Deciphering the role of Epstein-Barr virus in the pathogenesis of T and NK cell lymphoproliferations

Epstein-Barr virus (EBV) is a highly successful herpesvirus, colonizing more than 90% of the adult human population worldwide, although it is also associated with various malignant diseases. Primary infection is usually clinically silent, and subsequent establishment of latency in the memory B lymphocyte compartment allows persistence of the virus in the infected host for life. EBV is so markedly B-lymphotropic when exposed to human lymphocytes in vitro that the association of EBV with rare but distinct types of T and NK cell lymphoproliferations was quite unexpected. Whilst relatively rare, these EBV-associated T and NK lymphoproliferations can be therapeutically challenging and prognosis for the majority of patients is dismal. In this review, we summarize the current knowledge on the role of EBV in the pathogenesis of these tumours, and the implications for treatment. \ud \u

GOLPH3 keeps the Golgi residents at home

In this issue of JCB, Welch et al. (2021. J. Cell Biol. https://doi.org/10.1083/jcb.202106115) show that GOLPH3 mediates the sorting of numerous Golgi proteins into recycling COPI transport vesicles. This explains how many resident proteins are retained at the Golgi and reveals a key role for GOLPH3 in maintaining Golgi homeostasis

The Planckian Conspiracy: String Theory and the Black Hole Information Paradox

It has been argued that the consistency of quantum theory with black hole physics requires nonlocality not present in ordinary effective field theory. We examine the extent to which such nonlocal effects show up in the perturbative S-matrix of string theory.Comment: 13 pages, harvma

A disruptive influence? "Prevent-ing" problems and countering violent extremism policy in practice

This article describes how disrupting the activities of suspected violent extremists has become an increasingly significant construct in the policy and practice of the Prevent strand of UK Counter-Terrorism. Informed by empirical data collected during semi-structured interviews with police officers involved in conducting disruptions and members of the communities where these occurred, blended with a limited amount of field observation, the analysis documents how and why a logic of disruption has assumed increasing prominence in counter terrorism work. In respect of police interventions in particular, implementing disruptions, rather than pursuing fully-fledged prosecutions, represents a pragmatic way of reconciling increasing demand with limited resources, as well as managing some of the difficulties of translating intelligence into legal evidence. Conceptualized in this way, the analysis positions disruption as a distinctive mode of crime prevention; one premised upon logics of near-event interdiction. As such, it is understood as rather different in its operations and functions to other forms of “early intervention” that are increasingly prominent in much contemporary crime prevention policy. By focusing upon how specific Prevent interventions are implemented and performed this analysis makes a particular contribution to our knowledge of counter terrorism work. This reflects the fact that most previous studies of Prevent and other countering violent extremism programs have provided analyses of community perceptions and reactions to policing and the policy frame, rather than the configuration of the interventions themselves

Early Scottish Monasteries and Prehistory: A Preliminary Dialogue

Reflecting oil the diversity of monastic attributes found in the east and west of Britain, the author proposes that prehistoric ritual practice was influential on monastic form. An argument is advanced that this was not based solely oil inspiration Front the landscape, nor oil conservative tradition, but oil the intellectual reconciliation of Christian and non-Christian ideas, with disparate results that account. for the differences in monumentality. Among more general matters tentatively credited with a prehistoric root are the cult of relics, the tonsure and the date of Easter

Long-term adherence to healthy dietary guidelines and chronic inflammation in the prospective Whitehall II study

Background Inflammation plays an important role in the cause of cardiovascular diseases and may contribute to the association linking an unhealthy diet to chronic age-related diseases. However, to date the long-term associations between diet and inflammation have been poorly described. Our aim was to assess the extent to which adherence to a healthy diet and dietary improvements over a 6-year exposure period prevented subsequent chronic inflammation over a 5-year follow-up in a large British population of men and women. Methods Data were drawn from 4600 adults (mean ± standard deviation, age 49.6 ± 6.1 years, 28% were women) from the prospective Whitehall cohort II study. Adherence to a healthy diet was measured using Alternative Healthy Eating Index (AHEI) scores in 1991-1993 (50.7 ± 11.9 points) and 1997-1999 (51.6 ± 12.4 points). Chronic inflammation, defined as average levels of serum interleukin-6 from 2 measures 5 years apart, was assessed in 1997-1999 and 2002-2004. Results After adjustment for sociodemographic factors, health behaviors, and health status, participants who maintained a high AHEI score (ie, a healthy diet, n = 1736, 37.7%) and those who improved this score over time (n = 681, 14.8%) showed significantly lower mean levels of interleukin-6 (1.84 pg/mL, 95% confidence interval [CI], 1.71-1.98 and 1.84 pg/mL, 95% CI, 1.70-1.99, respectively) than those who had a low AHEI score (n = 1594, 34.6%) over the 6-year exposure period (2.01 pg/mL, 95% CI, 1.87-2.17). Conclusions These data suggest that maintaining and improving adherence to healthy dietary recommendations may reduce the risk of long-term inflammation.</p

A performance evaluation of commercial fibrinogen reference preparations and assays for Clauss and PT-derived fibrinogen

The wide availability of fibrinogen estimations based on the prothrombin time (PT-Fg) has caused concern about the variability and clinical utility of fibrinogen assays. In a multi-centre study, we investigated fibrinogen assays using various reagents and analysers, Clauss assays generally gave good agreement, although one reagent gave 15-30% higher values in DIC and thrombolysis. Two commercial reference preparations had much lower potencies than the manufacturers declared, and plasma turbidity influenced parallelism in some Clauss assays, PT-Fg assays gave higher values than Clauss and showed calibrant dependent effects, the degree of disparity correlating with calibrant and test sample turbidity. Analyser and thromboplastin dependent differences were noted. The relationship between Clauss and PT-Fg assays was sigmoid, and the plateau of maximal PT-Fg differed by about 2 g/l between reagents. ELISA and immunonephelometric assays correlated well, but with a high degree of scatter. Antigen levels were higher than Clauss, but slightly lower than PT-Fg assays, which appeared to be influenced by degraded fibrinogen. Clauss assays are generally reproducible between centres, analysers and reagents, but PT-Fg assays are not reliable in clinical settings

Discovery and characterization of potent, efficacious, orally available antimalarial Plasmepsin X inhibitors and preclinical safety assessment of UCB7362

Plasmepsin X (PMX) is an essential aspartyl protease controlling malaria parasite egress and invasion of erythrocytes, development of functional liver merozoites (prophylactic activity), and blocking transmission to mosquitoes, making it a potential multistage drug target. We report the optimization of an aspartyl protease binding scaffold and the discovery of potent, orally active PMX inhibitors with in vivo antimalarial efficacy. Incorporation of safety evaluation early in the characterization of PMX inhibitors precluded compounds with a long human half-life