bluuebunny/crossref_metadata_2025 huggingface dataset:
Fish oil and neurovascular control in humans
Authors: Carter Jason R. , Schwartz Christopher E. , Yang Huan , Joyner Michael J.
Published: June 2012

The antihypertensive influence of fish oil is controversial, and the mechanisms remain unclear. Because the inverse relation between fish oil and hypertension appears to be partially dependent on the degree of hypertension, we tested the hypothesis that fish oil would elicit more dramatic reductions in mean arterial pressure (MAP) and muscle sympathetic nerve activity (MSNA) in prehypertensive (PHT) compared with normotensive (NT) subjects. Resting MAP, MSNA, and heart rate (HR) were examined before and after 8 wk of fish oil (9 g/day; 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid) or placebo (olive oil; 9 g/day) in 38 NT (19 fish oil; 19 placebo) and 29 PHT (15 fish oil; 14 placebo) volunteers. Fish oil did not alter resting MAP, MSNA, or HR in either NT (80 ± 1 to 80 ± 1 mmHg; 11 ± 2 to 10 ± 1 bursts/min; 71 ± 2 to 71 ± 2 beats/min) or PHT (88 ± 2 to 87 ± 1 mmHg; 11 ± 2 to 10 ± 2 bursts/min; 73 ± 2 to 73 ± 2 beats/min) subjects. When NT and PHT groups were consolidated, analysis of covariance confirmed that pretreatment resting MAP was not associated with changes in MSNA after fish oil. In contrast, pretreatment resting HR was correlated with changes in MSNA ( r = 0.47; P = 0.007) and MAP ( r = 0.42; P < 0.007) after fish oil but not placebo. In conclusion, fish oil did not alter sympathetic neural control in NT or PHT subjects. However, our findings suggest that fish oil is associated with modest sympathoinhibition in individuals with higher resting heart rates, a finding that is consistent with a recent meta-analysis examining the relations among fish oil, HR, and the risk of cardiovascular disease.
The role of the E2F1 transcription factor in the innate immune response to systemic LPS
Authors: Warg Laura A. , Oakes Judy L. , Burton Rachel , Neidermyer Amanda J. , Rutledge Holly R. , Groshong Steve , Schwartz David A. , Yang Ivana V.
Published: June 2012

Previous publications from our and other groups identified E2F1 as a transcription factor involved in the regulation of inflammatory response to Toll-like receptor ligands including LPS. In this study, we challenged E2F1-deficient mice with LPS systemically and demonstrated decreased survival despite attenuated inflammatory response compared with controls. Gene expression profiling of liver tissue identified a dampened transcriptional response in the coagulation cascade in B6;129E2F1−/− compared with B6x129 F2 mice. These data were further corroborated by increased prothrombin time, activated partial thromboplastin time, and fibrin split products in the blood of E2F1-deficient mice, suggesting disseminated intravascular coagulation as a consequence of uncontrolled sepsis providing at least a partial explanation for their decreased survival despite attenuated inflammatory response. To identify novel miRNAs involved in the innate immune response to LPS, we also performed miRNA profiling of liver tissue from B6;129E2F1−/− and B6x129 F2 mice treated with LPS systemically. Our analysis identified a set of miRNAs and their mRNA targets that are significantly differentially regulated in E2F1-deficient but not control mice including let-7g, miR-101b, miR-181b, and miR-455. These miRNAs represent novel regulators of the innate immune response. In summary, we used transcriptional and miRNA profiling to characterize the response of E2F1-deficient mice to systemic LPS.
Adenosine receptor A2b on hematopoietic cells mediates LPS-induced migration of PMNs into the lung interstitium
Authors: Konrad Franziska M. , Witte Esther , Vollmer Irene , Stark Stefanie , Reutershan Jörg
Published: June 2012

Uncontrolled transmigration of polymorphonuclear leukocytes (PMNs) into the different compartments of the lungs (intravascular, interstitial, alveolar) is a critical event in the early stage of acute lung injury and acute respiratory distress syndrome. Adenosine receptor A2b is highly expressed in the inflamed lungs and has been suggested to mediate cell trafficking. In a murine model of LPS-induced lung inflammation, we investigated the role of A2b on migration of PMNs into the different compartments of the lung. In A2b−/− mice, LPS-induced accumulation of PMNs was significantly higher in the interstitium, but not in the alveolar space. In addition, pulmonary clearance of PMNs was delayed in A2b−/− mice. Using chimeric mice, we identified A2b on hematopoietic cells as crucial for PMN migration. A2b did not affect the release of relevant chemokines into the alveolar space. LPS-induced microvascular permeability was under the control of A2b on both hematopoietic and nonhematopoietic cells. Activation of A2b on endothelial cells also reduced formation of LPS-induced stress fibers, highlighting its role for endothelial integrity. A specific A2b agonist (BAY 60–6583) was effective in decreasing PMN migration into the lung interstitium and microvascular permeability. In addition, in vitro transmigration of human PMNs through a layer of human endothelial or epithelial cells was A2b dependent. Activation of A2b on human PMNs reduced oxidative burst activity. Together, our results demonstrate anti-inflammatory effects of A2b on two major characteristics of acute lung injury, with a distinct role of hematopoietic A2b for cell trafficking and endothelial A2b for microvascular permeability.
“I Live Quite a Good Balanced Life”: A Pilot Study on the Life Experiences of Ageing Individuals Living with HIV
Authors: Ribeiro Nobre Nuno , Kylmä Jari , Kirsi Tapio
Published: June 2012

An ageing population is accompanied by an increased number of older adults living with HIV. So far, our knowledge regarding the life experiences of older adults living with HIV is still poor and under researched. The purpose of this study is to present new knowledge by interviewing nine Finnish HIV-positive individuals of 50 years of age and older. The data were analysed by inductive content analysis. Living with HIV is shaped by unique personal life experiences. These experiences played an important role on how the interviewees assessed their lives and their future as HIV positive individuals. Most of the participants reacted negatively to their HIV-positive diagnosis. However, throughout time they had found meaning in their lives and had developed a degree of positive attitude towards life and future which was articulated in terms of a good overall balanced life. Since caring is the tenor of the nursing profession, nurses should be able to identify and implement methods for assessing how successfully older adults living with HIV age and intervene in an informed way whenever needed.
Age- and Gender-Specific Prevalence of Risk Factors in Patients with First-Ever Ischemic Stroke in China
Authors: Yao Xiao-ying , Lin Yan , Geng Jie-li , Sun Ya-meng , Chen Ying , Shi Guo-wen , Xu Qun , Li Yan-sheng
Published: June 2012

Background. Evidences are accumulating that age and gender have great impact on the distribution of stroke risk factors. Such data are lacking in Chinese population.Methods. 1027 patients with first-ever ischemic stroke (IS) were recruited and divided into young adult (<50 years), middle-aged (50∼80 years), and very old (>80 years) groups according to stroke onset ages. Vascular risk factors were collected and compared among groups.Results. Female patients were globally older than male patients at stroke onset and having higher prevalence of diabetes mellitus (DM), heart diseases, and atrial fibrillation (AF). However, females were less likely to drink heavily or smoke than males. Young patients had a much higher proportion of smoking and drinking than middle-aged and very old patients and the highest family history of hypertension, while very old patients had the highest prevalence of heart diseases and AF but lowest proportion of positive family history of vascular diseases. Hypertension and DM were equally frequent among three groups.Conclusion. Our study showed that vascular risk factors had a specific age and gender distribution pattern in Chinese IS patients. Secondary prevention strategy should emphasize on the control of different risk factors based on patient’s age and gender.
Isorhamnetin, A Flavonol Aglycone fromGinkgo bilobaL., Induces Neuronal Differentiation of Cultured PC12 Cells: Potentiating the Effect of Nerve Growth Factor
Authors: Xu Sherry L. , Choi Roy C. Y. , Zhu Kevin Y. , Leung Ka-Wing , Guo Ava J. Y. , Bi Dan , Xu Hong , Lau David T. W. , Dong Tina T. X. , Tsim Karl W. K.
Published: June 2012

Flavonoids, a group of compounds mainly derived from vegetables and herbal medicines, share a chemical resemblance to estrogen, and indeed some of which have been used as estrogen substitutes. In searching for possible functions of flavonoids, the neuroprotective effect in brain could lead to novel treatment, or prevention, for neurodegenerative diseases. Here, different subclasses of flavonoids were analyzed for its inductive role in neurite outgrowth of cultured PC12 cells. Amongst the tested flavonoids, a flavonol aglycone, isorhamnetin that was isolated mainly from the leaves ofGinkgo bilobaL. showed robust induction in the expression of neurofilament, a protein marker for neurite outgrowth, of cultured PC12 cells. Although isorhamnetin by itself did not show significant inductive effect on neurite outgrowth of cultured PC12 cells, the application of isorhamnetin potentiated the nerve growth factor- (NGF-)induced neurite outgrowth. In parallel, the expression of neurofilaments was markedly increased in the cotreatment of NGF and isorhamnetin in the cultures. The identification of these neurite-promoting flavonoids could be very useful in finding potential drugs, or food supplements, for treating various neurodegenerative diseases, including Alzheimer’s disease and depression.
From Transcriptome to Noncoding RNAs: Implications in ALS Mechanism
Authors: Gagliardi Stella , Milani Pamela , Sardone Valentina , Pansarasa Orietta , Cereda Cristina
Published: June 2012

In the last years, numerous studies have focused on understanding the metabolism of RNA and its implication in disease processes but abnormal RNA metabolism is still unknown. RNA plays a central role in translating genetic information into proteins and in many other catalytic and regulatory tasks. Recent advances in the study of RNA metabolism revealed complex pathways for the generation and maintenance of functional RNA in amyotrophic lateral sclerosis (ALS). Interestingly, perturbations in RNA processing have been described in ALS at various levels such as gene transcription, mRNA stabilization, transport, and translational regulations. In this paper, we will discuss the alteration of RNA profile in ALS disease, starting from transcription, the first step leading to gene expression, through the posttranscriptional regulation, including RNA/DNA binding proteins and aberrant exon splicing to protein noncoding RNAs, as lncRNA and microRNA.
Quality of Life, Depression, and Healthcare Resource Utilization among Adults with Type 2 Diabetes Mellitus and Concomitant Hypertension and Obesity: A Prospective Survey
Authors: Green Andrew J. , Bazata Debbra D. , Fox Kathleen M. , Grandy Susan
Published: June 2012

Background. This study compared quality of life, depression, and healthcare resource utilization among adults with type 2 diabetes mellitus (T2DM) and comorbid hypertension (HTN) and obesity with those of adults reporting T2DM alone.Methods. Respondents to the US SHIELD survey self-reported their height, weight, comorbid conditions, hospitalizations, and outpatient visits and completed the Short Form-12 (SF-12) and Patient Health Questionnaire (PHQ-9). Respondents reporting T2DM and HTN and obesity (body mass index, BMI, ≥30 kg/m2) were compared with a T2DM-alone group.Results. Respondents with T2DM, HTN, and obesity (n=1292) had significantly lower SF-12 Physical and Mental Component Summary scores (37.3 and 50.9, resp.) than T2DM-alone respondents (n=349) (45.8 and 53.5, resp.,P<0.0001). Mean PHQ-9 scores were significantly higher among T2DM respondents with comorbid HTN and obesity (5.0 versus 2.5,P<0.0001), indicating greater depression burden. Respondents with T2DM, HTN, and obesity had significantly more resource utilization with respect to physician visits and emergency room visits but not hospitalizations than respondents with T2DM alone (P=0.03).Conclusions. SHIELD respondents with comorbid conditions of T2DM, HTN, and obesity reported greater healthcare resource utilization, more depression symptoms, and lower quality of life than the T2DM-alone group.
How Do Cytokines Trigger Genomic Instability?
Authors: Aivaliotis Ioannis L. , Pateras Ioannis S. , Papaioannou Marilena , Glytsou Christina , Kontzoglou Konstantinos , Johnson Elizabeth O. , Zoumpourlis Vassilis
Published: June 2012

Inflammation is a double-edged sword presenting a dual effect on cancer development, from one hand promoting tumor initiation and progression and from the other hand protecting against cancer through immunosurveillance mechanisms. Cytokines are crucial components of inflammation, participating in the interaction between the cells of tumor microenvironment. A comprehensive study of the role of cytokines in the context of the inflammation-tumorigenesis interplay helps us to shed light in the pathogenesis of cancer. In this paper we focus on the role of cytokines in the development of genomic instability, an evolving hallmark of cancer.
Biological Principles and Physiology of Bone Regeneration under the Schneiderian Membrane after Sinus Lift Surgery: A Radiological Study in 14 Patients Treated with the Transcrestal Hydrodynamic Ultrasonic Cavitational Sinus Lift (Intralift)
Authors: Troedhan A. , Kurrek A. , Wainwright M.
Published: June 2012

Introduction. Sinus lift procedures are a commonly accepted method of bone augmentation in the lateral maxilla with clinically good results. Nevertheless the role of the Schneiderian membrane in the bone-reformation process is discussed controversially. Aim of this study was to prove the key role of the sinus membrane in bone reformation in vivo.Material and Methods. 14 patients were treated with the minimal invasive tHUCSL-Intralift, and 2 ccm collagenous sponges were inserted subantrally and the calcification process followed up with CBCT scans 4 and 7 months after surgery.Results. An even and circular centripetal calcification under the sinus membrane and the antral floor was detected 4 months after surgery covering 30% of the entire augmentation width/height/depth at each wall. The calcification process was completed in the entire augmentation volume after 7 months. A loss of approximately 13% of absolute augmentation height was detected between the 4th and 7th month.Discussion. The results of this paper prove the key role of the sinus membrane as the main carrier of bone reformation after sinus lift procedures as multiple experimental studies suggested. Thus the importance of minimal invasive and rupture free sinuslift procedures is underlined and does not depend on the type of grafting material used.
Influence of Birth Weight on the Renal Development and Kidney Diseases in Adulthood: Experimental and Clinical Evidence
Authors: Franco Maria C. P. , Oliveira Vanessa , Ponzio Beatriz , Rangel Marina , Palomino Zaira , Gil Frida Zaladek
Published: June 2012

Several clinical and experimental studies support the hypothesis that foetal programming is an important determinant of nephropathy, hypertension, coronary heart disease, and type 2 diabetes during adulthood. In this paper, the renal repercussions of foetal programming are emphasised, and the physiopathological mechanisms are discussed. The programming of renal diseases is detailed based on the findings of kidney development and functional parameters.
Reviving a Legacy Citizen Science Project to Illuminate Shifts in Bird Phenology
Authors: Zelt Jessica , Courter Jason , Arab Ali , Johnson Ron , Droege Sam
Published: June 2012

Climate change has been of high interest to both the scientific community and the public at large since the phenomenon was first suggested. Subsequently, and with growing evidence of its impending ramifications, numerous studies have attempted to illuminate climate change impacts on bird migration. Migration is a key event in the annual cycle in the reproductive success of birds, and changes in migration in response to climate may indicate that species populations are at risk. Previous studies report earlier arrival dates in response to climate change in many bird species, although specific mechanisms are often difficult to explain at broad spatial and temporal scales. Using a newly revived dataset of historical migration cards for over 870 species and spanning 90 years throughout North America, we are developing an historical baseline of bird arrival dates to compare with contemporary records. Here we chronicle the history and reemergence of the North American Bird Phenology Program. We present two case studies illustrating how data from this program has been used to model historical arrival dates of Ruby-Throated Hummingbird (Archilochus colubris) and Purple Martin (Progne subis) throughout eastern North America. Our results show the importance of considering spatial and temporal variability in understanding patterns of bird spring arrivals.
Flexible Sierpinski Carpet Fractal Antenna on a Hilbert Slot Patterned Ground
Authors: Radonić Vasa , Palmer Keith , Stojanović Goran , Crnojević-Bengin Vesna
Published: June 2012

This paper presents a novel design of fractal antenna on a flexible substrate that operates in UMTS band (universal mobile telecommunication system, 1.92–2.17 GHz). The antenna consists of a Sierpinski carpet fractal radiator, which reduces the overall size of the antenna, and it is realized on top of a Hilbert slot in the ground layer, to achieve required impedance matching. The antenna is compact with the overall dimensions equal to 70 mm × 31 mm × 0.075 mm. Influence that folding has on the initial planar topology is investigated in detail. The obtained results show that the proposed antenna is more tolerant to folding than the conventional patch and that it exhibits relatively stable radiation patterns even when folded in complex manners.
MAX and MYC: A Heritable Breakup
Authors: Cascón Alberto , Robledo Mercedes
Published: June 2012

The overexpression of MYC, which occurs in many tumors, dramatically disrupts the equilibrium between activation and repression of the oncogenic MYC/MYC-associated protein X (MAX)/MAX dimerization protein 1 (MXD1) network, favoring MYC–MAX complexes and thereby impairing differentiation and promoting cell growth. Although for some time it has appeared that MAX is necessary for both the activation and repression of the axis, recent evidence shows that MYC retains considerable biologic function in the absence of MAX. The presence of germline MAX mutations in patients with hereditary pheochromocytoma supports the predominant role of MAX as a negative regulator of the network and suggests that MYC deregulation plays a role in hereditary cancer predisposition. This finding also confirms the importance of impairment of the MYC/MAX/MXD1 axis in the development of aggressive neural tumors, because MYCN overexpression is an established genetic hallmark of malign neuroblastoma, and it is likely that MXI1 plays a relevant role in the development of medulloblastoma and glioblastoma. Finally, the likely malignant behavior of tumors with mutations in MAX points to MYC as a candidate therapeutic target in the treatment of metastatic pheochromocytoma. Cancer Res; 72(13); 3119–24. ©2012 AACR.
The Retinoblastoma Gene Undergoes Rearrangements in BRCA1-Deficient Basal-like Breast Cancer
Authors: Jönsson Göran , Staaf Johan , Vallon-Christersson Johan , Ringnér Markus , Gruvberger-Saal Sofia K. , Saal Lao H. , Holm Karolina , Hegardt Cecilia , Arason Adalgeir , Fagerholm Rainer , Persson Camilla , Grabau Dorthe , Johnsson Ellinor , Lövgren Kristina , Magnusson Linda , Heikkilä Päivi , Agnarsson Bjarni A. , Johannsson Oskar T. , Malmström Per , Fernö Mårten , Olsson Håkan , Loman Niklas , Nevanlinna Heli , Barkardottir Rosa B. , Borg Åke
Published: June 2012

Breast tumors from BRCA1 germ line mutation carriers typically exhibit features of the basal-like molecular subtype. However, the specific genes recurrently mutated as a consequence of BRCA1 dysfunction have not been fully elucidated. In this study, we used gene expression profiling to molecularly subtype 577 breast tumors, including 73 breast tumors from BRCA1/2 mutation carriers. Focusing on the RB1 locus, we analyzed 33 BRCA1-mutated, 36 BRCA2-mutated, and 48 non-BRCA1/2–mutated breast tumors using a custom-designed high-density oligomicroarray covering the RB1 gene. We found a strong association between the basal-like subtype and BRCA1-mutated breast tumors and the luminal B subtype and BRCA2-mutated breast tumors. RB1 was identified as a major target for genomic disruption in tumors arising in BRCA1 mutation carriers and in sporadic tumors with BRCA1 promoter methylation but rarely in other breast cancers. Homozygous deletions, intragenic breaks, or microdeletions were found in 33% of BRCA1-mutant tumors, 36% of BRCA1 promoter–methylated basal-like tumors, 13% of non-BRCA1–deficient basal-like tumors, and 3% of BRCA2-mutated tumors. In conclusion, RB1 was frequently inactivated by gross gene disruption in BRCA1 hereditary breast cancer and BRCA1-methylated sporadic basal-like breast cancer but rarely in BRCA2 hereditary breast cancer and non-BRCA1–deficient sporadic breast cancers. Together, our findings show the existence of genetic heterogeneity within the basal-like breast cancer subtype that is based upon BRCA1 status. Cancer Res; 72(16); 4028–36. ©2012 AACR.
IGKV3 Proteins as Candidate “Off-the-Shelf” Vaccines for Kappa-Light Chain–Restricted B-Cell Non-Hodgkin Lymphomas
Authors: Martorelli Debora , Guidoboni Massimo , De Re Valli , Muraro Elena , Turrini Riccardo , Merlo Anna , Pasini Elisa , Caggiari Laura , Romagnoli Luca , Spina Michele , Mortarini Roberta , Gasparotto Daniela , Mazzucato Mario , Carbone Antonino , Rosato Antonio , Anichini Andrea , Dolcetti Riccardo
Published: June 2012

Purpose: An increasing set of B-cell non-Hodgkin lymphomas (B-NHL) show a biased usage of IGKV3-20 and IGKV3-15 immunoglobulin genes, a feature that could be exploited for the development of ready-to-use, broadly applicable cancer vaccines.

Experimental Design: The immunogenic properties of clonal IGKV3-20 and IGKV3-15 proteins were analyzed with particular focus on their ability to elicit cross-reactive responses against molecularly related IGKV proteins expressed by different B-cell lymphoproliferative disorders.

Results: IGK+ lymphoma patients show humoral and T-cell responses to IGKV3-20 and IGKV3-15 proteins and IGKV3-specific cytotoxic T lymphocytes (CTL) can be easily induced ex vivo. IGKV3-20–specific CTLs cross-react against different IGKV3 proteins, an effect mediated by the presence of 21 shared, sometimes promiscuous, T-cell epitopes, presented by common HLA class I allele products, thus assuring a broad HLA coverage of IGKV3-based vaccines. Many natural epitope variants are carried by IGK light chains expressed by a broad spectrum of B-NHLs and we show that IGKV3-20–specific CTLs cross-react also against several of these variant epitopes. Both humoral and CTL-specific responses were induced by KLH-conjugated IGKV3-20 protein in HLA-A2-transgenic mice and coinjection of IGKV3-20–specific CTLs with IGKV3-20+ or IGKV3-15+ lymphoma cells into SCID mice totally prevented tumor growth, thus confirming the ability of these effectors to mediate efficient and cross-reactive cytotoxic responses also in vivo.

Conclusions: These results provide the rationale to exploit IGKV3 proteins as “off-the-shelf” vaccines for a large fraction of lymphoma patients. Clin Cancer Res; 18(15); 4080–91. ©2012 AACR.
TNF-α Induces Epithelial–Mesenchymal Transition of Renal Cell Carcinoma Cells via a GSK3β-Dependent Mechanism
Authors: Ho Ming-Yi , Tang Shye-Jye , Chuang Mei-Jen , Cha Tai-Lung , Li Jing-Yao , Sun Guang-Huan , Sun Kuang-Hui
Published: June 2012

TNF-α is a cytokine with antitumorigenic property. In contrast, low dose, chronic TNF-α production by tumor cells or stromal cells may promote tumor growth and metastasis. Serum levels of TNF-α are significantly elevated in renal cell carcinoma (RCC) patients. Here, we showed that TNF-α induced epithelial–mesenchymal transition (EMT) and promoted tumorigenicity of RCC by repressing E-cadherin, upregulating vimentin, activating MMP9, and invasion activities. In addition, TNF-α treatment inhibited glycogen synthase kinase 3β (GSK-3β) activity through serine-9 phosphorylation mediated by the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway in RCC cells. Inhibition of PI3K/AKT by LY294002 reactivated GSK-3β and suppressed the TNF-α–induced EMT of RCC cells. Inactivation of GSK-3β by LiCl significantly increased MMP9 activity and EMT of RCC cells. Activation of GSK-3β by transduction of constitutively active GSK-3β into RCC cells suppressed TNF-α–mediated anchorage-independent growth in soft agar and tumorigenicity in nude mice. Overexpression of a kinase-deficient GSK-3β, in contrast, potentiated EMT, anchorage-independent growth and drastically enhanced tumorigenicity in vivo. Most importantly, a 15-fold inactivation of GSK-3β activity, 3-fold decrease of E-cadherin, and 2-fold increase of vimentin were observed in human RCC tumor tissues. These results indicated that inactivation of GSK-3β plays a pivotal role in the TNF-α–mediated tumorigenesis of RCC. Mol Cancer Res; 10(8); 1109–19. ©2012 AACR.
Janus Kinase 3–Activating Mutations Identified in Natural Killer/T-cell Lymphoma
Authors: Koo Ghee Chong , Tan Soo Yong , Tang Tiffany , Poon Song Ling , Allen George E. , Tan Leonard , Chong Soo Ching , Ong Whee Sze , Tay Kevin , Tao Miriam , Quek Richard , Loong Susan , Yeoh Kheng-Wei , Yap Swee Peng , Lee Kuo Ann , Lim Lay Cheng , Tan Daryl , Goh Christopher , Cutcutache Ioana , Yu Willie , Young Ng Cedric Chuan , Rajasegaran Vikneswari , Heng Hong Lee , Gan Anna , Ong Choon Kiat , Rozen Steve , Tan Patrick , Teh Bin Tean , Lim Soon Thye
Published: June 2012

The molecular pathogenesis of natural killer/T-cell lymphoma (NKTCL) is not well understood. We conducted whole-exome sequencing and identified Janus kinase 3 (JAK3) somatic–activating mutations (A572V and A573V) in 2 of 4 patients with NKTCLs. Further validation of the prevalence of JAK3 mutations was determined by Sanger sequencing and high-resolution melt (HRM) analysis in an additional 61 cases. In total, 23 of 65 (35.4%) cases harbored JAK3 mutations. Functional characterization of the JAK3 mutations support its involvement in cytokine-independent JAK/STAT constitutive activation leading to increased cell growth. Moreover, treatment of both JAK3-mutant and wild-type NKTCL cell lines with a novel pan-JAK inhibitor, CP-690550, resulted in dose-dependent reduction of phosphorylated STAT5, reduced cell viability, and increased apoptosis. Hence, targeting the deregulated JAK/STAT pathway could be a promising therapy for patients with NKTCLs.

Significance: Gene mutations causing NKTCL have not been fully identified. Through exome sequencing, we identified activating mutations of JAK3 that may play a significant role in the pathogenesis of NKTCLs. Our findings have important implications for the management of patients with NKTCLs. Cancer Discov; 2(7); 591–7. ©2012 AACR.

This article is highlighted in the In This Issue feature, p. 569.
Agonist-Induced Hypertrophy and Diastolic Dysfunction Are Associated With Selective Reduction in Glucose Oxidation
Authors: Mori Jun , Basu Ratnadeep , McLean Brent A. , Das Subhash K. , Zhang Liyan , Patel Vaibhav B. , Wagg Cory S. , Kassiri Zamaneh , Lopaschuk Gary D. , Oudit Gavin Y.
Published: June 2012

Background—

Activation of the renin-angiotensin and sympathetic nervous systems may alter the cardiac energy substrate preference, thereby contributing to the progression of heart failure with normal ejection fraction. We assessed the qualitative and quantitative effects of angiotensin II (Ang II) and the α-adrenergic agonist, phenylephrine (PE), on cardiac energy metabolism in experimental models of hypertrophy and diastolic dysfunction and the role of the Ang II type 1 receptor.

Methods and Results—

Ang II (1.5 mg·kg
−1
·day
−1
) or PE (40 mg·kg
−1
·day
−1
) was administered to 9-week-old male C57/BL6 wild-type mice for 14 days via implanted microosmotic pumps. Echocardiography showed concentric hypertrophy and diastolic dysfunction, with preserved systolic function in Ang II- and PE-treated mice. Ang II induced marked reduction in cardiac glucose oxidation and lactate oxidation, with no change in glycolysis and fatty acid β-oxidation. Tricarboxylic acid acetyl coenzyme A production and ATP production were reduced in response to Ang II. Cardiac pyruvate dehydrogenase kinase 4 expression was upregulated by Ang II and PE, resulting in a reduction in the pyruvate dehydrogenase activity, the rate-limiting step for carbohydrate oxidation. Pyruvate dehydrogenase kinase 4 upregulation correlated with the activation of the cyclin/cyclin-dependent kinase-retinoblastoma protein-E2F pathway in response to Ang II. Ang II type 1 receptor blockade normalized the activation of the cyclin/cyclin-dependent kinase-retinoblastoma protein-E2F pathway and prevented the reduction in glucose oxidation but increased fatty acid oxidation.

Conclusions—

Ang II- and PE-induced hypertrophy and diastolic dysfunction is associated with reduced glucose oxidation because of the cyclin/cyclin-dependent kinase-retinoblastoma protein-E2F–induced upregulation of pyruvate dehydrogenase kinase 4, and targeting these pathways may provide novel therapy for heart failure with normal ejection fraction.
Normal Left Ventricular Myocardial Thickness for Middle-Aged and Older Subjects With Steady-State Free Precession Cardiac Magnetic Resonance
Authors: Kawel Nadine , Turkbey Evrim B. , Carr J. Jeffrey , Eng John , Gomes Antoinette S. , Hundley W. Gregory , Johnson Craig , Masri Sofia C. , Prince Martin R. , van der Geest Rob J. , Lima João A.C. , Bluemke David A.
Published: June 2012

Background—

Increased left ventricular myocardial thickness (LVMT) is a feature of several cardiac diseases. The purpose of this study was to establish standard reference values of normal LVMT with cardiac magnetic resonance and to assess variation with image acquisition plane, demographics, and left ventricular function.

Methods and Results—

End-diastolic LVMT was measured on cardiac magnetic resonance steady-state free precession cine long and short axis images in 300 consecutive participants free of cardiac disease (169 women; 65.6±8.5 years) of the Multi-Ethnic Study of Atherosclerosis cohort. Mean LVMT on short axis images at the mid-cavity level was 5.3±0.9 mm and 6.3±1.1 mm for women and men, respectively. The average of the maximum LVMT at the mid-cavity for women/men was 7/9 mm (long axis) and 7/8 mm (short axis). Mean LVMT was positively associated with weight (0.02 mm/kg;
P
=0.01) and body surface area (1.1 mm/m
2
;
P
<0.001). No relationship was found between mean LVMT and age or height. Greater mean LVMT was associated with lower left ventricular end-diastolic volume (0.01 mm/mL;
P
<0.01), a lower left ventricular end-systolic volume (−0.01 mm/mL;
P
=0.01), and lower left ventricular stroke volume (−0.01 mm/mL;
P
<0.05). LVMT measured on long axis images at the basal and mid-cavity level were slightly greater (by 6% and 10%, respectively) than measurements obtained on short axis images; apical LVMT values on long axis images were 20% less than those on short axis images.

Conclusions—

Normal values for wall thickness are provided for middle-aged and older subjects. Normal LVMT is lower for women than men. Observed values vary depending on the imaging plane for measurement.
Functional Urban Schools Amid Dysfunctional Settings
Authors: Mawdsley Ralph D. , Bipath Keshni , Mawdsley James L.
Published: June 2012

Similar to Dickens’s Tale of Two Cities, this research study is about a tale of two schools. The first type of school is a dysfunctional school. Dysfunctional schools are schools in a state of chaos (Shipengrower & Conway, 1998). The second school is that of order. The researchers refer to this school as a functional school. In 2003, the functional school in this research project scored a 100% pass rate in the Senior Certificate Examination (SCE), whereas the dysfunctional school scored 57.35%. Dysfunctional schools, known as “failing schools” are usually found in the poorest neighborhood, where children are mostly Black or immigrants who are not proficient in English. One of the casualties of the apartheid era has been the diminishing authority of the school principal. The aim of this research is to investigate the role of the leader in managing a functional school situated in a dysfunctional environment in the Gauteng province of South Africa. The research study is also directed at predicting the characteristics of dysfunctional/functional schools in the Gauteng province of South Africa.
How Dangerous Is Looking Away From the Road? Algorithms Predict Crash Risk From Glance Patterns in Naturalistic Driving
Authors: Liang Yulan , Lee John D. , Yekhshatyan Lora
Published: June 2012

Objective:

In this study, the authors used algorithms to estimate driver distraction and predict crash and near-crash risk on the basis of driver glance behavior using the data set of the 100-Car Naturalistic Driving Study.

Background:

Driver distraction has been a leading cause of motor vehicle crashes, but the relationship between distractions and crash risk lacks detailed quantification.

Method:

The authors compared 24 algorithms that varied according to how they incorporated three potential contributors to distraction—glance duration, glance history, and glance location—on how well the algorithms predicted crash risk.

Results:

Distraction estimated from driver eye-glance patterns was positively associated with crash risk. The algorithms incorporating ongoing off-road glance duration predicted crash risk better than did the algorithms incorporating glance history. Augmenting glance duration with other elements of glance behavior—1.5th power of duration and duration weighted by glance location—produced similar prediction performance as glance duration alone.

Conclusions:

The distraction level estimated by the algorithms that include current glance duration provides the most sensitive indicator of crash risk.

Application:

The results inform the design of algorithms to monitor driver state that support real-time distraction mitigation systems.
‘Lift as you rise’: Union women’s leadership talk
Authors: Kirton Gill , Healy Geraldine
Published: June 2012

There is now an abundant and rich literature on gender and leadership in the corporate context, where concepts of masculine and feminine leadership are widely debated. This article provides a bridge between this literature and the women and unions literature, where women’s leadership is under-researched but where feminist strategies are widely discussed. The article uses the relatively novel lens of masculine, feminine and feminist leadership for interpreting the leadership talk of an ethnically diverse group of American and British union women. We argue that when women lead in heavily masculinized settings, their leadership discourses and orientations are almost bound to reflect the dominant culture. The study reveals that while there is a discursive space within unions for alternative (feminine and feminist) visions of leadership, in practice women union leaders also engage in different combinations (often simultaneously) of (masculine) status quo and (feminine and feminist) transformative leadership talk.
Rapport in Negotiation
Authors: Bronstein Ilan , Nelson Noa , Livnat Zohar , Ben-Ari Rachel
Published: June 2012

This study examined the contribution of verbal behavior to the creation of rapport in negotiation, while methodologically addressing the issue of dependence between dyadic measures, which is inherent to the concept of rapport, with the Actor-Partner Interdependence model. The approach adopted is substantially different from that of past research, which emphasized the contribution of nonverbal behavior to rapport and used averaged rapport to asses it. Drawing both from the theoretical concept of rapport and from Politeness theory, the authors developed the Verbal Rapport Assessment scale. The authors found that rapport is indeed encoded in the verbal behavior and that various verbal behaviors contribute to negotiators’ sense of rapport, as well as to the judgment of negotiators’ rapport behaviors. Likewise, the authors found that a negotiator’s sense of rapport was primarily affected by his partners’ verbal behavior and by the interaction between behaviors of both sides. These findings emphasize the importance of the verbal channel and the dyad in creating rapport in negotiation. Negotiation in the twenty-first century is often characterized by exclusively verbal interactions (via telephone, chat, and e-mails); negotiators from many different fields can benefit from these findings.
Attitudes Toward Diversity and the School Choice Process
Authors: Kimelberg Shelley McDonough , Billingham Chase M.
Published: June 2012

White flight from urban public schools has been well documented, but little attention has been paid to middle-class reinvestment in urban schools. This article combines findings from interviews with middle-class parents of Boston Public School students with demographic data from the city’s public elementary schools to examine the motivations of these parents and assess the potential ramifications of their decisions. While providing their children with a diverse school environment is a major consideration for these families, the process by which they select schools may, in the aggregate, contribute to an increase in racial segregation across the district as a whole.
Negative Affect and Emotion Dysregulation
Authors: Miller Drew J. , Vachon David D. , Aalsma Matthew C.
Published: June 2012

Previous research has shown negative affect and emotion dysregulation to be significant predictors of adverse outcomes. Because justice-involved adolescents have demonstrated more negative emotionality and fewer adaptive emotion regulation strategies than their non-justice-involved peers, they may be particularly susceptible to maladaptive behavior. The current study investigated the extent to which negative affect and facets of emotion dysregulation were associated with violence and risky sexual behavior. Participants included 94 justice-involved adolescents who were recruited while waiting for their court date and asked to complete several questionnaires. Results suggest that global negative affect and emotion dysregulation are not associated with violence or risky sexual behavior. However, specific aspects of negative affect (anger) and emotion dysregulation (impulse control difficulties) did predict violence. Examination of conditional effects also suggested that negative affect is significantly associated with violence and risky sexual behavior in adolescents who have specific difficulties regulating their emotions (e.g., poor emotional clarity and limited access to emotion regulation strategies). This study demonstrates the utility of examining negative affect and emotion regulation as heterogeneous constructs that interact in specific ways to predict violence.
The Instituto Indigenista Peruano
Authors: Gonzales Osmar
Published: June 2012

The creation of the Instituto Indigenista Peruano (Peruvian Indigenist Institute—IIP) in 1946 was the result of several decades of discussion regarding the role of indigenous people in the Peruvian nation-state. The debate led to at least two main stances: that the indigenous presence constituted an obstacle to the constitution of the Peruvian nationality and that the nation had indigenous foundations. The IIP took a middle path by proposing a gradual, state-led process of assimilation that focused on cultural and pedagogical factors. Its creation involved the defeat of radical proposals and the conversion of those intellectuals who at some point took revolutionary stances.

La creación del Instituto Indigenista Peruano en 1946 fue el resultado de varias décadas de discusiones en torno al papel de los pueblos indígenas en el estado peruano. El debate conllevó a por lo menos dos posturas fundamentales: que le presencia indígena constituido un obstáculo a la constitución nacional del Perú y que la nación tenia fundaciones indígenas. El IIP tomó el camino intermedio, proponiendo un proceso gradual de asimilación que priorizaba factores culturales y pedagógicos. Su creación involucró la derrota de propuestas radicales y la conversión de esos intelectuales quienes habían tomado, en un momento dado, posturas revolucionarias.
Looking for the Causes of Instability in Spatial Econometric Models
Authors: Mur Jesús , Angulo Ana M. , López Fernando A.
Published: June 2012

It is relatively easy to find symptoms of misspecification in a model that suffers from instability. Problems arise in relation to their interpretation: They may be due to a wrong selection of the functional form. There may be a problem of omitted variables or the parameters of the model may not be homogeneous across space. The authors focus their attention on the last aspect. Specifically, the intention is to develop a strategy to analyze the hypothesis of stability in the parameters of a spatial econometric model. It is important that this procedure should provide the user with information about the cause of instability. The content of the article is mixed. First, the authors develop a collection of robust Multipliers to test the hypothesis of stability in the main elements of a spatial econometric model. Then, they solve a Monte Carlo to analyze the behavior of the Multipliers. Finally, they present an application to the case of the Spanish elections by municipalities.
Has the Association Between Parental Divorce and Young Adults’ Psychological Problems Changed Over Time? Evidence From Sweden, 1968-2000
Authors: Gähler Michael , Garriga Anna
Published: June 2012

A large number of studies have shown that parental divorce is associated with psychological maladjustment in children. Less is known about whether the magnitude of this association has changed over time. This is mainly because of the lack of repeated data, containing identical measures over time. In the present article, the authors use data from two waves of the Swedish Level of Living Survey, conducted in 1968 and 2000, to analyze whether the association between parental divorce and psychological adjustment in 19- to 34-year-olds (i.e., born during 1934-1949 and 1966-1981) has changed between the two survey years. Results indicate a weakening association over time, but the change does not reach statistical significance. A reason for the persisting link seems to be that parental divorce is still associated with economic hardship and, above all, family dissension, two conditions that in turn are strongly associated with psychological problems in children.
The Intergenerational Effects of Relocation Policies on Indigenous Families
Authors: Walls Melissa L. , Whitbeck Les B.
Published: June 2012

This research uses life course perspective concepts of linked lives and historical time and place to examine the multigenerational effects of relocation experiences on Indigenous families. Data were collected from a longitudinal study currently underway on four American Indian reservations in the Northern Midwest and four Canadian First Nation reserves where residents share a common Indigenous cultural heritage. This article includes information from 507 10- to 12-year-old Indigenous youth and their biological mothers who participated in the study. Results of path analysis revealed significant direct and indirect effects whereby grandparent-generation participation in government relocation programs negatively affects not only grandparent-generation well-being but also ripples out to affect subsequent generations.
Coresident Extended Kin and Time Allocation Among Employed Mothers in Mexico
Authors: Shin Heeju
Published: June 2012

The proportion of mothers living without male partners is growing fast in Mexico, and time is a valuable resource determining their quality of life. Using the 2002 Mexican Family Life Survey ( N = 1,818), the author examined the effects of coresident extended household members on time allocation by employed mothers. Results indicate that female extended kin have greater influence than male kin on the time allocation of single mothers in Mexico. Female extended household members also play more important roles in making activity time available for single mothers than for mothers with partners. This study supports the hypothesis that household extension functions as a safety net for employed single mothers facing time and material constraints in Mexico.
Physical Health Effects of Intimate Partner Abuse
Authors: Sillito Carrie LeFevre
Published: June 2012

Although intimate partner violence has been recognized as both a social problem and health issue, the extent to which it is a health issue for both males and females in the general population is largely unknown. This longitudinal research uses data from the National Survey of Family and Households (1987-2003). Random effects logistic regression models are used to assess physical health outcomes of exposure to intimate partner abuse for males and females. Results indicate that females are significantly more likely to report poor health if exposed to intimate partner abuse. The same is not true for males. Findings of this research indicate a need to explore further sex differences in violence outcomes. These findings are likely to be of interest to those who study families, intimate partner abuse, and health.
A qualitative study to explore psychological distress and illness burden associated with opioid-induced constipation in cancer patients with advanced disease
Authors: Dhingra Lara , Shuk Elyse , Grossman Bella , Strada Alessandra , Wald Emily , Portenoy Allison , Knotkova Helena , Portenoy Russell
Published: June 2012

Background:

Constipation affects many patients receiving long-term opioid therapy for cancer pain. Little is known about the nature of psychological distress and the burden associated with this problem. This information may inform the development of effective treatment strategies and ameliorate distress.

Aim:

The objective was to use qualitative research methods to better understand psychological distress and the burden associated with opioid-induced constipation and its treatment in advanced cancer patients.

Design:

In this qualitative study, semi-structured interviews explored perceptions of psychological distress and burden from opioid-induced constipation. Interviews were analyzed using a thematic content analysis approach involving descriptive and interpretive coding and identification of recurring themes.

Setting/participants:

Twelve advanced cancer patients with opioid-induced constipation were recruited from a large urban hospital.

Results:

Patients experienced various types of negative affect and cognitions associated with opioid-induced constipation. Analyses indicated three major themes: (1) irrational thoughts and educational needs; (2) psychological distress from constipation and (3) the effects of constipation on the decision to use opioid analgesics. Irrational thoughts and educational needs included beliefs that nutrition could improve constipation, the supposition that constipation indicated deteriorating health, and catastrophic beliefs. Psychological distress included depressive symptoms and anticipatory anxiety related to constipation. Decision-making revealed cognitive dissonance about using opioids and conflicting preferences about continuing use.

Conclusions:

Future investigation of the multiple components of cognitive and affective burden from opioid-induced constipation is warranted. Understanding the varied nature of this burden may improve clinical recognition and assessment and promote more intensive management consistent with the distress it produces.