bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of low-level culling of feral cats in open populations: a case study from the forests of southern Tasmania
Authors: Lazenby Billie T. , Mooney Nicholas J. , Dickman Christopher R.
Published: February 2015

Context
Feral cats (Felis catus) threaten biodiversity in many parts of the world, including Australia. Low-level culling is often used to reduce their impact, but in open cat populations the effectiveness of culling is uncertain. This is partly because options for assessing this management action have been restricted to estimating cat activity rather than abundance.

Aims
We measured the response, including relative abundance, of feral cats to a 13-month pulse of low-level culling in two open sites in southern Tasmania.

Methods
To do this we used remote cameras and our analysis included identification of individual feral cats. We compared estimates of relative abundance obtained via capture–mark–recapture and minimum numbers known to be alive, and estimates of activity obtained using probability of detection and general index methods, pre- and post-culling. We also compared trends in cat activity and abundance over the same time period at two further sites where culling was not conducted.

Key results
Contrary to expectation, the relative abundance and activity of feral cats increased in the cull-sites, even though the numbers of cats captured per unit effort during the culling period declined. Increases in minimum numbers of cats known to be alive ranged from 75% to 211% during the culling period, compared with pre- and post-cull estimates, and probably occurred due to influxes of new individuals after dominant resident cats were removed.

Conclusions
Our results showed that low-level ad hoc culling of feral cats can have unwanted and unexpected outcomes, and confirmed the importance of monitoring if such management actions are implemented.

Implications
If culling is used to reduce cat impacts in open populations, it should be as part of a multi-faceted approach and may need to be strategic, systematic and ongoing if it is to be effective.
Effects of fast‐velocity eccentric resistance training on early and late rate of force development
Authors: Oliveira Anderson Souza , Corvino Rogério Bulhões , Caputo Fabrizio , Aagaard Per , Denadai Benedito Sérgio
Published: February 2015

This study examined whether short‐term maximal resistance training employing fast‐velocity eccentric knee extensor actions would induce improvements in maximal isometric torque and rate of force development (RFD) at early (<100 ms) and late phases (>100 ms) of rising torque. Twenty healthy men were assigned to two experimental groups: eccentric resistance training (TG) or control (CG). Participants on the TG trained three days a week for a total of eight weeks. Training consisted of maximal unilateral eccentric knee extensors actions performed at 180°s‐1. Maximal isometric knee extensor torque (MVC) and incremental RFD in successive 50 ms time‐windows from the onset contraction were analysed in absolute terms (RFDINC) or when normalised relative to MVC (RFDREL). After eight weeks, TG demonstrated increases in MVC (28%), RFDINC (0–50 ms: 30%; 50–100 ms: 31%) and RFDREL (0–50 ms: 29%; 50–100 ms: 32%). Moreover, no changes in the late phase of incremental RFD were observed in TG. No changes were found in the CG. In summary, we have demonstrated, in active individuals, that a short period of resistance training performed with eccentric fast‐velocity isokinetic muscle contractions is able to enhance RFDINC and RFDREL obtained at the early phase of rising joint torque.
Measuring the Political Salience of Supreme Court Cases
Authors: Clark Tom S. , Lax Jeffrey R. , Rice Douglas
Published: February 2015

While Supreme Court cases are generally salient or important, some are many degrees more important than others. A wide range of theoretical and empirical work throughout the study of judicial politics implicates this varying salience. Some work considers salience a variable to be explained, perhaps with judicial behavior the explanatory factor. The currently dominant measure of salience is the existence of newspaper coverage of a decision, but decisions themselves are an act of judicial politics. Because this coverage measure is affected only after a decision is announced, using it limits the types of inferences we can draw about salience. We develop a measure of latent salience, one that builds on existing work, but that also explicitly incorporates and models predecision information. This measure has the potential to ameliorate concerns of causal inference, put research findings on sounder footing, and add to our understanding of judicial behavior.
Understanding Judicial Power
Authors: Hall Matthew E. K. , Windett Jason Harold
Published: February 2015

High courts are widely believed to influence the criminal justice system, yet judicial impact varies widely across political and institutional contexts. Here, we seek to identify the factors that constrain judicial influence on state incarceration rates. We find that the preferences of justices on state courts of last resort and the US Supreme Court influence incarceration; however, high-court impact is conditional on two factors. Judicial influence is stronger in states with divided partisan governments and occurs more quickly in states that lack intermediate appellate courts. Our findings suggest that legislative gridlock and institutional thickness significantly constrain judicial impact.
The Role of Wall Shear Stress in the Assessment of Right Ventricle Hydraulic Workload
Authors: Kheyfets Vitaly , Thirugnanasambandam Mirunalini , Rios Lourdes , Evans Daniel , Smith Triston , Schroeder Theodore , Mueller Jeffrey , Murali Srinivas , Lasorda David , Spotti Jennifer , Finol Ender
Published: February 2015

Pulmonary hypertension (PH) is a devastating disease affecting approximately 15–50 people per million, with a higher incidence in women. PH mortality is mostly attributed to right ventricle (RV) failure, which results from RV hypotrophy due to an overburdened hydraulic workload. The objective of this study is to correlate wall shear stress (WSS) with hemodynamic metrics that are generally accepted as clinical indicators of RV workload and are well correlated with disease outcome. Retrospective right heart catheterization data for 20 PH patients were analyzed to derive pulmonary vascular resistance (PVR), arterial compliance (C), and an index of wave reflections (Γ). Patient‐specific contrast‐enhanced computed tomography chest images were used to reconstruct the individual pulmonary arterial trees up to the seventh generation. Computational fluid dynamics analyses simulating blood flow at peak systole were conducted for each vascular model to calculate WSS distributions on the endothelial surface of the pulmonary arteries. WSS was found to be decreased proportionally with elevated PVR and reduced C. Spatially averaged WSS (SAWSS) was positively correlated with PVR (R2 = 0.66), C (R2 = 0.73), and Γ (R2 = 0.5) and also showed promising preliminary correlations with RV geometric characteristics. Evaluating WSS at random cross sections in the proximal vasculature (main, right, and left pulmonary arteries), the type of data that can be acquired from phase‐contrast magnetic resonance imaging, did not reveal the same correlations. In conclusion, we found that WSS has the potential to be a viable and clinically useful noninvasive metric of PH disease progression and RV health. Future work should be focused on evaluating whether SAWSS has prognostic value in the management of PH and whether it can be used as a rapid reactivity assessment tool, which would aid in selection of appropriate therapies.
Radiation fields for semilinear wave equations
Authors: Baskin Dean , Sá Barreto Antônio
Published: February 2015

We define the radiation fields of solutions to critical semilinear wave equations in

R

3

\mathbb {R}^3

and use them to define the scattering operator. We also prove a support theorem for the radiation fields with radial initial data. This extends the well-known support theorem for the Radon transform to this setting and can also be interpreted as a Paley-Wiener theorem for the distorted nonlinear Fourier transform of radial functions.
Isoperimetric inequalities in Euclidean convex bodies
Authors: Ritoré Manuel , Vernadakis Efstratios
Published: February 2015

In this paper we consider the problem of minimizing the relative perimeter under a volume constraint in the interior of a convex body, i.e., a compact convex set in Euclidean space with interior points. We shall not impose any regularity assumption on the boundary of the convex set. Amongst other results, we shall prove that Hausdorff convergence in the space of convex bodies implies Lipschitz convergence, the continuity of the isoperimetric profile with respect to the Hausdorff distance, and the convergence in Hausdorff distance of sequences of isoperimetric regions and their free boundaries. We shall also describe the behavior of the isoperimetric profile for small volume and the behavior of isoperimetric regions for small volume.
DrosophilaCLIP-190 and mammalian CLIP-170 display reduced microtubule plus end association in the nervous system
Authors: Beaven Robin , Dzhindzhev Nikola S. , Qu Yue , Hahn Ines , Dajas-Bailador Federico , Ohkura Hiroyuki , Prokop Andreas
Published: February 2015

Axons act like cables, electrically wiring the nervous system. Polar bundles of microtubules (MTs) form their backbones and drive their growth. Plus end–tracking proteins (+TIPs) regulate MT growth dynamics and directionality at their plus ends. However, current knowledge about +TIP functions, mostly derived from work in vitro and in nonneuronal cells, may not necessarily apply to the very different context of axonal MTs. For example, the CLIP family of +TIPs are known MT polymerization promoters in nonneuronal cells. However, we show here that neither Drosophila CLIP-190 nor mammalian CLIP-170 is a prominent MT plus end tracker in neurons, which we propose is due to low plus end affinity of the CAP-Gly domain–containing N-terminus and intramolecular inhibition through the C-terminus. Instead, both CLIP-190 and CLIP-170 form F-actin–dependent patches in growth cones, mediated by binding of the coiled-coil domain to myosin-VI. Because our loss-of-function analyses in vivo and in culture failed to reveal axonal roles for CLIP-190, even in double-mutant combinations with four other +TIPs, we propose that CLIP-190 and -170 are not essential axon extension regulators. Our findings demonstrate that +TIP functions known from nonneuronal cells do not necessarily apply to the regulation of the very distinct MT networks in axons.
Control of lipid organization and actin assembly during clathrin-mediated endocytosis by the cytoplasmic tail of the rhomboid protein Rbd2
Authors: Cortesio Christa L. , Lewellyn Eric B. , Drubin David G.
Published: February 2015

Clathrin-mediated endocytosis (CME) is facilitated by a precisely regulated burst of actin assembly. PtdIns(4,5)P2 is an important signaling lipid with conserved roles in CME and actin assembly regulation. Rhomboid family multipass transmembrane proteins regulate diverse cellular processes; however, rhomboid-mediated CME regulation has not been described. We report that yeast lacking the rhomboid protein Rbd2 exhibit accelerated endocytic-site dynamics and premature actin assembly during CME through a PtdIns(4,5)P2-dependent mechanism. Combined genetic and biochemical studies showed that the cytoplasmic tail of Rbd2 binds directly to PtdIns(4,5)P2 and is sufficient for Rbd2's role in actin regulation. Analysis of an Rbd2 mutant with diminished PtdIns(4,5)P2-binding capacity indicates that this interaction is necessary for the temporal regulation of actin assembly during CME. The cytoplasmic tail of Rbd2 appears to modulate PtdIns(4,5)P2 distribution on the cell cortex. The syndapin-like F-BAR protein Bzz1 functions in a pathway with Rbd2 to control the timing of type 1 myosin recruitment and actin polymerization onset during CME. This work reveals that the previously unstudied rhomboid protein Rbd2 functions in vivo at the nexus of three highly conserved processes: lipid regulation, endocytic regulation, and cytoskeletal function.
Characteristics and Prognosis of Allergic Proctocolitis in Infants
Authors: Kaya Aysenur , Toyran Muge , Civelek Ersoy , Misirlioglu Emine , Kirsaclioglu Ceyda , Kocabas Can N.
Published: February 2015

Objectives:

The dietary protein proctocolitis, also known as allergic proctocolitis (AP), is characterized by the presence of mucoid, frothy, and bloody stools in an otherwise healthy infant. The aim of this study was to describe a group of children with AP, diagnosed according to the criterion‐standard method, food challenge to provide clinicians with more information on typical presentation, and an overview on nutritional management strategies and prognosis.

Methods:

We collected data on infants with AP in our allergy and gastroenterology outpatient clinics. Any other conditions that may cause bloody diarrhea were ruled out. Skin prick tests and atopy patch tests were performed for diagnosis, and patients were studied for resolution. To the patients whose rectal bleeding did not recover with oligoantigenic maternal diet in addition to amino acid–based formula, endoscopic evaluation was performed to confirm the diagnosis and to exclude other reasons of rectal bleeding.

Results:

Sixty patients were diagnosed as having AP. The age of onset was 1.7 ± 1.32 months. All of the patients were triggered by milk, 6.6% with milk and egg, 3.3% with milk and chicken, 1.7% with milk and wheat, 1.7% with milk and potato, and 3.3% had multiple food allergy. 53.3% (n = 32) acquired tolerance by age 1, 25.0% (n = 15) by 2 years, 5% (n = 3) by 3, and 1.7% (n = 1) by 4 years.

Conclusions:

Milk was a triggering factor for all of the patients. Resolution of AP is usually within 1 year but symptoms of some patients may continue even longer. An extension of the follow‐up period is required according to our study.
Knowledge and Practices of Pediatricians Regarding Functional Constipation in the State of Minas Gerais, Brazil
Authors: Torres Marcia R.F. , de Melo Maria do Carmo B. , Purcino Flávia A.C. , Maia Joana C. , Aliani Natália A. , Rocha Henrique C.
Published: February 2015

Objectives:

The aim of the study was to analyze the knowledge, approaches, and practices of pediatricians participating in a regional pediatric conference regarding functional constipation (FC) to identify knowledge gaps.

Methods:

Cross‐sectional regional study based on a semistructured questionnaire related to the Rome III criteria and the participant profiles.

Results:

Of 400 questionnaires distributed, 264 (66.0%) were completed. Most pediatricians (76.7%) did not recognize the Rome III criteria, but the majority did recognize the following risk factors for FC: low‐fiber diet (97.8%), family history (86.6%), onset of toilet training (76.4%), and weaning (62.4%). Foods considered high in fiber were oats (95.7%), leafy vegetables (95.3%), and wheat bran (93.2%). Digital rectal examination was not performed by 57.7% of nongastroenterologists. Complementary examinations were ordered in 27.5% and 72.5% of patients by general pediatricians and pediatric gastroenterologists, respectively, although the sample of gastroenterologists was not representative. The most prescribed drugs by nongastroenterologists were mineral oil (72.6%), magnesium hydroxide (52.1%), lactulose (41.0%), and polyethylene glycol (25.2%). Pediatric gastroenterologists prescribed magnesium hydroxide (91.7%), polyethylene glycol (91.7%), and mineral oil (58.3%). Most pediatricians (70.0%) considered the average treatment duration to be less than 1 year, although gastroenterologists considered it to be more than 1 year (54.6%).

Conclusions:

The knowledge of pediatricians regarding FC is inadequate. Constipation may not receive the public health attention it deserves within pediatric residency programs. The authors suggest that better education regarding FC should be included in medical school and residency program curricula to improve patient care.
Aortic Intima‐Media Thickness as an Early Marker of Atherosclerosis in Children With Inflammatory Bowel Disease
Authors: Aloi Marina , Tromba Luciana , Rizzo Valentina , D'Arcangelo Giulia , Dilillo Anna , Blasi Sara , Civitelli Fortunata , Kiltzanidi Dimitra , Redler Adriano , Viola Franca
Published: February 2015

Objectives:

The aims of this study were to determine the presence of endothelial dysfunction by measuring aortic intima‐media thickness (aIMT) and carotid intima‐media thickness (cIMT) and to evaluate the role of traditional risk factors for premature atherosclerosis in children with inflammatory bowel disease (IBD).

Methods:

Thirty‐four children with IBD (25 Crohn disease [CD] and 9 ulcerative colitis [UC]; mean age 11.1 years) and 27 healthy subjects matched for sex and age were enrolled. In all of the patients, demographic characteristics and risk factors for atherosclerosis (age, sex, body mass index, blood pressure, dyslipidemia, active and passive smoking, and family history for cardiovascular diseases), CD and UC clinical activity scores, and inflammatory markers were evaluated. aIMT and cIMT were measured by high‐resolution B‐mode ultrasound.

Results:

aIMT was significantly higher in patients than in controls (P < 0.0005). No significant differences were found for cIMT, although the carotid thickness was higher in patients with IBD than in healthy subjects. At a univariate analysis, inflammatory markers levels and tobacco smoking exposure were significantly related to higher aIMT values, whereas in a multivariate regression model, the inflammatory status was the only independent variable correlated with high aIMT.

Conclusions:

aIMT is an earlier marker of preclinical atherosclerosis than cIMT in young children with active IBD. The inflammatory status and the smoking exposure are significantly correlated with the premature endothelial dysfunction. These data emphasize the importance of controlling the chronic intestinal inflammation and endorsing smoke‐free environments for children and adolescents with IBD.
Primary Care Follow-up After Emergency Department Visits for Routine Complaints
Authors: Chen Jessica , Singer Eric
Published: February 2015

Objectives

Given that the vast majority of pediatric patients that present to the emergency department (ED) are discharged home after their visit, one issue for study is the appropriate recommendations for follow-up after the ED visit. Numerous PubMed searches using various keywords revealed a gap in the literature regarding the desires of primary care physicians (PCPs) concerning follow-up after ED visits. This study was conducted to determine how pediatric emergency medicine (PEM) physicians' recommendations for follow-up align with the desires of (PCPs) for follow-up after ED visits.

Methods

An electronic survey was distributed to pediatric emergency physicians at one community-based academic institution regarding current recommendations for follow-up with PCPs for 12 common diagnoses seen in the ED. A similar survey was sent to pediatricians in the same community inquiring about their desires for follow-up after their patients are seen in the ED for the same diagnoses.

Results

Completion rates for the survey were 40/40 (100%) for PEM physicians and 78/145 (54%) for pediatricians. In 11/12 of the diagnoses included, PEM physicians recommended a statistically significant (P < 0.05) closer follow-up than desired by the PCPs.

Conclusions

Recommendations for follow-up made by PEM physicians and desired by PCPs vary significantly. Overall, PEM physicians recommend closer follow-up than desired by PCPs for low acuity complaints. Closing of this gap may allow for a better allocation of resources and consistency of care.
Extreme strength observed in limpet teeth
Authors: Barber Asa H. , Lu Dun , Pugno Nicola M.
Published: February 2015

The teeth of limpets exploit distinctive composite nanostructures consisting of high volume fractions of reinforcing goethite nanofibres within a softer protein phase to provide mechanical integrity when rasping over rock surfaces during feeding. The tensile strength of discrete volumes of limpet tooth material measured usingin situatomic force microscopy was found to range from 3.0 to 6.5 GPa and was independent of sample size. These observations highlight an absolute material tensile strength that is the highest recorded for a biological material, outperforming the high strength of spider silk currently considered to be the strongest natural material, and approaching values comparable to those of the strongest man-made fibres. This considerable tensile strength of limpet teeth is attributed to a high mineral volume fraction of reinforcing goethite nanofibres with diameters below a defect-controlled critical size, suggesting that natural design in limpet teeth is optimized towards theoretical strength limits.
Sources of variability in cytosolic calcium transients triggered by stimulation of homogeneous uro-epithelial cell monolayers
Authors: Appleby Peter A. , Shabir Saqib , Southgate Jennifer , Walker Dawn
Published: February 2015

Epithelial tissue structure is the emergent outcome of the interactions between large numbers of individual cells. Experimental cell biology offers an important tool to unravel these complex interactions, but current methods of analysis tend to be limited to mean field approaches or representation by selected subsets of cells. This may result in bias towards cells that respond in a particular way and/or neglect local, context-specific cell responses. Here, an automated algorithm was applied to examine in detail the individual calcium transients evoked in genetically homogeneous, but asynchronous populations of cultured non-immortalized normal human urothelial cells when subjected to either the global application of an external agonist or a localized scratch wound. The recorded calcium transients were classified automatically according to a set of defined metrics and distinct sub-populations of cells that responded in qualitatively different ways were observed. The nature of this variability in the homogeneous cell population was apportioned to two sources: intrinsic variation in individual cell responses and extrinsic variability due to context-specific factors of the environment, such as spatial heterogeneity. Statistically significant variation in the features of the calcium transients evoked by scratch wounding according to proximity to the wound edge was identified. The manifestation of distinct sub-populations of cells is considered central to the coordination of population-level response resulting in wound closure.
Regional ejection fraction and regional area strain for left ventricular function assessment in male patients after first-time myocardial infarction
Authors: Teo Soo-Kng , Vos F. J. A. , Tan Ru-San , Zhong Liang , Su Yi
Published: February 2015

In this work, we present a method to assess left ventricle (LV) regional function from cardiac magnetic resonance (CMR) imaging based on the regional ejection fraction (REF) and regional area strain (RAS). CMR scans were performed for 30 patients after first-time myocardial infarction (MI) and nine age- and sex-matched healthy volunteers. The CMR images were processed to reconstruct three-dimensional LV geometry, and the REF and RAS in a 16-segment model were computed using our proposed methodology. The method of computing the REF was tested and shown to be robust against variation in user input. Furthermore, analysis of data was feasible in all patients and healthy volunteers without any exclusions. The REF correlated well with the RAS in a nonlinear manner (quadratic fit—R2= 0.88). In patients after first-time MI, the REF and RAS were significantly reduced across all 16 segments (REF:p< 0.05; RAS:p< 0.01). Moreover, the REF and RAS significantly decreased with the extent of transmural scar obtained from late gadolinium-enhanced CMR images. In addition, we show that the REF and RAS can be used to identify regions with compromised function in the patients with preserved global ejection fraction with reasonable accuracy (more than 78%). These preliminary results confirmed the validity of our approach for accurate analysis of LV regional function. Our approach potentially offers physicians new insights into the local characteristics of the myocardial mechanics after a MI.
Membrane blebbing as a recovery manoeuvre in site-specific sonoporation mediated by targeted microbubbles
Authors: Leow Ruen Shan , Wan Jennifer M. F. , Yu Alfred C. H.
Published: February 2015

Site-specific perforation of the plasma membrane can be achieved through ultrasound-triggered cavitation of a single microbubble positioned adjacent to the cell. However, for this perforation approach (sonoporation), the recovery manoeuvres invoked by the cell are unknown. Here, we report new findings on how membrane blebbing can be a recovery manoeuvre that may take place in sonoporation episodes whose pores are of micrometres in diameter. Each sonoporation site was created using a protocol involving single-shot ultrasound exposure (frequency: 1 MHz; pulse length: 30 cycles; peak negative pressure: 0.45 MPa) which triggered inertial cavitation of a single targeted microbubble (diameter: 1–5 µm). Over this process, live confocal microscopy was conductedin situto monitor membrane dynamics, model drug uptake kinetics and cytoplasmic calcium ion (Ca2+) distribution. Results show that blebbing would occur at a recovering sonoporation site after its resealing, and it may emerge elsewhere along the membrane periphery. The bleb size was correlated with the pre-exposure microbubble diameter, and 99% of blebbing cases at sonoporation sites were inflicted by microbubbles larger than 1.5 µm diameter (analysed over 124 sonoporation episodes). Blebs were not observed at irreversible sonoporation sites or when sonoporation site repair was inhibited via extracellular Ca2+chelation. Functionally, the bleb volume was found to serve as a buffer compartment to accommodate the cytoplasmic Ca2+excess brought about by Ca2+influx during sonoporation. These findings suggest that membrane blebbing would help sonoporated cells restore homeostasis.
On the energy partition in oscillations and waves
Authors: Slepyan Leonid I.
Published: February 2015

A class of generally nonlinear dynamical systems is considered, for which the Lagrangian is represented as a sum of homogeneous functions of the displacements and their derivatives. It is shown that an energy partition as a single relation follows directly from the Euler–Lagrange equation in its general form. The partition is defined solely by the homogeneity orders. If the potential energy is represented by a single homogeneous function, as well as the kinetic energy, the partition between these energies is defined uniquely. For a steady-state solitary wave, where the potential energy consists of two functions of different orders, the Derrick–Pohozaev identity is involved as an additional relation to obtain the partition. Finite discrete systems, finite continuous bodies, homogeneous and periodic-structure waveguides are considered. The general results are illustrated by examples of various types of oscillations and waves: linear and nonlinear, homogeneous and forced, steady-state and transient, periodic and non-periodic, parametric and resonant, regular and solitary.
Size-dependent energy in crystal plasticity and continuum dislocation models
Authors: Mesarovic Sinisa Dj. , Forest Samuel , Jaric Jovo P.
Published: February 2015

In the light of recent progress in coarsening the discrete dislocation mechanics, we consider two questions relevant for the development of a mesoscale, size-dependent plasticity: (i) can the phenomenological expression for size-dependent energy, as quadratic form of Nye's dislocation density tensor, be justified from the point of view of dislocation mechanics and under what conditions? (ii) how can physical or phenomenological expressions for size-dependent energy be computed from dislocation mechanics in the general case of elastically anisotropic crystal? The analysis based on material and slip system symmetries implies the negative answer to the first question. However, the coarsening method developed in response to the second question, and based on the physical interpretation of the size-dependent energy as the coarsening error in dislocation interaction energy, introduces additional symmetries. The result is that the equivalence between the phenomenological and the physical expressions is possible, but only if the multiplicity of characteristic lengths associated with different slip systems, is sacrificed. Finally, we discuss the consequences of the assumption that a single length scale governs the plasticity of a crystal, and note that the plastic dissipation at interfaces has a strong dependence on the length scale embedded in the energy expression.
Systematic discovery and classification of human cell line essential genes
Authors: Hart Traver , Chandrashekhar Megha , Aregger Michael , Steinhart Zachary , Brown Kevin R. , Angers Stephane , Moffat Jason
Published: February 2015

The study of gene essentiality in human cells is crucial for elucidating gene function and holds great potential for finding therapeutic targets for diseases such as cancer. Technological advances in genome editing using clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 systems have set the stage for identifying human cell line core and context-dependent essential genes. However, first generation negative selection screens using CRISPR technology demonstrate extreme variability across different cell lines. To advance the development of the catalogue of human core and context-dependent essential genes, we have developed an optimized, ultracomplex, genome-scale gRNA library of 176,500 guide RNAs targeting 17,661 genes and have applied it to negative and positive selection screens in a human cell line. Using an improved Bayesian analytical approach, we find CRISPR-based screens yield double to triple the number of essential genes than were previously observed using systematic RNA interference, including many genes at moderate expression levels that are largely refractory to RNAi methods. We further characterized four essential genes of unknown significance and found that they all likely exist in protein complexes with other essential genes. For example, RBM48 and ARMC7 are both essential nuclear proteins, strongly interact and are commonly amplified across major cancers. Our findings suggest the CRISPR-Cas9 system fundamentally alters the landscape for systematic reverse genetics in human cells for elucidating gene function, identifying disease genes, and uncovering therapeutic targets.
Syntheses and crystal structures of two magnesium–tetrazole compounds in salt and polymeric forms
Authors: Bensegueni Mohamed Abdellatif , Cherouana Aouatef , Dahaoui Slimane
Published: February 2015

Two alkaline earth–tetrazole compounds, namelycatena-poly[[[triaquamagnesium(II)]-μ-5,5′-(azanediyl)ditetrazolato-κ3N1,N1′:N5] hemi{bis[μ-5,5′-(azanediyl)ditetrazolato-κ3N1,N1′:N2]bis[triaquamagnesium(II)]} monohydrate], {[Mg(C2HN9)(H2O)3][Mg2(C2HN9)2(H2O)6]0.5·H2O}n, (I), and bis[5-(pyrazin-2-yl)tetrazolate] hexaaquamagnesium(II), (C5H3N6)[Mg(H2O)6], (II), have been prepared under hydrothermal conditions. Compound (I) is a mixed dimer–polymer based on magnesium ion centres and can be regarded as the first example of a magnesium–tetrazolate polymer in the crystalline form. The structure shows a complex three-dimensional hydrogen-bonded network that involves magnesium–tetrazolate dimers, solvent water molecules and one-dimensional magnesium–tetrazolate polymeric chains. The intrinsic cohesion in the polymer chains is ensured by N—H...N hydrogen bonds, which formR22(7) rings, thus reinforcing the propagation of the polymer chain along theaaxis. The crystal structure of magnesium tetrazole salt (II) reveals a mixed ribbon of hydrogen-bonded rings, of typesR22(7),R22(9) andR24(10), running along thecaxis, which are linked byR24(16) rings, generating a 4,8-cflunet.
Cocrystals of 6-methyl-2-thiouracil: presence of the acceptor–donor–acceptor/donor–acceptor–donor synthon
Authors: Hützler Wilhelm Maximilian , Egert Ernst
Published: February 2015

The results of seven cocrystallization experiments of the antithyroid drug 6-methyl-2-thiouracil (MTU), C5H6N2OS, with 2,4-diaminopyrimidine, 2,4,6-triaminopyrimidine and 6-amino-3H-isocytosine (viz.2,6-diamino-3H-pyrimidin-4-one) are reported. MTU features anADA(A= acceptor andD= donor) hydrogen-bonding site, while the three coformers show complementaryDADhydrogen-bonding sites and therefore should be capable of forming anADA/DADN—H...O/N—H...N/N—H...S synthon with MTU. The experiments yielded one cocrystal and six cocrystal solvates, namely 6-methyl-2-thiouracil–2,4-diaminopyrimidine–1-methylpyrrolidin-2-one (1/1/2), C5H6N2OS·C4H6N4·2C5H9NO, (I), 6-methyl-2-thiouracil–2,4-diaminopyrimidine (1/1), C5H6N2OS·C4H6N4, (II), 6-methyl-2-thiouracil–2,4-diaminopyrimidine–N,N-dimethylacetamide (2/1/2), 2C5H6N2OS·C4H6N4·2C4H9NO, (III), 6-methyl-2-thiouracil–2,4-diaminopyrimidine–N,N-dimethylformamide (2/1/2), C5H6N2OS·0.5C4H6N4·C3H7NO, (IV), 2,4,6-triaminopyrimidinium 6-methyl-2-thiouracilate–6-methyl-2-thiouracil–N,N-dimethylformamide (1/1/2), C4H8N5+·C5H5N2OS−·C5H6N2OS·2C3H7NO, (V), 6-methyl-2-thiouracil–6-amino-3H-isocytosine–N,N-dimethylformamide (1/1/1), C5H6N2OS·C4H6N4O·C3H7NO, (VI), and 6-methyl-2-thiouracil–6-amino-3H-isocytosine–dimethyl sulfoxide (1/1/1), C5H6N2OS·C4H6N4O·C2H6OS, (VII). Whereas in cocrystal (I) anR22(8) interaction similar to the Watson–Crick adenine/uracil base pair is formed and a two-dimensional hydrogen-bonding network is observed, the cocrystals (II)–(VII) contain the triply hydrogen-bondedADA/DADN—H...O/N—H...N/N—H...S synthon and show a one-dimensional hydrogen-bonding network. Although 2,4-diaminopyrimidine possesses only oneDADhydrogen-bonding site, it is, due to orientational disorder, triply connected to two MTU molecules in (III) and (IV).
Structure of the dodecamer of the aminopeptidase APDkam598 from the archaeonDesulfurococcus kamchatkensis
Authors: Petrova T. E. , Slutskaya E. S. , Boyko K. M. , Sokolova O. S. , Rakitina T. V. , Korzhenevskiy D. A. , Gorbacheva M. A. , Bezsudnova E. Y. , Popov V. O.
Published: February 2015

The crystal structure of the aminopeptidase APDkam589 from the thermophilic crenarchaeonDesulfurococcus kamchatkensiswas determined at a resolution of 3.0 Å. In the crystal, the monomer of APDkam589 and its symmetry-related monomers are densely packed to form a 12-subunit complex. Single-particle electron-microscopy analysis confirms that APDkam589 is present as a compact dodecamer in solution. The APDkam589 molecule is built similarly to the molecules of the PhTET peptidases, which have the highest sequence identity to APDkam589 among known structures and were isolated from the more thermostable archaeonPyrococcus horikoshii. A comparison of the interactions of the subunits in APDkam589 with those in PhTET1, PhTET2 and PhTET3 reveals that APDkam589 has a much lower total number of salt bridges, which correlates with the lower thermostability of APDkam589. The monomer of APDkam589 has six Trp residues, five of which are on the external surface of the dodecamer. A superposition of the structure of APDkam589 with those having a high sequence similarity to APDkam589 reveals that, although the positions of Trp45, Trp252 and Trp358 are not conserved in the sequences, the spatial locations of the Trp residues in these models are similar.
Crystallization and preliminary X-ray diffraction analysis of the arginine repressor ArgR fromBacillus halodurans
Authors: Kang Jina , Park Young Woo , Yeo Hyun Ku , Lee Jae Young
Published: February 2015

The arginine repressor (ArgR) is a transcriptional regulator which regulates genes encoding proteins involved in arginine biosynthesis and the arginine catabolic pathway. ArgR from the alkaliphilic bacteriumBacillus haloduranswas cloned and overexpressed inEscherichia coli. ArgR (Bh2777) fromB. haloduransis composed of 149 amino-acid residues with a molecular mass of 16 836 Da. ArgR was crystallized at 296 K using 1,2-propanediol as a precipitant. Crystals of N-terminally His-tagged ArgR were obtained by the sitting-drop vapour-diffusion method. Dehydrated crystals showed a dramatic improvement in diffraction quality and diffracted to 2.35 Å resolution. The crystals belonged to the cubic space groupI23, with unit-cell parametersa=b=c= 104.68 Å. The asymmetric unit contained one monomer of ArgR, which generates a trimer by the threefold axis of the space group, giving a crystal volume per mass (VM) of 2.98 Å3 Da−1and a solvent content of 56.8%.
Crystallization and preliminary crystallographic analysis of acetophenone reductase fromGeotrichum candidumNBRC 4597
Authors: Sugiyama Yosuke , Senda Miki , Senda Toshiya , Matsuda Tomoko
Published: February 2015

Acetophenone reductase (APRD) fromGeotrichum candidiumNBRC 4597 was crystallized by the hanging-drop vapour-diffusion method using PEG 3350 as a precipitant. The crystal belonged to space groupP6522, with unit-cell parametersa=b= 104.5,c= 273.7 Å, and diffracted to 2.6 Å resolution. Phasing using the single-wavelength anomalous diffraction method was successful. Model building and crystallographic refinement are in progress.
The structure of C290A:C393A Aurora A provides structural insights into kinase regulation
Authors: Burgess Selena G. , Bayliss Richard
Published: February 2015

Aurora A is a Ser/Thr protein kinase that functions in cell-cycle regulation and is implicated in cancer development. During mitosis, Aurora A is activated by autophosphorylation on its activation loop at Thr288. The Aurora A catalytic domain (amino acids 122–403) expressed inEscherichia coliautophosphorylates on two activation-loop threonine residues (Thr288 and Thr287), whereas a C290A,C393A double point mutant of the Aurora A catalytic domain autophosphorylates only on Thr288. The structure of the complex of this mutant with ADP and magnesium was determined to 2.1 Å resolution using molecular replacement. This is an improvement on the existing 2.75 Å resolution structure of the equivalent wild-type complex. The structure confirms that single phosphorylation of the activation loop on Thr288 is insufficient to stabilize a `fully active' conformation of the activation loop in the absence of binding to TPX2.
Protein production, crystallization and preliminary X-ray analysis of two isoforms of the Dscam1 Ig7 domain
Authors: Li Shu-Ang , Cheng Linna , Yu Yamei , Chen Qiang
Published: February 2015

DrosophilaDown syndrome cell adhesion molecule 1 (Dscam1) plays a critical role in neural development. It can potentially form 38 016 isoforms through alternative RNA splicing, and exhibits isoform-specific homophilic interaction through three variable Ig domains (Ig2, Ig3 and Ig7). The diversity and homophilic interaction are essential for its functions. Ig7 has 33 isoforms and is the most variable among the three variable Ig domains. However, only one isoform of Ig7 (isoform 30) has been structurally determined to date. Here, two isoforms of Dscam1 Ig7 (isoforms 5 and 9; Ig75and Ig79) were produced and crystallized. Diffraction data from Ig75and Ig79crystals were processed to resolutions of 1.95 and 2.37 Å, respectively. Comparison of different Dscam1 Ig7 isoforms will provide insight into the mechanism of its binding specificity.
High-resolution crystal structure of a polyextreme GH43 glycosidase fromHalothermothrix oreniiwith α-L-arabinofuranosidase activity
Authors: Hassan Noor , Kori Lokesh D. , Gandini Rosaria , Patel Bharat K. C. , Divne Christina , Tan Tien Chye
Published: February 2015

A gene from the heterotrophic, halothermophilic marine bacteriumHalothermothrix oreniihas been cloned and overexpressed inEscherichia coli. This gene encodes the only glycoside hydrolase of family 43 (GH43) produced byH. orenii. The crystal structure of theH. oreniiglycosidase was determined by molecular replacement and refined at 1.10 Å resolution. As for other GH43 members, the enzyme folds as a five-bladed β-propeller. The structure features a metal-binding site on the propeller axis, near the active site. Based on thermal denaturation data, theH. oreniiglycosidase depends on divalent cations in combination with high salt for optimal thermal stability against unfolding. A maximum melting temperature of 76°C was observed in the presence of 4 MNaCl and Mn2+at pH 6.5. The gene encoding theH. oreniiGH43 enzyme has previously been annotated as a putative α-L-arabinofuranosidase. Activity was detected withp-nitrophenyl-α-L-arabinofuranoside as a substrate, and therefore the nameHoAraf43 was suggested for the enzyme. In agreement with the conditions for optimal thermal stability against unfolding, the highest arabinofuranosidase activity was obtained in the presence of 4 MNaCl and Mn2+at pH 6.5, giving a specific activity of 20–36 µmol min−1 mg−1. The active site is structurally distinct from those of other GH43 members, including arabinanases, arabinofuranosidases and xylanases. This probably reflects the special requirements for degrading the unique biomass available in highly saline aqueous ecosystems, such as halophilic algae and halophytes. The amino-acid distribution ofHoAraf43 has similarities to those of mesophiles, thermophiles and halophiles, but also has unique features, for example more hydrophobic amino acids on the surface and fewer buried charged residues.
Presenting social media information on mobile devices using multiple contexts
Authors: Tan Esther MengYoke , Hoe-Lian Goh Dion
Published: February 2015

Purpose

– Research has shown that when presenting large amounts of social media information on small devices, design should consider multiple contexts which include user preferences, time, location, environment and so on. It should also take into account the purpose of use, for example, the kind of tasks undertaken by users. However, little research has been done on the organization of social media information by multiple context and tasks. The paper aims to discuss these issues.

Design/methodology/approach

– Using tourism as a domain, the authors conducted a user evaluation study with a prototype to investigate users’ preferred ways of organizing different types of social media information based on multiple contexts.

Findings

– In this paper, the authors present a sequence of context types for organizing four types of social media information (recommendations, events, friends and media elements). The study revealed that users preferred to view recommendations by location and environment context, events by location and temporal context, contacts by location and identity context and finally, list of media elements by environment and identity context.

Research limitations/implications

– There may be different sequences of context types for organizing social media information in domains other than tourism. Researchers are encouraged to analyze users’ needs in other domains so as to find their preferred ways of organizing social media information.

Practical implications

– This paper includes implications for the design and development of user interface, in particular, for mobile applications presenting large amount of social media information.

Originality/value

– It presents a new way of organizing social media information using multiple context types and with consideration of users’ needs.
Web service for connecting visually impaired people with libraries
Authors: Tesendic Danijela , Boberic Krsticev Danijela
Published: February 2015

Purpose

– The purpose of this paper is to describe a case study of developing a web service that will act as an intermediary between the Audio Library system for the visually impaired and the library management systems. The Audio Library is based on speech recognition and text-to-speech engines and it produces synthesized speech from various electronic materials. It has its own database with a limited number of books and textual materials. Web services described in this paper should enable access to a larger number of electronic resources provided by libraries.

Design/methodology/approach

– In this paper, the author specified software architecture of a web service analyzing different approaches for search and retrieval.

Findings

– Web service described in this paper is the first software solution addressing the problem of lending e-books in Serbia. It aggregates collections of different libraries in a single access point for the Audio Library system. In this way, users of the Audio Library system are provided with larger number of electronic resources.

Originality/value

– Communication between the Audio Library and this web service is achieved by using standardized protocols for exchanging library data. However, those protocols did not fulfill all necessary requirements, so the authors propose some extensions to overcome those issues.
Human multiple information task behavior on the web
Authors: Park Minsoo
Published: February 2015

Purpose

– The purpose of this paper is to explore the general nature of human multiple information task behavior in Web information seeking and retrieval contexts and identify the factors that influence the processes of prioritizing mul.tiple information tasks.

Design/methodology/approach

– Experiments were conducted in a laboratory setting to collect data from multiple sources including search logs, think aloud reports during the searches and interviews, questionnaires, and post-search interviews. Quantitative and qualitative analysis techniques were both used.

Findings

– The findings of this study reveal that effort, time and perception may all be necessary factors in producing good performance in dynamic and complex information situations, but how the author effectively manages the emotions ultimately yields successful performance. High mental effort, even when accompanied by productive time management, is not sufficient to produce high performance unless the author effectively deal with the emotions and feelings in such situations.

Originality/value

– A comprehensive understanding of the affective, cognitive, and physical processes underlying the human multiple information task behavior is vital if the author is to design emotionally intelligent information systems that can support people when managing dynamic and complex information situations in hi-tech environments.