Paradise revealed: first-class science rocked by the sound of the waves

Univ São Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508900 São Paulo, BrazilInst Nacl Ciencia & Tecnol, Inst Invest Imunol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ciencias Biol, Diaderna, SP, BrazilFundacao Oswaldo Cruz, Inst Oswaldo Cruz, Lab Imunofarmacol, Rio de Janeiro, BrazilUniv São Paulo, Fac Med, BR-05508900 São Paulo, BrazilInst Nacl Canc, Div Biol Celular, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Dept Ciencias Biol, Diaderna, SP, BrazilWeb of Scienc

Pattern Recognition Receptors and the Host Cell Death Molecular Machinery

Pattern Recognition Receptors (PRRs) are proteins capable of recognizing molecules frequently found in pathogens (the so-called Pathogen-Associated Molecular Patterns—PAMPs), or molecules released by damaged cells (the Damage-Associated Molecular Patterns—DAMPs). They emerged phylogenetically prior to the appearance of the adaptive immunity and, therefore, are considered part of the innate immune system. Signals derived from the engagement of PRRs on the immune cells activate microbicidal and pro-inflammatory responses required to eliminate or, at least, to contain infectious agents. Molecularly controlled forms of cell death are also part of a very ancestral mechanism involved in key aspects of the physiology of multicellular organism, including the elimination of unwanted, damaged or infected cells. Interestingly, each form of cell death has its particular effect on inflammation and on the development of innate and adaptive immune responses. In this review article, we discuss some aspects of the molecular interplay between the cell death machinery and signals initiated by the activation of PRRs by PAMPs and DAMPs

Planejamento territorial em bacias urbanas da cidade de Tabatinga – Amazonas/Brasil / Territoral planning in urban basins of Tabatinga city - Amazonas / Brazil

Nas últimas décadas, ocorreu no Brasil um crescimento significativo da população urbana, como consequência deste processo houve o aumento de impactos ambientais, dentre os quais se destaca a poluição hídrica. No Amazonas, as cidades são densamente drenadas por pequenos rios ou canais de drenagem, paisagem comum nesta região, devido à grande quantidade de rios que compõe a maior bacia hidrográfica do mundo, a bacia Amazônica. As áreas de preservação permanente – APPs são áreas de risco natural, todavia na maior parte das cidades brasileiras a ocupação dessas áreas é intensa. Na cidade de Tabatinga localizada no estado do Amazonas, região de tríplice fronteira entre Brasil, Colômbia e Peru não é diferente, pois se constatou que os canais de drenagem se encontram degradados pela ineficiente e/ou ausente infraestrutura de saneamento básico na cidade. Segundo Índice de Qualidade da Água – IQA da Agência Nacional de Águas – ANA, o presente estudo revelou que dos seis pontos de coleta de água, dois estão com pH abaixo dos parâmetros normais com 5.35 na bacia do São Francisco a jusante área central da cidade e 5.60 na bacia do Paraíso a montante na área de expansão urbana, indicando que nas duas bacias há poluição de suas águas. Neste contexto, este trabalho visa o planejamento territorial a partir das bacias hidrográficas na cidade de Tabatinga com o intuito de identificar de modo pontual as possíveis causas e/ou fatores que contribuem para degradação do manancial hídrico

Epigenetic regulation of nitric oxide synthase 2, inducible (Nos2) by NLRC4 inflammasomes involves PARP1 cleavage

Nitric oxide synthase 2, inducible (Nos2) expression is necessary for the microbicidal activity of macrophages. However, NOS2 over-activation causes multiple inflammatory disorders, suggesting a tight gene regulation is necessary. Using cytosolic flagellin as a model for inflammasome-dependent NOS2 activation, we discovered a surprising new role for NLRC4/caspase-1 axis in regulating chromatin accessibility of the Nos2 promoter. We found that activation of two independent mechanisms is necessary for NOS2 expression by cytosolic flagellin: caspase-1 and NF-kappa B activation. NF-kappa B activation was necessary, but not sufficient, for NOS2 expression. Conversely, caspase-1 was necessary for NOS2 expression, but dispensable for NF-kappa B activation, indicating that this protease acts downstream NF-kappa B activation. We demonstrated that epigenetic regulation of Nos2 by caspase-1 involves cleavage of the chromatin regulator PARP1 (also known as ARTD1) and chromatin accessibility of the NF-kappa B binding sites located at the Nos2 promoter. Remarkably, caspase-1-mediated Nos2 transcription and NO production contribute to the resistance of macrophages to Salmonella typhimurium infection. Our results uncover the molecular mechanism behind the constricted regulation of Nos2 expression and open new therapeutic opportunities based on epigenetic activities of caspase-1 against infectious and inflammatory diseases.Kanton of ZurichUniversity Research Priority Program (URPP) in Translational Cancer Biology at the University of ZurichSwiss National Science FoundationCancer Research SocietyCanadian Cancer SocietyNSERCOntario Institute for Cancer Research (OICR)province of OntarioPrincess Margaret Cancer FoundationUniversity of Toronto McLaughlin CentreFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP - Brazil)Brazilian Research Council (CNPq-Brazil)CAPESINCTVUniv Fed Sao Paulo, Ctr Terapia Celular & Mol CTC Mol, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Ciencias Biol, Sao Paulo, BrazilUniv Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, Sao Paulo, BrazilUniv Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 2M9, CanadaUniv Sao Paulo, Inst Ciencias Biomed, Sao Paulo & Inst Invest Imunol, Inst Nacl Ciencia Tecnol INCT 3, Sao Paulo, BrazilInst Nacl Ciencia Tecnol INCT III, Inst Invest Imunol, Sao Paulo, BrazilUniv Zurich, Dept Mol Mech Dis, Zurich, SwitzerlandUniv Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, CanadaUniv Fed Sao Paulo, Ctr Terapia Celular & Mol CTC Mol, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Ciencias Biol, Sao Paulo, BrazilSwiss National Science Foundation: 310030B_138667Cancer Research Society: CRS19092Cancer Research Society: CRS19091Canadian Cancer Society: CCSRI 703279Canadian Cancer Society CCSRI 703716NSERC: 489073University of Toronto McLaughlin Centre: MC-2015-02FAPESP: 2013/16010-5FAPESP: 2015/18003-1Web of Scienc

Regulation of TRAIL expression by PRAME and EZH2 as potential therapeutic target against solid tumors

We thank the Department of Pathologic Anatomy and the International Center for Research, from AC Camargo Hospital for the tissue microarray assays and for the donation of cancer cell lines, respectively. We thank Dr. René Bernards (Amsterdam, The Netherlands) for the gift of PRAME and EZH2 short hairpin RNA vectors

Chemodynamical Properties and Ages of Metal-Poor Stars in S-PLUS

Metal-poor stars are key to our understanding of the early stages of chemical evolution in the Universe. New multi-filter surveys, such as the Southern Photometric Local Universe Survey (S-PLUS), are greatly advancing our ability to select low-metallicity stars. In this work, we analyse the chemodynamical properties and ages of 522 metal-poor candidates selected from the S-PLUS data release 3. About 92% of these stars were confirmed to be metal-poor ([Fe/H] $\leq -1$) based on previous medium-resolution spectroscopy. We calculated the dynamical properties of a subsample containing 241 stars, using the astrometry from Gaia Data Release 3. Stellar ages are estimated by a Bayesian isochronal method formalized in this work. We analyse the metallicity distribution of these metal-poor candidates separated into different subgroups of total velocity, dynamical properties, and ages. Our results are used to propose further restrictions to optimize the selection of metal-poor candidates in S-PLUS. The proposed astrometric selection ($\mathrm{parallax}>0.85$ mas) is the one that returns the highest fraction of extremely metal-poor stars (16.3% have [Fe/H] $\leq -3$); the combined selection provides the highest fraction of very metal-poor stars (91.0% have [Fe/H] $\leq -2$), whereas the dynamical selection (eccentricity > 0.35 and diskness < 0.75) is better for targetting metal-poor (99.5% have [Fe/H] $\leq -1$). Using only S-PLUS photometric selections, it is possible to achieve selection fractions of 15.6%, 88.5% and 98.3% for metallicities below $-$3, $-$2 and $-$1, respectively. We also show that it is possible to use S-PLUS to target metal-poor stars in halo substructures such as Gaia-Sausage/Enceladus, Sequoia, Thamnos and the Helmi stream.Comment: 18 pages, 13 figures. To be published in MNRAS main journal (accepted 15-may-2023

Xylem Transcription Profiles Indicate Potential Metabolic Responses For Economically Relevant Characteristics Of Eucalyptus Species.

Eucalyptus is one of the most important sources of industrial cellulose. Three species of this botanical group are intensively used in breeding programs: E. globulus, E. grandis and E. urophylla. E. globulus is adapted to subtropical/temperate areas and is considered a source of high-quality cellulose; E. grandis grows rapidly and is adapted to tropical/subtropical climates; and E. urophylla, though less productive, is considered a source of genes related to robustness. Wood, or secondary xylem, results from cambium vascular differentiation and is mostly composed of cellulose, lignin and hemicelluloses. In this study, the xylem transcriptomes of the three Eucalyptus species were investigated in order to provide insights on the particularities presented by each of these species. Data analysis showed that (1) most Eucalyptus genes are expressed in xylem; (2) most genes expressed in species-specific way constitutes genes with unknown functions and are interesting targets for future studies; (3) relevant differences were observed in the phenylpropanoid pathway: E. grandis xylem presents higher expression of genes involved in lignin formation whereas E. urophylla seems to deviates the pathway towards flavonoid formation; (4) stress-related genes are considerably more expressed in E. urophylla, suggesting that these genes may contribute to its robustness. The comparison of these three transcriptomes indicates the molecular signatures underlying some of their distinct wood characteristics. This information may contribute to the understanding of xylogenesis, thus increasing the potential of genetic engineering approaches aiming at the improvement of Eucalyptus forest plantations productivity.1420

Anticancer efficacy of the hypoxia-activated prodrug evofosfamide is enhanced in combination with proapoptotic receptor agonists against osteosarcoma

Tumor hypoxia is a major cause of treatment failure for a variety of malignancies. However, hypoxia also leads to treatment opportunities as demonstrated by the development of compounds that target regions of hypoxia within tumors. Evofosfamide is a hypoxia-activated prodrug that is created by linking the hypoxia-seeking 2-nitroimidazole moiety to the cytotoxic bromo-isophosphoramide mustard (Br-IPM). When evofosfamide is delivered to hypoxic regions of tumors, the DNA cross-linking toxin, Br-IPM, is released leading to cell death. This study assessed the anticancer efficacy of evofosfamide in combination with the Proapoptotic Receptor Agonists (PARAs) dulanermin and drozitumab against human osteosarcoma in vitro and in an intratibial murine model of osteosarcoma. Under hypoxic conditions in vitro, evofosfamide cooperated with dulanermin and drozitumab, resulting in the potentiation of cytotoxicity to osteosarcoma cells. In contrast, under the same conditions, primary human osteoblasts were resistant to treatment. Animals transplanted with osteosarcoma cells directly into their tibiae developed mixed osteosclerotic/osteolytic bone lesions and consequently developed lung metastases 3 weeks post cancer cell transplantation. Tumor burden in the bone was reduced by evofosfamide treatment alone and in combination with drozitumab and prevented osteosarcoma-induced bone destruction while also reducing the growth of pulmonary metastases. These results suggest that evofosfamide may be an attractive therapeutic agent, with strong anticancer activity alone or in combination with either drozitumab or dulanermin against osteosarcoma.Vasilios Liapis, Aneta Zysk, Mark DeNichilo, Irene Zinonos, Shelley Hay, Vasilios Panagopoulos, Alexandra Shoubridge, Christopher Difelice, Vladimir Ponomarev, Wendy Ingman, Gerald J. Atkins, David M. Findlay, Andrew C. W. Zannettino and Andreas Evdokio