Sleep and memory consolidation: The role of electrophysiological neuroimaging

Summary Memory consolidation involves a complex series of molecular, cellular and network-level processes that take place on time scales from millisecond to months. Evidence from a wide range of experimental observations supports the hypothesis that parts of these processes occur during sleep when the brain is not engaged in processing and encoding incoming information. Indeed, sleep seems to be favorable for brain plasticity. Experience-dependent cortical plasticity observed during sleep has been hypothesized to be part of the global process of memory consolidation. Thus, studying task-dependent, regionally specific reactivation of neuronal assemblies during posttraining sleep may make important contributions to elucidating the role of sleep in memory trace processing. A new methodology – low-resolution brain electromagnetic tomography (LORETA) – offers the possibility of localizing electrical activity produced by cortical neuronal generators under normal (undisturbed) sleeping conditions. The high time resolution of brain electrical data can be exploited to produce neuroimages for specific EEG spectral frequency bands (e.g. delta, theta, or spindle bands). This makes it possible to investigate, dependent on the type of memory, when – in which sleep stages (S2 sleep, SWS, REM sleep) – and where – in which cortical brain regions (primary sensory cortex, higher association cortex) – experience-dependent reactivation occurs.     

Über polymere Alloxazine, 2

A new synthesis for 7-vinylalloxazine ( 4 ) was developed. It was neither polymerizable in DMSO nor in DMF. Poly(7-vinylalloxazine) ( 7 ) was obtained by polymer-analogous reactions starting from poly(4-aminostyrene). Its ability to form complexes with Ag⁺-und Hg²⁺-ions was investigated.     

A Direct Comparison of the Skin Conductance and Skin Resistance Methods

The purpose of the present study was a direct comparison between simultaneous recordings of skin conductance and skin resistance. Sixty male students received a series of 30 white noise stimuli, while measures were taken continuously from four sites on the palmar surfaces of the fingers. Evaluations were made for response amplitudes, recovery, and for an approximate area measure. Magnitude of reactions and reliabilities were compared using ANOVA procedures. Behavioral concordances were estimated as correlations with the subjects' ratings of stimulus intensities. Conductance and resistance measures do not differ in amplitude, in area, or in strength of their reliabilities and behavioral concordances. No differences in any respect are found between sites. Skin conductance yields significantly (p < .01) shorter recovery times than skin resistance, which is discussed in terms of membrane permeability change.     

Zum Ursprung der Normalantikörper

Zusammenfassung In allen Studien mit modernen Methoden der keimfreien Forschung, der Serologie und der Genetik hat sich als die Ursachenachweisbarer normaler Hämagglutinine immunogene Stimulation beweisen oder hochwahrscheinlich machen lassen. Ererbt ist die Fähigkeit, Antikörper zu bilden. Genetische Faktoren dürften bei der Induktion der Antikörpersynthese durch Antigene bedeutungsvoll sein. Auch ist nach dem heutigen Stande des Wissens die primäre Globulinstruktur genetisch bedingt.Die eigenen hier referierten Versuche wurden von der U.S. National Science Foundation durch Grant G-3516 und durch Grant DA 49-007-MD-463 der Research and Development Division, Office of the Surgeon General, Department of the Army, Washington, D.C., unterstützt.Established Investigator of the American Heart Association.     

C4d]FlowPRA screening--a specific assay for selective detection of complement-activating anti-HLA alloantibodies

On waiting lists, transplant candidates are routinely screened for potentially harmful complement-fixing alloantibodies using complement-dependent cytotoxicity (CDC) panel-reactive antibody (PRA) testing. We have recently developed a novel cell-independent assay for assessment of complement-activating panel reactivity ([C4d]FlowPRA), which is based on selective flow-cytometric detection of alloantibody-triggered C4 complement split product deposition to human leukocyte antigen (HLA)-coated FlowPRA beads. Serum specimens selected from 120 transplant candidates were evaluated by [C4d]FlowPRA (HLA class I vs II) in comparison with FlowPRA IgG alloantibody screening (HLA class I vs II), a method detecting both complement- and noncomplement-activating alloantibodies, and with CDC-PRA on separated T (T-CDC) or B cells (B-CDC, evaluation on platelet-absorbed sera). For each assay, >/=10% PRA reactivity was considered positive. Comparing complement-dependent PRA assays with standard FlowPRA, the specificity calculated for [C4d]FlowPRA (HLA class I: 92%; class II: 100%) was found to be superior to that of CDC testing (T-CDC-PRA: 79%; B-CDC-PRA: 86%). Because noncomplement-activating alloreactivities were not detected for both techniques, low sensitivities were calculated ([C4d]FlowPRA HLA class I: 61%; class II: 31%; T-CDC-PRA: 70%; B-CDC-PRA: 55%). Compared with CDC-PRA, [C4d]FlowPRA gave a high specificity (HLA class I compared with T-CDC: 89%, HLA class II compared with B-CDC: 95%) but, at least in part because of false-positive CDC results, a modest sensitivity (66% and 38%, respectively). For both HLA classes, we found a highly significant association between absolute [C4d]FlowPRA and CDC-PRA levels (p < 0.0001). Our results suggest that detection of C4 split product deposition to FlowPRA beads may represent an attractive HLA-specific and time-effective alternative to CDC-PRA screening.     

Cardiomyopathy associated with Leigh's disease

Summary Clinical and postmortem findings in a female infant, suffering from Leigh's disease and cardiomegaly are described. The cardiac enlargement was due to symmetrical thickening of both ventricular walls and the septum. On light microscopy a widespread fibre disarray with a slight predilection for the ventricular septum was observed. Ultrastructural changes included an extreme reduction in the number of myofibrils and an excess of mitochondria. Abnormalities of the mitochondrial structure with tubular and myelinic transformation of the cristae suggested that a mitochondriopathy is responsible for the cardiomegaly in Leigh's disease.Dedicated to Prof. Dr. Waldemar Hort on the occasion to his 60th birthday     

Serotonin transporter binding in Tourette Syndrome

Recent studies provided evidence for an involvement of the dopaminergic system in the pathophysiology of Tourette Syndrome (TS). However, little is known about possible impairment of other neurotransmitter systems. In obsessive-compulsive disorder (OCD), a common comorbidity in TS, it is suggested that the serotonergic system plays a major role in the pathogenesis. We, therefore, used [I-123]2[beta]-carbomethoxy-3[beta]-(4-iodophenyl)tropane ([123I]beta-CIT) and single photon emission computed tomography (SPECT) to investigate serotonin transporter (SERT) binding capacity in 12 patients with TS with various degrees of associated obsessive compulsive behaviour (OCB) and 16 age-matched healthy controls. Binding ratios in TS patients not receiving serotonin reuptake inhibitors (SSRI) (n=8) were significantly reduced compared to age-adjusted ratios from normal controls (2.8 versus 3.2, p=0.003). Treatment with SSRI resulted in a significant reduction of SERT availability. Performing linear regression analysis for this small group, SSRI-free patients indicated trends for a negative correlation between [123I]beta-CIT binding on SERT and OCB (r=-0.78, p=0.023) as well as complex motor tics (r=-0.68, p=0.064). In healthy controls, but not in the TS group, we found an age-related decline in SERT binding capacity (0.28% decrease per year, p=0.038). Our data are in agreement with previous results suggesting an impairment of the serotonergic system in TS. It can be speculated that the reduction in SERT binding capacity is associated with the degree of comorbid OCB.     

Periodontitis is associated with a low concentration of vitamin C in plasma

This study aimed to clarify how concentrations of vitamin C in plasma relate to the serology of periodontitis. The random sample used comprised 431 men, 194 from Finland and 237 from Russia. The plasma vitamin C concentration was determined by o-phtaldialdehyde-fluorometry, and serum immunoglobulin G antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were determined by a multiserotype enzyme-linked immunosorbent assay (ELISA). The mean plasma vitamin C concentration was higher (P < 0.001) in Finnish subjects (mean +/- standard deviation, 4.5 +/- 2.8 mg/liter) than in Russian subjects (1.4 +/- 1.8 mg/liter). Mean antibody levels to both A. actinomycetemcomitans (4.7 +/- 3.6 versus 5.2 +/- 3.1 ELISA units [P = 0.05]) and P. gingivalis (5.7 +/- 2.5 versus 7.6 +/- 2.9 ELISA units [P < 0.001]) were lower in Finnish men than in Russian men. In the combined Finnish and Russian population, the antibody levels to P. gingivalis were negatively correlated with vitamin C concentrations (r = -0.22; P < 0.001); this association remained statistically significant (P = 0.010) in a linear regression model after adjustment for confounding factors. The proportion of P. gingivalis-seropositive subjects decreased with increasing vitamin C concentrations (P for trend, <0.01), but no trend was seen among A. actinomycetemcomitans-seropositive subjects. In conclusion, P. gingivalis infection is associated with low concentrations of vitamin C in plasma, which may increase colonization of P. gingivalis or disturb the healing of the infected periodontium.     

The Bioperl toolkit: Perl modules for the life sciences

The Bioperl project is an international open-source collaboration of biologists, bioinformaticians, and computer scientists that has evolved over the past 7 yr into the most comprehensive library of Perl modules available for managing and manipulating life-science information. Bioperl provides an easy-to-use, stable, and consistent programming interface for bioinformatics application programmers. The Bioperl modules have been successfully and repeatedly used to reduce otherwise complex tasks to only a few lines of code. The Bioperl object model has been proven to be flexible enough to support enterprise-level applications such as EnsEMBL, while maintaining an easy learning curve for novice Perl programmers. Bioperl is capable of executing analyses and processing results from programs such as BLAST, ClustalW, or the EMBOSS suite. Interoperation with modules written in Python and Java is supported through the evolving BioCORBA bridge. Bioperl provides access to data stores such as GenBank and SwissProt via a flexible series of sequence input/output modules, and to the emerging common sequence data storage format of the Open Bioinformatics Database Access project. This study describes the overall architecture of the toolkit, the problem domains that it addresses, and gives specific examples of how the toolkit can be used to solve common life-sciences problems. We conclude with a discussion of how the open-source nature of the project has contributed to the development effort.     

Experimental double infection of Biomphalaria glabrata snails with Angiostrongylus cantonensis and Schistosoma mansoni

Summary Two groups of Biomphalaria glabrata snails primarily infected with Angiostrongylus cantonensis were secondarily exposed to infection with Schistosoma mansoni. To investigate any antagonistic effect of a first infection on a superimposed one and to compare to singly and non-infected snails, a series of experiments was undertaken in which snails were individually exposed, variously, to 1,000 and 2,000 first-stage larvae of A. cantonensis and then to 5 and 10 miracidia of S. mansoni 1 day and 3 weeks later.Snails became infected with S. mansoni in both groups of snails with double infections and shed cercariae after the same incubation period as in the singly infected groups. The number of snails shedding cercariae simultaneously was similar in single and double infection groups during the first two weeks of shedding, after which this number decreased somewhat in doubly infected groups. Snails with double infection showed higher cumulative mortality rates than in snail groups with single infection with either A. cantonensis or S. mansoni. Therefore, initial infection of B. glabrata with A. cantonensis produced no inhibitory or retarding effect on subsequent infection of snails with S. mansoni.

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Zusammenfassung Zwei Gruppen der Süßwasserschnecke Biomphalaria glabrata, die zuvor mit 1000 bzw. 2000 ersten Larven von Angiostrongylus cantonensis pro Schnecke infiziert worden waren, wurden zur Feststellung eines eventuellen antagonistischen Effekts zwischen beiden Parasiten, einen Tag und drei Wochen später mit 5 bzw. 10 Miracidien von Schistosoma mansoni infiziert. Nicht infizierte und mit jeweils nur einer der beiden Parasitenarten infizierte Schnecken dienten als Kontrolle.In beiden doppelt infizierten Gruppen ging die S. mansoni-Infektion sehr gut an, und die Ausscheidung von Cercarien begann nach der gleichen Entwicklungszeit wie bei den nur mit S. mansoni infizierten Kontrollgruppen. Die Anzahl Cercarien ausscheidender Schnecken war in den beiden ersten Wochen bei den jeweils einzeln und doppelt infizierten Gruppen sehr ähnlich, während sie sich in der Folgezeit in den doppelt infizierten Gruppen rasch verminderte. In Gruppen mit Doppelinfektion zeigte sich eine höhere Mortalität als bei den jeweils nur mit A. cantonensis oder S. mansoni infizierten Schnecken. Eine Beeinflussung der Entwicklung von S. mansoni durch die vorausgegangene Nematodeninfektion konnte nicht nachgewiesen werden.