bluuebunny/crossref_metadata_2025 huggingface dataset:
Single Nucleotide Polymorphisms in the Toll-Like Receptor 3 and CD44 Genes Are Associated with Persistence of Vaccine-Induced Immunity to the Serogroup C Meningococcal Conjugate Vaccine
Authors: Moore Catrin E. , Hennig Branwen J. , Perrett Kirsten P. , Hoe J. Claire , Lee Sue J. , Fletcher Helen , Brocklebank Denise , O'Connor Daniel , Snape Matthew D. , Hall Andrew J. , Segal Shelley , Hill Adrian V. S. , Pollard Andrew J.
Published: December 2011

The rate of decay of antibody concentration following serogroup C meningococcal (MenC) polysaccharide-protein conjugate vaccination varies between individuals. This depends partly on vaccination age but may be influenced by human genetics. We studied 721 single nucleotide polymorphisms (SNPs) across 131 candidate genes in a first cohort of 905 Caucasians (11 to 21 years old; mean time after vaccination, 4.9 years) and 30 SNPs across 17 genes in a replication study using 155 children, aged 6 to 12 years (mean time after vaccination, 6.7 years), and 196 infants (1 year old; mean time after vaccination, 8 months). Individuals were classified as responders or nonresponders for total MenC IgG concentration and MenC serum bactericidal antibody (SBA) measurements. Associated genes were examined further for quantitative outcome measures. Fifty-nine SNPs in 37 genes were associated with IgG persistence (adjusted for age at measurement), and 56 SNPs in 36 genes were associated with SBA persistence (adjusted for age at measurement and vaccine used). Three SNPs each within the Toll-like receptor 3 (TLR3) (rs3775291, rs3775292, and rs5743312) and CD44 (rs11033013, rs353644, and rs996076) genes were associated with IgG (adjusted for age at measurement) or SBA (adjusted for age at measurement and vaccine used) persistence in the initial genetic study (P, 0.02 to 0.04). Single SNPs within the TLR3 (rs7657186) (P= 0.004 [unadjusted]) and CD44 (rs12419062) (P= 0.01 [unadjusted]) genes were associated with IgG persistence in the replication study. These results suggest that genetic polymorphisms in the TLR3 and CD44 genes are associated with the persistence of the immune response to MenC vaccines 1 to 6 years after vaccination.
Immunological Correlates of Vaccination and Infection for Equine Herpesvirus 1
Authors: Goodman Laura B. , Wimer Christine , Dubovi Edward J. , Gold Carvel , Wagner Bettina
Published: December 2011

Equine herpesvirus 1 (EHV-1) induces a variety of disease manifestations, including respiratory disease, abortions, and myeloencephalopathy. Several vaccines are commercially available but could not previously be distinguished by serologic testing from infection with EHV-1 (or the closely related EHV-4). Currently available vaccines are not reliably protective against the severe manifestations of the disease, including fatal myeloencephalopathy. We determined immunological parameters that can differentiate vaccinated from previously infected animals by comparing humoral and cellular EHV-1-specific responses in clinically healthy horses 10 months after vaccination. Forty-seven horses with known histories of vaccination and infection were studied, including a group of horses that survived a severe neurological outbreak 5 years prior to vaccination. Results of serum virus neutralization (SN), serum IgG isotyping, and cytokine profiling of lymphocyte subsets were compared. IgG4/7 levels strongly correlated with virus neutralization (
P
< 0.0001). IgG1/3 and SN values distinguished vaccinated/outbreak-exposed (vacc/outbreak) horses from vaccinated horses (
P
< 0.05). EHV-1-specific gamma interferon (IFN-γ)-producing CD4
+
(but not CD8
+
) T-cell numbers were also increased in vacc/outbreak horses, which distinguished them from vaccinated horses (
P
< 0.01). IFN-α secretion was similar between all groups and independent of previous exposure or vaccination. Our data suggest that IgG isotype responses to EHV-1 are more diverse under field conditions than is revealed by experimental studies and that the current modified-live virus (MLV) vaccine induces a more restricted IgG isotype response than does natural exposure to EHV-1. Since these parameters can be assessed in a high-throughput manner, they may prove useful in screening future vaccine candidates and assessing levels of protection.
Complete Genome Sequences of Three Pseudomonas aeruginosa Isolates with Phenotypes of Polymyxin B Adaptation and Inducible Resistance
Authors: Boyle Brian , Fernandez Lucia , Laroche Jerome , Kukavica-Ibrulj Irena , Mendes Caio M. F. , Hancock Robert W. , Levesque Roger C.
Published: December 2011

Clinical “superbug” isolates of
Pseudomonas aeruginosa
were previously observed to be resistant to several antibiotics, including polymyxin B, and/or to have a distinct, reproducible adaptive polymyxin resistance phenotype, identified by observing “skipped” wells (appearance of extra turbid wells) during broth microdilution testing. Here we report the complete assembled draft genome sequences of three such polymyxin resistant
P. aeruginosa
strains (9BR, 19BR, and 213BR).
Genome Sequencing of Bacillus subtilis SC-8, Antagonistic to the Bacillus cereus Group, Isolated from Traditional Korean Fermented-Soybean Food
Authors: Yeo In-Cheol , Lee Nam Keun , Hahm Young Tae
Published: December 2011

Bacillus subtilis
SC-8 is a Gram-positive bacterium displaying narrow antagonistic activity for the
Bacillus cereus
group.
B. subtilis
SC-8 was isolated from Korean traditional fermented-soybean food. Here we report the draft genome sequence of
B. subtilis
SC-8, including biosynthetic genes for antibiotics that may have beneficial effects for control of food-borne pathogens.
Genetic Relationships of Phage Types and Single Nucleotide Polymorphism Typing of Salmonella enterica Serovar Typhimurium
Authors: Pang Stanley , Octavia Sophie , Reeves Peter R. , Wang Qinning , Gilbert Gwendolyn L. , Sintchenko Vitali , Lan Ruiting
Published: December 2011

Salmonella enterica
serovar Typhimurium is one of the leading causes of gastroenteritis in humans. Phage typing has been used for the epidemiological surveillance of
S
. Typhimurium for over 4 decades. However, knowledge of the evolutionary relationships between phage types is very limited. In this study, we used single nucleotide polymorphisms (SNPs) as molecular markers to determine the relationships between common
S
. Typhimurium phage types. Forty-four SNPs, including 24 identified in a previous study and 20 from 6 available whole-genome sequences, were used to analyze 215
S
. Typhimurium isolates belonging to 45 phage types. Altogether, 215 isolates and 6 genome strains were differentiated into 33 SNP profiles and four distinctive phylogenetic clusters. Fourteen phage types, including DT9, one of the most common phage types in Australia, were differentiated into multiple SNP profiles. These SNP profiles were distributed into different phylogenetic clusters, indicating that they have arisen independently multiple times. This finding suggests that phage typing may not be useful for long-term epidemiological studies over long periods (years) and diverse localities (different countries or continents). SNP typing provided a discriminative power similar to that of phage typing. However, 12 SNP profiles contained more than one phage type, and more SNPs would be needed for further differentiation. SNP typing should be considered as a replacement for phage typing for the identification of
S
. Typhimurium strains.
Cell-Associated Hemolysis Induced by Helicobacter pylori Is Mediated by Phospholipases with Mitogen-Activated Protein Kinase-Activating Properties
Authors: Sitaraman Ramakrishnan , Israel Dawn A. , Romero-Gallo Judith , Peek Richard M.
Published: December 2011

PathogenicHelicobacter pyloristrains can selectively activate epithelial mitogen-activated protein kinase (MAPK) signaling pathways linked with disease. We now demonstrate thatH. pylori-induced hemolysis is strain specific and is mediated by phospholipases PldA1 and PldD. Inactivation of PldD inhibited activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), indicating thatH. pylorihemolytic phospholipases also harbor MAPK-activating properties.
Combination of Single Nucleotide Polymorphism and Variable-Number Tandem Repeats for Genotyping a Homogenous Population of Mycobacterium tuberculosis Beijing Strains in China
Authors: Luo Tao , Yang Chongguang , Gagneux Sebastien , Gicquel Brigitte , Mei Jian , Gao Qian
Published: December 2011

The standard 15- and 24-locus variable-number tandem repeat (VNTR) genotyping methods have demonstrated adequate discriminatory power and a small homoplasy effect for tracing tuberculosis (TB) transmission and predicting
Mycobacterium tuberculosis
lineages in European and North American countries. However, its validity for the definition of transmission in homogenous
M. tuberculosis
populations in settings with high TB burdens has been questioned. Here, we genotyped a population-based collection of 191 Beijing strains based on standard 15-locus VNTR (VNTR-15) and 8 single nucleotide polymorphisms (SNPs) in Shanghai, China. Limited discriminatory power and high rates of VNTR homoplasy were observed in the homogenous population of evolutionarily “modern” Beijing strains. Additional typing of three hypervariable loci (VNTR3820, VNTR4120, and VNTR3232) was performed for VNTR-15-based clusters. High variations of hypervariable alleles were observed in clusters with inconsistent SNP sublineages. We concluded that SNPs and hypervariable VNTR loci are helpful to enhance the discriminatory power and decrease the VNTR homoplasy effect for defining clusters. We recommend the combination of standard VNTR-15 and SNPs as first-line typing methods and the hypervariable loci for second-line typing of clustered strains for molecular epidemiology studies of homogenous
M. tuberculosis
populations.
Use of Illumina Deep Sequencing Technology To Differentiate Hepatitis C Virus Variants
Authors: Ninomiya Masashi , Ueno Yoshiyuki , Funayama Ryo , Nagashima Takeshi , Nishida Yuichiro , Kondo Yasuteru , Inoue Jun , Kakazu Eiji , Kimura Osamu , Nakayama Keiko , Shimosegawa Tooru
Published: December 2011

Hepatitis C virus (HCV) is a positive-strand enveloped RNA virus that shows diverse viral populations even in one individual. Though Sanger sequencing has been used to determine viral sequences, deep sequencing technologies are much faster and can perform large-scale sequencing. We demonstrate the successful use of Illumina deep sequencing technology and subsequent analyses to determine the genetic variants and amino acid substitutions in both treatment-naïve (patient 1) and treatment-experienced (patient 7) isolates from HCV-infected patients. As a result, almost the full nucleotide sequence of HCV was detectable for patients 1 and 7. The reads were mapped to the HCV reference sequence. The coverage was 99.8% and the average depth was 69.5× for patient 7, with values of 99.4% (coverage) and 51.1× (average depth) for patient 1. In patient 7, amino acid (aa) 70 in the core region showed arginine, with methionine at aa 91, by Sanger sequencing. Major variants showed the same amino acid sequence, but minor variants were detectable in 18% (6/34 sequences) of sequences, with replacement of methionine by leucine at aa 91. In NS3, 8 amino acid positions showed mixed variants (T72T/I, K213K/R, G237G/S, P264P/S/A, S297S/A, A358A/T, S457S/C, and I615I/M) in patient 7. In patient 1, 3 amino acid positions showed mixed variants (L14L/F/V, S61S/A, and I586T/I). In conclusion, deep sequencing technologies are powerful tools for obtaining more profound insight into the dynamics of variants in the HCV quasispecies in human serum.
“Candidatus Neoehrlichia mikurensis,” Anaplasma phagocytophilum, and Lyme Disease Spirochetes in Questing European Vector Ticks and in Feeding Ticks Removed from People
Authors: Richter Dania , Matuschka Franz-Rainer
Published: December 2011

To estimate the likelihood of people coming into contact with the recently described tick-borne agent “
Candidatus
Neoehrlichia mikurensis,” we compared its prevalence to those of Lyme disease spirochetes and
Anaplasma phagocytophilum
in questing adult
Ixodes ricinus
ticks collected in various Central European sites and examined ticks, which had been removed from people, for the presence of these pathogens. Whereas spirochetes infected questing adult ticks most frequently (22.3%), fewer than a third as many ticks were infected by “
Ca
. Neoehrlichia mikurensis” (6.2%), and about a sixth harbored
A. phagocytophilum
(3.9%). On average, every twelfth encounter of a person with an
I. ricinus
tick (8.1%) may bear the risk of acquiring “
Ca
. Neoehrlichia mikurensis.” Although a fifth of the people (20%) had removed at least one tick infected by “
Ca
. Neoehrlichia mikurensis,” none displayed symptoms described for this pathogen, suggesting that its transmission may not be immediate and/or that immunocompetent individuals may not be affected. Because immunosuppressed patients may be at a particular risk of developing symptoms, it should be considered that “
Ca
. Neoehrlichia mikurensis” appears to be the second most common pathogen in
I. ricinus
ticks. In our survey, only
Borrelia afzelii
appears to infect Central European vector ticks more frequently.
Genotype 3 Diversity and Quantification of Hepatitis E Virus RNA
Authors: Abravanel Florence , Sandres-Saune Karine , Lhomme Sebastien , Dubois Martine , Mansuy Jean-Michel , Izopet Jacques
Published: December 2011

Genotype 3 hepatitis E viruses (HEVs) are distributed across the world and are now considered to be an emerging public health concern in industrialized countries. At least 10 genotype 3 subtypes have been identified in humans and animals worldwide. It was recently reported that the sensitivities of HEV RNA assays differ greatly. We have assessed the influence of genotype 3 diversity on the performances of two HEV RNA assays: one targeting the ORF3 gene and the other targeting the ORF2 gene. We tested a panel of 5 HEV-positive reference samples of genotypes 3a, 3b, 3c, 3e, and 3f at 10-fold serial dilutions. The HEV RNA concentrations obtained with both reverse transcription (RT)-PCRs were correlated, but the RT-PCR based on ORF2 underestimated the HEV RNA concentrations. The mean [ORF3 − ORF2] difference was 1.41 log copies/ml. We also tested 34 clinical specimens of genotypes 3c (
n
= 15), 3e (
n
= 4), and 3f (
n
= 15), representing the most prevalent subtypes in Europe. The mean [ORF3 − ORF2] differences were 1.41 log copies/ml for genotype 3c, 0.96 log copies/ml for genotype 3e, and 0.70 log copies/ml for genotype 3f. The bias between the 2 RT-PCR assays was significantly greater for genotype 3c than for genotype 3f (
P
= 0.007). We therefore recommend the use of an RT-PCR protocol based on ORF3 to quantify HEV RNA of genotype 3 strains.
Cross-Reactivity of Fusarium spp. in the Aspergillus Galactomannan Enzyme-Linked Immunosorbent Assay
Authors: Tortorano Anna Maria , Esposto Maria Carmela , Prigitano Anna , Grancini Anna , Ossi Cristina , Cavanna Caterina , Cascio Giuliana Lo
Published: December 2011

Nine of 11 hematological patients with disseminated/deep-seated
Fusarium
infection tested at least twice for
Aspergillus
galactomannan (GM) had repeated positive results in the absence of
Aspergillus
isolation in culture. The centrifuged supernatants of 12
Fusarium
isolates were tested by a GM enzyme-linked immunosorbent assay (EIA). All the isolates produced positive reactions when tested undiluted. These results show cross-reactivity of
Fusarium
spp. with
Aspergillus
GM that may constitute a drawback with respect to the specificity of the Platelia EIA.
Recurrent Urinary Infection with Bifidobacterium scardovii
Authors: Barberis Claudia M. , Cittadini Roxana M. , Almuzara Marisa N. , Feinsilberg Alejandro , Famiglietti Angela M. , Ramírez Maria Soledad , Vay Carlos A.
Published: December 2011

Bifidobacteriumspecies are difficult to identify and may be underreported or not recovered by many laboratories because of their slow growth. We emphasize the importance of the Gram stain in urine samples and the addition of enriched media and enhanced atmosphere over time for urine cultures with pyuria. This is the first report of aBifidobacterium scardoviirecurrent urinary infection in an elderly woman.
Molecular Epidemiology of Avian Leukosis Virus Subgroup J in Layer Flocks in China
Authors: Gao Yulong , Yun Bingling , Qin Liting , Pan Wei , Qu Yue , Liu Zaisi , Wang Yongqiang , Qi Xiaole , Gao Honglei , Wang Xiaomei
Published: December 2011

Avian leukosis virus subgroup J (ALV-J) was first isolated from meat-type chickens in 1988. No field cases of ALV-J infection or tumors in layer chickens were observed worldwide until 2004. However, layer flocks in China have experienced outbreaks of this virus in recent years. The molecular epidemiology of ALV-J strains isolated from layer flocks was investigated. The
env
genes of 77.8% (21/27) of the ALV-J layer isolates with a high degree of genetic variation were significantly different from the
env
genes of the prototype strain of ALV-J (HPRS-103) and American and Chinese strains from meat-type chickens (designated ALV-J broiler isolates). A total of 205 nucleotides were deleted from the 3′ untranslated region of 89.5% (17/19) of the ALV-J layer isolates. Approximately 94.7% (16/17) of the layer isolates contained a complete E element of 146 to 149 residues. The U3 sequences of 84.2% (16/19) of the ALV-J layer isolates displayed less than 92.5% sequence homology to those of the ALV-J broiler isolates, although the transcriptional regulatory elements that are typical of avian retroviruses were highly conserved. Several unique nucleotide substitutions in the
env
gene, the U3 region, and the E element of most of the ALV-J layer isolates were detected. These results suggested that the
env
gene, E element, and U3 region in the ALV-J layer isolates have evolved rapidly and were significantly different from those of the ALV-J broiler isolates. These findings will contribute to a better understanding of the pathogenic mechanism of layer tumor diseases induced by ALV-J.
First Report of Sepsis Caused by Rhodococcus corynebacterioides in a Patient with Myelodysplastic Syndrome
Authors: Kitamura Yuka , Sawabe Etsuko , Ohkusu Kiyofumi , Tojo Naoko , Tohda Shuji
Published: December 2011

We report a case of sepsis caused byRhodococcus corynebacterioides, identified using 16S rRNA gene sequencing, in a myelodysplastic syndrome patient who had undergone hematopoietic stem cell transplantation. This is the first report ofR. corynebacterioidesinfection in a human.
Do Differences in Panton-Valentine Leukocidin Production among International Methicillin-Resistant Staphylococcus aureus Clones Affect Disease Presentation and Severity?
Authors: Boakes Eve , Kearns Angela M. , Badiou Cederic , Lina Gerard , Hill Robert L. , Ellington Matthew J.
Published: December 2011

Panton-Valentine leukocidin (PVL) production by methicillin-resistant
Staphylococcus aureus
(MRSA) was determined
in vitro
using the enzyme-linked immunosorbent assay (ELISA), and associations with clinical presentation and bacterial genetic characteristics were examined. PVL production ranged from 0.02 to 4.865 μg/ml and correlated with a multilocus sequence type (MLST) clonal complex associated with specific PVL phage types. A relationship between PVL production and clinical presentation or patient demographics could not be demonstrated.
Identification of a Pyridopyrimidinone Inhibitor of Orthopoxviruses from a Diversity-Oriented Synthesis Library
Authors: Dower Ken , Filone Claire Marie , Hodges Erin N. , Bjornson Zach B. , Rubins Kathleen H. , Brown Lauren E. , Schaus Scott , Hensley Lisa E. , Connor John H.
Published: December 2011

Orthopoxviruses include the prototypical vaccinia virus, the emerging infectious agent monkeypox virus, and the potential biothreat variola virus (the causative agent of smallpox). There is currently no FDA-approved drug for humans infected with orthopoxviruses. We screened a diversity-oriented synthesis library for new scaffolds with activity against vaccinia virus. This screen identified a nonnucleoside analog that blocked postreplicative intermediate and late gene expression. Viral genome replication was unaffected, and inhibition could be elicited late in infection and persisted upon drug removal. Sequencing of drug-resistant viruses revealed mutations predicted to be on the periphery of the highly conserved viral RNA polymerase large subunit. Consistent with this, the compound had broad-spectrum activity against orthopoxviruses
in vitro
. These findings indicate that novel chemical synthesis approaches are a potential source for new infectious disease therapeutics and identify a potentially promising candidate for development to treat orthopoxvirus-infected individuals.
The Human Cytomegalovirus Protein TRS1 Inhibits Autophagy via Its Interaction with Beclin 1
Authors: Chaumorcel Magali , Lussignol Marion , Mouna Lina , Cavignac Yolaine , Fahie Kamau , Cotte-Laffitte Jacqueline , Geballe Adam , Brune Wolfram , Beau Isabelle , Codogno Patrice , Esclatine Audrey
Published: December 2011

Human cytomegalovirus modulates macroautophagy in two opposite directions. First, HCMV stimulates autophagy during the early stages of infection, as evident by an increase in the number of autophagosomes and a rise in the autophagic flux. This stimulation occurs independently of
de novo
viral protein synthesis since UV-inactivated HCMV recapitulates the stimulatory effect on macroautophagy. At later time points of infection, HCMV blocks autophagy (M. Chaumorcel, S. Souquere, G. Pierron, P. Codogno, and A. Esclatine, Autophagy 4:1–8, 2008) by a mechanism that requires
de novo
viral protein expression. Exploration of the mechanisms used by HCMV to block autophagy unveiled a robust increase of the cellular form of Bcl-2 expression. Although this protein has an anti-autophagy effect via its interaction with Beclin 1, it is not responsible for the inhibition induced by HCMV, probably because of its phosphorylation by c-Jun N-terminal kinase. Here we showed that the HCMV TRS1 protein blocks autophagosome biogenesis and that a TRS1 deletion mutant is defective in autophagy inhibition. TRS1 has previously been shown to neutralize the PKR antiviral effector molecule. Although phosphorylation of eIF2α by PKR has been described as a stimulatory signal to induce autophagy, the PKR-binding domain of TRS1 is dispensable to its inhibitory effect. Our results show that TRS1 interacts with Beclin 1 to inhibit autophagy. We mapped the interaction with Beclin 1 to the N-terminal region of TRS1, and we demonstrated that the Beclin 1-binding domain of TRS1 is essential to inhibit autophagy.
Bovine Herpesvirus Type 4 Glycoprotein L Is Nonessential for Infectivity but Triggers Virion Endocytosis during Entry
Authors: Lété Céline , Machiels Bénédicte , Stevenson Philip G. , Vanderplasschen Alain , Gillet Laurent
Published: December 2011

The core entry machinery of mammalian herpesviruses comprises glycoprotein B (gB), gH, and gL. gH and gL form a heterodimer with a central role in viral membrane fusion. When archetypal alpha- or betaherpesviruses lack gL, gH misfolds and progeny virions are noninfectious. However, the gL of the rhadinovirus murid herpesvirus 4 (MuHV-4) is nonessential for infection. In order to define more generally what role gL plays in rhadinovirus infections, we disrupted its coding sequence in bovine herpesvirus 4 (BoHV-4). BoHV-4 lacking gL showed altered gH glycosylation and incorporated somewhat less gH into virions but remained infectious. However, gL
−
virions showed poor growth associated with an entry deficit. Moreover, a major part of their entry defect appeared to reflect impaired endocytosis, which occurs upstream of membrane fusion itself. Thus, the rhadinovirus gL may be more important for driving virion endocytosis than for incorporating gH into virions, and it is nonessential for membrane fusion.
CD4 T Cells Promote CD8 T Cell Immunity at the Priming and Effector Site during Viral Encephalitis
Authors: Phares Timothy W. , Stohlman Stephen A. , Hwang Mihyun , Min Booki , Hinton David R. , Bergmann Cornelia C.
Published: December 2011

CD4 T cell activation during peripheral infections not only is essential in inducing protective CD8 T cell memory but also promotes CD8 T cell function and survival. However, the contributions of CD4 T cell help to antiviral CD8 T cell immunity during central nervous system (CNS) infection are not well established. Encephalitis induced by the sublethal coronavirus JHMV was used to identify when CD4 T cells regulate CD8 T cell responses following CNS infection. Peripheral expansion of virus-specific CD8 T cells was impaired when CD4 T cells were ablated prior to infection but not at 4 days postinfection. Delayed CD4 T cell depletion abrogated CD4 T cell recruitment to the CNS but only slightly diminished CD8 T cell recruitment. Nevertheless, the absence of CNS CD4 T cells was associated with reduced gamma interferon (IFN-γ) and granzyme B expression by infiltrating CD8 T cells, increased CD8 T cell apoptosis, and impaired control of infectious virus. CD4 T cell depletion subsequent to CD4 T cell CNS migration restored CD8 T cell activity and virus control. Analysis of γc-dependent cytokine expression indicated interleukin-21 (IL-21) as a primary candidate optimizing CD8 T cell activity within the CNS. These results demonstrate that CD4 T cells play critical roles in both enhancing peripheral activation of CD8 T cells and prolonging their antiviral function within the CNS. The data highlight the necessity for temporally and spatially distinct CD4 T cell helper functions in sustaining CD8 T cell activity during CNS infection.
Evidence for a Common Evolutionary Origin of Coronavirus Spike Protein Receptor-Binding Subunits
Authors: Li Fang
Published: December 2011

Among different coronavirus genera, the receptor-binding S1 subunits of their spike proteins differ in primary, secondary, and tertiary structures. This study identified shared structural topologies (connectivity of secondary structural elements) in S1 domains of different coronavirus genera. The results suggest that coronavirus S1 subunits share a common evolutionary origin but have attained diverse sequences and structures following extensive divergent evolution. The results also increase understanding of the structures and functions of coronavirus S1 domains whose tertiary structures are currently unknown.
GROTHENDIECK GROUPS AND A CATEGORIFICATION OF ADDITIVE INVARIANTS
Authors: SCHÜRMANN JÖRG , YOKURA SHOJI
Published: December 2011

A topologically-invariant and additive homology class is mostly not a natural transformation as it is. In this paper we discuss turning such a homology class into a natural transformation; i.e. a "categorification" of it. In a general categorical set-up we introduce a generalized relative Grothendieck group from a cospan of functors of categories and also consider a categorification of additive invariants on objects. As an example, we obtain a general theory of characteristic homology classes of singular varieties.
ON PROJECTIVE MANIFOLDS SWEPT OUT BY CUBIC VARIETIES
Authors: WATANABE KIWAMU
Published: December 2011

We study structures of embedded projective manifolds swept out by cubic varieties. We show if an embedded projective manifold is swept out by high-dimensional smooth cubic hypersurfaces, then it admits an extremal contraction which is a linear projective bundle or a cubic fibration. As an application, we give a characterization of smooth cubic hypersurfaces. We also classify embedded projective manifolds of dimension at most five swept out by copies of the Segre threefold ℙ1 × ℙ2. In the course of the proof, we classify projective manifolds of dimension five swept out by planes.
SEARCHING EFFICIENCY ON COMPLEX NETWORKS UNDER VISUAL RANGE OF NODES
Authors: LIU BIN , DENG HONGZHONG , WU XIAOYUE
Published: December 2011

We study the searching efficiency of complex networks considering node's visual range within which a node can see its neighbors and knows the topology. We firstly introduce the network generating models and searching strategies. Using the generating function method, in both random networks and scale-free networks we derive the most-effective-visual-range (MEVR) which means every step of random walkers can find most of new nodes and we also obtain the searching-cost (SC) under visual range. To validate the generating function method, we perform simulations in random networks and scale-free networks. We also explain why the deviation between numerical simulation and theoretical prediction in scale-free networks is much larger than that in random networks. By studying the visual range of nodes in the networks, the results open the possibility to learn about the searching on networks with unknown topologies.
PROPER COVERS OF RESTRICTION SEMIGROUPS AND W-PRODUCTS
Authors: SZENDREI MÁRIA B.
Published: December 2011

Each factor semigroup of a free restriction (ample) semigroup over a congruence contained in the least cancellative congruence is proved to be embeddable into a W-product of a semilattice by a monoid. Consequently, it is established that each restriction semigroup has a proper (ample) cover embeddable into such a W-product.
CONSTRUCTION OF BLOW-UP SEQUENCES FOR THE PRESCRIBED SCALAR CURVATURE EQUATION ON SnI: UNIFORM CANCELLATION
Authors: LEUNG MAN CHUN
Published: December 2011

For n ≥ 6, using the Lyapunov–Schmidt reduction method, we describe how to construct (scalar curvature) functions on Sn, so that each of them enables the conformal scalar curvature equation to have an infinite number of positive solutions, which form a blow-up sequence. The prescribed scalar curvature function is shown to have Cn - 1,βsmoothness. We present the argument in two parts. In this first part, we discuss the uniform cancellation property in the Lyapunov–Schmidt reduction method for the scalar curvature equation. We also explore relation between the Kazdan–Warner condition and the first-order derivatives of the reduced functional, and symmetry in the second-order derivatives of the reduced functional.
HÖLDER CONTINUITY OF WEAK SOLUTIONS FOR DEGENERATE QUASILINEAR SUBELLIPTIC SYSTEMS WITH DIFFERENT WEIGHTS
Authors: CUI XUEWE , NIU PENGCHENG , WANG YONGZHONG
Published: December 2011

We establish Hölder continuity of weak solutions for degenerate quasilinear subelliptic systems with different weights, with weak Harnack inequalities obtained here and a generalization of Caffarelli's idea.
AMALGAMATION OF RINGS DEFINED BY BÉZOUT-LIKE CONDITIONS
Authors: KABBOUR MOHAMMED , MAHDOU NAJIB
Published: December 2011

Let f : A → B be a ring homomorphism and let J be an ideal of B. In this paper, we investigate the transfer of notions elementary divisor ring, Hermite ring and Bézout ring to the amalgamation A ⋈fJ. We provide necessary and sufficient conditions for A ⋈fJ to be an elementary divisor ring where A and B are integral domains. In this case it is shown that A ⋈fJ is an Hermite ring if and only if it is a Bézout ring. In particular, we study the transfer of the previous notions to the amalgamated duplication of a ring A along an A-submodule E of Q(A) such that E2⊆ E.
SEMIDUALIZING MODULES AND RELATED MODULES
Authors: ZHANG DONGDONG , OUYANG BAIYU
Published: December 2011

In this paper, we prove that the Bass class [Formula: see text] with respect to a semidualizing bimodule C contains all FP-injective S-modules. We introduce the definition of C-FP-injective modules, and give some characterizations of right coherent rings in terms of the C-flat S-modules and C-FP-injective S op -modules. We discuss when every S-module has an C-flat preenvelope which is epic (or monic). In addition, we investigate the left and right [Formula: see text]-resolutions of R-modules by left derived functors Ext n(-, -) over a left Noetherian ring S. As applications, some new characterizations of left perfect rings are induced by these modules associated with C. A few classical results of these rings are obtained as corollaries.
A TRIPARTITE CLUSTERING ANALYSIS ON MICRORNA, GENE AND DISEASE MODEL
Authors: SHEN CHENGCHENG , LIU YING
Published: December 2011

Alteration of gene expression in response to regulatory molecules or mutations could lead to different diseases. MicroRNAs (miRNAs) have been discovered to be involved in regulation of gene expression and a wide variety of diseases. In a tripartite biological network of human miRNAs, their predicted target genes and the diseases caused by altered expressions of these genes, valuable knowledge about the pathogenicity of miRNAs, involved genes and related disease classes can be revealed by co-clustering miRNAs, target genes and diseases simultaneously. Tripartite co-clustering can lead to more informative results than traditional co-clustering with only two kinds of members and pass the hidden relational information along the relation chain by considering multi-type members. Here we report a spectral co-clustering algorithm for k-partite graph to find clusters with heterogeneous members. We use the method to explore the potential relationships among miRNAs, genes and diseases. The clusters obtained from the algorithm have significantly higher density than randomly selected clusters, which means members in the same cluster are more likely to have common connections. Results also show that miRNAs in the same family based on the hairpin sequences tend to belong to the same cluster. We also validate the clustering results by checking the correlation of enriched gene functions and disease classes in the same cluster. Finally, widely studied miR-17-92 and its paralogs are analyzed as a case study to reveal that genes and diseases co-clustered with the miRNAs are in accordance with current research findings.
NUMERICAL MODELING OF TRANSIENT MAGNETO-THERMO-VISCOELASTIC WAVES IN A ROTATING NONHOMOGENEOUS ANISOTROPIC SOLID UNDER INITIAL STRESS
Authors: FAHMY MOHAMED ABDELSABOUR
Published: December 2011

A numerical model based on the dual-reciprocity boundary element method (DRBEM) for studying the transient magneto-thermo-viscoelastic waves in a rotating nonhomogeneous anisotropic solid is presented. The formulation is tested through its application to the problem of an initially stressed solid placed in a constant primary magnetic field acting in the direction of the z-axis and rotating about this axis with a constant angular velocity. In the case of plane deformation, a numerical scheme for the implementation of the method is presented and the numerical computations are carried out for the temperature, displacement components and thermal stress components. The validity of DRBEM is examined by considering a magneto-thermo-viscoelastic solid occupies a rectangular region and good agreement is obtained with existent results. The results obtained are presented graphically to show the influence of initial stress on the displacement components and thermal stress components.
Lipoxin A4 inhibits immune cell binding to salivary epithelium and vascular endothelium
Authors: Chinthamani Sreedevi , Odusanwo Olutayo , Mondal Nandini , Nelson Joel , Neelamegham Sriram , Baker Olga J.
Published: December 2011

Lipoxins are formed by leukocytes during cell-cell interactions with epithelial or endothelial cells. Native lipoxin A4 (LXA4) binds to the G protein-coupled lipoxin receptors formyl peptide receptor 2 (FPR2)/ALX and CysLT1. Furthermore, LXA4 inhibits recruitment of neutrophils, by attenuating chemotaxis, adhesion, and transmigration across vascular endothelial cells. LXA4 thus appears to serve as an endogenous “stop signal” for immune cell-mediated tissue injury (Serhan CN; Annu Rev Immunol 25: 101–137, 2007). The role of LXA4 has not been addressed in salivary epithelium, and little is known about its effects on vascular endothelium. Here, we determined that interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) receptor activation in vascular endothelium and salivary epithelium upregulated the expression of adhesion molecules that facilitates the binding of immune cells. We hypothesize that the activation of the ALX/FPR2 and/or CysLT1 receptors by LXA4 decreases this cytokine-mediated upregulation of cell adhesion molecules that enhance lymphocyte binding to both the vascular endothelium and salivary epithelium. In agreement with this hypothesis, we observed that nanomolar concentrations of LXA4 blocked IL-1β- and TNF-α-mediated upregulation of E-selectin and intercellular cell adhesion molecule-1 (ICAM-1) on human umbilical vein endothelial cells (HUVECs). Binding of Jurkat cells to stimulated HUVECs was abrogated by LXA4. Furthermore, LXA4 preincubation with human submandibular gland cell line (HSG) also blocked TNF-α-mediated upregulation of vascular cell adhesion molecule-1 (VCAM-1) in these cells, and it reduced lymphocyte adhesion. These findings suggest that ALX/FPR2 and/or CysLT1 receptor activation in endothelial and epithelial cells blocks cytokine-induced adhesion molecule expression and consequent binding of lymphocytes, a critical event in the pathogenesis of Sjögren's syndrome (SS).
Insight into molecular pathways of retinal metabolism, associated with vitellogenesis in zebrafish
Authors: Levi Liraz , Ziv Tamar , Admon Arie , Levavi-Sivan Berta , Lubzens Esther
Published: December 2011

Retinal is the main retinoid stored in oviparous eggs of fish, amphibians, and reptiles, reaching the oocytes in association with vitellogenins, the yolk precursor proteins. During early presegmentation stages of zebrafish embryos, retinal is metabolized to retinoic acid (RA), which regulates genes involved in cell proliferation, differentiation, and tissue function and is therefore essential for normal embryonic development. While synthesis of vitellogenin and its regulation by 17β-estradiol (E2) were extensively investigated, pathways for retinal synthesis remain obscure. We determined the expression pattern of 46 candidate genes, aiming at identifying enzymes associated with retinal synthesis, ascertaining whether they were regulated by E2, and finding pathways that could fulfill the demand for retinoids during vitellogenesis. Genes associated with retinal synthesis were upregulated in liver ( rdh10, rdh13, sdr) and surprisingly also in intestine ( rdh13) and ovary ( rdh1, sdr), concomitantly with higher gene expression and synthesis of vitellogenins in liver but also in extrahepatic tissues, shown here for the first time. Vitellogenin synthesis in the ovary was regulated by E2. Gene expression studies suggest that elevated retinal synthesis in liver, intestine, and ovary also depends on cleavage of carotenoids (by Bcdo2 or Bmco1), but in the ovary it may also be contingent on higher uptake of retinol from the circulatory system (via Stra6) and retinol synthesis from retinyl esters (by Lpl). Decrease in oxidation (by Raldh2 or Raldh3) of retinal to RA and/or degradation of RA (by Cyp26a1) may also facilitate higher hepatic retinal levels. Together, these processes enable meeting the putative demands of retinal for binding to vitellogenins. Bioinformatic tools reveal multiple hormone response elements in the studied genes, suggesting complex and intricate regulation of these processes.
Influence of hyperglycemia during and after pregnancy on postpartum vascular function
Authors: Davenport Margie H. , Goswami Ruma , Shoemaker J. Kevin , Mottola Michelle F.
Published: December 2011

Endothelial dysfunction is commonly observed in women with a previous diagnosis of gestational diabetes mellitus (GDM). Whether arterial stiffness is also related to pregnancy and/or postpartum glucose intolerance has not been determined. We examined the influence of GDM during pregnancy and hyperglycemia in the postpartum period on arterial function. Thirty postpartum women were stratified into one of three groups: 1) normoglycemic pregnancy, normoglycemic postpartum (NORM), 2) GDM during pregnancy, normoglycemic postpartum (GDM-N); and 3) GDM during pregnancy, hyperglycemic postpartum (GDM-H). Ten never-pregnant controls were also recruited (Control). All measures were made at 2 mo postpartum or in the early follicular phase in Control women. Arterial stiffness was assessed by pulse wave velocity (PWV) and brachial and carotid artery distensibility. Endothelial function was determined by flow-mediated dilation (FMD). PWV was not different between the four groups. Distensibility of the brachial and carotid arteries was lower in GDM-N women (brachial: 1.1 × 10−3mmHg−1± 3.6 × 10−4; carotid: 2.0 × 10−3± 3.3 × 10−4) and GDM-H (brachial: 1.4 × 10−3mmHg−1± 4.1 × 10−4; carotid: 1.8 × 10−3mmHg−1± 5.0 × 10−4) compared with NORM women (brachial: 3.4 × 10−3mmHg−1± 7.0 × 10−4; carotid: 3.9 × 10−3± 7.4 × 10−4). However, only brachial artery distensibility returned to Control levels by 2 mo postpartum in the NORM women. FMD was lower in previously GDM women (GDM-N: 4.1% ± 2.3; GDM-H: 4.4% ± 0.9) compared with NORM women (10.8% ± 1.3; P < 0.01). These findings suggest that the vascular function of women in the early postpartum period is influenced by GDM during pregnancy and the persistence of clinical and/or subclinical hyperglycemia after delivery.
Activation of the central melanocortin system contributes to the increased arterial pressure in obese Zucker rats
Authors: do Carmo Jussara M. , da Silva Alexandre A. , Rushing John S. , Hall John E.
Published: December 2011

We have previously demonstrated that leptin-mediated activation of the central nervous system (CNS) melanocortin system reduces appetite and increases sympathetic activity and blood pressure (BP). In the present study we examined whether endogenous melanocortin system activation, independent of leptin's actions, contributes to the regulation of BP and metabolic functions in obese Zucker rats, which have mutated leptin receptors. The long-term cardiovascular and metabolic effects of central melanocortin-3/4 receptor (MC3/4R) antagonism with SHU-9119 were assessed in lean ( n = 6) and obese ( n = 8) Zucker rats. BP and heart rate (HR) were measured 24-h/day by telemetry and an intracerebroventricular cannula was placed in the brain lateral ventricle. After stable control measurements, SHU-9119 was infused intracerebroventricularlly (1 nmol/h) for 10 days followed by a 10-day recovery period. Chronic CNS MC3/4R antagonism significantly increased food intake and body weight in lean (20 ± 1 to 45 ± 2 g and 373 ± 11 to 432 ± 14 g) and obese (25 ± 2 to 35 ± 2 g and 547 ± 10 to 604 ± 11 g) rats. No significant changes were observed in plasma glucose levels in lean or obese rats, whereas plasma leptin and insulin levels markedly increased in lean Zucker rats during CNS MC3/4R antagonism. Chronic SHU-9119 infusion in obese Zucker rats reduced mean arterial pressure (MAP) and HR by 6 ± 1 mmHg and 24 ± 5 beats/min, whereas in lean rats SHU-9119 infusion reduced HR by 31 ± 9 beats/min while causing only a transient decrease in MAP. These results suggest that in obese Zucker rats the CNS melanocortin system contributes to elevated BP independent of leptin receptor activation.
Proteins regulating cap-dependent translation are downregulated during total knee arthroplasty
Authors: Ratchford Stephen M. , Bailey Ashley N. , Senesac Hilary A. , Hocker Austin D. , Smolkowski Keith , Lantz Brick A. , Jewett Brian A. , Gilbert Jeffrey S. , Dreyer Hans C.
Published: December 2011

Total knee arthroplasty (TKA) utilizes a tourniquet to reduce blood loss, maintain a clear surgical “bloodless” field, and to ensure proper bone-implant cementing. In 2007, over 600,000 TKAs were performed in the United States, and this number is projected to increase to 3.48 million procedures performed annually by 2030. The acute effects of tourniquet-induced ischemia-reperfusion (I/R) on human skeletal muscle cells are poorly understood and require critical investigation, as muscle atrophy following this surgery is rapid and represents the most significant clinical barrier to long-term normalization of physical function. To determine the acute effects of I/R on skeletal muscle cells, biopsies were obtained at baseline, maximal ischemia (prior to tourniquet release), and reperfusion (following tourniquet release). Quadriceps volume was determined before and 2 wk post-TKA by MRI. We measured a 36% decrease in phosphorylation of Akt Ser473during ischemia and 37% during reperfusion ( P < 0.05). 4E-BP1 Thr37/46phosphorylation decreased 29% during ischemia and 22% during reperfusion ( P < 0.05). eEF2 Thr56phosphorylation increased 25% during ischemia and 43% during reperfusion ( P < 0.05). Quadriceps volume decreased 12% in the TKA leg ( P < 0.05) and tended to decrease (6%) in the contralateral leg ( P = 0.1). These data suggest cap-dependent translation initiation, and elongation may be inhibited during and after TKA surgery. We propose that cap-dependent translational events occurring during surgery may precipitate postoperative changes in muscle cells that contribute to the etiology of muscle atrophy following TKA.
Potassium excretion through ROMK potassium channel expressed in gill mitochondrion-rich cells of Mozambique tilapia
Authors: Furukawa Fumiya , Watanabe Soichi , Kimura Satoshi , Kaneko Toyoji
Published: December 2011

Despite recent progress in physiology of fish ion homeostasis, the mechanism of plasma K+regulation has remained unclear. Using Mozambique tilapia, a euryhaline teleost, we demonstrated that gill mitochondrion-rich (MR) cells were responsible for K+excretion, using a newly invented technique that insolubilized and visualized K+excreted from the gills. For a better understanding of the molecular mechanism of K+excretion in the gills, cDNA sequences of renal outer medullary K+channel (ROMK), potassium large conductance Ca2+-activated channel, subfamily M (Maxi-K), K+-Cl−cotransporters (KCC1, KCC2, and KCC4) were identified in tilapia as the candidate molecules that are involved in K+handling. Among the cloned candidate molecules, only ROMK showed marked upregulation of mRNA levels in response to high external K+concentration. In addition, immunofluorescence microscopy revealed that ROMK was localized in the apical opening of gill MR cells, and that the immunosignals were most intense in the fish acclimated to the environment with high K+concentration. To confirm K+excretion via ROMK, K+insolubilization-visualization technique was applied again in combination with K+channel blockers. The K+precipitation was prevented in the presence of Ba2+, indicating that ROMK has a pivotal role in K+excretion. The present study is the first to demonstrate that the fish excrete K+from the gill MR cells, and that ROMK expressed in the apical opening of the MR cells is a main molecular pathway responsible for K+excretion.