| 1. |
- Brasko, Csilla, et al.
(författare)
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Intelligent image-based in situ single-cell isolation
- 2018
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Quantifying heterogeneities within cell populations is important for many fields including cancer research and neurobiology; however, techniques to isolate individual cells are limited. Here, we describe a high-throughput, non-disruptive, and cost-effective isolation method that is capable of capturing individually targeted cells using widely available techniques. Using high-resolution microscopy, laser microcapture microscopy, image analysis, and machine learning, our technology enables scalable molecular genetic analysis of single cells, targetable by morphology or location within the sample.
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| 2. |
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| 3. |
- Tuka, Bernadett, et al.
(författare)
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Release of PACAP-38 in episodic cluster headache patients - An exploratory study
- 2016
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Ingår i: Journal of Headache and Pain. - : Springer Science and Business Media LLC. - 1129-2369 .- 1129-2377. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Activation of the trigeminal-autonomic reflex, involving the trigeminal ganglion, the superior salivatory nucleus and the sphenopalatine ganglion (SPG) is crucial in the pathophysiology of cluster headache (CH). Since pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) is present both in the SPG and the trigeminal ganglion (TG) and its role in migraine has been described, our aim was to determine the plasma PACAP-38 levels in different phases of episodic CH (ECH). Peripheral cubital fossa blood samples were taken during the ictal and inter-bout periods of male ECH patients and from age-matched healthy controls (n = 9). Plasma PACAP-38-like immunoreactivity (LI) was measured with specific and sensitive radioimmunoassay. Findings: Significantly lower plasma PACAP-38-LI was detected in the inter-bout period of ECH patients than in healthy controls. However, PACAP-38 was significantly elevated in the plasma during CH attacks as compared to the inter-bout phase in the same subjects (n =5). Conclusions: This exploratory study suggests that PACAP-38 may be released during the attacks of ECH. Further patients and long-term follow-up are necessary to reveal its function.
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| 4. |
- Gáll, Tamás, et al.
(författare)
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Heme induces endoplasmic reticulum stress (Hier stress) in human aortic smooth muscle cells
- 2018
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 9:NOV
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Tidskriftsartikel (refereegranskat)abstract
- Accumulation of damaged or misfolded proteins resulted from oxidative protein modification induces endoplasmic reticulum (ER) stress by activating the pathways of unfolded protein response. In pathologic hemolytic conditions, extracellular free hemoglobin is submitted to rapid oxidation causing heme release. Resident cells of atherosclerotic lesions, after intraplaque hemorrhage, are exposed to heme leading to oxidative injury. Therefore, we raised the question whether heme can also provoke ER stress. Smooth muscle cells are one of the key players of atherogenesis; thus, human aortic smooth muscle cells (HAoSMCs) were selected as a model cell to reveal the possible link between heme and ER stress. Using immunoblotting, quantitative polymerase chain reaction and immunocytochemistry, we quantitated the markers of ER stress. These were: phosphorylated eIF2α, Activating transcription factor-4 (ATF4), DNA-damage-inducible transcript 3 (also known as C/EBP homology protein, termed CHOP), X-box binding protein-1 (XBP1), Activating transcription factor-6 (ATF6), GRP78 (glucose-regulated protein, 78kDa) and heme responsive genes heme oxygenase-1 and ferritin. In addition, immunohistochemistry was performed on human carotid artery specimens from patients who had undergone carotid endarterectomy. We demonstrate that heme increases the phosphorylation of eiF2α in HAoSMCs and the expression of ATF4. Heme also enhances the splicing of XBP1 and the proteolytic cleavage of ATF6. Consequently, there is up-regulation of target genes increasing both mRNA and protein levels of CHOP and GRP78. However, TGFβ and collagen type I decreased. When the heme binding proteins, alpha-1-microglobulin (A1M) and hemopexin (Hpx) are present in cell media, the ER stress provoked by heme is inhibited. ER stress pathways are also retarded by the antioxidant N-acetyl cysteine (NAC) indicating that reactive oxygen species are involved in heme-induced ER stress. Consistent with these findings, elevated expression of the ER stress marker GRP78 and CHOP were observed in smooth muscle cells of complicated lesions with hemorrhage compared to either atheromas or healthy arteries. In conclusion, heme triggers ER stress in a time- and dose-dependent manner in HAoSMCs. A1M and Hpx as well as NAC effectively hamper heme-induced ER stress, supporting their use as a potential therapeutic approach to reverse such a deleterious effects of heme toxicity.
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| 5. |
- Kiraly, Laszlo, et al.
(författare)
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Virtual museum of congenital heart defects : digitization and establishment of a database for cardiac specimens.
- 2019
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Ingår i: Quantitative imaging in medicine and surgery. - : AME Publishing Company. - 2223-4292 .- 2223-4306. ; 9:1, s. 115-126
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Tidskriftsartikel (refereegranskat)abstract
- Education and training of morphology for medical students, and professionals specializing in pediatric cardiology and surgery has traditionally been based on hands-on encounter with congenitally malformed cardiac specimens. Large international archives are no longer widely available due to stricter data protection rules, a reduced number of autopsies, attrition rate of existing specimens, and most importantly due to a higher survival rate of patients. Our Cardiac Archive houses about 400 cardiac specimens with congenital heart disease. The collection spans almost 60 years and thus goes back to pre-surgical era. Unfortunately, attrition rate due to desiccation has led to an increased natural decay in recent years. The present multi-institutional project focuses on saving the collection by digitization. Specimens are scanned by high-resolution micro-CT/MRI. Virtual 3D-models are segmented and a comprehensive database is built. We now report an initial feasibility study with six test specimens that provided promising results, however, adequate presentation of the intracardiac anatomy, including septa and cardiac valves requires further refinements. Computer assisted design methods are necessary to overcome consequences of pathological examination, shrinkage and/or distortion of the specimens. For a next step, we anticipate an expandable web-based virtual museum with interactive reference and training tools. Web access for professional third parties will be provided by registration/subscription. In a future phase, segmental wall motion data could be added to virtual models. 3D-printed models may replace actual specimens and serve as hands-on surgical training to elucidate complex morphologies, promote surgical emulation, and extract more accurate procedural knowledge based on such a collection.
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| 6. |
- Kish, Laszlo, et al.
(författare)
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Brain : Biological Noise-Based Logic
- 2015
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Ingår i: Advances in Cognitive Neurodynamics (IV). - Dordrecht, Tyskland : Springer Science+Business Media B.V.. - 9789401795487 ; , s. 319-322
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Bokkapitel (refereegranskat)abstract
- Neural spikes in the brain form stochastic sequences, i.e., belong to the class of pulse noises. This stochasticity is a counterintuitive feature because extracting information-such as the commonly supposed neural information of mean spike frequency-requires long times for reasonably low error probability. The mystery could be solved by noise-based logic, wherein randomness has an important function and allows large speed enhancements for special-purpose tasks, and the same mechanism is at work for the brain logic version of this concept.
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| 7. |
- Malina, Tamás, et al.
(författare)
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Individual variability of venom from the European adder (Vipera berus berus) from one locality in Eastern Hungary
- 2017
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Ingår i: Toxicon. - : Elsevier BV. - 0041-0101 .- 1879-3150. ; 135, s. 59-70
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Tidskriftsartikel (refereegranskat)abstract
- We have revealed intra-population variability among venom samples from several individual European adders (Vipera berus berus) within a defined population in Eastern Hungary. Individual differences in venom pattern were noticed, both gender-specific and age-related, by one-dimensional electrophoresis. Gelatin zymography demonstrated that these individual venoms have different degradation profiles indicating varying protease activity in the specimens from adders of different ages and genders. Some specimens shared a conserved region of substrate degradation, while others had lower or extremely low protease activity. Phospholipase A(2) activity of venoms was similar but not identical. Interspecimen diversity of the venom phospholipase A(2)-spectra (based on the components' molecular masses) was detected by MALDI-TOF MS. The lethal toxicity of venoms (LD50) also showed differences among individual snakes. Extracted venom samples had varying neuromuscular paralysing effect on chick biventer cervicis nerve-muscle preparations. The paralysing effect of venom was lost when calcium in the physiological salt solution was replaced by strontium; indicating that the block of twitch responses to nerve stimulation is associated with the activity of a phospholipase-dependent neurotoxin. In contrast to the studied V.b. berus venoms from different geographical regions so far, this is the first V.b berus population discovered to have predominantly neurotoxic neuromuscular activity. The relevance of varying venom yields is also discussed. This study demonstrates that individual venom variation among V.b. berus living in particular area of Eastern Hungary might contribute to a wider range of clinical manifestations of V.b. hems envenoming than elsewhere in Europe.
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| 8. |
- Nemes, Orsolya, et al.
(författare)
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Predictors of post-traumatic pituitary failure during long-term follow-up
- 2015
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Ingår i: Hormones - journal of endocrinology and metabolism. - : Hellenic Endocrine Society. - 1109-3099. ; 14:3, s. 383-391
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: There is increasing awareness among physicians of the risks of traumatic brain injury (TBI)-induced hypopituitarism. We have assessed the prevalence and risk factors of post-traumatic hypopituitarism by analyzing the TBI database of the University of Pecs.DESIGN: This consecutive analysis of 126 TBI survivors (mean age: 42.4 years, average follow-up time: 48 months) revealed that 60.3% had severe and 39.7% moderately severe trauma based on GCS score. Subdural hemorrhage (29.3%) and diffuse injury (27%) were the most common types of injury; 17.5% of patients suffered basal skull fractures.RESULTS: The prevalence of major anterior pituitary failure was 57.1%. Occurrence of total and partial growth hormone deficiency (GHD/GHI) was 39.7%, while LH/FSH, TSH and ACTH deficiencies were less frequent, namely 23.0%, 16.7% and 10.3%, respectively. Of the 82 patients with multiple endocrine evaluations, 31.7% presented significant changes in hormonal deficiencies during the follow-up period: new hormone deficiencies developed in 16 patients, while hormonal disturbances resolved in 10 subjects. Looking for factors influencing the prevalence of pituitary dysfunction, endocrine results were analyzed in relation to age, gender, GCS scores, injury types, basal skull fracture, ventricular drain insertion and necessity of neurosurgical intervention. All hormonal disturbances were more prevalent after severe trauma (OR: 3.25, p=0.002), while the need for surgery proved to be an independent determinant of multiple and GH deficits (OR: 3.72 (p=0.004) and 9.33 (p=0.001)).CONCLUSION: Post-traumatic hypopituitarism is common and may evolve or resolve over time. Victims of severe TBI and/or patients who have undergone neurosurgical intervention for head injury are the most prone to post-traumatic hypopituitarism.
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| 9. |
- Szabó, Tamás, et al.
(författare)
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Stability and dye inclusion of graphene oxide/polyelectrolyte layer-by-layer self-assembled films in saline, acidic and basic aqueous solutions
- 2017
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Ingår i: Carbon. - : Elsevier. - 0008-6223 .- 1873-3891. ; 111, s. 350-357
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate that a simple spectrophotometric method can be efficiently applied for the characterization of structural and chemical stability and adsorption properties of composite graphene oxide (GO) films in various solutions. The immersion stability of GO layer-by-layer (LbL) self-assembled with a polycation into ultrathin multilayered films was studied in water and in concentrated salty, acidic and basic solutions by UV-visible spectroscopy. These films were found to retain both their chemical stability and physical integrity in water, salt and HCl solutions with a slight rearrangement of the nanoscale structure as shown by the change in their visible spectrum. However, immersion into NaOH solutions above molar concentration led to the deconstruction of the multilayer structure by base-induced deoxygenation of GO. The adsorption of methylene blue on polymer/GO LbL films of various thicknesses revealed that the multilayers are largely impermeable towards this cationic dye.
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