Structure-function relationships of variegin: A novel class of thrombin inhibitors

Ph.DDOCTOR OF PHILOSOPH

Rapid genomic evolution drives the diversification of male reproductive genes in dung beetles

10.1093/gbe/evab172Genome Biology and Evolutio

Metalloproteases Affecting Blood Coagulation, Fibrinolysis and Platelet Aggregation from Snake Venoms: Definition and Nomenclature of Interaction Sites

Snake venom metalloproteases, in addition to their contribution to the digestion of the prey, affect various physiological functions by cleaving specific proteins. They exhibit their activities through activation of zymogens of coagulation factors, and precursors of integrins or receptors. Based on their structure–function relationships and mechanism of action, we have defined classification and nomenclature of functional sites of proteases. These metalloproteases are useful as research tools and in diagnosis and treatment of various thrombotic and hemostatic conditions. They also contribute to our understanding of molecular details in the activation of specific factors involved in coagulation, platelet aggregation and matrix biology. This review provides a ready reference for metalloproteases that interfere in blood coagulation, fibrinolysis and platelet aggregation

From Snake Venoms to Therapeutics: A Focus on Natriuretic Peptides

Snake venom is a cocktail of multifunctional biomolecules that has evolved with the purpose of capturing prey and for defense. These biomolecules are classified into different classes based on their functions. They include three-finger toxins, natriuretic peptides, phospholipases and metalloproteinases. The focus for this review is on the natriuretic peptide (NP), which is an active component that can be isolated from the venoms of vipers and mambas. In these venoms, NPs contribute to the lowering of blood pressure, causing a rapid loss of consciousness in the prey such that its mobility is reduced, paralyzing the prey, and often death follows. Over the past 30 years since the discovery of the first NP in the venom of the green mamba, venom NPs have shown potential in the development of drug therapy for heart failure. Venom NPs have long half-lives, different pharmacological profiles, and may also possess different functions in comparison to the mammalian NPs. Understanding their mechanisms of action provides the strategies needed to develop new NPs for treatment of heart failure. This review summarizes the venom NPs that have been identified over the years and how they can be useful in drug development

Unveiling the potential role of natriuretic peptide receptor a isoforms in fine-tuning the cGMP production and tissue-specific function

Abstract Atrial natriuretic peptide (ANP) is a peptide hormone that regulates blood pressure and volume. ANP interacts with natriuretic peptide receptor-A (NPR-A) to lower the blood pressure through vasodilation, diuresis and natriuresis. Previously, we designed two human ANP analogues, one with exclusively diuretic function (DGD-ANP) and the other with exclusively vasodilatory function (DRD-ANP). Although both ANP analogues interact with NPR-A, their ability to produce cGMP was different. Three alternatively spliced isoforms of NPR-A were previously identified in rodents. Here, we evaluated the putative human isoforms for their cGMP production independently and in combination with WT NPR-A in various percentages. All three NPR-A isoforms failed to produce cGMP in the presence of ANP, DGD-ANP, or DRD-ANP. Co-expression of isoforms with WT NPR-A were found to significantly impair cGMP production. Considering the differential tissue expression levels of all three spliced isoforms in rodents have previously been demonstrated, the existence of these non-functional receptor isoforms may act as negative regulator for ANP/NPR-A activation and fine-tune cGMP production by WT NPR-A to different degree in different tissues. Thus, NPR-A isoforms potentially contribute to tissue-specific functions of ANP

CHARACTERIZATION OF A NOVEL INHIBITOR OF COAGULATION FACTOR XIA IDENTIFIED FROM SALIVARY GLAND TRANSCRIPTS OF THE LONE STAR TICK, AMBLYOMMA AMERICANUM

10.1016/j.toxicon.2019.12.083TOXICON177S44-S4

Antithrombotic and Flow Drag‐Reducing Material for Blood‐Contacting Medical Devices

Abstract Blood‐contacting medical devices are often associated with shear‐induced and contact activation thrombosis. Superhydrophobic materials have shown promise to reduce flow drag forces, but not contact activation. Here, a strategy of selectively grafting a potent anti‐thrombin compound on the tips of the surface microstructures of a superhydrophobic polytetrafluoroethylene foam, is presented, to concurrently achieve drag reduction and anti‐thrombosis. This work shows that two grafting approaches – Argon plasma or piranha solution treatment – followed by covalent cross‐linking can successfully graft the drug to the outer tips of the foam and provide anti‐thrombotic functionality. By avoiding grafting to the inner regions of the foam, the surface's drag reduction properties can be retained. The functional durability of the grafted surfaces is evaluated by strong water jetting, which demonstrates that the plasma approach can withstand substantial fluid shearing but not the piranha approach, although the plasma approach involves stronger compromise to the drag reduction capabilities. As the proposed selective grafting strategy is applied to a bulk foam, it can be complemented with a previously proposed strategy of supplying air pressure to the foam pores to bolster resistance to fluid impalement and plastron dissolution, allowing the material to be used in medical devices with high fluid pressures

TOXIN TO LEAD: AN INHIBITOR OF FACTOR XIA ENGINEERED FROM BANDED KRAIT VENOM TOXIN FASXIATOR SHOWED SUPERIOR IN VIVO EFFICACY-SAFETY PROFILE COMPARED TO HEPARIN

10.1016/j.toxicon.2019.12.022TOXICON177S27-S2

Avathrin: a novel thrombin inhibitor derived from a multicopy precursor in the salivary glands of the ixodid tick, Amblyomma variegatum

10.1096/fj.201601216RFASEB JOURNAL3172981-299

Foreign aid, poverty reduction, and democracy

Eradication of poverty is the most pervasive goal of donors' foreign aid programmes. As a result, there has been much research on the degree of correlation between aid and poverty reduction. However, this work to date has shed little light on the direction of causation between the two variables. Using the method of Granger causality, and conditioning aid and poverty on the state of democracy in developing countries, this study asks whether aid flows impact poverty, whether poverty influences aid flows, or whether causality proceeds in both directions simultaneously. While the results identify no causal relationships in some of the sub-samples, they point to the existence of a multitude of relationships across others.