Physical Activity and Sedentary Behavior of Cancer Survivors and Non-Cancer Individuals: Results from a National Survey

Increasing physical activity and decreasing sedentary behavior are associated with a higher quality of life and lower mortality rates for cancer survivors, a growing population group. Studies detailing the behavior of cancer survivors are limited. Therefore, we investigated physical activity and sedentary behavior of cancer survivors using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2010. Participants were those who provided physical activity and sedentary behavior data. Those who were pregnant, <20 years old, or <3 years from their cancer diagnosis were excluded. A cancer case was a self-reported diagnosis by a physician. We identified 741 cancer survivors and 10,472 non-cancer participants. After adjustment for age, race, gender, education status, body mass index, and smoking status, cancer survivors (n = 10,472) reported significantly longer duration of sedentary behavior (OR = 1.42, 95% CI (1.12, 1.80) for 8 or more hours, p-value for trend = 0.09), compared to non-cancer participants (n = 741). They also reported non-significant increases in maximum intensity, duration, frequency, and energy expenditure, whereas they reported significant increases in moderate intensity (OR = 1.26, 95% CI (1.01, 1.57)), moderate frequency (1–4 times/week) (OR = 1.32, 95% CI (1.00, 1.74)), and moderate energy expenditure (4018.5–7623.5 kcal) (OR = 1.30, 95% CI (1.00, 1.71)) of physical activity, compared to non-cancer participants. These patterns are similar for breast and prostate cancer survivors, with prostate cancer survivors more likely to engage in physical activity for more than one hour per day (OR = 1.98, 95% CI (1.05, 3.71)). Our findings suggest that cancer survivors tend to have more physical activity, but they are also more likely to engage in sedentary behavior.     

Gap junctions assemble in the presence of cytoskeletal inhibitors, but enhanced assembly requires microtubules

The role of cytoskeletal elements in gap junction (GJ) assembly has been studied using Novikoff hepatoma cells treated with cytochalasin B (CB) to disrupt actin filaments or with colchicine or nocodazole to disrupt microtubules. After 60 min of cell reaggregation, freeze-fracture was used to evaluate quantitatively the "initiation," "maturation," and "growth" phases of GJ assembly. The development of junctional permeability to fluorescent dyes was also analyzed. The only effects of CB on the structure or permeability of the developing junctions involved an elongation of GJ aggregates and a small decrease in formation plaque areas. Colchicine (but not the inactive form, lumicolchicine) prevented the enhancement of GJ growth by cholesterol, but its effect on basal growth was equivocal. Nocodazole inhibited the growth of GJ, even under basal conditions, without an effect on initiation. Nocodazole also blocked the forskolin-enhanced increase in the growth of GJs and, in living MDCK cells, reduced the movement of transport intermediates containing green fluorescent protein-tagged connexin43. Thus, neither actin filaments nor microtubules appear to restrict GJ assembly by anchoring intramembrane GJ proteins, nor are they absolutely required for functional GJs to form. However, microtubules are necessary for enhanced GJ growth and likely for facilitating connexin trafficking under basal conditions.     

Association of myelin basic protein with detergent micelles

Equilibrium measurements of the binding of central nervous system myelin basic protein to sodium dodecyl sulphate, sodium deoxycholate and lysophosphatidylcholine have been obtained by gel permeation chromatography and dialysis. This protein associates with large amounts of each of these surfactants: the apparent saturation weight ratios (surfactant/protein) being $\text{3.58 ± 0.12}\text{and}\text{2.30 ± 0.15}$ for dodecyl sulphate at ionic strengths 0.30 and 0.10, respectively, $\text{1.34 ± 0.10}$ for deoxycholate (at 0.12 ionic strength) and $\text{4.0 ± 0.5}$ for lysophosphatidylcholine. Binding to the ionic surfactants increases markedly close to their critical micelle concentrations. Sedimentation analysis shows that at 0.30 ionic strength in excess dodecyl sulphate the protein is monomeric. It becomes dimeric when the binding ratio falls below 1 at a free detergent concentration of approximately 0.25 mM: below this concentration much of the protein and detergent forms an insoluble complex. The amount of dodecyl sulphate bound at high concentrations and at both above-mentioned ionic strengths corresponds closely to that expected for interaction of a single polypeptide with two micelles. Variability of deoxycholate micelle size on interaction with other molecules precludes a similar analysis for this surfactant. Association was observed only with single micelles of lysophosphatidylcholine. The results provide strong evidence for dual lipid-binding sites on basic protein and indicate that lipid bilayer cross-linking by this protein may be effected by single molecules.     

The L33F darunavir resistance mutation acts as a molecular anchor reducing the flexibility of the HIV-1 protease 30s and 80s loops

HIV-1 protease (PR) is a 99 amino acid protein responsible for proteolytic processing of the viral polyprotein – an essential step in the HIV-1 life cycle. Drug resistance mutations in PR that are selected during antiretroviral therapy lead to reduced efficacy of protease inhibitors (PI) including darunavir (DRV). To identify the structural mechanisms associated with the DRV resistance mutation L33F, we performed X-ray crystallographic studies with a multi-drug resistant HIV-1 protease isolate that contains the L33F mutation (MDR769 L33F). In contrast to other PR L33F DRV complexes, the structure of MDR769 L33F complexed with DRV reported here displays the protease flaps in an open conformation. The L33F mutation increases noncovalent interactions in the hydrophobic pocket of the PR compared to the wild-type (WT) structure. As a result, L33F appears to act as a molecular anchor, reducing the flexibility of the 30s loop (residues 29–35) and the 80s loop (residues 79–84). Molecular anchoring of the 30s and 80s loops leaves an open S1/S1′ subsite and distorts the conserved hydrogen-bonding network of DRV. These findings are consistent with previous reports despite structural differences with regards to flap conformation.     

Comparative analysis of the plasmids from two isolates of "Candidatus Phytoplasma australiense"

Two plasmids from the plant-pathogenic mollicute "Candidatus Phytoplasma australiense" were completely sequenced from two isolates derived from different plant hosts. Plasmid pPAPh2 (3607bp) was obtained from Phormium showing Phormium yellow leaf symptoms and pPASb11 (3635bp) from strawberry showing strawberry lethal yellows symptoms. The plasmids varied in their copy number and nucleotide sequence yet contained the same four open reading frames (ORFs). The deduced amino acid sequence derived from ORF1 shares similarity with hypothetical proteins encoded on the plasmids from onion yellows and beet leafhopper-transmitted virescence agent phytoplasmas. The deduced amino acid sequences of both ORF2 and ORF3 share similarity with functionally unknown proteins on the chromosome of onion yellows phytoplasma. An ORF with a similar sequence to ORF2 is also present on the chromosome of "Ca. P. australiense." The deduced amino acid sequence derived from ORF4 is most similar to replication proteins encoded by other phytoplasma plasmids and by geminiviruses, the only protein on the plasmids for which a putative function can be assigned. The identities of the deduced amino acid sequences of ORF1, ORF2, ORF3, and ORF4 between pPAPh2 and pPASb11 were 89, 68, 91, and 68%, respectively; the differences being consistent with the subgroup status of the parental phytoplasmas.     

The elastic fiber. I. The separation and partial characterization of its macromolecular components

The two morphologically different constituents of the mature elastic fiber, the central amorphous and the peripheral microfibrillar components, have been separated and partially characterized. A pure preparation of elastic fibers was obtained from fetal bovine ligamentum nuchae by extraction of the homogenized ligament with 5 M guanidine followed by digestion with collagenase. The resultant preparation consisted of elastic fibers which were morphologically identical with those seen in vivo. The microfibrillar components of these elastic fibers were removed either by proteolytic enzymes or by reduction of disulfide bonds with dithioerythritol in 5 M guanidine. The microfibrils solubilized by both methods were rich in polar, hydroxy, and sulfur-containing amino acids and contained less glycine, valine, and proline than the amorphous component of the elastic fiber. In contrast, the amino acid composition of the amorphous component was identical with that previously described for elastin. This component demonstrated selective susceptibility to elastase digestion, but was relatively resistant to the action of other proteolytic enzymes and to reduction. These observations establish that the microfibrils consist of a different connective tissue protein (or proteins) that is neither collagen nor elastin. During embryologic development the microfibrils form an aggregate structure before the amorphous component is secreted. These microfibrils may therefore play a primary role in the morphogenesis of the elastic fiber.     

Physiological cost of running while wearing spring-boots

The purpose of the study was to investigate the physiological cost of running in spring-boots compared with running in running shoes at different speeds. During testing, subjects (n = 7) completed running trials while wearing spring-boots and running shoes. Three speed conditions (2.23, 2.68, and 3.13 m.s(-1)) were completed per shoe condition (i.e., spring-boots and running shoes). Rate of oxygen consumption (Vo(2)), heart rate (HR), rating of perceived exertion (RPE), and stride frequency were recorded for each condition. Order of shoe conditions was balanced, with speeds tested continuously from slow to fast. There was no difference in Vo(2), HR, or RPE between shoe conditions across speeds (p > 0.05). Stride frequency was lower during running in spring-boots vs. running shoes at each speed (speed of spring-boots vs. running shoes for 2.23 m x s(-1): 69.9 +/- 2.9 strides x min(-1) vs. 75.6 +/- 3.5 strides x min(-1); for 2.68 m x s(-1): 71.3 +/- 5.2 strides x min(-1) vs. 79.4 +/- 5.0 strides x min(-1); for 3.13 m x s(-1): 73.6 +/- 7.3 strides x min(-1) vs. 83.1 +/- 8.2 strides x min(-1); p < 0.05). Despite the added mass to the lower extremity and change in stride frequency during running in spring-boots, the physiological cost of running was similar to that of running in running shoes. Exercising while running in spring-boots may provide less impact force with no change in running economy.     

The evolution and suppression of male suicide under paternal genome elimination

Different genetic systems can be both the cause and the consequence of genetic conflict over the transmission of genes, obscuring their evolutionary origin. For instance, with paternal genome elimination (PGE), found in some insects and mites, both sexes develop from fertilized eggs, but in males the paternally derived chromosomes are either lost (embryonic PGE) or deactivated (germline PGE) during embryogenesis and not transmitted to the next generation. Evolution of germline PGE requires two transitions: (1) elimination of the paternal genome during spermatogenesis; (2) deactivation of the paternal genome early in development. Hypotheses for the evolution of PGE have mainly focused on the first transition. However, maternal genes seem to be responsible for the deactivation and here we investigate if maternal suppression could have evolved in response to paternally expressed male suicide genes. We show that sibling competition can cause such genes to spread quickly and that inbreeding is necessary to prevent fixation of male suicide, and subsequent population extinction. Once male-suicide has evolved, maternally expressed suppressor genes can invade in the population. Our results highlight the rich opportunity for genetic conflict in asymmetric genetic systems and the counterintuitive phenotypes that can evolve as a result.     

Multiple carbohydrate receptors on lymphocytes revealed by adhesion to immobilized polysaccharides

Phosphomannan polysaccharides and fucoidan, a polymer of fucose 4-sulfate, have been demonstrated to inhibit adhesion of lymphocytes to tissue sections that contain high endothelial venules (Stoolman, L. M., T. S. Tenforde, and S. D. Rosen, 1984, J. Cell Biol., 99:1535-1540). We have investigated the potential cell surface carbohydrate receptors involved by quantitating adhesion of rat cervical lymph node lymphocytes to purified polysaccharides immobilized on otherwise inert polyacrylamide gels. One-sixth of the lymphocytes adhered specifically to surfaces derivatized with PPME (a phosphomannan polysaccharide prepared from Hansenula holstii yeast), whereas up to half of the cells adhered to surfaces derivatized with fucoidan. Several lines of evidence demonstrated that two distinct receptors were involved. Adhesion to PPME-derivatized gels was labile at 37 degrees C (decreasing to background levels within 120 min) whereas adhesion to fucoidan-derivatized gels was stable. Soluble PPME and other phosphomannans blocked adhesion only to PPME-derivatized gels; fucoidan and a structurally related fucan blocked adhesion to fucoidan-derivatized gels. Other highly charged anionic polysaccharides, such as heparin, did not block adhesion to either polysaccharide-derivatized gel. Adhesion to PPME-derivatized gels was dependent on divalent cations, whereas that to fucoidan-derivatized gels was not. The PPME-adherent lymphocytes were shown to be a subpopulation of the fucoidan-adhesive lymphocytes which contained both saccharide receptors. These data reveal that at least two distinct carbohydrate receptors can be found on peripheral lymphocytes.