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

Powerful proteins from polyp possessing predators

Cnidarians are soft bodied animals possessing complex venom systems which have evolved to allow for the capture of arthropod and vertebrate prey, as well as to defend themselves against such predators. The effects of these venoms on humans, as a result of envenomation, has been studied for many decades, whereas the possibility of using these proteins to fight human disease is in its infancy. Drug discovery utilisation of Cnidarian venoms has been hampered by availability of animals and suitable extraction techniques that allow for study of such protein toxins. Studies of toxins that have been suitably purified for drug discovery have, by in large, only investigated target engagement and negated to investigate other drug like properties such as absorption, dispersion, metabolism, and excretion (ADME). This chapter will review the sourcing of Cnidaria for drug discovery, extraction of venom components, actions of venoms on drug relevant targets and their suitability as drug like molecules

Beauty from the deep: cnidarians in cosmetics

Cnidarian proteins are considered useful for the development of therapeutics, as well as this they have also received the attention of biotechnology and the cosmetic industries. In 2017 the first ever sea anemone venom peptide cosmetic, named SensAmone P5, was launched by Mibelle Biochemistry. This synthetic peptide is based on the interaction of APHC1, from Heteractis crispa, on the pain relevant ion channel TRPV1. This peptide reduces TRPV1 signalling in-vitro and skin sensitivity in human volunteers. Aside from venoms, jellyfish mucus and collagen are both used in cosmetic preparations. Many legal definitions of animals do not include the invertebrates and thus it is likely that invertebrate proteins are more acceptable as an alternative to mammalian proteins. Mucins are important proteins for moisturisers and using jellyfish as the source appears to be a suitable alternative to bovine and porcine proteins which were previously used. The main structural protein that supports the soft bodied jellyfish is collagen. This collagen appears to be biocompatible with human tissues and thus has been successful as a cosmetic, as well as being used in-vitro for 3D tissue engineering scaffolds. This short communication will discuss the use of Cnidarian proteins in cosmetics

Revival and the Holy Spirit

This article discusses the Avondale revival of 1939

National Trim Bulletin, Summer 1998

National Trim Bulletin, lower taxes through less government.https://digitalcommons.csumb.edu/samfarr_campaign/1011/thumbnail.jp

How the market driving approach can create brand value through a digital platform.

This paper examines how the value of a brand is enhanced through a learning process that incorporates customer dialogue and results in co-creation and the incorporation of a consumer oriented relationship marketing approach. We adopted the market driving concept and related it to how companies can strengthen their competitive standing by increasing the knowledge transfer capability by utilizing data collected through social media technology (SMT). A qualitative research strategy was deployed involving a critical friendship group and a group interview, and a number of constructs were identified and then grouped according to a number of underlying themes. Our findings, a Digital Stakeholder Communication Platform (DSCP) framework, supports and explains how the concept of market driving enhances a pro-active strategic capability. It highlights the importance of learning and managing a value system that reflects on societal values, and the need for companies to consider how they contribute to societal well being

A Cross-Sectional Study of Phthalate Exposure and Inflammation Biomarker Levels Among Postmenopausal Women

Phthalates are industrial chemicals added to plastics found in products such as children’s toys, cosmetics, and household items, and some laboratory studies suggest phthalates may increase levels of inflammation. Chronic inflammation is associated with many chronic health conditions, such as diabetes and rheumatoid arthritis. Although research is limited, recent studies suggest a strong positive relationship between mono-butyl phthalate (MBP), mono-isobutyl phthalate (MiBP), and monocarboxynonyl phthalate (MCNP) and c-reactive protein (CRP), as well as monoethyl phthalate (MEP) and mono-3-carboxypropyl phthalate (MCPP) and interleukin-6 (IL-6). Additionally, this relationship has not been examined among postmenopausal women, a population that is at higher risk of developing chronic health conditions. Our aim was to examine the association between urinary phthalate biomarkers and inflammation biomarkers among postmenopausal women using baseline data from a subset of participants of the Women’s Health Initiative (WHI) (n=443). Phthalate exposure was assessed using phthalate biomarkers (i.e. phthalate metabolites or their molar sum) from urine samples collected at WHI clinical centers from 1993-1998. We measured 13 phthalate metabolites: MEP, MBP, mono-hydroxybutyl phthalate (MHBP), MiBP, mono-hydroxyisobutyl phthalate (MHiBP), monobenzyl phthalate (MBzP), MCPP, mono (2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), mono (2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-carboxyoctyl phthalate (MCOP), and MCNP. Serum and plasma inflammatory biomarker levels (i.e. CRP, IL-6) were measured in separate WHI ancillary studies, using blood samples collected at baseline. We used multivariable linear regression to analyze associations between each phthalate biomarker and inflammation biomarker, adjusting for important covariates. Phthalate biomarkers MCNP (Model 1: b = 0.523; Model 2: b = 0.362) and MCOP (Model 1: b = 0.384; Model 2: b = 0.240) were positively associated with CRP. Additionally, MCNP (Model 1: b = 0.369; Model 2: b = 0.181) was positively associated with IL-6. Statistically significant associations were not observed among the remaining phthalate biomarkers. Our findings suggest that certain phthalates may be related to increasing levels of inflammation

I Am Not Thinking About Dying?: Suicide Ideation Among Individualistic and Collectivistic Cultures in a Seventh-Day Adventist University

Suicide is the third leading cause of death for 15-24 year olds in the United States of America. Suicide ideation involves having desirability or thoughts of harming or killing oneself. This generally precedes suicide attempts and completions. Any consideration of suicide ideation must be made within the context of culture, and its associated aspects such as gender, since these create a world view that influences all aspects of life. The purpose of this study was to describe and compare cultural and gender differences in suicide ideation in a sample of 140 participants attending a Seventh-day Adventist University in Southeast Tennessee. Specifically, cultural differences in responsibility to family and moral objections in participants representing individualistic and collectivistic cultures were examined. Participants completed the 97 item Life Experience Scale. Although men had higher suicide ideation scores than women, there was no statistical significance in this minor difference, the results are inconclusive. In addition, there are slight cultural differences in family responsibility and moral objections that are inconclusive. Possible reasons for these findings and an agenda for research are discussed. Keywords: suicide ideation, collectivistic, individualistic, culture, Seventh-day Adventist