bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogeny and Identification of
Nocardia
Species on the Basis of Multilocus Sequence Analysis
Authors: McTaggart L. R. , Richardson S. E. , Witkowska M. , Zhang S. X.
Published: September 2010

Nocardia
species identification is difficult due to a complex and rapidly changing taxonomy, the failure of 16S rRNA and cellular fatty acid analysis to discriminate many species, and the unreliability of biochemical testing. Here,
Nocardia
species identification was achieved through multilocus sequence analysis (MLSA) of gyrase B of the β subunit of DNA topoisomerase (
gyrB
), 16S rRNA (16S), subunit A of SecA preprotein translocase (
secA1
), the 65-kDa heat shock protein (
hsp65
), and RNA polymerase (
rpoB
) applied to 190 clinical, 36 type, and 11 reference strains. Phylogenetic analysis resolved 30 sequence clusters with high (>85%) bootstrap support. Since most clusters contained a single type strain and the analysis corroborated current knowledge of
Nocardia
taxonomy, the sequence clusters were equated with species clusters and MLSA was deemed appropriate for species identification. By comparison, single-locus analysis was inadequate because it failed to resolve species clusters, partly due to the presence of foreign alleles in 22.1% of isolates. While MLSA identified the species of the majority (71.3%) of strains, it also identified clusters that may correspond to new species. The correlation of the identities by MLSA with those determined on the basis of microscopic examination, biochemical testing, and fatty acid analysis was 95%; however, MLSA was more discriminatory.
Nocardia cyriacigeorgica
(21.58%) and
N. farcinica
(14.74%) were the most frequently encountered species among clinical isolates. In summary, five-locus MLSA is a reliable method of elucidating taxonomic data to inform
Nocardia
species identification; however, three-locus (
gyrB
-16S-
secA1
) or four-locus (
gyrB
-16S-
secA1
-
hsp65
) MLSA was nearly as reliable, correctly identifying 98.5% and 99.5% of isolates, respectively, and would be more feasible for routine use in a clinical reference microbiology laboratory.
Rapid Differentiation of
Mycobacterium tuberculosis
and
M. bovis
by High-Resolution Melt Curve Analysis
Authors: Ereqat Suheir , Bar-Gal Gila Kahila , Nasereddin Abedelmajeed , Azmi Kifaya , Qaddomi Sharif E. , Greenblatt Charles L. , Spigelman Mark , Abdeen Ziad
Published: September 2010

Identification and characterization of the
Mycobacterium tuberculosis
strains are important for clinical and therapeutic management of tuberculosis. Real-time PCR with a high-resolution melt assay was found to improve the diagnostic process. The assay includes differentiation between
M. tuberculosis
and
Mycobacterium
bovis
based on one single-nucleotide polymorphism (SNP) in the
narGHJI
and
oxyR
genes and determination of
M. bovis
based on the region of differences 1 (RD1). This assay correctly identified the 7 tested
Mycobacterium
reference strains and 52 clinical samples with a sensitivity of 2 pg DNA. This assay will help in prescribing adequate treatment and monitoring disease dynamics.
Carbapenem Heteroresistance in VIM-1-Producing
Klebsiella pneumoniae
Isolates Belonging to the Same Clone: Consequences for Routine Susceptibility Testing
Authors: Tato M. , Morosini M. , García L. , Albertí S. , Coque M. T. , Cantón R.
Published: September 2010

Susceptibility results with low reproducibility by the same or different methods have been observed for metallo-beta-lactamase (MBL)-producing
Enterobacteriaceae
. Eighteen VIM-1-producing
Klebsiella pneumoniae
isolates (one per patient) belonging to a single epidemic clone in our hospital (2005 to 2008) but with different susceptibilities to carbapenems were studied. Imipenem MICs ranged from 8 to >128 mg/liter by standard CLSI microdilution, from ≤1 to >8 mg/liter by the semiautomatic Wider system, and from 0.75 to >32 mg/liter by Etest. Meropenem MICs ranged from 0.5 to 128, ≤1 to >8, and 0.38 to >32 mg/liter, respectively. Ertapenem MICs by CLSI microdilution and Etest ranged from 1 to 64 and 0.75 to >32 mg/liter, respectively. The rates of essential agreement (±1 log
2
dilution) for imipenem and meropenem MICs between the Wider system and the reference microdilution method were 45% and 49%, respectively. Those between Etest and the reference microdilution method for imipenem, meropenem, and ertapenem MICs were 33%, 67%, and 84%. The rates of very major errors for the Wider system and Etest were 33% and 28% for imipenem and 25% and 75% for meropenem, respectively. Low MIC reproducibility was observed even when the same inoculum was used (differences up to 4-fold dilutions). Heteroresistance was suspected due to the presence of colonies in the Etest inhibition zone. It was confirmed by population analysis profiles of 4 isolates displaying different imipenem MICs, with the exception of an OmpK36-porin-deficient isolate that homogeneously expressed carbapenem resistance (MIC, >128 mg/liter). Low carbapenem MIC reproducibility could be due to the presence of resistant subpopulations and variable expression of the resistance mechanisms. Since carbapenem MICs are not good markers of MBL production, reliable and reproducible phenotypic methods are needed to detect the presence of this mechanism.
Unique Hepatitis B Virus Subgenotype in a Primitive Tribal Community in Eastern India
Authors: Ghosh Sumantra , Banerjee Priyanka , RoyChoudhury Arindam , Sarkar Sumanta , Ghosh Alip , Santra Amal , Banerjee Soma , Das Kausik , Dwibedi Bhagirathi , Kar Shantanu K. , Rao Vikas Gangadhar , Bhat Jyothi T. , Singh Neeru , Chowdhury Abhijit , Datta Simanti
Published: September 2010

Hepatitis B virus (HBV) strains isolated from members of the primitive Paharia ethnic community of Eastern India were studied to gain insight into the genetic diversity and evolution of the virus. The Paharia tribe has remained quite separate from the rest of the Indians and differs culturally, genetically, and linguistically from the mainstream East Indian population, whose HBV strains were previously characterized. Full-length HBV DNA was PCR amplified, cloned, and sequenced. Phylogenetic relationships between the tribal sequences and reference sequences from the mainstream population were assessed, and divergence times of subgenotypes of HBV genotype D were estimated. HBV was found in 2% of the Paharias participating in the study. A predominance of hepatitis B e antigen-negative infection (73%) was observed among the Paharias, and the genome sequences of the HBV strains exhibited relative homogeneity, with a very low prevalence of mutations. The novel feature of Paharia HBV was the exclusive presence of the D5 subgenotype, which was recently identified in Eastern India. Analysis of the four open reading frames (ORFs) of these tribal HBV D5 sequences and comparison with previously reported D1 to D7 sequences enabled the identification of 27 specific amino acid residues, including 6 unique ones, that could be considered D5 signatures. The estimated divergence times among subgenotypes D1 to D5 suggest that D5 was the first to diverge and hence is the most ancient of the D subgenotypes. The presence of a specific, ancient subgenotype of HBV within an ethnically primitive, endogamous population highlights the importance of studies of HBV genetics in well-separated human populations to understand viral transmission between communities and genome evolution.
Detection of Oseltamivir Resistance during Treatment of 2009 H1N1 Influenza Virus Infection in Immunocompromised Patients: Utility of Cycle Threshold Values of Qualitative Real-Time Reverse Transcriptase PCR
Authors: Mehta Tejal , McGrath Eric , Bheemreddy Suchitha , Salimnia Hossein , Abdel-Haq Nahed , Ang Jocelyn Y. , Lum Lawrence , Chandrasekar Pranatharthi , Alangaden George J.
Published: September 2010

Two immunocompromised patients with 2009 H1N1 influenza pneumonia had viral shedding for over 5 weeks despite therapy with oseltamivir. Declining or persistently low cycle threshold values noted on serial qualitative real-time reverse transcriptase PCR (rRT-PCR) of respiratory specimens implied increasing viral load and probable drug resistance. Oseltamivir resistance was later confirmed by pyrosequencing.
Better Detection of
Staphylococcus aureus
Nasal Carriage by Use of Nylon Flocked Swabs
Authors: Verhoeven Paul , Grattard Florence , Carricajo Anne , Pozzetto Bruno , Berthelot Philippe
Published: September 2010

Flocked swabs (Copan) were compared to rayon swabs (Copan) for the nasal detection of
Staphylococcus aureus
in 90 healthy volunteers sampled sequentially during a 5-week period. The use of flocked swabs improved the number of nasal carriers (
P
= 0.026), the number of positive specimens (
P
= 0.01), and the quantity of bacteria in positive samples (
P
= 0.004).
Regulation of Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Receptor Protein (TWEAKR) Expression by Kaposi's Sarcoma-Associated Herpesvirus MicroRNA Prevents TWEAK-Induced Apoptosis and Inflammatory Cytokine Expression
Authors: Abend Johanna R. , Uldrick Thomas , Ziegelbauer Joseph M.
Published: September 2010

Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is the causative agent of KS, the second most common AIDS-associated malignancy. KSHV expresses at least 18 different mature microRNAs (miRNAs) during latency. To identify cellular targets of KSHV miRNAs, we have analyzed a previously reported series of microarrays examining changes in cellular gene expression in the presence of KSHV miRNAs. Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) receptor (TWEAKR) was among the most consistently and robustly downregulated genes in the presence of KSHV miR-K12-10a (miR-K10a). Results from luciferase assays with reporter plasmids containing the 3′ untranslated region (UTR) of TWEAKR suggest a targeting of TWEAKR by miR-K10a. The mutation of two predicted miR-K10a recognition sites within the 3′ UTR of TWEAKR completely disrupts inhibition by miR-K10a. The expression of TWEAKR was downregulated in cells transfected with miR-K10a as well as during
de novo
KSHV infection. In a KS tumor-derived endothelial cell line, the downregulation of TWEAKR by miR-K10a resulted in reduced levels of TWEAK-induced caspase activation. In addition, cells transfected with miR-K10a showed less induction of apoptosis by annexin V staining and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assays. Finally, the downregulation of TWEAKR by miR-K10a in primary human endothelial cells resulted in a decrease in levels of expression of the proinflammatory cytokines interleukin-8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) in response to TWEAK. These results identify and validate an important cellular target of KSHV miRNAs. Furthermore, we demonstrate that a viral miRNA protects cells from apoptosis and suppresses a proinflammatory response, which may have significant implications in the complex context of KS lesions.
Antagonism of Type I Interferon Responses by New World Hantaviruses
Authors: Levine Jessica R. , Prescott Joseph , Brown Kyle S. , Best Sonja M. , Ebihara Hideki , Feldmann Heinz
Published: September 2010

Evasion of interferon (IFN)-mediated antiviral signaling is a common defense strategy for pathogenic RNA viruses. To date, research on IFN antagonism by hantaviruses is limited and has focused on only a subset of the numerous recognized hantavirus species. The host IFN response has two phases, an initiation phase, resulting in the induction of alpha/beta IFN (IFN-α/β), and an amplification phase, whereby IFN-α/β signals through the Jak/STAT pathway, resulting in the establishment of the cellular antiviral state. We examined interactions between these critical host responses and the New World hantaviruses. We observed delayed cellular responses in both Andes virus (ANDV)- and Sin Nombre virus (SNV)-infected A549 and Huh7-TLR3 cells. We found that IFN-β induction is inhibited by coexpression of ANDV nucleocapsid protein (NP) and glycoprotein precursor (GPC) and is robustly inhibited by SNV GPC alone. Downstream amplification by Jak/STAT signaling is also inhibited by SNV GPC and by either NP or GPC of ANDV. Therefore, ANDV- and SNV-encoded proteins have the potential for inhibiting both IFN-β induction and signaling, with SNV exhibiting the more potent antagonism ability. Herein we identify ANDV NP, a previously unrecognized inhibitor of Jak/STAT signaling, and show that IFN antagonism by ANDV relies on expression of both the glycoproteins and NP, whereas the glycoproteins appear to be sufficient for antagonism by SNV. These data suggest that IFN antagonism strategies by hantaviruses are quite variable, even between species with similar disease phenotypes, and may help to better elucidate species-specific pathogenesis.
Potent and Broadly Reactive HIV-2 Neutralizing Antibodies Elicited by a Vaccinia Virus Vector Prime-C2V3C3 Polypeptide Boost Immunization Strategy
Authors: Marcelino José Maria , Borrego Pedro , Rocha Cheila , Barroso Helena , Quintas Alexandre , Novo Carlos , Taveira Nuno
Published: September 2010

Human immunodeficiency virus type 2 (HIV-2) infection affects about 1 to 2 million individuals, the majority living in West Africa, Europe, and India. As for HIV-1, new strategies for the prevention of HIV-2 infection are needed. Our aim was to produce new vaccine immunogens that elicit the production of broadly reactive HIV-2 neutralizing antibodies (NAbs). Native and truncated envelope proteins from the reference HIV-2ALI isolate were expressed in vaccinia virus or in bacteria. This source isolate was used due to its unique phenotype combining CD4 independence and CCR5 usage. NAbs were not elicited in BALB/c mice by single immunization with a truncated and fully glycosylated envelope gp125 (gp125t) or a recombinant polypeptide comprising the C2, V3, and C3 envelope regions (rpC2-C3). A strong and broad NAb response was, however, elicited in mice primed with gp125t expressed in vaccinia virus and boosted with rpC2-C3. Serum from these animals potently neutralized (median 50% neutralizing titer, 3,200) six of six highly divergent primary HIV-2 isolates. Coreceptor usage and the V3 sequence of NAb-sensitive isolates were similar to that of the vaccinating immunogen (HIV-2ALI). In contrast, NAbs were not reactive on three X4 isolates that displayed major changes in V3 loop sequence and structure. Collectively, our findings demonstrate that broadly reactive HIV-2 NAbs can be elicited by using a vaccinia virus vector-prime/rpC2-C3-boost immunization strategy and suggest a potential relationship between escape to neutralization and cell tropism.
Whole-Genome Characterization of Human and Simian Immunodeficiency Virus Intrahost Diversity by Ultradeep Pyrosequencing
Authors: Bimber Benjamin N. , Dudley Dawn M. , Lauck Michael , Becker Ericka A. , Chin Emily N. , Lank Simon M. , Grunenwald Haiying L. , Caruccio Nicholas C. , Maffitt Mark , Wilson Nancy A. , Reed Jason S. , Sosman James M. , Tarosso Leandro F. , Sanabani Sabri , Kallas Esper G. , Hughes Austin L. , O'Connor David H.
Published: September 2010

Rapid evolution and high intrahost sequence diversity are hallmarks of human and simian immunodeficiency virus (HIV/SIV) infection. Minor viral variants have important implications for drug resistance, receptor tropism, and immune evasion. Here, we used ultradeep pyrosequencing to sequence complete HIV/SIV genomes, detecting variants present at a frequency as low as 1%. This approach provides a more complete characterization of the viral population than is possible with conventional methods, revealing low-level drug resistance and detecting previously hidden changes in the viral population. While this work applies pyrosequencing to immunodeficiency viruses, this approach could be applied to virtually any viral pathogen.
Interaction of Hantavirus Nucleocapsid Protein with Ribosomal Protein S19
Authors: Haque Absarul , Mir Mohammad A.
Published: September 2010

Hantaviruses, members of the
Bunyaviridae
family, are emerging category A pathogens that initiate the translation of their capped mRNAs by a novel mechanism mediated by viral nucleocapsid protein (N). N specifically binds to the mRNA 5′ m7G cap and 40S ribosomal subunit, a complex of 18S rRNA and multiple ribosomal proteins. Here, we show that N specifically interacts with the ribosomal protein S19 (RPS19), located at the head region of the 40S subunit. We suggest that this N-RPS19 interaction facilitates ribosome loading on capped mRNAs during N-mediated translation initiation.
Nuclear Export of Human Papillomavirus Type 31 E1 Is Regulated by Cdk2 Phosphorylation and Required for Viral Genome Maintenance
Authors: Fradet-Turcotte Amélie , Moody Cary , Laimins Laimonis A. , Archambault Jacques
Published: September 2010

The initiator protein E1 from human papillomavirus (HPV) is a helicase essential for replication of the viral genome. E1 contains three functional domains: a C-terminal enzymatic domain that has ATPase/helicase activity, a central DNA-binding domain that recognizes specific sequences in the origin of replication, and a N-terminal region necessary for viral DNA replication
in vivo
but dispensable
in vitro
. This N-terminal portion of E1 contains a conserved nuclear export signal (NES) whose function in the viral life cycle remains unclear. In this study, we provide evidence that nuclear export of HPV31 E1 is inhibited by cyclin E/A-Cdk2 phosphorylation of two serines residues, S92 and S106, located near and within the E1 NES, respectively. Using E1 mutant proteins that are confined to the nucleus, we determined that nuclear export of E1 is not essential for transient viral DNA replication but is important for the long-term maintenance of the HPV episome in undifferentiated keratinocytes. The findings that E1 nuclear export is not required for viral DNA replication but needed for genome maintenance over multiple cell divisions raised the possibility that continuous nuclear accumulation of E1 is detrimental to cellular growth. In support of this possibility, we observed that nuclear accumulation of E1 dramatically reduces cellular proliferation by delaying cell cycle progression in S phase. On the basis of these results, we propose that nuclear export of E1 is required, at least in part, to limit accumulation of this viral helicase in the nucleus in order to prevent its detrimental effect on cellular proliferation.
Novel Immunodominant Peptide Presentation Strategy: a Featured HLA-A*2402-Restricted Cytotoxic T-Lymphocyte Epitope Stabilized by Intrachain Hydrogen Bonds from Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Protein
Authors: Liu Jun , Wu Peng , Gao Feng , Qi Jianxun , Kawana-Tachikawa Ai , Xie Jing , Vavricka Christopher J. , Iwamoto Aikichi , Li Taisheng , Gao George F.
Published: September 2010

Antigenic peptides recognized by virus-specific cytotoxic T lymphocytes (CTLs) are presented by major histocompatibility complex (MHC; or human leukocyte antigen [HLA] in humans) molecules, and the peptide selection and presentation strategy of the host has been studied to guide our understanding of cellular immunity and vaccine development. Here, a severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid (N) protein-derived CTL epitope, N1 (QFKDNVILL), restricted by HLA-A*2402 was identified by a series ofin vitrostudies, including a computer-assisted algorithm for prediction, stabilization of the peptide by co-refolding with HLA-A*2402 heavy chain and β2-microglobulin (β2m), and T2-A24 cell binding. Consequently, the antigenicity of the peptide was confirmed by enzyme-linked immunospot (ELISPOT), proliferation assays, and HLA-peptide complex tetramer staining using peripheral blood mononuclear cells (PBMCs) from donors who had recovered from SARS donors. Furthermore, the crystal structure of HLA-A*2402 complexed with peptide N1 was determined, and the featured peptide was characterized with two unexpected intrachain hydrogen bonds which augment the central residues to bulge out of the binding groove. This may contribute to the T-cell receptor (TCR) interaction, showing a host immunodominant peptide presentation strategy. Meanwhile, a rapid and efficient strategy is presented for the determination of naturally presented CTL epitopes in the context of given HLA alleles of interest from long immunogenic overlapping peptides.
Reduction of Immune Activation with Chloroquine Therapy during Chronic HIV Infection
Authors: Murray Shannon M. , Down Carrie M. , Boulware David R. , Stauffer William M. , Cavert Winston P. , Schacker Timothy W. , Brenchley Jason M. , Douek Daniel C.
Published: September 2010

Increased levels of activated T cells are a hallmark of the chronic stage of human immunodeficiency virus (HIV) infection and are highly correlated with HIV disease progression. We evaluated chloroquine (CQ) as a potential therapy to reduce immune activation during HIV infection. We found that the frequency of CD38
+
HLA-DR
+
CD8 T cells, as well as Ki-67 expression in CD8 and CD4 T cells, was significantly reduced during CQ treatment. Our data indicate that treatment with CQ reduces systemic T-cell immune activation and, thus, that its use may be beneficial for certain groups of HIV-infected individuals.
Species-Specific Regions of Occludin Required by Hepatitis C Virus for Cell Entry
Authors: Michta Maria L. , Hopcraft Sharon E. , Narbus Christopher M. , Kratovac Zerina , Israelow Benjamin , Sourisseau Marion , Evans Matthew J.
Published: September 2010

Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. As HCV infects only human and chimpanzee cells, antiviral therapy and vaccine development have been hampered by the lack of a convenient small-animal model. In this study we further investigate how the species tropism of HCV is modulated at the level of cell entry. It has been previously determined that the tight junction protein occludin (OCLN) is essential for HCV host cell entry and that human OCLN is more efficient than the mouse ortholog at mediating HCV cell entry. To further investigate the relationship between OCLN sequence and HCV species tropism, we compared OCLN proteins from a range of species for their ability to mediate infection of naturally OCLN-deficient 786-O cells with lentiviral pseudoparticles bearing the HCV glycoproteins. While primate sequences function equivalently to human OCLN, canine, hamster, and rat OCLN had intermediate activities, and guinea pig OCLN was completely nonfunctional. Through analysis of chimeras between these OCLN proteins and alanine scanning mutagenesis of the extracellular domains of OCLN, we identified the second half of the second extracellular loop (EC2) and specific amino acids within this domain to be critical for modulating the HCV cell entry factor activity of this protein. Furthermore, this critical region of EC2 is flanked by two conserved cysteine residues that are essential for HCV cell entry, suggesting that a subdomain of EC2 may be defined by a disulfide bond.
Response of 70-year-old white spruce to thinning and fertilization in interior Alaska
Authors: Cleve Keith Van , Zasada John C.
Published: September 2010

Applications of 112 kg ha−1 N as NH4NO3, 56 kg ha−1 P as treble superphosphate, and 112 kg ha−1 K as KCl in combination with thinning of 61% of initial basal area increased diameter increment 3.6 times over the control within one summer.Fertilizer was applied annually at these rates for 5 years to maintain high levels of tree nutrition and accurately assess growth response. After 5 years, growth increment continued. Thinning alone resulted in significant increases in soil moisture content and moderate increases in soil temperature. Changes in soil temperature and moisture regime did not appear to affect tree nutrition. For 70-year-old white spruce (Piceaglauca (Moench) Voss) growing on upland sites, a combination of both thinning and fertilization appears necessary to obtain maximum growth response.
Fomesannosus stump colonization and fungus development in the California mixed-conifer type
Authors: Hunt Richard S. , Cobb Jr. Fields W. , Parmeter Jr John R.
Published: September 2010

The pattern and rate of colonization of ponderosa pine (Pinusponderosa Laws.) stumps and stump roots by Fomes annosus (Fr.) Karsten were determined by sampling inoculated stumps periodically. Colonization occurred in the sapwood and wood–bark interface. Downward growth was fastest in the wood–bark interface and large stump roots were completely colonized in less than 1.5 years. Comparisons were made among colonization patterns and rates in ponderosa pine, sugar pine (P. lambertiana Dougl.), and Douglas–fir (Pseudotsugamenziesii (Mirb.) Franco) stumps.Conidiophores were observed only during the early periods of bark loosening and were produced in 'tubes' and beetle galleries of inoculated and non-inoculated stumps. Mycelial plaques formed during the later stages of bark loosening in both inoculated and non-inoculated stumps. Basidiocarps developed on inoculated stumps within 1.5 years and on older non-inoculated stumps.
The effect of rooting volume and container configuration on the early growth of white spruce seedlings
Authors: Carlson Lester W. , Endean Frank
Published: September 2010

White spruce (Piceaglauca (Moench) Voss) seedlings were germinated and grown for 20 weeks in containers ranging in volume from 10 cm3 to 524 cm3. Containers for four of the six volumes were constructed in three different ratios of height to diameter (1:1, 3:1, and 6:1), with the remaining two volumes at 3:1. Both container diameter and volume had prounced effects on seedling growth. White spruce produced significantly more roots in the top quarter of the container than did lodgepole pine (Pinnscontorta Dougl. var. latifolia Engelm.), indicating that white spruce and lodgepole pine require containers of different configuration for optimum growth.
TWO-CONNECTION RENORMALIZATION AND NON-HOLONOMIC GAUGE MODELS OF EINSTEIN GRAVITY
Authors: VACARU SERGIU I.
Published: September 2010

A new framework for perturbative quantum gravity is proposed following the geometry of non-holonomic distributions on (pseudo)Riemannian manifolds. There are considered such distributions and adap-ted connections, also completely defined by a metric structure, when gravitational models with infinite many couplings reduce to two-loop renormalizable effective actions. We use a key result from our partner work arXiv: 0902.0911 that the classical Einstein gravity theory can be reformulated equivalently as a non-holonomic gauge model in the bundle of affine/de Sitter frames on pseudo-Riemannian space–time. It is proven that (for a class of non-holonomic constraints and splitting of the Levi–Civita connection into a "renormalizable" distinguished connection, on a base background manifold, and a gauge-like distortion tensor, in total space) a non-holonomic differential renormalization procedure for quantum gravitational fields can be elaborated. Calculation labor is reduced to one- and two-loop levels and renormalization group equations for non-holonomic configurations.
κ-DEFORMED POINCARÉ ALGEBRAS AND QUANTUM CLIFFORD–HOPF ALGEBRAS
Authors: DA ROCHA ROLDÃO , BERNARDINI ALEX E. , VAZ JAYME
Published: September 2010

The Minkowski space–time quantum Clifford algebra structure associated with the conformal group and the Clifford–Hopf alternative κ-deformed quantum Poincaré algebra is investigated in the Atiyah–Bott–Shapiro mod 8 theorem context. The resulting algebra is equivalent to the deformed anti-de Sitter algebra [Formula: see text], when the associated Clifford–Hopf algebra is taken into account, together with the associated quantum Clifford algebra and a (not braided) deformation of the periodicity Atiyah–Bott–Shapiro theorem.
RICCI FLOW OF UNWARPED AND WARPED PRODUCT MANIFOLDS
Authors: DAS SANJIT , PRABHU KARTIK , KAR SAYAN
Published: September 2010

We analyze Ricci flow (normalized/unnormalized) of product manifolds — unwarped as well as warped, through a study of generic examples. First, we investigate such flows for the unwarped scenario with manifolds of the type 𝕊n × 𝕊m, 𝕊n × ℍm, ℍm × ℍn and also, similar multiple products. We are able to single out generic features such as singularity formation, isotropization at particular values of the flow parameter and evolution characteristics. Subsequently, motivated by warped braneworlds and extra dimensions, we look at Ricci flows of warped space–times. Here, we are able to find analytic solutions for a special case by variable separation. For others, we numerically solve the equations and draw certain useful inferences about the evolution of the warp factor, the scalar curvature as well as the occurrence of singularities at finite values of the flow parameter. We also investigate the dependence of the singularities of the flow on the initial conditions. We expect our results to be useful in any physical/mathematical context where such product manifolds may arise.
CLOSED-LOOP AND CONSTRAINED MECHANICAL SYSTEMS
Authors: GRILLO S. , MACIEL F. , PÉREZ D.
Published: September 2010

In this paper, we study the relationship between closed-loop mechanical systems (CLMS) and higher-order constrained systems (HOCS). We show that second-order constraints, i.e. constraints in acceleration, can be used to construct a CLMS, where the control law is given by the related constraint force. As an example we show that, by means of appropriate constraints of this kind, stabilization can be achieved for the inertia wheel pendulum. We also consider the inverse problem, that is to say: can every CLMS be constructed from a HOCS, i.e. can every control law be seen as the constraint force related to a given set of constraints? We answer this question affirmatively, reflecting a deep connection between feedback systems and systems with constraints. Also, we study when these constraints can be integrated to constraints in velocities. We prove that this is possible for CLMSs constructed by means of linear methods and also by some global ones, as the kinetic shaping method with symmetry.
Ion transporters in secretory and cyclically modulating ameloblasts: a new hypothesis for cellular control of preeruptive enamel maturation
Authors: Josephsen Kaj , Takano Yoshiro , Frische Sebastian , Praetorius Jeppe , Nielsen Søren , Aoba Takaaki , Fejerskov Ole
Published: September 2010

Mature enamel consists of densely packed and highly organized large hydroxyapatite crystals. The molecular machinery responsible for the formation of fully matured enamel is poorly described but appears to involve oscillative pH changes at the enamel surface. We conducted an immunohistochemical investigation of selected transporters and related proteins in the multilayered rat incisor enamel organ. Connexin 43 (Cx-43) is found in papillary cells and ameloblasts, whereas Na+-K+-ATPase is heavily expressed during maturation in the papillary cell layer only. Given the distribution of Cx-43 channels and Na+-K+-ATPase, we suggest that ameloblasts and the papillary cell layer act as a functional syncytium. During enamel maturation ameloblasts undergo repetitive cycles of modulation between ruffle-ended (RA) and smooth-ended (SA) ameloblast morphologies. Carbonic anhydrase II and vacuolar H+-ATPase are expressed simultaneously at the beginning of the maturation stage in RA cells. The proton pumps are present in the ruffled border of RA and appear to be internalized during the SA stage. Both papillary cells and ameloblasts express plasma membrane acid/base transporters (AE2, NBC, and NHE1). AE2 and NHE1 change position relative to the enamel surface as localization of the tight junctions changes during ameloblast modulation cycles. We suggest that the concerted action of the papillary cell layer and the modulating ameloblasts regulates the enamel microenvironment, resulting in oscillating pH fluctuations. The pH fluctuations at the enamel surface may be required to keep intercrystalline spaces open in the surface layers of the enamel, enabling degraded enamel matrix proteins to be removed while hydroxyapatite crystals grow as a result of influx of calcium and phosphate ions.
Force enhancement following stretch in a single sarcomere
Authors: Leonard T. R. , DuVall M. , Herzog W.
Published: September 2010

It has been accepted for half a century that, for a given level of activation, the steady-state isometric force of a muscle sarcomere depends exclusively on the amount of overlap between the contractile filaments actin and myosin, or equivalently sarcomere length (Gordon AM et al., J Physiol 184: 170–192, 1966). Moreover, according to the generally accepted paradigm of muscle contraction, the cross-bridge theory (Huxley AF, Prog Biophys Biophys Chem 7: 255–318, 1957), this steady-state isometric sarcomere force is independent of the muscle's contractile history (Huxley AF, Prog Biophys Biophys Chem 7: 255–318, 1957; Walcott S and Herzog W, Math Biosci 216: 172–186, 2008); i.e., it is independent of whether a muscle is held at a constant length before and during the contraction or whether the muscle is shortened or lengthened to the same constant length. This, however, is not the case, as muscles and single fibers that are stretched show greatly increased steady-state isometric forces compared with preparations that are held at a constant length (Abbott BC and Aubert XM, J Physiol 117: 77–86, 1952; De Ruiter CJ et al., J Physiol 526.3: 671–681, 2000; Edman KAP et al., J Physiol 281: 139–155, 1978; Edman KAP et al., J Gen Physiol 80: 769–784, 1982; Edman KAP and Tsuchiya T, J Physiol 490.1: 191–205, 1996). This so-called “residual force enhancement” (Edman KAP et al., J Gen Physiol 80: 769–784, 1982) offers a perplexing puzzle for muscle physiologists. Many theories have been advanced to address the discrepancy between prediction and observation with the most popular and accepted being the sarcomere length nonuniformity theory (Morgan DL, Biophys J 57: 209–221, 1990), which explains the residual force enhancement with the development of large nonuniformities in sarcomere lengths during muscle stretching. Here, we performed experiments in mechanically isolated sarcomeres and observed that the residual force enhancement following active stretching is preserved. Since our preparation utilizes a single sarcomere, a redistribution of the length of neighboring sarcomeres to produce the higher force following stretch is, by design, precluded. Furthermore, the enhanced forces in the single sarcomeres always exceed the isometric forces on the plateau of the force-length relationship, thereby eliminating the possibility that our result might have been obtained because of a redistribution of half-sarcomere lengths. Since force enhancement in single myofibrils has been associated with actin-titin interactions (Kulke M et al., Circ Res 89: 874–881, 2001; Li Q et al., Biophys J 69: 1508–1518, 1995) and calcium binding to titin (Joumaa V et al., Am J Physiol Cell Physiol 294: C74–C78, 2008; Labeit D et al., Proc Natl Acad Sci USA 100: 13716–13721, 2003), titin may regulate the sarcomeric force enhancement observed here.
Circulation and metabolic rates in a natural hibernator: an integrative physiological model
Authors: Hampton Marshall , Nelson Bethany T. , Andrews Matthew T.
Published: September 2010

Small hibernating mammals show regular oscillations in their heart rate and body temperature throughout the winter. Long periods of torpor are abruptly interrupted by arousals with heart rates that rapidly increase from 5 beats/min to over 400 beats/min and body temperatures that increase by ∼30°C only to drop back into the hypothermic torpid state within hours. Surgically implanted transmitters were used to obtain high-resolution electrocardiogram and body temperature data from hibernating thirteen-lined ground squirrels ( Spermophilus tridecemlineatus ). These data were used to construct a model of the circulatory system to gain greater understanding of these rapid and extreme changes in physiology. Our model provides estimates of metabolic rates during the torpor-arousal cycles in different model compartments that would be difficult to measure directly. In the compartment that models the more metabolically active tissues and organs (heart, brain, liver, and brown adipose tissue) the peak metabolic rate occurs at a core body temperature of 19°C approximately midway through an arousal. The peak metabolic rate of the active tissues is nine times the normothermic rate after the arousal is complete. For the overall metabolic rate in all tissues, the peak-to-resting ratio is five. This value is high for a rodent, which provides evidence for the hypothesis that the arousal from torpor is limited by the capabilities of the cardiovascular system.
t10,c12-CLA decreases adiposity in peripubertal mice without dose-related detrimental effects on mammary development, inflammation status, and metabolism
Authors: Foote M. R. , Giesy S. L. , Bernal-Santos G. , Bauman D. E. , Boisclair Y. R.
Published: September 2010

The trans 10, cis 12-conjugated linoleic acid (10,12-CLA) isomer reduces adiposity in several animal models. In the mouse, however, this effect is associated with adipose tissue inflammation, hyperinsulinemia and hepatic lipid accumulation. Moreover, 10,12-CLA was recently shown to promote mammary ductal hyperplasia and ErbB2/Her2-driven mammary cancer in the mouse. Reasons for detrimental effects of 10,12-CLA on the mouse mammary gland could relate to its effect on the mammary fat pad (MFP), which is essential for normal development. Accordingly, we hypothesized that mammary effects of 10,12-CLA were mediated through the MFP in a dose-dependent manner. Female FVB mice were fed 10,12-CLA at doses of 0%, 0.1%, 0.2%, or 0.5% of the diet from day 24 of age, and effects on mammary development and metabolism were measured on day 49. The 0.5% dose reduced ductal elongation and caused premature alveolar budding. These effects were associated with increased expression of inflammatory markers and genes shown to alter epithelial growth (IGF binding protein-5) and alveolar budding (TNF-α and receptor of activated NF-κB ligand). The 0.5% dose also caused hyperinsulinemia and hepatic lipid accumulation. In contrast, the 0.1% 10,12-CLA dose had no adverse effects on mammary development, metabolic events, and inflammatory responses, but remained effective in decreasing adipose weights and lipogenic gene expression. These results show that a low dose of 10,12 -CLA reduces adiposity in the mouse without negative effects on mammary development, inflammation, and metabolism, and suggest that previously reported detrimental effects relate to the use of excessive doses.
Mice lacking the matrix metalloproteinase-9 gene reduce renal interstitial fibrosis in obstructive nephropathy
Authors: Wang Xiaohua , Zhou Yang , Tan Ruoyun , Xiong Mingxia , He Weichun , Fang Li , Wen Ping , Jiang Lei , Yang Junwei
Published: September 2010

Matrix metalloproteinase-9 (MMP-9) is one of the major components of the matrix proteolytic network, and its role in the pathogenesis of renal interstitial fibrosis remains largely unknown. Here, we demonstrate that ablation of MMP-9 attenuated renal interstitial fibrotic lesions in obstructive nephropathy. Mice lacking MMP-9 were less likely to develop morphological injury, which was characterized by a reduced disruption of tubular basement membrane (TBM) and expression of fibronectin as well as deposition of total tissue collagen in the kidneys after sustained ureteral obstruction compared with their wild-type counterparts. Deficiency of MMP-9 blocked tubular epithelial-to-myofibroblast transition (EMT) but did not alter the induction of transforming growth factor (TGF)-β1 axis expression in the obstructed kidneys. In vitro, TBM, which was digested by MMP-9 instead of MMP-9 itself, induces EMT and enhances migration of transformed cells. Thus increased MMP-9 is detrimental in renal interstitial fibrogenesis through a cascade of events that leads to TBM destruction and in turn to promotion of EMT. Our findings establish a crucial and definite importance of MMP-9 in the pathogenesis of renal interstitial fibrosis at the whole-animal level.
Endurance training-induced accumulation of muscle triglycerides is coupled to upregulation of stearoyl-CoA desaturase 1
Authors: Dobrzyn Pawel , Pyrkowska Aleksandra , Jazurek Magdalena , Szymanski Konrad , Langfort Jozef , Dobrzyn Agnieszka
Published: September 2010

Stearoyl-CoA desaturase (SCD), a rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids, has recently been shown to be a critical control point in regulation of liver and skeletal muscle metabolism. Herein, we demonstrate that endurance training significantly increases both SCD1 mRNA and protein levels in the soleus muscle, whereas it does not affect SCD1 expression in the EDL muscle and liver. Desaturation index (18:1Δ9/18:0 ratio), an indirect indicator of SCD1 activity, was also significantly higher (3.6-fold) in soleus of trained rats compared with untrained animals. Consistent with greater SCD1 expression/activity, the contents of free fatty acids, diacylglycerol, and triglyceride were elevated in soleus of trained rats. However, training did not affect lipid concentration in EDL and liver. Additionally, endurance training activated the AMP-activated protein kinase pathway as well as increased peroxisome proliferator-activated receptor (PPAR)-δ and PPARα gene expression and activity in soleus and liver. Increased lipid accumulation in soleus was coupled with elevated protein levels of fatty acid synthase, mRNA levels of diacylglycerol acyltransferase and glycerol-3-phosphate transferase, as well as increased levels of proteins involved in fatty acid transport (fatty acid translocase/CD36, fatty acid transport protein 1). Interestingly, sterol regulatory element-binding protein (SREBP)-1c expression and SREBP-1 protein levels were not affected by exercise training. Together, the obtained data suggest that SCD1 upregulation plays an important role in adaptation of oxidative muscle to endurance training.
Inhibition of Steady-State Smooth Pursuit and Catch-Up Saccades by Abrupt Visual and Auditory Onsets
Authors: Kerzel Dirk , Born Sabine , Souto David
Published: September 2010

It is known that visual transients prolong saccadic latency and reduce saccadic frequency. The latter effect was attributed to subcortical structures because it occurred only 60–70 ms after stimulus onset. We examined the effects of large task-irrelevant transients on steady-state pursuit and the generation of catch-up saccades. Two screen-wide stripes of equal contrast (4, 20, or 100%) were briefly flashed at equal eccentricities (3, 6, or 12°) from the pursuit target. About 100 ms after flash onset, we observed that pursuit gain dropped by 6–12% and catch-up saccades were entirely suppressed. The relatively long latency of the inhibition suggests that it results from cortical mechanisms that may act by promoting fixation or the deployment of attention over the visual field. In addition, we show that a loud irrelevant sound is able to generate the same inhibition of saccades as visual transients, whereas it only induces a weak modulation of pursuit gain, indicating a privileged access of acoustic information to the saccadic system. Finally, irrelevant changes in motion direction orthogonal to pursuit had a smaller and later inhibitory effect.
Irritancy Expectancy Alters Odor Perception: Evidence From Olfactory Event-Related Potential Research
Authors: Bulsing Patricia J. , Smeets Monique A. M. , Gemeinhardt Christian , Laverman Martin , Schuster Benno , Van den Hout Marcel A. , Hummel Thomas
Published: September 2010

The aim of the present research was to investigate the influences of cognition on temporal processing of olfactory information in a health-relevant context. We investigated whether expecting an odor to cause adverse health effects alters perception of that odor. An irritation-free odor (Study 1: H2S; Study 2: phenyl ethyl alcohol [PEA]) was presented after which participants expected to experience either adverse sensory irritation (caused by intranasal CO2presentation) in one condition or no adverse effects in another condition, depending on a previously presented visual cue. Olfactory event-related potentials (OERPs) were measured to assess effects of expectations on the temporal course of olfactory processing. When participants expected irritancy after perceiving the odor of H2S, N1 and P3 peak amplitude and N1 latency were increased and shortened, respectively, suggesting more intense and faster processing of the odor as well as effects on salience and anticipation of sensory irritation. When the odor was PEA, only the N1 amplitude was increased. These results, obtained with OERP, provide converging evidence for comparable conclusions regarding the influence of cognition on odor perception reached with functional magnetic resonance imaging. Furthermore, the results suggest that a priori hedonic valence of an odor affects how susceptible the olfactory percept is to modulation via expectations.
Cannabinoids Reveal Separate Controls for Whisking Amplitude and Timing in Rats
Authors: Pietr Maciej Dominik , Knutsen Per Magne , Shore David I. , Ahissar Ehud , Vogel Zvi
Published: September 2010

Whisking is controlled by multiple, possibly functionally segregated, motor sensory-motor loops. While testing for effects of endocannabinoids on whisking, we uncovered the first known functional segregation of channels controlling whisking amplitude and timing. Channels controlling amplitude, but not timing, were modulated by cannabinoid receptor type 1 (CB1R). Systemic administration of CB1R agonist Δ9-tetrahydrocannabinol (Δ9-THC) reduced whisking spectral power across all tested doses (1.25–5 mg/kg), whereas whisking frequency was affected at only very high doses (5 mg/kg). Concomitantly, whisking amplitude and velocity were significantly reduced in a dose-dependent manner (25–43 and 26–50%, respectively), whereas cycle duration and bilateral synchrony were hardly affected (3–16 and 3–9%, respectively). Preadministration of CB1R antagonist SR141716A blocked Δ9-THC–induced kinematic alterations of whisking, and when administered alone, increased whisking amplitude and velocity but affected neither cycle duration nor synchrony. These findings indicate that whisking amplitude and timing are controlled by separate channels and that endocannabinoids modulate amplitude control channels.
Reflectance Confocal Microscopy as an Aid to Dermoscopy to Improve Diagnosis on Equivocal Lesions: Evaluation of Three Bluish Nodules
Authors: Bassoli Sara , Seidenari Stefania , Pellacani Giovanni , Longo Caterina , Cesinaro Anna Maria
Published: September 2010

Nodular lesions can be difficult to diagnose under dermoscopy alone, since they often lack specific diagnostic features. Confocal microscopy can be used as an aid to dermoscopy, to increase the diagnostic accuracy on equivocal skin lesions. We report three cases of bluish nodular lesions, difficult to diagnose under dermoscopy alone. Confocal features were very useful in these cases to lead us to the correct diagnosis, recognizing benign versus malignant entities. Histopathology is also reported, with high correspondence compared to the confocal imaging.
Comparative Study of Pure and Doped Single Crystals of Lead Iodide Dihydrate and Lead Tartrate Dihydrate Grown in Silica Gel Using Fourier Transform Raman Spectra
Authors: Lillybai G. , Rahimkutty M. H.
Published: September 2010

It is presented the FT-Raman spectroscopic investigation of the lead tartrate dihydrate and lead iodide dihydrate.The difference in the spectroscopic behavior of these salts were found which can be attributed to a different geometry of the tartrate and iodide ions. The structural differences between the coordination environments of lead atoms are discussed in connection with Raman frequencies. The compounds have been synthesized using sodium metasilicate gel at ordinary temperature and pressure.