Deposition of iron and beta-amyloid plaques is associated with cortical cellular damage in rabbits fed with long-term cholesterol-enriched diets

Hypercholesterolemia is a potential trigger of Alzheimer's disease, and is thought to increase brain levels of beta-amyloid (Abeta) and iron. However, animal models to address the mechanisms by which Abeta and iron accumulation may cause neuronal damage are poorly defined. To address this question, we fed adult rabbits a 1% cholesterol-enriched diet for 7 months. This diet was associated with increased regional deposition of both iron and Abeta peptide in the brain. Iron preferentially accumulated around Abeta plaques in the adjacent cortex, but was not found in the hippocampus. Co-localization of iron and Abeta was accompanied by apoptosis, DNA damage, blood-brain barrier (BBB) disruption, as well as dysregulation in the level of the iron-regulatory proteins, ferritin and heme-oxygenase-1. We further demonstrate that the cholesterol diet-induced apoptosis is mediated by the activation of the endoplasmic reticulum stress pathway, involving the down-regulation of the endoplasmic reticulum chaperones, calreticulin, grp78 and grp94, and the activation of the growth and arrest DNA damage protein, gadd153. Our results suggest that BBB damage and disturbances in iron metabolism may render the cortex more vulnerable than the hippocampus to the cholesterol-induced cellular stress.     

Restricted Hematopoietic Progenitors and Erythropoiesis Require SCF from Leptin Receptor+ Niche Cells in the Bone Marrow

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Display of an Inedible Prop as a Signal of Aggression? Adaptive Significance of Leaf‐Display by the Turquoise‐Browed Motmot,Eumomota superciliosa

The incorporation of an inedible object (prop) into a behavioral display is rare among birds. Only four avian taxa have been reported to display with a prop, and in all studied species, prop use has been found to play a role in mate acquisition. However, little is known about the context and adaptive significance of prop use by the motmots. Both male and female motmots perform a leaf‐display, whereby a leaf is held horizontally in the tip of the bill for an extended period. I collected observational data on leaf‐display by the turquoise‐browed motmots (Eumomota superciliosa) to investigate the potential role of this display as a mate‐choice or agonistic signal. Observations of 61 leaf‐displays by 27 individuals indicate that males and females are similarly likely to perform the leaf‐display, that the leaf‐display is performed throughout the long‐breeding season, and that the display is performed by both paired and unpaired birds. These observations suggest that the leaf‐display does not play a role in mate‐attraction. However, the leaf‐display was often performed in association with a chase or fight with a same‐sex individual, and the display was sometimes performed in conjunction with an agonistic display at nest sites, suggesting that the leaf‐display may function in both sexes as a signal of aggressive intent or as a signal of status.     

Lipid metabolism and cell composition of the oleaginous yeast Apiotrichum curvatum grown at different carbon to nitrogen ratios

Apiotrichum curvatum ATCC 20509, an oleaginous yeast that can accumulate up to 60% of its cellular dry weight as intracellular lipid when grown with excess carbon, was grown in nitrogen-limited, balanced, and lactose-free medium with asparagine as nitrogen source and lactose as carbon source. Biomass and lipid accumulation were measured, cell composition was analyzed, and catalase activity was followed as marker enzyme for peroxisomes. The organism accumulated 54% of its dry weight as total cellular lipid when grown under nitrogen limitation and accumulated only 20-25% of its dry weight as lipid when grown in balanced medium. When starved for carbon, cells utilized endogenous lipid and carbohydrate as carbon and energy sources; the intracellular contents of lipid and carbohydrate decreased by 31 and 26%, respectively. Intracellular carbohydrates also seemed to be used as intermediates for lipid accumulation and lipid turnover. Catalase activity was strongly induced (over 10-fold increase in specific activity) when cells metabolized endogenous lipid. The lipid content of cells was inversely related to catalase activity and to intracellular protein or total nitrogen content. Lipid content showed no correlation with intracellular carbohydrate content.     

Effect of Bafilomycin A1 and Nocodazole on Endocytic Transport in HeLa Cells: Implications for Viral Uncoating and Infection

Bafilomycin A1 (baf), a specific inhibitor of vacuolar proton ATPases, is commonly employed to demonstrate the requirement of low endosomal pH for viral uncoating. However, in certain cell types baf also affects the transport of endocytosed material from early to late endocytic compartments. To characterize the endocytic route in HeLa cells that are frequently used to study early events in viral infection, we used ³⁵S-labeled human rhinovirus serotype 2 (HRV2) together with various fluid-phase markers. These virions are taken up via receptor-mediated endocytosis and undergo a conformational change to C-antigenic particles at a pH of <5.6, resulting in release of the genomic RNA and ultimately in infection (E. Prchla, E. Kuechler, D. Blaas, and R. Fuchs, J. Virol. 68:3713–3723, 1994). As revealed by fluorescence microscopy and subcellular fractionation of microsomes by free-flow electrophoresis (FFE), baf arrests the transport of all markers in early endosomes. In contrast, the microtubule-disrupting agent nocodazole was found to inhibit transport by accumulating marker in endosomal carrier vesicles (ECV), a compartment intermediate between early and late endosomes. Accordingly, lysosomal degradation of HRV2 was suppressed, whereas its conformational change and infectivity remained unaffected by this drug. Analysis of the subcellular distribution of HRV2 and fluid-phase markers in the presence of nocodazole by FFE revealed no difference from the control incubation in the absence of nocodazole. ECV and late endosomes thus have identical electrophoretic mobilities, and intraluminal pHs of <5.6 and allow uncoating of HRV2. As bafilomycin not only dissipates the low endosomal pH but also blocks transport from early to late endosomes in HeLa cells, its inhibitory effect on viral infection could in part also be attributed to trapping of virus in early endosomes which might lack components essential for uncoating. Consequently, inhibition of viral uncoating by bafilomycin cannot be taken to indicate a low pH requirement only.     

The db mutation improves memory in younger mice in a model of Alzheimer's disease

Alzheimer's disease (AD) is the most common age-related neurodegenerative disease, while obesity is a major global public health problem associated with the metabolic disorder type 2 diabetes mellitus (T2DM). Chronic obesity and T2DM have been identified as invariant risk factors for dementia and late-onset AD, while their impacts on the occurrence and development of AD remain unclear. As shown in our previous study, the diabetic mutation (db, Lepr^db/db) induces mixed or vascular dementia in mature to middle-aged APP^ΔNL/ΔNL x PS1^P264L/P264L knock-in mice (db/AD). In the present study, the impacts of the db mutation on young AD mice at 10 weeks of age were evaluated. The db mutation not only conferred young AD mice with severe obesity, impaired glucose regulation and activated mammalian target of rapamycin (mTOR) signaling pathway in the mouse cortex, but lead to a surprising improvement in memory. At this young age, mice also had decreased cerebral Aβ content, which we have not observed at older ages. This was unlikely to be related to altered Aβ synthesis, as both β- and γ-secretase were unchanged. The db mutation also reduced the cortical IL-1β mRNA level and IBA1 protein level in young AD mice, with no significant effect on the activation of microglia and astrocytes. We conclude that the db mutation could transitorily improve the memory of young AD mice, a finding that may be partially explained by the relatively improved glucose homeostasis in the brains of db/AD mice compared to their counterpart AD mice, suggesting that glucose regulation could be a strategy for prevention and treatment of neurodegenerative diseases like AD.     

Estimating site occupancy and detectability of the threatened partridge pigeon (Geophaps smithii) using camera traps

Since European settlement, many granivorous birds of northern Australia's savanna landscapes have declined. One such example, the partridge pigeon (Geophaps smithii), has suffered a significant range contraction, disappearing from at least half of its pre‐European range. Multiple factors have been implicated in this decline, including the loss of traditional Aboriginal burning practices, grazing by large exotic herbivores and predation by feral cats (Felis catus). While populations of partridge pigeon on the Tiwi Islands may be particularly important for the long‐term persistence of this species, they too may be at risk of decline. However, as a reliable method to detect this species has not yet been developed and tested, we lack the ability to identify, at an early stage, the species' decline in a given location or region. This severely limits our capacity to make informed management decisions. Here, we demonstrate that the standard camera trapping approach for native mammal monitoring in northern Australia attained an overall probability of detecting partridge pigeon greater than 0.98. We thus provide a robust estimate of partridge pigeon site occupancy (0.30) on Melville Island, the larger of the two main Tiwi Islands. The information presented here for the partridge pigeon represents a critical first step towards the development of optimal monitoring programmes with which to gauge population trajectories, as well as the response to remedial management actions. In the face of ongoing biodiversity loss, such baseline information is vital for management agencies to make informed decisions and should therefore be sought for as many species as possible.     

Non-kin cooperation in bats

Many bats are extremely social. In some cases, individuals remain together for years or even decades and engage in mutually beneficial behaviours among non-related individuals. Here, we summarize ways in which unrelated bats cooperate while roosting, foraging, feeding or caring for offspring. For each situation, we ask if cooperation involves an investment, and if so, what mechanisms might ensure a return. While some cooperative outcomes are likely a by-product of selfish behaviour as they are in many other vertebrates, we explain how cooperative investments can occur in several situations and are particularly evident in food sharing among common vampire bats (Desmodus rotundus) and alloparental care by greater spear-nosed bats (Phyllostomus hastatus). Fieldwork and experiments on vampire bats indicate that sharing blood with non-kin expands the number of possible donors beyond kin and promotes reciprocal help by strengthening long-term social bonds. Similarly, more than 25 years of recapture data and field observations of greater spear-nosed bats reveal multiple cooperative investments occurring within stable groups of non-kin. These studies illustrate how bats can serve as models for understanding how cooperation is regulated in social vertebrates.