6,463 research outputs found
The LIM and SH3 domain protein family: structural proteins or signal transducers or both?
LIM and SH3 Protein 1 (LASP-1) was initially identified from a cDNA library of metastatic axillary lymph nodes (MLN) more than a decade ago. It was found to be overexpressed in human breast and ovarian cancer and became the first member of a newly defined LIM-protein subfamily of the nebulin group characterized by the combined presence of LIM and SH3 domains. LASP2, a novel LASP1-related gene was first identified and characterized in silico. Subsequently it proved to be a splice variant of the Nebulin gene and therefore was also termed LIM/nebulette. LASP-1 and -2 are highly conserved in their LIM, nebulin-like and SH3 domains but differ significantly at their linker regions. Both proteins are ubiquitously expressed and involved in cytoskeletal architecture, especially in the organization of focal adhesions. Here we present the first systematic review to summarize all relevant data concerning their domain organization, expression profiles, regulating factors and function. We compile evidence that both, LASP-1 and LASP-2, are important during early embryo- and fetogenesis and are highly expressed in the central nervous system of the adult. However, only LASP-1 seems to participate significantly in neuronal differentiation and plays an important functional role in migration and proliferation of certain cancer cells while the role of LASP-2 is more structural. The increased expression of LASP-1 in breast tumours correlates with high rates of nodal-metastasis and refers to a possible relevance as a prognostic marker
The space of Anosov diffeomorphisms
We consider the space \X of Anosov diffeomorphisms homotopic to a fixed
automorphism of an infranilmanifold . We show that if is the 2-torus
then \X is homotopy equivalent to . In contrast,
if dimension of is large enough, we show that \X is rich in homotopy and
has infinitely many connected components.Comment: Version 2: referee suggestions result in a better expositio
Almost Hermitian 6-Manifolds Revisited
A Theorem of Kirichenko states that the torsion 3-form of the characteristic
connection of a nearly K\"ahler manifold is parallel. On the other side, any
almost hermitian manifold of type admits a unique connection
with totally skew symmetric torsion. In dimension six, we generalize
Kirichenko's Theorem and we describe almost hermitian -manifolds
with parallel torsion form. In particular, among them there are only two types
of -manifolds with a non-abelian holonomy group, namely twistor
spaces of 4-dimensional self-dual Einstein manifolds and the invariant
hermitian structure on the Lie group \mathrm{SL}(2, \C). Moreover, we
classify all naturally reductive hermitian -manifolds with small
isotropy group of the characteristic torsion.Comment: 26 pages, revised versio
The Einstein-Dirac Equation on Riemannian Spin Manifolds
We construct exact solutions of the Einstein-Dirac equation, which couples
the gravitational field with an eigenspinor of the Dirac operator via the
energy-momentum tensor. For this purpose we introduce a new field equation
generalizing the notion of Killing spinors. The solutions of this spinorial
field equation are called weak Killing spinors (WK-spinors). They are special
solutions of the Einstein-Dirac equation and in dimension n=3 the two equations
essentially coincide. It turns out that any Sasakian manifold with Ricci tensor
related in some special way to the metric tensor as well as to the contact
structure admits a WK-spinor. This result is a consequence of the investigation
of special spinorial field equations on Sasakian manifolds (Sasakian
quasi-Killing spinors). Altogether, in odd dimensions a contact geometry
generates a solution of the Einstein-Dirac equation. Moreover, we prove the
existence of solutions of the Einstein-Dirac equations that are not WK-spinors
in all dimensions n > 8.Comment: Latex2.09, 47 page
Methyl CpG–binding proteins induce large-scale chromatin reorganization during terminal differentiation
Pericentric heterochromatin plays an important role in epigenetic gene regulation. We show that pericentric heterochromatin aggregates during myogenic differentiation. This clustering leads to the formation of large chromocenters and correlates with increased levels of the methyl CpG–binding protein MeCP2 and pericentric DNA methylation. Ectopic expression of fluorescently tagged MeCP2 mimicked this effect, causing a dose-dependent clustering of chromocenters in the absence of differentiation. MeCP2-induced rearrangement of heterochromatin occurred throughout interphase, did not depend on the H3K9 histone methylation pathway, and required the methyl CpG–binding domain (MBD) only. Similar to MeCP2, another methyl CpG–binding protein, MBD2, also increased during myogenic differentiation and could induce clustering of pericentric regions, arguing for functional redundancy. This MeCP2- and MBD2-mediated chromatin reorganization may thus represent a molecular link between nuclear genome topology and the epigenetic maintenance of cellular differentiation
Sclerosing Epithelioid Fibrosarcoma of the Bone: A Case Report of High Resistance to Chemotherapy and a Survey of the Literature
Sclerosing epithelioid fibrosarcoma (SEF) is a rare soft tissue sarcoma mostly occurring in extraosseous sites. SEF represents a clinically challenging entity especially because no standardized treatment regimens are available. Intraosseous localization is an additional challenge with respect to the therapeutical approach. We report on a 16-year-old patient with SEF of the right proximal tibia. The patient underwent standardized neoadjuvant chemotherapy analogous to the EURAMOS-1 protocol for the treatment of osteosarcoma followed by tumor resection and endoprosthetic reconstruction. Histopathological analysis of the resected tumor showed >90% vital tumor cells suggesting no response to chemotherapy. Therefore, therapy was reassigned to the CWS 2002 High-Risk protocol for the treatment of soft tissue sarcoma. To date (22 months after diagnosis), there is no evidence of relapse or metastasis. Our data suggest that SEF may be resistant to a chemotherapy regimen containing Cisplatin, Doxorubicin, and Methotrexate, which should be considered in planning treatment for patients with SEF
Mesenchymal stromal cells for treatment of steroid-refractory GvHD : a review of the literature and two pediatric cases
Severe acute graft versus host disease (GvHD) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation. Human mesenchymal stromal cells (MSCs) play an important role in endogenous tissue repair and possess strong immune-modulatory properties making them a promising tool for the treatment of steroid-refractory GvHD. To date, a few reports exist on the use of MSCs in treatment of GvHD in children indicating that children tend to respond better than adults, albeit with heterogeneous results. We here present a review of the literature and the clinical course of two instructive pediatric patients with acute steroid-refractory GvHD after haploidentical stem cell transplantation, which exemplify the beneficial effects of third-party transplanted MSCs in treatment of acute steroid-refractory GvHD. Moreover, we provide a meta-analysis of clinical studies addressing the outcome of patients with steroid-refractory GvHD and treatment with MSCs in adults and in children (n = 183; 122 adults, 61 children). Our meta-analysis demonstrates that the overall response-rate is high (73.8%) and confirms, for the first time, that children indeed respond better to treatment of GvHD with MSCs than adults (complete response 57.4% vs. 45.1%, respectively). These data emphasize the significance of this therapeutic approach especially in children and indicate that future prospective studies are needed to assess the reasons for the observed differential response-rates in pediatric and adult patients. Additional file 1: MSCs expansion and release criteria.his file contains a detailed description of the MSCs expansion and release criteria for Case A and Case B
The CACNA1B R1389H variant is not associated with myoclonus-dystonia in a large European multicentric cohort.
Myoclonus-dystonia (M-D) is a very rare movement disorder, caused in ∼30-50% of cases by mutations in SGCE. The CACNA1B variant c.4166G>A; (p.R1389H) was recently reported as the likely causative mutation in a single 3-generation Dutch pedigree with five subjects affected by a unique dominant M-D syndrome and cardiac arrhythmias. In an attempt to replicate this finding, we assessed by direct sequencing the frequency of CACNA1B c.4166G>A; (p.R1389H) in a cohort of 520 M-D cases, in which SGCE mutations had been previously excluded. A total of 146 cases (28%) had a positive family history of M-D. The frequency of the variant was also assessed in 489 neurologically healthy controls and in publicly available data sets of genetic variation (1000 Genomes, Exome Variant Server and Exome Aggregation Consortium). The variant was detected in a single sporadic case with M-D, but in none of the 146 probands with familial M-D. Overall, the variant was present at comparable frequencies in M-D cases (1 out of 520; 0.19%) and healthy controls (1 out of 489; 0.2%). A similar frequency of the variant was also reported in all publicly available databases. These results do not support a causal association between the CACNA1B c.4166G>A; (p.R1389H) variant and M-D
Managing delays and incidents at intermodal airport hubs in a more efficient way
Der Beitrag untersucht verschiedene Möglichkeiten des Verspätungsmanagements an intermodalen Hubflughäfen. Im Ergebnis ist ein kooperativer Ansatz zwischen allen Stakeholdern sowohl aus verkehrlicher als auch aus ökonomischer Sicht von Vorteil
Towards a national ecosystem assessment in Germany
We present options for a National Ecosystem Assessment in Germany (NEA-DE) that could inform decision-makers on the state and trends of ecosystems and ecosystem services. Characterizing a NEA-DE, we argue that its cross-sectoral, integrative approach would have the advantages of increased scientific understanding, addressing specific policy questions and creating science-policy dialogues. Challenges include objections against a utilitarian perspective, reservations concerning power relations, and responsibilities concerning the funding
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