Venom Diversity and Evolution in the Most Divergent Cone Snail Genus Profundiconus

Profundiconus is the most divergent cone snail genus and its unique phylogenetic position, sister to the rest of the family Conidae, makes it a key taxon for examining venom evolution and diversity. Venom gland and foot transcriptomes of Profundiconus cf. vaubani and Profundiconus neocaledonicus were de novo assembled, annotated, and analyzed for differential expression. One hundred and thirty-seven venom components were identified from P. cf. vaubani and 82 from P. neocaledonicus, with only four shared by both species. The majority of the transcript diversity was composed of putative peptides, including conotoxins, profunditoxins, turripeptides, insulin, and prohormone-4. However, there were also a significant percentage of other putative venom components such as chymotrypsin and L-rhamnose-binding lectin. The large majority of conotoxins appeared to be from new gene superfamilies, three of which are highly different from previously reported venom peptide toxins. Their low conotoxin diversity and the type of insulin found suggested that these species, for which no ecological information are available, have a worm or molluscan diet associated with a narrow dietary breadth. Our results indicate that Profundiconus venom is highly distinct from that of other cone snails, and therefore important for examining venom evolution in the Conidae family

Protein Structure

Since the dawn of recorded history, and probably even before, men and women have been grasping at the mechanisms by which they themselves exist. Only relatively recently, did this grasp yield anything of substance, and only within the last several decades did the proteins play a pivotal role in this existence. In this expose on the topic of protein structure some of the current issues in this scientific field are discussed. The aim is that a non-expert can gain some appreciation for the intricacies involved, and in the current state of affairs. The expert meanwhile, we hope, can gain a deeper understanding of the topic

Washington University Record, April 3, 1997

https://digitalcommons.wustl.edu/record/1754/thumbnail.jp

The effect of animal venom in the treatment of pancreatic and colorectal cancer

Pancreatic and colorectal cancer are aggressive, difficult to target cancers with new therapeutic options desperately required to improve prognosis. Animal venoms are useful in drug discovery due to huge variety of bioactive components evolved over millions of years. Venom has already been utilised in drug discovery with several venom derived drugs currently on the market. A plate-based resazurin assay was used to determine cytotoxicity of a panel of cobra venoms against BxPC-3 pancreatic and SW620 colorectal cancer cell lines in-vitro. African spitting cobra (Afronaja) venoms displayed selective toxicity against SW620 cells compared to non-spitting and Asian cobra venoms. Five Afronaja venoms were fractionated using HPLC then the venom components were rescreened in a miniaturised resazurin assay. Dose response curves for both lines were performed using selected fractions, giving IC50 values between 17-225 μg/ml. Four venom fractions were analysed using Mass Spectrometry (MS) and identified as cytotoxins. MS outputs plus bioinformatic techniques predicted likely sequences for each fraction. A structure activity relationship was performed and AA residue 7 and AAs 26-29 were identified as conferring the most significant selective toxicity. Finally, a preliminarily qPCR study assessed the effect of each fraction on the tested cell lines. This study investigated 20 genes commonly mis-regulated in pancreatic and colorectal cancer. The cell lines were exposed to three venom fractions and regulation of each gene assessed compared to untreated controls. SMAD4, Tp53, WNT1 and EGFR genes were significantly upregulated following addition of venom and MMP9 and Bcl-2 were significantly downregulated in this preliminary study. A larger scale qPCR study should be performed to confirm these findings and assess other potential genetic alterations caused by the venom fraction to assess the potential for development into an anti-cancer treatment option

Using Tangible Interaction and Virtual Reality to Support Spatial Perspective Taking Ability

According to several large-scale and longitudinal studies, spatial ability, one of the primary mental abilities, has been shown as a significant predictor for STEM learning (Science, Technology, Engineering, and Mathematics) and career success. Frameworks in HCI (Human-Computer Interaction) and TEI (Tangible and Embodied Interaction) also indicated how the spatial-related aspects of interaction are a common design theme for interfaces using emerging technologies. However, currently only very few interactive systems (using TEI) are designed around a target spatial ability. TEI’s direct effects on spatial ability are also not well-investigated. Meanwhile, a growing body of research from cognitive sciences, such as embodied cognition and Common Coding Theory, shows that physical movements can enhance cognition in aspects that involve spatial thinking. Also, virtual reality (VR) affords better 3D perception for digital environments, and provides design opportunities to engage users with spatial tasks that may not be otherwise imagined or achieved in the real world. This research describes how we designed and built the system TASC (Tangibles for Augmenting Spatial Cognition), which combines body movement tracking and tangible objects with VR. We recap our design process and design rationales, along with how the finalized system was designed to enhance embodiment as a means to activate, support, engage, and hopefully augment spatial perspective taking ability. We conducted a user study with qualitative and quantitative evaluation methods. Respectively, the qualitative evaluation aimed to understand how the participants used the system; the quantitative evaluation was a multi-condition experiment with pre-tests and post-tests used to investigate if and how the system could improve spatial perspective taking ability. We built the digital pre/post-tests based on PTSOT (Perspective Taking/Spatial Orientation Test) (Hegarty, Kozhevnikov, & Waller, 2008). The study in total involved 52 participants: 6 participants (3M/3F) in the pilot study, 46 in the main study (3 conditions, around 15 per condition, each condition was overall gender-balanced). The qualitative analysis focused on the VR-TEI condition (the “main system”). Using thematic analysis with the video clips and written notes (both taken during the participants’ interaction), and audio clips (recorded during the post-interaction interview), we synthesized the qualitative results into 4 themes: (1) Spatial strategies: akin but unique; (2) The use of gestures & verbalization; (3) Positive experience with the system; (4) The potentials of the system. The quantitative statistical analysis, using ANOVA and t-test for the 3-condition experiment, showed that every condition yielded perspective taking improvement from taking the test twice. However, only the VR-TEI condition led to statistically significant improvement. We conclude the research with discussion and future possibilities in these themes of: (a) The role of embodiment; (2) Further explorations of intermediate conditions; (3) A deeper look at sample size and validity; (4) Designing & evaluating TEIs for other spatial abilities; (5) Integration with STEM curriculum. The main contribution of this dissertation is that it reports how a VR-TEI system can be designed, built, and evaluated for a target spatial ability. We hope this research also contributes to bridging some knowledge gaps between interaction design, cognitive science, and STEM learning

Washington University Magazine, Spring 2008

https://digitalcommons.wustl.edu/ad_wumag/1183/thumbnail.jp

Celebrating 120 Years of Butantan Institute Contributions for Toxinology

This is collection of original and review articles selected in recognition of the contribution of Instituto Butantan to the field of toxinology and its continued and relevant role in this field in the 120 years since its foundation. Congratulations to the Butantan Institute, its house scientists, and collaborators on its 120th anniversary

Snake evolution and prospecting of snake venom

In this thesis I have shown that snakes have undergone multiple changes in their genome and embryonic development that has provided them with the variation to which natural selection could act. This thesis provides evidence for the variable mechanisms of venom gene evolution, which presumably is much more flexible than previously thought. But it also underscores the potential use of the many different types of snake venom toxins that could be screened for use against human disorders. And most of all, I hope I have contributed towards the fact that snakes are just an incredibly interesting group of vertebrates from both the perspective of ecology and life-style, as well as from a genomic and molecular perspective. They are, and will always be, my first and true love.LEI Universiteit LeidenThe work described in this thesis was supported by a Toptalent grant from the Netherlands Organization for Scientific Research under grant number 021.002.034 and funding from the Naturalis Biodiversity Center (Leiden).Animal science