Lipoprotein-associated phospholipase A2 and cardiovascular disease risk in HIV infection.

OBJECTIVES: HIV-infected patients on antiretroviral therapy (ART) have an increased cardiovascular disease (CVD) risk as a result of heightened inflammation and immune activation, despite at times having normal lipids and few traditional risk factors. Biomarkers are needed to identify such patients before a clinical event. Lipoprotein-associated phospholipase A2 (Lp-PLA2 ) predicts CVD events in the general population. This study investigated the relationship between Lp-PLA2 and markers of CVD risk, systemic inflammation, immune activation, and coagulation in HIV infection. METHODS: One hundred subjects on stable ART with normal fasting low-density lipoprotein (LDL) cholesterol were enrolled in the study. Plasma Lp-PLA2 concentrations were measured by enzyme-linked immunosorbent assay (ELISA; > 200 ng/mL was considered high CVD risk). Subclinical atherosclerosis, endothelial function, inflammation, immune activation and fasting lipids were also evaluated. RESULTS: The median age of the patients was 47 years and 77% were male. Median (range) Lp-PLA2 was 209 (71-402) ng/mL. Fifty-seven per cent of patients had Lp-PLA2 concentrations > 200 ng/mL. Lp-PLA2 was positively correlated with soluble markers of inflammation or immune activation (tumour necrosis factor receptor-II, intercellular and vascular cellular adhesion molecules, and CD14; all R = 0.3; P < 0.01), and negatively correlated with coagulation markers (D-dimer and fibrinogen; both R = -0.2; P < 0.04). Lp-PLA2 was not correlated with lipids, coronary artery calcium score, or flow-mediated vasodilation, but trended towards a significant correlation with carotid intima-media thickness (R = 0.2; P = 0.05). CONCLUSIONS: In this population with stable ART and normal LDL cholesterol, Lp-PLA2 was in the high CVD risk category in the majority of subjects. Lp-PLA2 appears to be associated with inflammation/immune activation, but also with anti-thrombotic effects. Lp-PLA2 may represent a valuable early biomarker of CVD risk in HIV infection before subclinical atherosclerosis can be detected.

Efficacy of pyramided Bt proteins Cry1F, Cry1A.105, and cry2Ab2 expressed in Smartstax corn hybrids against lepidopteran insect pests in the northern United States.

Commercial field corn (Zea mays L.) hybrids transformed to express some or all of the lepidopteran insect-resistant traits present in SmartStax corn hybrids were evaluated for insecticidal efficacy against a wide range oflepidopteran corn pests common to the northern United States, during 2008 to 2011 at locations in 15 states. SmartStax hybrids contain a pyramid of two Bacillus thuringiensis (Bt) derived events for lepidopteran control: event TC1507 expressing Cry1F protein and MON 89034 expressing CrylA.105 + Cry2Ab2. These studies focused on characterization of the relative efficacy of each event when expressed alone or in combination, and compared with non-Bt hybrid. Corn hybrids containing pyramided insecticidal proteins Cry1F + Cry1A.105 + Cry2Ab2 (SmartStax) consistently showed reduced plant feeding damage by a wide range of lepidopteran larvae compared with single event and non-Bt hybrids. Corn hybrids expressing TC1507 or MON 89034 as single or pyramided events were consistently efficacious against Ostrinia nubilalis (Hübner). SmartStax hybrids had less injury from Agrotis ipsilon (Hufnagel) and Striacosta albicosta (Smith) than corn hybrids containing only event MON 89034 but were not more efficacious than single event TC1507 hybrids. Corn hybrids with event MON 89034 provided better control of Helicoverpa zea (Boddie), than event TC1507 alone. Spodoptera frugiperda (J.E. Smith) efficacy was higher for hybrids with pyramid events and single events compared with the non-Bt hybrids. The spectra of activity of events TC1507 and MON 89034 differed. The combination of TC1507 + MON 89034 provided redundant control of some pests where the spectra overlapped and thereby are expected to confer a resistance management benefit.

Markers of inflammation and CD8 T-cell activation, but not monocyte activation, are associated with subclinical carotid artery disease in HIV-infected individuals.

OBJECTIVES: The aim of the study was to explore the relationships between lymphocyte and monocyte activation, inflammation, and subclinical vascular disease among HIV-1-infected patients on antiretroviral therapy (ART). METHODS: Baseline mean common carotid artery (CCA) intima-media thickness (IMT) and carotid plaque (IMT > 1.5 cm) were evaluated in the first 60 subjects enrolled in the Stopping Atherosclerosis and Treating Unhealthy Bone with Rosuvastatin in HIV (SATURN-HIV) trial. All subjects were adults on stable ART with evidence of heightened T-cell activation (CD8(+)CD38(+)HLA-DR(+) ≥ 19%) or increased inflammation (high-sensitivity C-reactive protein ≥ 2 mg/L). All had fasting low-density lipoprotein (LDL) cholesterol ≤ 130 mg/dL. RESULTS: Seventy-eight per cent of patients were men and 65% were African-American. Median (interquartile range) age and CD4 count were 47 (43, 52) years and 648 (511, 857) cells/µL, respectively. All had HIV-1 RNA < 400 HIV-1 RNA copies/mL. Mean CCA-IMT was correlated with log-transformed CD8(+)CD38(+)HLA-DR(+) percentage (r = 0.326; P = 0.043), and concentrations of interleukin-6 (r = 0.283; P = 0.028), soluble vascular cell adhesion molecule (sVCAM; r = 0.434; P = 0.004), tumour necrosis factor-α receptor-I (TNFR-I; r = 0.591; P < 0.0001) and fibrinogen (r = 0.257; P = 0.047). After adjustment for traditional cardiovascular disease (CVD) risk factors, the association with TNFR-I (P = 0.007) and fibrinogen (P = 0.033) remained significant. Subjects with plaque (n = 22; 37%) were older [mean (standard deviation) 51 (7.7) vs. 43 (9.4) years, respectively; P = 0.002], and had a higher CD8(+)CD38(+)HLA-DR(+) percentage [median (interquartile range) 31% (24, 41%) vs. 23% (20, 29%), respectively; P = 0.046] and a higher sVCAM concentration [mean (standard deviation) 737 (159) vs. 592 (160) ng/mL, respectively; P = 0.008] compared with those without plaque. Pro-inflammatory monocyte subsets and serum markers of monocyte activation (soluble CD163 and soluble CD14) were not associated with CCA-IMT or plaque. CONCLUSIONS: Participants in SATURN-HIV have a high level of inflammation and immune activation that is associated with subclinical vascular disease despite low serum LDL cholesterol.

Evaluation of corn hybrids expressing Cry34Ab1/Cry35Ab1 and Cry3BbL against the western corn rootworm (Coleoptera: Chrysomelidae).

Studies were conducted across nine U.S. states, over 5 yr, to characterize the efficacy of transgenic corn (Zea mays L.) hybrids producing insecticidal proteins derived from Bacillus thuringiensis (Bt) for control of western corn rootworm, Diabrotica virgifera virgifera Le Conte. Hybrids tested had the same genetic background, contained one of two single events (DAS-59122-7 expressing Cry34Ab1/Cry35Ab1 or MON 88017 expressing Cry3Bb1) or a pyramid consisting of both rootworm-active events (SmartStax traits) and were compared with a non-Bt near isoline. Frequency analyses of root feeding data showed that hybrids containing both events sustained less root damage (0-3 node injury scale) than hybrids containing either event alone. The levels of root protection provided by MON 88017 and DAS-59122-7 were not different from each other. Efficacy was also evaluated based on consistency of protection, based on the proportion of plants with root ratings of either < or = 0.25 or < 1.00 on the node injury scale. The combination of two modes of action in SmartStax provided greater product consistency over a single mode of action at the 0.25 level and all hybrids producing Bt proteins provided equally high consistency at the 1.00 level. Overall these data show single and multiple mode of action hybrids provided high, consistent protection over the past 5 yr across the trial geography; however, pyramiding the rootworm Bt events provided greater and more consistent root protection. These findings also support that pyramided traits like SmartStax (Cry3Bb1 + Cry34Ab1/Cry35Ab1) remain a viable strategy for delaying resistance to either trait.

Effects of in utero antiretroviral exposure on mitochondrial DNA levels, mitochondrial function and oxidative stress.

OBJECTIVES: HIV and antiretroviral (ART) exposure in utero may have deleterious effects on the infant, but uncertainty still exists. The objective of this study was to evaluate aspects of mitochondrial DNA (mtDNA) content, mitochondrial function and oxidative stress simultaneously in placenta, umbilical cord blood and infant blood in HIV/ART-exposed infants compared with uninfected controls. METHODS: HIV-1-infected pregnant women and HIV-1-uninfected healthy pregnant controls were enrolled in the study prospectively. Placenta and umbilical cord blood were obtained at delivery and infant blood was obtained within 48 h of delivery. mtDNA content was determined for each specimen. Nuclear [subunit IV of cytochrome c-oxidase (COX IV)]- and mitochondrial (COX II)-encoded polypeptides of the oxidative phosphorylation enzyme cytochrome c-oxidase were quantified in cord and infant blood. Placental mitochondria malondialdehyde (MDA) concentrations were measured as a marker of oxidative stress. RESULTS: Twenty HIV-positive/HIV-exposed and 26 control mother-infant pairs were enrolled in the study. All HIV-infected women and their infants received ART. Placental MDA concentration and mtDNA content in placenta and cord blood were similar between groups. The cord blood COX II:IV ratio was lower in the HIV-positive group than in the controls, whereas the infant peripheral blood mtDNA content was higher in the HIV-exposed infants, but the infant peripheral blood COX II:IV ratio was similar. No infant had clinical evidence of mitochondrial disease or acquired HIV infection. In multivariable regression analyses, the significant findings in cord and infant blood were both most associated with HIV/ART exposure. CONCLUSIONS: HIV-exposed infants showed reduced umbilical cord blood mitochondrial enzyme expression with increased infant peripheral blood mitochondrial DNA levels, the latter possibly reflecting a compensatory mechanism to overcome HIV/ART-associated mitochondrial toxicity.

Inheritance of Cry1F resistance in laboratory-selected European corn borer and its survival on transgenic corn expressing the Cry1F toxin.

A major assumption of the high-dose/refuge strategy proposed for insect resistance management strategies for transgenic crop plants that express toxins from Bacillus thuringiensis is that resistance traits that evolve in pest species will be recessive. The inheritance of Cry1F resistance and larval survival on commercially available Cry1F corn hybrids were determined in a laboratory-selected strain of European corn borer, Ostrinia nubilalis (Hübner), displaying more than 3000-fold resistance to Cry1F. Concentration-response bioassays of reciprocal parental crosses indicated that the resistance is autosomal and recessive. Bioassays of the backcross of the F1 generation with the selected strain were consistent with the hypothesis that a single locus, or a set of tightly linked loci, is responsible for the resistance. Greenhouse experiments with Cry1F-expressing corn hybrids indicated that some resistant larvae survived the high dose of toxin delivered by Cry1F-expressing plants although F1 progeny of susceptible by resistant crosses had fitness close to zero. These results provide the first direct evidence that the high dose/refuge strategy currently in place to manage resistance in Cry1F-expressing corn is appropriate.

Effects of Bt Corn and Egg Density on Western Corn Rootworm (Coleoptera: Chrysomelidae) Adult Emergence and Estimation of Effective Bt Dose.

Since 2003, rootworm-protected transgenic corn has been commercially deployed in the United States as a principal method of control of western corn rootworm, Diabrotica virgifera virgifera LeConte. Durability of this technology depends partly on larval mortality ("dose") exerted by the traits, but density-dependent mortality can confound calculations of dose. Research reported here examined the effects of density-dependent mortality on adult emergence and estimates of trait dose. At sites in Illinois and Indiana, western corn rootworm eggs were infested at four densities on non-Bt corn and at a single density on corn hybrids with transgenic events MON 88017 (VT Triple PRO), DAS-59122-7 (Herculex Insect Protection), and MON 88017 × DAS-59122-7 (SmartStax corn). Beetles were collected weekly in large emergence cages. Density-dependent mortality and the effect of Bt traits were examined using percent survival from egg to adult, sex ratio, and beetle mass. Beetle emergence from Bt treatments was very low, and percent survival from non-Bt treatments was greatest at the lowest egg density (410 eggs per row-meter). Therefore, emergence from the lowest infestation density on non-Bt corn was used to estimate the effective dose of the Bt treatments. Sex ratio and beetle mass were unaffected by density-dependent effects and were not consistently affected by Bt traits. Dose was estimated at 97.4-99.3% for MON 88017, 98.8-99.9% for DAS-59122-7, and 99.7-100.0% for MON 88017 × DAS-59122-7. This study confirms the need to account for density-dependent mortality when estimating dose of corn rootworm protection events even at relatively low egg infestation densities.

Life history traits of Helicoverpa zea (Lepidoptera: Noctuidae) on non-Bt and Bt transgenic corn hybrids in eastern North Carolina.

Transgenic varieties of field corn that express the CrylAb B. thuringiensis (Bt) toxin in ear tissue present the potential of reducing ear feeding by the corn earworm, Helicoverpa zea (Lepidoptera: Noctuidae), and for reducing the size of populations of the insect infesting other host crops. Life history parameters of H. zea feeding on ears of conventional and Bt field corn varieties were measured in field plots in eastern North Carolina in 1997 and 1998. Transformation events investigated were Mon-810 and Bt-11. Bt corn was found to cause a steady mortality of larvae during development, but permitted approximately 15-40% survival to the prepupal stage compared with non-Bt corn. Mortality of prepupae and pupae from Bt corn was also higher than from non-Bt corn, reducing overall adult production by 65-95%. The larvae that did survive grew more slowly on Bt than on non-Bt corn, and produced pupae that weighed 33% less. Pupation and adult eclosion were delayed by 6-10 d by feeding on Bt corn ears. Corn varieties expressing Bt in ear tissue have the potential to reduce H. zea ear feeding by up to 80%, and the potential to reduce populations emerging from ear-stage corn fields to infest cotton, soybean and other crops by around 75%. To have a measurable effect on area-wide populations, Bt corn varieties would need to be planted in large proportions of corn fields. Extensive planting of varieties such as those tested here, having only moderate effects on H. zea, would raise concerns about rapid evolution of resistance.

Co-injection strategies to modify radiation sensitivity and tumor initiation in transgenic Zebrafish.

The zebrafish has emerged as a powerful genetic model of cancer, but has been limited by the use of stable transgenic approaches to induce disease. Here, a co-injection strategy is described that capitalizes on both the numbers of embryos that can be microinjected and the ability of transgenes to segregate together and exert synergistic effects in forming tumors. Using this mosaic transgenic approach, gene pathways involved in tumor initiation and radiation sensitivity have been identified.

The hard sciences and the soft: some sociological observations.

The paper focuses on the implications of the terms "hard" and "soft" as they are used to characterize different branches of science; this is one approach to understanding some of the relations between knowledge and social organization. Given the importance to scientists of having their work evaluated accurately, it can be seen that the more rigorously a body of knowledge is organized, the more readily professional recognition can be appropriately assigned. The degree of rigor seems directly related to the extent to which mathematics is used in a science, and it is this that makes a science "hard." Data are presented in support of the hypothesis that "harder" sciences are characterized by more impersonality in their members' relationships where impersonality is indexed by the frequency that only first initials are used in footnotes. Finally, some parallels between the economic and the scientific sectors of society are suggested, viewing money and professional recognition as "generalized media" and noting certain analogies in science to inflation and deflation in the economic system. Implications for the obsolescence of parts of the literature of science are discussed, and the relevance of this analysis to Kuhn's work on scientific revolutions is briefly noted.

Life systems of polyphagous arthropod pests in temporally unstable cropping systems.

Annual cropping systems consist of a shifting mosaic of habitats that vary through time in their availability and suitability to insect pests. Agroecosystem instability results from changes that occur within a season with crop planting, development, and harvest. Further instability results from continuous alterations in biotic and abiotic insect life system components and from agricultural inputs. Changes to agroecosystems occur across seasons with changing agricultural practices, changing cropping patterns, and technological innovations. Much of this instability is a result of events unconnected with pest management. The abilities of polyphagous pest species to move among and utilize different habitat patches in response to changes in suitability enable the pests to exploit unstable cropping systems. These pest characteristics determine the location and timing of damaging populations. Habitat suitability is influenced by plant species and cultivar, crop phenology, and agricultural inputs. Pest movement is affected by a suite of intrinsic factors, such as population age structure and mobility, and extrinsic factors, including weather systems and habitat distribution. The life systems of three selected polyphagous pests are presented to demonstrate how an understanding of such systems in agricultural ecosystems improves our ability to predict and hence manage these populations.