Simulation and analysis of in vitro DNA evolution

We study theoretically the in vitro evolution of a DNA sequence by binding to a transcription factor. Using a simple model of protein-DNA binding and available binding constants for the Mnt protein, we perform large-scale, realistic simulations of evolution starting from a single DNA sequence. We identify different parameter regimes characterized by distinct evolutionary behaviors. For each regime we find analytical estimates which agree well with simulation results. For small population sizes, the DNA evolutional path is a random walk on a smooth landscape. While for large population sizes, the evolution dynamics can be well described by a mean-field theory. We also study how the details of the DNA-protein interaction affect the evolution.Comment: 11 pages, 11 figures. Submitted to PNA

Roles of stiffness and excluded volume in DNA denaturation

The nature and the universal properties of DNA thermal denaturation are investigated by Monte Carlo simulations. For suitable lattice models we determine the exponent c describing the decay of the probability distribution of denaturated loops of length l, $P \sim l^{-c}$. If excluded volume effects are fully taken into account, c= 2.10(4) is consistent with a first order transition. The stiffness of the double stranded chain has the effect of sharpening the transition, if it is continuous, but not of changing its order and the value of the exponent c, which is also robust with respect to inclusion of specific base-pair sequence heterogeneities.Comment: RevTeX 4 Pages and 4 PostScript figures included. Final version as publishe

Why is the DNA Denaturation Transition First Order?

We study a model for the denaturation transition of DNA in which the molecules are considered as composed of a sequence of alternating bound segments and denaturated loops. We take into account the excluded-volume interactions between denaturated loops and the rest of the chain by exploiting recent results on scaling properties of polymer networks of arbitrary topology. The phase transition is found to be first order in d=2 dimensions and above, in agreement with experiments and at variance with previous theoretical results, in which only excluded-volume interactions within denaturated loops were taken into account. Our results agree with recent numerical simulations.Comment: Revised version. To appear in Phys. Rev. Let

The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement.

Routinely collected health data, obtained for administrative and clinical purposes without specific a priori research goals, are increasingly used for research. The rapid evolution and availability of these data have revealed issues not addressed by existing reporting guidelines, such as Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). The REporting of studies Conducted using Observational Routinely collected health Data (RECORD) statement was created to fill these gaps. RECORD was created as an extension to the STROBE statement to address reporting items specific to observational studies using routinely collected health data. RECORD consists of a checklist of 13 items related to the title, abstract, introduction, methods, results, and discussion section of articles, and other information required for inclusion in such research reports. This document contains the checklist and explanatory and elaboration information to enhance the use of the checklist. Examples of good reporting for each RECORD checklist item are also included herein. This document, as well as the accompanying website and message board (http://www.record-statement.org), will enhance the implementation and understanding of RECORD. Through implementation of RECORD, authors, journals editors, and peer reviewers can encourage transparency of research reporting

Synergies Among Environmental Science Research and Monitoring Networks: A Research Agenda

Many research and monitoring networks in recent decades have provided publicly available data documenting environmental and ecological change, but little is known about the status of efforts to synthesize this information across networks. We convened a working group to assess ongoing and potential cross-network synthesis research and outline opportunities and challenges for the future, focusing on the US-based research network (the US Long-Term Ecological Research network, LTER) and monitoring network (the National Ecological Observatory Network, NEON). LTER-NEON cross-network research synergies arise from the potentials for LTER measurements, experiments, models, and observational studies to provide context and mechanisms for interpreting NEON data, and for NEON measurements to provide standardization and broad scale coverage that complement LTER studies. Initial cross-network syntheses at co-located sites in the LTER and NEON networks are addressing six broad topics: how long-term vegetation change influences C fluxes; how detailed remotely sensed data reveal vegetation structure and function; aquatic-terrestrial connections of nutrient cycling; ecosystem response to soil biogeochemistry and microbial processes; population and species responses to environmental change; and disturbance, stability and resilience. This initial study offers exciting potentials for expanded cross-network syntheses involving multiple long-term ecosystem processes at regional or continental scales. These potential syntheses could provide a pathway for the broader scientific community, beyond LTER and NEON, to engage in cross-network science. These examples also apply to many other research and monitoring networks in the US and globally, and can guide scientists and research administrators in promoting broad-scale research that supports resource management and environmental policy

Rapid climate-driven circulation changes threaten conservation of endangered north atlantic right whales

As climate trends accelerate, ecosystems will be pushed rapidly into new states, reducing the potential efficacy of conservation strategies based on historical patterns. In the Gulf of Maine, climate-driven changes have restructured the ecosystem rapidly over the past decade. Changes in the Atlantic meridional overturning circulation have altered deepwater dynamics, driving warming rates twice as high as the fastest surface rates. This has had implications for the copepod Calanus finmarchicus, a critical food supply for the endangered North Atlantic right whale (Eubalaena glacialis). The oceanographic changes have driven a deviation in the seasonal foraging patterns of E. glacialis upon which conservation strategies depend, making the whales more vulnerable to ship strikes and gear entanglements. The effects of rapid climate-driven changes on a species at risk undermine current management approaches.publishedVersio

A descriptive exploratory study of how admissions caused by medication-related harm are documented within inpatients' medical records.

BACKGROUND: Adverse drug reactions, poor patient adherence and errors, here collectively referred to as medication-related harm (MRH), cause around 2.7-8.0% of UK hospital admissions. Communication gaps between successive healthcare providers exist, but little is known about how MRH is recorded in inpatients' medical records. We describe the presence and quality of MRH documentation for patients admitted to a London teaching hospital due to MRH. Additionally, the international classification of disease 10th revision (ICD-10) codes attributed to confirmed MRH-related admissions were studied to explore appropriateness of their use to identify these patients. METHODS: Clinical pharmacists working on an admissions ward in a UK hospital identified patients admitted due to suspected MRH. Six different data sources in each patient's medical record, including the discharge summary, were subsequently examined for MRH-related information. Each data source was examined for statements describing the MRH: symptom and diagnosis, identification of the causative agent, and a statement of the action taken or considered. Statements were categorised as 'explicit' if unambiguous or 'implicit' if open to interpretation. ICD-10 codes attributed to confirmed MRH cases were recorded. RESULTS: Eighty-four patients were identified over 141 data collection days; 75 met our inclusion criteria. MRH documentation was generally present (855 of 1307 statements were identified; 65%), and usually explicit (705 of 855; 82%). The causative agent had the lowest proportion of explicit statements (139 of 201 statements were explicit; 69%). For two (3%) discharged patients, the causal agent was documented in their paper medical record but not on the discharge summary. Of 64 patients with a confirmed MRH diagnosis at discharge, only six (9%) had a MRH-related ICD-10 code. CONCLUSIONS: Availability of information in the paper medical record needs improving and communication of MRH-related information could be enhanced by using explicit statements and documenting reasons for changing medications. ICD-10 codes underestimate the true occurrence of MRH

Polysulfates block SARS‐CoV‐2 uptake through electrostatic interactions

Here we report that negatively charged polysulfates can bind to the spike protein of SARS-CoV-2 via electrostatic interactions. Using a plaque reduction assay, we compare inhibition of SARS-CoV-2 by heparin, pentosan sulfate, linear polyglycerol sulfate (LPGS) and hyperbranched polyglycerol sulfate (HPGS). Highly sulfated LPGS is the optimal inhibitor, with a half-maximal inhibitory concentration (IC50) of 67 μg/mL (approx. 1.6 μM). This synthetic polysulfates exhibit more than 60-fold higher virus inhibitory activity than heparin (IC50: 4084 μg/mL), along with much lower anticoagulant activity. Furthermore, in molecular dynamics simulations, we verified that LPGS can bind stronger to the spike protein than heparin, and that LPGS can interact even more with the spike protein of the new N501Y and E484K variants. Our study demonstrates that the entry of SARS-CoV-2 into host cells can be blocked via electrostatic interaction, therefore LPGS can serve as a blueprint for the design of novel viral inhibitors of SARS-CoV-2