Student effort and educational attainment: Using the England football team to identify the education production function.

We use a sharp, exogenous and repeated change in the value of leisure to identify the impact of student effort on educational achievement. The treatment arises from the partial overlap of the world’s major international football tournaments with the exam period in England. Our data enable a clean difference-in-difference design. Performance is measured using the high-stakes tests that all students take at the end of compulsory schooling. We find a strongly significant effect: the average impact of a fall in effort is 0.12 SDs of student performance, significantly larger for male and disadvantaged students, as high as many educational policies.student effort, educational achievement, schools

Human rhinovirus infection up-regulates MMP-9 production in airway epithelial cells via NF-{kappa}B

Human rhinovirus (HRV) infections up-regulate proinflammatory mediators and growth factors that are associated with exacerbations of inflammatory airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Matrix metalloproteinase (MMP)-9 was shown to be increased in the airways of patients with asthma and COPD. We sought to determine whether HRV infection modulated the expression of MMP-9 and its highest-affinity inhibitor, the tissue inhibitor of metalloproteinase (TIMP)-1, and we explored the mechanism by which this modulation occurs. In vitro studies, using RT-PCR, ELISA, zymography, and a fluorescent activity assay, demonstrated that MMP-9 mRNA, protein, and activity were increased upon infection with HRV, whereas TIMP-1 mRNA and protein remained unchanged. These results were verified in vivo, using nasal lavage samples obtained from subjects with confirmed rhinovirus infections. Human rhinovirus infections were shown to up-regulate NF-kappaB, and NF-kappaB has also been reported to play a role in the expression of MMP-9. We therefore investigated the role of NF-kappaB in HRV-induced MMP-9 expression. Using two inhibitors of IkappaBalpha kinase beta, we observed a concentration-dependent decrease in HRV-induced MMP-9 expression. The role of NF-kappaB in HRV-induced MMP-9 expression was further confirmed using MMP-9 promoter luciferase constructs, which demonstrated that an NF-kappaB site at -620/-607 base pairs was necessary for HRV-induced MMP-9 expression. Electrophoretic mobility shift assays and supershift assays confirmed the nuclear translocation and binding of p50/p65 NF-kappaB subunits to an MMP-9-specific NF-kappaB oligonucleotide. This increase in MMP-9 may be a mechanism by which rhinovirus infections contribute to airway inflammation and, potentially, to airway remodeling

MAP Kinase-Interacting Kinases—Emerging Targets against Cancer

Mitogen-activated protein kinase (MAPK)-interacting kinases (Mnks) regulate the initiation of translation through phosphorylation of eukaryotic initiation factor 4E (eIF4E). Mnk-mediated eIF4E activation promotes cancer development and progression. While the phosphorylation of eIF4E is necessary for oncogenic transformation, the kinase activity of Mnks seems dispensable for normal development. For this reason, pharmacological inhibition of Mnks could represent an ideal mechanism-based and nontoxic therapeutic strategy for cancer treatment. In this review, we discuss the current understanding of Mnk biological roles, structures, and functions, as well as clinical implications. Importantly, we propose different strategies for identification of highly selective small molecule inhibitors of Mnks, including exploring a structural feature of their kinase domain, DFD motif, which is unique within the human kinome. We also argue that a combined targeting of Mnks and other pathways should be considered given the complexity of cancer

Advancing Our Understanding of the Inheritance and Transmission of Pectus Excavatum

Pectus excavatum is the most common congenital chest wall abnormality expressed in children, yet its inheritance is poorly understood. Here we present the first comprehensive assessment of the inheritance of this disorder. After evaluating 48 pedigrees and 56 clinical traits of probands and family members, we find strong evidence of autosomal recessive, genetic control for this disorder. Additionally there is likely more than one pectus disease-associated allele, as well as a relatively large number of disease allele carriers in the human population. Some clinical traits appear important and may serve as reliable indicators for predicting the likelihood of pectus excavatum in children before severe symptoms present. Quantifying sex-ratio bias in probands demonstrates a highly significant male bias associated with pectus excavatum. When combined with pedigree data, sex-bias is indicative of sex-linked, sex-limited, and/or epigenetic control such as X-inactivation, reiterating a point made with pedigrees alone, which is that more than one mutation is likely responsible for this disorder

Comparison of Methods for Monitoring the Body Condition of Dairy Cows

Dairy cows are known to mobilize body fat to achieve their genetic potential for milk production, which can have a detrimental impact on the health, fertility and survival of the cow. Better monitoring of cows with poor body condition (low or high body fat) will lead to improvements in production efficiencies and less wasted resources when producing milk from dairy cows. The aim of this study was to compare different methods for monitoring the body condition (body fat) of dairy cows. The methods used to measure body condition were: ultrasound scanner, manual observation, and a still digital image of the cow. For comparison, each measure was expressed as a body condition score (BCS) on a scale of extremely thin (1) to very fat (5) in quarter intervals. A total of 209 cows at various stages of lactation were assessed. Lin's concordance correlation coefficient (CCC) and the root mean square prediction error (RMSPE) were used to compare the accuracy of methods. The average BCS across cows was 2.10 for ultrasound, 2.76 for manual and 2.41 for digital methods. The study found that both manual (r = 0.790) and digital (r = 0.819) approaches for monitoring cow body condition were highly correlated with ultrasound BCS measurements. After adjusting correlation coefficients for prediction bias relative to a 45° line through the origin, the digital BCS had a higher CCC of 0.789 when compared to the ultrasound BCS than the manual BCS with a CCC of 0.592. The digital BCS also had a lower prediction error (RMSPE = 28.3%) when compared with ultrasound BCS than the manual BCS (RMSPE = 42.7%). The prediction error for digital and manual BCS methods were similar for cows with a BCS of 2.5 or more (RMSPE = 20.5 and 19.0%, respectively) but digital BCS was more accurate for cows of < 2.5 BCS (RMSPE = 35.5 and 63.8%, respectively). Digital BCS can provide a more accurate assessment of cow body fat than manual BCS observations, with the added benefit of more automated and frequent monitoring potentially improving the welfare and sustainability of high production systems

The <i>Plasmodium</i> eukaryotic initiation factor-2α kinase IK2 controls the latency of sporozoites in the mosquito salivary glands

Sporozoites, the invasive form of malaria parasites transmitted by mosquitoes, are quiescent while in the insect salivary glands. Sporozoites only differentiate inside of the hepatocytes of the mammalian host. We show that sporozoite latency is an active process controlled by a eukaryotic initiation factor-2α (eIF2α) kinase (IK2) and a phosphatase. IK2 activity is dominant in salivary gland sporozoites, leading to an inhibition of translation and accumulation of stalled mRNAs into granules. When sporozoites are injected into the mammalian host, an eIF2α phosphatase removes the PO4 from eIF2α-P, and the repression of translation is alleviated to permit their transformation into liver stages. In IK2 knockout sporozoites, eIF2α is not phosphorylated and the parasites transform prematurely into liver stages and lose their infectivity. Thus, to complete their life cycle, Plasmodium sporozoites exploit the mechanism that regulates stress responses in eukaryotic cells

CD98hc facilitates B cell proliferation and adaptive humoral immunity.

The proliferation of antigen-specific lymphocytes and resulting clonal expansion are essential for adaptive immunity. We report here that B cell-specific deletion of the heavy chain of CD98 (CD98hc) resulted in lower antibody responses due to total suppression of B cell proliferation and subsequent plasma cell formation. Deletion of CD98hc did not impair early B cell activation but did inhibit later activation of the mitogen-activated protein kinase Erk1/2 and downregulation of the cell cycle inhibitor p27. Reconstitution of CD98hc-deficient B cells with CD98hc mutants showed that the integrin-binding domain of CD98hc was required for B cell proliferation but that the amino acid-transport function of CD98hc was dispensable for this. Thus, CD98hc supports integrin-dependent rapid proliferation of B cells. We propose that the advantage of adaptive immunity favored the appearance of CD98hc in vertebrates

Toll-like receptor 3 blockade in rhinovirus-induced experimental asthma exacerbations:A Randomized Controlled Study

BACKGROUND: Human rhinoviruses (HRVs) commonly precipitate asthma exacerbations. Toll-like receptor 3, an innate pattern recognition receptor, is triggered by HRV, driving inflammation that can worsen asthma. OBJECTIVE: We sought to evaluate an inhibitory mAb to Toll-like receptor 3, CNTO3157, on experimental HRV-16 inoculation in healthy subjects and asthmatic patients. METHODS: In this double-blind, multicenter, randomized, parallel-group study in North America and Europe, healthy subjects and patients with mild-to-moderate stable asthma received single or multiple doses of CNTO3157 or placebo, respectively, and were then inoculated with HRV-16 within 72 hours. All subjects were monitored for respiratory symptoms, lung function, and nasal viral load. The primary end point was maximal decrease in FEV1 during 10 days after inoculation. RESULTS: In asthmatic patients (n = 63) CNTO3157 provided no protection against FEV1 decrease (least squares mean: CNTO3157 [n = 30] = -7.08% [SE, 8.15%]; placebo [n = 25] = -5.98% [SE, 8.56%]) or symptoms after inoculation. In healthy subjects (n = 12) CNTO3157 versus placebo significantly attenuated upper (P = .03) and lower (P = .02) airway symptom scores, with area-under-the-curve increases of 9.1 (15.1) versus 34.9 (17.6) and 13.0 (18.4) versus 50.4 (25.9) for the CNTO3157 (n = 8) and placebo (n = 4) groups, respectively, after inoculation. All of the severe and 4 of the nonserious asthma exacerbations occurred while receiving CNTO3157. CONCLUSION: In summary, CNTO3157 was ineffective in attenuating the effect of HRV-16 challenge on lung function, asthma control, and symptoms in asthmatic patients but suppressed cold symptoms in healthy subjects. Other approaches, including blockade of multiple pathways or antiviral agents, need to be sought for this high unmet medical need

Disaggregation of SMOS soil moisture over West Africa using the Temperature and Vegetation Dryness Index based on SEVIRI land surface parameters

The overarching objective of this study was to produce a disaggregated SMOS Soil Moisture (SM) product using land surface parameters from a geostationary satellite in a region covering a diverse range of ecosystem types. SEVIRI data at 15 minute temporal resolution were used to derive the Temperature and Vegetation Dryness Index (TVDI) that served as SM proxy within the disaggregation process. West Africa (3 N, 26 W; 28 N, 26 E) was selected as a case study as it presents both an important North-South climate gradient and a diverse range of ecosystem types. The main challenge was to set up a methodology applicable over a large area that overcomes the constraints of SMOS (low spatial resolution) and TVDI (requires similar atmospheric forcing and triangular shape formed when plotting morning rise temperature versus fraction of vegetation cover) in order to produce a 0.05 degree resolution disaggregated SMOS SM product at sub-continental scale. Consistent cloud cover appeared as one of the main constraints for deriving TVDI, especially during the rainy season and in the southern parts of the region and a large adjustment window (105x105 SEVIRI pixels) was therefore deemed necessary. Both the original and the disaggregated SMOS SM products described well the seasonal dynamics observed at six locations of in situ observations. However, there was an overestimation in both products for sites in the humid southern regions; most likely caused by the presence of forest. Both TVDI and the associated disaggregated SM product was found to be highly sensitive to algorithm input parameters; especially of conditions of high fraction of vegetation cover. Additionally, seasonal dynamics in TVDI did not follow the seasonal patters of SM. Still, its spatial heterogeneity was found to be a good proxy for disaggregating SMOS SM data; main river networks and spatial patterns of SM extremes (i.e. droughts and floods) not seen in the original SMOS SM product were revealed in the disaggregated SM product for a test case of July-September 2012. The disaggregation methodology thereby successfully increased the spatial resolution of SMOS SM, with potential application for local drought/flood monitoring of importance for the livelihood of the population of West Africa