An autopsy-confirmed case of progressive supranuclear palsy with predominant postural instability

Postural instability and supranuclear gaze palsy represent the key symptoms of Richardson's syndrome, the most frequent clinical manifestation of progressive supranuclear palsy (PSP). However, a proportion of PSP patients never develops ocular motor symptoms, which prevents clinicians from establishing the diagnosis during lifetime according to current diagnostic criteria. We present one instructive autopsy-confirmed PSP case with prospective video-documented clinical course, showing striking temporal divergence of initially present postural instability and delayed development of ocular motor dysfunction. Brain imaging and autopsy findings were typical of PSP, but the temporal sequence of symptoms was unusual with isolated postural instability predominating the clinical course for many years and slowing of vertical saccades/supranuclear gaze palsy evolving not until the 9th/11th year after disease onset. Although other differential diagnoses were unlikely, this patient did not pass the threshold for possible or probable diagnosis of PSP according to current diagnostic criteria until very late in the disease course. This first well documented, autopsy confirmed case of PSP with predominant postural instability further expands the clinical spectrum of PSP and points out the need of new clinical diagnostic criteria with sufficient sensitivity and specificity for an early and reliable diagnosis

Die chinesische Führung bekräftigt ihren Kurs

"Vom 5. bis 16. März 2007 tagte in Beijing der 10. Nationale Volkskongress (NVK). Internationale Aufmerksamkeit erregte vor allem die Verabschiedung eines Gesetzes zum Schutz privaten Eigentums. Die NVK-Tagung machte als letzte große Tagung vor dem voraussichtlich Ende September stattfindenden 17. Parteitag der KP Chinas die Prioritäten der gegenwärtigen Partei- und Staatsführung deutlich und kann damit auch als Indikator für den Stand intraelitärer Debatten um politische Schwerpunktsetzungen und Richtungsentscheidungen gelten. Die Agenda und die Beschlüsse der diesjährigen NVK-Tagung entsprechen der seit 2002 erarbeiteten Entwicklungskonzeption der 'harmonischen sozialistischen Gesellschaft'. Im ideologischen Richtungsstreit um die Fortführung des Reformkurses mit liberalen und konservativen Kritikern gelang der Führungsspitze ein Durchbruch. Mit einer Bestätigung ihrer Reformpolitik ist somit auch auf dem Parteitag zu rechnen. Mit der Ratifizierung des Gesetzes zum Schutz privater Eigentumsrechte setzte sich die Führung um Partei- und Staatschef Hu Jintao und Ministerpräsident Wen Jiabao gegen Kritiker durch und bekräftigte, dass sie ihren marktorientierten Reformkurs fortführen werde. Von der neuen Gesetzgebung werden insbesondere Unternehmer und die entstehende Mittelklasse profitieren. Die Partei- und Staatsführung ist sich deutlich bewusst, dass sie zur eigenen Absicherung die Vergrößerung der Kluft zwischen Stadt und Land und das Anwachsen sozialer Widersprüche stoppen muss. Ob ihr dies allerdings gelingen wird, ist zweifelhaft. Andererseits hat sie nach der Öffnung der KP-Mitgliedschaft für Privatunternehmer ihre Mittelstandsorientierung eindringlich unterstrichen." (Autorenreferat

Coherent Population Trapping with Controlled Interparticle Interactions

We investigate Coherent Population Trapping in a strongly interacting ultracold Rydberg gas. Despite the strong van der Waals interactions and interparticle correlations, we observe the persistence of a resonance with subnatural linewidth at the single-particle resonance frequency as we tune the interaction strength. This narrow resonance cannot be understood within a meanfield description of the strong Rydberg--Rydberg interactions. Instead, a many-body density matrix approach, accounting for the dynamics of interparticle correlations, is shown to reproduce the observed spectral features

Proteomics as a quality control tool of pharmaceutical probiotic bacterial lysate products

Probiotic bacteria have a wide range of applications in veterinary and human therapeutics. Inactivated probiotics are complex samples and quality control (QC) should measure as many molecular features as possible. Capillary electrophoresis coupled to mass spectrometry (CE/MS) has been used as a multidimensional and high throughput method for the identification and validation of biomarkers of disease in complex biological samples such as biofluids. In this study we evaluate the suitability of CE/MS to measure the consistency of different lots of the probiotic formulation Pro-Symbioflor which is a bacterial lysate of heat-inactivated Escherichia coli and Enterococcus faecalis. Over 5000 peptides were detected by CE/MS in 5 different lots of the bacterial lysate and in a sample of culture medium. 71 to 75% of the total peptide content was identical in all lots. This percentage increased to 87–89% when allowing the absence of a peptide in one of the 5 samples. These results, based on over 2000 peptides, suggest high similarity of the 5 different lots. Sequence analysis identified peptides of both E. coli and E. faecalis and peptides originating from the culture medium, thus confirming the presence of the strains in the formulation. Ontology analysis suggested that the majority of the peptides identified for E. coli originated from the cell membrane or the fimbrium, while peptides identified for E. faecalis were enriched for peptides originating from the cytoplasm. The bacterial lysate peptides as a whole are recognised as highly conserved molecular patterns by the innate immune system as microbe associated molecular pattern (MAMP). Sequence analysis also identified the presence of soybean, yeast and casein protein fragments that are part of the formulation of the culture medium. In conclusion CE/MS seems an appropriate QC tool to analyze complex biological products such as inactivated probiotic formulations and allows determining the similarity between lots

Environmental considerations and current status of grouping and regulation of engineered nanomaterials

This article reviews the current status of nanotechnology with emphasis on application and related environmental considerations as well as legislation. Application and analysis of nanomaterials in infrastructure (construction, building coatings, and water treatment) is discussed, and in particular nanomaterial release during the lifecycle of these applications. Moreover, possible grouping approaches with regard to ecotoxicological and toxicological properties, and the fate of nanomaterials in the environment are evaluated. In terms of potential exposure, the opportunities that arise from leveraging advances in several key areas, such as water treatment and construction are addressed. Additionally, this review describes challenges with regard to the European Commission’s definition of ‘nanomaterial’. The revised REACH information requirements, intended to enable a comprehensive risk assessment of nanomaterials, are outlined

Alkylwanderungen bei Sextettumlagerungen

Die Wanderungstendenzen von Alkylgruppen bei der Beckmann- Criegee- und Isonitril-Nitril-Umlagerung werden untersucht. Aus den relativen Reaktionsgeschwindigkeiten der substituierten Benzylreste werden Rückschlüsse auf die Ladungsverteilung im Übergangszustand dieser Reaktionen gezogen und aus dem Verhältnis der Wanderungstendenzen des exo und endo- 2- Norbornylrestes auf die Geometrie der wandernden Gruppe im Übergangszustand. Der in verschiedenen Sextettumlagerungen unterschiedliche Einfluß der -Methylverzweigung in der wandernden Gruppe wird interpretiert

Functional Fluorescent Ca(2+) Indicator Proteins in Transgenic Mice under TET Control

Genetically encoded fluorescent calcium indicator proteins (FCIPs) are promising tools to study calcium dynamics in many activity-dependent molecular and cellular processes. Great hopes—for the measurement of population activity, in particular—have therefore been placed on calcium indicators derived from the green fluorescent protein and their expression in (selected) neuronal populations. Calcium transients can rise within milliseconds, making them suitable as reporters of fast neuronal activity. We here report the production of stable transgenic mouse lines with two different functional calcium indicators, inverse pericam and camgaroo-2, under the control of the tetracycline-inducible promoter. Using a variety of in vitro and in vivo assays, we find that stimuli known to increase intracellular calcium concentration (somatically triggered action potentials (APs) and synaptic and sensory stimulation) can cause substantial and rapid changes in FCIP fluorescence of inverse pericam and camgaroo-2

Alterations of cell cycle kinetics and vimentin expression in TPA−treated, asynchronous MPC−11 mouse plasmacytoma cells

Vimentin expression throughout the cell cycle has been analyzed at the single−cell level in asynchronously growing MPC−11 cells using multiparameter flow cytometry. We have previously shown that these cells normally lack detectable amounts of intermediate filament proteins. In the presence of the phorbol ester 12−O−tetradecanoylphorbol−13−acetate (TPA), cell proliferation ceases and large quantities of the intermediate filament protein vimentin are synthesized and accumulate in most of the cells. In the present study, the short−term effect of TPA on distribution of cells within the cell cycle was a depletion in early S phase followed by a depletion in mid− and late S phase. In parallel, the G1−phase fraction increased significantly. In addition, a delay in progression through G2/M phase was observed. These data strongly suggest an inhibition of progression of cells through the cell cycle in G1 phase as the primary event on cell cycle kinetics elicited by TPA. Vimentin accumulation could be detected by flow cytometry as early as 2 h after TPA addition; at this time, the percentage of vimentin−positive cells was highest in G2/M phase. Prolonged TPA treatment induced vimentin accumulation in cells of all cell cycle phases. However, even at later times, the G1−phase population consisted of two subpopulations with low and high vimentin content, respectively. The fraction of cells which displayed a higher level of vimentin probably represents those G1−phase cells which previously had undergone cell division in the presence of TPA. Our data indicate that TPA−induced vimentin synthesis is regulated in a cell cycle−dependent manner and is maximally induced in cells which have passed a putative cell cycle restriction point in G1 phas

Similar effects of electroporational stress and treatment with the phorbol ester 12−O−tetradecanoylphorbol−13−acetate on vimentin expression in mouse plasmacytoma cells

In mouse plasmacytoma cells (MPC−11), an activation of the normally repressed vimentin gene was observed as a response to transfectional stress. Effects of electroporation on vimentin gene expression were compared at the cellular and chromatin level to those caused by treatment with 12−O−tetradecanoylphorbol−13−acetate (TPA). At the cellular level, similar changes in vimentin gene activity and cell−cycle distribution were observed by flow cytometry, whereas at the chromatin level similar changes in patterns of hypersensitive regions were detected by DNase I mapping. Additionally, a region located 700 bp upstream of the transcriptional start became hypersensitive to DNase I digestion upon electroporation and TPA treatment. This region overlaps two adjacent AP−1−like binding elements and generates specific DNA/AP−1 complexes in bandshift experiments. Therefore, the transcription factor AP−1 seems to play a central role in the activation of vimentin gene expression induced by these 2 different forms of stres

TPA induces apoptosis in MPC−11 mouse plasmacytoma cells grown in serum−free medium

Apoptotic−like events could be rapidly induced by the phorbol ester 12−O−tetradecanoylphorbol−13−acetate (TPA) in cells of the mouse plasmacytoma cell line MPC−11 grown in serum−free medium. Indicators for apoptosis were morphological changes visualized by light and electron microscopy, such as chromatin condensation and the formation of cellular buds and fragments, as well as biochemical indices like the appearance of the so−called 'DNA ladder'. Additionally, in these cells which are usually devoid of significant amounts of cytoplasmic intermediate filament (cIF) proteins, synthesis and accumulation of the cIF protein vimentin was rapidly induced by TPA treatment and almost all cells became vimentin−positive. Later on, substantial amounts of vimentin and lamin B degradation products appeared, and an increasing fraction of cells displayed low or even undetectable quantities of intact vimentin. This subpopulation was characterized via microscopy to be in the late stages of apoptosis. We suggest that in MPC−11 cells undergoing apoptosis in response to TPA treatment vimentin as well as lamin B are degraded, leading to a rearrangement and eventual loss of their respective filament network