bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Membrane-Proximal Region (MPR) of Herpes Simplex Virus gB Regulates Association of the Fusion Loops with Lipid Membranes
Authors: Shelly Spencer S. , Cairns Tina M. , Whitbeck J. Charles , Lou Huan , Krummenacher Claude , Cohen Gary H. , Eisenberg Roselyn J. 
Published: November 2012

ABSTRACT
Glycoprotein B (gB), gD, and gH/gL constitute the fusion machinery of herpes simplex virus (HSV). Prior studies indicated that fusion occurs in a stepwise fashion whereby the gD/receptor complex activates the entire process, while gH/gL regulates the fusion reaction carried out by gB. Trimeric gB is a class III fusion protein. Its ectodomain of 773 amino acids contains a membrane-proximal region (MPR) (residues 731 to 773) and two fusion loops (FLs) per protomer. We hypothesized that the highly hydrophobic MPR interacts with the FLs, thereby masking them on virions until fusion begins. To test this hypothesis, we made a series of deletion, truncation, and point mutants of the gB MPR. Although the full-length deletion mutants were expressed in transfected cells, they were not transported to the cell surface, suggesting that removal of even small stretches of the MPR was highly detrimental to gB folding. To circumvent this limitation, we used a baculovirus expression system to generate four soluble proteins, each lacking the transmembrane region and cytoplasmic tail. All retained the FLs and decreasing portions of the MPR [gB(773t) (gB truncated at amino acid 773), gB(759t), gB(749t), and gB(739t)]. Despite the presence of the FLs, all were compromised in their ability to bind liposomes compared to the control, gB(730t), which lacks the MPR. We conclude that residues 731 to 739 are sufficient to mask the FLs, thereby preventing liposome association. Importantly, mutation of two aromatic residues (F732 and F738) to alanine restored the ability of gB(739t) to bind liposomes. Our data suggest that the MPR is important for modulating the association of gB FLs with target membranes.

IMPORTANCE
To successfully cause disease, a virus must infect host cells. Viral infection is a highly regulated, multistep process. For herpesviruses, genetic material transfers from the virus to the target cell through fusion of the viral and host cell lipid membranes. Here, we provide evidence that the ability of the herpes simplex virus (HSV) glycoprotein B (gB) fusion protein to interact with the host membrane is regulated by its membrane-proximal region (MPR), which serves to cover or shield its lipid-associating moieties (fusion loops). This in turn prevents the premature binding of gB with host cells and provides a level of regulation to the fusion process. These findings provide important insight into the complex regulatory steps required for successful herpesvirus infection.
Combined balloon stent technique with the Scepter C balloon and low-profile visualized intraluminal stent for the treatment of intracranial aneurysms
Authors: Spiotta Alejandro M , Miranpuri Amrendra , Chaudry M Imran , Turner Raymond D , Turk Aquilla S 
Published: November 2012

BackgroundThe ‘balloon-then-stent’ method involves stent placement after completion of a balloon-assisted embolization. The drawback to this technique is that the coil mass achieved during balloon remodeling must be crossed prior to stent deployment. This additional maneuver introduces the potential risk of coil disruption. We describe the first report of a novel technique employing the ‘balloon-then-stent’ method.MethodsA 51-year-old patient with an unruptured right middle cerebral artery bifurcation aneurysm was treated with balloon remodeling employing a 4×10 mm Scepter C balloon catheter. Following coil embolization, a low-profile visualized intraluminal stent (LVIS) Jr 2.5 mm×16 mm was delivered via the coaxial balloon catheter and deployed across the aneurysm neck.ResultsFollow-up angiograms demonstrated that the coil mass was well-seated within the aneurysm sac and the parent vessel was widely patent with satisfactory vessel wall apposition by the stent.ConclusionsWe describe a technique for balloon remodeling followed by stenting for aneurysm coil embolization that incorporates the use of a coaxial dual-lumen balloon catheter system through which a novel self-expanding stent can be deployed. In the case described, we found this technique to be safe and feasible, reducing both the number of steps involved in this technique and the opportunities for mechanical coil-related complications.
Extremely low volume, whole-body aerobic–resistance training improves aerobic fitness and muscular endurance in females
Authors: McRae Gill , Payne Alexa , Zelt Jason G.E. , Scribbans Trisha D. , Jung Mary E. , Little Jonathan P. , Gurd Brendon J. 
Published: November 2012

The current study evaluated changes in aerobic fitness and muscular endurance following endurance training and very low volume, whole-body, high-intensity, interval-style aerobic–resistance training. Subjects’ enjoyment and implementation intentions were also examined prior to and following training. Subjects (22 recreationally active females (20.3 ± 1.4 years)) completed 4 weeks of exercise training 4 days per week consisting of either 30 min of endurance treadmill training (~85% maximal heart rate; n = 7) or whole-body aerobic–resistance training involving one set of 8 × 20 s of a single exercise (burpees, jumping jacks, mountain climbers, or squat thrusts) separated by 10 s of rest per session (n = 7). A third group was assigned to a nontraining control group (n = 8). Following training, [Formula: see text]O2peakwas increased in both the endurance (~7%) and interval (~8%) groups (p < 0.05), whereas muscle endurance was improved (p < 0.05) in the interval group (leg extensions, +40%; chest presses, +207%; sit-ups, +64%; push-ups, +135%; and back extensions, +75%). Perceived enjoyment of, and intentions to engage in, very low volume, high-intensity, whole-body interval exercise were both increased following training (p < 0.05). No significant changes were observed for any variable in the control (nontraining) group. These data demonstrate that although improvements in cardiovascular fitness are induced by both endurance and extremely low volume interval-style training, whole-body aerobic–resistance training imparted addition benefit in the form of improved skeletal muscle endurance.
Physical activity, energy intake, and obesity prevalence among urban and rural schoolchildren aged 11–12 years in Japan
Authors: Itoi Aya , Yamada Yosuke , Watanabe Yoshiyuki , Kimura Misaka 
Published: November 2012

The prevalence of childhood overweight and obesity has been shown to differ among regions, including rural–urban regional differences within nations. This study obtained simultaneous accelerometry-derived physical activity, 24 h activity, and food records to clarify the potential contributing factors to rural–urban differences in childhood overweight and obesity in Japan. Sixth-grade children (n = 227, 11–12 years old) from two urban elementary schools in Kyoto and four rural elementary schools in Tohoku participated in the study. The children were instructed to wear a pedometer that included a uniaxial accelerometer and, assisted by their parents, keep minute-by-minute 24 h activity and food records. For 12 children, the total energy expenditure was measured by the doubly labeled water method that was used to correct the Lifecorder-predicted activity energy expenditure and physical activity level. The overweight and obesity prevalence was significantly higher in rural than in urban children. The number of steps per day, activity energy expenditure, physical activity level, and duration of walking to school were significantly lower in rural than in urban children. In contrast, the reported energy intake did not differ significantly between the regions. The physical activity and duration of the walk to school were significantly correlated with body mass index. Rural children had a higher prevalence of overweight and obesity, and this may be at least partly caused by lower physical activity, especially less time spent walking to school, than urban children.
Macrophage Delivery of an Oncolytic Virus Abolishes Tumor Regrowth and Metastasis after Chemotherapy or Irradiation
Authors: Muthana Munitta , Rodrigues Samuel , Chen Yung-Yi , Welford Abigail , Hughes Russell , Tazzyman Simon , Essand Magnus , Morrow Fiona , Lewis Claire E. 
Published: November 2012

Abstract
Frontline anticancer therapies such as chemotherapy and irradiation often slow tumor growth, but tumor regrowth and spread to distant sites usually occurs after the conclusion of treatment. We recently showed that macrophages could be used to deliver large quantities of a hypoxia-regulated, prostate-specific oncolytic virus (OV) to prostate tumors. In the current study, we show that administration of such OV-armed macrophages 48 hours after chemotherapy (docetaxel) or tumor irradiation abolished the posttreatment regrowth of primary prostate tumors in mice and their spread to the lungs for up to 27 or 40 days, respectively. It also significantly increased the lifespan of tumor-bearing mice compared with those given docetaxel or irradiation alone. These new findings suggest that such a novel, macrophage-based virotherapy could be used to markedly increase the efficacy of chemotherapy and irradiation in patients with prostate cancer. Cancer Res; 73(2); 490–5. ©2012 AACR.
Competing Risks and Multistate Models
Authors: Schmoor Claudia , Schumacher Martin , Finke Jürgen , Beyersmann Jan 
Published: November 2012

AbstractComplex clinical endpoints are present in studies in cancer. Especially in studies on hematopoietic stem-cell transplantation (HSCT), various risks exist after HSCT. Patients can experience acute and chronic graft versus host disease (GVHD) or need to undergo immunosuppressive therapy (IST), a relapse can occur, or patients can die after relapse or without former relapse (nonrelapse mortality, NRM). Sometimes, endpoints can be reasonably combined in a composite endpoint, as, for example, relapse and NRM are combined into disease-free survival (DFS). In this case, standard survival techniques, as Kaplan–Meier estimation of the DFS probability, can be applied.Often, interest focuses on endpoints for which competing risks are present, as, for example, GVHD, with death without prior GVHD as competing risk. This results in a competing risks model, a special case of a multistate model. A more complex multistate model is required when the effects of events occurring in the course of the study on further disease process shall be investigated, as, for example, the effect of GVHD on relapse and NRM. Another endpoint of interest is time under IST. As patients usually experience multiple episodes of IST, thus switching back and forth between “IST” and “no IST” during follow-up, the multistate model used for analysis must be adapted for this event structure.The aim of this nontechnical report is to explain use and interpretation of Cox-type regression models suitable for the different situations in a randomized trial on the effects of anti-T-cell globulin as GVHD prophylaxis. Clin Cancer Res; 19(1); 12–21. ©2012 AACR.
Mitogen-Activated Protein Kinase 14 Is a Novel Negative Regulatory Switch for the Vascular Smooth Muscle Cell Contractile Gene Program
Authors: Long Xiaochun , Cowan Sarah L. , Miano Joseph M. 
Published: November 2012

Objective—
Several studies have shown through chemical inhibitors that p38 mitogen-activated protein kinase (MAPK) promotes vascular smooth muscle cell (VSMC) differentiation. Here, we evaluate the effects of knocking down a dominant p38MAPK isoform on VSMC differentiation.

Methods and Results—

Knockdown of p38MAPKα (
MAPK14
) in human coronary artery SMCs unexpectedly increases VSMC differentiation genes, such as
miR145
,
ACTA2
,
CNN1
,
LMOD1
, and
TAGLN
, with little change in the expression of serum response factor (SRF) and 2 SRF cofactors, myocardin (
MYOCD
) and myocardin-related transcription factor A (
MKL1
). A variety of chemical and biological inhibitors demonstrate a critical role for a RhoA-MKL1-SRF–dependent pathway in mediating these effects. MAPK14 knockdown promotes MKL1 nuclear localization and VSMC marker expression, an effect partially reversed with Y27632; in contrast, MAP2K6 (MKK6) blocks MKL1 nuclear import and VSMC marker expression. Immunostaining and Western blotting of injured mouse carotid arteries reveal elevated MAPK14 (both total and phosphorylated) and reduced VSMC marker expression.

Conclusion—
Reduced MAPK14 expression evokes unanticipated increases in VSMC contractile genes, suggesting an unrecognized negative regulatory role for MAPK14 signaling in VSMC differentiation.
Effects of Postmenopausal Hormone Therapy on Incident Atrial Fibrillation
Authors: Perez Marco V. , Wang Paul J. , Larson Joseph C. , Virnig Beth A. , Cochrane Barbara , Curb J. David , Klein Liviu , Manson JoAnn E. , Martin Lisa W. , Robinson Jennifer , Wassertheil-Smoller Sylvia , Stefanick Marcia L. 
Published: November 2012

Background—
Atrial fibrillation (AF) is less prevalent in women versus men, but associated with higher risks of stroke and death in women. The role hormone therapy plays in AF is not well understood.

Methods and Results—

The Women’s Health Initiative randomized postmenopausal women to placebo or conjugated equine estrogens (0.625 mg/d) plus medroxyprogesterone acetate (2.5 mg/d) if they had a uterus (N=16 608) or to conjugated equine estrogens only if they had prior hysterectomy (N=10 739). Incident AF was identified by ECG and diagnosis codes from Medicare claims or hospitalization records. Hazard ratios for incident AF were estimated using Cox proportional hazards regression. After excluding participants with baseline AF, there were 611 incident AF cases over a mean of 5.6 years among 16 128 estrogen plus progestin participants, and 683 cases over a mean of 7.1 years among 10 251 conjugated equine estrogens alone participants. Incident AF was more frequent in the active groups of both trials, reaching statistical significance in the trial of conjugated equine estrogens alone in women with prior hysterectomy (hazard ratio, 1.17; CI, 1.00–1.36;
P
=0.045) and in the pooled analysis (hazard ratio, 1.12; CI, 1.00–1.24;
P
=0.05), but not in the estrogen plus progestin trial (hazard ratio, 1.07; CI, 0.91–1.25;
P
=0.44). These results were only minimally affected by adjustment for incident stroke, coronary heart disease, and heart failure.

Conclusions—
Incident AF was modestly elevated in hysterectomized women randomized to postmenopausal E-alone, and in the pooled group randomized to E-alone or estrogen plus progestin. The trend in women with intact uterus receiving estrogen plus progestin, considered separately, was not statistically significant.
Low Serum Magnesium and the Development of Atrial Fibrillation in the Community
Authors: Khan Abigail May , Lubitz Steven A. , Sullivan Lisa M. , Sun Jenny X. , Levy Daniel , Vasan Ramachandran S. , Magnani Jared W. , Ellinor Patrick T. , Benjamin Emelia J. , Wang Thomas J. 
Published: November 2012

Background—
Low serum magnesium has been linked to increased risk of atrial fibrillation (AF) after cardiac surgery. It is unknown whether hypomagnesemia predisposes to AF in the community.

Methods and Results—

We studied 3530 participants (mean age, 44 years; 52% women) from the Framingham Offspring Study who attended a routine examination and were free of AF and cardiovascular disease. We used Cox proportional hazard regression analysis to examine the association between serum magnesium at baseline and risk of incident AF. Analyses were adjusted for conventional AF risk factors, use of antihypertensive medications, and serum potassium. During up to 20 years of follow-up, 228 participants developed AF. Mean serum magnesium was 1.88 mg/dL. The age- and sex-adjusted incidence rate of AF was 9.4 per 1000 person-years (95% confidence interval, 6.7–11.9) in the lowest quartile of serum magnesium (≤1.77 mg/dL) compared with 6.3 per 1000 person-years (95% confidence interval, 4.1–8.4) in the highest quartile (≥1.99 mg/dL). In multivariable-adjusted models, individuals in the lowest quartile of serum magnesium were ~50% more likely to develop AF (adjusted hazard ratio, 1.52; 95% confidence interval, 1.00–2.31;
P
=0.05) compared with those in the upper quartiles. Results were similar after the exclusion of individuals on diuretics.

Conclusions—
Low serum magnesium is moderately associated with the development of AF in individuals without cardiovascular disease. Because hypomagnesemia is common in the general population, a link with AF may have potential clinical implications. Further studies are warranted to confirm our findings and to elucidate the underlying mechanisms.
Pivotal Role of Rho-Associated Kinase 2 in Generating the Intrinsic Circadian Rhythm of Vascular Contractility
Authors: Saito Toshiro , Hirano Mayumi , Ide Tomomi , Ichiki Toshihiro , Koibuchi Noriyuki , Sunagawa Kenji , Hirano Katsuya 
Published: November 2012

Background—
The circadian variation in the incidence of cardiovascular events may be attributable to the circadian changes in vascular contractility. The circadian rhythm of vascular contractility is determined by the interplay between the central and peripheral clocks. However, the molecular mechanism of the vascular intrinsic clock that generates the circadian rhythm of vascular contractility still remains largely unknown.

Methods and Results—

The agonist-induced phosphorylation of myosin light chain in cultured smooth muscle cells synchronized by dexamethasone pulse treatment exhibited an apparent circadian oscillation, with a 25.4-hour cycle length. The pharmacological inhibition and knockdown of Rho-associated kinase 2 (ROCK2) abolished the circadian rhythm of myosin light chain phosphorylation. The expression and activity of ROCK2 exhibited a circadian rhythm in phase with that of myosin light chain phosphorylation. A clock gene, RORα, activated the promoter of the ROCK2 gene, whereas its knockdown abolished the rhythmic expression of ROCK2. In the mouse aorta, ROCK2 expression exhibited the circadian oscillation, with a peak at Zeitgeber time 0/24 and a nadir at Zeitgeber time 12. The myofilament Ca
2+
sensitization induced by GTPγS and U46619, a thromboxane A2 analog, at Zeitgeber time 0/24 was greater than that seen at Zeitgeber time 12. The circadian rhythm of ROCK2 expression and myofilament Ca
2+
sensitivity was abolished in
staggerer
mutant mice, which lack a functional RORα.

Conclusions—
ROCK2 plays a pivotal role in generating the intrinsic circadian rhythm of vascular contractility by receiving a cue from RORα. The ROCK2-mediated intrinsic rhythm of vascular contractility may underlie the diurnal variation of the incidence of cardiovascular diseases.
A Multisensor Perspective on the Radiative Impacts of Clouds and Aerosols
Authors: Henderson David S. , L’Ecuyer Tristan , Stephens Graeme , Partain Phil , Sekiguchi Miho 
Published: November 2012

AbstractThe launch of CloudSat and Cloud–Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) in 2006 provided the first opportunity to incorporate information about the vertical distribution of cloud and aerosols directly into global estimates of atmospheric radiative heating. Vertical profiles of radar and lidar backscatter from CloudSat’s Cloud Profiling Radar (CPR) and the Cloud–Aerosol Lidar with Orthogonal Polarization (CALIOP) aboard CALIPSO naturally complement Moderate Resolution Imaging Spectroradiometer (MODIS) radiance measurements, providing a nearly complete depiction of the cloud and aerosol properties that are essential for deriving high-vertical-resolution profiles of longwave (LW) and shortwave (SW) radiative fluxes and heating rates throughout the atmosphere. This study describes a new approach for combining vertical cloud and aerosol information from CloudSat and CALIPSO with MODIS data to assess impacts of clouds and aerosols on top-of-atmosphere (TOA) and surface radiative fluxes. The resulting multisensor cloud–aerosol product is used to document seasonal and annual mean distributions of cloud and aerosol forcing globally from June 2006 through April 2011. Direct comparisons with Clouds and the Earth’s Radiant Energy System (CERES) TOA fluxes exhibit a close correlation, with improved errors relative to CloudSat-only products. Sensitivity studies suggest that remaining uncertainties in SW fluxes are dominated by uncertainties in CloudSat liquid water content estimates and that the largest sources of LW flux uncertainty are prescribed surface temperature and lower-tropospheric humidity. Globally and annually averaged net TOA cloud radiative effect is found to be −18.1 W m−2. The global, annual mean aerosol direct radiative effect is found to be −1.6 ± 0.5 W m−2 (−2.5 ± 0.8 W m−2 if only clear skies over the ocean are considered), which, surprisingly, is more consistent with past modeling studies than with observational estimates that were based on passive sensors.
Feasibility of High-Density Climate Reconstruction Based on Forest Inventory and Analysis (FIA) Collected Tree-Ring Data
Authors: DeRose R. Justin , Wang Shih-Yu , Shaw John D. 
Published: November 2012

Abstract
This study introduces a novel tree-ring dataset, with unparalleled spatial density, for use as a climate proxy. Ancillary Douglas fir and piñon pine tree-ring data collected by the U.S. Forest Service Forest Inventory and Analysis Program (FIA data) were subjected to a series of tests to determine their feasibility as climate proxies. First, temporal coherence between the FIA data and previously published tree-ring chronologies was found to be significant. Second, spatial and temporal coherence between the FIA data and water year precipitation was strong. Third, the FIA data captured the El Niño–Southern Oscillation dipole and revealed considerable latitudinal fluctuation over the past three centuries. Finally, the FIA data confirmed the quadrature-phase coupling between wet/dry cycles and Pacific decadal variability known to exist for the Intermountain West. The results highlight the possibility of further developing high-spatial-resolution climate proxy datasets for the western United States. (The preliminary FIA data are provided online at http://cliserv.jql.usu.edu/FIAdata/ in both station and gridded format.)
Barra da Tijuca
Authors: Herzog Lawrence A. 
Published: November 2012

In Rio de Janeiro, Brazil’s second-largest metropolis, an important new form of early-twenty-first-century peripheral development that deserves critical inquiry has emerged—the “global suburb.” In Brazil, these suburbs take the form of gated high-rise compounds providing upper- and middle- upper-income residents enclaves of security amidst what they perceive as the chaos and uncertainty of cities overrun by favelas, crime, and gang-related conflict. The Barra da Tijuca suburban enclave in Rio de Janeiro offers a poignant case study of a development project that was initially conceived as an innovative urban design plan for a modernist “new town” but, with little opposition from government officials and planners, was subsequently absorbed by private developers and turned into an elite, U.S.-style suburb. En Rio de Janeiro, metrópolis segunda mas grande de Brasil, emerge al comienzo del siglo veintiuno una forma de desarrollo periférico importante y nueva que se merece una pregunta critica—el “suburbio global.” En Brasil estos suburbios toman la forma de recitos amurallados de edificios de gran altura los cuales proveen a las clases de gran y alto-medio ingreso enclavas de seguridad en medio de lo que perciben es el caos y incertidumbre de ciudades sobrantes de favelas, el crimen, y el conflicto relacionado con el pandillismo. La enclava suburbana de la Barra de Tijuca en Rio de Janeiro ofrece un caso conmovedor de un proyecto urbano originalmente concebido como un diseño urbano innovador para un “pueblo nuevo” modernizado pero, con poca oposición de parte de los oficiales gubernamentales y planificadores, fue absorbido por el fomento privado y convertido en un suburbio tipo Estados Unidos para una elite.