Short-term resource allocation during extensive athletic competition

Abstract Objectives: Following predictions from life history theory, we sought to identify acute trade-offs between reproductive effort (as measured by psychological arousal) and somatic maintenance (via functional measures of innate immunity) during conditions of severe energetic imbalance. Methods: Sixty-six male ultramarathon runners (ages 20 to 37 years) were sampled before and after a lengthy race. Saliva and sera were collected for testosterone and immunological analyses (hemolytic complement activity and bacterial killing ability). Lean body mass was assessed by bioelectrical impedance, and libido was measured using a slideshow of arousing and neutral images. Results: Following predictions, there was a significant decrease in salivary testosterone levels (109.59 pg/mL versus 97.61 pg/mL, P<.001) and arousal scores in response to provocative images (5.40 versus 4.89, P5.001) between prerace and postrace time points. Additionally, participant bacterial killing ability (P5.035) and hemolytic complement activity (P5.021) increased between prerace and postrace. Conclusions: Decreased libido and testosterone with concomitant heightened innate immune responses suggest a shift in energetic priorities away from reproduction and toward maintenance/defense during a period of energetic stress

Testing stock market convergence: a non-linear factor approach

This paper applies the Phillips and Sul (Econometrica 75(6):1771–1855, 2007) method to test for convergence in stock returns to an extensive dataset including monthly stock price indices for five EU countries (Germany, France, the Netherlands, Ireland and the UK) as well as the US between 1973 and 2008. We carry out the analysis on both sectors and individual industries within sectors. As a first step, we use the Stock and Watson (J Am Stat Assoc 93(441):349–358, 1998) procedure to filter the data in order to extract the long-run component of the series; then, following Phillips and Sul (Econometrica 75(6):1771–1855, 2007), we estimate the relative transition parameters. In the case of sectoral indices we find convergence in the middle of the sample period, followed by divergence, and detect four (two large and two small) clusters. The analysis at a disaggregate, industry level again points to convergence in the middle of the sample, and subsequent divergence, but a much larger number of clusters is now found. Splitting the cross-section into two subgroups including euro area countries, the UK and the US respectively, provides evidence of a global convergence/divergence process not obviously influenced by EU policies

Stimulation of Na⁺/H⁺ Exchanger Isoform 1 Promotes Microglial Migration

Regulation of microglial migration is not well understood. In this study, we proposed that Na+/H+ exchanger isoform 1 (NHE-1) is important in microglial migration. NHE-1 protein was co-localized with cytoskeletal protein ezrin in lamellipodia of microglia and maintained its more alkaline intracellular pH (pHi). Chemoattractant bradykinin (BK) stimulated microglial migration by increasing lamellipodial area and protrusion rate, but reducing lamellipodial persistence time. Interestingly, blocking NHE-1 activity with its potent inhibitor HOE 642 not only acidified microglia, abolished the BK-triggered dynamic changes of lamellipodia, but also reduced microglial motility and microchemotaxis in response to BK. In addition, NHE-1 activation resulted in intracellular Na+ loading as well as intracellular Ca2+ elevation mediated by stimulating reverse mode operation of Na+/Ca2+ exchange (NCXrev). Taken together, our study shows that NHE-1 protein is abundantly expressed in microglial lamellipodia and maintains alkaline pHi in response to BK stimulation. In addition, NHE-1 and NCXrev play a concerted role in BK-induced microglial migration via Na+ and Ca2+ signaling. © 2013 Shi et al

Circulating mRNAs are differentially expressed in pregnancies with severe placental insufficiency and at high risk of stillbirth

Background Fetuses affected by placental insufficiency do not receive adequate nutrients and oxygenation, become growth restricted and acidemic, and can demise. Preterm fetal growth restriction is a severe form of placental insufficiency with a high risk of stillbirth. We set out to identify maternal circulating mRNA transcripts that are differentially expressed in preterm pregnancies complicated by very severe placental insufficiency, in utero fetal acidemia, and are at very high risk of stillbirth. Methods We performed a cohort study across six hospitals in Australia and New Zealand, prospectively collecting blood from 128 pregnancies complicated by preterm fetal growth restriction (delivery < 34 weeks’ gestation) and 42 controls. RNA-sequencing was done on all samples to discover circulating mRNAs associated with preterm fetal growth restriction and fetal acidemia in utero. We used RT-PCR to validate the associations between five lead candidate biomarkers of placental insufficiency in an independent cohort from Europe (46 with preterm fetal growth restriction) and in a third cohort of pregnancies ending in stillbirth. Results In the Australia and New Zealand cohort, we identified five mRNAs that were highly differentially expressed among pregnancies with preterm fetal growth restriction: NR4A2, EMP1, PGM5, SKIL, and UGT2B1. Combining three yielded an area under the receiver operative curve (AUC) of 0.95. Circulating NR4A2 and RCBTB2 in the maternal blood were dysregulated in the presence of fetal acidemia in utero. We validated the association between preterm fetal growth restriction and circulating EMP1, NR4A2, and PGM5 mRNA in a cohort from Europe. Combining EMP1 and PGM5 identified fetal growth restriction with an AUC of 0.92. Several of these genes were differentially expressed in the presence of ultrasound parameters that reflect placental insufficiency. Circulating NR4A2, EMP1, and RCBTB2 mRNA were differentially regulated in another cohort destined for stillbirth, compared to ongoing pregnancies. EMP1 mRNA appeared to have the most consistent association with placental insufficiency in all cohorts. Conclusions Measuring circulating mRNA offers potential as a test to identify pregnancies with severe placental insufficiency and at very high risk of stillbirth. Circulating mRNA EMP1 may be promising as a biomarker of severe placental insufficiency

Artificial Neural Network Inference (ANNI): A Study on Gene-Gene Interaction for Biomarkers in Childhood Sarcomas

Objective: To model the potential interaction between previously identified biomarkers in children sarcomas using artificial neural network inference (ANNI). Method: To concisely demonstrate the biological interactions between correlated genes in an interaction network map, only 2 types of sarcomas in the children small round blue cell tumors (SRBCTs) dataset are discussed in this paper. A backpropagation neural network was used to model the potential interaction between genes. The prediction weights and signal directions were used to model the strengths of the interaction signals and the direction of the interaction link between genes. The ANN model was validated using Monte Carlo cross-validation to minimize the risk of over-fitting and to optimize generalization ability of the model. Results: Strong connection links on certain genes (TNNT1 and FNDC5 in rhabdomyosarcoma (RMS); FCGRT and OLFM1 in Ewing’s sarcoma (EWS)) suggested their potency as central hubs in the interconnection of genes with different functionalities. The results showed that the RMS patients in this dataset are likely to be congenital and at low risk of cardiomyopathy development. The EWS patients are likely to be complicated by EWS-FLI fusion and deficiency in various signaling pathways, including Wnt, Fas/Rho and intracellular oxygen. Conclusions: The ANN network inference approach and the examination of identified genes in the published literature within the context of the disease highlights the substantial influence of certain genes in sarcomas

Economic growth, law, and corruption: evidence from India

Is corruption influenced by economic growth? Are legal institutions such as the ‘Right to Information Act (RTI) 2005’ in India effective in curbing corruption? Using a panel dataset covering 20 Indian states for the years 2005 and 2008 we estimate the effects of growth and law on corruption. Accounting for endogeneity, omitted fixed factors, and other nationwide changes we find that economic growth reduces overall corruption as well as corruption in banking, land administration, education, electricity, and hospitals. Growth reduces bribes but has little impact on corruption perception. In contrast the RTI Act reduces both corruption experience and corruption perceptio

Relationship between perceived body weight and body mass index based on self- reported height and weight among university students: a cross-sectional study in seven European countries

Mikolajczyk RT, Maxwell AE, El Ansari W, Stock C, Petkeviciene J, Guillen-Grima F. Relationship between perceived body weight and body mass index based on self- reported height and weight among university students: a cross-sectional study in seven European countries. BMC Public Health. 2010;10(1): 40.Background Despite low rates of obesity, many university students perceive themselves as overweight, especially women. This is of concern, because inappropriate weight perceptions can lead to unhealthy behaviours including eating disorders. Methods We used the database from the Cross National Student Health Survey (CNSHS), consisting of 5,900 records of university students from Bulgaria, Denmark, Germany, Lithuania, Poland, Spain and Turkey to analyse differences in perceived weight status based on the question: "Do you consider yourself much too thin, a little too thin, just right, a little too fat or much too fat?". The association between perceived weight and body mass index (BMI) calculated from self-reported weight and height was assessed with generalized non-parametric regression in R library gam. Results Although the majority of students reported a normal BMI (72-84% of males, 65-83% of females), only 32% to 68% of students considered their weight "just right". Around 20% of females with BMI of 20 kg/m2 considered themselves "a little too fat" or "too fat", and the percentages increased to 60% for a BMI of 22.5 kg/m2. Male students rarely felt "a little too fat" or "too fat" below BMI of 22.5 kg/m2, but most felt too thin with a BMI of 20 kg/m2. Conclusions Weight ideals are rather uniform across the European countries, with female students being more likely to perceive themselves as "too fat" at a normal BMI, while male students being more likely to perceive themselves as "too thin". Programs to prevent unhealthy behaviours to achieve ill-advised weight ideals may benefit students

BIM mediates synergistic killing of B-cell acute lymphoblastic leukemia cells by BCL-2 and MEK inhibitors

B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematological disease that kills ~50% of adult patients. With the exception of some BCR-ABL1(+) patients who benefit from tyrosine kinase inhibitors, there are no effective targeted therapies for adult B-ALL patients and chemotherapy remains first-line therapy despite adverse side effects and poor efficacy. We show that, although the MEK/ERK pathway is activated in B-ALL cells driven by different oncogenes, MEK inhibition does not suppress B-ALL cell growth. However, MEK inhibition synergized with BCL-2/BCL-XL family inhibitors to suppress proliferation and induce apoptosis in B-ALL cells. We show that this synergism is mediated by the pro-apoptotic factor BIM, which is dephosphorylated as a result of MEK inhibition, allowing it to bind to and neutralize MCL-1, thereby enhancing BCL-2/BCL-XL inhibitor-induced cell death. This cooperative effect is observed in B-ALL cells driven by a range of genetic abnormalities and therefore has significant therapeutic potential

MRS-guided HDR brachytherapy boost to the dominant intraprostatic lesion in high risk localised prostate cancer

BACKGROUND: It is known that the vast majority of prostate cancers are multifocal. However radical radiotherapy historically treats the whole gland rather than individual cancer foci.Magnetic resonance spectroscopy (MRS) can be used to non-invasively locate individual cancerous tumours in prostate. Thus an intentionally non-uniform dose distribution treating the dominant intraprostatic lesion to different dose levels than the remaining prostate can be delivered ensuring the maximum achievable tumour control probability.The aim of this study is to evaluate, using radiobiological means, the feasibility of a MRS-guided high dose rate (HDR) brachytherapy boost to the dominant lesion.\ud \ud METHODS: Computed tomography and MR/MRS were performed for treatment planning of a high risk localised prostate cancer. Both were done without endorectal coil, which distorts shape of prostate during the exams.Three treatment plans were compared:- external beam radiation therapy (EBRT) only- combination of EBRT and HDR brachytherapy- combination of EBRT and HDR brachytherapy with a synchronous integrated boost to the dominant lesionThe criteria of plan comparison were: the minimum, maximum and average doses to the targets and organs at risk; dose volume histograms; biologically effective doses for organs at risk and tumour control probability for the target volumes consisting of the dominant lesion as detected by MR/MRS and the remaining prostate volume.\ud \ud RESULTS: Inclusion of MRS information on the location of dominant lesion allows a safe increase of the dose to the dominant lesion while dose to the remaining target can be even substantially decreased keeping the same, high tumour control probability. At the same time an improved urethra sparing was achieved comparing to the treatment plan using a combination of EBRT and uniform HDR brachytherapy.\ud \ud CONCLUSIONS: MRS-guided HDR brachytherapy boost to dominant lesion has the potential to spare the normal tissue, especially urethra, while keeping the tumour control probability high

Acidic Extracellular pH Promotes Activation of Integrin αvβ3

Acidic extracellular pH is characteristic of the cell microenvironment in several important physiological and pathological contexts. Although it is well established that acidic extracellular pH can have profound effects on processes such as cell adhesion and migration, the underlying molecular mechanisms are largely unknown. Integrin receptors physically connect cells to the extracellular matrix, and are thus likely to modulate cell responses to extracellular conditions. Here, we examine the role of acidic extracellular pH in regulating activation of integrin [alpha]v[beta]3. Through computational molecular dynamics simulations, we find that acidic extracellular pH promotes opening of the [alpha]v[beta]3 headpiece, indicating that acidic pH can thereby facilitate integrin activation. This prediction is consistent with our flow cytometry and atomic force microscope-mediated force spectroscopy assays of integrin [alpha]v[beta]3 on live cells, which both demonstrate that acidic pH promotes activation at the intact cell surface. Finally, quantification of cell morphology and migration measurements shows that acidic extracellular pH affects cell behavior in a manner that is consistent with increased integrin activation. Taken together, these computational and experimental results suggest a new and complementary mechanism of integrin activation regulation, with associated implications for cell adhesion and migration in regions of altered pH that are relevant to wound healing and cancer.National Institute of Biomedical Imaging and Bioengineering (U.S.) (Award Number T32EB006348)Massachusetts Institute of Technology (Collamore-Rogers Fellowship)National Institutes of Health (U.S.) (NIH Cell Migration Consortium Grant U54-GM069668)National Science Foundation (U.S.) (CAREER Award)Singapore-MIT Alliance for Research and Technology (BioSystem and Micromechanics (BioSyM) Interdisciplinary Research Group