Carnosine:can understanding its actions on energy metabolism and protein homeostasis inform its therapeutic potential?

The dipeptide carnosine (β-alanyl-L-histidine) has contrasting but beneficial effects on cellular activity. It delays cellular senescence and rejuvenates cultured senescent mammalian cells. However, it also inhibits the growth of cultured tumour cells. Based on studies in several organisms, we speculate that carnosine exerts these apparently opposing actions by affecting energy metabolism and/or protein homeostasis (proteostasis). Specific effects on energy metabolism include the dipeptide's influence on cellular ATP concentrations. Carnosine's ability to reduce the formation of altered proteins (typically adducts of methylglyoxal) and enhance proteolysis of aberrant polypeptides is indicative of its influence on proteostasis. Furthermore these dual actions might provide a rationale for the use of carnosine in the treatment or prevention of diverse age-related conditions where energy metabolism or proteostasis are compromised. These include cancer, Alzheimer's disease, Parkinson's disease and the complications of type-2 diabetes (nephropathy, cataracts, stroke and pain), which might all benefit from knowledge of carnosine's mode of action on human cells. © 2013 Hipkiss et al.; licensee Chemistry Central Ltd.

The Specialist: Coming Soon To Your Local Hotel

In an article entitled - The Specialist: Coming Soon To Your Local Hotel - by Stan Bromley, Regional Vice President and General Manager, Four Seasons Clift Hotel, San Francisco, the author’s introduction states: “An experienced hotelier discusses the importance of the delivery of a high “quality-to-value” ratio consistently to guests, particularly as the hotel market becomes specialized and a distinction is drawn between a “property” and a “hotel.” The author’s primary intention is to make you, the reader, aware of changes in the hospitality/hotel marketplace. From the embryo to the contemporary, the hotel market has consistently evolved; this includes but is not limited to mission statement, marketing, management, facilities, and all the tangibles and intangibles of the total hotel experience. “Although we are knocking ourselves out trying to be everything to everyone, I don't think hotel consumers are as interested in “mixing and matching” as they were in the past,” Bromley says. “Today's hotel guest is looking for “specialized care,” and is increasingly skeptical of our industry-wide hotel ads and promises of greatness.” As an example Bromley makes an analogy using retail outlets such as Macy’s, Saks, and Sears, which cater to their own unique market segment. Hotels now follow the same outline, he allows. “In my view, two key factors will make a hotel a success,” advises Bromley. “First, know your specialty and market to that segment. Second, make sure you consistently offer a high quality-to-value ratio. That means every day.” To emphasize that second point, Bromley offers this bolstering thought, “The second factor that will make or break your business is your ability to deliver a high "quality/value" ratio-and to do so consistently.” The author evidently considers quality-to-value ratio to be an important element. Bromley emphasizes the importance of convention and trade show business to the hotel industry. That business element cannot be over-estimated in his opinion. This doesn’t mean an operator who can accommodate that type of business should exclude other client opportunities outside the target market. It does mean, however, these secondary opportunities should only be addressed after pursuing the primary target strategy. After all, the largest profit margin lies in the center of the target. To amplify the above statement, and in reference to his own experience, Bromley says, “Being in the luxury end of the business I, on the other hand, need to uncover and book individuals and small corporate meetings more than convention or association business.

Altered Landscape or Arms Race? Making Sense of Military Spending in South America

In 2009, South American military spending reached a total of $51.8 billion, a fifty percent increased from 2000 expenditures. The five-year moving average of arms transfers to South America was 150 percent higher from 2005 to 2009 than figures for 2000 to 2004.[1] These figures and others have led some observers to conclude that Latin America is engaged in an arms race. Other reasons, however, account for Latin America’s large military expenditure. Among them: Several countries have undertaken long-prolonged modernization efforts, recently made possible by six years of consistent regional growth.[2] A generational shift is at hand. Armed Forces are beginning to shed the stigma and association with past dictatorial regimes.[3] Countries are pursuing specific individual strategies, rather than reacting to purchases made by neighbors. For example, Brazil wants to attain greater control of its Amazon rainforests and offshore territories, Colombia’s spending demonstrates a response to internal threats, and Chile is continuing a modernization process begun in the 1990s.[4] Concerns remain, however: Venezuela continues to demonstrate poor democratic governance and a lack of transparency; neighbor-state relations between Colombia and Venezuela, Peru and Chile, and Bolivia and Paraguay, must all continue to be monitored; and Brazil’s military purchases, although legitimate, will likely result in a large accumulation of equipment.[5] These concerns can be best addressed by strengthening and garnering greater participation in transparent procurement mechanism.[6] The United States can do its part by supporting Latin American efforts to embrace the transparency process. _________________ [1] Bromley, Mark, “An Arms Race in Our Hemisphere? Discussing the Trends and Implications of Military Expenditures in South America,” Brookings Institution Conference, Washington, D.C., June 3rd, 2010, Transcript Pgs. 12,13, and 16 [2] Robledo, Marcos, “The Rearmament Debate: A Chilean Perspective,” Power Point presentation, slide 18, 2010 Western Hemisphere Security Colloquium, Miami, Florida, May 25th-26th, 2010 [3] Yopo, Boris, “¿Carrera Armamentista en la Regiόn?” La Tercera, November 2nd, 2009, http://www.latercera.com/contenido/895_197084_9.shtml, accessed October 8th, 2010 [4] Walser, Ray, “An Arms Race in Our Hemisphere? Discussing the Trends and Implications of Military Expenditures in South America,” Brookings Institution Conference, Washington, D.C., June 3rd, 2010, Transcript Pgs. 49,50,53 and 54 [5] Ibid., Guevara, Iñigo, Pg. 22 [6] Ibid., Bromley, Mark, Pgs. 18 and 19

Active Energy: Three Mills - open workshop

On 14th May, as part of National Mills Weekend, an open workshop was held outside the 18th century House Mill in Bromley by Bow, the world's largest tidal mill. Members of the Geezers Club in Bow worked in the open air with an engineer to construct the stream wheel, which is being developed in ‘flat pack’ format to maximize transferability. The wheel will be installed in the River Lea later this year.

Fossil associations from the middle and upper Eocene strata of the Pamplona Basin and surrounding areas (Navarre, western Pyrenees)

Fossil associations from the middle and upper Eocene (Bartonian and Priabonian) sedimentary succession of the Pamplona Basin are described. This succession was accumulated in the western part of the South Pyrenean peripheral foreland basin and extends from deep-marine turbiditic (Ezkaba Sandstone Formation) to deltaic (Pamplona Marl, Ardanatz Sandstone and Ilundain Marl formations) and marginal marine deposits (Gendulain Formation). The micropalaeontological content is high. It is dominated by foraminifera, and common ostracods and other microfossils are also present. The fossil ichnoasssemblages include at least 23 ichnogenera and 28 ichnospecies indicative of Nereites, Cruziana, Glossifungites and ?Scoyenia-Mermia ichnofacies. Body macrofossils of 78 taxa corresponding to macroforaminifera, sponges, corals, bryozoans, brachiopods, annelids, molluscs, arthropods, echinoderms and vertebrates have been identified. Both the number of ichnotaxa and of species (e. g. bryozoans, molluscs and condrichthyans) may be considerably higher. Body fossil assemblages are comparable to those from the Eocene of the Nord Pyrenean area (Basque Coast), and also to those from the Eocene of the west-central and eastern part of South Pyrenean area (Aragon and Catalonia). At the European scale, the molluscs assemblages seem endemic from the Pyrenean area, although several Tethyan (Italy and Alps) and Northern elements (Paris basin and Normandy) have been recorded. Palaeontological data of studied sedimentary units fit well with the shallowing process that throughout the middle and late Eocene occurs in the area, according to the sedimentological and stratigraphical data.