The plastidial retrograde signal methyl erythritol cyclopyrophosphate is a regulator of salicylic acid and jasmonic acid crosstalk.

The exquisite harmony between hormones and their corresponding signaling pathways is central to prioritizing plant responses to simultaneous and/or successive environmental trepidations. The crosstalk between jasmonic acid (JA) and salicylic acid (SA) is an established effective mechanism that optimizes and tailors plant adaptive responses. However, the underlying regulatory modules of this crosstalk are largely unknown. Global transcriptomic analyses of mutant plants (ceh1) with elevated levels of the stress-induced plastidial retrograde signaling metabolite 2-C-methyl-D-erythritol cyclopyrophosphate (MEcPP) revealed robustly induced JA marker genes, expected to be suppressed by the presence of constitutively high SA levels in the mutant background. Analyses of a range of genotypes with varying SA and MEcPP levels established the selective role of MEcPP-mediated signal(s) in induction of JA-responsive genes in the presence of elevated SA. Metabolic profiling revealed the presence of high levels of the JA precursor 12-oxo-phytodienoic acid (OPDA), but near wild type levels of JA in the ceh1 mutant plants. Analyses of coronatine-insensitive 1 (coi1)/ceh1 double mutant plants confirmed that the MEcPP-mediated induction is JA receptor COI1 dependent, potentially through elevated OPDA. These findings identify MEcPP as a previously unrecognized central regulatory module that induces JA-responsive genes in the presence of high SA, thereby staging a multifaceted plant response within the environmental context

Attitudes towards gender roles and prevalence of intimate partner violence perpetrated against pregnant and postnatal women: Differences between women immigrants from conflict-affected countries and women born in Australia

BACKGROUND: The aim was to compare, for the first time in a large systematic study, women born in conflict-affected countries who immigrated to Australia with women born in Australia for attitudes towards gender roles and men\u27s use of IPV and the actual prevalence of IPV. The study also examined if any associations remained across the two timepoints of pregnancy and postpartum. METHODS: Women were interviewed during their first visit to one of three Australian public hospital antenatal clinics and re-interviewed at home six months after giving birth. A total of 1111 women completed both interviews, 583 were born in conflict-affected countries and 528 born in Australia. Associations between attitudes towards gender roles and men\u27s use of IPV, socio-demographic characteristics and reported actual experiences of IPV were examined using bivariate and multiple logistic regression analyses. RESULTS: Attitudes toward inequitable gender roles including those that condone men\u27s use of IPV, and prevalence of IPV, were significantly higher (p \u3c 0.001) among women born in conflict-affected countries compared to Australia-born women. Women born in conflict-affected countries with the strongest held attitudes towards gender roles and men\u27s use of IPV had an adjusted odds ratio (aOR) of 3.18 for IPV at baseline (95% CI 1.85-5.47) and an aOR of 1.83 for IPV at follow-up (95% CI 1.11-3.01). Women born in Australia with the strongest held attitudes towards gender roles and IPV had an aOR of 7.12 for IPV at baseline (95% CI 2.12-23.92) and an aOR of 10.59 for IPV at follow-up (95% CI 2.21-50.75). CONCLUSIONS: Our results underscore the need for IPV prevention strategies sensitively targeted to communities from conflict-affected countries, and for awareness among clinicians of gender role attitudes that may condone men\u27s use of IPV, and the associated risk of IPV. The study supports the need for culturally informed national strategies to promote gender equality and to challenge practices and attitudes that condone men\u27s violence in spousal relationships

Shadowing in Inelastic Scattering of Muons on Carbon, Calcium and Lead at Low XBj

Nuclear shadowing is observed in the per-nucleon cross-sections of positive muons on carbon, calcium and lead as compared to deuterium. The data were taken by Fermilab experiment E665 using inelastically scattered muons of mean incident momentum 470 GeV/c. Cross-section ratios are presented in the kinematic region 0.0001 < XBj <0.56 and 0.1 < Q**2 < 80 GeVc. The data are consistent with no significant nu or Q**2 dependence at fixed XBj. As XBj decreases, the size of the shadowing effect, as well as its A dependence, are found to approach the corresponding measurements in photoproduction.Comment: 22 pages, incl. 6 figures, to be published in Z. Phys.

Research misconduct in the fields of ethics and philosophy: researchers’ perceptions in Spain

This is the Author’s Original Manuscript (AOM) (also called a “preprint”) sent to review to Science and Engineering Ethics on 11/10/2020. The final version of the article was published online at SEE on 21/01/2021. The online version is available at: https://doi.org/10.1007/s11948-021-00278-wEmpirical studies have revealed a disturbing prevalence of research misconduct in a wide variety of disciplines, although not, to date, in the areas of ethics and philosophy. This study aims to provide empirical evidence on perceptions of how serious a problem research misconduct is in these two disciplines in Spain, particularly regarding the effects that the model used to evaluate academics’ research performance may have on their ethical behaviour. The methodological triangulation applied in the study combines a questionnaire, a debate at the annual meeting of scientific association, and in-depth interviews. Of the 541 questionnaires sent out, 201 responses were obtained (37.1% of the total sample), with a significant difference in the participation of researchers in philosophy (30.5%) and in ethics (52.8%); 26 researchers took part in the debate and 14 interviews were conducted. The questionnaire results reveal that 91.5% of the respondents considered research misconduct to be on the rise; 63.2% considered at least three of the fraudulent practices referred to in the study to be commonplace, and 84.1% identified two or more such practices. The researchers perceived a high prevalence of duplicate publication (66.5%) and self-plagiarism (59.0%), use of personal influence (57.5%) and citation manipulation (44.0%), in contrast to a low perceived incidence of data falsification or fabrication (10.0%). The debate and the interviews corroborated these data. Researchers associated the spread of these misconducts with the research evaluation model applied in Spain

The mammalian gene function resource: the International Knockout Mouse Consortium.

In 2007, the International Knockout Mouse Consortium (IKMC) made the ambitious promise to generate mutations in virtually every protein-coding gene of the mouse genome in a concerted worldwide action. Now, 5 years later, the IKMC members have developed high-throughput gene trapping and, in particular, gene-targeting pipelines and generated more than 17,400 mutant murine embryonic stem (ES) cell clones and more than 1,700 mutant mouse strains, most of them conditional. A common IKMC web portal (www.knockoutmouse.org) has been established, allowing easy access to this unparalleled biological resource. The IKMC materials considerably enhance functional gene annotation of the mammalian genome and will have a major impact on future biomedical research

The mammalian gene function resource: The International Knockout Mouse Consortium

In 2007, the International Knockout Mouse Consortium (IKMC) made the ambitious promise to generate mutations in virtually every protein-coding gene of the mouse genome in a concerted worldwide action. Now, 5 years later, the IKMC members have developed highthroughput gene trapping and, in particular, gene-targeting pipelines and generated more than 17,400 mutant murine embryonic stem (ES) cell clones and more than 1,700 mutant mouse strains, most of them conditional. A common IKMC web portal (www.knockoutmouse.org) has been established, allowing easy access to this unparalleled biological resource. The IKMC materials considerably enhance functional gene annotation of the mammalian genome and will have a major impact on future biomedical research

Symmetric ligand binding using tunable de novo designed symmetric protein dimers

Thesis (Ph.D.)--University of Washington, 2020Cyclic two-fold (C2) symmetric ligands are common in nature, synthetic chemistry, and medicine. Additionally, we can now design millions of C2 symmetric peptides with an incredible diversity of sizes, shapes, and chemistries. De novo proteins capable of binding these C2 symmetric ligands could be useful in various applications, but scaffolds and methods to do this have been lacking. To solve this problem, I created a diverse set of C2 symmetric proteins with central cavities. I first designed curved repeat protein monomers sampling a continuum of curvatures, and then docked these into homodimers, generating a very wide range of C2 cavity shapes and sizes for functionalization. In total, 77 scaffolds were experimentally characterized, and of these, 23 (30%) appear to be folded as designed based on Small Angle X-ray Scattering data. Furthermore, crystallographic data for 4 designs (2 scaffolds and 2 functionalized binders) confirms the proteins fold as expected. A third scaffold design was determined to be monomeric by crystallographic analysis. Despite its failure to form the designed homodimer, the solved monomer was in close agreement with the design model. We believe that these diverse scaffolds provide a rich set of starting points for binding a very wide range of C2 compounds. Advantages of this conception are that the cavities can be very diverse in size, shape, and available sidechain chemistry, and as the protein hydrophobic core is separated from the pocket because the cavity lining residues are on the exterior of the monomers, functionalization to create binding interactions for specific compounds is unlikely to destabilize either the monomers or the dimer interface. Finally, we used these scaffolds to bind symmetric chlorophyll dimers, which could have applications in synthetic light-harvesting, as well as to bind a C2 symmetric peptide, which could become a platform for the creation of entirely bioorthogonal chemically induced dimers

Inhibition of TOR in Chlamydomonas reinhardtii Leads to Rapid Cysteine Oxidation Reflecting Sustained Physiological Changes

The target of rapamycin (TOR) kinase is a master metabolic regulator with roles in nutritional sensing, protein translation, and autophagy. In Chlamydomonas reinhardtii, a unicellular green alga, TOR has been linked to the regulation of increased triacylglycerol (TAG) accumulation, suggesting that TOR or a downstream target(s) is responsible for the elusive &ldquo;lipid switch&rdquo; in control of increasing TAG accumulation under nutrient limitation. However, while TOR has been well characterized in mammalian systems, it is still poorly understood in photosynthetic systems, and little work has been done to show the role of oxidative signaling in TOR regulation. In this study, the TOR inhibitor AZD8055 was used to relate reversible thiol oxidation to the physiological changes seen under TOR inhibition, including increased TAG content. Using oxidized cysteine resin-assisted capture enrichment coupled with label-free quantitative proteomics, 401 proteins were determined to have significant changes in oxidation following TOR inhibition. These oxidative changes mirrored characterized physiological modifications, supporting the role of reversible thiol oxidation in TOR regulation of TAG production, protein translation, carbohydrate catabolism, and photosynthesis through the use of reversible thiol oxidation. The delineation of redox-controlled proteins under TOR inhibition provides a framework for further characterization of the TOR pathway in photosynthetic eukaryotes