Prevalent positive epistasis in Escherichia coli and Saccharomyces cerevisiae metabolic networks

Epistasis refers to the interaction between genes. Although high-throughput epistasis data from model organisms are being generated and used to construct genetic networks(1-3), the extent to which genetic epistasis reflects biologically meaningful interactions remains unclear(4-6). We have addressed this question through in silico mapping of positive and negative epistatic interactions amongst biochemical reactions within the metabolic networks of Escherichia coli and Saccharomyces cerevisiae using flux balance analysis. We found that negative epistasis occurs mainly between nonessential reactions with overlapping functions, whereas positive epistasis usually involves essential reactions, is highly abundant and, unexpectedly, often occurs between reactions without overlapping functions. We offer mechanistic explanations of these findings and experimentally validate them for 61 S. cerevisiae gene pairs.

The sequence and de novo assembly of the giant panda genome

Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.

Chemical Constituents from the Leaves and Stems of Schisandra lancifolia

A new nortriterpenoid, 20-hydroxymicrandilactone D (1) and a novel lignan glycoside, lancilignanside A (2) were isolated from leaves and stems of Schisandra lancifolia, together with three known nortriterpenoids (3-5) and nine known phenolics (6-14). The structures of new compounds 1 and 2 were determined by detailed analysis of their 1D and 2D NMR spectra, and chemical evidences. In addition, compounds 1-2, 6-7, and 9-11 showed anti-human immunodeficiency virus (HIV)-1 activities with 50% effective concentration (EC50) in the range of 3.0-99.0 mu g/ml. Compound 12 was not bioactive in this assay with EC50 more than 200 mu g/ml.

Study biological characteristics related with development and reproduction in Barbus capito on the southern coast of the Caspian Sea, Gilan Province

In the present research, a total of 207 pieces of fish from 25 sampling stations in Gilan Province coasts in the years 2001-2002 were biologically studied in terms of their growth and development, reproduction and feeding. The average length and weight of the fishes are increased, as they get older. The highest index of length and weight growth is observed in the years 1 to 2. As the age increases, gradient of length and weight growth diagrams decrease. In studying the relation between length and weight, it was observed that proportionate to the total length, the weight is increased progressively. The fatness coefficient index in the initial years of life and prior to maturity is higher than the post maturity period. As the age increases, the decrease of this index is observable. The fatness coefficient index rate is directly related to index of fullness. The highest Gonadosomatic Index is seen in the months of June and July, i.e. at the times of spawning; and the lowest index rate is observed in the months of November and December. The appropriate temperature for reproduction of these species is from 18 to 22 degree centigrade. The Gonadosomatic Index is higher in spring and summer seasons as compared with autumn and winter. Besides, as the fishes become aged, the amount of the said index increases in a manner that the gradient of it in the years to maturity is less than the maturity time and thereafter. Sexual maturity stages in different months are directly related to Gonadosomatic index, and increase as the age increases. The sexual ratio of male fishes to the female fishes in terms of number is plus one prior to maturity; about one at the time of maturity and minus after maturity. In general the frequency of male fishes as compared with female fishes in all group ages is approximately two times. The fecundity mean, and the diameter and the rate of eggs will substantially increase, as the Gonadosomatic index rises. The maturity age in the male fishes is 3 to 4 years and in female fishes is 4 to 5 years. The spawning of this species in rivers occurs repeatedly and in different time intervals, and do not take place once (Asyncronous). The Gastrosomatic index is directly related to index of fullness and will decrease, as the age increases. The index of fullness is relatively the months of April and May. The underlying reason is the need of the fishes to energy for reproduction. As the spawning time commences, the index of fullness moves down and the downward direction continues. After spa g mg and reduction of the volume of energy in the body, the index of fullness rises, and it will be substantially high until the beginning of fall. In fall and winter as it gets cold, the index of fullness moves downward and the body fat deposits are used. A correlation is shown between the changes in vacuity index and fullness indices. This means that as the fullness index rises, the vacuity index decreases, and vice versa. The Hepatosomatic index prior to the reproduction is at the highest amount and after spawning is at the lowest. No correlation is observed between the fullness and Hepatosomatic indices. In other words reproduction is an inherent and instinct originated matter; and its cycle goes on, alternately and in an orderly manner, upon completion of germinal cells, even when it coincides with reduction or stoppage of somatic cell growth. The rising trend of Hepatosomatic starts in August and will continue until the next July. The volume of fat around digestive tract is severely reduced in early spring and this trend will reach its apex in summer season. In the cold seasons, i.e. the fall and winter, the accumulation of fat around digestive tract increases. Consequently, a meaningful and inverse relation is observed between index of fullness, also the progress of sexual maturity stages and the volume of fat.

Stress within the postseizure time window inhibits seizure recurrence

Recurrence is a key characteristic in the development of epilepsy. It remains unclear whether seizure recurrence is sensitive to postseizure stress. Here, tonic-clonic seizures were induced with a convulsive dose of pentylenetetrazole (PTZ), and acute seizure recurrence was evoked with a subconvulsive dose of the drug. We found that stress inhibited seizure recurrence when applied 30 minutes or 2 hours, but not 4 hours, after the tonic-clonic seizure. The time-dependent anti-recurrence effect of stress was mimicked by the stress hormone corticosterone and blocked by co-administration of mineralocorticoid and glucocorticoid receptor antagonists. Furthermore, in a PTZ-induced epileptic kindling model, corticosterone administered 30 minutes after each seizure decreased the extent of seizures both during the kindling establishment and in the following challenge test. These results provide novel insights into both the mechanisms of and therapeutic strategies for epilepsy. (C) 2010 Elsevier Inc. All rights reserved.

Molecular and morphological analysis of endangered species Gymnodiptychus integrigymnatus (Teleostei: Cyprinidae)

Gymnodiptychus integrigymnatus is a critically endangered species endemic to the Gaoligongshan Mountains. It was thought to be only distributed in several headwater-streams of the Longchuanjiang River (west slope of the Gaoligongshan Mountains, belonging to the Irrawaddy River drainage). In recent years, dozens of G. integrigymnatus specimens have been collected in some streams on the east slope of the Gaoligongshan Mountains (the Salween drainage). We performed a morphological and genetic analyses (based on cytochrome b and D-loop) of the newly discovered populations of G. integrigymnatus to determine whether the degree of separation of these populations warrants species status. Our analysis from the cytochrome b gene revealed that nine individuals from the Irrawaddy drainage area and seven individuals from the Salween drainage area each have only one unique haplotype. The genetic distance between the two haplotypes is 1.97%. Our phylogenetic analysis revealed that G. integrigymnatus is closely related to highly specialized schizothoracine fishes. Analysis from the mitochondrial control region revealed that G. integrigymnatus has relatively high genetic diversity (pi was 0.00891 and h was 0.8714), and individuals from different river drainages do not share the same haplotypes. The AMOVA results indicated 87.27% genetic variability between the Salween and Irrawaddy populations. Phylogenetic trees show two major geographic groups corresponding to the river systems. We recommend that G. integrigymnatus should be considered as a high priority for protected species status in the Gaoligongshan Mountains National Nature Reserve, and that the area of the Gaoligongshan Mountains National Nature Reserve should be expanded to cover the entire distribution of G. integrigymnatus. Populations of G. integrigymnatus from different river systems should be treated as evolutionarily significant units.

The technical potential for reducing metal requirements through lightweight product design

Metal production consumes around 10% of all global energy, so is a significant driver of climate change and other concerns about sustainability. Demand for metal is rising and forecast to double by 2050 through a combination of growing total demand from developing countries, and ongoing replacement demand in developed economies. Metal production is already extremely efficient, so the major opportunities for emissions abatement in the sector are likely to arise from material efficiency - using less new metal to meet demand for services. Therefore this paper examines the opportunity to reduce requirements for steel and aluminium by lightweight design. A set of general principles for lightweight design are proposed by way of a simple analytical example, and are then applied to five case study products which cumulatively account for 30% of global steel product output. It is shown that exploiting lightweight design opportunities for these five products alone could reduce global steel requirements by 5%, and similar savings in aluminium products could reduce global aluminium requirements by 7%. If similar savings to those in the design case studies were possible in all steel and aluminium products, total material requirements could be reduced by 25-30%. However, many of these light-weighting measures are, at present, economically unattractive, and may take many years to implement. © 2011 Elsevier B.V. All rights reserved.

Displacement and mixing ventilation driven by opposing wind and buoyancy

The effect of an opposing wind on the stratification and flow produced by a buoyant plume rising from a heat source on the floor of a ventilated enclosure is investigated. Ventilation openings located at high level on the windward side of the enclosure and at low level on the leeward side allow a wind-driven flow from high to low level, opposite to the buoyancy-driven flow. One of two stable steady flow regimes is established depending on a dimensionless parameter F that characterizes the relative magnitudes of the wind-driven and buoyancy-driven velocities within the enclosure, and on the time history of the flow. A third, unstable steady flow solution is identified. For small opposing winds (small F) a steady, two-layer stratification and displacement ventilation is established. Exterior fluid enters through the lower leeward openings and buoyant interior fluid leaves through the upper windward openings. As the wind speed increases, the opposing wind may cause a reversal in the flow direction. In this case, cool exterior fluid enters through the high windward openings and mixes the interior fluid, which exits through the leeward openings. There are now two possibilities. If the rate of heat input by the source exceeds the rate of heat loss through the leeward openings, the temperature of the interior increases and this flow reversal is only maintained temporarily. The buoyancy force increases with time, the flow reverts to its original direction, and steady two-layer displacement ventilation is re-established and maintained. In this regime, the increase in wind speed increases the depth and temperature of the warm upper layer, and reduces the ventilation flow rate. If, on the other hand, the heat loss exceeds the heat input, the interior cools and the buoyancy-driven flow decreases. The reversed flow is maintained, the stratification is destroyed and mixing ventilation occurs. Further increases in wind speed increase the ventilation rate and decrease the interior temperature. The transitions between the two ventilation flow patterns exhibit hysteresis. The change from displacement ventilation to mixing ventilation occurs at a higher F than the transition from mixing to displacement. Further, we find that the transition from mixing to displacement ventilation occurs at a fixed value of F, whereas the transition from displacement to mixing flow is dependent on the details of the time history of the flow and the geometry of the openings, and is not determined solely by the value of F. Theoretical models that predic t the steady stratification profiles and flow rates for the displacement and mixing ventilation, and the transitions between them, are presented and compared with measurements from laboratory experiments. The transition between these ventilation patterns completely changes the internal environment, and we discuss some of the implications for the natural ventilation of buildings. © 2004 Cambridge University Press.

New evidence for the origin and behaviour of deep ocean 'crusts'

In situ tests in deep waterWest African clays show crust-like shear strengths within the top few metres of sediment. Typical strength profiles show su rising from mud-line to 10 kPa to 15 kPa before dropping back to normally consolidated strengths of 3 kPa to 4 kPa by 1.5m to 2m depth. A Cam-shear device is used to better understand the mechanical behaviour of undisturbed crust samples under pipelines. Extremely variable peak and residual shear strengths are observed for a range of pipeline consolidation stresses and test shear rates, with residual strengths approximating zero. ESEM of undisturbed samples and wet-sieved samples from various core depths show the presence of numerous randomly-located groups of invertebrate faecal pellets. It is therefore proposed that the cause of strength variability during shear testing and, indeed, of the crust's origin, is the presence of random groups of faecal pellets within the sediment. © 2011 Taylor & Francis Group, London.

Insight into differences in nanoindentation properties of bone.

Nanoindentation provides the ideal framework to determine mechanical properties of bone at the tissue scale without being affected by the size, shape, and porosity of the bone. However, the values of tissue level mechanical properties vary significantly between studies. Since the differences in the bone sample, hydration state, and test parameters complicate direct comparisons across the various studies, these discrepancies in values cannot be compared directly. The objective of the current study is to evaluate and compare mechanical properties of the same bones using a broad range of testing parameters. Wild type C56BL6 mice tibiae were embedded following different processes and tested in dry and rehydrated conditions. Spherical and Berkovich indenter probes were used, and data analysis was considered within the elasto-plastic (Oliver-Pharr), viscoelastic and visco-elastic-plastic frameworks. The mean values of plane strain modulus varied significantly depending on the hydration state, probe geometry and analysis method. Indentations in dry bone analyzed using a visco-elastic-plastic approach gave values of 34 GPa. After rehydrating the same bones and indenting them with a spherical tip and utilizing a viscoelastic analysis, the mean modulus value was 4 GPa, nearly an order of magnitude smaller. Results suggest that the hydration state, probe geometry and the limitations and assumptions of each analysis method influence significantly the measured mechanical properties. This is the first time that such a systematic study has been carried out and it has been concluded that the discrepancies in the mechanical properties of bone measured by nanoindentation found in the literature should not be attributed only to the differences between the bones themselves, but also to the testing and analysis protocols.

Classical plume theory: 1937-2010 and beyond

Developing a theoretical description of turbulent plumes, the likes of which may be seen rising above industrial chimneys, is a daunting thought. Plumes are ubiquitous on a wide range of scales in both the natural and the man-made environments. Examples that immediately come to mind are the vapour plumes above industrial smoke stacks or the ash plumes forming particle-laden clouds above an erupting volcano. However, plumes also occur where they are less visually apparent, such as the rising stream of warmair above a domestic radiator, of oil from a subsea blowout or, at a larger scale, of air above the so-called urban heat island. In many instances, not only the plume itself is of interest but also its influence on the environment as a whole through the process of entrainment. Zeldovich (1937, The asymptotic laws of freely-ascending convective flows. Zh. Eksp. Teor. Fiz., 7, 1463-1465 (in Russian)), Batchelor (1954, Heat convection and buoyancy effects in fluids. Q. J. R. Meteor. Soc., 80, 339-358) and Morton et al. (1956, Turbulent gravitational convection from maintained and instantaneous sources. Proc. R. Soc. Lond. A, 234, 1-23) laid the foundations for classical plume theory, a theoretical description that is elegant in its simplicity and yet encapsulates the complex turbulent engulfment of ambient fluid into the plume. Testament to the insight and approach developed in these early models of plumes is that the essential theory remains unchanged and is widely applied today. We describe the foundations of plume theory and link the theoretical developments with the measurements made in experiments necessary to close these models before discussing some recent developments in plume theory, including an approach which generalizes results obtained separately for the Boussinesq and the non-Boussinesq plume cases. The theory presented - despite its simplicity - has been very successful at describing and explaining the behaviour of plumes across the wide range of scales they are observed. We present solutions to the coupled set of ordinary differential equations (the plume conservation equations) that Morton et al. (1956) derived from the Navier-Stokes equations which govern fluid motion. In order to describe and contrast the bulk behaviour of rising plumes from general area sources, we present closed-form solutions to the plume conservation equations that were achieved by solving for the variation with height of Morton's non-dimensional flux parameter Γ - this single flux parameter gives a unique representation of the behaviour of steady plumes and enables a characterization of the different types of plume. We discuss advantages of solutions in this form before describing extensions to plume theory and suggesting directions for new research. © 2010 The Author. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

Thermal stratification produced by plumes and jets in enclosed spaces

The airflow and thermal stratification produced by a localised heat source located at floor level in a closed room is of considerable practical interest and is commonly referred to as a 'filling box'. In rooms with low aspect ratios H/R ≲ 1 (room height H to characteristic horizontal dimension R) the thermal plume spreads laterally on reaching the ceiling and a descending horizontal 'front' forms separating a stably stratified, warm upper region from cooler air below. The stratification is well predicted for H/R ≲ 1 by the original filling box model of Baines and Turner (J. Fluid. Mech. 37 (1968) 51). This model represents a somewhat idealised situation of a plume rising from a point source of buoyancy alone-in particular the momentum flux at the source is zero. In practical situations, real sources of heating and cooling in a ventilation system often include initial fluxes of both buoyancy and momentum, e.g. where a heating system vents warm air into a space. This paper describes laboratory experiments to determine the dependence of the 'front' formation and stratification on the source momentum and buoyancy fluxes of a single source, and on the location and relative strengths of two sources from which momentum and buoyancy fluxes were supplied separately. For a single source with a non-zero input of momentum, the rate of descent of the front is more rapid than for the case of zero source momentum flux and increases with increasing momentum input. Increasing the source momentum flux effectively increases the height of the enclosure, and leads to enhanced overturning motions and finally to complete mixing for highly momentum-driven flows. Stratified flows may be maintained by reducing the aspect ratio of the enclosure. At these low aspect ratios different long-time behaviour is observed depending on the nature of the heat input. A constant heat flux always produces a stratified interior at large times. On the other hand, a constant temperature supply ultimately produces a well-mixed space at the supply temperature. For separate sources of momentum and buoyancy, the developing stratification is shown to be strongly dependent on the separation of the sources and their relative strengths. Even at small separation distances the stratification initially exhibits horizontal inhomogeneity with localised regions of warm fluid (from the buoyancy source) and cool fluid. This inhomogeneity is less pronounced as the strength of one source is increased relative to the other. Regardless of the strengths of the sources, a constant buoyancy flux source dominates after sufficiently large times, although the strength of the momentum source determines whether the enclosure is initially well mixed (strong momentum source) or stably stratified (weak momentum source). © 2001 Elsevier Science Ltd. All rights reserved.

Properties of trench defects in InGaN/GaN quantum well structures

The structural and optical properties of trench defects, which are poorly understood yet commonly occurring defects observed on the surfaces of InGaN multiple quantum wells (MQW), are reported. These defects comprise near-circular trenches which enclose areas of MQW which give rise to a red shift in peak photoluminescence emission and a change in cathodoluminescence intensity with respect to the surrounding material. Atomic force microscopy shows that the height of trench-enclosed areas differs from that of the surrounding quantum well structure, and that trenches are unrelated to the commonly observed V-defects in InGaN films, despite being occasionally intersected by them. Cross-sectional electron microscopy analysis of trenches with raised centres suggests that the red shift in the observed cathodoluminescence peak emission may be due to the quantum wells being thicker in the trench-enclosed regions than in the surrounding quantum well area. The mechanism of trench formation and its implication for the control of the emission properties of light-emitting diodes is discussed. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A global model for effective use and evaluation of e-learning in health.

Healthcare systems worldwide face a wide range of challenges, including demographic change, rising drug and medical technology costs, and persistent and widening health inequalities both within and between countries. Simultaneously, issues such as professional silos, static medical curricula, and perceptions of "information overload" have made it difficult for medical training and continued professional development (CPD) to adapt to the changing needs of healthcare professionals in increasingly patient-centered, collaborative, and/or remote delivery contexts. In response to these challenges, increasing numbers of medical education and CPD programs have adopted e-learning approaches, which have been shown to provide flexible, low-cost, user-centered, and easily updated learning. The effectiveness of e-learning varies from context to context, however, and has also been shown to make considerable demands on users' motivation and "digital literacy" and on providing institutions. Consequently, there is a need to evaluate the effectiveness of e-learning in healthcare as part of ongoing quality improvement efforts. This article outlines the key issues for developing successful models for analyzing e-health learning.

Correlations between the morphology and emission properties of trench defects in InGaN/GaN quantum wells

Atomic force microscopy (AFM) and scanning electron microscopy (SEM) with cathodoluminescence (CL) were performed on exactly the same defects in a blue-emitting InGaN/GaN multiple quantum well (QW) sample enabling the direct correlation of the morphology of an individual defect with its emission properties. The defects in question are observed in AFM and SEM as a trench partially or fully enclosing a region of the QW having altered emission properties. Their sub-surface structure has previously been shown to consist of a basal plane stacking fault (BSF) in the plane of the QW stack, and a stacking mismatch boundary (SMB) which opens up into a trench at the sample surface. In CL, the material enclosed by the trench may emit more or less intensely than the surrounding material, but always exhibits a redshift relative to the surrounding material. A strong correlation exists between the width of the trench and both the redshift and the intensity ratio, with the widest trenches surrounding regions which exhibit the brightest and most redshifted emission. Based on studies of the evolution of the trench width with the number of QWs from four additional MQW samples, we conclude that in order for a trench defect to emit intense, strongly redshifted light, the BSF must be formed in the early stages of the growth of the QW stack. The data suggest that the SMB may act as a non-radiative recombination center. © 2013 American Institute of Physics.