Impact of myelodysplasia-related and additional gene mutations in intensively treated patients with -mutated AML.

This study aimed to evaluate the impact of the myelodysplasia-related gene (MRG) as well as additional gene mutations on outcomes in intensively treated patients with -mutated ( ) AML. Targeted DNA sequencing of 263 genes was performed in 568 AML patients (median age: 59 years) entered into the prospective AMLSG 09-09 treatment trial. Most commonly co-mutated genes were (49.

Measurable residual disease monitoring in AML with FLT3-ITD treated with intensive chemotherapy plus midostaurin.

Measurable residual disease (MRD) monitoring in acute myeloid leukemia (AML) with an FLT3 internal tandem duplication (FLT3-ITDpos) has been hampered by the broad heterogeneity of ITD mutations. Using our recently developed FLT3-ITD paired-end next-generation sequencing (NGS)-based MRD assay (limit of detection 10-4 to 10-5), we evaluated the prognostic impact of MRD at different time points in 157 patients with FLT3-ITDpos AML who were enrolled in the German-Austrian Acute Myeloid Leukemia Study Group 16-10 trial and who were treated with a combination of intensive chemotherapy and midostaurin, followed by midostaurin maintenance. MRD negativity (MRDneg) after 2 cycles of chemotherapy (Cy2), which was observed in 111 of 142 (78%) patients, was predictive of superior 4-year rates of cumulative incidence of relapse (CIR) (4y-CIR; 26% vs 46%; P = .

Adipose-derived stem cells applied in skin diseases, wound healing and skin defects: a review.

Adipose tissue presents a comparably easy source for obtaining stem cells, and more studies are increasingly investigating the therapeutic potential of adipose-derived stem cells. Wound healing, especially in chronic wounds, and treatment of skin diseases are some of the fields investigated. In this narrative review, the authors give an overview of some of the latest studies concerning wound healing as well as treatment of several skin diseases and concentrate on the different forms of application of adipose-derived stem cells.

Identification of ZBTB26 as a Novel Risk Factor for Congenital Hypothyroidism.

Congenital primary hypothyroidism (CH; OMIM 218700) is characterized by an impaired thyroid development, or dyshormonogenesis, and can lead to intellectual disability and growth retardation if untreated. Most of the children with congenital hypothyroidism present thyroid dysgenesis, a developmental anomaly of the thyroid. Various genes have been associated with thyroid dysgenesis, but all known genes together can only explain a small number of cases.

Genetic compensation prevents myopathy and heart failure in an in vivo model of Bag3 deficiency.

Mutations in the molecular co-chaperone Bcl2-associated athanogene 3 (BAG3) are found to cause dilated cardiomyopathy (DCM), resulting in systolic dysfunction and heart failure, as well as myofibrillar myopathy (MFM), which is characterized by protein aggregation and myofibrillar disintegration in skeletal muscle cells. Here, we generated a CRISPR/Cas9-induced Bag3 knockout zebrafish line and found the complete preservation of heart and skeletal muscle structure and function during embryonic development, in contrast to morpholino-mediated knockdown of Bag3. Intriguingly, genetic compensation, a process of transcriptional adaptation which acts independent of protein feedback loops, was found to prevent heart and skeletal muscle damage in our Bag3 knockout model.

3D microtissue-derived human stem cells seeded on electrospun nanocomposites under shear stress: Modulation of gene expression.

Objective: Different microenvironments trigger distinct differentiation of stem cells. Even without chemical supplementation, mechanical stimulation by shear stress may help to induce the desired differentiation. The cell format, such as three-dimensional (3D) microtissues (MTs), MT-derived cells or single cells (SCs), may have a pivotal impact as well.

A dual function of FGF signaling in left-right axis formation.

Organ left-right (LR) asymmetry is a conserved vertebrate feature, which is regulated by left-sided activation of Nodal signaling. Nodal asymmetry is established by a leftward fluid-flow generated at the ciliated LR organizer (LRO). Although the role of fibroblast growth factor (FGF) signaling pathways during mesoderm development is conserved, diverging results from different model organisms suggest a non-conserved function in LR asymmetry.

An Early Function of Polycystin-2 for Left-Right Organizer Induction in Xenopus.

Nodal signaling controls asymmetric organ placement during vertebrate embryogenesis. Nodal is induced by a leftward fluid flow at the ciliated left-right organizer (LRO). The mechanism of flow sensing, however, has remained elusive.

Mediator complex subunit Med12 regulates cardiac jelly development and AV valve formation in zebrafish.

The molecular mechanism essential for the formation of heart valves involves complex interactions of signaling molecules and transcription factors. The Mediator Complex (MC) functions as multi-subunit machinery to orchestrate gene transcription, especially for tissue-specific fine-tuning of transcriptional processes during development, also in the heart. Here, we analyzed the role of the MC subunit Med12 during atrioventricular canal (AVC) development and endocardial cushion formation, using the Med12-deficient zebrafish mutant trapped (tpd).

Improved vasculogenesis and bone matrix formation through coculture of endothelial cells and stem cells in tissue-specific methacryloyl gelatin-based hydrogels.

The coculture of osteogenic and angiogenic cells and the resulting paracrine signaling via soluble factors are supposed to be crucial for successfully engineering vascularized bone tissue equivalents. In this study, a coculture system combining primary human adipose-derived stem cells (hASCs) and primary human dermal microvascular endothelial cells (HDMECs) within two types of hydrogels based on methacryloyl-modified gelatin (GM) as three-dimensional scaffolds was examined for its support of tissue specific cell functions. HDMECs, together with hASCs as supporting cells, were encapsulated in soft GM gels and were indirectly cocultured with hASCs encapsulated in stiffer GM hydrogels additionally containing methacrylate-modified hyaluronic acid and hydroxyapatite particles.

Bistability in two simple symmetrically coupled oscillators with symmetry-broken amplitude- and phase-locking.

In the model system of two instantaneously and symmetrically coupled identical Stuart-Landau oscillators, we demonstrate that there exist stable solutions with symmetry-broken amplitude- and phase-locking. These states are characterized by a non-trivial fixed phase or amplitude relationship between both oscillators, while simultaneously maintaining perfectly harmonic oscillations of the same frequency. While some of the surrounding bifurcations have been previously described, we present the first detailed analytical and numerical description of these states and present analytically and numerically how they are embedded in the bifurcation structure of the system, arising both from the in-phase and the anti-phase solutions, as well as through a saddle-node bifurcation.

Cyclic uniaxial compression of human stem cells seeded on a bone biomimetic nanocomposite decreases anti-osteogenic commitment evoked by shear stress.

Objective: Chemical supplementation of culture media to induce differentiation of adult stem cells seeded on a scaffold may mask other differentiation triggers such as scaffold stiffness, chemical composition or mechanical stimulation. However, stem cells can be differentiated towards osteoblasts without any supplementation given an appropriate osteogenic scaffold and an adequate mechanical stimulation.

Materials And Methods: Electrospun meshes of poly-lactic-co-glycolic acid and amorphous calcium phosphate nanoparticles (PLGA/aCaP) in a weight ratio of 60:40 were seeded with human adipose-derived stem cells (ASCs) and cultured in DMEM.

Leftward Flow Determines Laterality in Conjoined Twins.

Conjoined twins fused at the thorax display an enigmatic left-right defect: although left twins are normal, laterality is disturbed in one-half of right twins [1-3]. Molecularly, this randomization corresponds to a lack of asymmetric Nodal cascade induction in right twins [4]. We studied leftward flow [5, 6] at the left-right organizer (LRO) [7, 8] in thoracopagus twins in Xenopus, which displayed a duplicated, fused, and ciliated LRO.

Stable and transient multicluster oscillation death in nonlocally coupled networks.

In a network of nonlocally coupled Stuart-Landau oscillators with symmetry-breaking coupling, we study numerically, and explain analytically, a family of inhomogeneous steady states (oscillation death). They exhibit multicluster patterns, depending on the cluster distribution prescribed by the initial conditions. Besides stable oscillation death, we also find a regime of long transients asymptotically approaching synchronized oscillations.

Wnt11b is involved in cilia-mediated symmetry breakage during Xenopus left-right development.

Breakage of bilateral symmetry in amphibian embryos depends on the development of a ciliated epithelium at the gastrocoel roof during early neurulation. Motile cilia at the gastrocoel roof plate (GRP) give rise to leftward flow of extracellular fluids. Flow is required for asymmetric gene expression and organ morphogenesis.

Delayed feedback control of three diffusively coupled Stuart-Landau oscillators: a case study in equivariant Hopf bifurcation.

The modest aim of this case study is the non-invasive and pattern-selective stabilization of discrete rotating waves ('ponies on a merry-go-round') in a triangle of diffusively coupled Stuart-Landau oscillators. We work in a setting of symmetry-breaking equivariant Hopf bifurcation. Stabilization is achieved by delayed feedback control of Pyragas type, adapted to the selected spatio-temporal symmetry pattern.

The nodal inhibitor Coco is a critical target of leftward flow in Xenopus.

Vertebrate laterality, which is manifested by asymmetrically placed organs [1], depends on asymmetric activation of the Nodal signaling cascade in the left lateral plate mesoderm [2]. In fish, amphibians, and mammals, a cilia-driven leftward flow of extracellular fluid acts upstream of the Nodal cascade [3-6]. The direct target of flow has remained elusive.

Multiple sequence alignment with user-defined constraints at GOBICS.

Most multi-alignment methods are fully automated, i.e. they are based on a fixed set of mathematical rules.