bluuebunny/crossref_metadata_2025 huggingface dataset:
Fast low‐angle shot diffusion tensor imaging with stimulated echo encoding in the muscle of rabbit shank
Authors: Hiepe Patrick , Herrmann Karl‐Heinz , Güllmar Daniel , Ros Christian , Siebert Tobias , Blickhan Reinhard , Hahn Klaus , Reichenbach Jürgen R.
Published: October 2013

In the past, spin‐echo (SE) echo planar imaging(EPI)‐based diffusion tensor imaging (DTI) has been widely used to study the fiber structure of skeletal muscles in vivo. However, this sequence has several shortcomings when measuring restricted diffusion in small animals, such as its sensitivity to susceptibility‐related distortions and a relatively short applicable diffusion time. To address these limitations, in the current work, a stimulated echo acquisition mode (STEAM) MRI technique, in combination with fast low‐angle shot (FLASH) readout (turbo‐STEAM MRI), was implemented and adjusted for DTI in skeletal muscles. Signal preparation using stimulated echoes enables longer effective diffusion times, and thus the detection of restricted diffusion within muscular tissue with intracellular distances up to 100 µm. Furthermore, it has a reduced penalty for fast T2 muscle signal decay, but at the expense of 50% signal loss compared with a SE preparation. Turbo‐STEAM MRI facilitates high‐resolution DTI of skeletal muscle without introducing susceptibility‐related distortions. To demonstrate its applicability, we carried out rabbit in vivo measurements on a human whole‐body 3 T scanner. DTI parameters of the shank muscles were extracted, including the apparent diffusion coefficient, fractional anisotropy, eigenvalues and eigenvectors. Eigenvectors were used to calculate maps of structural parameters, such as the planar index and the polar coordinates θ and ϕ of the largest eigenvector. These parameters were compared between three muscles. θ and ϕ showed clear differences between the three muscles, reflecting different pennation angles of the underlying fiber structures. Fiber tractography was performed to visualize and analyze the architecture of skeletal pennate muscles. Optimization of tracking parameters and utilization of T2‐weighted images for improved muscle boundary detection enabled the determination of additional parameters, such as the mean fiber length. The presented results support the applicability of turbo‐STEAM MRI as a promising method for quantitative DTI analysis and fiber tractography in skeletal muscles. Copyright © 2013 John Wiley & Sons, Ltd.
Whole exome sequencing identifies variation in CYB5A and RNF10 associated with adiposity and type 2 diabetes
Authors: Huang Ke , Nair Anup K. , Muller Yunhua Li , Piaggi Paolo , Bian Li , del Rosario Melissa , Knowler William C. , Kobes Sayuko , Hanson Robert L. , Bogardus Clifton , Baier Leslie J.
Published: October 2013

Objective

Few coding variants in genes associated with type 2 diabetes (T2D) have been identified, and the underlying physiologic mechanisms whereby susceptibility genes influence T2D risk are often unknown. The objective of this study was to identify coding variation that increases risk for T2D via an effect on a pre‐diabetic trait.

Methods

Whole exome sequencing was done in 177 Pima Indians. Selected variants (N = 345) were genotyped in 555 subjects characterized for body fatness, glucose disposal rates during a clamp, acute insulin response to glucose, and 2‐h plasma glucose concentrations during an OGTT, and were also genotyped in up to 5,880 subjects with longitudinal measures of BMI. Variants associated with quantitative traits were assessed for association with T2D in 7,667 subjects.

Results

rs7238987 in CYB5A associated with body fatness (P = 7.0 × 10−6). This SNP and a novel SNP in RNF10 also associated with maximum recorded BMI (P = 6.2 × 10−7 and P = 7.2 × 10−4) and maximum childhood BMI z‐score (P = 5.9 × 10−4 and P = 8.5 × 10−7). The BMI increasing alleles increased the risk for T2D (P = 0.01; OR = 1.13 [1.03‐1.24] and 9.5 × 10−3; OR = 1.49 [1.10‐2.02]).

Conclusions

CYB5A, which has a role in stearyl‐CoA‐desaturase activity, and RNF10, with an unknown role in weight regulating pathways, associated with adiposity and nominally increased the risk for T2D in American Indians.
Influence of nano‐organomontmorillonite on the viscoelasticity of the poly(trimethylene terephthalate)/glass fiber/organomontmorillonite hybrid nanocomposites materials
Authors: Liu Feng , Li Na , Bai Yuqing , Run Mingtao
Published: October 2013

The influences of organically modified montmorillonite (OMMT) on the viscoelasticity of poly(trimethylene terephthalate)/glass fiber/OMMT (PTT/GF/OMMT) hybrid nanocomposite materials at liquid, elastic and glassy states, respectively, were investigated by using the rotational rheometer and dynamic mechanical analyzer (DMA). The viscoelasticity results suggest that OMMT has many important influences on the structure, modulus and toughness of the hybrid nanocomposite materials. At melton state, the shear‐thinning phenomena of the hybrid composite melts become remarkable with increasing OMMT content. At low frequency, the shear storage modulus (G′) and shear loss modulus (G″) of the melts increase with increasing OMMT content. The melt's elastic response increases by OMMT, and OMMT improves the creep resistance of the melts; in addition, the stress relaxation of the hybrid composite melts become slow with increasing OMMT content, and the stress leavings becomes much higher with increasing OMMT content. At glassy state, the storage modulus of the hybrid nanocomposites increases with increasing OMMT content, while the materials' loss modulus increases first and then decreases with increasing OMMT content; therefore, OMMT nanosheets have reinforcement effect on the composites, and it also has definite toughening effect on the hybrid composite when the OMMT content is no >2 wt%. At rubbery state, the hybrid composites show lower decreasing storage modulus but have lower cold‐crystallization ability than that of pure PTT and PTT/GF composite. POLYM. COMPOS., 35:795–805, 2014. © 2013 Society of Plastics Engineers
Facile synthesis of magnetic metal organic frameworks for the enrichment of low‐abundance peptides for MALDI‐TOF MS analysis
Authors: Zhao Man , Deng Chunhui , Zhang Xiangmin , Yang Pengyuan
Published: October 2013

In this work, core‐shell magnetic metal organic framework (MOF) microspheres were successfully synthesized by coating magnetite particles with mercaptoacetic acid and subsequent reactions with ethanol solutions of Cu(OAc)2 and benzene‐1,3,5‐tricarboxylic acid (designated as H3btc) alternately. The resulting Fe3O4@[Cu3(btc)2] possess strong magnetic responsiveness. We applied the novel nanocomposites in the enrichment of low‐concentration standard peptides, peptides in MYO and BSA tryptic digests and in human urine in combination with MALDI‐TOF MS analysis for the first time. In addition, the Cu3(btc)2 MOF shells exhibit strong affinity to peptides, thus providing a rapid and convenient approach to the concentration of low‐abundance peptides. Notably, peptides at an extremely low concentration of 10 pM could be detected by MALDI‐TOF MS after enrichment with the magnetic MOF composites. In brief, the facile synthesis and efficient enrichment process of the Fe3O4@[Cu3(btc)2] microspheres make them promising candidates for the isolation of peptides in even complex biological environments.
Piperlongumine inhibits NF‐κB activity and attenuates aggressive growth characteristics of prostate cancer cells
Authors: Ginzburg Serge , Golovine Konstantin V. , Makhov Petr B. , Uzzo Robert G. , Kutikov Alexander , Kolenko Vladimir M.
Published: October 2013

BACKGROUND

Elevated NF‐κB activity has been previously demonstrated in prostate cancer cell lines as hormone‐independent or metastatic characteristics develop. We look at the effects of piperlongumine (PL), a biologically active alkaloid/amide present in piper longum plant, on the NF‐κB pathway in androgen‐independent prostate cancer cells.

METHODS

NF‐κB activity was evaluated using Luciferase reporter assays and Western blot analysis of p50 and p65 nuclear translocation. IL‐6, IL‐8, and MMP‐9 levels were assessed using ELISA. Cellular adhesion and invasiveness properties of prostate cancer cells treated with PL were also assessed.

RESULTS

NF‐κB DNA‐binding activity was directly down‐regulated with increasing concentrations of PL, along with decreased nuclear translocation of p50 and p65 subunits. Expression of IL‐6, IL‐8, MMP‐9, and ICAM‐1 was attenuated, and a decrease of cell‐to‐matrix adhesion and invasiveness properties of prostate cancer cells were observed.

CONCLUSIONS

PL‐mediated inhibition of NF‐κB activity decreases aggressive growth characteristics of prostate cancer cells in vitro. Prostate 74:177–186, 2014. © 2013 Wiley Periodicals, Inc.
Early over‐expression of GRP receptors in prostatic carcinogenesis
Authors: Körner Meike , Waser Beatrice , Rehmann Ruth , Reubi Jean Claude
Published: October 2013

BACKGROUND

The GRP receptor shows high over‐expression in prostatic adenocarcinoma and high grade PIN, but low expression in normal prostate glands. This represents the molecular basis for GRP receptor imaging of prostate cancer with radioactive compounds. However, a focal, high density GRP receptor expression can be observed in hitherto uncharacterized prostate glands.

METHODS

GRP receptors were quantitatively measured with in vitro receptor autoradiography using 125I‐Tyr4‐bombesin in samples from 115 prostates. On successive tissue sections, 125I‐Tyr4‐bombesin autoradiography was compared with H&E staining and MIB‐1 and 34βE12 immunohistochemistry.

RESULTS

On one hand, it was confirmed that GRP receptors were expressed in adenocarcinoma and high grade PIN in high density and high incidence (77% and 73%, respectively), but in normal prostate glands in low density and low frequency (18%). On the other hand, a novel and intriguing observation was the existence of focal non‐invasive prostate glands with high GRP receptor density, characterized by low grade nuclear atypia and increased proliferation, compatible with lower grade PIN. There was a significant GRP receptor density gradient (P ≤ 0.005), increasing from normal prostate glands (mean relative optical density, ROD, of 125I‐Tyr4‐bombesin binding: 0.17) over atypical glands without increased MIB‐1 labeling (0.28) and atypical glands with increased MIB‐1 expression (0.44) to high grade PIN and adenocarcinoma (0.64 and 0.58, respectively).

CONCLUSIONS

GRP receptor over‐expression may be a novel, specific marker of early prostatic neoplastic transformation, arising in low grade PIN, and progressively increasing during malignant progression. This should be considered when interpreting in vivo GRP receptor imaging in males. Prostate 74:217–224, 2014. © 2013 Wiley Periodicals, Inc.
Semiglobal stabilization of saturated linear systems via multiple parametric Lyapunov equations
Authors: Wang Qingling , Yu Changbin , Gao Huijun
Published: October 2013

This paper investigates the problem of semiglobal stabilization with guaranteed flexible pole placement for saturated linear systems. To retain the advantages of the parametric Lyapunov equation, matrix‐partitioning idea is used to derive a new pole shift lemma. Starting from system matrix transformations, a recursive algorithm is proposed to shift every eigenvalue of a linear system separately without mode decomposition in each step. A new method introducing various parameters to every Lyapunov equation in each step is presented. As an application, the semiglobal stabilization with guaranteed flexible pole placement for saturated linear systems can be achieved by this method. Finally, its effectiveness and advantages are demonstrated via a simulation example. Copyright © 2013 John Wiley & Sons, Ltd.
Twice‐weighted multiple interval estimation of a marginal structural model to analyze cost‐effectiveness
Authors: Goldfeld K.S.
Published: October 2013

Cost‐effectiveness analysis is an important tool that can be applied to the evaluation of a health treatment or policy. When the observed costs and outcomes result from a nonrandomized treatment, making causal inference about the effects of the treatment requires special care. The challenges are compounded when the observation period is truncated for some of the study subjects. This paper presents a method of unbiased estimation of cost‐effectiveness using observational study data that is not fully observed. The method—twice‐weighted multiple interval estimation of a marginal structural model—was developed in order to analyze the cost‐effectiveness of treatment protocols for advanced dementia residents living nursing homes when they become acutely ill. A key feature of this estimation approach is that it facilitates a sensitivity analysis that identifies the potential effects of unmeasured confounding on the conclusions concerning cost‐effectiveness. Copyright © 2013 John Wiley & Sons, Ltd.
Cognitive enhancement
Authors: Farah Martha J. , Smith M. Elizabeth , Ilieva Irena , Hamilton Roy H.
Published: October 2013

Cognitive enhancement refers to the improvement of cognitive ability in normal healthy individuals. In this article, we focus on the use of pharmaceutical agents and brain stimulation for cognitive enhancement, reviewing the most common methods of pharmacologic and electronic cognitive enhancement, and the mechanisms by which they are believed to work, the effectiveness of these methods and their prevalence. We note the many gaps in our knowledge of these matters, including open questions about the size, reliability and nature of the enhancing effects, and we conclude with recommendations for further research. WIREs Cogn Sci 2014, 5:95–103. doi: 10.1002/wcs.1250

This article is categorized under:

Psychology > Brain Function and Dysfunction

Neuroscience > Cognition
Synthesis, Characterization and Biological Evaluation of Two Silver(I) trans‐Cinnamate Complexes as Urease Inhibitors
Authors: Li Xia , Wang Yan , Li Yuguang , Gou Yi , Wang Qiang
Published: October 2013

Two new silver(I) trans‐cinnamates, namely [Ag(2‐cca)(H2O)]2 (1) and [Ag(4‐cca)]n (2) (2‐ccaH = 2‐chlorocinnamic acid and 4‐ccaH = 4‐chlorocinnamic acid), were synthesized and structurally characterized. Single crystal X‐ray studies reveal that each silver(I) atom in 1 is two‐coordinate by a 2‐chlorocinnamate ligand and one water molecule to afford a discrete centrosymmetric dimer with the ligand‐unsupported Ag···Ag interactions (3.218(4) Å), while a pair of symmetry‐related silver(I) atoms in 2 are clamped by two μ2‐η1:η1 4‐chlorocinnamate ligands to yield a binuclear silver(I) moiety incorporating a ligand‐supported Ag···Ag interaction (2.819(5) Å). Both complexes 1 and 2 show potent urease inhibitory activities with the respective IC50 values of 0.66 and 1.10 μM.
Antenna showers with one-loop matrix elements
Authors: Hartgring L. , Laenen E. , Skands P.
Published: October 2013

Abstract

We consider the probability for a colour-singlet
$ q\overline{q} $
pair to emit a gluon, in strongly and smoothly ordered antenna showers. We expand to second order in α
s and compare to the second-order QCD matrix elements for Z → 3 jets, neglecting terms suppressed by
$ {1 \left/ {{N_C^2}} \right.} $
. We give a prescription that corrects the shower to the matrix-element result at this order for both soft and hard emissions, thereby explicitly reducing its dependence on evolution- and renormalization-scale choices. We confirm that the choice of p
⊥ for both of these scales absorbs all logarithms through
$ \mathcal{O}\left( {\alpha_s^2} \right) $
, and contrast this with various alternatives. We include these corrections in the vincia shower generator and study the impact on LEP event-shape and fragmentation observables. An uncertainty estimate is provided for each event, in the form of a vector of alternative weights.
Patientenregistrierung im Massenanfall
Authors: Donner A. , Adler C.
Published: October 2013

Hintergrund

Die effiziente Bewältigung eines Massenanfalls von Verletzten und Erkrankten erfordert sowohl gut abgestimmte und geübte Vorgehensweisen der Einsatzkräfte als auch reibungslosen Informationsaustausch zwischen allen Beteiligten und durch alle Führungsebenen. Bestehende Systeme für die Patientensichtung, -registrierung und Rettungsmitteldisposition basieren auf händisch gepflegten Listen, die sprachlich per Funk und Telefon abgeglichen werden müssen. Elektronische Hilfsmittel können Informationsflüsse deutlich beschleunigen. Aus dem komplexen, nicht planbaren Einsatzgeschehen ergeben sich vielfältige Anforderungen an die Technik und an ein zukünftiges elektronisches Dokumentationssystem, die zu berücksichtigen sind und die sich aus der Arbeit von mehreren Forschungsprojekten in den letzten Jahren entwickelt haben.

Schlussfolgerung

Eine bundesweite Harmonisierung von Vorgehensweisen und Schnittstellen ist notwendig, sodass reibungslose überregionale Zusammenarbeit möglich ist.
Coming of age on the streets: Survival sex among homeless young women in Hollywood
Authors: Warf Curren W. , Clark Leslie F. , Desai Mona , Rabinovitz Susan J. , Agahi Golnaz , Calvo Richard , Hoffmann Jenny
Published: October 2013

This study examined childhood physical or sexual abuse, involvement in dependency or delinquency systems, psychiatric hospitalization, and suicide as possible risk factors for survival sex among homeless young women. Homeless young women were found to have similarly high rates of childhood sexual abuse, dependency and delinquency systems involvement, and psychiatric hospitalization. Homeless young women involved in survival sex disclosed higher rates of attempted suicide and reported marginally higher rates of childhood physical abuse. Analysis of qualitative data showed that those engaged in survival sex were motivated primarily by desperation to meet basic needs including a place to stay, food and money, and one third mentioned that peers commonly were influential in decisions to engage in survival sex. Others were influenced by coercion (10%) or pursuit of drugs (10%). Young women engaged in survival sex generally experienced regret and shame about their experience.
Body-rock or lift-off in flow
Authors: Smith Frank T. , Wilson Phillip L.
Published: October 2013

Conditions are investigated under which a body lying at rest or rocking on a solid horizontal surface can be removed from the surface by hydrodynamic forces or instead continues rocking. The investigation is motivated by recent observations on Martian dust movement as well as other small- and large-scale applications. The nonlinear theory of fluid–body interaction here has unsteady motion of an inviscid fluid interacting with a moving thin body. Various shapes of body are addressed together with a range of initial conditions. The relevant parameter space is found to be subtle as evolution and shape play substantial roles coupled with scaled mass and gravity effects. Lift-off of the body from the surface generally cannot occur without fluid flow but it can occur either immediately or within a finite time once the fluid flow starts up: parameters for this are found and comparisons are made with Martian observations.
Multi-clone infections and the impact of intraspecific competition on trematode colonies with a division of labour
Authors: LLOYD MELANIE M. , POULIN ROBERT
Published: October 2013

A division of labour occurs in colonies of the trematodePhilophthalmussp. within their first intermediate hosts. Two castes exist: one which reproduces and one which does not reproduce. It has been hypothesized that the benefit of the non-reproductive caste is in competitive interactions. Evidence for this from past experiments withPhilophthalmussp. colonies has been contradictory: the non-reproductive caste appears to benefit the colony in some way but not necessarily by combating interspecific competitors. The aims of this study were to consider intraspecific competition as a possible cause of the division of labour inPhilophthalmussp. colonies. Results show that mixed genotype infections occur inPhilophthalmussp. infected hosts and thus intraspecific competition is likely. Furthermore, the total number of individuals per colony is reduced in mixed genotype infections, indicating that intraspecific competition reduces colony fitness. However, the results do not indicate that the division of labour inPhilophthalmussp. plays a role in competitive interactions as the ratio of small, non-reproductive to large, reproductive individuals is unaffected by the presence of intraspecific competition. This is the first study to identify and quantify intraspecific competition inPhilophthalmussp., and to assess its selective role in this species’ division of labour.
Association of regional body fat with metabolic risks in Chinese women
Authors: Fu Xiaohua , Song Aihua , Zhou Yunjie , Ma Xiaoguang , Jiao Jingjing , Yang Min , Zhu Shankuan
Published: October 2013

Objective

To investigate the association of regional fat depots with metabolic risk factors in Chinese women.

Design

Total and regional fat depots including android fat and gynoid fat were measured by dual-energy X-ray absorptiometry. Central fat distribution was defined as android:gynoid fat ratio. Metabolic risk factors were defined as elevated TAG, reduced HDL-cholesterol, elevated blood pressure and elevated fasting plasma glucose. Logistic regression analyses were performed to examine the associations of regional fat depots with metabolic risk factors. The odds ratios of metabolic risks were further calculated according to tertiles of android fat and gynoid fat.

Setting

Participants were recruited from a community-based cross-sectional study. Face-to-face questionnaires, anthropometric and dual-energy X-ray absorptiometry measures were conducted.

Subjects

Chinese women (n 609) aged 18–79 years.

Results

Android fat and android:gynoid fat ratio were associated with significantly increased odds (OR = 1·4–3·7; P < 0·01) for almost all risk factors, whereas gynoid fat was independently associated with significantly decreased odds (OR = 0·3–0·6; P < 0·01). The inverse associations of gynoid fat with metabolic risk factors remained after adjusting for android fat. Even if their android fat level was in high, women in the highest tertile of gynoid fat had lower odds of having at least two metabolic risk factors compared with women in the lowest gynoid fat tertile (P for trend < 0·01).

Conclusions

There were opposite associations of android and gynoid fat with metabolic risks in Chinese women. Gynoid fat rather than android fat might be a more important inclusion in metabolic disease risk evaluation in female Asians.
Interfacial Properties of Three Different Bioactive Dentine Substitutes
Authors: Gjorgievska Elizabeta S. , Nicholson John W. , Apostolska Sonja M. , Coleman Nichola J. , Booth Samantha E. , Slipper Ian J. , Mladenov Mitko I.
Published: October 2013

Three different bioactive materials suitable as dentine substitutes in tooth repair have been studied: glass-ionomer cement, particulate bioglass, and calcium-silicate cement. On 15 permanent human molars, Class V cavities were prepared and the bottom of each cavity was de-mineralized by an artificial caries gel. After the de-mineralization, the teeth were restored with: (1) Bioglass®45S5 and ChemFil® Superior; (2) Biodentine™ and ChemFil® Superior; and (3) ChemFil® Superior for a complete repair. The teeth were stored for 6 weeks in artificial saliva, then cut in half along the longitudinal axis: the first half was imaged in a scanning electron microscope (SEM) and the other half was embedded in resin and analyzed by SEM using energy-dispersive X-ray analysis. The glass-ionomer and the bioglass underwent ion exchange with the surrounding tooth tissue, confirming their bioactivity. However, the particle size of the bioglass meant that cavity adaptation was poor. It is concluded that smaller particle size bioglasses may give more acceptable results. In contrast, both the glass-ionomer and the calcium-silicate cements performed well as dentine substitutes. The glass-ionomer showed ion exchange properties, whereas the calcium silicate gave an excellent seal resulting from its micromechanical attachment.
A Simple and Efficient Method to Observe Internal Structures of Helminths by Scanning Electron Microscopy
Authors: Adnet Fernando Antônio de O. , Gonçalves Júlia P. , de Souza Wanderley , Attias Márcia
Published: October 2013

Morphological studies of helminths by scanning electron microscopy are generally limited to the external topography of the organisms. In this work, we present a simple technique using ethanol as a cryoprotectant without postfixation in osmium tetroxide that allows for observation of the inner organization of helminths and preserves cellular structures. We tested the technique in three helminths: Echinostoma paraensei, Cruzia tentaculata, and Hassalstrongylus epsilon. The results show that this technique could potentially be applied to study the morphology, ultrastructure, and taxonomy of helminths.
Effect of the serotonin transporter gene and of environment on the continuity of anxiety and depression traits throughout adolescence
Authors: Nobile M. , Greco A. , Perna G. , Colombo P. , Bianchi V. , Bellina M. , Giorda R. , Monzani D. , Carlet O. , Griez E. , Molteni M.
Published: October 2013

Aims.

Many studies of various stress reactive phenotypes suggest that 5-HTTLPR short allele carriers (S-carriers) are characterised by the stable trait of negative affectivity that is converted to psychopathology only under conditions of stress. In this study, we examined the moderating role of the 5-HTTLPR on the relationship between two objective chronic risk factors, i.e. socioeconomic status (SES) and family structure, and internalising symptoms across adolescence.

Methods.

A multigroup path analysis was employed in a general adolescent population sample of a 5-year follow-up study.

Results.

Internalising problems were significantly more stable in theS-carriers. The focus on the main dimensions of internalising problems, i.e. anxiety and depression, revealed two different developmental patterns. In theS-carriers Anxiety problems seemed to be more stable and to predict a possible evolution towards the development of Depressive problems. In the long allele homozygotes (LL-subjects) the anxiety trait was significantly less stable, and, in late-adolescence, seemed to be significantly predicted by SES, suggesting a possible gene–environment interaction (G × E). Family structure seemed to play a role in a G × E perspective only until early-adolescence, while during late-adolescence SES seemed to play a pivotal role in interaction with 5-HTTLPR, with the S-allele playing a protective role.

Conclusions.

Future models of the developmental link between environmental adversities and internalising behaviour therefore need to consider that the effect of G × E interaction, may be associated with internalising behaviour via different mechanisms during different time frames and that shifts in the strength of this effect should be expected across development.
PARP1 orchestrates variant histone exchange in signal‐mediated transcriptional activation
Authors: O'Donnell Amanda , Yang Shen‐Hsi , Sharrocks Andrew D
Published: October 2013

Transcriptional activation is accompanied by multiple molecular events that remodel the local chromatin environment in promoter regions. These molecular events are often orchestrated in response to the activation of signalling pathways, as exemplified by the response of immediate early genes such as FOS to ERK MAP kinase signalling. Here, we demonstrate that inducible NFI recruitment permits PARP1 binding to the FOS promoter by a mutually reinforcing loop. PARP1 and its poly(ADP‐ribosyl)ation activity are required for maintaining FOS activation kinetics. We also show that the histone variant H2A.Z associates with the FOS promoter and acts in a transcription‐suppressive manner. However, in response to ERK pathway signalling, H2A.Z is replaced by H2A; PARP1 activity is required to promote this exchange. Thus, our work has revealed an additional facet of PARP1 function in promoting dynamic remodelling of promoter‐associated nucleosomes to allow transcriptional activation in response to cellular signalling.
Co‐expression of S. Typhi GroEL and IL‐22 gene augments immune responses against Salmonella infection
Authors: Kaur Gurpreet , STS Chitradevi , Nimker Charu , Singh Mrinalini , Saraswat Deepika , Saxena Shweta , Bansal Anju
Published: October 2013

Recombinant DNA vaccines represent a novel method for generating in situ expression of vaccine antigens. Intramuscular injections of naked DNA are able to elicit potent humoral and cellular immune responses but still numerous factors limit the immunogenicity of DNA vaccines. Co‐expression of cytokines with antigen encoding genes in DNA vectors can improve the immune responses and modify Th1/Th2 balance. In this study, the immunomodulatory effect of Interleukin 22 (IL‐22) as an adjuvant was studied by DNA vaccination with S. Typhi Heat shock protein 60 (HSP60/GroEL) in mice. Further, DNA construct of IL‐22 gene fused with GroEL was developed and immunization studies were carried out in mice. DNA vaccination with GroEL alone stimulated humoral and cell‐mediated immune responses. Co‐immunization (IL‐22+GroEL) further resulted in increase in T‐cell proliferative responses, antibody titres (IgG, IgG1, IgG2a) and secretion of IFNγ (Th1), IL‐1β and Th2 (IL‐4, IL‐6) cytokines. Co‐expression (IL‐22‐GroEL DNA) also promoted antibody titres and cytokine levels were significantly higher as compared to co‐immunized group. A reduction in bacterial load in spleen, liver and intestine was seen in all the immunized groups as compared to control, with least organ burden in fusion DNA construct group (co‐expression). Improved protective efficacy (90%) against lethal challenge by Salmonella was observed with IL‐22‐GroEL co‐expressing DNA vector as compared with plasmid encoding GroEL only (50–60%) or co‐immunization group (75–80%). This study thus shows that co‐expression of IL‐22 and GroEL genes enhances the immune responses and protective efficacy, circumventing the need of any adjuvant.
Experimental evidence suggests the existence of evolutionary conserved global operation principles governing microbial metabolism
Authors: Bordel Sergio
Published: October 2013

The search for optimization principles in microbial metabolism, such as biomass or ATP yields or growth rate optimization, has attracted substantial research efforts in the recent years. Here we use the results of C13 labeling experiments together with genome scale metabolic networks of S cerevisiae and E coli in order to assess if there are relationships between systemic variables that are present in both organisms. Strong correlations between the total flux per unit of substrate and the ATP turnover rate per unit of substrate and between the growth rate divided by the total flux and the total flux per unit of substrate were observed for both organisms. We also observed that the common assumption of biomass yield optimization is not consistent with the experiments.
Characterization of the recombinant Candida albicans β-1,2-mannosyltransferase that initiates the β-mannosylation of cell wall phosphopeptidomannan
Authors: Fabre Emeline , Sfihi-Loualia Ghenima , Pourcelot Marilyne , Coddeville Bernadette , Krzewinski Frédéric , Bouckaert Julie , Maes Emmanuel , Hurtaux Thomas , Dubois Romaric , Fradin Chantal , Mallet Jean-Maurice , Poulain Daniel , Delplace Florence , Guerardel Yann
Published: October 2013

The presence of β-mannosides in their cell walls confers specific features on the pathogenic yeasts Candida albicans and Candida glabrata compared with non-pathogenic yeasts. In the present study, we investigated the enzymatic properties of Bmt1 (β-mannosyltransferase 1), a member of the recently identified β-mannosyltransferase family, from C. albicans. A recombinant soluble enzyme lacking the N-terminal region was expressed as a secreted protein from the methylotrophic yeast Pichia pastoris. In parallel, functionalized natural oligosaccharides isolated from Saccharomyces cerevisiae and a C. albicans mutant strain, as well as synthetic α-oligomannosides, were prepared and used as potential acceptor substrates. Bmt1p preferentially utilizes substrates containing linear chains of α-1,2-linked mannotriose or mannotetraose. The recombinant enzyme consecuti-vely transfers two mannosyl units on to these acceptors, leading to the production of α-mannosidase-resistant oligomannosides. NMR experiments further confirmed the presence of a terminal βMan (β-1,2-linked mannose) unit in the first enzyme product. In the future, a better understanding of specific β-1,2-mannosyltransferase molecular requirements will help the design of new potential antifungal drugs.
Supporting Positive Employment Outcomes for Individuals With Autism Who Use AAC
Authors: McNaughton David , Richardson Laura
Published: October 2013

Employment is a valued transition outcome for many individuals with autism who use augmentative and alternative communication (AAC). As for anyone, a successful employment experience will require careful planning during the school years and the provision of appropriate supports in the workplace. Consideration of the individual's skills, preferences, and needed supports will play a critical role in ensuring positive workplace participation. This article will describe key strategies for supporting positive outcomes for individuals with autism who use AAC and illustrate these approaches with case examples.
Curve stripping and nonlinear fitting of polyexponential functions to data using a microcomputer
Authors: Kirkup L. , Sutherland J.
Published: October 2013

An iterative curve stripping and optimization program for fitting functions consisting of a sum of exponential terms to data using a microcomputer is presented. Examples of program output are given for biexponential and triexponential functions fitted to simulated data with Gaussian noise added. Advantages of using a microcomputer as an alternative to mini- and mainframe computers for such a purpose are identified. Application of the program to the determination of excited-state lifetime measurements in sintered cadmium sulfide is described.
Application of Lanczos and conjugate gradient methods to a class of computational problems in physics
Authors: Vasavada Kashyap V. , Freed Jack H.
Published: October 2013

It is shown that the equivalence of the Lanczos and the conjugate gradient algorithms can be used to give a very powerful method to study linear systems in which complex symmetric matrices arise. This method is illustrated for electron spin resonance calculations, but is applicable to a wide class of problems in physics and engineering.
Spinor software tools in C++
Authors: Dreitlein Joseph F. , Sauer Jon R.
Published: October 2013

A first step is taken in the creation of a flexible tool kit for the exploration of physics problems requiring elaborate and efficient mathematical manipulations. Data abstraction features of C++ are used to create the object Matrix. Code for the manipulation of spinors and the group SL (2,C) is given as a simple example of object-oriented programming. A problem in relativistic kinematics is briefly treated as an example of the use of the spinor toolkit.
A Chebyshev/radiation function pseudospectral method for wave scattering
Authors: Boyd John P.
Published: October 2013

Wave scattering from a potential well or barrier cannot be solved via a standard pseudospectral method. The reason is that none of the usual infinite interval basis sets can model the incoming and outgoing waves. In this article, it is shown that by constructing special ‘‘radiation functions’’ the transmission and reflection coefficients may be computed with exponential accuracy. This problem is ideally suited to pseudospectral methods because either the reflection or transmission coefficient is an exponential function of the wavenumber k. For k≫1, the overall wave field must be computed to many decimal places of accuracy to calculate the exponentially small coefficient with any precision at all.
Synthesis, Dye Encapsulation, and Highly Efficient Colouring Application of Amphiphilic Hyperbranched Polymers
Authors: Weng Zhulin , Zheng Yaochen , Tang Aijin , Gao Chao
Published: October 2013

A novel kind of amphiphilic hyperbranched polymer (AHP), poly(2-(dimethylamino)ethyl methacrylate)-co-polystyrene (HPTAM-co-PS), was synthesized via the combination of reversible addition–fragmentation chain-transfer polymerization and self-condensing vinyl polymerization (RAFT-SCVP). HPTAM-co-PS was functionalized via the highly efficient Menschutkin click reaction, resulting in hyperbranched poly(propargyl quaternary ammonium methacrylate)-co-polystyrene (HPPrAM-co-PS) with a hydrophilic quaternary ammonium salt core and hydrophobic PS shell. The average numbers of dye molecules trapped by each molecule of HPPrAM-co-PS (24.2 kDa) were 24.1 for methyl orange (MO), 22.0 for fluorescein sodium (FS), 24.2 for rose bengal (RB), and 238.4 for Congo red (CR). The polymer–dye complexes show excellent colouring effects for both PS and poly(styrene-b-butadiene-b-styrene) (SBS) membranes; the colour of the membrane containing AHP is very stable and uniform. Our work opens an avenue for the design of efficient dye-colouring additives and for the application of hyperbranched polymers in the field of polymer colouring.
Environmental assessment of erosion following prescribed burning in the Mount Lofty Ranges, Australia
Authors: Morris Rowena H. , Bradstock Ross A. , Dragovich Deirdre , Henderson Meredith K. , Penman Trent D. , Ostendorf Bertram
Published: October 2013

Erosion following fire has the potential to affect water quality, alter soil profiles and detrimentally affect human infrastructure. There is a clear need for environmental assessments to have regard for erosion concerns from prescribed burning. This study focussed on 10 prescribed burns conducted in the Southern Mount Lofty Ranges. Generalised additive modelling was used to determine the main significant environmental variables influencing the presence of sediment movement at 505 field-assessed sites. Sediment movement after the 10 prescribed burns was minor. Fire severity was a highly significant environmental determinant for the presence of sediment movement after prescribed burning. To predict erosion concerns, a suite of environmental variables is more reliable than focusing solely on slope steepness, as occurred before this study. These results indicate that erosion assessments need to consider a range of environmental variables to assess potential erosion and that land managers and scientists need to incorporate spatial sampling designs into erosion assessments.
Mutualists and antagonists drive among-population variation in selection and evolution of floral display in a perennial herb
Authors: Ågren Jon , Hellström Frida , Toräng Per , Ehrlén Johan
Published: October 2013

Significance

A prominent floral display may increase attractiveness to pollinators but also the risk of damage from herbivores. Here, we show experimentally that differences in the relative strength of interactions with grazers and pollinators could explain variation in selection on floral display among natural populations of an insect-pollinated primrose. In addition, we demonstrate that differences in selection translate into rather rapid changes in the genetic composition of local plant populations. The results indicate that interactions with mutualists and antagonists can drive adaptive differentiation not only across broad geographic scales but also among populations across relatively short distances.
Increased dry-season length over southern Amazonia in recent decades and its implication for future climate projection
Authors: Fu Rong , Yin Lei , Li Wenhong , Arias Paola A. , Dickinson Robert E. , Huang Lei , Chakraborty Sudip , Fernandes Katia , Liebmann Brant , Fisher Rosie , Myneni Ranga B.
Published: October 2013

Significance

Whether the dry-season length will increase is a central question in determining the fate of the rainforests over Amazonia and the future global atmospheric CO
2
concentration. We show observationally that the dry-season length over southern Amazonia has increased significantly since 1979. We do not know what has caused this change, although it resembles the effects of anthropogenic climate change. The global climate models that were presented in the Intergovernmental Panel on Climate Change’s fifth assessment report seem to substantially underestimate the variability of the dry-season length. Such a bias implies that the future change of the dry-season length, and hence the risk of rainforest die-back, may be underestimated by the projections of these models.
Earth-viewing satellite perspectives on the Chelyabinsk meteor event
Authors: Miller Steven D. , Straka William C. , Bachmeier A. Scott , Schmit Timothy J. , Partain Philip T. , Noh Yoo-Jeong
Published: October 2013

Significance

Satellite observations of large meteors (superbolides) offer important insight on trajectory through the atmosphere, and by extension, to orbital parameters that enable source attribution. On February 15, 2013, at 0920 local time, a superbolide exploded in the stratosphere near Chelyabinsk, Russia, issuing a large shock wave that damaged structures and injured hundreds below. The event was captured by Earth-viewing environmental satellites that provided multiangle views of the debris trail within minutes of formation. This paper documents these observations and their use to derive trajectory details. Results compare favorably with surface-based camera/video estimates, demonstrating the unconventional utility of satellites to characterize events that are more likely to occur away from a dense surface network.
Overexpression of calcium-activated potassium channels underlies cortical dysfunction in a model of
PTEN
-associated autism
Authors: Garcia-Junco-Clemente Pablo , Chow David K. , Tring Elaine , Lazaro Maria T. , Trachtenberg Joshua T. , Golshani Peyman
Published: October 2013

Significance

Advances in human genetics have identified many gene alterations that cause autism, but how these mutations lead to cortical dysfunction is not understood. Mutations in the gene phosphatase and tensin homolog on chromosome ten (
PTEN
) cause autism and intellectual disability. We have discovered that single-copy deletion of
Pten
results in overexpression of the small-conductance calcium-activated potassium channel in cortical neurons. This overexpression leads to decreased sensitivity of cortical neurons to incoming inputs. In vivo, this diminished excitability leads to decreased primary visual cortical responsiveness to visual stimuli. We hypothesize that diminished cortical responses in primary sensory regions lead to poor recruitment of secondary sensory cortices, leading to sensory processing deficits. Our findings identify a unique target for potential pharmacological intervention.
Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth
Authors: Higgins Claire A. , Chen James C. , Cerise Jane E. , Jahoda Colin A. B. , Christiano Angela M.
Published: October 2013

Significance

Growth of de novo hair follicles in adult skin occurs by a process known as hair neogenesis. One way of initiating neogenesis is to place dermal papillae isolated from the hair follicle in contact with an overlying epidermis where they reprogram the epidermis to adopt a follicular fate. This approach, however, has not been successful using cultured human dermal papilla cells in human skin because the cells lose their ability to induce hair growth after expansion in vitro. In this paper, we demonstrate that by manipulating cell culture conditions to establish three-dimensional papilla spheroids, we restore dermal papilla inductivity. We also use several systems biology approaches to gain a comprehensive understanding of the molecular mechanisms that underlie this regenerative process.
Critical clamp loader processing by an essential AAA+ protease in
Caulobacter crescentus
Authors: Vass Robert H. , Chien Peter
Published: October 2013

Significance

Chromosome replication requires sliding clamps that are loaded by clamp loader complexes. In
Escherichia coli
, these complexes exist as long (tau) and short (gamma) forms produced by programmed ribosome frameshifting during translation of the DnaX clamp loader subunit. Because many bacterial
dnaX
genes lack a frameshift site and because
E. coli
does not require gamma for normal growth, the biological significance of both forms has been unclear. Here we show that in
Caulobacter crescentus
, partial proteolysis of DnaX by the casein lytic proteinase (Clp) XP generates shorter gamma-like forms that are required for normal growth and DNA damage tolerance. This novel route of gamma-production illustrates that clamp loader diversity is common in bacteria and, given our results, may generally impact replication and repair.
Ultrafast folding kinetics and cooperativity of villin headpiece in single-molecule force spectroscopy
Authors: Žoldák Gabriel , Stigler Johannes , Pelz Benjamin , Li Hongbin , Rief Matthias
Published: October 2013

Significance

Proteins are amazing nanomachines that achieve their functionality through a complex three-dimensional folding process. Some proteins can fold within microseconds. Only a few experimental techniques are available for studying folding on this timescale. In this paper, we expanded the use of single-molecule force spectroscopy toward ultrafast folding proteins. Using this technique, we demonstrate that rapid folding transitions of a single villin headpiece (HP35) can be experimentally monitored and analyzed using distribution moment analysis and autocorrelation functions. We show differences in the folding dynamics and cooperativity between wild-type HP35 and a stable mutant. Brownian dynamics simulations reproduce all key features of our experiments.
Neuroprotective Sirtuin ratio reversed by ApoE4
Authors: Theendakara Veena , Patent Alexander , Peters Libeu Clare A. , Philpot Brittany , Flores Sonia , Descamps Olivier , Poksay Karen S. , Zhang Qiang , Cailing Gabriellee , Hart Matthew , John Varghese , Rao Rammohan V. , Bredesen Dale E.
Published: October 2013

Significance

This manuscript links ApoE4-mediated signaling with Sirtuin function. Specifically, we show that ApoE4, but not ApoE3, reduces neuroprotective SirT1 levels. Our data support the hypothesis that neuronal connectivity, as reflected in the ratios of critical mediators such as sAPPα:Aβ, SirT1:SirT2, APP:p-APP, and Tau:p-Tau, is programmatically altered by ApoE4. Thus ApoE4, SirT1/2, p-Tau, and p-APP, all may be part of a signaling network that is affected in AD, providing a model for therapeutic candidate screening in AD drug discovery. These findings offer a unique insight into the mechanism by which ApoE4 confers risk for the development of Alzheimer’s disease.
Human genome–guided identification of memory-modulating drugs
Authors: Papassotiropoulos Andreas , Gerhards Christiane , Heck Angela , Ackermann Sandra , Aerni Amanda , Schicktanz Nathalie , Auschra Bianca , Demougin Philippe , Mumme Eva , Elbert Thomas , Ertl Verena , Gschwind Leo , Hanser Edveena , Huynh Kim-Dung , Jessen Frank , Kolassa Iris-Tatjana , Milnik Annette , Paganetti Paolo , Spalek Klara , Vogler Christian , Muhs Andreas , Pfeifer Andrea , de Quervain Dominique J.-F.
Published: October 2013

Significance

In the last decade there has been an exponential increase in knowledge about the genetic basis of complex human traits. It is not clear, however, to what extent this knowledge can be used as a starting point for drug identification, one of the central hopes of the human genome project. Here, we report that by using genomic information related to aversive memory—a trait central to posttraumatic stress disorder—we identified several potential drug targets and compounds. In a subsequent pharmacological study with one of the identified compounds, we found a drug-induced reduction of aversive memory. These findings indicate that genomic information can be used as a starting point for the identification of memory-modulating compounds.