"European" race-specific metacentrics in East Siberian common shrews (Sorex araneus): a description of two new chromosomal races, Irkutsk and Zima.

Karyotype studies of common shrews in the vicinity of Lake Baikal (Irkutsk Region, Eastern Siberia) resulted in the description of two new chromosomal races of Sorex araneus Linnaeus, 1758 (Lypotyphla, Mammalia), additional to 5 races formerly found in Siberia. In the karyotypes of 12 specimens from 3 locations, the polymorphism of metacentric and acrocentric chromosomes of the Robertsonian type was recorded and two distinct groups of karyotypes interpreted as the chromosomal races were revealed. They are geographically distant and described under the racial names Irkutsk (Ir) and Zima (Zi). Karyotypes of both races were characterized by species-specific (the same for all 74 races known so far) metacentric autosomes af, bc, tu and jl, and the typical sex chromosome system - XX/XY1Y2. The race-specific arm chromosome combinations include three metacentrics and four acrocentrics in the Irkutsk race (gk, hi, nq, m, o, p, r) and four metacentrics and two acrocentrics in the Zima race (gm, hi, ko, nq, p, r). Within the races, individuals with polymorphic chromosomes were detected (g/m, k/o, n/q, p/r). The presence of the specific metacentric gk allowed us to include the Irkutsk race into the Siberian Karyotypic Group (SKG), distributed in surrounding regions. The Zima race karyotype contained two metacentrics, gm and ko, which have been never found in the Siberian part of the species range, but appear as the common feature of chromosomal races belonging to the West European Karyotypic Group (WEKG). Moreover, the metacentrics of that karyotype are almost identical to the Åkarp race (except the heterozygous pair p/r) locally found in the southern Sweden. One of two Siberian races described here for the first time, the Zima race, occurs in an area considerably distant from Europe and shares the common metacentrics (gm, hi, ko) with races included in WEKG. This fact may support a hypothesis of independent formation of identical arm chromosome combinations due to occurrence of the same centric fusions in different parts of the species range.

In vivo imaging of brain metabolism activity using a phosphorescent oxygen-sensitive probe.

Several approaches have been adopted for real-time imaging of neural activity in vivo. We tested a new cell-penetrating phosphorescent oxygen-sensitive probe, NanO2-IR, to monitor temporal and spatial dynamics of oxygen metabolism in the neocortex following peripheral sensory stimulation. Probe solution was applied to the surface of anesthetized mouse brain; optical imaging was performed using a MiCAM-02 system. Trains of whisker stimuli were delivered and associated changes in phosphorescent signal were recorded in the contralateral somatosensory ("barrel") cortex. Sensory stimulation led to changes in oxygenation of activated areas of the barrel cortex. The oxygen imaging results were compared to those produced by the voltage-sensitive dye RH-1691. While the signals emitted by the two probes differed in shape and amplitude, they both faithfully indicated specific whisker evoked cortical activity. Thus, NanO2-IR probe can be used as a tool in visualization and real-time analysis of sensory-evoked neural activity in vivo.

Conformational fingerprinting of the angiotensin I-converting enzyme (ACE). 1. Application in sarcoidosis.

Fine epitope mapping of monoclonal antibodies (mAbs) to 16 epitopes on human angiotensin I-converting enzyme (ACE) revealed that the epitopes of all mAbs contained putative glycosylation sites. ACE glycosylation is both cell- and tissue-specific and, therefore, the local conformation of ACE produced by different cells could be also unique. The pattern of ACE binding by a set of mAbs to 16 epitopes of human ACE - "conformational fingerprint of ACE" - is the most sensitive marker of ACE conformation and could be cell- and tissue-specific. The recognition of ACEs by mAbs to ACE was estimated using an immune-capture enzymatic plate precipitation assay. Precipitation patterns of soluble recombinant ACE released from Chinese hamster ovary (CHO)-ACE cells was influenced by conditions that alter ACE glycosylation. This pattern was also strongly cell type specific. Patients with sarcoidosis exhibited conformational fingerprints of tissue ACE (lungs and lymph nodes), as well as blood ACE, which were distinct from controls. Conformational fingerprinting of ACE may detect ACE originated from the cells other than endothelial cells in the blood and when combined with elevated blood ACE levels in patients with sarcoidosis may potentially reflect extrapulmonary sarcoidosis involvement (bone marrow, spleen, liver). If proven true, this would serve as a biomarker of enormous potential clinical significance.

Methadone restores local and remote EEG functional connectivity in opioid-dependent patients.

Currently it has been proposed that normal brain function is critically dependent upon a dynamical balance between functions of local neuronal assemblies and global integrative processes. A loss of such metastable balance in favor of either independent or hyper-ordered processing is considered as the reflection of a brain disease. It has been shown that opioid dependence can be characterized as a disease of brain metastable balance, wherein local functional connectivity (synchronicity within neuronal assemblies) increased and remote functional connectivity (synchronicity between neuronal assemblies) decreased. Since methadone may be used as a maintenance treatment for opioid-dependent patients, the aim of this research was to study how methadone would influence the temporal and metastable cortical organization through the measures of local and remote electroencephalogram (EEG) functional connectivity in six opioid-depended patients who manage to complete at least six-month methadone treatment. The present study demonstrated that average parameters of temporal and metastable organization of the cortical dynamics (indexed by local and remote EEG functional connectivity) in such opioid-dependent patients did not differ from normal values of healthy subjects. We interpret these findings as a capability of the methadone to restore a normal temporal and metastable structure of brain activity in opioid-dependent patients after many months of methadone treatment. To our knowledge, present preliminary study is the first where the influence of methadone on temporal and metastable structure of EEG activity is demonstrated.

Composition of EEG oscillations and their temporal characteristics: methadone treatment.

In this study, we examine the composition of electroencephalographic (EEG) oscillations within a broad frequency band (0.5-30 Hz) for opioid abuse (22 patients), during withdrawal (13 patients), and after 6 months of methadone treatment (6 patients) and in 14 healthy subjects during a resting condition (closed eyes). The exact compositions of EEG oscillations and their temporal behaviour were assessed using the probability-classification analysis of short-term EEG spectral patterns. The study reveals the dynamics of particular EEG oscillations throughout the conditions of opioid dependency, withdrawal and methadone-based treatment. It was shown that methadone maintenance treatment normalized considerably the composition of EEG oscillations and their percentage ratio and restored the temporal structure of patients' EEG comparable with healthy subjects. The importance of the methadone's ability to restore a normal temporal structure of the brain's activity is discussed.

Opioid withdrawal results in an increased local and remote functional connectivity at EEG alpha and beta frequency bands.

Withdrawal may be a natural model to study craving and compulsive drug seeking, since craving can be viewed as a conditioned dysphoric state. It has been suggested that functional connectivity between brain areas may be of major value in explaining excessive craving and compulsive drug seeking by providing essential link between psychological and biological processes. Considering that withdrawal initiates a widespread activation of cortical regions responsible for compulsive drug seeking and desire for the drug, we predict that withdrawal would result in a significant increase in functional cortical connectivity. We applied the novel operational architectonics approach that enables us to estimate both local and remote functional cortical connectivity by means of EEG structural synchrony measure. In 13 withdrawal opioid-dependent patients we found the evidence that local and remote cortical functional connectivity was indeed significantly enhanced (for both alpha and beta frequency oscillations). Additionally, statistical relationship between functional connectivity and the severity of opioid withdrawal has been found.

Reorganization of the composition of brain oscillations and their temporal characteristics in opioid dependent patients.

In the present study, we examined the composition of electroencephalographic (EEG) brain oscillations in broad frequency band (0.5-30 Hz) in 22 opioid-dependent patients and 14 healthy subjects during resting condition (closed eyes). The exact compositions of brain oscillations and their temporal behavior were assessed by the probability-classification analysis of short-term EEG spectral patterns. It was demonstrated that EEG of patients with opioid dependence was characterized by (a) significant reorganization of brain oscillations with increase in the percentage of beta- and mostly fast-alpha-rhythmic segments, (b) longer periods of temporal stabilization for alpha and beta brain oscillations and by shorter periods of temporal stabilization for theta and polyrhythmic activity when compared with control subjects, and (c) right-sided dominance (significantly larger relative presence of particular spectral patterns in EEG channels of the right hemisphere). These effects were widely distributed across the cortex with the maximum magnitude in the occipital, right parietal, temporal, and frontal areas. Taken together the present study suggested (a) an allostatic state with neuronal activation, and (b) high sensitivity of the right hemisphere to adverse opioid effects.

Increased local and decreased remote functional connectivity at EEG alpha and beta frequency bands in opioid-dependent patients.

RATIONALE: Although researchers now have a working knowledge of key brain structures involved in realization of actions of substance abuse and addiction, deeper understanding will require examination of network interactions between cortical neuronal assemblies and their subcortical tails in the effects of opioid dependence. OBJECTIVES: Given that repeated exposure to opiates initiates a widespread reorganization of cortical regions, we predict that opioid dependence would result in a considerable reorganization of local and remote functional connectivity in the neocortex. METHODS: We applied the novel operational architectonics approach that enables us to estimate two local and remote functional cortex connectivities by means of electroencephalogram structural synchrony measure. RESULTS: In 22 opioid-dependent patients, we found the evidence that brain functional connectivity was indeed disrupted by chronic opioid abuse (i.e., the local functional connectivity increased and remote functional connectivity decreased in opioid abusers). This significant difference between "opioid" and "control" populations was the same for alpha and beta frequency bands. Additionally, significant negative relations between duration (years) of daily opioid abuse and the number/strength of functional connections in the posterior section of the cortex were found.

Structural (operational) synchrony of EEG alpha activity during an auditory memory task.

Memory paradigms are often used in psycho-physiological experiments in order to understand the neural basis underlying cognitive processes. One of the fundamental problems encountered in memory research is how specific and complementary cortical structures interact with each other during episodic encoding and retrieval. A key aspect of the research described below was estimating the coupling of rapid transition processes (in terms of EEG description) which occur in separate cortical areas rather than estimating the routine phase-frequency synchrony in terms of correlation and coherency. It is assumed that these rapid transition processes in the EEG amplitude correspond to the "switching on/off" of brain elemental operations. By making a quantitative estimate of the EEG structural synchrony of alpha-band power between different EEG channels, it was shown that short-term memory has the emergent property of a multiregional neuronal network, and is not the product of strictly hierarchical processing based on convergence through association regions. Moreover, it was demonstrated that the dynamic temporal structure of alpha activity is strongly correlated to the dynamic structure of working memory.