bluuebunny/crossref_metadata_2025 huggingface dataset:
Low Endocytic pH and Capsid Protein Autocleavage Are Critical Components of Flock House Virus Cell Entry
Authors: Odegard Amy L. , Kwan Maggie H. , Walukiewicz Hanna E. , Banerjee Manidipa , Schneemann Anette , Johnson John E.
Published: June 2009

The process by which nonenveloped viruses cross cell membranes during host cell entry remains poorly defined; however, common themes are emerging. Here, we use correlated in vivo and in vitro studies to understand the mechanism of Flock House virus (FHV) entry and membrane penetration. We demonstrate that low endocytic pH is required for FHV infection, that exposure to acidic pH promotes FHV-mediated disruption of model membranes (liposomes), and particles exposed to low pH in vitro exhibit increased hydrophobicity. In addition, FHV particles perturbed by heating displayed a marked increase in liposome disruption, indicating that membrane-active regions of the capsid are exposed or released under these conditions. We also provide evidence that autoproteolytic cleavage, to generate the lipophilic γ peptide (4.4 kDa), is required for membrane penetration. Mutant, cleavage-defective particles failed to mediate liposome lysis, regardless of pH or heat treatment, suggesting that these particles are not able to expose or release the requisite membrane-active regions of the capsid, namely, the γ peptides. Based on these results, we propose an updated model for FHV entry in which (i) the virus enters the host cell by endocytosis, (ii) low pH within the endocytic pathway triggers the irreversible exposure or release of γ peptides from the virus particle, and (iii) the exposed/released γ peptides disrupt the endosomal membrane, facilitating translocation of viral RNA into the cytoplasm.
Vaccinia Virus H7 Protein Contributes to the Formation of Crescent Membrane Precursors of Immature Virions
Authors: Satheshkumar P. S. , Weisberg Andrea , Moss Bernard
Published: June 2009

Crescent membranes are the first viral structures that can be discerned during poxvirus morphogenesis. The crescents consist of a lipoprotein membrane and an outer lattice scaffold, which provides uniform curvature. Relatively little is known regarding the composition of the crescent membrane or its mode of formation. Here, we show that the H7 protein, which is conserved in all vertebrate poxviruses but has no discernible functional motifs or nonpoxvirus homologs, contributes to the formation of crescents and immature virions. Synthesis of the 17-kDa H7 protein was dependent on DNA replication and occurred late during vaccinia virus infection. Unlike many late proteins, however, H7 was not incorporated into mature virions or localized in cellular organelles. To gain insight into the role of H7, an inducible mutant was constructed and shown to have a conditional lethal phenotype: H7 expression and infectious virus formation were dependent on isopropyl-beta-
d
-thiogalactopyranoside. In the absence of inducer, viral late proteins were made, but membrane and core proteins were not processed by the I7 protease. A block in morphogenesis was demonstrated by transmission electron microscopy: neither typical crescents nor immature virions were detected in the absence of inducer. Instead, factory areas of the cytoplasm contained large, electron-dense inclusions, some of which had partially coated membrane segments at their surfaces. Separate, lower-density inclusions containing the D13 scaffold protein and endoplasmic reticulum membranes were also present. These features are most similar to those previously seen when expression of A11, another conserved nonvirion protein, is repressed.
Site-Specific Phosphorylation Regulates Human T-Cell Leukemia Virus Type 2 Rex Function In Vivo
Authors: Kesic Matthew , Ward Michael , Semmes O. John , Green Patrick L.
Published: June 2009

Human T-cell leukemia virus type 2 (HTLV-2) Rex is a transacting regulatory protein required for efficient cytoplasmic expression of the unspliced and incompletely spliced viral mRNA transcripts encoding the structural and enzymatic proteins. Previously, it was demonstrated that phosphorylation of Rex-2, predominantly on serine residues, is correlated with an altered conformation, as observed by a gel mobility shift and the detection of two related protein species (p24
Rex
and p26
Rex
). Rex-2 phosphorylation is required for specific binding to its viral-mRNA target sequence and inhibition of mRNA splicing and may be linked to subcellular compartmentalization. Thus, the phosphorylation-induced structural state of Rex in the infected cell may be a switch that determines whether HTLV exists in a latent or productive state. We conducted a phosphoryl and functional mapping of both structural forms of mammalian-cell-expressed Rex 2 using affinity purification, liquid chromatography-tandem mass spectrometry, and site-directed substitutional mutational analysis. We identified two phosphorylation sites in p24
Rex
at Ser-117 and Thr-164. We also identified six phosphorylation sites in p26
Rex
at Thr-19, Ser-117, Ser-125, Ser-151, Ser-153, and Thr-164. We evaluated the functional significance of these phosphorylation events and found that phosphorylation on Thr-164, Ser-151, and Ser-153 is critical for Rex-2 function in vivo and that phosphorylation of Ser-151 is correlated with nuclear/nucleolar subcellular localization. Overall, this work is the first to completely map the phosphorylation sites in Rex-2 and provides important insight into the phosphorylation continuum that tightly regulates Rex-2 structure, cellular localization, and function.
Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8 K-bZIP Modulates Latency-Associated Nuclear Protein-Mediated Suppression of Lytic Origin-Dependent DNA Synthesis
Authors: Rossetto Cyprian , Yamboliev Irena , Pari Gregory S.
Published: June 2009

The original cotransfection replication assay identified eight human herpesvirus 8 (HHV8)-encoded proteins required for origin-dependent lytic DNA replication. Previously, we demonstrated that under conditions where K-Rta is overexpressed, a K-bZIP knockout bacmid displayed an aberrant subcellular localization pattern for the latency-associated nuclear protein (LANA). Additionally, these same studies demonstrated that K-bZIP interacts with LANA in the absence of K-Rta and that K-bZIP does not directly participate in, but may facilitate, the initiation of lytic DNA synthesis. We developed a modification of the transient cotransfection replication assay wherein both lytic (oriLyt) and latent (terminal repeat) DNA replication are evaluated simultaneously. We now show that LANA represses origin-dependent lytic DNA replication in a dose dependent manner when added to the cotransfection replication assay. This repression was overcome by increasing amounts of a K-bZIP expression plasmid in the cotransfection mixture or by dominant-negative inhibition of the interaction of LANA with K-bZIP by the overexpression of the K-bZIP-LANA binding domain. Chromatin immunoprecipitation assays show that LANA interacts with oriLyt in the absence of K-bZIP expression, suggesting that suppression of lytic replication by LANA is mediated by direct binding. The interaction of K-bZIP with oriLyt was dependent upon the expression of LANA; however, LANA interacted with oriLyt independently of K-bZIP expression. These data suggest that the interaction of LANA with K-bZIP modulates lytic and latent replication and that K-bZIP facilitates lytic DNA replication and modulates the switch from the latent phase of the virus.
Is Single-Strand Conformation Polymorphism Analysis of the Full 5′ Untranslated Region an Adequate Approach To Study Hepatitis C Virus Quasispecies Distribution?
Authors: Vera-Otarola Jorge , Barría María Inés , León Ursula , Carvallo Pilar , Soza Alejandro , López-Lastra Marcelo
Published: June 2009

Single-strand conformation polymorphism (SSCP) analysis is used by many laboratories to study the quasispecies distribution of the hepatitis C virus (HCV). Here we question the validity of this experimental approach, as conclusions are drawn from the analysis of the migration patterns of two ssDNA molecules and not from RNA. Using previously characterized mutants of the HCV 5′ untranslated regions, we show that contrary to what has been predicted, SSCP migration patterns of DNA amplicons with differences in their nucleotide sequences generated from the full 5′ UTR of HCV are not necessarily unique.
Mutational Analysis of the Herpes Simplex Virus Type 1 DNA Packaging Protein UL33
Authors: Beilstein Frauke , Higgs Martin R. , Stow Nigel D.
Published: June 2009

The UL33 protein of herpes simplex virus type 1 (HSV-1) is thought to be a component of the terminase complex that mediates the cleavage and packaging of viral DNA. In this study we describe the generation and characterization of a series of 15 UL33 mutants containing insertions of five amino acids located randomly throughout the 130-residue protein. Of these mutants, seven were unable to complement the growth of the UL33-null virus
dl
UL33 in transient assays and also failed to support the cleavage and packaging of replicated amplicon DNA into capsids. The insertions in these mutants were clustered between residues 51 and 74 and between 104 and 116, within the most highly conserved regions of the protein. The ability of the mutants to interact with the UL28 component of the terminase was assessed in immunoprecipitation and immunofluorescence assays. All four mutants with insertions between amino acids 51 and 74 were impaired in this interaction, whereas two of the three mutants in the second region (with insertions at positions 111 and 116) were not affected. These data indicate that the ability of UL33 to interact with UL28 is probably necessary, but not sufficient, to support viral growth and DNA packaging.
Identification of Unusual E6 and E7 Proteins within Avian Papillomaviruses: Cellular Localization, Biophysical Characterization, and Phylogenetic Analysis
Authors: Van Doorslaer Koenraad , Ould M'hamed Ould Sidi Abdellahi , Zanier Katia , Rybin Vladimir , Deryckère François , Rector Annabel , Burk Robert D. , Lienau E. Kurt , van Ranst Marc , Travé Gilles
Published: June 2009

Papillomaviruses (PVs) are a large family of small DNA viruses infecting mammals, reptiles, and birds. PV infection induces cell proliferation that may lead to the formation of orogenital or skin tumors. PV-induced cell proliferation has been related mainly to the expression of two small oncoproteins, E6 and E7. In mammalian PVs, E6 contains two 70-residue zinc-binding repeats, whereas E7 consists of a natively unfolded N-terminal region followed by a zinc-binding domain which folds as an obligate homodimer. Here, we show that both the novel francolin bird PV
Francolinus leucoscepus
PV type 1 (FlPV-1) and the chaffinch bird PV
Fringilla coelebs
PV contain unusual E6 and E7 proteins. The avian E7 proteins contain an extended unfolded N terminus and a zinc-binding domain of reduced size, whereas the avian E6 proteins consist of a single zinc-binding domain. A comparable single-domain E6 protein may have existed in a common ancestor of mammalian and avian PVs. Mammalian E6 C-terminal domains are phylogenetically related to those of single-domain avian E6, whereas mammalian E6 N-terminal domains seem to have emerged by duplication and subsequently diverged from the original ancestral domain. In avian and mammalian cells, both FlPV-1 E6 and FlPV-1 E7 were evenly expressed in the cytoplasm and the nucleus. Finally, samples of full-length FlPV-1 E6 and the FlPV-1 E7 C-terminal zinc-binding domain were prepared for biophysical analysis. Both constructs were highly soluble and well folded, according to nuclear magnetic resonance spectroscopy measurements.
Toll-Like Receptor 4 Deficiency Increases Disease and Mortality after Mouse Hepatitis Virus Type 1 Infection of Susceptible C3H Mice
Authors: Khanolkar Aaruni , Hartwig Stacey M. , Haag Brayton A. , Meyerholz David K. , Harty John T. , Varga Steven M.
Published: June 2009

Severe acute respiratory syndrome (SARS) is characterized by substantial acute pulmonary inflammation with a high mortality rate. Despite the identification of SARS coronavirus (SARS-CoV) as the etiologic agent of SARS, a thorough understanding of the underlying disease pathogenesis has been hampered by the lack of a suitable animal model that recapitulates the human disease. Intranasal (i.n.) infection of A/J mice with the CoV mouse hepatitis virus strain 1 (MHV-1) induces an acute respiratory disease with a high lethality rate that shares several pathological similarities with SARS-CoV infection in humans. In this study, we examined virus replication and the character of pulmonary inflammation induced by MHV-1 infection in susceptible (A/J, C3H/HeJ, and BALB/c) and resistant (C57BL/6) strains of mice. Virus replication and distribution did not correlate with the relative susceptibilities of A/J, BALB/c, C3H/HeJ, and C57BL/6 mice. In order to further define the role of the host genetic background in influencing susceptibility to MHV-1-induced disease, we examined 14 different inbred mouse strains. BALB.B and BALB/c mice exhibited MHV-1-induced weight loss, whereas all other strains ofH-2bandH-2dmice did not show any signs of disease following MHV-1 infection.H-2kmice demonstrated moderate susceptibility, with C3H/HeJ mice exhibiting the most severe disease. C3H/HeJ mice harbor a natural mutation in the gene that encodes Toll-like receptor 4 (TLR4) that disrupts TLR4 signaling. C3H/HeJ mice exhibit enhanced morbidity and mortality following i.n. MHV-1 infection compared to wild-type C3H/HeN mice. Our results indicate that TLR4 plays an important role in respiratory CoV pathogenesis.
The CREB Site in the Proximal Enhancer Is Critical for Cooperative Interaction with the Other Transcription Factor Binding Sites To Enhance Transcription of the Major Intermediate-Early Genes in Human Cytomegalovirus-Infected Cells
Authors: Lashmit Philip , Wang Shuhui , Li Hongmei , Isomura Hiroki , Stinski Mark F.
Published: June 2009

One of the two SP1 sites in the proximal enhancer of the human cytomegalovirus (HCMV) major immediate-early (MIE) promoter is essential for transcription in human fibroblast cells (H. Isomura, M. F. Stinski, A. Kudoh, T. Daikoku, N. Shirata, and T. Tsurumi, J. Virol. 79:9597-9607, 2005). Upstream of the two SP1 sites to −223 relative to the +1 transcription start site, there are an additional five DNA binding sites for eukaryotic transcription factors. We determined the effects of the various transcription factor DNA binding sites on viral MIE RNA transcription, viral gene expression, viral DNA synthesis, or infectious virus production. We prepared recombinant HCMV bacterial artificial chromosome (BAC) DNAs with either one site missing or one site present upstream of the two SP1 sites. Infectious recombinant HCMV BAC DNAs were transfected into various cell types to avoid the effect of the virion-associated transactivators. Regardless of the cell type, which included human fibroblast, endothelial, and epithelial cells, the CREB site had the most significant and independent effect on the MIE promoter. The other sites had a minor independent effect. However, the combination of the different transcription factor DNA binding sites was significantly stronger than multiple duplications of the CREB site. These findings indicate that the CREB site in the presence of the other sites has a major role for the replication of HCMV.
Analysis of the Kinetics of Transcription and Replication of the Rotavirus Genome by RNA Interference
Authors: Ayala-Breton Camilo , Arias Marisol , Espinosa Rafaela , Romero Pedro , Arias Carlos F. , López Susana
Published: June 2009

Rotaviruses have a genome composed of 11 segments of double-stranded RNA (dsRNA) surrounded by three protein layers. The virus contains an RNA-dependent RNA polymerase that synthesizes RNA transcripts corresponding to all segments of the viral genome. These transcripts direct the synthesis of the viral proteins and also serve as templates for the synthesis of the complementary strand to form the dsRNA genome. In this work, we analyzed the kinetics of transcription and replication of the viral genome throughout the replication cycle of the virus using quantitative reverse transcription-PCR. The role of the proteins that form double-layered particles ([DLPs] VP1, VP2, VP3, and VP6) in replication and transcription of the viral genome was analyzed by silencing their expression in rotavirus-infected cells. All of them were shown to be essential for the replication of the dsRNA genome since in their absence there was little synthesis of viral mRNA and dsRNA. The characterization of the kinetics of RNA transcription and replication of the viral genome under conditions where these proteins were silenced provided direct evidence for a second round of transcription during the replication of the virus. Interestingly, despite the decrease in mRNA accumulation when any of the four proteins was silenced, the synthesis of viral proteins decreased when VP2 and VP6 were knocked down, whereas the absence of VP1 and VP3 did not have a severe impact on viral protein synthesis. Characterization of viral particle assembly in the absence of VP1 and VP3 showed that while the formation of triple-layered particles and DLPs was decreased, the amount of assembled lower-density particles, often referred to as empty particles, was not different from the amount in control-infected cells, suggesting that viral particles can assemble in the absence of either VP1 or VP3.
Trp64Arg polymorphism inADRB3gene is associated with elite endurance performance: Table 1
Authors: Santiago Catalina , Ruiz Jonatan R , Buxens Amaya , Artieda Marta , Arteta David , González-Freire Marta , Rodríguez-Romo Gabriel , Altmäe Signe , Lao José I , Gómez-Gallego Félix , Lucia Alejandro
Published: June 2009

In this study, allele and genotype frequencies of theADRB1Arg389Gly (rs1801253),ADRB2Gly16Arg (rs1042713) and Gln27Glu (rs1042714), andADRB3Trp64Arg (rs4994) variations were compared in the following three groups of Spanish (Caucasian) men: (1) world-class endurance athletes (E; runners and cyclists, n=100), (2) elite power athletes (P; sprinters, jumpers and throwers, n=53) and (3) non-athletic controls (C; n=100). No significant differences were observed in genotype and allele distributions among the study groups except for theADRB3Trp64Arg polymorphism in E versus C (27% vs 8% of carriers of the Arg allele in E and C, p<0.001; frequency of the minor Arg (C) allele of 14% vs 4% in E and C, p=0.001). Heterozygosity for theADRB3Trp64Arg polymorphism seems to be associated with elite endurance performance, while other variants of the β-adrenergic receptors' genes do not seem to significantly influence top-level sports performance, at least in athletes of Spanish origin.
Rugby league injuries in New Zealand: a review of 8 years of Accident Compensation Corporation injury entitlement claims and costs
Authors: King D A , Hume P A , Milburn P , Gianotti S
Published: June 2009

Aim:

This paper provides an overview of the epidemiology of rugby league injuries and associated costs in New Zealand requiring medical treatment.

Method:

New Zealand national Accident Compensation Corporation injury data for the period 1999 to 2007 were searched for rugby league injury cases. Data were analysed by demographics, body region, nature/severity of injury, and medical procedure and costs.

Results:

A total of 5941 injury entitlement claims were recorded over the study period with a significant decrease observed in the injury rate between the 1999–2000 and 2002–2003 reporting years. The total cost of the injuries for the study period was $42 822 048 (equivalent to £15 916 072). The mean (SD) number of injury entitlement claims per year was 743 (271) and yearly cost was $5 352 760 (£1 989 880) ($2 485 535 (£923 994)). The knee was the most commonly reported injury site (225 per 1000 entitlement claims; $8 750 147 (£3 252 020)) and soft tissue injuries were the most common injury types (474 per 1000 entitlement claims; $17 324 214 (£6 438 599)). Accounting for only 1.8% of total injury entitlement claims, concussion/brain injuries accounted for 6.3% of injury entitlement costs and had the highest mean cost per claim ($25 347 (£9420)). The upper and lower arm recorded the highest mean injury site claim cost of $43 096 (£16 016) per claim. The 25–29 age group recorded 27.7% of total injury entitlement claims and 29.6% of total injury entitlement costs, which was slightly more than the 20–24 age group (27.3% claims; 24.7% costs). Nearly 15% of total moderate to serious injury entitlement claims and 20% of total costs were recorded from participants 35 years or older.

Discussion:

This study identified that the knee was the most common injury site and soft tissue injuries were the most common injury type requiring medical treatment, which is consistent with other international studies on rugby league epidemiology. This study also highlights that the rate of injury and the average age of injured rugby league players increased over time. The high cost of concussion/brain injuries is a cause for concern as it reflects the severity of the injuries.

Conclusion:

Injury prevention programmes for rugby league should focus on reducing the risk of concussion/brain injury and knee and soft tissue injury, and should target participants in the 20–30 years old age range. More longitudinal epidemiological studies with specific details on injury mechanisms and participation data are warranted to further identify the injury circumstances surrounding participation in rugby league activities.
Ischaemic heart disease mortality study among workers with occupational exposure to ammonium perfluorooctanoate
Authors: Sakr C J , Symons J M , Kreckmann K H , Leonard R C
Published: June 2009

Objectives:

Ammonium perfluorooctanoate (APFO) is a biopersistent surfactant used in the manufacture of several types of fluoropolymers. Based on previous findings of increased serum lipid levels associated with exposure to APFO, we evaluated ischaemic heart disease (IHD) mortality in a cohort of occupationally exposed workers.

Methods:

Relative risks (RR) were estimated from exposure–response analyses of cumulative exposure measures using proportional hazards regression models.

Results:

239 IHD deaths have occurred in the cohort of 4747 workers with work histories from 1948 through 2002. RR estimates indicate no statistically significant increased mortality risk for IHD associated with estimated cumulative exposure. We observed a positive trend only at an exposure lag of 10 years. This finding was not reproduced in other 5-year exposure lags and was attenuated when different cutpoints for exposure categorisation were used.

Conclusion:

This exposure–response study shows no convincing evidence of increased IHD mortality risk for APFO-exposed workers at this plant. Further studies evaluating the incidence of IHD are being conducted.
A POLYNOMIAL-TIME APPROXIMATION ALGORITHM FOR A GEOMETRIC DISPERSION PROBLEM
Authors: BENKERT MARC , GUDMUNDSSON JOACHIM , KNAUER CHRISTIAN , VAN OOSTRUM RENÉ , WOLFF ALEXANDER
Published: June 2009

We consider the following packing problem. Let α be a fixed real in (0, 1]. We are given a bounding rectangle ρ and a set [Formula: see text] of n possibly intersecting unit disks whose centers lie in ρ. The task is to pack a set [Formula: see text] of m disjoint disks of radius α into ρ such that no disk in B intersects a disk in [Formula: see text], where m is the maximum number of unit disks that can be packed. In this paper we present a polynomial-time algorithm for α = 2/3. So far only the case of packing squares has been considered. For that case, Baur and Fekete have given a polynomial-time algorithm for α = 2/3 and have shown that the problem cannot be solved in polynomial time for any α > 13/14 unless [Formula: see text].
MODELLING EPIDEMICS AND VIRUS MUTATIONS BY METHODS OF THE MATHEMATICAL KINETIC THEORY FOR ACTIVE PARTICLES
Authors: DE LILLO S. , DELITALA M. , SALVATORI M. C.
Published: June 2009

The present study is devoted to modelling the onset and the spread of epidemics. The mathematical approach is based on the generalized kinetic theory for active particles. The modelling includes virus mutations and the role of the immune system. Moreover, the heterogeneous distribution of patients is also taken into account. The structure allows the derivation of specific models and of numerical simulations related to real systems.
Commentary and Analysis
Authors: Laporte Claire , Smith DeAnn F. , Younkin Jeremy A.
Published: June 2009

Facing ITC Investigation? What Chinese Biotechnology Companies Should Know About Patent Litigation in the United States International Trade Commission.
ABEL'S METHOD ON SUMMATION BY PARTS FOR ELLIPTIC HYPERGEOMETRIC SERIES
Authors: CHU WENCHANG , JIA CANGZHI
Published: June 2009

By means of Abel's lemma on summation by parts, a new approach for evaluating elliptic hypergeometric series is presented. Some well-known terminating series identities are reviewed and several new transformation and summation formulae are established.
SOBOLEV INEQUALITIES WITH SYMMETRY
Authors: CHO YONGGEUN , OZAWA TOHRU
Published: June 2009

In this paper, we derive some Sobolev inequalities for radially symmetric functions in Ḣswith 1/2 < s < n/2. We show the end point case s = 1/2 on the homogeneous Besov space [Formula: see text]. These results are extensions of the well-known Strauss' inequality [13]. Also non-radial extensions are given, which show that compact embeddings are possible in some Lpspaces if a suitable angular regularity is imposed.
ASYMPTOTIC BEHAVIOR OF BLOWUP SOLUTIONS FOR ELLIPTIC EQUATIONS WITH EXPONENTIAL NONLINEARITY AND SINGULAR DATA
Authors: ZHANG LEI
Published: June 2009

We consider a sequence of blowup solutions of a two-dimensional, second-order elliptic equation with exponential nonlinearity and singular data. This equation has a rich background in physics and geometry. In a work of Bartolucci–Chen–Lin–Tarantello, it is proved that the profile of the solutions differs from global solutions of a Liouville-type equation only by a uniformly bounded term. The present paper improves their result and establishes an expansion of the solutions near the blowup points with a sharp error estimate.
A SHARP INEQUALITY AND ITS APPLICATIONS
Authors: LI SUYU , ZHU MEIJUN
Published: June 2009

We establish the analog Bliss and Hardy inequalities with sharp constant involving exponential weight function. One special case of the inequalities (for n = 2) leads to a direct proof of Onofri inequality on S2.
HOMOGENIZATION OF ENERGIES DEFINED ON PAIRS SET-FUNCTION
Authors: SOLCI MARGHERITA
Published: June 2009

In the present work, we deal with the problem of the asymptotic behavior of a sequence of non-homogeneous energies depending on a pair set-function of the form [Formula: see text] with u ∈ H1(Ω), E regular open set and the energy densities f and φ both 1-periodic in the first variable; this leads, in the Γ-limit, to a problem of homogenization. We prove a Γ-convergence result for the sequence {Fε}, showing that there is no interaction between the homogenized bulk and surface energy density; that is, even though the effect of the bulk and surface energies are at the same energy scale, oscillations in the bulk term can be neglected close to the surfaces ∂*E and S(u), where surface oscillations are dominant.
HYPERGEOMETRIC FUNCTIONS AND SINGULAR SOLUTIONS OF WAVE EQUATIONS WITH LORENTZ-INVARIANT POTENTIAL
Authors: BENTRAD ALI , KICHENASSAMY SATYANAD
Published: June 2009

New solutions of equation utt- Δu + Au/(r2- t2) = 0, in the series of hypergeometric functions (HGF), are constructed. A sharpened estimate on hypergeometric functions is derived to prove the convergence of the series.
CANONICAL SYMPLECTIC STRUCTURES AND DEFORMATIONS OF ALGEBRAIC SURFACES
Authors: CATANESE FABRIZIO
Published: June 2009

We show that a minimal surface of general type has a canonical symplectic structure (unique up to symplectomorphism) which is invariant for smooth deformation. We show that the symplectomorphism type is also invariant for deformations which allow certain normal singularities, provided one remains in the same smoothing component. We use this technique to show that the Manetti surfaces yield examples of surfaces of general type which are not deformation equivalent but are canonically symplectomorphic.
A Palaeozoic Northwest Passage: incursion of Caledonian, Baltican and Siberian terranes into eastern Panthalassa, and the early evolution of the North American Cordillera
Authors: Colpron Maurice , Nelson Joanne L.
Published: June 2009

Palaeozoic to early Mesozoic terranes of the North American Cordillera mostly originated from three distinct regions in Palaeozoic time: the western peri-Laurentian margin, western (Asian) Panthalassa, and the northern Caledonides–Siberia. A review of geological history, fossil and provenance data for the Caledonian–Siberian terranes suggests that they probably occupied an intermediate position between northern Baltica, northeastern Laurentia and Siberia, in proximity to the northern Caledonides, in early Palaeozoic time. Dispersion of these terranes and their westward incursion into eastern Panthalassa are interpreted to result from development of a Caribbean- or Scotia-style subduction system between northern Laurentia and Siberia in mid-Palaeozoic time, termed here the Northwest Passage. Westward propagation of a narrow subduction zone coupled with a global change in plate motion, related to the collision of Gondwana with Laurentia–Baltica, are proposed to have led to initiation of subduction along the western passive margin of Laurentia and development of the peri-Laurentian terranes as a set of rifted continental fragments, superimposed arcs and marginal ocean basin(s) in mid- to late Palaeozoic time. Diachronous orogenic activity from Late Silurian in Arctic Canada, to Early Devonian in north Yukon and adjacent Alaska, Middle Devonian in southeastern British Columbia, and Late Devonian–Early Mississippian in the western USA records progressive development of the Northwest Passage and southward propagation of subduction along western Laurentia.
Arc imbrication during thick-skinned collision within the northern Cordilleran accretionary orogen, Yukon, Canada
Authors: Tizzard A. M. , Johnston S. T. , Heaman L. M.
Published: June 2009

We present the results of geological mapping and geochronological studies of the Tally Ho shear zone (THSZ) and adjacent rocks. The shear zone crops out near the west margin of Stikinia, an oceanic arc and the largest of the accreted terranes within the Cordilleran orogen of western North America. The hanging wall of the largely flat-lying shear zone consists of coarsely crystalline leucogabbro and cumulate pyroxenite interpreted as the lower crustal and possibly lithospheric mantle roots of a magmatic arc. Rocks in the footwall consist of volcanic and volcano-sedimentary sequences of the Lewes River Arc, a Late Triassic magmatic arc characteristic of Stikinia. Because the shear zone places lower crustal plutonic rocks over a supracrustal sequence, we interpret it as a crustal-scale thrust fault. Kinematic indicators imply top-to-the-east displacement across the shear zone. The geometry of folds of the shear zone is consistent with deformation in response to displacement over ramps in deeper-seated thrust faults kinematically linked to the THSZ. Crystallization of the hanging-wall leucogabbro at 208±4.3 Ma provides a maximum age constraint for deformation, whereas a post-kinematic granitoid pluton that plugs the shear zone and that crystallized at about 173 Ma provides a lower age limit. The THSZ is, therefore, coeval with: (1) a series of latest Triassic–Early Jurassic shear and fault zones that characterize the length of the west margin of Stikinia; (2) the termination of isotopically juvenile arc magmatism of the Lewes River Arc; (3) crustal loading of Stikinia giving rise to a foreland basin that rapidly filled with westerly derived orogenic molasse that includes clasts of ultrahigh-pressure metamorphic rocks; and (4) juxtaposition of Stikinia against continental crust of the Nisling Assemblage of the Yukon–Tanana terrane to the west. These constraints are consistent with a model of deformation in response to the entry of the continental Nisling Assemblage into the trench of the west-facing Lewes River Arc, terminating subduction and imbricating the arc along a series of east-verging thrust faults, including the THSZ.
The Eurasian SE Asian margin as a modern example of an accretionary orogen
Authors: Hall Robert
Published: June 2009

The Eurasian margin in SE Asia is a geologically complex region situated at the edge of the Sundaland continent, and is mainly within Indonesia. The external margins of Sundaland are tectonically active zones characterized by intense seismicity and volcanic activity. The region is an obvious modern analogue for older orogens, with a continental core reassembled from blocks rifted from Gondwana, and surrounded by subduction zones for much of the Mesozoic and Cenozoic. It is a mountain belt in the process of formation, and contains many features typically associated with older Pacific margin orogens: there is active subduction, transfer of material at subduction and strike-slip boundaries, collision of oceanic plate buoyant features, arcs and continents, and abundant magmatism. The orogenic belt surrounds Sundaland and stretches from Sumatra into eastern Indonesia and the Philippines. The orogen changes character and width from west to east. Its development can be tectonically described only in terms of several small plates and it includes several suture zones. The western part of the orogenic belt, where the Indian plate is subducted beneath continental crust, is a relatively narrow single suture. Further east the orogenic belt includes multiple sutures and is up to 2000 km wide; there is less continental crust and more arc and ophiolitic crust, and there are several marginal oceanic basins. The orogen has grown to its present size during the Mesozoic and Cenozoic as a result of subduction. Continental growth has occurred in an episodic way, related primarily to arrival of continental fragments at subduction margins, after which subduction resumed in new locations. There have been subordinate contributions from ophiolite accretion, and arc magmatism. Relatively small amounts of material have been accreted during subduction from the downgoing plate. In eastern Indonesia the wide plate boundary zone includes continental fragments and several arcs, but the arcs are most vulnerable to destruction and disappearance. Rollback in the Banda region has produced major extension within the collision zone, but future contraction will eliminate most of the evidence for it, leaving a collage of continental fragments, similar to the older parts of Sundaland.
The underestimated Proterozoic component of the Canadian Cordillera accretionary margin
Authors: Snyder D. B. , Pilkington M. , Clowes R. M. , Cook F. A.
Published: June 2009

Analysis of several types of seismic and potential field geophysical data consistently indicate that the majority of the crust underlying the Canadian Cordillera and much of western Canada was originally Proterozoic sedimentary rocks shed off the Canadian Shield into rift or basin structures between 1.84 and 0.54 Ga. These variably metamorphosed strata were primarily quartz- and limestone‐rich sediments and thus have distinctive geophysical signatures because of their lower density, lower magnetization, and lower Poisson's ratio compared with more mafic rocks. The sediments formed a prograding wedge that has a distinctive, internally reflective, seismic stratigraphy. In the east, these Proterozoic sedimentary rocks thicken at a ‘hinge line’ defined by the margin of the pre-1.84 Ga crystalline basement of the Canadian Shield; previous work mapped this hinge line locally using deep reflection profiles and regionally using distinctive gravity gradients. Here we assemble previously published results of several geophysical methods to define the overall shape of the wedge along the margin and westward to where it pinches out at the modern Moho beneath the crustal collage of exotic and suspect terranes accreted onto North America during the Mesozoic. The volume of crust occupied by this wedge limits the thickness of most accreted terranes to several kilometres and suggests that deeper portions of the accreted blocks detached or underthrust the wedge during accretion and are no longer contiguous to crust exposed at the surface. This type Cenozoic accretionary orogen thus spent most of its prior geological history as a passive or extensional margin punctuated by only a few, brief convergent or accretionary events.
The Science of Neural Interface Systems
Authors: Hatsopoulos Nicholas G. , Donoghue John P.
Published: June 2009

The ultimate goal of neural interface research is to create links between the nervous system and the outside world either by stimulating or by recording from neural tissue to treat or assist people with sensory, motor, or other disabilities of neural function. Although electrical stimulation systems have already reached widespread clinical application, neural interfaces that record neural signals to decipher movement intentions are only now beginning to develop into clinically viable systems to help paralyzed people. We begin by reviewing state-of-the-art research and early-stage clinical recording systems and focus on systems that record single-unit action potentials. We then address the potential for neural interface research to enhance basic scientific understanding of brain function by offering unique insights in neural coding and representation, plasticity, brain-behavior relations, and the neurobiology of disease. Finally, we discuss technical and scientific challenges faced by these systems before they are widely adopted by severely motor-disabled patients.
Physiology and Pharmacology of Striatal Neurons
Authors: Kreitzer Anatol C.
Published: June 2009

The basal ganglia occupy the core of the forebrain and consist of evolutionarily conserved motor nuclei that form recurrent circuits critical for motivation and motor planning. The striatum is the main input nucleus of the basal ganglia and a key neural substrate for procedural learning and memory. The vast majority of striatal neurons are spiny GABAergic projection neurons, which exhibit slow but temporally precise spiking in vivo. Contributing to this precision are several different types of interneurons that constitute only a small fraction of total neuron number but play a critical role in regulating striatal output. This review examines the cellular physiology and modulation of striatal neurons that give rise to their unique properties and function.
Neuropathic Pain: A Maladaptive Response of the Nervous System to Damage
Authors: Costigan Michael , Scholz Joachim , Woolf Clifford J.
Published: June 2009

Neuropathic pain is triggered by lesions to the somatosensory nervous system that alter its structure and function so that pain occurs spontaneously and responses to noxious and innocuous stimuli are pathologically amplified. The pain is an expression of maladaptive plasticity within the nociceptive system, a series of changes that constitute a neural disease state. Multiple alterations distributed widely across the nervous system contribute to complex pain phenotypes. These alterations include ectopic generation of action potentials, facilitation and disinhibition of synaptic transmission, loss of synaptic connectivity and formation of new synaptic circuits, and neuroimmune interactions. Although neural lesions are necessary, they are not sufficient to generate neuropathic pain; genetic polymorphisms, gender, and age all influence the risk of developing persistent pain. Treatment needs to move from merely suppressing symptoms to a disease-modifying strategy aimed at both preventing maladaptive plasticity and reducing intrinsic risk.
Representation of Number in the Brain
Authors: Nieder Andreas , Dehaene Stanislas
Published: June 2009

Number symbols have allowed humans to develop superior mathematical skills that are a hallmark of technologically advanced cultures. Findings in animal cognition, developmental psychology, and anthropology indicate that these numerical skills are rooted in nonlinguistic biological primitives. Recent studies in human and nonhuman primates using a broad range of methodologies provide evidence that numerical information is represented and processed by regions of the prefrontal and posterior parietal lobes, with the intraparietal sulcus as a key node for the representation of the semantic aspect of numerical quantity.
Axon Growth and Guidance: Receptor Regulation and Signal Transduction
Authors: O'Donnell Michael , Chance Rebecca K. , Bashaw Greg J.
Published: June 2009

The development of precise connectivity patterns during the establishment of the nervous system depends on the regulated action of diverse, conserved families of guidance cues and their neuronal receptors. Determining how these signaling pathways function to regulate axon growth and guidance is fundamentally important to understanding wiring specificity in the nervous system and will undoubtedly shed light on many neural developmental disorders. Considerable progress has been made in defining the mechanisms that regulate the correct spatial and temporal distribution of guidance receptors and how these receptors in turn signal to the growth cone cytoskeleton to control steering decisions. This review focuses on recent advances in our understanding of the mechanisms mediating growth cone guidance with a particular emphasis on the control of guidance receptor regulation and signaling.
The Influence of Stress Hormones on Fear Circuitry
Authors: Rodrigues Sarina M. , LeDoux Joseph E. , Sapolsky Robert M.
Published: June 2009

Fear arousal, initiated by an environmental threat, leads to activation of the stress response, a state of alarm that promotes an array of autonomic and endocrine changes designed to aid self-preservation. The stress response includes the release of glucocorticoids from the adrenal cortex and catecholamines from the adrenal medulla and sympathetic nerves. These stress hormones, in turn, provide feedback to the brain and influence neural structures that control emotion and cognition. To illustrate this influence, we focus on how it impacts fear conditioning, a behavioral paradigm widely used to study the neural mechanisms underlying the acquisition, expression, consolidation, reconsolidation, and extinction of emotional memories. We also discuss how stress and the endocrine mediators of the stress response influence the morphological and electrophysiological properties of neurons in brain areas that are crucial for fear-conditioning processes, including the amygdala, hippocampus, and prefrontal cortex. The information in this review illuminates the behavioral and cellular events that underlie the feedforward and feedback networks that mediate states of fear and stress and their interaction in the brain.
Neurocognitive Mechanisms in Depression: Implications for Treatment
Authors: Clark Luke , Chamberlain Samuel R. , Sahakian Barbara J.
Published: June 2009

Mood disorders collectively account for a substantial proportion of disease burden across the globe and have a devastating impact on quality of life and occupational function. Here we evaluate recent progress in understanding the neurocognitive mechanisms involved in the manifestation of mood disorders. We focus on four domains of cognitive function that are altered in patients with depression: executive control, memory, affective processing, and feedback sensitivity. These alterations implicate a distributed neural circuit composed of multiple sectors of the prefrontal cortex in interaction with subcortical regions (striatum, thalamus) and temporal lobe structures (amygdala, hippocampus). Affective processing and feedback sensitivity are highly sensitive to serotonergic manipulation and are targeted by antidepressant treatments. By drawing together cognitive, neuroanatomical, and pharmacological tiers of research, we identify treatment targets and directions for future investigation to identify people at risk, minimize relapse, and maximize long-term beneficial outcomes for those suffering from depression.
Land Use and Climate Change Interactions
Authors: Mendelsohn Robert , Dinar Ariel
Published: June 2009

Land use and land-use change can result in the emissions of greenhouse gases that cause climate change. Climate change also affects the productivity of land, which in turn leads to further land-use change. This paper explores the growing research on both topics. The land-use emission literature has focused on deforestation (harvests) and ignored the fact that harvests have led to a much younger and therefore growing global forest. Taking this into account, mankind’s current and future influence over land use will have a small positive effect on reducing greenhouse gas emissions. Although the literature initially focused on climate impacts alone, when adaptation is taken into account we find that climate change is likely to have benign net global impacts on market sectors related to land use. Climate impacts on nonmarket sectors, however, are much more poorly understood or measured. Furthermore, it is not yet clear whether governments will adapt or maladapt to climate change.
Effect of resveratrol and zinc on intracellular zinc status in normal human prostate epithelial cells
Authors: Zhang Jun Jun , Wu Min , Schoene Norberta W. , Cheng Wen-Hsing , Wang Thomas T. Y. , Alshatwi Ali A. , Alsaif Mohammed , Lei Kai Y.
Published: June 2009

To evaluate the influence of resveratrol on cellular zinc status, normal human prostate epithelial (NHPrE) cells were treated with resveratrol (0, 0.5, 1, 2.5, 5, and 10 μM) and zinc [0, 4, 16, and 32 μM, representing zinc-deficient (ZD), zinc-normal (ZN), zinc-adequate (ZA), and zinc-supplemented (ZS) conditions, respectively]. A progressive reduction in cell growth was observed in cells treated with increasing amounts of resveratrol (2.5–10 μM). Resveratrol at 5 and 10 μM resulted in a dramatic increase in cellular total zinc concentration, especially in ZS cells. Flow cytometry indicated that 10 μM resveratrol induced arrest of the cell cycle at the G2/M phase in association with the observed cell growth inhibition. Data from an in vitro experiment using zinquin as an indicator of intracellular free Zn(II) status demonstrated complex interactions between resveratrol and Zn(II). Fluorescence spectrofluorometry and fluorescence microscopic analyses revealed that intracellular free labile zinc was progressively elevated from nearly twofold in ZS cells with no resveratrol to multifold in ZA and ZS cells with 10 μM resveratrol compared with the corresponding ZN cells. Furthermore, increases in cellular zinc status were associated with elevated levels of reactive oxygen species and senescence, as evidenced by morphological and histochemical changes in cells treated with 2.5 or 10 μM resveratrol, especially in ZA and ZS cells. Taken together, the interaction between resveratrol and zinc in NHPrE cells increases total cellular zinc and intracellular free labile zinc status and, subsequently, reactive oxygen species production and senescence.