Emergence of Patterned Stem Cell Differentiation Within Multicellular Structures

The ability of stem cells to differentiate into specified lineages in the appropriate locations is vital to morphogenesis and adult tissue regeneration. Although soluble signals are important regulators of patterned differentiation, here we show that gradients of mechanical forces can also drive patterning of lineages. In the presence of soluble factors permitting osteogenic and adipogenic differentiation, human mesenchymal stem cells at the edge of multicellular islands differentiate into the osteogenic lineage, whereas those in the center became adipocytes. Interestingly, changing the shape of the multicellular sheet modulated the locations of osteogenic versus adipogenic differentiation. Measuring traction forces revealed gradients of stress that preceded and mirrored the patterns of differentiation, where regions of high stress resulted in osteogenesis, whereas stem cells in regions of low stress differentiated to adipocytes. Inhibiting cytoskeletal tension suppressed the relative degree of osteogenesis versus adipogenesis, and this spatial patterning of differentiation was also present in three-dimensional multicellular clusters. These findings demonstrate a role for mechanical forces in linking multicellular organization to spatial differentials of cell differentiation, and they represent an important guiding principle in tissue patterning that could be exploited in stem cell-based therapies

A mild TCEP-based para-azidobenzyl cleavage strategy to transform reversible cysteine thiol labelling reagents into irreversible conjugates

It has recently emerged that the succinimide linkage of a maleimide thiol addition product is fragile, which is a major issue in fields where thiol functionalisation needs to be robust. Herein we deliver a strategy that generates selective cysteine thiol labelling reagents, which are stable to hydrolysis and thiol exchange

Nanotechnology for Cell–Substrate Interactions

In the pursuit to understand the interaction between cells and their underlying substrates, the life sciences are beginning to incorporate micro- and nanotechnology-based tools to probe and measure cells. The development of these tools portends endless possibilities for new insights into the fundamental relationships between cells and their surrounding microenvironment that underlie the physiology of human tissue. Here, we review techniques and tools that have been used to study how a cell responds to the physical factors in its environment. We also discuss unanswered questions that could be addressed by these approaches to better elucidate the molecular processes and mechanical forces that dominate the interactions between cells and their physical scaffolds

What about the partner? -factors associated with patient-perceived partner dyspareunia in men with Peyronie\u27s disease

Background: Limited data are available on how partners of men with Peyronie\u27s disease (PD) are affected by the disease. We sought to characterize PD patients whose curvatures result in pain for their partners during penetrative intercourse. Methods: We queried a database of all men undergoing initial evaluation for PD at a single clinic between March 2014 and June 2016. Patients were administered a questionnaire regarding sexual health concerns with domains including erectile dysfunction, ejaculatory dysfunction, libido, and penile curvature. In the penile curvature section, patients were specifically asked: Does the curvature cause your partner any pain during penetrative intercourse? (Y/N). Patients\u27 partners were not directly evaluated for conditions associated with dyspareunia. Additionally, patients interested in treatment for PD underwent objective curve assessment after intracavernosal injection of erectogenic medications along with penile duplex Doppler ultrasound. Statistical analysis was performed to identify differences in clinicopathologic variables and patient-responses to questionnaire prompts between patients who did and did not report partner pain with intercourse. Results: A total of 322 patients with information available on partner pain were included in the study. Patients who reported partner pain had significantly higher subjective erectile rigidity (mean 5.9/10 Conclusions: Men with superior erectile function, higher degrees of penile curvature and ventral curvatures were more likely to report partner pain during penetrative intercourse. These specific disease characteristics reported in this series may assist clinicians in identifying men who are more motivated to select more invasive therapies

Gas-phase electronic spectroscopy of nuclear spin isomer separated H₂O@C and D₂O@C

Gas-phase electronic spectra of H2O@C60+ and D2O@C60+ are presented. These data were obtained by one-photon dissociation of weakly bound helium complexes synthesised in a 3 K ion trap. Measurements were recorded in the vicinity of the 2Ag,2Bg←X2Au electronic transitions of the C60+ cage. Two-colour hole burning experiments enabled nuclear spin isomer pure data to be obtained. The spectra are rich in structure with many absorptions attributed to internal excitation of the encapsulated molecule accompanying the C60+ electronic transition. The experimental data are complemented with density functional theory calculations using the B3LYP functional and 6-31++G** basis set.</p

An inhibitory role for FAK in regulating proliferation: a link between limited adhesion and RhoA-ROCK signaling

Focal adhesion kinase (FAK) transduces cell adhesion to the extracellular matrix into proliferative signals. We show that FAK overexpression induced proliferation in endothelial cells, which are normally growth arrested by limited adhesion. Interestingly, displacement of FAK from adhesions by using a FAK−/− cell line or by expressing the C-terminal fragment FRNK also caused an escape of adhesion-regulated growth arrest, suggesting dual positive and negative roles for FAK in growth regulation. Expressing kinase-dead FAK-Y397F in FAK−/− cells prevented uncontrolled growth, demonstrating the antiproliferative function of inactive FAK. Unlike FAK overexpression–induced growth, loss of growth control in FAK−/− or FRNK-expressing cells increased RhoA activity, cytoskeletal tension, and focal adhesion formation. ROCK inhibition rescued adhesion-dependent growth control in these cells, and expression of constitutively active RhoA or ROCK dysregulated growth. These findings demonstrate the ability of FAK to suppress and promote growth, and underscore the importance of multiple mechanisms, even from one molecule, to control cell proliferation

Visual Depth Mapping from Monocular Images using Recurrent Convolutional Neural Networks

A reliable sense-and-avoid system is critical to enabling safe autonomous operation of unmanned aircraft. Existing sense-and-avoid methods often require specialized sensors that are too large or power intensive for use on small unmanned vehicles. This paper presents a method to estimate object distances based on visual image sequences, allowing for the use of low-cost, on-board monocular cameras as simple collision avoidance sensors. We present a deep recurrent convolutional neural network and training method to generate depth maps from video sequences. Our network is trained using simulated camera and depth data generated with Microsoft's AirSim simulator. Empirically, we show that our model achieves superior performance compared to models generated using prior methods.We further demonstrate that the method can be used for sense-and-avoid of obstacles in simulation

THz and IR spectroscopy of endofullerene H₂O@C₆₀

Terahertz time-domain and infrared Fourier-transform spectroscopy techniques are used to investigate the properties of H2O@C60 endofullerene in 6 K – 300 K temperature interval. A number of absorption lines associated with rotational transitions of water molecule entrapped inside C60 cages are observed and assigned. Fitting the resonances with Lorenzian lineshapes allowed us to obtain temperature dependencies of absorption lines parameters – frequency, strength and damping

Rotational coherence of encapsulated ortho and para water in fullerene-C₆₀ revealed by time-domain terahertz spectroscopy

We resolve the real-time coherent rotational motion of isolated water molecules encapsulated in fullerene-C60 cages by time-domain terahertz (THz) spectroscopy. We employ single-cycle THz pulses to excite the low-frequency rotational motion of water and measure the subsequent coherent emission of electromagnetic waves by water molecules. At temperatures below ~ 100&nbsp;K, C60 lattice vibrational damping is mitigated and the quantum dynamics of confined water are resolved with a markedly long rotational coherence, extended beyond 10&nbsp;ps. The observed rotational transitions agree well with low-frequency rotational dynamics of single water molecules in the gas phase. However, some additional spectral features with their major contribution at ~2.26 THz are also observed which may indicate interaction between water rotation and the C60 lattice phonons. We also resolve the real-time change of the emission pattern of water after a sudden cooling to 4&nbsp;K, signifying the conversion of ortho-water to para-water over the course of 10s hours. The observed long coherent rotational dynamics of isolated water molecules confined in C60 makes this system an attractive candidate for future quantum technology