The psychophysiological correlates of cognitive dissonance.

This preregistered study uses a combination of physiological measures to explore both the activation and reduction components of cognitive dissonance theory. More precisely, we use skin conductance to identify dissonance arousal, a short-term affective response to counter-attitudinal stimuli, and then use heart rate variability to measure dissonance reduction, which reflects longer-term patterns of emotional regulation and information processing. Our preliminary tests find weak evidence of dissonance arousal and no evidence of dissonance reduction using this physiological approach. We consequently reconsider (albeit optimistically) the use of physiology in future work on cognitive dissonance. We also discuss the implications of our findings for selective exposure and motivated reasoning.

Design and evaluation of a biosynthesized cellulose drug releasing duraplasty.

Decompressive craniectomy (DC) is a standard surgical procedure performed on stroke patients in which a portion of a skull is removed and a duraplasty membrane is applied onto the brain. While DC can significantly reduce the risk of death, it does not reverse the stroke damage. In this study, a novel biosynthesized cellulose (BC)-based drug releasing duraplasty was developed and studied. The BC duraplasty fabrication process allowed readily incorporation of growth factors (GFs) in a sterile manner and control of physical and mechanical properties of the resulting duraplasty. Our results showed that BC duraplasty containing the highest amount of dry cellulose presented swelling ratio of 496 ± 27%, Young's modulus of 0.37 ± 0.02 MPa, ultimate tensile strength of 0.96 ± 0.02 MPa, while releasing GFs for over 10 days. In addition, neural stem/progenitor cell (NSPC) cultures demonstrated that the GFs released from the BC duraplasty promoted NSPC proliferation and differentiation in vitro. Finally, animal studies revealed that the BC duraplasty did not cause any inflammatory reactions after the DC procedure in vivo. In summary, this newly developed GF loaded BC membrane demonstrates a promising potential as drug releasing duraplasty, not only for stroke treatments but also for traumatic brain injuries and spinal cord injuries.

The protein tyrosine phosphatase PTPRJ/DEP-1 contributes to the regulation of the Notch-signaling pathway and sprouting angiogenesis.

The Dll4-Notch-signaling pathway regulates capillary sprouting via the specification of endothelial tip cells. While VEGF is a potent inducer of Dll4 expression, the intracellular mediators that stimulate its expression remain poorly defined. The protein tyrosine phosphatase PTPRJ/DEP-1 is required for angiogenesis in normal or pathological contexts through its modulation of VEGF signaling. Here, we show that in DEP-1 KO mice, retinas at post-natal day 5 show enlarged blood vessels, as well as an increased number of tip cells and vessel branching points at the migrating front of the vascular plexus. Consistent with these observations, the proliferation of endothelial cells is increased in the retinas of DEP-1 KO mice, as revealed by phospho-histone H3 staining, and increased phosphorylation of ERK1/2 in HUVECs transfected with DEP-1 siRNA. The expression of Dll4 was decreased in retinas of DEP-1 KO mice and was associated with decreased Notch activation. Mechanistically, reduced Dll4 expression in the absence of DEP-1 was correlated with the inhibition of the Src/Akt/ß-Catenin-signaling pathway in HUVECs. Conversely, overexpression of WT DEP-1 in cultured endothelial cells, but not of mutants unable to activate Src-dependent signaling, promoted Dll4 expression. Inhibition of Src, Akt, and ß-catenin transcriptional activity, leading to the inhibition of Dll4 expression, further suggested that their activation through a DEP-1-dependent pathway was required to promote Dll4 expression in VEGF-stimulated endothelial cells. Altogether, these data demonstrate that DEP-1, via Akt and ß-catenin, is a significant promoter of the VEGF-induced Dll4-Notch pathway, and can contribute to the regulation of the tip and stalk cell phenotypes of endothelial cells.

Cross-national evidence of a negativity bias in psychophysiological reactions to news.

What accounts for the prevalence of negative news content? One answer may lie in the tendency for humans to react more strongly to negative than positive information. "Negativity biases" in human cognition and behavior are well documented, but existing research is based on small Anglo-American samples and stimuli that are only tangentially related to our political world. This work accordingly reports results from a 17-country, 6-continent experimental study examining psychophysiological reactions to real video news content. Results offer the most comprehensive cross-national demonstration of negativity biases to date, but they also serve to highlight considerable individual-level variation in responsiveness to news content. Insofar as our results make clear the pervasiveness of negativity biases on average, they help account for the tendency for audience-seeking news around the world to be predominantly negative. Insofar as our results highlight individual-level variation, however, they highlight the potential for more positive content, and suggest that there may be reason to reconsider the conventional journalistic wisdom that "if it bleeds, it leads."

[Forests and health: Discourse and practises from the 18st to the 21st century]. / Forêt et santé : discours et pratiques du XVIIIe au XXIe siècle.

The relations between forests and health carry ambivalent representations anchored in a long history. The dangers of deforestation and the usefulness of woodland to counter the "miasmas" and later the "pollution" are consistent with a Hippocratic approach that was reinterpreted at the end of the 18th century in the light of new knowledge in chemistry and biology. As of the 1970's, biodiversity was taken into consideration for the purposes of protecting and preserving forests seen as indispensable factors for public health. Conversely, the threats coming from tropical forests, that had been recognized for at least three centuries, and forest zoonoses that have been better identified all over the world in recent decades, are the negative side of this health-oriented representation of the role of forests. The analysis conducted in this article focuses on showing how these seemingly opposite views are actually complementary: once the mechanisms behind the diseases are better understood, the conservation of forests and their renewal become major goals for the populations concerned and for public authorities on the local, national and international scales, acting through numerous scientific studies and the establishment of public and private organisations. In this area, the role played by France is still too limited. A scrutiny of the last three centuries provides a better understanding of the essential character of social demands, cultural representations and medical expertise in the implementation of forest therapy and health-oriented environmental policies.

Genotypic and environmental effects on the level of ascorbic acid, phenolic compounds and related gene expression during pineapple fruit development and ripening.

Pineapple (Ananas comosus (L.) Merr.) is a non-climacteric tropical fruit whose ripening could be accompanied by oxidative processes and the concurrent activation of enzymatic and non-enzymatic reactive oxygen species (ROS) scavenging systems. To better understand the variability of these processes among climatic environments or genotypes in pineapple, the temporal expression dynamics for genes encoding oxidative and antioxidative stress enzymes were analyzed by real-time RT-PCR during fruit development and ripening, among three cultivars: Queen Victoria, Flhoran 41 and MD-2 hybrid, and in two climatic areas. Pineapple development and ripening involved changes in the levels of transcripts encoding for polyphenol oxidase and transcripts involved in the first steps of the phenylpropanoid pathway and in the balance of ROS, especially those encoding for ascorbate peroxydase and metallothioneins, regardless of the cultivar. Our results confirm the same dynamic in gene expression from the two environmental crop areas, however climatic conditions influenced the level of the expression of the major transcripts studied that were linked to these oxidative and antioxidant metabolisms. MT3a and MT3b transcripts were not influenced by genetic factor. The genetic effect was not significant on the various transcripts linked to the first steps of the phenylpropanoid pathway and to phenol oxidation, except 4CL ones. In ripe pineapple, highly significant relationships were found between the contents in antioxidant metabolites, i.e., ascorbic acid and total phenolic compounds, and the transcript levels of genes involved in the enzymatic ROS-scavenging system and in the biosynthesis or regeneration of ROS-scavenging compounds, like phenylpropanoids, ascorbic acid, metallothioneins.

Tyrosine Phosphatase PTPRJ/DEP-1 Is an Essential Promoter of Vascular Permeability, Angiogenesis, and Tumor Progression.

The protein tyrosine phosphatase PTPRJ/DEP-1 has been implicated in negative growth regulation in endothelial cells, where its expression varies at transitions between proliferation and contact inhibition. However, in the same cells, DEP-1 has also been implicated in VEGF-dependent Src activation, permeability, and capillary formation, suggesting a positive role in regulating these functions. To resolve this dichotomy in vivo, we investigated postnatal angiogenesis and vascular permeability in a DEP-1-deficient mouse. In this study, we report that DEP-1 is required for Src activation and phosphorylation of its endothelial cell-specific substrate, VE-cadherin, after systemic injection of VEGF. Accordingly, VEGF-induced vascular leakage was abrogated in the DEP-1-deficient mice. Furthermore, capillary formation was impaired in murine aortic tissue rings or Matrigel plugs infused with VEGF. In the absence of DEP-1, angiogenesis triggered by ischemia or during tumor formation was defective, which in the latter case was associated with reduced tumor cell proliferation and increased apoptosis. Macrophage infiltration was also impaired, reflecting reduced vascular permeability in the tumors or a possible cell autonomous effect of DEP-1. Consequently, the formation of spontaneous and experimental lung metastases was strongly decreased in DEP-1-deficient mice. In clinical specimens of cancer, less vascularized tumors exhibited lower microvascular expression of DEP-1. Altogether, our results established DEP-1 as an essential driver of VEGF-dependent permeability, angiogenesis, and metastasis, suggesting a novel therapeutic route to cancer treatment. Cancer Res; 76(17); 5080-91. ©2016 AACR.

CdGAP/ARHGAP31, a Cdc42/Rac1 GTPase regulator, is critical for vascular development and VEGF-mediated angiogenesis.

Mutations in the CdGAP/ARHGAP31 gene, which encodes a GTPase-activating protein for Rac1 and Cdc42, have been reported causative in the Adams-Oliver developmental syndrome often associated with vascular defects. However, despite its abundant expression in endothelial cells, CdGAP function in the vasculature remains unknown. Here, we show that vascular development is impaired in CdGAP-deficient mouse embryos at E15.5. This is associated with superficial vessel defects and subcutaneous edema, resulting in 44% embryonic/perinatal lethality. VEGF-driven angiogenesis is defective in CdGAP(-/-) mice, showing reduced capillary sprouting from aortic ring explants. Similarly, VEGF-dependent endothelial cell migration and capillary formation are inhibited upon CdGAP knockdown. Mechanistically, CdGAP associates with VEGF receptor-2 and controls VEGF-dependent signaling. Consequently, CdGAP depletion results in impaired VEGF-mediated Rac1 activation and reduced phosphorylation of critical intracellular mediators including Gab1, Akt, PLCγ and SHP2. These findings are the first to demonstrate the importance of CdGAP in embryonic vascular development and VEGF-induced signaling, and highlight CdGAP as a potential therapeutic target to treat pathological angiogenesis and vascular dysfunction.

Novel radiolabeled peptides for breast and prostate tumor PET imaging: (64)Cu/and (68)Ga/NOTA-PEG-[D-Tyr(6),ßAla(11),Thi(13),Nle(14)]BBN(6-14).

Bombesin (BBN)-based radiolabeled peptides exhibit promising properties for targeted imaging of gastrin-releasing peptide receptors (GRPR)-positive tumors. The aim of this study was to evaluate with positron emission tomography (PET) the pharmacokinetic and imaging properties of two novel BBN-based radiolabeled peptides, (64)Cu/and (68)Ga/NOTA-PEG-BBN(6-14), for diagnosis of breast and prostate cancers using small animal models. Competitive binding assays on T47D breast and PC3 prostate cancer cells showed that the affinity for GRPR depends on the complexed metal and can vary up to a factor of about 3; (64)Cu/NOTA-PEG-BBN(6-14) was found to have the lowest inhibition constant (1.60 ± 0.59 nM). (64)Cu/and (68)Ga/NOTA-PEG-BBN(6-14) presented similar cell uptake on T47D and PC3 cells and were stable in vivo. Biodistribution studies of radiolabeled peptides carried out in Balb/c and tumor-bearing Balb/c nude mice showed that (64)Cu/NOTA-PEG-BBN(6-14) presented higher GRPR-mediated uptake in pancreas and adrenal glands, but comparable PC3 tumor uptake as (68)Ga/NOTA-PEG-BBN(6-14). Finally, receptor-dependent responses were observed during blocking studies with unlabeled peptide in both biodistribution and small-animal PET imaging studies. Our results confirmed the dependence of the affinity and pharmacokinetics of BBN-based radiopeptides on the complexed radiometal. Interspecies differences between mouse and human GRPR binding properties were also noted in these preclinical studies. Considering their good imaging characteristics, both (64)Cu/NOTA-PEG-BBN(6-14) and (68)Ga/NOTA-PEG-BBN(6-14) are promising candidates for GRPR-targeted PET imaging of breast and prostate cancers.

Annexin-1-mediated endothelial cell migration and angiogenesis are regulated by vascular endothelial growth factor (VEGF)-induced inhibition of miR-196a expression.

Endothelial cell migration induced in response to vascular endothelial growth factor (VEGF) is an essential step of angiogenesis. It depends in part on the activation of the p38/MAPKAP kinase-2/LIMK1/annexin-A1 (ANXA1) signaling axis. In the present study, we obtained evidence indicating that miR-196a specifically binds to the 3'-UTR region of ANXA1 mRNA to repress its expression. In accordance with the role of ANXA1 in cell migration and angiogenesis, the ectopic expression of miR-196a is associated with decreased cell migration in wound closure assays, and the inhibitory effect of miR-196a is rescued by overexpressing ANXA1. This finding highlights the fact that ANXA1 is a required mediator of VEGF-induced cell migration. miR-196a also reduces the formation of lamellipodia in response to VEGF suggesting that ANXA1 regulates cell migration by securing the formation of lamellipodia at the leading edge of the cell. Additionally, in line with the fact that cell migration is an essential step of angiogenesis, the ectopic expression of miR-196a impairs the formation of capillary-like structures in a tissue-engineered model of angiogenesis. Here again, the effect of miR-196a is rescued by overexpressing ANXA1. Moreover, the presence of miR-196a impairs the VEGF-induced in vivo neo-vascularization in the Matrigel Plug assay. Interestingly, VEGF reduces the expression of miR-196a, which is associated with an increased level of ANXA1. Similarly, the inhibition of miR-196a with an antagomir results in an increased level of ANXA1. We conclude that the VEGF-induced decrease of miR-196a expression may participate to the angiogenic switch by maintaining the expression of ANXA1 to levels required to enable p38-ANXA1-dependent endothelial cell migration and angiogenesis in response to VEGF.

Comparative study of 64Cu/NOTA-[D-Tyr6,ßAla11,Thi13,Nle14]BBN(6-14) monomer and dimers for prostate cancer PET imaging.

BACKGROUND: Gastrin-releasing peptide receptors [GRPR] are highly over-expressed in multiple cancers and have been studied as a diagnostic target. Multimeric gastrin-releasing peptides are expected to have enhanced tumor uptake and affinity for GRPR. In this study, a 64Cu-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid [NOTA]-monomer and two NOTA-dimers of [D-Tyr6,ßAla11, Thi13, Nle14]bombesin(6-14) ] [BBN(6-14)] were compared. METHODS: Monomeric and dimeric peptides were synthesized on solid phase support and radiolabeled with 64Cu. NOTA-dimer 1 consists of asymmetrically linked BBN(6-14), while NOTA-dimer 2 has similar spacer between the two BBN(6-14) ligands and the chelator. In vitro GRPR-binding affinities were determined with competitive binding assays on PC3 human prostate cancer cells. In vivo stability and biodistribution of radiolabeled compounds were assessed in Balb/c mice. Cellular uptake and efflux were measured with radiolabeled NOTA-monomer and NOTA-dimer 2 on PC3 cells for up to 4 h. In vivo biodistribution kinetics were measured in PC3 tumor-bearing Balb/c nude mice by µ-positron emission tomography [µPET] imaging and confirmed by dissection and counting. RESULTS: NOTA-monomer, NOTA-dimers 1 and 2 were prepared with purity of 99%. The inhibition constants of the three BBN peptides were comparable and in the low nanomolar range. All 64Cu-labeled peptides were stable up to 24 h in mouse plasma and 1 h in vivo. 64Cu/NOTA-dimer 2 featuring a longer spacer between the two BBN(6-14) ligands is a more potent GRPR-targeting probe than 64Cu/NOTA-dimer 1. PC3 tumor uptake profiles are slightly different for 64Cu/NOTA-monomer and 64Cu/NOTA-dimer 2; the monomeric BBN-peptide tracer exhibited higher tumor uptake during the first 0.5 h and a fast renal clearance resulting in higher tumor-to-muscle ratio when compared to 64Cu/NOTA-dimer 2. The latter exhibited higher tumor-to-blood ratio and was retained longer at the tumor site when compared to 64Cu/NOTA-monomer. Lower ratios of tumor-to-blood and tumor-to-muscle in blocking experiments showed GRPR-dependant tumor uptake for both tracers. CONCLUSION: Both 64Cu/NOTA-monomer and 64Cu/NOTA-dimer 2 are suitable for detecting GRPR-positive prostate cancer in vivo by PET. Tumor retention was improved in vivo with 64Cu/NOTA-dimer 2 by applying polyvalency effect and/or statistical rebinding.

Evaluation of 64Cu-labeled bifunctional chelate-bombesin conjugates.

Several bifunctional chelates (BFCs) were investigated as carriers of (64)Cu for PET imaging. The most widely used chelator for (64)Cu labeling of BFCs is DOTA (1,4,7,10-tetraazacyclododecane-N,N',N″,N'''-tretraacetic acid), even though this complex exhibits only moderate in vivo stability. In this study, we prepared a series of alternative chelator-peptide conjugates labeled with (64)Cu, measured in vitro receptor binding affinities in human breast cancer T47D cells expressing the gastrin-releasing peptide receptor (GRPR) and compared their in vivo stability in mice. DOTA-, NOTA-(1,4,7-triazacyclononane-1,4,7-triacetic acid), PCTA-(3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid), and Oxo-DO3A-(1-oxa-4,7,10-triazacyclododecane-4,7,10-triacetic acid) peptide conjugates were prepared using H(2)N-Aoc-[d-Tyr(6),ßAla(11),Thi(13),Nle(14)]bombesin(6-14) (BBN) as a peptide template. The BBN moiety was selected since it binds with high affinity to the GRPR, which is overexpressed on human breast cancer cells. A convenient synthetic approach for the attachment of aniline-BFC to peptides on solid support is also presented. To facilitate the attachment of the aniline-PCTA and aniline-Oxo-DO3A to the peptide via an amide bond, a succinyl spacer was introduced at the N-terminus of BBN. The partially protected aniline-BFC (p-H(2)N-Bn-PCTA(Ot-Bu)(3) or p-H(2)N-Bn-DO3A(Ot-Bu)(3)) was then coupled to the resulting N-terminal carboxylic acid preactivated with DEPBT/ClHOBt on resin. After cleavage and purification, the peptide-conjugates were labeled with (64)Cu using [(64)Cu]Cu(OAc)(2) in 0.1 M ammonium acetate buffer at 100 °C for 15 min. Labeling efficacy was >90% for all peptides; Oxo-DO3A-BBN was incubated an additional 150 min at 100 °C to achieve this high yield. Specific activities varied from 76 to 101 TBq/mmol. Competition assays on T47D cells showed that all BFC-BBN complexes retained high affinity for the GRPR. All BFC-BBN (64)Cu-conjugates were stable for over 20 h when incubated at 37 °C in mouse plasma samples. However, in vivo, only 37% of the (64)Cu/Oxo-DO3A complex remained intact after 20 h while the (64)Cu/DOTA-BBN complex was completely demetalated. In contrast, both (64)Cu/NOTA- and (64)Cu/PCTA-BBN conjugates remained stable during the 20 h time period. Our results indicate that it is possible to successfully conjugate aniline-BFC with peptide on solid support. Our data also show that (64)Cu-labeled NOTA- and PCTA-BBN peptide conjugates are promising radiotracers for PET imaging of many human cancers overexpressing the GRP receptor.

Development and evaluation of a new method for sampling and monitoring the symphylid population in pineapple.

BACKGROUND: Symphylids (Hanseniella sp.) are polyphagous soilborne parasites. Today, symphylid populations on pineapple are monitored by observing root symptoms and the presence of symphylids at the bottom of basal leaves. The authors developed a reliable method with a bait and trap device to monitor symphylid populations in pineapple or fallow crops. The spatial distribution of the symphylid populations was evaluated using the variance/mean ratios and spatial analyses based on Moran's and Geary's indices. The method has been tested to monitor symphylid populations at different developmental stages of pineapple. RESULTS: Adding potato baits to the soil samples increased the trapping efficiency of symphylids when compared with 'soil only' and 'bait only' methods. The handling of the samples is also facilitated by the new device. Results showed that the vertical distribution of symphylids may be uniform deeply inside the soil profile under pineapple, up to 50 cm. Results showed that symphylid populations are highly aggregated, showing a spot area about 4-6 m wide for their development. CONCLUSION: The new method allows better and easier evaluation of symphylid populations. It may be very useful in the evaluation of new IPM methods to control symphylids under pineapple.

[Lys(DOTA)4]BVD15, a novel and potent neuropeptide Y analog designed for Y1 receptor-targeted breast tumor imaging.

We substituted a truncated neuropeptide Y (NPY) analog, [Pro(30), Tyr(32), Leu(34)]NPY(28-36)NH(2) also called BVD15, at various positions with DOTA (1,4,7,10-tetraazacyclododecane-1,4,7-10-tetraacetic acid) and evaluated the effect of the coupling position with the binding affinity for NPY Y(1) receptors (NPY1R). Our data suggest that [Lys(DOTA)(4)]BVD15 (K(i)=63+/-25 nM vs. K(i)=39+/-34 nM for BVD15) is a potent NPY analog suitable for radiolabeling with metallo positron emitters for PET imaging of breast cancer.

Total solid-phase synthesis of NOTA-functionalized peptides for PET imaging.

A convenient approach to functionalize peptides either at the N-terminal or on a lysine side chain with 1,4,7-triazacyclononane-N,N',N''-triacetic acid (NOTA) chelating unit has been developed on solid support. The chelate was assembled in a two-step process starting with bromo-acetylated peptides. Deprotection and cleavage of the resin-bound NOTA peptides were performed with use of trifluoroacetic acid (TFA) in the presence of thioanisole and water to give free NOTA peptides.

[A study on the management of short term care for elderly patients aged 75 and over in the Nord-Pas de Calais region]. / Enquête sur la prise en charge des personnes âgées de 75 ans et plus dans les services de court séjour "Médecine" de la région Nord-Pas-de-Calais.

The development of the geriatrics portion of the third national health plan in the Nord-Pas de Calais presented an interesting opportunity to analyse the management of health care for an ageing population in one of France's youngest regions. This work served as a means to establish recommendations for the improvement of the organisation and planning of health care services for this particular population group in the region. In this article reporting on the study's outcomes, the authors present the results on the management of health care for elderly people in hospitals and other short term medical care facilities.