Biomechanical Forces Promote Immune Regulatory Function of Bone Marrow Mesenchymal Stromal Cells.

Mesenchymal stromal cells (MSCs) are believed to mobilize from the bone marrow in response to inflammation and injury, yet the effects of egress into the vasculature on MSC function are largely unknown. Here we show that wall shear stress (WSS) typical of fluid frictional forces present on the vascular lumen stimulates antioxidant and anti-inflammatory mediators, as well as chemokines capable of immune cell recruitment. WSS specifically promotes signaling through NFκB-COX2-prostaglandin E2 (PGE2 ) to suppress tumor necrosis factor-α (TNF-α) production by activated immune cells. Ex vivo conditioning of MSCs by WSS improved therapeutic efficacy in a rat model of traumatic brain injury, as evidenced by decreased apoptotic and M1-type activated microglia in the hippocampus. These results demonstrate that force provides critical cues to MSCs residing at the vascular interface which influence immunomodulatory and paracrine activity, and suggest the potential therapeutic use of force for MSC functional enhancement. Stem Cells 2017;35:1259-1272.

Developing effective communication materials on the health effects of climate change for vulnerable groups: a mixed methods study.

BACKGROUND: Individuals with chronic health conditions or low socioeconomic status (SES) are more vulnerable to the health impacts of climate change. Health communication can provide information on the management of these impacts. This study tested, among vulnerable audiences, whether viewing targeted materials increases knowledge about the health impacts of climate change and strength of climate change beliefs, and whether each are associated with stronger intentions to practice recommended behaviors. METHODS: Low-SES respondents with chronic conditions were recruited for an online survey in six cities. Respondents were shown targeted materials illustrating the relationship between climate change and chronic conditions. Changes in knowledge and climate change beliefs (pre- and post-test) and behavioral intentions (post-test only) were tested using McNemar tests of marginal frequencies of two binary outcomes or paired t-tests, and multivariable linear regression. Qualitative interviews were conducted among target audiences to triangulate survey findings and make recommendations on the design of messages. RESULTS: Respondents (N = 122) reflected the target population regarding income, educational level and prevalence of household health conditions. (1) Knowledge. Significant increases in knowledge were found regarding: groups that are most vulnerable to heat (children [p < 0.001], individuals with heart disease [p < 0.001], or lung disease [p = 0.019]); and environmental conditions that increase allergy-producing pollen (increased heat [p = 0.003], increased carbon dioxide [p < 0.001]). (2) Strength of certainty that climate change is happening increased significantly between pre- and post-test (p < 0.001), as did belief that climate change affected respondents' health (p < 0.001). (3) Behavioral intention. At post-test, higher knowledge of heat vulnerabilities and environmental conditions that trigger pollen allergies were associated with greater behavioral intention scores (p = 0.001 and p = 0.002, respectively). In-depth interviews (N = 15) revealed that vulnerable audiences are interested in immediate-term advice on health management and protective behaviors related to their chronic conditions, but took less notice of messages about collective action to slow or stop climate change. Respondents identified both appealing and less favorable design elements in the materials. CONCLUSIONS: Individuals who are vulnerable to the health effects of climate change benefit from communication materials that explain, using graphics and concise language, how climate change affects health conditions and how to engage in protective adaptation behaviors.

Dietary nitrate ingested with and without pomegranate supplementation does not improve resistance exercise performance.

This study tested the hypothesis that co-ingesting nitrate (NO3-)-rich beetroot juice (BR) and pomegranate powder (POM) would enhance neuromuscular performance during vertical countermovement jumps, explosive kneeling countermovement push-ups, and back squats compared to BR ingestion alone. Fifteen recreationally-active males were assigned in a double-blind, randomized, crossover design, to supplement in 3 conditions: (1) NO3--depleted beetroot juice (PL; 0.10 mmol NO3-) with two empty gelatin capsules; (2) NO3--rich beetroot juice (BR; 11.8 mmol NO3-) with two empty gelatin capsules, and (3) BR with 1,000 mg of POM powder in two capsules (BR + POM). Participants completed 5 countermovement jumps and 5 kneeling countermovement push-ups interspersed by 1 min of recovery. Subsequently, participants performed 2 sets of 2 × 70% one-repetition maximum back squats, interspersed by 2 min of recovery. Plasma [NO3-] and nitrite ([NO2-]) were elevated following BR and BR + POM compared with PL and POM (p < 0.001) with no differences between BR and BR + POM (p > 0.05) or PL and POM (p > 0.05). Peak power during countermovement jumps increased by 3% following BR compared to BR + POM (88.50 ± 11.46 vs. 85.80 ± 10.14 W/Kg0.67, p = 0.009) but not PL (88.50 ± 11.46 vs. 85.58 ± 10.05 W/Kg0.67, p = 0.07). Neuromuscular performance was not different between conditions during explosive kneeling push-ups and back squats (p > 0.05). These data provide insight into the efficacy of NO3- to modulate explosive resistance exercise performance and indicate that supplementing with BR alone or combined with POM has limited ergogenic potential on resistance exercise. Furthermore, caution is required when combining BR with POM, as this could compromise aspects of resistance exercise performance, at least when compared to BR ingested independently.

Effects of Dietary Nitrate Supplementation on Performance and Muscle Oxygenation during Resistance Exercise in Men.

The purpose of the current study was to assess the effects of acute and short-term nitrate (NO3−)-rich beetroot juice (BR) supplementation on performance outcomes and muscle oxygenation during bench press and back squat exercise. Fourteen recreationally active males were assigned in a randomized, double-blind, crossover design to supplement for 4 days in two conditions: (1) NO3−-depleted beetroot juice (PL; 0.10 mmol NO3− per day) and (2) BR (11.8 mmol NO3− per day). On days 1 and 4 of the supplementation periods, participants completed 2 sets of 2 × 70%1RM interspersed by 2 min of recovery, followed by one set of repetitions-to-failure (RTF) at 60%1RM for the determination of muscular power, velocity, and endurance. Quadriceps and pectoralis major tissue saturation index (TSI) were measured throughout exercise. Plasma [NO3−] and nitrite ([NO2−]) were higher after 1 and 4 days of supplementation with BR compared to PL (p < 0.05). Quadriceps and pectoralis major TSI were not different between conditions (p > 0.05). The number of RTF in bench press was 5% greater after acute BR ingestion compared to PL (PL: 23 ± 4 vs. BR: 24 ± 5, p < 0.05). There were no differences between BR and PL for RTF for back squat or power and velocity for back squat or bench press (p > 0.05). These data improve understanding on the ergogenic potential of BR supplementation during resistance exercise.

Uniform Growth of Sub-5-Nanometer High-κ Dielectrics on MoS2 Using Plasma-Enhanced Atomic Layer Deposition.

Regardless of the application, MoS2 requires encapsulation or passivation with a high-quality dielectric, whether as an integral aspect of the device (as with top-gated field-effect transistors (FETs)) or for protection from ambient conditions. However, the chemically inert surface of MoS2 prevents uniform growth of a dielectric film using atomic layer deposition (ALD)-the most controlled synthesis technique. In this work, we show that a plasma-enhanced ALD (PEALD) process, compared to traditional thermal ALD, substantially improves nucleation on MoS2 without hampering its electrical performance, and enables uniform growth of high-κ dielectrics to sub-5 nm thicknesses. Substrate-gated MoS2 FETs were studied before/after ALD and PEALD of Al2O3 and HfO2, indicating the impact of various growth conditions on MoS2 properties, with PEALD of HfO2 proving to be most favorable. Top-gated FETs with high-κ films as thin as ∼3.5 nm yielded robust performance with low leakage current and strong gate control. Mechanisms for the dramatic nucleation improvement and impact of PEALD on the MoS2 crystal structure were explored by X-ray photoelectron spectroscopy (XPS). In addition to providing a detailed analysis of the benefits of PEALD versus ALD on MoS2, this work reveals a straightforward approach for realizing ultrathin films of device-quality high-κ dielectrics on 2D crystals without the use of additional nucleation layers or damage to the electrical performance.

Fluid shear stress activates YAP1 to promote cancer cell motility.

Mechanical stress is pervasive in egress routes of malignancy, yet the intrinsic effects of force on tumour cells remain poorly understood. Here, we demonstrate that frictional force characteristic of flow in the lymphatics stimulates YAP1 to drive cancer cell migration; whereas intensities of fluid wall shear stress (WSS) typical of venous or arterial flow inhibit taxis. YAP1, but not TAZ, is strictly required for WSS-enhanced cell movement, as blockade of YAP1, TEAD1-4 or the YAP1-TEAD interaction reduces cellular velocity to levels observed without flow. Silencing of TEAD phenocopies loss of YAP1, implicating transcriptional transactivation function in mediating force-enhanced cell migration. WSS dictates expression of a network of YAP1 effectors with executive roles in invasion, chemotaxis and adhesion downstream of the ROCK-LIMK-cofilin signalling axis. Altogether, these data implicate YAP1 as a fluid mechanosensor that functions to regulate genes that promote metastasis.