Mechanical response of neural cells to physiologically relevant stiffness gradients

Understanding the influence of the mechanical environment on neurite behavior is crucial in the development of peripheral nerve repair solutions, and could help tissue engineers to direct and guide regeneration. In this study, a new protocol to fabricate physiologically relevant hydrogel substrates with controlled mechanical cues is proposed. These hydrogels allow the analysis of the relative effects of both the absolute stiffness value and the local stiffness gradient on neural cell behavior, particularly for low stiffness values (1–2 kPa). NG108‐15 neural cell behavior is studied using well‐characterized collagen gradient substrates with stiffness values ranging from 1 to 10 kPa and gradient slopes of either 0.84 or 7.9 kPa mm^{-1}. It is found that cell orientation is influenced by specific combinations of stiffness value and stiffness gradient. The results highlight the importance of considering the type of hydrogel as well as both the absolute value of the stiffness and the steepness of its gradient, thus introducing a new framework for the development of tissue engineered scaffolds and the study of substrate stiffness

Seismotectonics of the 2001 Bhuj earthquake (Mw 7.7) in western India: Constraints from aftershocks

ABSTRACT More than 500 aftershocks (M > 2.0) are relocated to study the source processes of the January 26, 2001 Bhuj earthquake (M W 7.7) in western part of the peninsular Indian shield. The maximum intensity reached to X on the MSK scale, but no primary surface rupture or fault was mapped. The aftershocks are relocated by simultaneous inversion with an average rms of 0.19s, and average error estimates of latitude, longitude and depth are 1.2 km, 1.1 km and 2.3 km, respectively. Most of the aftershocks occurred in an area of 70 x 35 sq km; the maximum activity was observed at a depth range of 12-37 km. A bimodal distribution of aftershocks indicates that the main shock rupture propagated both in the upward and downward directions. Further, the best located larger magnitude aftershocks show two trends, one in northeast, parallel to the isoseismal trend and to the major Anjar Rapar Lineament/Delhi -Aravalli trend, and the other in northwest parallel to the Bhachau Lineament and a 8 km long secondary rupture. Fault-plane solutions of the northeast trending aftershocks indicate reverse faulting with left-lateral strike-slip motion; these are comparable to the main shock mechanism. The northwest trending aftershocks, on the other hand, show reverse faulting with right-lateral strike-slip motion. 3D-velocity, gravity, magnetic, ground positioning system (GPS) and satellite observations suggest block uplift during the main shock. These observations are comparable to the earthquake locations and source mechanisms of the main shock and aftershocks

Mobility enhancement in CVD-grown monolayer MoS2 via patterned substrate induced non-uniform straining

The extraordinary mechanical properties of 2D TMDCs make them ideal candidates for investigating strain-induced control of various physical properties. Here we explore the role of non-uniform strain in modulating optical, electronic and transport properties of semiconducting, chemical vapour deposited monolayer MoS2, on periodically nanostructured substrates. A combination of spatially resolved spectroscopic and electronic properties explore and quantify the differential strain distribution and carrier density on a monolayer, as it conformally drapes over the periodic nanostructures. The observed accumulation in electron density at the strained regions is supported by theoretical calculations which form the likely basis for the ensuing 60x increase in field effect mobility in strained samples. Though spatially non-uniform, the pattern induced strain is shown to be readily controlled by changing the periodicity of the nanostructures thus providing a robust yet useful macroscopic control on strain and mobility in these systems

Accumulation of Immature Langerhans Cells in Human Lymph Nodes Draining Chronically Inflamed Skin

The coordinated migration and maturation of dendritic cells (DCs) such as intraepithelial Langerhans cells (LCs) is considered critical for T cell priming in response to inflammation in the periphery. However, little is known about the role of inflammatory mediators for LC maturation and recruitment to lymph nodes in vivo. Here we show in human dermatopathic lymphadenitis (DL), which features an expanded population of LCs in one draining lymph node associated with inflammatory lesions in its tributary skin area, that the Langerin/CD207+ LCs constitute a predominant population of immature DCs, which express CD1a, and CD68, but not CD83, CD86, and DC–lysosomal-associated membrane protein (LAMP)/CD208. Using LC-type cells generated in vitro in the presence of transforming growth factor (TGF)-β1, we further found that tumor necrosis factor (TNF)-α, as a prototype proinflammatory factor, and a variety of inflammatory stimuli and bacterial products, increase Langerin expression and Langerin dependent Birbeck granules formation in cell which nevertheless lack costimulatory molecules, DC–LAMP/CD208 and potent T cell stimulatory activity but express CCR7 and respond to the lymph node homing chemokines CCL19 and CCL21. This indicates that LC migration and maturation can be independently regulated events. We suggest that during DL, inflammatory stimuli in the skin increase the migration of LCs to the lymph node but without associated maturation. Immature LCs might regulate immune responses during chronic inflammation

Nuclear Respiratory Factor 1 (NRF-1) Controls the Activity Dependent Transcription of the GABA-A Receptor Beta 1 Subunit Gene in Neurons

While the exact role of β1 subunit-containing GABA-A receptors (GABARs) in brain function is not well understood, altered expression of the β1 subunit gene (GABRB1) is associated with neurological and neuropsychiatric disorders. In particular, down-regulation of β1 subunit levels is observed in brains of patients with epilepsy, autism, bipolar disorder and schizophrenia. A pathophysiological feature of these disease states is imbalance in energy metabolism and mitochondrial dysfunction. The transcription factor, nuclear respiratory factor 1 (NRF-1), has been shown to be a key mediator of genes involved in oxidative phosphorylation and mitochondrial biogenesis. Using a variety of molecular approaches (including mobility shift, promoter/reporter assays, and overexpression of dominant negative NRF-1), we now report that NRF-1 regulates transcription of GABRB1 and that its core promoter contains a conserved canonical NRF-1 element responsible for sequence specific binding and transcriptional activation. Our identification of GABRB1 as a new target for NRF-1 in neurons suggests that genes coding for inhibitory neurotransmission may be coupled to cellular metabolism. This is especially meaningful as binding of NRF-1 to its element is sensitive to the kind of epigenetic changes that occur in multiple disorders associated with altered brain inhibition