OECD 414 supplementary prenatal developmental toxicity study of sodium molybdate dihydrate in the rat and benchmark dose evaluation.

In a continuing investigation of the potential for reproductive and developmental toxicity of molybdenum (Mo), consequent to the previous published OECD studies [1,2] and as directed by the European Chemicals Agency [3], a supplemental rat GLP-compliant Prenatal Developmental Toxicity (PNDT) study was conducted to investigate higher dose levels of sodium molybdate dihydrate (SMD) in an identical study design (OECD 414)[4] to Murray et al. 2014a [1], at dietary concentrations calculated to provide target Mo levels of 80 and 120 mg/kg bw/day (the maximum-tolerated dose). There was no effect on post-implantation loss, litter size, sex ratio or the incidence of external, visceral or skeletal fetal malformations or variations. Fetal weight was reduced proportionate to maternal dose. Minimal differences observed in the ossification status of some extremities of fetuses from females receiving 120 mg Mo/kg bw/day were confirmed as transient by skeletal examination of PND 21 pups from a further group of females receiving the same dose regime. There was no evidence of copper depletion in serum, placenta or liver. A benchmark dose evaluation using continuous and dichotomous approaches by combining the fetal body weight data from this study and the previous study determined that the BMD05 ranged from 47 to 57 mg Mo/kg bw/day, depending on the modelling approach and the BMDL05 estimates ranged from 37 to 47 mg Mo/kg bw/day. These levels are considered a more statistically robust point of departure for risk assessment for reproductive effects than the established NOAEL of 40 mg Mo/kg bw/day.

A proteome-integrated, carbon source dependent genetic regulatory network in Saccharomyces cerevisiae.

Integrated regulatory networks can be powerful tools to examine and test properties of cellular systems, such as modelling environmental effects on the molecular bioeconomy, where protein levels are altered in response to changes in growth conditions. Although extensive regulatory pathways and protein interaction data sets exist which represent such networks, few have formally considered quantitative proteomics data to validate and extend them. We generate and consider such data here using a label-free proteomics strategy to quantify alterations in protein abundance for S. cerevisiae when grown on minimal media using glucose, galactose, maltose and trehalose as sole carbon sources. Using a high quality-controlled subset of proteins observed to be differentially abundant, we constructed a proteome-informed network, comprising 1850 transcription factor interactions and 37 chaperone interactions, which defines the major changes in the cellular proteome when growing under different carbon sources. Analysis of the differentially abundant proteins involved in the regulatory network pointed to their significant roles in specific metabolic pathways and function, including glucose homeostasis, amino acid biosynthesis, and carbohydrate metabolic process. We noted strong statistical enrichment in the differentially abundant proteome of targets of known transcription factors associated with stress responses and altered carbon metabolism. This shows how such integrated analysis can lend further experimental support to annotated regulatory interactions, since the proteomic changes capture both magnitude and direction of gene expression change at the level of the affected proteins. Overall this study highlights the power of quantitative proteomics to help define regulatory systems pertinent to environmental conditions.

Protection of Pea Aphids Associated with Coinfecting Bacterial Symbionts Persists During Superparasitism by a Braconid Wasp.

Bacterial endosymbionts that associate facultatively with insect herbivores can influence insect fitness and trophic interactions. The pea aphid, Acyrthosiphon pisum, can be protected from parasitism by the braconid wasp Aphidius ervi when harbouring particular symbiotic bacteria, with specific endosymbiont coinfections providing almost complete protection. However, studies often quantify aphid mummification with no control over parasitoid oviposition per aphid; thus, if mummy production fails or is low, the causes are often unclear. Here, we show that the high level of protection associated with the coinfecting endosymbionts Hamiltonella defensa and X-type is maintained even when pea aphids are superparasitised. This contrasts strongly with the protection provided by H. defensa alone, which has been shown by others to be overcome by superparasitism. By dissecting aphids exposed to two parasitoid attacks, we reveal that A. ervi deposits eggs equally freely in endosymbiont-infected and uninfected nymphs, and lack of mummification in endosymbiont-protected nymphs arises from failure of the wasp eggs to hatch or emerging larvae to develop.

What are the characteristics of breast cancers misclassified as benign by quantitative ultrasound shear wave elastography?

OBJECTIVES: Shear wave elastography (SWE) is a promising adjunct to greyscale ultrasound in differentiating benign from malignant breast masses. The purpose of this study was to characterise breast cancers which are not stiff on quantitative SWE, to elucidate potential sources of error in clinical application of SWE to evaluation of breast masses. METHODS: Three hundred and two consecutive patients examined by SWE who underwent immediate surgery for breast cancer were included. Characteristics of 280 lesions with suspicious SWE values (mean stiffness >50 kPa) were compared with 22 lesions with benign SWE values (<50 kPa). Statistical significance of the differences was assessed using non-parametric goodness-of-fit tests. RESULTS: Pure ductal carcinoma in situ (DCIS) masses were more often soft on SWE than masses representing invasive breast cancer. Invasive cancers that were soft were more frequently: histological grade 1, tubular subtype, ≤10 mm invasive size and detected at screening mammography. No significant differences were found with respect to the presence of invasive lobular cancer, vascular invasion, hormone and HER-2 receptor status. Lymph node positivity was less common in soft cancers. CONCLUSION: Malignant breast masses classified as benign by quantitative SWE tend to have better prognostic features than those correctly classified as malignant. KEY POINTS: • Over 90 % of cancers assessable with ultrasound have a mean stiffness >50 kPa. • 'Soft' invasive cancers are frequently small (≤10 mm), low grade and screen-detected. • Pure DCIS masses are more often soft than invasive cancers (>40 %). • Large symptomatic masses are better evaluated with SWE than small clinically occult lesions. • When assessing small lesions, 'softness' should not raise the threshold for biopsy.

Breed differences over time and heritability estimates for production and reproduction traits of dairy goats in the United States.

To aid in improvement of breeding programs for production and reproduction traits of US dairy goats, breed differences over time were documented and genetic parameters were estimated. Data were from herds with ≥2 breeds (Alpine, LaMancha, Nubian, Oberhasli, Saanen, or Toggenburg), but only purebred data were analyzed. Three kidding periods were examined: 1976 through 1984, 1985 through 1994, and 1995 through 2005. Univariate repeatability mixed models were used to estimate least squares means by kidding period-breed and genetic parameters for milk, fat, and protein yields, combined fat and protein yield, fat and protein percentages, protein:fat ratio, age at first kidding, and kidding interval. Trends across kidding periods were favorable for most yield traits for all breeds but generally unfavorable for reproduction traits. Saanens had the highest milk (1,063 to 1,125 kg) and protein yields (31 to 33 kg). Nubians had the highest fat yields (37 to 40 kg) and lowest milk yields (791 to 851 kg). Oberhaslis had the lowest fat (31 to 33 kg) and protein (23 to 27 kg) yields. Alpines had the largest increase in milk yield (7.4%); Oberhaslis had the largest increase in protein (17.4%) and combined fat and protein (13.2%) yields. Combined fat and protein yield was higher for Nubians, Saanens, and Alpines (65 to 72 kg) than for LaManchas, Toggenburgs, and Oberhaslis (53 to 67 kg). Nubians had the highest fat (4.7 to 4.8%) and protein (3.6 to 3.8%) percentages. Only Nubians increased in fat percentage (2.1%); protein percentage increased most for Toggenburgs (7.4%) and Alpines (7.1%). Protein:fat ratio was highest for Toggenburgs (0.84 to 0.89) and lowest for Nubians (0.76 to 0.81), but Nubians had the largest increase in protein:fat ratio (6.6%). Saanens were oldest at first kidding (509 to 589 d), and Toggenburgs and LaManchas generally were youngest (435 to 545 d); age at first kidding increased most for Alpines (21.8%) and LaManchas (21.6%). Kidding intervals generally were shorter for Oberhaslis, LaManchas, and Nubians (350 to 377 d) than for Toggenburgs, Alpines, and Saanens (373 to 387 d). Kidding interval increased most for Nubians (3.9%) and Saanens (3.8%) and decreased only for Oberhaslis (5.4%). Heritability estimates across breeds were 0.35 for milk and fat yields, 0.37 for protein yield and protein:fat ratio, 0.36 for combined fat and protein yield, 0.52 for fat percentage, 0.54 for protein percentage, 0.23 for age at first kidding, and 0.05 for kidding interval. Genetic selection within breed is feasible for production and reproduction traits of US dairy goats.

What are the implications of variation in root hair length on tolerance to phosphorus deficiency in combination with water stress in barley (Hordeum vulgare)?

BACKGROUND AND AIMS: Phosphorus commonly limits crop yield and is frequently applied as fertilizer; however, supplies of quality rock phosphate for fertilizer production are diminishing. Plants have evolved many mechanisms to increase their P-fertilizer use efficiency, and an understanding of these traits could result in improved long-term sustainability of agriculture. Here a mutant population is utilized to assess the impact of root hair length on P acquisition and yield under P-deficient conditions alone or when combined with drought. METHODS: Mutants with various root hair phenotypes were grown in the glasshouse in pots filled with soil representing sufficient and deficient P treatments and, in one experiment, a range of water availability was also imposed. Plants were variously harvested at 7 d, 8 weeks and 14 weeks, and variables including root hair length, rhizosheath weight, biomass, P accumulation and yield were measured. KEY RESULTS: The results confirmed the robustness of the root hair phenotypes in soils and their relationship to rhizosheath production. The data demonstrated that root hair length is important for shoot P accumulation and biomass, while only the presence of root hairs is critical for yield. Root hair presence was also critical for tolerance to extreme combined P deficit and drought stress, with genotypes with no root hairs suffering extreme growth retardation in comparison with those with root hairs. CONCLUSIONS: The results suggest that although root hair length is not important for maintaining yield, the presence of root hairs is implicit to sustainable yield of barley under P-deficient conditions and when combined with extreme drought. Root hairs are a trait that should be maintained in future germplasm.

How conserved are the bacterial communities associated with aphids? A detailed assessment of the Brevicoryne brassicae (Hemiptera: Aphididae) using 16S rDNA.

Aphids harbor a community of bacteria that include obligate and facultative endosymbionts belonging to the Enterobacteriaceae along with opportunistic, commensal, or pathogenic bacteria. This study represents the first detailed analysis of the identity and diversity of the bacterial community associated with the cabbage aphid, Brevicoryne brassicae (L.). 16S rDNA sequence analysis revealed that the community of bacteria associated with B. brassicae was diverse, with at least four different bacterial community types detected among aphid lines, collected from widely dispersed sites in Northern Britain. The bacterial sequence types isolated from B. brassicae showed little similarity to any bacterial endosymbionts characterized in insects; instead, they were closely related to free-living extracellular bacterial species that have been isolated from the aphid gut or that are known to be present in the environment, suggesting that they are opportunistic bacteria transmitted between the aphid gut and the environment. To quantify variation in bacterial community between aphid lines, which was driven largely by differences in the proportions of two dominant bacterial orders, the Pseudomonales and the Enterobacteriales, we developed a novel real-time (Taqman) qPCR assay. By improving our knowledge of aphid microbial ecology, and providing novel molecular tools to examine the presence and function of the microbial community, this study forms the basis of further research to explore the influence of the extracellular bacterial community on aphid fitness, pest status, and susceptibility to control by natural enemies.

Visual Data Analysis as an Integral Part of Environmental Management.

The U.S. Department of Energy's (DOE) Office of Environmental Management (DOE/EM) currently supports an effort to understand and predict the fate of nuclear contaminants and their transport in natural and engineered systems. Geologists, hydrologists, physicists and computer scientists are working together to create models of existing nuclear waste sites, to simulate their behavior and to extrapolate it into the future. We use visualization as an integral part in each step of this process. In the first step, visualization is used to verify model setup and to estimate critical parameters. High-performance computing simulations of contaminant transport produces massive amounts of data, which is then analyzed using visualization software specifically designed for parallel processing of large amounts of structured and unstructured data. Finally, simulation results are validated by comparing simulation results to measured current and historical field data. We describe in this article how visual analysis is used as an integral part of the decision-making process in the planning of ongoing and future treatment options for the contaminated nuclear waste sites. Lessons learned from visually analyzing our large-scale simulation runs will also have an impact on deciding on treatment measures for other contaminated sites.

Risk factors associated with Salmonella status of broiler flocks delivered to grow-out farms.

In a prospective field observational study in the southeastern USA, we sampled gastrointestinal (GI) tracts from chicks of 65 broiler flocks delivered to conventional grow-out farms for rearing. The flocks were hatched at seven broiler hatcheries. The mean within-flock prevalence of Salmonella-positive samples was 6.5% and ranged from 0% to 86.7%. Of the 65 flocks studied, 25 (38.5%) had at least one Salmonella-positive sample. Accounting for confounding variability among the hatcheries and broiler companies, we tested whether the probability of detecting Salmonella in GI tracts of the chicks delivered was associated with certain characteristics of parent breeder flocks; hatchery production volume; hatchery ventilation system; hatchery egg-room conditions; egg incubation, candling, hatching, eggshell and bird separation, and bird-processing procedures; management of hatchery-to-farm transportation; day of week of hatch; weather conditions during transportation; or season of the hatch. Two risk factor models were adopted. The first model indicated that a greater number of parent flocks, manual separation of eggshell and bird, and a greater amount of fluff and feces on tray liners used during hatchery-to-farm transportation at delivery were associated with increased probability of detecting Salmonella in chick GI tracts, whereas a greater number of birds in the delivery vehicle was associated with decreased probability. The second model indicated that broiler flocks hatched on Tuesdays versus either Mondays or Thursdays (with no hatches on Wednesdays, Fridays or week-ends), increased average hatchability of the eggs from the parent flocks, and greater amounts of fluff and feces on the transport tray liners at delivery were all associated with increased probability of detecting Salmonella in chick GI tracts. The results of this study suggest potential management decisions to lessen Salmonella contamination of broilers supplied by commercial hatcheries and areas for further research.

Associations between vaccinations against protozoal and viral infections and Salmonella in broiler flocks.

Reducing the burden of Salmonella in broiler flocks presents a challenge for public health. Worldwide, grow-out broilers are routinely vaccinated to prevent or lessen clinical manifestation of other infections. In this exploratory analysis we tested if details of a routine vaccination programme delivered to conventional grow-out broilers were associated with the burden of Salmonella in the flock as it progressed through its production cycle. None of the flocks studied were vaccinated against Salmonella or received a competitive exclusion product. The flocks were reared on conventional grow-out farms in southeastern USA, and sampled in a prospective field observational study. We observed significant associations between the content and design of a grow-out vaccination programme targeting other infections and the probability of detecting Salmonella in the broiler flock at different time points throughout the production cycle. To the best of the authors' knowledge, this is the first field report of such associations.

Risk factors associated with detection of Salmonella in broiler litter at the time of new flock placement.

In this study, we investigated risk factors associated with the probability to detect Salmonella in samples of litter collected within 2 h prior to new flock placement in 76 grow-out houses on 38 conventional broiler farms located in the US states of Mississippi, Alabama and Texas. We evaluated characteristics of location and layout of the farm; area adjacent to and surrounding the house; house construction; condition and type of equipment in the house; litter management and other production, sanitation, visitation and biosecurity practices; non-broiler animal species on the farm; and weather conditions on the 3 days leading up to flock placement. Logistic regression was used to model the relationships between probability to detect Salmonella in litter and potential risk factors. In the screening process, each risk factor was evaluated as a single fixed effects factor in a multilevel model that accounted for variability among the sampled farms and their production complexes and companies. Of almost 370 risk factors screened, 24 were associated with the probability to detect Salmonella in litter. These were characteristics of the surroundings of the house, house construction and conditions, litter management, length of downtimes between flocks in the house, biosecurity and farm location. After investigation of collinearity between these variables and building of models for important risk factor categories, the list of candidate variables for the final model was refined to eight factors. The final model demonstrated that a higher probability of detecting Salmonella in litter was strongly associated with the use of wood to construct the base of the walls or to cover the inside of the broiler house foundation, and with the use of fresh wood shavings to top-dress or completely replace the litter between flocks.

Inter-relationships of Salmonella status of flock and grow-out environment at sequential segments in broiler production and processing.

In this study, we investigated how the likelihoods of Salmonella presence in various samples from broilers and their grow-out environment throughout one production cycle were related. Sixty-four broiler flocks from 10 complexes of two companies in the southern United States were included in the study. Samples from the gastrointestinal tracts of chicks, transport tray pads and litter and drag swabs from the house were collected on the day of placement of each flock. Approximately, 1 week before harvest, whole bird carcass rinses, caecum and crop samples were collected from birds from these same flocks. On the day of harvest, litter and drag swab samples were also taken from the house after the birds were removed. Upon arrival of the flocks at the processing plant, whole carcass rinses, caecum and crop samples were collected. As the flocks were processed, carcass rinses were collected just before the carcasses entered the immersion chill tank and as they exited the chill tank. Logistic regression was used to model the relationships between the likelihood of Salmonella in samples of each type collected at each sampling point and Salmonella frequencies in all the samples taken from the flock and grow-out environment at preceding production stages. The analysis demonstrated that increased likelihood of Salmonella contaminated carcasses entering the immersion chill tank was associated with higher contamination of the exteriors and crops of birds at arrival for processing as well as house environmental samples at the time of harvest and prior to placement. The best predictors of post-chill broiler carcass Salmonella status were the frequencies of Salmonella in the litter on the day of harvest and prior to placement. The immersion chilling appeared to disrupt some of the relationships between the processing plant and pre-harvest samples.

Cross species proteomics.

Proteomics has advanced in leaps and bounds over the past couple of decades. However, the continuing dependency of mass spectrometry-based protein identification on the searching of spectra against protein sequence databases limits many proteomics experiments. If there is no sequenced genome for a given species, then cross species proteomics is required, attempting to identify proteins across the species boundary, typically using the sequenced genome of a closely related species. Unlike sequence searching for homologues, the proteomics equivalent is confounded by small differences in amino acid sequences, leading to large differences in peptide masses; this renders mass matching of peptides and their product ions difficult. Therefore, the phylogenetic distance between the two species and the attendant level of conservation between the homologous proteins play a huge part in determining the extent of protein identification that is possible across the species boundary. In this chapter, we review the cross species challenge itself, as well as various approaches taken to deal with it and the success met with in past studies. This is followed by recommendations of best practice and suggestions to researchers facing this challenge as well as a final section predicting developments, which may help improve cross species proteomics in the future.

Feedbacks between hydrological heterogeneity and bioremediation induced biogeochemical transformations.

For guiding optimal design and interpretation of in situ treatments that strongly perturb subsurface systems, knowledge about the spatial and temporal patterns of mass transport and reaction intensities are important. Here, a procedure was developed and applied to time-lapse concentrations of a conservative tracer (bromide), an injected amendment (acetate) and reactive species (iron(II), uranium(VI) and sulfate) associated with two field scale biostimulation experiments, which were conducted successively at the same field location over two years. The procedure is based on a temporal moment analysis approach that relies on a streamtube approximation. The study shows that biostimulated reactions can be considerably influenced by subsurface hydrological and geochemical heterogeneities: the delivery of bromide and acetate and the intensity of the sulfate reduction is interpreted to be predominantly driven by the hydrological heterogeneity, while the intensity of the iron reduction is interpreted to be primarily controlled by the geochemical heterogeneity. The intensity of the uranium(VI) reduction appears to be impacted by both the hydrological and geochemical heterogeneity. Finally, the study documents the existence of feedbacks between hydrological heterogeneity and remediation-induced biogeochemical transformations at the field scale, particularly the development of precipitates that may cause clogging end flow rerouting.

Reproductive status of Holstein and Jersey cows in the United States.

Reproductive information since 1995 from the USDA national dairy database was used to calculate yearly Holstein and Jersey means for days to first breeding after calving (DFB), 70-d nonreturn rate, conception rate (CR), number of breedings per lactation (NB), interval between first and last breedings during the lactation, days to last breeding after calving (DLB), pregnancy rate (PR), calving interval (CI), and interval between consecutive breedings. Data were from nearly 20 million breedings during >8 million lactations of >5 million cows in >23,000 herds. Means were also calculated for some traits by parity and breeding number for both breeds and by geographical region and synchronization status for Holsteins. The DFB declined for Holsteins from 92 d in 1996 to 85 d in 2007; the trend in yearly differences was not as consistent for Jerseys. First- and all-breeding 70-d nonreturn rate declined 5 to 9 percentage units over time. First- and all-breeding CR declined 2 to 4 percentage units. The DFB were longer for later parities of Holsteins than for early parities. Second- and third-breeding CR were sometimes 1 to 2 percentage units above first-breeding CR for Holsteins but lower (1 to 7 percentage units) for Jerseys. The CR within breeding number declined across parities for both breeds. The NB increased by 0.3 to 0.4 breedings over time but remained constant (2.5 or 2.6 breedings) across parities for Holsteins and increased (from 2.2 to 2.4 breedings) for Jerseys. Holstein DFB were fewest in the Northwest (78 d) and greatest in the Mountain region (92 d). Regional CR was highest for the Northeast and Southwest (33%) and lowest for the Southeast (26%); NB was fewest for the Northeast (2.3) and greatest for the Southeast (2.7). Mean DLB was fewest for the Southwest (127 d) and greatest for the Mountain region (157 d); CI was shortest for the Southwest (406 d) and longest for the Mideast (434 d). Mean PR was highest for the Southwest (28.3%) and lowest for the Mideast and Southeast (22.2%). Use of timed artificial insemination following synchronized estrus appears to have reduced DFB, lowered CR, and increased NB while reducing DLB and CI. However, synchronized breeding was not a primary cause of Holstein regional differences for reproductive traits. Since 2002, phenotypic performance for CR, DLB, and CI as well as genetic merit for daughter PR have stopped their historical declines and started to improve.

Genetic and environmental factors that affect gestation length in dairy cattle.

Genetic and environmental factors that might affect gestation length (GL) were investigated. Data included information from >11 million parturitions from 1999 through 2006 for 7 US dairy breeds. Effects examined were year, herd-year, month, and age within parity of conception; parturition code (sex and multiple-birth status); lactation length and standardized milk yield of cow; service sire; cow sire; and cow. All effects were fixed except for service sire, cow sire, and cow. Mean GL for heifers and cows, respectively, were 277.8 and 279.4 d for Holsteins, 278.4 and 280.0 d for Jerseys, 279.3 and 281.1 d for Milking Shorthorns, 281.6 and 281.7 d for Ayrshires, 284.8 and 285.7 d for Guernseys, and 287.2 and 287.5 d for Brown Swiss. Estimated standard deviations of GL were greatly affected by data restrictions but generally were approximately 5 to 6 d. Year effects on GL were extremely small, but month effects were moderate. For Holstein cows, GL was 2.0 d shorter for October conceptions than for January and February conceptions; 4.7 and 5.6 d shorter for multiple births of the same sex than for single-birth females and males, respectively; 0.8 d longer for lactations of < or =250 d than for lactations of > or =501 d; and 0.6 d shorter for standardized yield of < or =8,000 kg than for yield of > or =14,001 kg. Estimates for GL heritability from parities 2 to 5 were 33 to 36% for service sire and 7 to 12% for cow sire; corresponding estimates from parity 1 were 46 to 47% and 10 to 12%. Estimates of genetic correlations between effects of service sire and cow sire on GL were 0.70 to 0.85 for Brown Swiss, Holsteins, and Jerseys, which indicates that those traits likely are controlled by many of the same genes and can be used to evaluate each other. More accurate prediction of calving dates can help dairy producers to meet management requirements of pregnant animals and to administer better health care during high-risk phases of animals' lives. However, intentional selection for either shorter or longer GL is not recommended without consideration of its possible effect on other dependent traits (e.g., calving ease and stillbirth).

Characterising alternate splicing and tissue specific expression in the chicken from ESTs.

Alternate splicing is believed to produce the greatest diversity in transcriptional complexity and function in eukaryotic species. In this study, we present an analysis of alternative splicing events that occur in the chicken, using the recently sequenced genomic sequence and over 580,000 EST sequences mapped back to the genome. A carefully controlled EST-to-genome mapping pipeline is presented, based around the EXONERATE program using the est2genome model, which also considers several quality control steps to filter out erroneous matches. The data is then used to estimate the level of alternate splicing events with respect to Ensembl predicted transcripts. The EST-genome mappings are characterised at the exon level, in order to classify individual splicing events and provide estimates of novel transcripts not currently annotated by the Ensembl genome database. This is the first large scale analysis of this kind in an avian species, and suggests that chicken displays a similar level of alternate splicing as that found in other higher vertebrates such as human and mouse, both in terms of the number of genes that undergo alternate splicing events, and the average number of transcripts produced per gene. The EST data suggests alternate splicing may occur in some 50-60% of the chicken gene set and with an average of around 2.3 transcripts per gene which undergo this process. The EST data is also used to look at gene and transcript usage in the tissues sequenced in embryonic and adult libraries. Genes which display notable biases were analysed in more detail, including twinfilin-2 and embryonic heavy chain myosin. This also highlights several as yet functionally un-annotated genes which appear to be important in embryonic tissues and also undergo alternate splicing events. The analysis also demonstrates some of the difficulties involved in using EST-based data to annotate transcriptional activity in eukaryotic genes, where a broad spectrum of tissues and a large number of sequenced transcripts are required in order to fully characterise alternate splicing and differential expression.

Rejection with hemodynamic compromise: objective evidence for efficacy of photopheresis.

BACKGROUND: Photopheresis therapy (photo) has been advocated as a therapy to improve outcome after recalcitrant or severe rejection, but objective evidence of a beneficial effect has been elusive. This study examined the hypothesis that photo provides protection against rejection, rejection with hemodynamic compromise (HC), and death from rejection after cardiac transplantation. METHODS: Between 1990 and 2003, 36 adult patients (from 343 adult transplant recipients) received at least 3 months of photo (2-day treatment every 3 to 6 weeks for a target of 18 months) after HC rejection (n = 12), recurrent/recalcitrant rejection (n = 20), or as prophylaxis in the presence of anti-donor antibodies (n = 4). Survival and risk factors were examined by analysis using multivariate hazard function modulated renewal function. RESULTS: Patients selected for photo were at greater risk for rejection (p < 0.0001) and HC rejection (p < 0.0001) than non-photo patients. After 3 months of photo therapy, rejection risk was decreased (p = 0.04). More importantly, the hazard for subsequent HC rejection or rejection death was significantly reduced toward the risk-adjusted level of lower-risk non-photo patients (p = 0.006). CONCLUSIONS: This study provides objective evidence that photo reduces the risk of subsequent HC rejection and/or death from rejection when initiated for patients with high rejection risk. Photopheresis is recommended as an important therapeutic modality after rejection with hemodynamic compromise, although further studies are needed to define the precise mechanism of the effect and the potential for benefit in other patient sub-sets.

A fully Bayesian model to cluster gene-expression profiles.

MOTIVATION: With cDNA or oligonucleotide chips, gene-expression levels of essentially all genes in a genome can be simultaneously monitored over a time-course or under different experimental conditions. After proper normalization of the data, genes are often classified into co-expressed classes (clusters) to identify subgroups of genes that share common regulatory elements, a common function or a common cellular origin. With most methods, e.g. k-means, the number of clusters needs to be specified in advance; results depend strongly on this choice. Even with likelihood-based methods, estimation of this number is difficult. Furthermore, missing values often cause problems and lead to the loss of data. RESULTS: We propose a fully probabilistic Bayesian model to cluster gene-expression profiles. The number of classes does not need to be specified in advance; instead it is adjusted dynamically using a Reversible Jump Markov Chain Monte Carlo sampler. Imputation of missing values is integrated into the model. With simulations, we determined the speed of convergence of the sampler as well as the accuracy of the inferred variables. Results were compared with the widely used k-means algorithm. With our method, biologically related co-expressed genes could be identified in a yeast transcriptome dataset, even when some values were missing. AVAILABILITY: The code is available at http://genome.tugraz.at/BayesianClustering/

Efficacy of orlistat as an adjunct to behavioral treatment in overweight African American and Caucasian adolescents with obesity-related co-morbid conditions.

This pilot study compared the efficacy of orlistat as an adjunctive treatment for obesity between African American and Caucasian adolescents. Twenty obese adolescents with obesity-related co-morbid conditions underwent measurements of body composition, glucose homeostasis by frequently sampled intravenous glucose tolerance test (FSIGT), and fasting lipids before and after 6 months treatment with orlistat 120 mg tid in conjunction with a comprehensive behavioral program. Weight (p < 0.05), BMI (p < 0.001), total cholesterol (p < 0.001), LDL cholesterol (p < 0.001), fasting insulin (p < 0.02) and fasting glucose (p < 0.003) were lower after treatment. Insulin sensitivity, measured during the FSIGT, improved significantly (p < 0.02), as did fasting indices such as the homeostasis model assessment for insulin resistance (p < 0.01). African American subjects exhibited significantly less improvement in weight (p < 0.05), BMI (p < 0.01), waist circumference (p = 0.03), and insulin sensitivity (p = 0.05). Improvements in cholesterol were not significantly different between African Americans and Caucasians. We conclude that Caucasians lost more weight and had greater improvements in insulin sensitivity than African Americans, but both exhibited improvements in plasma lipids. The true benefit of orlistat treatment over a comprehensive behavioral program remains to be determined in placebo-controlled trials.