bluuebunny/crossref_metadata_2025 huggingface dataset:
Enzymatic Activity Analysis and Catalytic Essential Residues Identification ofBrucella abortusMalate Dehydrogenase
Authors: Han Xiangan , Tong Yongliang , Tian Mingxing , Zhang Yuxi , Sun Xiaoqing , Wang Shaohui , Qiu Xusheng , Ding Chan , Yu Shengqing
Published: May 2014

Malate dehydrogenase (MDH) plays important metabolic roles in bacteria. In this study, the recombinant MDH protein (His-MDH) ofBrucella abortuswas purified and its ability to catalyze the conversion of oxaloacetate (OAA) to L-malate (hereon referred to as MDH activity) was analyzed. Michaelis Constant (Km) and Maximum Reaction Velocity (Vmax) of the reaction were determined to be6.45×10−3M and 0.87 mM L−1 min−1, respectively.In vitrostudies showed that His-MDH exhibited maximal MDH activity in pH 6.0 reaction buffer at 40°C. The enzymatic activity was 100%, 60%, and 40% inhibited by Cu2+, Zn2+, and Pb2+, respectively. In addition, six amino acids in the MDH were mutated to investigate their roles in the enzymatic activity. The results showed that the substitutions of amino acids Arg 89, Asp 149, Arg 152, His 176, or Thr 231 almost abolished the activity of His-MDH. The present study will help to understand MDH’s roles inB. abortusmetabolism.
Comparison of Different Approaches to Construct First Integrals for Ordinary Differential Equations
Authors: Naz Rehana , Freire Igor Leite , Naeem Imran
Published: May 2014

Different approaches to construct first integrals for ordinary differential equations and systems of ordinary differential equations are studied here. These approaches can be grouped into three categories: direct methods, Lagrangian or partial Lagrangian formulations, and characteristic (multipliers) approaches. The direct method and symmetry conditions on the first integrals correspond to first category. The Lagrangian and partial Lagrangian include three approaches: Noether’s theorem, the partial Noether approach, and the Noether approach for the equation and its adjoint as a system. The characteristic method, the multiplier approaches, and the direct construction formula approach require the integrating factors or characteristics or multipliers. The Hamiltonian version of Noether’s theorem is presented to derive first integrals. We apply these different approaches to derive the first integrals of the harmonic oscillator equation. We also study first integrals for some physical models. The first integrals for nonlinear jerk equation and the free oscillations of a two-degree-of-freedom gyroscopic system with quadratic nonlinearities are derived. Moreover, solutions via first integrals are also constructed.
Ly49 Family Receptors Are Required for Cancer Immunosurveillance Mediated by Natural Killer Cells
Authors: Tu Megan M. , Mahmoud Ahmad Bakur , Wight Andrew , Mottashed Amelia , Bélanger Simon , Rahim Mir Munir A. , Abou-Samra Elias , Makrigiannis Andrew P.
Published: May 2014

According to the missing-self hypothesis, natural killer (NK) cells survey for target cells that lack MHC-I molecules. The Ly49 receptor family recognizes loss of MHC-I and is critical for educating NK cells, conferring the ability to eliminate transformed or infected cells. In this study, we evaluated their requirement in innate immune surveillance of cancer cells using genetically manipulated mice with attenuated expression of Ly49 receptors (NKCKD) in several models of carcinoma and metastasis. We found that NKCKD mice exhibited uncontrolled tumor growth and metastases. Expression of two MHC-I alleles, H-2Kb and H-2Db, was decreased in tumors from NKCKD mice in support of the likelihood of NK-mediated tumor immunoediting. These tumor cells exhibited directed alterations to their cell surface expression in response to the genetically altered immune environment to evade host recognition. Immunoediting in NKCKD mice was restricted to MHC-I molecules, which are ligands for Ly49 receptors, while expression of Rae-1 and Mult1, ligands for another NK cell receptor, NKG2D, were unaffected. Restoring NK cell education in NKCKD mice with a transgene for the inhibitory self-MHC-I receptor Ly49I restored suppression of cancer onset and growth. Interestingly, immune surveillance mediated by activating Ly49 receptors remained intact in NKCKD mice, as demonstrated by the ability to stimulate the NKG2D receptor with tumor cells or splenocytes expressing Rae-1. Together, our results genetically establish the integral role of Ly49 in NK cell-mediated control of carcinogenesis through MHC-I–dependent missing-self recognition. Cancer Res; 74(14); 3684–94. ©2014 AACR.
Loss of Cdk2 and Cyclin A2 Impairs Cell Proliferation and Tumorigenesis
Authors: Gopinathan Lakshmi , Tan Shawn Lu Wen , Padmakumar V. C. , Coppola Vincenzo , Tessarollo Lino , Kaldis Philipp
Published: May 2014

Cell-cycle inhibition has yet to offer a generally effective approach to cancer treatment, but a full evaluation of different combinations of cell-cycle inhibitors has not been evaluated. Cyclin A2, a core component of the cell cycle, is often aberrantly expressed in cancer where it may impact cell proliferation. In this study, we investigated the role of cyclin A2 in tumorigenesis using a conditional genetic knockout mouse model. Cyclin A2 deletion in oncogene-transformed mouse embryonic fibroblasts (MEF) suppressed tumor formation in immunocompromised mice. These findings were confirmed in mice with cyclin A2–deficient hepatocytes, where a delay in liver tumor formation was observed. Because cyclin A2 acts in complex with Cdk2 in the cell cycle, we explored a hypothesized role for Cdk2 dysregulation in this effect through conditional deletions of both genes. In oncogene-transformed MEFs lacking both genes, tumor formation was strongly suppressed in a manner associated with decreased proliferation, premature senescence, and error-prone recovery from serum deprivation after immortalization. Whereas loss of cyclin A2 led to a compensatory increase in Cdk1 activity, this did not occur with loss of both Cdk2 and cyclin A2. Our work offers a rationale to explore combinations of Cdk1 and Cdk2 inhibitors as a general approach in cancer therapy. Cancer Res; 74(14); 3870–9. ©2014 AACR.
Reducing Prostate Cancer Racial Disparity: Evidence for Aggressive Early Prostate Cancer PSA Testing of African American Men
Authors: Powell Isaac J. , Vigneau Fawn D. , Bock Cathryn H. , Ruterbusch Julie , Heilbrun Lance K.
Published: May 2014

Background: There is continuing controversy about prostate cancer testing and the recent American Urological Association guidelines. We hypothesize that the reduction and elimination of racial survival disparity among African American men (AAM; high-risk group) compared with European American men (EAM; intermediate-risk group) during the PSA testing era compared with the pre-PSA era strongly supports the use of PSA testing in AAM.

Methods: We used Surveillance, Epidemiology, and End Results (SEER) data to investigate relative survival disparities between AAM and EAM. To evaluate pre-PSA testing era, we selected malignant first primary prostate cancer in AAM and EAM, all stages, diagnosed during 1973–1994. To evaluate relative survival disparities in the current PSA testing era, we selected malignant first primary local, regional, and distant stage prostate cancers diagnosed during 1998–2005 to calculate 5-year relative survival rates.

Results: Age-adjusted 5-year relative survival of prostate cancer diagnosed during 1973–1994 in the national SEER data revealed significantly shorter survival for AAM compared with EAM (P < 0.0001). The SEER-based survival analysis from 1995 to 2005 indicated no statistical difference in relative survival rates between AAM and EAM by year of diagnosis of local, regional, or distant stage prostate cancer.

Conclusion: We conclude that the elimination of prostate cancer racial disparity of local, regional, and metastatic prostate cancer relative survival in the current PSA testing era compared with pre-PSA era as an endpoint to test PSA efficacy as a marker for prostate cancer diagnosis is evidence for aggressive testing of AAM.

Impact: Evidence for screening AAM. Cancer Epidemiol Biomarkers Prev; 23(8); 1505–11. ©2014 AACR.
Molecular Profiling of Patient-Matched Brain and Extracranial Melanoma Metastases Implicates the PI3K Pathway as a Therapeutic Target
Authors: Chen Guo , Chakravarti Nitin , Aardalen Kimberly , Lazar Alexander J. , Tetzlaff Michael T. , Wubbenhorst Bradley , Kim Sang-Bae , Kopetz Scott , Ledoux Alicia A. , Gopal Y.N. Vashisht , Pereira Cristiano Goncalves , Deng Wanleng , Lee Ju-Seog , Nathanson Katherine L. , Aldape Kenneth D. , Prieto Victor G. , Stuart Darrin , Davies Michael A.
Published: May 2014

Purpose: An improved understanding of the molecular pathogenesis of brain metastases, one of the most common and devastating complications of advanced melanoma, may identify and prioritize rational therapeutic approaches for this disease. In particular, the identification of molecular differences between brain and extracranial metastases would support the need for the development of organ-specific therapeutic approaches.

Experimental Design: Hotspot mutations, copy number variations (CNV), global mRNA expression patterns, and quantitative analysis of protein expression and activation by reverse-phase protein array (RPPA) analysis were evaluated in pairs of melanoma brain metastases and extracranial metastases from patients who had undergone surgical resection for both types of tumors.

Results: The status of 154 previously reported hotspot mutations, including driver mutations in BRAF and NRAS, were concordant in all evaluable patient-matched pairs of tumors. Overall patterns of CNV, mRNA expression, and protein expression were largely similar between the paired samples for individual patients. However, brain metastases demonstrated increased expression of several activation-specific protein markers in the PI3K/AKT pathway compared with the extracranial metastases.

Conclusions: These results add to the understanding of the molecular characteristics of melanoma brain metastases and support the rationale for additional testing of the PI3K/AKT pathway as a therapeutic target in these highly aggressive tumors. Clin Cancer Res; 20(21); 5537–46. ©2014 AACR.
The Microenvironment Matters: Estrogen Deficiency Fuels Cancer Bone Metastases
Authors: Wright Laura E. , Guise Theresa A.
Published: May 2014

Factors released during osteoclastic bone resorption enhance disseminated breast cancer cell progression by stimulating invasiveness, growth, and a bone-resorptive phenotype in cancer cells. Postmenopausal bone loss may accelerate progression of breast cancer growth in bone, explaining the anticancer benefit of the bone-specific antiresorptive agent zoledronic acid in the postmenopausal setting. Clin Cancer Res; 20(11); 2817–9. ©2014 AACR.
BET Bromodomain Inhibitors Block Growth of Pancreatic Cancer Cells in Three-Dimensional Collagen
Authors: Sahai Vaibhav , Kumar Krishan , Knab Lawrence M. , Chow Christina R. , Raza Sania S. , Bentrem David J. , Ebine Kazumi , Munshi Hidayatullah G.
Published: May 2014

Pancreatic ductal adenocarcinoma (PDAC) is associated with pronounced fibrosis that contributes to chemoresistance, in part, through increased histone acetylation. Because bromodomain (BRD) and extra terminal domain (BET) proteins are “readers” of histone acetylation marks, we targeted BET proteins in PDAC cells grown in three-dimensional collagen. We show that treatment with BET inhibitors decreases growth of PDAC cells (AsPC1, CD18, and Panc1) in collagen. Transfection with siRNA against BRD4, which is increased in human PDAC tumors, also decreases growth of PDAC cells. BET inhibitors additionally decrease growth in collagen of PDAC cells that have undergone epithelial-to-mesenchymal transition or have become resistant to chemotherapy. Although BET inhibitors and BRD4 siRNA repress c-MYC only in AsPC1 and CD18 cells, downregulating c-MYC decreases growth of all three PDAC cell lines in collagen. FOSL1, which is also targeted by BET inhibitors and BRD4 siRNA in AsPC1, CD18, and Panc1 cells, additionally regulates growth of all three PDAC cell lines in collagen. BET inhibitors and BRD4 siRNA repress HMGA2, an architectural protein that modulates chromatin state and also contributes to chemoresistance, in PDAC cells grown in collagen. Importantly, we show that there is a statistically significant correlation between BRD4 and HMGA2 in human PDAC tumors. Significantly, overexpression of HMGA2 partially mitigates the effect of BET inhibitors on growth and c-MYC and/or FOSL1 expression in collagen. Overall, these results demonstrate that BET inhibitors block growth of PDAC cells in collagen and that BET proteins may be potential targets for the treatment of pancreatic cancer. Mol Cancer Ther; 13(7); 1907–17. ©2014 AACR.
CAF-Secreted IGFBPs Regulate Breast Cancer Cell Anoikis
Authors: Weigel Kelsey J. , Jakimenko Ana , Conti Brooke A. , Chapman Sarah E. , Kaliney William J. , Leevy W. Matthew , Champion Matthew M. , Schafer Zachary T.
Published: May 2014

Carcinoma-associated fibroblasts (CAFs) are now widely appreciated for their contributions to tumor progression. However, the ability of CAFs to regulate anoikis, detachment-induced cell death, has yet to be investigated. Here, a new role for CAFs in blocking anoikis in multiple cell lines, facilitating luminal filling in three-dimensional cell culture, and promoting anchorage-independent growth is defined. In addition, a novel mechanism underlying anoikis inhibition is discovered. Importantly, it was demonstrated that CAFs secrete elevated quantities of insulin-like growth factor–binding proteins (IGFBPs) that are both necessary for CAF-mediated anoikis inhibition and sufficient to block anoikis in the absence of CAFs. Furthermore, these data reveal a unique antiapoptotic mechanism for IGFBPs: the stabilization of the antiapoptotic protein Mcl-1. In aggregate, these data delineate a novel role for CAFs in promoting cell survival during detachment and unveil an additional mechanism by which the tumor microenvironment contributes to cancer progression. These results also identify IGFBPs as potential targets for the development of novel chemotherapeutics designed to eliminate detached cancer cells.

Implications: The ability of CAF-secreted IGFBPs to block anoikis in breast cancer represents a novel target for the development of therapeutics aimed at specifically eliminating extracellular matrix–detached breast cancer cells. Mol Cancer Res; 12(6); 855–66. ©2014 AACR.
Emerging Functions of SRSF1, Splicing Factor and Oncoprotein, in RNA Metabolism and Cancer
Authors: Das Shipra , Krainer Adrian R.
Published: May 2014

Serine/Arginine Splicing Factor 1 (SRSF1) is the archetype member of the SR protein family of splicing regulators. Since its discovery over two decades ago, SRSF1 has been repeatedly surprising and intriguing investigators by the plethora of complex biologic pathways it regulates. These include several key aspects of mRNA metabolism, such as mRNA splicing, stability, and translation, as well as other mRNA-independent processes, such as miRNA processing, protein sumoylation, and the nucleolar stress response. In this review, the structural features of SRSF1 are discussed as they relate to the intricate mechanism of splicing and the multiplicity of functions it performs. Similarly, a list of relevant alternatively spliced transcripts and SRSF1 interacting proteins is provided. Finally, emphasis is given to the deleterious consequences of overexpression of the SRSF1 proto-oncogene in human cancers, and the complex mechanisms and pathways underlying SRSF1-mediated transformation. The accumulated knowledge about SRSF1 provides critical insight into the integral role it plays in maintaining cellular homeostasis and suggests new targets for anticancer therapy. Mol Cancer Res; 12(9); 1195–204. ©2014 AACR.
Teens Impulsively React rather than Retreat from Threat
Authors: Dreyfuss Michael , Caudle Kristina , Drysdale Andrew T. , Johnston Natalie E. , Cohen Alexandra O. , Somerville Leah H. , Galván Adriana , Tottenham Nim , Hare Todd A. , Casey B.J.
Published: May 2014

There is a significant inflection in risk taking and criminal behavior during adolescence, but the basis for this increase remains largely unknown. An increased sensitivity to rewards has been suggested to explain these behaviors, yet juvenile offences often occur in emotionally charged situations of negative valence. How behavior is altered by changes in negative emotional processes during adolescence has received less attention than changes in positive emotional processes. The current study uses a measure of impulsivity in combination with cues that signal threat or safety to assess developmental changes in emotional responses to threat cues. We show that adolescents, especially males, impulsively react to threat cues relative to neutral ones more than adults or children, even when instructed not to respond. This adolescent-specific behavioral pattern is paralleled by enhanced activity in limbic cortical regions implicated in the detection and assignment of emotional value to inputs and in the subsequent regulation of responses to them when successfully suppressing impulsive responses to threat cues. In contrast, prefrontal control regions implicated in detecting and resolving competing responses show an adolescent-emergent pattern (i.e. greater activity in adolescents and adults relative to children) during successful suppression of a response regardless of emotion. Our findings suggest that adolescence is a period of heightened sensitivity to social and emotional cues that results in diminished regulation of behavior in their presence.
Prevalence and Correlates of Psychopathology in Children and Adolescents Evaluated with the Strengths and Difficulties Questionnaire Dysregulation Profile in a Clinical Setting
Authors: Carballo Juan José , Serrano-Drozdowskyj Elena , García Nieto Rebeca , Díaz de Neira-Hernando Mónica , Pérez-Fominaya Margarita , Molina-Pizarro Cristian Antonio , De León-Martínez Victoria , Baca-García Enrique
Published: May 2014

Background: The clinical presentation of children and adolescents referred to mental health services is frequently complicated by comorbid and severe affective and behavioral dysregulation. This dysregulation phenotype seems to be an indicator of overall psychopathology, symptom severity and functional impairment. Currently, this phenotype is assessed by the Child Behavior Checklist. However, the widely used Strengths and Difficulties Questionnaire (SDQ) has been recently validated to screen the Dysregulation Profile (SDQ-DP) in clinical settings. The objective of this study was to determine the prevalence and demographic, psychosocial and clinical correlates of the SDQ-DP phenotype in a Spanish clinical sample. Sampling and Methods: In a clinical sample of 623 consecutively referred children and adolescents (4-17 years old), we compared clinical and sociodemographic correlates between subjects who met the SDQ-DP criteria (DP) and those who did not (NO_DP). Sociodemographic data, parent-rated SDQ, Children's Global Assessment Scale, Clinical Global Impression, family Apgar scale and clinical diagnoses were collected by experienced child and adolescent psychiatrists. Results: Overall in our sample, 175 subjects (28.1%) met the SDQ-DP criteria (DP group). Compared with the NO_DP group, the DP subjects had significantly higher scores on internalizing and externalizing psychopathology, problems with peers and overall problems as well as significantly lower scores on prosocial behavior. Clinical diagnoses assigned revealed that DP subjects showed significantly greater psychiatric comorbidity. DP subjects also showed significantly worse family functioning and increased symptom severity and significantly lower scores on psychosocial functioning. Conclusions: A high prevalence of children and adolescents with the dysregulated profile, assessed by the SDQ-DP, was found in our clinical setting. The SDQ-DP may serve as an index of overall psychological severity and functional impairment. In addition, it may indicate family dysfunction. Further research is needed to validate the clinical value of SDQ-DP by examining longitudinal stability, heritability, adult outcome, risk factors and diagnostic correlates.
Long-Term Follow-Up of MRI-Guided Bilateral Anterior Capsulotomy in Patients with Refractory Schizophrenia
Authors: Liu Wei , Hao Qianqian , Zhan Shikun , Li Dianyou , Pan Sijian , Li Yongchao , Lin Guozhen , Pan Guihua , Mahyoub Radfan , Sun Bomin
Published: May 2014

Aim: To determine whether there is a long-term benefit of MRI-guided bilateral anterior capsulotomy in the treatment of refractory schizophrenia. Methods: 116 patients (16 patients did not complete the follow-up evaluation) with refractory schizophrenia who underwent capsulotomy were included. The treatment effect was evaluated using a series of international rating scales. Evaluations were performed at baseline, 3 weeks and 24 months after surgery. Results: The rate of effectiveness was 74% according to the Clinical Global Impression evaluation, and there was an obvious improvement based on the statistical analysis for Positive and Negative Symptom Scale (baseline vs. 24 months after surgery, 6.86 ± 8.12, 10.70 ± 8.70 vs. 26.65 ± 4.85, 21.66 ± 7.19), Brief Psychiatric Rating Scale (14.75 ± 13.21 vs. 44.97 ± 9.36), Activities of Daily Living Scale (18.06 ± 6.58 vs. 24.61 ± 8.95), Social Disability Screening Schedule (6.69 ± 6.12 vs. 15.06 ± 3.18) and Global Assessment Scale (74.35 ± 12.75 vs. 48.74 ± 9.18). Among all the symptoms of schizophrenia, aggressive behavior (82% response rate), hallucination, (71% response rate) and delusion (70% response rate) showed the best response. Conclusion: Our research indicates that capsulotomy is a relatively safe and effective intervention for patients with refractory schizophrenia. It could be an alternative therapy for those patients with chronic and severe schizophrenia. But there must be strict inclusion criteria considering the complications and irreversibility of this procedure.
Focal Segmental Glomerulosclerosis Secondary to Juxtaglomerular Cell Tumor during Pregnancy: A Case Report
Authors: Ohashi Yasushi , Kobayashi Shizuka , Arai Taichi , Nemoto Tetsuo , Aoki Chizu , Nagata Masato , Sakai Ken
Published: May 2014

Juxtaglomerular cell tumor is a rare renal neoplasm. Secondary hypertension with juxtaglomerular cell tumor can be seen in females in their 20s and 30s. We present a case of juxtaglomerular cell tumor during pregnancy. A 32-year-old female was hospitalized for refractory hypertension and nephrotic syndrome in the 23rd gestational week. One year before admission, she had been diagnosed with hypertension; plasma renin activity at that time had been 2.3 ng/ml/h. Her blood pressure was uncontrolled during pregnancy, and proteinuria was detected in the 12th gestational week despite the administration of antihypertensive medications. Laboratory data showed proteinuria, hypokalemia, and hypoalbuminemia. In the 25th gestational week, she underwent surgical termination of the pregnancy because of congestive heart failure and acute renal injury. After the termination of the pregnancy and the delivery of a viable fetus, her hypertension and nephrotic syndrome were found to persist with a high plasma renin activity (13 ng/ml/h). Ultrasonography showed a 5.5-cm left renal cystic mass with a partially solid component at the lower renal pole. The left kidney with the renal mass was excised by laparoscopic nephrectomy. Plasma renin activity normalized the next day, with a decrease in blood pressure to 120-130/80-90 mm Hg; however, proteinuria remained at ≥3.5 g/day. On the basis of histopathological findings, the patient was diagnosed with a juxtaglomerular cell tumor and focal segmental glomerulosclerosis. Juxtaglomerular cell tumor is a rare renin-secreting tumor associated with refractory hypertension in young females and is a possible cause of hypertension during pregnancy.
Effectiveness of a Clinical Decision Support System for Reducing the Risk of QT Interval Prolongation in Hospitalized Patients
Authors: Tisdale James E. , Jaynes Heather A. , Kingery Joanna R. , Overholser Brian R. , Mourad Noha A. , Trujillo Tate N. , Kovacs Richard J.
Published: May 2014

Background—

We evaluated the effectiveness of a computer clinical decision support system (CDSS) for reducing the risk of QT interval prolongation in hospitalized patients.

Methods and Results—

We evaluated 2400 patients admitted to cardiac care units at an urban academic medical center. A CDSS incorporating a validated risk score for QT
c
prolongation was developed and implemented using information extracted from patients’ electronic medical records. When a drug associated with torsades de pointes was prescribed to a patient at moderate or high risk for QT
c
interval prolongation, a computer alert appeared on the screen to the pharmacist entering the order, who could then consult the prescriber on alternative therapies and implement more intensive monitoring. QT
c
interval prolongation was defined as QT
c
interval >500 ms or increase in QT
c
of ≥60 ms from baseline; for patients who presented with QT
c
>500 ms, QT
c
prolongation was defined solely as increase in QT
c
≥60 ms from baseline. End points were assessed before (n=1200) and after (n=1200) implementation of the CDSS. CDSS implementation was independently associated with a reduced risk of QT
c
prolongation (adjusted odds ratio, 0.65; 95% confidence interval, 0.56–0.89;
P
<0.0001). Furthermore, CDSS implementation reduced the prescribing of noncardiac medications known to cause torsades de pointes, including fluoroquinolones and intravenous haloperidol (adjusted odds ratio, 0.79; 95% confidence interval, 0.63–0.91;
P
=0.03).

Conclusions—

A computer CDSS incorporating a validated risk score for QT
c
prolongation influences the prescribing of QT-prolonging drugs and reduces the risk of QT
c
interval prolongation in hospitalized patients with torsades de pointes risk factors.
Adaptive (T and B Cells) Immunity and Control by Dendritic Cells in Atherosclerosis
Authors: Ait-Oufella Hafid , Sage Andrew P. , Mallat Ziad , Tedgui Alain
Published: May 2014

Chronic inflammation in response to lipoprotein accumulation in the arterial wall is central in the development of atherosclerosis. Both innate and adaptive immunity are involved in this process. Adaptive immune responses develop against an array of potential antigens presented to effector T lymphocytes by antigen-presenting cells, especially dendritic cells. Functional analysis of the role of different T-cell subsets identified the Th1 responses as proatherogenic, whereas regulatory T-cell responses exert antiatherogenic activities. The effect of Th2 and Th17 responses is still debated. Atherosclerosis is also associated with B-cell activation. Recent evidence established that conventional B-2 cells promote atherosclerosis. In contrast, innate B-1 B cells offer protection through secretion of natural IgM antibodies. This review discusses the recent development in our understanding of the role of T- and B-cell subsets in atherosclerosis and addresses the role of dendritic cell subpopulations in the control of adaptive immunity.
Bone Marrow Mononuclear Cell Therapy for Acute Myocardial Infarction
Authors: Simari Robert D. , Pepine Carl J. , Traverse Jay H. , Henry Timothy D. , Bolli Roberto , Spoon Daniel B. , Yeh Ed , Hare Joshua M. , Schulman Ivonne Hernandez , Anderson R. David , Lambert Charles , Sayre Shelly L. , Taylor Doris A. , Ebert Ray F. , Moyé Lemuel A.
Published: May 2014

To understand the role of bone marrow mononuclear cells in the treatment of acute myocardial infarction, this overview offers a retrospective examination of strengths and limitations of 3 contemporaneous trials with attention to critical design features and provides an analysis of the combined data set and implications for future directions in cell therapy for acute myocardial infarction.
MicroRNA-133 Modulates the β
1
-Adrenergic Receptor Transduction Cascade
Authors: Castaldi Alessandra , Zaglia Tania , Di Mauro Vittoria , Carullo Pierluigi , Viggiani Giacomo , Borile Giulia , Di Stefano Barbara , Schiattarella Gabriele Giacomo , Gualazzi Maria Giovanna , Elia Leonardo , Stirparo Giuliano Giuseppe , Colorito Maria Luisa , Pironti Gianluigi , Kunderfranco Paolo , Esposito Giovanni , Bang Marie-Louise , Mongillo Marco , Condorelli Gianluigi , Catalucci Daniele
Published: May 2014

Rationale
:

The sympathetic nervous system plays a fundamental role in the regulation of myocardial function. During chronic pressure overload, overactivation of the sympathetic nervous system induces the release of catecholamines, which activate β-adrenergic receptors in cardiomyocytes and lead to increased heart rate and cardiac contractility. However, chronic stimulation of β-adrenergic receptors leads to impaired cardiac function, and β-blockers are widely used as therapeutic agents for the treatment of cardiac disease. MicroRNA-133 (miR-133) is highly expressed in the myocardium and is involved in controlling cardiac function through regulation of messenger RNA translation/stability.

Objective
:

To determine whether miR-133 affects β-adrenergic receptor signaling during progression to heart failure.

Methods and Results
:

Based on bioinformatic analysis, β
1
-adrenergic receptor (β
1
AR) and other components of the β
1
AR signal transduction cascade, including adenylate cyclase VI and the catalytic subunit of the cAMP-dependent protein kinase A, were predicted as direct targets of miR-133 and subsequently validated by experimental studies. Consistently, cAMP accumulation and activation of downstream targets were repressed by miR-133 overexpression in both neonatal and adult cardiomyocytes following selective β
1
AR stimulation. Furthermore, gain-of-function and loss-of-function studies of miR-133 revealed its role in counteracting the deleterious apoptotic effects caused by chronic β
1
AR stimulation. This was confirmed in vivo using a novel cardiac-specific TetON-miR-133 inducible transgenic mouse model. When subjected to transaortic constriction, TetON-miR-133 inducible transgenic mice maintained cardiac performance and showed attenuated apoptosis and reduced fibrosis compared with control mice.

Conclusions
:

miR-133 controls multiple components of the β
1
AR transduction cascade and is cardioprotective during heart failure.
Statins Improve Survival in Patients With Cardioembolic Stroke
Authors: Choi Jeong-Yoon , Seo Woo-Keun , Kang Sung Hoon , Jung Jin-Man , Cho Kyung-Hee , Yu Sungwook , Oh Kyungmi
Published: May 2014

Background and Purpose—

The objective of this study was to investigate the potential benefits of statin therapy on mortality and stroke recurrence after cardioembolic stroke.

Methods—

In this retrospective observational study, we analyzed data from 535 patients with first-ever cardioembolic stroke. Patients were classified into nonstatin, low-potency statin, and high-potency statin groups. The primary outcomes were time to mortality and time to recurrent stroke.

Results—

The mean duration of follow-up was 22.2 months. The cumulative mortality rate was 7% at the end of the first year and 10% at the end of the third year. Statin therapy was independently associated with reduced mortality (hazard ratio, 0.237; 95% confidence interval, 0.080–0.703 for nonstatin versus low-potency statin; hazard ratio, 0.158; 95% confidence interval, 0.037–0.686 for nonstatin versus high-potency statin). Statin treatment did not affect the incidence of recurrent stroke in patients with cardioembolic stroke.

Conclusions—

Statin therapy could be associated with reduced mortality in patients with cardioembolic stroke.
Interaction between WSSV envelope protein VP31 and triosephosphate isomerase in haemocytes of the Chinese shrimp, Fenneropenaeus chinensis (Osbeck, 1765) (Decapoda, Penaeoidea)
Authors: Zhao J. M. , Tang X. Q. , Zhan W. B.
Published: May 2014

To investigate the interaction between white spot syndrome virus (WSSV) envelope protein VP31 and haemocytes of the Chinese shrimp, Fenneropenaeus chinensis (Osbeck, 1765), the VP31 protein was recombinantly expressed in Escherichia coli (Migula, 1895) as a fusion protein with glutathione S-transferase tag (GST-tag). By Far Western Blotting, a prominent protein band of 26 kDa in haemocytes of F. chinensis was recognized by the recombinant VP31 (rVP31), which was identified as triosephosphate isomerase (TPI) by mass spectrometric analysis. Then, the TPI gene of F. chinensis was cloned and expressed as a fusion protein with thioredoxin/Histone/S-protein tag (Trx/His/S-tag) using the pET-32(a)+ vector, and the binding interaction between the recombinant TPI (rTPI) and rVP31 was further confirmed by pull-down assay. The expression of the TPI gene in haemocytes was significantly down-regulated in response to WSSV challenge. Moreover, the rTPI appeared to be able to partially block the WSSV infection and delay the death of infected shrimp in in vivo neutralization assay. These results indicate that TPI might play an important role in WSSV infection in F. chinensis.
Reflections on the Indictment of Sitting Heads of State and Government and Its Consequences for Peace and Stability and Reconciliation in Africa
Authors: Jalloh Charles Chernor
Published: May 2014

Abstract

In these remarks, the author considers the most recent challenge to the application of international criminal justice in Africa: Kenya’s controversial November 2013 proposal to amend the Rome Statute of the International Criminal Court to temporarily exempt from prosecution sitting presidents accused of involvement with international crimes. He examines several legal and practical reasons why such a proposal is untenable. Instead, citing the principle of complementarity and urging the principled use of judicial and prosecutorial discretion, he contends that much of the African Union’s current concerns about the Kenya Situation can be addressed within the confines of existing Rome Law. This is important because, even if it is possible for African countries to secure amendments to the Rules of Procedure and Evidence, African States Parties are unlikely able to secure the global consensus required to effect substantive amendments to the 1998 treaty. On the other hand, the author suggests that the International Criminal Court officials, especially the judges and the chief prosecutor, can help bridge the apparent gap between the Court and its African supporters. Towards that end, they should consider taking a more flexible and more nuanced approach to their interpretations and application of several important provisions contained in their founding statute. Eschewing a one-size fits all approach, it is submitted that each African situation is unique – both in the scope of the problem, and in the solution required in the necessary fight against impunity in Africa.
Legitimacy of Regional Economic Integration Courts in Africa
Authors: Oppong Richard Frimpong
Published: May 2014

Abstract

The expansion of economic integration initiatives in Africa has been accompanied by an increase in the number of regional courts currently operating on the continent. Four of these courts have been particularly active, spinning off judgments on issues ranging from the legality of national elections to the free movement of persons. There is a modest but growing body of scholarship on the jurisprudence of the courts. However, to date, there has been little or no attempt in the academic literature to examine the legitimacy of the courts. The issue of the courts’ legitimacy is important because of the potential impact of their judgments on national legal systems and policies. This paper examines that issue. While acknowledging that the concept of legitimacy is not free of debate, it identifies a number of factors that influence the legitimacy of international courts and applies them to the regional courts. An earlier draft of this paper was presented at a workshop on the legitimacy of international courts at the Centre for International and Comparative Law, Duke University School of Law.
Yves Congar and Hans Küng at Vatican II
Authors: Ruddy Christopher
Published: May 2014

Yves Congar’s and Hans Küng’s modes of participation at Vatican II reflect different visions of ecclesial reform. Congar followed an ‘inside’ path, working on the conciliar commissions that produced Vatican II’s documents; Küng chose an ‘outside’ path, pursuing his own writing projects and engaging the mass-media. Their choice of differing paths was neither arbitrary nor merely temperamental, but cohered in both instances with substantial theologies of reform. Attending to the inseparability of the historical-biographical and systematic dimensions of their respective trajectories, this article first examines Congar’s evaluation of his own role at the Council and of the roles of other participants, as witnessed by his conciliar journal spanning the years 1960 to 1966. The article then does likewise for Küng, drawing primarily upon his memoirs. It concludes by comparing their paths of reform and addressing the implications of their differences.
Pope John XXII and the Michaelists
Authors: Brunner Melanie
Published: May 2014

The theoretical poverty controversy in 1322–1323 concerned the question of the Franciscan doctrine that Christ and the apostles had renounced both individual and communal property. This article examines Pope John XXII’s final and often neglected text on the question of Franciscan poverty, the bull Quia vir reprobus published in 1329. It was only in this late bull that the pope addressed the question of the scriptural title of Franciscan poverty, and he used the bull to establish the (temporal) dominion of Christ through biblical exegesis. The middle section of John’s bull constitutes an almost completely self-contained treatise on the role of dominion in Scripture, and it is therefore as close as we can get to a personal statement of the pope on his own definition of both the dominion and the poverty of Christ. The pope’s preoccupation with the reconstruction of Christ’s lordship and poverty from biblical texts shows a different aspect of John XXII’s relationship with the Franciscans from the primarily legal argumentation in his earlier bulls, and it illustrates that his dissatisfaction with the Franciscan poverty ideal went beyond legal and administrative concerns.
Three-Way Chess
Authors: Krabbendam Hans
Published: May 2014

By following the career and networks of Dutch missionary and diplomat Arie Kok (1883–1951), this essay explores the motives for creating a transatlantic fundamentalist network after World War II. Using private correspondence, interviews, institutional records, and periodicals, the essay demonstrates that the goal, means, and strategy of American fundamentalists tied them closely to other American Protestant groups active in postwar Europe. Apart from the exclusivist doctrine and antithetical style, which burdened the chances for positive cooperation among traditional Protestants, it was the national agenda of Carl McIntire, the American father of international fundamentalism that nullified Kok’s transnational endeavors. Despite these limitations, Kok succeeded briefly in captivating a group of Europeans, shaping the discourse and the religious activities of the Americans on the European continent, and causing the emerging evangelicals serious concern.
الخط الكوفي الهندسي الشكل حلية زخرفية بجامع البرديني بالقاهرة "دراسة تحليلية مقارنة" (Geometric Kufic Script A Decorative Ornament in al-Bardini Mosque in Cairo ‘A Comparative Analysis Study’)
Authors: محمد زكي أحمد احمد
Published: May 2014

The Mosque of al-Khawaja Karim al-Din ibn Ahmad al-Bardini al-Shafei (1025-1038 AH/1616-1629 CE) monument no. 201, Daudi street, (previously Darb al-Fawakhir), north of Queen Safeya Mosque, Darb al-Ahmar, south of Cairo, in Mamluk style and its layout comprises a lounge perpendicular to it from the south-east is the Qibla Iwan (Mecca direction locator), with a curtain/drape on the inner left-side of its main door. It is perpendicular north- west to the lounge. The sheath is marble inlaid with mother-of-pearl in different areas, decorated with rectangular fillings including 12 star-shaped plates, and other various geometric motifs. This paper deals with the geometric kufic script in the Mosque. The author reads each inscription, carefully analyzes it, measures it, and compares it to other similar samples from previous historical periods.

(Please note that this article is in Arabic)
Diversity and systematics of Haminoeidae gastropods (Heterobranchia: Cephalaspidea) in the tropical West Pacific Ocean: new data on the genera Aliculastrum, Atys, Diniatys and Liloa
Authors: TOO CHIN CHIN , CARLSON CLAY , HOFF PATTY JO , MALAQUIAS MANUEL ANTÓNIO E.
Published: May 2014

Four genera of Haminoeidae gastropods inhabiting the tropical West Pacific (Aliculastrum, Atys, Diniatys, and Liloa) were studied based on the combined analyses of live animals, external morphology, anatomy and shells aided by scanning electron microscopy and molecular sequencing. Eleven species are described including two new to Science, namely Atys pittmani sp. nov. and Atys ukulele sp. nov.. The putative synapomorphies of the genera Aliculastrum, Diniatys, and Liloa are discussed. High levels of morpho-anatomical variability were found among representatives of the genus Atys, which hampered the recognition of synapomorphies.
The Hawkmoth Fauna of Pakistan (Lepidoptera: Sphingidae)
Authors: RAFI MUHAMMAD ATHER , SULTAN AMIR , KITCHING IAN J. , PITTAWAY Anthony R. , MARKHASIOV MAXIM , KHAN MUHAMMAD RAFIQUE , NAZ FALAK
Published: May 2014

This study represents the first complete modern account of the Sphingidae of Pakistan and takes the form of an annotated checklist, based on several national collections and those of a number of individuals. Of the 60 species and subspecies found, 14 are new records to the fauna of Pakistan, namely Agnosia orneus, Langia zenzeroides subsp. zenzeroides, Polyptychus trilineatus subsp. trilineatus, Dolbina inexacta, Ambulyx sericeipennis subsp. sericeipennis, Thamnoecha uniformis, Macroglossum belis, Macroglossum stellatarum, Cechetra scotti, Hippotion boerhaviae, Hyles euphorbiae subsp. euphorbiae, Rhagastis olivacea, Rethera brandti subsp. euteles and Theretra latreillii subsp. lucasii. Anambulyx elwesi subsp. kitchingi and Clanis deucalion subsp. thomaswitti are not recognised as valid subspecies and are synonymized with their respective nominotypical subspecies. An additional list is given of 30 taxa which may yet be found in Pakistan as they are present in neighbouring countries close to the border. Of the species/subspecies found, 24 are part of the Palaearctic fauna, 27 are part of the Oriental fauna and nine are Palaeo-Oriental/Palaeotropical. This reconfirms the transitional biogeographical position of the Pakistan fauna.
A new species of land flatworm (Platyhelminthes: Continenticola) from areas of Araucaria Forest in southern Brazil
Authors: ROSSI ILANA , FONTOURA MARCELA , AMARAL SILVANA , LEAL-ZANCHET ANA M.
Published: May 2014

The genus Cratera Carbayo et al. was proposed to encompass five species of Geoplaninae from southeastern Brazil that were mainly recorded in the state of São Paulo. Here we describe a new species of the genus, C. steffeni sp. nov., that occurs in areas of Araucaria Forest in southern Brazil, which augments the known distribution of Cratera. The new species is distinguished from others of the genus by its characteristic colour pattern and a combination of internal morphological characters.
A review of the genus Syrastrenopsis Grünberg, 1914 (Lepidoptera, Lasiocampidae)
Authors: ZOLOTUHIN VADIM V. , SALDAITIS AIDAS
Published: May 2014

The genus Syrastrenopsis Grünberg, 1914 is revised and two new species, S. panga Zolotuhin & Saldaitis, sp. nov. and S. hun Zolotuhin & Saldaitis, sp. nov. are described from North Sichuan and Shaanxi Provinces of China, respectively. All species of the genus are illustrated including the male of S. imperiatus Zolotuhin, 2001 which is described for the first time.
Two new species of Didicrum Enderlein (Diptera, Psychodidae, Psychodinae) from Argentinean Patagonia
Authors: OMAD GUILLERMO
Published: May 2014

Two new species of Didicrum from Argentina are described and illustrated: Didicrum naimae and Didicrum letitiae, based on male and female specimens. Specimens were collected with Malaise traps located in Nahuel Huapi National Park, Patagonian region. Including the two new species of Didicrum, twelve are described from South America.
Arctic Air Pollution: New Insights from POLARCAT-IPY
Authors: Law Katharine S. , Stohl Andreas , Quinn Patricia K. , Brock Charles A. , Burkhart John F. , Paris Jean-Daniel , Ancellet Gerard , Singh Hanwant B. , Roiger Anke , Schlager Hans , Dibb Jack , Jacob Daniel J. , Arnold Steve R. , Pelon Jacques , Thomas Jennie L.
Published: May 2014

Given the rapid nature of climate change occurring in the Arctic and the difficulty climate models have in quantitatively reproducing observed changes such as sea ice loss, it is important to improve understanding of the processes leading to climate change in this region, including the role of short-lived climate pollutants such as aerosols and ozone. It has long been known that pollution produced from emissions at midlatitudes can be transported to the Arctic, resulting in a winter/spring aerosol maximum known as Arctic haze. However, many uncertainties remain about the composition and origin of Arctic pollution throughout the troposphere; for example, many climate–chemistry models fail to reproduce the strong seasonality of aerosol abundance observed at Arctic surface sites, the origin and deposition mechanisms of black carbon (soot) particles that darken the snow and ice surface in the Arctic is poorly understood, and chemical processes controlling the abundance of tropospheric ozone are not well quantified. The International Polar Year (IPY) Polar Study using Aircraft, Remote Sensing, Surface Measurements and Models, Climate, Chemistry, Aerosols and Transport (POLARCAT) core project had the goal to improve understanding about the origins of pollutants transported to the Arctic; to detail the chemical composition, optical properties, and climate forcing potential of Arctic aerosols; to evaluate the processes governing tropospheric ozone; and to quantify the role of boreal forest fires. This article provides a review of the many results now available based on analysis of data collected during the POLARCAT aircraft-, ship-, and ground-based field campaigns in spring and summer 2008. Major findings are highlighted and areas requiring further investigation are discussed.