Physical Interactions With Bacteria and Protozoan Parasites Establish the Scavenger Receptor SSC4D as a Broad-Spectrum Pattern Recognition Receptor

Since the pioneering discoveries, by the Nobel laureates Jules Hoffmann and Bruce Beutler, that Toll and Toll-like receptors can sense pathogenic microorganisms and initiate, in vertebrates and invertebrates, innate immune responses against microbial infections, many other families of pattern recognition receptors (PRRs) have been described. One of such receptor clusters is composed by, if not all, at least several members of the scavenger receptor cysteine-rich (SRCR) superfamily. Many SRCR proteins are plasma membrane receptors of immune cells; however, a small subset consists of secreted receptors that are therefore in circulation. We here describe the first characterization of biological and functional roles of the circulating human protein SSC4D, one of the least scrutinized members of the family. Within leukocyte populations, SSC4D was found to be expressed by monocytes/macrophages, neutrophils, and B cells, but its production was particularly evident in epithelial cells of several organs and tissues, namely, in the kidney, thyroid, lung, placenta, intestinal tract, and liver. Similar to other SRCR proteins, SSC4D shows the capacity of physically binding to different species of bacteria, and this opsonization can increase the phagocytic capacity of monocytes. Importantly, we have uncovered the capacity of SSC4D of binding to several protozoan parasites, a singular feature seldom described for PRRs in general and here demonstrated for the first time for an SRCR family member. Overall, our study is pioneer in assigning a PRR role to SSC4D.This work was funded by National Funds through FCT– Fundação para a Ciência e a Tecnologia, I.P., under the projects SRecognite Infect-ERA/0003/2015 and UIDB/04293/ 2020. Individual funding to JT was provided by FCT through CEECIND/02362/2017. MC, RS, and MS were recipients of studentships from FCT, respectively, SFRH/BD/116791/2016, SFRH/BD/110691/2015, and SFRH/BD/133485/2017. This paper is dedicated to our colleague and friend Rui Appelberg (1960-2020). The authors acknowledge the support of the i3S Scientific Platform BioSciences Screening, member of the national infrastructure PPBI–Portuguese Platform of Bioimaging (PPBI-POCI-01-0145-FEDER-022122) and PT-OPENSCREEN. Tissue sections were kindly provided by Amaro Frutuoso, Department of Complementary Means of Diagnosis and Therapy, Service of Pathology, Hospital Pedro Hispano, Matosinhos

Modulation of CD4 T cell function via CD6-targeting

In recent years molecules involved on the immune synapse became successful targets for therapeutic immune modulation. CD6 has been extensively studied, yet, results regarding CD6 biology have been controversial, in spite of the ubiquitous presence of this molecule on virtually all CD4 T cells. We investigated the outcome of murine and human antibodies targeting CD6 domain 1. We found that CD6-targeting had a major impact on the functional specialization of CD4 cells, both human and murine. Differentiation of CD4 T cells towards a Foxp3+ Treg fate was prevented with increasing doses of anti-CD6, while Th1 polarization was favoured. No impact was observed on Th2 or Th17 specialization. These in vitro results provided an explanation for the dose-dependent outcome of in vivo anti-CD6 administration where the anti-inflammatory action is lost at the highest doses. Our data show that therapeutic targeting of the immune synapse may lead to paradoxical dose-dependent effects due to modification of T cell fate.Funded by UID/BIM/50005/2019, project funded by Fundação para a Ciência e a Tecnologia (FCT) / Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) throught Fundos do Orçamento do Estado, pela Fundação para a Ciência e a Tecnologia (FCT) ( PTDC/DTP-FTO/3080/2014 ); and by the project SRecognite Infect - ERA/0003/2015 using national funds through FCT . Funders did not have a role in study design, data collection, analysis, and interpretation, or in the writing of the manuscript

Temperature responses of Rubisco from Paniceae grasses provide opportunities for improving C3 photosynthesis.

Enhancing the catalytic properties of the CO2-fixing enzyme Rubisco is a target for improving agricultural crop productivity. Here, we reveal extensive diversity in the kinetic response between 10 and 37 °C by Rubisco from C3 and C4 species within the grass tribe Paniceae. The CO2 fixation rate (kcatc) for Rubisco from the C4 grasses with nicotinamide adenine dinucleotide (NAD) phosphate malic enzyme (NADP-ME) and phosphoenolpyruvate carboxykinase (PCK) photosynthetic pathways was twofold greater than the kcatc of Rubisco from NAD-ME species across all temperatures. The declining response of CO2/O2 specificity with increasing temperature was less pronounced for PCK and NADP-ME Rubisco, which would be advantageous in warmer climates relative to the NAD-ME grasses. Modelled variation in the temperature kinetics of Paniceae C3 Rubisco and PCK Rubisco differentially stimulated C3 photosynthesis relative to tobacco above and below 25 °C under current and elevated CO2. Amino acid substitutions in the large subunit that could account for the catalytic variation among Paniceae Rubisco are identified; however, incompatibilities with Paniceae Rubisco biogenesis in tobacco hindered their mutagenic testing by chloroplast transformation. Circumventing these bioengineering limitations is critical to tailoring the properties of crop Rubisco to suit future climates

Adverse childhood experiences and suicide attempts in morbidly obese adults

Introdução: As tentativas de suicídio surgem frequentemente associadas a problemas alimentares, tanto anorexia quanto bulimia. Do mesmo modo, tem-se verifi cado uma elevada ocorrência de suicídio entre obesos. Investigações têm mostrado que a adversidade na infância pode ser um fator de risco para as tentativas de suicídio. Objetivos: Caracterizar e compreender a relação entre experiências de adversidade na infância e tentativas de suicídio em 100 obesos mórbidos candidatos a cirurgia bariátrica. Métodos: Um total de 100 pacientes foram selecionados de setembro de 2007 a outubro de 2007 e de janeiro de 2008 a janeiro de 2009, sendo que 20 pacientes eram do sexo feminino. A média de idade era de 38,89±9,87 anos, e a média do peso máximo era de 136,43±14 kg. O Questionário da História de Adversidade na Infância foi utilizado para avaliar experiências adversas. Resultados: 88% dos pacientes relataram a existência de pelo menos uma experiência de adversidade na infância, e 25% relataram já ter realizado pelo menos uma tentativa de suicídio. A adversidade na infância esteve associada a um risco aumentado para realizar tentativas de suicídio (odds ratio = 2,026). Conclusão: Esses dados devem ser levados em consideração na avaliação e no acompanhamento desses pacientes.Introduction: Suicide attempts are often associated with eating disorders, both anorexia and bulimia. Likewise, a high incidence of suicide has been observed among obese patients. Previous studies have shown that adverse experiences in childhood may be a risk factor for suicide attempts. Objectives: To characterize and to understand the relationship between adverse experiences and suicide attempts in 100 morbidly obese patients referred for bariatric surgery. Methods: A total of 100 patients were selected from September 2007 to October 2007 and from January 2008 to January 2009. Of these, 20 patients were females. Mean age was 38.89±9.87 years, and mean maximum weight was 136.43±14 kg. The Portuguese version of the Family ACE (Adverse Childhood Experiences) Questionnaire was used to assess the occurrence of adverse events. Results: 88% of the patients reported the existence of at least one adverse experience in childhood, and 25% reported at least one previous suicide attempt. Adversity in childhood was associated with an increased risk for suicide attempts (odds ratio = 2.026). Conclusion: These data should be taken into account in the assessment and monitoring of these patients.Fundação para a Ciência e a Tecnologia (FCT); (SFRH/BD/37069/2007)