bluuebunny/crossref_metadata_2025 huggingface dataset:
Overview of the ARGOS X-ray framing camera for Laser MegaJoule
Authors: Trosseille C. , Aubert D. , Auger L. , Bazzoli S. , Beck T. , Brunel P. , Burillo M. , Chollet C. , Gazave J. , Jasmin S. , Maruenda P. , Moreau I. , Oudot G. , Raimbourg J. , Soullié G. , Stemmler P. , Zuber C.
Published: August 2014

Commissariat à l’Énergie Atomique et aux Énergies Alternatives has developed the ARGOS X-ray framing camera to perform two-dimensional, high-timing resolution imaging of an imploding target on the French high-power laser facility Laser MegaJoule. The main features of this camera are: a microchannel plate gated X-ray detector, a spring-loaded CCD camera that maintains proximity focus in any orientation, and electronics packages that provide remotely-selectable high-voltages to modify the exposure-time of the camera. These components are integrated into an “air-box” that protects them from the harsh environmental conditions. A miniaturized X-ray generator is also part of the device for in situ self-testing purposes.
Excitation energies, photoionization cross sections, and asymmetry parameters of the methyl and silyl radicals
Authors: Velasco A. M. , Lavín C. , Dolgounitcheva O. , Ortiz J. V.
Published: August 2014

Vertical excitation energies of the methyl and silyl radicals were inferred from ab initio electron propagator calculations on the electron affinities of CH3+ and SiH3+. Photoionization cross sections and angular distribution of photoelectrons for the outermost orbitals of both CH3 and SiH3 radicals have been obtained with the Molecular Quantum Defect Orbital method. The individual ionization cross sections corresponding to the Rydberg channels to which the excitation of the ground state's outermost electron gives rise are reported. Despite the relevance of methyl radical in atmospheric chemistry and combustion processes, only data for the photon energy range of 10–11 eV seem to be available. Good agreement has been found with experiment for photoionization cross section of this radical. To our knowledge, predictions of the above mentioned photoionization parameters on silyl radical are made here for the first time, and we are not aware of any reported experimental measurements. An analysis of our results reveals the presence of a Cooper minimum in the photoionization of the silyl radical. The adequacy of the two theoretical procedures employed in the present work is discussed.
Sideband characterization and atmospheric observations with various 340 GHz heterodyne receivers
Authors: Renker Matthias , Murk Axel , Rea Simon P. , Emrich A. , Frisk U.
Published: August 2014

This paper describes sideband response measurements and atmospheric observations with a double sideband and two Single Sideband (SSB) receiver prototypes developed for the multi-beam limb sounder instrument stratosphere-troposphere exchange and climate monitor radiometer. We first show an advanced Fourier-Transform Spectroscopy (FTS) method for sideband response and spurious signal characterization. We then present sideband response measurements of the different prototype receivers and we compare the results of the SSB receivers with sideband measurements by injecting a continuous wave signal into the upper and lower sidebands. The receivers were integrated into a total-power radiometer and atmospheric observations were carried out. The observed spectra were compared to forward model spectra to conclude on the sideband characteristics of the different receivers. The two sideband characterization methods show a high degree of agreement for both SSB receivers with various local oscillator settings. The measured sideband response was used to correct the forward model simulations. This improves the agreement with the atmospheric observations and explains spectral features caused by an unbalanced sideband response. The FTS method also allows to quantify the influence of spurious harmonic responses of the receiver.
Eigenvalue problem for radial potentials in space with SU(2) fuzziness
Authors: Mirahmadi Marjan-S. , Fatollahi Amir H.
Published: August 2014

The eigenvalue problem for radial potentials is considered in a space whose spatial coordinates satisfy the SU(2) Lie algebra. As the consequence, the space has a lattice nature and the maximum value of momentum is bounded from above. The model shows interesting features due to the bound, namely, a repulsive potential can develop bound-states, or an attractive region may be forbidden for particles to propagate with higher energies. The exact radial eigen-functions in momentum space are given by means of the associated Chebyshev functions. For the radial stepwise potentials, the exact energy condition and the eigen-functions are presented. For a general radial potential, it is shown that the discrete energy spectrum can be obtained in desired accuracy by means of given forms of continued fractions.
Global gyrokinetic stability of collisionless microtearing modes in large aspect ratio tokamaks
Authors: Swamy Aditya K. , Ganesh R. , Chowdhury J. , Brunner S. , Vaclavik J. , Villard L.
Published: August 2014

Linear full radius gyrokinetic calculations show the existence of unstable microtearing modes (MTMs) in purely collisionless, high temperature, large aspect ratio tokamak plasmas. The present study takes into account fully gyrokinetic highly passing ions and electrons. The global 2-D structures of the collisionless mode with full radius coupling of the poloidal modes is obtained and compared with another electromagnetic mode, namely, the Alfvén Ion Temperature Gradient (AITG) mode (or Kinetic Ballooning Mode, KBM) for the same equilibrium profile. Several important characteristics of the modes are brought out and compared, such as a clear signature in the symmetry properties of the two modes, the plasma–β dependence, and radial and poloidal length scales of the electrostatic and magnetic vector potential fluctuations. Extensive parameter scans for this collisionless microtearing mode reveal the scaling of the growth rate with β and the electron temperature gradient ηe. Scans at different β values show an inverse relationship between the ηe threshold and β, leading to a stability diagram, and implying that the mode might exist at moderate to strong temperature gradients for finite β plasmas in large aspect ratio tokamaks. In contrast to small aspect ratio tokamaks where the trapped electron magnetic drift resonance is found to be important, in large aspect ratio tokamaks, a strong destabilization due to the magnetic drift resonance of passing electrons is observed and is identified as a possible collisionless drive mechanism for the collisionless MTM.
Effect of composition on the pressure-driven ferroelectric to antiferroelectric phase transformation behavior of (Pb0.97La0.02)(Zr1−x−ySnxTiy)O3 ceramics
Authors: Jo Hwan R. , Lynch Christopher S.
Published: August 2014

Power can be generated by rapidly driving a poled ferroelectric material through a ferroelectric to antiferroelectric phase transformation. The power generated depends on the maximum remnant polarization that can be obtained in the ferroelectric state and the minimum dielectric permittivity that can be obtained in the antiferroelectric state. In this study, the effect of composition on these properties was measured for compositions in the (Pb0.97La0.02)(Zr1−x−ySnxTiy)O3 system. Specimens were fabricated and characterized in the ferroelectric and antiferroelectric state under hydrostatic loading. The results are discussed in terms of their impact on an energy harvesting cycle that utilizes a ferroelectric to antiferroelectric phase transformation. The calculated maximum theoretical energy density based on the measurements was 14.5 J/cm3.
Thickness dependence of magnetoelectric response for composites of Pb(Zr0.52Ti0.48)O3 films on CoFe2O4 ceramic substrates
Authors: Wang Jing , Wu Xia , Peng Renci , Wang Jianjun , Deng Chaoyong , Zhu Kongjun
Published: August 2014

Using chemical solution spin-coating we grew Pb(Zr0.52Ti0.48)O3 films of different thicknesses on highly dense CoFe2O4 ceramics. X-ray diffraction revealed no other phases except Pb(Zr0.52Ti0.48)O3 and CoFe2O4. In many of these samples we observed typical ferroelectric hysteresis loops, butterfly-shaped piezoelectric strains, and the magnetic-field-dependent magnetostriction. These behaviors caused appreciable magnetoelectric responses based on magnetic-mechanical-electric coupling. Our results indicated that the thickness of the Pb(Zr0.52Ti0.48)O3 film was important in obtaining strong magnetoelectric coupling.
Uniaxial in-plane magnetization of iron nanolayers grown within an amorphous matrix
Authors: Ghafari M. , Mattheis R. , McCord J. , Hahn H. , Brand R. A. , Macedo W. A. A.
Published: August 2014

Conversion electron Mössbauer spectroscopy is used to determine the magnetic ground state at zero magnetic field of four-monolayer thick amorphous iron layers as part of a CoFeB-Fe multilayer stack. By comparing the intensities of the magnetic hyperfine field, an easy in-plane axis of the amorphous embedded Fe layer is verified, which is collinear to the uniaxial anisotropy axis of the neighboring amorphous CoFeB. Despite the soft magnetic character of the Fe layers, external fields up to 4 T perpendicular to the film plane are insufficient to completely align the embedded Fe moments parallel to the magnetic field due to a local disorder of the magnetic moments of the Fe atoms.
RNA and RNA–Protein Complex Crystallography and its Challenges
Authors: Flores Janine K. , Walshe James L. , Ataide Sandro F.
Published: August 2014

RNA biology has changed completely in the past decade with the discovery of non-coding RNAs. Unfortunately, obtaining mechanistic information about these RNAs alone or in cellular complexes with proteins has been a major problem. X-ray crystallography of RNA and RNA–protein complexes has suffered from the major problems encountered in preparing and purifying them in large quantity. Here, we review the available techniques and methods in vitro and in vivo used to prepare and purify RNA and RNA–protein complex for crystallographic studies. We also discuss the future directions necessary to explore the vast number of RNA species waiting for their atomic-resolution structure to be determined.
Trithorax complex component Menin controls differentiation and maintenance of T helper 17 cells
Authors: Watanabe Yukiko , Onodera Atsushi , Kanai Urara , Ichikawa Tomomi , Obata-Ninomiya Kazushige , Wada Tomoko , Kiuchi Masahiro , Iwamura Chiaki , Tumes Damon J. , Shinoda Kenta , Yagi Ryoji , Motohashi Shinichiro , Hirahara Kiyoshi , Nakayama Toshinori
Published: August 2014

Significance

Epigenetic modifications, including various histone modifications, play important roles in regulating gene expression. The Trithorax group (TrxG) complex induces permissive histone modifications to activate transcription. We herein investigate the role for Menin, a component of the TrxG complex, in T helper (Th) cell differentiation, and find a critical role for Menin in differentiation and maintenance of Th17 cells. Menin is required for Th17 cell differentiation in vitro through the direct regulation ofIl17aexpression. Menin controls IL-17–mediated pathology in vivo. Menin is also required to maintain expression ofRorc, the gene encoding RORγt, a key transcription factor for Th17 cell function. Thus, Menin orchestrates Th17 cell differentiation and function by regulating both induction and maintenance of target gene expression.
Valuing vaccination
Authors: Bärnighausen Till , Bloom David E. , Cafiero-Fonseca Elizabeth T. , O’Brien Jennifer Carroll
Published: August 2014

Vaccination has led to remarkable health gains over the last century. However, large coverage gaps remain, which will require significant financial resources and political will to address. In recent years, a compelling line of inquiry has established the economic benefits of health, at both the individual and aggregate levels. Most existing economic evaluations of particular health interventions fail to account for this new research, leading to potentially sizable undervaluation of those interventions. In line with this new research, we set forth a framework for conceptualizing the full benefits of vaccination, including avoided medical care costs, outcome-related productivity gains, behavior-related productivity gains, community health externalities, community economic externalities, and the value of risk reduction and pure health gains. We also review literature highlighting the magnitude of these sources of benefit for different vaccinations. Finally, we outline the steps that need to be taken to implement a broad-approach economic evaluation and discuss the implications of this work for research, policy, and resource allocation for vaccine development and delivery.
Unleashing the potential of NOD- and Toll-like agonists as vaccine adjuvants
Authors: Maisonneuve Charles , Bertholet Sylvie , Philpott Dana J. , De Gregorio Ennio
Published: August 2014

Innate immunity confers an immediate nonspecific mechanism of microbial recognition through germ line-encoded pattern recognition receptors (PRRs). Of these, Toll-like receptors (TLRs) and nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) have shaped our current understanding of innate regulation of adaptive immunity. It is now recognized that PRRs are paramount in instructing an appropriate adaptive immune response. Their ligands have been the focus of adjuvant research with the goal of generating modern vaccine combinations tailored to specific pathogens. In this review we will highlight the recent findings in the field of adjuvant research with a particular focus on the potential of TLR and NLR ligands as adjuvants and their influence on adaptive immune responses.
Tomato yellow leaf curl virus resistance by
Ty-1
involves increased cytosine methylation of viral genomes and is compromised by cucumber mosaic virus infection
Authors: Butterbach Patrick , Verlaan Maarten G. , Dullemans Annette , Lohuis Dick , Visser Richard G. F. , Bai Yuling , Kormelink Richard
Published: August 2014

Significance

Tomato yellow leaf curl virus disease causes enormous yield losses in tomato production worldwide and is caused by different begomoviruses, with tomato yellow leaf curl virus (TYLCV) as the most important one. Recently, we have cloned to our knowledge the first resistance gene against TYLCV, namely
Ty-1
, which encodes an RNA-dependent RNA polymerase and has unveiled a new class of resistance genes. Here we provide data that indicate that
Ty-1
confers resistance to TYLCV and other geminiviruses by enhancing transcriptional gene silencing, a part of the antiviral RNAi defense mechanism. Furthermore, we show that this resistance is compromised by infection with cucumber mosaic virus, another important and widely distributed RNA virus, likely due to its ability to suppress RNAi at different levels.
Submesoscale dispersion in the vicinity of the
Deepwater Horizon
spill
Authors: Poje Andrew C. , Özgökmen Tamay M. , Lipphardt Bruce L. , Haus Brian K. , Ryan Edward H. , Haza Angelique C. , Jacobs Gregg A. , Reniers A. J. H. M. , Olascoaga Maria Josefina , Novelli Guillaume , Griffa Annalisa , Beron-Vera Francisco J. , Chen Shuyi S. , Coelho Emanuel , Hogan Patrick J. , Kirwan Albert D. , Huntley Helga S. , Mariano Arthur J.
Published: August 2014

Significance

We report here on results obtained from the largest upper-ocean dispersion field program conducted to date. The observations provided, for the first time to our knowledge, an accurate and nearly simultaneous description of the ocean surface velocity field on spatial scales ranging from 100 m to 100 km. We show conclusively that ocean flows contain significant energy at scales below 10 km and that their fluctuations dictate the initial spread of tracer/pollutant clouds. Neither state-of-the art operational models nor satellite altimeters capture the flows needed for accurately estimating the dispersion of surface particles.
A lipid zipper triggers bacterial invasion
Authors: Eierhoff Thorsten , Bastian Björn , Thuenauer Roland , Madl Josef , Audfray Aymeric , Aigal Sahaja , Juillot Samuel , Rydell Gustaf E. , Müller Stefan , de Bentzmann Sophie , Imberty Anne , Fleck Christian , Römer Winfried
Published: August 2014

Significance

Entry of bacteria into host cells critically depends on their proper engulfment by the plasma membrane. So far, actin polymerization has been described as a major driving force in this process. However, our study reveals that the interaction of the bacterial surface lectin LecA with the host cell glycosphingolipid Gb3 is fully sufficient to promote engulfment of
Pseudomonas aeruginosa
, whereas actin polymerization is dispensable. Hence, the formation of a “lipid zipper” represents a previously unidentified mechanism of bacterial uptake and demonstrates that bacterial pathogens have evolved lipid-based invasion strategies that may function in addition to protein receptor-based ones. Furthermore, by identifying the LecA/Gb3 interaction as the major invasion-promoting factor, our study provides new targets for drugs that may prevent bacterial invasion and dissemination.
Direct measurement of the dielectric polarization properties of DNA
Authors: Cuervo Ana , Dans Pablo D. , Carrascosa José L. , Orozco Modesto , Gomila Gabriel , Fumagalli Laura
Published: August 2014

Significance

The strength of DNA–DNA and DNA–ligand electrostatic interactions crucially depends on the electric polarizability of DNA, represented by its dielectric constant. This has remained unknown owing to the lack of experimental techniques able to measure it. Here, we experimentally determined the dielectric constant of double-stranded DNA in a native condensed state inside a single bacteriophage as well as the dielectric constants of the protein shell and tail that compose the viral capsid using scanning force microscopy. We supported the experimental data by theoretically determining the DNA dielectric constant using atomistic simulations. Both approaches yield a dielectric constant of DNA around 8, sensibly higher than commonly assumed, thus revealing a DNA intrinsic property essential for realistic computational description of DNA.
Activated group 3 innate lymphoid cells promote T-cell–mediated immune responses
Authors: von Burg Nicole , Chappaz Stéphane , Baerenwaldt Anne , Horvath Edit , Bose Dasgupta Somdeb , Ashok Devika , Pieters Jean , Tacchini-Cottier Fabienne , Rolink Antonius , Acha-Orbea Hans , Finke Daniela
Published: August 2014

Significance

Group 3 innate lymphoid cells (ILC3s) play decisive roles in mammalian physiology including tissue repair, lymphoid tissue development, and immune regulation. So far, the functions of ILC3s in the adult immune system have been mainly linked to their capacity to release cytokines in response to microbial or inflammatory signals. The results presented here show that activated ILC3s can alter the outcome of adaptive immune responses by directly stimulating CD4
+
T cells. Indeed, IL-1β–activated ILC3s express costimulatory molecules and induce cognate CD4
+
T-cell responses. More importantly, antigen-driven T- and B-cell responses are impaired in vivo when this cellular interaction is disrupted. Overall, our data show that peripheral ILC3s play a yet unappreciated role in T-cell–mediated immunity.
Endothelial Akt1 mediates angiogenesis by phosphorylating multiple angiogenic substrates
Authors: Lee Monica Y. , Luciano Amelia K. , Ackah Eric , Rodriguez-Vita Juan , Bancroft Tara A. , Eichmann Anne , Simons Michael , Kyriakides Themis R. , Morales-Ruiz Manuel , Sessa William C.
Published: August 2014

Significance

The expression of multiple isoforms of a protein kinase in cells raises the question of which substrates are preferentially phosphorylated by each isoform. Endothelial cells (ECs) that line all blood vessels express the protein kinases, Akt1 and Akt2, and we demonstrate here that endothelial nitric oxide synthase (eNOS) is a preferential Akt1 substrate and supraphysiological overexpression of Akt2 is needed to phosphorylate eNOS and promote NO release. In mice, the endothelial loss of Akt1, but not Akt2, retards vessel growth, and quantitative assessment of the phosphoproteomes in ECs isolated from these mice shows that Akt1 uniquely phosphorylates several important proteins regulating vascular function. Thus, despite the presence of both isoforms of Akt in the endothelium, substrate phosphorylation by Akt1 is nonredundant.
IL-6/STAT3 promotes regeneration of airway ciliated cells from basal stem cells
Authors: Tadokoro Tomomi , Wang Yang , Barak Larry S. , Bai Yushi , Randell Scott H. , Hogan Brigid L. M.
Published: August 2014

Significance

The airways of the lungs are lined by ciliated and secretory epithelial cells important for mucociliary clearance. When these cells are damaged or lost, they are replaced by the differentiation of basal stem cells. Little is known about how this repair is orchestrated by signaling pathways in the epithelium and underlying stroma. We present evidence using cultured airway cells and genetic manipulation of a mouse model of airway repair that the cytokine IL-6 promotes the differentiation of ciliated vs. secretory cells. This process involves direct Stat3 regulation of genes controlling both cell fate (Notch1) and the differentiation of multiciliated cells (Multicilin and forkhead box protein J1). Moreover, the major producer of IL-6 appears to be mesenchymal cells in the stroma rather than immune cells.
Fluvial network organization imprints on microbial co-occurrence networks
Authors: Widder Stefanie , Besemer Katharina , Singer Gabriel A. , Ceola Serena , Bertuzzo Enrico , Quince Christopher , Sloan William T. , Rinaldo Andrea , Battin Tom J.
Published: August 2014

Significance

Microbial communities orchestrate most biogeochemical processes on Earth. In streams and rivers, surface-attached and matrix-enclosed biofilms dominate microbial life. Despite the relevance of these biofilms for ecosystem processes (e.g., metabolism and nutrient cycling), it remains unclear how features inherent to stream and river networks affect the fundamental organization of biofilm communities in these ecosystems. We combined co-occurrence analyses of biofilms based on next-generation sequencing with a probabilistic hydrological model, and showed how fragementation of microbial co-occurrence networks change across stream networks. Our analyses offer potential insights into the response of microbial community organization and persistence to human pressures that increasingly change the hydrological regime and biodiversity dynamics in fluvial networks.
Genetic and pharmacological reactivation of the mammalian inactive X chromosome
Authors: Bhatnagar Sanchita , Zhu Xiaochun , Ou Jianhong , Lin Ling , Chamberlain Lynn , Zhu Lihua J. , Wajapeyee Narendra , Green Michael R.
Published: August 2014

Significance

In somatic cells of female mammals, one of the two X chromosomes is randomly silenced, a phenomenon called X-chromosome inactivation (XCI). XCI is initiated
in cis
by a noncoding RNA called
Xist
, but
trans
-acting factors that mediate XCI remain largely unknown. In this study, we perform a large-scale RNA interference screen and identify new
trans
-acting factors that are required for mammalian XCI. Chemical inhibitors of some of these factors can reversibly reactivate the inactive X chromosome. Our results have therapeutic implications for certain human diseases, in particular the neurodevelopmental disorder Rett syndrome, which is caused by loss-of-function mutations in the X-linked
MECP2
gene. Reactivation of the silenced wild-type
MECP2
allele is a potential strategy for treating the disease.
Molecular mechanism of pH-dependent substrate transport by an arginine-agmatine antiporter
Authors: Wang Sheng , Yan Renhong , Zhang Xi , Chu Qi , Shi Yigong
Published: August 2014

Significance

Enteropathogenic bacteria, exemplified by
Escherichia coli
strain O157:H7, rely on elaborate acid-resistance systems (ARs) to survive the extremely acidic environment of the stomach. The amino acid antiporter AdiC plays a key role in AR3 and is activated only under acidic pH conditions. Despite elucidation of crystal structures, the molecular mechanism by which AdiC senses acidic pH remains unknown. In this study, we have identified a single aromatic amino acid, Tyr74, as a pH sensor in AdiC. The pH-sensing mechanism appears to be mediated by cation–π interactions between proton and the aromatic side chain of Tyr74. The identification of the pH sensor and the proposed mechanism of pH sensing contribute to mechanistic understanding of the pH-dependent acid resistance in bacteria.
Test–retest reliability of second lactate turnpoint using two different criteria in competitive cyclists
Authors: Hoefelmann Camila Peter , Diefenthaeler Fernando , Costa Vitor Pereira , de Lucas Ricardo Dantas , Shambrook Philip , Guglielmo Luiz Guilherme Antonacci
Published: August 2014

The aim of this study was to determine the relative and absolute reliability of second lactate turnpoint using fixed and individual blood lactate method in competitive cyclists. Twenty‐eight male, well‐trained cyclists (30.2 ± 10.1 years, 72.0 ± 7.4 kg, 177.3 ± 4.7 cm) were recruited to participate in this study. Cyclists completed two incremental cycling tests to exhaustion over a period of 7 days to determine their peak power output, maximal oxygen uptake, maximal heart rate, maximal blood lactate concentration and two lactate turnpoint criteria. The fixed blood concentration criterion (3.5 mM) and an individual criterion were assessed by a lactate‐power curve, considering power output, heart rate and oxygen uptake. The main finding of this study was that both lactate turnpoint criteria showed identical low within‐subject variation for power output (2.8% coefficient of variation). High values for test–retest correlations ranging from r = 0.70 to r = 0.94 were found for all variables in both threshold criteria. In conclusion, the individual and fixed method to determine the second lactate turnpoint showed similar high absolute and relative reliability in competitive cyclists.
Classical Flt3L-dependent dendritic cells control immunity to protein vaccine
Authors: Anandasabapathy Niroshana , Feder Rachel , Mollah Shamim , Tse Sze-Wah , Longhi Maria Paula , Mehandru Saurabh , Matos Ines , Cheong Cheolho , Ruane Darren , Brane Lucas , Teixeira Angela , Dobrin Joseph , Mizenina Olga , Park Chae Gyu , Meredith Matthew , Clausen Björn E. , Nussenzweig Michel C. , Steinman Ralph M.
Published: August 2014

DCs are critical for initiating immunity. The current paradigm in vaccine biology is that DCs migrating from peripheral tissue and classical lymphoid-resident DCs (cDCs) cooperate in the draining LNs to initiate priming and proliferation of T cells. Here, we observe subcutaneous immunity is Fms-like tyrosine kinase 3 ligand (Flt3L) dependent. Flt3L is rapidly secreted after immunization; Flt3 deletion reduces T cell responses by 50%. Flt3L enhances global T cell and humoral immunity as well as both the numbers and antigen capture capacity of migratory DCs (migDCs) and LN-resident cDCs. Surprisingly, however, we find immunity is controlled by cDCs and actively tempered in vivo by migDCs. Deletion of Langerin+ DC or blockade of DC migration improves immunity. Consistent with an immune-regulatory role, transcriptomic analyses reveals different skin migDC subsets in both mouse and human cluster together, and share immune-suppressing gene expression and regulatory pathways. These data reveal that protective immunity to protein vaccines is controlled by Flt3L-dependent, LN-resident cDCs.
RUNX1-dependent RAG1 deposition instigates human TCR-δ locus rearrangement
Authors: Cieslak Agata , Le Noir Sandrine , Trinquand Amélie , Lhermitte Ludovic , Franchini Don-Marc , Villarese Patrick , Gon Stéphanie , Bond Jonathan , Simonin Mathieu , Vanhille Laurent , Reimann Christian , Verhoeyen Els , Larghero Jerome , Six Emmanuelle , Spicuglia Salvatore , André-Schmutz Isabelle , Langerak Anton , Nadel Bertrand , Macintyre Elizabeth , Payet-Bornet Dominique , Asnafi Vahid
Published: August 2014

V(D)J recombination of TCR loci is regulated by chromatin accessibility to RAG1/2 proteins, rendering RAG1/2 targeting a potentially important regulator of lymphoid differentiation. We show that within the human TCR-α/δ locus, Dδ2-Dδ3 rearrangements occur at a very immature thymic, CD34+/CD1a−/CD7+dim stage, before Dδ2(Dδ3)-Jδ1 rearrangements. These strictly ordered rearrangements are regulated by mechanisms acting beyond chromatin accessibility. Importantly, direct Dδ2-Jδ1 rearrangements are prohibited by a B12/23 restriction and ordered human TCR-δ gene assembly requires RUNX1 protein, which binds to the Dδ2-23RSS, interacts with RAG1, and enhances RAG1 deposition at this site. This RUNX1-mediated V(D)J recombinase targeting imposes the use of two Dδ gene segments in human TCR-δ chains. Absence of this RUNX1 binding site in the homologous mouse Dδ1-23RSS provides a molecular explanation for the lack of ordered TCR-δ gene assembly in mice and may underlie differences in early lymphoid differentiation between these species.
Long-term survival of influenza virus infected club cells drives immunopathology
Authors: Heaton Nicholas S. , Langlois Ryan A. , Sachs David , Lim Jean K. , Palese Peter , tenOever Benjamin R.
Published: August 2014

Respiratory infection of influenza A virus (IAV) is frequently characterized by extensive immunopathology and proinflammatory signaling that can persist after virus clearance. In this report, we identify cells that become infected, but survive, acute influenza virus infection. We demonstrate that these cells, known as club cells, elicit a robust transcriptional response to virus infection, show increased interferon stimulation, and induce high levels of proinflammatory cytokines after successful viral clearance. Specific depletion of these surviving cells leads to a reduction in lung tissue damage associated with IAV infection. We propose a model in which infected, surviving club cells establish a proinflammatory environment aimed at controlling virus levels, but at the same time contribute to lung pathology.
Prevalence of Nasal Colonization and Strain Concordance in Patients with Community-AssociatedStaphylococcus aureusSkin and Soft-Tissue Infections
Authors: Ellis Michael W. , Schlett Carey D. , Millar Eugene V. , Crawford Katrina B. , Cui Tianyuan , Lanier Jeffrey B. , Tribble David R.
Published: August 2014

Objective.

Determine the prevalence and relatedness ofStaphylococcus aureusanterior nares colonization in individuals with community-associated staphylococcal skin and soft-tissue infection (SSTI)

Design.

Observational cohort.

Setting.

US Army soldiers undergoing infantry training.

Participants.

Trainees who developed SSTI from May 2010 to January 2012.

Methods.

Participants underwent anterior nares culture at the time of presentation for purulent SSTI. We determined the prevalence ofS. aureusnasal colonization and strain relatedness between colonizing and clinical isolates with pulsed-field gel electrophoresis (PFGE).

Results.

We enrolled 1,203 SSTI participants, of whom 508 had culture-confirmedS. aureusSSTI. Overall, 70% (357/508) were colonized withS. aureus. Phenotypically, concordant colonization was more common with methicillin-susceptibleS. aureus(MSSA; 56%; 122/218) than methicillin-resistantS. aureus(MRSA) SSTI (41%; 118/290;P< .01). With PFGE, 48% (121 of 254) of clinical-colonizing pairs were indistinguishable, and concordant colonization was more common with MRSA (53%; 92/173) than MSSA SSTI (36%; 29/81;P< .01). Restricting analysis to concomitant MRSA-MRSA or MSSA-MSSA pairs, 92% (92/100) of MRSA SSTI were indistinguishable, and 40% (29/72) MSSA SSTI were indistinguishable (P< .01). All 92 MRSA pairs were USA300.

Conclusions.

On the phenotypic level, concordant anterior nares colonization with incident staphylococcal SSTI is more common in MSSA than MRSA; however, the opposite is observed when accounting for molecular typing, and MRSA SSTI displays greater concordance. USA300 was responsible for strain concordance with MRSA SSTI. Studies are needed to examine the roles of nasal and extra-nasal carriage, colonization preceding infection, and increased virulence in the pathogenesis of MRSA SSTI.

Trial registration.

ClinicalTrials.gov identifier: NCT01105767.

Infect Control Hosp Epidemiol2014;35(10):1251–1256
An extremely low gas-to-dust ratio in the dust-lane lenticular galaxy NGC 5485
Authors: Baes Maarten , Allaert Flor , Sarzi Marc , De Looze Ilse , Fritz Jacopo , Gentile Gianfranco , Hughes Thomas M. , Puerari Ivânio , Smith Matthew W. L. , Viaene Sébastien
Published: August 2014

Evidence is mounting that a significant fraction of the early-type galaxy population contains substantial reservoirs of cold interstellar gas and dust. We investigate the gas and dust in NGC 5485, an early-type galaxy with a prominent minor-axis dust lane. Using new Herschel PACS and SPIRE imaging data, we detect 3.8 × 106 M⊙ of cool interstellar dust in NGC 5485, which is in stark contrast with the non-detection of the galaxy in sensitive H i and CO observations from the ATLAS3D consortium. The resulting gas-to-dust ratio upper limit is Mgas/Md < 14.5, almost an order of magnitude lower than the canonical value for the Milky Way. We scrutinize the reliability of the dust, atomic gas and molecular gas mass estimates, but these do not show systematic uncertainties that can explain the extreme gas-to-dust ratio. Also a warm or hot ionized gas medium does not offer an explanation. A possible scenario could be that NGC 5485 merged with an SMC-type metal-poor galaxy with a substantial CO-dark molecular gas component and that the bulk of atomic gas was lost during the interaction, but it remains to be investigated whether such a scenario is possible.
Barriers and Facilitators to Successful Transition from Pediatric to Adult Inflammatory Bowel Disease Care from the Perspectives of Providers
Authors: Paine Christine W. , Stollon Natalie B. , Rabelais Em , Brumley Lauren D. , Poole Erika S. , Peyton Tamara , Grant Anne W. , Jan Sophia , Trachtenberg Symme , Zander Miriam , Mamula Petar , Bonafide Christopher P. , Schwartz Lisa A.
Published: August 2014

Background

For adolescents and young adults (AYA) with inflammatory bowel disease (IBD), the transition from pediatric to adult care is often challenging and associated with gaps in care. Our study objectives were to (1) identify outcomes for evaluating transition success and (2) elicit the major barriers and facilitators of successful transition.

Methods

We interviewed pediatric and adult IBD providers from across the United States with experience caring for AYAs with IBD until thematic saturation was reached after 12 interviews. We elicited the participants' backgrounds, examples of successful and unsuccessful transition of AYAs for whom they cared, and recommendations for improving transition using the Social–Ecological Model of Adolescent and Young Adult Readiness to Transition framework. We coded interview transcripts using the constant comparative method and identified major themes.

Results

Participants reported evaluating transition success and failure using health care utilization outcomes (e.g., maintaining continuity with adult providers), health outcomes (e.g., stable symptoms), and quality of life outcomes (e.g., attending school). The patients' level of developmental maturity (i.e., ownership of care) was the most prominent determinant of transition outcomes. The style of parental involvement (i.e., helicopter parent versus optimally involved parent) and the degree of support by providers (e.g., care coordination) also influenced outcomes.

Conclusions

IBD transition success is influenced by a complex interplay of patient developmental maturity, parenting style, and provider support. Multidisciplinary IBD care teams should aim to optimize these factors for each patient to increase the likelihood of a smooth transfer to adult care.
Management of Chronic Intractable Constipation in Children
Authors: Kerur Basavaraj , Kantekure Kanchan , Bonilla Silvana , Orkin Bruce , Flores Alejandro F.
Published: August 2014

Background:

Chronic intractable constipation (CIC) is a debilitating disease that is challenging to manage. Treatment options in children include medications, enemas, and surgical management in selected cases.

Method:

We reviewed medical records of pediatric patients diagnosed as having CIC at Tufts Medical Center from 2005 to 2012. Demographic variables, diagnostic procedures, and medical and surgical outcomes were collected. Clinical outcome was defined using the Rome III criteria.

Results:

A total of 14 patients were included in the study (10 boys). The age range was 10 to 21 years. All of the patients had the diagnosis of CIC. Eleven patients had cecostomy placement. During the follow‐up period, 10 patients underwent total abdominal colectomy with ileorectal anastomosis, 1 had total colectomy with ileostomy, and 1 had partial colectomy with colorectal anastomosis. Successful clinical outcome was reported in 7 patients with 3 patients reporting persistent fecal incontinence. Colonic motility studies were performed on 12 patients (colonic neuropathy in 11 patients and normal study in 1 patient). Defecography was consistent with isolated pelvic floor dysfunction in 1 patient, abnormal motility and anatomy in 1 patient, pelvic floor dysfunction and abnormal motility in 2 patients, and found abnormal motility only in 5. Defecography study was normal in 5 patients. All of the patients with abnormal colonic manometry underwent a surgical procedure.

Conclusions:

Anorectal manometry, colonic manometry, and defecography help in understanding the pathophysiology of defecation disorders in children. The majority of patients with abnormal colonic manometry underwent TAC‐IRA. There was no statistical correlation between individual investigations (anorectal manometry, colonic manometry, and defecography) with surgical intervention (P > 0.35). TAC‐IRA may be safe and useful intervention in a subset of patients when other treatment options have failed.
The RNA-centred view of the synapse: non-coding RNAs and synaptic plasticity
Authors: Smalheiser Neil R.
Published: August 2014

If mRNAs were the only RNAs made by a neuron, there would be a simple mapping of mRNAs to proteins. However, microRNAs and other non-coding RNAs (ncRNAs; endo-siRNAs, piRNAs, BC1, BC200, antisense and long ncRNAs, repeat-related transcripts, etc.) regulate mRNAs via effects on protein translation as well as transcriptional and epigenetic mechanisms. Not only are genes ON or OFF, but their ability to be translated can be turned ON or OFF at the level of synapses, supporting an enormous increase in information capacity. Here, I review evidence that ncRNAs are expressed pervasively within dendrites in mammalian brain; that some are activity-dependent and highly enriched near synapses; and that synaptic ncRNAs participate in plasticity responses including learning and memory. Ultimately, ncRNAs can be viewed as the post-it notes of the neuron. They have no literal meaning of their own, but derive their functions from where (and to what) they are stuck. This may explain, in part, why ncRNAs differ so dramatically from protein-coding genes, both in terms of the usual indicators of functionality and in terms of evolutionary constraints. ncRNAs do not appear to be direct mediators of synaptic transmission in the manner of neurotransmitters or receptors, yet they orchestrate synaptic plasticity—and may drive species-specific changes in cognition.
An evolving view of epigenetic complexity in the brain
Authors: Qureshi Irfan A. , Mehler Mark F.
Published: August 2014

Recent scientific advances have revolutionized our understanding of classical epigenetic mechanisms and the broader landscape of molecular interactions and cellular functions that are inextricably linked to these processes. Our current view of epigenetics includes an increasing appreciation for the dynamic nature of DNA methylation, active mechanisms for DNA demethylation, differential functions of 5-methylcytosine and its oxidized derivatives, the intricate regulatory logic of histone post-translational modifications, the incorporation of histone variants into chromatin, nucleosome occupancy and dynamics, and direct links between cellular signalling pathways and the actions of chromatin ‘reader’, ‘writer’ and ‘eraser’ molecules. We also have an increasing awareness of the seemingly ubiquitous roles played by diverse classes of selectively expressed non-coding RNAs in transcriptional, post-transcriptional, post-translational and local and higher order chromatin modulatory processes. These perspectives are still evolving with novel insights continuing to emerge rapidly (e.g. those related to epigenetic regulation of mobile genetic elements, epigenetic mechanisms in mitochondria, roles in nuclear architecture and ‘RNA epigenetics’). The precise functions of these epigenetic factors/phenomena are largely unknown. However, it is unequivocal that they serve as key mediators of brain complexity and flexibility, including neural development and aging, cellular differentiation, homeostasis, stress responses, and synaptic and neural network connectivity and plasticity.
The role of long non-coding RNAs in neurodevelopment, brain function and neurological disease
Authors: Roberts Thomas C. , Morris Kevin V. , Wood Matthew J. A.
Published: August 2014

Long non-coding RNAs (lncRNAs) are transcripts with low protein-coding potential that represent a large proportion of the transcriptional output of the cell. Many lncRNAs exhibit features indicative of functionality including tissue-restricted expression, localization to distinct subcellular structures, regulated expression and evolutionary conservation. Some lncRNAs have been shown to associate with chromatin-modifying activities and transcription factors, suggesting that a common mode of action may be to guide protein complexes to target genomic loci. However, the functions (if any) of the vast majority of lncRNA transcripts are currently unknown, and the subject of investigation. Here, we consider the putative role(s) of lncRNAs in neurodevelopment and brain function with an emphasis on the epigenetic regulation of gene expression. Associations of lncRNAs with neurodevelopmental/neuropsychiatric disorders, neurodegeneration and brain cancers are also discussed.
Systematic identification of 3′-UTR regulatory elements in activity-dependent mRNA stability in hippocampal neurons
Authors: Cohen Jonathan E. , Lee Philip R. , Fields R. Douglas
Published: August 2014

Ongoing neuronal activity during development and plasticity acts to refine synaptic connections and contributes to the induction of plasticity and ultimately long-term memory storage. Activity-dependent, post-transcriptional control of mRNAs occurs through transport to axonal and dendritic compartments, local translation and mRNA stability. We have identified a mechanism that contributes to activity-dependent regulation of mRNA stability during synaptic plasticity in rat hippocampal neurons. In this study, we demonstrate rapid, post-transcriptional control over process-enriched mRNAs by neuronal activity. Systematic analysis of the 3′-UTRs of destabilized transcripts, identifies enrichment in sequence motifs corresponding to microRNA (miRNA)-binding sites. The miRNAs that were identified, miR-326-3p/miR-330-5p, miR-485-5p, miR-666-3p and miR-761 are predicted to regulate networks of genes important in plasticity and development. We find that these miRNAs are developmentally regulated in the hippocampus, many increasing by postnatal day 14. We further find that miR-485-5p controls NGF-induced neurite outgrowth in PC12 cells, tau expression and axonal development in hippocampal neurons. miRNAs can function at the synapse to rapidly control and affect short- and long-term changes at the synapse. These processes likely occur during refinement of synaptic connections and contribute to the induction of plasticity and learning and memory.
The methylated-DNA binding protein MBD2 enhances NGFI-A (egr-1)-mediated transcriptional activation of the glucocorticoid receptor
Authors: Weaver Ian C. G. , Hellstrom Ian C. , Brown Shelley E. , Andrews Stephen D. , Dymov Sergiy , Diorio Josie , Zhang Tie-Yuan , Szyf Moshe , Meaney Michael J.
Published: August 2014

Variations in maternal care in the rat influence the epigenetic state and transcriptional activity of glucocorticoid receptor (GR) gene in the hippocampus. The mechanisms underlying this maternal effect remained to be defined, including the nature of the relevant maternally regulated intracellular signalling pathways. We show here that increased maternal licking/grooming (LG), which stably enhances hippocampal GR expression, paradoxically increases hippocampal expression of the methyl-CpG binding domain protein-2 (MBD2) and MBD2 binding to the exon 1
7
GR promoter. Knockdown experiments of MBD2 in hippocampal primary cell culture show that MBD2 is required for activation of exon 1
7
GR promoter. Ectopic co-expression of nerve growth factor-inducible protein A (NGFI-A) with MBD2 in HEK 293 cells with site-directed mutagenesis of the NGFI-A response element within the methylated exon 1
7
GR promoter supports the hypothesis that MBD2 collaborates with NGFI-A in binding and activation of this promoter. These data suggest a possible mechanism linking signalling pathways, which are activated by behavioural stimuli and activation of target genes.
MicroRNA-8 promotes robust motor axon targeting by coordinate regulation of cell adhesion molecules during synapse development
Authors: Lu Cecilia S. , Zhai Bo , Mauss Alex , Landgraf Matthias , Gygi Stephen , Van Vactor David
Published: August 2014

Neuronal connectivity and specificity rely upon precise coordinated deployment of multiple cell-surface and secreted molecules. MicroRNAs have tremendous potential for shaping neural circuitry by fine-tuning the spatio-temporal expression of key synaptic effector molecules. The highly conserved microRNA miR-8 is required during late stages of neuromuscular synapse development inDrosophila. However, its role in initial synapse formation was previously unknown. Detailed analysis of synaptogenesis in this system now reveals that miR-8 is required at the earliest stages of muscle target contact by RP3 motor axons. We find that the localization of multiple synaptic cell adhesion molecules (CAMs) is dependent on the expression of miR-8, suggesting that miR-8 regulates the initial assembly of synaptic sites. Using stable isotope labellingin vivoand comparative mass spectrometry, we find that miR-8 is required for normal expression of multiple proteins, including the CAMs Fasciclin III (FasIII) and Neuroglian (Nrg). Genetic analysis suggests that Nrg and FasIII collaborate downstream of miR-8 to promote accurate target recognition. Unlike the function of miR-8 at mature larval neuromuscular junctions, at the embryonic stage we find that miR-8 controls key effectors on both sides of the synapse. MiR-8 controls multiple stages of synapse formation through the coordinate regulation of both pre- and postsynaptic cell adhesion proteins.