Plasma membrane cholesterol is a key molecule in shear stress-dependent activation of extracellular signal-regulated kinase

Shear stress, the dragging force generated by fluid flow, differentially activates extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) in bovine aortic endothelial cells (BAEC) (Jo, H., Sipos, K., Go, Y. M., Law, R., Rong, J., and McDonald, J. M. (1997) J. Biol. Chem. 272, 1395-1401). Here, we examine whether cholesterol-enriched compartments in the plasma membrane are responsible for such differential regulation. Pretreatment of BAEC with a cholesterol-binding antibiotic, filipin, did not inhibit shear-dependent activation of JNK. In contrast, filipin and other membrane-permeable cholesterol-binding agents (digitonin and nystatin), but not the lipid-binding agent xylazine, inhibited shear-dependent activation of ERK. The effect of cholesterol-binding drugs did not appear to be due to membrane permeabilization, since treatment of BAEC with a detergent, Triton X-100 which also permeabilizes membranes, did not inhibit shear-dependent activation of ERK. Furthermore, shear-dependent activation of ERK, but not JNK, was inhibited by cyclodextrin, a membrane-impermeable cholesterol-binding agent, which removes cell-surface cholesterol. Moreover, the effects of cyclodextrin were prevented by adding cholesterol during the incubation. These results indicate that cholesterol or cholesterol-sensitive compartments in the plasma membrane play a selective and essential role in activation of ERK, but not JNK, by shear stress. Although exposure to shear stress (1 h) increased the number of caveolae by 3-fold, treatment with filipin had no effect in either control or shear-exposed cells suggesting that caveolae density per se is not a crucial determinant in shear-dependent ERK activation. In summary, the current study suggests that cholesterol-sensitive microdomains in the plasma membrane, such as caveolae-like domains, play a critical role in differential activation of ERK and JNK by shear stress.     

Blood-gas measurements adjusted for temperature at three sites during incremental exercise in the horse

Rectal temperature (Tre) is often used to adjust measurements of blood gases, but these adjusted measurements may not approximate temperatures during intense exercise at main sites of gas exchange: muscle and lung. To evaluate differences in blood gases between sites, temperatures (T) were measured with thermocouples in the rectum (re), in mixed venous blood (v), in gluteal muscle (mu), and on the skin (sk) in seven Arabian horses as they underwent an incremental exercise test on a treadmill. Blood samples were drawn from the carotid artery and pulmonary artery (mixed venous) 30 s before each increase in speed and during recovery. Blood gases and pH were measured at 37 degreesC, and all variables were adjusted to Tre, Tv, and Tmu. Adjusted variables during exercise and recovery were significantly different from each other at the three sites. Linear and polynomial equations described the time course of venous temperature and from Tre and Tsk during exercise and from Tsk during recovery. Interpretation of changes in muscle metabolism and gas exchanges based on blood-gas measurements is improved if they are adjusted appropriately to Tmu or Tv, which may be predicted from Tsk in addition to Tre during strenuous exercise and from Tsk during recovery.     

Harold H. Kelley (1921-2003).

This obituary reports the death of Harold Harding Kelley, Professor Emeritus of Psychology at University of California (1921-2003). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Gender Congruency Effect and the Selection of Freestanding and Bound Morphemes: Evidence From Croatian.

The authors report 3 picture-word interference experiments in which they explore some properties of the agreement process in speech production. In Experiment 1, Croatian speakers were asked to produce utterances in which the noun's gender value had an impact on the selection of gender-marked freestanding morphemes (pronouns) while ignoring the presentation of same- or different-gender distractor words. In Experiments 2 and 3, Croatian speakers were asked to name the same pictures using noun phrases in which the noun's gender value surfaced as an inflectional suffix. Different-gender distractors interfered more than same-gender distractors (the gender congruency effect) in Experiment 1, but not in Experiments 2 and 3. These contrasting results show that the cause of the gender congruency effect is not at the level where lexical-grammatical information is selected but at the level of selection of freestanding morphemes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interaction of a free-living soil nematode, Caenorhabditis elegans, with surrogates of foodborne pathogenic bacteria

Free-living nematodes may harbor, protect, and disperse bacteria, including those ingested and passed in viable form in feces. These nematodes are potential vectors for human pathogens and may play a role in foodborne diseases associated with fruits and vegetables eaten raw. In this study, we evaluated the associations between a free-living soil nematode, Caenorhabditis elegans, and Escherichia coli, an avirulent strain of Salmonella Typhimurium, Listeria welshimeri, and Bacillus cereus. On an agar medium, young adult worms quickly moved toward colonies of all four bacteria; over 90% of 3-day-old adult worms entered colonies within 16 min after inoculation. After 48 h, worms moved in and out of colonies of L. welshimeri and B. cereus but remained associated with E. coli and Salmonella Typhimurium colonies for at least 96 h. Young adult worms fed on cells of the four bacteria suspended in K medium. Worms survived and reproduced with the use of nutrients derived from all test bacteria, as determined for eggs laid by second-generation worms after culturing for 96 h. Development was slightly slower for worms fed gram-positive bacteria than for worms fed gram-negative bacteria. Worms that fed for 24 h on bacterial lawns formed on tryptic soy agar dispersed bacteria over a 3-h period when they were transferred to a bacteria-free agar surface. The results of this study suggest that C. elegans and perhaps other free-living nematodes are potential vectors for both gram-positive and gram-negative bacteria, including foodborne pathogens in soil.     

Choking under pressure: Multiple routes to skill failure.

Poor performance in pressure-filled situations, or “choking under pressure,” has largely been explained by two different classes of theories. Distraction theories propose that choking occurs because attention needed to perform the task at hand is coopted by task-irrelevant thoughts and worries. Explicit monitoring theories claim essentially the opposite—that pressure prompts individuals to attend closely to skill processes in a manner that disrupts execution. Although both mechanisms have been shown to occur in certain contexts, it is unclear when distraction and/or explicit monitoring will ultimately impact performance. The authors propose that aspects of the pressure situation itself can lead to distraction and/or explicit monitoring, differentially harming skills that rely more or less on working memory and attentional control. In Experiments 1–2, it is shown that pressure that induces distraction (involving performance-contingent outcomes) hurts rule-based category learning heavily dependent on attentional control. In contrast, pressure that induces explicit monitoring of performance (monitoring by others) hurts information-integration category learning thought to run best without heavy demands on working memory and attentional control. In Experiment 3, the authors leverage knowledge about how specific types of pressure impact performance to design interventions to eliminate choking. Finally, in Experiment 4, the selective effects of monitoring-pressure are replicated in a different procedural-based task: the serial reaction time task. Skill failure (and success) depends in part on how the performance environment influences attention and the extent to which skill execution depends on explicit attentional control. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Nonuniform and Unsteady Solute Transport in Furrow Irrigation. I: Model Development

A cross-section-averaged advection-dispersion equation (ADE) model was developed to simulate the transport of fertilizer in furrow irrigation. The advection and dispersion processes were solved separately at each time step by implementing a method of characteristics with cubic-spline interpolation and a time-weighted finite-difference scheme, respectively. The upstream boundary condition was a prescribed concentration. Downstream, a zero-flux boundary condition during advance and a concentration gradient following completion of advance were prescribed. Local pseudosteady state was assumed in order to apply Fischer’s longitudinal dispersion equation under nonuniform and unsteady furrow flow conditions. Statistical parameters were used to evaluate the ADE model performance.     

A frequent activated smoothened mutation in sporadic basal cell carcinomas

Basal-cell carcinomas (BCCs) are the most common cancer in Caucasians. It has been reported that the patched gene is inactivated in 30-40% sporadic BCCs and 20% sporadic medulloblastomas via loss of heterozygosity and nonsense mutations. Recently, two activating smoothened mutations have been found in the sporadic basal cell carcinomas. One, at base pair 1604 (G-to-T transversion) of exon 9, changes codon 535 from tryptophan to leucine, and the other, at base pair 1685 (G-to-A transition) of exon 10, changes codon 562 from arginine to glutamine (Xie et al., 1998). In our study, 1604G-->T was found in 20 out of 97 (20.6%) sporadic BCCs. The high prevalence indicates that 1604G is the mutation hot spot in our tumor samples. This mutation was detected in all three histological subtypes of BCCs, suggesting that smoothened mutation is an early event during the development of the tumor. Our finding of a high smoothened mutation rate, together with high frequent patched gene mutations reported recently, indicates that activation of the hedgehog signal transduction pathway is the most common and early event in the development of sporadic BCCs. Additionally, to determine whether smoothened, like patched, is also involved in the carcinogenesis of medulloblastomas, we screened medulloblastoma samples for these two mutations by restriction analysis. We have found the 1604G-->T mutation in 1 out of 21 medulloblastomas. This result confirmed smoothened gene involvement in the carcinogenesis of medulloblastoma.     

Procedure to Calibrate and Verify Numerical Models of Estuarine Hydrodynamics

In most hydrodynamic models, friction and turbulent diffusion∕dispersion coefficients are the important calibration parameters affecting the calculation of surface elevation, velocity and salinity distribution. This paper presents a rational approach to calibrate and verify a hydrodynamic model of partially stratified estuaries. The calibration procedures and verification requirements are demonstrated with the application of a vertical (laterally averaged) two-dimensional model to a branched estuarine river system. The friction coefficient is calibrated and verified with model simulation of barotropic flow, and the turbulent diffusion and dispersion coefficients are calibrated through comparison of salinity distributions. The overall model verification is suggested to be achieved with comparisons of Eulerian residual circulation and salinity distribution. In the case of the Tanshui River system, the available prototype current records are too short to calculate slowly varying residual currents. The snapshots of the model-computed and field-measured residual currents are provided to qualitatively agree with theoretical analysis. The overall performance of the model is verified with an additional set of salinity data.