Precision of herbivore tolerance experiments with imposed and natural damage

Tiffin and Inouye (2000) discussed the use of natural and imposed (controlled) damage in experiments of herbivore tolerance. They constructed a statistical model of the effect of herbivory on plant fitness, including damage level and an environmental factor as the independent factors, in which tolerance is defined as a slope of the regression line when damage level is regressed with plant fitness. They claim that while experiments with imposed damage are more accurate (i.e., they give a more correct estimate of tolerance), experiments with natural damage are more precise under a wide range of parameter values (i.e., tolerance estimates explain a larger part of variation in fitness). I show, however, that experiments with imposed damage are less precise only when an experimenter uses an experimental design that has weaker statistical power than in experiments with natural herbivory. The experimenter can nevertheless control the damage levels to optimize the experimental designs. For instance, when half of the experimental plants are left undamaged and the other half treated with maximal relevant damage level, experiments with imposed damage are almost always much more precise than experiments with natural damage.     

No evidence of interaction between known lipid-associated genetic variants and smoking in the multi-ethnic PAGE population

Genome-wide association studies (GWAS) have identified many variants that influence high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and/or triglycerides. However, environmental modifiers, such as smoking, of these known genotype–phenotype associations are just recently emerging in the literature. We have tested for interactions between smoking and 49 GWAS-identified variants in over 41,000 racially/ethnically diverse samples with lipid levels from the Population Architecture Using Genomics and Epidemiology (PAGE) study. Despite their biological plausibility, we were unable to detect significant SNP × smoking interactions.     

Metabolic changes in some acclimation phenomena

Summary 1. Acclimation to constant cold also causes in mice a decrease in the intensity of muscle shivering in cold and an increase in the metabolic rate of the animal and in the succinic dehydrogenase complex activity in the liver and skeletal muscles.2. The succinic dehydrogenase complex activity in the liver depends on the acclimation temperature at least over a range from 5° to 32° C.3. Acclimation of mice to short-term exposures to cold does not affect metabolic rate of the animals or the succinic dehydrogenase complex activity in the liver but causes an increase in the metabolic response to injected l-noradrenaline.4. The induced tolerance to the hypothermisant effect of promazine in mice develops slower in a thermoneutral environment than at room temperature.

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Stoffwechselveränderungen bei einigen Akklimatisierungsphänomenen

Kurzfassung Schon in früheren Untersuchungen wurde nachgewiesen, daß die Akklimatisierung von Ratten an konstante niedrige Temperaturen von stoffwechselphysiologischen Veränderungen im Bereich der Zellen begleitet werden. Nach unseren Untersuchungen verursacht Anpassung an konstante niedrige Temperaturen auch bei Laboratoriumsmäusen eine Abnahme der Intensität des Muskelzitterns in der Kälte, einen Anstieg der Stoffwechselrate des Tieres sowie der Aktivität des Sukzinodehydrogenase-Komplexes in Leber und Skelettmuskeln. Die Sukzinodehydrogenaseaktivität in der Leber männlicher Mäuse zeigt eine Abhängigkeit von der Anpassungstemperatur, zumindest über den Bereich von 5° bis 32° C. Mäuse können ferner daran angepaßt werden, daß sie wirksamer auf kurzfristige Kälteeinwirkungen reagieren. Derartige Anpassungen beeinflussen jedoch nicht die Stoffwechselrate oder die Aktivität des Sukzinodehydrogenase-Komplexes in der Leber, sondern verursachen eine gesteigerte stoffwechselphysiologische Reaktion auf injiziertes 1-Noradrenalin. Die induzierte Widerstandsfähigkeit gegenüber der temperatursenkenden Wirkung des Phenothiazinderivates Promazin entfaltet sich bei Mäusen in einer thermoneutralen Umgebung langsamer als bei Zimmertemperatur. Dieser Umstand deutet auf Ähnlichkeiten hin, welche bei den ersten Stadien der Promazintoleranz und der Akklimatisierung an kurzfristige Kälteeinwirkungen bestehen.

     

Chromosomal localization of the human hexabrachion (tenascin) gene and evidence for recent reduplication within the gene

Using analysis of rodent-human somatic cell hybrids as well as in situ hybridization of hexabrachion cDNA probes to normal human metaphase chromosomes, we have localized the human hexabrachion gene to chromosome 9, bands q32-q34. We also put forward the hypothesis that there has been a recent reduplication of a small segment of the human hexabrachion gene. We support this hypothesis by comparison of codon usage in this segment of the gene to codon usage in the remainder of the gene. This hypothesis is also supported by comparison of the sequence of human hexabrachion to that of the chicken hexabrachion. In addition, the latter comparison shows that the reduplication most likely occurred after the divergence of mammalian and avian species.     

Mechanisms of human immunodeficiency virus type 2 RNA packaging: efficient trans packaging and selection of RNA copackaging partners

Human immunodeficiency virus type 2 (HIV-2) has been reported to have a distinct RNA packaging mechanism, referred to as cis packaging, in which Gag proteins package the RNA from which they were translated. We examined the progeny generated from dually infected cell lines that contain two HIV-2 proviruses, one with a wild-type gag/gag-pol and the other with a mutant gag that cannot express functional Gag/Gag-Pol. Viral titers and RNA analyses revealed that mutant viral RNAs can be packaged at efficiencies comparable to that of viral RNA from which wild-type Gag/Gag-Pol is translated. These results do not support the cis-packaging hypothesis but instead indicate that trans packaging is the major mechanism of HIV-2 RNA packaging. To further characterize the mechanisms of HIV-2 RNA packaging, we visualized HIV-2 RNA in individual particles by using fluorescent protein-tagged RNA-binding proteins that specifically recognize stem-loop motifs in the viral genomes, an assay termed single virion analysis. These studies revealed that >90% of the HIV-2 particles contained viral RNAs and that RNAs derived from different viruses were copackaged frequently. Furthermore, the frequencies of heterozygous particles in the viral population could be altered by changing a 6-nucleotide palindromic sequence at the 5'-untranslated region of the HIV-2 genome. This finding indicates that selection of copackaging RNA partners occurs prior to encapsidation and that HIV-2 Gag proteins primarily package one dimeric RNA rather than two monomeric RNAs. Additionally, single virion analyses demonstrated a similar RNA distribution in viral particles regardless of whether both viruses had a functional gag or one of the viruses had a nonfunctional gag, providing further support for the trans-packaging hypothesis. Together, these results revealed mechanisms of HIV-2 RNA packaging that are, contrary to previous studies, in many respects surprisingly similar to those of HIV-1.     

Skeletal muscle blood flow and oxygen uptake at rest and during exercise in humans: a pet study with nitric oxide and cyclooxygenase inhibition

The aim of the present study was to determine the effect of nitric oxide and prostanoids on microcirculation and oxygen uptake, specifically in the active skeletal muscle by use of positron emission tomography (PET). Healthy males performed three 5-min bouts of light knee-extensor exercise. Skeletal muscle blood flow and oxygen uptake were measured at rest and during the exercise using PET with H(2)O(15) and (15)O(2) during: 1) control conditions; 2) nitric oxide synthase (NOS) inhibition by arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA), and 3) combined NOS and cyclooxygenase (COX) inhibition by arterial infusion of L-NMMA and indomethacin. At rest, inhibition of NOS alone and in combination with indomethacin reduced (P < 0.05) muscle blood flow. NOS inhibition increased (P < 0.05) limb oxygen extraction fraction (OEF) more than the reduction in muscle blood flow, resulting in an ～20% increase (P < 0.05) in resting muscle oxygen consumption. During exercise, muscle blood flow and oxygen uptake were not altered with NOS inhibition, whereas muscle OEF was increased (P < 0.05). NOS and COX inhibition reduced (P < 0.05) blood flow in working quadriceps femoris muscle by 13%, whereas muscle OEF and oxygen uptake were enhanced by 51 and 30%, respectively. In conclusion, by specifically measuring blood flow and oxygen uptake by the use of PET instead of whole limb measurements, the present study shows for the first time in humans that inhibition of NO formation enhances resting muscle oxygen uptake and that combined inhibition of NOS and COX during exercise increases muscle oxygen uptake.     

Dose effects of transfected c-Ha-ras oncogene in transformed cell clones

We have examined the expression of the transformed phenotype in a series of clonal lines of NIH/3T3 cells transfected with the human c-Ha-ras^{Val 12} oncogene and the neomycin phosphotransferase gene. Cells from individual transformed foci were cloned and subjected to detailed analyses of the ras sequences. Three clones were found that expressed approximately one, 2–4, or 4–8 copies of the human c-ras oncogene, respectively. A fourth clone had multiple copies of the transfected sequences, and expressed abundant c-Ha-ras RNA. Analysis of the tranformed phenotype of various clones indicated that cells expressing low levels of mutant c-Ha-ras had lost some of their extracellular fibronectin network, and were barely altered in their cytoskeleton. In contrast, cells expressing abundant c-Ha-ras had lost both their actin and fibronectin networks and showed an increase in plasminogen activator activity. Cells with amplified c-Ha-ras^{Val 12} grew better in low serum, formed large colonies in soft agar and showed enhanced activity of ornithine decarboxylase, the rate-controlling enzyme in polyamine biosynthesis. These results show that the dosage level of the mutant oncogene makes a significant contribution to the transformed phenotype of c-Ha-ras oncogene-transformed cells.     

Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDGene database

More than 800 published genetic association studies have implicated dozens of potential risk loci in Parkinson's disease (PD). To facilitate the interpretation of these findings, we have created a dedicated online resource, PDGene, that comprehensively collects and meta-analyzes all published studies in the field. A systematic literature screen of -27,000 articles yielded 828 eligible articles from which relevant data were extracted. In addition, individual-level data from three publicly available genome-wide association studies (GWAS) were obtained and subjected to genotype imputation and analysis. Overall, we performed meta-analyses on more than seven million polymorphisms originating either from GWAS datasets and/or from smaller scale PD association studies. Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls. Eleven loci showed genome-wide significant (P < 5 × 10(-8)) association with disease risk: BST1, CCDC62/HIP1R, DGKQ/GAK, GBA, LRRK2, MAPT, MCCC1/LAMP3, PARK16, SNCA, STK39, and SYT11/RAB25. In addition, we identified novel evidence for genome-wide significant association with a polymorphism in ITGA8 (rs7077361, OR 0.88, P = 1.3 × 10(-8)). All meta-analysis results are freely available on a dedicated online database (www.pdgene.org), which is cross-linked with a customized track on the UCSC Genome Browser. Our study provides an exhaustive and up-to-date summary of the status of PD genetics research that can be readily scaled to include the results of future large-scale genetics projects, including next-generation sequencing studies.