Membrane tension is becoming recognized as an important mechanical regulator of motile cell behavior. Although membrane-tension measurements have been performed in various cell types, the tension ...distribution along the plasma membrane of motile cells has been largely unexplored. Here, we present an experimental study of the distribution of tension in the plasma membrane of rapidly moving fish epithelial keratocytes. We find that during steady movement the apparent membrane tension is ∼30% higher at the leading edge than at the trailing edge. Similar tension differences between the front and the rear of the cell are found in keratocyte fragments that lack a cell body. This front-to-rear tension variation likely reflects a tension gradient developed in the plasma membrane along the direction of movement due to viscous friction between the membrane and the cytoskeleton-attached protein anchors embedded in the membrane matrix. Theoretical modeling allows us to estimate the area density of these membrane anchors. Overall, our results indicate that even though membrane tension equilibrates rapidly and mechanically couples local boundary dynamics over cellular scales, steady-state variations in tension can exist in the plasma membranes of moving cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
OBJECTIVE To assess the association between erectile dysfunction (ED) and the long-term risk of coronary artery disease (CAD) and the role of age as a modifier of this association. PARTICIPANTS AND ...METHODS From January 1, 1996, to December 31, 2005, we biennially screened a random sample of 1402 community-dwelling men with regular sexual partners and without known CAD for the presence of ED. Incidence densities of CAD were calculated after age stratification and adjusted for potential confounders by time-dependent Cox proportional hazards models. RESULTS The prevalence of ED was 2% for men aged 40 to 49 years, 6% for men aged 50 to 59 years, 17% for men aged 60 to 69 years, and 39% for men aged 70 years or older. The CAD incidence densities per 1000 person-years for men without ED in each age group were 0.94 (40-49 years), 5.09 (50-59 years), 10.72 (60-69 years), and 23.30 (≥70 years). For men with ED, the incidence densities of CAD for each age group were 48.52 (40-49 years), 27.15 (50-59 years), 23.97 (60-69 years), and 29.63 (≥70 years). CONCLUSION ED and CAD may be differing manifestations of a common underlying vascular pathology. When ED occurs in a younger man, it is associated with a marked increase in the risk of future cardiac events, whereas in older men, ED appears to be of little prognostic importance. Young men with ED may be ideal candidates for cardiovascular risk factor screening and medical intervention.
CONTEXT The initial report of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found no reduction in risk of prostate cancer with either selenium or vitamin E supplements but a ...statistically nonsignificant increase in prostate cancer risk with vitamin E. Longer follow-up and more prostate cancer events provide further insight into the relationship of vitamin E and prostate cancer. OBJECTIVE To determine the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men. DESIGN, SETTING, AND PARTICIPANTS A total of 35 533 men from 427 study sites in the United States, Canada, and Puerto Rico were randomized between August 22, 2001, and June 24, 2004. Eligibility criteria included a prostate-specific antigen (PSA) of 4.0 ng/mL or less, a digital rectal examination not suspicious for prostate cancer, and age 50 years or older for black men and 55 years or older for all others. The primary analysis included 34 887 men who were randomly assigned to 1 of 4 treatment groups: 8752 to receive selenium; 8737, vitamin E; 8702, both agents, and 8696, placebo. Analysis reflect the final data collected by the study sites on their participants through July 5, 2011. INTERVENTIONS Oral selenium (200 μg/d from L-selenomethionine) with matched vitamin E placebo, vitamin E (400 IU/d of all rac-α-tocopheryl acetate) with matched selenium placebo, both agents, or both matched placebos for a planned follow-up of a minimum of 7 and maximum of 12 years. MAIN OUTCOME MEASURES Prostate cancer incidence. RESULTS This report includes 54 464 additional person-years of follow-up and 521 additional cases of prostate cancer since the primary report. Compared with the placebo (referent group) in which 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer (hazard ratio HR, 1.17; 99% CI, 1.004-1.36, P = .008); as did 575 in the selenium group (HR, 1.09; 99% CI, 0.93-1.27; P = .18), and 555 in the selenium plus vitamin E group (HR, 1.05; 99% CI, 0.89-1.22, P = .46). Compared with placebo, the absolute increase in risk of prostate cancer per 1000 person-years was 1.6 for vitamin E, 0.8 for selenium, and 0.4 for the combination. CONCLUSION Dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men. TRIAL REGISTRATION Clinicaltrials.gov Identifier: NCT00006392
This randomized trial tested the idea that finasteride, which inhibits the production of androgens within the prostate, can prevent prostate cancer. The participants were to receive finasteride or a ...placebo daily for seven years. Prostate cancer was found in 18.4 percent of the men in the finasteride group and in 24.4 percent of those in the placebo group. Higher-grade cancers (Gleason score, 7, 8, 9, or 10) were more common in the finasteride group than in the placebo group. Sexual dysfunction was more common in the finasteride group, and urinary difficulties were more common in the placebo group.
A test of the idea that finasteride can prevent prostate cancer.
To date, the management of prostate cancer, the most common nondermatologic neoplasm in men in the United States, has focused on early diagnosis and treatment. Given that the development of prostate cancer is a long-term process involving multiple steps, however, prevention may be a more effective approach.
There is abundant evidence that androgens influence the development of prostate cancer.
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The development of finasteride, an inhibitor of steroid 5α-reductase, the enzyme that converts testosterone to the more potent androgen dihydrotestosterone, created an opportunity to test the possibility that lowering the androgen levels in the prostate would reduce the risk of . . .
In plant tissue culture research, the non-traditional growth regulators, methylglyoxal and ascorbic acid, have been used to induce and promote in vitro morphogenesis from plant callus, generally ...having the initial characteristics of a type of neoplasm, and in many cases overcoming recalcitrant morphogenesis. In other investigations methylglyoxal, most likely with ascorbic acid, also promoted such morphogenesis. In the various investigations, low concentrations of methylglyoxal were used and proved to be the most effective in promoting in vitro morphogenesis. In many cases, the growth of such neoplastic-like calli was concurrently inhibited on culture media containing these chemicals. When methylglyoxal was present in high concentration, morphogenesis was also inhibited. Such chemicals, it would appear likely, allowed for the generation of cohesive forces within regions of the calli, reversing the neoplastic state in such regions, due to very low internal cohesion, and through such cohesive forces of particular magnitude, morphogenesis ensued, as an adaptive response to the stress of such cohesive forces. This would suggest a deeper, underlying biological process, with developmental features, that is perhaps universal among plants and perhaps in all biological organisms. This particular, consistent avenue and theme of plant tissue culture research, manifested over four decades and across four continents, may have revealed a unifying, dynamical process in both the biological and physical worlds, with constructive implications for agriculture and medicine.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The issue of forces, the dimensional universal constants, their dimensionless components, marked by the constant ratio of spiral generation, PHI, the golden ratio (1.618), and the feasible existence ...of a universal principle, are again addressed. As described in earlier articles, PHI is a dimensionless component or feature of most, if not all, of the respective physical, dimensional universal constants. In this rendition, the subject is further elucidated, focusing on various physical theories and their suggested unity through PHI. In this context, the subject is further developed from various perspectives, including epistemological, which serves to bring about more, perhaps deeper insights on the situation. As pointed out, with the exception of the Special Theory of Relativity, and the early stages of quantum mechanics during the early 20th century, modern physical theories have not focused explicitly on any of the dimensional universal constants as center pieces of their theories. With regard to those universal constants, focusing on their dimensionless components, further clarification is intended and illustrated in this article, such as pertaining to wave mechanics and string theory, and their relation to the universal constants. In doing so, one discusses basic questions. Could such universal constants have been proposed or predicted in a physical theory before they were discovered through experiment? Also, can experiments be devised that indicate the feasible existence of a universal principle of completion connected to or executed through the universal constants, that is, through their dimensionless or trans-dimensional features? Can such a principle involve or implicate a deeper ultra-reality of universais? Does such a principle indicate an unfolding of reality, a developmental process, a temporal directionality? In this article, the relevancy of such universal constants, their dimensionless features, marked by PHI, to programmed computer simulations are also shown. These are tangible, visible figures on a computer screen that involve vortical, fractal features, which are connected to PHI and to other dimensionless constants. These are creations due to the human mind's involvement with the mathematical design of computer processes that represent reality. These computer generated figures of developing vortical features, displayed on a computer screen, may be mirrored in a vortical, developing reality of matter-energy and in the higher-ordered morphologies of organisms. In this connection, based on research, the function of the human brain, and by extension, the mind, appears to be dependent on the anatomical presence of the dimensionless biological constant PHI, the golden ratio. What becomes clear throughout this article, while repeatedly addressing PHI and other dimensionless constants, and referring to various, possibly united, scientific approaches via PHI, is the subtle indication of a universal causation throughout various, natural phenomena on all scales. Such phenomena and their causation, it is feasibly theorized, would be generated, supported, and guided vortically, completely, stably and developmentally by means of the universal constants through their dimensionless features or components, such as PHI and its powers. The various or specific phenomena, or the theories pertaining to such, are thus unified in this manner via PHI. This process of vortical regeneration involving completing forces would occur along with the support of other dimensionless constants such as n and the exponential constant, e. A non-relative, temporal directionality, a guided unfolding, via a guided completion through the universal constants, would be manifest via such a regeneration of completion. In that context, randomness becomes a limiting case, and perhaps, has been, at best, a constructive illusion in the history of science. KEYWORDS: Algebra; Brain; Causation; Completion; Computer; Constants; Dimensionless; Forces; Fractal, geometry; Golden ratio; Guiding; Morphology; Potential; Prediction; Principle; Reality; Scale; Simulation; Stability; Template; Testability; Unfolding; Unified; Universal; Vortica
Reviewing the older, different approaches in physics may enable one to integrate them. This may provide new insights into physical existence. The theoretical approaches of Albert Einstein and Paul ...Dirac, during the earlier part of the twentieth century, indicate remarkable similarities, even though their approaches respectively addressed different levels of existence, with seemingly different structures. Because of such similarity or unity, both theories or approaches predicted the positively charged electron. Having the same predictions experimentally confirmed in 1932, validating the two theories, both theories would have been common avenues to revealing a deeper feature of reality, universally present and marked by a new universal constant. It is unknown as to why both men did not see this and subsequently collaborate on elaborating such a unification and its implications. A new generation of physicists and philosophers, with new perspectives, may be able to do so. KEYWORDS: Approaches; Dirac; Einstein; Electron; New paradigm; Predictions; Theoretical; Unity; Universal constant
Previous studies of in vitro and in vivo morphogenesis in plants may suggest a more inclusive principle governing biological and physical processes. Forces, including those of adhesion and cohesion, ...may reflect and enable the deep role of the dimensional, universal physical constants of physics through a constant, regenerative-defining, dimensionless component of those constants. It is the existence of such universal constants from which comes and reflects stability, coherence and constancy in nature through constraints or forces enabled within a neo-aether, and occurring through a non-uniform space-time. These are situations most displayed in biological processes. And a further study of the connections between such universal constants may give us deep insights into such natural processes and situations. Such as, the morphogenic becoming of such situations may thus be shown to reflect specifically a unifying principle governing the stabilization of physical and biological phenomena, with relevance for human society. Published and unpublished information, pertaining to the physical, dimensional universal constants and forces, which indirectly illustrate this proposed principle, is presented. This may serve a heuristic function for devising and conceptualizing new experimental approaches and designs, where an investigation of biological processes becomes a unifying study of and approach to all natural processes through all scales. A biological-based epistemology is also suggested, which should serve the constructive evolution and stabilization of science, especially social science. In this connection, the issue of indeterminacy and determinacy in science is also addressed. KEYWORDS: Accommodation; Adhesion; Biology; Cohesion; Completion; Correspondence; Dimensional/ dimensionless constants; Evolutionary; Eorce; Fractal; Golden ratio; Morphogenesis; physics; Principle; Stability; Stress; Unifying; Universal
Lateral tension in cell plasma membranes plays an essential role in regulation of a number of membrane-related intracellular processes and cell motion. Understanding the physical factors generating ...the lateral tension and quantitative determination of the tension distribution along the cell membrane is an emerging topic of cell biophysics. Although experimental data are accumulating on membrane tension values in several cell types, the tension distribution along the membranes of moving cells remains largely unexplored. Here we suggest and analyze a theoretical model predicting the tension distribution along the membrane of a cell crawling on a flat substrate. We consider the tension to be generated by the force of actin network polymerization against the membrane at the cell leading edge. The three major factors determining the tension distribution are the membrane interaction with anchors connecting the actin network to the lipid bilayer, the membrane interaction with cell adhesions, and the force developing at the rear boundary due to the detachment of the remaining cell adhesion from the substrate in the course of cell crawling. Our model recovers the experimentally measured values of the tension in fish keratocytes and their dependence on the number of adhesions. The model predicts, quantitatively, the tension distribution between the leading and rear membrane edges as a function of the area fractions of the anchors and the adhesions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
CONTEXT Secondary analyses of 2 randomized controlled trials and supportive epidemiologic and preclinical data indicated the potential of selenium and vitamin E for preventing prostate cancer. ...OBJECTIVE To determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men. DESIGN, SETTING, AND PARTICIPANTS A randomized, placebo-controlled trial (Selenium and Vitamin E Cancer Prevention Trial SELECT) of 35 533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups (selenium, vitamin E, selenium + vitamin E, and placebo) in a double-blind fashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serum prostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination not suspicious for prostate cancer. INTERVENTIONS Oral selenium (200 μg/d from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/d of all rac-α-tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years. MAIN OUTCOME MEASURES Prostate cancer and prespecified secondary outcomes, including lung, colorectal, and overall primary cancer. RESULTS As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17-7.33 years). Hazard ratios (99% confidence intervals CIs) for prostate cancer were 1.13 (99% CI, 0.95-1.35; n = 473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n = 432) for selenium, and 1.05 (99% CI, 0.88-1.25; n = 437) for selenium + vitamin E vs 1.00 (n = 416) for placebo. There were no significant differences (all P>.15) in any other prespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P = .06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P = .16) but not in the selenium + vitamin E group. CONCLUSION Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men. TRIAL REGISTRATION clinicaltrials.gov identifier: NCT00006392Published online December 9, 2008 (doi:10.1001/jama.2008.864).
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