bluuebunny/crossref_metadata_2025 huggingface dataset:
Human herpesvirus 6 (HHV-6) alters E2F1/Rb pathways and utilizes the E2F1 transcription factor to express viral genes
Authors: Sharon Eyal , Volchek Ludmila , Frenkel Niza
Published: December 2013

Significance

Human herpesvirus 6A (HHV-6A) and HHV-6B are prevalent viruses causing mild up to grave lethal diseases. Viruses modulate cell-cycle progression so as to use cellular replication machinery. The retinoblastoma (Rb) tumor suppressor protein represses the E2F1 transcription factor. This induces entry to the S phase, enabling efficient replication. Viruses employ different mechanisms modulating the Rb–E2F1 pathway. However, the mechanism(s) used by HHV-6 are unknown. We have found that HHV-6A infection induced Rb degradation while producing elevated levels of active E2F1 and DP1. Surprisingly, several cellular E2F target genes were not up-regulated, whereas active E2F1 was used to transcribe selected viral genes containing the E2F binding site in their promoters. These viral genes play significant roles in viral DNA synthesis.
Identifying the location and importance of spawning sites of Western Baltic herring using a particle backtracking model
Authors: Bauer R. K. , Gräwe U. , Stepputtis D. , Zimmermann C. , Hammer C.
Published: December 2013

The recruitment success of some herring stocks fluctuates strongly, and apparently, success is often already determined during the early life stages, i.e. before metamorphosis. In studying the survival of early life stages and its affecting factors, particularly those during the egg stage, it is crucial to examine the processes at the spawning sites, which often cannot be explored directly. A recent decline in the recruitment of Western Baltic spring-spawning herring (WBSSH) increases the urgency of filling the knowledge gap for this stock, especially because one bottleneck in the recruitment seems to occur before hatching. We examined the successful 2003–2009 spawning sites of WBSSH in the main spawning ground, the Greifswalder Bodden lagoon. Instead of using common techniques such as diving or underwater videography, which are usually unsuitable for mapping large areas, we applied a model approach. We tracked herring larvae at length 6–10 mm, recorded by larval surveys during March–June of the respective years, back to their hatching sites using a Lagrangian particle backtracking model. We compared the spawning areas identified by the model with the results of earlier field studies; however, we also analysed variations between years, larval length groups, and different applied growth models, which are needed to define hatch-dates. Although spawning sites could not be identified with high precision because of the strong diffusion in the area studied, results indicate that larvae up to 10 mm length are caught near their hatching sites. However, the location of successful spawning sites varied largely between years, with the main hatching sites situated in the Strelasund and the eastern entrance of the lagoon. This may reflect variations in spawning-site selection or quality. A better knowledge of the locations and relative importance of, and the processes occurring on, the different spawning sites will provide an important contribution to the sustainable management of this commercially valuable herring stock.
Bioinformatic analysis of the protein/DNA interface
Authors: Schneider Bohdan , Černý Jiří , Svozil Daniel , Čech Petr , Gelly Jean-Christophe , de Brevern Alexandre G.
Published: December 2013

To investigate the principles driving recognition between proteins and DNA, we analyzed more than thousand crystal structures of protein/DNA complexes. We classified protein and DNA conformations by structural alphabets, protein blocks [de Brevern, Etchebest and Hazout (2000) (Bayesian probabilistic approach for predicting backbone structures in terms of protein blocks. Prots. Struct. Funct. Genet., 41:271–287)] and dinucleotide conformers [Svozil, Kalina, Omelka and Schneider (2008) (DNA conformations and their sequence preferences. Nucleic Acids Res., 36:3690–3706)], respectively. Assembling the mutually interacting protein blocks and dinucleotide conformers into ‘interaction matrices’ revealed their correlations and conformer preferences at the interface relative to their occurrence outside the interface. The analyzed data demonstrated important differences between complexes of various types of proteins such as transcription factors and nucleases, distinct interaction patterns for the DNA minor groove relative to the major groove and phosphate and importance of water-mediated contacts. Water molecules mediate proportionally the largest number of contacts in the minor groove and form the largest proportion of contacts in complexes of transcription factors. The generally known induction of A-DNA forms by complexation was more accurately attributed to A-like and intermediate A/B conformers rare in naked DNA molecules.
Piezotronics and piezo-phototronics: fundamentals and applications
Authors: Wang Zhong Lin , Wu Wenzhuo
Published: December 2013

Technology advancement that can provide new solutions and enable augmented capabilities to complementary metal–oxide–semiconductor (CMOS)-based technology, such as active and adaptive interaction between machine and human/ambient, is highly desired. Piezotronic nanodevices and integrated systems exhibit potential in achieving these application goals. Utilizing the gating effect of piezopotential over carrier behaviors in piezoelectric semiconductor materials under externally applied deformation, the piezoelectric and semiconducting properties together with optoelectronic excitation processes can be coupled in these materials for the investigation of novel fundamental physics and the implementation of unprecedented applications. Piezopotential is created by the strain-induced ionic polarization in the piezoelectric semiconducting crystal. Piezotronics deal with the devices fabricated using the piezopotential as a ‘gate’ voltage to tune/control charge-carrier transport across the metal–semiconductor contact or the p–n junction. Piezo-phototronics is to use the piezopotential for controlling the carrier generation, transport, separation and/or recombination for improving the performance of optoelectronic devices. This review intends to provide an overview of the rapid progress in the emerging fields of piezotronics and piezo-phototronics. The concepts and results presented in this review show promises for implementing novel nano-electromechanical devices and integrating with micro/nano-electromechanical system technology to achieve augmented functionalities to the state-of-the-art CMOS technology that may find applications in the human–machine interfacing, active flexible/stretchable electronics, sensing, energy harvesting, biomedical diagnosis/therapy, and prosthetics.
SAXS Merge: an automated statistical method to merge SAXS profiles using Gaussian processes
Authors: Spill Yannick G. , Kim Seung Joong , Schneidman-Duhovny Dina , Russel Daniel , Webb Ben , Sali Andrej , Nilges Michael
Published: December 2013

Small-angle X-ray scattering (SAXS) is an experimental technique that allows structural information on biomolecules in solution to be gathered. High-quality SAXS profiles have typically been obtained by manual merging of scattering profiles from different concentrations and exposure times. This procedure is very subjective and results vary from user to user. Up to now, no robust automatic procedure has been published to perform this step, preventing the application of SAXS to high-throughput projects. Here,SAXS Merge, a fully automated statistical method for merging SAXS profiles using Gaussian processes, is presented. This method requires only the buffer-subtracted SAXS profiles in a specific order. At the heart of its formulation is non-linear interpolation using Gaussian processes, which provides a statement of the problem that accounts for correlation in the data.
`0'- and `8'-shaped complexes generated from a nano-sized oxadiazole-containing organic ligand with CdI2and CuI
Authors: Liu Zhao-Cai , Liu Qi-Kui , Li Yan-An , Ma Jian-Ping , Dong Yu-Bin
Published: December 2013

A new nano-sized rigid double-armed oxadiazole-bridged organic ligand, 2,5-bis{2-methyl-5-[2-(pyridin-3-yl)ethenyl]phenyl}-1,3,4-oxadiazole, C30H20N4O,Lor (I), which adopts acisconformation in the solid state, has been synthesized and used to create the two novel metallocycle complexes (2,5-bis{2-methyl-5-[2-(pyridin-3-yl-κN)ethenyl]phenyl}-1,3,4-oxadiazole)diiodidocadmium(II) dichloromethane monosolvate, [CdI2(C30H20N4O)]·CH2Cl2, (II), and di-μ-iodido-bis[(2,5-bis{2-methyl-5-[2-(pyridin-3-yl-κN)ethenyl]phenyl}-1,3,4-oxadiazole)copper(I)], [Cu2I2(C30H20N4O)2], (III). Molecules of complex (II) adopts a 20-membered `0'-shaped metallocycle structure with crystallographic mirror symmetry. The discrete units are linked into one-dimensional chains through intermolecular π–π and C—H...π interactions. In (III), the two I atoms and two CuIatoms form a {Cu2(μ-I)2} cluster. One {Cu2(μ-I)2} cluster and twoLligands form two 20-membered monometallic rings in a head-to-head fashion, leading to a discrete centrosymmetric `8'-shaped metallocyclic complex. These metallocycles stack togetherviatwo kinds of intermolecular π–π interactions to generate a two-dimensional network in theacplane. The luminescence properties of (I)–(III) were investigated in the solid state at room temperature and displayed an obvious red shift.
Conformation of a terminally protected βγ hybrid dipeptide Boc-Ant-Gpn-OMe stabilized by C6/C7hydrogen bonds
Authors: Wani Naiem Ahmad , Gupta Vivek Kumar , Kant Rajni , Aravinda Subrayashastry , Rai Rajkishor
Published: December 2013

The hybrid βγ dipeptide, methyl 2-[1-({2-[(tert-butoxycarbonyl)amino]benzamido}methyl)cyclohexyl]acetate (Boc-Ant-Gpn-OMe), C22H32N2O5, adopts a folded conformation stabilized by intramolecular six- (C6) and seven-membered (C7) hydrogen-bonded rings, together with weak C—H...O and C—H...π interactions, resulting in a ribbon-like structure.
New insights in the formation of polyhydroxyalkanoate granules (carbonosomes) and novel functions of poly(3‐hydroxybutyrate)
Authors: Jendrossek Dieter , Pfeiffer Daniel
Published: December 2013

The metabolism of polyhydroxybutyrate (PHB) and related polyhydroxyalkanoates (PHAs) has been investigated by many groups for about three decades, and good progress was obtained in understanding the mechanisms of biosynthesis and biodegradation of this class of storage molecules. However, the molecular events that happen at the onset of PHB synthesis and the details of the initiation of PHB/PHA granule formation, as well as the complex composition of the proteinaceous surface layer of PHB/PHA granules, have only recently come into the focus of research and were not reviewed yet. In this contribution, we summarize the progress in understanding the initiation and formation of the PHA granule complex at the example of Ralstonia eutropha H16 (model organism of PHB‐accumulating bacteria). Where appropriate, we include information on PHA granules of Pseudomonas putida as a representative species for medium‐chain‐length PHA‐accumulating bacteria. We suggest to replace the previous micelle mode of PHB granule formation by the Scaffold Model in which the PHB synthase initiation complex is bound to the bacterial nucleoid. In the second part, we highlight data on other forms of PHB: oligo‐PHB with ≈100 to 200 3‐hydroxybutyrate (3HB) units and covalently bound PHB (cPHB) are unrelated in function to storage PHB but are presumably present in all living organisms, and therefore must be of fundamental importance.
Isolation and characterization of lipid rafts in Emiliania huxleyi: a role for membrane microdomains in host–virus interactions
Authors: Rose Suzanne L. , Fulton James M. , Brown Christopher M. , Natale Frank , Van Mooy Benjamin A. S. , Bidle Kay D.
Published: December 2013

Coccolithoviruses employ a suite of glycosphingolipids (GSLs) to successfully infect the globally important coccolithophore Emiliania huxleyi. Lipid rafts, chemically distinct membrane lipid microdomains that are enriched in GSLs and are involved in sensing extracellular stimuli and activating signalling cascades through protein–protein interactions, likely play a fundamental role in host–virus interactions. Using combined lipidomics, proteomics and bioinformatics, we isolated and characterized the lipid and protein content of lipid rafts from control E. huxleyi cells and those infected with EhV86, the type strain for Coccolithovirus. Lipid raft‐enriched fractions were isolated and purified as buoyant, detergent‐resistant membranes (DRMs) in OptiPrep density gradients. Transmission electron microscopy of vesicle morphology, polymerase chain reaction amplification of the EhV major capsid protein gene and immunoreactivity to flotillin antisera served as respective physical, molecular and biochemical markers. Subsequent lipid characterization of DRMs via high performance liquid chromatography‐triple quadrapole mass spectrometry revealed four distinct GSL classes. Parallel proteomic analysis confirmed flotillin as a major lipid raft protein, along with a variety of proteins affiliated with host defence, programmed cell death and innate immunity pathways. The detection of an EhV86‐encoded C‐type lectin‐containing protein confirmed that infection occurs at the interface between lipid rafts and cellular stress/death pathways via specific GSLs and raft‐associated proteins.
Evaluation of a Headspace Solid‐Phase Microextraction Method for the Analysis of Ignitable Liquids in Fire Debris
Authors: Fettig Ina , Krüger Simone , Deubel Jan H. , Werrel Martin , Raspe Tina , Piechotta Christian
Published: December 2013

The chemical analysis of fire debris represents a crucial part in fire investigations to determine the cause of a fire. A headspace solid‐phase microextraction (HS‐SPME) procedure for the detection of ignitable liquids in fire debris using a fiber coated with a mixture of three different sorbent materials (Divinylbenzene/Carboxen/Polydimethylsiloxane, DVB/CAR/PDMS) is described. Gasoline and diesel fuel were spiked upon a preburnt matrix (wood charcoal), extracted and concentrated with HS‐SPME and then analyzed with gas chromatography/mass spectrometry (GC/MS). The experimental conditions—extraction temperature, incubation and exposure time—were optimized. To assess the applicability of the method, fire debris samples were prepared in the smoke density chamber (SDC) and a controlled‐atmosphere cone calorimeter. The developed methods were successfully applied to burnt particleboard and carpet samples. The results demonstrate that the procedure that has been developed here is suitable for detecting these ignitable liquids in highly burnt debris.
Engineering of a green‐light inducible gene expression system in Synechocystis sp. PCC6803
Authors: Abe Koichi , Miyake Kotone , Nakamura Mayumi , Kojima Katsuhiro , Ferri Stefano , Ikebukuro Kazunori , Sode Koji
Published: December 2013

In order to construct a green‐light‐regulated gene expression system for cyanobacteria, we characterized a green‐light sensing system derived from Synechocystis sp. PCC6803, consisting of the green‐light sensing histidine kinase CcaS, the cognate response regulator CcaR, and the promoter of cpcG2 (PcpcG2). CcaS and CcaR act as a genetic controller and activate gene expression from PcpcG2 with green‐light illumination. The green‐light induction level of the native PcpcG2 was investigated using GFPuv as a reporter gene inserted in a broad‐host‐range vector. A clear induction of protein expression from native PcpcG2 under green‐light illumination was observed; however, the expression level was very low compared with Ptrc, which was reported to act as a constitutive promoter in cyanobacteria. Therefore, a Shine‐Dalgarno‐like sequence derived from the cpcB gene was inserted in the 5′ untranslated region of the cpcG2 gene, and the expression level of CcaR was increased. Thus, constructed engineered green‐light sensing system resulted in about 40‐fold higher protein expression than with the wild‐type promoter with a high ON/OFF ratio under green‐light illumination. The engineered green‐light gene expression system would be a useful genetic tool for controlling gene expression in the emergent cyanobacterial bioprocesses.
Achieving consensus in ultrasonography synovitis scoring in rheumatoid arthritis
Authors: Cheung Peter P. , Kong Kok Ooi , Chew Li‐Ching , Chia Faith L. , Law Weng Giap , Lian Tsui Yee , Tan York Kiat , Cheng Yew Kuang
Published: December 2013

Objective

Ultrasonography is sensitive for synovitis detection but interobserver variation in both acquisition and image interpretation is still a concern. The objective was to assess if a short collegiate consensus would improve inter‐observer reliability in scoring of synovitis.

Methods

Eight rheumatologists (Singapore) participated in a 1‐day consensus meeting divided into: (i) still‐image interpretation and consensus followed by; (ii) image acquisition and interpretation, according to definitions and synovitis scoring rules endorsed by Outcome Measures in Rheumatology (OMERACT) and TUI (Targeted Ultrasound Initiative). Interobserver reliability of semiquantitative scoring in B‐mode, Power Doppler (PDUS) and European League Against Rheumatism (EULAR)‐OMERACT PDUS composite score was assessed by intraclass correlation co‐efficient (ICC). Agreement at the joint region level was calculated using prevalence‐adjusted‐biased‐adjusted‐kappa (PABAK).

Results

For B‐mode still images, ICC was good at 0.75 (95% CI 0.66–0.82) while for PDUS images this was excellent at ICC = 0.88 (95% CI 0.83–0.92) with ICC improving by 12% for B‐mode and 13% for PDUS respectively. During image acquisition and interpretation, B‐mode scoring showed ICC = 0.75 (95% CI 0.66–0.84) while for PDUS the ICC was lower at 0.59 (95% CI 0.48–0.72). The ICC for OMERACT PDUS composite synovitis scoring was good at 0.77 (95% CI 0.68–0.85). At the joint level, agreement varied with PABAK being excellent in the small joints of the hands but poor to fair in the wrists, elbows, ankles and metatarsophalangeal joints, and no agreement at the knees (PABAK range −0.34 to 0.85).

Conclusion

A consensus meeting was useful in improving interobserver variation in US synovitis scoring of still images, but image acquisition and interpretation especially in non‐hand joints require further standardization.
Predicting local and non‐local effects of resources on animal space use using a mechanistic step selection model
Authors: Potts Jonathan R. , Bastille‐Rousseau Guillaume , Murray Dennis L. , Schaefer James A. , Lewis Mark A.
Published: December 2013

Predicting space use patterns of animals from their interactions with the environment is fundamental for understanding the effect of habitat changes on ecosystem functioning. Recent attempts to address this problem have sought to unify resource selection analysis, where animal space use is derived from available habitat quality, and mechanistic movement models, where detailed movement processes of an animal are used to predict its emergent utilization distribution. Such models bias the animal's movement towards patches that are easily available and resource‐rich, and the result is a predicted probability density at a given position being a function of the habitat quality at that position. However, in reality, the probability that an animal will use a patch of the terrain tends to be a function of the resource quality in both that patch and the surrounding habitat.

We propose a mechanistic model where this non‐local effect of resources naturally emerges from the local movement processes, by taking into account the relative utility of both the habitat where the animal currently resides and that of where it is moving. We give statistical techniques to parametrize the model from location data and demonstrate application of these techniques to GPS location data of caribou (Rangifer tarandus) in Newfoundland.

Steady‐state animal probability distributions arising from the model have complex patterns that cannot be expressed simply as a function of the local quality of the habitat. In particular, large areas of good habitat are used more intensively than smaller patches of equal quality habitat, whereas isolated patches are used less frequently. Both of these are real aspects of animal space use missing from previous mechanistic resource selection models.

Whilst we focus on habitats in this study, our modelling framework can be readily used with any environmental covariates and therefore represents a unification of mechanistic modelling and step selection approaches to understanding animal space use.
Chronic Ethanol Consumption Modulates Growth Factor Release, Mucosal Cytokine Production, and MicroRNA Expression in Nonhuman Primates
Authors: Asquith Mark , Pasala Sumana , Engelmann Flora , Haberthur Kristen , Meyer Christine , Park Byung , Grant Kathleen A. , Messaoudi Ilhem
Published: December 2013

Background

Chronic alcohol consumption has been associated with enhanced susceptibility to both systemic and mucosal infections. However, the exact mechanisms underlying this enhanced susceptibility remain incompletely understood.

Methods

Using a nonhuman primate model of ethanol (EtOH) self‐administration, we examined the impact of chronic alcohol exposure on immune homeostasis, cytokine, and growth factor production in peripheral blood, lung, and intestinal mucosa following 12 months of chronic EtOH exposure.

Results

EtOH exposure inhibited activation‐induced production of growth factors hepatocyte growth factor (HGF), granulocyte colony‐stimulating factor (G‐CSF), and vascular‐endothelial growth factor (VEGF) by peripheral blood mononuclear cells (PBMC). Moreover, EtOH significantly reduced the frequency of colonic Th1 and Th17 cells in a dose‐dependent manner. In contrast, we did not observe differences in lymphocyte frequency or soluble factor production in the lung of EtOH‐consuming animals. To uncover mechanisms underlying reduced growth factor and Th1/Th17 cytokine production, we compared expression levels of microRNAs in PBMC and intestinal mucosa. Our analysis revealed EtOH‐dependent up‐regulation of distinct microRNAs in affected tissues (miR‐181a and miR‐221 in PBMC; miR‐155 in colon). Moreover, we were able to detect reduced expression of the transcription factors STAT3 and ARNT, which regulate expression of VEGF, G‐CSF, and HGF and contain targets for these microRNAs. To confirm and extend these observations, PBMC were transfected with either mimics or antagomirs of miR‐181 and miR‐221, and protein levels of the transcription factors and growth factors were determined. Transfection of microRNA mimics led to a reduction in both STAT3/ARNT as well as VEGF/HGF/G‐CSF levels. The opposite outcome was observed when microRNA antagomirs were transfected.

Conclusions

Chronic EtOH consumption significantly disrupts both peripheral and mucosal immune homeostasis, and this dysregulation may be mediated by changes in microRNA expression.
Greater externalizing personality traits predict less error‐related insula and anterior cingulate cortex activity in acutely abstinent cigarette smokers
Authors: Carroll Allison J. , Sutherland Matthew T. , Salmeron Betty Jo , Ross Thomas J. , Stein Elliot A.
Published: December 2013

Attenuated activity in performance‐monitoring brain regions following erroneous actions may contribute to the repetition of maladaptive behaviors such as continued drug use. Externalizing is a broad personality construct characterized by deficient impulse control, vulnerability to addiction and reduced neurobiological indices of error processing. The insula and dorsal anterior cingulate cortex (dACC) are regions critically linked with error processing as well as the perpetuation of cigarette smoking. As such, we examined the interrelations between externalizing tendencies, erroneous task performance, and error‐related insula and dACC activity in overnight‐deprived smokers (n = 24) and non‐smokers (n = 20). Participants completed a self‐report measure assessing externalizing tendencies (Externalizing Spectrum Inventory) and a speeded Flanker task during functional magnetic resonance imaging scanning. We observed that higher externalizing tendencies correlated with the occurrence of more performance errors among smokers but not non‐smokers. Suggesting a neurobiological contribution to such suboptimal performance among smokers, higher externalizing also predicted less recruitment of the right insula and dACC following error commission. Critically, this error‐related activity fully mediated the relationship between externalizing traits and error rates. That is, higher externalizing scores predicted less error‐related right insula and dACC activity and, in turn, less error‐related activity predicted more errors. Relating such regional activity with a clinically relevant construct, less error‐related right insula and dACC responses correlated with higher tobacco craving during abstinence. Given that inadequate error‐related neuronal responses may contribute to continued drug use despite negative consequences, these results suggest that externalizing tendencies and/or compromised error processing among subsets of smokers may be relevant factors for smoking cessation success.
Expression and in situ localization of GATA4, 5 and 6 mRNAs in ovine conceptuses and uterine endometria during the peri‐implantation period
Authors: Bai Hanako , Sakurai Toshihiro , Godkin James D. , Imakawa Kazuhiko
Published: December 2013

In vertebrates, six GATA transcription factors, GATA1 through GATA6, have been identified and GATA1‐3 is known to be involved in hematopoietic developments, while GATA4‐6 play roles in cardiac and endoderm developments. Recently, we and others have found that GATA2 and GATA3 found in the trophectoderm plays a role in gene expression specific to this cell type, but GATA4‐6 have not been well characterized in early embryonic developments. Using quantitative polymerase chain reaction (qPCR) and in situ hybridization, we examined the expression of GATA4, 5 and 6 messenger RNAs (mRNAs) in ovine conceptuses and uteri during the peri‐implantation period. In ovine conceptuses, GATA4, 5 and 6 transcripts were present on days 15, 17 and 21 (day 0 = day of mating), and high GATA5 and 6 mRNAs were found on day 21, most of which were localized in the trophectoderm and endoderm. Moreover, minute and substantial GATA4 and 5 mRNAs were found in days 15 and 21 uterine endometria, respectively. Increase in GATA4‐6 transcripts in day 21 uteri indicates that in addition to GATA1‐3, GATA4‐6 may also play a potentially novel role in the development of ovine trophectoderm, endoderm and/or uterine endometria following conceptus attachment to the uterine epithelium.
Genetic selection for resistance to mycoplasmal pneumonia of swine (MPS) in the Landrace line influences the expression of soluble factors in blood after MPS vaccine sensitization
Authors: Shimazu Tomoyuki , Borjigin Liushiqi , Katayama Yuki , Li Meihua , Satoh Takumi , Watanabe Kouichi , Kitazawa Haruki , Roh Sang‐gun , Aso Hisashi , Kazuo Katoh , Suda Yoshihito , Sakuma Akiko , Nakajo Mituru , Suzuki Keiichi
Published: December 2013

We recently developed a Landrace line that is resistant to mycoplasmal pneumonia of swine (MPS) infection by genetic selection for five generations, and we reported that the immunophenotype of this line is different from that of the non‐selected line in terms of changes in peripheral blood leukocyte population after MPS vaccination. This study followed up previous findings demonstrating changes in soluble factors in blood, namely, hormones, Mycoplasma hyopneumoniae‐specific immunoglobulin G (IgG), and cytokines. These two lines were injected with MPS vaccine on days −7 and 0 after blood sampling on those days, and blood samples were collected on days −14, −7, 0, 2, 7 and 14. We found changes in the levels of many hormones and cytokines in both lines. However, we found that only growth hormone (GH) and interferon (IFN)‐γ levels were statistically different between these two lines. GH concentration was reduced (day 0) and IFN‐γ concentration was increased (day 14) in the MPS‐selected line compared with the non‐selected line, despite unchanged IFN‐γ messenger RNA expression in blood cells. Although detailed mechanisms underlying these phenotypes remain unsolved, these traits would be useful to improve MPS resistance in pig production and provide an insight into MPS infection.
Immunomodulatory agents lenalidomide and pomalidomide co‐stimulate T cells by inducing degradation of T cell repressors Ikaros and Aiolos via modulation of the E3 ubiquitin ligase complex CRL4CRBN
Authors: Gandhi Anita K. , Kang Jian , Havens Courtney G. , Conklin Thomas , Ning Yuhong , Wu Lei , Ito Takumi , Ando Hideki , Waldman Michelle F. , Thakurta Anjan , Klippel Anke , Handa Hiroshi , Daniel Thomas O. , Schafer Peter H. , Chopra Rajesh
Published: December 2013

Cereblon (CRBN), the molecular target of lenalidomide and pomalidomide, is a substrate receptor of the cullin ring E3 ubiquitin ligase complex, CRL4CRBN. T cell co‐stimulation by lenalidomide or pomalidomide is cereblon dependent: however, the CRL4CRBN substrates responsible for T cell co‐stimulation have yet to be identified. Here we demonstrate that interaction of the transcription factors Ikaros (IKZF1, encoded by the IKZF1 gene) and Aiolos (IKZF3, encoded by the IKZF3 gene) with CRL4CRBN is induced by lenalidomide or pomalidomide. Each agent promotes Aiolos and Ikaros binding to CRL4CRBN with enhanced ubiquitination leading to cereblon‐dependent proteosomal degradation in T lymphocytes. We confirm that Aiolos and Ikaros are transcriptional repressors of interleukin‐2 expression. The findings link lenalidomide‐ or pomalidomide‐induced degradation of these transcriptional suppressors to well documented T cell activation. Importantly, Aiolos could serve as a proximal pharmacodynamic marker for lenalidomide and pomalidomide, as healthy human subjects administered lenalidomide demonstrated Aiolos degradation in their peripheral T cells. In conclusion, we present a molecular model in which drug binding to cereblon results in the interaction of Ikaros and Aiolos to CRL4CRBN, leading to their ubiquitination, subsequent proteasomal degradation and T cell activation.
Decline in usually visiting the dentist for a problem in Australia, 1994 to 2010: an age–period–cohort analysis
Authors: Luzzi Liana , Chrisopoulos Sergio , Brennan David S.
Published: December 2013

Objectives

To determine the extent to which age, period and cohort factors have contributed to variation in problem‐oriented dental visiting over time.

Methods

Data were obtained from four National Dental Telephone Interview Surveys of Australian residents aged 5 years and over conducted in 1994, 1999, 2004 and 2010 (response rates 48–72%). The trend in the percentage of persons usually visiting the dentist for a problem was analysed by means of a standard cohort table and by a nested models framework for age–period–cohort analyses.

Results

The percentage of persons usually visiting the dentist for a problem generally decreased over the periods examined (from 42.5% in 1994 to 31.5% in 2010). Problem visiting tended to be lower for children and adolescents compared with adult age groups at each point in time. Model fit tests revealed that the age–period–cohort model provided the best fit for the data (Hosmer–Lemeshow test statistic = 5.3; d.f. = 8; P‐value = 0.72), indicating that both period and cohort factors were influential in problem visiting.

Conclusion

This study found similar, consistent stories for both the age–period and age–cohort models, with usually visiting for a problem tending to be higher in older age groups and older cohorts. Problem visiting tended to decline over time for most age groups and most age cohorts. Understanding patterns of dental service use over time can be used to help inform service delivery policies that promote and facilitate appropriate use of dental services.
The BRAFV600E mutation in papillary thyroid microcarcinoma: does the mutation have an impact on clinical outcome?
Authors: Walczyk Agnieszka , Kowalska Aldona , Kowalik Artur , Sygut Jacek , Wypiórkiewicz Elżbieta , Chodurska Renata , Pięciak Liliana , Góźdź Stanisław
Published: December 2013

Context

An activating mutation in the gene BRAF has been correlated with poorer prognosis and more aggressive clinical course in papillary thyroid carcinoma (PTC). We therefore hypothesized that the good prognosis, high 5‐year disease‐free rate and high survival rate of patients with less aggressive papillary thyroid microcarcinoma (pT1aNo‐x) would be associated with a lower incidence of the BRAFV600E mutation.

Objectives

To evaluate the frequency of the activating mutation BRAFV600E in low‐risk papillary thyroid microcarcinoma (pT1aNo‐x at the moment of diagnosis) and the association of the mutation with the clinical outcome in a retrospective analysis.

Study Design

BRAFV600E was characterized in 113 PTC patients diagnosed with pT1aNo‐x (one PTC focus with a diameter <1 cm, without lymph node or distant metastases according to IUCC/AJCC TNM staging system 2010). Genotyping was performed on DNA extracted from thyroid tumour tissue using direct capillary sequencing, and allele‐specific amplification PCR was used to resolve equivocal results. Retrospective analysis of the clinical course of PTC was then correlated with BRAF status in the primary tumour tissue.

Results

The BRAFV600E mutation was detected in 78 of the 113 pT1aNo‐x patients (69·0%). We observed no persistence, locoregional recurrence, lymph node or distant metastases or deaths in the study group during the 12‐year study (January 2001 to December 2012).

Conclusions

The presence of the activating BRAFV600E mutation in a significant percentage of papillary thyroid microcarcinoma indicates that further analyses are required to verify its usefulness as a predictor of clinical outcome in PTC. In this study, there was no correlation between BRAF‐positive primary focus of papillary microcarcinoma and more aggressive or recurrent disease.
Single incision laparoscopic right colectomy: a systematic review and meta‐analysis
Authors: Vettoretto N. , Cirocchi R. , Randolph J. , Parisi A. , Farinella E. , Romano G.
Published: December 2013

Aim

A meta‐analysis was performed to compare the outcome of single incision laparoscopic right hemicolectomy with standard multiport laparoscopic right hemicolectomy.

Method

A systematic search of databases was carried out to extract comparative studies (randomized and non‐randomized, prospective and retrospective). Data were analysed according to Cochrane Collaboration guidelines. A meta‐analysis was performed when the data permitted this form of analysis.

Results

Nine comparative studies were retrieved comprising 241 patients with single incision and standard laparoscopy. None of these was randomized. There was no significant difference between the two methods for the primary end‐points of mortality, morbidity and cancer‐specific parameters and for the secondary end‐points of operation time, blood loss, ileus, hospital stay and conversion. It was not possible to analyse pain and cosmetics data owing to insufficient information.

Conclusion

Single incision laparoscopic right hemicolectomy is comparable with standard multiport laparoscopic right hemicolectomy in primary and secondary outcomes. Given current information it is justified to use single incision laparoscopic right hemicolectomy, but there is a need for a prospective randomized study.
Barriers and facilitators to attending pre‐pregnancy care services: the ATLANTIC‐DIP experience
Authors: O'Higgins S. , McGuire B. E. , Mustafa E. , Dunne F.
Published: December 2013

Aims

Pre‐pregnancy care programmes can help to reduce morbidity and mortality associated with pregnancy in women with diabetes. However, uptake of a free pre‐pregnancy care programme along the Irish Atlantic seaboard was only 30%. This study sought to better understand why women with diabetes mellitus (Type 1 and Type 2) choose to attend pre‐pregnancy care services and to identify perceived barriers to attendance.

Methods

A participative health research method called the participative research process was used to facilitate 14 women with diabetes mellitus to create ‘webs of ideas’ on the reasons for attendance and non‐attendance at a pre‐pregnancy care programme, and potential solutions for each obstacle.

Results

The participants identified information on the risks of pregnancy as crucial for all childbearing women with diabetes, as lack of information was a major obstacle to attendance at pre‐pregnancy care programmes. Practical constraints such as childcare difficulties and work commitments were also identified. Participants stressed that health practitioners need to focus on positive aspects of pregnancy and childbearing rather than focusing solely on the problematic aspects for women with diabetes mellitus.

Conclusions

Women with diabetes need support and reassurance about their ability to control blood glucose and have a successful pregnancy while coping with the multiple challenges inherent in diabetes management and pregnancy. To increase uptake of pre‐pregnancy care, a norm needs to be established that situates pre‐pregnancy care as something every woman with diabetes will do, whether or not she is actively contemplating becoming a mother at the time. Active use of social media and facilitating peer support should be encouraged in pre‐pregnancy services to facilitate attendance. The time has come to incorporate the skills of a clinical psychologist in the delivery of a pre‐pregnancy service.
Rankings, Diversity and the Power of Renewal in Science. A Comparison between Germany, the UK and the US
Authors: Münch Richard , Schäfer Len Ole
Published: December 2013

Rankings are part and parcel of the neoliberal agenda in science aiming at increasing the competitive allocation of funds among universities. This article focuses on the decreasing power of renewal in science as a result of this agenda particularly because of its increasingly consolidated stratification of the academic system into élite and mass institutions. A comparison based on data from the Academic Ranking of World Universities of the Shanghai Jiao Tong University between the less stratified German system, the more strongly stratified British system, and the most strongly stratified, though at its heart still diverse US‐American system provides a first test of the hypotheses.
Systems biology of human epilepsy applied to patients with brain tumors
Authors: Mittal Sandeep , Shah Aashit K. , Barkmeier Daniel T. , Loeb Jeffrey A.
Published: December 2013

Epilepsy is a disease of recurrent seizures that can be associated with a wide variety of acquired and developmental brain lesions. Current medications for patients with epilepsy can suppress seizures; they do not cure or modify the underlying disease process. On the other hand, surgical removal of focal brain regions that produce seizures can be curative. This surgical procedure can be more precise with the placement of intracranial recording electrodes to identify brain regions that generate seizure activity as well as those that are critical for normal brain function. The detail that goes into these surgeries includes extensive neuroimaging, electrophysiology, and clinical data. Combined with precisely localized tissues removed, these data provide an unparalleled opportunity to learn about the interrelationships of many “systems” in the human brain not possible in just about any other human brain disorder. Herein, we describe a systems biology approach developed to study patients who undergo brain surgery for epilepsy and how we have begun to apply these methods to patients whose seizures are associated with brain tumors. A central goal of this clinical and translational research program is to improve our understanding of epilepsy and brain tumors and to improve diagnosis and treatment outcomes of both.
MRI in the diagnosis and management of epileptomas
Authors: Duncan John S. , de Tisi Jane
Published: December 2013

High‐resolution magnetic resonance imaging (MRI) is invaluable for identifying cerebral tumors that cause epilepsy. Serial voxel‐based automated quantitative analyses are more sensitive than visual reading for detecting change in a lesion. Eloquent cortex can be identified with functional MRI (fMRI), with cautions about the precise location and extent of critical cortex. Tractography is useful for delineating critical white matter tracks as are MR venography and computerized tomography (CT) angiography for displaying veins and arteries. These data may be combined into a three‐dimensional (3D) multimodal MR data presentation and displayed interoperatively to increase the precision and minimize the risk of neurosurgical treatment, and for the illustrations.
Depths and grids in brain tumors: Implantation strategies, techniques, and complications
Authors: Sweet Jennifer A. , Hdeib Alia M. , Sloan Andrew , Miller Jonathan P.
Published: December 2013

Patients with intracranial mass lesions are at increased risk of intractable epilepsy even after tumor resection due to the potential epileptogenicity of lesional and perilesional tissue. Risk factors for tumoral epilepsy include tumor location, histology, and extent of tumor resection. In epilepsy that occurs after tumor resection, the epileptogenic zone often does not correspond precisely with the area of abnormality on imaging, and seizures often arise from a relatively restricted area despite widespread changes on imaging. Invasive monitoring via subdural grids and/or depth electrodes can therefore be helpful to delineate areas of eloquence and localize the epileptogenic zone for subsequent resection. Subdural grids offer excellent contiguous coverage of superficial cortex and allow resection using the same craniotomy, facilitating understanding of anatomic relationships. Depth electrodes offer superior coverage of deep structures, are easier to use in cases where a previous craniotomy is present, are not associated with anatomic distortion due to brain shift, and may be associated with a lower complication rate. We review the biology of focal postoperative epilepsy and invasive diagnostic strategies for the surgical evaluation of medically refractory epilepsy in patients who have undergone resection of intracranial mass lesions.
Choosing the tumoral epilepsy surgery candidate
Authors: Rheims Sylvain , Ducray François , Ryvlin Philippe
Published: December 2013

The management of epilepsy is an essential clinical issue in many patients with brain tumors. Tumoral epilepsy is often drug resistant and is associated with poor quality of life. Surgery represents a key therapeutic option in the management of patients with refractory tumoral epilepsy, with high rates of postoperative seizure freedom, especially when gross total resection can be performed. The selection of surgical candidates first requires extrapolation of the presumed underlying pathology and its potential for malignant transformation from clinical and imaging data, especially MRI characteristics. These data determine the decision for surgery, as well as its timing and technical aspects in relation to the risk of postoperative deficit. In glioneuronal tumors, where seizures are often drug‐resistant and risk of malignant transformation is very low, epilepsy surgery is usually recommended to alleviate disabling seizures and side effects of antiepileptic drugs. However, the risk of postoperative deficit may outweigh potential benefits of surgery in tumors located within eloquent cortex. This issue is particularly relevant for glioneuronal tumors located within the dominant mesial temporal structures in patients in whom seizure control might require additional hippocampectomy, associated with a high risk of memory decline. In contrast, in patients with low‐grade gliomas or aggressive brain neoplasms, both the decision to perform surgery and selection of the best surgical approach primarily rely on the oncologic imperative rather than epileptologic considerations. In these patients, the extent of tumor resection correlates with improved survival, progression‐free survival, as well as with the chances of postoperative seizure control.
Calcium concentration in leaf litter affects the abundance and survival of crustaceans in streams draining warm–temperate forests
Authors: Ohta Tamihisa , Niwa Shigeru , Hiura Tsutom
Published: December 2013

Stream ecosystems receive large quantities of nutrients from terrestrial ecosystems that influence community dynamics. However, few studies have investigated the effects of subsidiary calcium, an essential element of animals, on stream ecosystems.

We focused on differences in calcium concentrations of leaf litter between tree species. In particular, litter of Japanese cedar (Cryptomeria japonica) has a higher concentration of calcium than other taxa, and the tree is planted in many parts of Japan. Therefore, we predicted that a C. japonica plantation would affect the supply of subsidiary calcium to stream ecosystems.

We compared calcium concentration of leaf litters, soils, stream water and stream benthic invertebrates sampled at nine sites in catchments composed of cedar plantations, evergreen broad‐leaved forest and clear‐cut areas. In addition, we placed 10 Gammarus nipponensis in each of 10 nylon cages in the nine streams and after one month surveyed the number of surviving individuals.

Calcium concentration in stream water and soil, and the density and survival of the dominant crustacean (Gammarus nipponensis) were significantly higher at sites dominated by C. japonica compared with other forest types. Furthermore, invertebrate community composition was correlated with total calcium and nitrate in stream water, indicating that terrestrial vegetation can affect stream invertebrate communities, particularly crustaceans.
Priming effect and microbial diversity in ecosystem functioning and response to global change: a modeling approach using the SYMPHONY model
Authors: Perveen Nazia , Barot Sébastien , Alvarez Gaël , Klumpp Katja , Martin Raphael , Rapaport Alain , Herfurth Damien , Louault Frédérique , Fontaine Sébastien
Published: December 2013

Integration of the priming effect (PE) in ecosystem models is crucial to better predict the consequences of global change on ecosystem carbon (C) dynamics and its feedbacks on climate. Over the last decade, many attempts have been made to model PE in soil. However, PE has not yet been incorporated into any ecosystem models. Here, we build plant/soil models to explore how PE and microbial diversity influence soil/plant interactions and ecosystem C and nitrogen (N) dynamics in response to global change (elevated CO2 and atmospheric N depositions). Our results show that plant persistence, soil organic matter (SOM) accumulation, and low N leaching in undisturbed ecosystems relies on a fine adjustment of microbial N mineralization to plant N uptake. This adjustment can be modeled in the SYMPHONY model by considering the destruction of SOM through PE, and the interactions between two microbial functional groups: SOM decomposers and SOM builders. After estimation of parameters, SYMPHONY provided realistic predictions on forage production, soil C storage and N leaching for a permanent grassland. Consistent with recent observations, SYMPHONY predicted a CO2‐induced modification of soil microbial communities leading to an intensification of SOM mineralization and a decrease in the soil C stock. SYMPHONY also indicated that atmospheric N deposition may promote SOM accumulation via changes in the structure and metabolic activities of microbial communities. Collectively, these results suggest that the PE and functional role of microbial diversity may be incorporated in ecosystem models with a few additional parameters, improving accuracy of predictions.