Формы и системы оплаты труда работникам предприятия (на примере ОАО «Гомельхлебпром» филиал «Мозырский хлебозавод»)

Ligands for identifying protein aggregates are of great interest as such deposits are the pathological hallmark of a wide range of severe diseases including Alzheimers and Parkinsons disease. Here we report the synthesis of an azide functionalized fluorescent pentameric oligothiophene that can be utilized as a ligand for multimodal detection of disease-associated protein aggregates. The azide functionalization allows for attachment of the ligand to a surface by conventional click chemistry without disturbing selective interaction with protein aggregates and the oligothiophene-aggregate interaction can be detected by fluorescence or surface plasmon resonance. In addition, a methodology where the oligothiophene ligand is employed as a capturing molecule selective for aggregated proteins in combination with an antibody detecting a distinct peptide/protein is also presented. We foresee that this methodology will offer the possibility to create a variety of multiplex sensing systems for sensitive and selective detection of protein aggregates, the pathological hallmarks of several neurodegenerative diseases.Funding Agencies|Swedish Foundation for Strategic Research; Ehrling Persson Foundation; ERC Starting Independent Researcher grant (Project: MUMID)</p

The default mode network as a biomarker for monitoring the therapeutic effects of meditation

The default mode network (DMN) is a group of anatomically separate regions in the brain found to have synchronized patterns of activation in functional magnetic resonance imaging (fMRI). Mentation associated with the DMN includes processes such as mind wandering, autobiographical memory, self-reflective thought, envisioning the future, and considering the perspective of others. Abnormalities in the DMN have been linked to symptom severity in a variety of mental disorders indicating that the DMN could be used as a biomarker for diagnosis. These correlations have also led to the use of DMN modulation as a biomarker for assessing pharmacological treatments. Concurrent research investigating the neurocorrelates of meditation have associated DMN modulation with practice. Furthermore, meditative practice is increasingly understood to have a beneficial role in the treatment of mental disorders. Therefore we propose the use of DMN measures as a biomarker for monitoring the therapeutic effects of meditation practices in mental disorders. Recent findings support this perspective, and indicate the utility of DMN monitoring in understanding and developing meditative treatments for these debilitating conditions

A Review of the Methodology, Taxonomy, and Definitions in Recent fMRI Research on Meditation

Objectives As meditation is increasingly employed for the promotion of good health, there is a growing interest in using neuroimaging methods to investigate the neural mechanisms by which meditation acts. In the wake of this rising interest, criticism regarding the lack of clarity concerning theory, definitions, and taxonomy, as well as deficient or poorly reported methodology, has arisen. The aim of this study was to investigate trends in current neuroimaging research on meditation and to provide guidelines for future studies. Methods We made a literature search for articles published during 2016-2019 using the search phrases "meditation" and "functional magnetic resonance imaging or fMRI". Inclusion criteria were limited to meditation studies using resting-state fMRI or such task-based fMRI examinations that were specifically targeting meditative states in healthy participants. Text analysis was performed using Nvivo 12 Mac (QSR International). Results Twenty-eight articles were included from which we identified four different intention-based dimensions of meditation practice: The present moment, Wholesome qualities to cultivate, Unwholesome qualities to avoid, and Attitudes. Half of the studies do not make assessments of subjective experience. The results were related to networks and brain regions describing cognitive, affective, somatic, and self domains of brain function. Most studies describe meditation-related brain function in terms of "processes". Conclusions We defined five areas of potential improvement regarding research methodology: (1) Provide clear and unambiguous definitions of constructs and practices, (2) Include measures of subjective experience, (3) Perform correct assessment of processes, (4) Combine methodologies for more substantiated conclusions, (5) Avoid the risk of overinterpretation.Funding Agencies|Linkoping University</p

Mantra meditation suppression of default mode beyond an active task : a pilot study

Within the field of neuroimaging, the discovery of a constellation of brain regions silently active when we are “resting” has provided a new view into the elusive effects of meditative practice. This network, called the default mode network (DMN), has been shown by functional neuroimaging to be active when an individual is at rest. Meta-analyses of the fMRI neurocorrelates of meditation have shown that across diverse practices, the most common general effect appears to be modulation of regions within the DMN. The specific ..

A Visual Environment for Hypothesis Formation and Reasoning in Studies with fMRI and Multivariate Clinical Data

We present an interactive visual environment for linked analysis of brain imaging and clinical measurements. The environment is developed in an iterative participatory design process involving neuroscientists investigating the causes of brain-related complex diseases. The hypotheses formation process about correlations between active brain regions and physiological or psychological factors in studies with hundreds of subjects is a central part of the investigation. Observing the reasoning patterns during hypotheses formation, we concluded that while existing tools provide powerful analysis options, they lack effective interactive exploration, thus limiting the scientific scope and preventing extraction of knowledge from available data.Based on these observations, we designed methods that support neuroscientists by integrating their existing statistical analysis of multivariate subject data with interactive visual explorationto enable them to better understand differences between patient groups and the complex bidirectional interplay between clinical measurement and the brain. These exploration concepts enable neuroscientists, for the first time during their investigations, to interactively move between and reason about questions such as ‘which clinical measurements are correlated with a specific brain region?’ or ‘are there differences in brain activity between depressed young and old subjects?’. The environment uses parallel coordinates for effective overview and selection of subject groups, Welch's t-test to filter out brain regions with statistically significant differences, and multiple visualizations of Pearson correlations between brain regions and clinical parameters to facilitate correlation analysis. A qualitative user study was performed with three neuroscientists from different domains. The study shows that the developed environment supports simultaneous analysis of more parameters, provides rapid pathways to insights, and is an effective support tool for hypothesis formation.Seeing Organ Functio

VisualNeuro : A Hypothesis Formation and Reasoning Application for Multi-Variate Brain Cohort Study Data

We present an application, and its development process, for interactive visual analysis of brain imaging data and clinical measurements. The application targets neuroscientists interested in understanding the correlations between active brain regions and physiological or psychological factors. The application has been developed in a participatory design process and has subsequently been released as the free software VisualNeuro. From initial observations of the neuroscientists workflow, we concluded that while existing tools provide powerful analysis options, they lack effective interactive exploration requiring the use of many tools side by side. Consequently, our application has been designed to simplify the workflow combining statistical analysis with interactive visual exploration. The resulting environment comprises parallel coordinates for effective overview and selection, Welchs t-test to filter out brain regions with statistically significant differences and multiple visualizations for comparison between brain regions and clinical parameters. These exploration concepts enable neuroscientists to interactively explore the complex bidirectional interplay between clinical and brain measurements and easily compare different patient groups. A qualitative user study has been performed with three neuroscientists from different domains. The study shows that the developed environment supports simultaneous analysis of more parameters, provides rapid pathways to insights and is an effective tool for hypothesis formation.Funding Agencies|grants Seeing Organ Function from the Knut and Alice Wallenberg Foundation (KAW) [2013-0076]; Swedish research councilSwedish Research Council [2015-05462]; SeRC (Swedish e-Science Research Centre); ELLIIT environment for strategic research in Sweden; Center for Medical Image science and Visualization (CMIV) at Linkoping University</p

Vasoactive intestinal polypeptide plasma levels associated with affective symptoms and brain structure and function in healthy females

Vasoactive intestinal polypeptide (VIP) is a neuroendocrine peptide distributed throughout the human body, including the CNS, where it is particularly abundant in brain regions associated with anxiety and depression. Based on earlier studies indicating that peripheral VIP may cross through the blood-brain barrier, we hypothesized plasma VIP levels to be associated with symptoms of anxiety and depression, as well as brain volume and resting-state functional connectivity in the amygdala, hippocampus, parahippocampus, and orbitofrontal cortex. Plasma VIP concentrations and anxiety/depression symptoms were measured in 37 healthy females. Functional and structural magnetic resonance imaging were used to evaluate functional connectivity and brain volume respectively, and their associations with VIP concentrations within brain regions associated with anxiety and depression. Negative correlations were found between VIP levels and symptoms of anxiety (r=- 0.44, p=0.002) and depression (r=- 0.50, p=0.001). Functional connectivity demonstrated significant VIP-dependent positive associations between the amygdala seed region with both the right parahippocampus (t((33))=3.1, p(FDR)=0.02) and right lateral orbitofrontal cortex (OFC; t((33))=2.9, p(FDR)=0.02). Moreover, VIP concentrations were significantly, positively correlated with brain volume in the left amygdala (r=0.28, p=0.007) and left lateral OFC (r=0.29, p=0.004). The present findings highlight a potential role for VIP in the neurobiology of affective symptoms.Funding Agencies|Linkoping University Library</p

Pentameric Thiophene-Based Ligands that Spectrally Discriminate Amyloid-b and Tau Aggregates Display Distinct Solvatochromism and Viscosity-Induced Spectral Shifts

A wide range of neurodegenerative diseases are characterized by the deposition of multiple protein aggregates. Ligands for molecular characterization and discrimination of these pathological hallmarks are thus important for understanding their potential role in pathogenesis as well as for clinical diagnosis of the disease. In this regard, luminescent conjugated oligothiophenes (LCOs) have proven useful for spectral discrimination of amyloid-beta (Aβ) and tau neurofibrillary tangles (NFTs), two of the pathological hallmarks associated with Alzheimer’s disease. Herein, the solvatochromism of a library of anionic pentameric thiophene-based ligands, as well as their ability to spectrally discriminate Aβ and tau aggregates, were investigated. Overall, the results from this study identified distinct solvatochromic and viscosity-dependent behavior of thiophene-based ligands that can be applied as indices to direct the chemical design of improved LCOs for spectral separation of Aβ and tau aggregates in brain tissue sections. The results also suggest that the observed spectral transitions of the ligands are due to their ability to conform by induced fit to specific microenvironments within the binding interface of each particular protein aggregate. We foresee that these findings might aid in the chemical design of thiophene-based ligands that are increasingly selective for distinct disease-associated protein aggregates

Synthesis of a library of oligothiophenes and their utilization as fluorescent ligands for spectral assignment of protein aggregates

Molecular probes for selective identification of protein aggregates are important to advance our understanding of the molecular pathogenesis underlying protein aggregation diseases. Here we report the chemical design of a library of anionic luminescent conjugated oligothiophenes (LCOs), which can be utilized as ligands for detection of protein aggregates. Certain molecular requirements were shown to be necessary for detecting (i) early non-thioflavinophilic protein assemblies of A beta 1-42 and insulin preceding the formation of amyloid fibrils and (ii) for obtaining distinct spectral signatures of the two main pathological hallmarks observed in human Alzheimers diease brain tissue (A beta plaques and neurofibrillary tangles). Our findings suggest that a superior anionic LCO-based ligand should have a backbone consisting of five to seven thiophene units and carboxyl groups extending the conjugated thiophene backbone. Such LCOs will be highly useful for studying the underlying molecular events of protein aggregation diseases and could also be utilized for the development of novel diagnostic tools for these diseases