4,578 research outputs found
Stem cell mechanobiology
Stem cells are undifferentiated cells that are capable of proliferation, self-maintenance and differentiation towards specific cell phenotypes. These processes are controlled by a variety of cues including physicochemical factors associated with the specific mechanical environment in which the cells reside. The control of stem cell biology through mechanical factors remains poorly understood and is the focus of the developing field of mechanobiology. This review provides an insight into the current knowledge of the role of mechanical forces in the induction of differentiation of stem cells. While the details associated with individual studies are complex and typically associated with the stem cell type studied and model system adopted, certain key themes emerge. First, the differentiation process affects the mechanical properties of the cells and of specific subcellular components. Secondly, that stem cells are able to detect and respond to alterations in the stiffness of their surrounding microenvironment via induction of lineage-specific differentiation. Finally, the application of external mechanical forces to stem cells, transduced through a variety of mechanisms, can initiate and drive differentiation processes. The coalescence of these three key concepts permit the introduction of a new theory for the maintenance of stem cells and alternatively their differentiation via the concept of a stem cell 'mechano-niche', defined as a specific combination of cell mechanical properties, extracellular matrix stiffness and external mechanical cues conducive to the maintenance of the stem cell population.<br/
Reduced density matrix approach to ultracold few-fermion systems in one dimension
The variational determination of the two-fermion reduced density matrix is
described for trapped, ultracold few-fermion systems in one dimension with
equal spin populations. This is accomplished by formulating the problem as a
semi-definite program, with the two-fermion reduced density matrix being
subject to the D, Q, G, T1, and T2 -representability conditions. The
ground-state energies of , and fermion systems are found by
utilising an augmented Lagrangian method for semi-definite programming. The
ground-state energies are found to match extremely well to those determined by
full-configuration interaction and coupled-cluster calculations. This
demonstrates the utility of the reduced density matrix approach to strongly
correlated, ultracold few-fermion systems.Comment: 13 pages, 3 figure
Polycystin-2 is required for chondrocyte mechanotransduction and traffics to the primary cilium in response to mechanical stimulation
Primary cilia and associated intraflagellar transport are essential for skeletal development, joint homeostasis, and the response to mechanical stimuli, although the mechanisms remain unclear. Polycystin-2 (PC2) is a member of the transient receptor potential polycystic (TRPP) family of cation channels, and together with Polycystin-1 (PC1), it has been implicated in cilia-mediated mechanotransduction in epithelial cells. The current study investigates the effect of mechanical stimulation on the localization of ciliary polycystins in chondrocytes and tests the hypothesis that they are required in chondrocyte mechanosignaling. Isolated chondrocytes were subjected to mechanical stimulation in the form of uniaxial cyclic tensile strain (CTS) in order to examine the effects on PC2 ciliary localization and matrix gene expression. In the absence of strain, PC2 localizes to the chondrocyte ciliary membrane and neither PC1 nor PC2 are required for ciliogenesis. Cartilage matrix gene expression (Acan, Col2a) is increased in response to 10% CTS. This response is inhibited by siRNA-mediated loss of PC1 or PC2 expression. PC2 ciliary localization requires PC1 and is increased in response to CTS. Increased PC2 cilia trafficking is dependent on the activation of transient receptor potential cation channel subfamily V member 4 (TRPV4) activation. Together, these findings demonstrate for the first time that polycystins are required for chondrocyte mechanotransduction and highlight the mechanosensitive cilia trafficking of PC2 as an important component of cilia-mediated mechanotransduction
Realistic lower bounds for the factorization time of large numbers on a quantum computer.
Published versio
The Secret Life of Collagen: Temporal Changes in Nanoscale Fibrillar Pre-Strain and Molecular Organization during Physiological Loading of Cartilage
Articular
cartilage is a natural biomaterial whose structure at
the micro- and nanoscale is critical for healthy joint function and
where degeneration is associated with widespread disorders such as
osteoarthritis. At the nanoscale, cartilage mechanical functionality
is dependent on the collagen fibrils and hydrated proteoglycans that
form the extracellular matrix. The dynamic response of these ultrastructural
building blocks at the nanoscale, however, remains unclear. Here we
measure time-resolved changes in collagen fibril strain, using small-angle
X-ray diffraction during compression of bovine and human cartilage
explants. We demonstrate the existence of a collagen fibril tensile
pre-strain, estimated from the D-period at approximately 1–2%,
due to osmotic swelling pressure from the proteoglycan. We reveal
a rapid reduction and recovery of this pre-strain which occurs during
stress relaxation, approximately 60 s after the onset of peak load.
Furthermore, we show that this reduction in pre-strain is linked to
disordering in the intrafibrillar molecular packing, alongside changes
in the axial overlapping of tropocollagen molecules within the fibril.
Tissue degradation in the form of selective proteoglycan removal disrupts
both the collagen fibril pre-strain and the transient response during
stress relaxation. This study bridges a fundamental gap in the knowledge
describing time-dependent changes in collagen pre-strain and molecular
organization that occur during physiological loading of articular
cartilage. The ultrastructural details of this transient response
are likely to transform our understanding of the role of collagen
fibril nanomechanics in the biomechanics of cartilage and other hydrated
soft tissues
On the 3n+l Quantum Number in the Cluster Problem
It has recently been suggested that an exactly solvable problem characterized
by a new quantum number may underlie the electronic shell structure observed in
the mass spectra of medium-sized sodium clusters. We investigate whether the
conjectured quantum number 3n+l bears a similarity to the quantum numbers n+l
and 2n+l, which characterize the hydrogen problem and the isotropic harmonic
oscillator in three dimensions.Comment: 8 pages, revtex, 4 eps figures included, to be published in
Phys.Rev.A, additional material available at
http://radix2.mpi-stuttgart.mpg.de/koch/Diss
Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders.
Common Variable Immunodeficiency Disorders (CVIDs) are the most prevalent cause of primary antibody failure. CVIDs are highly variable and a genetic causes have been identified in <5% of patients. Here, we performed whole genome sequencing (WGS) of 34 CVID patients (94% sporadic) and combined them with transcriptomic profiling (RNA-sequencing of B cells) from three patients and three healthy controls. We identified variants in CVID disease genes TNFRSF13B, TNFRSF13C, LRBA and NLRP12 and enrichment of variants in known and novel disease pathways. The pathways identified include B-cell receptor signalling, non-homologous end-joining, regulation of apoptosis, T cell regulation and ICOS signalling. Our data confirm the polygenic nature of CVID and suggest individual-specific aetiologies in many cases. Together our data show that WGS in combination with RNA-sequencing allows for a better understanding of CVIDs and the identification of novel disease associated pathways
Growth and Water Use of Perennial Ryegrass and Tall Fescue under Different Irrigation Treatments
The reversible polydisperse Parking Lot Model
We use a new version of the reversible Parking Lot Model to study the
compaction of vibrated polydisperse media. The particle sizes are distributed
according to a truncated power law. We introduce a self-consistent desorption
mechanism with a hierarchical initialization of the system. In this way, we
approach densities close to unity. The final density depends on the
polydispersity of the system as well as on the initialization and will reach a
maximum value for a certain exponent in the power law.Comment: 7 pages, Latex, 12 figure
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