Eukaryotic DNA Polymerases: Proposal for a Revised Nomenclature

Pol polymeraseIn 1975, a Greek letter nomenclature system was introduced to designate DNA polymerases from mammalian cells (1). Ten years ago, progress in the biochemical analysis of eukaryotic DNA polymerases and in the isolation of their genes, particularly in the yeast Saccharomyces cerevisiae, necessitated a revision of the Greek letter nomenclature system and an expansion to include all eukaryotic organisms (2). Until a few years ago, this system sufficed to designate the six known DNA polymerases α, β, γ, δ, ε, and ζ

The violent frontline: space, ethnicity and confronting the state in Edwardian Spitalfields and 1980s Brixton

This article discusses in comparative terms the relationship between space, ethnic identity, subaltern status and anti-state violence in twentieth century London. It does so by comparing two examples in which the control of the state, as represented by the Metropolitan Police, was challenged by minority groups through physical force. It will examine the Spitalfields riots of 1906, which began as strike action by predominantly Jewish bakers and escalated into a general confrontation between the local population and the police, and the Brixton riots of 1981, a response to endemic police harassment of mainly Caribbean youth and long-term economic discrimination in that area of South London. It will begin by dissecting the association of physical metropolitan space with the diasporic ‘other’ in the Edwardian East End and post-consensus South London, and how this ‘othering’ was influenced both by the state and the anti-migrant far right. It will then interrogate the difficult relationship between the Metropolitan Police and Jewish and Caribbean working class communities, and how this deteriorating relationship exploded into in extreme violence in 1906 and 1981. The article will conclude by assessing how the relationships between space, identity and violence influenced long-term national and communal narratives of Jewish and Caribbean interactions with the British state

TRIALS STUDY PROTOCOL Open Access

A double-blind, randomized controlled trial to compare the effect of biannual peripheral magnetic resonance imaging, radiography and standard of care disease progression monitoring on pharmacotherapeutic escalation in rheumatoid and undifferentiated inflammatory arthritis: study protocol for a randomized controlled tria

Trading Places: How Do DNA Polymerases Switch during Translesion DNA Synthesis?

The replicative bypass of base damage in DNA (translesion DNA synthesis [TLS]) is a ubiquitous mechanism for relieving arrested DNA replication. The process requires multiple polymerase switching events during which the high-fidelity DNA polymerase in the replication machinery arrested at the primer terminus is replaced by one or more polymerases that are specialized for TLS. When replicative bypass is fully completed, the primer terminus is once again occupied by high-fidelity polymerases in the replicative machinery. This review addresses recent advances in our understanding of DNA polymerase switching during TLS in bacteria such as E. coli and in lower and higher eukaryotes

Bandgap Engineering of Coal-Derived Graphene Quantum Dots

Bandgaps of photoluminescent graphene quantum dots (GQDs) synthesized from anthracite have been engineered by controlling the size of GQDs in two ways: either chemical oxidative treatment and separation by cross-flow ultrafiltration, or by a facile one-step chemical synthesis using successively higher temperatures to render smaller GQDs. Using these methods, GQDs were synthesized with tailored sizes and bandgaps. The GQDs emit light from blue-green (2.9 eV) to orange-red (2.05 eV), depending on size, functionalities and defects. These findings provide a deeper insight into the nature of coal-derived GQDs and demonstrate a scalable method for production of GQDs with the desired bandgaps

TERT promoter mutations and other prognostic factors in patients with advanced urothelial carcinoma treated with an immune checkpoint inhibitor.

Immune checkpoint inhibitors (ICI) can achieve durable responses in a subset of patients with locally advanced or metastatic urothelial carcinoma (aUC). The use of tumor genomic profiling in clinical practice may help suggest biomarkers to identify patients most likely to benefit from ICI. We undertook a retrospective analysis of patients treated with an ICI for aUC at a large academic medical center. Patient clinical and histopathological variables were collected. Responses to treatment were assessed for all patients with at least one post-baseline scan or clear evidence of clinical progression following treatment start. Genomic profiling information was also collected for patients when available. Associations between patient clinical/genomic characteristics and objective response were assessed by logistic regression; associations between the characteristics and progression-free survival (PFS) and overall survival (OS) were examined by Cox regression. Multivariable analyses were performed to identify independent prognostic factors. We identified 119 aUC patients treated with an ICI from December 2014 to January 2020. Genomic profiling was available for 78 patients. Overall response rate to ICI was 29%, and median OS (mOS) was 13.4 months. Favorable performance status at the start of therapy was associated with improved OS (HR 0.46, p=0.025) after accounting for other covariates. Similarly, the presence of a TERT promoter mutation was an independent predictor of improved PFS (HR 0.38, p=0.012) and OS (HR 0.32, p=0.037) among patients who had genomic profiling available. Patients with both a favorable performance status and a TERT promoter mutation had a particularly good prognosis with mOS of 21.1 months as compared with 7.5 months in all other patients (p=0.03). The presence of a TERT promoter mutation was an independent predictor of improved OS in a cohort of aUC patients treated with an ICI who had genomic data available. Most of the clinical and laboratory variables previously shown to be prognostic in aUC patients treated with chemotherapy did not have prognostic value among patients treated with an ICI. Genomic profiling may provide important prognostic information and affect clinical decision making in this patient population. Validation of these findings in prospective patient cohorts is needed