Acute and chronic effects of particles on hospital admissions in New-England

Background

Many studies have reported significant associations between exposure to PM_2.5 and hospital admissions, but all have focused on the effects of short-term exposure. In addition all these studies have relied on a limited number of PM_2.5 monitors in their study regions, which introduces exposure error, and excludes rural and suburban populations from locations in which monitors are not available, reducing generalizability and potentially creating selection bias.

Methods

Using our novel prediction models for exposure combining land use regression with physical measurements (satellite aerosol optical depth) we investigated both the long and short term effects of PM_2.5 exposures on hospital admissions across New-England for all residents aged 65 and older. We performed separate Poisson regression analysis for each admission type: all respiratory, cardiovascular disease (CVD), stroke and diabetes. Daily admission counts in each zip code were regressed against long and short-term PM_2.5 exposure, temperature, socio-economic data and a spline of time to control for seasonal trends in baseline risk.

Results

We observed associations between both short-term and long-term exposure to PM_2.5 and hospitalization for all of the outcomes examined. In example, for respiratory diseases, for every10-µg/m³ increase in short-term PM_2.5 exposure there is a 0.70 percent increase in admissions (CI = 0.35 to 0.52) while concurrently for every10-µg/m³ increase in long-term PM_2.5 exposure there is a 4.22 percent increase in admissions (CI = 1.06 to 4.75).

Conclusions

As with mortality studies, chronic exposure to particles is associated with substantially larger increases in hospital admissions than acute exposure and both can be detected simultaneously using our exposure models.     

Mapping the depth dependence of shear properties in articular cartilage

Determining the depth dependence of the shear properties of articular cartilage is essential for understanding the structure-function relation in this tissue. Here, we measured spatial variations in the shear modulus G of bovine articular cartilage using a novel technique that combines shear testing, confocal imaging and force measurement. We found that G varied by up to two orders of magnitude across a single sample, exhibited a global minimum 50-250 microm below the articular surface in a region just below the superficial zone and was roughly constant at depths > 1000 microm (the "plateau region"). For plateau strains gamma(plateau) approximately 0.75% and overall compressive strains epsilon approximately 5%, G(min) and G(plateau) were approximately 70 and approximately 650 kPa, respectively. In addition, we found that the shear modulus profile depended strongly on the applied shear and axial strains. The greatest change in G occurred at the global minimum where the tissue was highly nonlinear, stiffening under increased shear strain, and weakening under increased compressive strain. Our results can be explained through a simple thought model describing the observed nonlinear behavior in terms of localized buckling of collagen fibers and suggest that compression may decrease the vulnerability of articular cartilage to shear-induced damage by lowering the effective strain on individual collagen fibrils.     

Germination strategy of Striga hermonthica involves regulation of ethylene biosynthesis

Ethylene involvement in germination of Striga hermonthica (Del.) Benth., an important root parasitic weed on poaceous crops, was investigated at the physiological and molecular levels. Seeds, conditioned at 30°C for 14 days, were treated with ethylene, ethephon or 1-aminocyclopropane-1-carboxylic acid (ACC). Ethylene consistently induced low germination. Ethephon and ACC effectively stimulated germination at concentrations of 0.01 and 1 m M , respectively. In contrast to ethylene, both ethephon and ACC acted in a concentration-dependent manner. Germination induced by the synthetic strigolactone GR24 was inhibited by aminoethoxyvinylglycine (AVG) and 1-methylcyclopropene. ACC reversed the inhibition caused by AVG. When seeds were treated with GR24 in sealed vials, ethylene concentration in headspace gas increased prior to the onset of germination. Total RNA extracted from germinating seeds 12 h after GR24 treatment was used for PCR-based amplification of cDNA fragments encoding the ACC synthase- and oxidase-active site domains. Two distinct cDNA fragments encoding ACC synthase ( SHACS1 and SHACS2 ) and one encoding ACC oxidase ( SHACO1 ) were cloned and sequenced. Southern analysis suggested that each of the cloned genes was present as a single copy in the genome of S. hermonthica . Northern analyses showed that SHACS1 exhibited a temporal change in expression peaking at 10 h after GR24 treatment, which coincided with a steady increase in ethylene concentration. SHACS2 was expressed at a low level with a similar trend. SHACO1 exhibited a temporal change in expression peaking at 15 days during conditioning, when seed response to GR24 was maximal. In summary, expression of ACC synthase and ACC oxidase genes was found to be responsive to a germination stimulant and to conditioning, respectively. The implications of these findings with respect to germination of S. hermonthica under field conditions are discussed.     

Detection of high CD44 expression in oral cancers using the novel monoclonal antibody,C44Mab-5

CD44 is a transmembrane glycoprotein that regulates a variety of genes related to cell-adhesion, migration, proliferation, differentiation, and survival. A large number of alternative splicing isoforms of CD44, containing various combinations of alternative exons, have been reported. CD44 standard (CD44s), which lacks variant exons, is widely expressed on the surface of most tissues and all hematopoietic cells. In contrast, CD44 variant isoforms show tissue-specific expression patterns and have been extensively studied as both prognostic markers and therapeutic targets in cancer and other diseases. In this study, we immunized mice with CHO-K1 cell lines overexpressing CD44v3-10 to obtain novel anti-CD44 mAbs. One of the clones, C₄₄Mab-5 (IgG₁, kappa), recognized both CD44s and CD44v3-10. C₄₄Mab-5 also reacted with oral cancer cells such as Ca9-22, HO-1-u-1, SAS, HSC-2, HSC-3, and HSC-4 using flow cytometry. Moreover, immunohistochemical analysis revealed that C₄₄Mab-5 detected 166/182 (91.2%) of oral cancers. These results suggest that the C₄₄Mab-5 antibody may be useful for investigating the expression and function of CD44 in various cancers.     

Identification of QTLs Associated with Conversion of Sucrose to Hexose in Mature Fruit of Japanese Pear

Sweetness is the most important trait for fruit breeding and is fundamentally determined by both total and individual sugar contents. We analyzed the contents of sucrose, fructose, glucose, and sorbitol in mature fruit in an F₁ population derived from crossing modern Japanese pear cultivar ‘Akizuki’ and breeding line ‘373-55’. A genetic linkage map was constructed using simple sequence repeats (SSRs) and single-nucleotide polymorphisms (SNP). We identified two regions associated with individual sugar contents on linkage group (LG) 1 and LG 7. The percentages of the variance in sucrose, fructose, and glucose explained by the quantitative trait loci (QTLs) were 26.6, 15.9, and 18.5%, respectively, for the region on LG 1, and 22.2, 20.0, and 9.5%, respectively, for the region on LG 7. In both regions, genotypes associated with increases in sucrose were associated with decreases in both fructose and glucose. The 1.5-LOD support intervals of the QTLs on LGs 1 and 7 include SSRs within the regions flanking acid invertase genes PPAIV3 and PPAIV1, respectively. Because acid invertase is a key enzyme in the conversion of sucrose to hexose, these are promising candidates for genes underlying those QTLs and controlling individual sugar contents. We also found one region on LG 11 that explained 21.4% of the variation in total sugar content but was not significantly associated with variation for individual sugars. The information obtained in this study will accelerate research and breeding programs to improve fruit sweetness.     

Two conformational states of the membrane-associated Bacillus thuringiensis Cry4Ba delta-endotoxin complex revealed by electron crystallography: implications for toxin-pore formation

The insecticidal nature of Cry delta-endotoxins produced by Bacillus thuringiensis is generally believed to be caused by their ability to form lytic pores in the midgut cell membrane of susceptible insect larvae. Here we have analyzed membrane-associated structures of the 65-kDa dipteran-active Cry4Ba toxin by electron crystallography. The membrane-associated toxin complex was crystallized in the presence of DMPC via detergent dialysis. Depending upon the charge of the adsorbed surface, 2D crystals of the oligomeric toxin complex have been captured in two distinct conformations. The projection maps of those crystals have been generated at 17A resolution. Both complexes appeared to be trimeric; as in one crystal form, its projection structure revealed a symmetrical pinwheel-like shape with virtually no depression in the middle of the complex. The other form revealed a propeller-like conformation displaying an obvious hole in the center region, presumably representing the toxin-induced pore. These crystallographic data thus demonstrate for the first time that the 65-kDa activated Cry4Ba toxin in association with lipid membranes could exist in at least two different trimeric conformations, conceivably implying the closed and open states of the pore.