Neuron Loss in Transgenic Mouse Models of Alzheimer's Disease

Since their initial generation in the mid 1990s, transgenic mouse models of Alzheimers's disease (AD) have been proven to be valuable model systems which are indispensable for modern AD research. Whereas most of these models are characterized by extensive amyloid plaque pathology, inflammatory changes and often behavioral deficits, modeling of neuron loss was much less successful. The present paper discusses the current achievements of modeling neuron loss in transgenic mouse models based on APP/Aβ and Tau overexpression and provides an overview of currently available AD mouse models showing these pathological alterations

Intracellular Accumulation of Amyloid-Beta – A Predictor for Synaptic Dysfunction and Neuron Loss in Alzheimer's Disease

Despite of long-standing evidence that beta-amyloid (Aβ) peptides have detrimental effects on synaptic function, the relationship between Aβ, synaptic and neuron loss is largely unclear. During the last years there is growing evidence that early intraneuronal accumulation of Aβ peptides is one of the key events leading to synaptic and neuronal dysfunction. Many studies have been carried out using transgenic mouse models of Alzheimer's disease (AD) which have been proven to be valuable model systems in modern AD research. The present review discusses the impact of intraneuronal Aβ accumulation on synaptic impairment and neuron loss and provides an overview of currently available AD mouse models showing these pathological alterations

Signatures of hermitian forms and the Knebusch Trace Formula

Signatures of quadratic forms have been generalized to hermitian forms over algebras with involution. In the literature this is done via Morita theory, which causes sign ambiguities in certain cases. In this paper, a hermitian version of the Knebusch Trace Formula is established and used as a main tool to resolve these ambiguities. The last page is an erratum for the published version. We inadvertently (I) gave an incorrect definition of adjoint involutions; (II) omitted dealing with the case $(H\times H, \widehat{\phantom{m}}\,)$. As $W(H\times H, \widehat{\phantom{m}}\,)= W(R\times R, \widehat{\phantom{m}}\,)=0$, the omission does not affect our reasoning or our results. For the sake of completeness we point out where some small changes should be made in the published version.Comment: This is the final version before publication. The last page is an updated erratum for the published versio

Donaldson-Thomas invariants and wall-crossing formulas

Notes from the report at the Fields institute in Toronto. We introduce the Donaldson-Thomas invariants and describe the wall-crossing formulas for numerical Donaldson-Thomas invariants.Comment: 18 pages. To appear in the Fields Institute Monograph Serie

Disturbed Copper Bioavailability in Alzheimer's Disease

Recent data from in vitro, animal, and human studies have shed new light on the positive roles of copper in many aspects of AD. Copper promotes the non-amyloidogenic processing of APP and thereby lowers the Aβ production in cell culture systems, and it increases lifetime and decreases soluble amyloid production in APP transgenic mice. In a clinical trial with Alzheimer patients, the decline of Aβ levels in CSF, which is a diagnostic marker, is diminished in the verum group (8 mg copper/day), indicating a beneficial effect of the copper treatment. These observations are in line with the benefit of treatment with compounds aimed at normalizing metal levels in the brain, such as PBT2. The data reviewed here demonstrate that there is an apparent disturbance in metal homeostasis in AD. More research is urgently needed to understand how this disturbance can be addressed therapeutically

Structural phase transitions in the Ag2Nb4O11 – Na2Nb4O11 solid solution

The phase transitions between various structural modifications of the natrotantite-structured system xAg2Nb4O11 – (1-x)Na2Nb4O11 have been investigated and a phase diagram constructed as a function of temperature and composition. This shows three separate phase transition types: (1) paraelectric – ferroelectric, (2) rhombohedral – monoclinic and (3) a phase transition within the ferroelectric rhombohedral zone between space groups R3c and R3. The parent structure for the entire series has space group R-3c. Compositions with x > 0.75 are rhombohedral at all temperatures whereas compositions with x < 0.75 are all monoclinic at room temperature and below. At x = 0.75, rhombohedral and monoclinic phases coexist with the phase boundary below room temperature being virtually temperature-independent. The ferroelectric phase boundary extends into the monoclinic phase field. No evidence was found for the R3–R3c phase boundary extending into the monoclinic phase field and it is concluded that a triple point is formed

Uncertainties in the land-use flux resulting from land-use change reconstructions and gross land transitions

Land-use and land-cover (LUC) changes are a key uncertainty when attributing changes in measured atmospheric CO2 concentration to its sinks and sources and must also be much better understood to determine the possibilities for land-based climate change mitigation, especially in the light of human demand on other land-based resources. On the spatial scale typically used in terrestrial ecosystem models (0.5 or 1°) changes in LUC over time periods of a few years or more can include bidirectional changes on the sub-grid level, such as the parallel expansion and abandonment of agricultural land (e.g. in shifting cultivation) or cropland–grassland conversion (and vice versa). These complex changes between classes within a grid cell have often been neglected in previous studies, and only net changes of land between natural vegetation cover, cropland and pastures accounted for, mainly because of a lack of reliable high-resolution historical information on gross land transitions, in combination with technical limitations within the models themselves. In the present study we applied a state-of-the-art dynamic global vegetation model with a detailed representation of croplands and carbon–nitrogen dynamics to quantify the uncertainty in terrestrial ecosystem carbon stocks and fluxes arising from the choice between net and gross representations of LUC. We used three frequently applied global, one recent global and one recent European LUC datasets, two of which resolve gross land transitions, either in Europe or in certain tropical regions. When considering only net changes, land-use-transition uncertainties (expressed as 1 standard deviation around decadal means of four models) in global carbon emissions from LUC (ELUC) are ±0.19, ±0.66 and ±0.47 Pg C a−1 in the 1980s, 1990s and 2000s, respectively, or between 14 and 39 % of mean ELUC. Carbon stocks at the end of the 20th century vary by ±11 Pg C for vegetation and ±37 Pg C for soil C due to the choice of LUC reconstruction, i.e. around 3 % of the respective C pools. Accounting for sub-grid (gross) land conversions significantly increased the effect of LUC on global and European carbon stocks and fluxes, most noticeably enhancing global cumulative ELUC by 33 Pg C (1750–2014) and entailing a significant reduction in carbon stored in vegetation, although the effect on soil C stocks was limited. Simulations demonstrated that assessments of historical carbon stocks and fluxes are highly uncertain due to the choice of LUC reconstruction and that the consideration of different contrasting LUC reconstructions is needed to account for this uncertainty. The analysis of gross, in addition to net, land-use changes showed that the full complexity of gross land-use changes is required in order to accurately predict the magnitude of LUC change emissions. This introduces technical challenges to process-based models and relies on extensive information regarding historical land-use transitions

Mena/VASP and αII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy

BACKGROUND: In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks. RESULTS: We generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired. CONCLUSIONS: Together, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities

Non-resonant dot-cavity coupling and its applications in resonant quantum dot spectroscopy

We present experimental investigations on the non-resonant dot-cavity coupling of a single quantum dot inside a micro-pillar where the dot has been resonantly excited in the s-shell, thereby avoiding the generation of additional charges in the QD and its surrounding. As a direct proof of the pure single dot-cavity system, strong photon anti-bunching is consistently observed in the autocorrelation functions of the QD and the mode emission, as well as in the cross-correlation function between the dot and mode signals. Strong Stokes and anti-Stokes-like emission is observed for energetic QD-mode detunings of up to ~100 times the QD linewidth. Furthermore, we demonstrate that non-resonant dot-cavity coupling can be utilized to directly monitor and study relevant QD s-shell properties like fine-structure splittings, emission saturation and power broadening, as well as photon statistics with negligible background contributions. Our results open a new perspective on the understanding and implementation of dot-cavity systems for single-photon sources, single and multiple quantum dot lasers, semiconductor cavity quantum electrodynamics, and their implementation, e.g. in quantum information technology.Comment: 17 pages, 4 figure