Boolean network model predicts cell cycle sequence of fission yeast

A Boolean network model of the cell-cycle regulatory network of fission yeast (Schizosaccharomyces Pombe) is constructed solely on the basis of the known biochemical interaction topology. Simulating the model in the computer, faithfully reproduces the known sequence of regulatory activity patterns along the cell cycle of the living cell. Contrary to existing differential equation models, no parameters enter the model except the structure of the regulatory circuitry. The dynamical properties of the model indicate that the biological dynamical sequence is robustly implemented in the regulatory network, with the biological stationary state G1 corresponding to the dominant attractor in state space, and with the biological regulatory sequence being a strongly attractive trajectory. Comparing the fission yeast cell-cycle model to a similar model of the corresponding network in S. cerevisiae, a remarkable difference in circuitry, as well as dynamics is observed. While the latter operates in a strongly damped mode, driven by external excitation, the S. pombe network represents an auto-excited system with external damping.Comment: 10 pages, 3 figure

Complex reconstructions in head and neck cancer surgery: decision making

Defects in head and neck after tumor resection often provide significant functional and cosmetic deformity. The challenge for reconstruction is not only the aesthetic result, but the functional repair. Cancer may involve composite elements and the in sano resection may lead to an extensive tissue defect. No prospective randomized controlled studies for comparison of different free flaps are available. There are many options to cover defects and restore function in the head and neck area, however we conclude from experience that nearly all defects in head and neck can be closed by 5 different free flaps: radial forearm flap, free fibula flap, anterior lateral thigh flap, lateral arm flap and parascapular flap

Determining the interviewer effect on CQ Index outcomes: a multilevel approach

<p>Abstract</p> <p>Background</p> <p>The CQ Index for the elderly, a quality-of-care questionnaire administered by conducting interviews, is used to assess clients' experiences in Dutch nursing homes and homes for the elderly. This article describes whether inter-interviewer differences influence the perceived quality of healthcare services reported by residents, the size of this interviewer effect and the influence of the interviewer characteristics on CQ Index dimensions for public reporting.</p> <p>Methods</p> <p>Data from 4345 questionnaires was used. Correlations were calculated, reliability analyses were performed, and a multilevel analysis was used to calculate the degree of correlation between two interviewers within one health care institution. Five models were constructed and the Intra Class Correlation (ICC) was calculated. Healthcare institutions were given 1-5 stars on every quality dimensions (1 = worst and 5 = best), adjusted for resident and interviewer characteristics. The effect of these characteristics on the assignment of the stars was investigated.</p> <p>Results</p> <p>In a multilevel approach, the ICC showed a significant amount of variance on five quality dimensions. Of the interviewer characteristics, only previous interviewing experience, the reason of interviewing and general knowledge of health care had a significant effect on the quality dimensions. Adjusting for interviewer characteristics did not affect the overall star assignment to the institutions regarding 7 of 12 quality dimensions. For the other five dimensions (Shared decision-making, Meals, Professional competency, Autonomy, and Availability of personnel) a minor effect was found.</p> <p>Conclusions</p> <p>We have shown that training, the use of experienced interviewers, written instructions, supervision and educational meetings do not automatically prevent interviewer effects. While the results of this study can be used to improve the quality of services provided by these institutions, several CQ index dimensions should be interpreted with caution for external purposes (accountability and transparency).</p

Three-dimensional mapping of mechanical activation patterns, contractile dyssynchrony and dyscoordination by two-dimensional strain echocardiography: Rationale and design of a novel software toolbox

<p>Abstract</p> <p>Background</p> <p>Dyssynchrony of myocardial deformation is usually described in terms of variability only (e.g. standard deviations SD's). A description in terms of the spatio-temporal distribution pattern (vector-analysis) of dyssynchrony or by indices estimating its impact by expressing dyscoordination of shortening in relation to the global ventricular shortening may be preferential. Strain echocardiography by speckle tracking is a new non-invasive, albeit 2-D imaging modality to study myocardial deformation.</p> <p>Methods</p> <p>A post-processing toolbox was designed to incorporate local, speckle tracking-derived deformation data into a 36 segment 3-D model of the left ventricle. Global left ventricular shortening, standard deviations and vectors of timing of shortening were calculated. The impact of dyssynchrony was estimated by comparing the end-systolic values with either early peak values only (early shortening reserve ESR) or with all peak values (virtual shortening reserve VSR), and by the internal strain fraction (ISF) expressing dyscoordination as the fraction of deformation lost internally due to simultaneous shortening and stretching. These dyssynchrony parameters were compared in 8 volunteers (NL), 8 patients with Wolff-Parkinson-White syndrome (WPW), and 7 patients before (LBBB) and after cardiac resynchronization therapy (CRT).</p> <p>Results</p> <p>Dyssynchrony indices merely based on variability failed to detect differences between WPW and NL and failed to demonstrate the effect of CRT. Only the 3-D vector of onset of shortening could distinguish WPW from NL, while at peak shortening and by VSR, ESR and ISF no differences were found. All tested dyssynchrony parameters yielded higher values in LBBB compared to both NL and WPW. CRT reduced the spatial divergence of shortening (both vector magnitude and direction), and improved global ventricular shortening along with reductions in ESR and dyscoordination of shortening expressed by ISF.</p> <p>Conclusion</p> <p>Incorporation of local 2-D echocardiographic deformation data into a 3-D model by dedicated software allows a comprehensive analysis of spatio-temporal distribution patterns of myocardial dyssynchrony, of the global left ventricular deformation and of newer indices that may better reflect myocardial dyscoordination and/or impaired ventricular contractile efficiency. The potential value of such an analysis is highlighted in two dyssynchronous pathologies that impose particular challenges to deformation imaging.</p

Clusters of galaxies : observational properties of the diffuse radio emission

Clusters of galaxies, as the largest virialized systems in the Universe, are ideal laboratories to study the formation and evolution of cosmic structures...(abridged)... Most of the detailed knowledge of galaxy clusters has been obtained in recent years from the study of ICM through X-ray Astronomy. At the same time, radio observations have proved that the ICM is mixed with non-thermal components, i.e. highly relativistic particles and large-scale magnetic fields, detected through their synchrotron emission. The knowledge of the properties of these non-thermal ICM components has increased significantly, owing to sensitive radio images and to the development of theoretical models. Diffuse synchrotron radio emission in the central and peripheral cluster regions has been found in many clusters. Moreover large-scale magnetic fields appear to be present in all galaxy clusters, as derived from Rotation Measure (RM) studies. Non-thermal components are linked to the cluster X-ray properties, and to the cluster evolutionary stage, and are crucial for a comprehensive physical description of the intracluster medium. They play an important role in the cluster formation and evolution. We review here the observational properties of diffuse non-thermal sources detected in galaxy clusters: halos, relics and mini-halos. We discuss their classification and properties. We report published results up to date and obtain and discuss statistical properties. We present the properties of large-scale magnetic fields in clusters and in even larger structures: filaments connecting galaxy clusters. We summarize the current models of the origin of these cluster components, and outline the improvements that are expected in this area from future developments thanks to the new generation of radio telescopes.Comment: Accepted for the publication in The Astronomy and Astrophysics Review. 58 pages, 26 figure

A T3 and T7 Recombinant Phage Acquires Efficient Adsorption and a Broader Host Range

It is usually thought that bacteriophage T7 is female specific, while phage T3 can propagate on male and female Escherichia coli. We found that the growth patterns of phages T7M and T3 do not match the above characteristics, instead showing strain dependent male exclusion. Furthermore, a T3/7 hybrid phage exhibits a broader host range relative to that of T3, T7, as well as T7M, and is able to overcome the male exclusion. The T7M sequence closely resembles that of T3. T3/7 is essentially T3 based, but a DNA fragment containing part of the tail fiber gene 17 is replaced by the T7 sequence. T3 displays inferior adsorption to strains tested herein compared to T7. The T3 and T7 recombinant phage carries altered tail fibers and acquires better adsorption efficiency than T3. How phages T3 and T7 recombine was previously unclear. This study is the first to show that recombination can occur accurately within only 8 base-pair homology, where four-way junction structures are identified. Genomic recombination models based on endonuclease I cleavages at equivalent and nonequivalent sites followed by strand annealing are proposed. Retention of pseudo-palindromes can increase recombination frequency for reviving under stress

Adult-Onset Obesity Reveals Prenatal Programming of Glucose-Insulin Sensitivity in Male Sheep Nutrient Restricted during Late Gestation

BACKGROUND: Obesity invokes a range of metabolic disturbances, but the transition from a poor to excessive nutritional environment may exacerbate adult metabolic dysfunction. The current study investigated global maternal nutrient restriction during early or late gestation on glucose tolerance and insulin sensitivity in the adult offspring when lean and obese. METHODS/PRINCIPAL FINDINGS: Pregnant sheep received adequate (1.0M; CE, n = 6) or energy restricted (0.7M) diet during early (1-65 days; LEE, n = 6) or late (65-128 days; LEL, n = 7) gestation (term approximately 147 days). Subsequent offspring remained on pasture until 1.5 years when all received glucose and insulin tolerance tests (GTT & ITT) and body composition determination by dual energy x-ray absorptiometry (DXA). All animals were then exposed to an obesogenic environment for 6-7 months and all protocols repeated. Prenatal dietary treatment had no effect on birth weight or on metabolic endpoints when animals were 'lean' (1.5 years). Obesity revealed generalised metabolic 'inflexibility' and insulin resistance; characterised by blunted excursions of plasma NEFA and increased insulin(AUC) (from 133 to 341 [s.e.d. 26] ng.ml(-1).120 mins) during a GTT, respectively. For LEL vs. CE, the peak in plasma insulin when obese was greater (7.8 vs. 4.7 [s.e.d. 1.1] ng.ml(-1)) and was exacerbated by offspring sex (i.e. 9.8 vs. 4.4 [s.e.d. 1.16] ng.ml(-1); LEL male vs. CE male, respectively). Acquisition of obesity also significantly influenced the plasma lipid and protein profile to suggest, overall, greater net lipogenesis and reduced protein metabolism. CONCLUSIONS: This study indicates generalised metabolic dysfunction with adult-onset obesity which also exacerbates and 'reveals' programming of glucose-insulin sensitivity in male offspring prenatally exposed to maternal undernutrition during late gestation. Taken together, the data suggest that metabolic function appears little compromised in young prenatally 'programmed' animals so long as weight is adequately controlled. Nutritional excess in adulthood exacerbates any programmed phenotype, indicating greater vigilance over weight control is required for those individuals exposed to nutritional thrift during gestation

Healthy ageing of cloned sheep

The health of cloned animals generated by somatic-cell nuclear transfer (SCNT) has been of concern since its inception; however, there are no detailed assessments of late-onset, non-communicable diseases. Here we report that SCNT has no obvious detrimental longterm health effects in a cohort of 13 cloned sheep. We perform musculoskeletal assessments, metabolic tests and blood pressure measurements in 13 aged (7–9 years old) cloned sheep, including four derived from the cell line that gave rise to Dolly. We also perform radiological examinations of all main joints, including the knees, the joint most affected by osteoarthritis in Dolly, and compare all health parameters to groups of 5- and 6-year-old sheep, and published reference ranges. Despite their advanced age, these clones are euglycaemic, insulin sensitive and normotensive. Importantly, we observe no clinical signs of degenerative joint disease apart from mild, or in one case moderate, osteoarthritis in some animals. Our study is the first to assess the long-term health outcomes of SCNT in large animals

Is caching the key to exclusion in corvids? The case of carrion crows (Corvus corone corone)

Recently, two corvid species, food-caching ravens and non-caching jackdaws, have been tested in an exclusion performance (EP) task. While the ravens chose by exclusion, the jackdaws did not. Thus, foraging behaviour may affect EP abilities. To investigate this possibility, another food-caching corvid species, the carrion crow (Corvus corone corone), was tested in the same exclusion task. We hid food under one of two cups and subsequently lifted either both cups, or the baited or the un-baited cup. The crows were significantly above chance when both cups were lifted or when only the baited cup was lifted. When the empty cup was lifted, we found considerable inter-individual variation, with some birds having a significant preference for the un-baited but manipulated cup. In a follow-up task, we always provided the birds with the full information about the food location, but manipulated in which order they saw the hiding or the removal of food. Interestingly, they strongly preferred the cup which was manipulated last, even if it did not contain any food. Therefore, we repeated the first experiment but controlled for the movement of the cups. In this case, more crows found the food reliably in the un-baited condition. We conclude that carrion crows are able to choose by exclusion, but local enhancement has a strong influence on their performance and may overshadow potential inferential abilities. However, these findings support the hypothesis that caching might be a key to exclusion in corvids