Targeted Assembly of Short Sequence Reads

As next-generation sequence (NGS) production continues to increase, analysis is becoming a significant bottleneck. However, in situations where information is required only for specific sequence variants, it is not necessary to assemble or align whole genome data sets in their entirety. Rather, NGS data sets can be mined for the presence of sequence variants of interest by localized assembly, which is a faster, easier, and more accurate approach. We present TASR, a streamlined assembler that interrogates very large NGS data sets for the presence of specific variants, by only considering reads within the sequence space of input target sequences provided by the user. The NGS data set is searched for reads with an exact match to all possible short words within the target sequence, and these reads are then assembled strin-gently to generate a consensus of the target and flanking sequence. Typically, variants of a particular locus are provided as different target sequences, and the presence of the variant in the data set being interrogated is revealed by a successful assembly outcome. However, TASR can also be used to find unknown sequences that flank a given target. We demonstrate that TASR has utility in finding or confirming ge-nomic mutations, polymorphism, fusion and integration events. Targeted assembly is a powerful method for interrogating large data sets for the presence of sequence variants of interest. TASR is a fast, flexible and easy to use tool for targeted assembly

Hmong Adults Self-Rated Oral Health: A Pilot Study

Since 1975, the Hmong refugee population in the U.S. has increased over 200%. However, little is known about their dental needs or self-rated oral health (SROH). The study aims were to: (1) describe the SROH, self-rated general health (SRGH), and use of dental/physician services; and (2) identify the factors associated with SROH among Hmong adults. A cross-sectional study design with locating sampling methodology was used. Oral health questionnaire was administered to assess SROH and SRGH, past dental and physician visits, and language preference. One hundred twenty adults aged 18–50+ were recruited and 118 had useable information. Of these, 49% rated their oral health as poor/fair and 30% rated their general health as poor/fair. Thirty-nine percent reported that they did not have a regular source of dental care, 46% rated their access to dental care as poor/fair, 43% visited a dentist and 66% visited a physician within the past 12 months. Bivariate analyses demonstrated that access to dental care, past dental visits, age and SRGH were significantly associated with SROH (P \u3c 0.05). Multivariate analyses demonstrated a strong association between access to dental care and good/excellent SROH. About half of Hmong adults rated their oral health and access to dental care as poor. Dental insurance, access to dental care, past preventive dental/physician visits and SRGH were associated with SROH

The emerging role of sarcopenia as a prognostic indicator in patients undergoing abdominal wall hernia repairs: a systematic review of the literature

Background There is strong evidence suggesting that excessive fat distribution, for example, in the bowel mesentery or a reduction in lean body mass (sarcopenia) can influence short-, mid-, and long-term outcomes from patients undergoing various types of surgery. Body composition (BC) analysis aims to measure and quantify this into a parameter that can be used to assess patients being treated for abdominal wall hernia (AWH). This study aims to review the evidence linking quantification of BC with short- and long-term abdominal wall hernia repair outcomes. Methods A systematic review was performed according to the PRISMA guidelines. The literature search was performed on all studies that included BC analysis in patients undergoing treatment for AWH using Medline, Google Scholar and Cochrane databases by two independent reviewers. Outcomes of interest included short-term recovery, recurrence outcomes, and long-term data. Results 201 studies were identified, of which 4 met the inclusion criteria. None of the studies were randomized controlled trials and all were cohort studies. There was considerable variability in the landmark axial levels and skeletal muscle(s) chosen for analysis, alongside the methods of measuring the cross-sectional area and the parameters used to define sarcopenia. Only two studies identified an increased risk of postoperative complications associated with the presence of sarcopenia. This included an increased risk of hernia recurrence, postoperative ileus and prolonged hospitalisation. Conclusion There is some evidence to suggest that BC techniques could be used to help predict surgical outcomes and allow early optimisation in AWH patients. However, the lack of consistency in chosen methodology, combined with the outdated definitions of sarcopenia, makes drawing any conclusions difficult. Whether body composition modification can be used to improve outcomes remains to be determined

Prevalence of Anaplasma phagocytophilum infection and effect on lamb growth

Background: A major challenge in sheep farming during the grazing season along the coast of south-western Norway is tick-borne fever (TBF) caused by the bacteria Anaplasma phagocytophilum that is transmitted by the tick Ixodes ricinus. Methods: A study was carried out in 2007 and 2008 to examine the prevalence of A. phagocytophilum infection and effect on weaning weight in lambs. The study included 1208 lambs from farms in Sunndal Ram Circle in Møre and Romsdal County in Mid-Norway, where ticks are frequently observed. All lambs were blood sampled and serum was analyzed by an indirect fluorescent antibody assay (IFA) to determine an antibody status (positive or negative) to A. phagocytophilum infection. Weight and weight gain and possible effect of infection were analyzed using ANOVA and the MIXED procedure in SAS. Results: The overall prevalence of infection with A. phagocytophilum was 55%. A lower weaning weight of 3% (1.34 kg, p < 0.01) was estimated in lambs seropositive to an A. phagocytophilum infection compared to seronegative lambs at an average age of 137 days. Conclusions: The results show that A. phagocytophilum infection has an effect on lamb weight gain. The study also support previous findings that A. phagocytophilum infection is widespread in areas where ticks are prevalent, even in flocks treated prophylactic with acaricides

Reducing bias in auditory duration reproduction by integrating the reproduced signal

Duration estimation is known to be far from veridical and to differ for sensory estimates and motor reproduction. To investigate how these differential estimates are integrated for estimating or reproducing a duration and to examine sensorimotor biases in duration comparison and reproduction tasks, we compared estimation biases and variances among three different duration estimation tasks: perceptual comparison, motor reproduction, and auditory reproduction (i.e. a combined perceptual-motor task). We found consistent overestimation in both motor and perceptual-motor auditory reproduction tasks, and the least overestimation in the comparison task. More interestingly, compared to pure motor reproduction, the overestimation bias was reduced in the auditory reproduction task, due to the additional reproduced auditory signal. We further manipulated the signal-to-noise ratio (SNR) in the feedback/comparison tones to examine the changes in estimation biases and variances. Considering perceptual and motor biases as two independent components, we applied the reliability-based model, which successfully predicted the biases in auditory reproduction. Our findings thus provide behavioral evidence of how the brain combines motor and perceptual information together to reduce duration estimation biases and improve estimation reliability

Biomarkers in dementia: clinical utility and new directions.

Imaging, cerebrospinal fluid (CSF) and blood-based biomarkers have the potential to improve the accuracy by which specific causes of dementia can be diagnosed in vivo, provide insights into the underlying pathophysiology, and may be used as inclusion criteria and outcome measures for clinical trials. While a number of imaging and CSF biomarkers are currently used for each of these purposes, this is an evolving field, with numerous potential biomarkers in varying stages of research and development. We review the currently available biomarkers for the three most common forms of neurodegenerative dementia, and give an overview of research techniques that may in due course make their way into the clinic

Bridging Time Scales in Cellular Decision Making with a Stochastic Bistable Switch

Cellular transformations which involve a significant phenotypical change of the cell's state use bistable biochemical switches as underlying decision systems. In this work, we aim at linking cellular decisions taking place on a time scale of years to decades with the biochemical dynamics in signal transduction and gene regulation, occuring on a time scale of minutes to hours. We show that a stochastic bistable switch forms a viable biochemical mechanism to implement decision processes on long time scales. As a case study, the mechanism is applied to model the initiation of follicle growth in mammalian ovaries, where the physiological time scale of follicle pool depletion is on the order of the organism's lifespan. We construct a simple mathematical model for this process based on experimental evidence for the involved genetic mechanisms. Despite the underlying stochasticity, the proposed mechanism turns out to yield reliable behavior in large populations of cells subject to the considered decision process. Our model explains how the physiological time constant may emerge from the intrinsic stochasticity of the underlying gene regulatory network. Apart from ovarian follicles, the proposed mechanism may also be of relevance for other physiological systems where cells take binary decisions over a long time scale.Comment: 14 pages, 4 figure

Accessory gland as a site for prothoracicotropic hormone controlled ecdysone synthesis in adult male insects

Insect steroid hormones (ecdysteroids) are important for female reproduction in many insect species and are required for the initiation and coordination of vital developmental processes. Ecdysteroids are also important for adult male physiology and behavior, but their exact function and site of synthesis remains unclear, although previous studies suggest that the reproductive system may be their source. We have examined expression profiles of the ecdysteroidogenic Halloween genes, during development and in adults of the flour beetle Tribolium castaneum. Genes required for the biosynthesis of ecdysone (E), the precursor of the molting hormone 20-hydroxyecdysone (20E), are expressed in the tubular accessory glands (TAGs) of adult males. In contrast, expression of the gene encoding the enzyme mediating 20E synthesis was detected in the ovaries of females. Further, Spookiest (Spot), an enzyme presumably required for endowing tissues with competence to produce ecdysteroids, is male specific and predominantly expressed in the TAGs. We also show that prothoracicotropic hormone (PTTH), a regulator of E synthesis during larval development, regulates ecdysteroid levels in the adult stage in Drosophila melanogaster and the gene for its receptor Torso seems to be expressed specifically in the accessory glands of males. The composite results suggest strongly that the accessory glands of adult male insects are the main source of E, but not 20E. The finding of a possible male-specific source of E raises the possibility that E and 20E have sex-specific roles analogous to the vertebrate sex steroids, where males produce primarily testosterone, the precursor of estradiol. Furthermore this study provides the first evidence that PTTH regulates ecdysteroid synthesis in the adult stage and could explain the original finding that some adult insects are a rich source of PTTH

A Review of Family-Based Tests for Linkage Disequilibrium between a Quantitative Trait and a Genetic Marker

Quantitative trait transmission/disequilibrium tests (quantitative TDTs) are commonly used in family-based genetic association studies of quantitative traits. Despite the availability of various quantitative TDTs, some users are not aware of the properties of these tests and the relationships between them. This review aims at outlining the broad features of the various quantitative TDT procedures carried out in the frequently used QTDT and FBAT packages. Specifically, we discuss the “Rabinowitz” and the “Monks-Kaplan” procedures, as well as the various “Abecasis” and “Allison” regression-based procedures. We focus on the models assumed in these tests and the relationships between them. Moreover, we discuss what hypotheses are tested by the various quantitative TDTs, what testing procedures are best suited to various forms of data, and whether the regression-based tests overcome population stratification problems. Finally, we comment on power considerations in the choice of the test to be used. We hope this brief review will shed light on the similarities and differences of the various quantitative TDTs

First Results from the Herschel and ALMA Spectroscopic Surveys of the SMC: The Relationship between [C ii ]-bright Gas and CO-bright Gas at Low Metallicity

The Small Magellanic Cloud (SMC) provides the only laboratory to study the structure of molecular gas at high resolution and low metallicity. We present results from the Herschel Spectroscopic Survey of the SMC (HS3), which mapped the key far-IR cooling lines [C ii], [O i], [N ii], and [O iii] in five star-forming regions, and new ALMA 7 m array maps of ${}^{12}\mathrm{CO}$ and ${}^{13}\mathrm{CO}$ $(2-1)$ with coverage overlapping four of the five HS3 regions. We detect [C ii] and [O i] throughout all of the regions mapped. The data allow us to compare the structure of the molecular clouds and surrounding photodissociation regions using ${}^{13}\mathrm{CO}$, ${}^{12}\mathrm{CO}$, [C ii], and [O i] emission at $\lesssim 10^{\prime\prime}$ ($\lt 3$ pc) scales. We estimate ${A}_{V}$ using far-IR thermal continuum emission from dust and find that the CO/[C ii] ratios reach the Milky Way value at high ${A}_{V}$ in the centers of the clouds and fall to \sim 1/5\mbox{--}1/10\times the Milky Way value in the outskirts, indicating the presence of translucent molecular gas not traced by bright ${}^{12}\mathrm{CO}$ emission. We estimate the amount of molecular gas traced by bright [C ii] emission at low ${A}_{V}$ and bright ${}^{12}\mathrm{CO}$ emission at high ${A}_{V}$. We find that most of the molecular gas is at low ${A}_{V}$ and traced by bright [C ii] emission, but that faint ${}^{12}\mathrm{CO}$ emission appears to extend to where we estimate that the ${{\rm{H}}}_{2}$-to-H i transition occurs. By converting our ${{\rm{H}}}_{2}$ gas estimates to a CO-to-${{\rm{H}}}_{2}$ conversion factor (X CO), we show that X CO is primarily a function of ${A}_{V}$, consistent with simulations and models of low-metallicity molecular clouds