miRNA Regulatory Networks Associated with Peripheral Vascular Diseases.

A growing body of evidence indicates a crucial role of miRNA regulatory function in a variety of mechanisms that contribute to the development of diseases. In our previous work, alterations in miRNA expression levels and targeted genes were shown in peripheral blood mononuclear cells (PBMCs) from patients with lower extremity artery disease (LEAD), abdominal aortic aneurysm (AAA), and chronic venous disease (CVD) in comparison with healthy controls. In this paper, previously obtained miRNA expression profiles were compared between the LEAD, AAA, and CVD groups to find either similarities or differences within the studied diseases. Differentially expressed miRNAs were identified using the DESeq2 method implemented in the R programming software. Pairwise comparisons (LEAD vs. AAA, LEAD vs. CVD, and AAA vs. CVD) were performed and revealed 10, 8, and 17 differentially expressed miRNA transcripts, respectively. The functional analysis of the obtained miRNAs was conducted using the miRNet 2.0 online tool and disclosed associations with inflammation and cellular differentiation, motility, and death. The miRNet 2.0 tool was also used to identify regulatory interactions between dysregulated miRNAs and target genes in patients with LEAD, AAA, and CVD. The presented research provides new information about similarities and differences in the miRNA-dependent regulatory mechanisms involved in the pathogenesis of LEAD, AAA, and CVD.

Application of OpenArray RT-qPCR for identification of microRNA expression signatures of lower extremity artery disease.

Lower extremity artery disease (LEAD) is an underestimated chronic vascular disease caused by the formation of atherosclerotic plaques in the lower limb arteries. The pathological processes underlying this disease are regulated by many various factors, including microRNAs (miRNAs). miRNAs constitute a pool of small, non-coding RNAs with a gene expression modulatory function. In the presented study, differentially expressed miRNAs were identified in peripheral blood mononuclear cells from 18 patients with LEAD compared to 10 healthy volunteers using OpenArray RT-qPCR. Sixteen miRNAs were significantly differentially expressed in the LEAD group. Four out of them, hsa-miR-138-5p, -34a-3p, -34a-5p, and -766-3p, were consistent with a previous next-generation sequencing study. The in silico analysis performed for these four miRNAs showed associations with vascular smooth muscle cells differentiation, inflammation, and apoptosis, potentially resulting from modulation of genes involved in cell cycle, cellular adhesion, and Notch signaling. The presented study expands our knowledge on the role of miRNA in the pathology of LEAD, providing potential candidates for biomarkers of this disease.

Relationships between Indicators of Lower Extremity Artery Disease and miRNA Expression in Peripheral Blood Mononuclear Cells.

Lower extremity artery disease (LEAD) is an underdiagnosed and globally underestimated vascular disease caused by the progressive and chronic formation of atherosclerotic plaques in the arteries of the lower limbs. Much evidence indicates that the abnormal course of pathophysiological processes underlying LEAD development is associated with altered miRNA modulatory function. In the presented study, relationships between miRNA expression and clinical indicators of this disease (ABI, claudication distance, length of arterial occlusion, Rutherford category, and plaque localization) were identified. MiRNA expression profiles were obtained using next-generation sequencing in peripheral blood mononuclear cells (PBMCs) of 40 LEAD patients. Correlation analysis performed using the Spearman rank correlation test revealed miRNAs related to ABI, claudication distance, and length of arterial occlusion. In the DESeq2 analysis, five miRNAs were found to be dysregulated in patients with Rutherford category 3 compared to patients with Rutherford category 2. No miRNAs were found to be differentially expressed between patients with different plaque localizations. Functional analysis performed using the miRNet 2.0 website tool determined associations of selected miRNAs with processes underlying vascular pathology, such as vascular smooth muscle cell differentiation, endothelial cell apoptosis, response to hypoxia, inflammation, lipid metabolism, and circadian rhythm. The most enriched functional terms for genes targeted by associated miRNAs were linked to regulation of the cell cycle, regulation of the transcription process, and nuclear cellular compartment. In conclusion, dysregulations of miRNA expression in PBMCs of patients with LEAD are indicative of the disease and could potentially be used in the prediction of LEAD progression.

Next-Generation Sequencing in the Assessment of the Transcriptomic Landscape of DNA Damage Repair Genes in Abdominal Aortic Aneurysm, Chronic Venous Disease and Lower Extremity Artery Disease.

Vascular diseases are one of the most common causes of death and morbidity. Lower extremity artery disease (LEAD), abdominal aortic aneurysm (AAA) and chronic venous disease (CVD) belong to this group of conditions and exhibit various presentations and courses; thus, there is an urgent need for revealing new biomarkers for monitoring and potential treatment. Next-generation sequencing of mRNA allows rapid and detailed transcriptome analysis, allowing us to pinpoint the most pronounced differences between the mRNA expression profiles of vascular disease patients. Comparison of expression data of 519 DNA-repair-related genes obtained from mRNA next-generation sequencing revealed significant transcriptomic marks characterizing AAA, CVD and LEAD. Statistical, gene set enrichment analysis (GSEA), gene ontology (GO) and literature analyses were applied and highlighted many DNA repair and accompanying processes, such as cohesin functions, oxidative stress, homologous recombination, ubiquitin turnover, chromatin remodelling and DNA double-strand break repair. Surprisingly, obtained data suggest the contribution of genes engaged in the regulatory function of DNA repair as a key component that could be used to distinguish between analyzed conditions. DNA repair-related genes depicted in the presented study as dysregulated in AAA, CVD and LEAD could be utilized in the design of new biomarkers or therapies associated with these diseases.

Identification of Transcriptomic Differences between Lower Extremities Arterial Disease, Abdominal Aortic Aneurysm and Chronic Venous Disease in Peripheral Blood Mononuclear Cells Specimens.

Several human tissues are investigated in studies of molecular biomarkers associated with diseases development. Special attention is focused on the blood and its components due to combining abundant information about systemic responses to pathological processes as well as high accessibility. In the current study, transcriptome profiles of peripheral blood mononuclear cells (PBMCs) were used to compare differentially expressed genes between patients with lower extremities arterial disease (LEAD), abdominal aortic aneurysm (AAA) and chronic venous disease (CVD). Gene expression patterns were generated using the Ion S5XL next-generation sequencing platform and were analyzed using DESeq2 and UVE-PLS methods implemented in R programming software. In direct pairwise analysis, 21, 58 and 10 differentially expressed genes were selected from the comparison of LEAD vs. AAA, LEAD vs. CVD and AAA vs. CVD patient groups, respectively. Relationships between expression of dysregulated genes and age, body mass index, creatinine levels, hypertension and medication were identified using Spearman rank correlation test and two-sided Mann-Whitney U test. The functional analysis, performed using DAVID website tool, provides potential implications of selected genes in pathological processes underlying diseases studied. Presented research provides new insight into differences of pathogenesis in LEAD, AAA and CVD, and selected genes could be considered as potential candidates for biomarkers useful in diagnosis and differentiation of studied diseases.

Electromagnetic Exposure of Personnel Involved in Cardiac MRI Examinations in 1.5T, 3T and 7T Scanners.

(1) Background: It has been hypothesised that a significant increase in the use of cardiac magnetic resonance (CMR), for example, when examining COVID-19 convalescents using magnetic resonance imaging (MRI), has an influence the exposure profiles of medical personnel to static magnetic fields (STmf). (2) Methods: Static exposure to STmf (SEmf) was recorded during activities that modelled performing CMR by radiographers. The motion-induced time variability of that exposure (TVEmf) was calculated from SEmf samples. The results were compared with: (i) labour law requirements; (ii) the distribution of vertigo perception probability near MRI magnets; and (iii) the exposure profile when actually performing a head MRI. (3) Results: The exposure profiles of personnel managing 42 CMR scans (modelled using medium (1.5T), high (3T) and ultrahigh (7T) field scanners) were significantly different than when managing a head MRI. The majority of SEmf and TVEmf samples (up to the 95th percentile) were at low vertigo perception probability (SEmf < 500 mT, TVEmf < 600 mT/s), but a small fraction were at medium/high levels; (4) Conclusion: Even under the "normal working conditions" defined for SEmf (STmf < 2T) by labour legislation (Directive 2013/35/EC), increased CMR usage increases vertigo-related hazards experienced by MRI personnel (a re-evaluation of electromagnetic safety hazards is suggested in the case of these or similar changes in work organisation).

Aberrant Structural Network Architecture in Leber's Hereditary Optic Neuropathy. Minimum Spanning Tree Graph Analysis Application into Diffusion 7T MRI.

Examining individuals with Leber's hereditary optic neuropathy (LHON) provides a rare opportunity to understand how changes in mitochondrial DNA and loss of vision can be related to changes in organization of the whole-brain structural network architecture. In comparison with the previous neuroimaging studies with LHON participants, which were focused mainly on analyzing changes which occur in different areas of the patient's brain, network analysis not only makes it possible to observe single white matter fibers' aberrations but also the whole-brain nature of these changes. The purpose of our study was to better understand whole-brain neural network changes in LHON participants and see the correlation between the clinical data and the changes. To achieve this, we examined fifteen LHON patients and seventeen age-matched healthy subjects with the usage of ultra-high filed 7T magnetic resonance imaging (MRI). Basing on the analysis on MRI diffusion tensor imaging (DTI) data, whole-brain structural neural networks were reconstructed with the use of the minimum spanning tree algorithm (MST) for every participant. Our results revealed that the structural network in LHON participants was altered at both the local and the global level. The global network structures of LHON subjects were less centralized with path-like organization and there was an imbalance in the main hub centrality. Moreover, the inspection of nodes and hubs in terms of their anatomical placement revealed that in the LHON participants the prominent hubs were located within the basal ganglia (i.e. bilateral caudate, left pallidum), which differed them from healthy controls. An analysis of the relationships between the global MST metrics and LHON participants' clinical characteristics revealed significant correlations between the global network metrics and the duration of illness. Furthermore, the nodal parameters of the optic chiasm were significantly correlated with the duration of illness and the averaged thickness of the right retinal nerve fiber layer (RNFL). These findings clearly showed that the progression of the disease is accompanied by alterations within the brain network structure and its efficiency.

Alteration within the Hippocampal Volume in Patients with LHON Disease-7 Tesla MRI Study.

PURPOSE: The aim of this study was to assess the volumetry of the hippocampus in the Leber's hereditary optic neuropathy (LHON) of blind patients. METHODS: A total of 25 patients with LHON were randomly included into the study from the national health database. A total of 15 patients were selected according to the inclusion criteria. The submillimeter segmentation of the hippocampus was based on three-dimensional spoiled gradient recalled acquisition in steady state (3D-SPGR) BRAVO 7T magnetic resonance imaging (MRI) protocol. RESULTS: Statistical analysis revealed that compared to healthy controls (HC), LHON subjects had multiple significant differences only in the right hippocampus, including a significantly higher volume of hippocampal tail (p = 0.009), subiculum body (p = 0.018), CA1 body (p = 0.002), hippocampal fissure (p = 0.046), molecular layer hippocampus (HP) body (p = 0.014), CA3 body (p = 0.006), Granule Cell (GC) and Molecular Layer (ML) of the Dentate Gyrus (DG)-GC ML DG body (p = 0.003), CA4 body (p = 0.001), whole hippocampal body (p = 0.018), and the whole hippocampus volume (p = 0.023). DISCUSSION: The ultra-high-field magnetic resonance imaging allowed hippocampus quality visualization and analysis, serving as a powerful in vivo diagnostic tool in the diagnostic process and LHON disease course assessment. The study confirmed previous reports regarding volumetry of hippocampus in blind individuals.

Decreased Volume of Lateral and Medial Geniculate Nuclei in Patients with LHON Disease-7 Tesla MRI Study.

Leber's hereditary optic neuropathy (LHON) is a maternally inherited genetic disorder leading to severe and bilateral loss of central vision, with a young male predilection. In recent years, multiple studies examined structural abnormalities in visual white matter tracts such as the optic tract and optic radiation. However, it is still unclear if the disease alters only some parts of the white matter architecture or whether the changes also affect grey matter parts of the visual pathway. This study aimed at improving our understanding of morphometric changes in the lateral (LGN) and medial (MGN) geniculate nuclei and their associations with the clinical picture in LHON by the application of a submillimeter surface-based analysis approach to the ultra-high-field 7T magnetic resonance imaging data. To meet these goals, fifteen LHON patients and fifteen age-matched healthy subjects were examined. A quantitative analysis of the LGN and MGN volume was performed for all individuals. Additionally, morphometric results of LGN and MGN were correlated with variables covering selected aspects of the clinical picture of LHON. In comparison with healthy controls (HC), LHON participants showed a significantly decreased volume of the right LGN and the right MGN. Nevertheless, the volume of the right LGN was strongly correlated with the averaged thickness value of the right retinal nerve fiber layer (RNFL). The abnormalities in the volume of the LHON patients' thalamic nuclei indicate that the disease can cause changes not only in the white matter areas constituting visual tracts but also in the grey matter structures. Furthermore, the correlation between the changes in the LGN volume and the RNFL, as well as the right optic nerve surface area located proximally to the eyeball, suggest some associations between the atrophy of these structures. However, to fully confirm this observation, longitudinal studies should be conducted.

Dysregulation of microRNA Modulatory Network in Abdominal Aortic Aneurysm.

Abdominal artery aneurysm (AAA) refers to abdominal aortic dilatation of 3 cm or greater. AAA is frequently underdiagnosed due to often asymptomatic character of the disease, leading to elevated mortality due to aneurysm rupture. MiRNA constitute a pool of small RNAs controlling gene expression and is involved in many pathologic conditions in human. Targeted panel detecting altered expression of miRNA and genes involved in AAA would improve early diagnosis of this disease. In the presented study, we selected and analyzed miRNA and gene expression signatures in AAA patients. Next, generation sequencing was applied to obtain miRNA and gene-wide expression profiles from peripheral blood mononuclear cells in individuals with AAA and healthy controls. Differential expression analysis was performed using DESeq2 and uninformative variable elimination by partial least squares (UVE-PLS) methods. A total of 31 miRNAs and 51 genes were selected as the most promising biomarkers of AAA. Receiver operating characteristics (ROC) analysis showed good diagnostic ability of proposed biomarkers. Genes regulated by selected miRNAs were determined in silico and associated with functional terms closely related to cardiovascular and neurological diseases. Proposed biomarkers may be used for new diagnostic and therapeutic approaches in management of AAA. The findings will also contribute to the pool of knowledge about miRNA-dependent regulatory mechanisms involved in pathology of that disease.

Volume of Lateral Geniculate Nucleus in Patients with Glaucoma in 7Tesla MRI.

The aim of the study was to assess the volume of the lateral geniculate nucleus (LGN) in patients with open-angle glaucoma in 7Tesla MRI and to evaluate its relation to RNFL thickness and VF indices. MATERIAL AND METHODS: The studied group consisted of 20 open-angle glaucoma patients with bilaterally the same stage of glaucoma (11 with early glaucoma and nine with advanced glaucoma) and nine healthy volunteers from the Department of Diagnostics and Microsurgery of Glaucoma, Medical University of Lublin, Poland. Circumpapillary RNFL-thickness measurements were performed using OCT in all patients and visual fields were performed in the glaucoma group. A 7Tesla MRI was performed to assess the volume of both lateral geniculate bodies. RESULTS: The LGN volume varied significantly between groups from 122.1 ± 14.4 mm3 (right LGN) and 101.6 ± 13.3 mm3 (left LGN) in the control group to 80.2 ± 17.7 mm3 (right LGN) and 71.8 ± 14.2 mm3 (left LGN) in the advanced glaucoma group (right LGN p = 0.003, left LGN p = 0.018). However, volume values from early glaucoma: right LGN = 120.2 ± 26.5 mm3 and left LGN = 103.2 ± 28.0 mm3 differed significantly only from values from the advanced group (right LGN p = 0.006, left LGN p = 0.012), but not from controls (right LGN p = 0.998, left LGN p = 0.986). There were no significant correlations between visual field indices (MD (mean deviation) and VFI (visual field index)) and LGN volumes in both glaucoma groups. Significant correlations between mean RNFL (retinal nerve fiber layers) thickness and corresponding and contralateral LGN were observed for the control group (corresponding LGN: p = 0.064; contralateral LGN: p = 0.031) and early glaucoma (corresponding LGN: p = 0.017; contralateral LGN: p = 0.008), but not advanced glaucoma (corresponding LGN: p = 0.496; contralateral LGN: p = 0.258). CONCLUSIONS: The LGN volume decreases in the course of glaucoma. These changes are correlated with RNFL thickness in early stages of glaucoma and are not correlated with visual field indices.

Dysregulations of MicroRNA and Gene Expression in Chronic Venous Disease.

Chronic venous disease (CVD) is a vascular disease of lower limbs with high prevalence worldwide. Pathologic features include varicose veins, venous valves dysfunction and skin ulceration resulting from dysfunction of cell proliferation, apoptosis and angiogenesis. These processes are partly regulated by microRNA (miRNA)-dependent modulation of gene expression, pointing to miRNA as a potentially important target in diagnosis and therapy of CVD progression. The aim of the study was to analyze alterations of miRNA and gene expression in CVD, as well as to identify miRNA-mediated changes in gene expression and their potential link to CVD development. Using next generation sequencing, miRNA and gene expression profiles in peripheral blood mononuclear cells of subjects with CVD in relation to healthy controls were studied. Thirty-one miRNAs and 62 genes were recognized as potential biomarkers of CVD using DESeq2, Uninformative Variable Elimination by Partial Least Squares (UVE-PLS) and ROC (Receiver Operating Characteristics) methods. Regulatory interactions between potential biomarker miRNAs and genes were projected. Functional analysis of microRNA-regulated genes revealed terms closely related to cardiovascular diseases and risk factors. The study shed new light on miRNA-dependent regulatory mechanisms involved in the pathology of CVD. MicroRNAs and genes proposed as CVD biomarkers may be used to develop new diagnostic and therapeutic methods.

Dysregulation of MicroRNA Regulatory Network in Lower Extremities Arterial Disease.

Atherosclerosis and its comorbidities are the major contributors to the global burden of death worldwide. Lower extremities arterial disease (LEAD) is a common manifestation of atherosclerotic disease of arteries of lower extremities. MicroRNAs belong to epigenetic factors that regulate gene expression and have not yet been extensively studied in LEAD. We aimed to indicate the most promising microRNA and gene expression signatures of LEAD, to identify interactions between microRNA and genes and to describe potential effect of modulated gene expression. High-throughput sequencing was employed to examine microRNAome and transcriptome of peripheral blood mononuclear cells of patients with LEAD, in relation to controls. Statistical significance of microRNAs and genes analysis results was evaluated using DESeq2 and uninformative variable elimination by partial least squares methods. Altered expression of 26 microRNAs (hsa-let-7f-1-3p, hsa-miR-34a-5p, -122-5p, -3591-3p, -34a-3p, -1261, -21-5p, -15a-5p, -548d-5p, -34b-5p, -424-3p, -548aa, -548t-3p, -4423-3p, -196a-5p, -330-3p, -766-3p, -30e-3p, -125b-5p, -1301-3p, -3184-5p, -423-3p, -339-3p, -138-5p, -99a-3p, and -6087) and 14 genes (AK5, CD248, CDS2, FAM129A, FBLN2, GGT1, NOG, NRCAM, PDE7A, RP11-545E17.3, SLC12A2, SLC16A10, SLC4A10, and ZSCAN18) were the most significantly differentially expressed in LEAD group compared to controls. Discriminative value of revealed microRNAs and genes were confirmed by receiver operating characteristic analysis. Dysregulations of 26 microRNAs and 14 genes were used to propose novel biomarkers of LEAD. Regulatory interactions between biomarker microRNAs and genes were studied in silico using R multiMiR package. Functional analysis of genes modulated by proposed biomarker microRNAs was performed using DAVID 6.8 tools and revealed terms closely related to atherosclerosis and, interestingly, the processes involving nervous system. The study provides new insight into microRNA-dependent regulatory mechanisms involved in pathology of LEAD. Proposed microRNA and gene biomarkers of LEAD may provide new diagnostic and therapeutic opportunities.

Analysis of fatigue loads of the knee joint during gait.

PURPOSE: The aim of the work was to show that the fatigue load of bone tissue causes permanent structural changes in it. METHODS: On the basis of the movie recording of gait, the time courses of angular changes in the joints of the lower limb were determined. Using the method of transforming Denavit-Hartenberg coordinate systems, the course of force loading the hip joint and, after that, the course of normal contact reaction of the femoral head of the knee joint during gait for the support phase were determined. On the basis of the Hertz formula, the course of contact stresses in the femoral joint head and the damage coefficient were determined according to the Palmgren-Miner damage accumulation hypothesis. RESULTS: A calculation example was made using own software. The course of the obtained damage factor was compared to the image fixed in the X-ray image after its appropriate processing. The thesis of the work has been confirmed to a satisfactory degree. CONCLUSIONS: The nature of the lesions is similar to the image of structural changes in the head of the joint. It should be assumed that the image fixed in the bone is the result of the stored history of loads. Analysis of the obtained image can be used to determine the state of bone strength.

General technical remarks on 1HMRS translational research in 7T.

PURPOSE: The aim of the work was to share the practical experience of preclinical and clinical proton magnetic resonance spectroscopy (1HMRS) studies conducted using a 7-Tesla magnetic field strength scanner, taking into account the specificity of both settings in the context of translational research. MATERIAL AND METHODS: 1HMRS volunteer studies conducted using a Discovery 950 GE 7T scanner, were carried out with PRESS sequence, and a VOI measuring 2.0 × 2.0 × 2.0 cm3 placed in the white matter at the parietal occipital lobe. Rodent spectra obtained using a 7T Bruker were measured with PRESS, with a VOI 2.0 × 2.0 × 5.5 mm3 placed over the hippocampus. RESULTS: 1HMRS data from humans and rats show that the brain spectra obtained in the same field are characterised by a similar neurochemical structure and spectral resolution. Spectra obtained from rats demonstrate the following metabolites: NAA, Glu, Gln, Ins, Cho, Cr, PCr, Tau, GABA, Lac, NAAG, and Asp. In turn, spectra from humans allowed estimation of the following metabolites: Ala, NAA, Glu, Gln, Ins, Cho, Cr, PCr, Tau, GABA, Lac, NAAG, and Asp. Signals from Gln, Glu with chemical shift around 2.4 ppm, from Cr, PCr, and GABA at 3 ppm, and signals from Cho and Tau at approximately 3.2 ppm, can be properly separated and estimated both in humans and in rats. CONCLUSIONS: These results are promising in terms of broadening the knowledge of many neurological diseases by inducing them on animal models and then transferring this knowledge to clinical practice. In spite of this, important distinctions in the technical aspects and methodological differences of high-field 1HMRS in both preclinical and clinical conditions should be taken into account.

The assessment of lenticulostriate arteries originating from middle cerebral artery using ultra high-field magnetic resonance time-of-flight angiography.

Time-of-flight angiography (ToF) was presented for the first time by Suryan and used by Hinshaw et al. This protocol allows to visualize blood flow within the vessels in vivo without the contrast administration, which is possible due to the large magnitude of magnetization, received from the moving spins and small magnitude of magnetization received from the stationary spins. Fourteen participants (male:female = 7:7) were analyzed, who have never been diagnosed with any central nervous system disease as well as any cardiovascular, metabolic disease and have never had any trauma. Although, the gold standard of cerebral vessel analysis is still DSA, ultra high-field 3D ToF-MRA shows clearer picture of all LSAs and the branches of LSAs in comparison to poor in contrast DSA imaging. Ultra high-field time-of-flight MRA is a valuable method in visualizing small perforating arteries, which can be used in the future as a diagnostic tool for clinical practice. The diversity of LSAs morphometry is vast and may alter during aging, thus the clinical anatomy of those vessels should be further investigated in vivo.

Effect of sodium dichloroacetate on apoptotic gene expression in human leukemia cell lines.

BACKGROUND: Sodium dichloroacetate (DCA) is an agent with anticancer properties against solid tumors. DCA also seems to have antileukemic activity. In order to affirm it we investigate the effect of DCA on cell viability and apoptotic gene expression profiles in leukemia cell lines: CEM/C1, CCRF/CEM, HL-60, HL-60/MX2. METHODS: Cell viability was assessed by trypan blue staining. The expression of 93 genes involved in the process of apoptosis was determined by real-time PCR method using Taqman Low Density Array (TLDA). RESULTS: CEM/C1, CCRF/CEM, HL-60, HL-60/MX2 cells were exposed to DCA for 24 h. The sensitivity of each cell line to DCA is different and depends on the concentration. CEM/C1 was the most sensitive with an half-maximal inhibitory concentration (IC50) value of 30 mM, while HL-60/MX2 was the most resistant with an IC50 value of 75 mM. Exposure of leukemia cells to DCA causes differences in gene expression profiles which cannot indicate that any particular pathway of apoptosis is initiated. However, the presence of 388 statistically significant correlations between expression pattern of gens was determined. CONCLUSION: We showed that DCA causes a decrease in viability of leukemia cells. The decline depends on DCA concentration. The induction of any particular apoptosis pathway is not shown in cells after DCA treatment. For that reason, studies on the molecular mechanism of cell death after exposure to DCA should be continued.

The influence of mass parameters and gear ratio on the speed and energy expenditure of a cyclist.

The wavelength of moment of active forces (driving forces) for a full cycle while pedaling with platform pedals was determined. There was defined the value of moment of passive forces, depending on drag, rolling resistance and grade of surface. Kinematic motion parameters were determined from the equation of motion of the machine, which was solved numerically. In numerical example, there were determined and compared the temporal courses of bicycle speed for possible gear ratios for the two different waveforms of the driving torque--the determined, the time-varying and the constant ones. There were compared extreme values of active and passive forces, the kinetic energy of the bike and work expended by the rider at a specified time.