bluuebunny/crossref_metadata_2025 huggingface dataset:
Qualitative Data Analysis and Interpretation in Counseling Psychology: Strategies for Best Practices
Authors: Yeh Christine J. , Inman Arpana G.
Published: April 2007

This article presents an overview of various strategies and methods of engaging in qualitative data interpretations and analyses in counseling psychology. The authors explore the themes of self, culture, collaboration, circularity, trustworthiness, and evidence deconstruction from multiple qualitative methodologies. Commonalities and differences that span across approaches are explored. Implications for how researchers address qualitative data analysis and interpretation in counseling psychology training and research are discussed.
Exposure to Chronic Community Violence
Authors: Jones Janine M.
Published: April 2007

In many African American communities, violence and poverty are often part of daily living. As a result, children are at risk for difficulties in all aspect of their lives, particularly their emotional well-being. This study explored the relationship between exposure to chronic community violence and the development of complex post-traumatic stress disorder (C-PTSD), a constellation of symptoms that occur as a result of repeated exposure to traumas, in the context of specific African American cultural beliefs and values that are used as coping mechanisms. It was anticipated that the coping mechanisms would act as stress moderators, or buffers, to the development of symptoms of C-PTSD. Participants in the study included 71 African American children between the ages of 9 and 11 years who lived in a high-crime, high-poverty community in Houston, Texas. The results indicated that formal kinship and spirituality, along with high levels of combined supports, demonstrated buffering effects on exposure to violence.
Black Milwaukee, Proletarianization, and the Making of Black Working-Class History
Authors: Jones William P.
Published: April 2007

A pioneering effort to understand working-class African Americans as historical agents, Black Milwaukee situated the Great Migration within an ongoing debate over workers' ability to shape the transition from agricultural to industrial society. By joining that debate, Trotter inherited an attention to class consciousness and the significance of work that distinguished the “new labor history” of the 1960s and 1970s, but he also adopted a teleological understanding of modernization that elided historical and geographical complexities of working-class experience. By developing a more flexible understanding of “proletarianization,” the author argues, contemporary scholars can benefit from Trotters' theoretical framework without replicating its conceptual blind spots.
Black Milwaukee, Women, and Gender
Authors: Williams Rhonda Y.
Published: April 2007

This article reflects upon the contributions and limits of Joe William Trotter Jr.'s Black Milwaukee by revisiting the book's proletarianization model. This model helped to complicate analyses and historical narratives of black urban experiences by departing from “ghetto”-based paradigms and focusing squarely on economy, class relations, and black people as laborers. But the model also proved limited, particularly as it related to the substantive versus “snapshot” incorporation of women's stories and gender analysis.
Black Milwaukee and Urban African American History
Authors: Pritchett Wendell E.
Published: April 2007

Over the past twenty years, Black Milwaukee has had a major impact in the fields of African American and American labor history, but its influence on students of urban history has been more ambiguous. Despite the significant growth over the past twenty years in the study of African Americans in cities, the subfields remain segregated. More recent work has made successful attempts to merge the study of change within American cities with an analysis of the role of African Americans in these processes. These studies' reliance on Black Milwaukee as a model shows its continuing relevance.
Effects of Job Features on Domestic Outsourcing as a Strategy for Combining Paid and Domestic Work
Authors: De Ruijter Esther , Van der Lippe Tanja
Published: April 2007

This article examines the influence of job features on domestic outsourcing. The central hypothesis is that households use outsourcing more often if the partners are less available for domestic chores and caregiving because of job demands. Analyses of data on 795 Dutch couples show that if they work longer hours, there is more of a demand for the outsourcing of female tasks. Flexible availability resulting from autonomy and working at home facilitates the use of outsourcing alternatives. Working at home by women reduces the amount of formal child care; however, for men it increases the outsourcing of child care.
Memories of C. Wright Mills
Authors: Form William
Published: April 2007

Although Mills was only age 45 years when he died, he had become the leading critic of the nation and its conscience. Mills insisted that for intellectuals, work and nonwork are inseparable. The author examines the relationship between Mills' theory of social structure and his biography. For data, the author draws on Mills' biographers, self-observations, letters, and the author's contacts with him as his dissertation director and later contacts. From infancy, Mills saw most relationships in terms of power and control. He was determined to remain autonomous, resist all attempts to control him. He was critical of the work of most sociologists and chose nonsociologists as friends.
The Public Sector, Family Structure, and Labor Market Behavior
Authors: Okun Barbara S. , Oliver Amalya L. , Khait-Marelly Orna
Published: April 2007

Recent research has suggested that the characteristics of paid work affect trade-offs between women's activities in the family and employment spheres. One argument suggests that public sector employment, more so than private sector employment, provides conditions that are amenable to the combination of paid work and family. In this article, the authors exploit panel-type data to compare the labor market behavior of Jewish Israeli women in the years following childbirth and focus on differential labor market activity among women with employment histories in the public and private sectors. Their findings point to significant interaction effects between previous sector of employment and childbearing behavior and suggest that the welfare state, through the provision of “family friendly” employment opportunities, plays a role in encouraging women's paid labor in the years following childbirth.
Understanding Failure of Condom Use Intention Among Adolescents
Authors: Bauman Laurie J. , Karasz Alison , Hamilton Adaoha
Published: April 2007

Although interventions based on cognitive theories can reduce rates of unsafe sexual behavior in adolescents, effect sizes remain small. This study was a qualitative investigation of inner-city adolescents' intentions to use condoms following participation in an intensive safer sex program. In-depth interviews with 26 adolescents were analyzed using standard qualitative methods. Although participants reported strong intentions to use condoms, they described many exceptions to their intention. Condom use intentions were also trumped by the presence of alternative, often conflicting intentions. Typical barriers to condom use played a minor role compared to exceptions and competing intentions. Boys and girls differed in the ways exception to intention and alternate intentions interfered with condom use; these reflected gender roles and norms, which are often neglected in HIV/STD prevention programs. The authors conclude that the barrier model to explain non-condom use is incomplete and that the concept of intention itself may need more conceptual work.
Leadership Development
Authors: Conner Jerusha Osberg , Strobel Karen
Published: April 2007

This study focuses on two girls' experiences in one youth leadership organization during a period of 3 years. Relying on an embedded case study design, the authors examine the links between leadership development and programmatic structures and supports. Specifically, the development of leadership capacities are analyzed along three dimensions: communication and interpersonal skills, analytic and critical reflection, and positive involvement in community affairs. Within the leadership organization, the authors consider structures that accommodate and validate different styles of youth leadership and different developmental trajectories, focusing on how these structures evolved along with the leaders they were designed to support. The conclusion discusses the relevance of the lessons that the two girls exposed and that the program internalized to adolescent development research and youth development programming.
No More 'Bois Ball
Authors: Clampet-Lundquist Susan
Published: April 2007

Over the past decade, tens of thousands of families have been relocated from public housing developments across the United States through HOPE VI redevelopment and demolition. The experiences of young people who, along with their families, are relocated from their homes are rarely given attention. In this article, the author analyzes qualitative interviews from 22 adolescents who were relocated from a public housing development 2 years before the interview. Themes drawn from the teens' narratives point to an overall loss in intergenerational connections and institutional ties in their new neighborhoods compared with their former neighborhoods. These findings have implications for how we view mixed outcomes for low-income adolescents in other relocation studies, such as the Moving To Opportunity demonstration.
Displaced Teacher and State Priorities in a High-Stakes Accountability Context
Authors: Watanabe Maika
Published: April 2007

Although previous research suggests that teachers align their instruction to testing demands in the context of high-stakes accountability programs, few studies examine how the policy plays out in the classroom using sustained observations. This research, based on ethnographic case studies of two teachers' classrooms and interviews with 13 teachers at five middle schools, illuminates how high-stakes testing narrows the curricula and displaces teachers' priorities for their students, priorities such as developing personal appreciation for literature and communication and collaboration skills, as well as “writing like a real writer writes.” These findings are noteworthy given that many of the teachers' priorities intersect with state standards.
Making Connections to Teaching Practice
Authors: Franz Coldren Amy , Spillane James P.
Published: April 2007

Administrators, particularly those who engage in instructional leadership, play a key role in school improvement. Past research describes the types of activities instructional leaders engage in but has paid little attention to how they do it. The authors use the case of one school to unpack instructional leadership as a practice, paying close attention to the tools that constitute that practice, the contextual factors that help to define it, and how it affects teaching. The authors find that two kinds of tools—boundary practices and boundary spanners—play a significant role in constituting instructional leadership practice. Contextual factors, including student and staff composition and leaders' values and beliefs, define instructional leadership practice in important ways. Finally, policy implications are discussed.
The Impact of Mock Jury Gender Composition on Deliberations and Conviction Rates in a Child Sexual Assault Trial
Authors: Golding Jonathan M. , Bradshaw Gregory S. , Dunlap Emily E. , Hodell Emily C.
Published: April 2007

This study investigated how the gender composition of mock juries affects deliberations and conviction rates in a child sexual assault (CSA) trial. As opposed to studies in which mock jurors make decisions as individuals, mock jury research allows for investigation of how individual decisions translate into group verdicts. Gender composition within mock juries was varied to examine whether well-established gender differences in individual judgments affect the jury-level decision-making process. Three hundred men and women, in 6-member mock juries, heard a fictional CSA trial. During deliberations, proprosecution/ prodefense statements by women were approximately equal, whereas men made more prodefense statements. Women switched votes during deliberations more than did men; jurors in woman majority mock juries changed from not guilty to guilty more often than did jurors in nonwoman majority juries, and vice versa; and woman majority mock juries convicted most often. Findings indicate that predeliberation gender differences led to unique jury deliberation strategies and voting patterns.
Parental Substance Use Disorders and Child Maltreatment: Overlap, Gaps, and Opportunities
Authors: Young Nancy K. , Boles Sharon M. , Otero Cathleen
Published: April 2007

There are relatively few empirically sound studies or nationally representative data on the number of children in Child Welfare Services (CWS) who are affected by their parents' substance abuse or dependence. The two systems that could systematically monitor this population, CWS and substance abuse treatment, are not required to capture the data elements that would identify families in both systems. The studies that are based on CWS populations or parents in treatment indicate that there is a substantial overlap in client populations. This review provides a summary of the available data; provides estimates of the overlap between populations, including the number of infants born each year with prenatal substance exposure; and suggests important opportunities to close the data gap between the systems. The findings underscore both the need for obtaining accurate data within the systems and the opportunities for states to improve their cross-system data efforts as part of their outcome monitoring.
Reconnecting with Our Roots
Authors: Corburn Jason
Published: April 2007

This article suggests that contemporary efforts to reconnect urban planning and public health can benefit from a critical historical review of the two fields, particularly strategies based on removal and displacement of waste and people, scientific rationality, moral environmentalism, and increased specialization. The article offers a set of reconnection strategies that draw from this review, emphasizing alternative paradigms of precaution and prevention, institution building, and local knowledge. I offer examples of specific practices that embody these ideas, such as health impact assessment, food systems planning, and promoting networks of community health workers, that address both the physical and social determinants of health and might effectively reconnect planning and public health to meet the challenges facing twenty-first-century cities.
The Attitudinal Effects of Minority Incorporation
Authors: Marschall Melissa , Shah Paru R.
Published: April 2007

Although trust in government has been declining for all Americans, Black Americans continue to be significantly less trusting than their White counterparts. Scholars have typically relied on the political reality model to explain this gap, arguing that lower trust among Blacks stems from their exclusion from power. Given contemporary gains in Black office holding, we revisit this question in the context of urban politics. Based on a sample of 104 municipalities we find that Black descriptive representation has very limited direct effects on trust, but appears to affect the distribution of policing policies across cities, and that substantive police policies increase Black and White Americans' trust in local police. Overall, our findings extend conventional conceptualizations of substantive benefits while raising questions about the symbolic value of Black political representation.
Planning the Competitive City-Region
Authors: Fulong Wu  , Jingxing Zhang
Published: April 2007

This article analyzes the emergence of the so-called urban strategic development plan in China during inter-city competition and new entrepreneurial governance. Driven by market-oriented development and globalization, the local government attempts to overcome the constraints of conventional statutory planning to promote a visionary city plan. Through case studies of Guangzhou and Hangzhou, we argue that the strategic plan is more or less a mission statement of the local political leaders and thus has a narrow social foundation. The emergence of the strategic plan reflects the overall shift of city planning towards being an important instrument for enhancing economic competitiveness.
Flt3-dependent transformation by inactivating c-Cbl mutations in AML
Authors: Sargin Bülent , Choudhary Chunaram , Crosetto Nicola , Schmidt Mirko H. H. , Grundler Rebekka , Rensinghoff Marion , Thiessen Christine , Tickenbrock Lara , Schwäble Joachim , Brandts Christian , August Benjamin , Koschmieder Steffen , Bandi Srinivasa Rao , Duyster Justus , Berdel Wolfgang E. , Müller-Tidow Carsten , Dikic Ivan , Serve Hubert
Published: April 2007

In acute myeloid leukemia (AML), mutational activation of the receptor tyrosine kinase (RTK) Flt3 is frequently involved in leukemic transformation. However, little is known about a possible role of highly expressed wild-type Flt3 in AML. The proto-oncogene c-Cbl is an important regulator of RTK signaling, acting through its ubiquitin ligase activity and as a platform for several signaling adaptor molecules. Here, we analyzed the role of c-Cbl in Flt3 signal transduction and myeloid transformation. C-Cbl physically interacted with Flt3 and was tyrosine phosphorylated in the presence of Flt3-ligand (FL). Overexpression of a dominant-negative form of c-Cbl (Cbl-70Z) inhibited FL-induced Flt3 ubiquitylation and internalization, indicating involvement of c-Cbl in Flt3 signaling. DNA sequencing of AML bone marrow revealed a case with a c-Cbl point mutation (Cbl-R420Q). Cbl-R420Q inhibited Flt3 internalization and ubiquitylation. Coexpression of Cbl-R420Q or Cbl-70Z with Flt3 induced cytokine-independent growth and survival of 32Dcl3 cells in the absence of FL. Also, the mutant Cbl proteins altered the amplitude and duration of Flt3-dependent signaling events. Our results indicate an important role of Cbl proteins in Flt3 signal modulation. Also, the data suggest a novel mechanism of leukemic transformation in AML by mutational inactivation of negative RTK regulators.
The Plasma Membrane Na+/Ca2+ Exchanger Is Cleaved by Distinct Protease Families in Neuronal Cell Death
Authors: BANO D. , MUNARRIZ E. , CHEN H. L. , ZIVIANI E. , LIPPI G. , YOUNG K. W. , NICOTERA P.
Published: April 2007

Abstract:  Neurodegenerative conditions commonly involve loss of neuronal connectivity, synaptic dysfunction with excessive pruning, and ionic imbalances. These often serve as a prelude to cell death either through the activation of apoptotic or necrotic death routines or excess autophagy. In many instances, a local or generalized Ca2+ deregulation is involved in signaling or executing cell death. We have recently shown that in brain ischemia, and during excitotoxicity triggered by excess glutamate, the irreversible Ca2+ deregulation leading to necrosis is due to calpain‐mediated modulation of the plasma membrane Na+/Ca2+ exchanger (NCX). Here we show that the NCX can also be cleaved by caspases in neurons undergoing apoptosis, which suggests that cleavage of the main Ca2+ extrusion pathway is a lethal event in multiple forms of cell death.
Plasma Membrane Calcium ATPase and Its Relationship to Nitric Oxide Signaling in the Heart
Authors: CARTWRIGHT ELIZABETH J. , OCEANDY DELVAC , NEYSES LUDWIG
Published: April 2007

Abstract:  The plasma membrane calcium/calmodulin‐dependent ATPase (PMCA) is a ubiquitously expressed calcium‐extruding enzymatic pump. In the majority of cells the main function of PMCA is as the only system to extrude calcium from the cytosol, however, in the excitable cells of the heart it has only a minor role in the bulk removal of calcium compared to the sodium–calcium exchanger. There is increasing evidence to suggest that PMCA has an additional role as a potential modulator of a number of signal transduction pathways. Of key interest in the heart is the functional interaction between the calcium/calmodulin‐dependent enzyme neuronal nitric oxide synthase (nNOS) and isoform 4 of PMCA. Nitric oxide production from nNOS is known to be important in the regulation of excitation–contraction (EC) coupling and subsequently contractility. This article will focus on recent evidence suggesting that PMCA4 has a regulatory role in the nitric oxide signaling pathway in the heart.
Directionality in Drug Action on Sodium–Calcium Exchange
Authors: NOBLE D. , BLAUSTEIN M. P.
Published: April 2007

Abstract:  In pathological conditions, the exchanger may generate deleterious calcium entry. A drug that inhibited calcium entry, while still allowing transport of calcium out of the cell would then seem attractive. In fact, this is impossible for thermodynamic reasons. Inhibitors may appear to be more effective when the exchanger is operating in net calcium entry mode than in calcium exit mode. This is, however, always attributable to differences in conditions because there is strong internal sodium dependence of drug action on the exchanger. When the exchanger is operating near equilibrium, drug action is found to be equally effective in both directions.
Na+/Ca2+ Exchanger Knockout Mice
Authors: POTT CHRISTIAN , HENDERSON SCOTT A. , GOLDHABER JOSHUA I. , PHILIPSON KENNETH D.
Published: April 2007

Abstract:  The Na+/Ca2+ exchanger (NCX) is the main Ca2+ extrusion mechanism of the cardiac myocyte. Nevertheless, cardiac‐specific NCX knockout (KO) mice are viable to adulthood. We have identified two adaptations of excitation–contraction coupling (ECC) to the absence of NCX in these animals: (a) a reduction of the L‐type Ca2+ current (ICa) with an increase in ECC gain and (b) a shortening of the action potential (AP) to further limit Ca2+ influx. Both mechanisms contribute to Ca2+ homeostasis by reducing Ca2+ influx while maintaining contractility. These adaptations may comprise important feedback mechanisms by which cardiomyocytes may be able to limit Ca2+ influx in situations of compromised Ca2+ extrusion capacity.
Increased Tolerance to Ischemic Neuronal Damage by Knockdown of Na+–Ca2+ Exchanger Isoform 1
Authors: LUO JING , WANG YANPING , CHEN XINZHI , CHEN HAI , KINTNER DOUGLAS B. , SHULL GARY E. , PHILIPSON KENNETH D. , SUN DANDAN
Published: April 2007

Abstract:  We hypothesize that stimulation of Na+–K+–Cl+ cotransporter (NKCC1) causes Na+ overload that may lead to reversal of Na+–Ca2+ exchanger isoform 1 (NCX1) and ischemic neuronal damage. NCX1 protein expression and Ca2+ influx via reversal of NCX were decreased by ∼70% in NCX1+/− neurons. Compared to NCX1+/+ neurons, NCX1+/− neurons exhibited significantly less cell death (∼30%) after 3 h oxygen and glucose deprivation (OGD) and 21 h reoxygenation. Additional neuroprotection was found in NCX1+/− neurons treated with NCX inhibitor KB‐R7943. Moreover, expression of NCX1 protein was ∼40% lower in NCX1+/− brains than in NCX1+/+ brains. However, there was no significant reduction in cerebral infarction in NCX1+/− mice following middle cerebral artery occlusion (MCAO). These data suggest that moderate reduction of NCX1 protein may be not enough to exert protection. We used small RNA‐interference (siRNA) approach to further elucidate the role of NCX1 in ischemic cell damage. Efficacy of anti‐NCX1 siRNA was tested in astrocytes and ∼50% knockdown of NCX1 protein expression was achieved after 24–72 h transfection. Reduction in NCX1 protein expression was also found in brains of NCX1+/− mice after the siRNA injection. NCX1+/− mice treated with siRNA showed ∼20% less MCAO‐induced infarction, compared to NCX1+/− mice. Approximately 50% neuroprotection was detected in NKCC1+/−/NCX1+/− mice following MCAO. In conclusion, these data suggest that NCX1 plays an important role in ischemia/reperfusion‐induced neuronal injury.
Resistance of Cardiac Cells to NCX Knockout
Authors: NOBLE DENIS , SARAI NOBUAKI , NOBLE PENELOPE J. , KOBAYASHI TSUTOMU , MATSUOKA SATOSHI , NOMA AKINORI
Published: April 2007

Abstract:  The effects of NCX knockout were determined in a variety of cardiac cell models. Those of the mouse and rat ventricles, and of atrial cells in other species behave similarly to the experiments on mouse ventricle showing only small effects, and considerable tolerance of NCX knockout. Models of ventricular cells with high action potential plateaus, however, are more sensitive and require compensatory mechanisms to adjust other conductance parameters to enable the cells to resist NCX knockout. The effects can therefore be expected to be species‐specific, and it is not possible to extrapolate the mouse results to those that may occur in the Guinea pig or human.
Role of Ca2+Transporters and Channels in the Cardiac Cell Volume Regulation
Authors: TAKEUCHI A. , TATSUMI S. , SARAI N. , TERASHIMA K. , MATSUOKA S. , NOMA A.
Published: April 2007

Abstract: Na+/K+pump is one of key mechanisms to maintain cell volume. When it is inhibited, cells are at risk of swelling. However, in guinea pig ventricular myocytes, the cell area as an index of cell volume was almost constant during 90 min Na+/K+pump blockade with 40 μM ouabain despite the marked membrane depolarization. In this study, involvements of Ca2+transporters and channels in the cardiac cell volume regulation were proposed by conducting the computer simulation in parallel with the experimental validation.
Plasma Membrane Ca2+ ATPases as Dynamic Regulators of Cellular Calcium Handling
Authors: STREHLER EMANUEL E. , CARIDE ARIEL J. , FILOTEO ADELAIDA G. , XIONG YUNING , PENNISTON JOHN T. , ENYEDI AGNES
Published: April 2007

Abstract:  Plasma membrane Ca2+ ATPases (PMCAs) are essential components of the cellular toolkit to regulate and fine‐tune cytosolic Ca2+ concentrations. Historically, the PMCAs have been assigned a housekeeping role in the maintenance of intracellular Ca2+ homeostasis. More recent work has revealed a perplexing multitude of PMCA isoforms and alternative splice variants, raising questions about their specific role in Ca2+ handling under conditions of varying Ca2+ loads. Studies on the kinetics of individual isoforms, combined with expression and localization studies suggest that PMCAs are optimized to function in Ca2+ regulation according to tissue‐ and cell‐specific demands. Different PMCA isoforms help control slow, tonic Ca2+ signals in some cells and rapid, efficient Ca2+ extrusion in others. Localized Ca2+ handling requires targeting of the pumps to specialized cellular locales, such as the apical membrane of cochlear hair cells or the basolateral membrane of kidney epithelial cells. Recent studies suggest that alternatively spliced regions in the PMCAs are responsible for their unique targeting, membrane localization, and signaling cross‐talk. The regulated deployment and retrieval of PMCAs from specific membranes provide a dynamic system for a cell to respond to changing needs of Ca2+ regulation.
Phosphorylation of Na+/Ca2+ Exchanger in TAB‐Induced Cardiac Hypertrophy
Authors: KATANOSAKA YUKI , KIM BONGJU , WAKABAYASHI SHIGEO , MATSUOKA SATOSHI , SHIGEKAWA MUNEKAZU
Published: April 2007

Abstract:  Both protein kinase Cα‐dependent Na+/Ca2+ exchanger1 (NCX1) phosphorylation and calcineurin activity are required for the depression of NCX activity observed in chronically phenylephrine (PE)‐treated hypertrophic neonatal rat cardiomyocytes. In this study, we explored the possibility that the same changes occur in vivo hypertrophy. In the hypertrophic hearts of thoracic aortic‐banded (TAB) mice, NCX1 phosphorylation increased significantly compared with control hearts. Furthermore, the TAB‐induced cardiac hypertrophy was much less prominent in transgenic mice overexpressing an NCX1 mutant having defective phosphorylation sites. These data suggest that the phosphorylation status of NCX1 may play an important role in the pathogenesis of load‐induced cardiac hypertrophy.
Gender Differences in Na/Ca Exchanger Current and β‐Adrenergic Responsiveness in Heart Failure in Pig Myocytes
Authors: WEI SHAO‐KUI , MCCURLEY JOHN M. , HANLON STEPHEN U. , HAIGNEY MARK C. P.
Published: April 2007

Abstract:  Clinical trials suggest females experience less heart failure (HF) progression, mortality, and arrhythmia frequency. HF increases Na/Ca exchanger (NCX) expression and activity contributing to both depressed contractility and ventricular arrhythmias, but whether gender modifies this effect is unknown. Left ventricular myocytes were isolated from control and from tachycardic pacing‐induced failing swine hearts of both sexes. The Ni‐sensitive NCX current (INCX) was measured in voltage clamp after blocking other channels. In control myocytes there is no difference in basal INCX and β‐adrenergic responsiveness between male and female animals. HF greatly increased INCX and reduced β‐adrenergic responsiveness in males compared to females, an effect that was eliminated by PP1. Diuretic therapy (furosemide, 1 mg/kg/day) further enhanced INCX and reduced β‐adrenergic responsiveness in females and eliminated the gender difference. Gender‐specific differences in calcium handling may contribute to improved survival of females in HF.
Inhibitory Mechanism of SN‐6, A Novel Benzyloxyphenyl Na+/Ca2+Exchange Inhibitor
Authors: KITA SATOMI , IWAMOTO TAKAHIRO
Published: April 2007

Abstract: We investigated the pharmacological properties of SN‐6, a new selective Na+/Ca2+exchanger (NCX) inhibitor. SN‐6 preferentially inhibited the45Ca2+uptake via NCX compared with the45Ca2+efflux via NCX in NCX‐transfected fibroblasts. SN‐6 was three‐ to fivefold more inhibitory to the45Ca2+uptake via NCX1 (IC50= 2.9 μM) than to that via NCX2 or NCX3. Our chimeric and site‐directed mutageneses revealed that Phe‐213, Val‐227, Tyr‐228, Gly‐833, and Asn‐839 in NCX1 are molecular determinants for interaction with SN‐6. We also found that SN‐6 potently protects against hypoxia/reoxygenation‐induced cell damage in renal tubular cells.
The Role of Na+/Ca2+ Exchanger in Endothelin‐1‐Aggravated Hypoxia/Reoxygenation‐Induced Injury in Renal Epithelial Cells
Authors: KITA SATOMI , FURUTA AYAKO , TAKANO YUKIO , IWAMOTO TAKAHIRO
Published: April 2007

Abstract:  We analyzed the role of the Na+/Ca2+ exchanger (NCX) in endothelin‐1‐aggravated hypoxia/reoxygenation‐induced injury in renal epithelial LLC‐PK1 cells. KB‐R7943, a selective NCX inhibitor, suppressed hypoxia/reoxygenation‐induced cell damage, whereas overexpression of NCX1 into cells enhanced it. Endothelin‐1 significantly aggravated hypoxia/reoxygenation‐induced injury in parental and NCX1‐overexpressing LLC‐PK1 cells. Such aggravation by endothelin‐1 was not observed in cells overexpressing a deregulated NCX1 mutant, which displays no protein kinase C‐dependent activation. These results suggest that Ca2+ overload via NCX plays a critical role in hypoxia/reoxygenation‐induced renal tubular injury, and that endothelin‐1 aggravates the cell damage through the activation of NCX.
Cyclosporin A‐Dependent Downregulation of the Na+/Ca2+ Exchanger Expression
Authors: RAHAMIMOFF H. , ELBAZ B. , ALPEROVICH A. , KIMCHI‐SARFATY C. , GOTTESMAN M. M. , LICHTENSTEIN Y. , ESKIN‐SHWARTZ M. , KASIR J.
Published: April 2007

Abstract:  Cyclosporin A (CsA) is an immunosuppressive drug commonly given to transplant patients. Its application is accompanied by severe side effects related to calcium, among them hypertension and nephrotoxicity. The Na+/Ca2+ exchanger (NCX) is a major calcium regulator expressed in the surface membrane of all excitable and many nonexcitable tissues. Three genes, NCX1, NCX2, and NCX3 code for Na+/Ca2+ exchange activity. NCX1 gene products are the most abundant. We have shown previously that exposure of NCX1‐transfected HEK 293 cells to CsA, leads to concentration‐dependent reduction of Na+/Ca2+ exchange activity and surface expression, without a reduction in total cell‐expressed NCX1 protein. We show now that the effect of CsA on NCX1 protein expression is not restricted to transfected cells overexpressing the NCX1 protein but exhibited also in cells expressing endogenously the NCX1 protein (L6, H9c2, and primary smooth muscle cells). Exposure of NCX2‐ and NCX3‐transfected cells to CsA results also in reduction of Na+/Ca2+ exchange activity and surface expression, though the sensitivity to the drug was lower than in NCX1‐transfected cells. Studying the molecular mechanism of CsA–NCX interaction suggests that cyclophilin (Cyp) is involved in NCX1 protein expression and its modulation by CsA. Deletion of 426 amino acids from the large cytoplasmic loop of the protein retains the CsA‐dependent downregulation of the truncated NCX1 suggesting that CsA–Cyp–NCX interaction involves the remaining protein domains.
Functional Significance of Na+/Ca2+ Exchangers Co‐localization with Ryanodine Receptors
Authors: SHER ANNA A. , HINCH ROBERT , NOBLE PENELOPE J. , GAVAGHAN DAVID J. , NOBLE DENIS
Published: April 2007

Abstract:  Co‐localization of Na+/Ca2+ exchangers (NCX) with ryanodine receptors (RyRs) is debated. We incorporate local NCX current in a biophysically detailed model of L‐type Ca2+ channels (LCCs) and RyRs and study the effect of NCX on the regulation of Ca2+‐induced Ca2+ release and the shape of the action potential. In canine ventricular cells, under pathological conditions, e.g., impaired LCCs, local NCXs become an enhancer of sarcoplasmic reticulum release. Under such conditions incorporation of local NCXs is critical to accurately capture mechanisms of excitation–contraction coupling.
Role of Na/Ca Exchange and the Plasma Membrane Ca2+–ATPase in β Cell Function and Death
Authors: HERCHUELZ ANDRÉ , KAMAGATE ADAMA , XIMENES HELENA , VAN EYLEN FRANÇOISE
Published: April 2007

Abstract:  Recent progresses concerning the Na/Ca exchanger (NCX) and the plasma membrane Ca2+–ATPase (PMCA) in the pancreatic β cell are reviewed. The rat β cell expresses two splice variants of NCX1 and six splice variants of the 4 PMCA isoforms. At the protein level, the most abundant forms are PMCA2 and PMCA3, providing the first evidence for the presence of these two isoforms in a non‐neuronal tissue. Overexpression of NCX1 in an insulinoma cell line altered the initial rise in cytosolic‐free Ca2+ concentration ([Ca2+]i) induced by membrane depolarization and the return of the [Ca2+]i to the baseline value on membrane repolarization, indicating that NCX contributes to both Ca2+ inflow and outflow in the β cell. In contrast, overexpression of the PMCA markedly reduced the global rise in Ca2+ induced by membrane depolarization, indicating that the PMCA has a capacity higher than expected to extrude Ca2+. Glucose, the main physiological stimulus of insulin release from the β cell, has opposite effect on NCX and PMCA transcription, expression and activity, inducing an increase in the case of NCX and a decrease in the case of the PMCA. This indicates that when exposed to glucose, the β cell switches from a low‐efficiency Ca2+ extruding mechanism, the PMCA, to a high‐capacity system, the NCX, in order to better face the increase in Ca2+ inflow induced by the sugar. To our knowledge, this is the first demonstration of a reciprocal change in PMCA and NCX1 expression and activity in response to a given stimulus in any tissue.
ncx1,ncx2, andncx3Gene Product Expression and Function in Neuronal Anoxia and Brain Ischemia
Authors: ANNUNZIATO L. , PIGNATARO G. , BOSCIA F. , SIRABELLA R. , FORMISANO L. , SAGGESE M. , CUOMO O. , GALA R. , SECONDO A. , VIGGIANO D. , MOLINARO P. , VALSECCHI V. , TORTIGLIONE A. , ADORNETTO A. , SCORZIELLO A. , CATALDI M. , DI RENZO G. F.
Published: April 2007

Abstract: Over the last few years, although extensive studies have focused on the relevant function played by the sodium–calcium exchanger (NCX) during focal ischemia, a thorough understanding of its role still remains a controversial issue. We explored the consequences of the pharmacological inhibition of this antiporter with conventional pharmacological approach, with the synthetic inhibitory peptide, XIP, or with an antisense strategy on the extent of brain damage induced by the permanent occlusion of middle cerebral artery (pMCAO) in rats. Collectively, the results of these studies suggest thatncx1andncx3genes could be play a major role to limit the severity of ischemic damage probably as they act to dampen [Na+]iand [Ca2+]ioverload. This mechanism seems to be normally activated in the ischemic brain as we found a selective upregulation of NCX1 and NCX3 mRNA levels in regions of the brain surviving to an ischemic insult. Despite this transcript increase, NCX1, NCX2, and NCX3 proteins undergo an extensive proteolytic degradation in the ipsilateral cerebral hemisphere. All together these results suggest that a rescue program centered on an increase NCX function and expression could halt the progression of the ischemic damage. On the basis of this evidence we directed our attention to the understanding of the transductional and transcriptional pathways responsible for NCX upregulation. To this aim, we are studying whether the brain isoform of Akt, Akt1, which is a downstream effector of neurotrophic factors, such as NGF can, in addition to affecting the other prosurvival cascades, also exert its neuroprotective effect by modulating the expression and activity ofncx1,ncx2, andncx3gene products.
Structure–Function Relationships of the NCKX2 Na+/Ca2+‐K+ Exchanger
Authors: SHIBUKAWA Y. , KANG K. J. , KINJO T. G. , SZERENCSEI R. T. , ALTIMIMI H. F. , PRATIKHYA P. , WINKFEIN R. J. , SCHNETKAMP P. P. M.
Published: April 2007

Abstract:  K+‐dependent Na+/Ca2+ exchangers (NCKX) have been shown to play important roles in physiological processes as diverse as phototransduction in rod photoreceptors, motor learning and memory in mice, and skin pigmentation in humans. Most structure–function studies on NCKX proteins have been carried out on the NCKX2 isoform, but sequence similarity suggests that the results obtained with the NCKX2 isoform are likely to apply to all NCKX1‐5 members of the human SLC24 gene family. Here we review our recent work on the NCKX2 protein concerning the topological arrangement of transmembrane segments carrying out cation transport, and concerning residues important for transport function and cation binding.
Topologic Investigation of the NCKX2 Na+/Ca2+‐K+ Exchanger α‐Repeats
Authors: KINJO TASHI G. , SZERENCSEI ROBERT T. , SCHNETKAMP PAUL P. M.
Published: April 2007

Abstract:  Algorithms suggest that NCKX proteins consist of an N‐terminal signal peptide and 11 transmembrane segments divided in two groups of 5 and 6, respectively, separated by a large cytoplasmic loop. This predicted topology places the NCKX α‐repeats with the same orientation in the plasma membrane. Using thiol‐specific drug treatment and site‐directed disulfide mapping, we have investigated the orientation of the NCKX2 α‐repeats. Our results suggest that the NCKX2 α‐repeats have an antiparallel orientation in the plasma membrane. In addition, these experiments suggest that the α‐repeats are found in close proximity in the mature configuration of the protein.
Examining Ca2+ Extrusion of Na+/Ca2+‐K+ Exchangers
Authors: ALTIMIMI HAIDER F. , SCHNETKAMP PAUL P. M.
Published: April 2007

Abstract:  Na+/Ca2+‐K+ exchangers (NCKX) are plasma membrane transporters that are thought to mainly mediate Ca2+ extrusion (along with K+) at the expense of the Na+ electrochemical gradient. However, because they are bidirectional, most assays have relied on measuring their activity in the reverse (Ca2+ import) mode. Herein we describe a method to control intracellular ionic conditions, and examine the forward (Ca2+ extrusion) mode of exchange of NCKX2.
Sodium–Calcium Exchangers in the Nucleus
Authors: LEDEEN ROBERT W. , WU GUSHENG
Published: April 2007

Abstract:  Whereas sodium–calcium exchangers (NCXs) have long been recognized as plasma membrane constituents that serve to maintain homeostatic concentrations of Ca2+ in the cytoplasm, they were recently shown to also occur in the nuclear envelope (NE) of neural and other cells where they function to regulate nuclear Ca2+. A unique feature of NCXs in the NE is their high‐affinity binding to GM1 ganglioside, this association being required for optimal exchanger activity. The NCX–GM1 complex occurs in the inner membrane of the NE and transfers Ca2+ from the nucleoplasm to the NE lumen. In neuronal cells, nuclear GM1 levels are low prior to differentiation but increase rapidly as axonal outgrowth progresses. Cells from genetically altered mice lacking GM1 have limited ability to regulate nuclear Ca2+, and the mice themselves showed similar deficit as seen in their high susceptibility to kainite‐induced seizures. These are attenuated by LIGA‐20, a derivative of GM1 that enters the nuclear membrane and restores nuclear NCX activity to normal level.
Regulation of the Cardiac Na+/Ca2+ Exchanger by Calcineurin and Protein Kinase C
Authors: SHIGEKAWA MUNEKAZU , KATANOSAKA YUKI , WAKABAYASHI SHIGEO
Published: April 2007

Abstract:  Na+/Ca2+ exchanger (NCX) activity is markedly inhibited in hypertrophic neonatal rat cardiomyocytes subjected to chronic phenylephrine treatment. This inhibition is reversed partially and independently by acute inhibition of calcineurin and protein kinase C (PKC) activities. Similar NCX inhibition occurs in CCL39 cells expressing cloned wild‐type NCX1, when they are infected with adenoviral vectors carrying activated calcineurin A and then treated acutely with phorbol myristoyl acetate or protein phosphatase‐1 inhibitors. The data obtained with these cells suggest that calcineurin activity, PKCα‐mediated NCX1 phosphorylation, and the central loop of NCX1 (possibly its β1 repeat) are required for the observed NCX inhibition. We observe partial inhibition of NCX activity independent of NCX1 phosphorylation when CCL39 cells are infected with activated calcineurin A but not further treated with phorbol myristoyl acetate or phosphatase inhibitors. Calcineurin thus appears to downregulate NCX activity via two independent mechanisms, one involving NCX1 phosphorylation and the other not involving NCX1 phosphorylation. These data indicate the existence of a novel regulatory mechanism for NCX1 involving calcineurin and PKC, which may be important in cardiac pathology.
The Role of the Cardiac Na+/Ca2+ Exchanger in Reverse Remodeling
Authors: TERRACCIANO CESARE M. N. , KOBAN MAREN U. , SOPPA GOPAL K. , SIEDLECKA URSZULA , LEE JOON , STAGG MARK A. , YACOUB MAGDI H.
Published: April 2007

Abstract:  Different strategies can, at least in certain conditions, prevent or reverse myocardial remodeling due to heart failure and induce myocardial functional improvement. Na+/Ca2+ exchanger (NCX) is considered a major player in the pathophysiology of heart failure but its role in reverse remodeling is unknown. A combination of mechanical unloading by left ventricular assist devices (LVADs) and pharmacological therapy has been shown to induce clinical recovery in a limited number of patients with end‐stage heart failure. In myocytes isolated from these patients we found that, after LVAD treatment, NCX1/SERCA2a mRNA was 38% higher than at device implant. We studied the ability of NCX to extrude Ca2+ during caffeine‐induced SR Ca2+ release in isolated ventricular myocytes from these patients. The time constant of decline was slower in heart failure. In myocytes from patients with clinical recovery following mechanical and pharmacological treatment, NCX1‐mediated Ca2+ extrusion was faster compared with myocytes from patient who, despite identical treatment, did not recover. We propose that increased NCX function may be associated with reverse remodeling in patients and that factors that regulate NCX function (i.e., phosphorylation or intracellular [Na+]) other than NCX expression levels alone, may have detrimental consequences on cardiac function.
Modulation Pathways of NCX mRNA Stability
Authors: MAEDA SACHIKO , MATSUOKA ISAO , KIMURA JUNKO
Published: April 2007

Abstract:  Cardiac Na+/Ca2+ exchanger 1 (NCX1) expression levels change under various pathophysiological conditions. However, its mechanism is unknown. We found that fluvastatin, an HMG‐CoA reductase inhibitor, decreased NCX1 mRNA and protein by inhibiting a small G protein, RhoB, in H9c2 cardiomyoblasts. Conversely, lysophosphatidylcholine (LPC) increased NCX1 mRNA and protein by activating RhoB. The effect of LPC was mediated by geranylgeranylation but not farnesylation of RhoB. Furthermore, we also detected that activation of RhoB increased NCX1 mRNA stability. Our results suggest that RhoB is involved in modulation of cardiac NCX1 mRNA expression.
Regulation of Na+/Ca2+ Exchange Current in the Normal and Failing Heart
Authors: REPPEL MICHAEL , FLEISCHMANN BERND K. , REUTER HANNES , PILLEKAMP FRANK , SCHUNKERT HERIBERT , HESCHELER JÜRGEN
Published: April 2007

Abstract:  Cardiac NCX is modulated by diverse regulatory elements. Although there is consensus about the regulatory function of Na+ and Ca2+ and other elements, for example, ATP, there is still a controversial debate about the functional role of cyclic nucleotides and protein kinases. Future studies should focus on that topic since disturbances of cAMP/cGMP concentration and kinase activity may lead to severe functional disorders in the diseased heart. S100A1 is presumably a novel regulator of NCX.
Non‐apoptogenic Ca2+‐Related Extrusion of Mitochondria in Anoxia/Reoxygenation Stress
Authors: DORIO ANNALISA , CERELLA CLAUDIA , DE NICOLA MILENA , D'ALESSIO MARIA , GUALANDI GIAMPIERO , GHIBELLI LINA
Published: April 2007

Abstract:  Tumor cells often develop molecular strategies for survival to anoxia/reoxygenation stress as part of tumor progression. Here we describe that the B lymphoma Epstein–Barr‐positive cells E2r survive reoxygenation in spite of a very high and long‐lasting increase in cytosolic Ca2+ and the loss of about half of their mitochondria due to specific extrusion of the organelles from the cells. The extrusion typically occurs 3 days after reoxygenation, and a regular mitochondrial asset is regained after further 24 h.
Notch signaling regulates neural precursor allocation and binary neuronal fate decisions in zebrafish
Authors: Shin Jimann , Poling Justin , Park Hae-Chul , Appel Bruce
Published: April 2007

Notch signaling plays a well-described role in regulating the formation of neurons from proliferative neural precursors in vertebrates but whether, as in flies, it also specifies sibling cells for different neuronal fates is not known. Ventral spinal cord precursors called pMN cells produce mostly motoneurons and oligodendrocytes, but recent lineage-marking experiments reveal that they also make astrocytes, ependymal cells and interneurons. Our own clonal analysis of pMN cells in zebrafish showed that some produce a primary motoneuron and KA′ interneuron at their final division. We investigated the possibility that Notch signaling regulates a motoneuron-interneuron fate decision using a combination of mutant, transgenic and pharmacological manipulations of Notch activity. We show that continuous absence of Notch activity produces excess primary motoneurons and a deficit of KA′ interneurons, whereas transient inactivation preceding neurogenesis results in an excess of both cell types. By contrast, activation of Notch signaling at the neural plate stage produces excess KA′ interneurons and a deficit of primary motoneurons. Furthermore, individual pMN cells produce similar kinds of neurons at their final division in mib mutant embryos, which lack Notch signaling. These data provide evidence that, among some postmitotic daughters of pMN cells, Notch promotes KA′ interneuron identity and inhibits primary motoneuron fate, raising the possibility that Notch signaling diversifies vertebrate neuron type by mediating similar binary fate decisions.