A Consensus Definitive Classification of Scavenger Receptors and Their Roles in Health and Disease

Scavenger receptors constitute a large family of proteins that are structurally diverse and participate in a wide range of biological functions. These receptors are expressed predominantly by myeloid cells and recognize a diverse variety of ligands including endogenous and modified host-derived molecules and microbial pathogens. There are currently eight classes of scavenger receptors, many of which have multiple names, leading to inconsistencies and confusion in the literature. To address this problem, a workshop was organized by theUnited StatesNational Institute of Allergy and Infectious Diseases, National Institutes of Health, to help develop a clear definition of scavenger receptors and a standardized nomenclature based on that definition. Fifteen experts in the scavenger receptor field attended the workshop and, after extensive discussion, reached a consensus regarding the definition of scavenger receptors and a proposed scavenger receptor nomenclature. Scavenger receptors were defined as cell surface receptors that typically bind multiple ligands and promote the removal of nonself or altered-self targets. They often function by mechanisms that include endocytosis, phagocytosis, adhesion, and signaling that ultimately lead to the elimination of degraded or harmful substances. Based on this definition, nomenclature and classification of these receptors into 10 classes were proposed. This classification was discussed at three national meetings and input from participants at these meetings was requested. The following manuscript is a consensus statement that combines the recommendations of the initial workshop and incorporates the input received from the participants at the three national meetings

VprBP Is Required for Efficient Editing and Selection of Igκ+ B Cells, but Is Dispensable for Igλ+ and Marginal Zone B Cell Maturation and Selection

Abstract B cell development past the pro-B cell stage in mice requires the Cul4-Roc1-DDB1 E3 ubiquitin ligase substrate recognition subunit VprBP. Enforced Bcl2 expression overcomes defects in distal VH-DJH and secondary Vκ-Jκ rearrangement associated with VprBP insufficiency in B cells and substantially rescues maturation of marginal zone and Igλ+ B cells, but not Igκ+ B cells. In this background, expression of a site-directed Igκ L chain transgene increases Igκ+ B cell frequency, suggesting VprBP does not regulate L chain expression from a productively rearranged Igk allele. In site-directed anti-dsDNA H chain transgenic mice, loss of VprBP function in B cells impairs selection of Igκ editor L chains typically arising through secondary Igk rearrangement, but not selection of Igλ editor L chains. Both H and L chain site-directed transgenic mice show increased B cell anergy when VprBP is inactivated in B cells. Taken together, these data argue that VprBP is required for the efficient receptor editing and selection of Igκ+ B cells, but is largely dispensable for Igλ+ B cell development and selection, and that VprBP is necessary to rescue autoreactive B cells from anergy induction.</jats:p

A Population-Based Study of Morbidity After Pancreatic Cancer Diagnosis

Background: Pancreatic cancer is an aggressive disease characterized by early and relentless tumor spread, thus leading healthcare providers to consider it a “distant disease.” However, local pancreatic tumor progression can lead to substantial morbidity. This study defines the long-term morbidity from local and nonlocal disease progression in a large population-based cohort. Methods: A total of 21,500 Medicare beneficiaries diagnosed with pancreatic cancer in 2000 through 2011 were identified. Hospitalizations were attributed to complications of either local disease (eg, biliary disorder, upper gastrointestinal ulcer/bleed, pain, pancreas-related, radiation toxicity) or nonlocal/distant disease (eg, thromboembolic events, cytopenia, dehydration, nausea/vomiting/motility problem, malnutrition and cachexia, ascites, pathologic fracture, and chemotherapy-related toxicity). Competing risk analyses were used to identify predictors of hospitalization. Results: Of the total cohort, 9,347 patients (43.5%) were hospitalized for a local complication and 13,101 patients (60.9%) for a nonlocal complication. After adjusting for the competing risk of death, the 12-month cumulative incidence of hospitalization from local complications was highest in patients with unresectable disease (53.1%), followed by resectable (39.5%) and metastatic disease (33.7%) at diagnosis. For nonlocal complications, the 12-month cumulative incidence was highest in patients with metastatic disease (57.0%), followed by unresectable (56.8%) and resectable disease (42.8%) at diagnosis. Multivariable analysis demonstrated several predictors of hospitalization for local and nonlocal complications, including age, race/ethnicity, location of residence, disease stage, tumor size, and diagnosis year. Radiation and chemotherapy had minimal impact on the risk of hospitalization. Conclusions: Despite the widely known predilection of nonlocal/distant disease spread in pancreatic cancer, local tumor progression also leads to substantial morbidity and frequent hospitalization.</jats:p

Weight gain on androgen deprivation therapy: which patients are at highest risk?

Abstract not availableDaniel M. Seible, Xiangmei Gu, Andrew S. Hyatt, Clair J. Beard, Toni K. Choueiri, Jason A.Efstathiou, David T.Miyamoto, TimurMitin, Neil E.Martin, Christopher J.Sweeney, Quoc-Dien Trinh, Joshua A. Beckman, Shehzad Basaria, and Paul L. Nguye

Strength and Deformability of Concrete Members Wrapped with Fibre-Reinforced Polymer Composites with a Large Rupture Strain

Recently, a new category of fibre-reinforced polymer (FRP) composites has emerged as a potential alternative to conventional FRPs, whose reinforcing fibres are usually made of carbon, glass or aramid. These new FRP composites are made of Polyacetal fibres (PAF), Polyethylene Naphthalate (PEN) fibres, or Polyethylene Terephthalate (PET) fibres, which are characterised by a large tensile rupture strain (LRS) (usually larger than 5%) and a relatively low elastic modulus. Compared to conventional FRPs, LRS FRPs are much cheaper and more environmentally friendly since they can be made of recycled plastics (e.g. PET bottles). This paper presents a summary of several completed/on-going research projects conducted in the authors’ research groups on the structural performance of concrete members wrapped with LRS FRP composites, including the compressive behaviour of LRS FRP-confined concrete, the deformability of RC columns confined or internally shear-reinforced with LRS FRP composites under seismic loading, and the shear strengthening of RC members with LRS FRP composites. It is demonstrated that, despite their relatively low elastic modulus, LRS FRP composites can become a very attractive option particularly for the seismic retrofit of RC columns. Besides, LRS FRP composites also have a good potential to be used as the internal shear reinforcement in RC members since their use can lead to a ­ductile shear failure.Department of Civil and Environmental Engineerin