Efficient inhibition of the Alzheimer's disease beta-secretase by membrane targeting

beta-Secretase plays a critical role in beta-amyloid formation and thus provides a therapeutic target for Alzheimer's disease. Inhibitor design has usually focused on active-site binding, neglecting the subcellular localization of active enzyme. We have addressed this issue by synthesizing a membrane-anchored version of a beta-secretase transition-state inhibitor by linking it to a sterol moiety. Thus, we targeted the inhibitor to active beta-secretase found in endosomes and also reduced the dimensionality of the inhibitor, increasing its local membrane concentration. This inhibitor reduced enzyme activity much more efficiently than did the free inhibitor in cultured cells and in vivo. In addition to effectively targeting beta-secretase, this strategy could also be used in designing potent drugs against other membrane protein targets.     

Estimating incidental takes of shearwaters in driftnet fisheries: lessons for the conservation of seabirds

We consider estimation of the magnitude of incidental fisheries ‘bycatch’ for two petrel species, sooty shearwaters (Puffinus griseus) and short-tailed shearwaters (Puffinus tenuirostris). There are clear statistical advantages in estimating bycatch for abundant species such as these, and our results may also guide the conservation and management of rarer species. We used fisheries statistics and observer data to estimate retrospectively the total numbers of sooty and short-tailed shearwaters bycatch in seven large-scale pelagic North Pacific driftnet fisheries between 1952 and 2001. Sensitivity analysis greatly simplified estimation of uncertainty by identifying four driftnet fisheries to be of particular importance in determining the magnitude and precision of the estimated bycatch totals. We estimated that between 1.0 and 12.8 million (95% CI) sooty shearwaters were killed by driftnets between 1952 and 2001. For short-tailed shearwaters we estimated between 4.6 and 21.2 million (95% CI) over the same period. More precise estimation was hampered by the paucity of available observer data, lack of reported detail and inconsistencies among data sources. Estimates may be strongly biased because some dead birds are misidentified or drop out of nets before hauling, or because some records were of live captures that were subsequently released. Improved estimation of overall take and its impact on populations of seabirds requires standardisation of reporting, allowance for potential sampling bias, as well as a clearer definition of the sampling unit and underlying bycatch probability distribution model, and knowledge of potential compensatory changes in population parameters.     

Rice R & D Thrusts in the Philippines

1THEPHILIPPINERICESITUA TIONDuringthelastdecade (1991- 2 0 0 0 ) ,annualgrowthin productionslightlyimprovedto 2 3%from 2 2 %duringthepreviousdecade (1981-1990 ) .Duringthelastdecade (1991- 2 0 0 0 ) ,annu algrowthinproductionslightlyimprovedto 2 3%from 2 2 %duringthe previousdecade (1981-1990 ) .Notwithstandingthesteadyincreaseinriceproduction ,thecountryremainedanetriceim porter .In 2 0 0 1,palay (paddy) productioninthecountryhit 12 95Mmtoraround 9 11Mmtofrice .However,inthes…     

Teaching small animal reproduction via virtual patients

Virtual patients have become an interesting alternative in medical education. Due to increasing demands regarding theoretical and clinical teaching and to improve an interdisciplinary approach, a new blended learning concept including virtual patients was developed and implemented in the veterinary curriculum of the Freie Universität Berlin. In the presented project, three virtual patients from the field of canine reproduction were developed. They focus on pregnancy diagnosis with suspected luteal insufficiency, pyometra and benign prostatic hyperplasia, respectively. The results of an evaluation by veterinary students of the 7th semester showed a high acceptance of virtual patients in a blended learning reproduction module in the interdisciplinary lectures. Students especially preferred videos, such as video lectures, hands-on videos and animations as well as a glossary for background information, to successfully and autonomously work on a virtual case. The content covered by the new modules that were developed in the context of this project is part of a spiral curriculum; they will be revised and enhanced during the clinical year.     

Limb‐sparing in dogs using patient‐specific,three‐dimensional‐printed endoprosthesis for distal radial osteosarcoma: A pilot study

Limb‐sparing for distal radial osteosarcoma has a high rate of complications. Using personalized three‐dimensional (3D)‐printed implants might improve outcome. The goals of this study were to optimize use of patient‐specific, 3D‐printed endoprostheses for limb‐sparing in dogs in the clinical environment and to report the outcome. This was a pilot study where five client‐owned dogs were enrolled. Computed tomography (CT) of the thoracic limbs was performed, which was used to create patient‐specific endoprostheses and cutting guides, and repeated on the day of surgery. Intra‐arterial (IA) carboplatin was introduced in the clinical management. Limb‐sparing was performed. Outcome measures were time required to produce the endoprosthesis and cutting guide, fit between cutting guide and endoprosthesis with host bones, gait analysis, size of the tumour, percent tumour necrosis, complications, disease‐free interval (DFI) and survival time (ST). Four dogs received IA carboplatin. Excessive tumour growth between planning CT and surgery did not occur in any dog. The interval between the CT and surgery ranged from 14 to 70 days. Fit between the cutting‐guide and endoprosthesis with the host bones was good to excellent. At least one complication occurred in all dogs. Two dogs were euthanized with STs of 192 and 531 days. The other dogs were alive with a follow up of 534 to 575 days. IA chemotherapy is a promising strategy to minimize the risk of excessive tumour growth while waiting for the endoprosthesis and cutting‐guide to be made. The design of the cutting‐guide was critical for best fit of the endoprosthesis with host bones.     

Seasonal development of above‐ and below‐ground organs of Trifolium pratense in grass–legume mixture on different soils

Grass–legume mixtures are suitable for crop rotations in organic farming. However, seasonal development of below‐ground organs of Trifolium pratense in mixtures and on different soils was neglected. We asked (1) how the diameter of the root neck, the maximum order of branching as well as (2) the nodule traits are affected by locality and time, and (3) how above‐ground plant traits of red clover vary in space and time. Red clover was investigated in grass–legume mixtures in the first year of vegetation. Five sites in S Germany were sampled at the day of cut at the end of May, the beginning of July, and at the end of August, respectively. Under similar climatic conditions root traits (diameter of the root neck, order of root branching, size of nodules, and proportion of senescent nodules) differed with soil conditions and time within the season. Root diameter increased during the season. Higher sand content fostered root branching and branched roots developed more nodules. Thinner roots had more active nodules (pink). Root diameter and non‐active senescent (green) or moribund (brown) nodules increased at the end of season. Nodule activity differed more according to season than to soil conditions. The number of nodules per plant (12.5–19.5) decreased from May to August. Cylindrical nodules were found on 85–100% of the plants and branched nodules only on 0–25%. The height of plants was lowest in May and increased in July. The mean number of stems per plant (3.3–6.3) was highest in August. Understanding red clover traits and N₂ fixation is interesting scientifically as well as agronomical. Organic and conventional farmers can both benefit of our findings.     

First biogeographical survey of Artemia in Tanzania

ABSTRACT

In an Artemia survey conducted along the coast of Tanzania between March and July 2017, 32 salt pans in Tanga, Dar es salaam, Pwani, Lindi, and Mtwara were assessed. Of all visited salt pans, 16 (50%) had either Artemia biomass or cysts or both. Body length ranged from 4.0 mm to 9.5 mm, while the mean and modal lengths were 6.2 mm and 6.0 mm, respectively. Temperature ranged from 27.2°C to 48.7°C, salinity from 20 g L^?1 to >140 g L^?1, pH from 5.8 to 7.8, dissolved oxygen (DO) from 3.1 mg L^?1 to 4.9 mg L^?1, water depth from 10 cm to 75 cm and conductivity from 42.0 ms cm^?1 to 176.6 ms cm^?1. A bisexual population of Artemia franciscana is suggested. Observed cyst states included concave, biconcave, spherical and cracking cysts. This is the first to report on the occurrence of Artemia in Tanzania.     

Diurnal patterns of water use in Eucalyptus victrix indicate pronounced desiccation-rehydration cycles despite unlimited water supply

Knowledge about nocturnal transpiration (E(night)) of trees is increasing and its impact on regional water and carbon balance has been recognized. Most of this knowledge has been generated in temperate or equatorial regions. Yet, little is known about E(night) and tree water use (Q) in semi-arid regions. We investigated the influence of atmospheric conditions on daytime (Q(day)) and nighttime water transport (Q(night)) of Eucalyptus victrix L.A.S. Johnson & K.D. Hill growing over shallow groundwater (not >1.5 m in depth) in semi-arid tropical Australia. We recorded Q(day) and Q(night) at different tree heights in conjunction with measurements of stomatal conductance (g(s)) and partitioned E(night) from refilling processes. Q of average-sized trees (200-400 mm diameter) was 1000-3000 l month(-1), but increased exponentially with diameter such that large trees (>500 mm diameter) used up to 8000 l month(-1). Q was remarkably stable across seasons. Water flux densities (J(s)) varied significantly at different tree heights during day and night. We show that g(s) remained significantly different from zero and E(night) was always greater than zero due to vapor pressure deficits (D) that remained >1.5 kPa at night throughout the year. Q(night) reached a maximum of 50% of Q(day) and was >0.03 mm h(-1) averaged across seasons. Refilling began during afternoon hours and continued well into the night. Q(night) eventually stabilized and closely tracked D(night). Coupling of Q(night) and D(night) was particularly strong during the wet season (R2?=?0.95). We suggest that these trees have developed the capacity to withstand a pronounced desiccation-rehydration cycle in a semi-arid environment. Such a cycle has important implications for local and regional hydrological budgets of semi-arid landscapes, as large nighttime water fluxes must be included in any accounting.