Multivariate heritability of shape in June sucker (Chasmistes liorus) and Utah sucker (Catostomus ardens): shape as a functional trait for discriminating closely related species.

Molecular genetic data suggest that June sucker (Chasmistes liorus) is only shallowly diverged from the co-occurring but phenotypically distinct Utah sucker (Catostomus ardens) in Utah Lake. Phenotypes representing both extreme morphologies (June sucker and Utah sucker) are observed in the small wild population, but relatively large numbers of intermediate phenotypes are also present. This relatively continuous variation between the two putative species could result from extensive hybridization (including reticulate evolutionary patterns) of genetically based phenotypes or incomplete divergence among lineages and extensive phenotypic plasticity with little genetic basis. To help inform the evolutionary history of June sucker and to provide critical information for management and restoration of June sucker populations, we evaluated the distribution of shape phenotypes among purebreds of each species and their hybrids and determined the heritability of shape and ecological performance between June sucker (C. liorus) and its sister species Utah sucker (C. ardens). Mouth shape of purebred June sucker and Utah sucker are located at the extremes, and hybrids are located midway between the purebreds. Multivariate heritability was relatively high for mouth shape at 0.27. Heritability for growth rate was high at 0.32-0.42, but variation was not associated with cross type. Genetically based variation in mouth shape has evolved fairly rapidly or has been maintained in the face of ongoing hybridization between the two species. Currently, there seems to be little evidence for differential selection between species that would maintain shape variation.

Pathoscope: species identification and strain attribution with unassembled sequencing data.

Emerging next-generation sequencing technologies have revolutionized the collection of genomic data for applications in bioforensics, biosurveillance, and for use in clinical settings. However, to make the most of these new data, new methodology needs to be developed that can accommodate large volumes of genetic data in a computationally efficient manner. We present a statistical framework to analyze raw next-generation sequence reads from purified or mixed environmental or targeted infected tissue samples for rapid species identification and strain attribution against a robust database of known biological agents. Our method, Pathoscope, capitalizes on a Bayesian statistical framework that accommodates information on sequence quality, mapping quality, and provides posterior probabilities of matches to a known database of target genomes. Importantly, our approach also incorporates the possibility that multiple species can be present in the sample and considers cases when the sample species/strain is not in the reference database. Furthermore, our approach can accurately discriminate between very closely related strains of the same species with very little coverage of the genome and without the need for multiple alignment steps, extensive homology searches, or genome assembly--which are time-consuming and labor-intensive steps. We demonstrate the utility of our approach on genomic data from purified and in silico "environmental" samples from known bacterial agents impacting human health for accuracy assessment and comparison with other approaches.

Costs of treating depression with individual versus family therapy.

Depression is one of the most common concerns that bring clients to treatment. Although marriage and family therapy has been shown to be an effective treatment, little research exists regarding the cost-effectiveness of related services. In this study, we examined claims data for 164,667 individuals diagnosed with depression to determine (a) differences in the cost of treating depression according to type of therapy and license type, (b) differences in recidivism rates by age, gender, type of therapy, and type of mental health professional, and (c) differences in cost-effectiveness by therapy modality and type of professional. The results showed that services provided by marriage and family therapists resulted in the lowest recidivism rate, and family therapy services were the least expensive.

The differential susceptibility of spores from virulent and attenuated Bacillus anthracis strains to aldehyde- and hypochlorite-based disinfectants.

This study compared the sensitivity of spores from virulent and attenuated Bacillus anthracis strains in suspension to inactivation by various chemical disinfectants. Spore suspensions from two virulent strains (A0256 and A0372) and two attenuated strains (Sterne and A0141) of B. anthracis were tested against two aldehyde-based disinfectants and one hypochlorite-based disinfectant. A novel statistical model was used to estimate 4-log(10) reduction times for each disinfectant/strain combination. Reduction times were compared statistically using approximate Z and χ(2) tests. Although there was no consistent correlation between virulence and increased sporicidal resistance across all three disinfectants, spores from the two virulent and two attenuated strains did display significantly different susceptibilities to different disinfectants. Significant disinfectant-strain interactions were observed for two of the three disinfectants evaluated. The comparative results suggest that the use of surrogate organisms to model the inactivation kinetics of virulent B. anthracis spores may be misleading. The accuracy of such extrapolations is disinfectant dependent and must be used with caution.

Cytotoxicity of Atriplex confertifolia.

The search for cancer treatment continues to be a global effort. As part of this global effort, many natural products have been tested against cancer cell lines, mostly from tropically located plants. This study reports that extracts of Atriplex confertifolia (Torr. and Frem.) S. Watson (Chenopodiaceae), a native North American plant (also known as shadscale or saltbush), has significant bioactivity against human breast cancer cell lines MCF-7, MDA-MB 435, MDA-MB 231, and HeLa cells (cervical cancer cells). The bioactivity of A. confertifolia extracts on these cells lines was compared to an FDA-approved cancer drug (Onxol((R))) and an industry-standard leukocyte control cell line. Active portions of the extracts were found primarily in the polar fractions of the plant. A dose-response curve of the extracts displayed significant cell death similar to Onxol((R)). The plant extracts did not significantly inhibit the viability of the leukocyte cell line. In a timed study, over 90% of cell lines MDA-MB 435 and HeLa died after 24 hours. Cell death appears to result from apoptosis.

Distribution of doxorubicin in rats undergoing ultrasonic drug delivery.

Ultrasound (US) increases efficacy of drugs delivered from micelles, but the pharmacokinetics have not been studied previously. In this study, US was used to deliver doxorubicin (Dox) sequestered in micelles in an in vivo rat model with bilateral leg tumors. One of two frequencies with identical mechanical index and intensity was delivered for 15 min to one tumor immediately after systemic injection of micellar Dox. Pharmacokinetics in myocardium, liver, skeletal muscle, and tumors were measured for 1 week. When applied in combination with micellar Dox, the ultrasoincated tumor had higher Dox concentrations at 30 min, compared to bilateral noninsonated controls. Initially, concentrations were highest in heart and liver, but within 24 h they decreased significantly. From 24 h to 7 days, concentrations remained highest in tumors, regardless of whether they received US or not. Comparison of insonated and noninsonated tumors showed 50% more Dox in the insonated tumor at 30 min posttreatment. Four weekly treatment produced additional Dox accumulation in the myocardium but not in liver, skeletal leg muscle, or tumors compared to single treatment. Controls showed that neither US nor the empty carrier impacted tumor growth. This study shows that US causes more release of drug at the targeted tumor.

Myogenic regulatory factor response to resistance exercise volume in skeletal muscle.

This study examined the impact of resistance exercise volume on myoD and myogenin in rodent quadriceps muscle. Six-month-old male Sprague-Dawley rats (316 +/- 2 g) performed either low-volume (LV; 10 sets x 10 contractions) or high-volume (HV; 20 sets x 10 contractions) resistance exercise at 75% one-repetition maximum. Muscles were analyzed for myogenin and myoD mRNA and protein expression 6, 12, 24 and 48 h post-exercise. In red quadriceps (RQ), myogenin mRNA was significantly elevated at 6 h following LV and this response was greater than HV at 6 h, while myogenin protein was significantly increased at 6 and 12 h following LV but only at 12 h following HV (P < 0.05). MyoD mRNA was increased at 6 and 12 h following LV and at 12 h following HV, while myoD protein was slightly decreased (LV; P < 0.05) or unchanged over time (HV). No changes were detected within the white quadriceps muscle. We conclude that acute resistance exercise can activate myogenin and myoD expression levels in RQ, but when exercise volume is doubled these myogenic responses are not proportional but delayed and blunted possibly because of excessive damage/injury. Further work is needed to determine the consequences of these specific myogenic responses on muscle hypertrophy following high-volume resistance exercise training.

Role of frequency and mechanical index in ultrasonic-enhanced chemotherapy in rats.

PURPOSE: The therapeutic effect of ultrasound and micellar-encapsulated doxorubicin was studied in vivo using a tumor-bearing rat model with emphasis on how tumor growth rate is affected by ultrasonic parameters such as frequency and intensity. METHODS: This study employed ultrasound of two different frequencies (20, 476 kHz) and two pulse intensities, but identical mechanical indices and temporal average intensities. Ultrasound was applied weekly for 15 min to one of two bilateral leg tumors (DHD/K12/TRb colorectal epithelial cell line) in the rat model immediately after intravenous injection of micelle-encapsulated doxorubicin. This therapy was applied weekly for 6 weeks. RESULTS: Results showed that tumors treated with drug and ultrasound displayed, on average, slower growth rates than non-insonated tumors (P = 0.0047). However, comparison between tumors that received 20 or 476-kHz ultrasound treatments showed no statistical difference (P = 0.9275) in tumor growth rate. CONCLUSION: Application of ultrasound in combination with drug therapy was effective in reducing tumor growth rate, irrespective of which frequency was employed.

The tetrad-pollen model fails to explain the bias in Mendel's pea (Pisum sativum) experiments.

For >40 years, geneticists and science historians have appealed to the tetrad-pollen model as an explanation of the bias toward expectation in Mendel's data, albeit without experimental support. Our experiments demonstrate that pollen sampling during self-pollination in pea conforms to the binomial distribution with no evidence of a tetrad-pollen effect.

Aerobic and resistance exercise sequence affects excess postexercise oxygen consumption.

Excess postexercise oxygen consumption (EPOC) may describe the impact of previous exercise on energy metabolism. Ten males completed Resistance Only, Run Only, Resistance-Run, and Run-Resistance experimental conditions. Resistance exercise consisted of 7 lifts. Running consisted of 25 minutes of treadmill exercise. Vo(2) was determined during treadmill exercise and after each exercise treatment. Our findings indicated that treadmill exercise Vo(2) was significantly higher for Resistance-Run compared with Run-Resistance and Resistance Only at all time intervals. At 10 minutes postexercise, Vo(2) was greater for Resistance Only and Run-Resistance than for Resistance-Run. At 20 and 30 minutes, Vo(2) following Resistance Only was significantly greater than following Run Only. In conclusion, EPOC is greatest following Run-Resistance; however, treadmill exercise is more physiologically difficult following resistance exercise. Furthermore, the sequence of resistance and treadmill exercise influences EPOC, primarily because of the effects of resistance exercise rather than the exercise combination. We recommend performing aerobic exercise before resistance exercise when combining them into 1 exercise session.

Treatment of biofilm infections on implants with low-frequency ultrasound and antibiotics.

Medical implants are sometimes colonized by biofilm-forming bacteria, which are very difficult to treat effectively. The combination of gentamicin and ultrasonic exposure for 24 hours was previously shown to reduce the viability of Escherichia coli biofilms in vivo. This article shows that such treatment for 48 hours reduced viable E coli bacteria to nearly undetectable levels. However, when Pseudomonas aeruginosa biofilms were implanted and treated for 24 and 48 hours, no significant ultrasonic-enhanced reduction of viable bacteria was observed. The difference in response of these 2 organisms is attributed to greater impermeability and stability of the outer membrane of P aeruginosa.

Ultrasonic-enhanced gentamicin transport through colony biofilms of Pseudomonas aeruginosa and Escherichia coli.

The hypothesis that ultrasound increases antibiotic transport through biofilms of Escherichia coli and Pseudomonas aeruginosa was investigated using colony biofilms. Biofilms grown on membrane filters were transferred to nutrient agar containing 50 microg/ml gentamicin. A smaller filter was placed on top of the biofilm and a blank concentration disk was situated atop the filter. Diffusion of antibiotic through the biofilms was allowed for 15, 30, or 45 min at 37 degrees C. Some of these biofilms were exposed to 70-kHz ultrasound and others were not. Each concentration disk was then placed on a nutrient agar plate spread with a lawn of E. coli. The resulting zone of inhibition was used to calculate the amount of gentamicin that was transported through the biofilm into the disk. The E. coli and P. aeruginosa biofilms grown for 13 and 24 h were exposed to two different ultrasonic power densities. Ultrasonication significantly increased the transport of gentamicin through the biofilm. Insonation of biofilms of E. coli for 45 min more than doubled the amount of gentamicin compared to their noninsonated counterparts. For P. aeruginosa biofilms, no detectable gentamicin penetrated the biofilm within 45 min without ultrasound; however, when insonated (1.5 W/cm2) for 45 min, the disks collected more than 0.45 microg antibiotic. Ultrasonication significantly increased transport of gentamicin across biofilms that normally blocked or slowed gentamicin transport when not exposed to ultrasound. This enhanced transport may be partially responsible for the increased killing of biofilm bacteria exposed to combinations of antibiotic and ultrasound.

Combination therapy with folic acid and methionine in the prevention of retinoic acid-induced cleft palate in mice.

BACKGROUND: During formation of the secondary palate, clefting may result when critical developmental events are altered. The purpose of this study was to reduce the incidence of retinoic acid (RA)-induced cleft palate (CP) in mice by the co-administration of folic acid (FA), methionine (ME) or a combination of both. METHODS: Four groups of time-pregnant Swiss Webster mice were injected intraperitoneally with 50 mg/kg RA on gestational day (GD) 10. Likewise, 4.0 mg/kg FA and 187 mg/kg ME were administered on GD 8-11. The experiment included a control group (RA plus H2O) and three experimental groups, (RA plus therapeutic doses of FA, ME, or FA + ME). Necropsies were carried out on GD 18 and pups were analyzed for teratogenic effects. RESULTS: Litters that received no therapy exhibited 100% CP with individual pups showing 76% susceptibility. Each therapy administered separately reduced the frequency of CP to approximately 6%, and the combination of FA and ME completely prevented the occurrence of RA-induced cleft palate (0%). A second experiment was conducted in which therapy levels were decreased by 25%. Litters that did not receive therapy experienced 100% clefting and individual pups exhibited CP at 86%. These therapies administered separately did not alter significantly the frequency of cleft palate. The combined doses of FA and ME, however, lowered significantly the frequency of cleft palate to 46%. Decreases in limb and tail defects with FA + ME therapy were also observed in both experiments. CONCLUSIONS: Although FA and ME, at appropriate levels, can reduce individually the frequency of RA-induced cleft palate and other defects in mice, the results from the present study suggest that there is an additive interaction between the two therapeutic agents that can reduce further the teratogenic impact of RA. Further studies are needed to assess the mechanism of action of concomitant doses of FA and ME in the reduction of drug-induced birth defects.