bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure and Function of Flavivirus NS5 Methyltransferase
Authors: Zhou Yangsheng , Ray Debashish , Zhao Yiwei , Dong Hongping , Ren Suping , Li Zhong , Guo Yi , Bernard Kristen A. , Shi Pei-Yong , Li Hongmin 
Published: February 2007

ABSTRACT

The plus-strand RNA genome of flavivirus contains a 5′ terminal cap 1 structure (m
7
GpppAmG). The flaviviruses encode one methyltransferase, located at the N-terminal portion of the NS5 protein, to catalyze both guanine N-7 and ribose 2′-OH methylations during viral cap formation. Representative flavivirus methyltransferases from dengue, yellow fever, and West Nile virus (WNV) sequentially generate GpppA → m
7
GpppA → m
7
GpppAm. The 2′-O methylation can be uncoupled from the N-7 methylation, since m
7
GpppA-RNA can be readily methylated to m
7
GpppAm-RNA. Despite exhibiting two distinct methylation activities, the crystal structure of WNV methyltransferase at 2.8 Å resolution showed a single binding site for
S
-adenosyl-
l
-methionine (SAM), the methyl donor. Therefore, substrate GpppA-RNA should be repositioned to accept the N-7 and 2′-O methyl groups from SAM during the sequential reactions. Electrostatic analysis of the WNV methyltransferase structure showed that, adjacent to the SAM-binding pocket, is a highly positively charged surface that could serve as an RNA binding site during cap methylations. Biochemical and mutagenesis analyses show that the N-7 and 2′-O cap methylations require distinct buffer conditions and different side chains within the K
61
-D
146
-K
182
-E
218
motif, suggesting that the two reactions use different mechanisms. In the context of complete virus, defects in both methylations are lethal to WNV; however, viruses defective solely in 2′-O methylation are attenuated and can protect mice from later wild-type WNV challenge. The results demonstrate that the N-7 methylation activity is essential for the WNV life cycle and, thus, methyltransferase represents a novel target for flavivirus therapy.
Hyperbaric oxygen (HBO2) treatment for a failing facial flap
Authors: McCrary Brian F 
Published: February 2007

Abstract
Hyperbaric oxygen (HBO2) is an approved treatment for 13 pathological entities. One of these indications—a failing facial flap—is presented in this case report of a traumatic wound to the face and right axilla after an unprovoked pit bull attack on a 4 year old girl. Surgical repair was started acutely but the facial flap became congested and ischaemic, indicating deterioration of the blood supply. HBO2 treatments were initiated twice a day, resulting in remarkably decreased swelling and discomfort after the first treatment. Leeching was also used to assist with reduction of venous congestion in the flap. The patient was discharged 5 days later with a well perfused, mostly intact, incision with minimal tenderness. Surgical repair was required for a small area of wound dehiscence. Photographs documenting the patient's progress with HBO2 are presented. A discussion of the mechanisms of action of HBO2 and its beneficial effects is provided in this case.
Downregulation of Bone Morphogenetic Protein 4 Expression in Coronary Arterial Endothelial Cells
Authors: Csiszar Anna , Labinskyy Nazar , Smith Kira E. , Rivera Aracelie , Bakker Erik N.T.P. , Jo Hanjoong , Gardner Jason , Orosz Zsuzsanna , Ungvari Zoltan 
Published: February 2007

Objective—Bone morphogenetic protein 4 (BMP-4) is a transforming growth factor β family member cytokine that exerts proinflammatory effects on the endothelium and is likely to play a role in atherogenesis. Recent studies suggested that atheroprotective levels of shear stress control endothelial BMP-4 expression; however, the underlying mechanisms remained unknown.Methods and Results—We found that shear stress downregulated BMP-4 expression in human and rat coronary arterial endothelial cells (CAECs) as well as in cultured mesenteric arterioles, although it had no effect on the expression of BMP-2, a related cytokine. In human coronary arterial endothelial cells, 8-bromo-cAMP, the adenylate cyclase activator forskolin, or a cAMP-dependent protein kinase (PKA) activator effectively decreased BMP-4 expression, mimicking the effects of shear stress. Indeed, shear stress induced the nuclear translocation of PKA-c, and inhibition of PKA attenuated the effects of shear stress and forskolin on BMP-4 expression. RNA decay assay and BMP-4 promoter-driven luciferase reporter gene assay showed that cAMP regulates BMP-4 expression at the transcriptional level.Conclusions—Laminar shear stress and the cAMP/PKA pathway are important negative regulators of BMP-4 expression in the vascular endothelium. Because BMP-4 elicits endothelial activation and dysfunction, hypertension, and vascular calcification, inhibition of BMP-4 expression by shear stress and the cAMP/PKA pathway is likely to exert antiatherogenic and vasculoprotective effects.
Plasmin Induces Endothelium-Dependent Nitric Oxide–Mediated Relaxation in the Porcine Coronary Artery
Authors: Fujiyoshi Tetsuhiro , Hirano Katsuya , Hirano Mayumi , Nishimura Junji , Takahashi Shosuke , Kanaide Hideo 
Published: February 2007

Objective—Plasmin is a key enzyme in fibrinolysis. We attempted to determine the possible role of plasmin in the regulation of vascular tone, while also investigating the mechanism of plasmin-induced vasorelaxation.Methods and Results—In porcine coronary artery, plasmin induced an endothelium-dependent relaxation. This relaxing effect was mostly abolished by a proteinase inhibitor, a plasmin inhibitor, or a nitric oxide (NO) synthase inhibitor. The preceding stimulation with plasmin significantly inhibited the subsequent relaxation induced by thrombin but not that induced by proteinase-activated receptor-1–activating peptide. The relaxation induced by trypsin and substance P remained unaffected by the preceding plasmin stimulation. The pretreatment with plasmin, thrombin, or trypsin significantly attenuated the plasmin-induced relaxation. In porcine coronary artery endothelial cells (PCAECs) and human umbilical vein endothelial cells (HUVECs), plasmin induced a transient elevation in the cytosolic Ca2+concentrations ([Ca2+]i). The preceding stimulation with plasmin inhibited the subsequent [Ca2+]ielevation induced by thrombin but not that induced by trypsin. In PCAECs, plasmin concentration-dependently induced NO production.Conclusions—The present study demonstrated, for the first time, that plasmin induced an endothelium-dependent NO-mediated relaxation in the porcine coronary artery, while also showing plasmin to specifically inactivate the thrombin receptor.
How Purely Wind-Driven Long Planetary Geostrophic Waves May Be Energized in the Western Part of Ocean Subtropical Gyres
Authors: Cerovečki Ivana , de Szoeke Roland 
Published: February 2007

Abstract
Satellite observations and idealized numerical studies reveal intensification of long-period (on the order of one cycle per year) waves in the western part of ocean basins. The authors explore the idea that the intensification is associated with the spatial growth of purely time periodic, but baroclinically unstable, motions. The framework is a simple idealized 2½-layer model in which only the upper layer is directly forced by the wind, a setting similar to the shadow zone of the Luyten–Pedlosky–Stommel (LPS) model. The upper two layers participate in the wave motion, which is driven by a large-scale wind stress fluctuating with the annual period, representing the seasonal cycle. Although possibly unstable solutions exist everywhere in the subtropical gyre on account of the nonzero meridional background flow, they are not seen in the eastern part of the basin in satellite observations nor are they excited there by model gyre-scale annual-period winds. Instead, energy injected into the model ocean at a fixed frequency and with zonal and meridional wavenumbers, such that the resulting flow perturbation is locally stable, refracts westward as it propagates through the spatially varying background flow without change of frequency and reaches distant regions where the spatial wavenumber becomes complex so that spatial growth occurs. This process results in spatially growing solutions of annual or near-annual frequency only in the southwestern part of the model subtropical gyre, thus explaining why the intensification is preferentially manifested in the southwestern subtropical gyre in published numerical model results. The paper concludes with a discussion of relevant satellite and in situ observations.
A Consistent Theory for Linear Waves of the Shallow-Water Equations on a Rotating Plane in Midlatitudes
Authors: Paldor Nathan , Rubin Shira , Mariano Arthur J. 
Published: February 2007

Abstract
The present study provides a consistent and unified theory for the three types of linear waves of the shallow-water equations (SWE) in a zonal channel on the β plane: Kelvin, inertia–gravity (Poincaré), and planetary (Rossby). The new theory is formulated from the linearized SWE as an eigenvalue problem that is a variant of the classical Schrödinger equation. The results of the new theory show that Kelvin waves exist on the β plane with vanishing meridional velocity, as is the case on the f plane, without any change in the dispersion relation, while the meridional structure of their height amplitude is trivially modified from exponential on the f plane to a one-sided Gaussian on the β plane. Similarly, inertia–gravity waves are only slightly modified in the new theory in comparison with their characteristics on the f plane. For planetary waves (which exist only on the β plane) the new theory yields a similar dispersion relation to the classical theory only for large gravity wave phase speed, such as those encountered in a barotropic ocean or an equivalent barotropic atmosphere. In contrast, for low gravity wave phase speed, for example, those in an equivalent barotropic ocean where the relative density jump at the interface is 10−3, the phase speed of planetary waves in the new theory is 2 times those of the classical theory. The ratio between the phase speeds in the two theories increases with channel width. This faster phase propagation is consistent with recent observation of the westward propagation of crests and troughs of sea surface height made by the altimeter aboard the Ocean Topography Experiment (TOPEX)/Poseidon satellite. The new theory also admits inertial waves, that is, waves that oscillate at the local inertial frequency, as a genuine solution of the eigenvalue problem.
Ulnar Collateral Ligament Reconstruction in Major League Baseball Pitchers
Authors: Gibson Brett W. , Webner David , Huffman G. Russell , Sennett Brian J. 
Published: February 2007

Background Ulnar collateral ligament reconstruction is commonly performed in major league pitchers, but little is known about pitching performance after a return to major league play. Hypothesis Pitching performance after ulnar collateral ligament reconstruction returns to baseline by the second season after surgery. Study Design Cohort study (prognosis); Level of evidence, 2. Methods Data were reviewed for 68 major league pitchers who pitched in at least 1 major league game before undergoing ulnar collateral ligament reconstruction between 1998 and 2003. Mean innings pitched per season, earned run average, and walks and hits per inning pitched were compared for each major league pitcher before and after surgery. All demographic and performance variables were analyzed for an association with ulnar collateral ligament insufficiency and a successful return to major league play. Results Fifty-six (82%) pitchers returned to major league play at a mean of 18.5 months after surgery with no significant change in mean earned run average or walks and hits per inning pitched. The mean innings pitched per season was not statistically different from controls by the second season after surgery. Starting pitchers demonstrated a higher risk of ulnar collateral ligament injury requiring reconstruction. More experienced pitchers and those with a higher earned run average were less likely to require ulnar collateral ligament reconstruction. No factors predictive of a successful return to play were identified. Conclusion Most major league pitchers return from ulnar collateral ligament reconstruction by the second season after surgery with no statistical change in mean innings pitched, earned run average, or walks and hits per inning pitched from preinjury levels.
Pain Relief through an Antinociceptive Effect after Radiofrequency Application
Authors: Takahashi Norimasa , Tasto James P. , Ritter Mark , Ochiai Nobuyasu , Ohtori Seiji , Moriya Hideshige , Amiel David 
Published: February 2007

Background Many patients with chronic tendinosis have experienced early pain relief after application of bipolar radiofrequency treatment. Pathologic nerve ingrowth or nerve irritation in the tendon has been considered as a possible cause of the pain experienced with tendinosis. Hypothesis Bipolar radiofrequency treatment will ablate nerve fibers, resulting in pain relief. Study Design Controlled laboratory study. Methods Eighteen Sprague-Dawley rats were used in this study. Eight rats were treated with 2 points of bipolar radiofrequency applications applied to the hind paws with the Topaz microdebrider device, 6 sham rats had a needle applied to the hind paws, and there were 4 control rats. Tissues were processed for neural class III β-tubulin (TUJ-1) or calcitonin gene-related peptide (CGRP) immunohistochemistry by using the free-floating avidin-biotin complex technique. The numbers of TUJ1-immunoreactive and CGRP-immunoreactive nerve fibers in the epidermis were counted and compared with sham and control. Results The number of nerve fibers demonstrated by both the antibodies of TUJ1 and CGRP were significantly decreased (P = .0002-.002) during the first 2 weeks after bipolar radiofrequency treatment. Macroscopically, the foot pad showed 2 dimples on the surface after bipolar radiofrequency treatment. Although it still showed a scar after 7 days, after 14 days it looked no different than the untreated contralateral control foot pad and foot pad of the sham group. Conclusion Bipolar radiofrequency treatment induced acute degeneration and/or ablation of sensory nerve fibers. Clinical Relevance Degeneration or ablation of nerve fibers after bipolar radiofrequency treatment may explain the early postoperative pain relief after microtenotomy for tendinosis.
The Effects of Core Proprioception on Knee Injury
Authors: Zazulak Bohdanna T. , Hewett Timothy E. , Reeves N. Peter , Goldberg Barry , Cholewicki Jacek 
Published: February 2007

Background In sports involving pivoting and landing, female athletes suffer knee injury at a greater rate than male athletes. Hypotheses Proprioceptive deficits in control of the body's core may affect dynamic stability of the knee. Female, but not male, athletes who suffered a knee injury during a 3-year follow-up period would demonstrate decreased core proprioception at baseline testing as compared with uninjured athletes. Study Design Cohort study (prognosis); Level of evidence, 2. Methods Study subjects were 277 collegiate athletes (140 female, 137 male) who were prospectively tested for core proprioception by active and passive proprioceptive repositioning. Athletes were monitored for injury for 3 years. An ANOVA and multivariate logistic regression were used to test whether core proprioception was related to knee injuries in athletes. Results Twenty-five athletes sustained knee injuries (11 women, 14 men). Deficits in active proprioceptive repositioning were observed in women with knee injuries (2.2°) and ligament/meniscal injuries (2.4°) compared with uninjured women (1.5°, P ≤ .05). There were no differences in average active proprioceptive repositioning error between injured men and uninjured men (P ≥ .05). Uninjured women demonstrated significantly less average error in active proprioceptive repositioning than uninjured men (1.5° vs 1.7°, P ≤ .05). For each degree increase in average active proprioceptive repositioning error, a 2.9-fold increase in the odds ratio of knee injury was observed, and a 3.3-fold increase in odds ratio of ligament/meniscal injury was observed (P ≤ .01). Active proprioceptive repositioning predicted knee injury status with 90% sensitivity and 56% specificity in female athletes. Conclusions Impaired core proprioception, measured by active proprioceptive repositioning of the trunk, predicted knee injury risk in female, but not male, athletes.
Defective targeting of hemojuvelin to plasma membrane is a common pathogenetic mechanism in juvenile hemochromatosis
Authors: Silvestri Laura , Pagani Alessia , Fazi Claudia , Gerardi Gianmario , Levi Sonia , Arosio Paolo , Camaschella Clara 
Published: February 2007

Abstract
Hemojuvelin (HJV) positively modulates the iron regulator hepcidin, and its mutations are the major cause of juvenile hemochromatosis (JH), a recessive disease leading to iron overload. Defective HJV reduces hepcidin up-regulation both in humans and in Hjv-deficient mice. To investigate the JH pathogenesis and the functional properties of human HJV we studied the biosynthesis and maturation of 6 HJV pathogenic mutants in HeLa and HepG2 cells. We show that proteolytic processing is defective in mutants F170S, W191C, and G320V, but not in G99V and C119F. Moreover, we show that mutants G99V and C119F are targeted to the cell surface, while F170S, W191C, G320V, and R326X (lacking the glycosilphosphatidylinositol [GPI] anchor) are mainly retained in the endoplasmic reticulum, although all mutants are released as soluble forms (s-HJV) in a proportion that is modulated by iron supplementation. Membrane HJV (m-HJV) is mainly composed of the cleaved protein, and its level is increased by iron in wild-type (WT) mice but not in the mutants. Altogether, the data demonstrate that the loss of HJV membrane export is central to the pathogenesis of JH, and that HJV cleavage is essential for the export. The results support a dual function for s- and m-HJV in iron deficiency and overload, respectively.
Bone marrow transplantation for severe aplastic anemia: a randomized controlled study of conditioning regimens
Authors: Champlin Richard E. , Perez Waleska S. , Passweg Jakob R. , Klein John P. , Camitta Bruce M. , Gluckman Eliane , Bredeson Christopher N. , Eapen Mary , Horowitz Mary M. 
Published: February 2007

AbstractThe addition of antithymocyte globulin (ATG) to a regimen of high-dose cyclophosphamide has been advocated to enhance engraftment after allogeneic bone marrow transplantation (BMT) for severe aplastic anemia (SAA). In a prospective clinical trial, 134 patients were randomly assigned to receive cyclophosphamide alone or in combination with ATG. All patients received T-cell–replete bone marrow from an HLA-matched sibling. With a median follow-up of 6 years, the 5-year probabilities of survival were 74% for the cyclophosphamide alone group and 80% for the cyclophosphamide plus ATG group (P = .44). Graft failure and graft-versus-host disease (GVHD) rates were similar in both groups. With the survival rates achieved, this study is not adequately powered to detect significant differences between the 2 treatment groups. In conclusion, the results of allogeneic BMT for SAA have improved over time related to advances in supportive care. The addition of ATG to the preparative regimen did not significantly improve the outcome.
Computational RNA secondary structure design: empirical complexity and improved methods
Authors: Aguirre-Hernández Rosalía , Hoos Holger H , Condon Anne 
Published: February 2007

Abstract

Background
We investigate the empirical complexity of the RNA secondary structure design problem, that is, the scaling of the typical difficulty of the design task for various classes of RNA structures as the size of the target structure is increased. The purpose of this work is to understand better the factors that make RNA structures hard to design for existing, high-performance algorithms. Such understanding provides the basis for improving the performance of one of the best algorithms for this problem, RNA-SSD, and for characterising its limitations.

Results
To gain insights into the practical complexity of the problem, we present a scaling analysis on random and biologically motivated structures using an improved version of the RNA-SSD algorithm, and also the RNAinverse algorithm from the Vienna package. Since primary structure constraints are relevant for designing RNA structures, we also investigate the correlation between the number and the location of the primary structure constraints when designing structures and the performance of the RNA-SSD algorithm. The scaling analysis on random and biologically motivated structures supports the hypothesis that the running time of both algorithms scales polynomially with the size of the structure. We also found that the algorithms are in general faster when constraints are placed only on paired bases in the structure. Furthermore, we prove that, according to the standard thermodynamic model, for some structures that the RNA-SSD algorithm was unable to design, there exists no sequence whose minimum free energy structure is the target structure.

Conclusion
Our analysis helps to better understand the strengths and limitations of both the RNA-SSD and RNAinverse algorithms, and suggests ways in which the performance of these algorithms can be further improved.
Heritable clustering and pathway discovery in breast cancer integrating epigenetic and phenotypic data
Authors: Wang Zailong , Yan Pearlly , Potter Dustin , Eng Charis , Huang Tim H-M , Lin Shili 
Published: February 2007

Abstract

Background
In order to recapitulate tumor progression pathways using epigenetic data, we developed novel clustering and pathway reconstruction algorithms, collectively referred to as heritable clustering. This approach generates a progression model of altered DNA methylation from tumor tissues diagnosed at different developmental stages. The samples act as surrogates for natural progression in breast cancer and allow the algorithm to uncover distinct epigenotypes that describe the molecular events underlying this process. Furthermore, our likelihood-based clustering algorithm has great flexibility, allowing for incomplete epigenotype or clinical phenotype data and also permitting dependencies among variables.

Results
Using this heritable clustering approach, we analyzed methylation data obtained from 86 primary breast cancers to recapitulate pathways of breast tumor progression. Detailed annotation and interpretation are provided to the optimal pathway recapitulated. The result confirms the previous observation that aggressive tumors tend to exhibit higher levels of promoter hypermethylation.

Conclusion
Our results indicate that the proposed heritable clustering algorithms are a useful tool for stratifying both methylation and clinical variables of breast cancer. The application to the breast tumor data illustrates that this approach can select meaningful progression models which may aid the interpretation of pathways having biological and clinical significance. Furthermore, the framework allows for other types of biological data, such as microarray gene expression or array CGH data, to be integrated.
Localisation of increased prefrontal white matter in
pathological liars
Authors: Yang Yaling , Raine Adrian , Narr Katherine L. , Lencz Todd , LaCasse Lori , Colletti Patrick , Toga Arthur W 
Published: February 2007

SummaryWe examined white matter volumes in four prefrontal subregions using
structural magnetic resonance imaging in 10 pathological liars, 14
antisocial controls, and 20 normal controls. Liars showed a relatively
widespread increase in white matter (23-36%) in orbitofrontal, middle and
inferior, but not superior, frontal gyri compared with antisocial and normal
controls. This white matter increase may predispose some individuals to
pathological lying.