Characterizing Venom Gene Expression, Function and Species Diversity in Predatory Marine Snails of the Terebridae

The Terebridae is a group of predatory marine snails that use their venom to feed on marine annelids. Similar to other venomous organisms, the Terebridae have evolved over millions of years, diverging from their closest relative in the Paleocene era. This thesis investigates what is driving terebrid evolution and species diversification by applying a multidimensional approach

Small Packages, Big Returns: Uncovering the Venom Diversity of Small Inverebrate Conoidean Snails

Venomous organisms used in research were historically chosen based on size and availability. This opportunity-driven strategy created a species bias in which snakes, scorpions, and spiders became the primary subjects of venom research. Increasing technological advancements have enabled interdisciplinary studies using genomics, transcriptomics, and proteomics to expand venom investigation to animals that produce small amounts of venom or lack traditional venom producing organs. One group of non-traditional venomous organisms that have benefitted from the rise of -omic technologies is the Conoideans. The Conoidean superfamily of venomous marine snails includes, the Terebridae, Turridae (s.l), and Conidae. Conoidea venom is used for both predation and defense, and therefore under strong selection pressures. The need for conoidean venom peptides to be potent and specific to their molecular targets has made them important tools for investigating cellular physiology and bioactive compounds that are beneficial to improving human health. A convincing case for the potential of Conoidean venom is made with the first commercially available conoidean venom peptide drug Ziconotide (Prialt®), an analgesic derived from Conus magus venom that is used to treat chronic pain in HIV and cancer patients. Investigation of conoidean venom using -omics technology provides significant insights into predator-driven diversification in biodiversity and identifies novel compounds for manipulating cellular communication, especially as it pertains to disease and disorders

From Mollusks to Medicine: A Venomics Approach for the Discovery and Characterization of Therapeutics from Terebridae Peptide Toxins

Animal venoms comprise a diversity of peptide toxins that manipulate molecular targets such as ion channels and receptors, making venom peptides attractive candidates for the development of therapeutics to benefit human health. However, identifying bioactive venom peptides remains a significant challenge. In this review we describe our particular venomics strategy for the discovery, characterization, and optimization of Terebridae venom peptides, teretoxins. Our strategy reflects the scientific path from mollusks to medicine in an integrative sequential approach with the following steps: (1) delimitation of venomous Terebridae lineages through taxonomic and phylogenetic analyses; (2) identification and classification of putative teretoxins through omics methodologies, including genomics, transcriptomics, and proteomics; (3) chemical and recombinant synthesis of promising peptide toxins; (4) structural characterization through experimental and computational methods; (5) determination of teretoxin bioactivity and molecular function through biological assays and computational modeling; (6) optimization of peptide toxin affinity and selectivity to molecular target; and (7) development of strategies for effective delivery of venom peptide therapeutics. While our research focuses on terebrids, the venomics approach outlined here can be applied to the discovery and characterization of peptide toxins from any venomous taxa

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

A Case of Lewis-Sumner Syndrome Showing Dramatic Improvement after Plasma Exchange

We report a patient with Lewis-Sumner syndrome (LSS) who showed an improvement only with plasma exchange (PE). The patient, 32-yr old man, had progressive multifocal motor-sensory deficits with persistent, multiple conduction blocks and marked slowing of NCVs. Nerve pathology supported a diagnosis of demyelinating neuropathy by revealing marked loss of myelinated fibers with inter- and intrafascicular variation. Although the patient was refractory to treatment with corticosteroid and intravenous immunoglobulin, PE produced a dramatic improvement. Our experience strongly proposes that PE should be tried for refractory LSS

International Guillain-Barré Syndrome Outcome Study (IGOS): protocol of a prospective observational cohort study on clinical and biological predictors of disease course and outcome in Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy with a highly variable clinical presentation, course, and outcome. The factors that determine the clinical variation of GBS are poorly understood which complicates the care and treatment of individual patients. The protocol of the ongoing International GBS Outcome Study (IGOS), a prospective, observational, multi-centre cohort study that aims to identify the clinical and biological determinants and predictors of disease onset, subtype, course and outcome of GBS is presented here. Patients fulfilling the diagnostic criteria for GBS, regardless of age, disease severity, variant forms, or treatment, can participate if included within two weeks after onset of weakness. Information about demography, preceding infections, clinical features, diagnostic findings, treatment, course and outcome is collected. In addition, cerebrospinal fluid and serial blood samples for serum and DNA is collected at standard time points. The original aim was to include at least 1000 patients with a follow-up of 1-3 years. Data are collected via a web-based data entry system and stored anonymously. IGOS started in May 2012 and by January 2017 included more than 1400 participants from 143 active centres in 19 countries across 5 continents. The IGOS data/biobank is available for research projects conducted by expertise groups focusing on specific topics including epidemiology, diagnostic criteria, clinimetrics, electrophysiology, antecedent events, antibodies, genetics, prognostic modelling, treatment effects and long-term outcome of GBS. The IGOS will help to standardize the international collection of data and biosamples for future research of GBS. ClinicalTrials.gov Identifier: NCT01582763

The Lantern Vol. 12, No. 1, January 1944

• In the Den of the Titans • Lass of Dimoch • For One Gone West • Tropical New Year • Nightfall • Hope From the Blue • Christmas Shopping, a Retrospective Glance • What Makes a Wing Lift? • 201 Main Street • Paradox • Stabilizing Americans • Sky-Islands • With Timbrel and Dance • Jazz • The Grave, a Translationhttps://digitalcommons.ursinus.edu/lantern/1031/thumbnail.jp

The Lantern Vol. 14, No. 2, February 1946

• Dog Daze • Locomotion • The Battle • Thoughts at Midnight • We Have a Race to Run • A Parable • Darkness at Dawn • Room for Error • Elegy Americana • Will This Happen Here • Last Mission • Free Trade • Love Letterhttps://digitalcommons.ursinus.edu/lantern/1038/thumbnail.jp

The Lantern Vol. 14, No. 1, December 1945

• Editorial • The Medal • Pain • Wonder • Warmth • Memory Lingers • Morning • Watch the Birdie • Poems • The War Dogs of the Devildogs • Joy in Every Heart • To Live in Hearts • The Operation • Moderately Well Done • Steak is King • Grateful America?https://digitalcommons.ursinus.edu/lantern/1037/thumbnail.jp

The Lantern Vol. 14, No. 1, December 1945

• Editorial • The Medal • Pain • Wonder • Warmth • Memory Lingers • Morning • Watch the Birdie • Poems • The War Dogs of the Devildogs • Joy in Every Heart • To Live in Hearts • The Operation • Moderately Well Done • Steak is King • Grateful America?https://digitalcommons.ursinus.edu/lantern/1037/thumbnail.jp