Complement Decay-Accelerating Factor is a modulator of influenza A virus lung immunopathology

Clearance of viral infections, such as SARS-CoV-2 and influenza A virus (IAV), must be fine-tuned to eliminate the pathogen without causing immunopathology. As such, an aggressive initial innate immune response favors the host in contrast to a detrimental prolonged inflammation. The complement pathway bridges innate and adaptive immune system and contributes to the response by directly clearing pathogens or infected cells, as well as recruiting proinflammatory immune cells and regulating inflammation. However, the impact of modulating complement activation in viral infections is still unclear. In this work, we targeted the complement decay-accelerating factor (DAF/CD55), a surface protein that protects cells from non-specific complement attack, and analyzed its role in IAV infections. We found that DAF modulates IAV infection in vivo, via an interplay with the antigenic viral proteins hemagglutinin (HA) and neuraminidase (NA), in a strain specific manner. Our results reveal that, contrary to what could be expected, DAF potentiates complement activation, increasing the recruitment of neutrophils, monocytes and T cells. We also show that viral NA acts on the heavily sialylated DAF and propose that the NA-dependent DAF removal of sialic acids exacerbates complement activation, leading to lung immunopathology. Remarkably, this mechanism has no impact on viral loads, but rather on the host resilience to infection, and may have direct implications in zoonotic influenza transmissions.This work was funded by Instituto Gulbenkian de Ciência (IGC), Fundac¸ão Calouste Gulbenkian (FCG) and Fundação para a Ciência e a Tecnologia (FCT) (PTDC/IMI-MIC/1142/2012). NBS was funded by Graduate Programme Science for Development (PGCD) and FCG. ZEVS was funded by FCT (SFRH/BD/52179/2013). CG was funded by FCT (POCI-01-0145-FEDER-29780, PTDC/MEDQUI/29780/2017). CAR was funded by FCT (POCI-01-0145-FEDER-007274, UID/BIM/04293). MJA is funded by FCT (2020.02373.CEECIND). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Seniors | Class of \u2712

PLEASE NOTE: Where applicable, the audio has been removed from this file due to copyrighted material. The garments shown here represent the Senior Class of \u2712. The garments were created in response to the following design challenges: Concepts in Color Collection: design a collection based on an individual concept with a focus on color and texture. Senior Thesis Collection: create a collection that reflects the essence and philosophies of your personal vision

Circulating KRAS G12D but not G12V is associated with survival in metastatic pancreatic ductal adenocarcinoma.

While high circulating tumor DNA (ctDNA) levels are associated with poor survival for multiple cancers, variant-specific differences in the association of ctDNA levels and survival have not been examined. Here we investigate KRAS ctDNA (ctKRAS) variant-specific associations with overall and progression-free survival (OS/PFS) in first-line metastatic pancreatic ductal adenocarcinoma (mPDAC) for patients receiving chemoimmunotherapy (PRINCE, NCT03214250), and an independent cohort receiving standard of care (SOC) chemotherapy. For PRINCE, higher baseline plasma levels are associated with worse OS for ctKRAS G12D (log-rank p = 0.0010) but not G12V (p = 0.7101), even with adjustment for clinical covariates. Early, on-therapy clearance of G12D (p = 0.0002), but not G12V (p = 0.4058), strongly associates with OS for PRINCE. Similar results are obtained for the SOC cohort, and for PFS in both cohorts. These results suggest ctKRAS G12D but not G12V as a promising prognostic biomarker for mPDAC and that G12D clearance could also serve as an early biomarker of response

Five Design Challenges

PLEASE NOTE: Where applicable, the audio has been removed from this file due to copyrighted material. The garments shown here represent the Classes of \u2712, \u2711 and \u2710 . The garments were created in response to the following five design challenges: Sophomores, Class of \u2712: Re-Innovative Design: explore the properties of recycled materials other than fabric while creating a wearable piece. Print Design Project create a garment that makes optimal use of an assigned printed fabric. Juniors, Class of \u2710: Knitwear Design: explore the properties of knits and design cut-and-sew and machine-knit garments. Tailoring Project: interpret traditional tailoring techniques to create a look with a jacket. Seniors, Class of \u2709: Coat Collection: design a collection with a coat as the key piece

Five Design Challenges

PLEASE NOTE: Where applicable, the audio has been removed from this file due to copyrighted material. The garments shown here represent the Classes of \u2713, \u2712 and \u2711 . The garments were created in response to the following five design challenges: Sophomores, Class of \u2713: Re-Innovative Design: explore the properties of recycled materials other than fabric while creating a wearable piece. Print Design Project create a garment that makes optimal use of printed fabric designed by a RISD Textiles student. Juniors, Class of \u2712: Knitwear Design: explore the properties of knits and design cut-and-sew and machine-knit garments. Tailoring Project: interpret traditional tailoring techniques to create a look with a jacket. Seniors, Class of \u2711: Cocktail Collection: design a collection of contemporary cocktail apparel in collaboration with the current RISD Museum exhibition Cocktail Culture: Ritual and Invention in American Fashion, 1920-1980

Racialized risk environments in a large sample of people who inject drugs in the United States

BACKGROUND: Substantial racial/ethnic disparities exist in HIV infection among people who inject drugs (PWID) in many countries. To strengthen efforts to understand the causes of disparities in HIV-related outcomes and eliminate them, we expand the “Risk Environment Model” to encompass the construct “racialized risk environments,” and investigate whether PWID risk environments in the United States are racialized. Specifically, we investigate whether black and Latino PWID are more likely than white PWID to live in places that create vulnerability to adverse HIV-related outcomes. METHODS: As part of the Centers for Disease Control and Prevention’s National HIV Behavioral Surveillance, 9,170 PWID were sampled from 19 metropolitan statistical areas (MSAs) in 2009. Self-reported data were used to ascertain PWID race/ethnicity. Using Census data and other administrative sources, we characterized features of PWID risk environments at four geographic scales (i.e., ZIP codes, counties, MSAs, and states). Means for each feature of the risk environment were computed for each racial/ethnic group of PWID, and were compared across racial/ethnic groups. RESULTS: Almost universally across measures, black PWID were more likely than white PWID to live in environments associated with vulnerability to adverse HIV-related outcomes. Compared to white PWID, black PWID lived in ZIP codes with higher poverty rates and worse spatial access to substance abuse treatment and in counties with higher violent crime rates. Black PWID were less likely to live in states with laws facilitating sterile syringe access (e.g., laws permitting over-the-counter syringe sales). Latino/white differences in risk environments emerged at the MSA level (e.g., Latino PWID lived in MSAs with higher drug-related arrest rates). CONCLUSION: PWID risk environments in the US are racialized. Future research should explore the implications of this racialization for racial/ethnic disparities in HIV-related outcomes, using appropriate methods

Towards complete and error-free genome assemblies of all vertebrate species.

High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for only a few non-microbial species1-4. To address this issue, the international Genome 10K (G10K) consortium5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling highly accurate and nearly complete reference genomes. Here we present lessons learned from generating assemblies for 16 species that represent six major vertebrate lineages. We confirm that long-read sequencing technologies are essential for maximizing genome quality, and that unresolved complex repeats and haplotype heterozygosity are major sources of assembly error when not handled correctly. Our assemblies correct substantial errors, add missing sequence in some of the best historical reference genomes, and reveal biological discoveries. These include the identification of many false gene duplications, increases in gene sizes, chromosome rearrangements that are specific to lineages, a repeated independent chromosome breakpoint in bat genomes, and a canonical GC-rich pattern in protein-coding genes and their regulatory regions. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an international effort to generate high-quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences

Towards complete and error-free genome assemblies of all vertebrate species.

High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for only a few non-microbial species1-4. To address this issue, the international Genome 10K (G10K) consortium5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling highly accurate and nearly complete reference genomes. Here we present lessons learned from generating assemblies for 16 species that represent six major vertebrate lineages. We confirm that long-read sequencing technologies are essential for maximizing genome quality, and that unresolved complex repeats and haplotype heterozygosity are major sources of assembly error when not handled correctly. Our assemblies correct substantial errors, add missing sequence in some of the best historical reference genomes, and reveal biological discoveries. These include the identification of many false gene duplications, increases in gene sizes, chromosome rearrangements that are specific to lineages, a repeated independent chromosome breakpoint in bat genomes, and a canonical GC-rich pattern in protein-coding genes and their regulatory regions. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an international effort to generate high-quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences