The use of PIB-PET as a dual pathological and functional biomarker in AD

Amyloid imaging with positron emission tomography (PET) is presently used in Alzheimer's disease (AD) research. In this study we investigated the possibility to use early frames (ePIB) of the PIB scans as a rough index of CBF by comparing normalised early PIB values with cerebral glucose metabolism (rCMRglc). PIB-PET and FDG-PET were performed in 37 AD patients, 21 subjects with mild cognitive impairment (MCI) and 6 healthy controls (HC). The patients were divided based on their PIB retention (amyloid load) as either PIB positive (PIB+) or PIB negative (PIB−). Data of the unidirectional influx K₁ from a subset of the subjects including 7 AD patients and 3 HC was used for correlative analysis. Data was analysed using regions of interest (ROI) analysis. A strong, positive correlation was observed across brain regions between K₁ and ePIB (r = 0.70; p ≤ 0.001). The ePIB values were significantly lower in the posterior cingulate (p ≤ 0.001) and the parietal cortices (p = 0.002) in PIB+ subjects compared to PIB−, although the group difference were stronger for rCMRglc in cortical areas (p ≤ 0.001). Strong positive correlations between ePIB and rCMRglc were observed in all cortical regions analysed, especially in the posterior cingulate and parietal cortices (p ≤ 0.001). A single dynamic PIB-PET scan may provide information about pathological and functional changes (amyloidosis and impaired blood flow). This might be important for diagnosis of AD, enrichment of patients in clinical trials and evaluation of treatment effects. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.     

Avian predation on a parasitic fly of cervids during winter: can host‐related cues increase the predation risk?

The deer ked (Lipoptena cervi) is an ectoparasitic fly on cervids that has expanded its distribution rapidly in Northern Europe. However, the regulating biotic factors such as predation remain unknown. The host‐independent pupal stage of the fly lasts for several months. Blackish pupae are visible against snow, especially on the bedding sites of hosts, and are thus exposed to predators. To evaluate the role of predation on the invasion dynamics and evolution of L. cervi, we monitored pupal predation on artificial bedding sites in three geographical areas in Finland during winter. We explored: (1) possible predators; (2) magnitude of predation; and (3) whether predation risk is affected by host‐derived cues. We demonstrate that pupae are predated by a number of tit species. Any reddish brown snow discoloration on bedding sites, indicating heavy infestation of the host, serves as an exploitable cue for avian predators, thereby increasing the risk of pupal predation. The ability of tits to use this host‐derived cue seems to be dependent on the prevalence of L. cervi and the period of invasion history, which suggests that it may be a learned behavioural response. Predation by tits may potentially affect the L. cervi population dynamics locally. © 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, 106 , 275–286.     

Senescence and steroid hormone receptor reactivities in accessory sex glands of elderly rats (Sprague-Dawley) following exogenous hormonal therapy

The aim of this study was to characterize the stromal and epithelial distribution of AR, ERα and ERβ reactivities in the different accessory sex glands of elderly rats and during strong hormonal changes. Ten month old male rats were divided into six senile groups and submitted to treatment: Senile/Control group (SC); Senile/Testosterone group (ST): Senile/Estrogen group (SE); Castrated group (CA); Castrated/Testosterone group (CT); Castrated/Estrogen group (CE). After a 30-day treatment, the prostatic ventral lobe (VL), dorsal lobe (DL) and coagulating gland (CG) samples were processed for immunohistochemistry and Western Blotting. The results showed that AR immunoreactivity was characterized in the epithelium of VL and DL in senile/control rats and senile rats submitted to exogenous hormonal therapy. AR reactivity in the coagulating gland was verified predominantly in the stromal cells in the different experimental groups. ERα reactivity occurred predominantly in the stromal compartment in all accessory sex glands. In the DL and CG, ERα immunoreactivities were intense in the groups which received testosterone (ST) and estrogen (SE). ERβ immunoreactivity in the CG was verified in the stromal compartment in the different experimental groups, showing a positive response to both increased testosterone and estrogen levels. ERβ reactivity, in the DL, was intensified in the stroma of senile rats with higher serum testosterone levels, and in senile rats with increased serum estrogen levels, especially in the glandular epithelium. Thus, the results revealed different distribution pattern of steroid hormone receptors in each one of the prostatic lobes in senescence, especially in the prostate dorsal lobe and coagulating gland, which is a fundamental factor due to the fact that major prostatic diseases occur in a later period of life.     

Foraging guild membership explains variation in waterbird responses to the hydrological regime of an arid‐region flood‐pulse river in Namibia

1. Little is known about hydrological influences on tropical waterbird communities. We used a 16‐year data set (1991–2007) of waterbird censuses, together with a classification of observed species into foraging guilds, to explore the relationships between natural variations in flow regime, foraging guild and the community composition of waterbirds at the Okavango River in the Caprivi Strip of north‐eastern Namibia, southern Africa. 2. We addressed three hypotheses to explain variation in waterbird community composition: (i) exploitation (birds move towards resource‐rich patches to exploit periods of high food abundance); (ii) escapism (declines in regional habitat quality force birds to aggregate in perennial waterbodies); and (iii) interaction (bird assemblages are dominated by intra‐ and interspecific interactions, such as flock formation for breeding or moulting, that can be explained better by life history demands or competition than by resource availability). 3. Waterbirds in different foraging guilds responded strongly but at different periods to changes in the hydrological environment, creating a complex but predictable successional pattern in community composition through time. Deep‐water feeders responded fastest (abundance peaking 2 months post‐flood), followed by shallow‐water feeders (4 months) and emergent vegetation feeders (7 months). Species that forage on short vegetation or in mud showed a bimodal response with peaks in abundance at 3 and 8 months post‐flood. 4. Our results indicated a strong effect of the local flow regime and hence supported the exploitation hypothesis. The foraging guild approach allowed us to identify clear patterns in a highly complex ecosystem and shows considerable promise as an analytical tool for similar data sets. Our results further suggest that while the entire bird community will be affected by hydrological alterations such as impoundments, water extraction and climate change, deep‐water feeders may be one of the most vulnerable groups.     

Modifications around the hydroxamic acid chelating group of fosmidomycin,an inhibitor of the metalloenzyme 1-deoxyxylulose 5-phosphate reductoisomerase (DXR)

Fosmidomycin derivatives in which the hydroxamic acid group has been replaced by several bidentate chelators as potential hydroxamic alternatives were prepared and tested against the DXR from Escherichia coli. These results illustrate the predominant role of the hydroxamate functional group as the most effective metal binding group in DXR inhibitors.     

Effect of sexual recombination on population diversity in aflatoxin production by Aspergillus flavus and evidence for cryptic heterokaryosis

Aspergillus flavus is the major producer of carcinogenic aflatoxins (AFs) in crops worldwide. Natural populations of A. flavus show tremendous variation in AF production, some of which can be attributed to environmental conditions, differential regulation of the AF biosynthetic pathway and deletions or loss‐of‐function mutations in the AF gene cluster. Understanding the evolutionary processes that generate genetic diversity in A. flavus may also explain quantitative differences in aflatoxigenicity. Several population studies using multilocus genealogical approaches provide indirect evidence of recombination in the genome and specifically in the AF gene cluster. More recently, A. flavus has been shown to be functionally heterothallic and capable of sexual reproduction in laboratory crosses. In the present study, we characterize the progeny from nine A. flavus crosses using toxin phenotype assays, DNA sequence‐based markers and array comparative genome hybridization. We show high AF heritability linked to genetic variation in the AF gene cluster, as well as recombination through the independent assortment of chromosomes and through crossing over within the AF cluster that coincides with inferred recombination blocks and hotspots in natural populations. Moreover, the vertical transmission of cryptic alleles indicates that while an A. flavus deletion strain is predominantly homokaryotic, it may harbour AF cluster genes at a low copy number. Results from experimental matings indicate that sexual recombination is driving genetic and functional hyperdiversity in A. flavus. The results of this study have significant implications for managing AF contamination of crops and for improving biocontrol strategies using nonaflatoxigenic strains of A. flavus.     

Aerobic capacity influences the spatial position of individuals within fish schools

The schooling behaviour of fish is of great biological importance, playing a crucial role in the foraging and predator avoidance of numerous species. The extent to which physiological performance traits affect the spatial positioning of individual fish within schools is completely unknown. Schools of juvenile mullet Liza aurata were filmed at three swim speeds in a swim tunnel, with one focal fish from each school then also measured for standard metabolic rate (SMR), maximal metabolic rate (MMR), aerobic scope (AS) and maximum aerobic swim speed. At faster speeds, fish with lower MMR and AS swam near the rear of schools. These trailing fish required fewer tail beats to swim at the same speed as individuals at the front of schools, indicating that posterior positions provide hydrodynamic benefits that reduce swimming costs. Conversely, fish with high aerobic capacity can withstand increased drag at the leading edge of schools, where they could maximize food intake while possibly retaining sufficient AS for other physiological functions. SMR was never related to position, suggesting that high maintenance costs do not necessarily motivate individuals to occupy frontal positions. In the wild, shifting of individuals to optimal spatial positions during changing conditions could influence structure or movement of entire schools.     

Conditionally immortalised neural stem cells promote functional recovery and brain plasticity after transient focal cerebral ischaemia in mice

Cell therapy has enormous potential to restore neurological function after stroke. The present study investigated effects of conditionally immortalised neural stem cells (ciNSCs), the Maudsley hippocampal murine neural stem cell line clone 36 (MHP36), on sensorimotor and histological outcome in mice subjected to transient middle cerebral artery occlusion (MCAO).Adult male C57BL/6 mice underwent MCAO by intraluminal thread or sham surgery and MHP36 cells or vehicle were implanted into ipsilateral cortex and caudate 2 days later. Functional recovery was assessed for 28 days using cylinder and ladder rung tests and tissue analysed for plasticity, differentiation and infarct size.MHP36-implanted animals showed accelerated and augmented functional recovery and an increase in neurons (MAP-2), synaptic plasticity (synaptophysin) and axonal projections (GAP-43) but no difference in astrocytes (GFAP), oligodendrocytes (CNPase), microglia (IBA-1) or lesion volumes when compared to vehicle group.This is the first study showing a potential functional benefit of the ciNSCs, MHP36, after focal MCAO in mice, which is probably mediated by promoting neuronal differentiation, synaptic plasticity and axonal projections and opens up opportunities for future exploitation of genetically altered mice for dissection of mechanisms of stem cell based therapy.     

Proteomics of rat biological fluids--the tenth anniversary update

In addition to a remarkable sexual dimorphism of serum and urine proteomes, the rat is exceptional for the wide difference between the serum patterns during an acute phase reaction vs baseline conditions. This feature allows monitoring with high sensitivity onset and progression of any pathological state that involves an inflammatory component as well as assessing the outcome of any therapeutic intervention. Reference maps have been defined for the proteomes of serum, urine, cerebrospinal fluid and bronchoalveolar lavage fluid. For both serum and urine most of the proteomic investigations have dealt with toxicological testing, for BALF with allergic or irritative reactions, whereas with CSF the main aim was the characterization of rat models of neurological disorders. When surveying more than ten years of literature on rat biological fluid proteomics, it is puzzling to see how seldom a consistent analytical plan has been set up for the comparative investigation on two or more types of sample, whether to fully characterize a disease model or to evaluate pharmacological/toxicological effects of a drug. It is also regrettable that in several cases only a negligible part of the results is discussed at length whereas most data are not even made known to the scientific community.