Air quality in Mecca and surrounding holy places in Saudi Arabia during Hajj: initial survey.

The Arabian Peninsula experiences severe air pollution, the extent and sources of which are poorly documented. Each year in Saudi Arabia this situation is intensified during Hajj, the Holy Pilgrimage of Islam that draws millions of pilgrims to Mecca. An initial study of air quality in Mecca and surrounding holy sites during the 2012 Hajj (October 24-27) revealed strongly elevated levels of the combustion tracer carbon monoxide (CO, up to 57 ppmv) and volatile organic compounds (VOCs) along the pilgrimage route-especially in the tunnels of Mecca-that are a concern for human health. The most abundant VOC was the gasoline evaporation tracer i-pentane, which exceeded 1200 ppbv in the tunnels. Even though VOC concentrations were generally lower during a follow-up non-Hajj sampling period (April 2013), many were still comparable to other large cities suffering from poor air quality. Major VOC sources during the 2012 Hajj study included vehicular exhaust, gasoline evaporation, liquefied petroleum gas, and air conditioners. Of the measured compounds, reactive alkenes and CO showed the strongest potential to form ground-level ozone. Because the number of pilgrims is expected to increase in the future, we present emission reduction strategies to target both combustive and evaporative fossil fuel sources

The influence of different length between match microcycles on neuromuscular, hormonal and perceptual responses in professional rugby league players

Optimal recovery between matches is critically important in team sports. Indeed, altered neuromuscular performance, hormone levels and increased fatigue can manifest in under recovered team sport athletes. However, the recovery patterns in these variables in the days following professional rugby league matches is unknown. The purpose of this study was to examine the influence of different between-match training periods on neuromuscular, hormonal and perceptual measures in professional rugby league players. Following familiarization, 12 professional rugby league players from the same team were assessed for changes in countermovement jump (CMJ) (force, power, flight time), perceptual responses (fatigue, well being and muscle soreness) and salivary hormone (testosterone (T) and cortisol (C)) levels during 5, 7 and 9 day periods between matches. Measures were taken 4h prior to the initial match, and then 1, 2, 4, 6*, 7*, 8* and 9* days following (*depending on group). All training was prescribed by the coaches and monitored using the session-RPE method. Lower daily training load was completed on the 5-day compared with the 7 and 9-day conditions (p\u3c0.05). Some CMJ variables (flight time and flight time:contraction time), perception of fatigue, well-being and muscle soreness were reduced in the 2 days following the match in each condition (p\u3c0.05). All CMJ variables returned to near baseline values following 4 days in each condition. Both CMJ maximum and relative power were lower in the 7 day condition when compared with the 9 day condition (p\u3c0.05). Fatigue levels were reduced at 48 h in the 7 and 9-day groups (p\u3c0.05) but had returned to baseline in the 5-day group. All perceptual measures returned to baseline levels prior to the following match in each condition and followed changes in training load. Salivary T and C did not change in response to the match. These results show that neuromuscular performance and perception of fatigue are reduced for at least 48 h following a rugby league match but these can be fully recovered within 4 days. CMJ variables involving flight time appear to be best for assessing acute fatigue caused by a match, and variables involving power may be useful in assessing accumulated fatigue. The perceptual measures were sensitive to both acute fatigue and accumulated fatigue. The salivary hormone analyses were of limited value for assessing recovery. These findings show that with correct training, it is possible to recover neuromuscular, perceptual and endocrine measures within 4 days after a rugby league match

The C. elegans CHP1 homolog, pbo-1, functions in innate immunity by regulating the pH of the intestinal lumen

This work is licensed under a Creative Commons Attribution 4.0 International License.Caenorhabditis elegans are soil-dwelling nematodes and models for understanding innate immunity and infection. Previously, we developed a novel fluorescent dye (KR35) that accumulates in the intestine of C. elegans and reports a dynamic wave in intestinal pH associated with the defecation motor program. Here, we use KR35 to show that mutations in the Ca2+-binding protein, PBO-1, abrogate the pH wave, causing the anterior intestine to be constantly acidic. Surprisingly, pbo-1 mutants were also more susceptible to infection by several bacterial pathogens. We could suppress pathogen susceptibility in pbo-1 mutants by treating the animals with pH-buffering bicarbonate, suggesting the pathogen susceptibility is a function of the acidity of the intestinal pH. Furthermore, we use KR35 to show that upon infection by pathogens, the intestinal pH becomes neutral in a wild type, but less so in pbo-1 mutants. C. elegans is known to increase production of reactive oxygen species (ROS), such as H2O2, in response to pathogens, which is an important component of pathogen defense. We show that pbo-1 mutants exhibited decreased H2O2 in response to pathogens, which could also be partially restored in pbo-1 animals treated with bicarbonate. Ultimately, our results support a model whereby PBO-1 functions during infection to facilitate pH changes in the intestine that are protective to the host

Near-Earth injection of MeV electrons associated with intense dipolarization electric fields: Van Allen Probes observations.

Substorms generally inject tens to hundreds of keV electrons, but intense substorm electric fields have been shown to inject MeV electrons as well. An intriguing question is whether such MeVelectron injections can populate the outer radiation belt. Here we present observations of a substorm injection of MeV electrons into the inner magnetosphere. In the premidnight sector at L ∼ 5.5, Van Allen Probes (Radiation Belt Storm Probes)-A observed a large dipolarization electric field (50 mV/m) over ∼40 s and a dispersionless injection of electrons up to ∼3 MeV. Pitch angle observations indicated betatron acceleration of MeV electrons at the dipolarization front. Corresponding signals of MeV electron injection were observed at LANL-GEO, THEMIS-D, and GOES at geosynchronous altitude. Through a series of dipolarizations, the injections increased the MeV electron phase space density by 1 order of magnitude in less than 3 h in the outer radiation belt (L > 4.8). Our observations provide evidence that deep injections can supply significant MeV electrons

Expanding the clinical phenotype of the 3q29 microdeletion syndrome and characterization of the reciprocal microduplication

<p>Abstract</p> <p>Background</p> <p>Interstitial deletions of 3q29 have been recently described as a microdeletion syndrome mediated by nonallelic homologous recombination between low-copy repeats resulting in an ~1.6 Mb common-sized deletion. Given the molecular mechanism causing the deletion, the reciprocal duplication is anticipated to occur with equal frequency, although only one family with this duplication has been reported.</p> <p>Results</p> <p>In this study we describe 14 individuals with microdeletions of 3q29, including one family with a mildly affected mother and two affected children, identified among 14,698 individuals with idiopathic mental retardation who were analyzed by array CGH. Eleven individuals had typical 1.6-Mb deletions. Three individuals had deletions that flank, span, or partially overlap the commonly deleted region. Although the clinical presentations of individuals with typical-sized deletions varied, several features were present in multiple individuals, including mental retardation and microcephaly. We also identified 19 individuals with duplications of 3q29, five of which appear to be the reciprocal duplication product of the 3q29 microdeletion and 14 of which flank, span, or partially overlap the common deletion region. The clinical features of individuals with microduplications of 3q29 also varied with few common features. <it>De novo </it>and inherited abnormalities were found in both the microdeletion and microduplication cohorts illustrating the need for parental samples to fully characterize these abnormalities.</p> <p>Conclusion</p> <p>Our report demonstrates that array CGH is especially suited to identify chromosome abnormalities with unclear or variable presentations.</p

Wetland Management Strategies that Maximize Marsh Bird Use in the Midwest: Final Performance Report: F14AP00485

We sought to investigate marsh bird occupancy and abundance across a wide range of representative wetlands types, hydrologic regimes, management practices, and former disturbance regimes in Illinois. We hypothesized that characteristics of wetlands that were actively and passively managed for waterfowl would be positively correlated with marsh bird occupancy and abundance in Illinois during the migration and breeding seasons. Our specific objectives were to: 1) compare marsh bird use of wetland impoundments managed for waterfowl across a continuum of management intensities and strategies to predict how impoundment management actions can increase use by both groups; 2) compare marsh bird use of restored and natural wetlands; and 3) determine characteristics of wetlands and the surrounding landscape that influence marsh bird use of restored wetlands. Our results are important to understanding spatiotemporal, hydrological, and vegetative conditions suitable for multi-species management of wetlands. Moreover, our research provided information regarding the effectiveness of conservation actions, particularly wetland restoration in meeting conservation priorities for migrating birds.U.S. Fish & Wildlife Service Wildlife and Sport Fish Restoration Programsunpublishednot peer reviewedOpe

Antibody-drug conjugate targeting CD46 eliminates multiple myeloma cells

Multiple myeloma is incurable by standard approaches because of inevitable relapse and development of treatment resistance in all patients. In our prior work, we identified a panel of macropinocytosing human monoclonal antibodies against CD46, a negative regulator of the innate immune system, and constructed antibody-drug conjugates (ADCs). In this report, we show that an anti-CD46 ADC (CD46-ADC) potently inhibited proliferation in myeloma cell lines with little effect on normal cells. CD46-ADC also potently eliminated myeloma growth in orthometastatic xenograft models. In primary myeloma cells derived from bone marrow aspirates, CD46-ADC induced apoptosis and cell death, but did not affect the viability of nontumor mononuclear cells. It is of clinical interest that the CD46 gene resides on chromosome 1q, which undergoes genomic amplification in the majority of relapsed myeloma patients. We found that the cell surface expression level of CD46 was markedly higher in patient myeloma cells with 1q gain than in those with normal 1q copy number. Thus, genomic amplification of CD46 may serve as a surrogate for target amplification that could allow patient stratification for tailored CD46-targeted therapy. Overall, these findings indicate that CD46 is a promising target for antibody-based treatment of multiple myeloma, especially in patients with gain of chromosome 1q

Novel Acid-Activated Fluorophores Reveal a Dynamic Wave of Protons in the Intestine of Caenorhabditis elegans

Unlike the digestive systems of vertebrate animals, the lumen of the alimentary canal of C. elegans is unsegmented and weakly acidic (pH ~ 4.4), with ultradian fluctuations to pH > 6 every 45 to 50 seconds. To probe the dynamics of this acidity, we synthesized novel acid-activated fluorophores termed Kansas Reds. These dicationic derivatives of rhodamine B become concentrated in the lumen of the intestine of living C. elegans and exhibit tunable pKa values (2.3–5.4), controlled by the extent of fluorination of an alkylamine substituent, that allow imaging of a range of acidic fluids in vivo. Fluorescence video microscopy of animals freely feeding on these fluorophores revealed that acidity in the C. elegans intestine is discontinuous; the posterior intestine contains a large acidic segment flanked by a smaller region of higher pH at the posterior-most end. Remarkably, during the defecation motor program, this hot spot of acidity rapidly moves from the posterior intestine to the anterior-most intestine where it becomes localized for up to 7 seconds every 45 to 50 seconds. Studies of pH-insensitive and base-activated fluorophores as well as mutant and transgenic animals revealed that this dynamic wave of acidity requires the proton exchanger PBO-4, does not involve substantial movement of fluid, and likely involves the sequential activation of proton transporters on the apical surface of intestinal cells. Lacking a specific organ that sequesters low pH, C. elegans compartmentalizes acidity by producing of a dynamic hot spot of protons that rhythmically migrates from the posterior to anterior intestine