Hemispheric specialization for global and local processing: the effect of stimulus category.

Neuropsychological evidence indicates that the global aspect of complex visual scenes is preferentially processed by the right hemisphere, and local aspects are preferentially processed by the left hemisphere. Using letter-based hierarchical stimuli (Navon figures), we recently demonstrated, in a directed-attention task, lateralized neural activity (assessed by positron emission tomography) in the left prestriate cortex during local processing, and in the right prestriate cortex during global processing. Furthermore, temporal-parietal cortex was critically activated bilaterally in a divided-attention task that involved varying the number of target switches between local and global levels of letter-based hierarchical stimuli. Little is known about whether such stimulus categories influence such hemispheric lateralization. We now present data on brain activity, derived from positron emission tomography, in normal subjects scanned during either local or global processing of object-based hierarchical stimuli. We again observe attentional modulation of neural activity in prestriate cortex. There is now greater right-sided activation for local processing and greater left-sided activation for global processing, which is the opposite of that seen with letter-based stimuli. The results suggest that the relative differential hemispheric activations in the prestriate areas during global and local processing are modified by stimulus category.     

Investigating a network model of word generation with positron emission tomography.

By using positron emission tomography (PET) we examined the biological validity of a network model describing changes in cerebral activity associated with intrinsic and extrinsic word generation. The production of words not specified by an extrinsic stimulus constitutes willed or intrinsic generation. Perceiving a heard word is an example of extrinsic generation. The model incorporates three neuronal systems: a pool that stores word representations in a distributed fashion, an afferent system conveying sensory input to the pool and a modulating system that alters the responsivity of neurons in the pool. Simulations based on the model suggested that intrinsic generation would be associated with low activity in the pool, consequent on reduced modulation, and extrinsic generation with high activity. We measured cerebral activity with PET during intrinsic (verbal fluency) and extrinsic (responding to heard words) word generation and found this pattern of changes in the left superior temporal region. We were able to designate this region the site of the distributed word store and implicate the left dorsolateral prefrontal cortex (DLPFC) as the source of modulation. The relation between the superior temporal gyrus and DLPFC was shown by examining the correlation between the two regions in terms of cerebral activity. We conclude that the left DLPFC is responsible for modulating the responsivity of a neural system in the superior temporal gyrus and is the probable mediator of changes in attentional and intentional states that underlies the intrinsic generation of words.     

Adenosylhomocysteinase:Adenosine complex

Adenosylhomocysteinase from yellow lupin seeds forms a specific complex with adenosine. The complex can be isolated either by nonequilibrium or equilibrium gel filtration. It is also adsorbed on nitrocellulose disks. Dissociation constant of the complex determined by nitrocellulose filter assay is 5 × 10^?8M.     

Generative FDG-PET and MRI Model of Aging and Disease Progression in Alzheimer's Disease

The failure of current strategies to provide an explanation for controversial findings on the pattern of pathophysiological changes in Alzheimer''s Disease (AD) motivates the necessity to develop new integrative approaches based on multi-modal neuroimaging data that captures various aspects of disease pathology. Previous studies using [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) and structural magnetic resonance imaging (sMRI) report controversial results about time-line, spatial extent and magnitude of glucose hypometabolism and atrophy in AD that depend on clinical and demographic characteristics of the studied populations. Here, we provide and validate at a group level a generative anatomical model of glucose hypo-metabolism and atrophy progression in AD based on FDG-PET and sMRI data of 80 patients and 79 healthy controls to describe expected age and symptom severity related changes in AD relative to a baseline provided by healthy aging. We demonstrate a high level of anatomical accuracy for both modalities yielding strongly age- and symptom-severity- dependant glucose hypometabolism in temporal, parietal and precuneal regions and a more extensive network of atrophy in hippocampal, temporal, parietal, occipital and posterior caudate regions. The model suggests greater and more consistent changes in FDG-PET compared to sMRI at earlier and the inversion of this pattern at more advanced AD stages. Our model describes, integrates and predicts characteristic patterns of AD related pathology, uncontaminated by normal age effects, derived from multi-modal data. It further provides an integrative explanation for findings suggesting a dissociation between early- and late-onset AD. The generative model offers a basis for further development of individualized biomarkers allowing accurate early diagnosis and treatment evaluation.     

Design and synthesis of 1-aryl-5-anilinoindazoles as c-Jun N-terminal kinase inhibitors

Starting from pyrazole HTS hit (1), a series of 1-aryl-1H-indazoles have been synthesized as JNK3 inhibitors with moderate selectivity against JNK1. SAR studies led to the synthesis of 5r as double digital nanomolar JNK3 inhibitor with good in vivo exposure.     

The determination of homocysteine-thiolactone in biological samples

Homocysteine-thiolactone, a cyclic thioester of homocysteine, is synthesized by methionyl-tRNA synthetase in all cell types. A new assay for the determination of homocysteine-thiolactone in biological samples is described. The assay involves separation of homocysteine-thiolactone from macromolecules by ultrafiltration. Homocysteine-thiolactone is further purified and quantified by high-pressure liquid chromatography either on a reverse phase or a cation exchange micro-bore column. The detection and quantitation are obtained by monitoring the absorbance at 240 nm, a maximum in a UV spectrum of homocysteine-thiolactone. The sensitivity of detection is 5 pmol. This assay has been applied to bacteria (Escherichia coli and Mycobacterium smegmatis), the yeast Saccharomyces cerevisiae, cultured human vascular endothelial cells, and human plasma. The data support the conclusion that homocysteine-thiolactone is a ubiquitous metabolite whose levels are directly related to homocysteine levels.     

Homocysteine is a protein amino acid in humans. Implications for homocysteine-linked disease

Homocysteine is thought to be a non-protein amino acid. However, in vitro studies suggest that homocysteine is likely to be incorporated by indirect mechanisms into proteins in living organisms. Here I show that homocysteine is a protein amino acid in humans. Homocysteine bound by amide or peptide linkages (Hcy-N-protein) is present in human hemoglobin, serum albumin, and gamma-globulins. 1 molecule of homocysteine per 1000 or 1670 molecules of methionine was present in hemoglobin or albumin, respectively. Other proteins, such as low density lipoprotein, high density lipoprotein, transferrin, antitrypsin, and fibrinogen, contained lower amounts of Hcy-N-protein. In human plasma, levels of Hcy-N-protein represented from 0.3 to 23% of total homocysteine. Thus, Hcy-N-protein is a significant component of homocysteine metabolism in humans, possibly contributing to adverse effects of homocysteine on human cells.     

Excitation Energy Transfer in Cyanobacteria Synechocystis Embedded in Polymer Film and Partially Bleached by Polarized Irradiation

The polarized absorption, photoacoustic, fluorescence emission, and fluorescence excitation spectra of whole cells of cyanobacteria Synechocystis sp. embedded in a polymer film were measured. The bacteria cells, as it follows from anisotropy of absorption and fluorescence spectra, were even in a non-stretched polyvinyl alcohol film oriented to a certain extent. The measurements were done for such film in order to avoid the deformation of cyanobacteria shapes. Part of the samples was bleached by irradiation with strong polarized radiation with electric vector parallel to the orientation axis of cells. The anisotropy of photoacoustic spectra was higher than that of absorption spectra and it was stronger changed by the irradiation. Polarized fluorescence was excited in four wavelength regions characterised by different contribution to absorption from various bacteria pigments. The shapes of emission spectra were different depending on wavelength of excitation, polarization of radiation, and previous irradiation of the sample. The fluorescence spectra were analysed on Gaussian components belonging to various forms of pigments from photosystems (PS) 1 and 2. The results inform about excitation energy transfer between pools of pigments, differently oriented in the cells. Energy of photons absorbed by phycobilisomes was transferred predominantly to the chlorophyll of PS2, whereas photons absorbed by carotenoids to chlorophylls of PS1.     

The Effect of Different Types of Musculoskeletal Injuries on Blood Concentration of Serum Amyloid A in Thoroughbred Racehorses

BackgroundTraining-induced muscle, skeletal and joint trauma may result in acute phase response reflected by the changes in the blood concentration of serum amyloid A (SAA) in racehorses. It remains yet unclear if such systemic reaction could be triggered by sport injuries and what is the impact of different types of musculoskeletal trauma on SAA concentrations in racehorses. This study aimed to determine changes in the SAA blood concentration in racehorses with different types of injuries of musculoskeletal system.ResultsMean SAA concentration within the first 4 days of the injury of muscle and tendon was significantly higher than in bone fractures, dorsal metacarpal disease, joint trauma or in the healthy horses (p<0,001). There were no significant differences between the other groups.ConclusionsStrain injuries of muscle and tendons can cause a moderate increase in SAA blood concentration in racehorses, reflecting the occurrence of the acute phase response. Similar reaction is not observed in the stress-related bone injuries.