THE MOLECULAR INTERACTION BETWEEN TYPE II DIABETES AND ALZHEIMER’S DISEASE THROUGH CROSS-SEEDING OF PROTEIN MISFOLDING

With the population of the world aging, the prominence of diseases such as Type II Diabetes (T2D) and Alzheimer’s disease (AD) are on the rise. In addition, patients with T2D have an increased risk of developing AD compared to age-matched individuals, and the number of AD patients with T2D is higher than among aged-matched non-AD patients. AD is a chronic and progressive dementia characterized by amyloid-beta (Aβ) plaques, neurofibrillary tangles (NFTs), neuronal loss, brain inflammation, and cognitive impairment. T2D involves the dysfunctional use of pancreatic insulin by the body resulting in insulin resistance, hyperglycemia, hyperinsulinemia, pancreatic beta cell (β-cell) death, and other complications. T2D and AD are considered protein misfolding disorders (PMDs). PMDs are characterized by the presence of misfolded protein aggregates, such as in T2D pancreas (islet amyloid polypeptide - IAPP) and in AD brain (amyloid– Aβ) of affected individuals. The misfolding and accumulation of these proteins follows a seeding-nucleation model where misfolded soluble oligomers act as nuclei to propagate misfolding by recruiting other native proteins. Cross-seeding occurs when oligomers composed by one protein seed the aggregation of a different protein. Our hypothesis is that the pathological interactions between T2D and AD may in part occur through cross-seeding of protein misfolding. To test this hypothesis, we examined how each respective aggregate (Aβ or IAPP) affects the disparate disease pathology through in vitro and in vivo studies. Assaying Aβ aggregates influence on T2D pathology, IAPP+/+/APPSwe+/- double transgenic (DTg) mice exhibited exacerbated T2D-like pathology as seen in elevated hyperglycemia compared to controls; in addition, IAPP levels in the pancreas are highest compared to controls. Moreover, IAPP+/+/APPSwe+/- animals demonstrate abundant plaque formation and greater plaque density in cortical and hippocampal areas in comparison to controls. Indeed, IAPP+/+/APPSwe+/- exhibit a colocalization of both misfolded proteins in cerebral plaques suggesting IAPP may directly interact with Aβ and aggravate AD pathology. In conclusion, these studies suggest that cross-seeding between IAPP and Aβ may occur, and that these protein aggregates exacerbate and accelerate disease pathology, respectively. Further mechanistic studies are necessary to determine how these two proteins interact and aggravate both pancreatic and brain pathologies.

Physical properties of firn cores from the 1995/96 and 1996/97 field seasons

The paper focuses on studies of snow-pit samples and shallow firn cores taken during the 1995-96 and 1996-97 field seasons at Amundsenisen, Dronning Maud Land, Antarctica. The dating of the firn is based on the artificial tritium distribution in the snow cover and on several reference horizons identified by electrical measurements. The early 1964 through 1965 horizon is marked by the deposition of sulfate released to the atmosphere during the eruption of the Agung volcano in March 1963; this horizon was detected by dielectric profiling and electrical conductivity measurements; the proof by chemical analysis has still to be seen. At the ten investigated sites on Amundsenisen the 1964-65 horizon was identified 4.1-5.7 m below the surface. The accumulation rates on Amundsenisen are 41-91 kg/m**2/a. The cores are up to 100 years old. A relationship between isotope content and the mean air temperature on a regional scale can be based on measurements of firn temperature at 10 m depth at the drilling sites. Between Neumayer station at the coast and Heimefrontfjella, the temperature gradient of the deuterium content is 9.6 per mil/K. South of Heimefrontfjella, on the Amundsenisen plateau, it is only 5.5 per mil/K. Time series of yearly accumulation rates show no significant trend. For the isotope records a significant trend to higher values with gradients of 0.1-0.2 d2H per mil/a can be seen in five of the ten time series.

Allocation of 14C assimilated in late spring to tissue and biochemical stem components of cork oak (Quercus suber L.) over the seasons

Carbon distribution in the stem of 2-year-old cork oak plants was studied by 14CO2 pulse labeling in late spring in order to trace the allocation of photoassimilates to tissue and biochemical stem components of cork oak. The fate of 14C photoassimilated carbon was followed during two periods: the first 72 h (short-term study) and the first 52 weeks (long-term study) after the 14CO2 photosynthetic assimilation. The results showed that 14C allocation to stem tissues was dependent on the time passed since photoassimilation and on the season of the year. In the first 3 h all 14C was found in the polar extractives. After 3 h, it started to be allocated to other stem fractions. In 1 day, 14C was allocated mostly to vascular cambium and, to a lesser extent, to primary phloem; no presence of 14C was recorded for the periderm. However, translocation of 14C to phellem was observed from 1 week after 14CO2 pulse labeling. The phellogen was not completely active in its entire circumference at labeling, unlike the vascular cambium; this was the tissue that accumulated most photoassimilated 14C at the earliest sampling. The fraction of leaf-assimilated 14C that was used by the stem peaked at 57% 1 week after 14CO2 plant exposure. The time lag between C photoassimilation and suberin accumulation was ∼8 h, but the most active period for suberin accumulation was between 3 and 7 days. Suberin, which represented only 1.77% of the stem weight, acted as a highly effective sink for the carbon photoassimilated in late spring since suberin specific radioactivity was much higher than for any other stem component as early as only 1 week after 14C plant labeling. This trend was maintained throughout the whole experiment. The examination of microautoradiographs taken over 1 year provided a new method for quantifying xylem growth. Using this approach it was found that there was more secondary xylem growth in late spring than in other times of the year, because the calculated average cell division time was much shorter.

Orchestration of gene expression across the seasons : Hypothalamic gene expression in natural photoperiod throughout the year in the Siberian hamster

Funding for work in the laboratory of PB was supported by Scottish Government Rural and Environment Science and Analytical Services Division, BBSRC (grant BB/M001504/1), British Society for Neuroendocrinology (research visit grant to IP). Work in the laboratory of SS was supported by a grant from the DFG (Ste 331/8-1). We thank Siegried Hilken, Marianne Brüning, Dr. Esther Lipokatic-Takacs and Dr. Frank Scherbarth at UVMH for technical assistance. We thank Graham Horgan of Bioinformatics, Statistics Scotland for assistance with some of statistical tests.

Seeding a Profession: The Intersection of the State, International Interests, and the Early Development of Brazilian Nursing

State and international entities can have profound effects on the development of a country’s nursing profession. Through a global health governance lens, this paper explores the development of nursing in Brazil during the early twentieth century, and its intersections with national and international interests. Accordingly, we will show how state policies established an environment that fostered the institutionalization of nursing as a profession in Brazil and supported it as a means to increase the presence of females in nation building processes. The State focused on recruiting elite women for nursing, in part due to the Rockefeller Foundation’s involvement in the country. Nurses who worked for Rockefeller came from well-educated classes within US society with specific ideas about who should be a nurse and the roles of nurses in a healthcare system. These women served as the primary vehicles for interacting with Brazilian health authorities responsible for health system development. Their early efforts did not, however, ensure a system capable of producing nursing human resources at a rate that, in present day Brazil, could meet the health needs of the country. Findings from this paper offer new avenues for historians to explore the early roots of professional nursing through a global health governance lens, improve the understanding of the intersection between international politics and professionalization, and highlight how these factors may impact nursing human resources production in the long term.