Non-invasive extraction of Cnidarian venom through the use of autotomised tentacles

The animals contained within the phylum Cnidaria have origins that can be dated back to around 750 million years ago (mya) and as such, they represent what is potentially the oldest known venomous lineage that is recognised today. The phylum Cnidaria, which includes Sea Anemones, Corals and Jellyfish are also one of the most under-studied as far as toxins go, likely a result of the constraints involved in obtaining samples. Over the last two decades there have been increased efforts to further our ability to obtain samples, however, the sampling techniques developed were invasive and generally required the dissection of tissues from the organism. Within recent years, there have been some developments in the chemical extraction of Cnidarian venom, using ethanol to trigger nematocyst firing. These developments have led to the formation of this research, which uses ethanol to elicit stimulation of nematocysts on naturally autotomised tentacles whilst being observed under light microscopy, before having protein content measured using microspectrophotometry. This paper focuses on a unique observation of Cnidaria that is unknown in any other animal taxa, passive autotomy of envenomation apparatus, the tentacles

Purified venom components inhibit EGFR phosphorylation in triple negative breast cancer

Abstract: EACR22-0963 Introduction Breast cancer remains the most commonly diagnosed type of cancer in both menopausal age women and adolescent/young adults. 10-20% of diagnosed breast cancers are deemed to be triple negative (TN), lacking expression of hormone receptors and HER2. Triple negative breast cancers (TNBC) present with poor patient prognosis, through their lack of effective treatment options. Studies report that epidermal growth factor receptor (EGFR) is expressed in 15–45% of all breast tumours and its expression is inversely related to hormone receptor expression. Expression of EGFR is indicative of poor prognosis, making it an attractive target for treatment in both TN and receptor expressing cancer subtypes. Development of resistance to current EGFR targeted therapeutics is common, leading to treatment failure and patient relapse, thus novel compound classes are needed. Venom peptides have evolved to be secreted into the lumen of the venom gland and stored ready for rapid delivery; therefore they are exceptionally stable. These proteins naturally act as ligands for a large variety of receptors and ion channels, making them a rich source of potentially novel drug like molecules. Material and Methods In this study the Venomtech Targeted-Venom Discovery ArrayEGFR (T-VDA™) containing 320 venom 2D HPLC fractions was screened using Abcam Human EGFR (pY1086) + total EGFR ELISA Kits to identify venom peptides with antagonistic activity against EGFR pY1086 phosphorylation. Optimal cell number, dosing and lysate concentrations were determined empirically. MDA-MB-468 TNBC cells were dosed at 20ug/ml for 2h with fractions, before being stimulated with 1x10-7M EGF for 5 mins. Further assay protocol was carried out as per manufacturer’s instructions. TMB Absorbance signal was measured using a CLARIOstarPLUS plate reader at 450nm (BMG LabTech). Results and Discussions Screening of the TVDAEGFR array (N=2) identified 7 hit fractions (2.2% hit rate) from the venoms of three distinct rattlesnake genera from Northern, Central and southern America, and 1 viper species from Northern Africa. These fractions were followed up with dose response, mass spec and drug like properties. Conclusion Purified protein components from the venoms of pit vipers and vipers show the capacity to antagonistically inhibit the phosphorylation of EGFR at specific tyrosine residues linked to downstream signalling pathways in TNBC cells. Thus, representing a novel chemical class for targeting EGF

Corelates of Legalism in a Global Sample of Seventh-day Adventists

The Seventh-day Adventist Church is often identified as a strict church (Iannaccone, 1994; Chen et al., 2019; McBride et al., 2020) in that it has specific dietary and behavioral requirements for joining and continued membership. These include abstinence from alcohol, tobacco, and illicit drugs as well as a strong emphasis on vegetarianism (McBride et al., 2020). This has resulted in longevity advantage for Adventists (Fraser et al., 2020). This focus on behavioral requirements have resulted in critics viewing Adventists as legalists (WELS, 2022). The purpose of this research is to examine the issue of legalism among Adventist Church members

Microbial adaptation to venom is common in snakes and spiders

Animal venoms are considered sterile sources of antimicrobial compounds with strong membrane disrupting activity against multi-drug resistant bacteria. However, bite wound infections are common in developing nations. Investigating the oral and venom microbiome of five snake and two spider species, we evidence viable microorganisms potentially unique to venom for black-necked spitting cobras (Naja nigricollis). Among these are two novel sequence types of Enterococcus faecalis misidentified by commonly used clinical biochemistry procedures as Staphylococcus; the genome sequence data of venom-specific isolates feature an additional 45 genes, at least 11 of which improve membrane integrity. Our findings challenge the dogma of venom sterility and indicate an increased primary infection risk in the clinical management of venomous animal bite wounds

Health Beliefs, Behavior, Spiritual Growth, and Salvation in a Global Population of Seventh‑day Adventists

Background The Seventh-day Adventist Church is a growing global denomination with strict substance use abstinence and recommended dietary requirements that together are called the “Health Message.” Abstinence from alcohol and tobacco is a requirement of membership and a plant-based diet is strongly advised. Purpose While a wide variety of research has reported the Adventist health advantage, very little research has been conducted on Adventist members’ attitudes toward and adherence to the Health Message. This research examines members\u27 views, from a global survey, about the health message, personal adherence, and belief that adherence ensures salvation. Methods The survey was conducted in 2017/2018 with a total N of 63,756. The questionnaire was translated into about 60 languages and then back-translated into English for improved accuracy. Results Over 80% of the respondents reported that they agreed the Adventist health message was wholistic, core to Adventist beliefs, supported by science, and increased the probability of a longer life. There were very few differences by global regions. About 80% also agreed that they should abstain from tobacco and alcohol and follow a healthy diet. However, about 45% believed that they could pick and choose which parts to follow with only a little over one-third reporting that they followed the Health Message a great deal. Strict adherence appeared to be in abstinence from alcohol (91%) and tobacco (97%). Only about 19% reported being vegetarian or vegan. Over 47%, mostly in the Southern Hemisphere, reported the belief that if they kept the Health Message completely, they would be assured of salvation, though this is at odds with formal doctrine. Conclusions and Implications The data suggest that church leadership has been successful in obtaining global acceptance of the Health Message, convincing members of its scientific basis, and to abstain from tobacco and alcohol use. However, the data also show almost half of members believe that they can pick and choose elements to follow. In addition, these data have major implications for church leadership in disentangling the implications and expectations of the Health Message from the Church’s fundamental belief that salvation is only through faith in Christ

Expanding, axisymmetric pure-radiation gravitational fields with a simple twist

New expanding, axisymmetric pure-radiation solutions are found, exploiting the analogy with the Euler-Darboux equation for aligned colliding plane waves.Comment: revtex, 5 page

From policy to pedagogy: widening the discourse and practice of the learning society in the European Union

This paper explores the policy turn of the learning society, and how the academic world is responding to new social and political demands. It highlights some of the criticisms levelled at the learning society, as well as the voices of support. The paper also showcases the European Language Portfolio and the Transferable Skills project as two examples of good practice. Cet article examine le tournant de la politique de la socie´te´ du savoir ainsi que la re´ponse du monde intellectuel face aux nouvelles exigences sociales et politiques. Il met en lumie`re certaines des critiques souleve´es par la socie´te´ du savoir ainsi que par les voix favorables. L’article s’appuie sur deux exemples pratiques, a` savoir le Portfolio Europe´en des Langues et le Project des Compe´tences Transmissibles

Developing a multivariable prediction model for functional outcome after reperfusion therapy for acute ischaemic stroke: study protocol for the Targeting Optimal Thrombolysis Outcomes (TOTO) multicentre cohort study.

INTRODUCTION:Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) is the only approved pharmacological reperfusion therapy for acute ischaemic stroke. Despite population benefit, IVT is not equally effective in all patients, nor is it without significant risk. Uncertain treatment outcome prediction complicates patient treatment selection. This study will develop and validate predictive algorithms for IVT response, using clinical, radiological and blood-based biomarker measures. A secondary objective is to develop predictive algorithms for endovascular thrombectomy (EVT), which has been proven as an effective reperfusion therapy since study inception. METHODS AND ANALYSIS:The Targeting Optimal Thrombolysis Outcomes Study is a multicenter prospective cohort study of ischaemic stroke patients treated at participating Australian Stroke Centres with IVT and/or EVT. Patients undergo neuroimaging using multimodal CT or MRI at baseline with repeat neuroimaging 24 hours post-treatment. Baseline and follow-up blood samples are provided for research use. The primary outcome is good functional outcome at 90 days poststroke, defined as a modified Rankin Scale (mRS) Score of 0-2. Secondary outcomes are reperfusion, recanalisation, infarct core growth, change in stroke severity, poor functional outcome, excellent functional outcome and ordinal mRS at 90 days. Primary predictive models will be developed and validated in patients treated only with rt-PA. Models will be built using regression methods and include clinical variables, radiological measures from multimodal neuroimaging and blood-based biomarkers measured by mass spectrometry. Predictive accuracy will be quantified using c-statistics and R2. In secondary analyses, models will be developed in patients treated using EVT, with or without prior IVT, reflecting practice changes since original study design. ETHICS AND DISSEMINATION:Patients, or relatives when patients could not consent, provide written informed consent to participate. This study received approval from the Hunter New England Local Health District Human Research Ethics Committee (reference 14/10/15/4.02). Findings will be disseminated via peer-reviewed publications and conference presentations

Bacterial Adaptation to Venom in Snakes and Arachnida

Animal venoms are considered sterile sources of antimicrobial compoundswith strong membrane-disrupting activity against multidrug-resistant bacteria. However,venomous bite wound infections are common in developing nations. Investigating theenvenomation organ and venom microbiota offive snake and two spider species, weobserved venom community structures that depend on the host venomous animal spe-cies and evidenced recovery of viable microorganisms from black-necked spitting cobra(Naja nigricollis) and Indian ornamental tarantula (Poecilotheria regalis) venoms. Amongthe bacterial isolates recovered fromN. nigricollis,weidentified two venom-resistant,novel sequence types ofEnterococcus faecaliswhose genomes feature 16 virulencegenes, indicating infectious potential, and 45 additional genes, nearly half of whichimprove bacterial membrane integrity. Ourfindings challenge the dogma of venom ste-rility and indicate an increased primary infection risk in the clinical management of ven-omous animal bite wounds