Scavenger Receptors: Promiscuous Players during Microbial Pathogenesis

Innate immunity is the most broadly effective host defense, being essential to clear the majority of microbial infections. Scavenger Receptors comprise a family of sensors expressed in a multitude of host cells, whose dual role during microbial pathogenesis gained importance over recent years. SRs regulate the recruitment of immune cells and control both host inflammatory response and bacterial load. In turn, pathogens have evolved different strategies to overcome immune response, avoid recognition by SRs and exploit them to favor infection. Here, we discuss the most relevant findings regarding the interplay between SRs and pathogens, discussing how these multifunctional proteins recognize a panoply of ligands and act as bacterial phagocytic receptors.This work received funding from Norte-01–0145-FEDER-000012– Structured program on bioengineered therapies for infectious diseases and tissue regeneration, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL Partnership Agreement, through the European Regional Development Fund (FEDER). R.P received an FCT Doctoral Fellowship [SFRH/BD/89542/2012] through FCT/MEC co-funded by QREN and POPH (Programa Operacional Potencial Humano). SS was supported by FCT Investigator program (COMPETE, POPH, and FCT)

The structure of blocks with a Klein four defect group

We prove Erdmann’s conjecture [16] stating that every block with a Klein four defect group has a simple module with trivial source, and deduce from this that Puig’s finiteness conjecture holds for source algebras of blocks with a Klein four defect group. The proof uses the classification of finite simple groups

Epithelial Keratins Modulate cMet Expression and Signaling and Promote InlB-Mediated Listeria monocytogenes Infection of HeLa Cells

The host cytoskeleton is a major target for bacterial pathogens during infection. In particular, pathogens usurp the actin cytoskeleton function to strongly adhere to the host cell surface, to induce plasma membrane remodeling allowing invasion and to spread from cell to cell and disseminate to the whole organism. Keratins are cytoskeletal proteins that are the major components of intermediate filaments in epithelial cells however, their role in bacterial infection has been disregarded. Here we investigate the role of the major epithelial keratins, keratins 8 and 18 (K8 and K18), in the cellular infection by Listeria monocytogenes. We found that K8 and K18 are required for successful InlB/cMet-dependent L. monocytogenes infection, but are dispensable for InlA/E-cadherin-mediated invasion. Both K8 and K18 accumulate at InlB-mediated internalization sites following actin recruitment and modulate actin dynamics at those sites. We also reveal the key role of K8 and K18 in HGF-induced signaling which occurs downstream the activation of cMet. Strikingly, we show here that K18, and at a less extent K8, controls the expression of cMet and other surface receptors such TfR and integrin β1, by promoting the stability of their corresponding transcripts. Together, our results reveal novel functions for major epithelial keratins in the modulation of actin dynamics at the bacterial entry sites and in the control of surface receptors mRNA stability and expression.This work received funding from Norte-01-0145-FEDER-000012 - Structured program on bioengineered therapies for infectious diseases and tissue regeneration, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). Publication Fees were supported by ICBAS, University of Porto. RC received an FCT Doctoral Fellowship (SFRH/BD/90607/2012) and IP-C a FCT Post-Doctoral Fellowship (SFRH/BPD/107901/2015) through FCT/MEC co-funded by QREN and POPH (Programa Operacional Potencial Humano). SS was supported by FCT Investigator program (COMPETE, POPH, and FCT). We thank IBMC facilities for technical assistance

Stabilin-1 plays a protective role against Listeria monocytogenes infection through the regulation of cytokine and chemokine production and immune cell recruitment

Scavenger receptors are part of a complex surveillance system expressed by host cells to efficiently orchestrate innate immune response against bacterial infections. Stabilin-1 (STAB-1) is a scavenger receptor involved in cell trafficking, inflammation, and cancer; however, its role in infection remains to be elucidated. Listeria monocytogenes (Lm) is a major intracellular human food-borne pathogen causing severe infections in susceptible hosts. Using a mouse model of infection, we demonstrate here that STAB-1 controls Lm-induced cytokine and chemokine production and immune cell accumulation in Lm-infected organs. We show that STAB-1 also regulates the recruitment of myeloid cells in response to Lm infection and contributes to clear circulating bacteria. In addition, whereas STAB-1 appears to promote bacterial uptake by macrophages, infection by pathogenic Listeria induces the down regulation of STAB-1 expression and its delocalization from the host cell membrane. We propose STAB-1 as a new SR involved in the control of Lm infection through the regulation of host defense mechanisms, a process that would be targeted by bacterial virulence factors to promote infection.This work was funded by National Funds through FCT—Fundação para a Ciência e a Tecnologia, I.P., under the project UIDB/04293/2020. R.P. and J.P. were supported by doctoral fellowships from FCT (SFRH/BD/89542/2012 and SFRH/BD/86871/2012). S.S. was supported by the FCT in the framework of the CEEC-Institutional 2017 program. The authors acknowledge the support of i3S Scientific Platforms: Advanced Light Microscopy, member of the national infrastructure PPBI-Portuguese Platform of BioImaging (supported by POCI-01-0145-FEDER-022122), and Translational Cytometry Unit (Tracy);Fundação para a Ciência e a Tecnologia [UIDB/04293/2020]

CINÉTICA DE HIDROXILACIÓN Y OXIDACIÓN DE COMPUESTOS FENÓLICOS POR POLIFENOL OXIDASA DE UVA MONASTRELL (VITIS VINIFERA)

Monastrell grape polyphenol oxidase was purified, showing both activity towards monophenols and o-diphenols. The kinetic parameters, Km and optimal temperature, were evaluated in both activities. Cresolase activity presents a particular lag period, which may be modified by the temperature, enzyme concentration, the presence of o-diphenols and substrate concentration.La enzima polifenol oxidasa ha sido purificada a partir de uva Monastrell mostrando actividad tanto en la oxidación de monofenoles (cresolasa) como en la de o-difenoles (catecolasa). Los parámetros cinéticos, Km y temperatura óptima, han sido evaluados en ambas actividades. La actividad cresolasa presenta un período de retardo característico, que puede ser modificado por la temperatura, la concentración de enzima, la presencia de o-difenoles y la concentración de sustrato

Genome sequence of Listeria monocytogenes 2542, a serotype 4b strain from a cheese-related outbreak in Portugal

We report here the draft genome sequence of Listeria monocytogenes 2542, a serotype 4b clinical strain recovered from a placental sample during a cheese-related listeriosis outbreak in Portugal.Work done by T.C. and T.H. was supported by LOEWE Medical RNomics (B3) and theGermanCentre for Infection Research, Justus-Liebig University Giessen. Financial sup-port for R.M. and V.F. was provided by Fundação para a Ciência e a Tecnologia(FCT)through Ph.D. (SFRH/BD/71704/2010) and postdoctoral (SFRH/BPD/72617/2010) fellow-ships, respectively. Open-access publication was cofinanced by the NEWFOOD NORTE-01-0246-FEDER-000043 project supported by the Norte Portugal Regional OperationalProgramme (NORTE 2020), under the Portugal 2020 Partnership Agreement throughthe European Regional Development Fund (ERDF). We also acknowledge the scientificcollaboration under the FCT project UID/Multi/50016/2013

Listeria monocytogenes induces host DNA damage and delays the host cell cycle to promote infection

Listeria monocytogenes (Lm) is a human intracellular pathogen widely used to uncover the mechanisms evolved by pathogens to establish infection. However, its capacity to perturb the host cell cycle was never reported. We show that Lm infection affects the host cell cycle progression, increasing its overall duration but allowing consecutive rounds of division. A complete Lm infectious cycle induces a S-phase delay accompanied by a slower rate of DNA synthesis and increased levels of host DNA strand breaks. Additionally, DNA damage/replication checkpoint responses are triggered in an Lm dose-dependent manner through the phosphorylation of DNA-PK, H2A.X, and CDC25A and independently from ATM/ATR. While host DNA damage induced exogenously favors Lm dissemination, the override of checkpoint pathways limits infection. We propose that host DNA replication disturbed by Lm infection culminates in DNA strand breaks, triggering DNA damage/replication responses, and ensuring a cell cycle delay that favors Lm propagation.We thank AFCU and ALM facilities (IBMC), T Duarte (IBMC), G Almeida, and R Guimarães (ESB) for technical support, M Moroso for the LmΔinlB strain and members of Maiato’s and Sunkel’s lab (IBMC) for fruitful discussions. This work was funded by the Fundo Europeu de Desenvolvimento Regional (FEDER) through the Operational Competitiveness Programme (COMPETE) and by National funds through FCT (Fundação para a Ciência e Tecnologia) under the projects (PTDC/BIA-BCM/111215/2009FCOMP-01-0124- FEDER-014178, ERANet-Pathogenomics LISTRESS ERAPTG/0003/2010); Project “NORTE-07-0124-FEDER-000002- Host-Pathogen Interactions” co-funded by Programa Operacional Regional do Norte (ON.2, O Novo Norte), under the Quadro de Referência Estratégico Nacional (QREN), through the FEDER and by FCT. E.L., A.C.C., and R.P. were supported by FCT grants (SFRH/BPD/62926/2009, SFRH/BPD/88769/2012 and SFRH/BD/89542/2012, respectively), L.C. by ERASMUS program and S.S. by Ciência 2008 program (COMPETE, POPH, and FCT)

Breast cancer and childhood anthropometry: emerging hypotheses?

In this issue of Breast Cancer Research, Baer and colleagues report a strong protective effect of childhood and adolescent body fatness on premenopausal breast cancer risk based on a large prospective study. Methodological issues are discussed, as are tentative biological interpretations regarding the findings

Identifying ancient water availability through phytolith analysis: An experimental approach.

Water management was critical to the development of complex societies but such systems are often difficult, if not impossible, to recognise in the archaeological record, particularly in prehistoric communities when water management began. This is because early irrigation systems are likely to have been ephemeral and as such would no longer be visible in the archaeological record. We conducted a three year crop growing experiment in Jordan to test the hypothesis that phytoliths (opaline silica bodies formed in plants) can be used to detect the level of past water availability and hence be used as a source of information for inferring past water management. Over a three year period we grew native land races of six-row barley (Hordeum vulgare) and durum wheat (Triticum durum) at three crop growing stations in Jordan with the crops being subjected to different irrigation regimes. Seeds were sown in the autumn and the crops harvested in the spring. The plants were then exported to the University of Reading for phytolith processing. Our results show that while there were unknown factors that influenced phytolith production between years, at the higher levels, the ratio of ‘fixed’ form phytoliths (those formed as a result of genetically determined Silicon uptake) to ‘sensitive’ form phytoliths (those whose Silicon uptake is environmentally controlled) can be used to assess past water availability. Our study is the first large scale experimental project to test this method and take into account multiple variables that can affect phytolith production such as soil composition and chemistry, location, climate and evapotranspiration rates. Results from the cereals grown at two of the crop growing stations, Deir ‘Alla and Ramtha, which received between 100 millimetres and 250 millimetres rainfall per annum, demonstrate that if the ratio of fixed to sensitive phytolith forms is >1, the level of past water availability can be predicted with 80% confidence. Results from the crops grown at the other growing station, Kherbet as-Samra, which received less than 100 millimetres of rainfall per year show that if the ratio of fixed to sensitive forms is >0.5, the level of past water availability can be predicted with 99% confidence. This demonstrates that phytolith analysis can be used as a method to identify past water availability