1,102 research outputs found
Widespread Expression of BORIS/CTCFL in Normal and Cancer Cells
No full textThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
The Medieval Russian Library (II) : Tales about Boris and Gleb
No full textThe author in this bulletine provides translations of three literary works supposed to have been created from the latter half of 11th century to the first half of 12th, which concerned the murders of the princes of Rus’(the old name of Russia) Boris and Greb. The names of the works are “The Tale and Passion and Panegyrcis to the Holy Matyrs Boris and Gleb”, “The Tales of the Miracles of the Holy Passion bearers Roman and David” and “Lesson concerning the Life and Assassination of the Blessed Passionbearers Boris and Gleb”. The murders occurred in 1015, when their father Vladimir died. Vladimir had converted Rus’into Christianity in 988. After his death the struggle for the kievan grand princedom started. The senioir son, so called “cursed” Sviatopolk, seized Kiev by force. But Sviatopolk, who was not satisfied by the occupation of the kievan princedom, undertook the erasure of his rivals, that is, his younger brothers Boris and Gleb. Boris and Gleb, who knew the malice of Sviatopolk, did not make any resistance against their elder brother and were killed. Because of their nonresistance and the respect for the family seniority Boris and Gleb were later kanonized as the first Christian saints in Rus’. The above-metioned three tales deal with this tragic political affair in the dawn of the Russian Orthodox Christianity.departmental bulletin pape
Boris Pilnyak as a Soviet Writer
No full textA study of the place of Boris Pilnyak in Soviet Literature faces several practical difficulties; biographical data are scanty, critical material is very scarce, and some of his works are unavailable or difficult to obtain. Until greater latitude is allowed to Soviet scholars and until the author's works are more readily available, non-Soviet scholarship can only render preliminary judgments upon Pilnyak and his works. There is always the possibility that a substantial amount of "desk-drawer literature" by the author will be published at a later date. The scope of this study is general, the basis of more detailed investigations in the future; Pilnyak is viewecl in the context of the 1920's and 1930's, the period in which he wrote the great majority of his novels and stories. Pilnyak is not only an interesting author, but also worthy of attention as a central figure in the struggle for power between various literary groups or camps. The first part of this thesis deals with Pilnyak the author -- his concern with the Revolution, his themes, and his characters. The second half of the thesis deals with Pilnyak the literary politician-- his role in the Union of Writers and his difficulties with the Soviet literary and political establishments. I hope to attain two goals as a result of this study: 1) to shed some light upon Boris Pilnyak as an author and personality; 2) to delineate the fratricidal struggle in the literary arena of the late twenties through the case of Boris Pilnyak. I have used the transliteration of the name "Pilnyak" which is most common in English; the correct form is "Pil'njak." All quotes from Pilnyak's works are in Russian, with the exception of those quotation which are llvailahle only in English. I wish to express my gratitude to Dr. Louis J. Shein, Chairmnn of the De-partment of Russian, McMaster University, and to Dr. C. ,J. G. Turner, for their advice and assistance. I also wish to thank McMaster University for granting financial assistance in the form of a Graduate Teaching Fellowship.Master of Arts (MA
Vasodilation and Exercise Capacity in Patients with End-Stage Renal Disease: A Prospective Proof-of-Concept Study.
No full textBACKGROUND
Previous data have pointed to the fact that vascular function is significantly impaired in patients with end-stage renal disease (ESRD). We aimed to better characterise vasodilation and exercise capacity in both ESRD and chronic heart failure (CHF) patients.
METHODS
A total of 30 ESRD patients (23 male; mean age 45.7 ± 9.9 years) were included in a prospective proof-of-concept study at a tertiary care academic centre. The patients underwent forearm venous plethysmography with post-ischaemic peak blood flow (PF) and flow-dependent flow (FDF) testing as well as cardiopulmonary exercise testing during the morning of the day following the last haemodialysis. After matching for age, gender, and body mass index, the data were compared to 30 patients with CHF and 20 age-matched healthy controls.
RESULTS
PF in ESRD patients was reduced when compared to that in CHF patients (12.5 ± 4.2 vs. 15.6 ± 6.9 ml/100 ml/min; p = 0.048) and healthy controls (26.4 ± 9.3 ml/100 ml/min; p < 0.001). When compared to controls, FDF was significantly reduced in ESRD patients (7.6 ± 3.1 vs. 6.0 ± 2.5 ml/100 ml/min; p = 0.03), but not in CHF patients, whereas resting blood flow did not differ between the ESRD, CHF, and healthy control groups. In contrast to indices of vasodilative capacity, maximum exercise capacity (peakVO2) was higher in ESRD when compared to CHF patients (23.8 ± 7.3 vs. 18.8 ± 5.2 ml/min/kg), but significantly impaired when compared to controls (32.8 ± 6.7 ml/min/kg; p < 0.001).
CONCLUSION
In this proof-of-concept study, exercise capacity was relatively preserved, while vasodilative capacity was substantially impaired in ESRD patients. Additional studies are warranted to examine the underlying mechanisms and potential clinical implications of our findings
Expression of the CTCF-paralogous cancer-testis gene, brother of the regulator of imprinted sites (BORIS), is regulated by three alternative promoters modulated by CpG methylation and by CTCF and p53 transcription factors
No full textThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License.-- et al.BORIS, like other members of the 'cancer/testis antigen' family, is normally expressed in testicular germ cells and repressed in somatic cells, but is aberrantly activated in cancers. To understand regulatory mechanisms governing human BORIS expression, we characterized its 5′-flanking region. Using 5′ RACE, we identified three promoters, designated A, B and C, corresponding to transcription start sites at -1447, -899 and -658 bp upstream of the first ATG. Alternative promoter usage generated at least five alternatively spliced BORIS mRNAs with different half-lives determined by varying 5′-UTRs. In normal testis, BORIS is transcribed from all three promoters, but 84% of the 30 cancer cell lines tested used only promoter(s) A and/or C while the others utilized primarily promoters B and C. The differences in promoter usage between normal and cancer cells suggested that they were subject to differential regulation. We found that DNA methylation and functional p53 contributes to the negative regulation of each promoter. Moreover, reduction of CTCF in normally BORIS-negative human fibroblasts resulted in derepression of BORIS promoters. These results provide a mechanistic basis for understanding cancer-related associations between haploinsufficiency of CTCF and BORIS derepression, and between the lack of functional p53 and aberrant activation of BORIS. © 2007 The Author(s).Peer Reviewe
Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy
No full textAbstract Temporal lobe epilepsy, a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter structural alterations in temporal lobe epilepsy relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry; or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multisite ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 temporal lobe epilepsy patients and 1418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in temporal lobe epilepsy, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity calculated using 207 healthy controls obtained from Human Connectome Project and an independent dataset containing 23 temporal lobe epilepsy patients and 53 healthy controls and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of temporal lobe epilepsy-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of temporal lobe epilepsy and may inform future discovery and validation of complementary MRI biomarkers in temporal lobe epilepsy
A worldwide ENIGMA study on epilepsy-related gray and white matter compromise across the adult lifespan
No full textABSTRACT
Objectives
Temporal lobe epilepsy (TLE) is commonly associated with mesiotemporal pathology and widespread alterations of grey and white matter structures. Evidence supports a progressive condition although the temporal evolution of TLE is poorly defined. This ENIGMA-Epilepsy study utilized multimodal magnetic resonance imaging (MRI) data to investigate structural alterations in TLE patients across the adult lifespan. We charted both grey and white matter changes and explored the covariance of age-related alterations in both compartments.
Methods
We studied 769 TLE patients and 885 healthy controls across an age range of 17-73 years, from multiple international sites. To assess potentially non-linear lifespan changes in TLE, we harmonized data and combined median split assessments with cross-sectional sliding window analyses of grey and white matter age-related changes. Covariance analyses examined the coupling of grey and white matter lifespan curves.
Results
In TLE, age was associated with a robust grey matter thickness/volume decline across a broad cortico-subcortical territory, extending beyond the mesiotemporal disease epicentre. White matter changes were also widespread across multiple tracts with peak effects in temporo-limbic fibers. While changes spanned the adult time window, changes accelerated in cortical thickness, subcortical volume, and fractional anisotropy (all decreased), and mean diffusivity (increased) after age 55 years. Covariance analyses revealed strong limbic associations between white matter tracts and subcortical structures with cortical regions.
Conclusions
This study highlights the profound impact of TLE on lifespan changes in grey and white matter structures, with an acceleration of aging-related processes in later decades of life. Our findings motivate future longitudinal studies across the lifespan and emphasize the importance of prompt diagnosis as well as intervention in patients
Structural network alterations in focal and generalized epilepsy assessed in a worldwide ENIGMA study follow axes of epilepsy risk gene expression
No full textEpilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem epilepsy risk gene expression patterns. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-transcriptomic signatures could potentially guide diagnosis or tailor therapeutic approaches to specific epilepsy syndromes.Gouvernement du Canada | Instituts de Recherche en Santé du Canada | CIHR Skin Research Training Centre https://doi.org/10.13039/501100007202Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada https://doi.org/10.13039/50110000279
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