Abstract Observations of magnetic reconnection at Earth's magnetopause often display asymmetric structures that are accompanied by strong magnetic field ( B ) fluctuations and large‐amplitude parallel electric fields ( E || ). The B turbulence is most intense at frequencies above the ion cyclotron frequency and below the lower hybrid frequency. The B fluctuations are consistent with a thin, oscillating current sheet that is corrugated along the electron flow direction (along the X line), which is a type of electromagnetic drift wave. Near the X line, electron flow is primarily due to a Hall electric field, which diverts ion flow in asymmetric reconnection and accompanies the instability. Importantly, the drift waves appear to drive strong parallel currents which, in turn, generate large‐amplitude (~100 mV/m) E || in the form of nonlinear waves and structures. These observations suggest that turbulence may be common in asymmetric reconnection, penetrate into the electron diffusion region, and possibly influence the magnetic reconnection process.
Keratins (K) 8 and 18 are the first intermediate filament proteins present in the early embryo, and form the backbone of the intermediate filament cytoskeleton in all simple internal epithelia. Mice with a combined deficiency in K8/K19 and K18/K19 suffer from midgestational lethality with full penetrance, which strongly supports an essential keratin function in extraembryonic epithelia. Moreover, mutations in K8 and K18 have been reported to present risk factors in liver disease of multiple aetiologies. This mutation analysis of the complete K8 and K18 genes, using DHPLC technology, involved screening blood samples from 256 patients diagnosed positive for various liver disorders, and from 100 individuals serving as controls. None of the previously reported mutations in K8 and K18 was found in any of the samples, nor was a positive correlation observed between K8 and K18 mutations to cryptogenic cirrhosis or to chronic liver disease of other origin. However, a novel polymorphism was detected in exon 4 of the K8 gene, leaving L227 unaltered, in both patient and control samples.
Type I and type II keratins belong to the large gene family coding for intermediate filament proteins. Among the 27 type I and 27 type II keratins known to exist in the human genome, type I K18 and type II K8 form copolymers and are coexpressed in all embryonic and internal epithelia.1 DNA linkage analysis and transgenic animal experiments have established that dominant acting point mutations in epidermal keratin genes lead to a large number of skin fragility syndromes, including epidermolysis bullosa simplex. The majority of these mutations are highly conserved with regard to their position.2 The molecular mechanism leading to cell fragility is not well understood, but it is clear that an intact cytoskeleton is required for epithelial homeostasis. A more detailed biochemical analysis has demonstrated a strong …
For the monitoring of vascular growth as well as adaptive or therapeutic (re)vascularization endothelial-specific reporter mouse models are valuable tools. However, currently available mouse models have limitations, because not all endothelial cells express the reporter in all developmental stages. We have generated PECAM/eGFP embryonic stem (ES) cell and mouse lines where the reporter gene labels PECAM+ endothelial cells and vessels with high specificity. Native eGFP expression and PECAM staining were highly co-localized in vessels of various organs at embryonic stages E9.5, E15.5 and in adult mice. Expression was found in large and small arteries, capillaries and in veins but not in lymphatic vessels. Also in the bone marrow arteries and sinusoidal vessel were labeled, moreover, we could detect eGFP in some CD45+ hematopoietic cells. We also demonstrate that this labeling is very useful to monitor sprouting in an aortic ring assay as well as vascular remodeling in a murine injury model of myocardial infarction. Thus, PECAM/eGFP transgenic ES cells and mice greatly facilitate the monitoring and quantification of endothelial cells ex vivo and in vivo during development and injury.
The paper presents an efficient algorithm based on ROAM for visualization of large scale terrain models in realtime. The quality and smoothness of the terrain data visualization within a 3D interactive environment is preserved, while the complexity of the algorithm is kept on a reasonable level. The main contribution of the paper is an introduction of a number of efficient techniques such as implicit coordinates method within the patch array representing ROAM and the viewpoint dependent triangle rendering method for dynamic level of detail (LOD) updates. In addition, the paper presents experimental comparison of a variety of culling techniques, including a newly introduced method: relational position culling. These techniques are incorporated in the visualization software, which allows to achieve more realistic terrain representation and the real-time level of detail reduction.
The co-chaperone BAG3 (Bcl-2 associated athanogene 3) is strongly expressed in cross-striated muscles and plays a key role in the turnover of muscle-proteins as a member of the CASA (chaperone-assisted selected autophagy) complex. An amino acid exchange (P209L) in the human BAG3 gene, caused by a single base mutation, gives rise to a severe dominant childhood muscular dystrophy, restrictive cardiomyopathy, and respiratory insufficiency. To get deeper insights into the pathophysiological mechanisms of the disease, we generated a transgenic mouse model of the human mutation BAG3 P209L , in which a fusion protein consisting of the human BAG3 P209L and the green fluorescent protein eGFP can be conditionally overexpressed. Ubiquitous overexpression of BAG3 P209L -eGFP leads to a severe phenotype between the second and fourth week of life, including decreased body weight, skeletal muscle weakness, and heart failure. Echocardiography revealed that the BAG3 P209L -mice suffer from restrictive cardiomyopathy and Sirius-red-staining of heart tissue showed extensive fibrosis. In cardiomyocytes, isolated from hearts of transgenic mice overexpressing BAG3 wt -eGFP or BAG3 P209L -eGFP, BAG3 wt -eGFP stringently localizes to sarcomeres and intercalated discs, whereas cardiomyocytes from BAG3 P209L -eGFP mice displayed formation of BAG3 containing aggregates and disruption of sarcomeres in vivo . While BAG3 P209L -eGFP binding to á-Hsp70, Filamin C and á-HspB8 was unchanged it was less soluble than BAG3 and had a tendency to aggregate, thereby sequestering BAG3 and its clients. Depletion of the BAG3 pool leads to an impairment of CASA and accumulation of damaged proteins, causing sarcomere disintegration leading to restrictive cardiomyopathy.
Cauterization of the root of the left coronary artery (LCA) in the neonatal heart at postnatal day 1 (P1) resulted in large reproducible lesions of the left ventricle (LV), and an attendant marked adaptive response in the right ventricle (RV). The response of both chambers to LV myocardial infarction involved enhanced cardiomyocyte (CM) division and binucleation, as well as LV re-vascularization, leading to restored heart function within 7 days post-surgery (7 dps). By contrast, infarction of P3 mice resulted in cardiac scarring without a significant regenerative and adaptive response of the LV and the RV leading to subsequent heart failure and death within 7 dps. The prominent RV myocyte expansion in P1 mice involved an acute increase in pulmonary arterial pressure and a unique gene regulatory response, leading to an increase in RV mass and preserved heart function. Thus, distinct adaptive mechanisms in the RV, such as CM proliferation and RV expansion, enable marked cardiac regeneration of the infarcted LV at P1 and full functional recovery.
We examined the myogenic response to infarction in neonatal and adult mice to determine the role of c-kit + cardiovascular precursor cells (CPC) that are known to be present in early heart development. Infarction of postnatal day 1–3 c-kit BAC -EGFP mouse hearts induced the localized expansion of (c-kit)EGFP + cells within the infarct, expression of the c-kit and Nkx2.5 mRNA, myogenesis, and partial regeneration of the infarction, with (c-kit)EGFP + cells adopting myogenic and vascular fates. Conversely, infarction of adult mice resulted in a modest induction of (c-kit)EGFP + cells within the infarct, which did not express Nkx2.5 or undergo myogenic differentiation, but adopted a vascular fate within the infarction, indicating a lack of authentic CPC. Explantation of infarcted neonatal and adult heart tissue to scid mice, and adoptive transfer of labeled bone marrow, confirmed the cardiac source of myogenic (neonate) and angiogenic (neonate and adult) cells. FACS-purified (c-kit)EGFP + /(αMHC)mCherry − (noncardiac) cells from microdissected infarcts within 6 h of infarction underwent cardiac differentiation, forming spontaneously beating myocytes in vitro; cre/LoxP fate mapping identified a noncardiac population of (c-kit)EGFP + myocytes within infarctions, indicating that the induction of undifferentiated precursors contributes to localized myogenesis. Thus, adult postinfarct myogenic failure is likely not due to a context-dependent restriction of precursor differentiation, and c-kit induction following injury of the adult heart does not define precursor status.
