Mechano-transduction: from molecules to tissues.

External forces play complex roles in cell organization, fate, and homeostasis. Changes in these forces, or how cells respond to them, can result in abnormal embryonic development and diseases in adults. How cells sense and respond to these mechanical stimuli requires an understanding of the biophysical principles that underlie changes in protein conformation and result in alterations in the organization and function of cells and tissues. Here, we discuss mechano-transduction as it applies to protein conformation, cellular organization, and multi-cell (tissue) function

Elephant-to-Human Transmission of Tuberculosis, 2009

In 2009, the Tennessee Department of Health received reports of 5 tuberculin skin test (TST) conversions among employees of an elephant refuge and isolation of Mycobacterium tuberculosis from a resident elephant. To determine the extent of the outbreak and identify risk factors for TST conversion, we conducted a cohort study and onsite assessment. Risk for conversion was increased for elephant caregivers and administrative employees working in the barn housing the M. tuberculosis–infected elephant or in offices connected to the barn (risk ratio 20.3, 95% confidence interval 2.8–146.7). Indirect exposure to aerosolized M. tuberculosis and delayed or inadequate infection control practices likely contributed to transmission. The following factors are needed to reduce risk for M. tuberculosis transmission in the captive elephant industry: increased knowledge about M. tuberculosis infection in elephants, improved infection control practices, and specific occupational health programs

Variations in Atmospheric CO2CO_2 Mixing Ratios across a Boston, MA Urban to Rural Gradient

Urban areas are directly or indirectly responsible for the majority of anthropogenic $CO_2$ emissions. In this study, we characterize observed atmospheric $CO_2$ mixing ratios and estimated $CO_2$ fluxes at three sites across an urban-to-rural gradient in Boston, MA, USA. $CO_2$ is a well-mixed greenhouse gas, but we found significant differences across this gradient in how, where, and when it was exchanged. Total anthropogenic emissions were estimated from an emissions inventory and ranged from $1.5 to 37.3 mg·C·ha^{-1}·yr^{-1}$ between rural Harvard Forest and urban Boston. Despite this large increase in anthropogenic emissions, the mean annual difference in atmospheric $CO_2$ between sites was approximately 5% $(20.6 \pm 0.4 ppm)$. The influence of vegetation was also visible across the gradient. Green-up occurred near day of year 126, 136, and 141 in Boston, Worcester and Harvard Forest, respectively, highlighting differences in growing season length. In Boston, gross primary production—estimated by scaling productivity by canopy cover—was ~75% lower than at Harvard Forest, yet still constituted a significant local flux of $3.8 mg·C·ha^{-1}·yr^{-1}$. In order to reduce greenhouse gas emissions, we must improve our understanding of the space-time variations and underlying drivers of urban carbon fluxes.Engineering and Applied Science

A critical role for cystathionine-β-synthase in hydrogen sulfide-mediated hypoxic relaxation of the coronary artery

Hypoxia-induced coronary artery vasodilatation protects the heart by increasing blood flow under ischemic conditions, however its mechanism is not fully elucidated. Hydrogen sulfide (H2S) is reported to be an oxygen sensor/transducer in the vasculature. The present study aimed to identify and characterise the role of H2S in the hypoxic response of the coronary artery, and to define the H2S synthetic enzymes involved. Immunoblotting and immunohistochemistry showed expression of all three H2S-producing enzymes, cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (MPST), in porcine coronary artery. Artery segments were mounted for isometric tension recording; hypoxia caused a transient endothelium-dependent contraction followed by prolonged endothelium-independent relaxation. The CBS inhibitor amino-oxyacetate (AOAA) reduced both phases of the hypoxic response. The CSE inhibitor dl-propargylglycine (PPG) and aspartate (limits MPST) had no effect alone, but when applied together with AOAA the hypoxic relaxation response was further reduced. Exogenous H2S (Na2S and NaHS) produced concentration-dependent contraction followed by prolonged relaxation. Responses to both hypoxia and exogenous H2S were dependent on the endothelium, NO, cGMP, K+ channels and Cl−/HCO3 − exchange. H2S production in coronary arteries was blocked by CBS inhibition (AOAA), but not by CSE inhibition (PPG). These data show that H2S is an endogenous mediator of the hypoxic response in coronary arteries. Of the three H2S-producing enzymes, CBS, expressed in the vascular smooth muscle, appears to be the most important for H2S generated during hypoxic relaxation of the coronary artery. A contribution from other H2S-producing enzymes only becomes apparent when CBS activity is inhibited

Variation of the Jovian Magnetopause Under Constant Solar Wind Conditions: Significance of Magnetodisc Dynamics

It is generally believed that variations in the upstream solar wind (SW) and interplanetary magnetic field (IMF) conditions are the main cause of changes of Jupiter's magnetopause (JM) location. However, most previous pressure balance models for the JM are axisymmetric and do not consider internal drivers, for example, the dynamics of the magnetodisc. We use three-dimensional global magnetosphere simulations to investigate the variation of the JM under constant SW/IMF conditions. These simulations show that even without variations in the upstream driving conditions, the JM can exhibit dynamic variations, suggesting a range as large as 50 Jupiter radii in the subsolar location. Our study shows that the interchange structures in the Jovian magnetodisc will introduce significant radial dynamic pressure, which can drive significant variation in the JM location. The results provide important new context for interpreting the JM location and dynamics, with key implications for other internally mass-loaded and/or rapidly rotating systems

UDP-sugars activate P2Y 14 receptors to mediate vasoconstriction of the porcine coronary artery

Aims UDP-sugars can act as extracellular signalling molecules, but relatively little is known about their cardiovascular actions. The P2Y14 receptor is a Gi/o-coupled receptor which is activated by UDP-glucose and related sugar nucleotides. In this study we sought to investigate whether P2Y14 receptors are functionally expressed in the porcine coronary artery using a selective P2Y14 receptor agonist, MRS2690, and a novel selective P2Y14 receptor antagonist, PPTN (4,7-disubstituted naphthoic acid derivative). Methods and results Isometric tension recordings were used to evaluate the effects of UDP-sugars in porcine isolated coronary artery segments. The effects of the P2 receptor antagonists suramin and PPADS, the P2Y14 receptor antagonist PPTN, and the P2Y6 receptor antagonist MRS2578, were investigated. Measurement of vasodilator-stimulated phosphoprotein (VASP) phosphorylation using flow cytometry was used to assess changes in cAMP levels. UDP-glucose, UDP-glucuronic acid UDP-N-acetylglucosamine (P2Y14 receptor agonists), elicited concentration-dependent contractions in the porcine coronary artery. MRS2690 was a more potent vasoconstrictor than the UDP-sugars. Concentration dependent contractile responses to MRS2690 and UDP-sugars were enhanced in the presence of forskolin (activator of cAMP), where the level of basal tone was maintained by addition of U46619, a thromboxane A2 mimetic. Contractile responses to MRS2690 were blocked by PPTN, but not by MRS2578. Contractile responses to UDP-glucose were also attenuated by PPTN and suramin, but not by MRS2578. Forskolin-induced VASP-phosphorylation was reduced in porcine coronary arteries exposed to UDP-glucose and MRS2690, consistent with P2Y14 receptor coupling to Gi/o proteins and inhibition of adenylyl cyclase activity. Conclusions Our data support a role of UDP-sugars as extracellular signalling molecules and show for the first time that they mediate contraction of porcine coronary arteries via P2Y14 receptors

The Northwest Tropical Atlantic Station (NTAS) : NTAS-2 mooring turnaround cruise report

The Northwest Tropical Atlantic Station (NTAS) was established to address the need for accurate air-sea flux estimates and upper ocean measurements in a region with strong sea surface temperature anomalies and the likelihood of significant local air–sea interaction on interannual to decadal timescales. The approach is to maintain a surface mooring outfitted for meteorological and oceanographic measurements at a site near 15°N, 51°W by successive mooring turnarounds. These observations will be used to investigate air–sea interaction processes related to climate variability. Deployment of the first NTAS mooring (NTAS-1) at 14°50′ N, 51°00′ W on 30 March 2001 was documented in a previous report (Plueddemann et al., 2001). This report documents recovery of the NTAS-1 mooring and deployment of the NTAS-2 mooring at the same site. Both moorings used 3-meter discus buoys as the surface element. These buoys were outfitted with two Air–Sea Interaction Meteorology (ASIMET) systems. Each system measures, records, and transmits via Argos satellite the surface meteorological variables necessary to compute air–sea fluxes of heat, moisture and momentum. The upper 120 m of the NTAS-1 mooring line, and the upper 150 m of the NTAS-2 mooring line, were outfitted with oceanographic sensors for the measurement of temperature and velocity. The mooring turnaround was done on the NOAA Ship Ronald H. Brown, Cruise RB-02-02, by the Upper Ocean Processes Group of the Woods Hole Oceanographic Institution. The cruise took place between 2 and 8 March 2002. A SeaBeam bathymetry survey of the site was done first, followed by deployment of the NTAS-2 mooring on 4 March at approximately 14°44.3′ N, 50°56.8′ W in 5043 m of water. A 24-hour intercomparison period followed, after which the NTAS-1 mooring was recovered. This report describes these operations, as well as some of the pre-cruise buoy preparations.Funding was provided by the National Oceanic and Atmospheric Administration and the Cooperative Institute for Climate and Ocean Research (CICOR) under Grant No. NA17RJ1223

The Northwest Tropical Atlantic Station (NTAS) : NTAS-1 mooring deployment cruise report

A surface mooring outfitted for meteorological and oceanographic measurement was deployed near 14°50'N, 51°00'W in the northwest tropical Atlantic on 30 March 2001. This was the initial deployment of the Northwest Tropical Atlantic Station (NTAS) project for air–sea flux measurement. These observations will be used to investigate air–sea interaction processes related to climate variability. The deployment was done on R/V Oceanus Cruise 365, Leg 5 by the Upper Ocean Processes Group (UOP) of the Woods Hole Oceanographic Institution. The 3-meter discus buoy was outfitted with two Air–Sea Interaction Meteorology (ASIMET) systems. Each system measures, records, and transmits via Argos satellite the surface meteorological variables necessary to compute air–sea fluxes of heat, moisture and momentum. The upper 120 m of the mooring line was outfitted with oceanographic sensors for the measurement of temperature and velocity. This report describes the initial deployment of the NTAS mooring (NTAS-1), including some of the pre-cruise buoy preparations and post cruise data comparisons.Funding was provided by the National Oceanic and Atmospheric Administration (NOAA) through the Cooperative Institute for Climate and Ocean Research (CICOR) under Grant No. NA87RJ0445