bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutagenesis of Adeno-Associated Virus Type 2 Capsid Protein VP1 Uncovers New Roles for Basic Amino Acids in Trafficking and Cell-Specific Transduction
Authors: Johnson Jarrod S. , Li Chengwen , DiPrimio Nina , Weinberg Marc S. , McCown Thomas J. , Samulski R. Jude
Published: June 2010

The N termini of the capsid proteins VP1 and VP2 of adeno-associated virus (AAV) play important roles in subcellular steps of infection and contain motifs that are highly homologous to a phospholipase A
2
(PLA
2
) domain and nuclear localization signals (NLSs). To more clearly understand how virion components influence infection, we have generated mutations in these regions and examined their effects on subcellular trafficking, capsid stability, transduction, and sensitivity to pharmacological enhancement. All mutants tested assembled into capsids; retained the correct ratio of VP1, VP2, and VP3; packaged DNA similarly to recombinant AAV2 (rAAV2); and displayed similar stability profiles when heat denatured. Confocal microscopy demonstrated that these mutants trafficked through a perinuclear region in the vicinity of the Golgi apparatus, with a subset of mutants displaying more-diffuse localization consistent with an NLS-deficient phenotype. When tested for viral transduction, two mutant classes emerged. Class I (BR1
−
, BR2
−
, and BR2+K) displayed partial transduction, whereas class II (VP3only,
75
HD/AN, BR3
−
, and BR3+K) were severely defective. Surprisingly, one class II mutant (BR3+K) trafficked identically to rAAV2 and accumulated in the nucleolus, a step recently described by our laboratory that occurs with wild-type infection. The BR3+K mutant, containing an alanine-to-lysine substitution in the third basic region of VP1, was 10- to 100-fold-less infectious than rAAV2 in transformed cell lines (such as HEK-293, HeLa, and CV1-T cells), but in contrast, it was indistinguishable from rAAV2 in several nontransformed cell lines, as well as in tissues (liver, brain, and muscle)
in vivo
. Complementation studies with pharmacological adjuvants or adenovirus coinfection suggested that additional positive charges in NLS regions restrict mobilization in the nucleus and limit transduction in a transformed-cell-specific fashion. Remarkably, besides displaying cell-type-specific transduction, this is the first description of a capsid mutant indicating that nuclear entry is not sufficient for AAV-mediated transduction and suggests that additional steps (i.e., subnuclear mobilization or uncoating) limit successful AAV infection.
Identification of Rep-Associated Factors in Herpes Simplex Virus Type 1-Induced Adeno-Associated Virus Type 2 Replication Compartments
Authors: Nicolas Armel , Alazard-Dany Nathalie , Biollay Coline , Arata Loredana , Jolinon Nelly , Kuhn Lauriane , Ferro Myriam , Weller Sandra K. , Epstein Alberto L. , Salvetti Anna , Greco Anna
Published: June 2010

Adeno-associated virus (AAV) is a human parvovirus that replicates only in cells coinfected with a helper virus, such as adenovirus or herpes simplex virus type 1 (HSV-1). We previously showed that nine HSV-1 factors are able to support AAV
rep
gene expression and genome replication. To elucidate the strategy of AAV replication in the presence of HSV-1, we undertook a proteomic analysis of cellular and HSV-1 factors associated with Rep proteins and thus potentially recruited within AAV replication compartments (AAV RCs). This study resulted in the identification of approximately 60 cellular proteins, among which factors involved in DNA and RNA metabolism represented the largest functional categories. Validation analyses indicated that the cellular DNA replication enzymes RPA, RFC, and PCNA were recruited within HSV-1-induced AAV RCs. Polymerase δ was not identified but subsequently was shown to colocalize with Rep within AAV RCs even in the presence of the HSV-1 polymerase complex. In addition, we found that AAV replication is associated with the recruitment of components of the Mre11/Rad50/Nbs1 complex, Ku70 and -86, and the mismatch repair proteins MSH2, -3, and -6. Finally, several HSV-1 factors were also found to be associated with Rep, including UL12. We demonstrated for the first time that this protein plays a role during AAV replication by enhancing the resolution of AAV replicative forms and AAV particle production. Altogether, these analyses provide the basis to understand how AAV adapts its replication strategy to the nuclear environment induced by the helper virus.
Identification of Cross-Reactive Norovirus CD4
+
T Cell Epitopes
Authors: LoBue Anna D. , Lindesmith Lisa C. , Baric Ralph S.
Published: June 2010

Immune responses and the components of protective immunity following norovirus infection in humans are poorly understood. Although antibody responses following norovirus infection have been partially characterized, T cell responses in humans remain largely undefined. In contrast, T cells have been shown to be essential for viral clearance of mouse norovirus (MNV) infection. In this paper, we demonstrate that CD4
+
T cells secrete gamma interferon (IFN-γ) in response to stimulation with MNV virus-like particles (VLPs) after MNV infection, supporting earlier reports for norovirus-infected mice and humans. Utilizing this model, we immunized mice with alphavirus vectors (Venezuelan equine encephalitis [VEE] virus replicon particles [VRPs]) expressing Norwalk virus (NV) or Farmington Hills virus (FH) virus-like particles to evaluate T cell epitopes shared between human norovirus strains. Stimulation of splenocytes from norovirus VRP-immunized mice with overlapping peptides from complete libraries of the NV or FH capsid proteins revealed specific amino acid sequences containing T cell epitopes that were conserved within genoclusters and genogroups. Immunization with heterologous norovirus VRPs resulted in specific cross-reactive IFN-γ secretion profiles following stimulation with NV and FH peptides in the mouse. Identification of unique strain-specific and cross-reactive epitopes may provide insight into homologous and heterologous T cell-mediated norovirus immunity and provide a platform for the study of norovirus-induced cellular immunity in humans.
Nucleocytoplasmic Shuttling of Human Cytomegalovirus UL84 Is Essential for Virus Growth
Authors: Gao Yang , Kagele Dominique , Smallenberg Kate , Pari Gregory S.
Published: June 2010

Human cytomegalovirus (HCMV) UL84 is a multifunctional protein that is the proposed initiator for lytic viral DNA synthesis. Recently it was shown that UL84 displays nucleocytoplasmic shuttling. The role of shuttling in lytic DNA replication and virus growth is unknown. We now show that expression of the nonshuttling UL84 mutant failed to complement oriLyt-dependent DNA replication in the transient assay under conditions where core replication and ancillary proteins were expressed under the control of their native promoters. However, constitutive expression of the core replication proteins, along with the nonshuttling UL84 mutant, resulted in efficient oriLyt amplification, suggesting that shuttling may contribute to the activity of one of the auxiliary replication proteins. A recombinant HCMV bacterial artificial chromosome plasmid (BACmid) expressing the nonshuttling UL84 mutant (NS84 BAC) was defective for production of infectious virus. Quantitative PCR showed that NS84 BAC had decreased accumulation of viral DNA in both cellular and supernatant samples. Analysis of the accumulation of select viral mRNAs showed no difference in total cellular mRNA accumulation for IE2, IRS1, TRS1, UL102, UL105, and UL75 in cells transfected with the NS84 BAC. However, examination of cytoplasmic RNA and subcellular localization of IRS1 revealed a decrease in IRS1 mRNA accumulation and displaced protein localization, strongly suggesting that UL84 facilitated the localization of IRS1 mRNA to the cytoplasm. RNA pulldown assays showed that UL84 interacted with IRS1 mRNA. These results indicate that nucleocytoplasmic shuttling is essential for virus growth and strongly suggest that UL84 is responsible for localization of at least one virus-encoded transcript, IRS1 mRNA.
CD25
+
Natural Regulatory T Cells Are Critical in Limiting Innate and Adaptive Immunity and Resolving Disease following Respiratory Syncytial Virus Infection
Authors: Lee Debbie C. P. , Harker James A. E. , Tregoning John S. , Atabani Sowsan F. , Johansson Cecilia , Schwarze Jürgen , Openshaw Peter J. M.
Published: June 2010

Regulatory CD4
+
T cells have been shown to be important in limiting immune responses, but their role in respiratory viral infections has received little attention. Here we observed that following respiratory syncytial virus (RSV) infection, CD4
+
Foxp3
+
CD25
+
natural regulatory T-cell numbers increased in the bronchoalveolar lavage fluid, lung, mediastinal lymph nodes, and spleen. The depletion of CD25
+
natural regulatory T cells prior to RSV infection led to enhanced weight loss with delayed recovery that was surprisingly accompanied by increased numbers of activated natural killer cells in the lung and bronchoalveolar lavage fluid on day 8 postinfection. Increased numbers of neutrophils were also detected within the bronchoalveolar lavage fluid and correlated with elevated levels of myeloperoxidase as well as interleukin-6 (IL-6) and gamma interferon (IFN-γ). CD25
+
natural regulatory T-cell depletion also led to enhanced numbers of proinflammatory T cells producing IFN-γ and tumor necrosis factor alpha (TNF-α) in the lung. Despite these increases in inflammatory responses and disease severity, the viral load was unaltered. This work highlights a critical role for natural regulatory T cells in regulating the adaptive and innate immune responses during the later stages of lung viral infections.
Tyrosines in the Influenza A Virus M2 Protein Cytoplasmic Tail Are Critical for Production of Infectious Virus Particles
Authors: Grantham Michael L. , Stewart Shaun M. , Lalime Erin N. , Pekosz Andrew
Published: June 2010

The cytoplasmic tail of the influenza A virus M2 protein is required for the production of infectious virions. In this study, critical residues in the M2 cytoplasmic tail were identified by single-alanine scanning mutagenesis. The tyrosine residue at position 76, which is conserved in >99% of influenza virus strains sequenced to date, was identified as being critical for the formation of infectious virus particles using both reverse genetics and a protein
trans
-complementation assay. Recombinant viruses encoding M2 with the Y76A mutation demonstrated replication defects in MDCK cells as well as in primary differentiated airway epithelial cell cultures, defects in the formation of filamentous virus particles, and reduced packaging of nucleoprotein into virus particles. These defects could all be overcome by a mutation of serine to tyrosine at position 71 of the M2 cytoplasmic tail, which emerged after blind passage of viruses containing the Y76A mutation. These data confirm and extend our understanding of the significance of the M2 protein for infectious virus particle assembly.
In Vitro
Assembly of the T=13 Procapsid of Bacteriophage T5 with Its Scaffolding Domain
Authors: Huet Alexis , Conway James F. , Letellier Lucienne , Boulanger Pascale
Published: June 2010

The
Siphoviridae
coliphage T5 differs from other members of this family by the size of its genome (121 kbp) and by its large icosahedral capsid (90 nm), which is organized with T=13 geometry. T5 does not encode a separate scaffolding protein, but its head protein, pb8, contains a 159-residue aminoterminal scaffolding domain (Δ domain) that is the mature capsid. We have deciphered the early events of T5 shell assembly starting from purified pb8 with its Δ domain (pb8p). The self assembly of pb8p is regulated by salt conditions and leads to structures with distinct morphologies. Expanded tubes are formed in the presence of NaCl, whereas Ca
2+
promotes the association of pb8p into contracted tubes and procapsids. Procapsids display an angular organization and 20-nm-long internal radial structures identified as the Δ domain. The T5 head maturation protease pb11 specifically cleaves the Δ domain of contracted and expanded tubes. Ca
2+
is not required for proteolytic activity but for the organization of the Δ domain. Taken together, these data indicate that pb8p carries all of the information in its primary sequence to assemble
in vitro
without the requirement of the portal and accessory proteins. Furthermore, Ca
2+
plays a key role in introducing the conformational diversity that permits the formation of a stable procapsid. Phage T5 is the first example of a viral capsid consisting of quasi-equivalent hexamers and pentamers whose assembly can be carried out
in vitro
, starting from the major head protein with its scaffolding domain, and whose endpoint is an icosahedral T=13 particle.
Characterization of the Host Immune Response in Human Ganglia after Herpes Zoster
Authors: Gowrishankar Kavitha , Steain Megan , Cunningham Anthony L. , Rodriguez Michael , Blumbergs Peter , Slobedman Barry , Abendroth Allison
Published: June 2010

Varicella-zoster virus (VZV) causes varicella (chicken pox) and establishes latency in ganglia, from where it reactivates to cause herpes zoster (shingles), which is often followed by postherpetic neuralgia (PHN), causing severe neuropathic pain that can last for years after the rash. Despite the major impact of herpes zoster and PHN on quality of life, the nature and kinetics of the virus-immune cell interactions that result in ganglion damage have not been defined. We obtained rare material consisting of seven sensory ganglia from three donors who had suffered from herpes zoster between 1 and 4.5 months before death but who had not died from herpes zoster. We performed immunostaining to investigate the site of VZV infection and to phenotype immune cells in these ganglia. VZV antigen was localized almost exclusively to neurons, and in at least one case it persisted long after resolution of the rash. The large immune infiltrate consisted of noncytolytic CD8+T cells, with lesser numbers of CD4+T cells, B cells, NK cells, and macrophages and no dendritic cells. VZV antigen-positive neurons did not express detectable major histocompatibility complex (MHC) class I, nor did CD8+T cells surround infected neurons, suggesting that mechanisms of immune control may not be dependent on direct contact. This is the first report defining the nature of the immune response in ganglia following herpes zoster and provides evidence for persistence of non-latency-associated viral antigen and inflammation beyond rash resolution.
The Ig-Like V-Type Domain of Paired Ig-Like Type 2 Receptor Alpha Is Critical for Herpes Simplex Virus Type 1-Mediated Membrane Fusion
Authors: Fan Qing , Longnecker Richard
Published: June 2010

Paired immunoglobulin (Ig)-like type 2 receptor alpha (PILRα) and PILRβ are paired receptors that are highly homologous to each other. When engaged by ligand, PILRα is inhibitory whereas PILRβ is activating. PILRα is a newly identified herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) receptor and is associated with membrane fusion and entry activity of HSV-1. PILRα is a 303-amino-acid protein with an Ig-like V (variable)-type domain from amino acid 31 to 150, whereas PILRβ is a 217-amino-acid protein with an Ig-like V-type domain from amino acid 21 to 143. We report that PILRβ is not a receptor for HSV-1 and HSV-2. Domain swaps between PILRα and PILRβ reveal that the Ig-like V-type domain of PILRα, but not PILRβ, plays a critical role in cell membrane fusion activity and the binding of PILRα to gB. Individual replacement of 13 amino acids in PILRα showed that most of these mutations had no effect on cell fusion activity. However, mutation of the tryptophan residue at amino acid 139 significantly impaired cell fusion activity for HSV-1 and eliminated binding to gB.
The Triplet Repeats of the Sin Nombre Hantavirus 5′ Untranslated Region Are Sufficient in
cis
for Nucleocapsid-Mediated Translation Initiation
Authors: Mir Mohammad A. , Panganiban Antonito T.
Published: June 2010

Hantavirus nucleocapsid protein (N) can replace the cellular cap-binding complex, eukaryotic initiation factor 4F (eIF4F), to mediate translation initiation. Although N can augment translation initiation of nonviral mRNA, initiation of viral mRNA by N is superior. All members of the
Bunyaviridae
family, including the species of the hantavirus genus, express either three or four primary mRNAs from their tripartite negative-sense genomes. The 5′ ends of the mRNAs contain nonviral heterologous oligonucleotides that originate from endonucleolytic cleavage of cellular mRNA during the process of cap snatching. In the hantaviruses these caps terminate with a 3′ G residue followed by nucleotides arising from the viral template. Further, the 5′ untranslated region (UTR) of viral mRNA uniformly contains, near the 5′ end, either two or three copies of the triplet repeat sequence, UAGUAG or UAGUAGUAG. Through analysis of a panel of mutants with mutations in the viral UTR, we found that the sequence GUAGUAG is sufficient for preferential N-mediated translation initiation and for high-affinity binding of N to the UTR. This heptanucleotide sequence is present in viral mRNA containing either two or three copies of the triplet repeat.
A geophysical model for the Kapuskasing uplift from seismic and gravity studies
Authors: Boland A. V. , Ellis R. M.
Published: June 2010

The Kapuskasing uplift is an oblique cross section of Archean crust exposed by a major thrusting event in Early Proterozoic times. Previous results from the traveltime and amplitude analysis of compressional-wave (P-wave) arrivals from a seismic-refraction experiment have been used to constrain the modelling of shear-wave (S-wave) arrivals and gravity anomalies along the seismic profiles. S-wave and P-wave velocity information have been combined to obtain the variations of Poisson's ratio within the crust. High and low Poisson's ratio values have been linked to the mafic and felsic content, respectively, of the Shield rocks. Density variations along the profiles, constrained by the P-wave velocity structures and the observed gravity anomalies, again have been linked to the lithological variations as observed in the exposed cross section. Geological models, constrained by the geophysical observations and the cross-sectional exposure, have been constructed for profiles across the northern and southern portions of the main uplift region. The results indicate an increase in pyroxene and garnetiferous gneisses with depth in the crust, as suggested by the high P-wave velocities (7.0–7.6 km/s), high densities (3050–3150 kg/m3, high Poisson's ratio values (0.26–0.28), and the petrological variations within the exposure. The presence of a low-velocity and low-density layer of tonalites under the surface greenstones has been established and can account for the low-velocity zones imaged along the Abitibi profile of this experiment and those imaged in other Shield refraction experiments.
Correlation of Settler Schist with Darrington Phyllite and Shuksan Greenschist and its tectonic implications, Coast and Cascade mountains, British Columbia and Washington
Authors: Monger J. W. H.
Published: June 2010

Amphibolite-facies Settler Schist in the southeastern Coast Mountains of British Columbia has long been correlated with Chiwaukum Schist of the Cascade metamorphic core, North Cascade Mountains, northwestern Washington. The additional correlation proposed here of Settler Schist with Darrington Phyllite and Shuksan Greenschist (and blueschist) of the Northwest Cascade System in Washington is based on along-strike near-continuity of outcrop areas, a similar protolith composition range, the same structural position relative to the Shuksan fault zone, and distinctive irregular structures in variably metamorphosed sandstone and pelite of both Darrington Phyllite and Settler Schist. If this correlation is valid, then the record of Early Cretaceous; subduction-related blueschist metamorphism of Shuksan–Darrington rocks was destroyed in Settler Schist by overprinting by early Late Cretaceous Barrovian metamorphism; only some distinctive, premetamorphic structures remain. The implication is that within the southeastern Coast Mountains, a cryptic record of subduction is overprinted by Barrovian metamorphism.
A post-Lake Minong transgressive event on the north shore of Lake Superior, Ontario: possible evidence of Lake Agassiz inflow
Authors: Phillips Brian A. M. , Fralick Philip W.
Published: June 2010

Modification of an ice-contact delta built on the margin of Lake Minong (9500 BP) is ascribed to a transgressive event. Reworking of fluvial sediments by wave action and the infilling of the lower end of a distributary valley demonstrate a post-Minong transgression and reoccupation of the lower portion of the delta. Estimated to be in the order of 18 m, this water-level oscillation may represent evidence of one of several catastrophic discharges of Lake Agassiz into the Superior basin, proposed to have occurred between 9.5 and 8.0 ka BP.
3mm POLARIZATION PROPERTIES OF OPTICAL AND γ-RAY CLASSES OF BLAZARS
Authors: AGUDO I. , THUM C. , WIESEMEYER H. , KRICHBAUM T. P.
Published: June 2010

We have performed the first 3.5 mm polarimetric survey of radio loud active galactic nuclei (AGN) with the IRAM 30 m Telescope. Unlike radio wavelengths, millimeter observations allow us to measure the intrinsic linearly polarized emission from AGN, thanks to the marginal effect of Faraday rotation and depolarization at mm wavelengths. The sample contains 145 sources, and it essentially consists of all flat-spectrum AGN with declinations accessible to the 30 m Telescope (Dec. ( J 2000.0) > -30°), and with 3 mm flux density ≳ 1 Jy, as measured from 1978 to 1994. LBAS quasars in our sample show larger luminosity than non-LBAS ones, which is consistent with previous work claiming larger Doppler factors for brighter γ-ray blazars. This effect cannot be claimed for BL Lacertae objects in our sample, which suggests that only quasars contribute to distribute LBAS blazars towards larger luminosities. We find a systematic 3.5 mm linear polarization degree excess by a factor of ~ 2 with regard to the one at 2 cm for all optical and γ-ray classes of sources considered here. Our sample shows a significant trend to increase the luminosity of their jets for decreasing linear polarization fraction. Unlike previous studies in the radio spectral range, we do not find a clear relation between the linear polarization angle and the jet structural position angle of any source class in our sample. This is interpreted as a markedly non-axisymmetric character of the 3 mm emitting region of radio loud AGN jets.
ROLE OF THE HALL EFFECT ON THE MAGNETOROTATIONAL INSTABILITY
Authors: BEJARANO CECILIA , GÓMEZ DANIEL
Published: June 2010

Within the framework of magnetohydrodynamics, the Hall effect might become significant either in fully ionized low density plasmas or in cold plasmas with a low ionization fraction. We address the role of the Hall current in the development of the magnetorotational instability. The instability criterion and the instability growth rate are derived from a one-dimensional model.
THE RELATION BETWEEN RADIO POLARIZATION AND GAMMA-RAY EMISSION IN AGN JETS
Authors: HOVATTA TALVIKKI , LISTER MATTHEW L. , KOVALEV YURI Y. , PUSHKAREV ALEXANDER B. , SAVOLAINEN TUOMAS
Published: June 2010

We have compared the parsec-scale jet linear polarization properties of the Fermi LAT-detected and non-detected sources in the complete flux-density-limited (MOJAVE-1) sample of highly beamed AGN. Of the 123 MOJAVE sources, 30 were detected by the LAT during its first three months of operation. We find that during the era since the launch of Fermi, the unresolved core components of the LAT-detected jets have significantly higher median fractional polarization at 15 GHz. This complements our previous findings that these LAT sources have higher apparent jet speeds, brightness temperatures and Doppler factors, and are preferentially found in higher activity states.
COUNTERPART CANDIDATES TO THE UNIDENTIFIED FERMI SOURCE 0FGL J1848.6-0138
Authors: LUQUE-ESCAMILLA P. L. , AYASO E. SÁNCHEZ , MARTÍ J. , MUÑOZ-ARJONILLA A. J. , SUTIL J. R. SÁNCHEZ , COMBI J. A.
Published: June 2010

Here we report the finding of a few counterpart candidates inside the 95% confidence error box of the Fermi LAT unidentified gamma-ray source 0FGL J1848.6-0138. Among them, the globular cluster GLIMPSE-C01 is specially remarkable. It offers a conceivable physical scenario for gamma-ray production and if confirmed to be counterpart it would be the second globular cluster (after 47 Tuc) associated to a Fermi source. The Fermi-observed spectrum is compared with theoretical predictions in the literature and the association is found to be plausible but not yet certain because of its low X–ray to gamma-ray luminosity ratio.
CURRENT-DRIVEN KINK INSTABILITY IN RELATIVISTIC JETS
Authors: MIZUNO YOSUKE , HARDEE PHILIP E. , LYUBARSKY YURI , NISHIKAWA KEN-ICHI
Published: June 2010

We have investigated the development of current-driven (CD) kink instability in relativistic jets via 3D RMHD simulations. In this investigation a static force-free equilibrium helical magnetic configuration is considered in order to study the influence of the initial configuration on the linear and nonlinear evolution of the instability. We found that the initial configuration is strongly distorted but not disrupted by the CD kink instability. The linear growth and nonlinear evolution of the CD kink instability depend moderately on the radial density profile and strongly on the magnetic pitch profile. Kink amplitude growth in the nonlinear regime for decreasing magnetic pitch leads to a slender helically twisted column wrapped by magnetic field. On the other hand, kink amplitude growth in the nonlinear regime nearly ceases for increasing magnetic pitch.
KINETIC PARTICLE-IN-CELL SIMULATIONS OF ASYMMETRIC QUASI-PARALLEL MILDLY RELATIVISTIC PLASMA COLLISIONS: FIELD AND ELECTRON DYNAMICS
Authors: MURPHY GARETH C. , DIECKMANN MARK E. , O'C DRURY LUKE
Published: June 2010

A gamma-ray burst (GRB) is triggered by a stellar implosion and the subsequent ejection of an ultrarelativistic jet. The prompt emissions are attributed to mildly relativistic collisions of plasma clouds within this jet. The resulting internal shocks are instrumental in the generation of the magnetic fields and the energetic electrons, which excite the observed electromagnetic emissions. We use particle-in-cell (PIC) simulations to examine such a shock. The colliding hot magnetized plasma clouds have densities that differ by a factor of 10. Current channels form rapidly in the 3D simulation, which resemble those in a Hammer–Rostoker equilibrium, are observed also in the 2D simulation. The 2D simulation also shows the formation of a shock, which is mediated by a strong electromagnetic wave, and the energy equipartition between electrons and ions.
MODEL FOR THE HIGH ENERGY EMISSION FROM CEN A
Authors: REYNOSO M. M. , MEDINA M. C. , ROMERO G. E. , ZECH A. , BOISSON C. , SOL H. , LENAIN J.-P.
Published: June 2010

Centaurus A (Cen A) is the closest active galaxy (3.8 Mpc) and presents strong activity over a wide spectral range from radio to very-high energy gamma-rays. We propose a lepto-hadronic model for the high-energy emission, assuming that particles can be shock-accelerated at the inner jets of this source. The primary electron and proton distributions are obtained in the acceleration zone, taking into account the relevant cooling processes such as synchrotron emission, inverse-Compton up-scattering of photons in both Thomson and Klein–Nishina regimes, proton–proton and proton–photon interactions. Considering the effects of internal absorption of gamma-rays, we compare our results with current observational data obtained by HESS and Fermi. We compute also the distribution of secondary pions and muons produced by hadronic interactions. The expected high-energy neutrino signal is calculated and the possibility of detection with KM3NET or similar arrays is discussed.
X–RAY AND GAMMA-RAY OBSERVATIONS OF THE INNER REGION OF MGRO J2019+37
Authors: ZABALZA V. , PAREDES J. M.
Published: June 2010

In order to better understand the puzzling extended TeV source MGRO J2019+37, we have performed a multiwavelength campaign from radio to X–ray covering most of its extent. Here we present an X–ray mosaic including a new observation and two archival observations performed by the X–ray observatory XMM-Newton. We have also observed the source with the gamma-ray observatory AGILE. We discuss new point-like and extended X–ray sources we have found in the field that could help elucidate the physics behind MGRO J2019+37.
POLARIZATION SWINGS FROM CURVED TRAJECTORIES OF THE EMITTING REGIONS
Authors: NALEWAJKO KRZYSZTOF
Published: June 2010

We present a model of polarization swings in blazars from axially symmetric blobs propagating on curved trajectories. If the minimum inclination of the velocity vector to the line of sight is smaller than Γ-1, the polarization angle maximum rotation rate is simultaneous with the polarization degree minimum and a spike in the total flux. By measuring the maximum rotation rate and the moment of the polarization maximum, it is possible to estimate the distance covered by the blob and thus its approximate position. We apply this model to the recent polarization event in blazar 3C 279.
MAGNETIC FIELD EFFECTS NEAR THE LAUNCHING REGION OF ASTROPHYSICAL JETS
Authors: DE GOUVEIA DAL PINO E. M. , KOWAL G. , KADOWAKI L. H. S. , PIOVEZAN P. , LAZARIAN A.
Published: June 2010

One of the fundamental properties of astrophysical magnetic fields is their ability to change topology through reconnection and in doing so, to release magnetic energy, sometimes violently. In this work, we review recent results on the role of magnetic reconnection and associated heating and particle acceleration in jet/accretion disk systems, namely young stellar objects (YSOs), microquasars, and active galactic nuclei (AGNs).
CAN MULTIBAND OBSERVATIONS CONSTRAIN EXPLANATIONS FOR KNOTTY JETS?
Authors: HARRIS D. E.
Published: June 2010

One can imagine a number of mechanisms that could be the cause of brighter/fainter segments of jets. In a sense, jets might be easier to understand if they were featureless. However we observe a wide variety of structures which we call "knots". By considering the ramifications of the various scenarios for the creation of knots, we determine which ones or which classes are favored by the currently available multiwavelength data.
ON THE INTERACTION OF JETS WITH STELLAR WINDS IN MASSIVE X–RAY BINARIES
Authors: PERUCHO MANEL , BOSCH-RAMON VALENTÍ , KHANGULYAN DMITRY
Published: June 2010

We present the first three-dimensional simulations of the evolution of a microquasar jet inside the binary star system. The aim is to study the interaction of these jets with the stellar wind from a massive companion and the possible locations of high-energy emission sites. We have simulated two jets with different injection power in order to give a hint on the minimum power required for the jet to escape the system and become visible in larger scales. In the setup, we include a massive star wind filling the grid through which the jet evolves. We show that jets should have powers of the order of 1037 erg s-1 or more in order not to be destroyed by the stellar wind. The jet–wind interaction results in regions in which high-energy emission could be produced. These results imply the possible existence of a population of X–ray binaries undetected in the radio band due to jet disruption inside the region dominated by the stellar wind.
MAGNETOHYDRODYNAMIC EFFECTS IN RELATIVISTIC EJECTA
Authors: MIZUNO YOSUKE , ZHANG BING , GIACOMAZZO BRUNO , NISHIKAWA KEN-ICHI , HARDEE PHILIP E. , NAGATAKI SHIGEHIRO , HARTMANN DIETER H.
Published: June 2010

We study the problem of deceleration of an arbitrarily magnetized relativistic ejecta in a static unmagnetized medium and its connection to the physics of gamma-ray bursts (GRBs). By computing exact solutions of the Riemann problem describing this scenario, we find that with the same initial Lorentz factor, the reverse shock becomes progressively weaker with increasing magnetization parameter σ (the Poynting-to-kinetic flux ratio). The reverse shock becomes a rarefaction wave when σ exceeds a critical value defined by the balance between magnetic pressure in the ejecta and thermal pressure in the forward shock. In the rarefaction wave regime, the rarefied region is accelerated to a Lorentz factor that is significantly larger than the initial value due to the strong magnetic pressure in the ejecta. We discuss the implications for models of GRBs.
NEW INSIGHT INTO GAMMA-RAY BLAZARS FROM THE FERMI-LAT
Authors:   On behalf of the Fermi-LAT collaboration, LOTT BENOIT
Published: June 2010

The first three months of sky-survey operation with the Large Area Telescope (LAT) on board the Fermi satellite revealed 132 bright sources at |b| > 10° with test statistic greater than 100 (corresponding to about 10σ). Two methods, based on the CGRaBS, CRATES and BZCat catalogs, indicated high-confidence associations of 106 of these sources with known AGNs. This sample is referred to as the LAT Bright AGN Sample (LBAS). It contains two radio galaxies, namely Centaurus A and NGC 1275, and 104 blazars consisting of 58 flat spectrum radio quasars (FSRQs), 42 BL Lac objects, and four blazars with unknown classification. Remarkably, the LBAS includes 10 high-energy-peaked BL Lacs. Only 33 of the sources, plus two at |b| < 10°, were previously detected with EGRET, probably due to variability. The analysis of the gamma-ray properties of the LBAS sources reveals that the average GeV spectra of BL Lac objects are significantly harder than the spectra of FSRQs. Other spectral and variability blazar properties are discussed. Some prominent Fermi-detected radiogalaxies are presented.
GAMMA-RAY BURSTS — OBSERVATIONS
Authors: GEHRELS N. , CANNIZZO J. K.
Published: June 2010

We are in an exciting period of discovery for gamma-ray bursts. The Swift observatory is detecting 100 bursts per year, providing arcsecond localizations and sensitive observations of the prompt and afterglow emission. The Fermi observatory is observing 250 bursts per year with its medium-energy GRB instrument and about 10 bursts per year with its high-energy LAT instrument. In addition, rapid-response telescopes on the ground are providing new capabilities to study optical emission during the prompt phase and spectral signatures of the host galaxies. The combined data set is enabling great advances in our understanding of GRBs including afterglow physics, short burst origin, and high-energy emission.
NONTHERMAL EMISSIONS FROM SHOCKED SHELLS DRIVEN BY POWERFUL AGN JETS
Authors: ITO HIROTAKA , KINO MOTOKI , KAWAKATU NOZOMU , YAMADA SHOICHI
Published: June 2010

We explore the emissions by accelerated electrons in shocked shells driven by jets in active galactic nuclei (AGNs). Focusing on powerful sources which host luminous quasars, the synchrotron radiation and inverse-Compton (IC) scattering of various photons that are mainly produced in the core are considered as radiation processes. We show that the radiative output is dominated by the IC emission for compact sources (≲ 30 kpc), whereas the synchrotron radiation is more important for larger sources. It is predicted that, for powerful sources (L j ~ 1047 ergs s -1), GeV – TeV gamma-rays produced via the IC emissions can be detected by the Fermi satellite and modern Cherenkov telescopes such as MAGIC, HESS and VERITAS if the source is compact.
MODELING X–RAY EMISSION OF A STRAIGHT JET: PKS 0920-397
Authors: SCHWARTZ D. A. , MASSARO F. , SIEMIGINOWSKA A. , WORRALL D. M. , BIRKINSHAW M. , MARSHALL H. , EVANS D. , PERLMAN E. , GELBORD J. M. , LOVELL J. E. J. , GODFREY L. , BICKNELL G. , OJHA R. , HARDCASTLE M. , JESTER S. , JORSTAD S. , STAWARZ L.
Published: June 2010

We summarize a study of PKS 0920-397 using our 42 ks Chandra observation in conjunction with our ATCA 20GHz image, and HST/ACS F814W and F475W images. We investigate the hypothesis that the jet X–ray emission is due to inverse-Compton (IC) scattering on the cosmic microwave background (CMB) from the same population of relativistic electrons that give rise to the radio emission. To calculate parameters intrinsic to the source, one must finesse the fact that we do not know the true angle of the jet to our line of sight. Typical assumptions are that the Doppler factor equals the bulk Lorentz factor, or that the Lorentz factor takes some fixed numerical value. While giving useful estimates, neither assumption can be exact in general. We try different constraints to determine the jet quantities. It is plausible that the kinetic flux is constant along the jet, prior to a terminal hotspot or lobe, and with minimal bending of the jet. Alternatively, because PKS 0920-397 appears straight in projection on the sky, we might assume the jet maintains a constant angle to our line of sight. Either approach gives bulk Lorentz factors of 6 to 8, with kinetic energy flux of order 1046 erg s-1, and with the jet at an angle 2° to 4° from our line of sight.
MODELING THE EMISSION FROM BLAZAR JETS: THE CASE OF PKS 2155-304
Authors: WEIDINGER MATTHIAS , SPANIER FELIX
Published: June 2010

A time-dependent synchrotron self-Compton model (SSC) which is able to motivate the used electron spectra of many SSC models as a balance of acceleration and radiative losses is introduced. Using stochastic acceleration as well as Fermi-I processes even electron spectra with a rising part can be explained, which are mandatory to fit the low state spectral energy distribution (SED) of PKS 2155-304 as constrained from Fermi LAT observations. Due to the time resolution the outburst of PKS 2155-304 observed by H.E.S.S. in 2006 can be modelled self-consistently as fluctuations along the jet axis without introducing new sets of parameters. The model makes the time evolution of the SED also accessible, hence giving new insights into the flaring behavior of blazars.
Eric Brewer
Authors: Goth Gregory
Published: June 2010

Eric Brewer's latest project involves designing and deploying low-cost wireless infrastructure in developing regions.
Positive and negative cis-regulatory elements directing postfertilization maternal mRNA translational control in mouse embryos
Authors: Potireddy Santhi , Midic Uros , Liang Cheng-Guang , Obradovic Zoran , Latham Keith E.
Published: June 2010

Mechanisms providing for temporally complex patterns of maternal mRNA translation after fertilization are poorly understood. We employed bioinformatics analysis to compare populations of mRNAs enriched specifically on polysomes at the metaphase II (MII) stage oocyte and late one-cell stages and a detailed deletion/truncation series to identify elements that regulate translation. We used the Bag4 3′ untranslated region (UTR) as a model. Bioinformatics analysis revealed one conserved motif, subsequently confirmed by functional studies to be a key translation repressor element. The deletion/truncation studies revealed additional regulatory motifs, most notably a strong translation activator element of <30 nt. Analysis of mRNA secondary structure suggests that secondary structure plays a key role in translation repression. Additional bioinformatics analysis of the regulated mRNA population revealed a diverse collection of regulatory motifs found in small numbers of mRNAs, highlighting a high degree of sequence diversity and combinatorial complexity in the overall control of the maternal mRNA population. We conclude that translational control after fertilization is driven primarily by negative regulatory mechanisms opposing strong translational activators, with stage-specific release of the inhibitory influences to permit recruitment. The combination of bioinformatics analysis and deletion/truncation studies provides the necessary approach for dissecting postfertilization translation regulatory mechanisms.
RNA interference screen for RGS protein specificity at muscarinic and protease-activated receptors reveals bidirectional modulation of signaling
Authors: Laroche Geneviève , Giguère Patrick M. , Roth Bryan L. , Trejo JoAnn , Siderovski David P.
Published: June 2010

Regulator of G protein signaling (RGS) proteins are considered key modulators of G protein-coupled receptor (GPCR)-mediated signal transduction. These proteins act directly on Gα subunits in vitro to increase their intrinsic rate of GTP hydrolysis; this activity is central to the prevailing view of RGS proteins as negative regulators of agonist-initiated GPCR signaling. However, the specificities of action of particular RGS proteins toward specific GPCRs in an integrated cellular context remain unclear. Here, we developed a medium-throughput assay to address this question in a wholly endogenous context using RNA interference. We performed medium-throughput calcium mobilization assays of agonist-stimulated muscarinic acetylcholine and protease-activated receptors in human embryonic kidney 293 (HEK293) cells transfected with individual members of a “pooled duplex” short interfering RNA library targeting all conventional human RGS transcripts. Only knockdown of RGS11 increased both carbachol-mediated calcium mobilization and inositol phosphate accumulation. Surprisingly, we found that knockdown of RGS8 and RGS9, but not other conventional RGS proteins, significantly decreased carbachol-mediated calcium mobilization, whereas only RGS8 knockdown decreased protease-activated receptor-1 (PAR-1)-mediated calcium mobilization. Loss of responsiveness toward carbachol and PAR-1 agonist peptide upon RGS8 knockdown appears due, at least in part, to a loss in respective receptor cell surface expression, although this is not the case for RGS9 knockdown. Our data suggest a cellular role for RGS8 in the stable surface expression of M3 muscarinic acetylcholine receptor and PAR-1, as well as a specific and opposing set of functions for RGS9 and RGS11 in modulating carbachol responsiveness similar to that seen in Caenorhabditis elegans .
Thujone, a component of medicinal herbs, rescues palmitate-induced insulin resistance in skeletal muscle
Authors: Alkhateeb Hakam , Bonen Arend
Published: June 2010

Thujone is thought to be the main constituent of medicinal herbs that have antidiabetic properties. Therefore, we examined whether thujone ameliorated palmitate-induced insulin resistance in skeletal muscle. Soleus muscles were incubated for ≤12 h without or with palmitate (2 mM). Thujone (0.01 mg/ml), in the presence of palmitate, was provided in the last 6 h of incubation. Palmitate oxidation, AMPK/acetyl-CoA carboxylase (ACC) phosphorylation and insulin-stimulated glucose transport, plasmalemmal GLUT4, and AS160 phosphorylation were examined at 0, 6, and 12 h. Palmitate treatment for 12 h reduced fatty acid oxidation (−47%), and insulin-stimulated glucose transport (−71%), GLUT4 translocation (−40%), and AS160 phosphorylation (−26%), but it increased AMPK (+51%) and ACC phosphorylations (+44%). Thujone (6–12 h) fully rescued palmitate oxidation and insulin-stimulated glucose transport, but only partially restored GLUT4 translocation and AS160 phosphorylation, raising the possibility that an increased GLUT4 intrinsic activity may also have contributed to the restoration of glucose transport. Thujone also further increased AMPK phosphorylation but had no further effect on ACC phosphorylation. Inhibition of AMPK phosphorylation with adenine 9-β-d-arabinofuranoside (Ara) (2.5 mM) or compound C (50 μM) inhibited the thujone-induced improvement in insulin-stimulated glucose transport, GLUT4 translocation, and AS160 phosphorylation. In contrast, the thujone-induced improvement in palmitate oxidation was only slightly inhibited (≤20%) by Ara or compound C. Thus, while thujone, a medicinal herb component, rescues palmitate-induced insulin resistance in muscle, the improvement in fatty acid oxidation cannot account for this thujone-mediated effect. Instead, the rescue of palmitate-induced insulin resistance appears to occur via an AMPK-dependent mechanism involving partial restoration of insulin-stimulated GLUT4 translocation.
Chronic hyperoxia alters the early and late phases of the hypoxic ventilatory response in neonatal rats
Authors: Bavis Ryan W. , Young Kristen M. , Barry Kevin J. , Boller Matthew R. , Kim Eugene , Klein Peter M. , Ovrutsky Alida R. , Rampersad Donna A.
Published: June 2010

Chronic hyperoxia during the first 1–4 postnatal weeks attenuates the hypoxic ventilatory response (HVR) subsequently measured in adult rats. Rather than focusing on this long-lasting plasticity, the present study considered the influence of hyperoxia on respiratory control during the neonatal period. Sprague-Dawley rats were born and raised in 60% O2 until studied at postnatal ages (P) of 4, 6–7, or 13–14 days. Ventilation and metabolism were measured in normoxia (21% O2) and acute hypoxia (12% O2) using head-body plethysmography and respirometry, respectively. Compared with age-matched rats raised in room air, the major findings were 1) diminished pulmonary ventilation and metabolic O2 consumption in normoxia at P4 and P6–7; 2) decreased breathing stability during normoxia; 3) attenuation of the early phase of the HVR at P6–7 and P13–14; and 4) a sustained increase in ventilation during hypoxia (vs. the normal biphasic HVR) at all ages studied. Attenuation of the early HVR likely reflects progressive impairment of peripheral arterial chemoreceptors while expression of a sustained HVR in neonates before P7 suggests that hyperoxia also induces plasticity within the central nervous system. Together, these results suggest a complex interaction between inhibitory and excitatory effects of hyperoxia on the developing respiratory control system.
Plyometric training effects on Achilles tendon stiffness and dissipative properties
Authors: Fouré Alexandre , Nordez Antoine , Cornu Christophe
Published: June 2010

The aim of this study was to determine the effects of 14 wk of plyometric training on mechanical properties of the Achilles tendon. Nineteen subjects were randomly assigned to trained or control group. Cross-sectional area (CSA), stiffness, and dissipation coefficient of the Achilles tendon were measured before and after the training period. In the trained group, a decrease in dissipation coefficient (−35.0%; P < 0.05) and an upward trend in stiffness (+24.1%) of the Achilles tendon was found, without any changes in Achilles tendon CSA ( P > 0.05). Plyometric training enhances the muscular tension transmission mainly through a reduction in energy dissipated by the tendon. The lack of changes in the Achilles tendon CSA indicates that changes in mechanical properties would mainly result from a qualitative change in tendinous tissues rather than from changes in the geometry of the Achilles tendon.