Energetics and Structural Characterization of the large-scale Functional Motion of Adenylate Kinase

Adenylate Kinase (AK) is a signal transducing protein that regulates cellular energy homeostasis balancing between different conformations. An alteration of its activity can lead to severe pathologies such as heart failure, cancer and neurodegenerative diseases. A comprehensive elucidation of the large-scale conformational motions that rule the functional mechanism of this enzyme is of great value to guide rationally the development of new medications. Here using a metadynamics-based computational protocol we elucidate the thermodynamics and structural properties underlying the AK functional transitions. The free energy estimation of the conformational motions of the enzyme allows characterizing the sequence of events that regulate its action. We reveal the atomistic details of the most relevant enzyme states, identifying residues such as Arg119 and Lys13, which play a key role during the conformational transitions and represent druggable spots to design enzyme inhibitors. Our study offers tools that open new areas of investigation on large-scale motion in proteins.

Surface temperature and precipitation variations in the western U.S. and their relation to large scale circulation indices [abstract]

EXTRACT (SEE PDF FOR FULL ABSTRACT): An analysis of the principal components of surface temperature and precipitation in the western U.S. is presented. Data consist of monthly mean temperature and total precipitation for 66 climate divisions west of the Continental Divide, for the years 1931-1984. The analysis is repeated for three separate combinations of months - the water year (Oct - Sept), the cool season (Oct - Mar) and the warm season (Apr - Sept). Inspection of monthly precipitation climatology indicates that selection of these combinations of months results in very few awkward splittings of the natural precipitation seasons found in the West.

Regulation of primary production in the Gulf of California through interaction of large-scale and local ocean processes [abstract]

EXTRACT (SEE PDF FOR FULL ABSTRACT): The suppression of primary productivity observed in eastern boundary ecosystems of the Pacific during El Nino episodes does not occur throughout the Gulf of California. On the contrary, analysis of the modern siliceous phytoplankton record from annually layered sediments and compilation of available primary productivity measurements indicate that production is significantly increased in the central Gulf during El Nino years compared to anti-El Nino years. Integrated observations of biological and physical variability during the spring of 1983, under the influence of the strong El Nino, show that very high primary productivity occurred along the eastern margin of the central Gulf. This resulted from the upwelling of a nutrient rich source provided by the locally formed Gulf water mass originating in the northern Gulf. Lower productivity and phytoplankton biomass were associated with the anomalous penetration of Tropical Surface Water along the western side of the Gulf.

Southern California's megaflood event of ca. 1605 AD linked to large-scale atmospheric forcing

A distinct, 1- to 2-cm-thick flood deposit found in Santa Barbara Basin with a varve-date of 1605 AD ± 5 years testifies to an intensity of precipitation that remains unmatched for later periods when historical or instrumental records can be compared against the varve record. The 1605 AD ± 5 event correlates well with Enzel's (1992) finding of a Silver Lake playa perennial lake at the terminus of the Mojave River (carbon-14-dated 1560 AD ± 90 years), in relative proximity to the rainfall catchment area draining into Santa Barbara Basin. According to Enzel, such a persistent flooding of the Silver Lake playa occurred only once during the last 3,500 years and required a sequence of floods, each comparable in magnitude to the largest floods in the modern record. To gain confidence in dating of the 1605 AD ± 5 event, we compare Southern California's sedimentary evidence against historical reports and multi-proxy time-series that indicate unusual climatic events or are sensitive to changes in large-scale atmospheric circulation patterns. The emerging pattern supports previous suggestions that the first decade of the 17th century was marked by a rapid cooling of the Northern Hemisphere, with some indications for global coverage. A burst of volcanism and the occurrence of El Nino seem to have contributed to the severity of the events. The synopsis of the 1605 AD ± 5 years flood deposit in Santa Barbara Basin, the substantial freshwater body at Silver Lake playa, and much additional paleoclimatic, global evidence testifies for an equatorward shift of global wind patterns as the world experienced an interval of rapid, intense, and widespread cooling.