bluuebunny/crossref_metadata_2025 huggingface dataset:
SLC22A4 and SLC22A5 gene polymorphisms and Crohn's disease in the Chinese Han population
Authors: FENG Yun , ZHENG Ping , ZHAO Hang , WU Kai
Published: July 2009

OBJECTIVE:  Recent genomic surveys have identified two single nucleotide polymorphisms (SNP) in SLC22A4 and SLC22A5 as susceptibility loci for Crohn's disease (CD). We conducted the present study to assess whether the two SNP and exon variants in SLC22A4 and SLC22A5 could be implicated in the vulnerability to CD of the Chinese Han population.

METHODS:  A total of 180 CD patients and 180 healthy controls were studied. Genotyping for the two positive sites and the SNP that we screened from all the exon regions in SLC22A4 and SLC22A5 were typed using the direct sequencing method.

RESULTS:  Neither individual SNP nor any haplotype was found to be associated with CD in our case‐control study.

CONCLUSION:  In contrast to the Caucasian population, SLC22A4 and SLC22A5 genes are unlikely to play a major role in susceptibility to CD in the Chinese Han population.
Drug‐induced liver disease: an 8‐year study of patients from one gastroenterological department
Authors: WANG Yi Ping , SHI Bin , CHEN Yue Xiang , XU Jing , JIANG Cai Feng , XIE Wei Fen
Published: July 2009

OBJECTIVE: To analyze drug‐induced liver disease over an 8‐year period from January 2000 to December 2007 in one gastroenterological department.

METHODS: International consensus of standard definitions and criteria for assessing causality of adverse drug reactions were applied to all patients with abnormal hepatic test results.

RESULTS: Drugs were implicated in hepatic injury in 30 patients (15 men and 15 women) in whom there was a causal or highly probable relationship between drug use and liver disease. The drugs responsible for liver damage were Chinese medicinal herbs (n = 12), cyclosporin (n = 2), fosfomycin, gentamicin, flutamide, acipimox and nimesulide (n = 1 each). Of the 30 patients, 19 (63.3%) were classified as having hepatocellular or mixed hepatitis, eight (26.7%) as having cholestatic injury and the remaining three as having a severe hepatic drug reaction (prothrombin < 50%), including death.

CONCLUSION: A thorough history of medication should be taken in all patients presenting with abnormal hepatic test results. Chinese medicinal herbs were the most frequent hepatotoxic factor in our patients, although the liver injury was not severe in most cases and was relieved after the prompt withdrawal of the suspected drug.
Giant esophageal squamous papilloma: a case report
Authors: TABATABAEI Sayed Abbas , MOGHADAM Noshin Afshar , AHMADINEJAD Mojtaba , MIRMOHAMMADSADEGHI Amir , MASOUDPOUR Hassan , ADIBI Peyman
Published: July 2009

Esophageal papilloma is a rare disorder that may cause hypopharyngeal symptoms. This patient was a 56‐year‐old man who presented with cough and choking symptoms. After the initial negative laryngoscopy, a fiberoptic endoscopy revealed a mass originating from the hypopharyngeal area, which was resected surgically and found to be non‐malignant.
Can ensemble forecasts improve the reliability of flood alerts?
Authors: Dietrich J. , Denhard M. , Schumann A.H.
Published: July 2009

A probabilistic evaluation of ensemble forecasts can be used to communicate uncertainty to decision makers. We present a flood forecast scheme, which combines forecasts from the European COSMO‐LEPS, SRNWP‐PEPS and COSMO‐DE (lagged average) ensemble prediction systems with a rainfall–runoff model. The methodology was demonstrated with a case study for the Central European Mulde River basin. In this paper, we summarize results from hindcast simulations for seven events from 2002 to 2008. The ensemble spread resulting from uncertainty in rainfall forecast was very high at 2–5 days lead time. The median of the medium‐ and short‐range forecasts and a lagged average ensemble of the very short‐range forecasts proved to be reliable regarding the probability of exceeding flood alert levels. However, the limited number of observed events does not allow for the postulation of prescriptive binary decision rules. Flood managers have to adapt their decisions when new information becomes available.
A semimechanistic model predicting the growth and production of the bioenergy crop Miscanthus×giganteus: description, parameterization and validation
Authors: MIGUEZ FERNANDO E. , ZHU XINGUANG , HUMPHRIES STEPHEN , BOLLERO GERMÁN A. , LONG STEPHEN P.
Published: July 2009

Biomass based bioenergy is promoted as a major sustainable energy source which can simultaneously decrease net greenhouse gas emissions. Miscanthus×giganteus (M.×giganteus), a C4 perennial grass with high nitrogen, water, and light use efficiencies, is regarded as a promising energy crop for biomass production. Mathematical models which can accurately predict M.×giganteus biomass production potential under different conditions are critical to evaluate the feasibility of its production in different environments. Although previous models based on light‐conversion efficiency have been shown to provide good predictions of yield, they cannot easily be used in assessing the value of physiological trait improvement or ecosystem processes. Here, we described in detail the physical and physiological processes of a previously published generic mechanistic eco‐physiological model, WIMOVAC, adapted and parameterized for M.×giganteus. Parameterized for one location in England, the model was able to realistically predict daily field diurnal photosynthesis and seasonal biomass at a range of other sites from European studies. The model provides a framework that will allow incorporation of further mechanistic information as it is developed for this new crop.
Re‐Emergence of West Nile Virus in Italy
Authors: Monaco F. , Lelli R. , Teodori L. , Pinoni C. , Di Gennaro A. , Polci A. , Calistri P. , Savini G.
Published: July 2009

In August 2008, West Nile disease re‐emerged in Italy. The infection is affecting the North Eastern regions and, as of November 2008, has caused 33 clinical cases and five fatalities in horses. Until now, no deaths have been reported in birds. Mosquitoes, blood, serum and tissue samples, from horses and birds, within and around the outbreak area, have been collected and tested by various methods both serologically and virologically. West Nile virus strains have been isolated from blood samples of one horse and one donkey and from pools of brain, kidneys, heart and spleen of a pigeon and three magpies. When compared to the strain isolated during the 1998 Tuscany outbreak, the 255 bp sequence of the genome region coding for the envelope (E) protein of the isolated WNV strains, exhibited a 98.8% and 100% similarity at nucleotide and amino‐acid level respectively.
Prevalence and Financial Effects of Hydatidosis in Cattle Slaughtered in Birre‐Sheleko and Dangila Abattoirs, Northwestern Ethiopia
Authors: Kebede N. , Gebre‐Egziabher Z. , Tilahun G. , Wossene A.
Published: July 2009

A cross‐sectional survey of bovine hydatidosis was carried out on local zebu cattle slaughtered at Birre‐Sheleko and Dangila Abattoirs from August 2007 to July 2008 to determine the prevalence and to estimate financial loss caused by the disease. Postmortem examination, hydatid cyst characterization and direct and indirect financial loss estimations were conducted. Out of the total of 521 animals examined (255 Birre‐Sheleko and 266 Dangila), 79 (15.2%) were found harbouring one or more hydatid cyst. The prevalence of the disease between the two abattoirs was not significantly different (P > 0.05). The result obtained from postmortem examination indicated that a total of 112 visceral organs were found harbouring one or more hydatid cysts. The involvement of lung, liver, spleen and kidney was found to be 70.5%, 21.4%, 6.3% and 1.8% respectively. From the total of 224 cysts counted, 147 (65.6%), 29 (12.9%), 3 (1.3%) and 45 (20.1%) were small, medium, large and calcified cysts respectively, and 114 (50.9%) and 65 (29%) were sterile and fertile cysts respectively. Viability rate of 47.7%, all from the lungs, and higher liver calcification rate were observed. The annual financial loss from organ condemnation and carcass weight loss due to bovine hydatidosis at Birre‐Sheleko and Dangila abattoirs were estimated to be $18911.6.
Comparative morphometric analysis of recurrent and nonrecurrent canine basal cell carcinomas: a preliminary report
Authors: Simeonov Radostin , Simeonova Galina
Published: July 2009

Background: Most reports of canine basal cell carcinomas (BCCs) focus on morphologic appearance rather than biologic behavior. Rare recurrences and no metastases have been reported in dogs. Quantitative nuclear morphometry may be useful in predicting tumor recurrence.

Objective: The aim of the present study was to compare quantitative nuclear parameters of canine BCCs that did not recur within 60 weeks of excision with those that recurred.

Methods: Cytologic specimens obtained from spontaneous BCCs from 11 dogs were analyzed by computerized nuclear morphometry. The dogs were monitored by their owners over a period of 60 weeks to detect local recurrence of the tumor; recurrent tumors were confirmed histologically. For each initial tumor specimen, nuclei of at least 100 neoplastic cells were measured by 2 independent observers, and mean nuclear area (MNA), mean nuclear perimeter (MNP), and mean nuclear diameter (MND) were calculated.

Results: Six nonrecurrent and 5 recurrent tumors were analyzed. Neoplastic cells from BCCs that subsequently recurred had higher MNA (102.41 ± 4.57 μm2), MNP (36.27 ± 0.61 μm), and MND (11.21 ± 0.27 μm) than cells from nonrecurrent BCCs (MNA 87.66 ± 4.79 μm2, MNP 33.51 ± 0.78 μm, MND 10.36 ± 0.29 μm) (P<.001; Mann–Whitney U‐test).

Conclusion: Based on these preliminary results, nuclear morphometry may be a useful tool to predict local recurrence of BCCs in dogs.
Revisiting the Foundations of Network Analysis
Authors: Butts Carter T.
Published: July 2009

Network analysis has emerged as a powerful way of studying phenomena as diverse as interpersonal interaction, connections among neurons, and the structure of the Internet. Appropriate use of network analysis depends, however, on choosing the right network representation for the problem at hand.
Structural Origin of Circularly Polarized Iridescence in Jeweled Beetles
Authors: Sharma Vivek , Crne Matija , Park Jung Ok , Srinivasarao Mohan
Published: July 2009

Bright Shiny Beetles

The beautiful iridescent colors found on the wings of butterflies and on the bodies of beetles have attracted the attention of brilliant minds over the past centuries, starting with Newton, who understood that these colors must involve “thin film structures.” In 1911 Michelson described the metallic appearance of these beetles, and in the late 1960s Neville and Caveney discussed the optical properties in the context of cholesteric liquid crystals.

Sharma
et al.

(p.
449
; see the Perspective by

Vukusic

) examined the metallic green beetle
Chrysina gloriosa
, which selectively reflects left circularly polarized light when illuminated with unpolarized light. The underlying cellular structure of the beetle exoskeleton is organized primarily in a hexagonal pattern, with variations in the pentagonal and heptagonal arrangements depending on the local curvature. Thus, the ordering of the cells in concentric, nested arcs is indeed analogous to the ordering of the molecules in a cholesteric (or chiral nematic) liquid crystal.
Chlamydomonas
Swims with Two “Gears” in a Eukaryotic Version of Run-and-Tumble Locomotion
Authors: Polin Marco , Tuval Idan , Drescher Knut , Gollub J. P. , Goldstein Raymond E.
Published: July 2009

All Together Now (Sometimes)

Motile cilia and flagella protrude from the surface of many eukaryotic cells. Understanding how cilia and flagella operate is important for understanding ciliated cells in metazoans, the ecology and behavior of motile microorganisms, and the mechanisms of molecular motors and signal transduction. Using very-high-speed video microscopy,

Polin
et al.

(p.
487
; see the Perspective by

Stocker and Durham

) discovered that the biflagellated cells of the single-cell alga
Chlamydomonas rheinhartii
switch between synchronous beating, which keeps the cells traveling forward, and asynchronous beating, which allows the organisms to make sharp turns. This random progression occurs in the dark and allows cells to diffuse, and it may underpin directional movement toward light in the same way that the run-and-tumble behavior of prokaryotes allows them to move up chemical gradients.
Scale-Free Networks: A Decade and Beyond
Authors: Barabási Albert-László
Published: July 2009

For decades, we tacitly assumed that the components of such complex systems as the cell, the society, or the Internet are randomly wired together. In the past decade, an avalanche of research has shown that many real networks, independent of their age, function, and scope, converge to similar architectures, a universality that allowed researchers from different disciplines to embrace network theory as a common paradigm. The decade-old discovery of scale-free networks was one of those events that had helped catalyze the emergence of network science, a new research field with its distinct set of challenges and accomplishments.
Can We Reinvent the Internet?
Authors: Mayer-Schönberger Viktor
Published: July 2009

To build a better Internet may require us to rewire the social communities that created its code.
Epidemiology of Enterovirus 71 in The Netherlands, 1963 to 2008
Authors: van der Sanden Sabine , Koopmans Marion , Uslu Gökhan , van der Avoort Harrie
Published: July 2009

The incidence of enterovirus 71 (EV71) infection has greatly increased in the Asian Pacific region since 1997. Several large outbreaks, caused by different subgenogroups of EV71, occurred with high rates of morbidity and a substantial number of deaths. In 2007, 58 cases of EV71 infection requiring hospitalization were reported in The Netherlands after a period of low endemicity of 21 years. These events triggered a study on the epidemiology of EV71 in The Netherlands. Genetic analysis of the VP1 capsid region of 199 EV71 isolates collected from 1963 to 2008 as part of enterovirus surveillance activities revealed a change in the prevailing subgenogroups over time. From 1963 to 1986 infections were caused by three different and successive lineages belonging to subgenogroup B (the novel lineage designated B0, as well as B1 and B2). In 1987, following a major epidemic the previous year, the B genogroup was replaced by genogroup C strains of lineages C1 and, later, C2. Analyses of the clinical data suggested that there were differences between infection with genogroup B and with genogroup C strains in terms of the age groups affected and the severity of illness. From comparative analysis with genomic data available in the public domain, we concluded that EV71 strain evolution shows a global pattern, which leads to the question of whether the recently emerged C4 lineage strains will also spread outside of Asia.
Algorithm Combining Toxin Immunoassay and Stool Culture for Diagnosis of
Clostridium difficile
Infection
Authors: Shin Bo-Moon , Kuak Eun Young , Lee Eun Joo , Songer J. Glenn
Published: July 2009

Enzyme immunoassays (EIA) to detect glutamate dehydrogenase or toxins A (TcdA) and B (TcdB), a cytotoxicity assay, and bacteriologic culture have disadvantages when applied individually to diagnosis of
Clostridium difficile
infections. Stool specimens (
n
= 1,596) were subjected to toxin detection via an enzyme-linked fluorescent immunoassay (ELFA; Vidas CDAB assay) and bacteriologic culture for toxigenic
C. difficile
in a three-step algorithm with additional toxigenic culture. Isolates (
n
= 163) from ELFA-negative stool specimens were examined via ELFA for toxin production. We amplified
tcdA
and
tcdB
from
C. difficile
isolates and
tcdB
from stool specimens that were ELFA positive or equivocal and culture negative, and we compared the results to those obtained with the three-step algorithm. More than 26% of stool specimens (419/1,596) were culture positive, yielding 248 isolates (59.2%) with both toxin genes (
tcdA
- and
tcdB
-positive isolates), 88 isolates (21.0%) with either
tcdA
or
tcdB
, and 83 (19.8%) that had no toxin genes (
tcdA
- and
tcdB
-negative isolates). Among 49 (culture-negative/ELFA-positive or -equivocal) stool specimens, 53.1% (26/49) represented
tcdB
-positive isolates. Therefore, the total number of PCR-positive cases was 362, and 27.1% (98/362) of these were detected through toxigenic culture. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 63.3%, 96.7%, 90.5%, and 92.4% (ELFA alone); 92.8%, 93.3%, 80.2%, and 97.8% (culture); and 70.7%, 91.4%, 95.5%, and 100% (three-step algorithm ELFA and bacterial culture with toxigenic culture), respectively, with culture and PCR for
tcdA
and
tcdB
as the standards. Thus, sensitivity and specificity were highest using culture and ELFA, respectively, but we recommend the three-step algorithm comprising EIA to detect both toxins and toxigenic culture for
C. difficile
as a practical method for achieving better PPV and NPV.
Prevalence of and Risk Factors for Colonization by Methicillin-Resistant
Staphylococcus aureus
among Adults in Community Settings in Taiwan
Authors: Wang Jann-Tay , Liao Chun-Hsing , Fang Chi-Tai , Chie Wei-Chu , Lai Mei-Shu , Lauderdale Tsai-Ling , Lee Wen-Sen , Huang Jeng-Hua , Chang Shan-Chwen
Published: July 2009

In order to determine the prevalence of methicillin (meticillin)-resistant
Staphylococcus aureus
(MRSA) colonization among adults in community settings in Taiwan and identify its risk factors, we conducted the present study. For a 3-month period, we enrolled all adults who attended mandatory health examinations at three medical centers and signed the informed consent. Nasal swabs were taken for the isolation of
S. aureus
. For each MRSA isolate, we performed multilocus sequence typing, identification of the staphylococcal cassette chromosome
mec
, tests for the presence of the Panton-Valentine leukocidin gene, and tests for drug susceptibilities. Risk factors for MRSA colonization were determined. The results indicated that the MRSA colonization rate among adults in the community settings in Taiwan was 3.8% (119/3,098). Most MRSA isolates belonged to sequence type 59 (84.0%). Independent risk factors for MRSA colonization included the presence of household members less than 7 years old (
P
< 0.0001) and the use of antibiotics within the past year (
P
= 0.0031). Smoking appeared to be protective against MRSA colonization (
P
< 0.0001).
BD Phoenix and Vitek 2 Detection of
mecA
-Mediated Resistance in
Staphylococcus aureus
with Cefoxitin
Authors: Junkins Alan D. , Lockhart Shawn R. , Heilmann Kristopher P. , Dohrn Cassie L. , Von Stein Diana L. , Winokur Patricia L. , Doern Gary V. , Richter Sandra S.
Published: July 2009

The BD Phoenix (BD Diagnostics, Sparks, MD) and Vitek 2 (bioMérieux, Durham, NC) automated susceptibility testing systems have implemented the use of cefoxitin to enhance the detection of methicillin (meticillin)-resistant
Staphylococcus aureus
(MRSA). To assess the impact of this change, 620 clinically significant
S. aureus
isolates were tested in parallel on Phoenix PMIC/ID-102 panels and Vitek 2 AST-GP66 cards. The results for oxacillin and cefoxitin generated by the automated systems were compared to those generated by two reference methods:
mecA
gene detection and MICs of oxacillin previously determined by broth microdilution according to CLSI guidelines. Testing of isolates with discordant results was repeated to attain a majority or consensus final result. There was 100% final agreement between the results of the two reference methods. For the 448 MRSA and 172 methicillin-susceptible
S
.
aureus
isolates tested, the rates of categorical agreement of the results obtained with the automated systems with those obtained by the reference methods were 99.8% for the Phoenix panels and 99.7% for the Vitek 2 cards. A single very major error occurred on each instrument (0.2%) with different MRSA isolates. The only major error was attributed to the Vitek 2 system overcalling oxacillin resistance. In 16 instances (9 on the Phoenix system, 7 on the Vitek 2 system), an oxacillin MIC in the susceptible range was correctly changed to resistant by the expert system on the basis of the cefoxitin result. The inclusion of cefoxitin in the Phoenix and Vitek 2 panels has optimized the detection of MRSA by both systems.
Adeno-Associated Virus Type 2 Induces Apoptosis in Human Papillomavirus-Infected Cell Lines but Not in Normal Keratinocytes
Authors: Alam Samina , Meyers Craig
Published: July 2009

The results of seroepidemiological studies suggest that infection with adeno-associated virus type 2 (AAV2) is negatively correlated with the incidence of human papillomavirus (HPV)-associated cervical cancer. We studied the potential of AAV2 oncosuppression of HPV and showed that HPV/AAV2 coinfection of cells culminated in apoptotic death, as determined by DNA laddering and caspase-3 cleavage. The induction of apoptosis coincided with AAV2 Rep protein expression; increased S-phase progression; upregulated pRb displaying both hyper- and hypophosphorylated forms; increased levels of p21WAF1, p16INK4, and p27KIP1proteins; and diminished levels of E7 oncoprotein. In contrast, normal keratinocytes that were infected with AAV2 or transfected with the cloned full-length AAV2 genome failed to express Rep proteins or undergo apoptosis. The failure of AAV2 to productively infect normal keratinocytes could be clinically advantageous. The delineation of the molecular mechanisms underlying the HPV/AAV2 interaction could be harnessed for developing novel AAV2-derived therapeutics for cervical cancer.
Human Cytomegalovirus UL28 and UL29 Open Reading Frames Encode a Spliced mRNA and Stimulate Accumulation of Immediate-Early RNAs
Authors: Mitchell Dora P. , Savaryn John P. , Moorman Nathaniel J. , Shenk Thomas , Terhune Scott S.
Published: July 2009

We have identified a spliced transcript that contains sequences from the HCMV UL29 and UL28 open reading frames. It contains amino-terminal UL29 sequences followed by UL28 sequences, and it includes a poly(A) signal derived from the 3′-untranslated region following the UL26 open reading frame. UL29/28 RNA is expressed with early kinetics, and a virus containing a FLAG epitope inserted at the amino terminus of UL29 expressed a tagged ∼79-kDa protein, pUL29/28, that was detected at 6 h postinfection. The virus also expressed a less-abundant tagged 41-kDa protein, which corresponds in size to a protein that could be produced by translation of an unspliced UL29/28 transcript. Consistent with this prediction, both unspliced and spliced UL29/28 transcript was present in RNA isolated from polysomes. FLAG-tagged protein from the UL29/28 locus accumulated within nuclear viral replication centers during the early phase of infection. Late after infection it was present in the cytoplasm as well, and the protein was present and resistant to proteinase treatment in partially purified preparations of viral particles. Disruption of the UL29/28 locus by mutation resulted in a 10-fold decrease in the levels of DNA replication along with a similar reduction in virus yield. Quantitative reverse transcription-PCR analysis revealed an ∼2-fold decrease in immediate-early gene expression at 4 to 10 h postinfection compared to the wild-type virus, and transient expression of pUL29/28 activated the major immediate-early promoter. Our results argue that the UL29/28 locus contributes to activation of immediate-early gene expression.
Elastase-Dependent Live Attenuated Swine Influenza A Viruses Are Immunogenic and Confer Protection against Swine Influenza A Virus Infection in Pigs
Authors: Masic Aleksandar , Booth Jayaum S. , Mutwiri George K. , Babiuk Lorne A. , Zhou Yan
Published: July 2009

Influenza A viruses cause significant morbidity in swine, resulting in a substantial economic burden. Swine influenza virus (SIV) infection also poses important human public health concerns. Vaccination is the primary method for the prevention of influenza virus infection. Previously, we generated two elastase-dependent mutant SIVs derived from A/Sw/Saskatchewan/18789/02(H1N1): A/Sw/Sk-R345V (R345V) and A/Sw/Sk-R345A (R345A). These two viruses are highly attenuated in pigs, making them good candidates for a live-virus vaccine. In this study, the immunogenicity and the ability of these candidates to protect against SIV infection were evaluated in pigs. We report that intratracheally administrated R345V and R345A induced antigen-specific humoral and cell-mediated immunity characterized by increased production of immunoglobulin G (IgG) and IgA antibodies in the serum and in bronchoalveolar lavage fluid, high hemagglutination inhibition titers in serum, an enhanced level of lymphocyte proliferation, and higher numbers of gamma interferon-secreting cells at the site of infection. Based on the immunogenicity results, the R345V virus was further tested in a protection trial in which pigs were vaccinated twice with R345V and then challenged with homologous A/Sw/Saskatchewan/18789/02, H1N1 antigenic variant A/Sw/Indiana/1726/88 or heterologous subtypic H3N2 A/Sw/Texas/4199-2/9/98. Our data showed that two vaccinations with R345V provided pigs with complete protection from homologous H1N1 SIV infection and partial protection from heterologous subtypic H3N2 SIV infection. This protection was characterized by significantly reduced macroscopic and microscopic lung lesions, lower virus titers from the respiratory tract, and lower levels of proinflammatory cytokines. Thus, elastase-dependent SIV mutants can be used as live-virus vaccines against swine influenza in pigs.
Matrix and Envelope Coevolution Revealed in a Patient Monitored since Primary Infection with Human Immunodeficiency Virus Type 1
Authors: Beaumont Elodie , Vendrame Daniela , Verrier Bernard , Roch Emmanuelle , Biron François , Barin Françis , Mammano Fabrizio , Brand Denys
Published: July 2009

Lentiviruses, including human immunodeficiency virus type 1 (HIV-1), typically encode envelope glycoproteins (Env) with long cytoplasmic tails (CTs). The strong conservation of CT length in primary isolates of HIV-1 suggests that this factor plays a key role in viral replication and persistence in infected patients. However, we report here the emergence and dominance of a primary HIV-1 variant carrying a natural 20-amino-acid truncation of the CT in vivo. We demonstrated that this truncation was deleterious for viral replication in cell culture. We then identified a compensatory amino acid substitution in the matrix protein that reversed the negative effects of CT truncation. The loss or rescue of infectivity depended on the level of Env incorporation into virus particles. Interestingly, we found that a virus mutant with defective Env incorporation was able to spread by cell-to-cell transfer. The effects on viral infectivity of compensation between the CT and the matrix protein have been suggested by in vitro studies based on T-cell laboratory-adapted virus mutants, but we provide here the first demonstration of the natural occurrence of similar mechanisms in an infected patient. Our findings provide insight into the potential of HIV-1 to evolve in vivo and its ability to overcome major structural alterations.
The Choice of Translation Initiation Site of the Rep Proteins from Goose Parvovirus P9-Generated mRNA Is Governed by Splicing and the Nature of the Excised Intron
Authors: Li Long , Qiu Jianming , Pintel David J.
Published: July 2009

The goose parvovirus (GPV) Rep 1 and Rep 2 proteins are encoded by P9-generated mRNAs that are either unspliced or spliced within the
rep
gene region, respectively. These mRNAs are present in an approximately equal ratio. The translation of Rep 1 was initiated from the first AUG in unspliced P9-generated mRNA; however, this AUG was bypassed in spliced P9-generated RNA and Rep 2 translation initiated predominately at the next initiating AUG downstream. We show that the choice of the site of initiation of translation of GPV Rep-encoding mRNAs is governed both by the splicing process itself and by the nature of the excised intron.
Evolution of Teleost Fish Retroviruses: Characterization of New Retroviruses with Cellular Genes
Authors: Basta Holly A. , Cleveland Sean B. , Clinton Rochelle A. , Dimitrov Alexander G. , McClure Marcella A.
Published: July 2009

The interactions between retroviruses and their hosts can be of a beneficial or detrimental nature. Some endogenous retroviruses are involved in development, while others cause disease. The Genome Parsing Suite (GPS) is a software tool to track and trace all Retroid agents in any sequenced genome (M. A. McClure et al., Genomics 85:512-523, 2005). Using the GPS, the retroviral content was assessed in four model teleost fish. Eleven new species of fish retroviruses are identified and characterized. The reverse transcriptase protein sequences were used to reconstruct a fish retrovirus phylogeny, thereby, significantly expanding the epsilonretrovirus family. Most of these novel retroviruses encode additional genes, some of which are homologous to cellular genes that would confer viral advantage. Although the fish divergence is much more ancient, retroviruses began infecting fish genomes approximately 4 million years ago.
COMPARING PEARSON, SPEARMAN AND HOEFFDING'S D MEASURE FOR GENE EXPRESSION ASSOCIATION ANALYSIS
Authors: FUJITA ANDRÉ , SATO JOÃO RICARDO , DEMASI MARCOS ANGELO ALMEIDA , SOGAYAR MARI CLEIDE , FERREIRA CARLOS EDUARDO , MIYANO SATORU
Published: July 2009

DNA microarrays have become a powerful tool to describe gene expression profiles associated with different cellular states, various phenotypes and responses to drugs and other extra- or intra-cellular perturbations. In order to cluster co-expressed genes and/or to construct regulatory networks, definition of distance or similarity between measured gene expression data is usually required, the most common choices being Pearson's and Spearman's correlations. Here, we evaluate these two methods and also compare them with a third one, namely Hoeffding's D measure, which is used to infer nonlinear and non-monotonic associations, i.e. independence in a general sense. By comparing three different variable association approaches, namely Pearson's correlation, Spearman's correlation and Hoeffding's D measure, we aimed at assessing the most approppriate one for each purpose. Using simulations, we demonstrate that the Hoeffding's D measure outperforms Pearson's and Spearman's approaches in identifying nonlinear associations. Our results demonstrate that Hoeffding's D measure is less sensitive to outliers and is a more powerful tool to identify nonlinear and non-monotonic associations. We have also applied Hoeffding's D measure in order to identify new putative genes associated with tp53. Therefore, we propose the Hoeffding's D measure to identify nonlinear associations between gene expression profiles.
THE NET-HMM APPROACH: PHYLOGENETIC NETWORK INFERENCE BY COMBINING MAXIMUM LIKELIHOOD AND HIDDEN MARKOV MODELS
Authors: SNIR SAGI , TULLER TAMIR
Published: July 2009

Horizontal gene transfer (HGT) is the event of transferring genetic material from one lineage in the evolutionary tree to a different lineage. HGT plays a major role in bacterial genome diversification and is a significant mechanism by which bacteria develop resistance to antibiotics. Although the prevailing assumption is of complete HGT, cases of partial HGT (which are also named chimeric HGT) where only part of a gene is horizontally transferred, have also been reported, albeit less frequently. In this work we suggest a new probabilistic model, the NET-HMM, for analyzing and modeling phylogenetic networks. This new model captures the biologically realistic assumption that neighboring sites of DNA or amino acid sequences are not independent, which increases the accuracy of the inference. The model describes the phylogenetic network as a Hidden Markov Model (HMM), where each hidden state is related to one of the network's trees. One of the advantages of the NET-HMM is its ability to infer partial HGT as well as complete HGT. We describe the properties of the NET-HMM, devise efficient algorithms for solving a set of problems related to it, and implement them in software. We also provide a novel complementary significance test for evaluating the fitness of a model (NET-HMM) to a given dataset. Using NET-HMM, we are able to answer interesting biological questions, such as inferring the length of partial HGT's and the affected nucleotides in the genomic sequences, as well as inferring the exact location of HGT events along the tree branches. These advantages are demonstrated through the analysis of synthetical inputs and three different biological inputs.
DETECTION AND QUANTIFICATION OF CONTROL VALVE NONLINEARITIES USING HILBERT–HUANG TRANSFORM
Authors: BABJI S. , GORAI P. , TANGIRALA A. K.
Published: July 2009

Two of the most important sources of degradation of control loop performance are (i) valve stiction and (ii) tight controller tuning, both of which lead to oscillations in closed–loop outputs. A factor that distinguishes these two sources is the nonlinear signature of the valve stiction; a tightly tuned controller produces oscillations due to a linear source. Detection and isolation of nonlinear fault sources is essential to correctly determine the cause of poor loop performance of control loops. Despite a rich research activity in this area, there is hardly a method which can isolate the simultaneous effects of these two sources. Moreover, the traditional spectral analysis based on Fourier Transforms is largely restricted by the assumption of stationarity in the data to detect and quantify valve nonlinearities. In this work, Hilbert–Huang Transform (HHT) is used to (i) detect valve nonlinearities and (ii) isolate linear and nonlinear fault sources. The key characteristic of HHT is that it represents nonlinearities as intra-wave frequency modulations allowing it to distinguish it from linearities which do not exhibit such modulations. The advantages of HHT-based methods are that (i) nonlinearities translate to a unique signature (ii) nonstationarities in data can be handled in a natural way. It is observed that nonlinearity is captured by a Intrinsic Mode Functions (IMF) obtained from the Empirical Mode Decomposition (EMD) of the process output. The Hilbert–Huang spectrum of these IMFs exhibits intra-wave frequency modulation. The power spectrum of the IMFs shows the presence of harmonics which is used to characterize the valve stiction nonlinearity. Subsequent to detection, quantification is done using the power spectrum of the IMFs. The proposed method is sensitive enough to detect low levels of valve stiction nonlinearities. Results from simulation using one-parameter valve stiction model are presented in support of the proposed methodology. The results demonstrate the advantage and potential of the HHT-based method.
THE MULTI-DIMENSIONAL ENSEMBLE EMPIRICAL MODE DECOMPOSITION METHOD
Authors: WU ZHAOHUA , HUANG NORDEN E. , CHEN XIANYAO
Published: July 2009

A multi-dimensional ensemble empirical mode decomposition (MEEMD) for multi-dimensional data (such as images or solid with variable density) is proposed here. The decomposition is based on the applications of ensemble empirical mode decomposition (EEMD) to slices of data in each and every dimension involved. The final reconstruction of the corresponding intrinsic mode function (IMF) is based on a comparable minimal scale combination principle.

For two-dimensional spatial data or images, f(x,y), we consider the data (or image) as a collection of one-dimensional series in both x-direction and y-direction. Each of the one-dimensional slices is decomposed through EEMD with the slice of the similar scale reconstructed in resulting two-dimensional pseudo-IMF-like components. This new two-dimensional data is further decomposed, but the data is considered as a collection of one-dimensional series in y-direction along locations in x-direction. In this way, we obtain a collection of two-dimensional components. These directly resulted components are further combined into a reduced set of final components based on a minimal-scale combination strategy.

The approach for two-dimensional spatial data can be extended to multi-dimensional data. EEMD is applied in the first dimension, then in the second direction, and then in the third direction, etc., using the almost identical procedure as for the two-dimensional spatial data. A similar comparable minimal-scale combination strategy can be applied to combine all the directly resulted components into a small set of multi-dimensional final components.

For multi-dimensional temporal-spatial data, EEMD is applied to time series of each spatial location to obtain IMF-like components of different time scales. All the ith IMF-like components of all the time series of all spatial locations are arranged to obtain ith temporal-spatial multi-dimensional IMF-like component. The same approach to the one used in temporal-spatial data decomposition is used to obtain the resulting two-dimensional IMF-like components. This approach could be extended to any higher dimensional temporal-spatial data.
Cytochrome c oxidase III as a mechanism for apoptosis in heart failure following myocardial infarction
Authors: Wu Changgong , Yan Lin , Depre Christophe , Dhar Sunil K. , Shen You-Tang , Sadoshima Junichi , Vatner Stephen F. , Vatner Dorothy E.
Published: July 2009

Cytochrome c oxidase (COX) is composed of 13 subunits, of which COX I, II, and III are encoded by a mitochondrial gene. COX I and II function as the main catalytic components, but the function of COX III is unclear. Because myocardial ischemia affects mitochondrial oxidative metabolism, we hypothesized that COX activity and expression would be affected during postischemic cardiomyopathy. This hypothesis was tested in a monkey model following myocardial infarction (MI) and subsequent pacing-induced heart failure (HF). In this model, COX I protein expression was decreased threefold after MI and fourfold after HF ( P < 0.05 vs. sham), whereas COX II expression remained unchanged. COX III protein expression increased 5-fold after MI and further increased 10-fold after HF compared with sham ( P < 0.05 vs. sham). The physiological impact of COX III regulation was examined in vitro. Overexpression of COX III in mitochondria of HL-1 cells resulted in an 80% decrease in COX I, 60% decrease in global COX activity, 60% decrease in cell viability, and threefold increase in apoptosis ( P < 0.05). Oxidative stress induced by H2O2 significantly ( P < 0.05) increased COX III expression. H2O2 decreased cell viability by 47 ± 3% upon overexpression of COX III, but only by 12 ± 5% in control conditions ( P < 0.05). We conclude that ischemic stress in vivo and oxidative stress in vitro lead to upregulation of COX III, followed by downregulation of COX I expression, impaired COX oxidative activity, and increased apoptosis. Therefore, upregulation of COX III may contribute to the increased susceptibility to apoptosis following MI and subsequent HF.
Caffeine inhibits nonselective cationic currents in interstitial cells of Cajal from the murine jejunum
Authors: Jin Nan Ge , Koh Sang Don , Sanders Kenton M.
Published: July 2009

Interstitial cells of Cajal (ICC) discharge unitary potentials in gastrointestinal muscles that constitute the basis for pacemaker activity. Caffeine has been used to block unitary potentials, but the ionic conductance responsible for unitary potentials is controversial. We investigated currents in cultured ICC from murine jejunum that may underlie unitary potentials and studied the effects of caffeine. Networks of ICC generated slow wave events under current clamp, and these events were blocked by caffeine in a concentration-dependent manner. Single ICC generated spontaneous transient inward currents (STICs) under voltage clamp at −60 mV and noisy voltage fluctuations in current clamp. STICs were unaffected when the equilibrium potential for Cl− ( ECl) was set to −60 mV (excluding Cl− currents) and reversed at 0 mV, demonstrating that a nonselective cationic conductance, and not a Cl− conductance, is responsible for STICs in ICC. Caffeine inhibited STICs in a concentration-dependent manner. Reduced intracellular Ca2+ and calmidazolium (CMZ; 1 μM) activated persistent inward, nonselective cation currents in ICC. Currents activated by CMZ and by dialysis of cells with 10 mM BAPTA were also inhibited by caffeine. Excised inside-out patches contained channels that exhibited spontaneous openings, and resulting currents reversed at 0 mV. Channel openings were increased by reducing Ca2+ concentration from 10−6 M to 10−8 M. CMZ (1 μM) also increased openings of nonselective cation channels. Spontaneous currents and channels activated by CMZ were inhibited by caffeine (5 mM). The findings demonstrate that the Ca2+-inhibited nonselective cation channels that generate STICs in ICC are blocked directly by caffeine. STICs are responsible for unitary potentials in intact muscles, and the block of these events by caffeine is consistent with the idea that a nonselective cation conductance underlies unitary potentials in ICC.
Interleukin-1 stimulates catabolism in C2C12 myotubes
Authors: Li Wei , Moylan Jennifer S. , Chambers Melissa A. , Smith Jeffrey , Reid Michael B.
Published: July 2009

Interleukin-1 (IL-1) is an inflammatory cytokine that has been linked to muscle catabolism, a process regulated by muscle-specific E3 proteins of the ubiquitin-proteasome pathway. To address cellular mechanism, we tested the hypothesis that IL-1 induces myofibrillar protein loss by acting directly on muscle to increase expression of two critical E3 proteins, atrogin1/muscle atrophy F-box (MAFbx) and muscle RING-finger 1 (MuRF1). Experiments were conducted using mature C2C12 myotubes to eliminate systemic cytokine effects and avoid paracrine signaling by nonmuscle cell types. Time-course protocols were used to define the sequence of cellular responses. We found that atrogin1/MAFbx mRNA and MuRF1 mRNA are elevated 60–120 min after myotube exposure to either IL-1α or IL-1β. These responses are preceded by signaling events that promote E3 expression. Both IL-1 isoforms stimulate phosphorylation of p38 mitogen-activated protein kinase and stimulate nuclear factor-κB (NF-κB) signaling; I-κB levels fall and NF-κB DNA binding activity increases. Other regulators of E3 expression are unaffected by IL-1 [cytosolic oxidant activity, Forkhead-O (Foxo) activity] or respond paradoxically (AKT). Chronic exposure of C2C12 myotubes over 48 h resulted in reduced myotube width and loss of sarcomeric actin. We conclude that IL-1α and IL-1β act via an oxidant- and AKT/Foxo-independent mechanism to activate p38 MAPK, stimulate NF-κB signaling, increase expression of atrogin1/MAFbx and MuRF1, and reduce myofibrillar protein in differentiated myotubes.
Cloning, localization, and functional expression of the electrogenic Na+ bicarbonate cotransporter (NBCe1) from zebrafish
Authors: Sussman Caroline R. , Zhao Jinhua , Plata Consuelo , Lu Jing , Daly Christopher , Angle Nathan , DiPiero Jennifer , Drummond Iain A. , Liang Jennifer O. , Boron Walter F. , Romero Michael F. , Chang Min-Hwang
Published: July 2009

Mutations in the electrogenic Na+/ nHCO3− cotransporter (NBCe1, SLC4A4) cause severe proximal renal tubular acidosis, glaucoma, and cataracts in humans, indicating NBCe1 has a critical role in acid-base homeostasis and ocular fluid transport. To better understand the homeostatic roles and protein ontogeny of NBCe1, we have cloned, localized, and downregulated NBCe1 expression in zebrafish, and examined its transport characteristics when expressed in Xenopus oocytes. Zebrafish NBCe1 (zNBCe1) is 80% identical to published mammalian NBCe1 cDNAs. Like other fish NBCe1 clones, zebrafish NBCe1 is most similar to the pancreatic form of mammalian NBC (Slc4a4-B) but appears to be the dominant isoform found in zebrafish. In situ hybridization of embryos demonstrated mRNA expression in kidney pronephros and eye by 24 h postfertilization (hpf) and gill and brain by 120 hpf. Immunohistochemical labeling demonstrated expression in adult zebrafish eye and gill. Morpholino knockdown studies demonstrated roles in eye and brain development and caused edema, indicating altered fluid and electrolyte balance. With the use of microelectrodes to measure membrane potential ( Vm), voltage clamp (VC), intracellular pH (pHi), or intracellular Na+ activity ( aNai), we examined the function of zNBCe1 expressed in Xenopus oocytes. Zebrafish NBCe1 shared transport properties with mammalian NBCe1s, demonstrating electrogenic Na+ and HCO3− transport as well as similar drug sensitivity, including inhibition by 4,4′-diiso-thiocyano-2,2′-disulfonic acid stilbene and tenidap. These data indicate that NBCe1 in zebrafish shares many characteristics with mammalian NBCe1, including tissue distribution, importance in systemic water and electrolyte balance, and electrogenic transport of Na+ and HCO3−. Thus zebrafish promise to be useful model system for studies of NBCe1 physiology.
Effects of losartan on hepatic expression of nonphagocytic NADPH oxidase and fibrogenic genes in patients with chronic hepatitis C
Authors: Colmenero Jordi , Bataller Ramón , Sancho-Bru Pau , Domínguez Marlene , Moreno Montserrat , Forns Xavier , Bruguera Miquel , Arroyo Vicente , Brenner David A. , Ginès Pere
Published: July 2009

Angiotensin II promotes liver fibrogenesis by stimulating nonphagocytic NADPH oxidase (NOX)-induced oxidative stress. Angiotensin II type 1 (AT1) receptor blockers attenuate experimental liver fibrosis, yet their effects in human liver fibrosis are unknown. We investigated the effects of losartan on hepatic expression of fibrogenic, inflammatory, and NOX genes in patients with chronic hepatitis C (CHC). Fourteen patients with CHC and liver fibrosis received oral losartan (50 mg/day) for 18 mo. Liver biopsies were performed at baseline and after treatment. The degree of inflammation and fibrosis was evaluated by histological analysis (METAVIR). Collagen content was measured by morphometric quantification of Sirius red staining. Overall collagen content and fibrosis stage remained stable in the whole series, yet the fibrosis stage decreased in seven patients. Inflammatory activity improved in seven patients. The effect of losartan on hepatic expression of 31 profibrogenic and inflammatory genes and components of the NOX complex was assessed by quantitative PCR. Losartan treatment was associated with a significant decrease in the expression of several profibrogenic and NOX genes including procollagen α1(I) and α1(IV), urokinase-type plasminogen activator, metalloproteinase type 2, NOX activator 1 (NOXA-1) and organizer 1 (NOXO-1), and Rac-1. Losartan was well tolerated in all patients and was effective in attenuating the activity of the systemic renin-angiotensin system. No effects on serum liver tests or viral load were observed. We conclude that prolonged administration of losartan, an oral AT1 receptor blocker, is associated with downregulation of NOX components and fibrogenic genes in patients with CHC. Controlled studies are warranted to assess the effect of AT1 receptor blockers in chronic liver injury.