bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological and Phylogenetic Characteristics of Yellow Fever Virus Lineages from West Africa
Authors: Stock Nina K. , Laraway Hewád , Faye Ousmane , Diallo Mawlouth , Niedrig Matthias , Sall Amadou A.
Published: December 2012

The yellow fever virus (YFV), the first proven human-pathogenic virus, although isolated in 1927, is still a major public health problem, especially in West Africa where it causes outbreaks every year. Nevertheless, little is known about its genetic diversity and evolutionary dynamics, mainly due to a limited number of genomic sequences from wild virus isolates. In this study, we analyzed the phylogenetic relationships of 24 full-length genomes from YFV strains isolated between 1973 and 2005 in a sylvatic context of West Africa, including 14 isolates that had previously not been sequenced. By this, we confirmed genetic variability within one genotype by the identification of various YF lineages circulating in West Africa. Further analyses of the biological properties of these lineages revealed differential growth behavior in human liver and insect cells, correlating with the source of isolation and suggesting host adaptation. For one lineage, repeatedly isolated in a context of vertical transmission, specific characteristics in the growth behavior and unique mutations of the viral genome were observed and deserve further investigation to gain insight into mechanisms involved in YFV emergence and maintenance in nature.
Unraveling of a Neutralization Mechanism by Two Human Antibodies against Conserved Epitopes in the Globular Head of H5 Hemagglutinin
Authors: Qian Mengran , Hu Hongxing , Zuo Teng , Wang Guiqin , Zhang Linqi , Zhou Paul
Published: December 2012

The rapid spread of highly pathogenic avian influenza (HPAI) H5N1 virus underscores the importance of effective antiviral treatment. Previously, we developed human monoclonal antibodies 65C6 and 100F4 that neutralize almost all (sub)clades of HPAI H5N1. The conserved 65C6 epitope was mapped to the globular head of HA. However, neither the 100F4 epitope nor the neutralization mechanism by these antibodies was known. In this study, we determined the 100F4 epitope and unraveled a neutralization mechanism by antibodies 65C6 and 100F4.
Herpes Simplex Virus 1 Tropism for Human Sensory Ganglion Neurons in the Severe Combined Immunodeficiency Mouse Model of Neuropathogenesis
Authors: Zerboni Leigh , Che Xibing , Reichelt Mike , Qiao Yanli , Gu Haidong , Arvin Ann
Published: December 2012

The tropism of herpes simplex virus (HSV-1) for human sensory neurons infected
in vivo
was examined using dorsal root ganglion (DRG) xenografts maintained in mice with severe combined immunodeficiency (SCID). In contrast to the HSV-1 lytic infectious cycle
in vitro
, replication of the HSV-1 F strain was restricted in human DRG neurons despite the absence of adaptive immune responses in SCID mice, allowing the establishment of neuronal latency. At 12 days after DRG inoculation, 26.2% of human neurons expressed HSV-1 protein and 13.1% expressed latency-associated transcripts (LAT). Some infected neurons showed cytopathic changes, but HSV-1, unlike varicella-zoster virus (VZV), only rarely infected satellite cells and did not induce fusion of neuronal and satellite cell plasma membranes. Cell-free enveloped HSV-1 virions were observed, indicating productive infection. A recombinant HSV-1-expressing luciferase exhibited less virulence than HSV-1 F in the SCID mouse host, enabling analysis of infection in human DRG xenografts for a 61-day interval. At 12 days after inoculation, 4.2% of neurons expressed HSV-1 proteins; frequencies increased to 32.1% at 33 days but declined to 20.8% by 61 days. Frequencies of LAT-positive neurons were 1.2% at 12 days and increased to 40.2% at 33 days. LAT expression remained at 37% at 61 days, in contrast to the decline in neurons expressing viral proteins. These observations show that the progression of HSV-1 infection is highly restricted in human DRG, and HSV-1 genome silencing occurs in human neurons infected
in vivo
as a consequence of virus-host cell interactions and does not require adaptive immune control.
Both Genome Segments Contribute to the Pathogenicity of Very Virulent Infectious Bursal Disease Virus
Authors: Escaffre Olivier , Le Nouën Cyril , Amelot Michel , Ambroggio Xavier , Ogden Kristen M. , Guionie Olivier , Toquin Didier , Müller Hermann , Islam Mohammed R. , Eterradossi Nicolas
Published: December 2012

Infectious bursal disease virus (IBDV) causes an economically significant disease of chickens worldwide. Very virulent IBDV (vvIBDV) strains have emerged and induce as much as 60% mortality. The molecular basis for vvIBDV pathogenicity is not understood, and the relative contributions of the two genome segments, A and B, to this phenomenon are not known. Isolate 94432 has been shown previously to be genetically related to vvIBDVs but exhibits atypical antigenicity and does not cause mortality. Here the full-length genome of 94432 was determined, and a reverse genetics system was established. The molecular clone was rescued and exhibited the same antigenicity and reduced pathogenicity as isolate 94432. Genetically modified viruses derived from 94432, whose vvIBDV consensus nucleotide sequence was restored in segment A and/or B, were produced, and their pathogenicity was assessed in specific-pathogen-free chickens. We found that a valine (position 321) that modifies the most exposed part of the capsid protein VP2 critically modified the antigenicity and partially reduced the pathogenicity of 94432. However, a threonine (position 276) located in the finger domain of the virus polymerase (VP1) contributed even more significantly to attenuation. This threonine is partially exposed in a hydrophobic groove on the VP1 surface, suggesting possible interactions between VP1 and another, as yet unidentified molecule at this amino acid position. The restored vvIBDV-like pathogenicity was associated with increased replication and lesions in the thymus and spleen. These results demonstrate that both genome segments influence vvIBDV pathogenicity and may provide new targets for the attenuation of vvIBDVs.
The Feline Calicivirus Leader of the Capsid Protein Is Associated with Cytopathic Effect
Authors: Abente Eugenio J. , Sosnovtsev Stanislav V. , Sandoval-Jaime Carlos , Parra Gabriel I. , Bok Karin , Green Kim Y.
Published: December 2012

Open reading frame 2 (ORF2) of the feline calicivirus (FCV) genome encodes a capsid precursor that is posttranslationally processed to release the mature capsid protein (VP1) and a small protein of 124 amino acids, designated the leader of the capsid (LC). To investigate the role of the LC protein in the virus life cycle, mutations and deletions were introduced into the LC coding region of an infectious FCV cDNA clone. Three cysteine residues that are conserved among all vesivirus LC sequences were found to be critical for the recovery of FCV with a characteristic cytopathic effect in feline kidney cells. A cell-rounding phenotype associated with the transient expression of wild-type and mutagenized forms of the LC correlated with the cytopathic and growth properties of the corresponding engineered viruses. The host cellular protein annexin A2 was identified as a binding partner of the LC protein, consistent with a role for the LC in mediating host cell interactions that alter the integrity of the cell and enable virus spread.
SAMHD1 Restricts HIV-1 Cell-to-Cell Transmission and Limits Immune Detection in Monocyte-Derived Dendritic Cells
Authors: Puigdomènech Isabel , Casartelli Nicoletta , Porrot Françoise , Schwartz Olivier
Published: December 2012

SAMHD1 is a viral restriction factor expressed in dendritic cells and other cells, inhibiting infection by cell-free human immunodeficiency virus type 1 (HIV-1) particles. SAMHD1 depletes the intracellular pool of deoxynucleoside triphosphates, thus impairing HIV-1 reverse transcription and productive infection in noncycling cells. The Vpx protein from HIV-2 or simian immunodeficiency virus (SIVsm/SIVmac) antagonizes the effect of SAMHD1 by triggering its degradation. A large part of HIV-1 spread occurs through direct contacts between infected cells and bystander target cells. Here, we asked whether SAMHD1 impairs direct HIV-1 transmission from infected T lymphocytes to monocyte-derived dendritic cells (MDDCs). HIV-1-infected lymphocytes were cocultivated with MDDCs that have been pretreated or not with Vpx or with small interfering RNA against SAMHD1. We show that in the cocultures, SAMHD1 significantly inhibits productive cell-to-cell transmission to target MDDCs and prevents the type I interferon response and expression of the interferon-stimulated gene MxA. Therefore, SAMHD1, by controlling the sensitivity of MDDCs to HIV-1 infection during intercellular contacts, impacts their ability to sense the virus and to trigger an innate immune response.
Integrin and Defensin Modulate the Mechanical Properties of Adenovirus
Authors: Snijder Joost , Reddy Vijay S. , May Eric R. , Roos Wouter H. , Nemerow Glen R. , Wuite Gijs J. L.
Published: December 2012

The propensity for capsid disassembly and uncoating of human adenovirus is modulated by interactions with host cell molecules like integrins and alpha defensins. Here, we use atomic force microscopy (AFM) nanoindentation to elucidate, at the single-particle level, the mechanism by which binding of these host molecules affects virus particle elasticity. Our results demonstrate the direct link between integrin or defensin binding and the mechanical properties of the virus. We show that the structure and geometry of adenovirus result in an anisotropic elastic response that relates to icosahedral symmetry. This elastic response changes upon binding host molecules. Whereas integrin binding softens the vertex regions, binding of a human alpha defensin has exactly the opposite effect. Our results reveal that the ability of these host molecules to influence adenovirus disassembly correlates with a direct effect on the elastic strength of the penton region. Host factors that influence adenovirus infectivity thus modulate the elastic properties of the capsid. Our findings reveal a direct link between virus-host interactions and capsid mechanics.
Amino Acid 316 of Hemagglutinin and the Neuraminidase Stalk Length Influence Virulence of H9N2 Influenza Virus in Chickens and Mice
Authors: Sun Yipeng , Tan Yuanyuan , Wei Kai , Sun Honglei , Shi Yi , Pu Juan , Yang Hanchun , Gao George F. , Yin Yanbo , Feng Wenhai , Perez Daniel R. , Liu Jinhua
Published: December 2012

H9N2 influenza viruses with an A316S substitution in hemagglutinin (HA) and a shorter neuraminidase (NA) stalk have become predominant in China. The A316S was shown to increase HA cleavage efficiency when combined with short stalk NA, and the short stalk NA improved NA enzyme activity and release of virus from erythrocytes. Single mutations or combinations of these mutations strengthened the virulence of H9N2 virus in chickens and mice.
A Novel Rabies Vaccine Based on a Recombinant Parainfluenza Virus 5 Expressing Rabies Virus Glycoprotein
Authors: Chen Zhenhai , Zhou Ming , Gao Xiudan , Zhang Guoqing , Ren Guiping , Gnanadurai Clement W. , Fu Zhen F. , He Biao
Published: December 2012

Untreated rabies virus (RABV) infection leads to death. Vaccine and postexposure treatment have been effective in preventing RABV infection. However, due to cost, rabies vaccination and treatment have not been widely used in developing countries. There are 55,000 human death caused by rabies annually. An efficacious and cost-effective rabies vaccine is needed. Parainfluenza virus 5 (PIV5) is thought to contribute to kennel cough, and kennel cough vaccines containing live PIV5 have been used in dogs for many years. In this work, a PIV5-vectored rabies vaccine was tested in mice. A recombinant PIV5 encoding RABV glycoprotein (G) (rPIV5-RV-G) was administered to mice via intranasal (i.n.), intramuscular (i.m.), and oral inoculation. The vaccinated mice were challenged with a 50% lethal challenge dose (LD
50
) of RABV challenge virus standard 24 (CVS-24) intracerebrally. A single dose of 10
6
PFU of rPIV5-RV-G was sufficient for 100% protection when administered via the i.n. route. The mice vaccinated with a single dose of 10
8
PFU of rPIV5-RV-G via the i.m. route showed very robust protection (90% to 100%). Intriguingly, the mice vaccinated orally with a single dose of 10
8
PFU of rPIV5-RV-G showed a 50% survival rate, which is comparable to the 60% survival rate among mice inoculated with an attenuated rabies vaccine strain, recombinant LBNSE. This is first report of an orally effective rabies vaccine candidate in animals based on PIV5 as a vector. These results indicate that rPIV5-RV-G is an excellent candidate for a new generation of recombinant rabies vaccine for humans and animals and PIV5 is a potential vector for oral vaccines.
Different Patterns of Epstein-Barr Virus Latency in Endemic Burkitt Lymphoma (BL) Lead to Distinct Variants within the BL-Associated Gene Expression Signature
Authors: Kelly Gemma L. , Stylianou Julianna , Rasaiyaah Jane , Wei Wenbin , Thomas Wendy , Croom-Carter Deborah , Kohler Christian , Spang Rainer , Woodman Ciaran , Kellam Paul , Rickinson Alan B. , Bell Andrew I.
Published: December 2012

Epstein-Barr virus (EBV) is present in all cases of endemic Burkitt lymphoma (BL) but in few European/North American sporadic BLs. Gene expression arrays of sporadic tumors have defined a consensus BL profile within which tumors are classifiable as “molecular BL” (mBL). Where endemic BLs fall relative to this profile remains unclear, since they not only carry EBV but also display one of two different forms of virus latency. Here, we use early-passage BL cell lines from different tumors, and BL subclones from a single tumor, to compare EBV-negative cells with EBV-positive cells displaying either classical latency I EBV infection (where EBNA1 is the only EBV antigen expressed from the wild-type EBV genome) or Wp-restricted latency (where an EBNA2 gene-deleted virus genome broadens antigen expression to include the EBNA3A, -3B, and -3C proteins and BHRF1). Expression arrays show that both types of endemic BL fall within the mBL classification. However, while EBV-negative and latency I BLs show overlapping profiles, Wp-restricted BLs form a distinct subgroup, characterized by a detectable downregulation of the germinal center (GC)-associated marker Bcl6 and upregulation of genes marking early plasmacytoid differentiation, notably IRF4 and BLIMP1. Importantly, these same changes can be induced in EBV-negative or latency I BL cells by infection with an EBNA2-knockout virus. Thus, we infer that the distinct gene profile of Wp-restricted BLs does not reflect differences in the identity of the tumor progenitor cellper sebut differences imposed on a common progenitor by broadened EBV gene expression.
Coxsackievirus B3 Infects the Bone Marrow and Diminishes the Restorative Capacity of Erythroid and Lymphoid Progenitors
Authors: Althof Nadine , Whitton J. Lindsay
Published: December 2012

Coxsackievirus B3 (CVB3) is known to infect stem cells in the neonatal central nervous system. Here, we evaluated the effects of CVB3 infection on the major source and repository of stem cells, the bone marrow (BM). Viral genome was detectable in BM within 24 h of infection, and productive infection of BM cells was evident, peaking at 48 h postinfection (p.i.), when ∼1 to 2% of BM cells produced infectious virus particles. Beginning at 2 to 3 days p.i., a dramatic and persistent loss of immature erythroid cells, B and T lymphocytes, and neutrophils was observed in BM and, by day 3 to 4 p.i., the femoral BM stroma was largely destroyed. Analysis of peripheral blood revealed a modest neutrophilia, a loss of reticulocytes, and a massive lymphopenia. The abundance of multipotent progenitor cells (Lin
−
/c-kit
+
/Flt3
+
) in BM declined ∼10-fold during CVB3 infection and, consistent with a deficiency of primitive hematopoietic progenitors, serum levels of the hematopoietic growth factor Flt3 ligand were dramatically elevated. Therefore, we analyzed the regenerative capacity of BM from CVB3-infected mice. Granulocyte/macrophage progenitors displayed a relatively normal proliferative ability, consistent with the fact that the peripheral blood level of neutrophils—which are very short-lived cells—remained high throughout infection. However, erythroid and lymphoid hematopoietic progenitors in BM from CVB3-infected mice showed a markedly reduced colony-forming capacity, consonant with the observed loss of both lymphocytes and immature erythroid cells/reticulocytes from the BM and peripheral blood. In summary, CVB3 infects the BM and exerts differential effects on the various hematopoietic progenitor populations.
Biophysical and Ultrastructural Characterization of Adeno-Associated Virus Capsid Uncoating and Genome Release
Authors: Horowitz Eric D. , Rahman K. Shefaet , Bower Brian D. , Dismuke David J. , Falvo Michael R. , Griffith Jack D. , Harvey Stephen C. , Asokan Aravind
Published: December 2012

We describe biophysical and ultrastructural differences in genome release from adeno-associated virus (AAV) capsids packaging wild-type DNA, recombinant single-stranded DNA (ssDNA), or dimeric, self-complementary DNA (scDNA) genomes. Atomic force microscopy and electron microscopy (EM) revealed that AAV particles release packaged genomes and undergo marked changes in capsid morphology upon heating in physiological buffer (pH 7.2). When different AAV capsids packaging ss/scDNA varying in length from 72 to 123% of wild-type DNA (3.4 to 5.8 kb) were incrementally heated, the proportion of uncoated AAV capsids decreased with genome length as observed by EM. Genome release was further characterized by a fluorimetric assay, which demonstrated that acidic pH and high osmotic pressure suppress genome release from AAV particles. In addition, fluorimetric analysis corroborated an inverse correlation between packaged genome length and the temperature needed to induce uncoating. Surprisingly, scAAV vectors required significantly higher temperatures to uncoat than their ssDNA-packaging counterparts. However, externalization of VP1 N termini appears to be unaffected by packaged genome length or self-complementarity. Further analysis by tungsten-shadowing EM revealed striking differences in the morphologies of ssDNA and scDNA genomes upon release from intact capsids. Computational modeling and molecular dynamics simulations suggest that the unusual thermal stability of scAAV vectors might arise from partial base pairing and optimal organization of packaged scDNA. Our work further defines the biophysical mechanisms underlying adeno-associated virus uncoating and genome release.
B Cells in Chronically Hepatitis C Virus-Infected Individuals Lack a Virus-Induced Mutation Signature in theTP53,CTNNB1, andBCL6Genes
Authors: Tucci Felicia Anna , Broering Ruth , Johansson Patricia , Schlaak Joerg F. , Küppers Ralf
Published: December 2012

Hepatitis C virus (HCV) is considered to have a causative role in B-cell lymphoproliferative diseases, including B-cell lymphomas, in chronic virus carriers. Previous data fromin vitroHCV-infected B-cell lines and peripheral blood mononuclear cells from HCV-positive individuals suggested that HCV might have a direct mutagenic effect on B cells, inducing mutations in the tumor suppressor gene TP53 and the proto-oncogenes BCL6 and CTNNB1 (β-catenin). To clarify whether HCV indeed has a mutagenic effect on B cellsin vivo, we analyzed naive and memory B cells from the peripheral blood of four chronic HCV carriers and intrahepatic B cells from the livers of two HCV-positive patients for mutations in the three reported target genes. However, no mutations were found in the TP53 and CTNNB1 genes. For BCL6, which is a physiological target of the somatic hypermutation process in germinal-center B cells, the mutation levels identified were not higher than those reported in the respective B-cell subsets in healthy individuals. Hence, we conclude that in chronic HCV carriers, the virus does not generally induce mutations in the cancer-related genes TP53, CTNNB1, and BCL6 in B cells. Based on these findings, new targets have to be investigated as potential mediators of HCV-associated B-cell lymphomagenesis.
Transgenic CCL2 Expression in the Central Nervous System Results in a Dysregulated Immune Response and Enhanced Lethality after Coronavirus Infection
Authors: Trujillo Jonathan A. , Fleming Erica L. , Perlman Stanley
Published: December 2012

Chemokine (C-C motif) ligand 2 (CCL2), a chemoattractant for macrophages, T cells, and cells expressing CCR2, is upregulated during acute and chronic inflammation. CCL2 has been implicated in both proinflammatory and anti-inflammatory responses and has been suggested as a target for therapy in some inflammatory disorders. To examine the role of CCL2 during virus infection, we infected mice transgenically expressing CCL2 in the central nervous system (CCL2 Tg) with an attenuated neurotropic coronavirus (rJ2.2 strain of mouse hepatitis virus). Infection of wild-type mice with rJ2.2 results in mild acute encephalitis, followed by a nonlethal, chronic demyelinating disease. Proinflammatory innate and adaptive immune responses mediate virus clearance. In marked contrast, CCL2 Tg mice infected with rJ2.2 ineffectively cleared virus and rapidly succumbed to the infection. CCL2 Tg mice mounted a dysregulated immune response, characterized by augmented accumulation of regulatory Foxp3+CD4+T cells and of nitric-oxide- and YM-1-expressing macrophages and microglia, suggestive of mixed M1/M2 macrophage activation. Further, macrophages from infected CCL2 Tg brains relative to non-Tg controls were less activated/mature, expressing lower levels of major histocompatibility complex class II (MHC-II), CD86, and CD40. Collectively, these results show that persistent CCL2 overexpression establishes and sustains an immunological milieu that is both inflammatory and immunosuppressive and predisposes mice to a defective immune response to a minimally lethal virus.
Structure of Alphacoronavirus Transmissible Gastroenteritis Virus nsp1 Has Implications for Coronavirus nsp1 Function and Evolution
Authors: Jansson Anna M.
Published: December 2012

Coronavirus nsp1 has been shown to induce suppression of host gene expression and to interfere with the host immune response. However, the mechanism is currently unknown. The only available structural information on coronavirus nsp1 is the nuclear magnetic resonance (NMR) structure of the N-terminal domain of nsp1 from severe acute respiratory syndrome coronavirus (SARS-CoV) from the betacoronavirus genus. Here we present the first nsp1 structure from an alphacoronavirus, transmissible gastroenteritis virus (TGEV) nsp1. It displays a six-stranded β-barrel fold with a long alpha helix on the rim of the barrel, a fold shared with SARS-CoV nsp1
13–128
. Contrary to previous speculation, the TGEV nsp1 structure suggests that coronavirus nsp1s have a common origin, despite the lack of sequence homology. However, comparisons of surface electrostatics, shape, and amino acid conservation between the alpha- and betacoronaviruses lead us to speculate that the mechanism for nsp1-induced suppression of host gene expression might be different in these two genera.
Disruption of Thiamine Uptake and Growth of Cells by Feline Leukemia Virus Subgroup A
Authors: Mendoza Ramon , Miller A. Dusty , Overbaugh Julie
Published: December 2012

Feline leukemia virus (FeLV) is still a major cause of morbidity and mortality in domestic cats and some wild cats despite the availability of relatively effective vaccines against the virus. FeLV subgroup A (FeLV-A) is transmitted in natural infections, and FeLV subgroups B, C, and T can evolve directly from FeLV-A by mutation and/or recombination with endogenous retroviruses in domestic cats, resulting in a variety of pathogenic outcomes. The cell surface entry receptor for FeLV-A is a putative thiamine transporter (THTR1). Here, we have addressed whether FeLV-A infection might disrupt thiamine uptake into cells and, because thiamine is an essential nutrient, whether this disruption might have pathological consequences. First, we cloned the cat ortholog of the other of the two known thiamine transporters in mammals, THTR2, and we show that feline THTR1 (feTHTR1) and feTHTR2 both mediate thiamine uptake, but feTHTR2 does not function as a receptor for FeLV-A. We found that feTHTR1 is widely expressed in cat tissues and in cell lines, while expression of feTHTR2 is restricted. Thiamine uptake mediated by feTHTR1 was indeed blocked by FeLV-A infection, and in feline fibroblasts that naturally express feTHTR1 and not feTHTR2, this blockade resulted in a growth arrest at physiological concentrations of extracellular thiamine. The growth arrest was reversed at high extracellular concentrations of thiamine. Our results show that FeLV-A infection can indeed disrupt thiamine uptake with pathological consequences. A prediction of these experiments is that raising the plasma levels of thiamine in FeLV-infected cats may ameliorate the pathogenic effects of infection.
Comparative Genomics of Carp Herpesviruses
Authors: Davison Andrew J. , Kurobe Tomofumi , Gatherer Derek , Cunningham Charles , Korf Ian , Fukuda Hideo , Hedrick Ronald P. , Waltzek Thomas B.
Published: December 2012

Three alloherpesviruses are known to cause disease in cyprinid fish: cyprinid herpesviruses 1 and 3 (CyHV1 and CyHV3) in common carp and koi and cyprinid herpesvirus 2 (CyHV2) in goldfish. We have determined the genome sequences of CyHV1 and CyHV2 and compared them with the published CyHV3 sequence. The CyHV1 and CyHV2 genomes are 291,144 and 290,304 bp, respectively, in size, and thus the CyHV3 genome, at 295,146 bp, remains the largest recorded among the herpesviruses. Each of the three genomes consists of a unique region flanked at each terminus by a sizeable direct repeat. The CyHV1, CyHV2, and CyHV3 genomes are predicted to contain 137, 150, and 155 unique, functional protein-coding genes, respectively, of which six, four, and eight, respectively, are duplicated in the terminal repeat. The three viruses share 120 orthologous genes in a largely colinear arrangement, of which up to 55 are also conserved in the other member of the genus
Cyprinivirus
, anguillid herpesvirus 1. Twelve genes are conserved convincingly in all sequenced alloherpesviruses, and two others are conserved marginally. The reference CyHV3 strain has been reported to contain five fragmented genes that are presumably nonfunctional. The CyHV2 strain has two fragmented genes, and the CyHV1 strain has none. CyHV1, CyHV2, and CyHV3 have five, six, and five families of paralogous genes, respectively. One family unique to CyHV1 is related to cellular JUNB, which encodes a transcription factor involved in oncogenesis. To our knowledge, this is the first time that JUNB-related sequences have been reported in a herpesvirus.
The Rnf Complex of Clostridium ljungdahlii Is a Proton-Translocating Ferredoxin:NAD
+
Oxidoreductase Essential for Autotrophic Growth
Authors: Tremblay Pier-Luc , Zhang Tian , Dar Shabir A. , Leang Ching , Lovley Derek R.
Published: December 2012

It has been predicted that the Rnf complex of
Clostridium ljungdahlii
is a proton-translocating ferredoxin:NAD
+
oxidoreductase which contributes to ATP synthesis by an H
+
-translocating ATPase under both autotrophic and heterotrophic growth conditions. The recent development of methods for genetic manipulation of
C. ljungdahlii
made it possible to evaluate the possible role of the Rnf complex in energy conservation. Disruption of the
C. ljungdahlii rnf
operon inhibited autotrophic growth. ATP synthesis, proton gradient, membrane potential, and proton motive force collapsed in the Rnf-deficient mutant with H
2
as the electron source and CO
2
as the electron acceptor. Heterotrophic growth was hindered in the absence of a functional Rnf complex, as ATP synthesis, proton gradient, and proton motive force were significantly reduced with fructose as the electron donor. Growth of the Rnf-deficient mutant was also inhibited when no source of fixed nitrogen was provided. These results demonstrate that the Rnf complex of
C. ljungdahlii
is responsible for translocation of protons across the membrane to elicit energy conservation during acetogenesis and is a multifunctional device also implicated in nitrogen fixation.

IMPORTANCE
Mechanisms for energy conservation in the acetogen
Clostridium ljungdahlii
are of interest because of its potential value as a chassis for the production of biocommodities with novel electron donors such as carbon monoxide, syngas, and electrons derived from electrodes. Characterizing the components implicated in the chemiosmotic ATP synthesis during acetogenesis by
C. ljungdahlii
is a prerequisite for the development of highly productive strains. The Rnf complex has been considered the prime candidate to be the pump responsible for the formation of an ion gradient coupled with ATP synthesis in multiple acetogens. However, experimental evidence for a proton-pumping Rnf complex has been lacking. This study establishes the
C. ljungdahlii
Rnf complex as a proton-translocating ferredoxin:NAD
+
oxidoreductase and demonstrates that
C. ljungdahlii
has the potential of becoming a model organism to study proton translocation, electron transport, and other functions of the Rnf complex in energy conservation or other processes.
Pilus Adhesin RrgA Interacts with Complement Receptor 3, Thereby Affecting Macrophage Function and Systemic Pneumococcal Disease
Authors: Orrskog Sofia , Rounioja Samuli , Spadafina Tiziana , Gallotta Marilena , Norman Martin , Hentrich Karina , Fälker Stefan , Ygberg-Eriksson Sofia , Hasenberg Mike , Johansson Björn , Uotila Liisa M. , Gahmberg Carl G. , Barocchi Michèle , Gunzer Matthias , Normark Staffan , Henriques-Normark Birgitta
Published: December 2012

Pneumococcal pili have been shown to influence pneumococcal colonization, disease development, and the inflammatory response in mice. The role of the pilus-associated RrgA adhesin in pneumococcal interactions with murine and human macrophages was investigated. Expression of pili with RrgA enhanced the uptake of pneumococci by murine and human macrophages that was abolished by antibodies to complement receptor 3 (CR3) and not seen in CR3-deficient macrophages. Recombinant RrgA, but not pilus subunit RrgC, promoted CR3-mediated phagocytosis of coated beads by murine and human macrophages. Flow cytometry showed that purified CR3 binds pneumococcal cells expressing RrgA, and purified RrgA was shown to interact with CR3 and its I domain.
In vivo
, RrgA facilitated spread of pneumococci from the upper airways and peritoneal cavity to the bloodstream. Earlier onset of septicemia and more rapidly progressing disease was observed in wild-type mice compared to CR3-deficient mice challenged intranasally or intraperitoneally with pneumococci. Motility assays and time-lapse video microscopy showed that pneumococcal stimulation of macrophage motility required RrgA and CR3. These findings, together with the observed RrgA-dependent increase of intracellular survivors up to 10 h following macrophage infection, suggest that RrgA-CR3-mediated phagocytosis promotes systemic pneumococcal spread from local sites.

IMPORTANCE
Streptococcus pneumoniae
is a major contributor to morbidity and mortality in infectious diseases globally. Symptomatology is mainly due to pneumococcal interactions with host cells leading to an inflammatory response. However, we still need more knowledge on how pneumococci talk to immune cells and the importance of this interaction. Recently, a novel structure was identified on the pneumococcal surface, an adhesive pilus found in about 30% of clinical pneumococcal isolates. The pilus has been suggested to be important for successful spread of antibiotic-resistant pneumococcal clones globally. Here we sought to identify mechanisms for how the pneumococcal pilin subunit RrgA contributes to disease development by interacting with host immune cells. Our data suggest a new way for how pneumococci may cross talk with phagocytic cells and affect disease progression. An increased understanding of these processes may lead to better strategies for how to treat these common infections.
Metabolic and neuromuscular responses at critical power from the 3-min all-out test
Authors: Bergstrom Haley C. , Housh Terry J. , Zuniga Jorge M. , Traylor Daniel A. , Lewis Robert W. , Camic Clayton L. , Schmidt Richard J. , Johnson Glen O.
Published: December 2012

The purpose of this study was to determine the specific metabolic and neuromuscular responses at critical power (CP) from the 3-min all-out test. Nine men (mean ± SD: aged 23.7 ± 3.3 years) performed an incremental test for the determination of peak oxygen consumption (V̇O2peak) and gas exchange threshold. CP was estimated for each subject from the 3-min all-out test. Oxygen consumption (V̇O2), the ventilation versus carbon dioxide production ratio (V̇E/V̇CO2 ratio), electromyographic (EMG) amplitude, and EMG mean power frequency (MPF) were examined during exhaustive rides at CP for each subject. There was no significant difference between the V̇O2 at exhaustion (40.6 ± 7.5 mL·kg−1·min−1) and V̇O2peak (42.9 ± 7.3 mL·kg−1·min−1). Furthermore, there were significant increases in EMG amplitude and the V̇E/V̇CO2 ratio during the exhaustive rides at CP. There was, however, no significant change in EMG MPF over time. Therefore, the current findings indicated that the 3-min all-out test overestimated CP and the demarcation between the heavy- and severe-intensity domains. Specifically, the V̇O2, ventilatory, and EMG amplitude responses were consistent with those observed during continuous exercise in the severe exercise intensity domain. It is likely that the ventilatory and EMG amplitude responses were associated with a common mechanism of fatigue that is different from what affects EMG MPF.
CONTRACT MANUFACTURING IN LATE INDUSTRIALIZATION
Authors: TUNG AN-CHI , WAN HENRY
Published: December 2012

Contract manufacturing is the catalyst shaping the world economy under globalization. Affirming the dominance of the open network in organizing worldwide value chains, it transformed Japan and US into trade partners rather than rivals. It allows firms like Apple, Nokia and Sony to outsource production tasks to People's Republic of China, which serves as the world's workplace, and provides a niche for Singapore and Taiwan in late industrialization. Tapping into the economy of scope from the pooling of capacity and information, contract manufacturers like Foxconn and Flextronics provide durable and significant benefit for their economies of domicile, hence a novel niche in late industrialization.
SELF-INTERACTING HOLOGRAPHIC DARK ENERGY
Authors: CHIMENTO LUIS P. , FORTE MÓNICA , RICHARTE MARTÍN G.
Published: December 2012

We investigate a spatially flat Friedmann–Robertson–Walker (FRW) universe where dark matter exchanges energy with a self-interacting holographic dark energy (SIHDE). Using the χ2-statistical method on the Hubble function, we obtain a critical redshift that seems to be consistent with both BAO and CMB data. We calculate the theoretical distance modulus for confronting with the observational data of SNe Ia for small redshift z ≤ 0.1 and large redshift 0.1 ≤ z ≤ 1.5. The model gets accelerated faster than the ΛCDM one and it can be a good candidate to alleviate the coincidence problem. We also examine the age crisis at high redshift associated with the old quasar APM 08279+5255.
THE MANY FACES OF THE MASSLESS TENSOR GAUGE FIELD OF DEGREE TWO
Authors: CIOROIANU EUGEN-MIHAITA
Published: December 2012

Starting from a generic second-order Lagrangian density (that describes the dynamics of an Abelian tensor gauge field of degree two and depends on two arbitrary real constants) we first perform the Dirac analysis. This procedure reveals seven distinct situations (dictated by the values of the real parameters that label the second-order Lagrangian density) in each of them one determines the number of degrees of freedom and also a generating set of gauge transformations. Second, with the help of some auxiliary gauge/matter tensor gauge fields of degree three, in each of the seven situations aforementioned, we construct the first-order Lagrangian density corresponding to the second-order one.
THIN STRUCTURE OF β-STABILITY LINE AND SYMMETRY ENERGY
Authors: KOLOMIETZ V. M. , SANZHUR A. I.
Published: December 2012

We suggest a particular procedure of derivation of the beta-stability line, the nuclear Coulomb energy and the isotopic symmetry energy. The approach is based on the analysis of the A-dependency of the shift of neutron–proton chemical potentials Δλ = λn-λp. We observe the nonmonotonic (sawtooth) shape of the β-stability line as a function of mass number A and establish the relation of local maxima of the β-stability line to the mass numbers of the double-closed shells. The behavior of the symmetry energy coefficient b sym (A) at fixed neutron excess Y = N-Z is analyzed. We show that, qualitatively, b sym (A) has canyon-like behavior for a given value of Y. The width and the position of the bottom of such "canyon" depend on neutron excess.
NUCLEAR REACTION CROSS-SECTION FOR DRIP-LINE NUCLEI IN THE FRAMEWORK OF GLAUBER MODEL USING RELATIVISTIC AND NONRELATIVISTIC DENSITIES
Authors: SHARMA MAHESH K. , MEHTA M. S. , PATRA S. K.
Published: December 2012

We study the nuclear reaction cross-sections for some of the neutron-rich nuclei in the lighter mass region of the periodic chart which are recently measured. The well-known Glauber formalism is used by taking deformed relativistic and nonrelativistic densities as input in the calculations. We find reasonable reaction cross-sections with both the densities. However with a better inspection of the results, it is noticed that the results obtained with relativistic densities are more closure to the experimental data than the nonrelativistic Skyrme densities.
POTENTIAL ENERGY SURFACES AND MICROWAVE SPECTRA FOR 20Ne–13C16O2, 22Ne–12C16O2 and 22Ne–13C16O2 COMPLEXES
Authors: CHEN RONG , ZHU HUA
Published: December 2012

We report averaged potential energy surfaces for isotopic Ne–CO2 complexes (20 Ne –13 C 16 O 2, 22 Ne –12 C 16 O 2 and 22 Ne –13 C 16 O 2). According to the latest ab initio potential of 20 Ne –12 C 16 O 2 (Chen R, Jiao EQ, Zhu H, Xie DQ, J Chem Phys133:104302, 2010) including the Q3 normal mode for the υ3 antisymmetric stretching vibration of the CO2 molecule. We obtain the averaged potentials for 20 Ne –13 C 16 O 2, 22 Ne –12 C 16 O 2 and 22 Ne –13 C 16 O 2 by the integration of the three-dimensional potential over the Q3 coordinate. The averaged potential surfaces are found to have a T-shaped global minimum and two equivalent linear local minima. The radial DVR/angular FBR method and the Lanczos algorithm are applied to calculate the rovibrational energy levels. Comparison with the available observed values showed an overall excellent agreement for all spectroscopic parameters and the microwave spectra.
INTERACTIONS OF THE NUCLEOTIDES WITH THE METAL IONS Mg2+, Ca2+, Mn2+, Na+, AND K+
Authors: QIN PENG-HUA , LU WEN-CAI , GUO PAN-JUAN , QIN WEI , ZHAO LI-ZHEN , SONG WEI
Published: December 2012

The interactions of the four typical nucleotides with the metal ions Mg 2+, Ca 2+, Mn 2+, Na +, and K + were studied by using the B3LYP/6-311++G(d,p)//B3LYP/6-31G(d,p) calculations in the PCM model. A lot of initial binding sites of the metal ions were designed and optimized to determine the most stable structures of the metal ion nucleotide compounds. It has been shown that the metal ions tend to attach at the center of the negatively charged atoms of the nucleotides. Furthermore, the vertical excitation energies of the metal ion nucleotide compounds were calculated at the same level with the TDDFT method, and also NBO charges were analyzed to understand the bonding characteristics between the metal ions and the nucleotides. That was also compared with the conclusion in the gas phase.
MOLECULAR DYNAMICS SIMULATIONS OF HELIX BUNDLE PROTEINS USING UNRES FORCE FIELD AND ALL-ATOM FORCE FIELD
Authors: GAO KAIFU , YANG MINGHUI
Published: December 2012

We have investigated the folding of two helix-bundle proteins, 36-residue Villin headpiece and 56-residue E-domain of Staphylococcal protein A, by combining molecular dynamics (MD) simulations with Coarse-Grained United-Residue (UNRES) Force Field and all-atom force field. Starting from extended structures, each of the proteins was folded to a stable structure within a short time frame using the UNRES model. However, the secondary structures of helices were not well formed. Further refinement using MD simulations with the all-atom force field was able to fold the protein structure into the native-like state with the smallest main-chain root-mean-square deviation of around 3 Å. Detailed analysis of the folding trajectories was presented and the performance of GPU-based MD simulations was also discussed.
A COMPARATIVE STUDY ON INTERMOLECULAR HYDROGEN BOND INTERACTIONS IN MOLECULAR DIMERS USING DIFFERENT LEVELS OF COMPUTATIONAL METHODS
Authors: WANG CUIHONG , ZHANG RUIQIN , LIN ZIJING
Published: December 2012

Hydrogen bond interactions in biological systems are important scientific issues but are challenging for their theoretical determinations at quantum-mechanical level of theory. Due to the different approximations, the available theoretical approaches often predict diverse hydrogen bond lengths and strengths. In this work, we evaluated the reliabilities of a number of widely used theoretical approaches including HF, SVWN, BLYP, PW91, B3LYP, BH and HLYP, B97D, M06L, MP2, and DFTB-D in studying hydrogen bonding, by calculating the hydrogen bond lengths and binding energies of 23 dimers formed by HCOOH , NH3 and Glycine. We also compared the effects of STO-3G, 6-31+G**, 6-311++G** and 6-311++G(2df,2p) basis sets on the results. Our result shows that, M06L, B3LYP and BHandHLYP methods can predict accurate dimer structures with a moderate basis set. Moreover, DFTB-D also gives reasonably reliable results with high efficiency and satisfactory precision, being a good choice for studying complex structures which contain hydrogen bonds.
FIRST-PRINCIPLES STUDY OF OXYGEN-VACANCYCu2O(111) SURFACE
Authors: WU HUANWEN , ZHANG NING , WANG HONGMING , HONG SANGUO
Published: December 2012

Geometric and electronic properties and vacancy formation energies for two kinds of oxygen-vacancy Cu2O (111) surfaces have been investigated by first-principles calculations. Results show that the relaxation happens mainly on the top three trilayers of surfaces. Two vacancies trap electrons of -0.11e and -0.27e, respectively. The effects of oxygen vacancies on the electronic structures are found rather localized. The electronic structures suggest that the oxygen vacancies enhance the electron donating ability of the surfaces to some extent. The energies of 1.75 and 1.43 eV for the formation of oxygen vacancies are rather low, which indicates the partially reduced surfaces are stable and easy to produce.
CHARACTERISTIC VIBRATIONAL MODES OF H2O ADSORBED MOLECULARLY AND DISSOCIATIVELY ON TITANIUM OXIDE CLUSTERS
Authors: DU HONGBO , DE SARKAR ABIR , JIA YU , ZHANG RUI-QIN
Published: December 2012

To provide useful information on dissociation of water molecule on ( TiO2 )n clusters for experimental verification, we have calculated the infrared (IR) and Raman spectra of three possible states involved, namely molecularly adsorbed state, metastable state and dissociatively adsorbed state, using density functional theory at the B3LYP/6-311G(d) level. We find that the characteristic bands of H2O molecules below 2000 cm-1 in both IR and Raman spectra vanish upon both molecular and dissociative adsorption of H2O . In the high frequency range of 3600–4200 cm-1, the adsorption caused the single IR peak of water to split into two bands, while the dissociation removed the one at lower frequency and blue shifted slightly the higher frequency band. The two Raman peaks of the water molecule in the same high frequency range were slightly blue shifted upon adsorption but the one at lower frequency was removed upon dissociation, while the one at high frequency blue shifted slightly. The intensities of vibrational modes of water in 3600–4200 cm-1 are generally significantly enhanced upon both molecular and dissociative adsorption. Our results show clearly signatures of dissociation of water molecule into hydroxyl radical at the terminal site.
QUASICLASSICAL TRAJECTORY STUDY OF PRODUCT POLARIZATIONS IN THEH(2S) +NH→N(4S) +H2REACTION
Authors: LI LIN , DONG SHUNLE
Published: December 2012

Based on the DMBE potential surface of the4A ″ ground-state, the product rotational polarizations in the title reaction are studied by using quasiclassical trajectory (QCT) calculation method. Three angular distributions of P(θr), P(Φr), P(θr, Φr) and the four polarization-dependent differential cross sections (PDDCSs) were calculated for the collision energy range of 1–20 kcal/mol. The results revealed that the product is backward-scattering and the product rotational angular momentum j′ is aligned and oriented. With the increment of collision energy, the degree of the product alignment and orientation is enhanced, showing the collision energy-dependent behaviors of the product polarizations.
FORMATION OF ULTRACOLD CESIUM MOLECULES IN THE GROUND ELECTRONIC STATE
Authors: HU XUE-JIN , ZHANG WEI , HUANG YIN , YANG JUN-FENG , CONG SHU-LIN
Published: December 2012

We investigate theoretically the preparation of ultracold photoassociated Cs 2 molecules in the lowest vibrational level of the ground electronic state via the stimulated Raman adiabatic passage (STIRAP) by solving the time-dependent Schrödinger equation using the mapped Fourier grid method. A negative chirped laser pulse is used to produce the unstable photoassociated molecules in the excited electronic state. A dump pulse is utilized to transfer a partial population of the unstable photoassociated molecules to the vibrational v″ = 18 level of the ground electronic state. This part of population is then transferred to the v″ = 0 level of the ground electronic state by the pump and Stokes laser pulses via an intermediate state which is taken to be the v′ = 7 level of the excited electronic state, forming the stable photoassociated molecules. The population transfer efficiency from v″ = 18 to v″ = 0 in the ground electronic state reaches 96.2% via the STIRAP.
THE SUBSTITUTION EFFECT ON THE AROMATICITY OF SOME N-PHENYLACETAMIDE DERIVATIVES: A DFT STUDY
Authors: FEREYDUNI EHSAN , KAMAEE MAHDI , SOLEYMANI REZA , AHMADI ROYA
Published: December 2012

The relative aromaticity of some N-phenylacetamide (NPA) derivatives were investigated in which the NPA was substituted by NO2, CN, CF3, Br, Cl, F, H, CH3 , and NH2 groups at two meta and para positions. For this purpose, density functional theory calculations were applied at the B3LYP/6-31+G(d,p) level to calculate the aromaticity indices including nucleus independent chemical shift (NICS), harmonic oscillator model of aromaticity (HOMA) and harmonic oscillator model of electron delocalization (HOMED). The obtained results indicated that the aromaticity of derivatives decreased in the order of NO 2 > CN > CF 3 > Br > Cl > F > H > CH 3 > NH 2 for both meta and para positions. Furthermore, the resulting order was directly related to the electron withdrawing and electron releasing strengths of the substituents. Finally, it was found that all the aromaticity indices of have a good correlation with the Hammett constant.
COMPUTATIONAL STUDY OF BRIDGE-MEDIATED INTERVALENCE ELECTRON TRANSFER II: COUPLINGS IN DIFFERENT METALLOCENE COMPLEXES
Authors: YU YINXI , WANG HAOBIN , CHEN SHAOWEI
Published: December 2012

The constrained density functional theory (CDFT) was used to study bridge-mediated electron transfer processes in mixed-valence systems with two identical metallocene (cobaltocene, ruthenocene, and nickelocene) moieties linked by various bridge structures. Based on the electronic coupling matrix elements obtained from the CDFT calculations, the relationship between the bridge linkage and the effectiveness of intervalence transfer was discussed.