Dopamine Synthesis in the Nigrostriatal Dopaminergic System in Patients at Risk of Developing Parkinson's Disease at the Prodromal Stage.

Parkinson's disease (PD) is diagnosed by the onset of motor symptoms and treated long after its onset. Therefore, the development of the early diagnosis of PD is a priority for neurology. Advanced methodologies for this include (1) searching for patients at risk of developing prodromal PD based on premotor symptoms; (2) searching for changes in the body fluids in these patients as diagnostic biomarkers; (3) verifying the diagnosis of prodromal PD and diagnostic-value biomarkers using positron emission tomography (PET); (4) anticipating the development of motor symptoms. According to our data, the majority of patients (n = 14) at risk of developing PD selected in our previous study show pronounced interhemispheric asymmetry in the incorporation of 18F-DOPA into dopamine synthesis in the striatum. This was assessed for the caudate nucleus and putamen separately using the specific binding coefficient, asymmetry index, and putamen/caudate nucleus ratio. Interhemispheric asymmetry in the incorporation of 18F-DOPA into the striatum provides strong evidence for its dopaminergic denervation and the diagnostic value of previously identified blood biomarkers. Of the 17 patients at risk of developing prodromal PD studied using PET, 3 patients developed motor symptoms within a year. Thus, our study shows the promise of using the described methodology for the development of early diagnosis of PD.

Water Will Be the Coal of the Future-The Untamed Dream of Jules Verne for a Solar Fuel.

This article evokes the futuristic visions of two giants, one a writer, Jules Verne, who foresaw water as the coal of the future, and the other a scientist, Giacomo Ciamician, who foresaw the utilization of solar energy as an energy source with which to drive photochemical and photocatalytic reactions for the betterment of mankind. Specifically, we examine briefly the early work of the 1960s and 1970s on the photosplitting of free water and water adsorbed on solid supports, based mostly on metal oxides, from which both hydrogen and oxygen evolve in the expected stoichiometric ratio of 2 to 1. The two oil crises of the 1970s (1973 and 1979) spurred the interest of researchers from various disciplines (photochemistry, photo-catalysis and photoelectrochemistry) in search of a Holy Grail photocatalyst, process, or strategy to achieve efficient water splitting so as to provide an energy source alternative to fossil fuels. Some approaches to the photosplitting of water adsorbed on solid insulators (high bandgap materials; Ebg ≥ 5 eV) and semiconductor photocatalysts (metal oxides) are described from which we deduce that metal oxides with bandgap energies around 5 eV (e.g., ZrO2) are more promising materials to achieve significant water splitting on the basis of quantum yields than narrower bandgap photocatalysts (e.g., TiO2; Ebg ≈ 3.0-3.2 eV), which tend to be relatively inactive by comparison. Although proof of concept of the photosplitting of water has been demonstrated repeatedly in the last four decades, much remains to be done to find the Holy Grail photocatalyst and/or strategy to achieve significant yields of hydrogen.

Changes of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in the model of experimental acute hydrocephalus in rabbits.

BACKGROUND: To study the integrity of white matter, we investigated the correlation between the changes in neuroradiological and morphological parameters in an animal model of acute obstructive hydrocephalus. METHODS: Hydrocephalus was induced in New Zealand rabbits (n = 10) by stereotactic injection of kaolin into the lateral ventricles. Control animals received saline in place of kaolin (n = 10). The progression of hydrocephalus was assessed using magnetic resonance imaging. Regional fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) were measured in several white matter regions before and after the infusion of kaolin. Morphology of myelinated nerve fibers as well as of the blood-brain barrier were studied with the help of transmission electron microscopy (TEM) and light microscopy. RESULTS: Compared with control animals, kaolin injection into the ventricles resulted in a dramatic increase in ventricular volume with compression of basal cisterns, brain shift and periventricular edema (as observed on magnetic resonance imaging [MRI]). The values of ADC in the periventricular and periaqueductal areas significantly increased in the experimental group (P < 0.05). FA decreased by a factor of 2 in the zones of periventricular, periaqueductal white matter and corpus collosum. Histological analysis demonstrated the impairment of the white matter and necrobiotic changes in the cortex. Microsctructural alterations of the myelin fibers were further proved with the help of TEM. Blood-brain barrier ultrastructure assessment showed the loss of its integrity. CONCLUSIONS: The study demonstrated the correlation of the neuroradiological parameters with morphological changes. The abnormality of the FA and ADC parameters in the obstructive hydrocephalus represents a significant implication for the diagnostics and management of hydrocephalus in patients.

An ER-fMRI study of Russian inflectional morphology.

The generation of regular and irregular past tense verbs has long been a testing ground for different models of inflection in the mental lexicon. Behavioral studies examined a variety of languages, but neuroimaging studies rely almost exclusively on English and German data. In our fMRI experiment, participants inflected Russian verbs and nouns of different types and corresponding nonce stimuli. Irregular real and nonce verbs activated inferior frontal and inferior parietal regions more than regular verbs did, while no areas were more activated in the opposite comparison. We explain this activation pattern by increasing processing load: a parametric contrast revealed that these regions are also more activated for nonce stimuli compared to real stimuli. A very similar pattern is found for nouns. Unlike most previously obtained results, our findings are more readily compatible with the single-system approach to inflection, which does not postulate a categorical difference between regular and irregular forms.

Novel atypical nucleotide insertions specifically at VH-DH junction generate exceptionally long CDR3H in cattle antibodies.

Some IgM cattle antibodies are amongst the largest known to exist in jawed vertebrates where CDR3H size may extend up to 61 amino acids. To understand the origin of such an exceptionally long CDR3H, bovine D(H) gene locus was completely characterized from Holstein cattle that revealed the presence of a total of eight D(H) genes, including D(H)Q52, with a distinct organization in sub-clusters. However, a total of 10 D(H) genes are identified at the polymorphic D-gene locus in cattle that are classified into four families, designated as BovD(H)A, BovD(H)B, BovD(H)C and BovD(H)D. In fetal B-cells, VDJ recombinations encoding long CDR3H (>50 codons) are directly encoded by the single germline V(H) gl.110.20, the longest D(H)2 and the J(H)1 genes, apart from few N- and P-nucleotide additions at the junctions. Further, non J-proximal D(H)7 gene is preferentially expressed in fetal B cells. The adult VDJ recombinations, however, are distinctly remarkable for 'conserved short nucleotide sequence' ('CSNS'; 13-18 nucleotides), of non-V(H) or D(H) gene origin, inserted specifically at V(H)-D(H) junctions resulting in extension of CDR3H size up to 61 codons. Together with P-nucleotides, N-additions (1-9 nucleotides) are noted at both the V(H)-D(H) and D(H)-J(H) junctions. Such 'CSNS' insertions at V(H)-D(H) junction of adult VDJ recombinations encoding exceptionally long CDR3H provide novel mechanism of antibody diversification in cattle, not yet observed in other species. Further, analysis of V(H)-D(H)-J(H) recombinations originating from fetal B-cells reveals the presence of substitution, deletion or addition mutations without prior exposure to external antigen. Thus, somatic hypermutations may contribute towards diversification of the developing nascent antibody repertoire in cattle. In conclusion, the outlined experiments provide novel antibody diversification mechanism via 'CSNS' insertions, specifically at the V(H)-D(H) junction, in generating exceptionally long CDR3H extending up to 61 codons in cattle antibodies.

Comparison of brain activation after sustained non-fatiguing and fatiguing muscle contraction: a positron emission tomography study.

The concept of fatigue refers to a class of acute effects that can impair motor performance, and not to a single mechanism. A great deal is known about the peripheral mechanisms underlying the process of fatigue, but our knowledge of the roles of the central structures in that process is still very limited. During fatigue, it has been shown that peripheral apparatus is capable of generating adequate force while central structures become insufficient/sub-optimal in driving them. This is known as central fatigue, and it can vary between muscles and different tasks. Fatigue induced by submaximal isometric contraction may have a greater central component than fatigue induced by prolonged maximal efforts. We studied the changes in regional cerebral blood flow (rCBF) of brain structures after sustained isometric muscle contractions of different submaximal force levels and of different durations, and compared them with the conditions observed when the sustained muscle contraction becomes fatiguing. Changes in cortical activity, as indicated by changes in rCBF, were measured using positron emission tomography (PET). Twelve subjects were studied under four conditions: (1) rest condition; (2) contraction of the m. biceps brachii at 30% of MVC, sustained for 60 s; (3) contraction at 30% of MVC, sustained for 120 s, and; (4) contraction at 50% of MVC, sustained for 120 s. The level of rCBF in the activated cortical areas gradually increased with the level and duration of muscle contraction. The fatiguing condition was associated with predominantly contralateral activation of the primary motor (MI) and the primary and secondary somatosensory areas (SI and SII), the somatosensory association area (SAA), and the temporal areas AA and AI. The supplementary motor area (SMA) and the cingula were activated bilaterally. The results show increased cortical activation, confirming that increased effort aimed at maintaining force in muscle fatigue is associated with increased activation of cortical neurons. At the same time, the activation spread to several cortical areas and probably reflects changes in both excitatory and inhibitory cortical circuits. It is suggested that further studies aimed at controlling afferent input from the muscle during fatigue may allow a more precise examination of the roles of each particular region involved in the processing of muscle fatigue.

Changes in human regional cerebral blood flow following hypertonic saline induced experimental muscle pain: a positron emission tomography study.

A positron emission tomography imaging study was performed on 16 healthy volunteers to reveal changes in cortical activation during acute muscle pain induced by intra-muscular injection of hypertonic saline into the left triceps brachii muscle. Changes in regional cerebral blood flow (rCBF) were measured with the use of [(15)O] labelled water during 'Rest1', 'Needle' (insertion of a needle without injection), 'Rest2' and 'Pain' conditions. Differences in rCBF were found in the comparison of Pain and Needle, and Pain and Rest2 conditions, revealing activation of the contralateral insula and putamen. The results are discussed with respect to possible differences in brain processing of muscle and cutaneous noxious inputs.

Comparison of brain activity during different types of proprioceptive inputs: a positron emission tomography study.

It has been shown that the primary and secondary somatosensory cortex, as well as the supplementary motor area (SMA), are involved in central processing of proprioceptive signals during passive and active arm movements. However, it is not clear whether different cortical areas are involved in processing of different proprioceptive inputs (skin, joint, muscle receptors), what their relative contributions might be, where kinesthetic sensations are formed within the CNS, and how they interact when the full peripheral proprioceptive machinery acts. In this study we investigated the representation of the brain structures involved in the perception of passive limb movement and illusory movement generated by muscle tendon vibration. Changes in cortical activity as indicated by changes in regional cerebral blood flow (rCBF) were measured using positron emission tomography (PET). Twelve subjects were studied under four conditions: (1) passive flexion-extension movement (PM) of the left forearm; (2) induced illusions of movements (VI) similar to the real PM, induced by alternating vibration of biceps and triceps tendons (70-80 Hz) at the elbow; (3) alternating vibration of biceps and triceps tendons (with 20-50 Hz) without induced kinesthetic illusions (VN); and (4) rest condition (RE). The results show different patterns of cortex activation. In general, the activation during passive movement was higher in comparison with both kinds of vibration, and activation during vibrations with induced illusions of movement was more prominent than during vibrations without induced illusions. When the PM condition was contrasted with the other conditions we found the following areas of activation -- the primary motor (MI) and somatosensory area (SI), the SMA and the supplementary somatosensory area (SSA). In conditions where passive movements and illusory movements were contrasted with rest, some temporal areas, namely primary and associative auditory cortex, were activated, as well as secondary somatosensory cortex (SII). Our data show that different proprioceptive inputs, which induce sensation of movement, are associated with differently located activation patterns in the SI/MI and SMA areas of the cortex. In general, the comparison of activation intensities under different functional conditions indicates the involvement of SII in stimulus perception generation and of the SI/MI and SMA areas in the processing of proprioceptive input. Activation of the primary and secondary auditory cortex might reflect the interaction between somatosensory and auditory systems in movement sense generation. SSA might also be involved in movement sense generation and/or maintenance.