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61.
A Titan but not Necessarily a Ruler: Assessing the Role of Titin During Thick Filament Patterning and Assembly
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The sarcomeres of striated muscle are among the most elaborate and dynamic eukaryotic cellular protein machinery, and the mechanisms by which these semicrystalline filament networks are initially patterned and assembled remain contentious. In addition to the acto‐myosin filaments that provide motor function, the sarcomere contains titin filaments, comprised of individual molecules of the giant Ig‐ and fibronectin domain‐rich protein titin. Titin is the largest known protein, containing many structurally distinct domains with a variety of proposed functions, including sarcomere stabilization, the prevention of over‐stretching, and returning to resting length after contraction. One molecule of titin, which binds to both the Z‐disk and the M‐line, spans a half‐sarcomere, and is proposed to serve as a “molecular ruler” that dictates the spacing of sarcomeres. The semirigid rod‐like A‐band region of titin has also been proposed to act as a scaffold for thick filament formation during muscle development, but despite decades of research, this hypothesis has not been rigorously tested. Recent studies in zebrafish have brought into question the necessity for the A‐band region of titin during the early stages of sarcomere patterning. In this review, we give an overview of the many different roles of titin in the development and function of striated muscle, and address the validity of the “molecular ruler” model of myofibrillogenesis in light of the current literature. Anat Rec, 297:1604–1614, 2014. © 2014 Wiley Periodicals, Inc. 相似文献
62.
Robert-William Welke Hannah Sabeth Sperber Ronny Bergmann Amit Koikkarah Laura Menke Christian Sieben Detlev H. Krüger Salvatore Chiantia Andreas Herrmann Roland Schwarzer 《Viruses》2022,14(3)
Hantaviruses are enveloped viruses that possess a tri-segmented, negative-sense RNA genome. The viral S-segment encodes the multifunctional nucleocapsid protein (N), which is involved in genome packaging, intracellular protein transport, immunoregulation, and several other crucial processes during hantavirus infection. In this study, we generated fluorescently tagged N protein constructs derived from Puumalavirus (PUUV), the dominant hantavirus species in Central, Northern, and Eastern Europe. We comprehensively characterized this protein in the rodent cell line CHO-K1, monitoring the dynamics of N protein complex formation and investigating co-localization with host proteins as well as the viral glycoproteins Gc and Gn. We observed formation of large, fibrillar PUUV N protein aggregates, rapidly coalescing from early punctate and spike-like assemblies. Moreover, we found significant spatial correlation of N with vimentin, actin, and P-bodies but not with microtubules. N constructs also co-localized with Gn and Gc albeit not as strongly as the glycoproteins associated with each other. Finally, we assessed oligomerization of N constructs, observing efficient and concentration-dependent multimerization, with complexes comprising more than 10 individual proteins. 相似文献
63.
Doppler echocardiography was used to measure cardiac stroke volume in 10 patients with coronary artery disease who were treated with cardioactive drugs. Stroke volume estimates were determined at the aortic orifice by multiplying area by systolic velocity integral measured both from the suprasternal and the apical approach. Recordings were done independently by 2 experienced observers on the same day and repeated once after 1 to 21 days. Analysis of variance showed that no systematic differences were introduced by the 2 observers and Doppler approaches or by measuring on different days. The coefficient of variation between any pair of measurements in each patient was 9%. This variability is probably a result of the method or spontaneous fluctuations of the stroke volume and not of the varying recording conditions. The ultrasonic method detects day-to-day changes of cardiac stroke volume larger than 20% with a probability greater than 0.95. 相似文献
64.
Gernot Beutel Ronny Perthel Mayuren Suntharalingam Stefanie M. Bode-Böger Jens Martens-Lobenhoffer Jan T. Kielstein Heike Kielstein 《Annals of hematology》2013,92(4):505-508
The endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) is elevated in both animal models of chronic inflammatory disorders as well as in patients with chronic inflammatory disease. In vivo data suggest that ADMA can increase the number of circulating monocytes and possibly affect their adhesion potential in vitro. The aim of our study was to evaluate possible effects of chronically elevated levels of ADMA on white blood cell count (WBC), leukocyte subsets, and WBC distribution pattern using a model of chronic exogenous ADMA infusion. Male Sprague–Dawley rats (n?=?20, 10 weeks of age) were randomized to receive either (1) isotonic saline or (2) ADMA applied by osmotic mini pumps. After 28 days of infusion, all animals were sacrificed for blood and tissue sampling. WBC count, flow cytometry for subtype assessment, and histological assessment were performed. Over a time period of 28 days, continuous ADMA infusion significantly increased mean plasma levels (1.26?±?0.07 μmol/l) as compared to saline infusion (0.57?±?0.02 μmol/l). Clinical side effects were not observed. Despite a physiologically relevant rise in ADMA plasma levels, measured by decrease of the l-arginine/AMDA ratio—a surrogate parameter of NO production capacity—there was no effect on WBC count or pattern of leukocyte subsets. Numbers and morphology of peripheral blood cells as well as number of NK-cells leveling liver and spleen were not affected by chronic ADMA infusion. Chronically elevated ADMA levels in otherwise healthy rats did not affect WBC counts or leukocyte subsets. Furthermore, anemia frequently found in patients with progressive renal failure and elevated ADMA levels, was not observed. In a chronic inflammatory state, elevated ADMA levels themselves are rather the result than the cause of the underlying inflammatory process. 相似文献
65.
Keser Tobias Kofler Mario Katzmayr Mariella Schiefecker Alois J. Rass Verena Ianosi Bogdan A. Lindner Anna Gaasch Maxime Beer Ronny Rhomberg Paul Schmutzhard Erich Pfausler Bettina Helbok Raimund 《Neurocritical care》2020,33(1):132-139
Neurocritical Care - Despite the tremendous impact of swallowing disorders on outcome following ischemic stroke, little is known about the incidence of dysphagia after subarachnoid hemorrhage (SAH)... 相似文献
66.
Ronny Redlich Ilona Schneider Nicole Kerkenberg Nils Opel Jonas Bauhaus Verena Enneking Jonathan Repple Elisabeth J. Leehr Dominik Grotegerd Claas Khler Katharina Frster Katharina Dohm Susanne Meinert Tim Hahn Harald Kugel Kathrin Schwarte Christiane Schettler Katharina Domschke Volker Arolt Walter Heindel Bernhard T. Baune Weiqi Zhang Christa Hohoff Udo Dannlowski 《Human brain mapping》2020,41(3):594-604
Epigenetic alterations of the brain‐derived neurotrophic factor (BDNF) gene have been associated with psychiatric disorders in humans and with differences in amygdala BDNF mRNA levels in rodents. This human study aimed to investigate the relationship between the functional BDNF‐Val66Met polymorphism, its surrounding DNA methylation in BDNF exon IX, amygdala reactivity to emotional faces, and personality traits. Healthy controls (HC, n = 189) underwent functional MRI during an emotional face‐matching task. Harm avoidance, novelty seeking and reward dependence were measured using the Tridimensional Personality Questionnaire (TPQ). Individual BDNF methylation profiles were ascertained and associated with several BDNF single nucleotide polymorphisms surrounding the BDNF‐Val66Met, amygdala reactivity, novelty seeking and harm avoidance. Higher BDNF methylation was associated with higher amygdala reactivity (x = 34, y = 0, z = ?26, t(166) = 3.00, TFCE = 42.39, p(FWE) = .045), whereby the BDNF‐Val66Met genotype per se did not show any significant association with brain function. Furthermore, novelty seeking was negatively associated with BDNF methylation (r = ?.19, p = .015) and amygdala reactivity (r = ?.17, p = .028), while harm avoidance showed a trend for a positive association with BDNF methylation (r = .14, p = .066). The study provides first insights into the relationship among BDNF methylation, BDNF genotype, amygdala reactivity and personality traits in humans, highlighting the multidimensional relations among genetics, epigenetics, and neuronal functions. The present study suggests a possible involvement of epigenetic BDNF modifications in psychiatric disorders and related brain functions, whereby high BDNF methylation might reduce BDNF mRNA expression and upregulate amygdala reactivity. 相似文献
67.
Rutenberg Michael S. Rotondo Ronny L. Rao Dinesh Holtzman Adam L. Indelicato Daniel J. Huh Soon Morris Christopher G. Mendenhall William M. 《Journal of neuro-oncology》2020,147(2):387-395
Journal of Neuro-Oncology - Craniopharyngioma is a benign tumor that commonly develops within the suprasellar region. The tumor and treatment can have debilitating consequences for pediatric and... 相似文献
68.
R Haaverstad G Nilsen H O Myhre O D Saether P A Rinck 《European journal of vascular surgery》1992,6(2):124-129
Magnetic resonance imaging (MRI) was used in the diagnosis of various conditions giving rise to leg oedema, with special attention to the oedema after femoro-distal vascular reconstruction for obliterative atherosclerosis (n = 14). Patients with deep venous thrombosis (n = 6), chronic lymphoedema (n = 6) and closed muscular compartment syndrome (n = 2) were also investigated. Leg volume increase was measured according to the formula of a truncated cone. Interstitial fluid hydrostatic pressure (Pif) was recorded with the wick-in-needle technique. Spin echo series with 10 mm transverse slices were obtained with MRI. Following vascular reconstructions, leg volume increased 26% on the operated side. In the operated leg, no gradient in Pif was found between the posterior muscular compartment and the subcutaneous tissue. However, there was a significantly higher Pif in the subcutaneous tissue compared to the anterior muscular compartment (p less than 0.05). In the operated group, MRI revealed oedema around the entire circumference of the leg, mainly restricted to the subcutaneous tissue. In contrast, oedema of the leg muscles, particularly in the posterior compartments, was typical for patients having deep venous thrombosis. The group with chronic lymphoedema showed circumferential subcutaneous oedema alone or in combination with a fibrotic honeycomb pattern. Oedema of the affected muscular compartment was easily observed in patients who had a closed compartment syndrome. In conclusion, the use of MRI is promising in the investigation of conditions giving rise to leg oedema. It is likely that the formation of post-reconstructive oedema is taking place in the subcutaneous tissue.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
69.
Tiffany C. Ho Boris Gutman Elena Pozzi Hans J. Grabe Norbert Hosten Katharina Wittfeld Henry Vlzke Bernhard Baune Udo Dannlowski Katharina Frster Dominik Grotegerd Ronny Redlich Andreas Jansen Tilo Kircher Axel Krug Susanne Meinert Igor Nenadic Nils Opel Richard Dinga Dick J. Veltman Knut Schnell Ilya Veer Henrik Walter Ian H. Gotlib Matthew D. Sacchet Andr Aleman Nynke A. Groenewold Dan J. Stein Meng Li Martin Walter Christopher R. K. Ching Neda Jahanshad Anjanibhargavi Ragothaman Dmitry Isaev Artemis Zavaliangos-Petropulu Paul M. Thompson Philipp G. Smann Lianne Schmaal 《Human brain mapping》2022,43(1):341-351
Alterations in regional subcortical brain volumes have been investigated as part of the efforts of an international consortium, ENIGMA, to identify reliable neural correlates of major depressive disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work by precisely mapping localized MDD-related differences in subcortical regions using shape analysis. In this meta-analysis of subcortical shape from the ENIGMA-MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta-analysis. Relative to CTL, patients with adolescent-onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum, cornu ammonis (CA) 1 of the hippocampus and basolateral amygdala (Cohen's d = ?0.164 to ?0.180). Relative to first-episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala (Cohen's d = ?0.173 to ?0.184). Our results suggest that previously reported MDD-associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features. 相似文献
70.
Point‐of‐care treatment of focal cartilage defects with selected chondrogenic mesenchymal stromal cells—An in vitro proof‐of‐concept study
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Oliver Petters Christian Schmidt Christian Thuemmler Frank Peinemann Matthias Zscharnack Jeremy S. Somerson Ronny M. Schulz 《Journal of tissue engineering and regenerative medicine》2018,12(7):1717-1727
Due to the poor self‐healing capacities of cartilage, innovative approaches are a major clinical need. The use of in vitro expanded mesenchymal stromal cells (MSCs) in a 2‐stage approach is accompanied by cost‐, time‐, and personnel‐intensive good manufacturing practice production. A 1‐stage intraoperative procedure could overcome these drawbacks. The aim was to prove the feasibility of a point‐of‐care concept for the treatment of cartilage lesions using defined MSC subpopulations in a collagen hydrogel without prior MSC monolayer expansion. We tested 4 single marker candidates (MSCA‐1, W4A5, CD146, CD271) for their effectiveness of separating colony‐forming units of ovine MSCs via magnetic cell separation. The most promising surface marker with regard to the highest enrichment of colony‐forming cells was subsequently used to isolate a MSC subpopulation for the direct generation of a cartilage graft composed of a collagen type I hydrogel without the propagation of MSCs in monolayer. We observed that separation with CD271 sustained the highest enrichment of colony‐forming units. We then demonstrated the feasibility of generating a cartilage graft with an unsorted bone marrow mononuclear cell fraction and with a characterized CD271 positive MSC subpopulation without the need for a prior cell expansion. A reduced volume of 6.25% of the CD271 positive MSCs was needed to achieve the same results regarding chondrogenesis compared with the unseparated bone marrow mononuclear cell fraction, drastically reducing the number of nonrelevant cells. This study provides a proof‐of‐concept and reflects the potential of an intraoperative procedure for direct seeding of cartilage grafts with selected CD271 positive cells from bone marrow. 相似文献