bluuebunny/crossref_metadata_2025 huggingface dataset:
Myostatin gene knockdown through lentiviral-mediated delivery of shRNA for in vitro production of transgenic bovine embryos
Authors: Milazzotto Marcella Pecora , Goissis Marcelo Demarchi , Feitosa Weber Beringui , Martins Leydson Ferreira , Strauss Bryan Eric , Bajgelman Marcio Chaim , Assumpção Mayra Elena Ortiz D'Ávila , Visintin Jose Antonio
Published: May 2010

Myostatin is described as a negative regulator of the skeletal muscle growth. Genetic engineering, in order to produce animals with double the muscle mass and that can transmit the characteristic to future progeny, may be useful. In this context, the present study aimed to analyse the feasibility of lentiviral-mediated delivery of short hairpin RNA (shRNA) targeting of myostatin into in vitro produced transgenic bovine embryos. Lentiviral vectors were used to deliver a transgene that expressed green fluorescent protein (GFP) and an shRNA that targeted myostatin. Vector efficiency was verified through in vitro murine myoblast (C2C12) cell morphology after inductive differentiation and by means of real-time PCR. The lentiviral vector was microinjected into the perivitellinic space of in vitro matured oocytes. Non-microinjected oocytes were used as the control. After injection, oocytes were fertilized and cultured in vitro. Blastocysts were evaluated by epifluorescence microscopy. Results demonstrated that the vector was able to inhibit myostatin mRNA in C2C12 cells, as the transducted group had a less amount of myostatin mRNA after 72 h of differentiation (p < 0.05) and had less myotube formation than the non-transduced group (p < 0.05). There was no difference in cleavage and blastocyst rates between the microinjected and control groups. After hatching, 3.07% of the embryos exhibited GFP expression, indicating that they expressed shRNA targeting myostatin. In conclusion, we demonstrate that a lentiviral vector effectively performed shRNA myostatin gene knockdown and gene delivery into in vitro produced bovine embryos. Thus, this technique can be considered a novel option for the production of transgenic embryos and double muscle mass animals.
BREAKING THE IDOL OF THE MARRIAGE PLOT INYEASTANDVILLETTE
Authors: Carens Timothy L.
Published: May 2010

Nineteenth-century Protestant culturegenerally held marriage in high esteem, and the notion that marriage was “made in heaven” often explicitly undergirds the conventional resolution of domestic fiction. Despite many indications of a harmonious relationship between human love and religious faith, a countervailing cultural trend reveals a deep conflict between the two. Victorian Protestants worried that passionate love for another mortal creature might lead to heretical extremes, that human love might slip into idolatry, the worship of false and material gods. Jane Eyre memorably confesses that she has “made an idol” of Rochester, although she, of course, looks back upon this transgression from the vantage of marital happiness (274). In this essay, I focus on works in which misgivings about idolatrous love arise with more disruptive force. The marriage plots of Charles Kingsley'sYeast: A Problem(1851) and Charlotte Brontë'sVillette(1853) both abruptly collapse, bringing into sharp focus a Protestant religious anxiety that subverts the conventional device with which Victorian domestic novels achieve closure.
Social capital and human development: an empirical investigation across European countries
Authors: CHRISTOFOROU ASIMINA
Published: May 2010

In this paper, we offer an empirical investigation of the relationship between social capital and human development across European countries for the post-war period. We argue that social organizations contribute directly to broader welfare aspects of development as part of the third sector of the economy, which undertakes the provision of public goods, such as health and education, in synergy with state institutions. This is counter to views that associate social organizations with anti-growth rent-seeking and lobbying activities. We begin with a multivariate regression analysis, which reveals that membership in social organizations is positively associated with human development, along with state institutions of public expenditure and the quality of governance. We then conduct a case study analysis to explore further the historical and cultural contextual factors of European welfare systems that determine the capacity of third sector organizations to enhance generalized co-operation, synergistic relations and social welfare against particularist interests.
Enhanced global continental erosion and exhumation driven by Oligo‐Miocene climate change
Authors: Clift Peter D.
Published: May 2010

Surface erosion is the most significant process responsible for the recycling of continental crust into the upper mantle, and controls both exhumation in mountain belts and the long‐term global climate via chemical weathering. Earlier studies have highlighted the importance of climate instability since the onset of Northern Hemispheric Glaciation (∼3 Ma) as being the primary influence causing high erosion rates since that time. Here I show that synchronous pulses of erosion and exhumation occurred across Eurasia, in North America and in Africa starting after 33 Ma, with a prominent peak around 16 Ma. Correlation of these erosional events with changes in global climate suggests that they are controlled by surface processes. Because these climate events involve both cooling and warming periods the importance of increased seasonality is emphasized as being the key factor in controlling global erosion and exhumation throughout the Cenozoic.
Partitioning evapotranspiration across gradients of woody plant cover: Assessment of a stable isotope technique
Authors: Wang Lixin , Caylor Kelly K. , Villegas Juan Camilo , Barron‐Gafford Greg A. , Breshears David D. , Huxman Travis E.
Published: May 2010

In water‐limited ecosystems, partitioning ecosystem‐scale evapotranspiration fluxes between plant transpiration and soil/canopy evaporation remains a theoretical and technical challenge. We used the Biosphere 2 glasshouse to assess partitioning of evapotranspiration across an experimentally manipulated gradient of woody plant cover using continuous measurements of near‐surface variations in the stable isotopic composition of water vapor (δ2H). Our technique employs a newly‐developed laser‐based isotope analyzer and the Keeling plot approach for surface flux partitioning. The applicability of the technique was verified by comparison to separate, simultaneous lysimeter and sap flow estimates of ET partitioning. The results showed an expected increase in fractional contribution of transpiration to evapotranspiration as woody cover increased—from T/ET = 0.61 at 25% woody cover to T/ET = 0.83 at 100% cover. Further development of this technique may enable field characterization of evapotranspiration partitioning across diverse woody cover gradients, a central issue in addressing dryland ecohydrological responses to land use and climate change.
Increased Soluble Leptin Receptor Levels in Morbidly Obese Patients With Insulin Resistance and Nonalcoholic Fatty Liver Disease
Authors: Medici Valentina , Ali MohamedR. , Seo Suk , Aoki Christopher A. , Rossaro Lorenzo , Kim Kyoungmi , Fuller Will D. , Vidovszky Tamas J. , Smith William , Jiang Joy X. , Maganti Kalyani , Havel Peter J. , Kamboj Amit , Ramsamooj Rajendra , Török Natalie J.
Published: May 2010

The adipocyte hormone, leptin has been demonstrated to have profibrogenic actionsin vitroand in animal models. However, no correlation was found between plasma leptin levels and fibrosis stage in humans. Thus, our aim was to study whether soluble leptin receptor (SLR) or free leptin index (FLI; calculated as the ratio of leptin to SLR), may correlate better with the features of metabolic syndrome and with the histological grade and stage of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). We studied a population (n= 104) of morbidly obese patients undergoing bariatric surgery. Data including BMI, type 2 diabetes mellitus, hypertension, and hyperlipidemia were obtained. Plasma fasting leptin and SLR, fasting glucose and insulin were measured, and homeostasis model of assessment insulin resistance (HOMAIR) index and FLI were calculated. All patients had intraoperative liver biopsies. Leptin levels correlated with the BMI. The multiple regression analysis indicated that increasing HOMA and decreasing FLI were predictors of steatosis in the liver (P< 0.0003). SLR levels were positively correlated with the presence of diabetes mellitus and the stage of fibrosis. In conclusion, increased SLR levels in morbidly obese patients with diabetes are correlated with the stage of liver fibrosis, and may reflect progressive liver disease.
Shear migration and chaotic mixing of particle suspensions in a time-periodic lid-driven cavity
Authors: Xu B. , Gilchrist J. F.
Published: May 2010

This work simulates segregation of noncolloidal particle suspensions in a two dimensional time-periodic flow. Two different mixing protocols having alternating moving boundaries in a cavity known to generate chaotic advection while maintaining a constant energy input rate are applied to each suspension. A diffusive flux model is used to capture the essence of shear-induced migration. In this system, fluid deformation drives both mixing and segregation where the local rheology is a function of particle volume fraction. The impact of migration strength, altered by varying the particle size and bulk volume fraction, and topology, altered by breaking symmetry in the flow when varying the period length, are investigated. As a result of the complex interplay between the flow topology and shear migration, the concentration profile ranges from that representing the underlying topology to that of steady flow in a lid-driven cavity and depends on the parameters mentioned above and the structure produced by the two mixing protocols. In this system, increasing the size of chaotic regions does not result in enhancing mixing. These results challenge conventional wisdom in designing small scale flows for mixing and separations in microscale applications.
Two mechanisms of exciton dissociation in rubrene single crystals
Authors: Najafov Hikmat , Lyu Byunggook , Biaggio Ivan , Podzorov Vitaly
Published: May 2010

Excitons in rubrene single crystals dissociate into free charge carriers via two mechanisms whose relative importance depends on the illumination wavelength through the optical penetration depth into the crystal. The first mechanism is defect-induced dissociation in less than 10 ns after photoexcitation. For low photoexcitation densities, about 10% of the excitons that survive radiative recombination dissociate through this channel. The second mechanism, affecting the remaining 90% of the excitons, involves a previously reported state localized close to the surface of the crystal that leads to a delayed release of photocarriers a fraction of a millisecond after photoexcitation.
Frank William Ernest Gibson 1923 - 2008
Authors: Pittard A. J. , Cox G. B.
Published: May 2010

Frank Gibson died in Canberra on 11 July 2008. Frank was a highly distinguished research scientist who will be remembered for his pioneering studies in identifying the branch-point compound in the pathway of biosynthesis of a large number of important aromatic compounds followed by a detailed biochemical and genetic analysis of many of the pathways leading to the aromatic amino acids and the so-called aromatic vitamins. Studies on ubiquinone synthesis and function led to an examination of oxidative phosphorylation and the structure and function of the F1F0-ATPase in the bacterium Escherichia coli. This work resulted in the formulation of a highly innovative model, involving rotating subunits of the F0 segment within the membrane and offering an explanation for the mechanism linking proton flow and ATP synthesis.
Richard Ernst Meyer 1919 - 2008
Authors: Stalker R. J. , Nicole Meyer E.
Published: May 2010

Richard E. Meyer was a mathematical physicist who specialized in the physics of fluid motion. His research career began with his doctorate at the Swiss Federal Institute of Technology, followed by a brief period of employment with the English Ministry of Aircraft Production. He then went to the University of Manchester, where he made his first major research contributions. In 1953 he left Manchester for the University of Sydney. By this time he was established as a theoretical supersonic aerodynamicist and he continued with this work as well as assuming the responsibilities of a research group leader. In 1957 he went to the USA and remained there for the rest of his life, essentially abandoning supersonic aerodynamics in favour of water-wave theory. His work was marked by an ability to analyse the approach to limiting conditions, or singularities, in models of physical processes. From the 1970s, he focused increasingly on developing the mathematical aspects of his work.
Chemical behavior of fluid and granular Mn and Zn fertilisers in alkaline soils
Authors: Hettiarachchi G. M. , Lombi E. , McLaughlin M. J. , Chittleborough D. J. , Johnston C.
Published: May 2010

The grain yield benefits of applying micronutrient fluid fertilisers over conventional granular products in calcareous sandy loam soils have been agronomically demonstrated. An understanding of the fundamental mechanisms and reactions occurring following application of these products to soils is critical to improve fertiliser management. We therefore examined the diffusion, solubility, and potential availability of manganese (Mn) and zinc (Zn) from both granular and fluid forms of Mn and Zn fertiliser in an alkaline calcareous and alkaline non-calcareous soil using laboratory incubation experiments in conjunction with an isotopic dilution technique with 54Mn and 65Zn. Enhanced mobility, solubility, and/or potential availability of Mn and Zn from fluid fertilisers were observed in comparison to Mn or Zn from granular fertilisers in both soils after 5 weeks of incubation. Differential behaviour of fluid and granular fertilisers for Mn and Zn appeared to be independent of their effects on soil pH. Most (~90%) of the Mn in granular fertiliser dissolved and diffused out of the granule but was retained within 4 mm of the point of granular placement, whereas most (~85%) of the Zn in the granular Zn fertiliser source remained in the granule. Our data suggest that the superior agronomic effectiveness of fluid Mn and Zn fertilisers observed in calcareous soils under field conditions may have resulted from the enhanced diffusion (Mn) and/or solubility/availability (Mn, Zn) of these micronutrients in soil when applied in fluid form.
Soil organic carbon and biological indicators in an Acrisol under tillage systems and organic management in north-eastern Brazil
Authors: Leite Luiz F. C. , Oliveira Francisco C. , Araújo Ademir S. F. , Galvão Sandra R. S. , Lemos Janyelle O. , Silva Elzane F. L.
Published: May 2010

No-tillage and organic farming are important strategies to improve soil quality. This study aimed to quantify the effects of the tillage systems and organic management on total organic carbon (TOC), labile C (CL), and biological indicators in an Acrisol in north-eastern Brazil. Five systems were studied: NV, native vegetation; NT/ORG, no-tillage plus organic fertiliser; NT/CHE, no-tillage plus chemical fertiliser; NT/CHE/ORG, no-tillage plus organic and chemical fertiliser; CT/CHE, conventional tillage plus chemical fertiliser. Soil samples were collected in the 0–0.10 and 0.10–0.20 m depths. TOC stocks were higher in NT/CHE/ORG (0–0.10 m, 14.0 Mg/ha; 0.10–0.20 m, 13.0 Mg/ha) and NT/ORG (0–0.10 m, 12.6 Mg/ha; 0.10–0.20 m, 11.6 Mg/ha) than in CT/CHE and NV systems. CL stocks were higher in NT/ORG (3.61 Mg/ha) at 0–0.10 m and in NT/ORG, NT/CHE, and NT/CHE/ORG at 0.10–0.20 m. At 0–0.10 m, microbial biomass C content was higher in the NT/CHE/ORG (190 mg/kg) and NT/ORG (155 mg/kg). Soil microbial respiration rate was similar in all systems. However, qCO2 was higher in the NT/CHE and CT/CHE systems, suggesting a stress in the soil microbial biomass. No-tillage and organic management promoted positive changes in soil organic carbon and soil microbial properties and improved soil quality.
Soil chemistry and morphology transects to assist wetland delineation in four semi-arid saline lakes, south-western Queensland
Authors: Biggs A. J. W. , Bryant K. , Watling K. M.
Published: May 2010

Soils at 4 saline lakes (Wyara, Numalla, Wombah and Bindegolly) in semi-arid south-western Queensland were described and sampled to determine soil attributes that assist in the delineation of wetlands. Up to 4 sites were described in transects perpendicular to the lake edge. Samples from fixed depths were analysed for limited ionic chemistry and, in some cases, selected acid sulfate soil parameters. Lakebed soils were alkaline Hypersalic Hydrosols, changing to a variety of soils, including alkaline Rudosols and Podosols on adjacent lunettes and beach ridges. Gley colours and mottling were indicative of lakebed soils, while redder colours and stratification were common in soils outside the wetland. Evaporative concentration of salts at the soil surface was common in lakebed and transition zone soils, whereas leaching of salts was common in sandier soils outside the wetlands. Analysis of acid sulfate soil parameters and field evidence in the beds of Lakes Wyara and Wombah confirmed the presence of unoxidised sulfidic sediments and extensive neutralising capacity. Wave action formation of beach ridges appeared to be the most prevalent land-forming process at 3 lakes, but wind-driven deflation with associated lunette-building was evident at Lake Bindegolly. The data confirmed the value of pedological features such as texture, colour, and salinity trends in determining the boundaries of these wetlands, but also highlighted the transient nature of these features.
Soil pH buffering capacity: a descriptive function and its application to some acidic tropical soils
Authors: Nelson Paul N. , Su Ninghu
Published: May 2010

Calculation of soil acidification rates requires knowledge of pH buffering capacity (pHBC), which is measured using titration methods. The pHBC is often quoted as a single value for a particular soil, implying a linear relationship between pH and the amount of acid or alkali added. However, over its whole range, the relationship is sigmoid rather than linear, and in many soils pH is low or high enough to be outside of the linear range. In this work we fitted a simple sigmoid function to pH buffer curves of 8 tropical Australian soils obtained using one titration method and 58 Papua New Guinean (PNG) soils obtained using another titration method. The function described the curves well for all soils (adjusted r2 > 0.93 for all samples and >0.99 for 90% of samples), irrespective of the titration method, allowing pHBC to be calculated as a function of pH across the range of pH values established. Using the function, the contribution of variable charge to pHBC was calculated for the PNG soils; on average it was 93% at the pH buffer curves’ inflection point, which corresponds with the soil’s minimum pHBC. Factors other than variable charge became important at pH (1 : 5, 0.002 m CaCl2) values <4.8 or >6.0. The relationship between pHBC and soil organic matter content was closest at pH 6.0–6.5. Application of the sigmoid function could facilitate more accurate assessments of acidification risks, acidification rates, and potential management interventions, particularly as soils become increasingly acidic.
The difference of being human: Morality
Authors: Ayala Francisco J.
Published: May 2010

In
The Descent of Man, and Selection in Relation to Sex
, published in 1871, Charles Darwin wrote: “I fully … subscribe to the judgment of those writers who maintain that of all the differences between man and the lower animals the moral sense or conscience is by far the most important.” I raise the question of whether morality is biologically or culturally determined. The question of whether the moral sense is biologically determined may refer either to the
capacity
for ethics (i.e., the proclivity to judge human actions as either right or wrong), or to the moral
norms
accepted by human beings for guiding their actions. I propose that the capacity for ethics is a necessary attribute of human nature, whereas moral codes are products of cultural evolution. Humans have a moral sense because their biological makeup determines the presence of three necessary conditions for ethical behavior: (
i
) the ability to anticipate the consequences of one's own actions; (
ii
) the ability to make value judgments; and (
iii
) the ability to choose between alternative courses of action. Ethical behavior came about in evolution not because it is adaptive in itself but as a necessary consequence of man's eminent intellectual abilities, which are an attribute directly promoted by natural selection. That is, morality evolved as an exaptation, not as an adaptation. Moral codes, however, are outcomes of cultural evolution, which accounts for the diversity of cultural norms among populations and for their evolution through time.
Adaptive specializations, social exchange, and the evolution of human intelligence
Authors: Cosmides Leda , Barrett H. Clark , Tooby John
Published: May 2010

Blank-slate theories of human intelligence propose that reasoning is carried out by general-purpose operations applied uniformly across contents. An evolutionary approach implies a radically different model of human intelligence. The task demands of different adaptive problems select for functionally specialized problem-solving strategies, unleashing massive increases in problem-solving power for ancestrally recurrent adaptive problems. Because exchange can evolve only if cooperators can detect cheaters, we hypothesized that the human mind would be equipped with a neurocognitive system specialized for reasoning about social exchange. Whereas humans perform poorly when asked to detect violations of most conditional rules, we predicted and found a dramatic spike in performance when the rule specifies an exchange and violations correspond to cheating. According to critics, people's uncanny accuracy at detecting violations of social exchange rules does not reflect a cheater detection mechanism, but extends instead to all rules regulating when actions are permitted (deontic conditionals). Here we report experimental tests that falsify these theories by demonstrating that deontic rules as a class do not elicit the search for violations. We show that the cheater detection system functions with pinpoint accuracy, searching for violations of social exchange rules only when these are likely to reveal the presence of someone who intends to cheat. It does not search for violations of social exchange rules when these are accidental, when they do not benefit the violator, or when the situation would make cheating difficult.
A Hypothetical‐Mathematical Model of Acute Myeloid Leukaemia Pathogenesis
Authors: Cucuianu Andrei , Precup Radu
Published: May 2010

Acute myeloid leukaemia is defined by the expansion of a mutated haematopoietic stem cell clone, with the inhibition of surrounding normal clones. Haematopoiesis can be seen as an evolutionary tree, starting with one cell that undergoes several divisions during the expansion phase, afterwards losing functional cells during the aging‐related contraction phase. During divisions, offspring cells acquire ‘variations’, which can be either normal or abnormal. If an abnormal variation is present in more than 25% of the final cells, a monoclonal, leukemic pattern occurs. Such a pattern develops if: (A1) The abnormal variation occurs early, during the first or second divisions; (A2) The variation confers exceptional proliferative capacity; (B) A sizable proportion of the normal clones are destroyed and a previously non‐significant abnormal clone gains relative dominance over a depleted environment; (C) The abnormal variation confers relative ‘immortality’, rendering it significant during the contraction phase. Combinations of these pathways further enhance the leukemic risk of the system. A simple mathematical model is used in order to characterize normal and leukemic states and to explain the above cellular processes generating monoclonal leukemic patterns.
Exit from the Golgi Is Required for the Expansion of the Autophagosomal Phagophore in YeastSaccharomyces cerevisiae
Authors: van der Vaart Aniek , Griffith Janice , Reggiori Fulvio
Published: May 2010

The delivery of proteins and organelles to the vacuole by autophagy involves membrane rearrangements that result in the formation of large vesicles called autophagosomes. The mechanism underlying autophagosome biogenesis and the origin of the membranes composing these vesicles remains largely unclear. We have investigated the role of the Golgi complex in autophagy and have determined that in yeast, activation of ADP-ribosylation factor (Arf)1 and Arf2 GTPases by Sec7, Gea1, and Gea2 is essential for this catabolic process. The two main events catalyzed by these components, the biogenesis of COPI- and clathrin-coated vesicles, do not play a critical role in autophagy. Analysis of the sec7 strain under starvation conditions revealed that the autophagy machinery is correctly assembled and the precursor membrane cisterna of autophagosomes, the phagophore, is normally formed. However, the expansion of the phagophore into an autophagosome is severely impaired. Our data show that the Golgi complex plays a crucial role in supplying the lipid bilayers necessary for the biogenesis of double-membrane vesicles possibly through a new class of transport carriers or a new mechanism.
Rapid Lytic Granule Convergence to the MTOC in Natural Killer Cells Is Dependent on Dynein But Not Cytolytic Commitment
Authors: Mentlik Ashley N. , Sanborn Keri B. , Holzbaur Erika L. , Orange Jordan S.
Published: May 2010

Natural killer cells are lymphocytes specialized to participate in host defense through their innate ability to mediate cytotoxicity by secreting the contents of preformed secretory lysosomes (lytic granules) directly onto a target cell. This form of directed secretion requires the formation of an immunological synapse and occurs stepwise with actin reorganization preceding microtubule-organizing center (MTOC) polarization to the synapse. Because MTOC polarization to the synapse is required for polarization of lytic granules, we attempted to define their interrelationship. We found that compared with the time required for MTOC polarization, lytic granules converged to the MTOC rapidly. The MTOC-directed movement of lytic granules was independent of actin and microtubule reorganization, dependent on dynein motor function, occurred before MTOC polarization, and did not require a commitment to cytotoxicity. This defines a novel paradigm for rapid MTOC-directed transport as a prerequisite for directed secretion, one that may prepare, but not commit cells for precision secretory function.
The Impact of Preferential Trade Arrangements on EU Imports from Developing Countries: The Case of Fresh Cut Flowers
Authors: Muhammad Andrew , Amponsah William A. , Dennis Jennifer H.
Published: May 2010

This study examines the effects that the Generalized System of Preferences schemes for developing countries (GSP + ) have on European Union (EU) demand for imported cut flowers. Without GSP + , a tariff would be applied to flowers from Colombia and Ecuador. Results show that Colombian carnation prices have a negative effect on EU flower expenditures, resulting in preferential treatment for Colombia being mostly trade‐creating. When a tariff is applied to Colombia, imports of Colombian carnations and Kenyan roses fell by 7.3% and 1.9%, respectively, and other flowers from Ecuador and Israel fell by 1.9% and 1.8%, respectively. Total EU flower imports fell by 1.4%.
Learning combinatorial transcriptional dynamics from gene expression data
Authors: Opper Manfred , Sanguinetti Guido
Published: May 2010

Motivation: mRNA transcriptional dynamics is governed by a complex network of transcription factor (TF) proteins. Experimental and theoretical analysis of this process is hindered by the fact that measurements of TF activity in vivo is very challenging. Current models that jointly infer TF activities and model parameters rely on either of the two main simplifying assumptions: either the dynamics is simplified (e.g. assuming quasi-steady state) or the interactions between TFs are ignored, resulting in models accounting for a single TF.

Results: We present a novel approach to reverse engineer the dynamics of multiple TFs jointly regulating the expression of a set of genes. The model relies on a continuous time, differential equation description of transcriptional dynamics where TFs are treated as latent on/off variables and are modelled using a switching stochastic process (telegraph process). The model can not only incorporate both activation and repression, but allows any non-trivial interaction between TFs, including AND and OR gates. By using a factorization assumption within a variational Bayesian treatment we formulate a framework that can reconstruct both the activity profiles of the TFs and the type of regulation from time series gene expression data. We demonstrate the identifiability of the model on a simple but non-trivial synthetic example, and then use it to formulate non-trivial predictions about transcriptional control during yeast metabolism.

Availability:  http://homepages.inf.ed.ac.uk/gsanguin/

Contact:  g.sanguinetti@ed.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
Protective Effect of Anthocyanins Extract from Blueberry on TNBS‐Induced IBD Model of Mice
Authors: Wu Lin-Hua , Xu Zeng-Lai , Dong Di , He Shan-An , Yu Hong
Published: May 2010

This study was carried out to evaluate the protective effect of anthocyanins extract of blueberry on trinitrobenzene sulfonic acid (TNBS)‐induced inflammatory bowel disease (IBD) model of mice. The study employed female C57BL/6 mice (n = 50), and colitis was induced by intracolonic injection of 0.5 mg of TNBS dissolved in 50% ethanol–phosphate buffered solution. The mice were divided into five groups (n = 10): vehicle, TNBS control and anthocyanins groups that received different doses of anthocyanins extract (10, 20 and 40 mg kg-1) daily for 6 days. Both increase in body weight and diarrhea symptoms were monitored each day. After 6 days, the animals were killed, and the following parameters were assessed: colon length, morphological score, histological score and biochemical assay (NO, myeloperoxidase (MPO), interleukin (IL)‐12, IL‐10, tumor necrosis factor (TNF)‐α and interferon (IFN)‐γ). The results showed that the anthocyanins extract of blueberry rendered strong protection against TNBS‐induced colonic damage at a dosage of 40 mg kg-1. When compared with the control, anthocyanins extract significantly prevented loss of body weight and ameliorated the scores of diarrhea, morphology and histology. Treatment with anthocyanins extract restored IL‐10 excretion, as well as caused reduction in the levels of NO, MPO, IL‐12, TNF‐α and IFN‐γ. Our research revealed the protective effect of anthocyanins extract from blueberry on TNBS‐induced experimental colitis in mice, as well as examined whether high levels of dietary blueberries would lower the risk or have protective effects on human IBD, which may require further investigation.
Jeremy Randall Knowles CBE. 28 April 1935 — 3 April 2008
Authors: Hansen David E. , Williams Robert J. P.
Published: May 2010

Jeremy Randall Knowles was remarkable both as a celebrated organic biochemist and as a wise administrator, and throughout his career he retained a lasting love of music and the arts. He was for several years a tutorial Fellow of Wadham College and a lecturer in chemistry at the University of Oxford, 1962–74. In 1974 he left Oxford permanently for Harvard University to become Professor of Chemistry; in 1979 he was named the Amory Houghton Professor of Chemistry and Biochemistry. To the surprise of many, he later gave up this chair to become the Dean of Harvard University's Faculty of Arts and Sciences, a post he held with great distinction from 1991 to 2002. He returned to Harvard's University Hall again as Interim Dean from 2006 to 2007.
Trisomy and triploidy are sources of embryo mortality in the zebra finch
Authors: Forstmeier Wolfgang , Ellegren Hans
Published: May 2010

Hatching failure is a surprisingly common phenomenon given that natural selection constantly works against it. In birds, an average of about 10 per cent of eggs across species fail to hatch, often owing to the death of embryos. While embryo mortality owing to inbreeding is both well-documented and evolutionarily plausible, this is not true for other sources of mortality. In fact, the basis for hatching failure in natural populations remains largely unexplained. Here, we demonstrate that embryo mortality in captive zebra finches (Taeniopygia guttata) follows from chromosomal aneuploidy or polyploidy. As part of microsatellite genotyping of a captive breeding population, we found 12 individuals (3.6%) with three alleles among 331 embryos that had died during development, while there were no such cases observed among 1210 adult birds. Subsequent genotyping of 1920 single nucleotide polymorphism markers distributed across the genome in birds with three alleles at microsatellite loci, and in greater than 1000 normal birds, revealed that the aberrant karyotypes involved cases of both trisomies and triploidy. Cases of both maternally and paternally inherited trisomies resulted from non-disjunction during meiosis. Maternally inherited cases of triploidy were attributable to failure of meiosis leading to diploid eggs, while paternally inherited triploidy could have arisen either from diploid sperm or from dispermy. Our initial microsatellite screening set only had the power to detect less than 10 per cent of trisomies and by extrapolation, our data therefore tentatively suggest that trisomy might be a major cause of embryo mortality in zebra finches.
Seasonal regulation of reproduction: altered role of melatonin under naturalistic conditions in hamsters
Authors: Butler Matthew P. , Turner Kevin W. , Park Jin Ho , Schoomer Elanor E. , Zucker Irving , Gorman Michael R.
Published: May 2010

The seasonal reproductive cycle of photoperiodic rodents is conceptualized as a series of discrete melatonin-dependent neuroendocrine transitions. Least understood is the springtime restoration of responsiveness to winter-like melatonin signals (breaking of refractoriness) that enables animals to once again respond appropriately to winter photoperiods the following year. This has been posited to require many weeks of long days based on studies employing static photoperiods instead of the annual pattern of continually changing photoperiods under which these mechanisms evolved. Maintaining Siberian hamsters under simulated natural photoperiods, we demonstrate that winter refractoriness is broken within six weeks after the spring equinox. We then test whether a history of natural photoperiod exposure can eliminate the requirement for long-day melatonin signalling. Hamsters pinealectomized at the spring equinox and challenged 10 weeks later with winter melatonin infusions exhibited gonadal regression, indicating that refractoriness was broken. A photostimulatory effect on body weight is first observed in the last four weeks of winter. Thus, the seasonal transition to the summer photosensitive phenotype is triggered prior to the equinox without exposure to long days and is thereafter melatonin-independent. Distinctions between photoperiodic and circannual seasonal organization erode with the incorporation in the laboratory of ecologically relevant day length conditions.
Submarine canyons: hotspots of benthic biomass and productivity in the deep sea
Authors: De Leo Fabio C. , Smith Craig R. , Rowden Ashley A. , Bowden David A. , Clark Malcolm R.
Published: May 2010

Submarine canyons are dramatic and widespread topographic features crossing continental and island margins in all oceans. Canyons can be sites of enhanced organic-matter flux and deposition through entrainment of coastal detrital export, dense shelf-water cascade, channelling of resuspended particulate material and focusing of sediment deposition. Despite their unusual ecological characteristics and global distribution along oceanic continental margins, only scattered information is available about the influence of submarine canyons on deep-sea ecosystem structure and productivity. Here, we show that deep-sea canyons such as the Kaikoura Canyon on the eastern New Zealand margin (42°01′ S, 173°03′ E) can sustain enormous biomasses of infaunal megabenthic invertebrates over large areas. Our reported biomass values are 100-fold higher than those previously reported for deep-sea (non-chemosynthetic) habitats below 500 m in the ocean. We also present evidence from deep-sea-towed camera images that areas in the canyon that have the extraordinary benthic biomass also harbour high abundances of macrourid (rattail) fishes likely to be feeding on the macro- and megabenthos. Bottom-trawl catch data also indicate that the Kaikoura Canyon has dramatically higher abundances of benthic-feeding fishes than adjacent slopes. Our results demonstrate that the Kaikoura Canyon is one of the most productive habitats described so far in the deep sea. A new global inventory suggests there are at least 660 submarine canyons worldwide, approximately 100 of which could be biomass hotspots similar to the Kaikoura Canyon. The importance of such deep-sea canyons as potential hotspots of production and commercial fisheries yields merits substantial further study.
Ecological factors driving the long-term evolution of influenza's host range
Authors: Cobey Sarah , Pascual Mercedes , Dieckmann Ulf
Published: May 2010

The evolution of a pathogen's host range is shaped by the ecology of its hosts and by the physiological traits that determine host specificity. For many pathogen traits, there is a trade-off: a phenotype suitable for infecting one set of hosts poorly infects another. Introducing and analysing a simple evo-epidemiological model, here we study how such a trade-off is expected to affect evolution of the host ranges of influenza viruses. We examine a quantitative trait underlying host specificity, given by an influenza virus's degree of adaptation to certain conformations of sialic acid receptors, and investigate how this receptor preference evolves in a minimal network of host species, including humans, that differ in life history and receptor physiology. Using adaptive dynamics theory, we establish thresholds in interspecific transmission rates and host population sizes that govern the emergence and persistence of human-adapted viruses. These ecological thresholds turn out to be largely independent of the strength of the evolutionary trade-off, underscoring the importance of ecological conditions in determining a disease's host range.
Spread of Q fever within dairy cattle herds: key parameters inferred using a Bayesian approach
Authors: Courcoul Aurélie , Vergu Elisabeta , Denis Jean-Baptiste , Beaudeau François
Published: May 2010

Q fever is a worldwide zoonosis caused by
Coxiella burnetii
. Although ruminants are recognized as the most important source of human infection, no previous studies have focused on assessing the characteristics of the bacterial spread within a cattle herd and no epidemic model has been proposed in this context. We assess the key epidemiological parameters from field data in a Bayesian framework that takes into account the available knowledge, missing data and the uncertainty of the observation process owing to the imperfection of diagnostic tests. We propose an original individual-based Markovian model in discrete time describing the evolution of the infection for each animal. Markov chain Monte Carlo methodology is used to estimate parameters of interest from data consisting of individual health states of 217 cows of five chronically infected dairy herds sampled every week for a four-week period. Outputs are the posterior distributions of the probabilities of transition between health states and of the environmental bacterial load. Our findings show that some herds are characterized by a very low infection risk while others have a mild infection risk and a non-negligible intermittent shedding probability. Moreover, the antibody status seems to be a key point in the bacterial spread (shedders with antibodies shed for a longer period of time than shedders without antibodies). In addition to the biological insights, these estimates also provide information for calibrating simulation models to assess control strategies for
C. burnetii
infection.
Rapid anti-pathogen response in ant societies relies on high genetic diversity
Authors: Ugelvig Line V. , Kronauer Daniel J. C. , Schrempf Alexandra , Heinze Jürgen , Cremer Sylvia
Published: May 2010

Social organisms are constantly exposed to infectious agents via physical contact with conspecifics. While previous work has shown that disease susceptibility at the individual and group level is influenced by genetic diversity within and between group members, it remains poorly understood how group-level resistance to pathogens relates directly to individual physiology, defence behaviour and social interactions. We investigated the effects of high versus low genetic diversity on both the individual and collective disease defences in the ant
Cardiocondyla obscurior
. We compared the antiseptic behaviours (grooming and hygienic behaviour) of workers from genetically homogeneous and diverse colonies after exposure of their brood to the entomopathogenic fungus
Metarhizium anisopliae
. While workers from diverse colonies performed intensive allogrooming and quickly removed larvae covered with live fungal spores from the nest, workers from homogeneous colonies only removed sick larvae late after infection. This difference was not caused by a reduced repertoire of antiseptic behaviours or a generally decreased brood care activity in ants from homogeneous colonies. Our data instead suggest that reduced genetic diversity compromises the ability of
Cardiocondyla
colonies to quickly detect or react to the presence of pathogenic fungal spores before an infection is established, thereby affecting the dynamics of social immunity in the colony.
ImmunoGrid: towards agent-based simulations of the human immune system at a natural scale
Authors: Halling-Brown Mark , Pappalardo Francesco , Rapin Nicolas , Zhang Ping , Alemani Davide , Emerson Andrew , Castiglione Filippo , Duroux Patrice , Pennisi Marzio , Miotto Olivo , Churchill Daniel , Rossi Elda , Moss David S. , Sansom Clare E. , Bernaschi Massimo , Lefranc Marie-Paule , Brunak Søren , Lund Ole , Motta Santo , Lollini Pier-Luigi , Murgo Annalisa , Palladini Arianna , Basford Kaye E. , Brusic Vladimir , Shepherd Adrian J.
Published: May 2010

The ultimate aim of the EU-funded ImmunoGrid project is to develop a natural-scale model of the human immune system—that is, one that reflects both the diversity and the relative proportions of the molecules and cells that comprise it—together with the grid infrastructure necessary to apply this model to specific applications in the field of immunology. These objectives present the ImmunoGrid Consortium with formidable challenges in terms of complexity of the immune system, our partial understanding about how the immune system works, the lack of reliable data and the scale of computational resources required.

In this paper, we explain the key challenges and the approaches adopted to overcome them. We also consider wider implications for the present ambitious plans to develop natural-scale, integrated models of the human body that can make contributions to personalized health care, such as the European Virtual Physiological Human initiative.

Finally, we ask a key question: How long will it take us to resolve these challenges and when can we expect to have fully functional models that will deliver health-care benefits in the form of personalized care solutions and improved disease prevention?
Prefrontal cortex lesions and sex differences in fear extinction and perseveration
Authors: Baran Sarah E. , Armstrong Charles E. , Niren Danielle C. , Conrad Cheryl D.
Published: May 2010

Electrolytic lesions of the medial prefrontal cortex (PFCX) were examined using fear conditioning to assess the recall of fear extinction and performance in the Y-maze, open field, and object location/recognition in male and female Sprague–Dawley rats. Rats were conditioned to seven tone/footshocks, followed by extinction after 1-h and 24-h delays, revealing PFCX effects and sex differences during all phases of fear conditioning. In male rats, PFCX impaired 24-h recall of fear extinction to tone, which required the 1-h delay extinction and was not attributed to nonassociative factors. In contrast, sham and PFCX females increased freezing to tone following a 24-h delay, whether or not 1-h delay tone extinction was presented. Moreover, PFCX females failed to extinguish to tone, contrasting to the robust extinction to tone that was observed for sham females, PFCX, and sham males. Also, sex differences were found during acquisition, with sham females acquiring fear conditioning slower than PFCX females. By the last tone-shock presentation, sham and PFCX females showed a slight but significant reduction in freezing to tone relative to those of sham and PFCX males. Of the other behavioral measures, PFCX females maintained exploration of a novel object during object recognition when sham females habituated. PFCX did not influence other behaviors in the remaining tasks. These findings show important sex differences in PFC function, with the PFC influencing the recall of fear extinction in males and contributing to the acquisition and maintenance of fear extinction memory in females, perhaps through altering perseveration.
Outcomes following early red blood cell transfusion in acute upper gastrointestinal bleeding
Authors: Hearnshaw S. A. , Logan R. F. A. , Palmer K. R. , Card T. R. , Travis S. P. L. , Murphy M. F.
Published: May 2010

Aliment Pharmacol Ther 2010; 32: 215–224

Background  Acute upper gastrointestinal bleeding (AUGIB) accounts for 14% of RBC units transfused in the UK. In exsanguinating AUGIB the value of RBC transfusion is self evident, but in less severe bleeding its value is less obvious.

Aim  To examine the relationship between early RBC transfusion, re‐bleeding and mortality following AUGIB, which is one of the most common indications for red blood cell (RBC) transfusion.

Method  Data were collected on 4441 AUGIB patients presenting to UK hospitals. The relationship between early RBC transfusion, re‐bleeding and death was examined using logistic regression.

Results  44% were transfused RBCs within 12 hours of admission. In patients transfused with an initial haemoglobin of <8 g/dl, re‐bleeding occurred in 23% and mortality was 13% compared with a re‐bleeding rate of 15%, and mortality of 13% in those not transfused. In patients transfused with haemoglobin >8 g/dl, re‐bleeding occurred in 24% and mortality was 11% compared with a re‐bleeding rate of 6.7%, and mortality of 4.3% in those not transfused. After adjusting for Rockall score and initial haemoglobin, early transfusion was associated with a two‐fold increased risk of re‐bleeding (Odds ratio 2.26, 95% CI 1.76–2.90) and a 28% increase in mortality (Odds ratio 1.28, 95% CI 0.94–1.74).

Conclusions  Early RBC transfusion in AUGIB was associated with a two‐fold increased risk of re‐bleeding and an increase in mortality, although the latter was not statistically significant. Although these findings could be due to residual confounding, they indicate that a randomized comparison of restrictive and liberal transfusion policies in AUGIB is urgently required.