Secretory proteins enter the secretory pathway by translocation across the membrane of the endoplasmic reticulum (ER) via a channel formed primarily by the Sec61 protein. Protein translocation is ...highly temperature dependent in mesophilic organisms. We asked whether the protein translocation machinery of organisms from extremely cold habitats was adapted to function at low temperature and found that post-translational protein import into ER-derived microsomes from Antarctic yeast at low temperature was indeed more efficient than into mesophilic yeast microsomes. Analysis of the amino-acid sequences of the core component of the protein translocation channel, Sec61p, from Antarctic yeast species did not reveal amino-acid changes potentially adaptive for function in the cold, because the sequences were too divergent. We therefore analyzed Sec61alpha (vertebrate Sec61p) sequences and protein translocation into the ER of Antarctic and Arctic fishes and compared them to Sec61alpha and protein translocation into the ER of temperate-water fishes and mammals. Overall, Sec61alpha is highly conserved amongst these divergent taxa; a number of amino-acid changes specific to fishes are evident throughout the protein, and, in addition, changes specific to cold-water fishes cluster in the lumenal loop between transmembrane domains 7 and 8 of Sec61alpha, which is known to be important for protein translocation across the ER membrane. Secretory proteins translocated more efficiently into fish microsomes than into mammalian microsomes at 10 degrees C and 0 degrees C. The efficiency of protein translocation at 0 degrees C was highest for microsomes from a cold-water fish. Despite substantial differences in ER membrane lipid composition, ER membrane fluidity was identical in Antarctic fishes, mesophilic fishes and warm-blooded vertebrates, suggesting that membrane fluidity, although typically important for the function of the transmembrane proteins, is not limiting for protein translocation across the ER membrane in the cold. Collectively, our data suggest that the limited amino-acid changes in Sec61alpha from fishes may be functionally significant and represent adaptive changes that enhance channel function in the cold.
Cancer cluster investigations rarely receive significant public health resource allocations due to numerous inherent challenges and the limited success of past efforts. In 2008, a cluster of ...polycythemia vera, a rare blood cancer with unknown etiology, was identified in northeast Pennsylvania. A multidisciplinary group of federal and state agencies, academic institutions, and local healthcare providers subsequently developed a multifaceted research portfolio designed to better understand the cause of the cluster. This research agenda represents a unique and important opportunity to demonstrate that cancer cluster investigations can produce desirable public health and scientific outcomes when necessary resources are available.
This paper addresses and rejects claims that one can demonstrate experimentally that most untutored subjects are systematically and incurably irrational in their probability judgements and in some ...deductive reasoning tasks. From within a strongly subjectivist theory of probability, it develops the notions of resiliency-a measure of stability of judgements-and robustness-a measure of expected stability. It then becomes possible to understand subjects' behaviour in the Wason selection task, in examples which have been claimed to involve a 'base-rate fallacy', in appearing to ignore laws of large numbers and to overestimate their own success rate as entirely rational: a matter of combining first-order probability assignments with judgements about the robustness of those assignments.
This thesis is a study of cultural interaction in Ulster between indigenous Gaelic, Anglo-Irish and English colonial society during the later sixteenth-century. It focuses particularly upon the ...period of the Nine Years’ War, a conflict between the native Gaelic lords and the Elizabethan crown which is traditionally dated 1594-1603. It does not examine how the two cultures encountered each other on the battlefield but how they did so through the built environment. As noted by Per Cornell (2015, 103) the archaeological profession encounters only traces of the past. In order to gather as many evidential traces as possible my study is rooted in historical archaeology, combining evidence from archaeological excavations, fieldwork and archive data with contemporary text records, cartographic sources and pictorial representations. By incorporating the work of historians, archaeologists and geographers the thesis research gathers more evidential traces than any single approach. The thesis challenges current narratives on the role and meaning of churches, crannogs and tower houses in the contemporary Ulster Gaelic landscape and society. It discusses for the first time evidence of Gaelic secular and military occupation of church buildings in sixteenth-century Ulster. It identifies the role of crannogs within sixteenth-century Ulster Gaelic society and reveals a new archaeological site-type, the crannog-bawn, from which crannogs were accessed and within which ceremonies of hospitality were initiated. It examines tower houses as texts, arguing that they were not built primarily for defence but to help elites display messages of status and identity. The thesis places discussion of Gaelic elite sites within wider debates, showing how the study of Gaelic Ulster can contribute to archaeological discussion at an international level.
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