bluuebunny/crossref_metadata_2025 huggingface dataset:
Feeding-induced rearrangement of green leaf volatiles reduces moth oviposition
Authors: Allmann Silke , Späthe Anna , Bisch-Knaden Sonja , Kallenbach Mario , Reinecke Andreas , Sachse Silke , Baldwin Ian T , Hansson Bill S
Published: May 2013

The ability to decrypt volatile plant signals is essential if herbivorous insects are to optimize their choice of host plants for their offspring. Green leaf volatiles (GLVs) constitute a widespread group of defensive plant volatiles that convey a herbivory-specific message via their isomeric composition: feeding of the tobacco hornworm Manduca sexta converts (Z)-3- to (E)-2-GLVs thereby attracting predatory insects. Here we show that this isomer-coded message is monitored by ovipositing M. sexta females. We detected the isomeric shift in the host plant Datura wrightii and performed functional imaging in the primary olfactory center of M. sexta females with GLV structural isomers. We identified two isomer-specific regions responding to either (Z)-3- or (E)-2-hexenyl acetate. Field experiments demonstrated that ovipositing Manduca moths preferred (Z)-3-perfumed D. wrightii over (E)-2-perfumed plants. These results show that (E)-2-GLVs and/or specific (Z)-3/(E)-2-ratios provide information regarding host plant attack by conspecifics that ovipositing hawkmoths use for host plant selection.
Controlling gain one photon at a time
Authors: Schwartz Gregory W , Rieke Fred
Published: May 2013

Adaptation is a salient property of sensory processing. All adaptational or gain control mechanisms face the challenge of obtaining a reliable estimate of the property of the input to be adapted to and obtaining this estimate sufficiently rapidly to be useful. Here, we explore how the primate retina balances the need to change gain rapidly and reliably when photons arrive rarely at individual rod photoreceptors. We find that the weakest backgrounds that decrease the gain of the retinal output signals are similar to those that increase human behavioral threshold, and identify a novel site of gain control in the retinal circuitry. Thus, surprisingly, the gain of retinal signals begins to decrease essentially as soon as background lights are detectable; under these conditions, gain control does not rely on a highly averaged estimate of the photon count, but instead signals from individual photon absorptions trigger changes in gain.
EBI2-mediated bridging channel positioning supports splenic dendritic cell homeostasis and particulate antigen capture
Authors: Yi Tangsheng , Cyster Jason G
Published: May 2013

Splenic dendritic cells (DCs) present blood-borne antigens to lymphocytes to promote T cell and antibody responses. The cues involved in positioning DCs in areas of antigen exposure in the spleen are undefined. Here we show that CD4+ DCs highly express EBI2 and migrate to its oxysterol ligand, 7α,25-OHC. In mice lacking EBI2 or the enzymes needed for generating normal distributions of 7α,25-OHC, CD4+ DCs are reduced in frequency and the remaining cells fail to situate in marginal zone bridging channels. The CD4+ DC deficiency can be rescued by LTβR agonism. EBI2-mediated positioning in bridging channels promotes DC encounter with blood-borne particulate antigen. Upon exposure to antigen, CD4+ DCs move rapidly to the T-B zone interface and promote induction of helper T cell and antibody responses. These findings establish an essential role for EBI2 in CD4+ DC positioning and homeostasis and in facilitating capture and presentation of blood-borne particulate antigens.
Manipulation of kynurenine pathway for enhanced daptomycin production in Streptomyces roseosporus
Authors: Liao Guojian , Wang Lei , Liu Qing , Guan Feifei , Huang Yuqi , Hu Changhu
Published: May 2013

Daptomycin is a cyclic lipopeptide natural product produced by Stretptomyces roseosporus, displaying good bactericidal activity against a wide range of gram‐positive pathogens. Daptomycin contains a 13 amino acid and kynurenine (Kyn) is essential for optimal activity of daptomycin. In this study, we characterized the Kyn pathway in S. roseosporus and investigated its role in supplying precursor for daptomycin biosynthesis. Two genes (dptJ and tdo) coding for tryptophan‐2,3‐dioxgenase existed in the chromosome. dptJ is located in the daptomycin biosynthetic gene cluster, while tdo is in other locus. Disruption of dptJ or tdo resulted in reduced yield by ∼50%. The introduction of an additional copy of dptJ but not tdo led to enhanced production of daptomycin by 110%. Furthermore, disruption of kyn encoding kynureninase showed improved daptomycin productivity by 30%. Our results demonstrated that the enhancement of Kyn supply through metabolic engineering approach is an efficient way to increase daptomycin production. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:847–852, 2013
Enzymatic digestion of alkaline‐sulfite pretreated sugar cane bagasse and its correlation with the chemical and structural changes occurring during the pretreatment step
Authors: Mendes Fernanda M. , Laurito Debora F. , Bazzeggio Mariana , Ferraz André , Milagres Adriane M. F.
Published: May 2013

Sugar cane bagasse is recalcitrant to enzymatic digestion, which hinders the efficient conversion of its polysaccharides into fermentable sugars. Alkaline‐sulfite pretreatment was used to overcome the sugar cane bagasse recalcitrance. Chemical and structural changes that occurred during the pretreatment were correlated with the efficiency of the enzymatic digestion of the polysaccharides. The first 30 min of pretreatment, which removed approximately half of the initial lignin and 30% of hemicellulose seemed responsible for a significant enhancement of the cellulose conversion level, which reached 64%. After the first 30 min of pretreatment, delignification increased slightly, and hemicellulose removal was not enhanced; however, acid groups continued to be introduced into the residual lignin. Water retention values were 145% to the untreated bagasse and 210% to the bagasse pretreated for 120 min and fiber widths increased from 10.4 to 30 μm, respectively. These changes were responsible for an additional increase in the efficiency of enzymatic hydrolysis of the cellulose, which reached 92% with the 120 min pretreated sample. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:890–895, 2013
Effect of Food, Antacid, and Age on the Pharmacokinetics of the Oral Thrombin Receptor Antagonist Vorapaxar (SCH 530348) in Healthy Volunteers
Authors: Kosoglou Teddy , Reyderman Larisa , Tseng Jack , Kumar Bharath , Xuan Fengjuan , Schiller James , Meehan Alan G. , Kim Kenneth , Cutler David L.
Published: May 2013

This randomized, open‐label, parallel group study examined the effects of food, antacid, and age on the pharmacokinetics of vorapaxar. In total, 101 subjects were enrolled including 83 young adults (18–45 years) and 18 elderly subjects (>65 years). Subjects received single‐dose vorapaxar 40 mg after a 10‐hour fast (young and elderly) or with extra‐strength antacid, food, or 1 or 2 hours after food (young only). Vorapaxar 40 mg was rapidly absorbed after a fast (median Tmax: 1 hour). Administration with food or 1 or 2 hours post‐meal modestly increased vorapaxar mean area under the curve (AUC) and Cmax and prolonged median Tmax by 1 hour. Concomitant food modestly increased vorapaxar AUC from time zero to infinity [AUC(I)] and Cmax 43% and 31%, respectively. Antacid modestly decreased vorapaxar AUC(I) by 15% and Cmax by 38%, and increased median Tmax by 1 hour. Vorapaxar AUC(I) and Cmax were 41% and 29% higher, respectively, in elderly versus young subjects. Concomitant food and older age were associated with modest increases, and antacid was associated with a small decrease in vorapaxar exposure, which are not expected to affect the drug's safety or efficacy.
Patterns of ecological specialization among microbial populations in the Red Sea and diverse oligotrophic marine environments
Authors: Thompson Luke R. , Field Chris , Romanuk Tamara , Kamanda Ngugi David , Siam Rania , El Dorry Hamza , Stingl Ulrich
Published: May 2013

Large swaths of the nutrient‐poor surface ocean are dominated numerically by cyanobacteria (Prochlorococcus), cyanobacterial viruses (cyanophage), and alphaproteobacteria (SAR11). How these groups thrive in the diverse physicochemical environments of different oceanic regions remains poorly understood. Comparative metagenomics can reveal adaptive responses linked to ecosystem‐specific selective pressures. The Red Sea is well‐suited for studying adaptation of pelagic‐microbes, with salinities, temperatures, and light levels at the extreme end for the surface ocean, and low nutrient concentrations, yet no metagenomic studies have been done there. The Red Sea (high salinity, high light, low N and P) compares favorably with the Mediterranean Sea (high salinity, low P), Sargasso Sea (low P), and North Pacific Subtropical Gyre (high light, low N). We quantified the relative abundance of genetic functions among Prochlorococcus, cyanophage, and SAR11 from these four regions. Gene frequencies indicate selection for phosphorus acquisition (Mediterranean/Sargasso), DNA repair and high‐light responses (Red Sea/Pacific Prochlorococcus), and osmolyte C1 oxidation (Red Sea/Mediterranean SAR11). The unexpected connection between salinity‐dependent osmolyte production and SAR11 C1 metabolism represents a potentially major coevolutionary adaptation and biogeochemical flux. Among Prochlorococcus and cyanophage, genes enriched in specific environments had ecotype distributions similar to nonenriched genes, suggesting that inter‐ecotype gene transfer is not a major source of environment‐specific adaptation. Clustering of metagenomes using gene frequencies shows similarities in populations (Red Sea with Pacific, Mediterranean with Sargasso) that belie their geographic distances. Taken together, the genetic functions enriched in specific environments indicate competitive strategies for maintaining carrying capacity in the face of physical stressors and low nutrient availability.
Mapping neurotransmitter networks with PET: An example on serotonin and opioid systems
Authors: Tuominen Lauri , Nummenmaa Lauri , Keltikangas‐Järvinen Liisa , Raitakari Olli , Hietala Jarmo
Published: May 2013

All functions of the human brain are consequences of altered activity of specific neural pathways and neurotransmitter systems. Although the knowledge of “system level” connectivity in the brain is increasing rapidly, we lack “molecular level” information on brain networks and connectivity patterns. We introduce novel voxel‐based positron emission tomography (PET) methods for studying internal neurotransmitter network structure and intercorrelations of different neurotransmitter systems in the human brain. We chose serotonin transporter and μ‐opioid receptor for this analysis because of their functional interaction at the cellular level and similar regional distribution in the brain. Twenty‐one healthy subjects underwent two consecutive PET scans using [11C]MADAM, a serotonin transporter tracer, and [11C]carfentanil, a μ‐opioid receptor tracer. First, voxel‐by‐voxel “intracorrelations” (hub and seed analyses) were used to study the internal structure of opioid and serotonin systems. Second, voxel‐level opioid–serotonin intercorrelations (between neurotransmitters) were computed. Regional μ‐opioid receptor binding potentials were uniformly correlated throughout the brain. However, our analyses revealed nonuniformity in the serotonin transporter intracorrelations and identified a highly connected local network (midbrain–striatum–thalamus–amygdala). Regionally specific intercorrelations between the opioid and serotonin tracers were found in anteromedial thalamus, amygdala, anterior cingulate cortex, dorsolateral prefrontal cortex, and left parietal cortex, i.e., in areas relevant for several neuropsychiatric disorders, especially affective disorders. This methodology enables in vivo mapping of connectivity patterns within and between neurotransmitter systems. Quantification of functional neurotransmitter balances may be a useful approach in etiological studies of neuropsychiatric disorders and also in drug development as a biomarker‐based rationale for targeted modulation of neurotransmitter networks. Hum Brain Mapp 35:1875–1884, 2014. © 2013 Wiley Periodicals, Inc.
Estimating streambed parameters for a disconnected river
Authors: Wang Wenke , Li Junting , Wang Wenming , Chen Xunhong , Cheng Donghui , Jia Jia
Published: May 2013

Evaluation of stream–aquifer interaction and water balance for a catchment often requires specific information on streambed parameters, such as streambed hydraulic conductivity, seepage flux across the streambed and so on. This paper describes a simple, inexpensive instrument that is used to measure these streambed parameters under the condition of a stream disconnected from groundwater. Our method includes a seepage cylinder for simulation of river water depth. The proposed method was applied to estimate the vertical hydraulic conductivity of a streambed and the changes in vertical seepage rate from stream to groundwater with varied stream water depth in the Manasi River of Xinjiang Uygur Autonomous Region, China. The vertical hydraulic conductivities of the streambed determined from 12 sites along the Manasi River vary from 1.01 to 29.m/day where the stream disconnects from the groundwater. The experimental results suggest that there are two kinds of relations between the vertical seepage rate and the simulated stream water depth. One is a linear relation between the two variables with low Reynolds numbers (less than 10); the other is a nonlinear relation (exponential relation) between the two variables with larger Reynolds numbers (greater than 10). This second relationship is quite different from the traditional model that usually calculates the vertical seepage rate from stream to groundwater under the condition of disconnection using a linear relation (Darcy's Law). Our results suggest that a linear relation can only be used for a limited range of river water depth. This method gives a convenient tool for rapidly estimating the streambed hydraulic conductivity and the changes in the vertical seepage rate across streambed with varied stream water depths for the case of a stream disconnected from groundwater. Copyright © 2013 John Wiley & Sons, Ltd.
Pharmacokinetics and Pharmacodynamics of Canagliflozin, a Sodium Glucose Co‐Transporter 2 Inhibitor, in Subjects With Type 2 Diabetes Mellitus
Authors: Devineni Damayanthi , Curtin Christopher R. , Polidori David , Gutierrez Maria J. , Murphy Joseph , Rusch Sarah , Rothenberg Paul L.
Published: May 2013

This study characterized single‐ and multiple‐dose pharmacokinetics of canagliflozin and its O‐glucuronide metabolites (M5 and M7) and pharmacodynamics (renal threshold for glucose [RTG], urinary glucose excretion [UGE0–24h], and 24‐hour mean plasma glucose [MPG0–24h]) of canagliflozin in subjects with type 2 diabetes. Thirty‐six randomized subjects received canagliflozin 50, 100, or 300 mg/day or placebo for 7 days. On Days 1 and 7, area under the plasma concentration‐time curve and maximum observed plasma concentration (Cmax) for canagliflozin and its metabolites increased dose‐dependently. Half‐life and time at which Cmax was observed were dose‐independent. Systemic molar M5 exposure was half that of canagliflozin; M7 exposure was similar to canagliflozin. Steady‐state plasma canagliflozin concentrations were reached by Day 4 in all active treatment groups. Pharmacodynamic effects were dose‐ and exposure‐dependent. All canagliflozin doses decreased RTG, increased UGE0–24h, and reduced MPG0–24h versus placebo on Days 1 and 7. On Day 7, placebo‐subtracted least‐squares mean decreases in MPG0–24h ranged from 42–57 mg/dL with canagliflozin treatment. Adverse events (AEs) were balanced between treatments; no treatment‐related serious AEs, AE‐related discontinuations, or clinically meaningful adverse changes in routine safety evaluations occurred. The observed pharmacokinetic/pharmacodynamic profile of canagliflozin in subjects with type 2 diabetes supports a once‐daily dosing regimen.
Potential of fibrous adsorbents for the binding and characterization of Porphyridium purpureum bioactive polysaccharides
Authors: Rwehumbiza Vincent M. , Vennapusa Rami Reddy , Gavara Poondi R. , Fernández‐Lahore Héctor M. , Al‐Karablieh Nehaya , Ullrich Matthias S. , Thomsen Claudia
Published: May 2013

BACKGROUND

Complex polysaccharides are important in the pharmaceutical industry, yet, due to their large molecular weight and reduced charges, their purification is a highly demanding process that requires binding matrices with unique properties. This work demonstrates for the first time that complex polysaccharides biosynthesized by microalga Porphyridium purpureum can be adsorbed onto Q fibrous anion exchangers.

RESULTS

When the polysaccharides were characterized, the extent of sulfation was higher in native polysaccharides than in ethanol‐ or alkali‐extracts. The zeta potentials increased with increasing pH and the highest charge was observed at pH 8, while the Z‐average diameters of the polysaccharide at pH 6 were highest for alkali‐extracts. Instead of pellicular resins, Q fibrous adsorbents were used to determine Langmuir thermodynamic properties and dynamic binding capacities. The parameters included static binding capacity and dissociation constant of 13.47 ± 1.02 mg g‐1 and 0.141 ± 0.027 mg mL‐1, and 10 and 50% breakthrough capacities of 4.46 ± 0.22 and 5.51 ± 0.28 mg g‐1, respectively. The antiviral activity of the polysaccharides was demonstrated by minimizing bacteriophage lysis of Streptococcus thermophilus.

CONCLUSION

This work demonstrates that polysaccharide extraction can be optimized and the adsorption and desorption of a complex polysaccharide onto Q fibrous matrix is feasible. These parameters could be exploited for up‐scaling of polysaccharides for nutraceutical and pharmaceutical applications. © 2013 Society of Chemical Industry
Neutron monitor yield function: New improved computations
Authors: Mishev A. L. , Usoskin I. G. , Kovaltsov G. A.
Published: May 2013

A ground‐based neutron monitor (NM) is a standard tool to measure cosmic ray (CR) variability near Earth, and it is crucially important to know its yield function for primary CRs. Although there are several earlier theoretically calculated yield functions, none of them agrees with experimental data of latitude surveys of sea‐level NMs, thus suggesting for an inconsistency. A newly computed yield function of the standard sea‐level 6NM64 NM is presented here separately for primary CR protons and α‐particles, the latter representing also heavier species of CRs. The computations have been done using the GEANT‐4 PLANETOCOSMICS Monte‐Carlo tool and a realistic curved atmospheric model. For the first time, an effect of the geometrical correction of the NM effective area, related to the finite lateral expansion of the CR induced atmospheric cascade, is considered, which was neglected in the previous studies. This correction slightly enhances the relative impact of higher‐energy CRs (energy above 5–10 GeV/nucleon) in NM count rate. The new computation finally resolves the long‐standing problem of disagreement between the theoretically calculated spatial variability of CRs over the globe and experimental latitude surveys. The newly calculated yield function, corrected for this geometrical factor, appears fully consistent with the experimental latitude surveys of NMs performed during three consecutive solar minima in 1976–1977, 1986–1987, and 1996–1997. Thus, we provide a new yield function of the standard sea‐level NM 6NM64 that is validated against experimental data.
Nightside midlatitude ionospheric arcs: TIMED/GUVI observations
Authors: Zhang Yongliang , Paxton Larry J. , Kil Hyosub
Published: May 2013

Midlatitude arcs (MLA) are the phenomenon of the nightside enhancements of ionospheric electron density at 20°‐45° magnetic latitudes in both hemispheres. We investigate the occurrence of MLA and its dependence on season using the Thermosphere, Ionosphere, Mesosphere Energetics and Dynamics/Global Ultraviolet Imager (TIMED/GUVI) O I 135.6 nm intensity data between March 2008 and March 2012. The 135.6 nm emission is mainly caused by radiant recombination between O+ ions and electrons in the nightside ionosphere. The GUVI data show that the MLA occurred in all seasons under geomagnetically quiet condition (mean Kp ~ 1.0) and during periods of low solar activity. Hemispheric symmetric MLA were observed during equinox. During solstice, the MLA were seen only in the winter hemisphere. The MLA were more frequently observed at local times between ~21:00 and 02:00 on nightside. They were rarely observed at local times between 03:00 and sun rise. The MLA were observed with an occurrence frequency of ~75% of the time. Coincident GPS total electron current data confirm that the MLA were due to enhanced ionospheric electron density. GUVI 135.6 nm limb data further show that the altitude of the MLA is higher than that of the equatorial arcs created by the equatorial ionization anomaly or fountain effect. The appearance of the MLA at higher altitude than the equatorial arcs supports the idea that the creation of the MLA is associated with the uplift of the ionosphere by the equatorward neutral wind.
Optimal estimation for global ground‐level fine particulate matter concentrations
Authors: van Donkelaar Aaron , Martin Randall V. , Spurr Robert J. D. , Drury Easan , Remer Lorraine A. , Levy Robert C. , Wang Jun
Published: May 2013

We develop an optimal estimation (OE) algorithm based on top‐of‐atmosphere reflectances observed by the MODIS satellite instrument to retrieve near‐surface fine particulate matter (PM2.5). The GEOS‐Chem chemical transport model is used to provide prior information for the Aerosol Optical Depth (AOD) retrieval and to relate total column AOD to PM2.5. We adjust the shape of the GEOS‐Chem relative vertical extinction profiles by comparison with lidar retrievals from the CALIOP satellite instrument. Surface reflectance relationships used in the OE algorithm are indexed by land type. Error quantities needed for this OE algorithm are inferred by comparison with AOD observations taken by a worldwide network of sun photometers (AERONET) and extended globally based upon aerosol speciation and cross correlation for simulated values, and upon land type for observational values. Significant agreement in PM2.5 is found over North America for 2005 (slope = 0.89; r = 0.82; 1‐σ error = 1 µg/m3 + 27%), with improved coverage and correlation relative to previous work for the same region and time period, although certain subregions, such as the San Joaquin Valley of California are better represented by previous estimates. Independently derived error estimates of the OE PM2.5 values at in situ locations over North America (of ±(2.5 µg/m3 + 31%) and Europe of ±(3.5 µg/m3 + 30%) are corroborated by comparison with in situ observations, although globally (error estimates of ±(3.0 µg/m3 + 35%), may be underestimated. Global population‐weighted PM2.5 at 50% relative humidity is estimated as 27.8 µg/m3 at 0.1° × 0.1° resolution.
The Impact of Dynamic Capabilities through Continuous Improvement on Innovation: the Role of Business Process Orientation
Authors: Kohlbacher Markus
Published: May 2013

Although there is much emphasis on the importance of continuous improvement as a dynamic capability and business process orientation, little attention has been paid to their interactions and joint effects on a firm's innovation performance. In this paper, we empirically explore the interaction effect of continuous improvement as a dynamic capability and business process orientation on time‐to‐market speed. By employing a unique and hand‐collected dataset of Austrian manufacturing companies, it is shown that firms increase their innovation performance when they implement both—a process‐oriented organizational design and continuous improvement methodologies. Copyright © 2013 John Wiley & Sons, Ltd.
Substrate versus inhibitor dynamics of P‐glycoprotein
Authors: Ma Jerome , Biggin Philip C.
Published: May 2013

By far the most studied multidrug resistance protein is P‐glycoprotein. Despite recent structural data, key questions about its function remain. P‐glycoprotein (P‐gp) is flexible and undergoes large conformational changes as part of its function and in this respect, details not only of the export cycle, but also the recognition stage are currently lacking. Given the flexibility, molecular dynamics (MD) simulations provide an ideal tool to examine this aspect in detail. We have performed MD simulations to examine the behaviour of P‐gp. In agreement with previous reports, we found that P‐gp undergoes large conformational changes which tended to result in the nucleotide‐binding domains coming closer together. In all simulations, the approach of the NBDs was asymmetrical in agreement with previous observations for other ABC transporter proteins. To validate the simulations, we make extensive comparison to previous cross‐linking data. Our results show very good agreement with the available data. We then went on to compare the influence of inhibitor compounds bound with simulations of a substrate (daunorubicin) bound. Our results suggest that inhibitors may work by keeping the NBDs apart, thus preventing ATP‐hydrolysis. On the other hand, repeat simulations of daunorubicin (substrate) in one particular binding pose suggest that the approach of the NBDs is not impaired and that the structure would be still be competent to perform ATP hydrolysis, thus providing a model for inhibition or substrate transport. Finally we compare the latter to earlier QSAR data to provide a model for the first part of substrate transport within P‐gp. Proteins 2013. © 2013 Wiley Periodicals, Inc.
Vector control and foliar nutrition to maintain economic sustainability of bearing citrus in Florida groves affected by huanglongbing
Authors: Stansly Philip A , Arevalo H Alejandro , Qureshi Jawwad A , Jones Moneen M , Hendricks Katherine , Roberts Pamela D , Roka Fritz M
Published: May 2013

BACKGROUND

Huanglongbing (HLB) or citrus greening is a bacterial disease vectored by the Asian citrus psyllid (ACP) causing tree decline, and yield loss. Vector control and foliar nutrition are used in Florida to slow the spread of HLB and mitigate debilitating effects of the disease.

A four year replicated field study was initiated February 2008 in a 5.2‐ha commercial block of young ‘Valencia’ orange trees employing a factorial design to evaluate individual and compound effects of vector management and foliar nutrition. Insecticides were sprayed during tree dormancy and when psyllid populations exceeded a nominal threshold. A mixture consisting primarily of micro‐ and macro‐nutrients was applied three times a year corresponding to the principal foliar flushes.

RESULTS

Differences in ACP numbers from five‐ to 13‐fold were maintained in insecticide treated and untreated plots. Incidence of HLB estimated by polymerase chain reaction (PCR), rose from 30% at the beginning of the study to 95% in only 18 months. Highest yields all four years were seen from trees receiving both foliar nutrition and vector control. Production for these trees in the fourth year was close to the pre‐HLB regional average for 10 year old ‘Valencia’ on ‘Swingle’. Nevertheless, at current juice prices, the extra revenue generated from the combined insecticide and nutritional treatment did not cover the added treatment costs.

CONCLUSIONS

This experiment demonstrated that vector control, especially when combined with enhanced foliar nutrition, could significantly increase yields in a citrus orchard with high incidence of HLB. Economic thresholds for both insecticide and nutrient applications are needed under different market and environmental conditions.
Validation of PREDICCS using LRO/CRaTER observations during three major solar events in 2012
Authors: Joyce C. J. , Schwadron N. A. , Wilson J. K. , Spence H. E. , Kasper J. C. , Golightly M. , Blake J. B. , Mazur J. , Townsend L. W. , Case A. W. , Semones E. , Smith S. , Zeitlin C. J.
Published: May 2013

PREDICCS (Predictions of Radiation from Release, EMMREM, and Data Incorporating the CRaTER, COSTEP and other SEP measurements, prediccs.sr.unh.edu) is an online system designed to provide a near real‐time characterization of the radiation environment of the inner heliosphere. PREDICCS utilizes data from various satellites in conjunction with numerical models such as the Earth‐Moon‐Mars Radiation Environment Module (EMMREM) to produce dose rate and particle flux data at the Earth, Moon and Mars. The Cosmic Ray Telescope for the Effects of Radiation (CRaTER) instrument launched aboard the Lunar Reconnaissance Orbiter (LRO) spacecraft in 2009 and designed to measure energetic particle radiation, offers an opportunity to test the capability of PREDICCS to accurately describe the lunar radiation environment. We provide comparisons between dose rates produced by PREDICCS with those measured by CRaTER during three major solar energetic particle (SEP) events that occurred in 2012. In addition, using EMMREM data products together with our archive of measured CRaTER dose rates, we compute the modulation potential at the Moon throughout the LRO mission and, using this, compute the background GCR dose rate during each event. We demonstrate reasonable agreement between PREDICCS and CRaTER dose rates and come to the conclusion that PREDICCS provides credible characterization of the lunar radiation environment. This study represents the first multi‐event validation, via in situ measurement, of radiation models such as EMMREM, which should prove to be valuable in future efforts in risk assessment and in the study of radiation in the inner heliosphere.
Robot‐assisted Gastrectomy for Gastric Cancer: Current Status and Technical Considerations
Authors: Coratti Andrea , Annecchiarico Mario , Di Marino Michele , Gentile Edoardo , Coratti Francesco , Giulianotti Pier Cristoforo
Published: May 2013

Background

Robot‐assisted gastrectomy has been reported as a safe alternative to the conventional laparoscopy or open approach for treating early gastric carcinoma. To date, however, there are a limited number of published reports available in the literature.

Methods

We assess the current status of robotic surgery in the treatment of gastric cancer, focusing on the technical details and oncological considerations.

Results

In gastric surgery, the biggest advantage of robotic surgery is the ease and reproducibility of D2‐lymphadenectomy. Reports show that even the intracorporeal digestive restoration is facilitated by use of the robotic approach, particularly following total gastrectomy. Additionally, the accuracy of robotic dissection is confirmed by decreased blood loss, as reported in series comparing robot‐assisted with laparoscopic gastrectomy. The learning curve and technical reproducibility also appear to be shorter with robotic surgery and, consequently, robotics can help to standardize and diffuse minimally invasive surgery in the treatment of gastric cancer, even in the later stages. This is important because the application of minimally invasive surgery is limited by the complexity of performing a D2‐lymphadenectomy. The potential to reproduce D2‐lymphadenectomy, enlarged resections, and complex reconstructions provides robotic surgery with an important role in the therapeutic strategy of advanced gastric cancer.

Conclusions

While published reports have shown no significant differences in surgical morbidity, mortality, or oncological adequacy between robot‐assisted and conventional laparoscopic gastrectomy, more studies are needed to assess the indications and oncological effectiveness of robotic use in the treatment of gastric carcinoma. Herein, the authors assess the current status of robotic surgery in the treatment of gastric cancer, focusing on the technical details and oncological considerations.
Positional Variations in Mammary Gland Development and Cancer
Authors: Veltmaat Jacqueline M. , Ramsdell Ann F. , Sterneck Esta
Published: May 2013

Most mammals develop their mammary glands in pairs of which the two counterparts are symmetrically displaced away from the ventral midline. Based on this symmetry and the same functional outcome as a milk-producing organ, the mammary glands are easily presumed to be mere copies of one another. Based on our analysis of published data with inclusion of new results related to mammary development and pathology in mice, we argue that this presumption is incorrect: Between and within pairs, mammary glands differ from one another, and tumor incidence and biology depend on the position along the anterior-posterior and the left-right axis as well. This insight has implications for experimental designs with mouse models and for data extrapolation between mammary glands within and between species. We suggest that improved documentation of location-specific mammary gland features will lead to more insights into the molecular mechanisms of mammary gland development and cancer biology in both mice and humans.
Nucleotide degradation and ribose salvage in yeast
Authors: Xu Yi‐Fan , Létisse Fabien , Absalan Farnaz , Lu Wenyun , Kuznetsova Ekaterina , Brown Greg , Caudy Amy A , Yakunin Alexander F , Broach James R , Rabinowitz Joshua D
Published: May 2013

Nucleotide degradation is a universal metabolic capability. Here we combine metabolomics, genetics and biochemistry to characterize the yeast pathway. Nutrient starvation, via PKA, AMPK/SNF1, and TOR, triggers autophagic breakdown of ribosomes into nucleotides. A protein not previously associated with nucleotide degradation, Phm8, converts nucleotide monophosphates into nucleosides. Downstream steps, which involve the purine nucleoside phosphorylase, Pnp1, and pyrimidine nucleoside hydrolase, Urh1, funnel ribose into the nonoxidative pentose phosphate pathway. During carbon starvation, the ribose‐derived carbon accumulates as sedoheptulose‐7‐phosphate, whose consumption by transaldolase is impaired due to depletion of transaldolase's other substrate, glyceraldehyde‐3‐phosphate. Oxidative stress increases glyceraldehyde‐3‐phosphate, resulting in rapid consumption of sedoheptulose‐7‐phosphate to make NADPH for antioxidant defense. Ablation of Phm8 or double deletion of Pnp1 and Urh1 prevent effective nucleotide salvage, resulting in metabolite depletion and impaired survival of starving yeast. Thus, ribose salvage provides means of surviving nutrient starvation and oxidative stress.
Determination of Isotherm for Acetate and Formate Adsorption at Pt(111) Electrode by Fast Scan Voltammetry
Authors: Xu Jie , Lin Chu-hong , Mei Dong , Zhang Zun-biao , Yuan Dao-fu , Chen Yan-xia
Published: May 2013

Fast scan voltammetry is an efficient tool to distinguish oxidative/reductive adsorption/desorption from that for bulk reaction. In this work, we provide a methodology that the isotherm of oxidative/reductive adsorption desorption processes at electrode surface can be obtained using just one solution with relatively low reactant concentration, by taking the advantage of varying the potential scan rate (relative of the diffusion rate) to tune the adsorption rate and proper mathematic treatment. The methodology is demonstrated by taking acetate adsorption at Pt(111) in acidic solution as an example. The possibility for extension of this method toward mechanistic studies of complicated electrocatalytic reactions is also given.
Music–color associations are mediated by emotion
Authors: Palmer Stephen E. , Schloss Karen B. , Xu Zoe , Prado-León Lilia R.
Published: May 2013

Experimental evidence demonstrates robust cross-modal matches between music and colors that are mediated by emotional associations. US and Mexican participants chose colors that were most/least consistent with 18 selections of classical orchestral music by Bach, Mozart, and Brahms. In both cultures, faster music in the major mode produced color choices that were more saturated, lighter, and yellower whereas slower, minor music produced the opposite pattern (choices that were desaturated, darker, and bluer). There were strong correlations (0.89 <r< 0.99) between the emotional associations of the music and those of the colors chosen to go with the music, supporting an emotional mediation hypothesis in both cultures. Additional experiments showed similarly robust cross-modal matches from emotionally expressive faces to colors and from music to emotionally expressive faces. These results provide further support that music-to-color associations are mediated by common emotional associations.
Using natural variation in
Drosophila
to discover previously unknown endoplasmic reticulum stress genes
Authors: Chow Clement Y. , Wolfner Mariana F. , Clark Andrew G.
Published: May 2013

Natural genetic variation is a rich resource for identifying novel elements of cellular pathways such as endoplasmic reticulum (ER) stress. ER stress occurs when misfolded proteins accumulate in the ER and cells respond with the conserved unfolded protein response (UPR), which includes large-scale gene expression changes. Although ER stress can be a cause or a modifying factor of human disease, little is known of the amount of variation in the response to ER stress and the genes contributing to such variation. To study natural variation in ER stress response in a model system, we measured the survival time in response to tunicamycin-induced ER stress in flies from 114 lines from the sequenced
Drosophila
Genetic Reference Panel of wild-derived inbred strains. These lines showed high heterogeneity in survival time under ER stress conditions. To identify the genes that may be driving this phenotypic variation, we profiled ER stress-induced gene expression and performed an association study. Microarray analysis identified variation in transcript levels of numerous known and previously unknown ER stress-responsive genes. Survival time was significantly associated with polymorphisms in candidate genes with known (i.e.,
Xbp1
) and unknown roles in ER stress. Functional testing found that 17 of 25 tested candidate genes from the association study have putative roles in ER stress. In both approaches, one-third of ER stress genes had human orthologs that contribute to human disease. This study establishes
Drosophila
as a useful model for studying variation in ER stress and identifying ER stress genes that may contribute to human disease.
A statistical framework for power calculations in ChIP-seq experiments
Authors: Zuo Chandler , Keleş Sündüz
Published: May 2013

Motivation: ChIP-seq technology enables investigators to study genome-wide binding of transcription factors and mapping of epigenomic marks. Although the availability of basic analysis tools for ChIP-seq data is rapidly increasing, there has not been much progress on the related design issues. A challenging question for designing a ChIP-seq experiment is how deeply should the ChIP and the control samples be sequenced? The answer depends on multiple factors some of which can be set by the experimenter based on pilot/preliminary data. The sequencing depth of a ChIP-seq experiment is one of the key factors that determine whether all the underlying targets (e.g. binding locations or epigenomic profiles) can be identified with a targeted power.

Results: We developed a statistical framework named CSSP (ChIP-seq Statistical Power) for power calculations in ChIP-seq experiments by considering a local Poisson model, which is commonly adopted by many peak callers. Evaluations with simulations and data-driven computational experiments demonstrate that this framework can reliably estimate the power of a ChIP-seq experiment at different sequencing depths based on pilot data. Furthermore, it provides an analytical approach for calculating the required depth for a targeted power while controlling the false discovery rate at a user-specified level. Hence, our results enable researchers to use their own or publicly available data for determining required sequencing depths of their ChIP-seq experiments and potentially make better use of the multiplexing functionality of the sequencers. Evaluation of power for multiple public ChIP-seq datasets indicate that, currently, typical ChIP-seq studies are powered well for detecting large fold changes of ChIP enrichment over the control sample, but they have considerably less power for detecting smaller fold changes.

Availability: Available at www.stat.wisc.edu/∼zuo/CSSP.

Contact:  keles@stat.wisc.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
GAGE-B: an evaluation of genome assemblers for bacterial organisms
Authors: Magoc Tanja , Pabinger Stephan , Canzar Stefan , Liu Xinyue , Su Qi , Puiu Daniela , Tallon Luke J. , Salzberg Steven L.
Published: May 2013

Motivation: A large and rapidly growing number of bacterial organisms have been sequenced by the newest sequencing technologies. Cheaper and faster sequencing technologies make it easy to generate very high coverage of bacterial genomes, but these advances mean that DNA preparation costs can exceed the cost of sequencing for small genomes. The need to contain costs often results in the creation of only a single sequencing library, which in turn introduces new challenges for genome assembly methods.

Results: We evaluated the ability of multiple genome assembly programs to assemble bacterial genomes from a single, deep-coverage library. For our comparison, we chose bacterial species spanning a wide range of GC content and measured the contiguity and accuracy of the resulting assemblies. We compared the assemblies produced by this very high-coverage, one-library strategy to the best assemblies created by two-library sequencing, and we found that remarkably good bacterial assemblies are possible with just one library. We also measured the effect of read length and depth of coverage on assembly quality and determined the values that provide the best results with current algorithms.

Contact:  salzberg@jhu.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Safety and tolerability of intensified, N‐terminal pro brain natriuretic peptide‐guided compared with standard medical therapy in elderly patients with congestive heart failure: results from TIME‐CHF
Authors: Sanders‐van Wijk Sandra , Muzzarelli Stefano , Neuhaus Michael , Kiencke Stephanie , Maeder Micha , Estlinbaum Werner , Tobler Daniel , Mayer Kurt , Erne Paul , Pfisterer Matthias E. , Brunner‐La Rocca Hans‐Peter ,   for the TIME‐CHF investigators
Published: May 2013

Aims

NT‐proBNP‐guided therapy results in intensification of medical heart failure (HF) therapy and is suggested to improve outcome. However, it is feared that an intensified, NT‐proBNP‐guided therapy carries a risk of adverse effects. Therefore, the safety and tolerability of NT‐proBNP‐guided therapy in the Trial of Intensified vs standard Medical therapy in Elderly patients with Congestive Heart Failure (TIME‐CHF) was assessed.

Methods and results

A total of 495 chronic HF patients, aged ≥60, with an LVEF ≤45%, NYHA class ≥II, randomized to NT‐proBNP‐guided or symptom‐guided therapy and ≥1 month follow‐up were included in the present safety analysis. All adverse events (AEs) were recorded during the 18‐month trial period. A total of 5212 AEs were noted, 433 of them serious. NT‐proBNP‐guided therapy led to a higher up‐titration of HF medication and was well tolerated, with a dropout rate (12% vs. 11%, P = 1.0) and AE profile [number of AEs/patient‐year 4.7 (2.8–9.4) vs. 5.4 (2.7–11.4), P = 0.69; number of severe AEs/patient‐year 0.7 (0–2.7) vs. 1.3 (0–3.9), P = 0.21] similar to that of symptom‐guided therapy, although most subjects in both treatment groups (96% vs. 95%, P = 0.55) experienced at least one AE. Age and number of co‐morbidities were associated with AEs and interacted with the safety profile of NT‐proBNP‐guided therapy: positive effects were more frequent in younger and less co‐morbid patients whereas potential negative effects—although small and related to non‐severe AEs only—were only seen in the older and more co‐morbid patients.

Conclusions

NT‐proBNP‐guided therapy is safe in elderly and highly co‐morbid HF patients.

Trial registration

ISRCTN43596477
Natural regulatory T cells are resistant to calcium release-activated calcium (CRAC/ORAI) channel inhibition
Authors: Jin Shu , Chin Jayne , Kitson Christopher , Woods John , Majmudar Rupal , Carvajal Valerie , Allard John , DeMartino Julie , Narula Satwant , Thomas-Karyat Dori A.
Published: May 2013

Organ transplant patients are often treated with immunosuppressants, such as the calcineurin phosphatase inhibitor, cyclosporin A, to block T cell-mediated graft rejection. The calcium release-activated calcium (CRAC/ORAI) channels, which act upstream of calcineurin, are essential for calcium entry and CD4+ T-cell activation. Although cyclosporine A has also been shown to inhibit FoxP3+ Tregs both in vitro and in vivo, the role of ORAI channel inhibition in natural Tregs (nTregs) or inducible Tregs (iTregs) has not been investigated. We found that, despite inhibition of calcium influx through the ORAI channels, ORAI channel inhibitors were unable to repress FoxP3 expression in mouse and human nTregs, whereas FoxP3 expression was inhibited in iTregs. In contrast, cyclosporin A inhibited FoxP3 expression in both nTregs and iTregs. We also generated mice with a T cell-specific, conditional knockout of ORAI1 and found that the mice have normal nTreg development and suppressive activity. Moreover, iTregs derived from ORAI1 conditional knockout mice develop normally and are still susceptible to ORAI channel inhibition. Our data indicate that unlike CD4+ T cells and iTregs, nTregs are resistant to ORAI-mediated inhibition. Targeting ORAI channels potentially offers a novel way to inhibit pathologic T cells, while sparing nTreg-mediated tolerance.
Actinopolyspora

mzabensis sp. nov., a halophilic actinomycete isolated from an Algerian Saharan soil
Authors: Meklat Atika , Bouras Noureddine , Zitouni Abdelghani , Mathieu Florence , Lebrihi Ahmed , Schumann Peter , Spröer Cathrin , Klenk Hans-Peter , Sabaou Nasserdine
Published: May 2013

A halophilic actinomycete strain, designated H55T, was isolated from Saharan soil sampled in the Mzab region (Ghardaïa, southern Algeria) and was characterized in a taxonomic study using a polyphasic approach. The cell wall was determined to contain meso-diaminopimelic acid and the characteristic whole-cell sugars were arabinose and galactose. The predominant menaquinones were found to be MK-10(H4) and MK-9(H4). The predominant cellular fatty acids were determined to be anteiso-C17 : 0, iso-C16 : 0 and iso-C15 : 0. The diagnostic phospholipid detected was phosphatidylcholine. The morphological and chemotaxonomic characteristics of the strain were consistent with those of members of the genus

Actinopolyspora

, and 16S rRNA gene sequence analysis confirmed that strain H55T was a member of this genus. DNA–DNA hybridization values between strain H55T and the type strains of the nearest species of the genus

Actinopolyspora

,

Actinopolyspora erythraea

and

A. alba

, were clearly below the 70 % threshold. The genotypic and phenotypic data showed that the organism represents a novel species of the genus

Actinopolyspora

, for which the name

Actinopolyspora

mzabensis sp. nov. is proposed, with the type strain H55T ( = DSM 45460T = CCUG 62965T).