bluuebunny/crossref_metadata_2025 huggingface dataset:
Entecavir Exhibits Inhibitory Activity against Human Immunodeficiency Virus under Conditions of Reduced Viral Challenge
Authors: Lin Pin-Fang , Nowicka-Sans Beata , Terry Brian , Zhang Sharon , Wang Chunfu , Fan Li , Dicker Ira , Gali Volodymyr , Higley Helen , Parkin Neil , Tenney Daniel , Krystal Mark , Colonno Richard
Published: March 2008

Entecavir (ETV) was developed for the treatment of chronic hepatitis B virus (HBV) infection and is globally approved for that indication. Initial preclinical studies indicated that ETV had no significant activity against human immunodeficiency virus type 1 (HIV-1) in cultured cell lines at physiologically relevant ETV concentrations, using traditional anti-HIV assays. In response to recent clinical observations of anti-HIV activity of ETV in HIV/HBV-coinfected patients not receiving highly active antiretroviral therapy (HAART), additional investigative studies were conducted to expand upon earlier results. An extended panel of HIV-1 laboratory and clinical strains and cell types was tested against ETV, along with a comparison of assay methodologies and resistance profiling. These latest studies confirmed that ETV has only weak activity against HIV, using established assay systems. However, a >100-fold enhancement of antiviral activity (equivalent to the antiviral activity of lamivudine) could be obtained when assay conditions were modified to reduce the initial viral challenge. Also, the selection of a M184I virus variant during the passage of HIV-1 at high concentrations of ETV confirmed that ETV can exert inhibitory pressure on the virus. These findings may have a significant impact on how future assays are performed with compounds to be used in patients infected with HIV. These results support the recommendation that ETV therapy should be administered in concert with HAART for HIV/HBV-coinfected patients.
Inhibitors of Strand Transfer That Prevent Integration and Inhibit Human T-Cell Leukemia Virus Type 1 Early Replication
Authors: Rabaaoui Samira , Zouhiri Fatima , Lançon Agnès , Leh Hervé , d'Angelo Jean , Wattel Eric
Published: March 2008

The replication of the retrovirus human T-cell leukemia virus type 1 (HTLV-1) is linked to the development of lymphoid malignancies and inflammatory diseases. Data from in vitro, ex vivo, and in vivo studies have revealed that no specific treatment can prevent or block HTLV-1 replication and therefore that there is no therapy for the prevention and/or treatment of HTLV-1-associated diseases in infected individuals. HTLV-1 and human immunodeficiency virus type 1 (HIV-1) integrases, the enzymes that specifically catalyze the integration of these retroviruses in host cell DNA, share important structural properties, suggesting that compounds that inhibit HIV-1 integration could also inhibit HTLV-1 integration. We developed quantitative assays to test, in vitro and ex vivo, the efficiencies of styrylquinolines and diketo acids, the two main classes of HIV-1 integrase inhibitors. The compounds were tested in vitro in an HTLV-1 strand-transfer reaction and ex vivo by infection of fresh peripheral blood lymphocytes with lethally irradiated HTLV-1-positive cells. In vitro, four styrylquinoline compounds and two diketo acid compounds significantly inhibited HTLV-1 integration in a dose-dependent manner. All compounds active in vitro decreased cell proliferation ex vivo, although at low concentrations; they also dramatically decreased both normalized proviral loads and the number of integration events during experimental ex vivo primary infection. Accordingly, diketo acids and styrylquinolines are the first drugs that produce a specific negative effect on HTLV-1 replication in vitro and ex vivo, suggesting their potential efficiency for the prevention and treatment of HTLV-1-associated diseases.
The Lys234Arg Substitution in the Enzyme SHV-72 Is a Determinant for Resistance to Clavulanic Acid Inhibition
Authors: Mendonça Nuno , Manageiro Vera , Robin Frédéric , Salgado M. José , Ferreira Eugénia , Caniça Manuela , Bonnet Richard
Published: March 2008

The new β-lactamase SHV-72 was isolated from clinical
Klebsiella pneumoniae
INSRA1229, which exhibited the unusual association of resistance to the amoxicillin-clavulanic acid combination (MIC, 64 μg/ml) and susceptibility to cephalosporins, aztreonam, and imipenem. SHV-72 (pI 7.6) harbored the three amino acid substitutions Ile8Phe, Ala146Val, and Lys234Arg. SHV-72 had high catalytic efficiency against penicillins (
k
cat
/
K

m

, 35 to 287 μM
−1
·s
−1
) and no activity against oxyimino β-lactams. The concentration of clavulanic acid necessary to inhibit the enzyme activity by 50% was 10-fold higher for SHV-72 than for SHV-1. Molecular-dynamics simulation suggested that the Lys234Arg substitution in SHV-72 stabilized an atypical conformation of the Ser130 side chain, which moved the Oγ atom of Ser130 around 3.5 Å away from the key Oγ atom of the reactive serine (Ser70). This movement may therefore decrease the susceptibility to clavulanic acid by preventing cross-linking between Ser130 and Ser70.
Genetic and Physiological Effects of Noncoherent Visible Light Combined with Hydrogen Peroxide on
Streptococcus mutans
in Biofilm
Authors: Steinberg Doron , Moreinos Daniel , Featherstone John , Shemesh Moshe , Feuerstein Osnat
Published: March 2008

Oral biofilms are associated with the most common infections of the oral cavity. Bacteria embedded in the biofilms are less sensitive to antibacterial agents than planktonic bacteria are. Recently, an antibacterial synergic effect of noncoherent blue light and hydrogen peroxide (H
2
O
2
) on planktonic
Streptococcus mutans
was demonstrated. In this study, we tested the effect of a combination of light and H
2
O
2
on the vitality and gene expression of
S. mutans
embedded in biofilm. Biofilms of
S. mutans
were exposed to visible light (wavelengths, 400 to 500 nm) for 30 or 60 s (equivalent to 34 or 68 J/cm
2
) in the presence of 3 to 300 mM H
2
O
2
. The antibacterial effect was assessed by microbial counts of each treated sample compared with that of the control. The effect of light combined with H
2
O
2
on the different layers of the biofilm was evaluated by confocal laser scanning microscopy. Gene expression was determined by real-time reverse transcription-PCR. Our results show that noncoherent light, in combination with H
2
O
2
, has a synergistic antibacterial effect through all of the layers of the biofilm. Furthermore, this treatment was more effective against bacteria in biofilm than against planktonic bacteria. The combined light and H
2
O
2
treatment up-regulated the expression of several genes such as
gtfB
,
brp
,
smu630
, and
comDE
but did not affect
relA
and
ftf
. The ability of noncoherent visible light in combination with H
2
O
2
to affect bacteria in deep layers of the biofilm suggests that this treatment may be applied in biofilm-related diseases as a minimally invasive antibacterial procedure.
Rapid Point-of-Care Test To Detect Broad Ranges of Protective Antigen-Specific Immunoglobulin G Concentrations in Recipients of the U.S.-Licensed Anthrax Vaccine
Authors: Bienek Diane R. , Biagini Raymond E. , Charlton David G. , Smith Jerome P. , Sammons Deborah L. , Robertson Shirley A.
Published: March 2008

Currently, there is no routine monitoring of an immune response to the anthrax vaccine. Simple on-site tests are needed to evaluate the antibody response of anthrax-vaccinated individuals in the Armed Forces and others at high risk. Using a prototype lateral flow assay (LFA) (R. E. Biagini, D. L. Sammons, J. P. Smith, B. A. MacKenzie, C. A. F. Striley, J. E. Snawder, S. A. Robertson, and C. P. Quinn, Clin. Vaccine Immunol. 13:541-546, 2006), we investigated the agreement between a validated anthrax protective antigen (PA) immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and the LFA for 335 unvaccinated and vaccinated subjects. We also investigated the performance of the LFA under the following conditions: thermal shock (i.e., thermal cycling between temperature extremes), high temperature/high relative humidity, high temperature/low relative humidity, and low temperature/low relative humidity. With the anti-PA ELISA used as a standard, the LFA was shown to be optimally diagnostic at 11 μg/ml anti-PA-specific IgG. At this concentration, the LFA specificity and sensitivity were 98% (95% confidence interval [CI], 97% to 100%) and 92% (CI, 88% to 97%), respectively. Receiver operating characteristic curve analysis yielded an area under the curve value of 0.988 (CI, 0.976 to 1.00), suggesting that the LFA is an extremely accurate diagnostic test. For ≤4 or ≥50 μg/ml PA-specific IgG, the LFA results for each environmental condition were identical to those obtained in the laboratory. These data indicate that this rapid point-of-care test would be a feasible tool in monitoring the serological antibody responses of individuals that have been vaccinated against anthrax.
Emergence of a Tetracycline-ResistantCampylobacter jejuniClone Associated with Outbreaks of Ovine Abortion in the United States
Authors: Sahin Orhan , Plummer Paul J. , Jordan Dianna M. , Sulaj Kapllan , Pereira Sonia , Robbe-Austerman Suelee , Wang Liping , Yaeger Michael J. , Hoffman Lorraine J. , Zhang Qijing
Published: March 2008

Campylobacterinfection is one of the major causes of ovine abortions worldwide. Historically,Campylobacter fetussubsp.fetuswas the major cause ofCampylobacter-associated abortion in sheep; however,Campylobacter jejuniis increasingly associated with sheep abortions. We examined the species distribution, genotypes, and antimicrobial susceptibilities of abortion-associatedCampylobacterisolates obtained from multiple lambing seasons on different farms in Iowa, Idaho, South Dakota, and California. We found thatC. jejunihas replacedC. fetusas the predominantCampylobacterspecies causing sheep abortion in the United States. Most strikingly, the vast majority (66 of 71) of theC. jejuniisolates associated with sheep abortion belong to a single genetic clone, as determined by pulsed-field gel electrophoresis, multilocus sequence typing, andcmpgene (encoding the major outer membrane protein) sequence typing. The in vitro antimicrobial susceptibilities of these isolates to the antibiotics that are routinely used in food animal production were determined using the agar dilution test. All of the 74 isolates were susceptible to tilmicosin, florfenicol, tulathromycin, and enrofloxacin, and 97% were sensitive to tylosin. However, all were resistant to tetracyclines, the only antibiotics currently approved in the United States for the treatment ofCampylobacterabortion in sheep. This finding suggests that feeding tetracycline for the prevention ofCampylobacterabortions is ineffective and that other antibiotics should be used for the treatment of sheep abortions in the United States. Together, these results indicate that a single tetracycline-resistantC. jejuniclone has emerged as the major cause ofCampylobacter-associated sheep abortion in the United States.
Emergence and Dissemination of a Community-Associated Methicillin-Resistant Panton-Valentine Leucocidin-Positive
Staphylococcus aureus
Clone Sharing the Sequence Type 5 Lineage with the Most Prevalent Nosocomial Clone in the Same Region of Argentina
Authors: Sola Claudia , Saka Hector A. ,   the Cordoba MRSA Collaborative Study Group, Vindel Ana , Bocco José Luis
Published: March 2008

Epidemiological surveillance for community-associated methicillin-resistant
Staphylococcus aureus
revealed prevalences of 33% and 13% in pediatric and adult patients, respectively, in Cordoba, Argentina, in 2005. This study describes for the first time the emergence and dissemination of the sequence type 5 (ST5) lineage as the most prevalent clone (89%) (pulsed-field gel electrophoresis type I-ST5-staphylococcal cassette chromosome type IVa-
spa
type 311) harboring the Panton-Valentine leukocidin and enterotoxin A genes.
Detection of Diarrheagenic
Escherichia coli
by Use of Melting-Curve Analysis and Real-Time Multiplex PCR
Authors: Guion Chase E. , Ochoa Theresa J. , Walker Christopher M. , Barletta Francesca , Cleary Thomas G.
Published: March 2008

Diarrheagenic
Escherichia coli
strains are important causes of diarrhea in children from the developing world and are now being recognized as emerging enteropathogens in the developed world. Current methods of detection are too expensive and labor-intensive for routine detection of these organisms to be practical. We developed a real-time fluorescence-based multiplex PCR for the detection of all six of the currently recognized classes of diarrheagenic
E. coli
. The primers were designed to specifically amplify eight different virulence genes in the same reaction:
aggR
for enteroaggregative
E. coli
,
stIa
/
stIb
and
lt
for enterotoxigenic
E. coli
,
eaeA
for enteropathogenic
E. coli
and Shiga toxin-producing
E. coli
(STEC),
stx
1
and
stx
2
for STEC,
ipaH
for enteroinvasive
E. coli
, and
daaD
for diffusely adherent
E. coli
(DAEC). Eighty-nine of ninety diarrheagenic
E. coli
and 36/36 nonpathogenic
E. coli
strains were correctly identified using this approach (specificity, 1.00; sensitivity, 0.99). The single false negative was a DAEC strain. The total time between preparation of DNA from
E. coli
colonies on agar plates and completion of PCR and melting-curve analysis was less than 90 min. The cost of materials was low. Melting-point analysis of real-time multiplex PCR is a rapid, sensitive, specific, and inexpensive method for detection of diarrheagenic
E. coli
.
Genotypic Diversity of Anaerobic Isolates from Bloodstream Infections
Authors: Simmon Keith E. , Mirrett Stanley , Reller L. Barth , Petti Cathy A.
Published: March 2008

Accurate species determination for anaerobes from blood culture bottles has become increasingly important with the reemergence of anaerobic bacteremia and prevalence of multiple-drug-resistant microorganisms. Our knowledge of the taxonomical diversity of anaerobes that cause bloodstream infections is extremely limited, because identification historically has relied on conventional methods. Over a 5-year period, we profiled anaerobic bacteremia at a large tertiary care hospital with 16S rRNA gene sequencing to gain a better understanding of the taxonomical diversity of the bacteria. Of 316 isolates, 16S rRNA gene sequencing and phylogenetic analysis identified 316 (100%) to the genus or taxonomical group level and 289 (91%) to the species level. Conventional methods identified 279 (88%) to the genus level and 208 (66%) to the species level; 75 (24%) were misidentified at the species level, and 33 (10%) results were inconclusive. High intragenus variability was observed for
Bacteroides
and
Clostridium
species, and high intraspecies variability was observed for
Bacteroides thetaiotaomicron
and
Fusobacterium nucleatum
. Sequence-based identification has potential benefits in comparison to conventional methods, because it more accurately characterizes anaerobes within taxonomically related clusters and thereby may enable better correlation with specific clinical syndromes and antibiotic resistance patterns.
Influenza A Virus Neuraminidase Limits Viral Superinfection
Authors: Huang I-Chueh , Li Wenhui , Sui Jianhua , Marasco Wayne , Choe Hyeryun , Farzan Michael
Published: March 2008

Enveloped viruses use multiple mechanisms to inhibit infection of a target cell by more than one virion. These mechanisms may be of particular importance for the evolution of segmented viruses, because superinfection exclusion may limit the frequency of reassortment of viral genes. Here, we show that cellular expression of influenza A virus neuraminidase (NA), but not hemagglutinin (HA) or the M2 proton pump, inhibits entry of HA-pseudotyped retroviruses. Cells infected with H1N1 or H3N2 influenza A virus were similarly refractory to HA-mediated infection and to superinfection with a second influenza A virus. Both HA-mediated entry and viral superinfection were rescued by the neuraminidase inhibitors oseltamivir carboxylate and zanamivir. These inhibitors also prevented the removal of α-2,3- and α-2,6-linked sialic acid observed in cells expressing NA or infected with influenza A viruses. Our data indicate that NA alone among viral proteins limits influenza A virus superinfection.
Casein Kinase II Motif-Dependent Phosphorylation of Human Papillomavirus E7 Protein Promotes p130 Degradation and S-Phase Induction in Differentiated Human Keratinocytes
Authors: Genovese Nicholas J. , Banerjee N. Sanjib , Broker Thomas R. , Chow Louise T.
Published: March 2008

The E7 proteins of human papillomaviruses (HPVs) promote S-phase reentry in differentiated keratinocytes of the squamous epithelia to support viral DNA amplification. In this study, we showed that nuclear p130 was present in the differentiated strata of several native squamous epithelia susceptible to HPV infection. In contrast, p130 was below the level of detection in HPV-infected patient specimens. In submerged and organotypic cultures of primary human keratinocytes, the E7 proteins of the high-risk mucosotrophic HPV-18, the benign cutaneous HPV-1, and, to a lesser extent, the low-risk mucosotropic HPV-11 destabilized p130. This E7 activity depends on an intact pocket protein binding domain and a casein kinase II (CKII) phosphorylation motif. Coimmunoprecipitation experiments showed that both E7 domains were important for binding to p130 in extracts of organotypic cultures. Metabolic labeling in vivo demonstrated that E7 proteins were indeed phosphorylated in a CKII motif-dependent manner. Moreover, the efficiencies of the E7 proteins of various HPV types or mutations to induce S-phase reentry in spinous cells correlated with their relative abilities to bind and to destabilize p130. Collectively, these data support the notion that p130 controls the homeostasis of the differentiated keratinocytes and is therefore targeted by E7 for degradation to establish conditions permissive for viral DNA amplification.
Importance of Protease Cleavage Sites within and Flanking Human Immunodeficiency Virus Type 1 Transframe Protein p6* for Spatiotemporal Regulation of Protease Activation
Authors: Ludwig Christine , Leiherer Andreas , Wagner Ralf
Published: March 2008

The human immunodeficiency virus type 1 (HIV-1) protease (PR) has recently been shown to be inhibited by its propeptide p6* in vitro. As p6* itself is a PR substrate, the primary goal of this study was to determine the importance of p6* cleavage for HIV-1 maturation and infectivity. For that purpose, short peptide variants mimicking proposed cleavage sites within and flanking p6* were designed and analyzed for qualitative and quantitative hydrolysis in vitro. Proviral clones comprising the selected cleavage site mutations were established and analyzed for Gag and Pol processing, virus maturation, and infectivity in cultured cells. Amino-terminal cleavage site mutation caused aberrant processing of nucleocapsid proteins and delayed replication kinetics. Blocking the internal cleavage site resulted in the utilization of a flanking site at a significantly decreased hydrolysis rate in vitro, which however did not affect Gag-Pol processing and viral replication. Although mutations blocking cleavage at the p6* carboxyl terminus yielded noninfectious virions exhibiting severe Gag processing defects, mutations retarding hydrolysis of this cleavage site neither seemed to impact viral infectivity and propagation in cultured cells nor seemed to interfere with overall maturation of released viruses. Interestingly, these mutants were shown to be clearly disadvantaged when challenged with wild-type virus in a dual competition assay. In sum, we conclude that p6* cleavage is absolutely essential to allow complete activation of the PR and subsequent processing of the viral precursors.
A Novel Methyltransferase MethylatesCucumber Mosaic Virus1a Protein and Promotes Systemic Spread
Authors: Kim Min Jung , Huh Sung Un , Ham Byung-Kook , Paek Kyung-Hee
Published: March 2008

In mammalian and yeast systems, methyltransferases have been implicated in the regulation of diverse processes, such as protein-protein interactions, protein localization, signal transduction, RNA processing, and transcription. TheCucumber mosaic virus(CMV) 1a protein is essential not only for virus replication but also for movement. Using a yeast two-hybrid system with tobacco plants, we have identified a novel gene encoding a methyltransferase that interacts with the CMV 1a protein and have designated this geneTcoi1(tobaccoCMV 1a-interacting protein1). Tcoi1 specifically interacted with the methyltransferase domain of CMV 1a, and the expression ofTcoi1was increased by CMV inoculation. Biochemical studies revealed that the interaction of Tcoi1 with CMV 1a protein was direct and that Tcoi1 methylated CMV 1a protein both in vitro and in vivo. The CMV 1a binding activity of Tcoi1 is in the C-terminal domain, which shows the methyltransferase activity. The overexpression of Tcoi1 enhanced the CMV infection, while the reduced expression of Tcoi1 decreased virus infectivity. These results suggest that Tcoi1 controls the propagation of CMV through an interaction with the CMV 1a protein.
“Where our women used to get the food”: cumulative effects and loss of ethnobotanical knowledge and practice; case study from coastal British ColumbiaThis paper was submitted for the Special Issue on Ethnobotany, inspired by the Ethnobotany Symposium organized by Alain Cuerrier, Montreal Botanical Garden, and held in Montreal at the 2006 annual meeting of the Canadian Botanical Association.
Authors: Turner Nancy J. , Turner Katherine L.
Published: March 2008

Knowledge and practices of indigenous peoples relating to local plants used for food, medicine, materials, and other purposes are threatened in many parts of the world. The reasons for declining knowledge and use of traditional resources are complex and multifaceted. We review a series of case examples of culturally valued food plants in British Columbia and identify a suite of interacting social and environmental factors that have resulted in decreased use of and dwindling cultural knowledge about these plants over the past 150 years. Reasons for this loss include compounding influences of changing knowledge systems owing to religious conversion and residential schools, loss of indigenous languages, loss of time and opportunity for traditional practices owing to participation in the wage economy, increasing urbanization of indigenous populations, loss of access to traditional resources, restriction of management practices for sustaining these resources, and most recently, forces of globalization and industrialization. Efforts to renew and restore traditional practices and relationships with plants and environments must recognize the cumulative effects of these factors and find ways to retain and reinforce the knowledge and practices still held by individuals and communities, to reverse some of the negative influences on cultural retention, and to develop new, relevant, and effective ways to revitalize languages, cultures, and ethnobotanical knowledge within contemporary contexts.
Medicinal plants used by the Inuit of Qikiqtaaluk (Baffin Island, Nunavut)This paper was submitted for the Special Issue on Ethnobotany, inspired by the Ethnobotany Symposium organized by Alain Cuerrier, Montréal Botanical Garden, and held in Montréal at the 2006 annual meeting of the Canadian Botanical Association/l’Association Botanique du Canada.
Authors: Black Paleah L. , Arnason John T. , Cuerrier Alain
Published: March 2008

The traditional medicinal uses of plants by the Inuit of Nunavut, Canada were analysed using quantitative ethnobotanical methodology. Traditional knowledge was collected during interviews with volunteer Inuit informants and from historical interview transcripts. A total of 13 different species were mentioned, which included 1 moss, 1 algae, 1 fungus, and 10 vascular plant species. An informant consensus index value, Fic > 0.7, for many use categories revealed a high level of informant agreement, consistent with a well-preserved oral tradition and low flora biodiversity. The documentation of this information is a useful tool for the preservation of Inuit culture, as well as for the integration of Inuit traditional medicine with Western medical practices in Arctic communities (Inuit Qaujimajatuqangit, IQ).
On the function of hermaphrodite florets in female inflorescences ofPetasites japonicus(Asteraceae)
Authors: Sakai Satoki , Suzuki Yuka , Itagaki Tomoyuki , Tsujisawa Hisashi , Makino Takashi T.
Published: March 2008

To examine the function of morphologically hermaphroditic, but functionally sterile, florets in female inflorescences of Petasites japonicus (Sieb. & Zucc.) Maxim., we conducted experiments in which all those florets were removed from female inflorescences. We hypothesize that those florets enhance female reproductive success by deceit, because they resemble the morphologically hermaphroditic, but functionally male florets, in male inflorescences. We found that the mean number of pollinator visits per inflorescence did not differ between the intact inflorescences and inflorescences in which such hermaphrodite florets had been removed. However, the mean duration of stay per visit to an inflorescence tended to be shorter in those with removed florets than in the intact inflorescences. The achene / female floret ratio was smaller in the inflorescences with removed florets than in the intact ones. We hence concluded that the hermaphrodite florets in female inflorescences enhance female reproductive success through prolonged duration of pollinator stay.
Atmospheric nitrogen dioxide at ambient levels stimulates growth and development of horticultural plants
Authors: Adam Suaad E.H. , Shigeto Jun , Sakamoto Atsushi , Takahashi Misa , Morikawa Hiromichi
Published: March 2008

We recently discovered that atmospheric nitrogen dioxide (NO2) at ambient levels acts as a signal to Nicotiana plumbaginifolia Viviani, causing these plants to double both their biomass and all of the cell contents. Herein, we addressed whether this effect of NO2 is also observed in various horticultural plants. Lettuce ( Lactuca sativa L.), sunflower ( Helianthus annuus L.), cucumber ( Cucumis sativus L.), and pumpkin ( Cucurbita moschata Duch. ex Lam.) were grown with 50, 200, 100, and 200 µL·L–1, respectively, of air supplemented with stable isotope-labelled (15N) NO2, for 5−6 weeks. Control plants were grown without NO2 (<5 µL·L–1). All plants were irrigated with nonlabelled nitrate. The presence of NO2 doubled both the aboveground and belowground biomass in sunflowers compared with their growth in the absence of NO2, whereas lettuce, cucumber, and pumpkin doubled in aboveground biomass only. Contents per shoot of carbon (C), nitrogen (N), phosphorus (P), potassium (K), calcium (Ca), and magnesium (Mg) were almost doubled during the “NO2-enhanced” growth in lettuce, but not in other plants. Mass spectrometry analysis of 15N/14N indicated that only a minor proportion (0.2%–14%) of total plant N was derived from NO2, implying that exogenous NO2 acts as a signal rather than a significant nutrient source in horticultural plants.
DISCRIMINATING QUANTUM CHANNELS WITH RELATIVE ENTROPY
Authors: QIN TAO , ZHAO MEISHENG , ZHANG YONGDE
Published: March 2008

We address the possibilities of distinguishing the quantum channels in terms of relative entropy. Particularly, depolarizing channels and bosonic Gaussian channels are considered. To some extent, the relative entropy can be treated as a measure to discriminate the quantum channels.
UV p-i-n PHOTODIODES MADE ON WIDE BANDGAP SEMICONDUCTORS
Authors: GASPARYAN FERDINAND V.
Published: March 2008

In this paper, results of investigations on the static and dynamic characteristics, responsivity, internal noises, detectivity and noise equivalent power of the forward biased p-i-n photodiode made on wide band gap semiconductors operating in double injection regime are presented. Numerical simulations were made for 4H-SiC and GaN . It is shown that forward biased p-i-n photodiodes have high values of responsivity (~ 0.03 A/W for 4H-SiC and ~ 0.15 A/W for GaN ), detectivity (~1011 cm Hz 1/2 W-1 for 4H-SiC and ~ 8×1013 cm Hz 1/2 W-1 for GaN ) and low level of internal noises at room temperature. It is shown also that dynamic negative resistance on the current–voltage characteristic can come into existence and that the reactive part of the impedance is the sign-changed function versus frequency.
ATTRIBUTION STYLE AND ENTREPRENEURIAL SUCCESS: A STUDY BASED ON INDIAN CULTURE
Authors: CHATTOPADHYAY RACHANA
Published: March 2008

Attribution theory is said to be one of the few psychological theories that can deal with entrepreneurial persistence and setbacks. To explain the question why some entrepreneurs “succeed” in establishing the firm and others do not, recently researchers are emphasizing upon the attribution style of the entrepreneurs. Moreover, US Panel Study of Entrepreneurial Dynamics (PSED) by Gartner and Shaver (2002) is also pointed out that nascent entrepreneurs show self serving bias in their attribution style. To know whether Indian nascent entrepreneurs show the same style of attribution, this study has been conducted. In this study, differentiation has been made upon high and low success group of nascent entrepreneurs in association with attribution style. Results of this study indicate different style of attribution among Indian nascent entrepreneurs.
SOFTWARE RELIABILITY MODELING BASED ON MIXED POISSON DISTRIBUTIONS
Authors: OKAMURA HIROYUKI , DOHI TADASHI
Published: March 2008

This paper considers a novel modeling framework of software reliability models (SRMs). The proposed SRMs are based on the mixed Poisson distribution (MPD), which can involve the non-homogeneous Poisson process (NHPP) based SRMs completely, but are not always equivalent to them. More precisely, the MPD-based SRMs provide a mixture of NHPPs, and their statistical properties follows the mixed Poisson process. We develop a parameter estimation method for the MPD-based SRMs based on EM algorithm. In numerical examples, we mainly investigate the difference between conventional NHPP-based SRMs and MPD-based SRMs in the viewpoints of estimating parameters and software reliability.
ANALYSIS OF PULSE PROPAGATION THROUGH A ONE-DIMENSIONAL RANDOM MEDIUM USING COMPLEX MARTINGALES
Authors: GARNIER JOSSELIN , PAPANICOLAOU GEORGE
Published: March 2008

We show that the propagation of pulses in a one-dimensional random medium can be characterized using a new complex martingale representation of the transmission coefficient. This representation holds in the frequency domain and in a certain asymptotic limit where diffusion approximations can be used.
THERMODYNAMIC FORMALISM FOR RANDOM TRANSFORMATIONS REVISITED
Authors: KIFER YURI
Published: March 2008

We return to the thermodynamic formalism constructions for random expanding in average transformations and for random subshifts of finite type with random rates of topological mixing, as well as to the Perron–Frobenius type theorem for certain random positive linear operators. Our previous expositions in [14, 19] and [21] were based on constructions which left some gaps and inaccuracies related to the measurability and uniqueness issues. Our approach here is based on Hilbert projective norms which were already applied in [5] for the thermodynamic formalism constructions for random subshifts of finite type but our method is somewhat different and more general so that it enables us to treat simultaneously both expanding and subshift cases.
OPTIMAL CONTROL FOR ROUGH DIFFERENTIAL EQUATIONS
Authors: MAZLIAK LAURENT , NOURDIN IVAN
Published: March 2008

In this note, we consider an optimal control problem associated to a differential equation driven by a Hölder continuous function g of index β > 1/2. We split our study into two cases. If the coefficient of dgtdoes not depend on the control process, we prove an existence theorem for a slightly generalized control problem, that is we obtain a literal extension of the corresponding situation for ordinary differential equations. If the coefficient of dgtdepends on the control process, we also prove an existence theorem but here we are obliged to restrict the set of controls to sufficiently regular functions.
TWO PLUS TWO DOES NOT EQUAL THREE: STATISTICAL TESTS FOR MULTIPLE GENOME COMPARISON
Authors: RAGHUPATHY NARAYANAN , HOBERMAN ROSE , DURAND DANNIE
Published: March 2008

Gene clusters that span three or more chromosomal regions are of increasing importance, yet statistical tests to validate such clusters are in their infancy. Current approaches either conduct several pairwise comparisons or consider only the number of genes that occur in all of the regions. In this paper, we provide statistical tests for clusters spanning exactly three regions based on genome models of typical comparative genomics problems, including analysis of conserved linkage within multiple species and identification of large-scale duplications. Our tests are the first to combine evidence from genes shared among all three regions and genes shared between pairs of regions. We show that our tests of clusters spanning three regions are more sensitive than existing approaches, and can thus be used to identify more diverged homologous regions.
COMPLEXITIES AND ALGORITHMS FOR GLYCAN SEQUENCING USING TANDEM MASS SPECTROMETRY
Authors: SHAN BAOZHEN , MA BIN , ZHANG KAIZHONG , LAJOIE GILLES
Published: March 2008

Determining glycan structures is vital to comprehend cell-matrix, cell-cell, and even intracellular biological events. Glycan sequencing, which determines the primary structure of a glycan using tandem mass spectrometry (MS/MS), remains one of the most important tasks in proteomics. Analogous to peptide de novo sequencing, glycan de novo sequencing determines the structure without the aid of a known glycan database. We show in this paper that glycan de novo sequencing is NP-hard. We then provide a heuristic algorithm and develop a software program to solve the problem in practical cases. Experiments on real MS/MS data of glycopeptides demonstrate that our heuristic algorithm gives satisfactory results on practical data.
Carbonic anhydrase 2-like a and 15a are involved in acid-base regulation and Na+ uptake in zebrafish H+-ATPase-rich cells
Authors: Lin Tzung-Yi , Liao Bo-Kai , Horng Jiun-Lin , Yan Jia-Jiun , Hsiao Chung-Der , Hwang Pung-Pung
Published: March 2008

H+-ATPase-rich (HR) cells in zebrafish gills/skin were found to carry out Na+ uptake and acid-base regulation through a mechanism similar to that which occurs in mammalian proximal tubular cells. However, the roles of carbonic anhydrases (CAs) in this mechanism in zebrafish HR cells are still unclear. The present study used a functional genomic approach to identify 20 CA isoforms in zebrafish. By screening with whole mount in situ hybridization, only zca2-like a and zca15a were found to be expressed in specific groups of cells in zebrafish gills/skin, and further analyses by triple in situ hybridization and immunocytochemistry demonstrated specific colocalizations of the two zca isoforms in HR cells. Knockdown of zca2-like a caused no change in and knockdown of zca15a caused an increase in H+ activity at the apical surface of HR cells at 24 h postfertilization (hpf). Later, at 96 hpf, both the zca2-like a and zca15a morphants showed decreased H+ activity and increased Na+ uptake, with concomitant upregulation of znhe3b and downregulation of zatp6v1a (H+-ATPase A-subunit) expressions. Acclimation to both acidic and low-Na+ fresh water caused upregulation of zca15a expression but did not change the zca2-like a mRNA level in zebrafish gills. These results provide molecular physiological evidence to support the roles of these two zCA isoforms in Na+ uptake and acid-base regulation mechanisms in zebrafish HR cells.
H9c2 cardiomyoblasts produce thyroid hormone
Authors: Meischl Christof , Buermans Henk P. , Hazes Thierry , Zuidwijk Marian J. , Musters René J. P. , Boer Christa , van Lingen Arthur , Simonides Warner S. , Blankenstein Marinus A. , Dupuy Corrine , Paulus Walter J. , Hack C. Erik , Ris-Stalpers Carrie , Roos Dirk , Niessen Hans W. M.
Published: March 2008

Thyroid hormone acts on a wide range of tissues. In the cardiovascular system, thyroid hormone is an important regulator of cardiac function and cardiovascular hemodynamics. Although some early reports in the literature suggested an unknown extrathyroidal source of thyroid hormone, it is currently thought to be produced exclusively in the thyroid gland, a highly specialized organ with the sole function of generating, storing, and secreting thyroid hormone. Whereas most of the proteins necessary for thyroid hormone synthesis are thought to be expressed exclusively in the thyroid gland, we now have found evidence that all of these proteins, i.e., thyroglobulin, DUOX1, DUOX2, the sodium-iodide symporter, pendrin, thyroid peroxidase, and thyroid-stimulating hormone receptor, are also expressed in cardiomyocytes. Furthermore, we found thyroglobulin to be transiently upregulated in an in vitro model of ischemia. When performing these experiments in the presence of 125I, we found that 125I was integrated into thyroglobulin and that under ischemia-like conditions the radioactive signal in thyroglobulin was reduced. Concomitantly we observed an increase of intracellularly produced, 125I-labeled thyroid hormone. In conclusion, our findings demonstrate for the first time that cardiomyocytes produce thyroid hormone in a manner adapted to the cell's environment.
Induced TRPC1 expression increases protein phosphatase 2A sensitizing intestinal epithelial cells to apoptosis through inhibition of NF-κB activation
Authors: Marasa Bernard S. , Xiao Lan , Rao Jaladanki N. , Zou Tongtong , Liu Lan , Wang Jian , Bellavance Emily , Turner Douglas J. , Wang Jian-Ying
Published: March 2008

Transient receptor potential canonical-1 (TRPC1) functions as a store-operated Ca2+ channel in intestinal epithelial cells (IECs), and induced TRPC1 expression sensitizes IECs to apoptosis by inhibiting NF-κB activation. However, the exact mechanism by which increased TRPC1 results in NF-κB inactivation remains elusive. Protein phosphatase 2A (PP2A) is a widely conserved protein serine/threonine phosphatase that is implicated in the regulation of a wide array of cellular functions including apoptosis. The present study tests the hypothesis that induced TRPC1 expression inhibits NF-κB activation by increasing PP2A activity through Ca2+ influx in IECs. The expression of TRPC1 induced by stable transfection with the wild-type TRPC1 gene increased PP2A activity as indicated by increases in levels of PP2A proteins and their phosphatase activity. Increased levels of PP2A activity in stable TRPC1-transfected IEC-6 cells (IEC-TRPC1) were associated with decreased nuclear levels of NF-κB proteins and a reduction in NF-κB-dependent transcriptional activity, although there were no changes in total NF-κB protein levels. Inhibition of PP2A activity by treatment with okadaic acid or PP2A silencing with small interfering RNA not only enhanced NF-κB transactivation but also prevented the increased susceptibility of IEC-TRPC1 cells to apoptosis induced by treatment with tumor necrosis factor-α (TNF-α)/cycloheximide (CHX). Decreasing Ca2+ influx by exposure to the Ca2+-free medium reduced PP2A mRNA levels, destabilized PP2A proteins, and induced NF-κB activation, thus blocking the increased sensitivity of IEC-TRPC1 cells to TNF-α/CHX-induced apoptosis. These results indicate that induced TRPC1 expression increases PP2A activity through Ca2+ influx and that increased PP2A sensitizes IECs to apoptosis as a result of NF-κB inactivation.
Anti-inflammatory effects of pigment epithelium-derived factor in diabetic nephropathy
Authors: Wang Joshua J. , Zhang Sarah X. , Mott Robert , Chen Ying , Knapp Ryan R. , Cao Wei , Ma Jian-xing
Published: March 2008

Previously, we have reported that pigment epithelium-derived factor (PEDF) ameliorates albuminuria and inhibits matrix protein deposition in the kidney of streptozotocin (STZ)-induced diabetic rats, suggesting a renoprotective effect of PEDF in early stages of diabetic nephropathy. As inflammation is a major contributor to the development and progression of diabetic nephropathy, we examined in the present study whether PEDF inhibits renal inflammation in diabetic kidney. Diabetic rats received an intravenous injection of an adenovirus expressing PEDF (Ad-PEDF) or the same titer of a control virus. Three wk after the injection, diabetic rats treated with the control virus showed significantly elevated renal levels of proinflammatory factors such as ICAM-1, MCP-1, TNF-α, and VEGF compared with age-matched nondiabetic controls. Ad-PEDF effectively suppressed the overexpression of these proinflammatory factors in diabetic kidneys. In cultured primary human renal mesangial cells (HMC), the high-glucose medium-induced upregulation of VEGF and MCP-1 was largely blocked by PEDF. Furthermore, PEDF inhibited high glucose-induced activation of NF-κB, a key transcription factor mediating inflammatory responses, and hypoxia-inducible factor-1, a major activator of VEGF expression in HMC. These results suggest that the renoprotective effect of PEDF against diabetic nephropathy may be partially through its anti-inflammatory activity, likely by blocking the NF-κB and HIF-1 pathways.
Modulation of Olfactory Information Processing in the Antennal Lobe ofManduca sextaby Serotonin
Authors: Dacks A. M. , Christensen T. A. , Hildebrand J. G.
Published: March 2008

The nervous system copes with variability in the external and internal environment by using neuromodulators to adjust the efficacy of neural circuits. The role of serotonin (5HT) as a neuromodulator of olfactory information processing in the antennal lobe (AL) of Manduca sexta was examined using multichannel extracellular electrodes to record the responses of ensembles of AL neurons to olfactory stimuli. In one experiment, the effects of 5HT on the concentration-response functions for two essential plant oils across a range of stimulus intensities were examined. In a second experiment, the effect of 5HT on the ability of ensembles to discriminate odorants from different chemical classes was examined. Bath application of 5HT enhanced AL unit responses by increasing response duration and firing rate, which in turn increased the amount of spike time cross-correlation and -covariance between pairs of units. 5HT had the greatest effect on overall ensemble activation at higher odorant concentrations, resulting in an increase in the gain of the dose-response function of individual units. Additionally, response thresholds shifted to lower odorant concentrations for some units, suggesting that 5HT increased their sensitivity. Serotonin enhanced ensemble discrimination of different concentrations of individual odorants as well as discrimination of structurally dissimilar odors at the same concentration. Given the known circadian fluctuations of 5HT in the AL of this species, these findings support the hypothesis that 5HT periodically enhances sensitivity and responsiveness in the AL of Manduca to maximize efficiency when the requirement for olfactory acuity is the greatest.
Improving Hypertension Control in Diabetes Mellitus
Authors: Naik Aanand D. , Kallen Michael A. , Walder Annette , Street Richard L.
Published: March 2008

Background—

Communication between patients and clinicians using collaborative goals and treatment plans may overcome barriers to achieving hypertension control in routine diabetes mellitus care. We assessed the interrelation of patient–clinician communication factors to determine their independent associations with hypertension control in diabetes care.

Methods and Results—

We identified 566 older adults with diabetes mellitus and hypertension at the DeBakey VA Medical Center in Houston, Tex. Clinical and pharmacy data were collected, and a patient questionnaire was sent to all participants. A total of 212 individuals returned surveys. Logistic regression analyses were performed to assess the effect of patient characteristics, self-management behaviors, and communication factors on hypertension control. Three communication factors had significant associations with hypertension control. Two factors, patients’ endorsement of a shared decision-making style (odds ratio 1.61, 95% confidence interval 1.01 to 2.57) and proactive communication with one’s clinician about abnormal results of blood pressure self-monitoring (odds ratio 1.89, 95% confidence interval 1.10 to 3.26), had direct, independent associations in multivariate regression. Path analysis was used to investigate the direct and indirect effects of communication factors and hypertension control. Decision-making style (β=0.20,
P
<0.01) and proactive communication (β=0.50,
P
<0.0001) again demonstrated direct effects on hypertension control. A third factor, clinicians’ use of collaborative communication when setting treatment goals, had a total effect on hypertension control of 0.16 (
P
<0.05) through its direct effects on decision-making style (β=0.28,
P
<0.001) and proactive communication (β=0.22,
P
<0.01).

Conclusions—

Three communication factors were found to have significant associations with hypertension control. Patient–clinician communication that facilitates collaborative blood pressure goals and patients’ input related to the progress of treatment may improve rates of hypertension control in diabetes care independent of medication adherence.
Targeted Inhibition of Cardiomyocyte Gi Signaling Enhances Susceptibility to Apoptotic Cell Death in Response to Ischemic Stress
Authors: DeGeorge Brent R. , Gao Erhe , Boucher Matthieu , Vinge Leif E. , Martini Jeffrey S. , Raake Philip W. , Chuprun J. Kurt , Harris David M. , Kim Gilbert W. , Soltys Stephen , Eckhart Andrea D. , Koch Walter J.
Published: March 2008

Background—

A salient characteristic of dysfunctional myocardium progressing to heart failure is an upregulation of the adenylyl cyclase inhibitory guanine nucleotide (G) protein α subunit, Gα
i2
. It has not been determined conclusively whether increased Gi activity in the heart is beneficial or deleterious in vivo. Gi signaling has been implicated in the mechanism of cardioprotective agents; however, no in vivo evidence exists that any of the Gα subunits are cardioprotective. We have created a novel molecular tool to specifically address the role of Gi proteins in normal and dysfunctional myocardium.

Methods and Results—

We have developed a class-specific Gi inhibitor peptide, GiCT, composed of the region of Gα
i2
that interacts specifically with G protein–coupled receptors. GiCT inhibits Gi signals specifically in vitro and in vivo, whereas Gs and Gq signals are not affected. In vivo expression of GiCT in transgenic mice effectively causes a “functional knockout” of cardiac Gα
i2
signaling. Inducible, cardiac-specific GiCT transgenic mice display a baseline phenotype consistent with nontransgenic mice. However, when subjected to ischemia/reperfusion injury, GiCT transgenic mice demonstrate a significant increase in infarct size compared with nontransgenic mice (from 36.9±2.5% to 50.9±4.3%). Mechanistically, this post-ischemia/reperfusion phenotype includes increased myocardial apoptosis and resultant decreased contractile performance.

Conclusions—

Overall, our results demonstrate the in vivo utility of GiCT to dissect specific mechanisms attributed to Gi signaling in stressed myocardium. Our results with GiCT indicate that upregulation of Gα
i2
is an adaptive protective response after ischemia to shield myocytes from apoptosis.
“No Harm to Kill Indians”: Equal Rights in a Time of War
Authors: Brown Richard D.
Published: March 2008

In December 1813, four white men were indicted for murdering an Indian. Over the course of the next five years—as trials, convictions, pleas for clemency, and punishments (or lack thereof) proceeded—the judiciary and executive attempted to define equal justice in the face of shifting public and political opinion.