Riviste scientifiche

Association between Traffic-Related Air Pollution in Schools and Cognitive Development in Primary School Children: A Prospective Cohort Study

PLoS Medicine - Ma, 03/03/2015 - 23:00

by Jordi Sunyer, Mikel Esnaola, Mar Alvarez-Pedrerol, Joan Forns, Ioar Rivas, Mònica López-Vicente, Elisabet Suades-González, Maria Foraster, Raquel Garcia-Esteban, Xavier Basagaña, Mar Viana, Marta Cirach, Teresa Moreno, Andrés Alastuey, Núria Sebastian-Galles, Mark Nieuwenhuijsen, Xavier Querol

Background

Air pollution is a suspected developmental neurotoxicant. Many schools are located in close proximity to busy roads, and traffic air pollution peaks when children are at school. We aimed to assess whether exposure of children in primary school to traffic-related air pollutants is associated with impaired cognitive development.

Methods and Findings

We conducted a prospective study of children (n = 2,715, aged 7 to 10 y) from 39 schools in Barcelona (Catalonia, Spain) exposed to high and low traffic-related air pollution, paired by school socioeconomic index; children were tested four times (i.e., to assess the 12-mo developmental trajectories) via computerized tests (n = 10,112). Chronic traffic air pollution (elemental carbon [EC], nitrogen dioxide [NO2], and ultrafine particle number [UFP; 10–700 nm]) was measured twice during 1-wk campaigns both in the courtyard (outdoor) and inside the classroom (indoor) simultaneously in each school pair. Cognitive development was assessed with the n-back and the attentional network tests, in particular, working memory (two-back detectability), superior working memory (three-back detectability), and inattentiveness (hit reaction time standard error). Linear mixed effects models were adjusted for age, sex, maternal education, socioeconomic status, and air pollution exposure at home.Children from highly polluted schools had a smaller growth in cognitive development than children from the paired lowly polluted schools, both in crude and adjusted models (e.g., 7.4% [95% CI 5.6%–8.8%] versus 11.5% [95% CI 8.9%–12.5%] improvement in working memory, p = 0.0024). Cogently, children attending schools with higher levels of EC, NO2, and UFP both indoors and outdoors experienced substantially smaller growth in all the cognitive measurements; for example, a change from the first to the fourth quartile in indoor EC reduced the gain in working memory by 13.0% (95% CI 4.2%–23.1%). Residual confounding for social class could not be discarded completely; however, the associations remained in stratified analyses (e.g., for type of school or high-/low-polluted area) and after additional adjustments (e.g., for commuting, educational quality, or smoking at home), contradicting a potential residual confounding explanation.

Conclusions

Children attending schools with higher traffic-related air pollution had a smaller improvement in cognitive development.

CD47 Agonist Peptides Induce Programmed Cell Death in Refractory Chronic Lymphocytic Leukemia B Cells via PLCγ1 Activation: Evidence from Mice and Humans

PLoS Medicine - Ma, 03/03/2015 - 23:00

by Ana-Carolina Martinez-Torres, Claire Quiney, Tarik Attout, Heloïse Boullet, Linda Herbi, Laura Vela, Sandrine Barbier, Danielle Chateau, Elise Chapiro, Florence Nguyen-Khac, Frédéric Davi, Magali Le Garff-Tavernier, Roba Moumné, Marika Sarfati, Philippe Karoyan, Hélène Merle-Béral, Pierre Launay, Santos A. Susin

Background

Chronic lymphocytic leukemia (CLL), the most common adulthood leukemia, is characterized by the accumulation of abnormal CD5+ B lymphocytes, which results in a progressive failure of the immune system. Despite intense research efforts, drug resistance remains a major cause of treatment failure in CLL, particularly in patients with dysfunctional TP53. The objective of our work was to identify potential approaches that might overcome CLL drug refractoriness by examining the pro-apoptotic potential of targeting the cell surface receptor CD47 with serum-stable agonist peptides.

Methods and Findings

In peripheral blood samples collected from 80 patients with CLL with positive and adverse prognostic features, we performed in vitro genetic and molecular analyses that demonstrate that the targeting of CD47 with peptides derived from the C-terminal domain of thrombospondin-1 efficiently kills the malignant CLL B cells, including those from high-risk individuals with a dysfunctional TP53 gene, while sparing the normal T and B lymphocytes from the CLL patients. Further studies reveal that the differential response of normal B lymphocytes, collected from 20 healthy donors, and leukemic B cells to CD47 peptide targeting results from the sustained activation in CLL B cells of phospholipase C gamma-1 (PLCγ1), a protein that is significantly over-expressed in CLL. Once phosphorylated at tyrosine 783, PLCγ1 enables a Ca2+-mediated, caspase-independent programmed cell death (PCD) pathway that is not down-modulated by the lymphocyte microenvironment. Accordingly, down-regulation of PLCγ1 or pharmacological inhibition of PLCγ1 phosphorylation abolishes CD47-mediated killing. Additionally, in a CLL-xenograft model developed in NOD/scid gamma mice, we demonstrate that the injection of CD47 agonist peptides reduces tumor burden without inducing anemia or toxicity in blood, liver, or kidney. The limitations of our study are mainly linked to the affinity of the peptides targeting CD47, which might be improved to reach the standard requirements in drug development, and the lack of a CLL animal model that fully mimics the human disease.

Conclusions

Our work provides substantial progress in (i) the development of serum-stable CD47 agonist peptides that are highly effective at inducing PCD in CLL, (ii) the understanding of the molecular events regulating a novel PCD pathway that overcomes CLL apoptotic avoidance, (iii) the identification of PLCγ1 as an over-expressed protein in CLL B cells, and (iv) the description of a novel peptide-based strategy against CLL.

Ultra-Sensitive Detection of Plasmodium falciparum by Amplification of Multi-Copy Subtelomeric Targets

PLoS Medicine - Ma, 03/03/2015 - 23:00

by Natalie Hofmann, Felista Mwingira, Seif Shekalaghe, Leanne J. Robinson, Ivo Mueller, Ingrid Felger

Background

Planning and evaluating malaria control strategies relies on accurate definition of parasite prevalence in the population. A large proportion of asymptomatic parasite infections can only be identified by surveillance with molecular methods, yet these infections also contribute to onward transmission to mosquitoes. The sensitivity of molecular detection by PCR is limited by the abundance of the target sequence in a DNA sample; thus, detection becomes imperfect at low densities. We aimed to increase PCR diagnostic sensitivity by targeting multi-copy genomic sequences for reliable detection of low-density infections, and investigated the impact of these PCR assays on community prevalence data.

Methods and Findings

Two quantitative PCR (qPCR) assays were developed for ultra-sensitive detection of Plasmodium falciparum, targeting the high-copy telomere-associated repetitive element 2 (TARE-2, ∼250 copies/genome) and the var gene acidic terminal sequence (varATS, 59 copies/genome). Our assays reached a limit of detection of 0.03 to 0.15 parasites/μl blood and were 10× more sensitive than standard 18S rRNA qPCR. In a population cross-sectional study in Tanzania, 295/498 samples tested positive using ultra-sensitive assays. Light microscopy missed 169 infections (57%). 18S rRNA qPCR failed to identify 48 infections (16%), of which 40% carried gametocytes detected by pfs25 quantitative reverse-transcription PCR. To judge the suitability of the TARE-2 and varATS assays for high-throughput screens, their performance was tested on sample pools. Both ultra-sensitive assays correctly detected all pools containing one low-density P. falciparum–positive sample, which went undetected by 18S rRNA qPCR, among nine negatives. TARE-2 and varATS qPCRs improve estimates of prevalence rates, yet other infections might still remain undetected when absent in the limited blood volume sampled.

Conclusions

Measured malaria prevalence in communities is largely determined by the sensitivity of the diagnostic tool used. Even when applying standard molecular diagnostics, prevalence in our study population was underestimated by 8% compared to the new assays. Our findings highlight the need for highly sensitive tools such as TARE-2 and varATS qPCR in community surveillance and for monitoring interventions to better describe malaria epidemiology and inform malaria elimination efforts.

Cheap wonder metals will make a faster, cleaner world

New Scientist - Ma, 03/03/2015 - 23:00
If only aluminium, titanium and magnesium were cheaper, they would replace steel and help us cut fuel bills and emissions. That day may not be far off






Here's the beef - think green and cut meat

New Scientist - Ma, 03/03/2015 - 22:00
The US panel advising the government on dietary guidelines urges Americans to eat less meat. There is nothing wrong with that, says Josh Voorhees






Test yourself on Facebook's intelligence questions

New Scientist - Ma, 03/03/2015 - 21:30
Fancy taking Facebook's AI exam for yourself? Here are some example questions that get progressively harder






Birth of a Theorem: Mathematics, Boltzmann and brio

New Scientist - Ma, 03/03/2015 - 21:00
Birth of a Theorem: A mathematical adventure by Fields medallist Cedric Villani is an exhilarating but exhausting journey with a fascinating mind






It's man flu! Real flu hits just twice a decade

New Scientist - Ma, 03/03/2015 - 20:00
Your girlfriend is right. Adults can expect to get flu only twice every 10 years, suggests an analysis of the antibodies in people's blood






Facebook invents an intelligence test for machines

New Scientist - Ma, 03/03/2015 - 19:25
Forget the Turing test. Facebook has come up with a simple quiz that will help work out the intelligence levels of your latest AI






Today on New Scientist

New Scientist - Ma, 03/03/2015 - 18:30
All the latest on newscientist.com: the real reasons for child obesity, alien invaders going by Suez, smelly handshakes, zombie simulator and more






2015 a watershed year for assisted suicide in the US

New Scientist - Ma, 03/03/2015 - 18:30
With bills introduced that could legalise the right to die in 20 more states, this year could be a turning point for the highly controversial practice






Tiny CubeSats could hitch a ride with ESA mission

New Scientist - Ma, 03/03/2015 - 17:47
The European Space Agency is calling for small, boxy spacecraft called CubeSats to hitch a ride with a mission in 2020 – perhaps the first CubeSat trip into deep space






Dawn spacecraft set for first visit to a dwarf planet

New Scientist - Ma, 03/03/2015 - 16:58
The asteroid-hopping spacecraft will arrive at Ceres on Friday, making it the first to visit a dwarf planet and the first to visit two different worlds






After handshakes, we sniff people's scent on our hand

New Scientist - Ma, 03/03/2015 - 15:00
People sniff their hands much of the time and especially after a handshake, suggesting the greeting might convey chemical signals






Victory declaration on net neutrality may be premature

New Scientist - Ma, 03/03/2015 - 13:30
The US Federal Communication Commission has taken an important step to ensure net neutrality – but dangers remain






I've found the real reason so many children are obese

New Scientist - Ma, 03/03/2015 - 13:15
Don't blame gluttony or genes for the obesity epidemic – it's our sedentary habits echoing down the generations, says obesity theorist Edward Archer (full text available to subscribers)






Giant robot eyes scan stars for dust

New Scientist - Ma, 03/03/2015 - 13:00
The huge eyes of the Large Binocular Telescope in Arizona are staring across vast cosmic distances in the hope of finding signs of alien life






Droughts in Syria and California linked to climate change

New Scientist - Lu, 02/03/2015 - 21:00
The two regions have recently suffered their worst droughts on record. And Syria's may have helped to trigger its civil war






Suez superhighway: Stopping the tide of alien invaders

New Scientist - Lu, 02/03/2015 - 21:00
We're creating a thoroughfare for invasive species to pour into the Mediterranean from the Red Sea – but for once there is a way to stem the flow (full text available to subscribers)






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