Identifying structural features of fibrillar islet amyloid polypeptide using site-directed spin labeling

Pancreatic amyloid deposits, composed primarily of the 37-residue islet amyloid polypeptide (IAPP), are a characteristic feature found in more than 90% of patients with type II diabetes. Although IAPP amyloid deposits are associated with areas of pancreatic islet beta-cell dysfunction and depletion and are thought to play a role in disease, their structure is unknown. We used electron paramagnetic resonance spectroscopy to analyze eight spin-labeled derivatives of IAPP in an effort to determine structural features of the peptide. In solution, all eight derivatives gave rise to electron paramagnetic resonance spectra with sharp lines indicative of rapid motion on the sub-nanosecond time scale. These spectra are consistent with a rapidly tumbling and highly dynamic peptide. In contrast, spectra for the fibrillar form exhibit reduced mobility and the presence of strong intermolecular spin-spin interactions. The latter implies that the peptide subunits are ordered and that the same residues from neighboring peptides are in close proximity to one another. Our data are consistent with a parallel arrangement of IAPP peptides within the amyloid fibril. Analysis of spin label mobility indicates a high degree of order throughout the peptide, although the N-terminal region is slightly less ordered. Possible similarities with respect to the domain organization and parallelism of Alzheimer's amyloid beta peptide fibrils are discussed.     

Membrane interaction of islet amyloid polypeptide

Increasing evidence suggests that the misfolding and deposition of IAPP plays an important role in the pathogenesis of type II, or non-insulin-dependent diabetes mellitus (T2DM). Membranes have been implicated in IAPP-dependent toxicity in several ways: Lipid membranes have been shown to promote the misfolding and aggregation of IAPP. Thus, potentially toxic forms of IAPP can be generated when IAPP interacts with cellular membranes. In addition, membranes have been implicated as the target of IAPP toxicity. IAPP has been shown to disrupt membrane integrity and to permeabilize membranes. Since disruption of cellular membranes is highly toxic, such a mechanism has been suggested to explain the observed IAPP toxicity. Here, we review IAPP-membrane interaction in the context of (1) catalyzing IAPP misfolding and (2) being a potential origin of IAPP toxicity.     

The future of high-quality Ceylon tea seems bleak in the face of climate change

International Journal of Biometeorology - Understanding the interactive effects and relationships between biochemical elements of tea leaves and the related factors, particularly climatic,...     

Organization of Ryanodine Receptors, Transverse Tubules, and Sodium-Calcium Exchanger in Rat Myocytes

Confocal and total internal reflection fluorescence imaging was used to examine the distribution of caveolin-3, sodium-calcium exchange (NCX) and ryanodine receptors (RyRs) in rat ventricular myocytes. Transverse and longitudinal optical sectioning shows that NCX is distributed widely along the transverse and longitudinal tubular system (t-system). The NCX labeling consisted of both punctate and distributed components, which partially colocalize with RyRs (27%). Surface membrane labeling showed a similar pattern but the fraction of RyR clusters containing NCX label was decreased and no nonpunctate labeling was observed. Sixteen percent of RyRs were not colocalized with the t-system and 1.6% of RyRs were found on longitudinal elements of the t-system. The surface distribution of RyR labeling was not generally consistent with circular patches of RyRs. This suggests that previous estimates for the number of RyRs in a junction (based on circular close-packed arrays) need to be revised. The observed distribution of caveolin-3 labeling was consistent with its exclusion from RyR clusters. Distance maps for all colocalization pairs were calculated to give the distance between centroids of punctate labeling and edges for distributed components. The possible roles for punctate NCX labeling are discussed.     

Electric field driven jetting: an emerging approach for processing living cells

This paper reports for the first time the ability to process living cellular materials by means of electrified jets at electric field strengths of up to 2 kV/mm. Bio-suspensions containing living human Jurkat cells at different concentrations were processed via this jetting approach. The jetting process was carried out at an electric field strength between 0.67 kV/mm and 2 kV/mm, corresponding to an applied voltage of 10-30 kV between two electrodes approximately 15 mm apart. The Jurkat cells were jetted under sterile conditions, collected in petri dishes and incubated for 24 and 48 hours. During and after incubation, cells were assessed for survival and structural damage; cells were found to be unharmed and to retain their integrity under all electric field strengths examined. At all field strengths jetting took place in the unstable mode. Good correlation was observed between droplet distribution plots generated by way of laser spectroscopy and estimated values from measurements of droplet relics.     

The distribution and status of the adder (Vipera berus L) in Scotland determined from questionnaire surveys

Abstract. During 1992 two questionnaire surveys, aimed at farmers and sections of the general public, were conducted to determine the distribution and status of the adder ( Vipera berus L.) in Scotland. In total, 94% of the Scottish mainland and inner isles were covered by the two surveys. The adder appears to be widespread throughout Scotland, although it is absent from much of the Central Valley, the Outer Hebrides and Northern Isles, and from much of the mountainous region between Inverness and Glasgow.
The distribution of the adder in Scotland was compared with the distributions of different habitat types defined in the ITE Land Class survey. Adders were strongly associated with areas of heterogeneous land use and negatively associated with intensively arable areas and rugged mountainous areas. Strong evidence was found to suggest that perceived adder abundance had declined during the last 10 years. Although the evidence suggesting that the distribution of adders in Scotland had changed was less strong, the results of the Farm Survey did indicate that it had contracted. The perceived change in status of the adder in Scotland during the last 10 years was compared with the observed changes in land use over the same period.     

Antholysis in Cassava (Manihot esculenta Crantz) Possibly Caused by Mycoplasma-Like Organisms

Phyllody and apostasis of cassava plants were frequently observed during recent disease surveys in the Cauca Valley of Colombia. Many valuable cassava clones have been affected rendering them unsuitable for hybridization. Light and electron microscopic observations have revealed the presence of mycoplasma-like organisms in the diseased phloem tissues. The causal agent is sensitive to tetracycline and streptomycin at 1000 ppm a. i., but not to penicillin.