Meteorological influences on respirable fragment release from Chinese elm pollen

Exposure to airborne pollen from certain plants can cause allergic disease, leading to acute respiratory symptoms. Whole pollen grains, 15&ndash;90 &mu; m-sized particles, provoke the upper respiratory symptoms of rhinitis (hay fever), while smaller pollen fragments capable of depositing in the lower respiratory tract have been proposed as the trigger for asthma. In order to understand factors leading to pollen release and fragmentation we have examined the rupture of Chinese elm pollen under controlled laboratory conditions and in the outdoor atmosphere. Within 30 minutes after immersion in water, 70% of fresh Chinese pollen ruptures, rapidly expelling cytoplasm. Chinese elm flowers, placed in a controlled atmosphere chamber, emitted pollen and pollen debris after a sequential treatment of 98% relative humidity followed by drying and a gentle disturbance. Immunologic assays of antigenic proteins specific to elm pollens revealed that fine particulate material (D p &lt; 2 &mu; m) collected from the chamber contained elm pollen antigens. In a temporal study of the outdoor urban atmosphere during the Chinese elm bloom season of 2004, peak concentrations of pollen and fine pollen fragments occurred at the beginning of the season when nocturnal relative humidity (RH) exceeded 90%. Following later periods of hot dry weather, pollen counts decreased to zero. The Chinese elm pollen fragments also decreased during the hot weather, but later displayed additional peaks following periods of more moderate RH and temperature, indicating that pollen counts underestimate total atmospheric pollen allergen concentrations. Pollen fragments thus increase the biogenic load in the atmosphere in a form that is no longer recognizable as pollen and, therefore, is not amenable to microscopic analysis. This raises the possibility of exposure of sensitive individuals to pollen allergens in the form of fine particles that can penetrate into the lower airways and pose potentially severe health risks.<br /

Allergens in Paved Road Dust and Airborne Particles

Paved road dust present on the surface of streets in Southern California consists of a complex mixture of soil dust, deposited motor vehicle exhaust particles, tire dust, brake lining wear dust, plant fragments, and other biological materials. The research presented here shows that allergens from at least 20 different source materials are found in the paved road dust. These include pollens and pollen fragments, animal dander, and molds. When paved road dust is resuspended into the atmosphere by passing vehicle traffic, allergen concentrations in the air are increased above the levels that would prevail without the vehicle traffic. Using immunological assays that measure the proteins extracted from environmental samples that bind to IgE antibodies present in the blood serum of allergenic patients, it is possible to measure the allergen concentrations present in paved road dust and in airborne particle samples. Total protein contributions to monthly average airborne TSP and PM_(10) concentrations are found to be in the range from 1 to 5.8 μg m^(-3), potentially accounting for a significant fraction of the airborne particulate organic material that has not been identified to date by GC/MS techniques. Results show that up to 5−12% of the allergenicity of atmospheric total suspended particulate matter samples at Long Beach and Rubidoux, CA, is attributable to paved road dust emissions. In an industrial area of urban central Los Angeles where there is less proximity to vegetation and domestic activities, the paved road dust contribution to airborne allergen concentrations is lower, accounting for approximately 0.5% of the total allergenic activity of the atmospheric particle samples. In conclusion, paved road dust when entrained into the atmosphere by passing traffic is a source of allergen exposure for the general population and could be more important in areas with more abundant vegetation or with closer proximity of populations to major highways than is the case for the Southern California air monitoring sites studied here

Allergens in Paved Road Dust and Airborne Particles

Paved road dust present on the surface of streets in Southern California consists of a complex mixture of soil dust, deposited motor vehicle exhaust particles, tire dust, brake lining wear dust, plant fragments, and other biological materials. The research presented here shows that allergens from at least 20 different source materials are found in the paved road dust. These include pollens and pollen fragments, animal dander, and molds. When paved road dust is resuspended into the atmosphere by passing vehicle traffic, allergen concentrations in the air are increased above the levels that would prevail without the vehicle traffic. Using immunological assays that measure the proteins extracted from environmental samples that bind to IgE antibodies present in the blood serum of allergenic patients, it is possible to measure the allergen concentrations present in paved road dust and in airborne particle samples. Total protein contributions to monthly average airborne TSP and PM_(10) concentrations are found to be in the range from 1 to 5.8 μg m^(-3), potentially accounting for a significant fraction of the airborne particulate organic material that has not been identified to date by GC/MS techniques. Results show that up to 5−12% of the allergenicity of atmospheric total suspended particulate matter samples at Long Beach and Rubidoux, CA, is attributable to paved road dust emissions. In an industrial area of urban central Los Angeles where there is less proximity to vegetation and domestic activities, the paved road dust contribution to airborne allergen concentrations is lower, accounting for approximately 0.5% of the total allergenic activity of the atmospheric particle samples. In conclusion, paved road dust when entrained into the atmosphere by passing traffic is a source of allergen exposure for the general population and could be more important in areas with more abundant vegetation or with closer proximity of populations to major highways than is the case for the Southern California air monitoring sites studied here

RhIGF-1 treatment increases bone mineral density and trabecular bone structure in children with PAPP-A2 deficiency

KARGER: "This is the peer-reviewed but unedited manuscript version of the following article: Hormone Research in Paediatrics 89.3 (2018): 200-204 DOI: 10.1159/000486336. The final, published version is available at http://www.karger.com/. http://doi.org/10.1159/000486336]."Aim: Our objective was to determine changes in bone mineral density (BMD), trabecular bone score (TBS), and body composition after 2 years of therapy with recombinant human insulin-like growth factor-1 (rhIGF-1) in 2 prepubertal children with a complete lack of circulating PAPP-A2 due to a homozygous mutation in PAPP-A2 (p.D643fs25∗) resulting in a premature stop codon. Methods: Body composition, BMD, and bone structure were determined by dual-energy X-ray absorptiometry at baseline and after 1 and 2 years of rhIGF-1 treatment. Results: Height increased from 132 to 145.5 cm (patient 1) and from 111.5 to 124.5 cm (patient 2). Bone mineral content increased from 933.40 to 1,057.97 and 1,152.77 g in patient 1, and from 696.12 to 773.26 and 911.51 g in patient 2, after 1 and 2 years, respectively. Whole-body BMD also increased after 2 years of rhIGF-1 from baseline 0.788 to 0.869 g/cm2in patient 1 and from 0.763 to 0.829 g/cm2in patient 2. After 2 years of treatment, both children had an improvement in TBS. During therapy, a slight increase in body fat mass was seen, with a concomitant increase in lean mass. No adverse effects were reported. Conclusion: Two years of rhIGF-1 improved growth, with a tendency to improve bone mass and bone microstructure and to modulate body composition.The authors are funded by Fondos de Investigación Sanitaria and FEDER (Grants PI1302195 and PI1600485 to J.A.), Ministerio de Ciencia e Innovación (BFU2014-51836-C2-2-R to J.A.C.), Centro de Investigación Biomédica en Red Fisiopatología de Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (J.A.), and Fundación Endocrinología y Nutrició

Genetic aetiology of self-harm ideation and behaviour

Family studies have identified a heritable component to self-harm that is partially independent from comorbid psychiatric disorders. However, the genetic aetiology of broad sense (non-suicidal and suicidal) self-harm has not been characterised on the molecular level. In addition, controversy exists about the degree to which suicidal and non-suicidal self-harm share a common genetic aetiology. In the present study, we conduct genome-wide association studies (GWAS) on lifetime self-harm ideation and self-harm behaviour (i.e. any lifetime self-harm act regardless of suicidal intent) using data from the UK Biobank (n > 156,000). We also perform genome wide gene-based tests and characterize the SNP heritability and genetic correlations between these traits. Finally, we test whether polygenic risk scores (PRS) for self-harm ideation and self-harm behaviour predict suicide attempt, suicide thoughts and non-suicidal self-harm (NSSH) in an independent target sample of 8,703 Australian adults. Our GWAS results identified one genome-wide significant locus associated with each of the two phenotypes. SNP heritability (h) estimates were ~10%, and both traits were highly genetically correlated (LDSC r > 0.8). Gene-based tests identified seven genes associated with self-harm ideation and four with self-harm behaviour. Furthermore, in the target sample, PRS for self-harm ideation were significantly associated with suicide thoughts and NSSH, and PRS for self-harm behaviour predicted suicide thoughts and suicide attempt. Follow up regressions identified a shared genetic aetiology between NSSH and suicide thoughts, and between suicide thoughts and suicide attempt. Evidence for shared genetic aetiology between NSSH and suicide attempt was not statistically significant

From cheek swabs to consensus sequences : an A to Z protocol for high-throughput DNA sequencing of complete human mitochondrial genomes

Background: Next-generation DNA sequencing (NGS) technologies have made huge impacts in many fields of biological research, but especially in evolutionary biology. One area where NGS has shown potential is for high-throughput sequencing of complete mtDNA genomes (of humans and other animals). Despite the increasing use of NGS technologies and a better appreciation of their importance in answering biological questions, there remain significant obstacles to the successful implementation of NGS-based projects, especially for new users. Results: Here we present an ‘A to Z’ protocol for obtaining complete human mitochondrial (mtDNA) genomes – from DNA extraction to consensus sequence. Although designed for use on humans, this protocol could also be used to sequence small, organellar genomes from other species, and also nuclear loci. This protocol includes DNA extraction, PCR amplification, fragmentation of PCR products, barcoding of fragments, sequencing using the 454 GS FLX platform, and a complete bioinformatics pipeline (primer removal, reference-based mapping, output of coverage plots and SNP calling). Conclusions: All steps in this protocol are designed to be straightforward to implement, especially for researchers who are undertaking next-generation sequencing for the first time. The molecular steps are scalable to large numbers (hundreds) of individuals and all steps post-DNA extraction can be carried out in 96-well plate format. Also, the protocol has been assembled so that individual ‘modules’ can be swapped out to suit available resources

Whole genome sequencing to evaluate the resistance landscape following antimalarial treatment failure with fosmidomycin-clindamycin

Novel antimalarial therapies are needed in the face of emerging resistance to artemisinin combination therapies. A previous study found a high cure rate in Mozambican children with uncomplicated Plasmodium falciparum malaria 7 days post treatment with a fosmidomycin-clindamycin combination. However, 28-day cure rates were low (45.9%), due to parasite recrudescence. We sought to identify any genetic changes underlying parasite recrudescence. To this end, we utilized a selective whole genome amplification method to amplify parasite genomes from blood spot DNA samples. Parasite genomes from pre-treatment and post-recrudescence samples were subjected to whole genome sequencing to identify nucleotide variants. We find that our data do not support the existence of a genetic change responsible for recrudescence following fosmidomycin-clindamycin treatment. Additionally, we find that previously described resistance alleles for these drugs do not represent biomarkers of recrudescence. Future studies should continue to optimize fosmidomycin combinations for use as antimalarial therapies