Cationic Host Defence Peptides:Potential as Antiviral Therapeutics

There is a pressing need to develop new antiviral treatments; of the 60 drugs currently available, half are aimed at HIV-1 and the remainder target only a further six viruses. This demand has led to the emergence of possible peptide therapies, with 15 currently in clinical trials. Advancements in understanding the antiviral potential of naturally occurring host defence peptides highlights the potential of a whole new class of molecules to be considered as antiviral therapeutics. Cationic host defence peptides, such as defensins and cathelicidins, are important components of innate immunity with antimicrobial and immunomodulatory capabilities. In recent years they have also been shown to be natural, broad-spectrum antivirals against both enveloped and non-enveloped viruses, including HIV-1, influenza virus, respiratory syncytial virus and herpes simplex virus. Here we review the antiviral properties of several families of these host peptides and their potential to inform the design of novel therapeutics

Effects of an Early Season Heat Wave on Ecophysiological Parameters Related to Productivity in Sugar Maple (Acer saccharum Marsh.)

Anticipated increases in the frequency, duration or intensity of high temperature events ('heat waves') have the potential to significantly impact forest form and functioning, but these events remain virtually unstudied in forest ecosystems. This thesis presents the results of an event-driven research effort into the impacts of three days of record-setting high temperatures in late May 2010 on key ecophysiological parameters in Sugar Maple (Acer saccharum. Marsh). High temperatures reduced photosynthetic capacity by ~66% versus previous years and total end-of-season leaf litter production by ~33% versus prior measurements. It is predicted that these reductions substantially reduced productivity for Sugar Maple in 2010. These results constitute the first description of the impacts of a short-duration heat wave on productivity-related parameters in a temperate forest tree. The predicted increase in high temperature events could make such impacts a significant, though so far overlooked, pathway of climate change impacts on temperate forests.MAS

Effects of an Early Season Heat Wave on Ecophysiological Parameters Related to Productivity in Sugar Maple (Acer saccharum Marsh.)

Anticipated increases in the frequency, duration or intensity of high temperature events ('heat waves') have the potential to significantly impact forest form and functioning, but these events remain virtually unstudied in forest ecosystems. This thesis presents the results of an event-driven research effort into the impacts of three days of record-setting high temperatures in late May 2010 on key ecophysiological parameters in Sugar Maple (Acer saccharum. Marsh). High temperatures reduced photosynthetic capacity by ~66% versus previous years and total end-of-season leaf litter production by ~33% versus prior measurements. It is predicted that these reductions substantially reduced productivity for Sugar Maple in 2010. These results constitute the first description of the impacts of a short-duration heat wave on productivity-related parameters in a temperate forest tree. The predicted increase in high temperature events could make such impacts a significant, though so far overlooked, pathway of climate change impacts on temperate forests.MAS

Practice Patterns in the Treatment of Patients With Severe Alcohol Withdrawal: A Multidisciplinary, Cross-Sectional Survey

Purpose: To characterize physicians’ stated practices in the treatment of patients with severe acute alcohol withdrawal syndrome (sAAWS) and to use intravenous (IV) phenobarbital as an adjuvant treatment for sAAWS. Methods: A multidisciplinary, cross-sectional, self-administered survey at 2 large academic centers specializing in inner-city healthcare. Results: We analyzed 105 of 195 questionnaires (53.8% response rate). On average, clinicians managed 32 cases of AAWS over a 6-month period, of which 7 (21.9%) were severe. Haloperidol (Haldol; 40 [39%]), clonidine (Catapres; 31 [30%]), phenobarbital (Luminal, Tedral; 29 [27%]) and propofol (Diprivan; 29 [28%]) were the most commonly used adjuvant medications for sAAWS. Sixty-three (60%) of respondents did not use phenobarbital in practice. Of phenobarbital users, 23 (55%) respondents used it early in patients who were refractory to symptom-triggered benzodiazepine treatment. Others waited until patients experienced seizures (5 [10%]) or required intensive care unit admission (8 [18%]). Respondents who used phenobarbital preferred to use the IV versus oral form (66% vs 29%, P &lt; .001). Most respondents, however, were unfamiliar with the pharmacokinetics, side effects, contraindications, and evidence supporting phenobarbital use for sAAWS. Although many respondents (64 [61%]) expressed discomfort using phenobarbital, 87 (83%) expressed comfort or neutrality with enrolling patients in a trial to evaluate IV phenobarbital in sAAWS. Conclusions: Considerable stated practice variation exists in how clinicians treat patients with sAAWS. Our findings support conduct of a pilot trial to evaluate IV phenobarbital as an adjuvant treatment to symptom-triggered benzodiazepines for sAAWS and have informed trial design. </jats:sec

Supplemental Material, Practice_Patterns_in_Phenobarbital_Questionnaire_(1) - Practice Patterns in the Treatment of Patients With Severe Alcohol Withdrawal: A Multidisciplinary, Cross-Sectional Survey

Supplemental Material, Practice_Patterns_in_Phenobarbital_Questionnaire_(1) for Practice Patterns in the Treatment of Patients With Severe Alcohol Withdrawal: A Multidisciplinary, Cross-Sectional Survey by Danielle Buell, Niall Filewod, Jonathan Ailon and Karen E. A. Burns in Journal of Intensive Care Medicine</p

Supplementary Material for: Signaling Pathways Mediating Chemokine Induction in Keratinocytes by Cathelicidin LL-37 and Flagellin

Cathelicidin LL-37 is a multifunctional immunomodulatory and antimicrobial host defense peptide that has an important role in the immune defenses of the skin and other epithelial barriers. We have previously demonstrated that at physiological concentrations LL-37 synergistically augments the production of immune mediators in response to microbial compounds in human primary keratinocytes. Here we define the signaling mechanisms responsible for this activity. We demonstrate that inhibition of Src family kinases (SFKs) strongly inhibited the synergistic chemokine production in response to LL-37 and flagellin in keratinocytes. SFK activation was induced by LL-37 stimulation and was required for the downstream activation of Akt (protein kinase B) and the transcription factors CREB and ATF1. In cells stimulated with LL-37 and flagellin together, Akt activation was primarily induced by LL-37, while both flagellin and LL-37 contributed to the activation of CREB and ATF1 and consequently chemokine induction. The purinergic receptor P2X₇ was identified as the receptor upstream of SFK activation in LL-37-stimulated keratinocytes. Overall, these findings established the P2X₇–SFK–Akt–CREB/ATF1 signaling pathway activated by LL-37 in primary keratinocytes. These signaling mechanisms mediated the synergistic effects of LL-37 on chemokine production in flagellin-stimulated keratinocytes, and thus might have a role in the immune defenses of the skin and possibly other epithelial barriers

Strong transparency required for carbon credit mechanisms

The credibility of carbon offset mechanisms is threatened by many issues related to their true effectiveness. We advocate that these issues cannot be effectively addressed without a dramatic improvement in transparency across the entire value chain of carbon offsetting, a crucial step for achieving a reduction in carbon emissions

Strong transparency required for carbon credit mechanisms

This is the author accepted manuscript. The final version is available from Nature Research via the DOI in this recordThe credibility of carbon offset mechanisms is threatened by many issues related to their true effectiveness. We advocate that these issues cannot be effectively addressed without a dramatic improvement in transparency across the entire value chain of carbon offsetting, a crucial step for achieving a reduction in carbon emissions.Natural Environment Research Council (NERC

Strong transparency required for carbon credit mechanisms

The credibility of carbon offset mechanisms is threatened by many issues related to their true effectiveness. We advocate that these issues cannot be effectively addressed without a dramatic improvement in transparency across the entire value chain of carbon offsetting, a crucial step for achieving a reduction in carbon emissions

Restoring credibility in carbon offsets through systematic ex post evaluation

A key factor undermining the credibility of carbon offsets is the evaluation of project baselines and their impact. The ex ante scenarios constructed by project developers in accordance with rules set by certification schemes have been challenged by ex post evaluations from scientists, who frequently document cases of credit allocations that overestimate the actual emission reductions. Increasing credibility requires methodologies that reliably measure project outcomes and prevent overcrediting—an objective that ex post evaluations may be well suited to achieve. We explore how systematic ex post evaluations could restore credibility to certification schemes in the voluntary carbon market