and phenotypic relationships between individuals. For this method, we analyzed a dataset of structural variants and phenotypes for 6,564 patients from the DECIPHER database, which encompasses one of the most comprehensive collections of pathogenic Copy Number Variations (CNVs) and their associated ontology-controlled phenotypes. We developed a computational strategy that identifies clusters of patients in a synthetic patient network according to their genetic overlap and phenotype enrichments. Results Many of these clusters of patients represent new genotype-phenotype associations, suggesting the identification of newly discovered phenotypically enriched loci (indicative of potential novel syndromes) that are currently absent from reference genomic disorder databases such as ClinVar, OMIM or DECIPHER itself. Conclusions We provide a high-resolution map of pathogenic phenotypes associated with their respective significant genomic regions and a new powerful tool for diagnosis of currently uncharacterized mutations leading to deleterious phenotypes and syndromes

Phenotype-loci associations in networks of patients with rare disorders: application to assist in the diagnosis of novel clinical cases

Copy number variations (CNVs) are genomic structural variations (deletions, duplications, or translocations) that represent the 4.8–9.5% of human genome variation in healthy individuals. In some cases, CNVs can also lead to disease, being the etiology of many known rare genetic/genomic disorders. Despite the last advances in genomic sequencing and diagnosis, the pathological effects of many rare genetic variations remain unresolved, largely due to the low number of patients available for these cases, making it difficult to identify consistent patterns of genotype–phenotype relationships. We aimed to improve the identification of statistically consistent genotype–phenotype relationships by integrating all the genetic and clinical data of thousands of patients with rare genomic disorders (obtained from the DECIPHER database) into a phenotype–patient–genotype tripartite network. Then we assessed how our network approach could help in the characterization and diagnosis of novel cases in clinical genetics. The systematic approach implemented in this work is able to better define the relationships between phenotypes and specific loci, by exploiting large-scale association networks of phenotypes and genotypes in thousands of rare disease patients. The application of the described methodology facilitated the diagnosis of novel clinical cases, ranking phenotypes by locus specificity and reporting putative new clinical features that may suggest additional clinical follow-ups. In this work, the proof of concept developed over a set of novel clinical cases demonstrates that this network-based methodology might help improve the precision of patient clinical records and the characterization of rare syndromes

Health Risk Assessment of Exposure to 15 Essential and Toxic Elements in Spanish Women of Reproductive Age: A Case Study

This case study investigates the exposure of 119 Spanish women of reproductive age to 5 essential (Co, Cu, Mn, V, Zn) and 10 toxic (Ba, Be, Cs, Ni, Pb, Pt, Sb, Th, Al, U) elements and assesses their risk. The essential elements (Co, Cu, Mn, V, and Zn) showed average concentrations (GM: geometric mean) of 0.8, 35, 0.5, 0.2, and 347 μg/L, respectively. Five of the toxic elements (Ba, Cs, Ni, Al, U) exhibited detection frequencies of 100%. The GM concentrations of the novel toxic elements were 12 μg/L (Al), 0.01 μg/L (Pt), 0.02 μg/L (U), 0.12 μg/L (Th), 0.009 μg/L (Be) and 4 μg/L (Cs). The urine analysis was combined with a survey to assess any variations between subgroups and potential predictors of exposure to elements in the female population. Significant differences were obtained between the rural and urban areas studied for the toxic element Cs, with higher levels found in mothers living in urban areas. In relation to diet, statistically significantly higher levels of essential (Cu) and toxic (Ba) elements were detected in women with a high consumption of fish, while mothers who consumed a large quantity of legumes presented higher levels of the toxic element Ni (p = 0.0134). In a risk-assessment context, hazard quotients (HQs) greater than 1 were only observed for the essential elements Zn and Cu in P95. No deficiency was found regarding the only essential element for which a biomonitoring equivalent for nutritional deficit is available (Zn). For the less-studied toxic elements (Al, Pt, U, Th, Be, and Cs), HQs were lower than 1, and thus, the health risk due to exposure to these elements is expected to be low for the female population under study

Assessment of proline function in higher plants under extreme temperatures

Climate change and abiotic stress factors are key players in crop losses worldwide. Among which, extreme temperatures (heat and cold) disturb plant growth and development, reduce productivity and, in severe cases, lead to plant death. Plants have developed numerous strategies to mitigate the detrimental impact of temperature stress. Exposure to stress leads to the accumulation of various metabolites, e.g. sugars, sugar alcohols, organic acids and amino acids. Plants accumulate the amino acid ‘proline’ in response to several abiotic stresses, including temperature stress. Proline abundance may result from de novo synthesis, hydrolysis of proteins, reduced utilization or degradation. Proline also leads to stress tolerance by maintaining the osmotic balance (still controversial), cell turgidity and indirectly modulating metabolism of reactive oxygen species. Furthermore, the crosstalk of proline with other osmoprotectants and signalling molecules, e.g. glycine betaine, abscisic acid, nitric oxide, hydrogen sulfide, soluble sugars, helps to strengthen protective mechanisms in stressful environments. Development of less temperature-responsive cultivars can be achieved by manipulating the biosynthesis of proline through genetic engineering. This review presents an overview of plant responses to extreme temperatures and an outline of proline metabolism under such temperatures. The exogenous application of proline as a protective molecule under extreme temperatures is also presented. Proline crosstalk and interaction with other molecules is also discussed. Finally, the potential of genetic engineering of proline-related genes is explained to develop ‘temperature-smart’ plants. In short, exogenous application of proline and genetic engineering of proline genes promise ways forward for developing ‘temperature-smart’ future crop plants.Research of FJC is supported by a European Regional Development Fund co-financed grant from the Ministry of Economy and Competitiveness/Science and Innovation (PID2019-10103924GB-I00), Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020) (P18-FR-1359), Spain. This work was also supported by grants from Bill & Melinda Foundation (Tropical Legumes Project, OPP1114827), and Food Futures Institute of Murdoch University to RKV

The EGR2 gene is involved in axonal Charcot-Marie-Tooth disease

[EN] Background and purpose: A three-generation family affected by axonal Charcot-Marie-Tooth disease (CMT) was investigated with the aim of discovering genetic defects and to further characterize the phenotype. Methods: The clinical, nerve conduction studies and muscle magnetic resonance images of the patients were reviewed. A whole exome sequencing was performed and the changes were investigated by genetic studies, in silico analysis and luciferase reporter assays. Results: A novel c.1226G>A change (p.R409Q) in the EGR2 gene was identified. Patients presented with a typical, late-onset axonal CMT phenotype with variable severity that was confirmed in the ancillary tests. The in silico studies showed that the residue R409 is an evolutionary conserved amino acid. The p.R409Q mutation, which is predicted as probably damaging, would alter the conformation of the protein slightly and would cause a decrease of gene expression. Conclusions: This is the first report of an EGR2 mutation presenting as an axonal CMT phenotype with variable severity. This study broadens the phenotype of the EGR2-related neuropathies and suggests that the genetic testing of patients suffering from axonal CMT should include the EGR2 gene.This collaborative joint project is awarded by IRDiRC and funded by the Instituto de Salud Carlos III (ISCIII) - Subdireccion General de Evaluacion y Fomento de la Investigacion within the framework of the National R+D+I Plan (Grants IR11/TREAT-CMT, PI12/00946 and PI12/00453), co-funded with FEDER funds. C.E. has a "Miguel Servet' contract funded by the ISCIII and Centro de Investigacion Principe Felipe (CIPF) (Grant no. CPII14/00002). We are also grateful to Itziar Llopis for sample management.Sevilla, T.; Sivera, R.; Martínez-Rubio, D.; Lupo, V.; Chumillas, M.; Calpena-Corpas, E.; Dopazo, J.... (2015). The EGR2 gene is involved in axonal Charcot-Marie-Tooth disease. European Journal of Neurology. 22(12):1548-1555. https://doi.org/10.1111/ene.1278215481555221

Regulation of RUVBL1-RUVBL2 AAA-ATPases by the nonsense-mediated mRNA decay factor DHX34, as evidenced by Cryo-EM

Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that degrades aberrant mRNAs and also regulates the expression of a wide range of physiological transcripts. RUVBL1 and RUVBL2 AAA-ATPases form an hetero-hexameric ring that is part of several macromolecular complexes such as INO80, SWR1, and R2TP. Interestingly, RUVBL1-RUVBL2 ATPase activity is required for NMD activation by an unknown mechanism. Here, we show that DHX34, an RNA helicase regulating NMD initiation, directly interacts with RUVBL1-RUVBL2 in vitro and in cells. Cryo-EM reveals that DHX34 induces extensive changes in the N-termini of every RUVBL2 subunit in the complex, stabilizing a conformation that does not bind nucleotide and thereby down-regulates ATP hydrolysis of the complex. Using ATPase-deficient mutants, we find that DHX34 acts exclusively on the RUVBL2 subunits. We propose a model, where DHX34 acts to couple RUVBL1-RUVBL2 ATPase activity to the assembly of factors required to initiate the NMD response.Spanish Ministry of Science and Innovation SAF2017-82632-P Andres Lopez-Perrote Carlos F Rodriguez Marina Serna Oscar Llorca. Autonomous Government of Madrid Y2018/BIO4747 Ana Gonzalez-Corpas Oscar Llorca. Autonomous Government of Madrid P2018/NMT4443 Ana Gonzalez-Corpas Oscar Llorca MRC Core funding Javier F Caceres Spanish Ministry of Science and Innovation BES-2015-071348 Carlos F Rodriguez The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.S

Chemical priming enhances plant tolerance to salt stress

Salt stress severely limits the productivity of crop plants worldwide and its detrimental effects are aggravated by climate change. Due to a significant world population growth, agriculture has expanded to marginal and salinized regions, which usually render low crop yield. In this context, finding methods and strategies to improve plant tolerance against salt stress is of utmost importance to fulfill food security challenges under the scenario of the ever-increasing human population. Plant priming, at different stages of plant development, such as seed or seedling, has gained significant attention for its marked implication in crop salt-stress management. It is a promising field relying on the applications of specific chemical agents which could effectively improve plant salt-stress tolerance. Currently, a variety of chemicals, both inorganic and organic, which can efficiently promote plant growth and crop yield are available in the market. This review summarizes our current knowledge of the promising roles of diverse molecules/compounds, such as hydrogen sulfide (HS), molecular hydrogen, nitric oxide (NO), hydrogen peroxide (HO), melatonin, chitosan, silicon, ascorbic acid (AsA), tocopherols, and trehalose (Tre) as potential primers that enhance the salinity tolerance of crop plants