Intracellular signaling events during positive and negative selection of CD4+CD8+ thymocytes in vitro

We have used in vitro models of thymocyte positive and negative selection in conjunction with selective inhibitors of the TCR-mediated signaling cascade to investigate the intracellular signaling events that mediate these processes. We report that Ro 31.8425, a potent and selective inhibitor of protein kinase C, which blocks the activation of mature T cells in a dose-dependent fashion, has no effect on either positive or negative selection of CD4+8+ thymocytes. In contrast, cyclosporin A fails to prevent negative selection, but inhibits positive selection through a direct effect on developing thymocytes, rather than through the perturbation of stromal cell support. Thus, our data suggest that positive and negative selection may operate via distinct intracellular signaling pathways.     

Personalities of octopuses (Octopus rubescens).

Large individual differences are commonly found in the behavior of octopuses, even in standardized situation. 44 Octopus rubescens were tested in 3 situations (alerting, threat, and feeding) to quantify this variation. A factor analysis of resulting behaviors isolated 3 orthogonal dimensions of their variability, Activity, Reactivity, and Avoidance, which accounted for 45% of the variance. The similarity of these factors to dimensions of personality in humans and individual differences in animals suggests there may be commonalities in such variation across phyla. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inhibition of HIV-1 gp160-dependent membrane fusion by a furin-directed alpha 1-antitrypsin variant

Furin is a membrane-associated calcium-dependent serine endoprotease that cleaves proproteins on the carboxyl side of the consensus sequence -Arg-X-Lys/Arg-Arg-. Using site-directed mutagenesis, a variant alpha 1-antitrypsin (alpha 1-AT) was constructed which contains in its reactive site -Arg-X-X-Arg-, the minimal sequence required for efficient processing by furin (Molloy, S. S., Bresnahan, P. A., Leppla, S. H., Klimpel, K. R., and Thomas, G. (1992) J. Biol. Chem. 267, 16396-16402). This alpha 1-AT variant, [Arg355 Arg358]alpha 1-AT (alpha 1-PDX), is greater than 3,000-fold more effective than [Arg358]alpha 1-AT (alpha 1-AT Pittsburgh, alpha 1-PIT) at inhibiting furin in vitro (K0.5 = 0.03 microgram/ml). Furthermore, the P4 Arg in alpha 1-PDX greatly attenuates the thrombin inhibitory properties of this serpin (> 300-fold) compared with alpha 1-PIT (which contains a P4 Ala), thus increasing the selectivity of alpha 1-PDX for furin. Expression studies show that alpha 1-PDX, and not alpha 1-PIT, blocks the processing of two furin substrates, pro-beta-nerve growth factor and human immunodeficiency virus (HIV)-1 gp160 in transfected cells. In addition, a syncytium assay shows that alpha 1-PDX blocks the membrane fusogenic properties of HIV-1 gp160. The potential use of alpha 1-PDX in manipulating the activation of proproteins in a tissue- and time-specific manner is discussed.     

The effect of yoghurt on the growth,lactose-utilizing gut organisms and β-glucuronidase activity of caecal contents of a lactose-fed,lactase-deficient animal

The chicken, which has no endogenous lactase, was assessed as a possible model for studies on lactose intolerance. The ability of yoghurt to reverse changes induced by lactose was examined. In the caecum lactose had little effect on the viable counts of three groups of organisms which utilize lactose and no effect on the water content. It suppressed body weight, induced gas formation in the caecum and slightly lowered caecum pH. None of these effects was reversed by yoghurt.The β-glucuronidase activity of the caecal contents was slightly reduced by lactose and markedly reduced in chickens receiving lactose and yoghurt. The additional effect of yoghurt also occurred with yoghurt which had been heated to kill the bacteria and inactivate the lactase. The suppression of β-glucuronidase activity was also achieved by supplements of yoghurt alone.     

Hematopoietic effects and clinical uses of granulocyte-macrophage colony-stimulating factor and PIXY321

We tested the influence of in vivo volume resuscitation on intrinsic contractile properties of left ventricular (LV) preparations of endotoxemic guinea pigs. Escherichia coli endotoxin (LPS)-injected animals were divided into nonresuscitated and resuscitated groups. Volume resuscitation improved cardiac output and stroke volume, increased arterial pH and body temperature, and decreased mortality. In isovolumetric LV preparations isolated 4 h after LPS injection, LV systolic pressures (in mmHg) preparations isolated 4 h after LPS injection, LV systolic pressures (in mmHg) of LPS with (42 +/- 3) and without (42 +/- 2) fluid resuscitation were consistently less than control values (70 +/- 3). LV end-diastolic pressure-volume (compliance) decreased in LPS-nonresuscitated hearts, while LV compliance of LPS-resuscitated hearts was similar to control. Thus, intravascular volume expansion selectively improved LV diastolic compliance of LPS hearts without affecting LV systolic function. These findings suggest that LV systolic and diastolic dysfunctions associated with endotoxemia and Gram-negative sepsis may involve separate pathogenic mechanisms.     

Whole-body leucine turnover in adults on conventional treatment for hypopituitarism

To assess the differential efficacy of two commonly used treatments for temporomandibular disorders (TMD), intraoral appliances (IAs) and biofeedback (BF), separately and in combination, two studies were conducted. The first study directly compared IA treatment, a combination of biofeedback and stress management (BF/SM), and a waiting list control group in a sample of 80 TMD patients. Both treatments were determined to be equally credible to patients, ruling out this potential threat to the validity of the results obtained. The results demonstrated that the IA treatment was more effective than the BF/SM treatment in reducing pain after treatment, but at a 6-month follow-up the IA group significantly relapsed, especially in depression, whereas the BF/SM maintained improvements on both pain and depression and continued to improve. The second study examined the combination of IA and BF/SM in a sample of 30 TMD patients. The results of this study demonstrated that the combined treatment approach was more effective than either of the single treatments alone, particularly in pain reduction, at the 6-month follow-up. These results support the importance of using both dental and psychologic treatments to successfully treat TMD patients if treatment gains are to be maintained.     

Effects of target distance and pupil size on letter contrast sensitivity with simultaneous vision bifocal contact lenses

Using simulated presbyopia we measured the effects of target vergence and pupil size on letter contrast sensitivity while subjects wore accurately centered simultaneous vision bifocal contact lenses. These experiments examined the increase in depth of focus provided by two bifocal contact lenses, and the effects of pupil size on near and distance vision. Monocular contrast sensitivity was assessed with three different designs of soft contact lenses. First, as a single vision control, we measured contrast sensitivity with a Bausch & Lomb, Optima 38 lens corrected for distance. We then measured contrast sensitivity with an Allergan Optical, Hydron Echelon, which is a diffractive simultaneous bifocal and a CIBA Vision, Spectrum, which is a concentric design, center-near, two-zone simultaneous vision bifocal. In general both bifocal contact lenses improved contrast sensitivity at near but decreased contrast sensitivity at distance (when compared to the single vision lens). With a fixed 3.5-mm artificial pupil, the Echelon lens had two clear peaks of sensitivity, one at distance (0.00 D) and one at near (-2.00 D), but the Spectrum lens had no clear peaks. Performance of the Spectrum lens depended on its center zone size. Near (-2.00 D) and distance (0.00 D) contrast sensitivity was measured with pupil sizes that ranged from 1 to 6 mm. The results showed that visual performance with a diffractive lens was almost independent of pupil diameter up to 3 to 4 mm but, as predicted, performance with the two-zone lens depended critically on pupil size.