bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Derivate of the Antibiotic Doxorubicin Is a Selective Inhibitor of Dengue and Yellow Fever Virus Replication
In Vitro
Authors: Kaptein Suzanne J. F. , De Burghgraeve Tine , Froeyen Mathy , Pastorino Boris , Alen Marijke M. F. , Mondotte Juan A. , Herdewijn Piet , Jacobs Michael , de Lamballerie Xavier , Schols Dominique , Gamarnik Andrea V. , Sztaricskai Ferenc , Neyts Johan 
Published: September 2010

ABSTRACT

A doxorubicin derivate, SA-17, that carries a squaric acid amide ester moiety at the carbohydrate (α-
l
-daunosaminyl) group was identified as a selective inhibitor of
in vitro
dengue virus (DENV) serotype 2 replication (50% effective concentration [EC
50
] = 0.34 ± 0.20 μg/ml [0.52 ± 0.31 μM]). SA-17 is markedly less cytostatic than the parent compound, resulting in a selectivity index value of ∼100. SA-17 also inhibits yellow fever virus 17D (YFV-17D) replication (EC
50
= 3.1 ± 1.0 μg/ml [4.8 ± 1.5 μM]), although less efficiently than DENV replication, but proved inactive against a variety of enveloped and nonenveloped viruses. SA-17 inhibits
in vitro
flavivirus replication in a dose-dependent manner, as was assessed by virus yield reduction assays and quantification of viral RNA by means of real-time quantitative reverse transcriptase PCR (RT-qPCR) (∼2 to 3 log reduction). The anti-DENV activity was confirmed using a
Renilla
luciferase-expressing dengue reporter virus. Time-of-drug-addition studies revealed that SA-17 acts at the very early stages of the viral replication cycle (i.e., virus attachment and/or virus entry). This observation was corroborated by the observation that SA-17, unlike the nucleoside analogue ribavirin, does not inhibit the replication of DENV subgenomic replicons. Preincubation of high-titer stocks of DENV or YFV-17D with ≥5 μg/ml SA-17 resulted in 100% inhibition of viral infectivity (≥3 log reduction). SA-17, however, did not prove virucidal.
Suitable Disk Antimicrobial Susceptibility Breakpoints Defining
Salmonella enterica
Serovar Typhi Isolates with Reduced Susceptibility to Fluoroquinolones
Authors: Parry Christopher M. , Thuy Chau Tran , Dongol Sabina , Karkey Abhilasha , Vinh Ha , Chinh Nguyen Tran , Duy Pham Thanh , Thieu Nga Tran Vu , Campbell James I. , Van Minh Hoang Nguyen , Arjyal Amit , Bhutta Zulfiqar A. , Bhattacharya Sujit K. , Agtini Magdarina D. , Dong Baiqing , Canh Do Gia , Naheed Aliya , Wain John , Tinh Hien Tran , Basnyat Buddha , Ochiai Leon , Clemens John , Farrar Jeremy J. , Dolecek Christiane , Baker Stephen 
Published: September 2010

ABSTRACT

Infections with
Salmonella enterica
serovar Typhi isolates that have reduced susceptibility to ofloxacin (MIC ≥ 0.25 μg/ml) or ciprofloxacin (MIC ≥ 0.125 μg/ml) have been associated with a delayed response or clinical failure following treatment with these antimicrobials. These isolates are not detected as resistant using current disk susceptibility breakpoints. We examined 816 isolates of
S.
Typhi from seven Asian countries. Screening for nalidixic acid resistance (MIC ≥ 16 μg/ml) identified isolates with an ofloxacin MIC of ≥0.25 μg/ml with a sensitivity of 97.3% (253/260) and specificity of 99.3% (552/556). For isolates with a ciprofloxacin MIC of ≥0.125 μg/ml, the sensitivity was 92.9% (248/267) and specificity was 98.4% (540/549). A zone of inhibition of ≤28 mm around a 5-μg ofloxacin disc detected strains with an ofloxacin MIC of ≥0.25 μg/ml with a sensitivity of 94.6% (246/260) and specificity of 94.2% (524/556). A zone of inhibition of ≤30 mm detected isolates with a ciprofloxacin MIC of ≥0.125 μg/ml with a sensitivity of 94.0% (251/267) and specificity of 94.2% (517/549). An ofloxacin MIC of ≥0.25 μg/ml and a ciprofloxacin MIC of ≥0.125 μg/ml detected 74.5% (341/460) of isolates with an identified quinolone resistance-inducing mutation and 81.5% (331/406) of the most common mutant (carrying a serine-to-phenylalanine mutation at codon 83 in the
gyrA
gene). Screening for nalidixic acid resistance or ciprofloxacin and ofloxacin disk inhibition zone are suitable for detecting
S.
Typhi isolates with reduced fluoroquinolone susceptibility.
Role of MyD88 and Toll-Like Receptors 2 and 4 in the Sensing ofParachlamydia acanthamoebae
Authors: Roger Thierry , Casson Nicola , Croxatto Antony , Entenza José Manuel , Pusztaszeri Marc , Akira Shizuo , Reymond Marlies Knaup , Le Roy Didier , Calandra Thierry , Greub Gilbert 
Published: September 2010

ABSTRACTParachlamydia acanthamoebaeis aChlamydia-related organism whose pathogenic role in pneumonia is supported by serological and molecular clinical studies and an experimental mouse model of lung infection. Toll-like receptors (TLRs) play a seminal role in sensing microbial products and initiating innate immune responses. The aim of this study was to investigate the roles of MyD88, TLR2, and TLR4 in the interaction ofParachlamydiawith macrophages. Here, we showed thatParachlamydiaentered bone-marrow derived macrophages (BMDMs) in a TLR-independent manner but did not multiply intracellularly. Interestingly, compared to live bacteria, heat-inactivatedParachlamydiainduced the production of substantial amounts of tumor necrosis factor alpha (TNF), interleukin-6 (IL-6), and IL-12p40 by BMDMs and of TNF and IL-6 by peritoneal macrophages as well as RAW 264.7 and J774 macrophage cell lines. Cytokine production by BMDMs, which was partially inhibited upon trypsin treatment ofParachlamydia, was dependent on MyD88, TLR4, and, to a lesser extent, TLR2. Finally, MyD88−/−, TLR4−/−, and TLR2−/−mice were as resistant as wild-type mice to lung infection following the intratracheal instillation ofParachlamydia. Thus, in contrast toChlamydia pneumoniae,Parachlamydia acanthamoebaeweakly stimulates macrophages, potentially compensating for its low replication capacity in macrophages by escaping the innate immune surveillance.
Late Palaeozoic-Early Cenozoic tectonic development of the Eastern Pontides (Artvin area), Turkey: stages of closure of Tethys along the southern margin of Eurasia
Authors: Ustaömer Ti̇mur , Robertson Alastair H. F. 
Published: September 2010

Abstract
Early Carboniferous–Eocene units exposed in the Arvin area document the development of the southerly, active continental margin of Eurasia. The oldest rocks exposed in the area are Early Carboniferous granites that regionally intrude schists and gneisses. The continental terrane rifted along the entire length of the Pontides (>1000 km east–west) during the Early–Middle Jurassic. Subsidence of the rift basin in the Artvin area was accompanied by terrigenous debris flows, turbidites and deep-sea radiolarian muds, and was associated with local extrusion of chemically ‘enriched’ basalts. Swarms of subduction-influenced basic, intermediate, to locally silicic dykes, intruded high-grade metamorphic basement within the rift. A basement horst within the rift was covered by condensed pink ammonite-bearing pelagic facies. Large volumes of subduction-influenced basalts erupted during the later stages of extensional basin development (Mid-Jurassic), associated with volcaniclastic sedimentation. The Artvin Basin is interpreted as a supra-subduction rift associated with incipient arc magmatism. The basin was stratigraphically inverted in response to Late Middle Jurassic ‘Neo-Cimmerian’ deformation. It was then partially eroded and covered by Upper Jurassic continental, to shallow-marine sediments, together with localized eruption of ‘enriched’ (non-subduction-influenced) basalts. The margin collapsed during the Late Jurassic–Early Cretaceous, initiating deposition of pelagic carbonates and mixed terrigenous, biogenic and volcaniclastic gravity flows. Subduction during the Late Cretaceous then constructed the east Pontide magmatic arc and a thick volcaniclastic fore-arc apron to the south. Supra-subduction-type ophiolites and accretionary melange formed within Neotethys to the south during the Late Cretaceous and were emplaced regionally northwards onto the leading edge of the Pontide active continental margin during the latest Cretaceous. Continental collision during the Mid-Eocene telescoped the distal part of the active margin which was emplaced northwards onto the east Pontide continental basement. The geological evolution of Artvin area correlates with the Pontides further west and with the southern and northern Transcaucasus to the east. Our favoured tectonic model involves long-lived, episodic, northward subduction of Tethys. Finally, there is no evidence of ‘Palaeotethyan’ ophiolites in the eastern Pontides region.
Recent tectonic stress evolution in the Lesser Caucasus and adjacent regions
Authors: Avagyan Ara , Sosson Marc , Karakhanian Arkadi , Philip Hervé , Rebai Samira , Rolland Yann , Melkonyan Rafael , Davtyan Vahan 
Published: September 2010

Abstract
The stress indicators describing the recent (provided by active tectonics framework) and palaeo-stress (provided by micro-fault kinematics and volcanic cluster) patterns show the scale and temporal changes in stress states since the beginning of Arabian–Eurasian collision. The recent stress derived from the active fault kinematics in the Lesser Caucasus and adjacent area corresponds to a strike–slip regime with both transtension and transpression characteristics. The kinematics of active structures of various scale are conditioned by tectonic stress field with general north–south compression and east–west extension. The distribution of Neogene to Quaternary volcanic cluster geometries and micro-fault kinematic data evidence the time and orientation variability of the stress field since the beginning of the Arabian–Eurasian collision. In addition to the general north–south compression orientation, two other – NW–SE and NE–SW – secondary orientations are observed. The first one was dominant between the Palaeogene and the late Early Miocene and the second one has prevailed between the Late Miocene and the Quaternary. Since the continental collision of Arabia with Eurasia the tectonic stress regime in the Lesser Caucasus and adjacent area changed from compression (thrusting and reverse faulting) to transtension-transpression (strike–slip faulting with various vertical components).
Telomerase Inhibition Potentiates the Effects of Genotoxic Agents in Breast and Colorectal Cancer Cells in a Cell Cycle–Specific Manner
Authors: Tamakawa Raina A. , Fleisig Helen B. , Wong Judy M.Y. 
Published: September 2010

Abstract
Previous studies have shown that telomerase facilitates DNA-damage repair and cell survival following stress. It is not clear how telomerase promotes DNA repair, or whether short-term telomerase inhibition, combined with genotoxic stress, can be exploited for cancer therapy. Here, we show that transient inhibition of telomerase activity by the specific inhibitor, GRN163L, increases the cytotoxicity of some, but not all, DNA-damaging agents. Such synergistic inhibition of growth requires the use of DNA-damaging agents that are toxic in the S/G2 phase of the cell cycle. Notably, inhibition of Ataxia Telangiectasia Mutated (ATM) kinase, together with telomerase inhibition, synergistically increases the cytotoxicity induced by the G2-specific topoisomerase II inhibitor etoposide. By varying the timing of telomerase inhibition, relative to the timing of DNA damage, it is apparent that the prosurvival functions of telomerase occur at early stages of DNA damage recognition and repair. Our results suggest that the protective role of telomerase in cell cycle–restricted DNA damage repair could be exploited for combined anticancer chemotherapy. Cancer Res; 70(21); 8684–94. ©2010 AACR.
In Vivo Measurement of Mitral Leaflet Surface Area and Subvalvular Geometry in Patients With Asymmetrical Septal Hypertrophy
Authors: Kim Dae-Hee , Handschumacher Mark D. , Levine Robert A. , Choi Yun-Sil , Kim Yun Jeong , Yun Sung-Cheol , Song Jong-Min , Kang Duk-Hyun , Song Jae-Kwan 
Published: September 2010

Background—
Analyzing the determinants of systolic anterior motion of the mitral valve and consequent left ventricular outflow tract (LVOT) obstruction in patients with asymmetrical septal hypertrophy requires a comprehensive 3-dimensional analysis of mitral leaflet (ML) area, papillary muscle (PM) geometry, and the distribution of left ventricular hypertrophy.

Methods and Results—

Real-time 3-dimensional echocardiography was performed in 47 patients with asymmetrical septal hypertrophy and 32 normal controls. Patients included 20 with resting LVOT obstruction (group I) and 27 without (group II). Customized software (Omni 4D) provided a validated measure of ML surface area, LVOT area, mitral annular area and nonplanarity, LVOT hypertrophy index by topography (percent area with wall thickness >16 mm), and 3-dimensional PM positions relative to annulus. ML area was more than twice as large in group I than normal and 1.4 times normal in group II (
P
<0.001). Group I patients were also characterized by higher LVOT hypertrophy index and medial and anterior displacements of both PMs, resulting in a shorter inter-PM distance. Independent determinants of LVOT obstruction were indexed total ML area (adjusted odds ratio, 5.651; 95% confidence interval, 1.573 to 20.304;
P
=0.008) and inter-PM distance (adjusted odds ratio, 0.416; 95% confidence interval, 0.203 to 0.854;
P
=0.0169). Minimal LVOT area during systole correlated well with peak LVOT pressure gradient (
R
2
=0.83,
P
<0.001); its independent determinants were left ventricular end-systolic volume (
P
=0.0183), indexed total ML area (
P
=0.0108), inter-PM distance (
P
=0.0378), annular height (
P
=0.0047), and LVOT hypertrophy index (
P
=0.0098).

Conclusions—
Myocardium is not the only tissue affected in patients with asymmetrical septal hypertrophy, and primary changes of the mitral apparatus, including ML area increase and PM displacement, are independent determinants of LVOT obstruction and provide a comprehensive mechanism that determines leaflet slack and anteriorly directed motion. Abnormal PM–mitral valve geometry assessed by real-time 3-dimensional echocardiography can provide reasonable new targets for individualized intervention.
Transcatheter Aortic Valve Implantation
Authors: Gurvitch R. , Wood D.A. , Tay E.L. , Leipsic J. , Ye J. , Lichtenstein S.V. , Thompson C.R. , Carere R.G. , Wijesinghe N. , Nietlispach F. , Boone R.H. , Lauck S. , Cheung A. , Webb J.G. 
Published: September 2010

Background—
Although short- and medium-term outcomes after transcatheter aortic valve implantation are encouraging, long-term data on valve function and clinical outcomes are limited.

Methods and Results—

Consecutive high-risk patients who had been declined as surgical candidates because of comorbidities but who underwent successful transcatheter aortic valve implantation with a balloon-expandable valve between January 2005 and December 2006 and survived past 30 days were assessed. Clinical, echocardiographic, and computed tomographic follow-up examinations were performed. Seventy patients who underwent successful procedures and survived longer than 30 days were evaluated at a minimum follow-up of 3 years. At a median follow-up of 3.7 years (interquartile range 3.4 to 4.3 years), survival was 57%. Survival at 1, 2, and 3 years was 81%, 74%, and 61%, respectively. Freedom from reoperation was 98.5% (1 patient with endocarditis). During this early procedural experience, 11 patients died within 30 days, and 8 procedures were unsuccessful. When these patients were included, overall survival was 51%. Transaortic pressure gradients increased from 10.0 mm Hg (interquartile range 8.0 to 12.0 mm Hg) immediately after the procedure to 12.1 mm Hg (interquartile range 8.6 to 16.0 mm Hg) after 3 years (
P
=0.03). Bioprosthetic valve area decreased from a mean of 1.7±0.4 cm
2
after the procedure to 1.4±0.3 cm
2
after 3 years (
P
<0.01). Aortic incompetence after implantation was trivial or mild in 84% of cases and remained unchanged or improved over time. There were no cases of structural valvular deterioration, stent fracture, deformation, or valve migration.

Conclusions—
Transcatheter aortic valve implantation demonstrates good medium- to long-term durability and preserved hemodynamic function, with no evidence of structural failure. The procedure appears to offer an adequate and lasting resolution of aortic stenosis in selected patients.
MicroRNA-494 Targeting Both Proapoptotic and Antiapoptotic Proteins Protects Against Ischemia/Reperfusion-Induced Cardiac Injury
Authors: Wang Xiaohong , Zhang Xiaowei , Ren Xiao-Ping , Chen Jing , Liu Hongzhu , Yang Junqi , Medvedovic Mario , Hu Zhuowei , Fan Guo-Chang 
Published: September 2010

Background—
MicroRNAs (miRs) participate in many cardiac pathophysiological processes, including ischemia/reperfusion (I/R)-induced cardiac injury. Recently, we and others observed that miR-494 was downregulated in murine I/R-injured and human infarcted hearts. However, the functional consequence of miR-494 in response to I/R remains unknown.

Methods and Results—
We generated a mouse model with cardiac-specific overexpression of miR-494. Transgenic hearts and wild-type hearts from multiple lines were subjected to global no-flow I/R with the Langendorff system. Transgenic hearts exhibited improved recovery of contractile performance over the reperfusion period. This improvement was accompanied by remarkable decreases in both lactate dehydrogenase release and the extent of apoptosis in transgenic hearts compared with wild-type hearts. In addition, myocardial infarction size was significantly reduced in transgenic hearts on I/R in vivo compared with wild-type hearts. Similarly, short-term overexpression of miR-494 in cultured adult cardiomyocytes demonstrated an inhibition of caspase-3 activity and reduced cell death on simulated I/R. In vivo treatment with antisense oligonucleotide miR-494 increased I/R-triggered cardiac injury relative to the administration of mutant antisense oligonucleotide miR-494 and saline controls. We further identified that 3 proapoptotic proteins (PTEN, ROCK1, and CaMKIIδ) and 2 antiapoptotic proteins (FGFR2 and LIF) were authentic targets for miR-494. Importantly, the Akt-mitochondrial signaling pathway was activated in miR-494–overexpressing myocytes.

Conclusions—
Our findings suggest that although miR-494 targets both proapoptotic and antiapoptotic proteins, the ultimate consequence is activation of the Akt pathway, leading to cardioprotective effects against I/R-induced injury. Thus, miR-494 may constitute a new therapeutic agent for the treatment of ischemic heart disease.
The Hybrid Kelvin–Edge Wave and Its Role in Tidal Dynamics
Authors: Ke Ziming , Yankovsky Alexander E. 
Published: September 2010

Abstract
A full set of long waves trapped in the coastal ocean over a variable topography includes a zero (fundamental) mode propagating with the coast on its right (left) in the Northern (Southern) Hemisphere. This zero mode resembles a Kelvin wave at lower frequencies and an edge wave (Stokes mode) at higher frequencies. At the intermediate frequencies this mode becomes a hybrid Kelvin–edge wave (HKEW), as both rotational effects and the variable depth become important. Furthermore, the group velocity of this hybrid mode becomes very small or even zero depending on shelf width. It is found that in midlatitudes a zero group velocity occurs at semidiurnal (tidal) frequencies over wide (∼300 km), gently sloping shelves. This notion motivated numerical experiments using the Regional Ocean Modeling System in which the incident HKEW with a semidiurnal period propagates over a wide shelf and encounters a narrowing shelf so that the group velocity becomes zero at some alongshore location. The numerical experiments have demonstrated that the wave energy increases upstream of this location as a result of the energy flux convergence while farther downstream the wave amplitude is substantially reduced. Instead of propagating alongshore, the wave energy radiates offshore in the form of Poincaré modes. Thus, it is concluded that the shelf areas where the group velocity of the HKEW becomes zero are characterized by an increased tidal amplitude and (consequently) high tidal energy dissipation, and by offshore wave energy radiation. This behavior is qualitatively consistent with the dynamics of semidiurnal tides on wide shelves narrowing in the direction of tidal wave propagation, including the Patagonia shelf and the South China Sea.
Internal Tides in Monterey Submarine Canyon
Authors: Hall Rob A. , Carter Glenn S. 
Published: September 2010

Abstract
The M2 internal tide in Monterey Submarine Canyon is simulated using a modified version of the Princeton Ocean Model. Most of the internal tide energy entering the canyon is generated to the south, on Sur Slope and at the head of Carmel Canyon. The internal tide is topographically steered around the large canyon meanders. Depth-integrated baroclinic energy fluxes are up canyon and largest near the canyon axis, up to 1.5 kW m−1 at the mouth of the upper canyon and increasing to over 4 kW m−1 around Monterey and San Gregorio Meanders. The up-canyon energy flux is bottom intensified, suggesting that topographic focusing occurs. Net along-canyon energy flux decreases almost monotonically from 9 MW at the canyon mouth to 1 MW at Gooseneck Meander, implying that high levels of internal tide dissipation occur. The depth-integrated energy flux across the 200-m isobath is order 10 W m−1 along the majority of the canyon rim but increases by over an order of magnitude near the canyon head, where internal tide energy escapes onto the shelf. Reducing the size of the model domain to exclude remote areas of high barotropic-to-baroclinic energy conversion decreases the depth-integrated energy flux in the upper canyon by 20%. However, quantifying the role of remote internal tide generation sites is complicated by a pressure perturbation feedback between baroclinic energy flux and barotropic-to-baroclinic energy conversion.
How I treat adenovirus in hematopoietic stem cell transplant recipients
Authors: Lindemans Caroline A. , Leen Ann M. , Boelens Jaap Jan 
Published: September 2010

AbstractAdenovirus (AdV) infections are very common in the general pediatric population. The delayed clearance in young persons imposes a threat to immunocompromised patients after hematopoietic stem cell transplantation (HSCT), who can reactivate the virus, resulting in life-threatening disseminated disease. Although a definitive cure requires adequate immune reconstitution, 2 approaches appear to be feasible and effective to improve the outcomes of AdV infections. Strict monitoring with AdV quantitative polymerase chain reaction followed by preemptive treatment with low-dose (1 mg/kg) cidofovir 3 times a week, is effective in most cases to bridge the severely immunocompromised period shortly after HSCT, with acceptable toxicity rates. For centers who have the access, AdV-specific cytotoxic T cells can be the other important cornerstone of anti-AdV therapy with promising results so far. Methods to positively influence the reconstitution of the immune system after HSCT and optimizing new and currently available cellular immunotherapies will make HSCT safer against the threat of AdV infection/reactivation and associated disease.