bluuebunny/crossref_metadata_2025 huggingface dataset:
Simple genomes, complex interactions: Epistasis in RNA virus
Authors: Elena Santiago F. , Solé Ricard V. , Sardanyés Josep
Published: July 2010

Owed to their reduced size and low number of proteins encoded, RNA viruses and other subviral pathogens are often considered as being genetically too simple. However, this structural simplicity also creates the necessity for viral RNA sequences to encode for more than one protein and for proteins to carry out multiple functions, all together resulting in complex patterns of genetic interactions. In this work we will first review the experimental studies revealing that the architecture of viral genomes is dominated by antagonistic interactions among loci. Second, we will also review mathematical models and provide a description of computational tools for the study of RNA virus dynamics and evolution. As an application of these tools, we will finish this review article by analyzing a stochastic bit-string model of in silico virus replication. This model analyzes the interplay between epistasis and the mode of replication on determining the population load of deleterious mutations. The model suggests that, for a given mutation rate, the deleterious mutational load is always larger when epistasis is predominantly antagonistic than when synergism is the rule. However, the magnitude of this effect is larger if replication occurs geometrically than if it proceeds linearly.
A systems-biology approach to modular genetic complexity
Authors: Carter Gregory W. , Rush Cynthia G. , Uygun Filiz , Sakhanenko Nikita A. , Galas David J. , Galitski Timothy
Published: July 2010

Multiple high-throughput genetic interaction studies have provided substantial evidence of modularity in genetic interaction networks. However, the correspondence between these network modules and specific pathways of information flow is often ambiguous. Genetic interaction and molecular interaction analyses have not generated large-scale maps comprising multiple clearly delineated linear pathways. We seek to clarify the situation by discerning the difference between genetic modules and classical pathways. We review a method to optimize the discovery of biologically meaningful genetic modules based on a previously described context-dependent information measure to obtain maximally informative networks. We compare the results of this method with the established measures of network clustering and find that it balances global and local clustering information in networks. We further discuss the consequences for genetic interaction networks and propose a framework for the analysis of genetic modularity.
A battery-based, low-noise voltage source
Authors: Wagner Anke , Sturm Sven , Schabinger Birgit , Blaum Klaus , Quint Wolfgang
Published: July 2010

A highly stable, low-noise voltage source was designed to improve the stability of the electrode bias voltages of a Penning trap. To avoid excess noise and ground loops, the voltage source is completely independent of the public electric network and uses a 12 V car battery to generate output voltages of ±15 and ±5 V. First, the dc supply voltage is converted into ac-voltage and gets amplified. Afterwards, the signal is rectified, filtered, and regulated to the desired output value. Each channel can deliver up to 1.5 A. The current as well as the battery voltage and the output voltages can be read out via a universal serial bus (USB) connection for monitoring purposes. With the presented design, a relative voltage stability of 7×10−7 over 6.5 h and a noise level equal or smaller than 30 nV/Hz is achieved.
Efficient fabrication of wafer scale thin film of individualized single-walled carbon nanotubes by dual-nozzle spin casting
Authors: Kim Yong Shin , Kwon Soongeun , Shin Dong Hun , Shim Hyung Cheoul , Woo Ju Yeon , Lim Donghyun , Kwak Yoon Keun , Kim Soohyun , Han Chang-Soo
Published: July 2010

In this paper, a dual-nozzle spin casting method was proposed to form a thin film of individualized single-walled carbon nanotubes (SWNTs) at the wafer scale. Each nozzle simultaneously ejected the SWNT solution and methanol, respectively. During the ejection process, two solutions were mixed at the contacting end of the nozzles and then dropped onto the substrate. Functionalization of the wafer substrate with the amine group improved the uniformity of the SWNT thin film as well as the adhesion between the individualized SWNTs and the substrate. The best condition of the spin casting involved the substrate functionalization using 3-aminopropyltriethosilane aqueous solution with a concentration of ∼10 mM and a deposition velocity of ∼5000 rpm. The root-mean-square roughness of the fabricated SWNT layer over the wafer substrate was found to be 1.4–1.8 nm, which indicated that the resultant thin film was one or two layers of SWNTs. The wafer scale SWNT thin film formed by dual-nozzle spin casting can be further used for the mass production and high integration of the SWNT nanoelectronic devices.
Integrated energy and environmental systems analysis methodology for achieving low carbon cities
Authors: Bhatt Vatsal , Friley Paul , Lee John
Published: July 2010

Cities are responsible for nearly 75% of the world’s energy consumption; expectedly, about 90% of future growth will occur in urban areas. However, we consider that cities will be at the forefront of implementing groundbreaking technologies and policies, as evidenced in the initiatives taken by many cities here and worldwide to resolve issues in energy and climate change. In addition to affording energy and environmental benefits, investments in energy efficient and renewable technologies have huge potential to boost local economies, as demonstrated by the recent federal allocation of stimulus funding. Inclined to give priority to stopgap measures, many cities tend to regard comprehensive long-term planning as secondary. However, such solutions would bring multiple benefits to the community. The paper showcases an energy and environment systems model to provide a quantitative vision of technology and management strategy options for effectively deploying energy efficiency and renewable energy for reducing the carbon footprint, while sustainably maintaining the energy demands of the community and the servicing environmental infrastructure. We provide results of a case study completed for New York City, to showcase usefulness of long-term planning for achieving low carbon cities. Combined with appropriate stakeholder participation, such a technology explicit bottom-up approach holds the promise of influencing the current energy planning, environmental regulatory regime, including multimedia aspects of carbon control for cities locally and internationally.
Financing the transition to a low-carbon society
Authors: Glemarec Yannick
Published: July 2010

In the absence of a significant reduction in global emissions from current levels between now and 2050, global temperatures could rise by 4 °C, and possibly 6 °C by 2100. The world now has 100–150 months to dramatically change the world’s energy supply trajectory and limit temperature rise to a “safe” 2 °C. The sums involved in a shift to a low-carbon economy are daunting but not impossible to achieve. Global capital markets, representing $178 trillion in financial assets, have the size and depth to rise up to the investment challenge. Rather than a problem of capital generation, the key challenge of financing the transition toward a low-carbon society is to redirect existing and planned capital flows from traditional high- to low-carbon climate resilient investments. Over the past few years, the international community has developed a number of public- and market-based instruments to shift investments from fossil fuels to more climate-friendly alternatives. As a result, investments in the sustainable energy market have grown from $22 billion in 2002 to $155 billion in 2008. They could reach $400–500 billion by 2020. Unfortunately, only a limited number of developing countries are benefiting from these new financing opportunities, as their markets have up until now failed to attract green investments. Contrary to a widespread view that climate change negotiations and efforts should focus on the largest greenhouse gas emitting countries, this paper argues that a failure to provide fair access to climate finance to all developing countries would have severe political, financial, and climate change consequences. Developing the capacity of low income countries to create conditions that enable markets and private investment flows to address pressing environmental problems is a key priority to finance the transition toward a low-carbon society. This paper proposes a novel country-driven, multistakeholder climate finance framework to assist developing countries to scale-up efforts to address climate change. The framework is built on four mechanisms at the country level: formulation of low carbon, climate resilient strategies—to bring about bottom-up national ownership, incorporate human development goals, and take a long-term outlook; financial and technical support platforms—to catalyze capital from businesses and households; nationally appropriate mitigation action/national adaptation plan-type instruments—to bring about balanced access to international public finance; coordinated implementation and monitoring, reporting, and verification systems—to bring about long-term, efficient results.
Laboratory experiment shows that noise can be lessened for LISA
Authors: Miller Johanna
Published: July 2010

With a proposed spaceborne interferometer that dwarfs the Moon’s orbit, researchers hope to detect gravitational waves. To do that, they need to eliminate the noise from laser frequency fluctuations.
Watching a Bose–Einstein condensate crystallize
Authors: Wilson Mark
Published: July 2010

If the interaction between ultracold atoms and photons in an optical cavity is strong enough, it gives rise to an intriguing quantum phase transition.
Obama’s nuclear weapons agenda is on multiple rapid tracks
Authors: Kramer David
Published: July 2010

Nonproliferation moves to the top of the president’s priority list; a new arms treaty with Moscow, a summit on nuclear security, and a UN disarmament conference cap a nuclear spring.
Airport checkpoint technologies take off
Authors: Matthews Jermey N. A.
Published: July 2010

From bench-top instruments to full-body scanners, the US government is testing new equipment to screen humans for explosives.
Working toward a world without nuclear weapons
Authors: Drell Sidney D.
Published: July 2010

Limiting the number of warheads is a good beginning, but getting to the end state calls for new thinking. Six specific steps can start us down that path.
Filming vortex lines reconnecting in a turbulent superfluid
Authors: Schwarzschild Bertram
Published: July 2010

Tiny tracer particles of hydrogen ice attach themselves to quantized vortex lines in superfluid helium-4, making it possible to study quantum turbulence with unprecedented resolution.
Disrupted imprinting status at the H19 differentially methylated region is associated with the resorbed embryo phenotype in rats
Authors: Pathak Shilpa , Saxena Madhurima , D'Souza Ryan , Balasinor N. H.
Published: July 2010

Igf2, an imprinted gene that is paternally expressed in embryos, encodes an embryonic growth factor. An important regulator of Igf2 expression is methylation of the H19 differentially methylated region (DMR). A significant association has been observed between sperm methylation status at the H19 DMR and post-implantation loss. In addition, tamoxifen treatment has been shown to increase post-implantation loss and reduce DNA methylation at the H19 DMR in rat spermatozoa. Because this DMR is a primary DMR transmitting epigenetic imprint information from the gametes to the embryo, the aim of the present study was to determine the imprinting status of H19 DMR in post-implantation normal and resorbed embryos (F1) and to compare it with the H19 DMR in the spermatozoa of the respective sires. Analysis of the H19 DMR revealed methylation errors in resorbed embryo that were also observed in their sires' spermatozoa in the control and tamoxifen-treated groups. Expression analysis of the reciprocally imprinted genes Igf2 and H19 showed significant downregulation of Igf2 protein without any effect on H19 transcript levels in the resorbed embryos. The results indicate an association between disrupted imprinting status at the H19 DMR in resorbed embryos and the spermatozoa from their respective sires regardless of treatment, implying a common mechanism of resorption. The results demonstrate transmission of methylation errors at the Igf2–H19 locus through the paternal germline to the subsequent generation, emphasising the role of paternal factors during embryogenesis.
Zebrafish (Danio rerio) and the egg size versus egg number trade off: effects of ration size on fecundity are not mediated by orthologues of the Fec gene
Authors: Forbes Erin L. , Preston Craig D. , Lokman P. Mark
Published: July 2010

Few studies have demonstrated plasticity of egg size within the confines of an egg size–number trade-off in response to trophic conditions in fishes. Moreover, the physiological mechanisms that govern this plasticity are not known. Growth differentiation factor 9 (Gdf9) and bone morphogenetic factor 15 (Bmp15) are oocyte-specific factors implicated in follicular growth and ovulation in mammals. In order to investigate whether expression levels of these genes were correlated with ration-dependent changes in fecundity in fish, zebrafish (Danio rerio) were subjected to four different feeding regimens. Counts of spawned eggs or vitellogenic follicles were used to estimate fecundity, whereas quantitative polymerase chain reaction analyses were performed to determine Gdf9 and Bmp15 mRNA levels in response to changes in ration size. Both relative fecundity and gonadosomatic index increased significantly with increased ration size, whereas egg size and hatching rate decreased significantly. No significant differences in Gdf9 or Bmp15 transcript abundance were evident between feeding regimens, suggesting that these growth factors do not govern fecundity in fish. However, favourable trophic conditions markedly affected follicle or egg size and number, with important implications for downstream egg quality and survival.
Seminal plasma proteins inhibit in vitro- and cooling-induced capacitation in boar spermatozoa
Authors: Vadnais Melissa L. , Roberts Kenneth P.
Published: July 2010

Dilute boar seminal plasma (SP) has been shown to inhibit in vitro capacitation and cooling-induced capacitation-like changes in boar spermatozoa, as assessed by the ability of the spermatozoa to undergo an ionophore-induced acrosome reaction. We hypothesised that the protein component of SP is responsible for this effect. To test this hypothesis, varying concentrations of total SP protein or SP proteins fractionated by heparin binding were assayed for their ability to inhibit in vitro capacitation, as well as cooling- and cryopreservation-induced capacitation-like changes. In vitro capacitation and cooling-induced capacitation-like changes were prevented by 10% whole SP, as well as by total proteins extracted from SP at concentrations greater than 500 μg mL−1. No amount of SP protein was able to prevent cryopreservation-induced capacitation-like changes. Total SP proteins were fractionated based on their heparin-binding properties and the heparin-binding fraction was shown to possess capacitation inhibitory activity at concentrations as low as 250 µg mL−1. The proteins in the heparin-binding fraction were subjected to mass spectrometry and identified. The predominant proteins were three members of the spermadhesin families, namely AQN-3, AQN-1 and AWN, and SP protein pB1. We conclude that one or more of these heparin-binding SP proteins is able to inhibit in vitro capacitation and cooling-induced capacitation-like changes, but not cryopreservation-induced capacitation-like changes, in boar spermatozoa.
Stability of graph communities across time scales
Authors: Delvenne J.-C. , Yaliraki S. N. , Barahona M.
Published: July 2010

The complexity of biological, social, and engineering networks makes it desirable to find natural partitions into clusters (or communities) that can provide insight into the structure of the overall system and even act as simplified functional descriptions. Although methods for community detection abound, there is a lack of consensus on how to quantify and rank the quality of partitions. We introduce here the stability of a partition, a measure of its quality as a community structure based on the clustered autocovariance of a dynamic Markov process taking place on the network. Because the stability has an intrinsic dependence on time scales of the graph, it allows us to compare and rank partitions at each time and also to establish the time spans over which partitions are optimal. Hence the Markov time acts effectively as an intrinsic resolution parameter that establishes a hierarchy of increasingly coarser communities. Our dynamical definition provides a unifying framework for several standard partitioning measures: modularity and normalized cut size can be interpreted as one-step time measures, whereas Fiedler’s spectral clustering emerges at long times. We apply our method to characterize the relevance of partitions over time for constructive and real networks, including hierarchical graphs and social networks, and use it to obtain reduced descriptions for atomic-level protein structures over different time scales.
Structural basis for recognition of phosphodiester-containing lysosomal enzymes by the cation-independent mannose 6-phosphate receptor
Authors: Olson Linda J. , Peterson Francis C. , Castonguay Alicia , Bohnsack Richard N. , Kudo Mariko , Gotschall Russell R. , Canfield William M. , Volkman Brian F. , Dahms Nancy M.
Published: July 2010

Mannose 6-phosphate (Man-6-P)-dependent trafficking is vital for normal development. The biogenesis of lysosomes, a major cellular site of protein, carbohydrate, and lipid catabolism, depends on the 300-kDa cation-independent Man-6-P receptor (CI-MPR) that transports newly synthesized acid hydrolases from the Golgi. The CI-MPR recognizes lysosomal enzymes bearing the Man-6-P modification, which arises by the addition of GlcNAc-1-phosphate to mannose residues and subsequent removal of GlcNAc by the uncovering enzyme (UCE). The CI-MPR also recognizes lysosomal enzymes that elude UCE maturation and instead display the Man-P-GlcNAc phosphodiester. This ability of the CI-MPR to target phosphodiester-containing enzymes ensures lysosomal delivery when UCE activity is deficient. The extracellular region of the CI-MPR is comprised of 15 repetitive domains and contains three distinct Man-6-P binding sites located in domains 3, 5, and 9, with only domain 5 exhibiting a marked preference for phosphodiester-containing lysosomal enzymes. To determine how the CI-MPR recognizes phosphodiesters, the structure of domain 5 was determined by NMR spectroscopy. Although domain 5 contains only three of the four disulfide bonds found in the other seven domains whose structures have been determined to date, it adopts the same fold consisting of a flattened β-barrel. Structure determination of domain 5 bound to
N
-acetylglucosaminyl 6-phosphomethylmannoside, along with mutagenesis studies, revealed the residues involved in diester recognition, including Y679. These results show the mechanism by which the CI-MPR recognizes Man-P-GlcNAc-containing ligands and provides new avenues to investigate the role of phosphodiester-containing lysosomal enzymes in the biogenesis of lysosomes.
Fast transforms: Banded matrices with banded inverses
Authors: Strang Gilbert
Published: July 2010

It is unusual for both
A
and
A
-1
to be banded—but this can be a valuable property in applications. Block-diagonal matrices
F
are the simplest examples; wavelet transforms are more subtle. We show that every example can be factored into
A
 = 
F
1
…
F

N

where
N
is controlled by the bandwidths of
A
and
A
-1
(but not by their size, so this extends to infinite matrices and leads to new matrix groups).
CIVIL SOCIETY IN THE OLD AND NEW MEMBER STATES
Authors: Lane David
Published: July 2010

The paper examines the significance of ‘civil society’ promotion as a component of the new modes of governance proposed within the EU and its member states. The concept of civil society has had different meanings and roles in the evolution of the old and post-communist new EU members. ‘Civil society’ is analysed as a form of political coordination under capitalism; as a reform ideology in the process of opposition under communism; as a policy legitimising democratisation; and as an ideological component of neo-liberalism in the enlargement of the European Union. The paper proposes a model distinguishing the different roles played by ‘civil society’ discourse in the transformation of state socialism. In the post-state socialist societies a process of democracy promotion has included the sponsorship of civil society. Analysed empirically, significant differences are shown between the nature of civil society organisations in the old EU member states, new members and post socialist non-members. These data indicate the important changes which have taken place in the new member states. However, in the context of the post-socialist states, in which traditional forms of government have been weakened, there are significant structural weaknesses in civil society organisations. It is shown that there is a serious deficiency with respect to the efficacy of civil society associations as agents in the democratising process, as well as for the articulation and defence of community interests. It is argued that furthering ‘civil society’ forms of participation and management are a part of a neo-liberal economic and political agenda. It is concluded that strengthening democratic state forms of administration and coordination should be major policy concerns.
Decrease in Staphylococcus aureus Colonization and Hospital-Acquired Infection in a Medical Intensive Care Unit after Institution of an Active Surveillance and Decolonization Program
Authors: Fraser Thomas G. , Fatica Cynthia , Scarpelli Michele , Arroliga Alejandro C. , Guzman Jorge , Shrestha Nabin K. , Hixson Eric , Rosenblatt Miriam , Gordon Steven M. , Procop Gary W.
Published: July 2010

Objective.

To evaluate the effects of an active surveillance program for Staphylococcus aureus linked to a decolonization protocol on the incidence of healthcare-associated infection and new nasal colonization due to S. aureus.

Design.

Retrospective quasi-experimental study.

Setting.

An 18-bed medical intensive care unit at a tertiary care center in Cleveland, Ohio.

Methods.

From January 1, 2006, through December 31, 2007, all patients in the medical intensive care unit were screened for S. aureus nasal carriage at admission and weekly thereafter. During the preintervention period, January 1 through September 30,2006, only surveillance occurred. During the intervention period, January 1 through December 31,2007, S. aureus carriers received mupirocin intranasally. Beginning in February 2007, carriers also received Chlorhexidine gluconate baths.

Results.

During the preintervention period, 604 (73.7%) of 819 patients were screened for S. aureus nasal carriage, yielding 248 prevalent carriers (30.3%). During the intervention period, 752 (78.3%) of 960 patients were screened, yielding 276 carriers (28.8%). The incidence of S. aureus carriage decreased from 25 cases in 3,982 patient-days (6.28 cases per 1,000 patient-days) before intervention to 18 cases in 5,415 patient-days (3.32 cases per 1,000 patient-days) (P = .04; relative risk [RR], 0.53 [95% confidence interval {CI}, 0.28-0.97]) and from 9.57 to 4.77 cases per 1,000 at-risk patient-days (P = .02; RR, 0.50 [95% CI, 0.27-0.91]). The incidence of S. aureus hospital-acquired bloodstream infection during the 2 periods was 2.01 and 1.11 cases per 1,000 patient-days, respectively (P = .28). The incidence of S. aureus ventilator-associated pneumonia decreased from 1.51 to 0.18 cases per 1,000 patient-days (P = .03; RR, 0.12 [95% CI, 0.01-0.83]). The total incidence of S. aureus hospital-acquired infection decreased from 3.52 to 1.29 cases per 1,000 patient-days (P = .03; RR, 0.37 [95% CI, 0.14-0.90]).

Conclusions.

Active surveillance for S. aureus nasal carriage combined with decolonization was associated with a decreased incidence of S. aureus colonization and hospital-acquired infection.
MSMS: a coalescent simulation program including recombination, demographic structure and selection at a single locus
Authors: Ewing Gregory , Hermisson Joachim
Published: July 2010

Motivation: We have implemented a coalescent simulation program for a structured population with selection at a single diploid locus. The program includes the functionality of the simulator ms to model population structure and demography, but adds a model for deme- and time-dependent selection using forward simulations. The program can be used, e.g. to study hard and soft selective sweeps in structured populations or the genetic footprint of local adaptation. The implementation is designed to be easily extendable and widely deployable. The interface and output format are compatible with ms. Performance is comparable even with selection included.

Availability: The program is freely available from http://www.mabs.at/ewing/msms/ along with manuals and examples. The source is freely available under a GPL type license.

Contact:  gregory.ewing@univie.ac.at

Supplementary information:  Supplementary data are available at Bioinformatics online.
Clinical and Nutritional Outcomes in Children With Idiopathic Superior Mesenteric Artery Syndrome
Authors: Shiu Jr‐Rung , Chao Hsun‐Chin , Luo Chih‐Cheng , Lai Ming‐Wei , Kong Man‐Shan , Chen Shih‐Yen , Chen Chien‐Chang , Wang Chao‐Jan
Published: July 2010

Objective:

There are no available data for outcomes in children's idiopathic superior mesenteric artery syndrome (SMAS) strictly treated conservatively. The aim of the study was to evaluate clinical and nutritional outcome in children with idiopathic SMAS.

Patients and Methods:

A 1‐year prospective observation study of effects of treatment and outcome was performed in 27 children (8 boys, 19 girls) with idiopathic SMAS who underwent an upper gastrointestinal (UGI) series, ultrasound measurement of the aortomesenteric angle, treatment, clinical assessment, growth evaluation, and regular clinical visits for more than 12 months.

Results:

Mean age of the patients was 11.77 ± 2.15 years. The major clinical complaints were postprandial pain or fullness (88.9%), vomiting (55.6%), and early satiety (51.9%). Eight patients (29.6%) had weight loss. The UGI series revealed typical features of SMAS. The aortomesenteric angle on ultrasound was 10° to 19°. The height of most patients (92.6%) was above the 10th percentile, whereas 15 (55.6%) patients weighed below the 10th percentile. Six patients underwent surgical intervention (3 for obstruction and 3 for persistent anorexia with weight loss), and their clinical symptoms and weight status improved steadily during the follow‐up months. Among the 21 patients not subject to surgical intervention, 11 (52.4%) experienced a reduction of symptoms >50% after 3 months of treatment, and weight‐for‐age percentile increased significantly after 6 months of treatment. Overall, a significant increase in the weight‐for‐age status was seen in the patients with surgical treatment or with medication only after 6 and 12 months of treatment.

Conclusions:

An aortomesenteric angle <20° is a constant phenomenon in children with idiopathic SMAS. A duodenojejunostomy can effectively relieve the obstructive symptoms, such as anorexia, and improve nutritional status, whereas long‐term medical treatment may aid in relieving the clinical symptoms, promoting appetite, and improving nutritional status in pediatric patients with idiopathic SMAS.
Incidental Gastric Eosinophils in Patients With Eosinophilic Esophagitis: Do They Matter?
Authors: Ammoury Rana F , Rosenman Marc B , Roettcher Donita , Gupta Sandeep K
Published: July 2010

Background and Aim:

Some patients with eosinophilic esophagitis (EE) (>15 eosinophils/high‐power field on esophageal mucosal biopsies and lack of response to acid suppression and/or normal pH probe study) demonstrate incidental eosinophilic inflammation of the gastric mucosa. It is unclear whether patients with EE and normal gastric biopsies (EE‐N) are phenotypically different from patients with EE and gastric mucosal abnormalities (EE‐A) (ie, >10 eos/hpf on gastric biopsies). The aim of the study was to compare the clinical features and response to therapy among patients with EE‐N and EE‐A.

Patients and Methods:

Medical records of all of the EE‐A and a random group of patients with EE‐N diagnosed during an 8‐year period were reviewed. A subgroup analysis of patients treated with swallowed fluticasone with a repeat esophagogastroduodenoscopy within 6 months of starting therapy was also performed.

Results:

During the study period, 41 patients had EE‐A. When compared to 50 random patients with EE‐N, no clinical differences were noted, including sex, age, presenting symptoms, esophageal histology, and atopy history. Eleven (27%) of the 41 EE‐A and 14 (28%) of the 50 EE‐N patients were treated with swallowed fluticasone, and the response was similar among the groups. The mean esophageal eosinophils/high‐power field among the EE‐A group dropped from 47 to 8 compared with a 46 to 7 drop among the EE‐N group treated with fluticasone therapy (P = 0.91). In 9 (82%) of the 11 patients with EE‐A treated with fluticasone, there was resolution (7 of 9) or significant improvement (2 of 9) of gastric eosinophilia.

Conclusions:

Patients with EE‐A and EE‐N have similar clinical presentations. Incidental gastric inflammation does not predict a worse response of esophageal inflammation to fluticasone and should not exclude its use in patients with EE‐A. In fact, gastric inflammation responded to swallowed fluticasone in the majority of patients with EE‐A. This observation should foster further investigation into pathogenesis of EE and presumed esophagogastric inflammatory axis.
Correlated evolution of brain regions involved in producing and processing facial expressions in anthropoid primates
Authors: Dobson Seth D. , Sherwood Chet C.
Published: July 2010

Anthropoid primates are distinguished from other mammals by having relatively large primary visual cortices (V1) and complex facial expressions. We present a comparative test of the hypothesis that facial expression processing coevolved with the expansion of V1 in anthropoids. Previously published data were analysed using phylogenetic comparative methods. The results of our study suggest a pattern of correlated evolution linking social group size, facial motor control and cortical visual processing in catarrhines, but not platyrrhines. Catarrhines that live in relatively large social groups tended to have relatively large facial motor nuclei, and relatively large primary visual cortices. We conclude that catarrhine brains are adapted for producing and processing complex facial displays.
A comparative analysis of synthetic genetic oscillators
Authors: Purcell Oliver , Savery Nigel J. , Grierson Claire S. , di Bernardo Mario
Published: July 2010

Synthetic biology is a rapidly expanding discipline at the interface between engineering and biology. Much research in this area has focused on gene regulatory networks that function as biological switches and oscillators. Here we review the state of the art in the design and construction of oscillators, comparing the features of each of the main networks published to date, the models used for
in silico
design and validation and, where available, relevant experimental data. Trends are apparent in the ways that network topology constrains oscillator characteristics and dynamics. Also, noise and time delay within the network can both have constructive and destructive roles in generating oscillations, and stochastic coherence is commonplace. This review can be used to inform future work to design and implement new types of synthetic oscillators or to incorporate existing oscillators into new designs.
Towards a dynamical theory of observation
Authors: Jaroszkiewicz George
Published: July 2010

We introduce a model of classical and quantum observation based on contextuality and dynamically evolving apparatus. Power sets of classical bits model the four classical states of elementary detectors, viz. the two normal yes/no signal states, the faulty or decommissioned state and the non-existence state. Operators over power-set registers are used to describe various physical scenarios such as the construction and decommissioning of physical devices in otherwise empty laboratories, the dynamics of signal states over those detectors, the extraction of information from those states and multiple observers. We apply our quantum formalism to the Elitzur–Vaidman bomb-tester experiment and the Hardy paradox experiment.
Crust formation in drying colloidal suspensions
Authors: Style Robert W. , Peppin Stephen S. L.
Published: July 2010

During the drying of colloidal suspensions, the desiccation process causes the suspension near the air interface to consolidate into a connected porous matrix or crust. Fluid transport in the porous medium is governed by Darcy’s law and the equations of poroelasticity, while the equations of colloid physics govern processes in the suspension. We derive new equations describing this process, including unique boundary conditions coupling the two regions, yielding a moving-boundary model of the concentration and stress profiles during drying. A solution is found for the steady-state growth of a one-dimensional crust during constant evaporation rate from the surface. The solution is used to demonstrate the importance of the system boundary conditions on stress profiles and diffusivity in a drying crust.
Motion perception and visual signal design in
Anolis
lizards
Authors: Fleishman Leo J. , Pallus Adam C.
Published: July 2010

Anolis
lizards communicate with displays consisting of motion of the head and body. Early portions of long-distance displays require movements that are effective at eliciting the attention of potential receivers. We studied signal-motion efficacy using a two-dimensional visual-motion detection (2DMD) model consisting of a grid of correlation-type elementary motion detectors. This 2DMD model has been shown to accurately predict
Anolis
lizard behavioural response. We tested different patterns of artificially generated motion and found that an abrupt 0.3° shift of position in less than 100 ms is optimal. We quantified motion in displays of 25 individuals from five species. Four species employ near-optimal movement patterns. We tested displays of these species using the 2DMD model on scenes with and without moderate wind. Display movements can easily be detected, even in the presence of windblown vegetation. The fifth species does not typically use the most effective display movements and display movements cannot be discerned by the 2DMD model in the presence of windblown vegetation. A number of
Anolis
species use abrupt up-and-down head movements approximately 10 mm in amplitude in displays, and these movements appear to be extremely effective for stimulating the receiver visual system.
Hantavirus infections in fluctuating host populations: the role of maternal antibodies
Authors: Kallio Eva R. , Begon Michael , Henttonen Heikki , Koskela Esa , Mappes Tapio , Vaheri Antti , Vapalahti Olli
Published: July 2010

Infected females may transfer maternal antibodies (MatAbs) to their offspring, which may then be transiently protected against infections the mother has encountered. However, the role of maternal protection in infectious disease dynamics in wildlife has largely been neglected. Here, we investigate the effects of Puumala hantavirus (PUUV)-specific MatAbs on PUUV dynamics, using 7 years' data from a cyclic bank vole population in Finland. For the first time to our knowledge, we partition seropositivity data from a natural population into separate dynamic patterns for MatAbs and infection. The likelihood of young of the year carrying PUUV-specific MatAbs during the breeding season correlated positively with infection prevalence in the overwintered parent population in the preceding spring. The probability of PUUV infection varied between seasons (highest in spring, lowest in late summer) and depended on population structure, but was also, in late autumn, notably, negatively related to summer MatAb prevalence, as well as to infection prevalence earlier in the breeding season. Hence, our results suggest that high infection prevalence in the early breeding season leads to a high proportion of transiently immune young individuals, which causes delays in transmission. This suggests, in turn, that MatAb protection has the potential to affect infection dynamics in natural populations.
Kin competition, natal dispersal and the moulding of senescence by natural selection
Authors: Ronce Ophélie , Promislow Daniel
Published: July 2010

Most theoretical models for the evolution of senescence have assumed a very large, well mixed population. Here, we investigate how limited dispersal and kin competition might influence the evolution of ageing by deriving indicators of the force of selection, similar to Hamilton (Hamilton 1966J. Theor. Biol.12, 12–45). Our analytical model describes how the strength of selection on survival and fecundity changes with age in a patchy population, where adults are territorial and a fraction of juveniles disperse between territories. Both parent–offspring competition and sib competition then affect selection on age-specific life-history traits. Kin competition reduces the strength of selection on survival. Mutations increasing mortality in some age classes can even be favoured by selection, but only when fecundity deteriorates rapidly with age. Population structure arising from limited dispersal however selects for a broader distribution of reproduction over the lifetime, potentially slowing down reproductive senescence. The antagonistic effects of limited dispersal on age schedules of fecundity and mortality cast doubts on the generality of conditions allowing the evolution of ‘suicide genes’ that increase mortality rates without other direct pleiotropic effects. More generally, our model illustrates how limited dispersal and social interactions can indirectly produce patterns of antagonistic pleiotropy affecting vital rates at different ages.
Gene copy-number polymorphism in nature
Authors: Schrider Daniel R. , Hahn Matthew W.
Published: July 2010

Differences between individuals in the copy-number of whole genes have been found in every multicellular species examined thus far. Such differences result in unique complements of protein-coding genes in all individuals, and have been shown to underlie adaptive phenotypic differences. Here, we review the evidence for copy-number variants (CNVs), focusing on the methods used to detect them and the molecular mechanisms responsible for generating this type of variation. Although there are multiple technical and computational challenges inherent to these experimental methods, next-generation sequencing technologies are making such experiments accessible in any system with a sequenced genome. We further discuss the connection between copy-number variation within species and copy-number divergence between species, showing that these values are exactly what one would expect from similar comparisons of nucleotide polymorphism and divergence. We conclude by reviewing the growing body of evidence for natural selection on copy-number variants. While it appears that most genic CNVs—especially deletions—are quickly eliminated by selection, there are now multiple studies demonstrating a strong link between copy-number differences at specific genes and phenotypic differences in adaptive traits. We argue that a complete understanding of the molecular basis for adaptive natural selection necessarily includes the study of copy-number variation.
The Prp19 complex and the Usp4Sart3 deubiquitinating enzyme control reversible ubiquitination at the spliceosome
Authors: Song Eun Joo , Werner Shannon L. , Neubauer Jakob , Stegmeier Frank , Aspden Julie , Rio Donald , Harper J. Wade , Elledge Stephen J. , Kirschner Marc W. , Rape Michael
Published: July 2010

The spliceosome, a dynamic assembly of proteins and RNAs, catalyzes the excision of intron sequences from nascent mRNAs. Recent work has suggested that the activity and composition of the spliceosome are regulated by ubiquitination, but the underlying mechanisms have not been elucidated. Here, we report that the spliceosomal Prp19 complex modifies Prp3, a component of the U4 snRNP, with nonproteolytic K63-linked ubiquitin chains. The K63-linked chains increase the affinity of Prp3 for the U5 snRNP component Prp8, thereby allowing for the stabilization of the U4/U6.U5 snRNP. Prp3 is deubiquitinated by Usp4 and its substrate targeting factor, the U4/U6 recycling protein Sart3, which likely facilitates ejection of U4 proteins from the spliceosome during maturation of its active site. Loss of Usp4 in cells interferes with the accumulation of correctly spliced mRNAs, including those for α-tubulin and Bub1, and impairs cell cycle progression. We propose that the reversible ubiquitination of spliceosomal proteins, such as Prp3, guides rearrangements in the composition of the spliceosome at distinct steps of the splicing reaction.
p53 loss promotes acute myeloid leukemia by enabling aberrant self-renewal
Authors: Zhao Zhen , Zuber Johannes , Diaz-Flores Ernesto , Lintault Laura , Kogan Scott C. , Shannon Kevin , Lowe Scott W.
Published: July 2010

The p53 tumor suppressor limits proliferation in response to cellular stress through several mechanisms. Here, we test whether the recently described ability of p53 to limit stem cell self-renewal suppresses tumorigenesis in acute myeloid leukemia (AML), an aggressive cancer in which p53 mutations are associated with drug resistance and adverse outcome. Our approach combined mosaic mouse models, Cre-lox technology, and in vivo RNAi to disable p53 and simultaneously activate endogenous KrasG12D—a common AML lesion that promotes proliferation but not self-renewal. We show that p53 inactivation strongly cooperates with oncogenic KrasG12D to induce aggressive AML, while both lesions on their own induce T-cell malignancies with long latency. This synergy is based on a pivotal role of p53 in limiting aberrant self-renewal of myeloid progenitor cells, such that loss of p53 counters the deleterious effects of oncogenic Kras on these cells and enables them to self-renew indefinitely. Consequently, myeloid progenitor cells expressing oncogenic Kras and lacking p53 become leukemia-initiating cells, resembling cancer stem cells capable of maintaining AML in vivo. Our results establish an efficient new strategy for interrogating oncogene cooperation, and provide strong evidence that the ability of p53 to limit aberrant self-renewal contributes to its tumor suppressor activity.
Effect of juvenile pretraining on adolescent structural hippocampal attributes as a substrate for enhanced spatial performance
Authors: Keeley Robin J. , Wartman Brianne C. , Häusler Alexander N. , Holahan Matthew R.
Published: July 2010

Research has demonstrated that Long–Evans rats (LER) display superior mnemonic function over Wistar rats (WR). These differences are correlated with endogenous and input-dependent properties of the hippocampus. The present work sought to determine if juvenile pretraining might enhance hippocampal structural markers and if this would be associated with spatial processing improvements. Male and female WR and LER were either handled or trained on a water maze task from postnatal day 16 (p16) to p26 (pretraining). All animals were then trained on the task from p40 to p44 followed by immunohistochemical assessment of synaptophysin (to mark presynaptic terminals), MAP-2 (to mark dendrites), and the phosphorylated (activated) form of the extracellular signal-regulated kinase-1 (pERK1) in the hippocampus. From p19 to p20, LER (both male and female) showed a dramatic improvement in locating the hidden platform compared to their WR counterparts. On the first day of training at p40, all pretrained groups showed shorter latencies to locate the platform compared to groups without pretraining. Over the next 4 d, only pretrained male LER showed enhanced memory. Immunohistochemical analysis revealed fewer pERK1-labeled neurons in the CA3 hippocampal region in all pretrained groups and fewer pERK1-labeled neurons in the CA1 region of pretrained male LER. Pretrained male LER also showed more MAP-2 staining in CA1 and dentate gyrus regions. Synaptophysin staining revealed a pattern of axonal redistribution in the CA3 region in the pretrained groups. Results suggest a pattern of structural hippocampal alterations that may help to identify network malleability following pretraining protocols.
Thawing Embryonic Stem (ES) Cells from a 96-Well Plate
Authors: Nagy Andras , Gertsenstein Marina , Vintersten Kristina , Behringer Richard
Published: July 2010

INTRODUCTION

The most widely used method to alter the genome of embryonic stem (ES) cells is to introduce a specifically designed DNA fragment using electroporation. The DNA will then integrate into the genome of ES cells. Colonies of cells containing the exogenous DNA are then picked, expanded, replica-plated, frozen in 96-well plates, and used as a source for genomic DNA preparation for genotyping. After ES candidate clones are identified by genomic Southern blot or polymerase chain reaction (PCR), the method of rescue of the cells from the frozen 96-well plates is very important. This protocol describes a method for thawing such cells.
Purification of Mediator from HeLa Cell Lines Expressing a Flag-Tagged Mediator Subunit
Authors: Carey Michael F. , Peterson Craig L. , Smale Stephen T.
Published: July 2010

INTRODUCTION

The Mediator (Med) complex plays a key role in promoter-specific activation of transcription by RNA polymerase II (Pol II). Med is a major target of activators and can be used in many types of affinity binding and immobilized template studies to evaluate interactions with individual activators. Additionally, all of the Med subunits have been cloned and can be subjected to individual structure-function analyses to learn how a specific activator interacts with a particular subunit. This protocol presents a simple affinity-based method to purify Med complex from HeLa cells stably expressing the Flag-tagged Intersex protein.
In Vivo Imaging of Tumors
Authors: Brown Edward , Munn Lance L. , Fukumura Dai , Jain Rakesh K.
Published: July 2010

INTRODUCTION

Light microscopy of tumors, as for other thick, scattering tissues such as the brain or the developing embryo, is limited by light penetration and optical access. because of these problems, epifluorescence and confocal microscopy are typically limited to the outer 50-100 μm of the accessible tumor tissue. Most mouse tumors must be exteriorized for examination under the light microscope, a procedure that limits the duration and repeatability of imaging. this protocol describes the generation of chronic window preparations in the mouse. These preparations allow an implanted tumor to grow for several weeks in an optically accessible location in vivo, making it possible to examine the living tumor with high-resolution light microscopy in a repetitive manner. Two chronic window preparations are described: (1) the dorsal skinfold chamber, which allows in vivo imaging of tumors growing in the subcutaneous space, and (2) the cranial window, which allows in vivo imaging of tumors growing on the brain surface.