| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
EDITORIAL
There is an unhealthy tendency in our media-saturated society to value only those things that receive the most hype. Our interests and opinions about the popular world are shaped by the tabloids that we all secretly read in supermarket checkout lines, which only enlighten us about Oscar winners, Most Valuable Players, supermodels, and the super rich. Our senses are seldom assaulted with stories about the less-visible members of the supporting cast. We rarely read about the legions of extraordinarily talented people who croon back-up vocals or who constitute an unassailable offensive line. I submit that we scientists are not infrequently guilty of this sort of cultish behavior when we stratify the relative importance of biological systems and their associated unanswered questions.
When I think about the eye, for example, I tend to think about the marquee players. I envision rods and cones, replete with rhodopsin, transducin, and cGMP-gated channels. I confess that I don’t tend to occupy my mind with the multitude of other cell types and pathways that must be in place for the photosensitive cell types to work their magic. The Emerging Topic in this issue by Hartzell et al. makes it abundantly clear just how myopic a viewpoint this is. Photoreceptor cells are constantly being trimmed by the phagocytic cells of the retinal pigment epithelium. The pigment that these cells ingest needs to be degraded. If its destruction is impeded it can accumulate in the retinal pigment epithelium, compromising these cells’ functional capacity, potentially leading to retinal damage. Mutations in the genes encoding the bestrophin chloride channels are responsible for Best’s macular dystrophy, a heritable form of macular degeneration. Hartzell and colleagues suggest the interesting hypothesis that the bestrophins are obligate participants in the acidification of the endosomal and lysosomal compartments in retinal pigment epithelial cells, providing a shunt pathway that reduces the electrical potential difference against which the H-ATPase has to work in order to pump protons. Just as the residents of New York City do not pay sufficient attention to sanitation workers until they go on strike in the month of August and the pungent garbage piles begin to mount, Best’s macular dystrophy reminds us that we tend not to be adequately impressed by the array of molecular machinery involved in the turnover of the photosensitive components of the retina unless its dysfunction threatens to impair the eye’s sensory functions.
The celebration of unsung heroes continues with other contributions in this month’s issue of Physiology.
O’Rourke et al. discuss ion channels in the mitochondrial membranes. These channels are probably not directly involved in the mitochondrion’s best-recognized role in energy generation. Their regulation, however, may be directly tied to the mitochondrion’s critical ancillary function as arbiter of some forms of programmed cell death.
The review by Rafii and colleagues focuses on the bone marrow vascular niche, a sleepy backwater of the circulatory system. This morphologically unremarkable compartment appears to serve as a critically important incubator for developing hematopoietic progenitor cells. Growing insight into the nature and role of this compartment may suggest valuable tools that can be used to facilitate bone marrow transplantation and regeneration.
Discussions of cancer most often relate to the proliferative aspects of this multifaceted disease. It is certainly true that the loss of growth control that follows oncogenic transformation is the proximal cause of cancer pathology. It is also true, however, that cancer is often a wasting disease. For many tumor types, loss of body mass, or cachexia, is a major factor limiting patient survival and quality of life. Although the consequences of cachexia are easy to recognize and hard to forget, the underlying causes of this condition remain fairly mysterious. The article by Tisdale reviews the interaction between tumor and host cell factors that contribute to this important paraneoplastic phenomenon.
We eukaryotes tend to think that we are considerably smarter and more sophisticated than our prokaryotic forbears. Many physiologists, therefore, may be guilty of paying insufficient attention to the fascinating lessons that bacteria can teach us about ourselves. Bacteria have spent eons of evolutionary time working out ever-more-effective ways to overcome our bodies’ defenses. The tricks that they have developed exploit all of the chinks in the armor of our innate and adaptive immune systems. It is becoming clear that elucidating these bacterial adaptations can provide us with fresh and exciting clues into the nature of immune and phagocytic cell function. The paper by Cornelis and Troisfontaines reviews the type III secretion system, a fascinating specialization through which bacteria mediate gene transfer and evade host defenses. Just as computer hackers teach software engineers about the vulnerabilities inherent in their systems, so too bacteria help to illuminate normal mechanisms employed by our own cells and the nefarious purposes to which they can be bent.
Among the collection of hormones that impact upon glucose metabolism, insulin certainly has the most name recognition. As this month’s article by Sinclair and Drucker points out, however, insulin does not work alone. Glucagon, its receptors, and its related hormones appear to play physiologically interesting and important roles. This timely review reveals how small peptides, acting paracrinely or endocrinely, will lead to new strategies in the treatment of disease.
Finally, the article by Hunter and Nielsen reviews new computational strategies that can be applied to integrating the ever-expanding wealth of experimental data into useful and coherent models. It may seem somewhat paradoxical to include a discussion of the "big picture" on my list of important but often underappreciated problems. For those of us who are intensely focused on our own little corner of physiological science, however, the macroscopic "big picture" does not always get the attention that it deserves. The task of creating intelligible and useful models of physiological systems is truly daunting. The increasing sophistication of mathematical modeling techniques, data-gathering methodologies, and computing power are rendering this goal ever more attainable. These efforts may someday unite the many individual (and sometimes unjustifiably undercelebrated) trees that constitute the diverse lines of modern physiological research into one really interesting forest.
| ||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
