bluuebunny/crossref_metadata_2025 huggingface dataset:
Simvastatin inactivates β1‐integrin and extracellular signal‐related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cells
Authors: Takeda Ikuko , Maruya Shin‐ichiro , Shirasaki Takashi , Mizukami Hiroki , Takahata Takenori , Myers Jeffrey N. , Kakehata Seiji , Yagihashi Soroku , Shinkawa Hideichi
Published: April 2007

The 3‐hydroxy‐3‐methylglutaryl (HMG)‐CoA reductase inhibitors, also called statins, are commonly used as lipid‐lowering drugs that inhibit cholesterol biosynthesis. An anticancer effect, as a pleiotropic function of certain statins, has been hypothesized. In the present study, we investigated the effect of simvastatin, one of the natural statins, on cell proliferation, cell cycle, invasive activity, and molecular expressions associated with cell–extracellular matrix adhesion, signal transduction, and DNA synthesis in Tu167 and JMAR cells from head and neck squamous cell carcinoma. The addition of simvastatin resulted in a dose‐dependent inhibition of cell growth and migration into the extracellular matrix. Considerable morphological changes occurred after treatment with simvastatin, demonstrating loss of cell adhesion and disruption of actin filaments in cytoplasm. The inhibitory effect of simvastatin on cell proliferation seemed to be associated with cell cycle arrest and increased expression of p21, p27, and activated caspase‐3. The expression of β1‐integrin, a counter adhesion for the extracellular matrix, phosphorylated FAK, and phosphorylated ERK was decreased by treatment with simvastatin. The proapoptotic effect of simvastatin was inhibited by treatment with mevalonate. cDNA microarray assay demonstrated that molecular changes resulting from treatment with simvastatin included the up‐regulation of cell cycle regulators and apoptosis‐inducing factors and the down‐regulation of integrin‐associated molecules and cell proliferation markers. Of down‐regulated genes induced by simvastatin treatment, a significant depletion of thymidylate synthase was confirmed using western blot analysis. These results imply that simvastatin has the potential to be effective for the prevention of the growth and metastasis of cancer cells. (Cancer Sci 2007; 98: 890–899)
Histopathological grade, mucinous differentiation and DNA ploidy in relation to prognosis in colorectal carcinoma
Authors: Purdie C A , Piris J
Published: April 2007

Aims

We investigated parameters which might help identify poor prognosis colorectal cancers and, in particular, we stratified Dukes' stage B carcinomas in order to identify those patients who would benefit from adjuvant therapy.

Methods and results

Histopathological parameters and DNA ploidy were analysed in a consecutive series of 256 resected colorectal cancers and their relationship with patient survival were investigated. By univariate analysis, Dukes' stage, degree of differentiation, nature of the invasive margin and DNA ploidy all correlated with prognosis. However, degree of differentiation assessed by the worst pattern seen anywhere in the tumour correlated more significantly with clinical outcome than did the predominant pattern. This was confirmed by multivariate analysis which showed only Dukes' stage and worst pattern differentiation as independent prognostic variables. Mucinous carcinomas showed no significant difference in outcome when compared to adenocarcinomas. DNA ploidy correlated with prognosis but only at a low level (P = 0.035) but this was maintained for Dukes' B carcinomas.

Conclusions

Dukes' stage and degree of differentiation provide independent prognostic information in colorectal cancer. However, differentiation should be assessed by the worst pattern and not by the predominant pattern as is currently recommended by the UKCCCR. DNA ploidy provides some prognostic information and does stratify Dukes' B cancers and thus might provide useful information on which to base decisions concerning adjuvant therapies in this difficult group. Mucinous differentiation has no prognostic significance.
Sphingosine kinase inhibitor suppresses dendritic cell migration by regulating chemokine receptor expression and impairing p38 mitogen‐activated protein kinase
Authors: Jung In Duk , Lee Jun Sik , Kim Yong Joo , Jeong Young‐Il , Lee Chang‐Min , Lee Min Goo , Ahn Soon‐Choel , Park Yeong‐Min
Published: April 2007

The migration of dendritic cells (DCs) to secondary lymphoid organs plays a crucial role in the initiation of adaptive immune responses. Although lipopolysaccharide enhances chemokine receptor 7 (CCR7) expression on DCs, the second signal for the migration of DCs toward the chemokine CCL19 remains unknown. In this study, we show that sphingosine kinase inhibitor (SKI) inhibits the migration of DCs toward CCL19 through the down‐regulation of CCR7. Inhibition of p38 mitogen‐activated protein kinase (MAPK) activation by SKI may be responsible for the SKI‐mediated effects on the regulation of chemokine receptor expression. Impairment of DC migration by the inhibition of p38 MAPK and down‐regulation of CCR7 expression may contribute to the protective effects of SKI in DC‐related disorders. These results suggest that sphingosine kinase‐mediated signalling plays a role in the innate and adaptive immune responses by altering DC migration.
Antibacterial substances of low molecular weight isolated from the blowfly, Lucilia sericata
Authors: HUBERMAN L. , GOLLOP N. , MUMCUOGLU K. Y. , BREUER E. , BHUSARE S. R. , SHAI Y. , GALUN R.
Published: April 2007

Abstract Low molecular weight compounds were isolated by high‐performance liquid chromatography from the maggot or haemolymph extracts of Lucilia sericata (Meigen) (Diptera: Calliphoridae). Using gas chromatography‐mass spectrometry analysis, three compounds were obtained: p‐hydroxybenzoic acid (molecular weight 138 Da), p‐hydroxyphenylacetic acid (molecular weight 152 Da) and octahydro‐dipyrrolo[1,2‐a;1′,2′‐d] pyrazine‐5,10‐dione (molecular weight 194 Da), also known as the cyclic dimer of proline (or proline diketopiperazine or cyclo[Pro,Pro]). All three molecules revealed antibacterial activity when tested against Micrococcus luteus and/or Pseudomonas aeruginosa, and the effect was even more pronounced when these molecules were tested in combination and caused lysis of these bacteria.
Intraspecific variation and population structure of the German cockroach,Blattella germanica, revealed with RFLP analysis of the non‐transcribed spacer region of ribosomal DNA
Authors: MUKHA D. V. , KAGRAMANOVA A. S. , LAZEBNAYA I. V. , LAZEBNYI O. E. , VARGO E. L. , SCHAL C.
Published: April 2007

AbstractLittle information is available on genetic variation within and between populations of pest cockroaches. In this study, intraspecificHindIII polymorphism was investigated in the German cockroach,Blattella germanica(Linnaeus) (Dictyoptera, Blattaria: Blattellidae), using restriction fragment length polymorphisms (RFLP) of the non‐transcribed spacer (NTS) region of ribosomal DNA (rDNA). Individual male insects were collected from infestations at three different pig farms. Each population was characterized byHindIII restriction fragment frequencies and haplotype (a particular X‐chromosome pattern) frequencies. The inheritance of the X‐chromosomeHindIII rDNA patterns over 12 generations (3 years) follows Mendelian patterns, and the stability of this polymorphic marker indicates infrequent genetic recombination of variable sites. Although pairwise genetic distance measures were uncorrelated with geographical distance, the pattern of genetic differentiation of the three cockroach populations suggests that human‐mediated transport of cockroaches is an important force in shaping the population genetic structure of cockroach infestations, at least at the regional scale of 10–100 km. Sequence variation in the ribosomal NTS is a useful marker, and RFLP of rDNA is a simple, robust and reproducible technique for differentiating recently diverged cockroach populations.
Low‐income minority mothers' reports of infant health care utilisation compared with medical records
Authors: Murray Kennan D. , El‐Mohandes Ayman A. E. , El‐Khorazaty M. Nabil , Kiely Michele
Published: April 2007

This study aimed to investigate mothers' reporting of the nature, location, frequency and content of health care visits for their infants, as compared with data abstracted from the infants' medical records. It was part of a community‐based parenting intervention designed to improve preventive health care utilisation among minority mothers in Washington, DC. Mothers ≥18 years old with newborn infants and with poor or no prenatal care were enrolled in the study. A total of 160 mother–infant dyads completed the 12‐month study. Mothers were interviewed when the infants were 4, 8 and 12 months old, and were asked to recall infant visits to all health care providers. Medical records from identified providers were used for verification. The number and type of immunisations given, types of providers visited, and reason for the visits were compared.

Only about a quarter of mothers agreed with their infants' medical records on the number of specific immunisations received. The mothers reported fewer polio (1.8 vs. 2.1, P = 0.006), diphtheria and tetanus toxoids and pertussis (DTP) (1.8 vs. 2.2, P = 0.002), and Haemophilus influenzae type b (HiB) (1.3 vs. 2.1, P < 0.0001) immunisations than were recorded. Similarly, about a quarter of the mothers were unaware of any polio, DTP or hepatitis B immunisations given, as documented in the medical records, and 38% did not know that their infant was immunised for HiB. Nearly half of the mothers recalled more infant doctors' visits than were recorded in the medical records (4.1 vs. 3.6 visits, P = 0.017). The mothers generally disagreed with the providers about the reason for a particular visit and reported fewer sick‐baby visits (1.5 vs. 3.3, P < 0.0001) than the providers recorded. Mothers' reports and medical records matched in only 19% of the cases. In 47%, mothers under‐reported and in 34% over‐reported the total number of visits. The strongest agreement between mothers' reports and medical records was in the case of emergency room visits (63%). In conclusion, in this population, mothers' reporting did not match that of providers with respect to specific information: the number of immunisations, the location where services were provided, and the classification of sick‐ vs. well‐baby visits. Future studies that evaluate health care utilisation data should take these discrepancies into consideration in their selection of information source, and in their interpretation of the data.
Reliability and determinants of anogenital distance and penis dimensions in male newborns from Chiapas, Mexico
Authors: Romano‐Riquer S. Patricia , Hernández‐Ávila Mauricio , Gladen Beth C. , Cupul‐Uicab Lea A. , Longnecker Matthew P.
Published: April 2007

Development of the perineum as well as the external genitalia is determined by dihydrotestosterone, resulting in a greater anogenital distance (AGD) in males than females. In animal experiments with hormonally active agents, anogenital distance is used as a bioassay of fetal androgen action. Use of anogenital distance in human studies has been rare. Because anogenital distance has been an easy‐to‐measure, sensitive outcome in animal studies, we developed an anthropometric protocol for measurement of anogenital distance in human males. In this paper we describe the method for measurement of three anogenital distances, their reliability, and an assessment of predictors for each in the context of an epidemiological study. We compare the reliabilities and predictors to those for stretched penis length and penis width.

A cross‐sectional study of 781 newly delivered male infants was conducted in 2002–03 in Chiapas, Mexico. Replicate measures were obtained on nearly all subjects. The reliability of the measures of anogenital distance (0.82–0.91) were higher than for stretched penis length (0.78) and width (0.75). Birthweight and gestational length were more strongly related to anogenital distance than to penis length. Anogenital distance was not related to penis length (r = 0.03).

Our large study clearly shows that AGD can be measured well in newborn males, and that the measurements were more reliable than those of penis length. Whether AGD measures in humans relate to clinically important outcomes, however, remains to be determined, as does its utility as a measure of androgen action in epidemiological studies.
Preterm delivery and exposure to active and passive smoking during pregnancy: a case–control study from Italy
Authors: Fantuzzi Guglielmina , Aggazzotti Gabriella , Righi Elena , Facchinetti Fabio , Bertucci Emma , Kanitz Stefano , Barbone Fabio , Sansebastiano Giuliano , Battaglia Mario Alberto , Leoni Valerio , Fabiani Leila , Triassi Maria , Sciacca Salvatore
Published: April 2007

The aim of this study was to assess the relationship between preterm/early preterm delivery and active smoking as well as environmental tobacco smoke (ETS) exposure in a sample of pregnant Italian women. A case–control study was conducted in nine cities in Italy between October 1999 and September 2000. Cases of preterm birth were singleton babies born before the 37th gestational week; babies born before the 35th gestational week were considered early preterm births. Controls were babies with gestational ages ≥ 37th week. A total of 299 preterm cases (including 105 early preterm) and 855 controls were analysed. A self‐administered questionnaire was used to assess active smoking and ETS exposure, as well as potential confounders. Multivariable logistic regression analysis showed a relationship between active smoking during pregnancy and preterm/early preterm delivery [adjusted ORs: 1.53; 95% CI 1.05, 2.21 and 2.00; 95% CI 1.16, 3.45, respectively]. A dose–response relationship was found for the number of cigarettes smoked daily. The adjusted ORs were 1.54 and 1.69 for preterm babies and 1.90 and 2.46 for early preterm babies for 1–10 and >10 cigarettes/day respectively. ETS exposure was associated with early preterm delivery [adjusted OR 1.56; 95% CI 0.99, 2.46] with a dose–response relationship with the number of smokers in the home. Smoking during pregnancy was strongly associated with preterm delivery with a dose–response effect. ETS exposure in non‐smoking women was associated only with early preterm delivery.
Codeine induces human mast cell chemokine and cytokine production: involvement of G‐protein activation
Authors: Sheen C. H. , Schleimer R. P. , Kulka M.
Published: April 2007

Background:  Activation of mast cells and the systemic release of histamine are common side effects of opiates such as codeine and morphine. In some individuals, codeine not only elicits a sizable early response due to mast cell degranulation, but can also lead to late cutaneous allergic inflammation possibly through the production of chemokines. However, individuals who exhibit a late phase reaction to codeine often do not react to its synthetic analog, meperidine. The goal of this study was to test whether codeine and meperidine induce secretion of inflammatory mediators in human mast cells.

Methods:  To characterize opiate activation of human mast cells, we stimulated cultured human (LAD2 cell line and CD34+‐derived) mast cells with codeine and meperidine and measured degranulation and chemokine production.

Results:  Codeine, but not meperidine, activated human mast cell degranulation within 30 min in a dose‐dependent manner. Degranulation was blocked by the phosphoinositol‐3 kinase (PI3K) inhibitor, wortmannin, and pertussis toxin but not by Ro‐31‐8220, a PKC inhibitor or forskolin, a cyclic adenylyl cyclase activator. After 3 and 8 h of stimulation, codeine, but not meperidine, activated human mast cells to release monocyte chemoattractant protein‐1 (CCL2), regulated on activation, normal T expressed and secreted (RANTES, CCL5) and interleukin‐8 (CXCL 8) but not inducible protein‐10 (CXCL10).

Conclusions:  Codeine activates human mast cell degranulation and chemokine production by activating protein kinase A and PI3 kinase, possibly leading to NF‐κB activation. Therefore, opiates may regulate late phase allergic inflammation by activating chemokine production by human mast cells.
Evaluation of the IgE cross‐reactions among vespid venoms. A possible approach for the choice of immunotherapy
Authors: Caruso B. , Bonadonna P. , Severino M. G. , Manfredi M. , Dama A. , Schiappoli M. , Rizzotti P. , Senna G. , Passalacqua G.
Published: April 2007

Background: Hymenoptera venom allergy can be effectively cured with specific immunotherapy, thus the correct identification of the allergen is essential. In the case of multiple skin and serum positivities it is important to know if a cross‐reaction among venoms is present. We studied by CAP‐inhibition assays the degree of cross‐reactivity betweenVespula vulgarisandPolistes dominulus.

Methods: Serum samples were obtained from consecutive patients with a clinical history of grade III–IV reactions to hymenoptera sting and with nondiscriminative skin/CAP positivity to bothVespulaandPolistes. Inhibition assays were carried out with a CAP method, incubating the sera separately with both venoms and subsequently measuring the specific immunoglobulin E (IgE) to venoms themselves.

Results: Forty‐five patients (33 male, mean age 40 years, age range 12–74, total serum IgE 242 ± 168 kU/l) were included. Their specific IgE toVespulaandPolisteswere 12.03 ± 5.70 kU/l and 10.7 ± 2.0 kU/l (P = NS), respectively. At the CAP‐inhibition assays, in 25 patients a >75% heterologous inhibition byP. dominulusvenom againstV. vulgaris‐specific IgE was found. In six subjectsV. vulgarisvenom effectively inhibited theP. dominulus‐specific IgE. In the remaining 14 cases the CAP‐inhibition test provided intermediate and not discriminative results.

Conclusion: In 31/45 patients, the double sensitizations to venoms were probably the result of cross‐reactions and the CAP‐inhibition allowed identifying the true double sensitizations. This approach may be helpful for the correct prescription of immunotherapy in the case ofV. vulgarisandP. dominulusdouble positivity.
Methanobactin‐promoted dissolution of Cu‐substituted borosilicate glass
Authors: KULCZYCKI E. , FOWLE D. A. , KNAPP C. , GRAHAM D. W. , ROBERTS J. A.
Published: April 2007

Mineral weathering plays an important role in the global cycling of carbon and metals and there is an increasing realization that subsurface microbial activity may be a key factor controlling specific biogeochemical reactions and their rates. Methanobactin (mb) is an extracellular copper‐binding compound excreted by methanotrophs to acquire copper for the regulation of methane oxidation. Bioavailable Cu regulates the expression and activity of pMMO vs. sMMO (particulate vs. soluble methane monooxygenase, respectively), key enzymes responsible for bacterial methane oxidation. In this study, we investigate the effect of mb on the dissolution of Cu‐substituted borosilicate glass at low temperature and near neutral pH conditions, using batch dissolution experiments. Methanobactin promotes the dissolution of Cu‐substituted glasses at rates faster than control experiments. Glasses with lower concentrations of copper (80 p.p.m.) or no copper are dissolved more rapidly by mb than those with more abundant copper (800 p.p.m.). Within the first 2 h of reaction, mb sorption onto glass surfaces limits mass transfer of Cu into solution, and at higher concentrations (100 µmol) of the ligand, inhibits dissolution rates of all glass formulations. These results suggest that both the concentration of mb in solution and the solid phase Cu concentration impact silicate weathering rates and related cycling of carbon in near‐surface geological settings.
Phosphorous availability influences the dissolution of apatite by soil fungi
Authors: ROSLING A. , SUTTLE K. B. , JOHANSSON E. , VAN HEES P. A. W. , BANFIELD J. F.
Published: April 2007

Apatite (Ca10(PO4)6(OH,F,Cl)2) is the primary inorganic source of phosphorus in the biosphere. Soil fungi are known to increase plant‐available phosphorus by promoting dissolution of various phosphate minerals. Yet no apatite dissolution studies exist using fungi as weathering agents, and regulation of fungal weathering activity in response to different levels of phosphorus availability is largely unknown.

Fungi were isolated from a grassland soil in northern California. Three pathways of tri‐calcium phosphate (Ca3(PO4)2) (TCP) dissolution in liquid culture were identified among biogeochemically active fungi: (1) acidification (pH 3.3 ± 0.16), (2) moderate acidification (pH 4.9 ± 0.11) and (3) no acidification. Isolates representing pathway 1 and 2 were Zygomycetes in the order of Mucorales. All non‐acidifying isolates in pathway 3 were Ascomycetes and cleared the media by altering TCP into hydroxyapatite (Ca10(PO4)6(OH)2) and sequestering it within mycelial spheres. One isolate representing each pathway was used in fluorapatite dissolution experiments either with the fungi present or under abiotic conditions using cell‐free liquid media conditioned by fungal growth at different phosphorus and calcium availabilities.

Both Mucorales isolates acidify their substrate when growing in the presence of phosphorus. Mucorales exudates were mainly oxalic acid, and conditioned cell‐free media with phosphorus induced fluorapatite dissolution at a rate of 10−0.9±0.14 and 10−1.2±0.22 µmol P m−2 s−1. The ascomycete isolate on the other hand, induced fluorapatite dissolution at a rate of 10−1.1±0.05 µmol P m−2 s−1 by lowering the pH of the media under phosphorus‐limited conditions, without producing significant amounts of low molecular weight organic acids (LMWOAs). Oxalate strongly etches fluorapatite along channels parallel to [001], forming needle‐like features, while exudates from the ascomycete‐induced surface rounding. We conclude that while LMWOAs are well‐studied weathering agents, these do not appear to be produced by fungi in response to phosphorus‐limiting growth conditions.
Response to Comment on "Wetland Sedimentation from Hurricanes Katrina and Rita"
Authors: Turner R. Eugene , Baustian Joseph J. , Swenson Erick M. , Spicer Jennifer S.
Published: April 2007

Törnqvist
et al
. accept the usefulness of our data but confuse hurricane landfall location with hurricane storm surge impacts, misrepresent our data interpretation, and misattribute conclusions to our study. Our study did not attempt to address the overall effectiveness of river diversions used for management purposes. We agree that river mouth sedimentation is an important geological process that may lead to marsh colonization.
Lymphotoxin ß ReceptorDependent Control of Lipid Homeostasis
Authors: Lo James C. , Wang Yugang , Tumanov Alexei V. , Bamji Michelle , Yao Zemin , Reardon Catherine A. , Getz Godfrey S. , Fu Yang-Xin
Published: April 2007

Hyperlipidemia, one of the most important risk factors for coronary heart disease, is often associated with inflammation. We identified lymphotoxin (LT) and LIGHT, tumor necrosis factor cytokine family members that are primarily expressed on lymphocytes, as critical regulators of key enzymes that control lipid metabolism. Dysregulation of LIGHT expression on T cells resulted in hypertriglyceridemia and hypercholesterolemia. In low-density lipoprotein receptor–deficient mice, which lack the ability to control lipid levels in the blood, inhibition of LT and LIGHT signaling with a soluble lymphotoxin β receptor decoy protein attenuated the dyslipidemia. These results suggest that the immune system directly influences lipid metabolism and that LT modulating agents may represent a novel therapeutic route for the treatment of dyslipidemia.
Protein Sequences from Mastodon and
Tyrannosaurus Rex
Revealed by Mass Spectrometry
Authors: Asara John M. , Schweitzer Mary H. , Freimark Lisa M. , Phillips Matthew , Cantley Lewis C.
Published: April 2007

Fossilized bones from extinct taxa harbor the potential for obtaining protein or DNA sequences that could reveal evolutionary links to extant species. We used mass spectrometry to obtain protein sequences from bones of a 160,000- to 600,000-year-old extinct mastodon (
Mammut americanum
) and a 68-million-year-old dinosaur (
Tyrannosaurus rex
). The presence of
T. rex
sequences indicates that their peptide bonds were remarkably stable. Mass spectrometry can thus be used to determine unique sequences from ancient organisms from peptide fragmentation patterns, a valuable tool to study the evolution and adaptation of ancient taxa from which genomic sequences are unlikely to be obtained.
Quantum Structure of the Intermolecular Proton Bond
Authors: Roscioli J. R. , McCunn L. R. , Johnson M. A.
Published: April 2007

A proton shared between two closed-shell molecules, [A·H
+
·B], constitutes a ubiquitous soft binding motif in biological processes. The vibrational transitions associated with the shared proton, which provide a direct probe of this interaction, have been extensively studied in the condensed phase but have yielded only limited detailed information because of their diffuse character. We exploited recent advances in gas-phase ion spectroscopy to identify sharp spectral features that can be assigned to both the shared proton and the two tethered molecules in a survey of 18 cold, isolated [A·H
+
·B] ions. These data yield a picture of the intermolecular proton bond at a microscopic scale, facilitating analysis of its properties within the context of a floppy polyatomic molecule.
Mobile DNA in Old World Monkeys: A Glimpse Through the Rhesus Macaque Genome
Authors: Han Kyudong , Konkel Miriam K. , Xing Jinchuan , Wang Hui , Lee Jungnam , Meyer Thomas J. , Huang Charles T. , Sandifer Erin , Hebert Kristi , Barnes Erin W. , Hubley Robert , Miller Webb , Smit Arian F. A. , Ullmer Brygg , Batzer Mark A.
Published: April 2007

The completion of the draft sequence of the rhesus macaque genome allowed us to study the genomic composition and evolution of transposable elements in this representative of the Old World monkey lineage, a group of diverse primates closely related to humans. The L1 family of long interspersed elements appears to have evolved as a single lineage, and
Alu
elements have evolved into four currently active lineages. We also found evidence of elevated horizontal transmissions of retroviruses and the absence of DNA transposon activity in the Old World monkey lineage. In addition, ∼100 precursors of composite SVA (short interspersed element, variable number of tandem repeat, and
Alu
) elements were identified, with the majority being shared by the common ancestor of humans and rhesus macaques. Mobile elements compose roughly 50% of primate genomes, and our findings illustrate their diversity and strong influence on genome evolution between closely related species.
Demographic Histories and Patterns of Linkage Disequilibrium in Chinese and Indian Rhesus Macaques
Authors: Hernandez Ryan D. , Hubisz Melissa J. , Wheeler David A. , Smith David G. , Ferguson Betsy , Rogers Jeffrey , Nazareth Lynne , Indap Amit , Bourquin Traci , McPherson John , Muzny Donna , Gibbs Richard , Nielsen Rasmus , Bustamante Carlos D.
Published: April 2007

To understand the demographic history of rhesus macaques (
Macaca mulatta
) and document the extent of linkage disequilibrium (LD) in the genome, we partially resequenced five Encyclopedia of DNA Elements regions in 9 Chinese and 38 captive-born Indian rhesus macaques. Population genetic analyses of the 1467 single-nucleotide polymorphisms discovered suggest that the two populations separated about 162,000 years ago, with the Chinese population tripling in size since then and the Indian population eventually shrinking by a factor of four. Using coalescent simulations, we confirmed that these inferred demographic events explain a much faster decay of LD in Chinese (
r
2
≈ 0.15 at 10 kilobases) versus Indian (
r
2
≈ 0.52 at 10 kilobases) macaque populations.
From the Big Bang to the Mind
Authors: Bohannon John
Published: April 2007

Orion
.
By Cesc Gelabert and the Gelabert-Azzopardi Dance Company
. Teatre Lliure, Barcelona, Spain. 22 February - March 2007.
www.gelabertazzopardi.com/pagines/english/orion.htm

This dance performance, created in collaboration with neuroscientist Óscar Vilarroya, is structured around the emergences of matter, life, and consciousness.
Improved Immunogenicity of a Vaccination Regimen Combining a DNA Vaccine Encoding
Brucella melitensis
Outer Membrane Protein 31 (Omp31) and Recombinant Omp31 Boosting
Authors: Cassataro Juliana , Velikovsky Carlos A. , Bruno Laura , Estein Silvia M. , de la Barrera Silvia , Bowden Raúl , Fossati Carlos A. , Giambartolomei Guillermo H.
Published: April 2007

In the present study, we report an attempt to improve the immunogenicity of the Omp31 antigen by a DNA prime-protein boost immunization regimen. We immunized BALB/c mice with an Omp31 DNA vaccine (pCIOmp31) followed by boosting with recombinant Omp31 (rOmp31) in incomplete Freund's adjuvant and characterized the resulting immune responses and the protective efficacy against
Brucella ovis
and
B. melitensis
infection. Immunoglobulin G1 (IgG1) and IgG2a titers were higher in sera from pCIOmp31/rOmp31-immunized mice than in sera from mice immunized with pCIOmp31 or rOmp31 alone. Splenocytes from pCIOmp31/rOmp31-immunized mice produced significantly higher levels of gamma interferon than did those from mice given rOmp31 alone. In contrast, interleukin 2 (IL-2) production levels were comparable between the two groups of immunized mice. Cells from all immunized mice produced undetectable levels of IL-4. Notably, rOmp31 stimulated IL-10 production in the pCIOmp31/rOmp31-immunized group but not in the pCIOmp31- or rOmp31-immunized group. Although the prime-boost regimen induced specific cytotoxic responses, these responses could not reach the levels achieved by the pCIOmp31 immunization. In conclusion, pCIOmp31 priming followed by rOmp31 boosting led to moderately improved protection against a challenge with
B. ovis
or
B. melitensis
.
Multicenter Evaluation of a New Disk Agar Diffusion Method for Susceptibility Testing of Filamentous Fungi with Voriconazole, Posaconazole, Itraconazole, Amphotericin B, and Caspofungin
Authors: Espinel-Ingroff A. , Arthington-Skaggs B. , Iqbal N. , Ellis D. , Pfaller M. A. , Messer S. , Rinaldi M. , Fothergill A. , Gibbs D. L. , Wang A.
Published: April 2007

The purpose of this study was to correlate inhibition zone diameters, in millimeters (agar diffusion disk method), with the broth dilution MICs or minimum effective concentrations (MECs) (CLSI M38-A method) of five antifungal agents to identify optimal testing guidelines for disk mold testing. The following disk diffusion testing parameters were evaluated for 555 isolates of the molds
Absidia corymbifera
,
Aspergillus
sp. (five species),
Alternaria
sp.,
Bipolaris spicifera
,
Fusarium
sp. (three species),
Mucor
sp. (two species),
Paecilomyces lilacinus
,
Rhizopus
sp. (two species), and
Scedosporium
sp. (two species): (i) two media (supplemented Mueller-Hinton agar [2% dextrose and 0.5 μg/ml methylene blue] and plain Mueller-Hinton [MH] agar), (ii) three incubation times (16 to 24, 48, and 72 h), and (iii) seven disks (amphotericin B and itraconazole 10-μg disks, voriconazole 1- and 10-μg disks, two sources of caspofungin 5-μg disks [BBL and Oxoid], and posaconazole 5-μg disks). MH agar supported better growth of all of the species tested (24 to 48 h). The reproducibility of zone diameters and their correlation with either MICs or MECs (caspofungin) were superior on MH agar (91 to 100% versus 82 to 100%;
R
, 0.71 to 0.93 versus 0.53 to 0.96 for four of the five agents). Based on these results, the optimal testing conditions for mold disk diffusion testing were (i) plain MH agar; (ii) incubation times of 16 to 24 h (zygomycetes), 24 h (
Aspergillus fumigatus
,
A. flavus
, and
A. niger
), and 48 h (other species); and (iii) the posaconazole 5-μg disk, voriconazole 1-μg disk, itraconazole 10-μg disk (for all except zygomycetes), BBL caspofungin 5-μg disk, and amphotericin B 10-μg (zygomycetes only).
Prevalence of PCR Ribotypes among
Clostridium difficile
Isolates from Pigs, Calves, and Other Species
Authors: Keel Kevin , Brazier Jon S. , Post Karen W. , Weese Scott , Songer J. Glenn
Published: April 2007

PCR ribotypes were obtained for 144
Clostridium difficile
isolates from neonatal pigs. Porcine isolates comprised four PCR ribotypes, but one, ribotype 078, predominated (83%). This was also the most common ribotype (94%) among 33 calf isolates but was rarely identified in other species.
Evaluation of Three Molecular Assays for Rapid Identification of Methicillin-Resistant
Staphylococcus aureus
Authors: Francois Patrice , Bento Manuela , Renzi Gesuele , Harbarth Stephan , Pittet Didier , Schrenzel Jacques
Published: April 2007

One home-developed assay and two commercial assays for the rapid identification of methicillin-resistant
Staphylococcus aureus
(MRSA) were compared by use of a collection of clinical isolates displaying highly diverse genetic backgrounds. Our results suggest that users of
orfX
-staphylococcal cassette chromosome
mec
-based assays should repeatedly monitor the local epidemiology to minimize the risks of detection bias and the omission of emerging MRSA clones.
Comparison of Tests for Detection of β-Lactamase-Producing Staphylococci
Authors: Pitkälä A. , Salmikivi L. , Bredbacka P. , Myllyniemi A.-L. , Koskinen M. T.
Published: April 2007

Penicillin resistance identification tests are important in veterinary medicine. Six enzyme assays and a PCR test were compared for the detection of β-lactamase production or the β-lactamase gene in 175 staphylococcal isolates. We conclude that the PCR test and two nitrocefin-based assays can be recommended for routine clinical use.
Comparison of the Phenotyping Methods ID 32E and VITEK 2 Compact GN with 16S rRNA Gene Sequencing for the Identification of
Enterobacter sakazakii
Authors: Fanjat Nadège , Leclercq Alexandre , Joosten Han , Robichon Denis
Published: April 2007

A total of 34 isolates (28
Enterobacter sakazakii
and 6
Enterobacteriaceae
) from infant formulae, milk powder, and the production environment of milk powder factories were identified using ID 32E and VITEK 2 compact GN systems (bioMérieux, France). The ID 32E version 3.0 and VITEK 2 compact GN version 01.01b correctly identified 100% (28) of the
Enterobacter sakazakii
isolates tested, whereas the previous software version 2.0 for ID 32E showed only 71.4% correct results. None of the non-
E. sakazakii
isolates tested were misidentified as
E. sakazakii
with either of the identification systems used.
Comparative Genomics of Canadian Epidemic Lineages of Methicillin-Resistant
Staphylococcus aureus
Authors: Christianson Sara , Golding George R. , Campbell Jennifer , Mulvey Michael R.
Published: April 2007

Methicillin-resistant
Staphylococcus aureus
(MRSA) is a pathogen that has disseminated throughout Canadian hospitals and communities. Pulsed-field gel electrophoresis of over 9,300 MRSA isolates obtained from the Canadian Nosocomial Infection Surveillance Program has identified 10 epidemic strain types in Canada (CMRSA1 to CMRSA10). In an attempt to determine specific genetic factors that have contributed to their high prevalence in community and/or hospital settings, the genomic content of representative isolates for each of the 10 Canadian epidemic types was compared using comparative genomic hybridizations. Comparison of the community-associated Canadian epidemic isolates (CMRSA7 and CMRSA10) with the hospital-associated Canadian epidemic isolates revealed one open reading frame (ORF) (SACOL0046) encoding a putative protein belonging to a metallo-beta-lactamase family, which was present only in the community-associated Canadian epidemic isolates. A more restricted comparison involving only the most common hospital-associated Canadian epidemic isolates (CMRSA1 and CMRSA2) with the community-associated Canadian epidemic isolates did reveal additional factors that might be contributing to their prevalence in the community and hospital settings, which included ORFs encoding potential virulence factors involved in capsular biosynthesis, serine proteases, epidermin, adhesion factors, regulatory functions, leukotoxins, and exotoxins.
Genetic Relatedness of
Streptococcus pneumoniae
Isolates from Paired Blood and Respiratory Specimens
Authors: Harrell L. J. , Sharps S. K. , Bean R. A. , Reller L. B.
Published: April 2007

To assess the relatedness of
Streptococcus pneumoniae
isolates recovered concurrently from blood and respiratory tract specimens from patients with pneumonia, we analyzed 24 paired isolates by pulsed-field gel electrophoresis (PFGE), serotyping, and antimicrobial susceptibility testing. PFGE, serotype, and/or susceptibility patterns were identical for 22 of 24 pairs. Susceptibility results for blood isolates should guide therapy.
Differential Outcome of Tolerance Induction in Naive versus Activated Theiler's Virus Epitope-Specific CD8+Cytotoxic T Cells
Authors: Getts Meghann Teague , Kim Byung S. , Miller Stephen D.
Published: April 2007

Tolerance induced by the intravenous injection of peptide-pulsed, ethylene carbodiimide (ECDI)-fixed splenic antigen-presenting cells (Ag-SP) is a safe and effective method of inducing specific unresponsiveness in CD4+T cells for the prevention and treatment of a variety of autoimmune diseases. We determined whether Ag-SP tolerance could also be used to tolerize CD8+T cells. We show in the Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease model of multiple sclerosis that CD8+T cells specific for both dominant and subdominant epitopes can be rendered tolerant. Interestingly, although virus clearance was delayed, lack of the virus-specific cytotoxic T-lymphocyte response did not result in the conversion of normally TMEV-resistant C57BL/6 mice to a susceptible phenotype. Importantly, we found that Ag-SP tolerance may not be a practical treatment for human diseases in which CD8+T cells play a major role in pathogenesis, as tolerance induction in mice previously infected with TMEV led to a severe, often fatal reaction.
Mucosal Innate Immune Response Associated with a Timely Humoral Immune Response and Slower Disease Progression after Oral Transmission of Simian Immunodeficiency Virus to Rhesus Macaques
Authors: Milush Jeffrey M. , Stefano-Cole Kelly , Schmidt Kimberli , Durudas Andre , Pandrea Ivona , Sodora Donald L.
Published: April 2007

Mucosal transmission is the predominant mode of human immunodeficiency virus (HIV) infection worldwide, and the mucosal innate interferon response represents an important component of the earliest host response to the infection. Our goal here was to assess the changes in mRNA expression of innate mucosal genes after oral simian immunodeficiency virus (SIV) inoculation of rhesus macaques (
Macaca mulatta
) that were followed throughout their course of disease progression. The SIV plasma viral load was highest in the macaque that progressed rapidly to simian AIDS (99 days) and lowest in the macaque that progressed more slowly (>700 days). The mRNA levels of six innate/effector genes in the oral mucosa indicated that slower disease progression was associated with increased expression of these genes. This distinction was most evident when comparing the slowest-progressing macaque to the intermediate and rapid progressors. Expression levels of alpha and gamma interferons, the antiviral interferon-stimulated gene product 2′-5′ oligoadenylate synthetase (OAS), and the chemokines CXCL9 and CXCL10 in the slow progressor were elevated at each of the three oral mucosal biopsy time points examined (day 2 to 4, 14 to 21, and day 70 postinfection). In contrast, the more rapidly progressing macaques demonstrated elevated levels of these cytokine/chemokine mRNA at lymph nodes, coincident with decreased levels at the mucosal sites, and a decreased ability to elicit an effective anti-SIV antibody response. These data provide evidence that a robust mucosal innate/effector immune response is beneficial following lentiviral exposure; however, it is likely that the anatomical location and timing of the response need to be coordinated to permit an effective immune response able to delay progression to simian AIDS.
The Abundant R2 mRNA Generated by Aleutian Mink Disease Parvovirus Is Tricistronic, Encoding NS2, VP1, and VP2
Authors: Qiu Jianming , Cheng Fang , Pintel David
Published: April 2007

The abundant R2 mRNA encoded by the single left-end promoter of Aleutian mink disease parvovirus is tricistronic; it not only expresses the capsid proteins VP1 and VP2 but is also the major source for the nonstructural protein NS2. A
cis
-acting sequence within the NS2 gene was shown to be required for efficient capsid protein production, and its effect displayed a distinct location dependence. Ribosome transit through the upstream NS2 gene region was necessary for efficient VP1 and VP2 expression; however, neither ablation nor improvement of the NS2 initiating AUG had an effect on capsid protein production, suggesting that the translation of the NS2 protein per se had little influence on VP1 and VP2 expression. Thus, proper control of the alternative translation of the tricistronic R2 mRNA, a process critical for viral replication, is governed in a complex manner.
Pocket Factors Are Unlikely To Play a Major Role in the Life Cycle of Human Rhinovirus
Authors: Katpally Umesh , Smith Thomas J.
Published: April 2007

Human rhinovirus 14 (HRV14) is a member of the rhinovirus genus, which belongs to the picornavirus family, which includes clinically and economically important members, such as poliovirus, foot-and-mouth disease virus, and endomyocarditis virus. Capsid stability plays an important role in the viral infection process, in that it needs to be stable enough to move from cell to cell and yet be able to release its genetic material upon the appropriate environmental cues from the host cell. It has been suggested that certain host cell molecules, “pocket factors,” bind to the WIN drug-binding cavity beneath the canyon floor and provide transient stability to a number of the picornaviruses. To directly test this hypothesis, HRV14 was mutated in (V1188M, C1199W, and V1188M/C1199W) and around (S1223G) the drug-binding pocket. Infectivity, limited proteolysis, and matrix-assisted laser desorption ionization analyses indicate that filling the drug-binding pocket with bulky side chains is not deleterious to the viral life cycle and lends some stabilization to the capsid. In contrast, studies with the S1223G mutant suggest that this mutation at least partially overcomes WIN drug-mediated inhibition of cell attachment and capsid breathing. Finally, HRV16, which is inherently more stable than HRV14 in a number of respects, was found to “breathe” only at 37°C and did not tolerate stabilizing mutations in the drug-binding cavity. These results suggest that it is the drug-binding cavity itself and not the putative pocket factor that is crucial for the capsid dynamics, which is, in turn, necessary for infection.
New Structure Model for the Packaging Signal in the Genome of Group IIa Coronaviruses
Authors: Chen Shih-Cheng , van den Born Erwin , van den Worm Sjoerd H. E. , Pleij Cornelis W. A. , Snijder Eric J. , Olsthoorn René C. L.
Published: April 2007

A 190-nucleotide (nt) packaging signal (PS) located in the 3′ end of open reading frame 1b in the mouse hepatitis virus, a group IIa coronavirus, was previously postulated to direct genome RNA packaging. Based on phylogenetic data and structure probing, we have identified a 95-nt hairpin within the 190-nt PS domain which is conserved in all group IIa coronaviruses but not in the severe acute respiratory syndrome coronavirus (group IIb), group I coronaviruses, or group III coronaviruses. The hairpin is composed of six copies of a repeating structural subunit that consists of 2-nt bulges and 5-bp stems. We propose that repeating AA bulges are characteristic features of group IIa PSs.
Herpes Simplex Virus Type 1 Induces CD83 Degradation in Mature Dendritic Cells with Immediate-Early Kinetics via the Cellular Proteasome
Authors: Kummer Mirko , Turza Nadine M. , Muhl-Zurbes Petra , Lechmann Matthias , Boutell Chris , Coffin Robert S. , Everett Roger D. , Steinkasserer Alexander , Prechtel Alexander T.
Published: April 2007

Mature dendritic cells (DCs) are the most potent antigen-presenting cells within the human immune system. However, Herpes simplex virus type 1 (HSV-1) is able to interfere with DC biology and to establish latency in infected individuals. In this study, we provide new insights into the mechanism by which HSV-1 disarms DCs by the manipulation of CD83, a functionally important molecule for DC activation. Fluorescence-activated cell sorter (FACS) analyses revealed a rapid downmodulation of CD83 surface expression within 6 to 8 h after HSV-1 infection, in a manner strictly dependent on viral gene expression. Soluble CD83 enzyme-linked immunosorbent assays, together with Western blot analysis, demonstrated that CD83 rapidly disappears from the cell surface after contact with HSV-1 by a mechanism that involves protein degradation rather than shedding of CD83 from the cell surface into the medium. Infection experiments with an ICP0 deletion mutant demonstrated an important role for this viral immediate-early protein during CD83 degradation, since this particular mutant strain leads to strongly reduced CD83 degradation. This hypothesis was further strengthened by cotransfection of plasmids expressing CD83 and ICP0 into 293T cells, which led to significantly reduced accumulation of CD83. In strong contrast, transfection of plasmids expressing CD83 and a mutant ICP0 defective in its RING finger-mediated E3 ubiquitin ligase function did not reduce CD83 expression. Inhibition of the proteasome, the cellular protein degradation machinery, almost completely restored CD83 surface expression during HSV-1 infection, indicating that proteasome-mediated degradation and HSV-1 ICP0 play crucial roles in this novel viral immune escape mechanism.
Construction and Characterization of a Full-Length Infectious Simian T-Cell Lymphotropic Virus Type 3 Molecular Clone
Authors: Chevalier Sébastien Alain , Walic Marine , Calattini Sara , Mallet Adeline , Prévost Marie-Christine , Gessain Antoine , Mahieux Renaud
Published: April 2007

Together with their simian T-cell lymphotropic virus (STLV) equivalent, human T-cell lymphotropic virus type 1 (HTLV-1), HTLV-2, and HTLV-3 form the primate T-cell lymphotropic virus (PTLV) group. Over the years, understanding the biology and pathogenesis of HTLV-1 and HTLV-2 has been widely improved by the creation of molecular clones. In contrast, so far, PTLV-3 experimental studies have been restricted to the overexpression of the
tax
gene using reporter assays. We have therefore decided to construct an STLV-3 molecular clone. We generated a full-length STLV-3 proviral clone (8,891 bp) by PCR amplification of overlapping fragments. This STLV-3 molecular clone was then transfected into 293T cells. Reverse transcriptase PCR experiments followed by sequence analysis of the amplified products allowed us to establish that both
gag
and
tax/rex
mRNAs were transcribed. Western blotting further demonstrated the presence of the STLV-3 p24

gag

protein in the cell culture supernatant from transfected cells. Transient transfection of 293T cells and of 293T-long terminal repeat-green fluorescent protein cells with the STLV-3 clone promoted syncytium formation, a hallmark of PTLV Env expression, as well as the appearance of fluorescent cells, also demonstrating that the Tax3 protein was expressed. Virus particles were visible by electron microscopy. These particles are infectious, as demonstrated by our cell-free-infection experiments with purified virions. All together, our data demonstrate that the STLV-3 molecular clone is functional and infectious. This clone will give us a unique opportunity to study in vitro the different pX transcripts and the putative presence of antisense transcripts and to evaluate the PTLV-3 pathogenicity in vivo.