Dual recognition of lipid A and DNA by human antibodies encoded by the VH4-21 gene: a possible link between infection and lupus

The VH4-21 (V4-34) gene segment, a member of the VH4 family, is expressed early in B-cell maturation and is utilized by approximately 6% of normal adult B lymphocytes. This prevalence indicates an importance of VH4-21 in the B-cell repertoire. The gene also encodes certain autoantibodies being mandatory for pathological IgM anti-red cell antibodies directed against the I/i antigen, and also capable of encoding anti-DNA antibodies. Recognition of I/i antigen or DNA appears to be via two distinct sites on VH, with I/i binding mediated by sequences in the framework region, and DNA binding correlating with the presence of positively charged amino acids in complementarity-determining region 3. However, these positively charged residues appear to suppress the ability of the framework region to interact with I/i, rendering a single sequence monospecific for I/i or DNA. The IgM anti-DNA antibodies also recognize bacterial lipid A, whereas the anti-I/i antibodies do not, indicating that CDR3 may be involved in binding the negatively charged lipid A. Structural similarities between the DNA backbone and lipid A provide a possible explanation for this cross-reactivity. This dual recognition of bacterial antigen and autoantigen provides a potential link between infection and autoimmunity.     

The Joint Evaluation Procedure for Active Substances contained in Plant Protection Products within the European Community – 10?Years of the ECCO-Project

Pflanzenschutzmittel müssen seit 1993 in den Mitgliedstaaten der Europ?ischen Gemeinschaft nach der Richtlinie 91/414/EWG des Rates bewertet und zugelassen werden. Das Programm zur Bewertung von alten Wirkstoffen (welche vor Juli 1993 auf dem Markt waren) beinhaltet mehrere Schritte und Stufen, die früher über einen Zeitraum von bis zu 10 Jahren zu bew?ltigen waren; heute sind dafür jedoch 15 Jahre vorgesehen. Das Programm wurde seit 1996 von der Europ?ischen Kommission mit Unterstützung des ECCO-Teams(European Community Co-Ordination) koordiniert. Das ECCO-Team bestand aus zwei Gruppen: eine im Pesticides Safety Directorate – PSD in York (Gro?britannien) und eine im Bundesamt für Verbraucherschutz und Lebensmittelsicherheit (BVL) bzw. vor November 2002 in der Biologischen Bundesanstalt für Land- und Forstwirtschaft in Braunschweig. Sie unterstüzten das Programm zur Bewertung von Wirkstoffen im Namen der Kommission in technischer und administrativer Hinsicht und zeichneten sich insbesondere für das ECCO Peer Review Programm (Expertenprüfungen) verantwortlich. Im November 2003 übernahm die Europ?ische Beh?rde für Lebensmittelsicherheit (EFSA) die Verantwortung für die wissenschaftliche überprüfung der von den Mitgliedstaaten erstellten Bewertungen durch Experten. Das ECCO-Team leistete jedoch weiterhin der Europ?ischen Kommission Unterstützung bei der Durchführung anderer Verfahrensaspekte, vor allem im Bereich der Managementaufgaben der Europ?ischen Kommission. Insgesamt war das Programm au?erordentlich erfolgreich. Es wurden für 162 Wirkstoffen zwischen 1996 und 2003 der Inhalt der von den Mitgliedstaaten erstellten Bewertungsberichte durch eine Expertengruppe diskutiert und füberprüft, was ma?geblich eine Entscheidungsfindung zur Akzeptabilitf?t dieser Wirkstoffe auf Gemeinschaftsebene erm?glicht hat.     

The changing face of emphysematous cholecystitis

Emphysematous cholecystitis is a variant of acute cholecystitis characterized by the presence of gas in the gall bladder lumen, wall or pericholecystic tissues in the absence of an abnormal communication between the biliary system and the gastrointestinal tract. In the past, the diagnosis has relied on the plain abdominal radiograph (AXR), since there are no clinical features to separate this condition from simple acute cholecystitis. The apparently high mortality and morbidity associated with emphysematous cholecystitis has previously emphasized the importance of emergency cholecystectomy. We have reviewed eight cases of emphysematous cholecystitis presenting to this hospital over the last 5 years. The diagnosis was made on AXR in only one of these cases. Ultrasound (US) scans were performed in all eight cases, of which five were positive and three negative, due to non-visualization of the gall bladder. In the three negative cases, the diagnosis was made on subsequent CT scans. On initial clinical examination, only one of the eight patients appeared systemically unwell and conservative management was employed in five of the patients. The remaining three patients underwent cholecystectomy within 3-5 days because of continuing signs or symptoms. It is concluded that the AXR is relatively insensitive in the diagnosis of emphysematous cholecystitis. As a result of the regular use of US in suspected hepatobiliary disease, emphysematous cholecystitis is being diagnosed with increased frequency, uncovering a broad spectrum of disease ranging from mild to severe. Previously, failure to separate milder cases from simple acute cholecystitis may have been responsible for reports of unremitting severity and progression requiring emergency cholecystectomy. Based on clinical assessment, conservative surgical management is possible in a significant proportion of patients.     

A novel mutation of presenilin 1 in familial Alzheimer's disease in Israel detected by denaturing gradient gel electrophoresis

Germline mutations in the presenilin 1 (PS1) gene apparently account for the majority of early-onset, familial Alzheimer's disease (AD). Using a mutation-screening strategy (denaturing gradient gel electrophoresis; DGGE), we analyzed a large family with early onset AD and seizures. The patients in this family showed a novel missense mutation in exon 5 of the PS1 gene (A to T change in codon 120, altering glutamine to aspartic acid). This novel mutation is located within the second hydrophilic domain of the molecule, a region not particularly involved in previously described germline mutations, and is of unknown biological significance. These results also demonstrate that DGGE can be used effectively to screen for mutations within this gene.     

Policy Analysis, Peer Reviewed: Evaluation of Bioaccumulation Factors in Regulating Metals

Regulations.     

SIR-C data quality and calibration results

The SIR-C/X-SAR imaging radar took its first flight on the Space Shuttle Endeavour in April 1994 and flew for a second time in October 1994. This multifrequency radar has fully polarimetric capability at L- and C-band, and a single polarization at X-band (X-SAR). The Endeavour missions were designated the Space Radar Laboratory-1 (SRL-1) and -2 (SRL-2). Calibration of polarimetric L- and C-band data for all the different modes SIR-C offers is an especially complicated problem. The solution involves extensive analysis of pre-flight test data to come up with a model of the system, analysis of in-flight test data to determine the antenna pattern and gains of the system during operation, and analysis of data from over fourteen calibration sites distributed around the SIR-C/X-SAR orbit track. The SRL missions were the first time a multifrequency polarimetric imaging radar employing a phased array antenna has been flown in space. Calibration of SIR-C data products involved some unique technical problems given the complexity of the radar system. In this paper, the approach adopted for calibration of SIR-C data is described and the calibration performance of the data products is presented     

Prediction of psychoticlike symptoms in hypothetically psychosis-prone college students.

Correlates of psychotic and psychoticlike symptoms were examined in 60 college students who scored deviantly high on the Perceptual Aberration Scale. High scorers on this scale who also scored high on both the Impulsive Nonconformity Scale and the Depression subscale of the General Behavior Inventory (GBI) showed the most deviant psychotic and psychoticlike symptoms. Moreover, performance on a task of referential communication, the Password Task, was significantly related to such symptoms. The Perceptual Aberration Scale, the Impulsive Nonconformity Scale, and the GBI Depression subscale are recommended for concurrent use in mass screening to select individuals likely to exhibit psychotic or psychoticlike symptoms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Monitoring neuronal oscillations and signal transmission betweencortical regions using time-frequency analysis ofelectroencephalographic activity

Oscillatory states in the electroencephalogram (EEG) reflect the rhythmic synchronous activity in large networks of neurons. Time-frequency (TF) methods, which quantify the spectral content of the EEG as a function of time, are well suited as tools for the study of spontaneous and induced changes in oscillatory states. The use of these methods provides insights into the temporal dynamics of EEG activity in both humans and experimental animals, and aids the study of the neuronal mechanisms that generate rhythmic EEG activity. Further the use of TF coherence analysts, which quantifies the consistency of phase relationships in multichannel EEG recordings, may contribute to the understanding of signal transmission between neuronal populations in different parts of the brain. We have used TF techniques to analyze the flow of activity patterns between two strongly connected brain structures: the entorhinal cortex and the hippocampus. Both of these structures are believed to be involved in information storage. By applying various frequencies of stimulation, we have found a peak in the spectral power in both sites at around 18 Hz, but the coherence between the EEG signals recorded from these sites was found to increase monotonically up to about 35 Hz. We have also found that long-term potentiation, a strong increase in the efficacy of excitatory synapses between these sites, either had no effect or decreased coherence