A distinct subset of podoplanin (gp38) expressing F4/80+ macrophages mediate phagocytosis and are induced following zymosan peritonitis

AbstractMacrophages are important tissue resident cells that regulate the dynamics of inflammation. However, they are strikingly heterogeneous. During studies looking at podoplanin (gp38) expression on stromal cells in the murine spleen and peritoneal cavity we unexpectedly discovered that podoplanin was expressed on a subset of F4/80+ macrophages; a subset which we have termed fibroblastic macrophages (FM). These cells function as phagocytes in vitro as measured by bead mediated phagocytosis assays. FM also exist at high frequency in the peritoneal cavity and in zymosan induced peritonitis in vivo. These FM represent a unique subgroup of F4/80+ macrophages and their presence in the inflamed peritoneum suggests that they play a role in zymosan induced peritonitis

Formative study of mobile phone use for family planning among young people in Sierra Leone : global systematic survey

Background: Teenage pregnancy remains high with low contraceptive prevalence among adolescents (aged 15-19 years) in Sierra Leone. Stakeholders leverage multiple strategies to address the challenge. Mobile technology is pervasive and presents an opportunity to reach young people with critical sexual reproductive health and family planning messages.Objective: The objectives of this research study are to understand how mobile health (mHealth) is used for family planning, understand phone use habits among young people in Sierra Leone, and recommend strategies for mobile-enabled dissemination of family planning information at scale.Methods: This formative research study was conducted using a systematic literature review and focus group discussions (FGDs). The literature survey assessed similar but existing interventions through a systematic search of 6 scholarly databases. Cross-sections of young people of both sexes and their support groups were engaged in 9 FGDs in an urban and a rural district in Sierra Leone. The FGD data were qualitatively analyzed using MAXQDA software (VERBI Software GmbH) to determine appropriate technology channels, content, and format for different user segments.Results: Our systematic search results were categorized using Grading of Recommended Assessment and Evaluation (GRADE) into communication channels, audiovisual messaging format, purpose of the intervention, and message direction. The majority of reviewed articles report on SMS-based interventions. At the same time, most intervention purposes are for awareness and as helpful resources. Our survey did not find documented use of custom mHealth apps for family planning information dissemination. From the FGDs, more young people in Sierra Leone own basic mobile phones than those that have feature capablilities or are smartphone. Young people with smartphones use them mostly for WhatsApp and Facebook. Young people widely subscribe to the social media–only internet bundle, with the cost ranging from 1000 leones (US $0.11) to 1500 leones (US$0.16) daily. Pupils in both districts top-up their voice call and SMS credit every day between 1000 leones (US $0.11) and 5000 leones (US$0.52).Conclusions: mHealth has facilitated family planning information dissemination for demand creation around the world. Despite the widespread use of social and new media, SMS is the scalable channel to reach literate and semiliterate young people. We have cataloged mHealth for contraceptive research to show SMS followed by call center as widely used channels. Jingles are popular for audiovisual message formats, mostly delivered as either push or pull only message directions (not both). Interactive voice response and automated calls are best suited to reach nonliterate young people at scale.peer-reviewe

An RxLR effector from phytophthora infestans prevents re-localisation of two plant NAC transcription factors from the endoplasmic reticulum to the nucleus

The plant immune system is activated following the perception of exposed, essential and invariant microbial molecules that are recognised as non-self. A major component of plant immunity is the transcriptional induction of genes involved in a wide array of defence responses. In turn, adapted pathogens deliver effector proteins that act either inside or outside plant cells to manipulate host processes, often through their direct action on plant protein targets. To date, few effectors have been shown to directly manipulate transcriptional regulators of plant defence. Moreover, little is known generally about the modes of action of effectors from filamentous (fungal and oomycete) plant pathogens. We describe an effector, called Pi03192, from the late blight pathogen Phytophthora infestans, which interacts with a pair of host transcription factors at the endoplasmic reticulum (ER) inside plant cells. We show that these transcription factors are released from the ER to enter the nucleus, following pathogen perception, and are important in restricting disease. Pi03192 prevents the plant transcription factors from accumulating in the host nucleus, revealing a novel means of enhancing host susceptibility

Genomic, Lipidomic and Metabolomic Analysis of Cyclooxygenase-null Cells: Eicosanoid Storm, Cross Talk, and Compensation by COX-1

AbstractThe constitutively-expressed cyclooxygenase 1 (COX-1) and the inducible COX-2 are both involved in the conversion of arachidonic acid (AA) to prostaglandins (PGs). However, the functional roles of COX-1 at the cellular level remain unclear. We hypothesized that by comparing differential gene expression and eicosanoid metabolism in lung fibroblasts from wild-type (WT) mice and COX-2-/- or COX-1-/- mice may help address the functional roles of COX-1 in inflammation and other cellular functions. Compared to WT, the number of specifically-induced transcripts were altered descendingly as follows: COX-2-/->COX-1-/->WT+IL-1β. COX-1-/- or COX-2-/- cells shared about 50% of the induced transcripts with WT cells treated with IL-1β, respectively. An interactive “anti-inflammatory, proinflammatory, and redox-activated” signature in the protein–protein interactome map was observed in COX-2-/- cells. The augmented COX-1 mRNA (in COX-2-/- cells) was associated with the upregulation of mRNAs for glutathione S-transferase (GST), superoxide dismutase (SOD), NAD(P)H dehydrogenase quinone 1 (NQO1), aryl hydrocarbon receptor (AhR), peroxiredoxin, phospholipase, prostacyclin synthase, and prostaglandin E synthase, resulting in a significant increase in the levels of PGE2, PGD2, leukotriene B4 (LTB4), PGF1α, thromboxane B2 (TXB2), and PGF2α. The COX-1 plays a dominant role in shifting AA toward the LTB4 pathway and anti-inflammatory activities. Compared to WT, the upregulated COX-1 mRNA in COX-2-/- cells generated an “eicosanoid storm”. The genomic characteristics of COX-2-/- is similar to that of proinflammatory cells as observed in IL-1β induced WT cells. COX-1-/- and COX-2-/- cells exhibited compensation of various eicosanoids at the genomic and metabolic levels

Measuring the predictability of life outcomes with a scientific mass collaboration.

How predictable are life trajectories? We investigated this question with a scientific mass collaboration using the common task method; 160 teams built predictive models for six life outcomes using data from the Fragile Families and Child Wellbeing Study, a high-quality birth cohort study. Despite using a rich dataset and applying machine-learning methods optimized for prediction, the best predictions were not very accurate and were only slightly better than those from a simple benchmark model. Within each outcome, prediction error was strongly associated with the family being predicted and weakly associated with the technique used to generate the prediction. Overall, these results suggest practical limits to the predictability of life outcomes in some settings and illustrate the value of mass collaborations in the social sciences

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Transcriptomic analyses of murine resolution-phase macrophages

Macrophages are either classically (M1) or alternatively-activated (M2). While this nomenclature was generated from monocyte-derived macrophages treated in vitro with defined cytokine stimuli, the phenotype of in vivo-derived macrophages is less understood. We completed Affymetrix-based transcriptomic analysis of macrophages from the resolution-phase of a zymosan-induced peritonitis. Compared to macrophages from hyper-inflamed mice possessing a pro-inflammatory nature as well as naive macrophages from the un-inflamed peritoneum, resolution-phase macrophages (rM) are similar to monocytes-derived dendritic cells (DC), being CD209a positive but lack CD11c. They are enriched for antigen processing/presentation (MHC-II [H2-Eb1, H2-Ab1, H2-Ob, H2-Aa], CD74, CD86), secrete T- and B-lymphocyte chemokines (Xcl1, Ccl5, Cxcl13) as well as factors that enhance macrophage/DC development and promote DC/T cells synapse formation (Clec2i, Tnfsf4, Clcf1). rM are also enriched for cell cycle/proliferation genes as well as Alox15, Timd4 and Tgfb2, key systems in the termination of leukocyte trafficking and clearance of inflammatory cells. Finally, comparison with in vitro-derived M1/M2 shows that rM are neither classically nor alternatively activated but possess aspects of both definitions consistent with an immune regulatory phenotype. We propose that macrophage in situ cannot be rigidly categorised as they can express many shades of the inflammatory spectrum determined by tissue, stimulus and phase-of-inflammation