bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying the true oysters (Bivalvia: Ostreidae) with mitochondrial phylogeny and distance‐based DNA barcoding
Authors: LIU JUN , LI QI , KONG LINGFENG , YU HONG , ZHENG XIAODONG 
Published: May 2011

AbstractOysters (family Ostreidae), with high levels of phenotypic plasticity and wide geographic distribution, are a challenging group for taxonomists and phylogenetics. As a useful tool for molecular species identification, DNA barcoding might offer significant potential for oyster identification and taxonomy. This study used two mitochondrial fragments, cytochrome c oxidase I (COI) and the large ribosomal subunit (16S rDNA), to assess whether oyster species could be identified by phylogeny and distance‐based DNA barcoding techniques. Relationships among species were estimated by the phylogenetic analyses of both genes, and then pairwise inter‐ and intraspecific genetic divergences were assessed. Species forming well‐differentiated clades in the molecular phylogenies were identical for both genes even when the closely related species were included. Intraspecific variability of 16S rDNA overlapped with interspecific divergence. However, average intra‐ and interspecific genetic divergences for COI were 0–1.4% (maximum 2.2%) and 2.6–32.2% (minimum 2.2%), respectively, indicating the existence of a barcoding gap. These results confirm the efficacy of species identification in oysters via DNA barcodes and phylogenetic analysis.
Effective inhibition of melanoma by BI‐69A11 is mediated by dual targeting of the AKT and NF‐κB pathways
Authors: Feng Yongmei , Barile Elisa , De Surya K. , Stebbins John L. , Cortez Apple , Aza‐Blanc Pedro , Villanueva Jessie , Heryln Meenhard , Krajewski Stan , Pellecchia Maurizio , Ronai Ze’ev A. , Chiang Gary G. 
Published: May 2011

SummaryIn melanoma, the activation of pro‐survival signaling pathways, such as the AKT and NF‐κB pathways, is critical for tumor growth. We have recently reported that the AKT inhibitor BI‐69A11 causes efficient inhibition of melanoma growth. Here, we show that in addition to its AKT inhibitory activity, BI‐69A11 also targets the NF‐κB pathway. In melanoma cell lines, BI‐69A11 inhibited TNF‐α‐stimulated IKKα/β and IκB phosphorylation as well as NF‐κB reporter gene expression. Furthermore, the effective inhibition of melanoma growth by BI‐69A11 was attenuated upon NF‐κB activation. Mechanistically, reduced NF‐κB signaling by BI‐69‐A11 is mediated by the inhibition of sphingosine kinase 1, identified in a screen of 315 kinases. Significantly, we demonstrate that BI‐69A11 is well tolerated and orally active against UACC 903 and SW1 melanoma xenografts. Our results demonstrate that BI‐69A11 inhibits both the AKT and the NF‐κB pathways and that the dual targeting of these pathways may be efficacious as a therapeutic strategy in melanoma.
The phosphatidyl inositol 3‐kinase pathway is central to the pathogenesis of Kit‐activated melanoma
Authors: Liang Ruixia , Wallace Andrea R. , Schadendorf Dirk , Rubin Brian P. 
Published: May 2011

SummaryMouse Kit L575P, the ortholog of human KIT L576P, a common KIT mutation found in human melanoma was expressed in an immortalized but non‐transformed mouse Ink4a‐Arf‐deficient melanocyte cell line. The resultant Ink4a‐Arf‐deficient Kit L575P‐expressing melanocytes exhibited increased proliferation, the ability to grow in soft agar, and increased migration. When these cells were injected subcutaneously into NOD/SCID/gamma(c) mice, melanomas arose in 5 of 7 (71%) mice. One of seven mice (14%) injected with these cells developed metastatic disease. Evaluation of signal transduction pathways downstream of constitutively activated Kit L575P revealed striking activation of the phosphatidyl inositol 3‐kinase (PI3K) pathway. Inhibition of the PI3K pathway pharmacologically or genetically abolished the transformation phenotypes gained by the L575P single mutant. These studies validate this Kit L575P‐activated model of melanoma and establish the PI3K pathway as a dominant signaling pathway downstream of Kit in melanoma.
Variability and adaptability of Miscanthus species evaluated for energy crop domestication
Authors: YAN JUAN , CHEN WENLI , LUO FAN , MA HONGZHENG , MENG AIPING , LI XINWEI , ZHU MING , LI SHANSHAN , ZHOU HAIFEI , ZHU WEIXING , HAN BIN , GE SONG , LI JIANQIANG , SANG TAO 
Published: May 2011

AbstractA growing body of evidence indicates that second‐generation energy crops can play an important role in the development of renewable energy and the mitigation of climate change. However, dedicated energy crops have yet to be domesticated in order to fully realize their productive potential under unfavorable soil and climatic conditions. To explore the possibility of domesticating Miscanthus crops in northern China where marginal and degraded land is abundant, we conducted common garden experiments at multiple locations to evaluate variation and adaptation of three Miscanthus species that are likely to serve as the wild progenitors of the energy crops. A total of 93 populations of Miscanthus sinensis, Miscanthus sacchariflorus, and Miscanthus lutarioriparius were collected across their natural distributional ranges in China and grown in three locations that represent temperate grassland with cold winter, the semiarid Loess Plateau, and relatively warm and wet central China. Evaluated with growth traits such as plant height, tiller number, tiller diameter, and flowering time, the Miscanthus species showed high levels of genetic variation within and between species. There were significant site × population interactions for almost all traits of M. sacchariflorus and M. sinensis, but not M. lutarioriparius. The northern populations of M. sacchariflorus had the highest establishment rates at the most northern site owing to their strong cold tolerance. An endemic species in central China, M. lutarioriparius, produced not only the highest biomass of the three species but also higher biomass at the Loess Plateau than the southern site near its native habitats. These results demonstrated that the wild species harbored a high level of genetic variation underlying traits important for crop establishment and production at sites that are colder and drier than their native habitats. The natural variation and adaptive plasticity found in the Miscanthus species indicated that they could provide valuable resources for the development of second‐generation energy crops.
Current drug discovery strategies for treatment of hepatitis C virus infection
Authors: Cheng K-C , Gupta Samir , Wang Hongwu , Uss Annette S , Njoroge George F , Hughes Eric 
Published: May 2011

Abstract

Objectives
Hepatitis C virus (HCV) infection represents a major worldwide-health problem. The current standard of care is combination therapy with pegylated interferon and ribavirin, which achieves a successful response in only approximately 40% of genotype I patients.

Key findings
The biology of HCV infection has been under intensive research and important progress has been made in understanding the replication cycle of the virus. Several therapeutic targets have been under investigation, such as NS3 protease, NS4A replicase and NS5B polymerase. New potential targets, such as NS2 protease, as well as CD-81 and claudin-1 entry co-receptors, have also been identified.

Summary
Clinical evaluations of drug candidates targeting NS3 protease, NS4A cofactor, and NS5B polymerase have demonstrated the potential of developing small molecules that interfere with the replication of the virus. Additional issues, including genotype coverage, resistant mutations, and combination therapy represent major challenges for future drug discovery efforts.
Gnaphaliin A and B relax smooth muscle of guinea-pig trachea and rat aorta via phosphodiesterase inhibition
Authors: Rodríguez-Ramos Fernando , González-Andrade Martín , Navarrete Andrés 
Published: May 2011

Abstract

Objectives
To explore the relaxant mechanism of action of gnaphaliin A and gnaphaliin B in guinea-pig trachea and rat aorta, and to investigate the theoretical and experimental phosphodiesterase (PDE) inhibitory activity of these flavones.

Methods
The relaxant effect and the inhibition of calcium chloride induced contractions of both flavones were evaluated on guinea-pig trachea and rat aorta rings. The PDE inhibitory activity was evaluated using a cyclic nucleotide PDE colorimetric assay kit with cAMP and cGMP as substrates. The docking analysis was carried out with AutoDock4 software and X-ray structure of PDE type 5. The activity of both gnaphaliins was compared with the activity of sildenafil, rolipram, aminophylline, IBMX and enoximone.

Key findings
Gnaphaliin A and B were more actives as relaxants on rat aorta than guinea-pig trachea. They were less potent in the relaxation of guinea-pig trachea and rat aorta than sildenafil, but they were equal or more potent than the other PDE inhibitors tested. The relaxant effect of these flavones was potentiated by nitroprusside and forskolin, and blocked by 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one but not by 2′,5′-dideoxyadenosine in guinea-pig trachea. L-NAME did not modify the relaxant effect of gnaphaliins. Gnaphaliins were more potent as PDE inhibitors when cGMP was used as substrate. Docking analysis revealed that gnaphaiins bind to the same binding site of sildenafil at PDE type 5.

Conclusions
The results suggest that the main relaxant mechanism of action of gnaphaliin A and B is inhibition of PDEs with a preference to inhibit the degradation of cGMP. The docking study suggested that these flavones bind with high specificity to the same binding site of sildenafil at PDE type 5.
Metronidazole leads to enhanced uptake of imatinib in brain, liver and kidney without affecting its plasma pharmacokinetics in mice
Authors: Tan Shin Yee , Kan Elaine , Lim Wei Yin , Chay Grace , Law Jason H K , Soo Gian Wan , Bukhari Nadeem Irfan , Segarra Ignacio 
Published: May 2011

Abstract

Objectives
The pharmacokinetic interaction between metronidazole, an antibiotic–antiparasitic drug used to treat anaerobic bacterial and protozoal infections, and imatinib, a CYP3A4, P-glycoprotein substrate kinase inhibitor anticancer drug, was evaluated.

Methods
Male imprinting control region mice were given 50 mg/kg imatinib PO (control group) or 50 mg/kg imatinib PO, 15 min after 40 mg/kg PO metronidazole (study group). Imatinib plasma, brain, kidney and liver concentrations were measured by HPLC and non-compartmental pharmacokinetic parameters estimated.

Key findings
Metronidazole coadministration resulted in a double-peak imatinib disposition profile. The maximum concentration (Cmax) decreased by 38%, the area under the curve (AUC0–∞) decreased by 14% and the time to Cmax (Tmax) was earlier (50%) in plasma. Apparent volume of distribution (VSS/F) and oral clearance (Cl/F) increased by 21% and 17%, respectively. Imatinib tissue penetration was higher after metronidazole coadministration, with 1.7 and 2.1-fold AUC0–∞ increases in liver and kidney, respectively. Metronidazole increased imatinib's tissue-to-plasma AUC0–∞ ratio in liver from 2.29 to 4.53 and in kidney from 3.04 to 7.57, suggesting higher uptake efficiency. Brain Cmax was 3.9-fold higher than control and AUC0–t last was 2.3-fold greater than plasma (3.5% in control group). No tissue-plasma concentration correlation was found.

Conclusions
Metronidazole slightly decreased imatinib systemic exposure but enhanced liver, kidney and brain penetration, probably due to metronidazole-mediated inhibition of P-glycoprotein and other efflux transporters. The high brain exposure opens possibilities for treatment of glioma and glioblastoma. Renal and hepatic functions may need to be monitored due to potential renal and hepatic toxicity.
Oral and Nasal DNA Vaccines Delivered by Attenuated Salmonella enterica Serovar Typhimurium Induce a Protective Immune Response against Infectious Bronchitis in Chickens
Authors: Jiao Hongmei , Pan Zhiming , Yin Yuelan , Geng Shizhong , Sun Lin , Jiao Xinan 
Published: May 2011

ABSTRACTSeveral studies have reported that intramuscular injection of DNA vaccines against infectious bronchitis virus (IBV) induces protective immune responses. In the present study, we developed oral and nasal DNA vaccines that carried the S1 gene and N gene of IBV delivered by attenuatedSalmonella entericaserovar Typhimurium strains SL/pV-S1 and SL/pV-N, respectively. The safety and stability of recombinantSalmonellavaccine were evaluated. Following oral and nasal administration to chickens, the serum and mucosal samples were collected and antibodies against IBV were measured. Chickens were then challenged with IBV strain M41 by the nasal-ocular route 3 weeks after boosting. The results showed that oral and nasal immunization with coadministered SL/pV-S1 and SL/pV-N elicited significant IBV-specific humoral and mucosal immune responses and conferred protective efficacy against IBV challenge higher than that in chickens immunized only with SL/pV-S1. The current study shows that novel DNA vaccines delivered by attenuatedS.Typhimurium may be promising candidates for the prevention of infectious bronchitis (IB).These vaccines are efficacious, easily produced economically, and able to be delivered orally and nasally rather than injected. Coadministration of SL/pV-S1 and SL/pV-N may represent an effective mucosal vaccination regimen.
Within-Subject Variability of Mycobacterium tuberculosis-Specific Gamma Interferon Responses in German Health Care Workers
Authors: Ringshausen Felix C. , Nienhaus Albert , Torres Costa José , Knoop Heiko , Schlösser Stephan , Schultze-Werninghaus Gerhard , Rohde Gernot 
Published: May 2011

ABSTRACTGamma interferon (IFN-γ) release assays (IGRAs) are used increasingly for the periodic tuberculosis (TB) screening of health care workers (HCWs), although data regarding the reproducibility and interpretation of serial testing results in countries with a low incidence of TB are scarce. The present study evaluated and compared the within-subject variability of dichotomous and continuous results of two commercial IGRAs, the QuantiFERON-TB Gold In-Tube (QFT) and the T-SPOT.TB (T-SPOT), in German HCWs during a 4-week period. Thirty-five immunocompetent HCWs with low or medium TB screening risk and without known recent TB exposure or tuberculin skin test application were tested repeatedly with both IGRAs at weekly intervals. A total of 158 valid results were obtained for each IGRA. Changes of about ±70% (QFT) and ±60% (T-SPOT) from the mean IFN-γ response accounted for 95% of the within-subject variability. However, according to the manufacturers' cutoffs, inconsistent results were observed more frequently for the QFT (28.6%; four conversions, six reversions) than for the T-SPOT (8.6%; three reversions;P< 0.001). The overall agreement between the IGRAs was good. Regression toward the means accounted for a significant decline in mean IFN-γ responses of about 25% between successive visits for both IGRAs. Although both assays were highly reliable and reproducible, we observed substantial within-subject variability and regression toward the means during a 4-week period, which should be considered when interpreting serial testing results in comparable populations and settings. Our data support the use of borderline zones for the interpretation of serial IGRA results and the retesting of borderline positive results before offering preventive chemotherapy.
Rapid Identification of Cryptococcus neoformans var. grubii, C. neoformans var. neoformans, and C. gattii by Use of Rapid Biochemical Tests, Differential Media, and DNA Sequencing
Authors: McTaggart Lisa , Richardson Susan E. , Seah Christine , Hoang Linda , Fothergill Annette , Zhang Sean X. 
Published: May 2011

ABSTRACT

Rapid identification of
Cryptococcus neoformans
var.
grubii
,
Cryptococcus neoformans
var.
neoformans
, and
Cryptococcus gattii
is imperative for facilitation of prompt treatment of cryptococcosis and for understanding the epidemiology of the disease. Our purpose was to evaluate a test algorithm incorporating commercial rapid biochemical tests, differential media, and DNA sequence analysis that will allow us to differentiate these taxa rapidly and accurately. We assessed 147 type, reference, and clinical isolates, including 6 other
Cryptococcus
spp. (10 isolates) and 14 other yeast species (24 isolates), using a 4-hour urea broth test (Remel), a 24-hour urea broth test (Becton Dickinson), a 4-hour caffeic acid disk test (Hardy Diagnostics and Remel), 40- to 44-hour growth assessment on
l
-canavanine glycine bromothymol blue (CGB) agar, and intergenic spacer (IGS) sequence analysis. All 123
Cryptococcus
isolates hydrolyzed urea, along with 7 isolates of
Rhodotorula
and
Trichosporon
. Eighty-five of 86
C. neoformans
(99%) and 26 of 27
C. gattii
(96%) isolates had positive caffeic acid results, unlike the other cryptococci (0/10) and yeast species (0/24). Together, these two tests positively identified virtually all
C. neoformans/C. gattii
isolates (98%) within 4 h. CGB agar or IGS sequencing further differentiated these isolates within 48 h. On CGB, 25 of 27 (93%)
C. gattii
strains induced a blue color change, in contrast to 0 of 86
C. neoformans
isolates. Neighbor-joining cluster analysis of IGS sequences differentiated
C. neoformans
var.
grubii
,
C. neoformans
var.
neoformans
, and
C. gattii
. Based on these results, we describe a rapid identification algorithm for use in a microbiology laboratory to distinguish clinically relevant
Cryptococcus
spp.
Isolation of Nocardia beijingensis from a Pulmonary Abscess Reveals Human Immunodeficiency Virus Infection
Authors: Martinaud Christophe , Verdonk Charles , Bousquet Aurore , MacNab Christine , Vaylet Fabien , Soler Charles , Samson Thierry , Margery Jacques 
Published: May 2011

ABSTRACT

A strain of
Nocardia
was isolated from a pulmonary abscess of a human immunodeficiency virus-infected patient in France. Comparative 16S rRNA gene sequence analysis revealed that the isolate represented a strain of
Nocardia beijingensis
. Antimicrobial susceptibility testing was essential to guide the clinicians to successfully treat this infection.
Acute Necrotizing Sinusitis Caused by Staphylococcus lugdunensis
Authors: Matthews Philippa C. , Lazarus Rajeka , Protheroe Andrew , Milford Christopher , Bowler Ian C. J. W. 
Published: May 2011

ABSTRACT

Staphylococcus lugdunensis
is most commonly associated with infections arising from the inguinal region, but here we report this organism as a cause of bacterial sinusitis, highlighting its potential niche as a commensal of the upper airways. The severity of necrosis demonstrates the potential for destructive pathology mimicking
Staphylococcus aureus
disease.
Xpert MTB/RIF: a New Pillar in Diagnosis of Extrapulmonary Tuberculosis?
Authors: Vadwai Viral , Boehme Catharina , Nabeta Pamela , Shetty Anjali , Alland David , Rodrigues Camilla 
Published: May 2011

ABSTRACT

Approximately 10 to 15% of tuberculosis (TB) cases in India are estimated to have extrapulmonary disease, and due to a lack of diagnostic means, they often remain untreated. The early detection of
Mycobacterium tuberculosis
and multidrug resistance is a priority in TB diagnosis to improve the successful treatment rate of TB and reduce transmission. The Xpert MTB/RIF (Xpert) test, recently endorsed by the World Health Organization for the detection of pulmonary TB, was evaluated to test its utility in 547 patients with suspected extrapulmonary tuberculosis. Five hundred forty-seven extrapulmonary specimens were split and processed simultaneously for both culture (solid and liquid) and Xpert testing. For culture, the sensitivity was low, 53% (150/283 specimens). Xpert sensitivity and specificity results were assessed in comparison to a composite reference standard made up of smear and culture results and clinical, radiological, and histological findings. The sensitivity of the Xpert assay was 81% (228/283 specimens) (64% [89/138] for smear-negative cases and 96% [139/145] for smear-positive cases), with a specificity of 99.6%. The sensitivity was found to be high for the majority of specimen types (63 to 100%) except for cerebrospinal fluid, the sensitivity of which was 29% (2/7 specimens). The Xpert test correctly identified 98% of phenotypic rifampin (RIF)-resistant cases and 94% of phenotypic RIF-susceptible cases. Sequencing of the 6 discrepant samples resolved 3 of them, resulting in an increased specificity of 98%. In conclusion, the results of this study suggest that the Xpert test also shows good potential for the diagnosis of extrapulmonary TB and that its ease of use makes it applicable for countries where TB is endemic.
Design and Performance of the CDC Real-Time Reverse Transcriptase PCR Swine Flu Panel for Detection of 2009 A (H1N1) Pandemic Influenza Virus
Authors: Shu Bo , Wu Kai-Hui , Emery Shannon , Villanueva Julie , Johnson Roy , Guthrie Erica , Berman LaShondra , Warnes Christine , Barnes Nathelia , Klimov Alexander , Lindstrom Stephen 
Published: May 2011

ABSTRACT

Swine influenza viruses (SIV) have been shown to sporadically infect humans and are infrequently identified by the Influenza Division of the Centers for Disease Control and Prevention (CDC) after being received as unsubtypeable influenza A virus samples. Real-time reverse transcriptase PCR (rRT-PCR) procedures for detection and characterization of North American lineage (N. Am) SIV were developed and implemented at CDC for rapid identification of specimens from cases of suspected infections with SIV. These procedures were utilized in April 2009 for detection of human cases of 2009 A (H1N1) pandemic (pdm) influenza virus infection. Based on genetic sequence data derived from the first two viruses investigated, the previously developed rRT-PCR procedures were optimized to create the CDC rRT-PCR Swine Flu Panel for detection of the 2009 A (H1N1) pdm influenza virus. The analytical sensitivity of the CDC rRT-PCR Swine Flu Panel was shown to be 5 copies of RNA per reaction and 10
−1.3∼−0.7
50% infectious doses (ID
50
) per reaction for cultured viruses. Cross-reactivity was not observed when testing human clinical specimens or cultured viruses that were positive for human seasonal A (H1N1, H3N2) and B influenza viruses. The CDC rRT-PCR Swine Flu Panel was distributed to public health laboratories in the United States and internationally from April 2009 until June 2010. The CDC rRT-PCR Swine Flu Panel served as an effective tool for timely and specific detection of 2009 A (H1N1) pdm influenza viruses and facilitated subsequent public health response implementation.