bluuebunny/crossref_metadata_2025 huggingface dataset:
An Electronic Bus Bar Lies in the Core of Cytochrome bc
1
Authors: Świerczek Monika , Cieluch Ewelina , Sarewicz Marcin , Borek Arkadiusz , Moser Christopher C. , Dutton P. Leslie , Osyczka Artur
Published: July 2010

Heme Communication Revealed by Asymmetry

An electronic bus bar is an electrical conductor that connects several circuits.

Świerczek
et al.

(p.
451
) now find that a similar strategy is used by the protein cytochrome bc
1
that plays a central role in cellular respiration and photosynthesis. Protein engineering was used to break the symmetry of a cytochrome bc
1
homodimer, which revealed that the dimer is bridged by electron transfer between two hemes. This allows electrons to move freely within and between dimers to distribute between four catalytic sites.
Inhalational Botulism in Rhesus Macaques Exposed to Botulinum Neurotoxin Complex Serotypes A1 and B1
Authors: Sanford Daniel C. , Barnewall Roy E. , Vassar Michelle L. , Niemuth Nancy , Metcalfe Karen , House Robert V. , Henderson Ian , Shearer Jeffry D.
Published: July 2010

A recombinant botulinum vaccine (rBV A/B) is being developed for protection against inhalational intoxication with botulinum neurotoxin (BoNT) complex serotype A, subtype A1 (BoNT/A1), and BoNT serotype B, subtype B1 (BoNT/B1). A critical component for evaluating rBV A/B efficacy will be the use of animal models in which the pathophysiology and dose-response relationships following aerosol exposure to well-characterized BoNT are thoroughly understood and documented. This study was designed to estimate inhaled 50% lethal doses (LD
50
) and to estimate 50% lethal exposure concentrations relative to time (LCt
50
) in rhesus macaques exposed to well-characterized BoNT/A1 and BoNT/B1. During the course of this study, clinical observations, body weights, clinical hematology results, clinical chemistry results, circulating neurotoxin levels, and telemetric parameters were documented to aid in the understanding of disease progression. The inhaled LD
50
and LCt
50
for BoNT/A1 and BoNT/B1 in rhesus macaques were determined using well-characterized challenge material. Clinical observations were consistent with the recognized pattern of botulism disease progression. A dose response was demonstrated with regard to the onset of these clinical signs for both BoNT/A1 and BoNT/B1. Dose-related changes in physiologic parameters measured by telemetry were also observed. In contrast, notable changes in body weight, hematology, and clinical chemistry parameters were not observed. Circulating levels of BoNT/B1 were detected in animals exposed to the highest levels of BoNT/B1; however, BoNT/A1 was not detected in the circulation at any aerosol exposure level. The rhesus macaque aerosol challenge model will be used for future evaluations of rBV A/B efficacy against inhalational BoNT/A1 and BoNT/B1 intoxication.
Molecular Epidemiological Evaluation of the Recent Resurgence in Mumps Virus Infections in Ireland
Authors: Carr Michael J. , Moss Eibhlín , Waters Allison , Dean Jonathan , Jin Li , Coughlan Suzie , Connell Jeff , Hall William W. , Hassan Jaythoon
Published: July 2010

Mumps is a vaccine-preventable disease; however, outbreaks have been reported in a number of countries with childhood immunization programs, particularly among young adults at the tertiary stage of education. We have retrospectively investigated the epidemiological, virological, and serological factors associated with mumps cases identified in Ireland from 2004 to 2009. Genetic analysis of mumps virus strain variability demonstrated that a single genotype, genotype G, was circulating, and it was also detected in cerebrospinal fluid samples obtained from patients with meningitis. We observed that younger individuals were disproportionately affected with neurological sequelae following mumps virus infection, and the average age of patients with mumps virus RNA detected in cerebrospinal fluid was 19.25 years (median, 19 years; range, 14 to 24 years). Our analysis showed a 4-fold rise in mumps cases in 2008-2009 and an increased incidence in infection in those ≥30 years of age. Over a 6-year period (2004 to 2009), a total of 7,805 serum samples were investigated; of this number, 1,813 (23%) were positive for mumps virus-specific IgM. We observed a strong bias for acute mumps virus infection in males compared to females (
P
< 10
−32
) that was independent of vaccination status.
Specific, Sensitive, and Rapid Diagnosis of Active Toxoplasmosis by a Loop-Mediated Isothermal Amplification Method Using Blood Samples from Patients
Authors: Lau Yee Ling , Meganathan Puviarasi , Sonaimuthu Parthasarathy , Thiruvengadam Girija , Nissapatorn Veeranoot , Chen Yeng
Published: July 2010

Loop-mediated isothermal amplification (LAMP), a rapid nucleic acid amplification method, was developed for the clinical diagnosis of toxoplasmosis. Three LAMP assays based on the
SAG1
,
SAG2
, and
B1
genes of
Toxoplasma gondii
were developed. The sensitivities and specificities of the LAMP assays were evaluated by comparison with the results of conventional nested PCR. The LAMP assays were highly sensitive and had a detection limit of 0.1 tachyzoite, and no cross-reactivity with the DNA of other parasites was observed. Blood was collected from 105 individuals to test the LAMP assays: 40 patients with active toxoplasmosis, 40 negative controls, and 25 patients with other parasitic infections. The
SAG2
-based LAMP (
SAG2
-LAMP) had a greater sensitivity (87.5%) than the
SAG1
-LAMP (80%),
B1
-LAMP (80%), and nested PCR (62.5%). All the LAMP assays and nested PCR were 100% specific. This is the first report of a study which applied the LAMP method to diagnose toxoplasmosis from human blood samples. Due to its simplicity, sensitivity, and specificity, LAMP is suggested as an appropriate method for routine diagnosis of active toxoplasmosis in humans.
Ability of
Bacillus cereus
Group Strains To Cause Food Poisoning Varies According to Phylogenetic Affiliation (Groups I to VII) Rather than Species Affiliation
Authors: Guinebretière Marie-Hélène , Velge Philippe , Couvert Olivier , Carlin Frédéric , Debuyser Marie-Laure , Nguyen-The Christophe
Published: July 2010

Cytotoxic activity levels of culture filtrates and toxin distributions varied according to the phylogenetic group (I to VII) within the
B
acillus
cereus
group, suggesting that these groups are of different clinical significance and are more suitable than species affiliations for determining food poisoning risk. A first-line, simple online tool (https://
www.tools.symprevius.org/Bcereus/english.php
) to assign strains to the different phylogenetic groups is presented.
The Viral Replication Complex Is Associated with the Virulence of Newcastle Disease Virus
Authors: Dortmans J. C. F. M. , Rottier P. J. M. , Koch G. , Peeters B. P. H.
Published: July 2010

Virulent strains of Newcastle disease virus ([NDV] also known as avian paramyxovirus type 1) can be discriminated from low-virulence strains by the presence of multiple basic amino acid residues at the proteolytic cleavage site of the fusion (F) protein. However, some NDV variants isolated from pigeons (pigeon paramyxovirus type 1 [PPMV-1]) have low levels of virulence, despite the fact that their F protein cleavage sites contain a multibasic amino acid sequence and have the same functionality as that of virulent strains. To determine the molecular basis of this discrepancy, we examined the role of the internal proteins in NDV virulence. Using reverse genetics, the genes encoding the nucleoprotein (NP), phosphoprotein (P), matrix protein (M), and large polymerase protein (L) were exchanged between the nonvirulent PPMV-1 strain AV324 and the highly virulent NDV strain Herts. Recombinant viruses were evaluated for their pathogenicities and replication levels in day-old chickens, and viral genome replication and plaque sizes were examined in cell culture monolayers. We also tested the contributions of the individual NP, P, and L proteins to the activity of the viral replication complex in an
in vitro
replication assay. The results showed that the replication proteins of Herts are more active than those of AV324 and that the activity of the viral replication complex is directly related to virulence. Although the M protein affected viral replication
in vitro
, it had only a minor effect on virulence.
Viral Mutation Rates
Authors: Sanjuán Rafael , Nebot Miguel R. , Chirico Nicola , Mansky Louis M. , Belshaw Robert
Published: July 2010

Accurate estimates of virus mutation rates are important to understand the evolution of the viruses and to combat them. However, methods of estimation are varied and often complex. Here, we critically review over 40 original studies and establish criteria to facilitate comparative analyses. The mutation rates of 23 viruses are presented as substitutions per nucleotide per cell infection (s/n/c) and corrected for selection bias where necessary, using a new statistical method. The resulting rates range from 10
−8
to10
−6
s/n/c for DNA viruses and from 10
−6
to 10
−4
s/n/c for RNA viruses. Similar to what has been shown previously for DNA viruses, there appears to be a negative correlation between mutation rate and genome size among RNA viruses, but this result requires further experimental testing. Contrary to some suggestions, the mutation rate of retroviruses is not lower than that of other RNA viruses. We also show that nucleotide substitutions are on average four times more common than insertions/deletions (indels). Finally, we provide estimates of the mutation rate per nucleotide per strand copying, which tends to be lower than that per cell infection because some viruses undergo several rounds of copying per cell, particularly double-stranded DNA viruses. A regularly updated virus mutation rate data set will be available at
www.uv.es/rsanjuan/virmut
.
Hyperphosphorylation of Histone Deacetylase 2 by Alphaherpesvirus US3 Kinases
Authors: Walters Matthew S. , Kinchington Paul R. , Banfield Bruce W. , Silverstein Saul
Published: July 2010

A serine/threonine (S/T) kinase encoded by the
US3
gene of herpes simplex virus type 1 (HSV-1) is conserved in varicella-zoster virus (VZV) and pseudorabies virus (PRV). Expression of US3 kinase in cells transformed with US3 expression plasmids or infected with each virus results in hyperphosphorylation of histone deacetylase 2 (HDAC2). Mapping studies revealed that each US3 kinase phosphorylates HDAC2 at the same unique conserved Ser residue in its C terminus. HDAC2 was also hyperphosphorylated in cells infected with PRV lacking US3 kinase, indicating that hyperphosphorylation of HDAC2 by PRV occurs in a US3-independent manner. Specific chemical inhibition of class I HDAC activity increases the plaquing efficiency of VZV and PRV lacking
US3
or its enzymatic activity, whereas only minimal effects are observed with wild-type viruses, suggesting that VZV and PRV US3 kinase activities target HDACs to reduce viral genome silencing and allow efficient viral replication. However, no effect was observed for wild-type or
US3
null HSV-1. Thus, we have demonstrated that while HDAC2 is a conserved target of alphaherpesvirus US3 kinases, the functional significance of these events is virus specific.
Interwoven Roles of Cyclin D3 and cdk4 Recruited by ICP0 and ICP4 in the Expression of Herpes Simplex Virus Genes
Authors: Kalamvoki Maria , Roizman Bernard
Published: July 2010

Elsewhere this laboratory reported that (i) ICP0 interacts with cyclin D3 but not D1 or D2. The 3 cyclins independently partially rescue ΔICP0 mutants. (ii) Interaction with cyclin D3 is required for the switch from nuclear to cytoplasmic accumulation of ICP0. (iii) In infected cells cdk4 is activated whereas cdk2 is not. Inhibition of cdk4 results in nuclear retention of ICP0. Overexpression of cyclin D3 reverses the effect of the inhibitor. Here we report the following. (i) cdk4 interacts with ICP0, ICP4, and possibly with ICP8. This interaction is required to recruit cdk4 initially to ND10 and later to the viral replication compartments. (ii) cdk4 inhibitor I reduced or delayed the transcription and ultimately translation of mRNAs of ICP4, ICP27, or ICP8 and to a lesser extent that of the ICP0 gene in wild-type virus-infected cells. (iii) Overexpression of cyclin D3 resulted in a more rapid transcription of these genes. In the presence of inhibitor, the rates of accumulation of the products of these genes resemble those of wild-type virus in the absence of inhibitor. (iv) Overexpression of cyclin D3 also results in mobilization of cdk6 in nuclei of infected cells. We conclude that ICP0 encodes a function that enhances the recruitment of cyclin D3 to ND10 structures to activate cdk4 and that ICP0 along with other viral proteins recruits cdk4 to ND10 structures and ultimately to replication compartments for enhanced expression of viral genes and viral DNA synthesis.
Reiteration in the short lived root-sprouting herbRorippa palustris: does the origin of buds matter?
Authors: Bartušková Alena , Klimešová Jitka
Published: July 2010

Regrowth of injured plants occurs from dormant meristems. Its success is known to be dependent on extrinsic factors, such as the severity of an injury and nutrient availability, although little is known about the effect of intrinsic factors. We conducted a growth-chamber experiment with the short-lived root-sprouting herb Rorippa palustris (L.) Besser, where we evaluated the role of bud origin on plant regrowth after disturbance. In particular, we investigated whether shoots sprouting from either axillary or adventitious buds differ in compensatory growth and architecture. We triggered resprouting from axillary versus adventitious buds by two levels of disturbance: (i) removal of the whole aboveground biomass, with axillary buds on the stem base and adventitious buds on roots left intact; and (ii) removal of whole aboveground biomass including axillary buds on the stem base, and only adventitious buds left intact. Despite the fact that the adventitious buds were larger and contained more leaf primordia than axillary buds at the time of disturbance, the latter preferentially resprouted when both types of buds were present. Both axillary and adventitious shoots compensated for lost aboveground biomass; nevertheless, only axillary shoots compensated for fruit production. Shoot reiteration after injury was only partial in both types of shoot; however, adventitious shoots in differed more in their architectural characteristics than axillary shoots did. We confirmed that the output of plant regeneration after disturbance depends also on intrinsic factors such as the origin of the buds.
Comparative Developmental Biology of Chum Salmon (Oncorhynchus keta) from the Fraser River, British Columbia
Authors: Beacham Terry D. , Murray Clyde B.
Published: July 2010

Eggs and alevins from 32 families of chum salmon (Oncorhynchus keta) from seven Fraser River stocks spawning at different times or in different tributaries were incubated in controlled water temperatures of 4, 8, and 12 °C. There were significant differences in egg and alevin survival among stocks and among families within stocks in the different incubation temperatures. Highest egg survival for a late-spawning Vedder River stock occurred at 4 °C, while egg survival from other stocks was highest at 8 °C. Late-spawning stocks had smaller eggs and earlier times of fry emergence than did early-spawning ones. There was no effect of spawning time on alevin hatching time. Alevins hatching at 8 °C were larger than those hatching at 4 or 12 °C, but there were no stock differences in alevin length or tissue weight. Stocks with greater egg sizes produced alevins of greater total weight. Fry emerging at 8 °C were larger than those emerging at 4 or 12 °C, and fry from early-spawning stocks were longer and had greater tissue weight than those from late-spawning ones. There were significant differences among families within stocks in size of alevins and fry, and family differences should be accounted for in studies of salmonid developmental biology.
Effects of Chronic Exposure to Sublethal pH on Growth, Egg Production, and Ovulation in Brook Trout, Salvelinus fontinalis
Authors: Tam W. H. , Payson P. D.
Published: July 2010

Hatchery-reared brook trout (Salvelinus fontinalis) were maintained in the laboratory at mean pH values of 7.34, 5.56, 5.16, and 4.48 from early February to early December. At pH 4.48, the mean growth rates of males were uniformly lowered during the entire experimental period. Among females, growth was inhibited during the first 5 mo, but their rate of weight gain recovered during the period of rapid oocyte development. At the end of the experiment, the body weights of both male and female fish in pH 5.16 and 4.48 were only 70.70–77.34% of the control fish at pH 7.34. Growth was not affected by exposure to pH 5.56. Rapid oocyte development occurred simultaneously over all pH groups in June, suggesting that the initiation of gametogenesis was not affected over the range of pH tested, the number of eggs produced was significantly correlated to body weight; consequently the number of eggs produced by the smaller pH 5.16–4.48 females was reduced. Ovulation was also significantly delayed in the acidic groups.
Changes in Mean Weight, Sea-Age Composition, and Catch-per-Unit-Effort of Atlantic Salmon (Salmo salar) Angled in the Godbout River, Quebec, 1859–1983
Authors: Bielak Alex T. , Power Geoffrey
Published: July 2010

A weight-age classification, based on recent catches, was retroactively applied to angled Atlantic salmon (Salmo salar) catches recorded in the log of the Godbout salmon club between 1859 and 1983. Over this period, numbers of salmon caught have fluctuated with a periodicity of 20–30 yr but catches have been maintained. There has been a big increase in fishing effort, and the proportion of two-sea-year to previously spawned fish has increased. The mean weight of these age groups has declined 0.005–0.009 kg∙yr−1. These changes are attributed to the selective effects of commercial fisheries on the stock.
Epilimnetic Phosphorus Cycling: Influence of Humic Materials and Iron on Coexisting Major Mechanisms
Authors: Francko David A.
Published: July 2010

Two major orthophosphate recycling mechanisms, alkaline phosphatase activity and the photodependent release of P from UV-sensitive complex P, cooccurred in epilimnetic samples from four trophically dissimilar lakes in northcentral Oklahoma. Both of these processes were strongly perturbed upon addition of low concentrations of dissolved humic material (DHM) and ferric iron, alone or in concert, to lake water samples. Planktonic orthophosphate uptake rates were also significantly altered by DHM/Fe addition, and, although the majority of P-uptake was accomplished by cells <3.0 μm in diameter, the effects of DHM/Fe were not size-selective. Additions of DHM/Fe to lake water appeared to promote elevated concentrations of orthophosphate and phosphomonoester substrates of alkaline phosphatase in lake water filtrates. Collectively, these data suggest that epilimnetic P cycling may be viewed as a continuum of processes and that the position of a given lake in the continuum is dynamic and influenced by DHM and Fe.
Light History, Phosphorus Status, and the Occurrence of Light Stimulation or Inhibition of Phosphate Uptake in Lake Superior Phytoplankton and Bacteria
Authors: Nalewajko C. , Paul B. , Lee K. , Shear H.
Published: July 2010

Phosphate uptake in Lake Superior was stimulated by light on 17 out of 34 occasions, inhibited on 10, and unaffected on 7. In a stepwise multiple regression model the variables explaining most of the variance in the light effect on phosphate uptake were, in decreasing order of importance, the light history as estimated by hours of sunshine in previous 3 d, phosphate turnover time, phytoplankton biovolume, and time of day. Stimulation was most common in spring at inshore stations, while inhibition occurred mainly in spring at offshore stations. We suggest that light-limited but phosphorus-sufficient phytoplankton show the former, but extremely low light adapted populations, the latter response. We discovered an apparent diurnal pattern in the response, with maximal stimulation by light during daylight hours and inhibition predominating at sunrise and sunset.
Whole human exome capture for high-throughput sequencing
Authors: Kim Dae-Won , Nam Seong-Hyeuk , Kim Ryong Nam , Choi Sang-Haeng , Park Hong-Seog
Published: July 2010

We captured the whole human exome by hybridization using synthesized oligonucleotides, based on a high-density microarray design, and we sequenced those captured human exons using high-throughput sequencing on a Genome Sequencer FLX instrument. Of the uniquely mapped reads, 71% fell within target regions, and these corresponded to coverage of 94% of human genes, 87% of exons, and 70% of the total base-pair length of the CCDS set. Our study provides strong evidence for the practical usefulness of this method on a genome-wide scale, showing the resequenced whole human exome database with 501 microRNAs and 307 novel SNPs.
Haloperidol promotes proliferation but inhibits differentiation in rat oligodendrocyte progenitor cell culturesThis 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: Niu Jianqin , Mei Feng , Li Nan , Wang Hanzhi , Li Xinmin , Kong Jiming , Xiao Lan
Published: July 2010

Haloperidol is a commonly used, typical, antipsychotic drug (APD) that acts strongly against positive symptoms, but has fewer therapeutic effects on, or may even aggravate, negative symptoms and cognitive deficits in patients with schizophrenia. Loss of oligodendrocytes has been suggested as a factor associated with the negative symptoms of schizophrenia. Recent study shows that chronic haloperidol treatment induced down-regulation of oligodendrocyte-related genes in certain brain regions of mouse. In this study, we used primary oligodendrocyte progenitor cell cultures from 1- to 3-day-postnatal rats to investigate the direct effects of haloperidol on the proliferation and differentiation of oligodendrocyte progenitor cells. Our results showed that (i) haloperidol (0–10.0 µmol·L–1) facilitated the proliferation of oligodendrocyte progenitor cells, (ii) chronic haloperidol (0.5 µmol·L–1) treatment decreased the number of myelin basic protein positive oligodendrocytes and reduced the oligodendrocytes cells possessing myelin-like membranes, resulting in inhibition of the terminal differentiation of oligodendrocytes, and (iii) D3 receptor mRNA was detected in oligodendrocyte progenitor cells, and haloperidol treatment induced a down-regulation of D3 receptor mRNA. These results suggest that the typical antipsychotic drug haloperidol affects the development of oligodendrocyte progenitor cells, and that D3 receptor down regulation may be involved. Our observations provide new insight into possible cellular mechanisms responsible for the side effects of typical antipsychotic drugs and support the concept that abnormality of oligodendrocytes may be involved in the pathogenesis of schizophrenia.
Reduction in cholesterol synthesis in response to serum starvation in lymphoblasts of a patient with Barth syndromeThis 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: Hauff Kristin D. , Hatch Grant M.
Published: July 2010

Barth syndrome is a rare X-linked disease in which mild hypocholesterolemia is observed in some patients. We investigated cholesterol biosynthesis in lymphoblasts from a normal and age-matched Barth syndrome patient. Control and Barth syndrome (ΔTAZ1) lymphoblasts were incubated in the presence or absence of serum to induce cholesterol synthesis and hydroxymethylglutaryl-coenzyme A reductase activity and expression, and cholesterol biosynthesis from radioactive precursors was determined. Cholesterol biosynthesis from [2-14C]pyruvate was stimulated 2-fold in control cells, but was unchanged in ΔTAZ1 lymphoblasts, and from [1-14C]acetate was stimulated 77% in control but only 26% in ΔTAZ1 lymphoblasts upon serum removal, indicating a lower ability of ΔTAZ1 cells to upregulate cholesterol biosynthesis. The reason was an inability to increase hydroxymethylglutaryl-coenzyme A reductase activity, which was already near maximum in ΔTAZ1 lymphoblasts, in response to serum removal, compared with control cells. The reduced ability to increase hydroxymethylglutaryl-coenzyme A reductase enzyme activity in ΔTAZ1 lymphoblasts was due to a decrease in hydroxymethylglutaryl-coenzyme A reductase messenger RNA. Although total cholesterol levels are similar under standard culture conditions, ΔTAZ1 lymphoblasts have a diminished capacity to respond to increased demand for cholesterol biosynthesis because of an already elevated level of synthesis under standard culture conditions.
Evidence that FOXO3a is involved in oocyte apoptosis in the neonatal rat ovaryThis 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: Sui Xu-Xia , Luo Li-Li , Xu Jin-Jie , Fu Yu-Cai
Published: July 2010

Previous studies have proposed that the forkhead transcription factor FOXO3a is involved in cell cycle arrest and apoptosis and that it may also repress follicular development by inducing cell cycle arrest in ovaries. We have recently demonstrated that FOXO3a induces oocyte apoptosis of neonatal rat ovaries under in vitro conditions. In the present study, we evaluated the role of FOXO3a in oocyte apoptosis under in vivo conditions. Ovaries from rats were obtained from newborns on postnatal day (PD) 1, 2, 3, and 4. TUNEL assay results showed that oocyte apoptosis occurred mainly on PD 1 and 2. Immunohistochemical staining of FOXO3a, Bim, Fas ligand (FasL), p27KIP1, caspase-8, and caspase-3 showed that they were all expressed mainly in naked oocytes on PD 1 and 2. The percentage of positive FOXO3a staining of oocytes reached peak levels in the ovaries of 2-day-old rats, which was consistent with the rate of the apoptotic profiles determined by TUNEL. The percentage between TUNEL-positive and FOXO3a-positive oocytes in the nucleus showed no statistical differences within the 4-day-old rat ovaries. Furthermore, the positive oocyte percentage of the target factors of FOXO3a (Bim, p27KIP1, and FasL) and pro-apoptotic proteins (caspase-3 and caspase-8) also reached peak levels in the ovaries of 2-day-old rats, which was similar to the rate of FOXO3a-positive oocytes. These results suggest that FOXO3a in the oocyte nucleus is involved in oocyte apoptosis; that is, FOXO3a-positive oocytes may be the apoptotic cells. To verify this, rat oocytes were subjected to TUNEL and immunofluorescent double-labeling assays. We found that TUNEL-positive cells were also FOXO3a-, Bim-, or FasL-positive. To identify the downstream target of FOXO3a, double immunofluorescent staining with antibodies to Bim and FasL was performed. We found that FOXO3a-positive cells were also Bim- and FasL-positive. We conclude that the overexpression of FOXO3a in the oocyte nucleus of neonatal rat ovaries may play an important role in the apoptosis of naked oocytes, and that Bim, FasL, and p27KIP1 are the key downstream factors of FOXO3a.
Effect of simultaneous silencing of HPV-18 E6 and E7 on inducing apoptosis in HeLa 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: Qi Zongli , Xu Xijin , Zhang Bao , Li Yan , Liu Junxiao , Chen Songjian , Chen Gangjian , Huo Xia
Published: July 2010

The objective of this investigation was to determine if simultaneous silencing of the human papillomavirus type 18 (HPV-18) E6 and E7 oncogenes using RNA interference (RNAi) would be a potential therapeutic approach against the carcinogenic activity of this virus. Two synthetic double-stranded oligonucleotides, encoding short hairpin transcripts corresponding to HPV-18 E6 and E7 genes, were cloned into pGenesilence (pGS) 1.0 vectors to produce pGS-E6, pGS-E7, and pGS-(E6+E7), respectively. Our results showed that the expression of HPV-18 E6 class 1 and HPV-18 E7 in HeLa cells was markedly decreased after being transfected with pGS-E6, pGS-E7, and pGS-(E6+E7) vectors. Of the three vectors, pGS-(E6+E7) had a greater ability to decrease the growth rate of HeLa cells, inhibit colony formation in soft agar, and significantly reduce tumor growth in nude mice. We also found that depletion of HPV-18 E6 and E7 in this manner promoted apoptosis of HeLa cells. Our data showed that simultaneously decreasing HPV-18 E6 and E7 gene expression in HeLa cells by RNAi could significantly inhibit tumor growth under in vitro conditions and in nude mice. These data suggest that gene therapy may be a possible therapeutic approach for HPV-positive cervical cancers.
Apoptosis induced by emodin is associated with alterations of intracellular acidification and reactive oxygen species in EC-109 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: Wang Q. J. , Cai X. B. , Liu M. H. , Hu H. , Tan X. J. , Jing X. B.
Published: July 2010

Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a natural anthraquinone derivative found in several herbal medicines, is highly active in suppressing the proliferation of various tumor cells such as breast, hepatocellular, and lung cancer cells under in vitro conditions. The mechanism of emodin-induced apoptosis in esophagus carcinoma cells, EC-109, is not completely understood. In this study, EC-109 cells treated with emodin underwent rapid apoptosis as judged by morphological changes and flow cytometry analysis. The addition of emodin to EC-109 cells led to the inhibition of growth in a time- and dose-dependent manner. Fluorescence measurements of cells indicated that the intracellular pH (pHi) decreased significantly by 0.47–0.78 units. The results obtained from flow cytometry suggested that bursts of reactive oxygen species took place after the application of emodin. The present study indicates that emodin may be a strong anticancer drug against esophagus cancer cells by causing various early events leading to growth inhibition, including the production of reactive oxygen species and decrease of pHi, which may result in cellular apoptosis.
Effect of sodium houttuyfonate on inhibiting ventricular remodeling induced by abdominal aortic banding in rats
Authors: Gao Jian Ping , Chen Chang Xun , Wu Qi , Gu Wei Liang , Li Xiang
Published: July 2010

Ventricular remodeling is an independent risk factor for many cardiovascular events. Inhibiting ventricular remodeling early may be an effective way to postpone heart failure for patients with cardiovascular illness. The study was designed to examine the effect of sodium houttuyfonate on ventricular remodeling induced by pressure overload in rats, as well as to explore the mechanisms involved. The model rats in which ventricular remodeling was induced abdominal aortic banding (AAB) were randomly divided into 4 groups: AAB control, AAB plus captopril (40 mg/kg), AAB plus low dose of sodium houttuyfonate (50 mg/kg), and AAB plus high dose of sodium houttuyfonate (100 mg/kg). One month after operation, hemodynamic parameters, heart mass indexes, size of cardiomyocytes, myocardial collagen volume, angiotensin II content in ventricular tissue, and serum concentrations of aldosterone and tumor necrosis factor (TNF)-α were evaluated. Sodium houttuyfonate significantly reduced heart mass indexes, the size of cardiomyocytes, and the myocardial collagen volume and decreased the levels of angiotensin II, aldosterone, and TNF-α. At the high dose, it decreased blood pressure and heart rate. In conclusion, sodium houttuyfonate attenuates ventricular remodeling induced by pressure overload in rats. The beneficial effects are in part associated with its alleviating the activation of renin–angiotensin–aldosterone system and decreasing the TNF-α level. Furthermore, its function seems to correlate with reduced blood pressure and heart rate.
Evaluation of the endothelin receptor antagonists ambrisentan, darusentan, bosentan, and sitaxsentan as substrates and inhibitors of hepatobiliary transporters in sandwich-cultured human hepatocytesThis article is one of a selection of papers published in the two-part special issue entitled 20 Years of Endothelin Research.
Authors: Hartman J. Craig , Brouwer Kenneth , Mandagere Arun , Melvin Lawrence , Gorczynski Richard
Published: July 2010

To evaluate potential mechanisms of clinical hepatotoxicity, 4 endothelin receptor antagonists (ERAs) were examined for substrate activity and inhibition of hepatic uptake and efflux transporters in sandwich-cultured human hepatocytes. The 4 transporters studied were sodium-dependent taurocholate cotransporter (NTCP), organic anion transporter (OATP), bile salt export pump (BSEP), and multidrug resistance-associated protein 2 (MRP2). ERA transporter inhibition was examined using the substrates taurocholate (for NTCP and BSEP), [3H]estradiol-17β-d-glucuronide (for OATP), and [2-d-penicillamine, 5-d-penicillamine]enkephalin (for MRP2). ERA substrate activity was evaluated using probe inhibitors ritonavir (OATP and BSEP), bromosulfalein (OATP), erythromycin (P-glycoprotein), probenecid (MRP2 and OATP), and cyclosporin (NTCP). ERAs were tested at 2, 20, and 100 µmol·L–1for inhibition and at 2 µmol·L–1as substrates. OATP, NTCP, or BSEP transport activity was not reduced by ambrisentan or darusentan. Bosentan and sitaxsentan attenuated NTCP transport at higher concentrations. Only sitaxsentan decreased OATP transport (52%), and only bosentan reduced BSEP transport (78%). MRP2 transport activity was unaltered. OATP inhibitors decreased influx of all ERAs. Darusentan influx was least affected (84%–100% of control), whereas bosentan was most affected (32%–58% of control). NTCP did not contribute to influx of ERAs. Only bosentan and darusentan were shown as substrates for both BSEP and P-glycoprotein efflux. All ERAs tested were substrates for at least one hepatic transporter. Bosentan and sitaxsentan, but not ambrisentan and darusentan, inhibited human hepatic transporters, which provides a potential mechanism for the increased hepatotoxicity observed for these agents in the clinical setting.
Apocynin attenuates pressure overload-induced cardiac hypertrophy in rats by reducing levels of reactive oxygen species
Authors: Liu Jinjun , Zhou Juan , An Wenjiao , Lin Yuanxi , Yang Yubai , Zang Weijin
Published: July 2010

It has been shown that angiotensin II (Ang II) is involved in cardiac remodeling mediated by NADPH oxidase-dependent reactive oxygen species (ROS). Accordingly, NADPH oxidase-dependent ROS may play a role in cardiac hypertrophy induced by pressure overload. In the present study, we sought to determine whether inhibition of NADPH oxidase prevents cardiac hypertrophy. After abdominal aorta banding to induce cardiac hypertrophy, rats were treated for 8 weeks with apocynin (Apo) or captopril (Cap). Measures of cardiac hypertrophy were evaluated. Treatment with Cap or Apo reduced the left ventricle / body weight ratio (LV/BW), LV transnuclear myocyte diameter, and atrial natriuretic factor (ANF) mRNA expression relative to those of untreated rats subjected to aorta banding. The activity of NADPH oxidase and the ROS levels were decreased in treated animals. Cap, but not Apo, decreased Ang II levels and inhibited expression of p22phox and p67phox in LVs. In conclusion, local expression of Ang II appears to contribute to pressure overload-induced cardiac hypertrophy by upregulating NADPH oxidase expression and promoting ROS synthesis. Inhibition of NADPH oxidase and elimination of ROS may prevent or repair damage due to cardiac hypertrophy.
Chemical ecology of predator–prey interactions in aquatic ecosystems: a review and prospectusThe present review is one in the special series of reviews on animal–plant interactions.
Authors: Ferrari Maud C.O. , Wisenden Brian D. , Chivers Douglas P.
Published: July 2010

The interaction between predator and prey is an evolutionary arms race, for which early detection by either party is often the key to success. In aquatic ecosystems, olfaction is an essential source of information for many prey and predators and a number of cues have been shown to play a key role in trait-mediated indirect interactions in aquatic communities. Here, we review the nature and role of predator kairomones, chemical alarm cues, disturbance cues, and diet cues on the behaviour, morphology, life history, and survival of aquatic prey, focusing primarily on the discoveries from the last decade. Many advances in the field have been accomplished: testing the survival value of those chemicals, providing field validation of laboratory results, understanding the extent to which chemically mediated learning may benefit the prey, understanding the role of these chemicals in mediating morphological and life-history adaptations, and most importantly, the selection pressures leading to the evolution of chemical alarm cues. Although considerable advances have been made, several key questions remain, the most urgent of which is to understand the chemistry behind these interactions.
FREQUENCY-DEPENDENT NONLINEAR CURRENT OSCILLATION AND CHAOTIC DYNAMICS IN SEMICONDUCTING CARBON NANOTUBES
Authors: WANG C. , CAO J. C.
Published: July 2010

We have analyzed the spatio-temporal patterns of current self-oscillation under DC bias and terahertz frequency-dependent nonlinear dynamics in semiconducting single-walled zigzag carbon nanotubes (CNTs). It is found that different transport states, including periodic and chaotic, appear with the influence of an external AC signal. The global transitions between periodic and chaotic states are clearly resolved from Poincaré bifurcation diagram. When the driving frequency is fixed at inverse golden mean ratio times natural frequency, the nonlinear CNT system exhibits a more complex transition behavior than at other driving frequencies.
Recurrent landslides predisposed by fault-induced weathering of flysch in the Western Carpathians
Authors: Pánek T. , Hradecký J. , Minár J. , Šilhán K.
Published: July 2010

The interrelationship between slope deformation and fault-induced weathering as a predisposing factor for the development of sliding is analysed through several case studies from the Western Carpathians in the Czech Republic. The study area comprises flysch nappes with alternating sandstone and shale of different permeability. These lithological structures are affected by systems of faults. Recurring slope instability is found associated with zones of deep weathering in tectonically weakened areas. Climatic variability of landslide activity can be identified during the Holocene by means of radiocarbon dating and pollen analysis. Areas affected by recurring landsliding suggest gradual and cyclic landslide frequency.
Very deep weathering and related landslides
Authors: Ollier C. D.
Published: July 2010

Some huge landslides have occurred in deeply weathered rock, but most geologists and engineers do not appreciate the great depths that weathering can attain. Rocks can be weathered to depths of hundreds of metres, often in a very irregular manner. Fresh rock is converted to weathered rock called saprolite by isometric chemical alteration. Some saprolite is later eroded, and fresh rock appears in the landscape in distinctive landforms. This erosion of an irregularly weathered landscape is called stripping (meaning the stripping of saprolite from fresh rock). The age of the weathering may be measured in geological periods, as can the age of stripping, and may be related to past climate different from that of today. Deep weathering occurs basically by hydrolysis, which requires groundwater. Slope failure in saprolite depends on the engineering property of the material, and its relation to bedrock and corestones, and relationship to degree of weathering of adjacent saprolite. This paper emphasizes the deep weathering phenomenon itself, but a few examples are given to illustrate the variety of landslides in deeply weathered material.
Deterioration processes of hard clays and clay shales
Authors: Picarelli L. , Di Maio C.
Published: July 2010

Soil deterioration is one of the main causes of slope failure in hard clays and clay shales, but so far a clear general framework of the causes of deterioration is still missing. Based on laboratory data, field observations and speculation, this paper examines some processes of deterioration of stiff overconsolidated clays and clay shales with particular regard to their influence on the stability of slopes. In particular, deterioration localized within soil bands or involving large soil masses is described with reference to its mechanical or physico-chemical causes. Coupling between mechanical and physico-chemical processes is considered.
Mass movement and landscape evolution in weathered granite and gneiss terrains
Authors: Migoń Piotr
Published: July 2010

The paper assesses the contribution of mass movement to the development of landforms in weathered granite and gneiss terrain, using examples from SE Brazil, southern Mexico, SE China, and other locations. The style of slope failures varies depending on local relief and the grade of weathering, which mutually influence each other. Shallow debris slides and boulder falls are common in less weathered rock and steep terrain, whereas rotational slides appear to dominate in highly weathered rock and in more subdued topography. In certain topographic circumstances, slides may turn into debris flows or earthflows. Extreme rainfall is a typical trigger of mass movement in weathered terrain. Mapping of past landslides may considerably assist in hazard assessment, as they usually leave a clear geomorphological record.
Degradation of marls; two case studies from the Iberian Peninsula
Authors: Alonso E. E. , Pineda J. A. , Cardoso R.
Published: July 2010

The strength degradation of two marl formations (Pamplona marls in Spain and Abadia marls in Portugal) is analysed in the paper. In the case of Pamplona marls, a number of large-scale direct shear tests on natural and saturated specimens of the undisturbed material were performed. Tests on marl–concrete interfaces were performed and are also presented. Both cases analysed show that the saturation of the marl leads to a strong reduction of friction and effective cohesion. Negative effects of suction changes on the mechanical behaviour of the marls were investigated in more detail in suction controlled tests on Abadia marls, a more plastic material. A numerical simulation of wetting effects on a marl fragment of finite size helps to identify the nature of degradation mechanisms, which are associated with the development of tensile surfaces inside the marl matrix. They, in turn, are due to the expansive behaviour of the clay fraction of the marl relative to suction changes.
Weathering processes, structural degradation and slope-structure stability of rock-hewn churches of Lalibela (Ethiopia)
Authors: Delmonaco G. , Margottini C. , Spizzichino D.
Published: July 2010

Lalibela is located in the northern–central part of Ethiopia,
c
. 600 km north of Addis Ababa in Northern Wollo (Ahmara Region). The town, which has about 12 000 inhabitants, is situated at an altitude of 2500 m. In its centre a unique complex of 11 rock-hewn Christian Orthodox churches is located, cut out of the rock some 800 years ago. Their construction is attributed to King Lalibela (1167–1207). All the churches exhibit widespread evidence of structural damage and weathering processes, which are posing a serious problem for the preservation of the monuments. Preliminary geological field surveys,
in situ
geotechnical analyses and laboratory tests have been carried out in the area to understand the cause of weathering and the likely consequences on the structural stability of the churches. Laboratory tests on volcanic materials detected a deep alteration of rocks as a result of the widespread presence of montmorillonite. This is the primary cause of the progressive deterioration of the physical and mechanical characteristics of the slope-forming rocks in Lalibela. Major consequences are the alveolar weathering of churches' façade, the degradation of the roofs and a reduction of rock strength, which are causing a progressive structural instability in some rock-hewn monuments. Also, sliding of façades along bedding joints was detected. Understanding the weathering processes affecting the Lalibela churches allows the detection of problems and the timely implementation of medium- to long-term protection strategies for conservation of the monuments.
Test case prioritization using ant colony optimization
Authors: Singh Yogesh , Kaur Arvinder , Suri Bharti
Published: July 2010

Regression testing is primarily a maintenance activity that is performed frequently to ensure the validity of the modified software. In such cases, due to time and cost constraints, the entire test suite cannot be run. Thus, it becomes essential to prioritize the tests in order to cover maximum faults in minimum time. In this paper, ant colony optimization is used, which is a new way to solve time constraint prioritization problem. This paper presents the regression test prioritization technique to reorder test suites in time constraint environment along with an algorithm that implements the technique.
SCORE
Authors: Mandrioli Dino , Fickas Stephen , Furia Carlo A. , Jazayeri Mehdi , Rossi Matteo , Young Michal
Published: July 2010

The Student Contest on Software Engineering (SCORE), organized for the first time in conjunction with the International Conference on Software Engineering (ICSE) 2009, attracted 50 student teams from around the world, produced an impressive and varied set of projects, and earned appreciative comments from participants and even from teams who chose not to submit their results to the competition. It was a remarkable success, but not without problems and setbacks. In this article we explain the objectives, constraints, and design philosophy of SCORE, particularly as they distinguish it from the tradition of computer science contests focused more narrowly on programming. We also recount key approaches taken to design and management of this novel kind of contest, the difficulties we met (some still outstanding), and the lessons learned.
Analysis of disparity distortions in omnistereoscopic displays
Authors: Couture Vincent , Langer Michael S. , Roy Sébastien
Published: July 2010

An omnistereoscopic image is a pair of panoramic images that enables stereoscopic depth perception all around an observer. An omnistereo projection on a cylindrical display does not require tracking of the observer's viewing direction. However, such a display introduces stereo distortions. In this article, we investigate two projection models for rendering 3D scenes in omnistereo. The first is designed to give zero disparity errors at the center of the visual field. The second is the well-known slit-camera model. For both models, disparity errors are shown to increase gradually in the periphery, as visual stereo acuity decreases. We use available data on human stereoscopic acuity limits to argue that depth distortions caused by these models are so small that they cannot be perceived.