bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haemophilus influenzae
Clinical Isolates with Plasmid pB1000 Bearing
bla
ROB-1
: Fitness Cost and Interspecies Dissemination
Authors: San Millan Alvaro , Garcia-Cobos Silvia , Escudero Jose Antonio , Hidalgo Laura , Gutierrez Belen , Carrilero Laura , Campos Jose , Gonzalez-Zorn Bruno 
Published: January 2010

ABSTRACT

Plasmid pB1000 is a mobilizable replicon bearing the
bla
ROB-1
β-lactamase gene that we have recently described in
Haemophilus parasuis
and
Pasteurella multocida
animal isolates. Here we report the presence of pB1000 and a derivative plasmid, pB1000′, in four
Haemophilus influenzae
clinical isolates of human origin. Pulsed-field gel electrophoresis showed unrelated patterns in all strains, indicating that the existence of pB1000 in
H. influenzae
isolates is not the consequence of clonal dissemination. The replicon can be transferred both by transformation and by conjugation into
H. influenzae
, giving rise to recipients resistant to ampicillin and cefaclor (MICs, ≥64 μg/ml). Stability experiments showed that pB1000 is stable in
H. influenzae
without antimicrobial pressure for at least 60 generations. Competition experiments between isogenic
H. influenzae
strains with and without pB1000 revealed a competitive disadvantage of 9% per 10 generations for the transformant versus the recipient. The complete nucleotide sequences of nine pB1000 plasmids from human and animal isolates, as well as the epidemiological data, suggest that animal isolates belonging to the
Pasteurellaceae
act as an antimicrobial resistance reservoir for
H. influenzae
. Further, since
P. multocida
is the only member of this family that can colonize both humans and animals, we propose that
P. multocida
is the vehicle for the transport of pB1000 between animal- and human-adapted members of the
Pasteurellaceae
.
Synergism between a Novel Chimeric Lysin and Oxacillin Protects against Infection by Methicillin-Resistant
Staphylococcus aureus
Authors: Daniel Anu , Euler Chad , Collin Mattias , Chahales Peter , Gorelick Kenneth J. , Fischetti Vincent A. 
Published: January 2010

ABSTRACT

Staphylococcus aureus
is the causative agent of several serious infectious diseases. The emergence of antibiotic-resistant
S. aureus
strains has resulted in significant treatment difficulties, intensifying the need for new antimicrobial agents. Toward this end, we have developed a novel chimeric bacteriophage (phage) lysin that is active against staphylococci, including methicillin-resistant
S. aureus
(MRSA). The chimeric lysin (called ClyS) was obtained by fusing the N-terminal catalytic domain of the
S. aureus
Twort phage lysin with the C-terminal cell wall-targeting domain from another
S. aureus
phage lysin (phiNM3), which displayed
Staphylococcus
-specific binding. ClyS was expressed in
Escherichia coli
, and the purified protein lysed MRSA, vancomycin-intermediate strains of
S. aureus
(VISA), and methicillin-sensitive (MSSA) strains of
S. aureus in vitro
. In a mouse nasal decolonization model, a 2-log reduction in the viability of MRSA cells was seen 1 h following a single treatment with ClyS. One intraperitoneal dose of ClyS also protected against death by MRSA in a mouse septicemia model. ClyS showed a typical pattern of synergistic interactions with both vancomycin and oxacillin
in vitro
. More importantly, ClyS and oxacillin at doses that were not protective individually protected synergistically against MRSA septic death in a mouse model. These results strongly support the development of ClyS as an attractive addition to the current treatment options of multidrug-resistant
S. aureus
infections and would allow for the reinstatement of antibiotics shelved because of mounting resistance.
In Vitro
Activities of Eight Antifungal Drugs against 55 Clinical Isolates of
Fonsecaea
spp
Authors: Najafzadeh Mohammad J. , Badali Hamid , Illnait-Zaragozi Maria Teresa , De Hoog G. Sybren , Meis Jacques F. 
Published: January 2010

ABSTRACT

The
in vitro
activities of eight antifungal drugs against clinical isolates of
Fonsecaea pedrosoi
(
n
= 21),
Fonsecaea monophora
(
n
= 25), and
Fonsecaea nubica
(
n
= 9) were tested. The resulting MIC
90
s for all strains (
n
= 55) were as follows, in increasing order: posaconazole, 0.063 μg/ml; itraconazole, 0.125 μg/ml; isavuconazole, 0.25 μg/ml; voriconazole, 0.5 μg/ml; amphotericin B, 2 μg/ml; caspofungin, 2 μg/ml; anidulafungin, 2 μg/ml; and fluconazole, 32 μg/ml.
Clinical Isolates of
Mycobacterium tuberculosis
in Four European Hospitals Are Uniformly Susceptible to Benzothiazinones
Authors: Pasca Maria Rosalia , Degiacomi Giulia , Ribeiro Ana Luisa de Jesus Lopes , Zara Francesca , De Mori Patrizia , Heym Beate , Mirrione Maurizio , Brerra Roberto , Pagani Laura , Pucillo Leopoldo , Troupioti Panajota , Makarov Vadim , Cole Stewart T. , Riccardi Giovanna 
Published: January 2010

ABSTRACT

The new antitubercular drug candidate 2-[2-
S
-methyl-1,4-dioxa-8-azaspiro[4.5]dec-8-yl]-8-nitro-6-(trifluoromethyl)-4H-1,3-benzothiazin-4-one (BTZ043) targets the DprE1 (Rv3790) subunit of the enzyme decaprenylphosphoryl-β-
d
-ribose 2′-epimerase. To monitor the potential development of benzothiazinone (BTZ) resistance, a total of 240 sensitive and multidrug-resistant
Mycobacterium tuberculosis
clinical isolates from four European hospitals were surveyed for the presence of mutations in the
dprE1
gene and for BTZ susceptibility. All 240 strains were susceptible, thus establishing the baseline prior to the introduction of BTZ043 in clinical trials.
The NF-κB p50 Subunit Is Protective during Intestinal
Entamoeba histolytica
Infection of 129 and C57BL/6 Mice
Authors: Cho Kyou-Nam , Becker Stephen M. , Houpt Eric R. 
Published: January 2010

ABSTRACT

Entamoeba histolytica
is the agent of amebic colitis. In this work we examined the intestinal NF-κB response to this parasite. Using an enzyme-linked immunosorbent assay (ELISA) and an electrophoretic mobility shift assay, we found that the NF-κB subunit p50 predominated in nuclear extracts of whole cecal tissue and of isolated crypts from mice inoculated with
E. histolytica
. p50 was protective, since C57BL/6 and 129 mice in which there was targeted deletion of this subunit were more susceptible to
E. histolytica
infection as measured by culture results, cecal parasite ELISA results, and/or histologic scores. The transepithelial electrical resistance of cecal explants from C57BL/6 and 129 p50 knockout mice decreased markedly in response to the parasite compared with the transepithelial electrical resistance of their wild-type counterparts, suggesting that a protective function of p50 was present in the epithelium itself. This work shows that NF-κB activity, particularly activity of the p50 subunit, is one factor that contributes to resistance of the gut to
E. histolytica
infection.
Contribution of
Vibrio parahaemolyticus
Virulence Factors to Cytotoxicity, Enterotoxicity, and Lethality in Mice
Authors: Hiyoshi Hirotaka , Kodama Toshio , Iida Tetsuya , Honda Takeshi 
Published: January 2010

ABSTRACT

Vibrio parahaemolyticus
, one of the human-pathogenic vibrios, causes three major types of clinical illness: gastroenteritis, wound infections, and septicemia. Thermostable direct hemolysin (TDH) secreted by this bacterium has been considered a major virulence factor of gastroenteritis because it has biological activities, including cytotoxic and enterotoxic activities. Previous reports revealed that
V. parahaemolyticus
strain RIMD2210633, which contains
tdh
, has two sets of type III secretion system (T3SS) genes on chromosomes 1 and 2 (T3SS1 and T3SS2, respectively) and that T3SS1 is responsible for cytotoxicity and T3SS2 is involved in enterotoxicity, as well as in cytotoxic activity. However, the relative importance and contributions of TDH and the two T3SSs to
V. parahaemolyticus
pathogenicity are not well understood. In this study, we constructed mutant strains with nonfunctional T3SSs from the
V. parahaemolyticus
strain containing
tdh
, and then the pathogenicities of the wild-type and mutant strains were evaluated by assessing their cytotoxic activities against HeLa, Caco-2, and RAW 264 cells, their enterotoxic activities in rabbit ileal loops, and their lethality in a murine infection model. We demonstrated that T3SS1 was involved in cytotoxic activities against all cell lines used in this study, while T3SS2 and TDH had cytotoxic effects on a limited number of cell lines. T3SS2 was the major contributor to
V. parahaemolyticus
-induced enterotoxicity. Interestingly, we found that both T3SS1 and TDH played a significant role in lethal activity in a murine infection model. Our findings provide new indications that these virulence factors contribute to and orchestrate each distinct aspect of the pathogenicity of
V. parahaemolyticus
.
Yersinia pestiswith Regulated Delayed Attenuation as a Vaccine Candidate To Induce Protective Immunity against Plague
Authors: Sun Wei , Roland Kenneth L. , Kuang Xiaoying , Branger Christine G. , Curtiss Roy 
Published: January 2010

ABSTRACTTwo mutant strains ofYersinia pestisKIM5+, a Δcrpmutant and a mutant with arabinose-dependent regulated delayed-shutoffcrpexpression (araCPBADcrp), were constructed, characterizedin vitro, and evaluated for virulence, immunogenicity, and protective efficacy in mice. Both strains were highly attenuated by the subcutaneous (s.c.) route. The 50% lethal doses (LD50s) of the ΔcrpandaraCPBADcrpmutants were approximately 1,000,000-fold and 10,000-fold higher than those ofY. pestisKIM5+, respectively, indicating that both strains were highly attenuated. Mice vaccinated s.c. with 3.8 × 107CFU of the Δcrpmutant developed high anti-Y. pestisand anti-LcrV serum IgG titers, both with a strong Th2 bias, and induced protective immunity against subcutaneous challenge with virulentY. pestis(80% survival) but no protection against pulmonary challenge. Mice vaccinated with 3.0 × 104CFU of thearaCPBADcrpmutant also developed high anti-Y. pestisand anti-LcrV serum IgG titers but with a more balanced Th1/Th2 response. This strain induced complete protection against s.c. challenge and partial protection (70% survival) against pulmonary challenge. Our results demonstrate that arabinose-dependent regulatedcrpexpression is an effective strategy to attenuateY. pestiswhile retaining strong immunogenicity, leading to protection against the pneumonic and bubonic forms of plague.
EXCHANGE RATE PASS-THROUGH IN ASEAN: IMPLICATIONS FOR THE PROSPECTS OF MONETARY INTEGRATION IN THE REGION
Authors: CORTINHAS CARLOS 
Published: January 2010

This paper investigates, for the first time, the degree of exchange rate pass-through to domestic prices in all five founding members of ASEAN. For this purpose, a three-variable-recursive VAR model was applied that uses the Choleski decomposition method along the distribution chain of pricing, using data for the period 1968 to 2001.The results show that a strong case for entering a currency union can be made for the cases of Singapore, Malaysia and Thailand, as in these countries there appears to be the case of exchange rate disconnect. A case for common currency can also be made for Indonesia but for entirely different reasons. For this country, an independent monetary policy is a clear source of shock to the economy and therefore a currency union would tend to eliminate them. Finally, a weaker case for a common currency can be made for the Philippines as evidence of some exchange rate pass-through to inflation was found but not to import prices.
Bile Acid Reflux Contributes to Development of Esophageal Adenocarcinoma via Activation of Phosphatidylinositol-Specific Phospholipase Cγ2 and NADPH Oxidase NOX5-S
Authors: Hong Jie , Behar Jose , Wands Jack , Resnick Murray , Wang Li Juan , DeLellis Ronald A. , Lambeth David , Cao Weibiao 
Published: January 2010

Abstract
Gastroesophageal reflux disease complicated by Barrett's esophagus (BE) is a major risk factor for esophageal adenocarcinoma (EA). However, the mechanisms of the progression from BE to EA are not fully understood. Besides acid reflux, bile acid reflux may also play an important role in the progression from BE to EA. In this study, we examined the role of phosphatidylinositol-specific phospholipase C (PI-PLC) and a novel NADPH oxidase NOX5-S in bile acid–induced increase in cell proliferation. We found that taurodeoxycholic acid (TDCA) significantly increased NOX5-S expression, hydrogen peroxide (H2O2) production, and cell proliferation in EA cells. The TDCA-induced increase in cell proliferation was significantly reduced by U73122, an inhibitor of PI-PLC. PI-PLCβ1, PI-PLCβ3, PI-PLCβ4, PI-PLCγ1, and PI-PLCγ2, but not PI-PLCβ2 and PI-PLCδ1, were detectable in FLO cells by Western blot analysis. Knockdown of PI-PLCγ2 or extracellular signal-regulated kinase (ERK) 2 mitogen-activated protein (MAP) kinase with small interfering RNAs (siRNA) significantly decreased TDCA-induced NOX5-S expression, H2O2 production, and cell proliferation. In contrast, knockdown of PI-PLCβ1, PI-PLCβ3, PI-PLCβ4, PI-PLCγ1, or ERK1 MAP kinase had no significant effect. TDCA significantly increased ERK2 phosphorylation, an increase that was reduced by U73122 or PI-PLCγ2 siRNA. We conclude that TDCA-induced increase in NOX5-S expression and cell proliferation may depend on sequential activation of PI-PLCγ2 and ERK2 MAP kinase in EA cells. It is possible that bile acid reflux present in patients with BE may increase reactive oxygen species production and cell proliferation via activation of PI-PLCγ2, ERK2 MAP kinase, and NADPH oxidase NOX5-S, thereby contributing to the development of EA. Cancer Res; 70(3); 1247–55
Proapoptotic Kinase MST2 Coordinates Signaling Crosstalk between RASSF1A, Raf-1, and Akt
Authors: Romano David , Matallanas David , Weitsman Gregory , Preisinger Christian , Ng Tony , Kolch Walter 
Published: January 2010

Abstract
Mammalian MST kinases function in stress-induced apoptosis to limit tumor progression. However, there is limited understanding about MST2 control by key regulators of cell division and survival. Raf-1 binds and inhibits MST2 kinase, whereas dissociation from Raf-1 and binding to tumor suppressor protein RASSF1A activates MST2. Akt phosphorylates MST2 in response to mitogens, oncogenic Ras, or depletion of tumor suppressor phosphatase and tensin homologue deleted on chromosome 10. We identified T117 and T384 as Akt phosphorylation sites in MST2. Mutation of these sites inhibited MST2 binding to Raf-1 kinase but enhanced binding to tumor suppressor RASSF1A, accentuating downstream c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase signaling and promoting apoptosis. We determined that MST2 phosphorylation by Akt limits MST2 activity in two ways: first, by blocking its binding to RASSF1A and by promoting its association into the Raf-1 inhibitory complex, and second, by preventing homodimerization of MST2, which is needed for its activation. Dissociation of the Raf-1–MST2 complex promoted mitogenic signaling and coordinately licensed apoptotic risk. Using Ras effector domain mutants, we found that Akt is essential to prevent MST2 activation after mitogenic stimulation. Our findings elucidate how MST2 serves as a hub to integrate biological outputs of the Raf-1 and Akt pathways. Cancer Res; 70(3); 1195–203
The Six-Nucleotide Deletion/Insertion Variant in the CASP8 Promoter Region Is Inversely Associated with Risk of Squamous Cell Carcinoma of the Head and Neck
Authors: Li Chunying , Lu Jiachun , Liu Zhensheng , Wang Li-E. , Zhao Hui , El-Naggar Adel K. , Sturgis Erich M. , Wei Qingyi 
Published: January 2010

Abstract
Caspase 8 (CASP8) is an apoptosis-related cysteine peptidase involved in the death receptor pathway and likely in the mitochondrial pathway. A CASP8 promoter region six-nucleotide deletion/insertion (−652 6N ins/del) variant and a coding region D302H polymorphism are reportedly important in cancer development, but no reported study has assessed the associations of these genetic variations with risk of head and neck cancer. In a hospital-based study of non-Hispanic whites, we genotyped CASP8 −652 6N del and 302H variants in 1,023 patients with squamous cell carcinoma of the head and neck (SCCHN) and 1,052 cancer-free controls. Crude and adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression models. The CASP8 −652 6N del variant genotypes or haplotypes were inversely associated with SCCHN risk (adjusted OR, 0.70; 95% CI, 0.57-0.85 for the ins/del + del/del genotypes compared with the ins/ins genotype; adjusted OR, 0.73; 95% CI, 0.55-0.97 for the del-D haplotype compared with the ins-D haplotype). Furthermore, the number of the CASP8 −652 6N del (but not 302H) variant allele tended to correlate with increased levels of camptothecin-induced p53-mediated apoptosis in T lymphocytes from 170 cancer-free controls. We concluded that the CASP8 −652 6N del variant allele may contribute to the risk of developing SCCHN in non-Hispanic white populations. Further validation by population-based case-control studies and rigorous mechanistic studies is warranted. Cancer Prev Res; 3(2); 246–53
Estimating the Attributable Fraction for Cancer: A Meta-analysis of Nevi and Melanoma
Authors: Olsen Catherine M. , Carroll Heidi J. , Whiteman David C. 
Published: January 2010

AbstractEpidemiologic research has shown convincingly that certain phenotypic attributes are associated with increased relative risks of melanoma. Although such findings have intrinsic utility, there have been few attempts to translate such knowledge into estimates of disease burden suitable for framing public health policy. We aimed to estimate the population attributable fraction (PAF) for melanoma associated with melanocytic nevi using relative risk estimates derived from a systematic review and meta-analysis. We identified eligible studies using citation databases, followed by manual review of retrieved references. Of 49 studies identified, 25 and 23, respectively, were included in meta-analyses of atypical and common nevi. For people with ≥1 atypical nevi, the summary relative risk was 3.63 (95% confidence interval, 2.85-4.62), with a PAF of 0.25. The relative risk increased by 1.017 (95% confidence interval, 1.014-1.020) for each common nevus; however, significant heterogeneity in risk estimates was observed. We estimated that 42% of melanomas were attributable to having ≥25 common nevi (PAF 25-49 nevi = 0.15; PAF ≥50 nevi = 0.27), whereas PAFs for low nevus counts were modest (PAF 0-10 nevi = 0.04; PAF 11-24 nevi = 0.07). We modeled PAF under scenarios of varying nevus prevalence; the highest melanoma burden was always among those with high nevus counts (PAF range of 0.31-0.62 for ≥25 common nevi). Patients with ≥25 common nevi and/or ≥1 atypical nevi are a high-risk group, which might be targeted for identification, screening, and education. This work is the necessary first step in designing targeted preventive strategies for melanoma, which must now be overlaid with information about cost and utility. Cancer Prev Res; 3(2); 233–45
The Effectiveness of Chemoprevention Agents Is Underestimated When Lesion Sizes Are Rounded
Authors: Taylor Thomas H. , Armstrong William B. , Meyskens Frank L. 
Published: January 2010

Abstract
Change in the area of premalignant lesions is an end point in estimating the efficacy of chemopreventive agents. When examiners round measurements of lesion length and width, they introduce variability, which perturbs the relative percent change in lesion area and, consequently, the percent of subjects showing a clinical response. We use simulations to illustrate the resulting bias when the agent under test is effective in reducing lesion area. We simulated 500 oral leukoplakia lesions per run, with 2,500 runs at each of five levels of agent effectiveness, namely, true relative percent reduction in area of 25%, 45%, 50%, 55%, and 75%. Realistic values of lesion lengths and widths were generated randomly and then rounded to the nearest multiple of five. The product is the distribution of mean relative percent change in lesion area and the corresponding percent of subjects showing a clinical response. Even the fifth percentile of the distribution of mean relative percent change in lesion area consistently underestimated the true value, by about 6 percentage points. The percent showing a clinical response was underestimated by 50%, 37%, and 11% for true values of reduction in lesion area of 50%, 55%, and 75%, respectively. This could easily double the required sample size for a modest phase II study. We suggest that it is cost-effective to train observers of lesion length and width to eschew rounding of measurements in the chemoprevention setting. Cancer Prev Res; 3(2); 136–9
Climate change and future energy consumption in UK housing stock
Authors: Collins Lisa , Natarajan Sukumar , Levermore Geoff 
Published: January 2010

This paper examines the likely effects on gas and electricity consumption and carbon emissions from heating and cooling systems in existing dwellings up to 2080, assuming a widespread uptake of cooling systems. This area of research is highly sensitive to the myriad of possible inputs and thus holds a wide range of predicted outcomes. However, general trends have been found, showing significant sensitivity to ventilation rate, U-values, occupant behaviour and location. Heating demand will still be dominant over cooling demand in UK dwellings by the 2080s, based on an UKCIP02 A1F1 weather scenario. A national worst case scenario for the 2050s, shows a 10 megatonne CO2 emissions saving on present levels largely due to a 20% reduction in gas consumption. Practical applications: The balance of heating and cooling demand causes more modest changes in CO 2 than first anticipated. Despite first perceptions of future energy use in housing and climate change, heating appears to remain the major load rather than cooling, even into the 2080s. These predictions of future CO 2 emissions will be useful to those in the building industry planning appropriate proportionate climate adaptation and climate mitigation measures. Also, the prediction of changes to future energy demands from the housing sector will be of interest to energy providers considering future demands for heating and cooling and may feed into larger bottom-up energy models.
Chemotherapy-induced nausea and vomiting: antiemetic trials that impacted clinical practice
Authors: Trigg Michael E , Higa Gerald M 
Published: January 2010

Objective. To review the scientific evidence related to serotonin and substance P and the clinical impact targeting these two neurotransmitters have had managing chemotherapy-induced nausea and vomiting (CINV). Data Source. A PubMed search (January 1968 to December 2008), restricted to English-language publications, was conducted using the key words antiemetics, cancer chemotherapy, cisplatin, serotonin, substance P, NK1, and 5-HT3. Abstracts emanating from the meetings of the American Society of Clinical Oncology and Multinational Association of Supportive Care in Cancer during the period May 2000 to June 2008 were also reviewed. Data Synthesis. Two important outcomes emanated from well-conducted antiemetic clinical trials (Table 1): first, evidence that serotonin and substance P are major mediators of acute and delayed symptoms and second, improved, though not complete, control of CINV. Conclusion. Serotonin-type 3 and neurokinin-1 receptor antagonists are the most effective agents currently available. In most cases, these agents are used in conjunction with glucocorticoids. The use of these three types of agents is incorporated into current clinical practice guidelines. Further understanding of the biological and biochemical basis of nausea and vomiting may enhance management of this potentially debilitating adverse effect.