Uncovering tomato quantitative trait loci and candidate genes for fruit cuticular lipid composition using the Solanum pennellii introgression line population

[EN] The cuticle is a specialized cell wall layer that covers the outermost surface of the epidermal cells and has important implications for fruit permeability and pathogen susceptibility. In order to decipher the genetic control of tomato fruit cuticle composition, an introgression line (IL) population derived from a biparental cross between Solanum pennellii (LA0716) and the Solanum lycopersicum cultivar M82 was used to build a first map of associated quantitative trait loci (QTLs). A total of 24 cuticular waxes and 26 cutin monomers were determined. They showed changes associated with 18 genomic regions distributed in nine chromosomes affecting 19 ILs. Out of the five main fruit cuticular components described for the wild species S. pennellii, three of them were associated with IL3.4, IL12.1, and IL7.4.1, causing an increase in n-alkanes (>= C-30), a decrease in amyrin content, and a decrease in cuticle thickness of similar to 50%, respectively. Moreover, we also found a QTL associated with increased levels of amyrins in IL3.4. In addition, we propose some candidate genes on the basis of their differential gene expression and single nucleotide polymorphism variability between the introgressed and the recurrent alleles, which will be the subjects of further investigation.Research at the IBMCP was supported by the Spanish Ministry of Education and Culture (BIO2013-42193-R) and H2020 TRADITOM (634561). AA, AG, and J-PF-M thank COST FA1106 Quality Fruit for STSM and networking activities. This work was supported by the Israel Science Foundation (ISF) personal grant to AA (grant no. 646/11). We would like to thank the Adelis Foundation, the Leona M. and Harry B. Helmsley Charitable Trust, the Jeanne and Joseph Nissim Foundation for Life Sciences, Tom and Sondra Rykoff Family Foundation Research, and the Raymond Burton Plant Genome Research Fund for supporting AA's laboratory activity. AA is the incumbent of the Peter J. Cohn Professorial Chair. We are very grateful to Prof. Dani Zamir for providing us the S. pennellii IL collection and to Prof. Antonio Heredia for his valuable advice in preparing the manuscript for publication. We would like to acknowledge the help offered by the Electron Microscopy Unit at the WIS (Israel) for the TEM sample preparation and imaging, especially Elena Kartvelishvily, Eugenia Klein, and Eyal Shimoni. Finally, we would also like to thank Calanit Raanan and Tamara Berkutzki (Department of Veterinary Resources, WIS) for their help in tissue fixation and embedding, as well as Hanna Levanony (Department of Plant Sciences, WIS) for her help in tissue staining for the light microscopy studies.Fernández Moreno, JP.; Levy-Samoha, D.; Malitsky, S.; Monforte Gilabert, AJ.; Orzáez Calatayud, DV.; Aharoni, A.; Granell Richart, A. (2017). Uncovering tomato quantitative trait loci and candidate genes for fruit cuticular lipid composition using the Solanum pennellii introgression line population. Journal of Experimental Botany. 68(11):2703-2716. https://doi.org/10.1093/jxb/erx134S27032716681

Altered somatic hypermutation patterns in COVID-19 patients classifies disease severity

IntroductionThe success of the human body in fighting SARS-CoV2 infection relies on lymphocytes and their antigen receptors. Identifying and characterizing clinically relevant receptors is of utmost importance.MethodsWe report here the application of a machine learning approach, utilizing B cell receptor repertoire sequencing data from severely and mildly infected individuals with SARS-CoV2 compared with uninfected controls.ResultsIn contrast to previous studies, our approach successfully stratifies non-infected from infected individuals, as well as disease level of severity. The features that drive this classification are based on somatic hypermutation patterns, and point to alterations in the somatic hypermutation process in COVID-19 patients.DiscussionThese features may be used to build and adapt therapeutic strategies to COVID-19, in particular to quantitatively assess potential diagnostic and therapeutic antibodies. These results constitute a proof of concept for future epidemiological challenges

Does cerebral lateralization develop? A study using functional transcranial Doppler ultrasound assessing lateralization for language production and visuospatial memory

In the majority of people, language production is lateralized to the left cerebral hemisphere and visuospatial skills to the right. However, questions remain as to when, how, and why humans arrive at this division of labor. In this study, we assessed cerebral lateralization for language production and for visuospatial memory using functional transcranial Doppler ultrasound in a group of 60 typically developing children between the ages of six and 16 years. The typical pattern of left-lateralized activation for language production and right-lateralized activation for visuospatial memory was found in the majority of the children (58%). No age-related change in direction or strength of lateralization was found for language production. In contrast, the strength of lateralization (independent of direction) for visuospatial memory function continued to increase with age. In addition, boys showed a trend for stronger right-hemisphere lateralization for visuospatial memory than girls, but there was no gender effect on language laterality. We tested whether having language and visuospatial functions in the same hemisphere was associated with poor cognitive performance and found no evidence for this “functional crowding” hypothesis. We did, however, find that children with left-lateralized language production had higher vocabulary and nonword reading age-adjusted standard scores than other children, regardless of the laterality of visuospatial memory. Thus, a link between language function and left-hemisphere lateralization exists, and cannot be explained in terms of maturational change

Monocytes induce STAT3 activation in human mesenchymal stem cells to promote osteoblast formation

A major therapeutic challenge is how to replace bone once it is lost. Bone loss is a characteristic of chronic inflammatory and degenerative diseases such as rheumatoid arthritis and osteoporosis. Cells and cytokines of the immune system are known to regulate bone turnover by controlling the differentiation and activity of osteoclasts, the bone resorbing cells. However, less is known about the regulation of osteoblasts (OB), the bone forming cells. This study aimed to investigate whether immune cells also regulate OB differentiation. Using in vitro cell cultures of human bone marrow-derived mesenchymal stem cells (MSC), it was shown that monocytes/macrophages potently induced MSC differentiation into OBs. This was evident by increased alkaline phosphatase (ALP) after 7 days and the formation of mineralised bone nodules at 21 days. This monocyte-induced osteogenic effect was mediated by cell contact with MSCs leading to the production of soluble factor(s) by the monocytes. As a consequence of these interactions we observed a rapid activation of STAT3 in the MSCs. Gene profiling of STAT3 constitutively active (STAT3C) infected MSCs using Illumina whole human genome arrays showed that Runx2 and ALP were up-regulated whilst DKK1 was down-regulated in response to STAT3 signalling. STAT3C also led to the up-regulation of the oncostatin M (OSM) and LIF receptors. In the co-cultures, OSM that was produced by monocytes activated STAT3 in MSCs, and neutralising antibodies to OSM reduced ALP by 50%. These data indicate that OSM, in conjunction with other mediators, can drive MSC differentiation into OB. This study establishes a role for monocyte/macrophages as critical regulators of osteogenic differentiation via OSM production and the induction of STAT3 signalling in MSCs. Inducing the local activation of STAT3 in bone cells may be a valuable tool to increase bone formation in osteoporosis and arthritis, and in localised bone remodelling during fracture repair

An Animal Model of Emotional Blunting in Schizophrenia

Schizophrenia is often associated with emotional blunting—the diminished ability to respond to emotionally salient stimuli—particularly those stimuli representative of negative emotional states, such as fear. This disturbance may stem from dysfunction of the amygdala, a brain region involved in fear processing. The present article describes a novel animal model of emotional blunting in schizophrenia. This model involves interfering with normal fear processing (classical conditioning) in rats by means of acute ketamine administration. We confirm, in a series of experiments comprised of cFos staining, behavioral analysis and neurochemical determinations, that ketamine interferes with the behavioral expression of fear and with normal fear processing in the amygdala and related brain regions. We further show that the atypical antipsychotic drug clozapine, but not the typical antipsychotic haloperidol nor an experimental glutamate receptor 2/3 agonist, inhibits ketamine's effects and retains normal fear processing in the amygdala at a neurochemical level, despite the observation that fear-related behavior is still inhibited due to ketamine administration. Our results suggest that the relative resistance of emotional blunting to drug treatment may be partially due to an inability of conventional therapies to target the multiple anatomical and functional brain systems involved in emotional processing. A conceptual model reconciling our findings in terms of neurochemistry and behavior is postulated and discussed

Wheat germ in vitro translation to produce one of the most toxic sodium channel specific toxins

Envenoming following scorpion sting is a common emergency in many parts of the world. During scorpion envenoming, highly toxic small polypeptides of the venom diffuse rapidly within the victim causing serious medical problems. The exploration of toxin structure-function relationship would benefit from the generation of soluble recombinant scorpion toxins in Escherichia coli. We developed an in vitro wheat germ translation system for the expression of the highly toxic Aah (Androctonus australis hector)II protein that requires the proper formation of four disulphide bonds. Soluble, recombinant N-terminal GST (glutathione S-transferase)-tagged AahII toxin is obtained in this in vitro translation system. After proteolytic removal of the GST-tag, purified rAahII (recombinant AahII) toxin, which contains two extra amino acids at its N terminal relative to the native AahII, is highly toxic after i.c.v. (intracerebroventricular) injection in Swiss mice. An LD50 (median lethal dose)-value of 10 ng (or 1.33 pmol), close to that of the native toxin (LD50 of 3 ng) indicates that the wheat germ in vitro translation system produces properly folded and biological active rAahII. In addition, NbAahII10 (Androctonus australis hector nanobody 10), a camel single domain antibody fragment, raised against the native AahII toxin, recognizes its cognate conformational epitope on the recombinant toxin and neutralizes the toxicity of purified rAahII upon injection in mice

Quantifying cerebral asymmetries for language in dextrals and adextrals with random-effects meta analysis

Speech and language-related functions tend to depend on the left hemisphere more than the right in most right-handed (dextral) participants. This relationship is less clear in non-right handed (adextral) people, resulting in surprisingly polarized opinion on whether or not they are as lateralized as right handers. The present analysis investigates this issue by largely ignoring methodological differences between the different neuroscientific approaches to language lateralization, as well as discrepancies in how dextral and adextral participants were recruited or defined. Here we evaluate the tendency for dextrals to be more left hemisphere dominant than adextrals, using random effects meta analyses. In spite of several limitations, including sample size (in the adextrals in particular), missing details on proportions of groups who show directional effects in many experiments, and so on, the different paradigms all point to proportionally increased left hemispheric dominance in the dextrals. These results are analyzed in light of the theoretical importance of these subtle differences for understanding the cognitive neuroscience of language, as well as the unusual asymmetry in most adextrals