102 research outputs found

    Evolving cell models for systems and synthetic biology

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    This paper proposes a new methodology for the automated design of cell models for systems and synthetic biology. Our modelling framework is based on P systems, a discrete, stochastic and modular formal modelling language. The automated design of biological models comprising the optimization of the model structure and its stochastic kinetic constants is performed using an evolutionary algorithm. The evolutionary algorithm evolves model structures by combining different modules taken from a predefined module library and then it fine-tunes the associated stochastic kinetic constants. We investigate four alternative objective functions for the fitness calculation within the evolutionary algorithm: (1) equally weighted sum method, (2) normalization method, (3) randomly weighted sum method, and (4) equally weighted product method. The effectiveness of the methodology is tested on four case studies of increasing complexity including negative and positive autoregulation as well as two gene networks implementing a pulse generator and a bandwidth detector. We provide a systematic analysis of the evolutionary algorithm’s results as well as of the resulting evolved cell models

    The Myosin Va Head Domain Binds to the Neurofilament-L Rod and Modulates Endoplasmic Reticulum (ER) Content and Distribution within Axons

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    The neurofilament light subunit (NF-L) binds to myosin Va (Myo Va) in neurons but the sites of interaction and functional significance are not clear. We show by deletion analysis that motor domain of Myo Va binds to the NF-L rod domain that forms the NF backbone. Loss of NF-L and Myo Va binding from axons significantly reduces the axonal content of ER, and redistributes ER to the periphery of axon. Our data are consistent with a novel function for NFs as a scaffold in axons for maintaining the content and proper distribution of vesicular organelles, mediated in part by Myo Va. Based on observations that the Myo Va motor domain binds to intermediate filament (IF) proteins of several classes, Myo Va interactions with IFs may serve similar roles in organizing organelle topography in different cell types

    Early childhood feeding practices and dental caries in preschool children: a multi-centre birth cohort study

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    Extent: 7p.Background Dental caries (decay) is an international public health challenge, especially amongst young children. Early Childhood Caries is a rapidly progressing disease leading to severe pain, anxiety, sepsis and sleep loss, and is a major health problem particularly for disadvantaged populations. There is currently a lack of research exploring the interactions between risk and protective factors in the development of early childhood caries, in particular the effects of infant feeding practises. Methods/Design This is an observational cohort study and involves the recruitment of a birth cohort from disadvantaged communities in South Western Sydney. Mothers will be invited to join the study soon after the birth of their child at the time of the first home visit by Child and Family Health Nurses. Data on feeding practices and dental health behaviours will be gathered utilizing a telephone interview at 4, 8 and 12 months, and thereafter at 6 monthly intervals until the child is aged 5 years. Information collected will include a) initiation and duration of breastfeeding, b) introduction of solid food, c) intake of cariogenic and non-cariogenic foods, d) fluoride exposure, and e) oral hygiene practices. Children will have a dental and anthropometric examination at 2 and 5 years of age and the main outcome measures will be oral health quality of life, caries prevalence and caries incidence. Discussion This study will provide evidence of the association of early childhood feeding practices and the oral health of preschool children. In addition, information will be collected on breastfeeding practices and the oral health concerns of mothers living in disadvantaged areas in South Western Sydney.Amit Arora, Jane A Scott, Sameer Bhole, Loc Do, Eli Schwarz and Anthony S Blinkhor

    The nature of organic records in impact excavated rocks on Mars

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    Impact ejected rocks are targets for life detection missions to Mars. The Martian subsurface is more favourable to organic preservation than the surface owing to an attenuation of radiation and physical separation from oxidising materials with increasing depth. Impact events bring materials to the surface where they may be accessed without complicated drilling procedures. On Earth, different assemblages of organic matter types are derived from varying depositional environments. Here we assess whether these different types of organic materials can survive impact events without corruption. We subjected four terrestrial organic matter types to elevated pressures and temperatures in piston-cylinder experiments followed by chemical characterisation using whole-rock pyrolysis-gas chromatography-mass spectrometry. Our data reveal that long chain hydrocarbon-dominated organic matter (types I and II; mainly microbial or algal) are unresistant to pressure whereas aromatic hydrocarbondominated organic matter types (types III and IV; mainly land plant, metamorphosed or degraded, displaying some superficial chemical similarities to abiotic meteoritic organic matter) are relatively resistant. This suggests that the impact excavated record of potential biology on Mars will be unavoidably biased, with microbial organic matter underrepresented while metamorphosed, degraded or abiotic meteoritic organic matter types will be selectively preserved

    Magnetic resonance imaging, knee arthroscopy, and clinical decision making: a descriptive study of five surgeons.

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    OBJECTIVES: A randomized controlled trial (RCT) showed magnetic resonance imaging for patients waiting for knee arthroscopy did not reduce the number of arthroscopies. Our study aimed to identify decisions made by orthopedic surgeons about whether patients on a waiting list should proceed to arthroscopy, and to describe surgeons' decisions. METHODS: Five surgeons were asked to Think Aloud (TA) as they made their decisions for twelve patients from the original RCT. Audiotapes of the decision making were transcribed for analysis. RESULTS: For five patients, surgeons agreed about proceeding with arthroscopy, although reasoning differed. In no cases did surgeons agree about not proceeding to arthroscopy. Agreement was more likely in patients with clinically diagnosed meniscal abnormality, and less likely in patients with osteoarthritis. CONCLUSIONS: Surgeons' decisions were influenced by patient wishes. For some patients, the decision to proceed with arthroscopy was based solely on clinical diagnosis; MRI may not be advantageous in these instances. Surgeons disagreed more often than they agreed about the decision to proceed with arthroscopy, particularly when OA was diagnosed. This has implications for decision making in the current NHS patient choice environment. Patients may choose a treatment provider from a list of available providers at time of original clinical assessment and diagnosis. The treating surgeon does not necessarily re-examine the patient until the day of surgery. Given the variation between surgeons about the merits of proceeding with arthroscopy, surgeons may end up in the invidious position of providing surgery to patients whom they do not believe will benefit from arthroscopy

    The VALUE national hysterectomy study: description of the patients and their surgery.

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    OBJECTIVES: To describe hysterectomies practised in 1994 and 1995: the patients, their surgery and short term outcomes. DESIGN: One of two large cohorts, with prospective follow up, recruited to compare the outcomes of endometrial destruction with those of hysterectomy. SETTING: England, Wales and Northern Ireland. POPULATION: All women who had hysterectomies for non-malignant indications carried out during a 12-month period. METHODS: Gynaecologists in NHS and independent hospitals were asked to report cases. Follow up data were obtained at outpatient follow up approximately six weeks post-surgery. MAIN OUTCOME MEASURES: Indication for surgery, method of hysterectomy, ovarian status post-surgery, surgical complications. RESULTS: 37,298 cases were reported which is estimated to reflect about 45% of hysterectomies performed during the period studied. The median age was 45 years, and the most common indication for surgery was dysfunctional uterine bleeding (46%). Most hysterectomies were carried out by consultants (55%). The proportions of women having abdominal, vaginal or laparoscopically-assisted hysterectomy were 67%, 30% and 3%, respectively. Forty-three percent of women had no ovaries conserved after surgery. The median length of stay was five days. The overall operative complication rate was 3.5%, and highest for the laparoscopic techniques. The overall post-operative complication rate was 9%. One percent of these was regarded as severe, with the highest rate for severe in the laparoscopic group (2%). There were no operative deaths; 14 deaths were reported within the six-week post-operative period: a crude mortality rate soon after surgery of 0.38 per thousand (95% CI 0.25-0.64). CONCLUSIONS: This large study describes women who undergo hysterectomy in the UK, and presents results on early complications associated with the surgery. Operative complications occurred in one in 30 women, and post-operative complications in at least one in 10. Laparoscopic techniques tend to be associated with higher complication rates than other methods
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