Germline allele-specific expression of TGFBR1 confers an increased risk of colorectal cancer

Much of the genetic predisposition to colorectal cancer (CRC) in humans is unexplained. Studying a Caucasian-dominated population in the United States, we showed that germline allele-specific expression (ASE) of the gene encoding transforming growth factor-beta (TGF-beta) type I receptor, TGFBR1, is a quantitative trait that occurs in 10 to 20% of CRC patients and 1 to 3% of controls. ASE results in reduced expression of the gene, is dominantly inherited, segregates in families, and occurs in sporadic CRC cases. Although subtle, the reduction in constitutive TGFBR1 expression alters SMAD-mediated TGF-beta signaling. Two major TGFBR1 haplotypes are predominant among ASE cases, which suggests ancestral mutations, but causative germline changes have not been identified. Conservative estimates suggest that ASE confers a substantially increased risk of CRC (odds ratio, 8.7; 95% confidence interval, 2.6 to 29.1), but these estimates require confirmation and will probably show ethnic differences.     

Numerical Comparison of Geomorphic Samples

The distribution of elevations representing a region can be shown as a cumulative frequency curve plotted on probability paper. Many elevation distributions are "zig-zag" curves which can be represented conveniently by measures of skewness and kurtosis. A plot of skewness versus kurtosis permits the recognition of six major, non-Gaussian forms, with countless gradations.     

Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum

Flow cytometry is an essential tool for dissecting the functional complexity of hematopoiesis. We used single-cell "mass cytometry" to examine healthy human bone marrow, measuring 34 parameters simultaneously in single cells (binding of 31 antibodies, viability, DNA content, and relative cell size). The signaling behavior of cell subsets spanning a defined hematopoietic hierarchy was monitored with 18 simultaneous markers of functional signaling states perturbed by a set of ex vivo stimuli and inhibitors. The data set allowed for an algorithmically driven assembly of related cell types defined by surface antigen expression, providing a superimposable map of cell signaling responses in combination with drug inhibition. Visualized in this manner, the analysis revealed previously unappreciated instances of both precise signaling responses that were bounded within conventionally defined cell subsets and more continuous phosphorylation responses that crossed cell population boundaries in unexpected manners yet tracked closely with cellular phenotype. Collectively, such single-cell analyses provide system-wide views of immune signaling in healthy human hematopoiesis, against which drug action and disease can be compared for mechanistic studies and pharmacologic intervention.     

LC-MS/MS analysis of neonicotinoid insecticides in honey: methodology and residue findings in Austrian honeys

An analytical method for the simultaneous determination of residues of eight neonicotinoid insecticides and two metabolites in honey using LC-MS/MS was developed and validated. Two approaches of sample preparation were investigated, with the final method involving acetonitrile extraction and subsequent cleanup by dispersive solid-phase extraction (QuEChERS type). Validation was based on quintuplicate analysis at three fortification levels and showed satisfactory recoveries (60-114%) and high precision (RSDs between 2.7 and 12.8%). Low limits of detection and quantification could be achieved for all analytes ranging from 0.6 to 5 μg/kg and from 2 to 10 μg/kg, respectively. Investigations of Austrian honey samples revealed the presence of acetamiprid, thiacloprid, and thiamethoxam residues in honey; however, no sample exceeded the maximum residue limits. On average, flower honey samples contained neonicotinoid residues in higher quantities compared to forest honey samples.     

Organic Acids in the Atmosphere and Bulk Deposition of Hong Kong

Results from the first study in Hong Kong, Southern China, to investigate the concentrations of organic acids in bulk deposition, aerosol and gas phase samples are presented. 57 daily bulk deposition samples were collected in central Kowloonand analyzed by ion chromatography, from May 1999 to May 2000. The volume-weighted (vw) mean concentrations for formate, acetate, propanoate and oxalate were 6.1, 4.5, 0.4 and 1.4 μeq dm^-3, respectively, with vw mean pH being 4.65.The maximum acidity contributions by formic and acetic acidsfor bulk deposition samples collected on a daily basis, withpH < 5.0, were 17 and 14%, respectively. The concentrationsof these acids were significantly correlated with each other, butnot with pH. Higher organic acid concentrations were foundin the dry, winter season, and for the synoptic weather systemtypes: approaching cyclone and cold front. Oxalate levels weregenerally higher in bulk deposition samples for north/northeasterly air masses, higher surface windspeeds, and low rainfall amounts. Formic and acetic acids were present at higher concentrations in the gas phase (mean concentrations at two sites were in the range from 3.2 to 6.5 μg m^-3, with formate usually < acetate), than in aerosols (mean concentration of formate, acetate or oxalate ≤2.2 μg m^-3). Higher levels of organic acids both in aerosols and in the gas phase were found at a busy roadside site than at a residential site. Deposition fluxes for formic and acetic acidsare reported.     

Methods of analysis for infant formula: Food and Drug Administration and Infant Formula Council Collaborative Study, Phase III

Phase III of the collaborative study of methods of assay for nutrients in infant formulas was conducted. The study included assay of chloride, phosphorus, proximates (ash, fat, protein, total solids, and carbohydrates), thiamine, total pantothenates, and vitamins A, B12, and E. Most of the methods were those in Official Methods of Analysis, 13th edition, with slight modifications, or methods of the Infant Formula Council. On the basis of the results obtained by the collaborators, the methods for chloride, phosphorus, proximates, thiamine, and vitamin B12 have been adopted official first action. Methods for total pantothenates, vitamin A, and vitamin E were not recommended for adoption at this time because of anticipated improvements in methodology in the foreseeable future.     

Adaptation of the Sensititre broth microdilution technique to antimicrobial susceptibility testing of Mycoplasma gallisepticum.

A technique is described for determining the antimicrobial susceptibility of Mycoplasma gallisepticum, using the Sensititre broth microdilution system. Fourteen M. gallisepticum field isolates and one reference isolate (R-strain) were tested in duplicate against seven antimicrobials. Isolates were susceptible to oxytetracycline, furaltadone, and lincomycin/spectinomycin, but not to amoxycillin and apramycin. Susceptibility to erythromycin and tylosin varied. These data are in agreement with those reported by other workers using more traditional methods, but this adaptation of the broth microdilution technique eliminates any variation attributable to the time-consuming preparation of antimicrobial dilutions associated with these methods.     

Serotypes of Erysipelothrix rhusiopathiae in Australian pigs, small ruminants, poultry, and captive wild birds and animals

Serotypes of 93 Australian isolates of Erysipelothrix rhusiopathiae from diseased domestic animals and poultry and a variety of captive wild birds and animals were determined by double diffusion gel precipitation. Two isolates, from the faeces of a swallow were also examined. Serotypes 1a, 1b and 2 were isolated from pigs and serotypes 1a, 1b, 2, 5, 15 and 21 from sheep or goats. Erysipelas in poultry was attributed to serotypes 1b, 5, 15 and 16. In captive wild birds serotypes 1b, 5, 6, 8, 14, 21 and an isolate reactive with antiserum to strain Seehecht were associated with septicaemic deaths. Single isolates from tissues of a bilby (Macrotis lagotis), black rat (Rattus rattus), brown snake (Pseudechis australis) and a bandicoot (Isoodon macrouris) were classified as serotypes 4, 4, 7, and 10 respectively. Six isolates were not able to be typed. Serotype 1b was the most widely distributed and most common (28%), being associated with disease in pigs, sheep, poultry and wild birds. Serotypes 1a or 2 were found in a more restricted range of animals, being commonly associated with erysipelas in pigs, less commonly in sheep and infrequently in other species. From diseased pigs, 26 of 33 isolates (79%) were serotypes 1a and 1b.