Making mistakes when predicting shifts in species range in response to global warming

Many attempts to predict the biotic responses to climate change rely on the 'climate envelope' approach, in which the current distribution of a species is mapped in climate-space and then, if the position of that climate-space changes, the distribution of the species is predicted to shift accordingly. The flaw in this approach is that distributions of species also reflect the influence of interactions with other species, so predictions based on climate envelopes may be very misleading if the interactions between species are altered by climate change. An additional problem is that current distributions may be the result of sources and sinks, in which species appear to thrive in places where they really persist only because individuals disperse into them from elsewhere. Here we use microcosm experiments on simple but realistic assemblages to show how misleading the climate envelope approach can be. We show that dispersal and interactions, which are important elements of population dynamics, must be included in predictions of biotic responses to climate change.     

Early inpatient rehabilitation after elective hip and knee arthroplasty

CONTEXT: Inpatient rehabilitation after elective hip and knee arthroplasty is often necessary for patients who cannot function at home soon after surgery, but how soon after surgery inpatient rehabilitation can be initiated has not been studied. OBJECTIVE: To test the hypothesis that high-risk patients undergoing elective hip and knee arthroplasty would incur less total cost and experience more rapid functional improvement if inpatient rehabilitation began on postoperative day 3 rather than day 7, without adverse consequences to the patients. DESIGN: Randomized controlled trial conducted from 1994 to 1996. SETTING: Tertiary care center. PARTICIPANTS: A total of 86 patients undergoing elective hip or knee arthroplasty and who met the following criteria for being high risk: 70 years of age or older and living alone, 70 years of age or older with 2 or more comorbid conditions, or any age with 3 or more comorbid conditions. Of the 86 patients, 71 completed the study. INTERVENTIONS: Random assignment to begin inpatient rehabilitation on postoperative day 3 vs postoperative day 7. MAIN OUTCOME MEASURES: Total length of stay and cost from orthopedic and rehabilitation hospital admissions, functional performance in hospitals using a subset of the functional independence measure, and 4-month follow-up assessment using the RAND 36-item health survey I and the functional status index. RESULTS: Patients who completed the study and began inpatient rehabilitation on postoperative day 3 exhibited shorter mean (+/-SD) total length of stay (11.7+/-2.3 days vs 14.5+/-1.9, P<.001), lower mean (+/-SD) total cost ($25891+/-$3648 vs $27762+/-$3626, P<.03), more rapid attainment of short-term functional milestones between days 6 and 10 (36.2+/-14.4 m ambulated vs 21.4+/-13.3 m, P<.001; 4.8+/-0.8 mean transfer functional independence measure score vs 4.3+/-0.7, P<.01), and equivalent functional outcome at 4-month follow-up. CONCLUSION: These data showed that high-risk individuals were able to tolerate early intensive rehabilitation, and this intervention yielded faster attainment of short-term functional milestones in fewer days using less total cost.     

Synergy between simulation and experiment in describing the energy landscape of protein folding

Experimental data from protein engineering studies and NMR spectroscopy have been used by theoreticians to develop algorithms for helix propensity and to benchmark computer simulations of folding pathways and energy landscapes. Molecular dynamic simulations of the unfolding of chymotrypsin inhibitor 2 (CI2) have provided detailed structural models of the transition state ensemble for unfolding/folding of the protein. We now have used the simulated transition state structures to design faster folding mutants of CI2. The models pinpoint a number of unfavorable local interactions at the carboxyl terminus of the single alpha-helix and in the protease-binding loop region of CI2. By removing these interactions or replacing them with stabilizing ones, we have increased the rate of folding of the protein up to 40-fold (tau = 0.4 ms). This correspondence, and other examples of agreement between experiment and theory in general, Phi-values and molecular dynamics simulations, in particular, suggest that significant progress has been made toward describing complete folding pathways at atomic resolution by combining experiment and simulation.     

Implication of eIF2B rather than eIF4E in the regulation of global protein synthesis by amino acids in L6 myoblasts

The present study was designed to investigate the mechanism through which leucine and histidine regulate translation initiation in L6 myoblasts. The results show that both amino acids stimulate initiation and coordinately regulate the activity of eukaryotic initiation factor eIF2B. The changes in eIF2B activity could be explained in part by modulation of the phosphorylation state of the alpha-subunit of eIF2. The activity changes might also be a result of modulation of the phosphorylation state of the eIF2B epsilon-subunit, because deprivation of either amino acid caused a decrease in eIF2Bepsilon kinase activity. Leucine, but not histidine, additionally caused a redistribution of eIF4E from the inactive eIF4E.4E-BP1 complex to the active eIF4E.eIF4G complex. The redistribution was a result of increased phosphorylation of 4E-BP1. The changes in 4E-BP1 phosphorylation and eIF4E redistribution associated with leucine deprivation were not observed in the presence of insulin. However, the leucine- and histidine-induced alterations in global protein synthesis and eIF2B activity were maintained in the presence of the hormone. Overall, the results suggest that both leucine and histidine regulate global protein synthesis through modulation of eIF2B activity. Furthermore, under the conditions employed herein, alterations in eIF4E availability are not rate-controlling for global protein synthesis but might be necessary for regulation of translation of specific mRNAs.     

Chitinolytic activity in Chromobacterium violaceum: substrate analysis and regulation by quorum sensing

Quorum sensing control mediated by N-acyl homoserine lactone (AHL) signaling molecules has been established as a key feature of the regulation of exoenzyme production in many gram-negative bacteria. In Chromobacterium violaceum ATCC 31532 a number of phenotypic characteristics, including production of the purple pigment violacein, hydrogen cyanide, antibiotics, and exoproteases are known to be regulated by the endogenous AHL N-hexanoyl-L-homoserine lactone (HHL). In this study we show that C. violaceum produces a set of chitinolytic enzymes whose production is regulated by HHL. The chitinolytic activity was induced in strains grown in the presence of chitin as the sole carbon source and quantitated in the secreted proteins by using p-nitrophenol analogs of disaccharide, trisaccharide, and tetrasaccharide oligomers of N-acetylglucosamine. By using 4-methylumbelliferyl analogs of the same oligomers of N-acetylglucosamine as substrates for proteins separated and renatured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, at least six enzymes were detected: a chitobiase with high specificity to a dimeric substrate of 87 kDa, two N-acetylglucosaminidases with apparent molecular masses of 162 and 133 kDa, two endochitinases of 108 and 67 kDa, and a chitobiosidase of 56 kDa. In addition, two unidentified bands of >205 kDa were found where a tetrameric chitin derivative was used as a substrate. A pleiotropic mini-Tn5 mutant of C. violaceum (CV026) that is defective in HHL production and other quorum-sensing-regulated factors was also found to be completely deficient in chitinolytic activity. Growth of this mutant on minimal medium with chitin supplemented with culture supernatant from the C. violaceum wild-type strain or 10 microM synthetic HHL restored chitinase production to the level shown by the parental strain. These results constitute the most complete evidence so far for regulation of chitinolytic activity by AHL signaling in a gram-negative bacterium.     

Pseudomonas keratitis. The role of an uncharacterized exoprotein, protease IV, in corneal virulence

PURPOSE: The role of exoproteins in the pathogenesis of Pseudomonas aeruginosa keratitis was investigated in three animal models by assessing the relationship between corneal virulence and the activities of exotoxin A, elastase, alkaline protease, and an uncharacterized protease, protease IV. METHODS: The four Pseudomonal strains tested included a prototype strain (ATCC 27853) producing exotoxin A, elastase, and alkaline protease; a parent strain (PA103) producing only exotoxin A and protease IV; a mutant (PA103-29) producing only protease IV; and a mutant (PA103-AP1) producing exotoxin A and having only approximately 5% of the protease IV activity of its parent. Corneal virulence was evaluated in the mouse scratch, rabbit scratch, and rabbit intrastromal models in terms of clinical signs (slit lamp examination, slit lamp examination), and viable bacteria. RESULTS: Protease IV, the only protease produced by PA103 and PA103-29, was found to produce a unique band on zymograms (120 kDa) and to react distinctively with a synthetic substrate. Evidence for the role of protease IV in corneal virulence included two findings: PA103-29,which produced protease IV but not the other exoproteins, caused infections that were as severe as those caused by the prototype strain (ATCC 27853) in all three models (P>0.24); and PA103-AP1, the strain deficient in 95% of the parent protease IV activity, mediated infections characterized by slit lamp examination scores significantly lower than those of infections caused by the parent (PA103) or the prototype strain (ATCC 27853) in the rabbit and mouse scratch models (P<0.02). CONCLUSIONS: Protease IV was found to be a novel Pseudomonas protease contributing to corneal virulence in rabbits and mice when infections were initiated at the corneal surface. Furthermore, production of protease IV in low quantities was sufficient for virulence when the topical stages of keratitis were bypassed by an intrastromal injection of Pseudomonas.     

Thoracoscopic T2-sympathetic block by clipping--a better and reversible operation for treatment of hyperhidrosis palmaris: experience with 326 cases

Although thoracoscopic sympathectomy or sympathicotomy is the best treatment for hyperhidrosis palmaris, a new approach of clipping only without transection of T2-sympathetic trunk is just as effective. Aside from the guaranteed cure of hyperhidrosis, this new method has fewer complications and has the advantage of recovery of the sympathetic tone in the hands if the procedure is reversed by the removal of the clips. Between March 18 and September 30 of 1996, 326 patients (190 female and 136 male with a mean age of 20.5 years) underwent thoracoscopic T2-sympathetic block by clipping to treat hyperhidrosis. Good results and few complications were noted during follow up six months to one year postoperatively. Five of the 326 patients, all female, had the operation reversed because of intolerable compensatory sweating. Three recovered from the compensatory sweating within two months and had less palmar sweating than before their sympathetic block; the fourth achieved relief of compensatory sweating after nine months, and the fifth reported no improvement.     

Normal relationships between cardiovascular variables in active orthostatism and clinostatism in postural change

OBJECTIVE: Autonomic modulation of hemodynamics, essential for the preservation of homeostasis, is well tested by the abrupt postural change from clinostatism to active orthostatism. The aim of this work was to study normal relationships between the cardiovascular variables in active orthostatism and those in clinostatism. METHODS: Hemodynamic parameters in clinostatism and orthostatism were easily measured in 20 healthy subjects of both sexes, aged between 33 and 78 years, without treatment, using the non-invasive thoracic electric bioimpedance method. RESULTS: Cardiovascular variables values in orthostatism are linearly related with their values in clinostatism. CONCLUSIONS: Results show that cardiovascular variables in active orthostatism are linearly related with their values in clinostatism, each variable being specially regulated. A clinostatism and orthostatism intraindividual correlation was obtained, which provides an easily accessible method of detection and interpretation of autonomic dysfunctions, without deleterious consequences for the subjects, which can be very useful for research on physiopathologic mechanisms.