bluuebunny/crossref_metadata_2025 huggingface dataset:
Protein Kinase C-Mediated Phosphorylation of a Single Serine Residue on the Rat Glial Glutamine Transporter SN1 Governs Its Membrane Trafficking
Authors: Nissen-Meyer Lise Sofie H. , Popescu Mark C. , Hamdani El Hassan , Chaudhry Farrukh A.
Published: April 2011

Molecular mechanisms involved in the replenishment of the fast neurotransmitters glutamate and GABA are poorly understood. Glutamine sustains their generation. However, glutamine formation from the recycled transmitters is confined to glial processes and requires facilitators for its translocation across the glial and neuronal membranes. Indeed, glial processes are enriched with the system N transporter SN1 (Slc38a3), which, by bidirectional transport, maintains steady extracellular glutamine levels and thereby furnishes neurons with the primary precursor for fast neurotransmitters. We now demonstrate that SN1 is phosphorylated by protein kinase Cα (PKCα) and PKCγ. Electrophysiological characterization shows that phosphorylation reducesVmaxdramatically, whereas no significant effects are seen on theKm. Phosphorylation occurs specifically at a single serine residue (S52) in the N-terminal rat (Rattus norvegicus) SN1 and results in sequestration of the protein into intracellular reservoirs. Prolonged activation of PKC results in partial degradation of SN1. These results provide the first demonstration of phosphorylation of SN1 and regulation of its activity at the plasma membrane. Interestingly, membrane trafficking of SN1 resembles that of the glutamate transporter GLT and the glutamate–aspartate transporter GLAST: it involves the same PKC isoforms and occurs in the same glial processes. This suggests that the glutamate/GABA–glutamine cycle may be modified at two key points by similar signaling events and unmasks a prominent role for PKC-dependent phosphorylation. Our data suggest that extracellular glutamine levels may be fine-tuned by dynamic regulation of glial SN1 activity, which may impact on transmitter generation, contribute to defining quantal size, and have profound effects on synaptic plasticity.
How Soft Is That Pillow? The Perceptual Localization of the Hand and the Haptic Assessment of Contact Rigidity
Authors: Pressman Assaf , Karniel Amir , Mussa-Ivaldi Ferdinando A.
Published: April 2011

A new haptic illusion is described, in which the location of the mobile object affects the perception of its rigidity. There is theoretical and experimental support for the notion that limb position sense results from the brain combining ongoing sensory information with expectations arising from prior experience. How does this probabilistic state information affect one's tactile perception of the environment mechanics? In a simple estimation process, human subjects were asked to report the relative rigidity of two simulated virtual objects. One of the objects remained fixed in space and had various coefficients of stiffness. The other virtual object had constant stiffness but moved with respect to the subjects. Earlier work suggested that the perception of an object's rigidity is consistent with a process of regression between the contact force and the perceived amount of penetration inside the object's boundary. The amount of penetration perceived by the subject was affected by varying the position of the object. This, in turn, had a predictable effect on the perceived rigidity of the contact. Subjects' reports on the relative rigidity of the object are best accounted for by a probabilistic model in which the perceived boundary of the object is estimated based on its current location and on past observations. Therefore, the perception of contact rigidity is accounted for by a stochastic process of state estimation underlying proprioceptive localization of the hand.
Protein Kinase M Maintains Long-Term Sensitization and Long-Term Facilitation inAplysia
Authors: Cai Diancai , Pearce Kaycey , Chen Shanping , Glanzman David L.
Published: April 2011

How the brain maintains long-term memories is one of the major outstanding questions in modern neuroscience. Evidence from mammalian studies indicates that activity of a protein kinase C (PKC) isoform, protein kinase Mζ (PKMζ), plays a critical role in the maintenance of long-term memory. But the range of memories whose persistence depends on PKMζ, and the mechanisms that underlie the effect of PKMζ on long-term memory, remain obscure. Recently, a PKM isoform, known as PKM Apl III, was cloned from the nervous system ofAplysia. Here, we tested whether PKM Apl III plays a critical role in long-term memory maintenance inAplysia. Intrahemocoel injections of the pseudosubstrate inhibitory peptide ZIP (ζ inhibitory peptide) or the PKC inhibitor chelerythrine erased the memory for long-term sensitization (LTS) of the siphon-withdrawal reflex (SWR) as late as 7 d after training. In addition, both PKM inhibitors disrupted the maintenance of long-term (≥24 h) facilitation (LTF) of the sensorimotor synapse, a form of synaptic plasticity previously shown to mediate LTS of the SWR. Together with previous results (Bougie et al., 2009), our results support the idea that long-term memory inAplysiais maintained via a positive-feedback loop involving PKM Apl III-dependent protein phosphorylation. The present data extend the known role of PKM in memory maintenance to a simple and well studied type of long-term learning. Furthermore, the demonstration that PKM activity underlies the persistence of LTF of theAplysiasensorimotor synapse, a form of synaptic plasticity amenable to rigorous cellular and molecular analyses, should facilitate efforts to understand how PKM activity maintains memory.
Axon Formation in Neocortical Neurons Depends on Stage-Specific Regulation of Microtubule Stability by the Dual Leucine Zipper Kinase–c-Jun N-Terminal Kinase Pathway
Authors: Hirai Syu-ichi , Banba Yumi , Satake Tomoko , Ohno Shigeo
Published: April 2011

Studies using cultured neurons have established the critical role of microtubule regulators in neuronal polarization. The c-Jun N-terminal kinase (JNK) pathway is one of the candidate signaling pathways driving microtubule regulation during neuronal polarization. However, the significance of the JNK pathway in axon formation, a fundamental step in neuronal polarization,in vivo, remains unclear. Here, we provide evidence supporting the notion that the JNK pathway contributes to axon formation,in vivo, by identifying the genetic interactions between mouse JNK1 and dual leucine zipper kinase (DLK). Double mutants exhibited severe defects in axon formation in the cerebral neocortex. Moreover, RNA interference rescue experiments,in vitro, showed that DLK and JNK1 function in a common pathway to support neuronal polarization by promoting short-neurite and axon formation. Defects in axon formation caused by perturbations of the DLK–JNK pathway were significantly improved by Taxol. However, defects in short-neurite formation caused by perturbations of the DLK–JNK pathway were enhanced by Taxol. Together, thesein vivoandin vitroobservations indicate that the DLK–JNK pathway facilitates axon formation in neocortical neurons via stage-specific regulation of microtubule stability.
Molecular Determinants Controlling NMDA Receptor Synaptic Incorporation
Authors: Storey Granville P. , Opitz-Araya Ximena , Barria Andres
Published: April 2011

Synaptic incorporation of NMDA receptors (NMDARs) is regulated by GluN2 subunits with different rules controlling GluN2A- and GluN2B-containing receptors; whereas GluN2B-containing receptors are constitutively incorporated into synapses, GluN2A incorporation is activity-dependent. We expressed electrophysiologically tagged NMDARs in rat hippocampal slices to identify the molecular determinants controlling the mode of synaptic incorporation of NMDARs. Expressing chimeric GluN2 subunits, we identified a putativeN-glycosylation site present in GluN2B, but not in GluN2A, as necessary and sufficient to drive NMDARs into synapses in an activity-independent manner. This suggests a novel mechanism for regulating activity-driven changes and trafficking of NMDARs to the synapse.
Elapsed Decision Time Affects the Weighting of Prior Probability in a Perceptual Decision Task
Authors: Hanks Timothy D. , Mazurek Mark E. , Kiani Roozbeh , Hopp Elisabeth , Shadlen Michael N.
Published: April 2011

Decisions are often based on a combination of new evidence with prior knowledge of the probable best choice. Optimal combination requires knowledge about the reliability of evidence, but in many realistic situations, this is unknown. Here we propose and test a novel theory: the brain exploits elapsed time during decision formation to combine sensory evidence with prior probability. Elapsed time is useful because (1) decisions that linger tend to arise from less reliable evidence, and (2) the expected accuracy at a given decision time depends on the reliability of the evidence gathered up to that point. These regularities allow the brain to combine prior information with sensory evidence by weighting the latter in accordance with reliability. To test this theory, we manipulated the prior probability of the rewarded choice while subjects performed a reaction-time discrimination of motion direction using a range of stimulus reliabilities that varied from trial to trial. The theory explains the effect of prior probability on choice and reaction time over a wide range of stimulus strengths. We found that prior probability was incorporated into the decision process as a dynamic bias signal that increases as a function of decision time. This bias signal depends on the speed–accuracy setting of human subjects, and it is reflected in the firing rates of neurons in the lateral intraparietal area (LIP) of rhesus monkeys performing this task.
State-Dependent Representation of Amplitude-Modulated Noise Stimuli in Rat Auditory Cortex
Authors: Marguet Stephan L. , Harris Kenneth D.
Published: April 2011

Cortical responses can vary greatly between repeated presentations of an identical stimulus. Here we report that both trial-to-trial variability and faithfulness of auditory cortical stimulus representations depend critically on brain state. A frozen amplitude-modulated white noise stimulus was repeatedly presented while recording neuronal populations and local field potentials (LFPs) in auditory cortex of urethane-anesthetized rats. An information-theoretic measure was used to predict neuronal spiking activity from either the stimulus envelope or simultaneously recorded LFP. Evoked LFPs and spiking more faithfully followed high-frequency temporal modulations when the cortex was in a desynchronized state. In the synchronized state, neural activity was poorly predictable from the stimulus envelope, but the spiking of individual neurons could still be predicted from the ongoing LFP. Our results suggest that although auditory cortical activity remains coordinated as a population in the synchronized state, the ability of continuous auditory stimuli to control this activity is greatly diminished.
Impairment of Select Forms of Spatial Memory and Neurotrophin-Dependent Synaptic Plasticity by Deletion of Glial Aquaporin-4
Authors: Skucas Vanessa A. , Mathews Ian B. , Yang Jianmin , Cheng Qi , Treister Andrew , Duffy Aine M. , Verkman Alan S. , Hempstead Barbara L. , Wood Marcelo A. , Binder Devin K. , Scharfman Helen E.
Published: April 2011

Aquaporin-4 (AQP4) is the major water channel in the CNS and is primarily expressed in astrocytes. Little is known about the potential for AQP4 to influence synaptic plasticity, although many studies have shown that it regulates the response of the CNS to injury. Therefore, we evaluated long-term potentiation (LTP) and long-term depression (LTD) in AQP4 knock-out (KO) and wild-type mice. KO mice exhibited a selective defect in LTP and LTD without a change in basal transmission or short-term plasticity. Interestingly, the impairment in LTP in KO mice was specific for the type of LTP that depends on the neurotrophin BDNF, which is induced by stimulation at theta rhythm [theta-burst stimulation (TBS)-LTP], but there was no impairment in a form of LTP that is BDNF independent, induced by high-frequency stimulation. LTD was also impaired in KO mice, which was rescued by a scavenger of BDNF or blockade of Trk receptors. TrkB receptors, which mediate effects of BDNF on TBS-LTP, were not altered in KO mice, but p75NTR, the receptor that binds all neurotrophins and has been implicated in some types of LTD, was decreased. The KO mice also exhibited a cognitive defect, which suggests a new role for AQP4 and astrocytes in normal cognitive function. This defect was evident using a test for location-specific object memory but not Morris water maze or contextual fear conditioning. The results suggest that AQP4 channels in astrocytes play an unanticipated role in neurotrophin-dependent plasticity and influence behavior.
An Equivalent Noise Investigation of Saccadic Suppression
Authors: Watson Tamara , Krekelberg Bart
Published: April 2011

Visual stimuli presented just before or during an eye movement are more difficult to detect than those same visual stimuli presented during fixation. This laboratory phenomenon—behavioral saccadic suppression—is thought to underlie the everyday experience of not perceiving the motion created by our own eye movements—saccadic omission. At the neural level, many cortical and subcortical areas respond differently to perisaccadic visual stimuli than to stimuli presented during fixation. Those neural response changes, however, are complex and the link to the behavioral phenomena of reduced detectability remains tentative. We used a well established model of human visual detection performance to provide a quantitative description of behavioral saccadic suppression and thereby allow a more focused search for its neural mechanisms.

We used an equivalent noise method to distinguish between three mechanisms that could underlie saccadic suppression. The first hypothesized mechanism reduces the gain of the visual system, the second increases internal noise levels in a stimulus-dependent manner, and the third increases stimulus uncertainty. All three mechanisms predict that perisaccadic stimuli should be more difficult to detect, but each mechanism predicts a unique pattern of detectability as a function of the amount of external noise.

Our experimental finding was that saccades increased detection thresholds at low external noise, but had little influence on thresholds at high levels of external noise. A formal analysis of these data in the equivalent noise analysis framework showed that the most parsimonious mechanism underlying saccadic suppression is a stimulus-independent reduction in response gain.
Human Dorsal Striatal Activity during Choice Discriminates Reinforcement Learning Behavior from the Gambler's Fallacy
Authors: Jessup Ryan K. , O'Doherty John P.
Published: April 2011

Reinforcement learning theory has generated substantial interest in neurobiology, particularly because of the resemblance between phasic dopamine and reward prediction errors. Actor–critic theories have been adapted to account for the functions of the striatum, with parts of the dorsal striatum equated to the actor. Here, we specifically test whether the human dorsal striatum—as predicted by an actor–critic instantiation—is used on a trial-to-trial basis at the time of choice to choose in accordance with reinforcement learning theory, as opposed to a competing strategy: the gambler's fallacy. Using a partial-brain functional magnetic resonance imaging scanning protocol focused on the striatum and other ventral brain areas, we found that the dorsal striatum is more active when choosing consistent with reinforcement learning compared with the competing strategy. Moreover, an overlapping area of dorsal striatum along with the ventral striatum was found to be correlated with reward prediction errors at the time of outcome, as predicted by the actor–critic framework. These findings suggest that the same region of dorsal striatum involved in learning stimulus–response associations may contribute to the control of behavior during choice, thereby using those learned associations. Intriguingly, neither reinforcement learning nor the gambler's fallacy conformed to the optimal choice strategy on the specific decision-making task we used. Thus, the dorsal striatum may contribute to the control of behavior according to reinforcement learning even when the prescriptions of such an algorithm are suboptimal in terms of maximizing future rewards.
Gap Junctions between Interneurons Are Required for Normal Spatial Coding in the Hippocampus and Short-Term Spatial Memory
Authors: Allen Kevin , Fuchs Elke C. , Jaschonek Hannah , Bannerman David M. , Monyer Hannah
Published: April 2011

Gap junctions containing connexin 36 electrically couple interneurons in many brain regions and synchronize their activity. We used connexin-36 knock-out mice (Cx36−/−) to study the importance of electrical coupling between interneurons for spatial coding in the hippocampus and for different forms of hippocampus-dependent spatial memory. Recordings in behaving mice revealed that the spatial selectivity of hippocampal pyramidal neurons was reduced and less stable inCx36−/−mice. Altered network activity was reflected in slower theta oscillations in the mutants. Temporal coding, assessed by determining the presence and characteristics of theta phase precession, had different dynamics inCx36−/−mice compared with controls. At the behavioral level,Cx36−/−mice displayed impaired short-term spatial memory but normal spatial reference memory. These results highlight the functional role of electrically coupled interneurons for spatial coding and cognition. Moreover, they suggest that the precise spatial selectivity of place cells is not essential for normal performance on spatial tasks assessing associative long-term memory.
Spermatogonial morphology and kinetics during testis development in mice: a high-resolution light microscopy approach
Authors: Drumond Ana Luiza , Meistrich Marvin L , Chiarini-Garcia Hélio
Published: April 2011

Despite the knowledge of spermatogonial biology in adult mice, spermatogonial development in immature animals has not been fully characterized. Thus, the aim of this study was to evaluate the ontogeny of the morphological development of the spermatogonial lineage inC57BL/6mouse testis, using high-resolution light microscopy. Spermatogonial morphology, chronology, and absolute number were determined for different agespostpartum(pp). The morphology of spermatogonia in immature mice was similar to that of adult spermatogonia, although their nuclear diameter was slightly smaller. The A1spermatogonia were first observed on day 2pp, and only 24 h later, differentiating type A3and A4spermatogonia were observed in the seminiferous cords. This result indicated a shortening of the spermatogonial phase for immature mice of about ∼2.5 days when compared with adult mice and suggests that gonocytes and/or A1spermatogonia could directly become A4spermatogonia, skipping the developmental sequence of type A spermatogonia. These A4spermatogonia are functional as they develop into type B spermatogonia by day 5pp. At day 8pp, while differentiation to spermatocytes begins, the Aundspermatogonia reach their maximal numbers, which are maintained through adulthood. The various details of the spermatogonial behavior in immature normal mice described in this study can be used as a baseline for further studies under experimental or pathological conditions.
Comparison of Fibrinolytic versus Surgical Therapy in the Treatment of Obstructive Prosthetic Valve Thrombosis: A Single-Center Experience
Authors: Ermis Necip , Atalay Hakan , Altay Hakan , Bilgi Muhammet , Binici Suleyman , Sezgin Alpay T.
Published: April 2011

Objective: Prosthetic heart valve thrombosis (PVT) is a rare but severe cardiac condition. There are only a few data regarding comparison of the fibrinolytic and surgical approaches for the treatment of PVT. In this study, we compared the results of fibrinolytic therapy versus surgery in patients who presented to our institution with a diagnosis of obstructive-type PVT.Methods: From January 2001 to August 2008 in our institution, 33 patients who met clinical and echocardiographic criteria for obstructive-type PVT were included in the study. Fifteen of these patients underwent fibrinolytic treatment with streptokinase, which consisted of an initial bolus of 250,000 U followed by 100,000 U/h. Eighteen patients were treated with surgery.Results: The 2 groups had similar baseline characteristics, including New York Heart Association functional status, types and positions of prosthetic valves, international normalized ratio values, and presentation symptoms. Full hemodynamic success was achieved in 12 patients who underwent fibrinolytic therapy and in 15 patients in the surgery group. The mean (SD) streptokinase infusion time was 17.8 11.1 hours. Two major hemorrhages and 2 cases of systemic embolism were observed in the fibrinolytic group. The 2 groups did not differ with respect to mortality rate (P = .79). The duration of hospitalization was longer in the fibrinolytic group than in the surgery group (10.7 6.6 days versus 6.9 6.7 days, P = .045).Conclusions: Although fibrinolytic therapy is generally recommended for the treatment of PVT for specific patient groups, our results suggest that it may be as efficacious and safe as surgery, depending on patient selection.
Aortic Valve Endocarditis with Splenic and Brain Abscesses: Difficult Management Issues
Authors: Attaran Saina , Wragg Andrew , Awad Wael Ibrahim
Published: April 2011

Staphylococcus aureus endocarditis is associated with a high incidence of complications, a poor prognosis, and high operative mortality. We present a complex case of aortic valve endocarditis in a critically ill patient, highlight the difficult management issues, and report a good outcome.
Dexmedetomidine in Cardiac Surgery Patients Who Fail Extubation and Present with a Delirium State
Authors: Yapici Nihan , Coruh Turkan , Kehlibar Tamer , Yapici Fikri , Tarhan Arif , Can Yesim , Ozler Azmi , Aykac Zuhal
Published: April 2011

Background: We evaluated the use of dexmedetomidine to facilitate the weaning of delirious postoperative patients from mechanical ventilation.Methods: We included 72 consecutive patients who underwent elective cardiac surgery in this prospective observational study. Each patient had failed at least 1 trial of continuous positive airway pressure (CPAP) and had agitation. Patients were assessed with the Richmond Agitation-Sedation Scale (RASS) and the Confusion Assessment Method for the Intensive Care Unit (CAMICU) 12 to 18 hours after their admission to the ICU. Midazolam and fentanyl were then given to all patients according to the sedation protocol. At 36 hours in the ICU, patients who had agitation and an inability to wean were randomly divided into 2 groups: group M, 34 patients who continued to follow the routine sedative protocol; and group D, 38 patients who were given dexmedetomidine. Arterial blood gas measurements, hemodynamic parameters, and time to extubation were recorded. Statistical analysis was performed with GraphPad InStat (version 2.02 for DOS).Results: All patients tested positive in the CAM-ICU assessment, and all had a delirium diagnosis. The 38 patients in group D tolerated a spontaneous breathing trial with CPAP and were extubated after a mean (SD) of 49.619 6.96 hours. The 2 groups had significantly different extubation times (58.389 3.958 hours versus 49.619 6.96 hours). The 2 groups had significantly different RASS scores at 48 and 60 hours and significantly different heart rates and PO2 values at 12 and 24 hours. The 2 groups showed no significant differences with regard to hemodynamic parameters.Conclusions: Dexmedetomidine may help to eliminate the emergence of agitation and can be a good treatment choice for the delirium state after cardiac surgery.
Resource Utilization in Off-Pump versus Conventional Coronary Artery Bypass Grafting in a Community Hospital: A Comparative Analysis Using Propensity Scoring
Authors: Schultz Scot C. , Woodward Scott , Ebra George
Published: April 2011

Background: At a time when cost containment in health care is under increased scrutiny, coronary artery bypass grafting remains the most widely performed cardiac surgical procedure in the world. This study compares 30-day mortality, morbidity, and resource use for off-pump coronary artery bypass (OPCAB) versus conventional coronary artery bypass (CCAB) revascularization.Methods: From January 2000 through December 2008, 1003 patients underwent OPCAB grafting by a single surgeon (S.C.S.). Data were prospectively collected, entered into a Society of Thoracic Surgeons adult cardiac surgery database, and analyzed retrospectively. We used propensity-matching techniques to match this cohort to a group of 1003 patients who underwent CCAB.Results: The hospital mortality rate was lower for the OPCAB patients than for the CCAB patients: 2.0% (20/1003) versus 2.8% (28/1003). Predictors of hospital mortality for the entire cohort included age (P = .001), cardiogenic shock (P = .001), congestive heart failure (P = .019), history of myocardial infarction (P = .001), and reoperation (P = .007). The overall incidence of morbidity was lower for the OPCAB patients (reoperation for bleeding, P = .011; prolonged ventilation, P = .035; stroke, P = .045; cardiac arrest, P = .004). OPCAB patients experienced significantly reduced procedure times (P = .001), postoperative ventilation times (P = .035), post-operative lengths of stay (P = .035), and blood product use (intraoperative, P = .001; postoperative, P = .001).Conclusion: These outcomes clearly demonstrate that OPCAB is a safe and effective procedure for myocardial revascularization. This retrospective, nonrandomized observational study has shown that the patients who underwent OPCAB had reduced morbidity and mortality, as well as decreased resource use, compared with those who underwent CCAB.
Aortic Dissection Caused by Giant Cell Arteritis
Authors: Strecker Thomas , Zimmermann Stephan , Wachter David-Lukas , Agaimy Abbas
Published: April 2011

Aortic dissection is a very serious condition mainly caused by degenerative diseases of the connective tissue and hypertension. Ascending aortic dissection as a consequence of aortitis in association with giant cell arteritis is very rarely seen. In this article we report on the successful surgical repair of a Stanford type A aortic dissection caused by giant cell arteritis in a 74-year-old patient. We could visualize this dissection via echocardiography and computed tomography. Histopathology confirmed this rare complication of giant cell aortitis.
A Transapical or Transluminal Approach to Aortic Valve Implantation Does Not Attenuate the Inflammatory Response
Authors: O'Brien Benjamin , Pasic Miralem , Kuppe Hermann , Hetzer Roland , Habazettl Helmut , Kukucka Marian
Published: April 2011

Background: Cardiopulmonary bypass (CPB) and cardiac surgery cause an inflammatory response, as measurable by an increase in the concentration of C-reactive protein (CRP), a nonspecific inflammation marker. Previous publications have demonstrated typical perioperative CRP concentration profiles in cases of uncomplicated aortic valve replacement (AVR) with CPB. A regression analysis for modifying factors showed that chronic disease (heart failure, diabetes, and pulmonary disease), along with obesity and sex, all tend to influence the CRP response. We analyzed the inflammatory response to aortic valve implantation (AVI) with interventional techniques, mainly transapical but also transfemoral and transaxillary approaches, in a retrospective case-control study design.Methods: Sixty-eight patients who underwent AVI by the transapical (59 patients), transfemoral (7 patients), or transaxillary (2 patients) approach were matched by age, sex, body mass index (BMI), and chronic-disease state (absence or presence of diabetes, pulmonary disease, and renal impairment) with 68 patients who underwent conventional AVR with CPB. We compared the 2 groups with respect to perioperative CRP concentration, EuroSCORE, and outcome data (time to extubation and 30-day mortality). All data were collected prospectively and analyzed retrospectively.Results: The 2 groupsthe study population (interventional) and the control population (conventional)were similar in age, sex distribution, BMI, and chronic-disease status. As expected, the study population had a significantly higher median EuroSCORE. The 2 groups had similar postoperative CRP profiles over time, but the interventional group had significantly higher peak concentrations on days 2, 3, and 4. The short-term outcomes, as assessed by ventilation time and 30-day mortality, were similar for the 2 groups.Conclusions: Using an interventional transcatheter approach to AVI (thereby eliminating CPB from the procedure and reducing surgical trauma) does not attenuate the patient's innate inflammatory response.
Surgical Repair of a Giant Atrial Septal Aneurysm with Patent Foramen Ovale
Authors: Hosoba Soh , Suzuki Tomoaki , Asai Tohru , Takashima Noriyuki
Published: April 2011

Atrial septal aneurysm (ASA) is a rare occurrence. Many studies have established a correlation between ASA and both ischemic stroke of unidentified cause and cardiac embolism. We describe the case of a 59-year-old woman who had a giant ASA with patent foramen ovale. The aneurysm was successfully removed. Although the detailed mechanism involved in the degeneration of the atrial septum is unclear, we recommend that such damage be surgically repaired to reduce the risk of cerebral embolism or heart failure in symptomatic patients. Surgery is recommended for larger ASA.
Turning the page
Authors: Fleischer Elizabeth L.
Published: April 2011

Behind the themes and between the lines
In To Africa: Teaching Nanoscience to Undergraduates in KwaZulu-Natal, South Africa
Authors: Augustine Brian H. , Munro Orde Q.
Published: April 2011

There has been considerable interest in developing curricular programs and materials for teaching undergraduate courses in nanoscience in the United States and other developed countries in the past decade. Materials science and nanoscience research programs are growing in developing countries in South America, Africa and Asia. However, there still exists a significant disconnect between the research efforts in developing countries and undergraduate coursework. This report will focus on the teaching of an upper-division one semester lecture/laboratory course developed at James Madison University (JMU) called “The Science of the Small: An Introduction to the Nanoworld” taught in the School of Chemistry at the University of KwaZulu-Natal in Pietermaritzburg (UKZN-PMB), South Africa in 2009 through the Fulbright U.S. Scholar program. We report insights into the preparation needed to teach a cutting-edge laboratory course in South Africa. Also addressed will be some of the challenges of teaching an instrument-intensive laboratory course in a developing country, academic preparation of the typical native isiZulu-speaking UKZN undergraduate student compared to a typical U.S. student, and pre and post attitudes and content assessment of students who were enrolled in the course. Further discussed will be observations of post-apartheid science and math education in South Africa, and the beginning of a pilot program bringing South African undergraduate students to the U.S. to gain undergraduate research experience.
Modeling of AlGaAs on Si tandem PV cells for extended spectral conversion
Authors: Emziane Mahieddine , Mokri Alaeddine
Published: April 2011

The primary objective of this modeling investigation is to optimize a two-junction three-terminal device under the AM1.5G spectrum. Based on previous studies, AlGaAs and Si cells, because of their energy bandgaps, can be combined together to achieve high-efficiency double-junction devices. In this study, the top cell is made of Al0.3Ga0.7As (1.817 eV) while the bottom cell is made of Si (1.124 eV). In order to avoid the losses and design constraints observed in two-terminal and four-terminal devices, the tandem cell AlGaAs/Si is designed with three-terminals. In order to determine the optimal structure of the device, the top and bottom junctions were investigated and optimized with regard to the thicknesses and doping level. The optimum configuration of the device shows an efficiency of 26.27% under the AM1.5G spectrum and one sun, which is higher than the efficiency of an optimized single-junction Si cell under the same illumination conditions. We also studied the effect of the optical concentration on the performance of the device and we found that the overall efficiency reaches over 31% under 50 suns.
Thermoresponsive Hydrogel Microvalve Based on Magnetic Nanoheaters for Microfluidics
Authors: Ghosh Santaneel , Neogi Arup , Yang Chao , Cai Tong , GhoshMitra Somesree , Diercks David , Hu Zhibing
Published: April 2011

A novel magneto-active gel based nanomaterial system is presented as an externally tunable flow controller inside a microfluidic channel using the thermoresponsive property of the structure. Integration of ferromagnetic nanoparticles (Fe3O4) in the temperature sensitive polymer-poly (N-isopropylacrylamide) (PNIPAM) provides the swelling and de-swelling behavior of magnetic stimuli controlled micro-component by generating the heat due to the hysteresis loss of Fe3o4 under exposure in an alternating magnetic field. The shrinkage rates of the nanomaterial system at the bulk and micro scale are investigated. Size dependent shrinkage rate and actuation efficiency are ideal for various applications like magnetic micro/nano pump, magnetic field controlled drug delivery devices and magnetic switch applications.
Aborto e coerção sexual: o contexto de vulnerabilidade entre mulheres jovens
Authors: Pilecco Flávia Bulegon , Knauth Daniela Riva , Vigo Álvaro
Published: April 2011

Neste estudo investigou-se a relação entre a prática do aborto e a declaração de coerção sexual. Os dados foram provenientes do GRAVAD, inquérito domiciliar com amostragem probabilística estratificada, realizado com jovens de 18 a 24 anos, no Rio de Janeiro, em Porto Alegre e em Salvador, Brasil. A amostra do presente artigo foi composta por 870 entrevistas de mulheres que reportaram ter tido gravidez. A declaração de aborto mostrou-se associada ao relato de uma experiência de coerção sexual, bem como à maior escolaridade da jovem, a não ter obtido as primeiras informações sobre relações sexuais com os pais e a um maior número de gravidezes e de parceiros. A associação entre o aborto e a coerção sexual evidencia um quadro de vulnerabilidade de gênero e denota a precariedade das negociações em termos de sexualidade e reprodução. O silenciamento da coerção sexual às instituições públicas contribui para aumentar a vulnerabilidade das jovens, impedindo o acesso a recursos educativos, jurídicos e de saúde, que poderiam auxiliar na ruptura das situações de coerção e prevenção de novas ocorrências.
Transtornos mentais comuns e qualidade de vida em jovens: uma amostra populacional de Pelotas, Rio Grande do Sul, Brasil
Authors: Jansen Karen , Mondin Thaíse Campos , Ores Liliane da Costa , Souza Luciano Dias de Mattos , Konradt Caroline Elizabeth , Pinheiro Ricardo Tavares , Silva Ricardo Azevedo da
Published: April 2011

O objetivo foi verificar a prevalência de transtornos mentais comuns (TMC) e sua associação com qualidade de vida em jovens da cidade de Pelotas, Rio Grande do Sul, Brasil. Estudo transversal de base populacional com jovens de 18 a 24 anos. A seleção amostral foi realizada por conglomerados. Para a investigação dos transtornos mentais comuns foi aplicado o Self Report Questionnaire (SRQ-20), enquanto os níveis de qualidade de vida foram mensurados por intermédio da Medical Outcomes Survey Short-form General Health Survey (SF-36). A prevalência de TMC na amostra estudada foi de 24,5% (N = 382), apresentando-se mais evidente entre as mulheres, entre aqueles que pertenciam à menor classe socioeconômica (D ou E), não estavam estudando, não estavam trabalhando, consumiram álcool e usaram tabaco pelo menos uma vez na última semana e que fizeram uso de alguma substância ilícita nos últimos três meses. Os jovens com TMC obtiveram uma menor média nos escores da SF-36 em todos os domínios de qualidade de vida avaliados. Deve-se investir em medidas preventivas de TMC no intuito de proporcionar uma melhor qualidade de vida à população.
Dilemas sobre o fim-da-vida: informações sobre a prática médica nas UTIs
Authors: Gaudencio Debora , Messeder Octavio
Published: April 2011

O objetivo desta pesquisa foi coletar informações acerca do conhecimento, opinião e conduta dos médicos intensivistas sobre questões a respeito das decisões em pacientes terminais. Neste estudo descritivo, de corte transversal, foi aplicado um questionário aos médicos que trabalham em UTIs e semi-UTIs de cinco hospitais em Salvador (BA). Pode-se perceber que existe uma tendência dos médicos que lidam com pacientes terminais a assumir condutas para fornecer conforto, deixando inclusive de introduzir um mecanismo de suporte de vida (MSV). Entretanto, a maioria dos participantes admitiu que omite informações no prontuário por receio de punições pelo código de ética e/ou código penal. Essa insegurança pode ser relacionada com a falta de informação por parte dos profissionais, bem como a ausência de uma legislação clara e objetiva sobre o assunto. Portanto, amplas discussões multidisciplinares acerca dessas questões fazem-se necessárias no ambiente hospitalar.
Current Status of Src Inhibitors in Solid Tumor Malignancies
Authors: Puls Lauren N. , Eadens Matthew , Messersmith Wells
Published: April 2011

Src is believed to play an important role in cancer, and several agents targeting Src are in clinical development.

Design.

We reviewed Src structure and function and preclinical data supporting its role in the development of cancer via a PubMed search. We conducted an extensive review of Src inhibitors by searching abstracts from major oncology meeting databases in the last 3 years and by comprehensively reviewing ongoing clinical trials on ClinicalTrials.gov.

Results.

In this manuscript, we briefly review Src structure and function, mechanisms involving Src that lead to the development of cancer, and Src inhibitors and key preclinical data establishing a rationale for clinical application. We then focus on clinical data supporting their use in solid tumor malignancies, a newer arena than their more well-established hematologic applications. Particularly highlighted are clinical trials investigating new biomarkers as well as ongoing studies assessing Src inhibitor activity in biomarker-selected patient populations. We also review newer investigational Src-targeting agents.

Conclusions.

Src inhibitors have shown little activity in monotherapy trials in unselected solid tumor patient populations. Combination studies and biomarker-driven clinical trials are under way.
Dimensionality and Psychometric Analysis of an Alcohol Protective Behavioral Strategies Scale
Authors: Novik Melinda G. , Boekeloo Bradley O.
Published: April 2011

Objective:

The current study examined the dimensionality of a protective behavioral strategies (PBS) measure among undergraduate, predominantly freshmen (92.5%) college students reporting recent alcohol use ( n = 320).

Method:

Participants completed a web-based survey assessing 22 PBS items. Factor analyses determined the underlying factor structure of the items. Congruence of the factor structure among gender and racial sub-groups was examined by rotating the sub-groups' matrices via the Procrustes rotation method. Reliability analyses determined internal consistency.

Results:

A 2-factor solution was retained utilizing 17 of the original items. Both PBS subscales (Limits and Avoidance) had acceptable internal consistency across all samples.

Conclusions:

This PBS Scale was determined to be bi-dimensional and reliable. The dimensions suggest two underlying foci: ways to limit alcohol intake and ways to avoid alcohol intake while socializing. Practical implications of these findings are discussed.
Substance Use and its Relationship to Family Functioning and Self-Image in Adolescents
Authors: Weiss Jie Wu , Merrill Vincent , Akagha Kathy
Published: April 2011

This study examined associations between substance use, family functioning, and self-image among four ethnic adolescent groups. Three thousand three hundred and fifteen 8th and 9th grade students were recruited from 10 schools in Los Angeles County. Participants completed a paper-and-pencil survey regarding their alcohol and marijuana use, along with their perceived family functioning and self-image and other demographic variables. Ordinal logistic regression was performed to examine associations. Results indicated that both family functioning and self-image were significantly associated with alcohol and marijuana use. Those who scored lower on family functioning and self-image were at increased risk for substance use. Furthermore, students who scored low in both family functioning and self-image were about twice as likely to report using alcohol.
Alcohol Prevention Strategies on College Campuses and Student Alcohol Abuse and Related Problems
Authors: Ringwalt Christopher L. , Paschall Mallie J. , Gitelman Amy M.
Published: April 2011

This study examined the relationship between colleges' alcohol abuse prevention strategies and students' alcohol abuse and related problems. Alcohol prevention coordinators and first year students in 22 colleges reported whether their schools were implementing 48 strategies in six domains, and students ( N = 2041) completed another survey concerning their use of alcohol and related consequences. Colleges were most likely to prevent alcohol use in public places on campus and the delivery and use of kegs. Four alcohol prevention domains were inversely associated with at least one of five outcomes related to student alcohol abuse or related consequences, and the alcohol policy and enforcement domain was inversely associated with all outcomes. Colleges should pay particular attention to strategies related to policy and enforcement.
A Non-Parametric Method for Detecting Specificity Determining Sites in Protein Sequence Alignments
Authors: Gilks Walter R , Wang Chinying
Published: April 2011

Specificity determining sites (SDSs) in alignments of protein sequences are sites at which subfamilies of the aligned sequences have been under differential selective pressure. Identifying SDSs is important because they are key in understanding the functional specificity of each subfamily. Differential selection at an SDS will result in differences between subfamilies in the distribution of amino-acids at that site. However, statistical analysis of such differences is complicated by phylogenetic relationships within each subfamily, which profoundly influence these differences. We develop a non-parametric approach to evaluating purely statistical SDS evidence in a sequence alignment, taking account of phylogeny through a novel tree-respecting randomisation based on the principle of parsimony. Our approach does not exploit bioinformatic measures based on amino-acid properties or rates of evolution, as do other methods. Our intention is thereby to supplement and strengthen other methods of SDS prediction, not to compete with them. Our methodology is implemented in the R package called SDSparsimony, freely downloadable from http://www.maths.leeds.ac.uk/%7Ewally.gilks/SDSparsimonyPackage/Welcome.html.
Measurement of Accumulation of Semiconductor Nanocrystal Quantum Dots by Pimephales Promelas
Authors: Leigh Kenton L. , Bouldin Jennifer L. , Buchanan Roger A.
Published: April 2011

As the production and use of nanomaterials increases, it is important to understand their environmental and biological fate. Because their unmatched chemical, physical, and optical properties make them useful in a wide variety of applications including biomedical imaging, photo-voltaics, and light emitting diodes, the use of semiconductor nanocrystals such as quantum dots (QDs) is increasing rapidly. Although QDs hold great potential in a wide variety of industrial and consumer applications, the environmental implications of these particles is largely unexplored. The nanocrystal core of many types of QDs contains the toxic metal cadmium (Cd), so possible release of Cd from the QD core is cause for concern. Because many types of QDs are miscible in water, QD interactions with aquatic organisms and their environment require more attention. In the present study we used fluorometry to measure time and dose dependent uptake, accumulation, and post-exposure clearance of accumulated QDs in the gut tract by the aquatic vertebrate Pimephales promelas. By using fluorometry, we were able to measure accumulated QD concentrations. To our knowledge, this is the first reported attempt to quantify accumulated QDs in an organism and is an important step in understanding the interactions among QDs in aquatic organisms and environments.
Fractalkine Is a Novel Human Adipochemokine Associated With Type 2 Diabetes
Authors: Shah Rachana , Hinkle Christine C. , Ferguson Jane F. , Mehta Nehal N. , Li Mingyao , Qu Liming , Lu Yun , Putt Mary E. , Ahima Rexford S. , Reilly Muredach P.
Published: April 2011

OBJECTIVE

Leukocyte infiltration of adipose is a critical determinant of obesity-related metabolic diseases. Fractalkine (CX3CL1) and its receptor (CX3CR1) comprise a chemokine system involved in leukocyte recruitment and adhesion in atherosclerosis, but its role in adipose inflammation and type 2 diabetes is unknown.

RESEARCH DESIGN AND METHODS

CX3CL1 mRNA and protein were quantified in subcutaneous adipose and blood during experimental human endotoxemia and in lean and obese human adipose. CX3CL1 cellular source was probed in human adipocytes, monocytes, and macrophages, and CX3CL1-blocking antibodies were used to assess its role in monocyte-adipocyte adhesion. The association of genetic variation in CX3CR1 with metabolic traits was determined in a community-based sample. Finally, plasma CX3CL1 levels were measured in a case-control study of type 2 diabetes.

RESULTS

Endotoxemia induced adipose CX3CL1 mRNA (32.7-fold, P < 1 × 10−5) and protein (43-fold, P = 0.006). Obese subjects had higher CX3CL1 levels in subcutaneous adipose compared with lean (0.420 ± 0.387 vs. 0.228 ± 0.187 ng/mL, P = 0.04). CX3CL1 was expressed and secreted by human adipocytes and stromal vascular cells. Inflammatory cytokine induction of CX3CL1 in human adipocytes (27.5-fold mRNA and threefold protein) was completely attenuated by pretreatment with a peroxisome proliferator–activated receptor-γ agonist. A putative functional nonsynonymous single nucleotide polymorphism (rs3732378) in CX3CR1 was associated with adipose and metabolic traits, and plasma CX3CL1 levels were increased in patients with type 2 diabetes vs. nondiabetics (0.506 ± 0.262 vs. 0.422 ± 0.210 ng/mL, P < 0.0001).

CONCLUSIONS

CX3CL1-CX3CR1 is a novel inflammatory adipose chemokine system that modulates monocyte adhesion to adipocytes and is associated with obesity, insulin resistance, and type 2 diabetes. These data provide support for CX3CL1 as a diagnostic and therapeutic target in cardiometabolic disease.