On passion and moral behavior in achievement settings: The mediating role of pride

The Dualistic Model of Passion (Vallerand et al., 2003) distinguishes two types of passion: harmonious passion (HP) and obsessive passion (OP) that predict adaptive and less adaptive outcomes, respectively. In the present research, we were interested in understanding the role of passion in the adoption of moral behavior in achievement settings. It was predicted that the two facets of pride (authentic and hubristic; Tracy & Robins, 2007) would mediate the passion-moral behavior relationship. Specifically, because people who are passionate about a given activity are highly involved in it, it was postulated that they should typically do well and thus experience high levels of pride when engaged in the activity. However, it was also hypothesized that while both types of passion should be conducive to authentic pride, only OP should lead to hubristic pride. Finally, in line with past research on pride (Carver, Sinclair, & Johnson, 2010; Tracy et al., 2009), only hubristic pride was expected to negatively predict moral behavior, while authentic pride was expected to positively predict moral behavior. Results of two studies conducted with paintball players (N=163, Study 1) and athletes (N=296, Study 2) supported the proposed model. Future research directions are discussed in light of the Dualistic Model of Passion

High-throughput proteomic analysis reveals systemic dysregulation in virally suppressed people living with HIV

BACKGROUND. People living with HIV (PLHIV) receiving antiretroviral therapy (ART) exhibit persistent immune dysregulation and microbial dysbiosis, leading to development of cardiovascular diseases (CVDs). We initially compared plasma proteomic profiles between 205 PLHIV and 120 healthy control participants (HCs) and validated the results in an independent cohort of 639 PLHIV and 99 HCs. Differentially expressed proteins (DEPs) were then associated to microbiome data. Finally, we assessed which proteins were linked with CVD development in PLHIV. METHODS. Proximity extension assay technology was used to measure 1,472 plasma proteins. Markers of systemic inflammation (C-reactive protein, D-dimer, IL-6, soluble CD14, and soluble CD163) and microbial translocation (IFABP) were measured by ELISA, and gut bacterial species were identified using shotgun metagenomic sequencing. Baseline CVD data were available for all PLHIV, and 205 PLHIV were recorded for development of CVD during a 5-year follow-up. RESULTS. PLHIV receiving ART had systemic dysregulation of protein concentrations, compared with HCs. Most of the DEPs originated from the intestine and lymphoid tissues and were enriched in immune- and lipid metabolism-related pathways. DEPs originating from the intestine were associated with specific gut bacterial species. Finally, we identified upregulated proteins in PLHIV (GDF15, PLAUR, RELT, NEFL, COL6A3, and EDA2R), unlike most markers of systemic inflammation, associated with the presence and risk of developing CVD during 5-year follow-up. CONCLUSION. Our findings suggest a systemic dysregulation of protein concentrations in PLHIV; some proteins were associated with CVD development. Most DEPs originated from the gut and were related to specific gut bacterial species.</p

Cerebellar astrocytes co-express several ADP receptors. Presence of functional P2Y13-like receptors

Astrocytes exhibit a form of excitability based on variations of intracellular Ca2+ concentration in response to various stimuli, including ADP, ATP, UTP and dinucleotides. Here, we investigate the presence of the recently cloned ADP-sensitive receptors, P2Y12 and P2Y13 subtypes, which are negatively coupled to adenylate cyclase, in cerebellar astrocytes. We checked the effect of specific agonists, 2-methylthioadenosine diphosphate (2MeSADP) and ADP, on adenylate cyclase stimulation induced by isoproterenol. Both agonists significantly reduced the cAMP accumulation induced by isoproterenol. The inhibitory effect was concentration-dependent with IC50 values of 46 ± 13 and 23 ± 14 nM for 2MeSADP and ADP, respectively. The experiments were carried out in the presence of MRS-2179, a specific antagonist of P2Y1 receptor, to avoid any contribution of this receptor. Using fura-2 microfluorimetry we also proved that astrocytes responded to 2MeSADP stimulations with calcium responses in the absence and also in the presence of MRS-2179. Both effects, inhibition of adenylate cyclase and intracellular calcium mobilization, were not modified by 2MeSAMP, an antagonist of P2Y12 receptor, suggesting that were mediated by P2Y13-like receptors

Detection of amyloid beta aggregates in the brain of BALB/c mice after Chlamydia pneumoniae infection

Neuroinflammation, initiated by cerebral infection, is increasingly postulated as an aetiological factor in neurodegenerative diseases such as Alzheimer’s disease (AD). We investigated whether Chlamydia pneumoniae (Cpn) infection results in extracellular aggregation of amyloid beta (Aβ) in BALB/c mice. At 1 week post intranasal infection (p.i.), Cpn DNA was detected predominantly in the olfactory bulbs by PCR, whereas brains at 1 and 3 months p.i. were Cpn negative. At 1 and 3 months p.i., extracellular Aβ immunoreactivity was detected in the brain of Cpn-infected mice but also in the brain of mock-infected mice and mice that were neither Cpn infected nor mock infected. However, these extracellular Aβ aggregates showed morphological differences compared to extracellular Aβ aggregates detected in the brain of transgenic APP751SL/PS1M146L mice. These data do not unequivocally support the hypothesis that Cpn infection induces the formation of AD-like Aβ plaques in the brain of BALB/c mice, as suggested before. However, future studies are required to resolve these differences and to investigate whether Cpn is indeed an etiological factor in AD pathogenesis

2009 Pandemic Influenza A (H1N1) Virus Outbreak and Response – Rwanda, October, 2009–May, 2010

BACKGROUND: In October 2009, the first case of pandemic influenza A(H1N1)pdm09 (pH1N1) was confirmed in Kigali, Rwanda and countrywide dissemination occurred within several weeks. We describe clinical and epidemiological characteristics of this epidemic. METHODS: From October 2009 through May 2010, we undertook epidemiologic investigations and response to pH1N1. Respiratory specimens were collected from all patients meeting the WHO case definition for pH1N1, which were tested using CDC's real time RT-PCR protocol at the Rwandan National Reference Laboratory (NRL). Following documented viral transmission in the community, testing focused on clinically severe and high-risk group suspect cases. RESULTS: From October 9, 2009 through May 31, 2010, NRL tested 2,045 specimens. In total, 26% (n = 532) of specimens tested influenza positive; of these 96% (n = 510) were influenza A and 4% (n = 22) were influenza B. Of cases testing influenza A positive, 96.8% (n = 494), 3% (n = 15), and 0.2% (n = 1) were A(H1N1)pdm09, Seasonal A(H3) and Seasonal A(non-subtyped), respectively. Among laboratory-confirmed cases, 263 (53.2%) were children <15 years and 275 (52%) were female. In total, 58 (12%) cases were hospitalized with mean duration of hospitalization of 5 days (Range: 2-15 days). All cases recovered and there were no deaths. Overall, 339 (68%) confirmed cases received oseltamivir in any setting. Among all positive cases, 26.9% (143/532) were among groups known to be at high risk of influenza-associated complications, including age <5 years 23% (122/532), asthma 0.8% (4/532), cardiac disease 1.5% (8/532), pregnancy 0.6% (3/532), diabetes mellitus 0.4% (2/532), and chronic malnutrition 0.8% (4/532). CONCLUSIONS: Rwanda experienced a PH1N1 outbreak which was epidemiologically similar to PH1N1 outbreaks in the region. Unlike seasonal influenza, children <15 years were the most affected by pH1N1. Lessons learned from the outbreak response included the need to strengthen integrated disease surveillance, develop laboratory contingency plans, and evaluate the influenza sentinel surveillance system

The plasticity of Plasmodium falciparum gametocytaemia in relation to age in Burkina Faso

BACKGROUND: Malaria transmission depends on the presence of gametocytes in the peripheral blood. In this study, the age-dependency of gametocytaemia was examined by microscopy and molecular tools. METHODS: A total of 5,383 blood samples from individuals of all ages were collected over six cross sectional surveys in Burkina Faso. One cross-sectional study used quantitative nucleic acid sequence based amplification (QT-NASBA) for parasite quantification (n = 412). The proportion of infections with concurrent gametocytaemia and median proportion of gametocytes among all parasites were calculated. RESULTS: Asexual parasite prevalence and gametocyte prevalence decreased with age. Gametocytes made up 1.8% of the total parasite population detected by microscopy in the youngest age group. This proportion gradually increased to 18.2% in adults (p < 0.001). Similarly, gametocytes made up 0.2% of the total parasite population detected by QT-NASBA in the youngest age group, increasing to 5.7% in adults (p < 0.001). This age pattern in gametocytaemia was also evident in the proportion of gametocyte positive slides without concomitant asexual parasites which increased from 13.4% (17/127) in children to 45.6% (52/114) in adults (OR 1.55, 95% CI 1.38-1.74, p < 0.001). CONCLUSIONS: The findings of this study suggest that although gametocytes are most commonly detected in children, the proportion of asexual parasites that is committed to develop into gametocytes may increase with age. These findings underscore the importance of adults for the human infectious reservoir for malaria

The relationship between fertility and lifespan in humans

Evolutionary theories of aging predict a trade-off between fertility and lifespan, where increased lifespan comes at the cost of reduced fertility. Support for this prediction has been obtained from various sources. However, which genes underlie this relationship is unknown. To assess it, we first analyzed the association of fertility with age at menarche and menopause, and with mortality in 3,575 married female participants of the Rotterdam Study. In addition, we conducted a candidate gene study where 1,664 single nucleotide polymorphisms (SNPs) in 25 candidate genes were analyzed in relation to number of children as a measure of fertility. SNPs that associated with fertility were analyzed for association with mortality. We observed no associations between fertility and age at menarche (p = 0.38) and menopause (p = 0.07). In contrast, fertility was associated with mortality. Women with two to three children had significantly lower mortality (hazard ratio (HR), 0.82; 95% confidence interval (95% CI), 0.69–0.97) compared to women with no children. No such benefit was observed for women with four or more children, who had a similar mortality risk (HR, 0.93; 95% CI, 0.76–1.13) as women with no children. The analysis of candidate genes revealed four genes that influence fertility after correction for multiple testing: CGB/LHB gene cluster (p = 0.0036), FSHR (p = 0.023), FST (p = 0.023), and INHBA (p = 0.021). However, none of the independent SNPs in these genes predicted mortality. In conclusion, women who bear two to three children live longer than those who bear none or many children, but this relationship was not mediated by the candidate genes analyzed in this study

The basal epithelial marker P-cadherin associates with breast cancer cell populations harboring a glycolytic and acid-resistant phenotype

"BMC Cancer 2014 14:734"BACKGROUND: Cancer stem cells are hypoxia-resistant and present a preponderant glycolytic metabolism. These characteristics are also found in basal-like breast carcinomas (BLBC), which show increased expression of cancer stem cell markers.Recently, we demonstrated that P-cadherin, a biomarker of BLBC and a poor prognostic factor in this disease, mediates stem-like properties and resistance to radiation therapy. Thus, the aim of the present study was to evaluate if P-cadherin expression was associated to breast cancer cell populations with an adapted phenotype to hypoxia. METHODS: Immunohistochemistry was performed to address the expression of P-cadherin, hypoxic, glycolytic and acid-resistance biomarkers in primary human breast carcinomas. In vitro studies were performed using basal-like breast cancer cell lines. qRT-PCR, FACS analysis, western blotting and confocal microscopy were used to assess the expression of P-cadherin after HIF-1a stabilization, achieved by CoCl2 treatment. siRNA-mediated knockdown was used to silence the expression of several targets and qRT-PCR was employed to evaluate the effects of P-cadherin on HIF-1a signaling. P-cadherin high and low breast cancer cell populations were sorted by FACS and levels of GLUT1 and CAIX were assessed by FACS and western blotting. Mammosphere forming efficiency was used to determine the stem cell activity after specific siRNA-mediated knockdown, further confirmed by western blotting. RESULTS: We demonstrated that P-cadherin overexpression was significantly associated with the expression of HIF-1a, GLUT1, CAIX, MCT1 and CD147 in human breast carcinomas. In vitro, we showed that HIF-1a stabilization was accompanied by increased membrane expression of P-cadherin and that P-cadherin silencing led to a decrease of the mRNA levels of GLUT1 and CAIX. We also found that the cell fractions harboring high levels of P-cadherin were the same exhibiting more GLUT1 and CAIX expression. Finally, we showed that P-cadherin silencing significantly decreases the mammosphere forming efficiency in the same range as the silencing of HIF-1a, CAIX or GLUT1, validating that all these markers are being expressed by the same breast cancer stem cell population. CONCLUSIONS: Our results establish a link between aberrant P-cadherin expression and hypoxic, glycolytic and acid-resistant breast cancer cells, suggesting a possible role for this marker in cancer cell metabolismo.This work was funded by FEDER funds through the COMPETE Program (Programa Operacional Factores de Competitividade) and by national funds through FCT (Portuguese Foundation for Science and Technology, Portugal), mainly in the context of the scientific project PTDC/SAU-GMG/120049/2010-FCOMP-01-0124-FEDER-021209, and partially by PTDC/SAU-FCF/104347/2008. FCT funded the research grants of BS (SFRH/BD/69353/2010), ASR (SFRH/BPD/75705/2011), ARN (grant from the project PTDC/SAU-GMG/120049/2010), CP (SFRH/BPD/69479/2010), AV (SFRH/BPD/90303/2012), as well as JP, with Programa Ciencia 2007 (Contratacao de Doutorados para o SCTN - financiamento pelo POPH - QREN - Tipologia 4.2 - Promocao do Emprego Cientifico, comparticipado pelo Fundo Social Europeu e por fundos nacionais do MCTES) and Programa IFCT (FCT Investigator). IPATIMUP is an Associate Laboratory of the Portuguese Ministry of Science, Technology and Higher Education and is partially supported by FCT