Recent Insights into the Pathogenesis of Type AA Amyloidosis

The amyloidoses are a group of life-threatening diseases in which fibrils made of misfolded proteins are deposited in organs and tissues. The fibrils are stable, insoluble aggregates of precursor proteins that have adopted an antiparallel β-sheet structure. In type AA, or reactive, amyloidosis, the precursor protein of the fibrils is serum amyloid A (SAA). SAA is a 104-amino-acid protein that is produced in the liver in response to proinflammatory cytokines. Although the protein that is produced by the liver contains 104 amino acids, only the N-terminal 66–76 amino acids are found in amyloid fibrils. Furthermore, SAA has been shown to have an α-helical structure primarily. Thus, for SAA to be incorporated into an amyloid fibril, two processes have to occur: C-terminal cleavage and conversion into a β-sheet. Only a minority of patients with elevated SAA levels develop amyloidosis. Factors that contribute to the risk of amyloidosis include the duration and degree of SAA elevation, polymorphisms in SAA, and the type of autoinflammatory syndrome. In the Hyper-IgD syndrome, amyloidosis is less prevalent than in the other autoinflammatory diseases. In vitro work has shown that the isoprenoid pathway influences amyloidogenesis by farnesylated proteins. Although many proteins contain domains that have a potential for self-aggregation, amyloidosis is only a very rare event. Heat shock proteins (HSPs) are chaperones that assist other proteins to attain, maintain, and regain a functional conformation. In this review, recent insights into the pathogenesis of amyloidosis are discussed, in addition to a new hypothesis for a role of HSPs in the pathogenesis of type AA

Imaging along-strike variations in mechanical properties of the Gofar transform fault, East Pacific Rise

Author Posting. © American Geophysical Union, 2014. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Solid Earth 119 (2014): 7175–7194, doi:10.1002/2014JB011270.A large part of global plate motion on mid-ocean ridge transform faults (RTFs) is not accommodated as major earthquakes. When large earthquakes do occur, they often repeat quasiperiodically. We focus here on the high slip rate (∼14 cm/yr) Gofar transform fault on the equatorial East Pacific Rise. This fault is subdivided into patches that slip during Mw 5.5–6 earthquakes every 5 to 6 years. These patches are separated by rupture barriers that accommodate slip through swarms of smaller events and/or aseismic creep. We performed an imaging study to investigate which spatiotemporal variations of the fault zone properties control this segmentation in mechanical behavior and could explain the specific behavior of RTFs at the global scale. We adopt a double-difference approach in a joint inversion of active air gun shots and microseismicity recorded for 1 year. This data set includes the 2008 Mw 6 Gofar earthquake. The along-strike P wave velocity structure reveals an abrupt transition between the barrier area, characterized by a damaged fault zone of 10–20% reduced Vp and a nearly intact fault zone in the asperity area. The importance of the strength of the damage zone on the mechanical behavior is supported by the temporal S wave velocity changes which suggest increased damage within the barrier area, during the week preceding the Mw 6 earthquake. Our results support the conclusion that extended highly damaged zones are the key factor in limiting the role of major earthquakes to accommodate plate motion along RTFs.The material presented here is based on work supported by the National Science Foundation grants 1232725 and 0242117.2015-03-2

The Survival Paradox of Elderly Patients After Major Liver Resections

The objective of this study is to assess the outcome of liver resections in the elderly in a matched control analysis. From a prospective single center database of 628 patients, 132 patients were aged 60 years or over and underwent a primary major liver resection. Of these patients, 93 could be matched one-to-one with a control patient, aged less than 60 years, with the same diagnosis and the same type of liver resection. The mean age difference was 16.7 years. Patients over 60 years of age had a significantly higher American Society of Anaesthesiologists (ASA) grade. All other demographics and operative characteristics were not different. In-hospital mortality and morbidity were higher in the patients over 60 years of age (11% versus 2%, p=0.017 and 47% versus 31%, p=0.024). One-, 3-, and 5-year survival rates in the patients over 60 years of age were 81%, 58%, and 42%, respectively, compared to 90%, 59%, and 42% in the control patients (p=0.558). Unified model Cox regression analysis showed that resection margin status (hazard ratio 2.51) and ASA grade (hazard ratio 2.26), and not age, were determining factors for survival. This finding underlines the important fact that in patient selection for major liver resections, ASA grade is more important than patient age

A geological and geophysical context for the Wenchuan earthquake of 12 May 2008, Sichuan, People's Republic of China

On 12 May 2008, a magnitude 7.9 earthquake ruptured the Longmen Shan margin of the eastern Tibetan plateau. This event occurred within the context of long-term uplift and eastward enlargement of the plateau. The area has numerous geological features not typical of active convergent mountain belts, including the presence of a steep mountain front (>4 km relief) but an absence of large-magnitude low-angle thrust faults; young high topography (post ca. 15 Ma) and thickened crust but low global positioning system (GPS) shortening rates (<3 mm/yr); and no coeval foreland subsidence. In our interpretation, crustal thickening beneath the eastern Tibetan plateau occurred without large-scale shortening of the upper crust but instead is caused by ductile thickening of the deep crust in a weak (low-viscosity) layer. Late Cenozoic shortening across the Longmen Shan could be as little as 10-20 km, with folding and faulting mainly accommodating differential surface uplift between the plateau and the Sichuan Basin. The earthquake of 12 May probably reflects long-term uplift with slow convergence and right-slip, of the eastern plateau relative to the Sichuan Basin. GPS-determined rates in the vicinity of the 12 May event suggest an average recurrence interval of ∼2,000-10,000 yr

Modeling of craton stability using a viscoelastic rheology

Archean cratons belong to the most remarkable features of our planet since they represent continental crust that has avoided reworking for several billions of years. Even more, it has become evident from both geophysical and petrological studies that cratons exhibit deep lithospheric keels which equally remained stable ever since the formation of the cratons in the Archean. Dating of inclusions in diamonds from kimberlite pipes gives Archean ages, suggesting that the Archean lithosphere must have been cold soon after its formation in the Archean (in order to allow for the existence of diamonds) and must have stayed in that state ever since. Yet, although strong evidence for the thermal stability of Archean cratonic lithosphere for billions of years is provided by diamond dating, the long-term thermal stability of cratonic keels was questioned on the basis of numerical modeling results. We devised a viscoelastic mantle convection model for exploring cratonic stability in the stagnant lid regime. Our modeling results indicate that within the limitations of the stagnant lid approach, the application of a sufficiently high temperature-dependent viscosity ratio can provide for thermal craton stability for billions of years. The comparison between simulations with viscous and viscoelastic rheology indicates no significant influence of elasticity on craton stability. Yet, a viscoelastic rheology provides a physical transition from viscously to elastically dominated regimes within the keel, thus rendering introduction of arbitrary viscosity cutoffs, as employed in viscous models, unnecessary