MR Angiography Series: Neurovascular MR Angiography.

Neurovascular MR angiography (MRA) is an evolving imaging technique and is crucial for the workup of numerous neurologic disorders. While CT angiography (CTA) provides a more rapid imaging assessment, in select patients it can impart a small risk of contrast material-induced nephrotoxicity or radiation-associated cancers. In addition, MRA offers some advantages over CTA for neurovascular evaluation, including higher temporal resolution and the capability for vessel wall imaging. This module is the third in a series created on behalf of the Society for Magnetic Resonance Angiography (SMRA), a group of researchers and clinicians who are passionate about the benefits of MRA but understand its challenges. The full digital presentation is available online. Work of the U.S. Government published under an exclusive license with the RSNA.

Distinct subcellular mechanisms for the enhancement of the surface membrane expression of SK2 channel by its interacting proteins, α-actinin2 and filamin A.

KEY POINTS: Ion channels are transmembrane proteins that are synthesized within the cells but need to be trafficked to the cell membrane for the channels to function. Small-conductance, Ca2+ -activated K+ channels (SK, KCa 2) are unique subclasses of K+ channels that are regulated by Ca2+ inside the cells; they are expressed in human atrial myocytes and responsible for shaping atrial action potentials. We have previously shown that interacting proteins of SK2 channels are important for channel trafficking to the membrane. Using total internal reflection fluorescence (TIRF) and confocal microscopy, we studied the mechanisms by which the surface membrane localization of SK2 (KCa 2.2) channels is regulated by their interacting proteins. Understanding the mechanisms of SK channel trafficking may provide new insights into the regulation controlling the repolarization of atrial myocytes. ABSTRACT: The normal function of ion channels depends critically on the precise subcellular localization and the number of channel proteins on the cell surface membrane. Small-conductance, Ca2+ -activated K+ channels (SK, KCa 2) are expressed in human atrial myocytes and are responsible for shaping atrial action potentials. Understanding the mechanisms of SK channel trafficking may provide new insights into the regulation controlling the repolarization of atrial myocytes. We have previously demonstrated that the C- and N-termini of SK2 channels interact with the actin-binding proteins α-actinin2 and filamin A, respectively. However, the roles of the interacting proteins on SK2 channel trafficking remain incompletely understood. Using total internal reflection fluorescence (TIRF) microscopy, we studied the mechanisms of surface membrane localization of SK2 (KCa 2.2) channels. When SK2 channels were co-expressed with filamin A or α-actinin2, the membrane fluorescence intensity of SK2 channels increased significantly. We next tested the effects of primaquine and dynasore on SK2 channels expression. Treatment with primaquine significantly reduced the membrane expression of SK2 channels. In contrast, treatment with dynasore failed to alter the surface membrane expression of SK2 channels. Further investigations using constitutively active or dominant-negative forms of Rab GTPases provided additional insights into the distinct roles of the two cytoskeletal proteins on the recycling processes of SK2 channels from endosomes. α-Actinin2 facilitated recycling of SK2 channels from both early and recycling endosomes while filamin A probably aids the recycling of SK2 channels from recycling endosomes.

Cross-Cultural Perspectives on Self-Change in Close Relationships: Evidence From Hong Kong Chinese and European Americans.

Three studies examined cultural perceptions of self-change in romantic relationships. In Study 1 (N = 191), Chinese participants perceived hypothetical couples who changed for the sake of the relationship to have better relationship quality than couples who did not, compared to European American participants. In Study 2 (N = 396), Chinese individuals in a dating relationship were more likely to perceive that they had changed in the relationship, and self-change was a stronger predictor of relationship quality for them than for American dating individuals. In Study 3 (N = 115 dyads), Chinese married couples perceived greater self-change, and their perceived self-change was due in part to higher endorsement of dutiful adjustment beliefs than American couples. Self-change was a stronger predictor of relationship quality for Chinese married couples than American couples. Our studies provide support for cultural differences in the role of self-change in romantic relationships, which have implications for partner regulation and relationship counseling across cultures.

Is It Helpful to Believe That Efforts Will Lead to Positive Outcomes? Two Cross-Lagged Panel Investigations among Adolescents and Young Adults.

Over the past few decades, the role of self-views in life satisfaction has been extensively investigated. Recently, growing attention has been directed to the question of whether an optimistic worldview, termed "reward for application", helps boost life satisfaction. Conceptually, the association between reward for application and life satisfaction can be paradoxical. Due to various methodological and theoretical shortfalls, previous investigations were unable to draw a robust conclusion on this association. To address these shortfalls, two cross-lagged panel studies were conducted with different time lags. Over and above the potential confounds of self-views (namely, self-esteem and self-rated personality traits), reward for application had a positive effect on lagged life satisfaction among both adolescents and young adults, while the reverse effect was not found. Moreover, we found support for the multiplicative effect between worldviews and self-views, in which the positive effect of reward for application on life satisfaction was attenuated by high self-esteem.

Electrotaxis of cardiac progenitor cells, cardiac fibroblasts, and induced pluripotent stem cell-derived cardiac progenitor cells requires serum and is directed via PI3'K pathways.

BACKGROUND: The limited regenerative capacity of cardiac tissue has long been an obstacle to treating damaged myocardium. Cell-based therapy offers an enormous potential to the current treatment paradigms. However, the efficacy of regenerative therapies remains limited by inefficient delivery and engraftment. Electrotaxis (electrically guided cell movement) has been clinically used to improve recovery in a number of tissues but has not been investigated for treating myocardial damage. OBJECTIVE: The purpose of this study was to test the electrotactic behaviors of several types of cardiac cells. METHODS: Cardiac progenitor cells (CPCs), cardiac fibroblasts (CFs), and human induced pluripotent stem cell-derived cardiac progenitor cells (hiPSC-CPCs) were used. RESULTS: CPCs and CFs electrotax toward the anode of a direct current electric field, whereas hiPSC-CPCs electrotax toward the cathode. The voltage-dependent electrotaxis of CPCs and CFs requires the presence of serum in the media. Addition of soluble vascular cell adhesion molecule to serum-free media restores directed migration. We provide evidence that CPC and CF electrotaxis is mediated through phosphatidylinositide 3-kinase signaling. In addition, very late antigen-4, an integrin and growth factor receptor, is required for electrotaxis and localizes to the anodal edge of CPCs in response to direct current electric field. The hiPSC-derived CPCs do not express very late antigen-4, migrate toward the cathode in a voltage-dependent manner, and, similar to CPCs and CFs, require media serum and phosphatidylinositide 3-kinase activity for electrotaxis. CONCLUSION: The electrotactic behaviors of these therapeutic cardiac cells may be used to improve cell-based therapy for recovering function in damaged myocardium.

Conceptualizing psychological processes in response to globalization: Components, antecedents, and consequences of global orientations.

The influences of globalization have permeated various aspects of life in contemporary society, from technical innovations, economic development, and lifestyles, to communication patterns. The present research proposed a construct termed global orientation to denote individual differences in the psychological processes of acculturating to the globalizing world. It encompasses multicultural acquisition as a proactive response and ethnic protection as a defensive response to globalization. Ten studies examined the applicability of global orientations among majority and minority groups, including immigrants and sojourners, in multicultural and relatively monocultural contexts, and across Eastern and Western cultures. Multicultural acquisition is positively correlated with both independent and interdependent self-construals, bilingual proficiency and usage, and dual cultural identifications. Multicultural acquisition is promotion-focused, while ethnic protection is prevention-focused and related to acculturative stress. Global orientations affect individuating and modest behavior over and above multicultural ideology, predict overlap with outgroups over and above political orientation, and predict psychological adaptation, sociocultural competence, tolerance, and attitudes toward ethnocultural groups over and above acculturation expectations/strategies. Global orientations also predict English and Chinese oral presentation performance in multilevel analyses and the frequency and pleasantness of intercultural contact in cross-lagged panel models. We discuss how the psychological study of global orientations contributes to theory and research on acculturation, cultural identity, and intergroup relations.

Molecular Mechanisms and New Treatment Paradigm for Atrial Fibrillation.

BACKGROUND: Atrial fibrillation represents the most common arrhythmia leading to increased morbidity and mortality, yet, current treatment strategies have proven inadequate. Conventional treatment with antiarrhythmic drugs carries a high risk for proarrhythmias. The soluble epoxide hydrolase enzyme catalyzes the hydrolysis of anti-inflammatory epoxy fatty acids, including epoxyeicosatrienoic acids from arachidonic acid to the corresponding proinflammatory diols. Therefore, the goal of the study is to directly test the hypotheses that inhibition of the soluble epoxide hydrolase enzyme can result in an increase in the levels of epoxyeicosatrienoic acids, leading to the attenuation of atrial structural and electric remodeling and the prevention of atrial fibrillation. METHODS AND RESULTS: For the first time, we report findings that inhibition of soluble epoxide hydrolase reduces inflammation, oxidative stress, atrial structural, and electric remodeling. Treatment with soluble epoxide hydrolase inhibitor significantly reduces the activation of key inflammatory signaling molecules, including the transcription factor nuclear factor κ-light-chain-enhancer, mitogen-activated protein kinase, and transforming growth factor-ß. CONCLUSIONS: This study provides insights into the underlying molecular mechanisms leading to atrial fibrillation by inflammation and represents a paradigm shift from conventional antiarrhythmic drugs, which block downstream events to a novel upstream therapeutic target by counteracting the inflammatory processes in atrial fibrillation.

Critical roles of a small conductance Ca²âº-activated K⁺ channel (SK3) in the repolarization process of atrial myocytes.

AIMS: Small conductance Ca(2+)-activated K(+) channels (K(Ca)2 or SK channels) have been reported in excitable cells, where they aid in integrating changes in intracellular Ca(2+) (Ca(i)²âº) with membrane potentials. We have recently reported the functional expression of SK channels in human and mouse cardiac myocytes. Additionally, we have found that the channel is highly expressed in atria compared with the ventricular myocytes. We demonstrated that human cardiac myocytes expressed all three members of SK channels (SK1, 2, and 3); moreover, the different members are capable of forming heteromultimers. Here, we directly tested the contribution of SK3 to the overall repolarization of atrial action potentials. METHODS AND RESULTS: We took advantage of a mouse model with site-specific insertion of a tetracycline-based genetic switch in the 5' untranslated region of the KCNN3 (SK3 channel) gene (SK3(T/T)). The gene-targeted animals overexpress the SK3 channel without interfering with the normal profile of SK3 expression. Whole-cell, patch-clamp techniques show a significant shortening of the action potential duration mainly at 90% repolarization (APD90) in atrial myocytes from the homozygous SK3(T/T) animals. Conversely, treatment with dietary doxycycline results in a significant prolongation of APD90 in atrial myocytes from SK3(T/T) animals. We further demonstrate that the shortening of APDs in SK3 overexpression mice predisposes the animals to inducible atrial arrhythmias. CONCLUSION: SK3 channel contributes importantly towards atrial action potential repolarization. Our data suggest the important role of the SK3 isoform in atrial myocytes.

[(Cyclen)(4)Ru(4)(pz)(4)](9+): a Creutz-Taube square.

The use of cyclen (1,4,7,10-tetraazacyclododecane) as a blocking ligand enables assembly of the mixed-valence square complex [(cyclen)4Ru4(pz)4]9+ (pz = pyrazine). A crystal structure determination shows the molecule to possess a regular square geometry wherein each Ru atom has an equivalent coordination environment. Consistent with the presence of one RuIII and three RuII centers, cyclic voltammetry reveals a single reversible reduction wave and three successive oxidation waves. The separation between the first oxidation and reduction waves indicates a comproportionation constant of Kc = 108.9 for the [(cyclen)4Ru6(pz)4]9+ square, suggesting a greater extent of electron delocalization than that observed for the Creutz-Taube ion. The closer spacing between oxidation waves suggests a lesser degree of delocalization in the [(cyclen)4Ru6(pz)4]10+ (Kc = 102.0) and [(cyclen)4Ru6(pz)4]11+ (Kc = 103.0) species, bearing the higher average oxidation states of Ru2.5+ and Ru2.75+, respectively.