Mechanoepigenetic regulation of extracellular matrix homeostasis via Yap and Taz.

Cells integrate mechanical cues to direct fate specification to maintain tissue function and homeostasis. While disruption of these cues is known to lead to aberrant cell behavior and chronic diseases, such as tendinopathies, the underlying mechanisms by which mechanical signals maintain cell function are not well understood. Here, we show using a model of tendon de-tensioning that loss of tensile cues in vivo acutely changes nuclear morphology, positioning, and expression of catabolic gene programs, resulting in subsequent weakening of the tendon. In vitro studies using paired ATAC/RNAseq demonstrate that the loss of cellular tension rapidly reduces chromatin accessibility in the vicinity of Yap/Taz genomic targets while also increasing expression of genes involved in matrix catabolism. Concordantly, the depletion of Yap/Taz elevates matrix catabolic expression. Conversely, overexpression of Yap results in a reduction of chromatin accessibility at matrix catabolic gene loci, while also reducing transcriptional levels. The overexpression of Yap not only prevents the induction of this broad catabolic program following a loss of cellular tension, but also preserves the underlying chromatin state from force-induced alterations. Taken together, these results provide novel mechanistic details by which mechanoepigenetic signals regulate tendon cell function through a Yap/Taz axis.

Microenvironmental mechanoactivation through Yap/Taz suppresses chondrogenic gene expression.

Chondrocyte phenotype is preserved when cells are round and the actin cytoskeleton is cortical. Conversely, these cells rapidly dedifferentiate in vitro with increased mechanoactive Rho signaling, which increases cell size and causes large actin stress fiber to form. While the effects of Rho on chondrocyte phenotype are well established, the molecular mechanism is not yet fully elucidated. Yap, a transcriptional coregulator, is regulated by Rho in a mechanotransductive manner and can suppress chondrogenesis in vivo. Here, we sought to elucidate the relationship between mechanoactive Rho and Yap on chondrogenic gene expression. We first show that decreasing mechanoactive state through Rho inhibition results in a broad increase in chondrogenic gene expression. Next, we show that Yap and its coregulator Taz are negative regulators of chondrogenic gene expression, and removal of these factors promotes chondrogenesis even in environments that promote cell spreading. Finally, we establish that Yap/Taz is essential for translating Rho-mediated signals to negatively regulate chondrogenic gene expression, and that its removal negates the effects of increased Rho signaling. Together, these data indicate that Rho is a mechanoregulator of chondrogenic differentiation, and that its impact on chondrogenic expression is exerted principally through mechanically induced translocation and activity of Yap and Taz.

Native annual forbs decline in California coastal prairies over 15 years despite grazing.

Livestock grazing is often used as a land management tool to maximize vegetation diversity in grassland ecosystems worldwide. Prior research has shown that cattle grazing benefits native annual forb species in California's coastal prairies, but drought and increasing aridity may alter this relationship. In 2016 and 2017, we resurveyed the vegetation structure, native annual forb cover, and native annual forb richness in ten grazed and ungrazed prairies that were originally measured in 2000 and 2001 along a 200-km gradient from Monterey to Sonoma counties in California. We found that grazed prairies continued to have significantly lower vegetation height and thatch depth than ungrazed prairies, and that shrub encroachment over the 15-year period was significantly greater in ungrazed prairies. Furthermore, grazed prairies continued to have greater native annual forb richness (4.9 species per site) than ungrazed sites (3.0 species per site), but native annual forb richness declined by 2.8 species per site in grazed prairies and 0.1 species per site in ungrazed prairies between survey periods. We suggest that severe drought and increasing aridity may be driving declines in native annual forb richness in grazed prairies. The species we recorded only in earlier surveys were disproportionately wetland-associated and had higher average specific leaf area than species that remained through the second survey period. Finally, the cover of native annual species increased regardless of whether prairies were grazed, suggesting that the high precipitation in 2017 may have benefitted the native annual forb species that persisted at sites between surveys. Our study shows that weather conditions affect the outcomes of land management strategies.

Crowdsourcing snake identification with online communities of professional herpetologists and avocational snake enthusiasts.

Species identification can be challenging for biologists, healthcare practitioners and members of the general public. Snakes are no exception, and the potential medical consequences of venomous snake misidentification can be significant. Here, we collected data on identification of 100 snake species by building a week-long online citizen science challenge which attracted more than 1000 participants from around the world. We show that a large community including both professional herpetologists and skilled avocational snake enthusiasts with the potential to quickly (less than 2 min) and accurately (69-90%; see text) identify snakes is active online around the clock, but that only a small fraction of community members are proficient at identifying snakes to the species level, even when provided with the snake's geographical origin. Nevertheless, participants showed great enthusiasm and engagement, and our study provides evidence that innovative citizen science/crowdsourcing approaches can play significant roles in training and building capacity. Although identification by an expert familiar with the local snake fauna will always be the gold standard, we suggest that healthcare workers, clinicians, epidemiologists and other parties interested in snakebite could become more connected to these communities, and that professional herpetologists and skilled avocational snake enthusiasts could organize ways to help connect medical professionals to crowdsourcing platforms. Involving skilled avocational snake enthusiasts in decision making could build the capacity of healthcare workers to identify snakes more quickly, specifically and accurately, and ultimately improve snakebite treatment data and outcomes.

Electronic mechanism of STM-induced diffusion of hydrogen on Si(100).

We have observed a scanning tunneling microscopy (STM) induced lateral transfer of a single hydrogen atom on the Si(100) surface. The transfer rate of the hydrogen atom is proportional to the electron dose, indicating an electron-assisted transfer mechanism. Measurements of the relations between the transfer rate and the sample bias and temperature give further support for an electronic mechanism. The bias dependence of the transfer rate shows a peak, and from a first principles electronic structure calculation we show that the position of the peak is related to the energy of a localized surface resonance. We propose that the hydrogen transfer is related to inelastic hole scattering with this surface resonance. We develop a microscopic model for the hydrogen transfer, and using the experimental data we extract information on the resonance lifetime and the transfer yield per resonant electron. The transfer takes place by tunneling through a small excited state transfer barrier. The transfer rate is increased if the hydrogen atom before the resonant excitation is vibrationally excited, and this gives rise to an increasing transfer rate with increasing sample temperature.

Formation of nanometer-scale grooves in silicon with a scanning tunneling microscope.

Grooves a few nanometers wide can be formed on a Si(111) surface with a scanning tunneling microscope when the tip is above a critical voltage. This may provide a promising approach to nanodevice fabrication. The dependence of the critical voltage on tunneling current, tip polarity, and tip material was studied with silver, gold, platinum, and tungsten tips. The results are consistent with field emission of positive and negative silicon ions. The variation of critical voltage with current is explained quantitatively by a simple tunneling equation that includes the effect of the contact potential between tip and sample.