Mass production of plastics started nearly 70 years ago and the production rate is expected to double over the next two decades. While serving many applications because of their durability, stability ...and low cost, plastics have deleterious effects on the environment. Plastic is known to release a variety of chemicals during degradation, which has a negative impact on biota. Here, we show that the most commonly used plastics produce two greenhouse gases, methane and ethylene, when exposed to ambient solar radiation. Polyethylene, which is the most produced and discarded synthetic polymer globally, is the most prolific emitter of both gases. We demonstrate that the production of trace gases from virgin low-density polyethylene increase with time, with rates at the end of a 212-day incubation of 5.8 nmol g-1 d-1 of methane, 14.5 nmol g-1 d-1 of ethylene, 3.9 nmol g-1 d-1 of ethane and 9.7 nmol g-1 d-1 of propylene. Environmentally aged plastics incubated in water for at least 152 days also produced hydrocarbon gases. In addition, low-density polyethylene emits these gases when incubated in air at rates ~2 times and ~76 times higher than when incubated in water for methane and ethylene, respectively. Our results show that plastics represent a heretofore unrecognized source of climate-relevant trace gases that are expected to increase as more plastic is produced and accumulated in the environment.
DNA polymerase (pol) β is a model polymerase involved in gap-filling DNA synthesis utilizing two metals to facilitate nucleotidyl transfer. Previous structural studies have trapped catalytic ...intermediates by utilizing substrate analogs (dideoxy-terminated primer or nonhydrolysable incoming nucleotide). To identify additional intermediates during catalysis, we now employ natural substrates (correct and incorrect nucleotides) and follow product formation in real time with 15 different crystal structures. We are able to observe molecular adjustments at the active site that hasten correct nucleotide insertion and deter incorrect insertion not appreciated previously. A third metal binding site is transiently formed during correct, but not incorrect, nucleotide insertion. Additionally, long incubations indicate that pyrophosphate more easily dissociates after incorrect, compared to correct, nucleotide insertion. This appears to be coupled to subdomain repositioning that is required for catalytic activation/deactivation. The structures provide insights into a fundamental chemical reaction that impacts polymerase fidelity and genome stability.
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•Crystal structures (15) of a DNAP captured during right or wrong nucleotide insertion•A third metal binding site observed during right, but not wrong, nucleotide insertion•A stable closed enzyme conformation is observed after right, but not wrong, insertion•Structures provide insights into the induced-fit mechanism for substrate selectivity
Time-resolved crystallography reveals key structural and biochemical distinctions between when a DNA polymerase inserts a correct versus an incorrect nucleotide, including the transient appearance of a third metal binding site.
Genomic DNA is susceptible to endogenous and environmental stresses that modify DNA structure and its coding potential. Correspondingly, cells have evolved intricate DNA repair systems to deter ...changes to their genetic material. Base excision DNA repair involves a number of enzymes and protein cofactors that hasten repair of damaged DNA bases. Recent advances have identified macromolecular complexes that assemble at the DNA lesion and mediate repair. The repair of base lesions generally requires five enzymatic activities: glycosylase, endonuclease, lyase, polymerase, and ligase. The protein cofactors and mechanisms for coordinating the sequential enzymatic steps of repair are being revealed through a range of experimental approaches. We discuss the enzymes and protein cofactors involved in eukaryotic base excision repair, emphasizing the challenge of integrating findings from multiple methodologies. The results provide an opportunity to assimilate biochemical findings with cell-based assays to uncover new insights into this deceptively complex repair pathway.
Skin and soft-tissue infections (SSTIs) are an important cause of morbidity and mortality among hospitalized patients and a major therapeutic challenge for clinicians. Although uncomplicated SSTIs ...are managed successfully on an outpatient basis, more serious infections extending to the subcutaneous tissue, fascia, or muscle require complex management. Early diagnosis, selection of appropriate antimicrobials, and timely surgical intervention are key to successful treatment. Surgical-site infections, an important category of SSTI, occur in approximately half a million patients in North America annually. SSTIs are also a potential source for life-threatening bacteremia and metastatic abscesses. Gram-positive organisms, such as Staphylococcus aureus and Streptococcus pyogenes, are the dominant organisms isolated early in the infectious process, whereas gram-negative organisms are found in chronic wounds. Methicillin-resistant S. aureus (MRSA) is a potential bloodstream invader that requires aggressive antimicrobial treatment and surgery. Recent concerns regarding vancomycin activity include heteroresistance in MRSA and increase in the minimum inhibitory concentrations (>1 or 2 μg/mL); however, alternative agents, such as telavancin, daptomycin, linezolid, ceftaroline, dalbavancin, oritavancin, and tedizolid, are now available for the treatment of severe MRSA infections. Here, we present a review of the epidemiology, etiology, and available treatment options for the management of SSTIs.
Emergency situations that cause damage to educational buildings or require the closure of schools due to unsafe health, environmental, or political conditions can be an unwelcomed interruption to ...education. Indeed, the recent COVID‐19 pandemic created the largest disruption of education in history, affecting 94% of the world's student population. In emergencies, technology is often utilised as part of a crisis response protocol by continuing education using emergency remote education (ERE). The purpose of this study is to determine how technology has been used to continue K‐12 learning remotely during an emergency. This systematic review included an aggregated and configurative synthesis to examine extant empirical work over eleven years, from January 2010 to December 2020. Following a rigorous, PRISMA selection process, 60 articles were included in the final analysis from 48 countries. Grounded coding of the strategies used for learning revealed the following categories: communication, delivery systems, student ERE readiness, partnerships, promoting student learning and engagement, and resources. Grounded coding of the technologies revealed that types of technologies used were divided into two major categories: Internet‐based and non‐Internet based, with the majority using Internet‐based technologies.
Practitioner notes
What is already known about this topic
The COVID‐19 pandemic has caused school closures across the globe and prevented in‐person school teaching.
The rapid shift to distance education in schools can be conceptualised as ‘emergency remote education’ (ERE).
Prior ERE research focused on bounded geographic locations where localised emergencies occurred.
What this paper adds
This provides the scholarly community with a unique systematic review of existing academic research on K‐12 ERE implementation in emergencies.
This provides aggregated data and analysis on the past 11 years of the types of emergencies, participants, subject domain, technologies used, and location information.
This provides findings of the types of remote teaching strategies involving technology used to continue K‐12 learning in emergency situations.
This provides a set of recommendations on ERE for teachers, school leaders, policy makers, and funders.
This provides researchers with a review of the field with identification of gaps and future research opportunities.
Implications for practice and/or policy
Recommendations regarding ERE are provided in this paper that will be of benefit to K‐12 teachers, school leaders policymakers, and funders in the continuing COVID‐19 pandemic and future emergencies.
The research gaps highlighted in this paper, such as the lack of studies conducted in low and low middle‐income countries, are presented with suggestions for much needed future research. This can lead to changes in practice and policy.
The expansion of trinucleotide repeat (TNR) sequences in human DNA is considered to be a key factor in the pathogenesis of more than 40 neurodegenerative diseases. TNR expansion occurs during DNA ...replication and also, as suggested by recent studies, during the repair of DNA lesions produced by oxidative stress. In particular, the oxidized guanine base 8-oxoguanine within sequences containing CAG repeats may induce formation of pro-expansion intermediates through strand slippage during DNA base excision repair (BER). In this article, we describe how oxidized DNA lesions are repaired by BER and discuss the importance of the coordinated activities of the key repair enzymes, such as DNA polymerase β, flap endonuclease 1 (FEN1) and DNA ligase, in preventing strand slippage and TNR expansion.
DNA polymerase (pol) β is a small eukaryotic DNA polymerase composed of two domains. Each domain contributes an enzymatic activity (DNA synthesis and deoxyribose phosphate lyase) during the repair of ...simple base lesions. These domains are termed the polymerase and lyase domains, respectively. Pol β has been an excellent model enzyme for studying the nucleotidyl transferase reaction and substrate discrimination at a molecular level. In this review, recent crystallographic studies of pol β in various liganded and conformational states during the insertion of right and wrong nucleotides as well as during the bypass of damaged DNA (apurinic sites and 8-oxoguanine) are described. Structures of these catalytic intermediates provide unexpected insights into mechanisms by which DNA polymerases enhance genome stability. These structures also provide an improved framework that permits computational studies to facilitate the interpretation of detailed kinetic analyses of this model enzyme.
This book identifies the 50 key scientific articles in the field of vascular and endovascular surgery. It provides commentary to each carefully selected paper and explains why these papers are so ...important, thus providing every surgeon with the foundation stones of knowledge in this fast- moving area.
There has been an exponential increase in the volume and quality of published research relating to vascular and endovascular surgery in recent decades. Amongst thousands of articles, a small fraction is truly "game changing". Such studies form the foundations of vascular surgery today and the selection of papers within this book provide the 50 landmark papers every 21st century vascular and endovascular surgeon needs to know.
A valuable reference not only to the established surgeon, but also to vascular surgery residents and trainees, as well as to more experienced surgeons as they continue to learn new techniques and approaches and to improve their knowledge of vascular disorders and treatments. The papers provide an evidence-based resource for those surgeons preparing for professional exams and may inspire clinicians to produce new research.
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