bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiviral Susceptibility of Avian and Swine Influenza Virus of the N1 Neuraminidase Subtype
Authors: Stoner Terri D. , Krauss Scott , DuBois Rebecca M. , Negovetich Nicholas J. , Stallknecht David E. , Senne Dennis A. , Gramer Marie R. , Swafford Seth , DeLiberto Tom , Govorkova Elena A. , Webster Robert G.
Published: July 2010

Influenza viruses of the N1 neuraminidase (NA) subtype affecting both animals and humans caused the 2009 pandemic. Anti-influenza virus NA inhibitors are crucial early in a pandemic, when specific influenza vaccines are unavailable. Thus, it is urgent to confirm the antiviral susceptibility of the avian viruses, a potential source of a pandemic virus. We evaluated the NA inhibitor susceptibilities of viruses of the N1 subtype isolated from wild waterbirds, swine, and humans. Most avian viruses were highly or moderately susceptible to oseltamivir (50% inhibitory concentration [IC50], <5.1 to 50 nM). Of 91 avian isolates, 7 (7.7%) had reduced susceptibility (IC50, >50 nM) but were sensitive to the NA inhibitors zanamivir and peramivir. Oseltamivir susceptibility ranged more widely among the waterbird viruses (IC50, 0.5 to 154.43 nM) than among swine and human viruses (IC50, 0.33 to 2.56 nM). Swine viruses were sensitive to oseltamivir, compared to human seasonal H1N1 isolated before 2007 (mean IC50, 1.4 nM). Avian viruses from 2007 to 2008 were sensitive to oseltamivir, in contrast to the emergence of resistant H1N1 in humans. Susceptibility remained high to moderate over time among influenza viruses. Sequence analysis of the outliers did not detect molecular markers of drug-resistance (e.g., H275Y NA mutation [N1 numbering]) but revealed mutations outside the NA active site. In particular, V267I, N307D, and V321I residue changes were found, and structural analyses suggest that these mutations distort hydrophobic pockets and affect residues in the NA active site. We determined that natural oseltamivir resistance among swine and wild waterbirds is rare. Minor naturally occurring variants in NA can affect antiviral susceptibility.
Genetic Analyses of HIV-1
env
Sequences Demonstrate Limited Compartmentalization in Breast Milk and Suggest Viral Replication within the Breast That Increases with Mastitis
Authors: Gantt Soren , Carlsson Jacquelyn , Heath Laura , Bull Marta E. , Shetty Avinash K. , Mutsvangwa Junior , Musingwini Georgina , Woelk Godfrey , Zijenah Lynn S. , Katzenstein David A. , Mullins James I. , Frenkel Lisa M.
Published: July 2010

The concentration of human immunodeficiency virus type 1 (HIV-1) is generally lower in breast milk than in blood. Mastitis, or inflammation of the breast, is associated with increased levels of milk HIV-1 and risk of mother-to-child transmission through breastfeeding. We hypothesized that mastitis facilitates the passage of HIV-1 from blood into milk or stimulates virus production within the breast. HIV-1
env
sequences were generated from single amplicons obtained from breast milk and blood samples in a cross-sectional study. Viral compartmentalization was evaluated using several statistical methods, including the Slatkin and Maddison (SM) test. Mastitis was defined as an elevated milk sodium (Na
+
) concentration. The association between milk Na
+
and the pairwise genetic distance between milk and blood viral sequences was modeled using linear regression. HIV-1 was compartmentalized within milk by SM testing in 6/17 (35%) specimens obtained from 9 women, but all phylogenetic clades included viral sequences from milk and blood samples. Monotypic sequences were more prevalent in milk samples than in blood samples (22% versus 13%;
P
= 0.012), which accounted for half of the compartmentalization observed. Mastitis was not associated with compartmentalization by SM testing (
P
= 0.621), but Na
+
was correlated with greater genetic distance between milk and blood HIV-1 populations (
P
= 0.041). In conclusion, local production of HIV-1 within the breast is suggested by compartmentalization of virus and a higher prevalence of monotypic viruses in milk specimens. However, phylogenetic trees demonstrate extensive mixing of viruses between milk and blood specimens. HIV-1 replication in breast milk appears to increase with inflammation, contributing to higher milk viral loads during mastitis.
Identification of Novel MicroRNA-Like Molecules Generated from Herpesvirus and Host tRNA Transcripts
Authors: Reese Tiffany A. , Xia Jing , Johnson L. Steven , Zhou Xiang , Zhang Weixiong , Virgin Herbert W.
Published: July 2010

We applied deep sequencing technology to small RNA fractions from cells lytically infected with murine gammaherpesvirus 68 (γHV68) in order to define in detail small RNAs generated from a cluster of tRNA-related polycistronic structures located at the left end of the viral genome. We detected 10 new candidate microRNAs (miRNAs), six of which were confirmed by Northern blot analysis, leaving four as provisional. In addition, we determined that previously identified and annotated viral miRNA molecules were not necessarily represented as the most abundant sequence originating from a transcript. Based on these new small RNAs and previously reported γHV68 miRNAs, we were able to further describe and annotate the distinctive γHV68 tRNA-miRNA structures. We used this deep sequencing data and computational analysis to identify similar structures in the mouse genome and validated that these host structures also give rise to small RNAs. This reveals a possible convergent usage of tRNA/polymerase III (pol III) transcripts to generate small RNAs from both mammalian and viral genomes.
Alterations in the Immunogenic Properties of Soluble Trimeric Human Immunodeficiency Virus Type 1 Envelope Proteins Induced by Deletion or Heterologous Substitutions of the V1 Loop
Authors: Ching Lance , Stamatatos Leonidas
Published: July 2010

HIV-1 gp140 envelope immunogens express conserved epitopes that are targeted by broadly cross-reactive neutralizing antibodies, but they fail to elicit similar antibodies upon immunization. The poor immunogenicity of conserved epitopes on gp140 could be linked to the high immunogenicity of variable Env regions on such constructs. Previous studies have shown that the first hypervariable region (V1 loop) is immunogenic on soluble gp140s but elicits type-specific antibodies. To address issues related to the high immunogenicity of the V1 loop, two conceptually opposite approaches were tested. In the first approach, we eliminated the V1 loop from our gp140 construct and examined how V1 deletion altered the immunogenic properties of other Env regions. In the second approach, we took advantage of the high immunogenicity of the V1 loop and engrafted four diverse V1 loops onto a common gp140 Env “scaffold.” These four scaffolds were used as a cocktail of immunogens to elicit diverse anti-V1 antibodies, under the hypothesis that eliciting diverse anti-V1 antibodies would expand the neutralizing breadth of immune sera. Our study indicates that three of four heterologous V1 loops were immunogenic on the common Env backbone “scaffold,” but heterologous anti-V1 neutralizing responses were observed in only one case. Both types of V1 modification dampened the immunogenicity of the V3 loop, differentially altered the immunogenicity of the transmembrane gp41 subunit, and altered the relative immunogenicities of unknown Env regions, including potentially the CD4-binding site (CD4-bs) and trimer-specific targets, which elicited cross-reactive neutralizing antibodies but of limited breadth.
Role of N-Linked Glycosylation of the 5-HT
2A
Receptor in JC Virus Infection
Authors: Maginnis Melissa S. , Haley Sheila A. , Gee Gretchen V. , Atwood Walter J.
Published: July 2010

JC virus (JCV) is a human polyomavirus and the causative agent of the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). JCV infection of host cells is dependent on interactions with cell surface asparagine (N)-linked sialic acids and the serotonin 5-hydroxytryptamine
2A
receptor (5-HT
2A
R). The 5-HT
2A
R contains five potential N-linked glycosylation sites on the extracellular N terminus. Glycosylation of other serotonin receptors is essential for expression, ligand binding, and receptor function. Also, glycosylation of cellular receptors has been reported to be important for JCV infection. Therefore, we hypothesized that the 5-HT
2A
R N-linked glycosylation sites are required for JCV infection. Treatment of 5-HT
2A
R-expressing cells with tunicamycin, an inhibitor of N-linked glycosylation, reduced JCV infection. Individual mutation of each of the five N-linked glycosylation sites did not affect the capacity of 5-HT
2A
R to support JCV infection and did not alter the cell surface expression of the receptor. However, mutation of all five N-linked glycosylation sites simultaneously reduced the capacity of 5-HT
2A
R to support infection and altered the cell surface expression. Similarly, tunicamycin treatment reduced the cell surface expression of 5-HT
2A
R. Mutation of all five N-linked glycosylation sites or tunicamycin treatment of cells expressing wild-type 5-HT
2A
R resulted in an altered electrophoretic mobility profile of the receptor. Treatment of cells with PNGase F, to remove N-linked oligosaccharides from the cell surface, did not affect JCV infection in 5-HT
2A
R-expressing cells. These data affirm the importance of 5-HT
2A
R as a JCV receptor and demonstrate that the sialic acid component of the receptor is not directly linked to 5-HT
2A
R.
Inhibition of the Type I Interferon Response in Human Dendritic Cells by Dengue Virus Infection Requires a Catalytically Active NS2B3 Complex
Authors: Rodriguez-Madoz Juan R. , Belicha-Villanueva Alan , Bernal-Rubio Dabeiba , Ashour Joseph , Ayllon Juan , Fernandez-Sesma Ana
Published: July 2010

Dengue virus (DENV) is the most prevalent arthropod-borne human virus, able to infect and replicate in human dendritic cells (DCs), inducing their activation and the production of proinflammatory cytokines. However, DENV can successfully evade the immune response in order to produce disease in humans. Several mechanisms of immune evasion have been suggested for DENV, most of them involving interference with type I interferon (IFN) signaling. We recently reported that DENV infection of human DCs does not induce type I IFN production by those infected DCs, impairing their ability to prime naive T cells toward Th1 immunity. In this article, we report that DENV also reduces the ability of DCs to produce type I IFN in response to several inducers, such as infection with other viruses or exposure to Toll-like receptor (TLR) ligands, indicating that DENV antagonizes the type I IFN production pathway in human DCs. DENV-infected human DCs showed a reduced type I IFN response to Newcastle disease virus (NDV), Sendai virus (SeV), and Semliki Forest virus (SFV) infection and to the TLR3 agonist poly(I:C). This inhibitory effect is DENV dose dependent, requires DENV replication, and takes place in DENV-infected DCs as early as 2 h after infection. Expressing individual proteins of DENV in the presence of an IFN-α/β production inducer reveals that a catalytically active viral protease complex is required to reduce type I IFN production significantly. These results provide a new mechanism by which DENV evades the immune system in humans.
A Novel Model of Lethal Hendra Virus Infection in African Green Monkeys and the Effectiveness of Ribavirin Treatment
Authors: Rockx Barry , Bossart Katharine N. , Feldmann Friederike , Geisbert Joan B. , Hickey Andrew C. , Brining Douglas , Callison Julie , Safronetz David , Marzi Andrea , Kercher Lisa , Long Dan , Broder Christopher C. , Feldmann Heinz , Geisbert Thomas W.
Published: July 2010

The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are emerging zoonotic paramyxoviruses that can cause severe and often lethal neurologic and/or respiratory disease in a wide variety of mammalian hosts, including humans. There are presently no licensed vaccines or treatment options approved for human or veterinarian use. Guinea pigs, hamsters, cats, and ferrets, have been evaluated as animal models of human HeV infection, but studies in nonhuman primates (NHP) have not been reported, and the development and approval of any vaccine or antiviral for human use will likely require efficacy studies in an NHP model. Here, we examined the pathogenesis of HeV in the African green monkey (AGM) following intratracheal inoculation. Exposure of AGMs to HeV produced a uniformly lethal infection, and the observed clinical signs and pathology were highly consistent with HeV-mediated disease seen in humans. Ribavirin has been used to treat patients infected with either HeV or NiV; however, its utility in improving outcome remains, at best, uncertain. We examined the antiviral effect of ribavirin in a cohort of nine AGMs before or after exposure to HeV. Ribavirin treatment delayed disease onset by 1 to 2 days, with no significant benefit for disease progression and outcome. Together our findings introduce a new disease model of acute HeV infection suitable for testing antiviral strategies and also demonstrate that, while ribavirin may have some antiviral activity against the henipaviruses, its use as an effective standalone therapy for HeV infection is questionable.
Human APOBEC3G-Mediated Editing Can Promote HIV-1 Sequence Diversification and Accelerate Adaptation to Selective Pressure
Authors: Kim Eun-Young , Bhattacharya Tanmoy , Kunstman Kevin , Swantek Peter , Koning Fransje A. , Malim Michael H. , Wolinsky Steven M.
Published: July 2010

Human apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G, hereinafter referred to as A3G) is an innate virus restriction factor that inhibits human immunodeficiency virus type 1 (HIV-1) replication and induces excessive deamination of cytidine residues in nascent reverse transcripts. To test the hypothesis that this enzyme can also help generate viral sequence diversification and the evolution of beneficial viral variants, we have examined the impact of A3G on the acquisition of (−)2′,3′-dideoxy-3′-thiacytidine (3TC) resistance
in vitro
. That characteristic resistance mutations are rapidly fixed in the presence of A3G and 3TC suggests that A3G-mediated editing can be an important source of genetic variation on which natural selection acts to shape the structure of HIV-1 populations.
Winter Survival and Growth of Chondrus crispus in Onshore Culture Tanks
Authors: Shacklock Peter F. , Craigie James S.
Published: July 2010

Commercial aquaculture of Chondrus crispus in eastern Canada required the development of reliable methods for ensuring the winter survival of a healthy, vegetative inoculum. Two procedures were investigated. Agitated cultures of C. crispus (stocking density <6 kg∙m−2) in running seawater grew at average rates of 0.21–0.34 kg∙m−2∙wk−1 during two winters under natural irradiance. Cultures maintained in undisturbed, outdoor tanks of seawater over three winters showed little or no net production; however, survival was excellent provided that the stocking density remained below approximately 10 kg∙m−2. The plants were capable of resuming growth when environmental conditions improved. We found no difference in the responses of the several haploid and diploid isolates examined. Large vegetative inocula required for commercial aquaculture can be maintained simply and reliably in tanks of clean seawater if they are undisturbed and an ice cover is allowed to form.
Environmental and Parental Influences on Age at Maturity in Sockeye Salmon (Oncorhynchus nerka) from the Fraser River, British Columbia
Authors: Peterman Randall M. , Bradford Michael J. , Anderson Judith L.
Published: July 2010

Commercial fisheries possess the potential for applying strong selection on size or age at maturity in the populations they exploit. It is therefore important to know the extent to which these traits are inherited. We examined regressions of the mean age at maturity of cohorts of offspring on the mean ages of the female and male spawners which produced them for four populations of sockeye salmon (Oncorhynchus nerka) from the Fraser River, British Columbia. Unlike previous researchers, we found that neither genetic nor maternal effects are important, relative to environmental variables, in influencing year-to-year variation in age at maturity in these stocks. The differences between our findings and earlier ones are due to a longer data series and more complete population statistics than were available previously. We further analyzed the age structure of the Adams River population, which has a cyclic pattern of abundance. Fluctuating population density appeared to account for variation in age structure among cycle years in the Adams stock. We concluded that serious concerns about the long-term effects of size-selective fishing on mean age at maturity are probably not warranted for Fraser River sockeye.
Does Algal–Bacterial Phosphorus Partitioning Vary Among Lakes? A Comparative Study of Orthophosphate Uptake and Alkaline Phosphatase Activity in Freshwater
Authors: Currie David J. , Bentzen Ellen , Kalff Jacob
Published: July 2010

In order to distinguish the activity of phytoplankton and bacterioplankton in 13 lakes of widely varying trophy, we size-fractionated orthophosphate uptake and alkaline phosphatase activity. In most lakes, orthophosphate uptake was consistently and overwhelmingly associated with the smallest particles. Based upon indicators of algal and bacterial presence in each size class, we inferred that the bacterioplankton are responsible for ≥95% of the orthophosphate uptake in situ, except in lakes that are not phosphorus-deficient. In contrast, a large portion of the alkaline phosphatase activity was free in solution (median 46%), and much of the remainder (median 44%) was apparently associated with algae.
Microbial Recycling of Phytopiankton Phosphorus
Authors: Pinto Joseph V. De , Young Thomas C. , Bonner James S. , Rodgers Paul W.
Published: July 2010

The remineralization of phytoplankton-bound phosphorus subsequent to nonpredatory phytopiankton mortality represents a significant source of algal-available phosphorus in many lakes. A unique experimental apparatus (A Dual Culture Diffusion Apparatus) was used to measure the rate and extent of this process and to elucidate some of the governing factors. It was demonstrated that this process is strongly influenced by heterotrophic decomposer activity, because phosphorus regeneration rates were less than 0.01/d for cultures not inoculated with a decomposer community, while they were two to five times higher for decomposer-inoculated cultures. In addition to the character and activity of the microbial decomposer community, the phytoplankton cell phosphorus content was shown to be a significant factor in the rate of phosphorus regeneration for a given cell decay rate. Cell phosphorus above the minimum cell quota appeared to be released in an available form quite rapidly upon algal death and lysis.
Dynamics of Lake Michigan Natural Phytoplankton Communities in Continuous Cultures Along a Si:P Loading Gradient
Authors: Kilham Susan Soltau
Published: July 2010

The hypothesis that phytoplankton species assort themselves along resource ratio gradients according to their relative competitive abilities for the potentially limiting resources was tested using natural communities from Lake Michigan. Algae were grown in six continuous cultures for 46 d on a gradient consisting of four silicon to phosphorus (Si:P) loading ratios: 313:1 (two cultures), 71:1, 4.6:1, and 0.9:1 (two cultures). Diatoms were the superior competitors for P and dominated the three high Si: P ratio cultures at steady state. Green algae dominated the three low Si: P ratio cultures. The two cultures at Si: P = 313 were very similar and were dominated by the diatom Synedra filiformis. Stable coexistence was demonstrated at Si: P = 71, where S. filiformis and Diatoma elongatum co-occurred. The three low Si: P ratio cultures were dominated by a green unicell. Six common species, including the three dominant species, were isolated and tested for their ability to grow under limitation by Si and P. Trade-offs in competitive ability predicted from continuous culture results were confirmed. Species were ranked in competitive ability for Si as follows: the green unicell and the green alga Monoraphidium contortion (with no Si requirements) were better than D. elongatum and Asterionella formosa, which were better than S. filiformis and Fragilaria crotonensis. The ranking for P was exactly the opposite. Results illustrate that phytoplankton natural community continuous cultures provide a method for evaluating potential changes in community structure resulting from long-term changes in loading ratios of resources.
A Radiotracer Study of Phosphorus Cycling in a Eutrophic Canadian Shield Lake, Lake 227, Northwestern Ontario
Authors: Levine S. N. , Stainton M. P. , Schindler D. W.
Published: July 2010

Phosphoric acid labelled with32P was added to the epilimnion of experimentally eutrophied Lake 227, northwestern Ontario, in August 1978 to trace the lake's phosphorus cycle during late stratification and fall overturn. Radiophosphate was incorporated into bacteria and microphytoplankton (<10 μm in diameter) within minutes of introduction. Thereafter, the bulk of32P exchange was between the microplankton, which typically held >90% of32P, dissolved phosphate, and a mobile subcompartment of "dissolved organic" phosphorus. Phytoplankton >10 μm in diameter and zooplankton acquired32P label very slowly and contained <5% of the radiotracer. In addition, about half of dissolved organic phosphorus failed to acquire a32P label over 17 d of incubation, indicating that this phosphorus may be functionally inert, at least at the time scale of biological phosphorus exchange. Movement of32P to the littoral zone of Lake 227 was much slower than in lakes with well-developed macrophyte communities, but losses to deep sediments were similar, about 2% of32P per day. Particles settled through the hypolimnion at a modal velocity of 28 cm∙d−1, losing 10% or less of their32P during descent. Most of the released phosphorus was reincorporated into particles and sedimented. Less than 1% of the32P that entered the hypolimnion in particles between August and October remained in the hypolimnion in late October.32P release from Lake 227′s hypolimnetic sediments during late summer and fall of 1978 was <5% of the32P that sedimented.
Phosphorus Enrichment, Silica Utilization, and Biogeochemical Silica Depletion in the Great Lakes
Authors: Schelske Claire L. , Stoermer Eugene F. , Fahnenstiel Gary L. , Haibach Mark
Published: July 2010

Our hypothesis that silica (Si) depletion in Lake Michigan and the severe Si depletion that characterizes the lower Great Lakes were induced by increased phosphorus (P) inputs was supported by bioassay experiments showing increased Si uptake by diatoms with relatively small P enrichments. We propose that severe Si depletion (Si concentrations being reduced to ≤0.39 mg SiO2∙L−1prior to thermal stratification) results when P levels are increased to the extent that increased diatom production reduces Si concentrations to limiting levels during the thermally mixed period. Large P enrichments such as those that characterized the eastern and central basis of Lake Erie and Lake Ontario in the early 1970s are necessary to produce severe Si depletion. It is clear that severe Si depletion in the lower lakes was produced by P enrichment because inflowing waters from Lake Huron have smaller P concentrations and larger Si concentrations than the outflowing waters of either Lake Erie or Lake Ontario. Severe Si depletion probably began in the 1940s or 1950s as the result of increased P loads from expanded sewering of an increasing urban population and the introduction of phosphate detergents. The model proposed for biogeochemical Si depletion is consistent with previous findings of high rates of internal recycling because, under steady-state conditions for Si inputs, any increase in diatom production will produce an increase in permanent sedimentation of biogenic Si provided some fraction of the increased biogenic Si production is not recycled or unless there is a compensating increase in dissolution of diatoms.
El Niño, Interannual Variability and Fisheries in the Northeast Pacific Ocean
Authors: Mysak Lawrence A.
Published: July 2010

In this review I describe the oceanic and atmospheric observations, physical mechanisms, and theories associated with El Niño – Southern Oscillation (ENSO) warming episodes in the tropical Pacific, and critically examine the means by which these anomalous events are believed to produce unusual conditions in the northeast Pacific. However, not all tropical ENSO episodes have a noticeable effect at higher latitudes. Also, because of anomalous local atmospheric forcing, significant warmings, strong coastal currents, and high sea levels along the west coast of North America can occur in years during which there are no tropical ENSO episodes. The possible impacts of ENSO-induced changes and of other interannual fluctuations in the northeast Pacific on various fisheries are described. Such impacts include changes in the migration routes of the bluefin tuna (Thunnus thynuus) and Fraser River sockeye salmon (Oncorhynchus nerka), increases in the Pacific herring (Clupea pallasi) recruitment, earlier return times for the Bristol Bay sockeye salmon, and increases in the weight of mature Fraser River sockeye several years after a local warming event.
Surprising roles for phospholipid binding proteins revealed by high throughput geneticsThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.
Authors: LeBlanc Marissa A. , McMaster Christopher R.
Published: July 2010

Saccharomyces cerevisiae remains an ideal organism for studying the cell biological roles of lipids in vivo, as yeast has phospholipid metabolic pathways similar to mammalian cells, is easy and economical to manipulate, and is genetically tractable. The availability of isogenic strains containing specific genetic inactivation of each non-essential gene allowed for the development of a high-throughput method, called synthetic genetic analysis (SGA), to identify and describe precise pathways or functions associated with specific genes. This review describes the use of SGA to aid in elucidating the function of two lipid-binding proteins that regulate vesicular transport, Sec14 and Kes1. Sec14 was first identified as a phosphatidylcholine (PC) – phosphatidylinositol (PI) transfer protein required for viability, with reduced Sec14 function resulting in diminished vesicular transport out of the trans-Golgi. Although Sec14 is required for cell viability, inactivating the KES1 gene that encodes for a member of the oxysterol binding protein family in cells lacking Sec14 function results in restoration of vesicular transport and cell growth. SGA analysis identified a role for Kes1 and Sec14 in regulating the level and function of Golgi PI-4-phosphate (PI-4-P). SGA also determined that Sec14 not only regulates vesicular transport out of the trans-Golgi, but also transport from endosomes to the trans-Golgi. Comparing SGA screens in databases, coupled with genetic and cell biological analyses, further determined that the PI-4-P pool affected by Kes1 is generated by the PI 4-kinase Pik1. An important biological role for Sec14 and Kes1 revealed by SGA is coordinate regulation of the Pik1-generated Golgi PI-4-P pool that in turn is essential for vesicular transport into and out of the trans-Golgi.
The inhibitory effect of celecoxib on mouse hepatoma H22 cell line on the arachidonic acid metabolic pathwayThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.
Authors: Xu Zhigang , Zhang Ming , Lv Xiaoyan , Xiang Dan , Zhang Xuewen , Chen Li
Published: July 2010

Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX-2). It may reduce the risk of cancer formation by affecting the metabolism of arachidonic acid (AA), which has been implicated in the development of cancer. Accordingly, this study was designed to determine the effects of celecoxib on the AA pathway in mouse hepatoma H22 cells. Celecoxib was found to inhibit the proliferation of H22 cells in a dose- and time-dependent manner. Low doses (50 and 100 µmol·L–1) of celecoxib caused an increase in the expression of cytosolic phospholipase A2 (cPLA2), but did not affect the expression of COX-2 in terms of the mRNA and protein levels. Surprisingly, the amount of AA was elevated and the level of prostaglandin E2 (PGE2) was unaltered in the culture supernatant. At higher celecoxib doses (200 and 400 µmol·L–1), the mRNA and protein of both COX-2 and cPLA2 were inhibited. The concentration of AA was increased, and PGE2 level was depressed in H22 cells. The ratio of AA to PGE2 was increased in a dose-dependent manner. Our findings suggest that the imbalance between AA and PGE2, characterized by increased AA at a low dosage and decreased PGE2 at a high dosage of celecoxib, was an important indicator of cytotoxicity of celecoxib on H22 cells.
Effects of leptin on the expression of α1 (I) collagen gene in human osteoblast-like MG63 cellsThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.
Authors: Peng Mian , Chen Shu , Fang Weiqiang , Yu Xuetao
Published: July 2010

The objective of this study was to examine the effects of leptin on alpha (α) 1 (I) collagen gene expression in a human osteoblast-like MG63 cell line. MG63 cells were incubated with different doses of leptin (10−8, 10−7, and 10−6 mol·L–1) for 24, 48, and 72 h. α1 (I) collagen gene expression in MG63 cells was detected by real-time fluorescence quantitative polymerase chain reaction (FQ-PCR), with 17β-estradiol (17β-E2) as the positive control. Expression of the α1 (I) collagen gene, regulated by leptin, was dose and time dependent, with maximal expression in the 10−7 mol·L–1 group at 72 h of incubation. As a positive control, 17β-E2 reached its maximal effect in the 10−7mol·L–1 group at 24 h. We conclude that leptin has the ability to up-regulate α1 (I) collagen gene expression in MG63 cells, with a more potent effect but a less rapid response than 17β- E2.
Calorie restriction on insulin resistance and expression of SIRT1 and SIRT4 in ratsThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.
Authors: Chen Yong-Ru , Fang Shi-Rong , Fu Yu-Cai , Zhou Xiao-Hui , Xu Ming-Yan , Xu Wen-Can
Published: July 2010

The sirtuin proteins are nicotinamide adenine dinucleotide dependent deacetylases and adenosine diphosphate (ADP)-ribosyl transferases associated with metabolic balance and lifespan extension. Sirtuin 1 (SIRT1) and sirtuin 4 (SIRT4) have been reported to regulate insulin secretion, but their association with the development of insulin resistance and nonalcoholic fatty liver disease remain undefined. The aim of this study was to determine the expression of SIRT1 and SIRT4 in the liver and pancreas of rats fed with different diets and analyze the association of these proteins with insulin resistance and nonalcoholic fatty liver disease. Male Sprague–Dawley rats were randomly divided into the following 4 diet treatment groups: normal control (NC), calorie restriction (CR), high-fat (HFa), and high-fructose (HFr), and these groups were maintained for 12 weeks. Blood biochemical analysis and histopathology indicated that HFa and HFr groups were insulin resistant and developed nonalcoholic fatty livers. SIRT1 was present in the nucleus and cytoplasm of the pancreatic β-cells, while SIRT4 was located in the cytoplasm. Treatment with the CR diet increased the expression of SIRT1 in both the pancreas and liver, while treatment with the HFa and HFr diets caused a decrease. SIRT4 was upregulated in the liver of rats treated with the HFa diet, but did not change with the CR diet treatment. These data suggest that SIRT1 and SIRT4 were both involved in the development of insulin resistance and nonalcoholic fatty liver disease.
Effects of plant polyphenols on ovarian follicular reserve in aging ratsThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.
Authors: Chen Zhen-Guo , Luo Li-Li , Xu Jin-Jie , Zhuang Xiao-Lan , Kong Xiao-Xia , Fu Yu-Cai
Published: July 2010

The pool of ovarian primordial follicles is established during embryonic development or at birth. During the development from primordial to primary, secondary, and antral follicles, only a small portion of follicles can mature and successfully ovulate; the others are destined to degenerate through apoptotic or atretic loss. As aging advances, females ultimately enter the cessation phase of the estrous cycle and are no longer capable of fertilization. The presumption is that if we can slow down the process of folliculogenesis or decrease follicle loss, females may have a larger ovarian follicular reserve and a longer reproductive lifespan. In our study, rats underwent intragastric administration with tea polyphenols, quercetin (meletin), genistein, or resveratrol, once a day for 4 months (from age 12 to 15 months), to test whether they have positive effects on follicular reserve or ovarian functions. The results showed that rats treated with tea polyphenols (27.8 ± 3.2) and quercetin (36.5 ± 4.1) had a comparable number of healthy follicles to those of controls (26.9 ± 3.8), although significantly fewer atretic follicles were observed in the tea polyphenol group (43.4 ± 5.9 vs 79.7 ± 7.5; p < 0.001). Remarkably, both genistein- and resveratrol-treated rats had more healthy follicles (respectively, 42.8 ± 3.9, p < 0.05; and 51.9 ± 6.4, p < 0.001) and fewer atretic follicles (respectively, 58.4 ± 8.0, p < 0.05; and 51.0 ± 6.2, p < 0.01) than controls. These results indicate that genistein and resveratrol can increase the ovarian follicular reserve and prolong the ovarian lifespan in rats, and their positive effects may be not only due to their intervention in the transition from primordial to primary follicle, but also due to the inhibiting effect on follicular atresia.
Chronic effects of venlafaxine on synaptophysin and neuronal cell adhesion molecule in the hippocampus of cerebral ischemic miceThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.
Authors: Fang Shaokuan , Yan Bin , Wang Daoyi , Bi Xiaoying , Zhang Yanbo , He Jue , Xu Haiyun , Yang Yi , Kong Jiming , Wu Jiang , Li Xin-Min
Published: July 2010

Venlafaxine, a novel antidepressant, inhibits serontonin and norepinephrine reuptake in the presynaptic cleft. Unlike typical selective serontonin reuptake inhibitors (SSRIs), venlafaxine may have modulatory effects on nerve terminals and neuronal plasticity. Our preliminary data found that 5 mg·kg–1·d–1 of venlafaxine treatment prevented decreased synaptophysin (SYP) in the hippocampus, which results from chronic restrained stress in the rat model. The present study investigates whether venlafaxine regulates alterations of synaptophysin and neuronal cell adhesion molecule (NCAM) in a post-stroke depression mouse model. We compared the expression level of SYP and NCAM in the hippocampus of global cerebral ischemic (GCI) mice treated with different doses of venlafaxine using immunohistological and Western blot analysis. Pre-treatment with intraperitoneal injection of venlafaxine (2.5 and 5.0 mg·kg–1·d–1) for 14 days significantly prevented the decrease of SYP in the hilus area of the hippocampus in vehicle-treated GCI mice. NCAM was significantly higher in the hippocampus of vehicle-treated GCI mice, and pretreatment with venlafaxine prevented alterations of NCAM, with the high-dose venlafaxine group comparable with vehicle-sham mice. The results suggest the alteration of neuronal remodeling proteins in the hippocampus may be an underlying mechanism of venlafaxine in treating post-stroke depression.
Bronchogenic and alveologenic tumors in mice induced byN-nitrosopiperidineThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.
Authors: Xie Xiao-Yuan , Shen Jian , Xu Li-Yan , Li En-Min , Shen Zhong-Ying
Published: July 2010

The aim of this study was to explore the histogenesis and carcinogenesis of pulmonary cancer induced by N-nitrosopiperidine (NPIP) in mice. NPIP is a form of N-nitrosamine found in tobacco smoke, which has been shown to be a genotoxic chemical as well as a mutagenic compound for inducing chromosome aberrations and severe clastogenicity. In this study, 80 BALB/C strain mice were injected with 0.2 mmol/kg NPIP intraperitoneally for 8 weeks, and experiments were conducted for a further 16 weeks. For the control group, 40 mice were injected with an equal volume of 0.9% NaCl. Pulmonary tissues and tumors in the NPIP-treated group were examined by light microscopy and transmission electron microscopy and compared with the control group at 4-week intervals. The mRNA levels of p53 (mutant), bcl-2, c-myc, ras, and subunits of telomerase — telomerase reverse transcriptase (TERT) and an RNA component, TR — were assayed by mPCR or RT–PCR. Twenty-two mice in the experimental group were found to develop pulmonary tumors, but none in the control group. All tumors found in the experimental group originated from alveolar type II epithelial cells. In addition, 6 of the 22 mice also developed tumors of bronchogenic origin. The expression of p53, bcl-2, c-myc, ras, and the subunits of telomerase were found to increase in all pulmonary tissues and tumors formed thereafter upon NPIP treatment. In summary, NPIP-induced mouse lung tumors exhibited morphological changes during carcinogenesis, which may be the consequence of overexpression of some genes associated with the development of carcinoma and changes in subunits of telomerase. This mouse model of lung tumor formation may be a useful tool to delineate the histogenesis and carcinogenesis of human pulmonary cancer.
Endocrine cells of the adenohypophysis in severe acute respiratory syndrome (SARS)This paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.
Authors: Wei Lan , Sun Shen , Zhang Jing , Zhu Hong , Xu Yun , Ma Qiang , McNutt Michael A. , Korteweg Christine , Gu Jiang
Published: July 2010

It is known that severe acute respiratory syndrome (SARS), a severe infectious illness, which caused an epidemic in Asia in 2003, has extensive and complex effects on human organ systems. It has been reported that the serum levels of prolactin (PRL), follicle stimulating hormone (FSH), and luteinizing hormone (LH) of SARS patients are significantly higher than those of control groups, while estradiol (E2), pregnancy hormone (P), and thyroid stimulating hormone (TSH) are considerably lower than those of normal controls. This phenomenon suggests that the adenohypophyseal endocrine cells in SARS patients may be damaged. However, up to now there has been no direct histological investigation on the endocrine cells of patients’ pituitary. Here we investigated the endocrine cells in the adenohypophysis obtained from autopsies of 5 SARS patients. The immunohistochemistry and quantitative image results showed that compared with control cases, both the number of positive cells and the staining intensity of immunoreactivity for growth hormone, TSH, and adrenocorticotrophic hormone in these cells were remarkably decreased, while that of PRL, FSH, and LH were significantly increased in all SARS cases studied. These findings indicated that alterations occurred in the patients’ adenohypophyseal endocrine cells, and these changes were consistent with the serum levels of relevant endocrine hormones reported previously. It appears that changes in these endocrine cells and their hormones are affected by the severity of this new infectious disease.
Le kétoconazole antagonise les effets immuno-gonadotropes au test de la nage forcée chez le rat mâle Wistar
Authors: Frih Hacène , Djenidi Réda , Ali Rachedi Bachir , Frih  Nabila , Tahraoui Abdelkrim , Bairi Abdel Majid
Published: July 2010

On a souvent rapporté que la dépression s’installe suite à des perturbations des activités de l’axe corticotrope et du système immunitaire. L’objectif de cette étude était d’explorer les effets du kétoconazole, un dérivé d’imidazole, inhibiteur de la stéroïdogénèse gonadique et surrénalienne, sur les variations du nombre de leucocytes totaux et des pourcentages de sous-populations leucocytaires, au cours de la nage forcée chez le rat (test de Porsolt), un test consiste à tester l’efficacité des antidépresseurs. Des cathéters ont été implantés, sous anesthésie générale, dans la carotide droite, et des prises de sang (0,2 mL) ont été réalisées à des intervalles de 15 min au cours de l’expérimentation, alors que les animaux pouvaient se comporter librement. Les degrés d’anxiété et d’activité locomotrice des rats ont été mesurés au labyrinthe en croix surélevée et au test des champs ouverts. La nage forcée a provoqué des fluctuations du système immunitaire et de la testostéronémie, lesquelles qui ont été inhibées suite au traitement des animaux au kétoconazole. Cet effet a été obtenu également sur le plan comportemental (labyrinthe en croix surélevée, nage forcée) dans le sens d’une amélioration (effets anxiolytique et antidépresseur). Ces résultats suggèrent que les réponses comportementales et physiologiques sont inter-reliées d’une manière multifactorielle et que la corticostérone joue un rôle clé dans la pathogénie des maladies psychiatriques.
The chemical ecology and evolution of bee–flower interactions: a review and perspectivesThe present review is one in the special series of reviews on animal–plant interactions.
Authors: Dötterl S. , Vereecken N. J.
Published: July 2010

Bees and angiosperms have shared a long and intertwined evolutionary history and their interactions have resulted in remarkable adaptations. Yet, at a time when the “pollination crisis” is of major concern as natural populations of both wild and honey bees ( Apis mellifera L., 1758) face alarming decline rates at a worldwide scale, there are important gaps in our understanding of the ecology and evolution of bee–flower interactions. In this review, we summarize and discuss the current knowledge about the role of floral chemistry versus other communication channels in bee-pollinated flowering plants, both at the macro- and micro-evolutionary levels, and across the specialization–generalization gradient. The available data illustrate that floral scents and floral chemistry have been largely overlooked in bee–flower interactions, and that pollination studies integrating these components along with pollinator behaviour in a phylogenetic context will help gain considerable insights into the sensory ecology and the evolution of bees and their associated flowering plants.
Variation in natural plant products and the attraction of bodyguards involved in indirect plant defenseThe present review is one in the special series of reviews on animal–plant interactions.
Authors: Mumm Roland , Dicke Marcel
Published: July 2010

Plants can respond to feeding or egg deposition by herbivorous arthropods by changing the volatile blend that they emit. These herbivore-induced plant volatiles (HIPVs) can attract carnivorous natural enemies of the herbivores, such as parasitoids and predators, a phenomenon that is called indirect plant defense. The volatile blends of infested plants can be very complex, sometimes consisting of hundreds of compounds. Most HIPVs can be classified as terpenoids (e.g., (E)-β-ocimene, (E,E)-α-farnesene, (E)-4,8-dimethyl-1,3,7-nonatriene), green leaf volatiles (e.g., hexanal, (Z)-3-hexen-1-ol, (Z)-3-hexenyl acetate), phenylpropanoids (e.g., methyl salicylate, indole), and sulphur- or nitrogen-containing compounds (e.g., isothiocyanates or nitriles, respectively). One highly intriguing question has been which volatiles out of the complex blend are the most important ones for the carnivorous natural enemies to locate "suitable host plants. Here, we review the methods and techniques that have been used to elucidate the carnivore-attracting compounds. Electrophysiological methods such as electroantennography have been used with parasitoids to elucidate which compounds can be perceived by the antennae. Different types of elicitors and inhibitors have widely been applied to manipulate plant volatile blends. Furthermore, transgenic plants that were genetically modified in specific steps in one of the signal transduction pathways or biosynthetic routes have been used to find steps in HIPV emission crucial for indirect plant defense. Furthermore, we provide an overview on biotic and abiotic factors that influence the emission of HIPVs and how this can affect the interactions between members of different trophic levels. Consequently, we review the progress that has been made in this exciting research field during the past 30 years since the first studies on HIPVs emerged and we highlight important issues to be addressed in the future.
Landslide mechanisms in Hong Kong
Authors: Hencher S. R. , Lee S. G.
Published: July 2010

This paper reviews the nature and mechanics of landslides in the weathered terrain of Hong Kong. The vast majority of landslides are very shallow (a few metres depth) and occur during intense rainstorms. Deeper-seated landslides, in contrast, may occur days or weeks after intense rainstorms. The time of occurrence of landslides can be linked to hydrological and hydrogeological factors, and a hydrogeological grouping of landslide mechanisms is introduced related to timing in a storm. A relationship is presented that links intensity of landsliding to 24 h rainfall. The gradual deterioration and internal erosion of slopes prior to detachment is discussed and allows some realistic opportunity for identifying progressive major landslides. In particular, the growth of natural piping systems and infilling of dilated fracture networks are recommended as important indicators of landslide development. The conclusions are supported by case examples of slope failures, the study of some of which has been taken to a forensic level.
Optimizing IT process management
Authors: Tony Lee Tony
Published: July 2010

In this paper, the author discusses some key concepts in IT process management. The paper also includes the recommendations in these following aspects: team organization, physical environment, project selection, politics, organizational communication, development environment, staff development, and organizational culture.