Climate change is catchy – but when will it really hurt?

Concern and general awareness about the impacts of climate change in all sectors of the social- ecological-economic system is growing as a result of improved climate science products and information, as well as increased media coverage of the apparent manifestations of the phenomenon in our society. However, scales of climate variability and change, in space and time, are often confused and so  attribution of impacts on various sectors, including the health sector, can be misunderstood and  misrepresented. In this review, we assess the mechanistic links between climate and infectious  diseases in particular, and consider how this relationship varies, and may vary according to different time scales, especially for aetiologically climate-linked diseases. While climate varies in the medium (inter- annual) time frame, this variability itself may be oscillating and/or trending on cyclical and long-term (climate change) scales because of regional and global scale climate phenomena such as the El-Niño southern oscillation coupled with global-warming drivers of  climate change. As several studies have shown, quantifying and modelling these linkages and associations at appropriate time and space scales is both necessary and increasingly feasible with improved climate science products and better epidemiological data. The application of this approach is considered for South Africa, and the need for a more concerted effort in this regard is supported

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

Tick saliva is a rich source of antihemostatic compounds. We amplified a cDNA from the salivary glands of the tropical bont tick (Amblyomma variegatum) using primers based on the variegin sequence, which we previously identified as a novel thrombin inhibitor from the same tick species. The transcript encodes a precursor protein comprising a signal peptide and 5 repeats of variegin-like sequences that could be processed into multiple short peptides. These peptides share 31 to 34% identity with variegin. Here, we structurally and functionally characterized one of these peptides named “avathrin.” Avathrin is a fast, tight binding competitive inhibitor with an affinity of 545 pM for thrombin and is 4 orders of magnitude more selective towards thrombin than to the other serine proteases of the coagulation cascade. The crystal structure of thrombin-avathrin complex at 2.09 Å revealed that avathrin interacts with the thrombin active site and exosite-I. Although avathrin is cleaved by thrombin, the C-terminal cleavage product continues to exert prolonged inhibition. Avathrin is more potent than hirulog-1 in a murine carotid artery thrombosis model. Such precursor proteins that could be processed into multiple thrombin inhibiting peptides appear to be widespread among Amblyomminae, providing an enormous library of molecules for development as potent antithrombotics

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

Tick saliva is a rich source of antihemostatic compounds. We amplified a cDNA from the salivary glands of the tropical bont tick (Amblyomma variegatum) using primers based on the variegin sequence, which we previously identified as a novel thrombin inhibitor from the same tick species. The transcript encodes a precursor protein comprising a signal peptide and 5 repeats of variegin-like sequences that could be processed into multiple short peptides. These peptides share 31 to 34% identity with variegin. Here, we structurally and functionally characterized one of these peptides named “avathrin.” Avathrin is a fast, tight binding competitive inhibitor with an affinity of 545 pM for thrombin and is 4 orders of magnitude more selective towards thrombin than to the other serine proteases of the coagulation cascade. The crystal structure of thrombin-avathrin complex at 2.09 Å revealed that avathrin interacts with the thrombin active site and exosite-I. Although avathrin is cleaved by thrombin, the C-terminal cleavage product continues to exert prolonged inhibition. Avathrin is more potent than hirulog-1 in a murine carotid artery thrombosis model. Such precursor proteins that could be processed into multiple thrombin inhibiting peptides appear to be widespread among Amblyomminae, providing an enormous library of molecules for development as potent antithrombotics

Electroweak parameters of the z0 resonance and the standard model

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