bluuebunny/crossref_metadata_2025_split huggingface dataset:
Angiotensin-Converting Enzyme 2 Deficiency in Whole Body or Bone Marrow–Derived Cells Increases Atherosclerosis in Low-Density Lipoprotein Receptor
−/−
Mice
Authors: Thatcher Sean E. , Zhang Xuan , Howatt Deborah A. , Lu Hong , Gurley Susan B. , Daugherty Alan , Cassis Lisa A. 
Published: January 2011

Objective—
The renin-angiotensin system contributes to atherosclerotic lesion formation. Angiotensin-converting enzyme 2 (ACE2) catabolizes angiotensin II (Ang II) to angiotensin 1–7 (Ang-(1–7)) to limit effects of the renin-angiotensin system. The purpose of this study was to define the role of ACE2 in atherosclerosis.

Methods and Results—

Male
Ace2

−/
y

mice in an low-density lipoprotein receptor–deficient background were fed a high-fat diet for 3 months. ACE2 deficiency increased atherosclerotic area (
Ace2

+/
y

, 17±1;
Ace2

−/
y

, 23±2 mm
2
,
P
<0.002). This increase was blunted by losartan. To determine whether leukocytic ACE2 influenced atherosclerosis, irradiated low-density lipoprotein receptor–deficient male mice were repopulated with bone marrow–derived cells from
Ace2

+/
y

or
Ace2

−/
y

mice and fed a high-fat diet for 3 months. ACE2 deficiency in bone marrow–derived cells increased atherosclerotic area (
Ace2

+/
y

, 1.6±0.3;
Ace2

−/
y

, 2.8±0.3 mm
2
;
P
<0.05). Macrophages from
Ace2

−/
y

mice exhibited increased Ang II secretion and elevated expression of inflammatory cytokines. Conditioned media from mouse peritoneal macrophages of
Ace2

−/
y

mice increased monocyte adhesion to human umbilical vein endothelial cells. Incubation of human umbilical vein endothelial cells with Ang II promoted monocyte adhesion, which was blocked by Ang-(1–7). Coinfusion of Ang-(1–7) with Ang II reduced atherosclerosis.

Conclusion—
These results demonstrate that ACE2 deficiency in bone marrow–derived cells promotes atherosclerosis through regulation of Ang II/Ang-(1–7) peptides.
Towards Modular Development of Typed Unification Grammars
Authors: Sygal Yael , Wintner Shuly 
Published: January 2011

Development of large-scale grammars for natural languages is a complicated endeavor: Grammars are developed collaboratively by teams of linguists, computational linguists, and computer scientists, in a process very similar to the development of large-scale software. Grammars are written in grammatical formalisms that resemble very-high-level programming languages, and are thus very similar to computer programs. Yet grammar engineering is still in its infancy: Few grammar development environments support sophisticated modularized grammar development, in the form of distribution of the grammar development effort, combination of sub-grammars, separate compilation and automatic linkage, information encapsulation, and so forth. This work provides preliminary foundations for modular construction of (typed) unification grammars for natural languages. Much of the information in such formalisms is encoded by the type signature, and we subsequently address the problem through the distribution of the signature among the different modules. We define signature modules and provide operators of module combination. Modules may specify only partial information about the components of the signature and may communicate through parameters, similarly to function calls in programming languages. Our definitions are inspired by methods and techniques of programming language theory and software engineering and are motivated by the actual needs of grammar developers, obtained through a careful examination of existing grammars. We show that our definitions meet these needs by conforming to a detailed set of desiderata. We demonstrate the utility of our definitions by providing a modular design of the HPSG grammar of Pollard and Sag.
Modulatory Effects of Levodopa on Cognitive Control in Young but not in Older Subjects: A Pharmacological fMRI Study
Authors: Onur Özgür A. , Piefke Martina , Lie Chuh-Hyoun , Thiel Christiane M. , Fink Gereon R. 
Published: January 2011

Abstract
Older individuals show decline of prefrontal cortex (PFC) functions which may be related to altered dopaminergic neurotransmission. We investigated the effects of aging and dopaminergic stimulation in 15 young and 13 older healthy subjects on the neural correlates of interference control using fMRI. In a double-blind, placebo-controlled within-subject design, subjects were measured after levodopa (100 mg) or placebo administration. In each session, subjects performed a visual–spatial interference task based on a Stroop/Simon-like paradigm. Across age groups, interference (incongruent relative to congruent trials) was associated with activations in the presupplementary motor area, ACC, and intraparietal cortex. Increased interference was found behaviorally in older volunteers. Differential activation in left dorsolateral PFC in young subjects and bilateral PFC activity in older subjects was observed to be associated with interference control. Performance deteriorated under levodopa only in young subjects. This was accompanied by an increase of neural activity in ACC (p &lt; .05; small-volume correction for multiple comparisons). Worsening of performance under levodopa in young subjects and the associated effect on ACC may indicate that overstimulation of the dopaminergic system compromises interference control. This supports the inverted-U-shaped model of neurotransmitter action.
Imatinib mesylate versus allogeneic hematopoietic stem cell transplantation for patients with chronic myelogenous leukemia in the accelerated phase
Authors: Jiang Qian , Xu Lan-Ping , Liu Dai-Hong , Liu Kai-Yan , Chen Shan-Shan , Jiang Bin , Jiang Hao , Chen Huan , Chen Yu-Hong , Han Wei , Zhang Xiao-Hui , Wang Yu , Qin Ya-Zhen , Liu Yan-Rong , Lai Yue-Yun , Huang Xiao-Jun 
Published: January 2011

Abstract
The relative merits of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and imatinib for chronic myelogenous leukemia in the accelerated phase (AP-CML) have not previously been evaluated. This cohort study was designed to compare the outcomes of imatinib (n = 87) versus allo-HSCT (n = 45) for AP-CML. A multivariate analysis of the total population revealed that a CML duration ≥ 12 months, hemoglobin < 100 g/L, and peripheral blood blasts ≥ 5% were independent adverse prognostic factors for both overall survival (OS) and progression-free survival (PFS). Both treatments resulted in similar survival in low-risk (no factor) patients, with 6-year event-free survival (EFS), OS, and PFS rates of more than 80.0%. Intermediate-risk (any factor) patients showed no difference in EFS and OS, but 6-year PFS rates were 55.7% versus 92.9% (P = .047) with imatinib versus allo-HSCT, respectively. Among high-risk (at least 2 factors) patients, imatinib was by far inferior to allo-HSCT, with 5-year EFS, OS, and PFS rates of 9.3% versus 66.7% (P = .034), 17.7% versus 100% (P = .008), and 18.8% versus 100% (P = .006), respectively. We conclude that allo-HSCT confers significant survival advantages for high- and intermediate-risk patients with AP-CML compared with imatinib treatment; however, the outcomes of the 2 therapies are equally good in low-risk patients. All trials were registered with the Chinese Clinical Trial Registry (www.chictr.org) as CHiCTR-TNC-10000955.
The discovery of potential acetylcholinesterase inhibitors: A combination of pharmacophore modeling, virtual screening, and molecular docking studies
Authors: Lu Shin-Hua , Wu Josephine W , Liu Hsuan-Liang , Zhao Jian-Hua , Liu Kung-Tien , Chuang Chih-Kuang , Lin Hsin-Yi , Tsai Wei-Bor , Ho Yih 
Published: January 2011

Abstract

Background
Alzheimer's disease (AD) is the most common cause of dementia characterized by progressive cognitive impairment in the elderly people. The most dramatic abnormalities are those of the cholinergic system. Acetylcholinesterase (AChE) plays a key role in the regulation of the cholinergic system, and hence, inhibition of AChE has emerged as one of the most promising strategies for the treatment of AD.

Methods
In this study, we suggest a workflow for the identification and prioritization of potential compounds targeted against AChE. In order to elucidate the essential structural features for AChE, three-dimensional pharmacophore models were constructed using Discovery Studio 2.5.5 (DS 2.5.5) program based on a set of known AChE inhibitors.

Results
The best five-features pharmacophore model, which includes one hydrogen bond donor and four hydrophobic features, was generated from a training set of 62 compounds that yielded a correlation coefficient of R = 0.851 and a high prediction of fit values for a set of 26 test molecules with a correlation of R2 = 0.830. Our pharmacophore model also has a high Güner-Henry score and enrichment factor. Virtual screening performed on the NCI database obtained new inhibitors which have the potential to inhibit AChE and to protect neurons from Aβ toxicity. The hit compounds were subsequently subjected to molecular docking and evaluated by consensus scoring function, which resulted in 9 compounds with high pharmacophore fit values and predicted biological activity scores. These compounds showed interactions with important residues at the active site.

Conclusions
The information gained from this study may assist in the discovery of potential AChE inhibitors that are highly selective for its dual binding sites.
Nogo-B regulates migration and contraction of airway smooth muscle cells by decreasing ARPC 2/3 and increasing MYL-9 expression
Authors: Xu Wujian , Hong Weijun , Shao Yan , Ning Yunye , Cai Zailong , Li Qiang 
Published: January 2011

Abstract

Background
Abnormal proliferation, apoptosis, migration and contraction of airway smooth muscle (ASM) cells in airway remodeling in asthma are basically excessive repair responses to a network of inflammatory mediators such as PDGF, but the mechanisms of such responses remain unclear. Nogo-B, a member of the reticulum family 4(RTN4), is known to play a key role in arteriogenesis and tissue repair. Further studies are needed to elucidate the role of Nogo-B in airway smooth muscle abnormalities.

Methods
A mouse model of chronic asthma was established by repeated OVA inhalation and subjected to Nogo-B expression analysis using immunohistochemistry and Western Blotting. Then, primary human bronchial smooth muscle cells (HBSMCs) were cultured in vitro and a siRNA interference was performed to knockdown the expression of Nogo-B in the cells. The effects of Nogo-B inhibition on PDGF-induced HBSMCs proliferation, migration and contraction were evaluated. Finally, a proteomic analysis was conducted to unveil the underlying mechanisms responsible for the function of Nogo-B.

Results
Total Nogo-B expression was approximately 3.08-fold lower in chronic asthmatic mice compared to naïve mice, which was obvious in the smooth muscle layer of the airways. Interference of Nogo-B expression by siRNA resulted nearly 96% reduction in mRNA in cultured HBSMCs. In addition, knockdown of Nogo-B using specific siRNA significantly decreased PDGF-induced migration of HBSMCs by 2.3-fold, and increased the cellular contraction by 16% compared to negative controls, but had limited effects on PDGF-induced proliferation. Furthermore, using proteomic analysis, we demonstrate that the expression of actin related protein 2/3 complex subunit 5 (ARPC 2/3) decreased and, myosin regulatory light chain 9 isoform a (MYL-9) increased after Nogo-B knockdown.

Conclusions
These data define a novel role for Nogo-B in airway remodeling in chronic asthma. Endogenous Nogo-B, which may exert its effects through ARPC 2/3 and MYL-9, is necessary for the migration and contraction of airway smooth muscle cells.
Effector granules in human T lymphocytes: the luminal proteome of secretory lysosomes from human T cells
Authors: Schmidt Hendrik , Gelhaus Christoph , Nebendahl Melanie , Lettau Marcus , Lucius Ralph , Leippe Matthias , Kabelitz Dietrich , Janssen Ottmar 
Published: January 2011

Abstract

Background
Cytotoxic cells of the immune system have evolved a lysosomal compartment to store and mobilize effector molecules. In T lymphocytes and NK cells, the death factor FasL is one of the characteristic marker proteins of these so-called secretory lysosomes, which combine properties of conventional lysosomes and exocytotic vesicles. Although these vesicles are crucial for immune effector function, their protein content in T cells has so far not been investigated in detail.

Results
In the present study, intact membranous vesicles were enriched from homogenates of polyclonally activated T cells and initially characterized by Western blotting and electron microscopic inspection. The vesicular fraction that contained the marker proteins of secretory lysosomes was subsequently analyzed by 2D electrophoresis and mass spectrometry. The proteome analysis and data evaluation revealed that 70% of the 397 annotated proteins had been associated with different lysosome-related organelles in previous proteome studies.

Conclusion
We provide the first comprehensive proteome map of T cell-derived secretory lysosomes with only minor contaminations by cytosolic, nuclear or other proteins. This information will be useful to more precisely address the activation-dependent maturation and the specific distribution of effector organelles and proteins in individual T or NK cell populations in future studies.
Human herpesvirus 6 major immediate early promoter has strong activity in T cells and is useful for heterologous gene expression
Authors: Matsuura Masaaki , Takemoto Masaya , Yamanishi Koichi , Mori Yasuko 
Published: January 2011

Abstract

Background
Human herpesvirus-6 (HHV-6) is a beta-herpesvirus. HHV-6 infects and replicates in T cells. The HHV-6-encoded major immediate early gene (MIE) is expressed at the immediate-early infection phase. Human cytomegalovirus major immediate early promoter (CMV MIEp) is commercially available for the expression of various heterologous genes. Here we identified the HHV-6 MIE promoter (MIEp) and compared its activity with that of CMV MIEp in various cell lines.

Methods
The HHV-6 MIEp and some HHV-6 MIEp variants were amplified by PCR from HHV-6B strain HST. These fragments and CMV MIEp were subcloned into the pGL-3 luciferase reporter plasmid and subjected to luciferase reporter assay. In addition, to investigate whether the HHV-6 MIEp could be used as the promoter for expression of foreign genes in a recombinant varicella-zoster virus, we inserted HHV-6 MIEp-DsRed expression casette into the varicella-zoster virus genome.

Results
HHV-6 MIEp showed strong activity in T cells compared with CMV MIEp, and the presence of intron 1 of the MIE gene increased its activity. The NF-κB-binding site, which lies within the R3 repeat, was critical for this activity. Moreover, the HHV-6 MIEp drove heterologous gene expression in recombinant varicella-zoster virus-infected cells.

Conclusions
These data suggest that HHV-6 MIEp functions more strongly than CMV MIEp in various T-cell lines.
Luteal blood flow in patients undergoing GnRH agonist long protocol
Authors: Takasaki Akihisa , Tamura Isao , Kizuka Fumie , Lee Lifa , Maekawa Ryo , Asada Hiromi , Taketani Toshiaki , Tamura Hiroshi , Shimamura Katsunori , Morioka Hitoshi , Sugino Norihiro 
Published: January 2011

Abstract

Background
Blood flow in the corpus luteum (CL) is closely related to luteal function. It is unclear how luteal blood flow is regulated. Standardized ovarian-stimulation protocol with a gonadotropin-releasing hormone agonist (GnRHa long protocol) causes luteal phase defect because it drastically suppresses serum LH levels. Examining luteal blood flow in the patient undergoing GnRHa long protocol may be useful to know whether luteal blood flow is regulated by LH.

Methods
Twenty-four infertile women undergoing GnRHa long protocol were divided into 3 groups dependent on luteal supports; 9 women were given ethinylestradiol plus norgestrel (Planovar) orally throughout the luteal phase (control group); 8 women were given HCG 2,000 IU on days 2 and 4 day after ovulation induction in addition to Planovar (HCG group); 7 women were given vitamin E (600 mg/day) orally throughout the luteal phase in addition to Planovar (vitamin E group). Blood flow impedance was measured in each CL during the mid-luteal phase by transvaginal color-pulsed-Doppler-ultrasonography and was expressed as a CL-resistance index (CL-RI).

Results
Serum LH levels were remarkably suppressed in all the groups. CL-RI in the control group was more than the cutoff value (0.51), and only 2 out of 9 women had CL-RI values < 0.51. Treatments with HCG or vitamin E significantly improved the CL-RI to less than 0.51. Seven of the 8 women in the HCG group and all of the women in the vitamin E group had CL-RI < 0.51.

Conclusion
Patients undergoing GnRHa long protocol had high luteal blood flow impedance with very low serum LH levels. HCG administration improved luteal blood flow impedance. This suggests that luteal blood flow is regulated by LH.
Coagulation and Fibrinolytic Disturbances in Women with Polycystic Ovary Syndrome
Authors: Mannerås-Holm Louise , Baghaei Fariba , Holm Göran , Janson Per Olof , Ohlsson Claes , Lönn Malin , Stener-Victorin Elisabet 
Published: January 2011

Abstract

Context:
Studies of fibrinolysis/coagulation status in women with polycystic ovary syndrome (PCOS) are contradictory.

Objectives:
The aim of the study was to investigate whether women with PCOS have disturbed circulating levels of fibrinolysis/coagulation markers and, if so, whether the disturbances are related to hemodynamics, metabolic variables, sex steroids, SHBG, lipids, and inflammatory variables in women with PCOS.

Design/Main Outcome Measures:
Anthropometric variables, hemodynamics, circulating hemostatic and inflammatory markers, and serum lipid profile were measured in women with untreated PCOS (n = 74) and controls (n = 31).

Results:
After adjustments for age and body mass index (BMI), circulating plasminogen activator inhibitor 1 (PAI-1) activity and fibrinogen levels were higher in women with PCOS than controls; lipid profile, blood pressure, and levels of D-dimer, von Willebrand factor, factor VIII, tissue plasminogen activator, and inflammatory markers were comparable in the two groups. In multiple linear regression analyses including women with PCOS, low SHBG and high insulin predicted high PAI-1 activity (R2 = 0.526; P &lt; 0.001); elevated high-sensitivity C-reactive protein and soluble E-selectin in combination with heart rate predicted high fibrinogen (R2 = 0.333; P &lt; 0.001). Differences in PAI-1 activity were not significant after adjustments for age, BMI, SHBG, and insulin.

Conclusions:
PCOS is characterized by a prothrombotic state, as reflected by increased PAI-1 activity and fibrinogen, without signs of dyslipidemia or a proinflammatory state. Low SHBG and high insulin may partly explain the BMI-independent difference in PAI-1 activity between women with PCOS and controls. High-sensitivity C-reactive protein and E-selectin may be involved in regulating fibrinogen in PCOS.
Surgical outcomes and prognostic factors of transsphenoidal surgery for prolactinoma in men: a single-center experience with 87 consecutive cases
Authors: Qu Xin , Wang Min , Wang Guodong , Han Tao , Mou Chengzhi , Han Lizhang , Jiang Meng , Qu Yuanming , Zhang Miao , Pang Qi , Xu Guangming 
Published: January 2011

ContextLittle systematic data on male prolactinomas treated with surgery are available.ObjectiveTo clarify the clinical features and confirm the efficacy of transsphenoidal surgery for male prolactinomas and predictive factors after initial surgery.Patients and methodsThis retrospective study included 87 male patients with prolactinoma treated by transsphenoidal surgery at an academic medical center. Hormonal and visual status, remission rates, and the rate of tumor relapse, as well as predictive factors, were evaluated.ResultsPostoperative initial remission was achieved in 52.9% of patients. The remission rate was markedly higher in microadenomas (83.3%) than in macroadenomas (44.9%). Logistic regression analysis showed that the predictive factors of the early negative outcomes were high preoperative prolactin (PRL) levels and tumor invasion. After a median follow-up of 45 months, the long-term remission rate was 42.5%, and relapse of hyperprolactinemia occurred in 19.6% of the cured patients. The 5-year recurrence-free survival was 78.2% (95% confidence interval, 62.3–88.1%). When surgery was followed by adjuvant treatment in uncured and recurrent patients, 78.8% of patients in the entire group in the absence of dopamine agonists obtained biochemical remission at the end of follow-up.ConclusionTranssphenoidal surgery is a viable treatment alternative for male prolactinomas. The remission rates of male patients with microadenomas and/or intrasellar macroprolactinomas by surgery alone remain excellent, and surgery followed by adjuvant therapy as necessary is required for optimizing management of male prolactinomas, especially for extrasellar macroprolactinomas. The early negative results are associated with preoperative PRL levels and tumor invasion.
Assessment of ACTH assay variability: a multicenter study
Authors: Pecori Giraldi Francesca , Saccani Andrea , Cavagnini Francesco , _ _ 
Published: January 2011

ObjectiveMeasurement of plasma ACTH plays a pivotal role in the diagnosis and treatment of several endocrine disorders. Little is known, however, on the variability of ACTH assay results and its impact on clinical practice. The aim of the present study was to assess the performance of routine plasma ACTH measurements.DesignTwenty-five fresh-frozen plasma samples collected from patients with either high, low, or normal ACTH concentrations were measured using seven different assays by 35 different laboratories. Assay precision, method agreement, and result classification were estimated.ResultsInter- and intra-assay coefficient of variation varied considerably with some assays achieving <10%, others consistently achieving >20%. Overall method agreement was good (mean ratio versus target value 1.02) but subject to exceedingly large excursion (lower and upper limits of agreement at 0.13 and 1.91 respectively). Both differences between assays and between laboratories contributed to variability of method agreement. Assays correctly classified most patients with normal and high ACTH concentrations (90% (95% CI 82–97%) and 95% (95% CI 86–100%) respectively), whereas only 60% (95% CI 52–67%) of measurements from patients with low ACTH values were assigned correctly.ConclusionsField ACTH assays have to be interpreted with caution as they are burdened by high variability and often fail to correctly identify patients with suppressed ACTH secretion. The endocrine community has to include ACTH assays among those requiring standardization.
Frequencies of Diploid Males in Natural Populations of Three North American Bumble Bee (Bombus) Species (Hymenoptera: Apidae)
Authors: Whidden Troy L , Owen Robin E 
Published: January 2011

Abstract
We used four DNA microsatellite markers and detected diploid males in two out of three species of North American bumble bees from Alberta, Canada. The estimated average proportion of diploid males, , in Bombus occidentalis Greene and Bombus perplexus Cresson was ≈ 3% (n = 112) and 6% (n = 104), respectively. However, there was no significant difference between these estimates. Because no diploid males were detected in the sample (n = 81) of Bombus terricola Kirby, no estimate of could be made directly, but the upper limit to that would be found in a sample of this size, was ≈ 4%. The average over the three species was ≈ 4%. This is the first report of diploid males in natural populations of North American bumble bees.