Tufts University

About: Tufts University is a education organization based out in Medford, Massachusetts, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 32800 authors who have published 66881 publications receiving 3451152 citations. The organization is also known as: Tufts College & Universitatis Tuftensis.

Roles of Cyclic Diguanylate in the Regulation of Bacterial Pathogenesis

Abstract: Cyclic diguanylate (c-di-GMP) is a bacterial second messenger of growing recognition involved in the regulation of a number of complex physiological processes. This review describes the biosynthesis and hydrolysis of c-di-GMP and several mechanisms of regulation of c-di-GMP metabolism. The contribution of c-di-GMP to regulating biofilm formation and motility, processes that affect pathogenesis of many bacteria, is described, as is c-di-GMP regulation of virulence gene expression. Finally, ways in which c-di-GMP may mediate these regulatory effects are proposed.

Bevacizumab plus Ipilimumab in Patients with Metastatic Melanoma

Abstract: Ipilimumab improves survival in advanced melanoma and can induce immune-mediated tumor vasculopathy. Besides promoting angiogenesis, vascular endothelial growth factor (VEGF) suppresses dendritic cell maturation and modulates lymphocyte endothelial trafficking. This study investigated the combination of CTLA4 blockade with ipilimumab and VEGF inhibition with bevacizumab. Patients with metastatic melanoma were treated in four dosing cohorts of ipilimumab (3 or 10 mg/kg) with four doses at 3-week intervals and then every 12 weeks, and bevacizumab (7.5 or 15 mg/kg) every 3 weeks. Forty-six patients were treated. Inflammatory events included giant cell arteritis (n = 1), hepatitis (n = 2), and uveitis (n = 2). On-treatment tumor biopsies revealed activated vessel endothelium with extensive CD8(+) and macrophage cell infiltration. Peripheral blood analyses demonstrated increases in CCR7(+/-)/CD45RO(+) cells and anti-galectin antibodies. Best overall response included 8 partial responses, 22 instances of stable disease, and a disease-control rate of 67.4%. Median survival was 25.1 months. Bevacizumab influences changes in tumor vasculature and immune responses with ipilimumab administration. The combination of bevacizumab and ipilimumab can be safely administered and reveals VEGF-A blockade influences on inflammation, lymphocyte trafficking, and immune regulation. These findings provide a basis for further investigating the dual roles of angiogenic factors in blood vessel formation and immune regulation, as well as future combinations of antiangiogenesis agents and immune checkpoint blockade.

Entanglement Breaking Channels

Abstract: This paper studies the class of stochastic maps, or channels, for which (I⊗Φ)(Γ) is always separable (even for entangled Γ). Such maps are called entanglement breaking, and can always be written in the form Φ(ρ)=∑kRkTrFkρ where each Rk is a density matrix and Fk>0. If, in addition, Φ is trace-preserving, the {Fk} must form a positive operator valued measure (POVM). Some special classes of these maps are considered and other characterizations given. Since the set of entanglement-breaking trace-preserving maps is convex, it can be characterized by its extreme points. The only extreme points of the set of completely positive trace preserving maps which are also entanglement breaking are those known as classical-quantum or CQ. However, for d≥3, the set of entanglement breaking maps has additional extreme points which are not extreme CQ maps.

Chaperone-Mediated Autophagy

Abstract: Chaperone-mediated autophagy (CMA) is a lysosomal pathway of proteolysis that is responsible for the degradation of 30% of cytosolic proteins under conditions of prolonged nutrient deprivation. Molecular chaperones in the cytosol and in the lysosomal lumen stimulate this proteolytic pathway. The molecular chaperones in the cytosol unfold substrate proteins prior to their translocation across the lysosomal membrane, while the chaperone in the lysosomal lumen is probably required to pull the substrate protein across the lysosomal membrane. A critical component for CMA is a receptor in the lysosomal membrane, the lysosome-associated membrane protein (LAMP) type 2A. LAMP-2A levels in the lysosomal membrane can be increased by reduced degradation and/or redistribution from the lysosomal lumen to the lysosomal membrane. Recent results show that CMA is also activated by oxidative stress, and in this case LAMP-2A is increased due to transcriptional regulation. CMA can be reduced by inhibitors of glucose-6-phosphate dehydrogenase and of the heat shock protein of 90 kDa. Reduction of levels of LAMP-2A using RNAi strategies reduces CMA activity, but macroautophagy is activated as a result. The decrease in CMA causes cells to be more susceptibile to oxidative and other stresses. LAMP-2A in the lysosomal membrane can be sequestered into cholesterol-rich microdomains where it is inactive. When CMA is activated, LAMP-2A moves out of these domains. The reduced CMA in aging is due to reduced LAMP-2A in the lysosomal membrane. This reduction is caused by an age-related increased degradation of LAMP-2A and an age-related reduced ability of LAMP-2A to reinsert into the lysosomal membrane. These findings reveal a rich complexity of mechanisms to control CMA activity.