A comparative study of carnivorous leaves in the genus Sarracenia

The carnivorous pitcher plant genus, Sarracenia, has modified leaves adapted to lure, trap, and digest insect prey. Little is known about surface microstructural ornamentation and variation throughout the genus. Four zones of the leaf were examined in four species throughout the range of the genus using scanning electron microscopy (SEM). Nine unique microstructures were identified in the carnivorous leaf. For the first time, microstructures (N=880) were systematically measured and zonal averages were compared among zones (with MANOVA) and species (with PCA). Microstructures are significantly different among zones of the same leaf and vary among different species. These data suggest that each zone is functionally distinct and that these closely related plant species have diverged in surface ornamentation, likely due to differences in prey and habitat. This work can be used to inform questions about plant: prey interactions, taxonomy, digestion mechanics and leaf development

A role for microRNA-29a mediating ER stress-induced apoptosis in neuronal cells in the mouse central nervous system.

A role for microRNA-29a mediating ER stress-induced apoptosis in neuronal cells in the mouse central nervous system Disturbances in the folding of proteins within the endoplasmic reticulum (ER) lead to the accumulation of mis-folded and aggregated proteins and the activation of the ER stress response and has been implicated in neurodegenerativo diseases such as amyotrophic lateral sclerosis. MicroRNAs are small ribonucleic acids which can modulate the expression of proteins post-translationally and in recent years have been implicated in major disease pathologies. The miR-29 family, of which miR-29a is a member, has been implicated in cancer and neurodegeneration through its effects on apoptosis. Firstly we investigated the role of miR-29a and its proposed target MCL-1 during ER stress-induced apoptosis. We show that miR-29a is significantly upregulated compared to other miRNAs following ER stress-induced apoptosis in primary cortical neurons. Increased miR-29a expression coincided with a decrease in MCL-1 protein expression. Contrasting this we identified a neuroprotective role for miR-29a antagomir in cortical neurons during ER stress. miR-29a knockdown was shown to increase Mcl-1 mRNA and we hypothesised that this could be mediating the cytoproptective effect. We identified the importance of MCL-1 in mediating ER stress-induced apoptosis, identifying protection of cortical neurons overexpressing MCL-1 during tunicamycin-induced ER stress. Furthermore we showed loss of MCL-1 sensitised cortical neurons to ER stress-induced cell death and demonstrated a cytoprotective role for MCL-1 in cortical neurons. In addition, cortical neurons were shown to be protected against tunicamycin-induced ER stress in the absence of PUMA or BAX, however we could not abrogate apoptosis and suggest that other mediators of apoptosis compensate for loss of members of the BCL-2 family. Indeed, MCL-1 overexpression was shown to decrease LC3II protein levels suggesting a further level of regulation within cortical neurons involving other apoptosis-mediating pathways such as autophagy. Having identified miR-29a as upregulated in the central nervous system (CNS) of C57 BL/6 mice, and reduced expression of Mcl-1 in the same CNS tissue, we confirmed miR-29a expression in lumbar spinal cord from SOD1 transgenic mice. While we could localise miR-29a expression to motoneurons in the lumbar spinal cord, miR- 29a knockdown in an SOD1G93A mouse model of ALS did not reduce motor dysfunction nor significantly increase lifespan

Palladate precatalysts for the formation of C-N and C-C bonds

A series of imidazolium-based palladate precatalysts has been synthesized and the catalytic activity of these air- and moisture-stable complexes evaluated as a function of the nature of the imidazolium counterion. These precatalysts can be converted under catalytic conditions to Pd-NHC species capable of enabling the Buchwald-Hartwig aryl amination and the alpha-arylation of ketones. Both reactions can be carried out efficiently under very mild operating conditions. The effectiveness of the protocol was tested on functionality-laden substrates

Endoplasmic reticulum stress-mediated upregulation of miR-29a enhances sensitivity to neuronal apoptosis.

Disturbance of homeostasis within the endoplasmic reticulum (ER) lumen leads to the accumulation of unfolded and misfolded proteins. This results in the activation of an evolutionary conserved stress response termed ER stress that, if unresolved, induces apoptosis. Previously the Bcl-2 homology domain 3-Only Protein Puma was identified as a mediator of ER stress-induced apoptosis in neurons. In the search of alternative contributors to ER stress-induced apoptosis, a downregulation of the anti-apoptotic Bcl-2 family protein Mcl-1 was noted during ER stress in both mouse cortical neurons and human SH-SY5Y neuroblastoma cells. Downregulation of Mcl-1 was associated with an upregulation of microRNA-29a (miR-29a) expression, and subsequent experiments showed that miR-29a targeted the 3\u27-untranslated region of the anti-apoptotic Bcl-2 family protein, Mcl-1. Inhibition of miR-29a expression using sequence-specific antagomirs or the overexpression of Mcl-1 decreased cell death following tunicamycin treatment, while gene silencing of Mcl-1 increased cell death. miR-29a did not alter the signalling branches of the ER stress response, rather its expression was controlled by the ER stress-induced transcription factor activating-transcription-factor-4 (ATF4). The current data demonstrate that the ATF4-mediated upregulation of miR-29a enhances the sensitivity of neurons to ER stress-induced apoptosis

Research needs for optimising wastewater-based epidemiology monitoring for public health protection

This is the final version. Available on open access from IWA Publishing via the DOI in this recordData availability statement: All relevant data are included in the paper or its Supplementary Information.Wastewater-based epidemiology (WBE) is an unobtrusive method used to observe patterns in illicit drug use, poliovirus, and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The pandemic and need for surveillance measures have led to the rapid acceleration of WBE research and development globally. With the infrastructure available to monitor SARS-CoV-2 from wastewater in 58 countries globally, there is potential to expand targets and applications for public health protection, such as other viral pathogens, antimicrobial resistance (AMR), pharmaceutical consumption, or exposure to chemical pollutants. Some applications have been explored in academic research but are not used to inform public health decision-making. We reflect on the current knowledge of WBE for these applications and identify barriers and opportunities for expanding beyond SARS-CoV-2. This paper critically reviews the applications of WBE for public health and identifies the important research gaps for WBE to be a useful tool in public health. It considers possible uses for pathogenic viruses, AMR, and chemicals. It summarises the current evidence on the following: (1) the presence of markers in stool and urine; (2) environmental factors influencing persistence of markers in wastewater; (3) methods for sample collection and storage; (4) prospective methods for detection and quantification; (5) reducing uncertainties; and (6) further considerations for public health use.Natural Environment Research Council (NERC)Engineering and Physical Sciences Research Council (EPSRC

Countryside Stewardship Facilitation Fund - Phase 3 Final Report LM04101

Executive Summary: Since 2017 Natural England has been analysing the Facilitation Fund in relation to its process and outcomes (phase 1 and 2 of Facilitation Fund evaluation). This report forms phase 3 of this evaluation process. The objective of this phase was to evaluate the benefits Facilitation Fund groups offer, measured against natural capital and social indicators with a particular focus on contributions to nature recovery and ecological restoration

Airway management during in-hospital cardiac arrest in adults: UK national survey and interview study with anaesthetic and intensive care trainees

Background: The optimal airway management strategy for in-hospital cardiac arrest is unknown. Methods: An online survey and telephone interviews with anaesthetic and intensive care trainee doctors identified by the United Kingdom Research and Audit Federation of Trainees. Questions explored in-hospital cardiac arrest frequency, grade and specialty of those attending, proportion of patients receiving advanced airway management, airway strategies immediately available, and views on a randomised trial of airway management strategies during in-hospital cardiac arrest. Results: Completed surveys were received from 128 hospital sites (76% response rate). Adult in-hospital cardiac arrests were attended by anaesthesia staff at 40 sites (31%), intensive care staff at 37 sites (29%) and a combination of specialties at 51 sites (40%). The majority (123/128, 96%) of respondents reported immediate access to both tracheal intubation and supraglottic airways. A bag-mask technique was used ‘very frequently’ or ‘frequently’ during in-hospital cardiac arrest by 111/128 (87%) of respondents, followed by supraglottic airways (101/128, 79%) and tracheal intubation (69/128, 54%). The majority (60/100, 60%) of respondents estimated that ≤30% of in-hospital cardiac arrest patients undergo tracheal intubation, while 34 (34%) estimated this to be between 31% and 70%. Most respondents (102/128, 80%) would be ‘likely’ or ‘very likely’ to recruit future patients to a trial of alternative airway management strategies during in-hospital cardiac arrest. Interview data identified several barriers and facilitators to conducting research on airway management in in-hospital cardiac arrest. Conclusions: There is variation in airway management strategies for adult in-hospital cardiac arrest across the UK. Most respondents would be willing to take part in a randomised trial of airway management during in-hospital cardiac arrest

A knowledge translation collaborative to improve the use of therapeutic hypothermia in post-cardiac arrest patients: protocol for a stepped wedge randomized trial

<p>Abstract</p> <p>Background</p> <p>Advances in resuscitation science have dramatically improved survival rates following cardiac arrest. However, about 60% of adults that regain spontaneous circulation die before leaving the hospital. Recently it has been shown that inducing hypothermia in cardiac arrest survivors immediately following their arrival in hospital can dramatically improve both overall survival and neurological outcomes. Despite the strong evidence for its efficacy and the apparent simplicity of this intervention, recent surveys show that therapeutic hypothermia is delivered inconsistently, incompletely, and often with delay.</p> <p>Methods and design</p> <p>This study will evaluate a multi-faceted knowledge translation strategy designed to increase the utilization rate of induced hypothermia in survivors of cardiac arrest across a network of 37 hospitals in Southwestern Ontario, Canada. The study is designed as a stepped wedge randomized trial lasting two years. Individual hospitals will be randomly assigned to four different wedges that will receive the active knowledge translation strategy according to a sequential rollout over a number of time periods. By the end of the study, all hospitals will have received the intervention. The primary aim is to measure the effectiveness of a multifaceted knowledge translation plan involving education, reminders, and audit-feedback for improving the use of induced hypothermia in survivors of cardiac arrest presenting to the emergency department. The primary outcome is the proportion of eligible OHCA patients that are cooled to a body temperature of 32 to 34°C within six hours of arrival in the hospital. Secondary outcomes will include process of care measures and clinical outcomes.</p> <p>Discussion</p> <p>Inducing hypothermia in cardiac arrest survivors immediately following their arrival to hospital has been shown to dramatically improve both overall survival and neurological outcomes. However, this lifesaving treatment is frequently not applied in practice. If this trial is positive, our results will have broad implications by showing that a knowledge translation strategy shared across a collaborative network of hospitals can increase the number of patients that receive this lifesaving intervention in a timely manner.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Trial Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00683683">NCT00683683</a></p

The effect of COVID rehabilitation for ongoing symptoms Post HOSPitalisation with COVID-19 (PHOSP-R):protocol for a randomised parallel group controlled trial on behalf of the PHOSP consortium

Introduction Many adults hospitalised with COVID-19 have persistent symptoms such as fatigue, breathlessness and brain fog that limit day-to-day activities. These symptoms can last over 2 years. Whilst there is limited controlled studies on interventions that can support those with ongoing symptoms, there has been some promise in rehabilitation interventions in improving function and symptoms either using face-to-face or digital methods, but evidence remains limited and these studies often lack a control group. Methods and analysis This is a nested single-blind, parallel group, randomised control trial with embedded qualitative evaluation comparing rehabilitation (face-to-face or digital) to usual care and conducted within the PHOSP-COVID study. The aim of this study is to determine the effectiveness of rehabilitation interventions on exercise capacity, quality of life and symptoms such as breathlessness and fatigue. The primary outcome is the Incremental Shuttle Walking Test following the eight week intervention phase. Secondary outcomes include measures of function, strength and subjective assessment of symptoms. Blood inflammatory markers and muscle biopsies are an exploratory outcome. The interventions last eight weeks and combine symptom-titrated exercise therapy, symptom management and education delivered either in a face-to-face setting or through a digital platform (www.yourcovidrecovery.nhs.uk). The proposed sample size is 159 participants, and data will be intention-to-treat analyses comparing rehabilitation (face-to-face or digital) to usual care. Ethics and dissemination Ethical approval was gained as part of the PHOSP-COVID study by Yorkshire and the Humber Leeds West Research NHS Ethics Committee, and the study was prospectively registered on the ISRCTN trial registry (ISRCTN13293865). Results will be disseminated to stakeholders, including patients and members of the public, and published in appropriate journals. Article summary Strengths and limitations of this study • This protocol utilises two interventions to support those with ongoing symptoms of COVID-19 • This is a two-centre parallel-group randomised controlled trial • The protocol has been supported by patient and public involvement groups who identified treatments of symptoms and activity limitation as a top priorit