bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrapericardial Triamcinolone Administration for Autoreactive Pericarditis
Authors: Glick Frasiolas Jorie A , Cahoon William D
Published: August 2010

Objective:

To review published literature regarding the safety and effectiveness of intrapericardial triamcinolone for the treatment of autoreactive pericarditis.

Data Sources:

Searches of MEDLINE (1966–June 2010) and Cochrane Database (1993–June 2010) were conducted. Limits included articles published in English reporting on human subjects. Additional data were identified through bibliographic reviews.

Study Selection and Data Extraction:

All English-language articles identified from the data sources were evaluated. Trials, studies, and case reports were eligible for inclusion if they evaluated the safety and/or efficacy of intrapericardial triamcinolone for the management of autoreactive pericarditis.

Data Synthesis:

Systemic corticosteroids offer an effective treatment option for autoreactive pericarditis; however, their use is limited by adverse effects and they are an independent risk factor for pericarditis recurrence. One case series and 3 open-label trials evaluating intrapericardial triamcinolone for the management of autoreactive pericarditis are reviewed. Included studies were limited by small sample sizes (N = 2–84), lack of control groups, short durations of follow-up (24 h to 12 mo), use of adjuvant agents, omission of patient demographic data, subjective report of symptom relief, and lack of consistent dose of intrapericardial triamcinolone. Despite these limitations, the data suggest symptom resolution and reduced pericarditis recurrence with administration of intrapericardial triamcinolone to patients with autoreactive pericarditis.

Conclusions:

There is growing evidence that intrapericardial triamcinolone is safe and effective for the management of autoreactive pericarditis. The appropriate regimen (dose and duration of treatment), adverse effect profile, and specific therapeutic role require further investigation.
Use of Psychostimulants in Patients with Dementia
Authors: Dolder Christian R , Nicole Davis Lauren , McKinsey Jonathan
Published: August 2010

Objective:

To review the efficacy and safety of psychostimulants for negative behavioral symptoms (ie, apathy, excessive daytime sedation) and cognition in patients with dementia.

Data Sources:

Literature was accessed through PubMed and MEDLINE (1966–June 2010), using the terms stimulant, psychostimulant, methyiphenidate, dexmethylphenidate, amphetamine, dextroamphetamine, lisdexamfetamine. atomoxetine, modafinil, armodafinil, dementia, Alzheimer disease, vascular dementia, Lewy body dementia, mixed dementia, frontotemporal dementia, therapy, treatment, and therapeutic. Additional references identified from the initial search were reviewed.

Study Selection and Data Extraction:

All relevant clinical trials published in English and involving primarily older adults with dementia were included. Case reports, review articles, and other preclinical literature were included as appropriate.

Data Synthesis:

Psychostimulants have been employed as a treatment for cognitive and behavioral symptoms in dementia for decades, but the literature has lagged behind this practice. Eight reports on use of psychostimulants as a treatment of apathy in dementia were reviewed. Methyiphenidate was the most frequently studied medication and improvements in apathy were consistently noted; however, the magnitude and duration of effect remain unclear. Six studies examining the cognitive effects of a variety of psychostimulants in patients with dementia were reviewed; psychostimulants had little to no effect on cognition. A lack of studies exists to draw conclusions about the use of psychostimulants for the treatment of excessive daytime sedation in dementia. The possibility of psychostimulants to increase blood pressure; elevate heart rate; and lead to irritability, agitation, and psychosis makes careful patient selection critical, especially in older adults with severe cardiovascular disease or other underlying cardiac abnormalities.

Conclusions:

Based on limited studies, methyiphenidate is a possible treatment for apathy in patients with dementia. Psychostimulants, as a group, do not appear to be broadly effective treatments for behavioral or cognitive symptoms of dementia. The potential utility of psychostimulants must be balanced with careful patient selection.
Immunochemical and Mass-Spectrometry–Based Serum Hepcidin Assays for Iron Metabolism Disorders
Authors: Kroot Joyce JC , Laarakkers Coby MM , Geurts-Moespot Anneke J , Grebenchtchikov Nicolaï , Pickkers Peter , van Ede Annelies E , Peters Hilde PE , van Dongen-Lases Edmée , Wetzels Jack FM , Sweep Fred CGJ , Tjalsma Harold , Swinkels Dorine W
Published: August 2010

BACKGROUND

Hepcidin is an iron-regulatory peptide hormone that consists of 3 isoforms: bioactive hepcidin-25, and inactive hepcidin-22 and hepcidin-20. Hepcidin is instrumental in the diagnosis and monitoring of iron metabolism disorders, but reliable methods for its quantification in serum are sparse, as is knowledge of their relative analytical strengths and clinical utility.

METHODS

We developed a competitive (c)-ELISA and an immunocapture TOF mass-spectrometry (IC-TOF-MS) assay. Exploiting these 2 methods and our previously described weak cation exchange (WCX)-TOF-MS assay, we measured serum hepcidin concentrations in 186 patients with various disorders of iron metabolism and in 23 healthy controls.

RESULTS

We found that (a) the relative differences in median hepcidin concentrations in various diseases to be similar, although the absolute concentrations measured with c-ELISA and WCX-TOF-MS differed; (b) hepcidin isoforms contributed to differences in hepcidin concentrations between methods, which were most prominent in patients with chronic kidney disease; and (c) hepcidin concentrations measured by both the c-ELISA and IC-TOF-MS correlated with ferritin concentrations <60 μg/L, and were suitable for distinguishing between iron deficiency anemia (IDA) and the combination of IDA and anemia of chronic disease.

CONCLUSIONS

c-ELISA is the method of choice for the large-scale quantification of serum hepcidin concentrations, because of its low limit of detection, low cost, and high-throughput. Because of its specificity for bioactive hepcidin-25, WCX-TOF-MS can be regarded as a valuable special-purpose assay for disorders with variable concentrations of hepcidin isoforms, such as chronic kidney disease.
Questioning the General Self-Esteem Vaccine: General Self-Esteem, Racial Discrimination, and Standardised Achievement Across Indigenous and Non-Indigenous Students
Authors: Bodkin-Andrews Gawaian H. , Seaton Marjorie , Nelson Genevieve F. , Craven Rhonda G. , Yeung Alexander S.
Published: August 2010

Psychological research and the popular media culture have repeatedly noted that self-esteem positively contributes to life satisfaction and performance indicators across a large variety of domains. However, while varying measures of self-esteem may be argued to have a positive influence on outcome measures, increasing evidence suggests that perceptions of racial discrimination may also have a negative impact across a wide variety of outcomes. The current investigation used structural equation modelling techniques to examine the potential impact of Indigenous and non-Indigenous Australian students' General Self-Esteem and their perceptions of racial discrimination on spelling and maths achievement. Results indicated that General Self-Esteem displayed little or no significant relations with the performance measures, yet perceived racial discrimination significantly and negatively predicted both spelling and maths achievement for the Indigenous and non-Indigenous students. In addition, no significant latent interaction between General Self-Esteem and perceived discrimination was identified, raising questions for the self-protective properties of General Self-Esteem, at least for achievement outcomes.
Examining School Related Factors Leading to Dropout Through Children's Conceptions and Experiences: Development of a Scale for Attitudes Towards Elementary School
Authors: Erktin Emine , Okcabol Rifat , Ural Ozana
Published: August 2010

Despite state support for mass education in Turkey, there are many primary school children who do not attend school or who drop out before finishing school. This study is part of a project investigating the problem of school dropout in a district of Istanbul. Factors related to school, such as failure, non-acceptance by teachers and peers, poor attendance, and low levels of involvement, have been associated with increased likelihood of dropout. Modifying the instructional environment, strengthening school membership, and creating alternative schools have been suggested as means to prevent dropout. A questionnaire assessing attitudes toward school was administered to 480 students from 13 elementary schools for the purpose of identifying the characteristics of schools that lead to dropout. Factor analysis results indicated five factors of school-related attitudes, including attitudes toward learning; toward teachers; toward school and school facilities; and students' perceptions of parent-school relationships.
A Person-Centred Perspective to Counselling in Educational and Vocational Agencies
Authors: Crisp Ross
Published: August 2010

This article focuses upon the application of Carl Rogers' person-centred approach (PCA) by educational and vocational counsellors. The discussion of PCA in educational and vocational counselling raises several key issues that have received attention in recent counselling psychology literature. PCA has been criticised for its highly individualistic approach that overlooks relational issues, its limited clinical application, and lack of technical expertise to sufficiently produce change in persons with significant mental and/or mood disorders. Three vignettes are presented to illustrate that contemporary PCA is a less individualistic and more socially contextualised practice than originally formulated by Rogers. They highlight some aspects of the work of counsellors who utilise the primary nondirective components of PCA (congruence, unconditional positive regard, empathy) with directive interventions when requested by clients, who are responsive to their clients' diverse socio-cultural backgrounds, and who are prepared to work within a medical framework.
The Relationship Between the Secondary School Students' Depression States and Their Feelings of Guilt and Shame
Authors: Sargin Nurten
Published: August 2010

Adolescence is believed to be a highly problematic period when depression is prevalent. This study aims to investigate the relationship between adolescents' depression states and their feelings of guilt and shame in respect to gender, age, school performance and parental education levels. The participants consisted of 187 teenagers; 88 (47.1%) girls and 99 (52.9%) boys. Beck's Depression Inventory (BDI), the Guilt and Shame Scale (GES, Şahin), and a personal information form developed by the researcher were used as instruments. The study found a relationship between guilt and shame, that levels of depression were higher in 17-year-olds, and also that levels of depression, guilt and shame were found to be higher in girls than in boys. There was also a negative relationship seen between increased guilt and shame, and a decrease in mothers' education level.
What Stresses University Students: An Interview Investigation of the Demands of Tertiary Studies
Authors: Bitsika Vicki , Sharpley Christopher F. , Rubenstein Vira
Published: August 2010

Although several previous scales have been developed to measure the presence and effects of the stressful demands encountered by university students, most of these have been validated with samples drawn from US universities, commonly using only undergraduate psychology students. In addition, many of the items used are from scales designed for application within general adult populations, with little focus upon the specific stressors met by students. In order to identify what are the major changes these students encounter that they find stressful, a sample of 32 university students from different degree areas within an Australian university was individually interviewed using a standardised protocol. Results indicated that (unlike US data) these students found dislocation to family, friend and partner relationships most stressful, followed by the time demands of study and financial restrictions. Limitations of the study, future research directions and implications for counsellors are discussed.
A Qualitative Approach to Understanding Turkish Mothers of Children With Autism: Implications for Counselling
Authors: Koydemir-Özden Selda , Tosun Ülkü
Published: August 2010

Most children with autism exhibit a variety of behaviours, which may create considerable stress in families. Parents of children with autism have to learn many strategies to support their children. Understanding the experiences of parents of autistic children is crucial in the design and delivery of the appropriate counselling services. The present study attempted to investigate the impact of having an autistic child on the lives of Turkish mothers. For this aim, a Consensual Qualitative Research (CQR) Approach was followed. Semi-structured interviews were conducted with 13 mothers of autistic children. The interview questions were designed to investigate many facets of the mothers' experiences. For the data analysis, steps of CQR were followed, namely transcription of data, identification of main domains and core ideas, identification of categories and subcategories, and cross analysis. The analyses resulted in a variety of domains such as the reactions to the disability of the child, experience of stress and burnout, involvement with the education of the child, and evaluation of the facilities of the special education centre. Recommendations for guidance and counselling were drawn based on the categories of each domain.
Effects of Conflict Resolution and Peer Mediation Training in a Turkish High School
Authors: Turnuklu Abbas , Kacmaz Tarkan , Sunbul Dilara , Ergul Hatice
Published: August 2010

The purpose of the research was to examine the effectiveness of Conflict Resolution and Peer Mediation (CRPM) training on high school students' interpersonal conflicts. The CRPM training program was developed by the researchers as a 31-hour program that addressed four basic conflict resolution skills; understanding the nature of interpersonal conflicts, communication skills, anger management skills, and negotiation and peer mediation skills. The study was conducted in a high school located in Izmir, Turkey which served students from low SES families. During the two-year study, a total of 830 students received training, and following the training, 12 peer mediator students were elected from each classroom by their friends. These peer mediators handled their friends' conflicts during three semesters. Data were collected through the peer mediation forms filled by the mediator students following the mediation sessions. A total of 253 mediation sessions were held; 240 (94.9%) resulted in resolution and 13 (5.1%) in no-resolution. Results of the study indicated that CRPM training could prove to be effective in resolving high school students' conflicts.
Sexual Education and Teacher Candidates' Attitudes Towards Sexuality
Authors: Gursimsek Isik
Published: August 2010

The aim of this study is to investigate teacher candidates' attitudes related to sexuality and homosexuality and to determine the relationship between these attitudes and course attendance, gender and cultural background. The sample of the study consist of teacher candidates that have ( n = 302) and have not ( n = 176) attended the sexual education course during the 2006–2007 academic year at a faculty of education in Izmir — a city in the western coastal region of Turkey. The Sexual Attitude Scale (SAS) and the Homosexuality Attitude Scale (HAS) were used to gather data at pre-test and post-test levels. Results demonstrate that sexuality education has a positive effect on participants' attitudes towards sexuality. In contrast, the course does not have any influence on candidates approach to homosexuality.
Social Skills and Problem Behaviours of Children with Different Cognitive Styles Who Attend Preschool Education
Authors: Seçer Zarife , Çeliköz Nadir , Koçyiğit Sezai , Seçer Fahri , Kayılı Gökhan
Published: August 2010

The study investigated whether social skills and problem behaviours of preschool children differ according to their cognitive styles. The sample group included 366 six-year-old children who attend preschools in Konya. Form A of the Kansas Reflection-Impulsivity Scale for Preschoolers (KRISP), developed by Wright (1971), was used to determine whether the participants had reflective or impulsive cognitive styles, while Preschool and Kindergarten Behaviour Scales (PKBS), developed by Merrell (2003), were used to evaluate social skills and problem behaviour dimensions. Results found that impulsive children were less efficient than reflective children in regards to their social cooperation and social interaction skills, and they exhibited more problem behaviours like self-centred/explosive behaviours, lack of attention/hyperactivity, antisocialism/aggression and social withdrawal.
Microstructural Brain Differences Predict Functional Hemodynamic Responses in a Reward Processing Task
Authors: Camara Estela , Rodriguez-Fornells Antoni , Münte Thomas F.
Published: August 2010

Many aspects of human behavior are driven by rewards, yet different people are differentially sensitive to rewards and punishment. In this study, we show that white matter microstructure in the uncinate/inferior fronto-occipital fasciculus, defined by fractional anisotropy values derived from diffusion tensor magnetic resonance images, correlates with both short-term (indexed by the fMRI blood oxygenation level-dependent response to reward in the nucleus accumbens) and long-term (indexed by the trait measure sensitivity to punishment) reactivity to rewards. Moreover, trait measures of reward processing were also correlated with reward-related functional activation in the nucleus accumbens. The white matter tract revealed by the correlational analysis connects the anterior temporal lobe with the medial and lateral orbitofrontal cortex and also supplies the ventral striatum. The pattern of strong correlations suggests an intimate relationship between white matter structure and reward-related behavior that may also play a role in a number of pathological conditions, such as addiction and pathological gambling.
Insulin Reveals Akt Signaling as a Novel Regulator of Norepinephrine Transporter Trafficking and Norepinephrine Homeostasis
Authors: Robertson Sabrina D. , Matthies Heinrich J. G. , Owens W. Anthony , Sathananthan Vidiya , Christianson Nicole S. Bibus , Kennedy J. Phillip , Lindsley Craig W. , Daws Lynette C. , Galli Aurelio
Published: August 2010

Noradrenergic signaling in the CNS plays an essential role in circuits involving attention, mood, memory, and stress as well as providing pivotal support for autonomic function in the peripheral nervous system. The high-affinity norepinephrine (NE) transporter (NET) is the primary mechanism by which noradrenergic synaptic transmission is terminated. Data indicate that NET function is regulated by insulin, a hormone critical for the regulation of metabolism. Given the high comorbidity of metabolic disorders such as diabetes and obesity with mental disorders such as depression and schizophrenia, we sought to determine how insulin signaling regulates NET function and thus noradrenergic homeostasis. Here, we show that acute insulin treatment, through the downstream kinase protein kinase B (Akt), significantly decreases NET surface expression in mouse hippocampal slices and superior cervical ganglion neuron boutons (sites of synaptic NE release).In vivomanipulation of insulin/Akt signaling, with streptozotocin, a drug that induces a type 1-like diabetic state in mice, also results in aberrant NET function and NE homeostasis. Notably, we also demonstrate that Akt inhibition or stimulation, independent of insulin, is capable of altering NET surface availability. These data suggest that aberrant states of Akt signaling such as in diabetes and obesity have the potential to alter NET function and noradrenergic tone in the brain. Furthermore, they provide one potential molecular mechanism by which Akt, a candidate gene for mood disorders such as schizophrenia and depression, can impact brain monoamine homeostasis.
Direction Opponency, Not Quadrature, Is Key to the 1/4 Cycle Preference for Apparent Motion in the Motion Energy Model
Authors: Heess Nicolas , Bair Wyeth
Published: August 2010

Sensitivity to visual motion is a fundamental property of neurons in the visual cortex and has received wide attention in terms of mathematical models. A key feature of many popular models for cortical motion sensors is the use of pairs of functions that are related by a 90° phase shift. This phase relationship, known as quadrature, is the hallmark of the motion energy model and played an important role in the development of a class of model dubbed elaborated Reichardt detectors. For decades, the literature has supported a link between quadrature and the observation that motion detectors and human observers often prefer a 1/4 cycle displacement of an apparent motion stimulus that consists of a pair of sinusoidal gratings. We show that there is essentially no link between quadrature and this preference. Quadrature is neither necessary nor sufficient for a motion sensor to prefer 1/4 cycle displacement, and motion energy is not maximized for a 1/4 cycle step. Other properties of motion sensors are the key: the opponent subtraction of two oppositely tuned stages that individually have sinusoidal displacement tuning curves. Thus, psychophysical and neurophysiological data revealing a preference at or near 1/4 cycle displacement do not offer specific support for common quadrature or energy-based motion models. Instead, they point to a broader class of model.
Rapamycin Activates Autophagy and Improves Myelination in Explant Cultures from Neuropathic Mice
Authors: Rangaraju Sunitha , Verrier Jonathan D. , Madorsky Irina , Nicks Jessica , Dunn William A. , Notterpek Lucia
Published: August 2010

Misexpression and cytosolic retention of peripheral myelin protein 22 (PMP22) within Schwann cells (SCs) is associated with a genetically heterogeneous group of demyelinating peripheral neuropathies. PMP22 overproducer C22 and spontaneous mutant Trembler J (TrJ) mice display neuropathic phenotypes and affected nerves contain abnormally localized PMP22. Nutrient deprivation-induced autophagy is able to suppress the formation of PMP22 aggregates in a toxin-induced cellular model, and improve locomotor performance and myelination in TrJ mice. As a step toward therapies, we assessed whether pharmacological activation of autophagy by rapamycin (RM) could facilitate the processing of PMP22 within neuropathic SCs and enhance their capacity to myelinate peripheral axons. Exposure of mouse SCs to RM induced autophagy in a dose- and time-dependent manner and decreased the accumulation of poly-ubiquitinated substrates. The treatment of myelinating dorsal root ganglion (DRG) explant cultures from neuropathic mice with RM (25 nm) improved the processing of PMP22 and increased the abundance and length of myelin internodes, as well as the expression of myelin proteins. Notably, RM is similarly effective in both the C22 and TrJ model, signifying that the benefit overlaps among distinct genetic models of PMP22 neuropathies. Furthermore, lentivirus-mediated shRNA knockdown of the autophagy-related gene 12 (Atg12) abolished the activation of autophagy and the increase in myelin proteins, demonstrating that autophagy is critical for the observed improvement. Together, these results support the potential use of RM and other autophagy-enhancing compounds as therapeutic agents for PMP22-associated demyelinating neuropathies.
Dynamics of the Parkinsonian Striatal Microcircuit: Entrainment into a Dominant Network State
Authors: Jáidar Omar , Carrillo-Reid Luis , Hernández Adán , Drucker-Colín René , Bargas José , Hernández-Cruz Arturo
Published: August 2010

Neuronal synchronization in basal ganglia circuits plays a key role in the encoding of movement, procedural memory storage and habit formation. Striatal dopamine (DA) depletion during Parkinsonism causes abnormal synchronization in corticobasal ganglia loops resulting in motor dysfunction. However, the dynamics of the striatal microcircuit underlying abnormal synchronization in Parkinsonism is poorly understood. Here we used targeted whole-cell recordings, calcium imaging allowing the recording from dozens of cells simultaneously and analytical approaches, to describe the striking alterations in network dynamics that the striatal microcircuit undergoes following DA depletion in a rat model of Parkinson disease (PD): In addition to a significant enhancement of basal neuronal activity frequent periods of spontaneous synchronization were observed. Multidimensional reduction techniques of vectorized network dynamics revealed that increased synchronization resulted from a dominant network state that absorbed most spontaneously active cells. Abnormal synchronous activity can be virtually abolished by glutamatergic antagonists, while blockade of GABAergic transmission facilitates the engagement of striatal cell assemblies in the dominant state. Finally, a dopaminergic receptor agonist was capable of uncoupling neurons from the dominant state. Abnormal synchronization and “locking” into a dominant state may represent the basic neuronal mechanism that underlies movement disorders at the microcircuit level.
Excitatory Glycine Responses of CNS Myelin Mediated by NR1/NR3 “NMDA” Receptor Subunits
Authors: Piña-Crespo Juan C. , Talantova Maria , Micu Ileana , States Bradley , Chen H.-S. Vincent , Tu Shichun , Nakanishi Nobuki , Tong Gary , Zhang Dongxian , Heinemann Stephen F. , Zamponi Gerald W. , Stys Peter K. , Lipton Stuart A.
Published: August 2010

NMDA receptors are typically excited by a combination of glutamate and glycine. Here we describe excitatory responses in CNS myelin that are gated by a glycine agonist alone and mediated by NR1/NR3 “NMDA” receptor subunits. Response properties include activation byd-serine, inhibition by the glycine-site antagonist CNQX, and insensitivity to the glutamate-site antagonistd-APV.d-Serine responses were abrogated in NR3A-deficient mice. Our results suggest the presence of functional NR1/NR3 receptors in CNS myelin.
Movement-Related Cortical Stimulation Can Induce Human Motor Plasticity
Authors: Thabit Mohamed Nasreldin , Ueki Yoshino , Koganemaru Satoko , Fawi Gharib , Fukuyama Hidenao , Mima Tatsuya
Published: August 2010

Repeated paired associative stimulation combining peripheral nerve stimulation and transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) can produce human motor plasticity. However, previous studies used paired artificial stimuli, so that it is not known whether repetitive natural M1 activity associated with TMS can induce plasticity or not. To test this hypothesis, we developed a movement-related cortical stimulation (MRCS) protocol, in which the left M1 was stimulated by TMS at specific timing with respect to the mean expected reaction time (RT) of voluntary movement during a simple reaction time task using the right abductor pollicis brevis (APB) muscle. Seventeen normal volunteers were subjected to repeated MRCS intervention (0.2 Hz, 240 pairs). Motor function was assessed before and after MRCS. When TMS was given 50 ms before the RT of movement [MRCS(−50)], motor-evoked potential (MEP) amplitude of the right APB, but not other muscles, increased for up to 15 min post-MRCS. The RT of the right APB was also shortened. However, spinal excitability measured by F-wave did not change. When TMS was given 100 ms after the RT [MRCS(+100)], MEP amplitude was decreased. These findings show that this new MRCS protocol can produce timing-dependent motor associative plasticity, which may be clinically useful.
Development and Regeneration of Sensory Transduction in Auditory Hair Cells Requires Functional Interaction Between Cadherin-23 and Protocadherin-15
Authors: Lelli Andrea , Kazmierczak Piotr , Kawashima Yoshiyuki , Müller Ulrich , Holt Jeffrey R.
Published: August 2010

Tip links are extracellular filaments that connect pairs of hair cell stereocilia and convey tension to mechanosensitive channels. Recent evidence suggests that tip links are formed by calcium-dependent interactions between the N-terminal domains of cadherin-23 (CDH23) and protocadherin-15 (PCDH15). Mutations in either CDH23 or PCDH15 cause deafness in mice and humans, indicating the molecules are required for normal inner ear function. However, there is little physiological evidence to support a direct role for CDH23 and PCDH15 in hair cell mechanotransduction. To investigate the contributions of CDH23 and PCDH15 to mechanotransduction and tip-link formation, we examined outer hair cells of mouse cochleas during development and after chemical disruption of tip links. We found that tip links and mechanotransduction with all the qualitative properties of mature transduction recovered within 24 h after disruption. To probe tip-link formation, we measured transduction currents after extracellular application of recombinant CDH23 and PCDH15 fragments, which included putative interaction domains (EC1). Both fragments inhibited development and regeneration of transduction but did not disrupt transduction in mature cells. PCDH15 fragments that carried a mutation in EC1 that causes deafness in humans did not inhibit transduction development or regeneration. Immunolocalization revealed wild-type fragments bound near the tips of hair cell stereocilia. Scanning electron micrographs revealed that hair bundles exposed to fragments had a reduced number of linkages aligned along the morphological axis of sensitivity of the bundle. Together, the data provide direct evidence implicating CDH23 and PCDH15 proteins in the formation of tip links during development and regeneration of mechanotransduction.
Development of a Large-Scale Functional Brain Network during Human Non-Rapid Eye Movement Sleep
Authors: Spoormaker Victor I. , Schröter Manuel S. , Gleiser Pablo M. , Andrade Katia C. , Dresler Martin , Wehrle Renate , Sämann Philipp G. , Czisch Michael
Published: August 2010

Graph theoretical analysis of functional magnetic resonance imaging (fMRI) time series has revealed a small-world organization of slow-frequency blood oxygen level-dependent (BOLD) signal fluctuations during wakeful resting. In this study, we used graph theoretical measures to explore how physiological changes during sleep are reflected in functional connectivity and small-world network properties of a large-scale, low-frequency functional brain network. Twenty-five young and healthy participants fell asleep during a 26.7 min fMRI scan with simultaneous polysomnography. A maximum overlap discrete wavelet transformation was applied to fMRI time series extracted from 90 cortical and subcortical regions in normalized space after residualization of the raw signal against unspecific sources of signal fluctuations; functional connectivity analysis focused on the slow-frequency BOLD signal fluctuations between 0.03 and 0.06 Hz. We observed that in the transition from wakefulness to light sleep, thalamocortical connectivity was sharply reduced, whereas corticocortical connectivity increased; corticocortical connectivity subsequently broke down in slow-wave sleep. Local clustering values were closest to random values in light sleep, whereas slow-wave sleep was characterized by the highest clustering ratio (gamma). Our findings support the hypothesis that changes in consciousness in the descent to sleep are subserved by reduced thalamocortical connectivity at sleep onset and a breakdown of general connectivity in slow-wave sleep, with both processes limiting the capacity of the brain to integrate information across functional modules.
Microglial Receptor for Advanced Glycation End Product-Dependent Signal Pathway Drives β-Amyloid-Induced Synaptic Depression and Long-Term Depression Impairment in Entorhinal Cortex
Authors: Origlia Nicola , Bonadonna Camilla , Rosellini Alfredo , Leznik Elena , Arancio Ottavio , Yan Shirley ShiDu , Domenici Luciano
Published: August 2010

Overproduction of β-amyloid (Aβ) is a pathologic feature of Alzheimer's disease, leading to cognitive impairment. Here, we investigated the impact of cell-specific receptor for advanced glycation end products (RAGE) on Aβ-induced entorhinal cortex (EC) synaptic dysfunction. We found both a transient depression of basal synaptic transmission and inhibition of long-term depression (LTD) after the application of Aβ in EC slices. Synaptic depression and LTD impairment induced by Aβ were rescued by functional suppression of RAGE. Remarkably, the rescue was only observed in slices from mice expressing a defective form of RAGE targeted to microglia, but not in slices from mice expressing defective RAGE targeted to neurons. Moreover, we found that the inflammatory cytokine IL-1β (interleukin-1β) and stress-activated kinases [p38 MAPK (p38 mitogen-activated protein kinase) and JNK (c-Jun N-terminal kinase)] were significantly altered and involved in RAGE signaling pathways depending on RAGE expression in neuron or microglia. These findings suggest a prominent role of microglial RAGE signaling in Aβ-induced EC synaptic dysfunction.
Insular Cortex Activity Is Associated with Effects of Negative Expectation on Nociceptive Long-Term Habituation
Authors: Rodriguez-Raecke Rea , Doganci Beril , Breimhorst Markus , Stankewitz Anne , Büchel Christian , Birklein Frank , May Arne
Published: August 2010

It is generally accepted that acute painful experience is influenced by context information shaping expectation and modulating attention, arousal, stress, and mood. However, little is known about the nature, duration, and extent of this effect, particularly regarding the negative expectation. We used a standardized longitudinal pain paradigm and painful heat test stimuli in healthy participants over a time course of 8 consecutive days, inducing nociceptive habituation over time. Thirty-eight healthy volunteers were randomly assigned to two different groups. One group received the information that the investigators expected the pain intensity to increase over time (context group). The other group was not given any information (control group). All participants rated the pain intensity of the daily standardized pain paradigm on a visual analog scale. In agreement with previous studies the pain ratings in the control group habituated over time. However, the context group reported no change of pain ratings over time. Functional imaging data showed a difference between the two groups in the right parietal operculum. These data suggest that a negative context not only has an effect on immediate pain but can modulate perception of pain in the future even without experience/conditioning. Neuronally, this process is mediated by the right opercular region.
Developmental Mechanisms for Suppressing the Effects of Delayed Release at the Endbulb of Held
Authors: Yang Hua , Xu-Friedman Matthew A.
Published: August 2010

Delayed release of neurotransmitter, also called asynchronous release, is commonly observed at synapses, yet its influence on transmission of spike information is unknown. We examined this issue at endbulb of Held synapses, which are formed by auditory nerve fibers onto bushy cells in the cochlear nucleus. Endbulbs from CBA/CaJ mice aged P6–P49 showed prominent delayed release when driven at physiologically relevant rates. In bushy cells from mice before the onset of hearing (P6–P12), spikes were driven by delayed release up to 100 ms after presynaptic activity. However, no such spikes were observed in bushy cells from mice after the onset of hearing (>P14). Dynamic-clamp experiments indicated that delayed release can drive spikes in older bushy cells provided synchronous release is absent, suggesting that activity normally suppresses these spikes. Application of apamin or α-dendrotoxin revealed late spikes in older bushy cells, suggesting that postsynaptic activation of KV1.x and SK channels during spiking suppresses the subsequent effects of delayed release. The developmental upregulation of these potassium channels would be highly adaptive for temporally precise auditory processing. Furthermore, delayed release appeared to influence synchronous neurotransmitter release. Enhancement of delayed release using strontium was correlated with lower firing probability in current clamp and smaller synchronous EPSCs in voltage clamp. EGTA-AM had the opposite effects. These effects were consistent with delayed and synchronous release competing for a single vesicle pool. Thus delayed release apparently has negative presynaptic and postsynaptic consequences at the endbulb, which are partly mitigated by postsynaptic potassium channel expression.
IdGene Regulation and Function in the Prosensory Domains of the Chicken Inner Ear: A Link between Bmp Signaling andAtoh1
Authors: Kamaid Andrés , Neves Joana , Giráldez Fernando
Published: August 2010

Bone morphogenetic proteins (Bmps) regulate the expression of the proneural geneAtoh1and the generation of hair cells in the developing inner ear. The present work explored the role ofInhibitor of Differentiationgenes (Id1-3) in this process. The results show thatIdgenes are expressed in the prosensory domains of the otic vesicle, along withBmp4andBmp7. Those domains exhibit high levels of the phosphorylated form of Bmp-responding R-Smads (P-Smad1,5,8), and of Bmp-dependent Smad transcriptional activity as shown by the BRE-tk-EGFP reporter. Increased Bmp signaling induces the expression ofId1-3along with the inhibition ofAtoh1. Conversely, the Bmp antagonist Noggin or the Bmp-receptor inhibitor Dorsomorphin elicit opposite effects, indicating that Bmp signaling is necessary forIdexpression andAtoh1regulation in the otocyst. The forced expression ofId3is sufficient to reduceAtoh1expression and to prevent the expression of hair cell differentiation markers. Together, these results suggest thatIdsare part of the machinery that mediates the regulation of hair cell differentiation exerted by Bmps. In agreement with that, during hair cell differentiationBmp4expression, P-Smad1,5,8 levels andIdexpression are downregulated from hair cells. However,Idsare also downregulated from the supporting cells which contrarily to hair cells exhibit high levels ofBmp4expression, P-Smad1,5,8, and BRE-tk-EGFP activity, suggesting that in these cellsIdsescape from Bmp/Smad signaling. The differential regulation ofIdsin time and space may underlie the multiple functions of Bmp signaling during sensory organ development.
Dependence on a Retinophilin/Myosin Complex for Stability of PKC and INAD and Termination of Phototransduction
Authors: Venkatachalam Kartik , Wasserman David , Wang Xiaoyue , Li Ruoxia , Mills Eric , Elsaesser Rebecca , Li Hong-Sheng , Montell Craig
Published: August 2010

Normal termination of signaling is essential to reset signaling cascades, especially those such as phototransduction that are turned on and off with great rapidity. Genetic approaches inDrosophilaled to the identification of several proteins required for termination, including protein kinase C (PKC), NINAC (neither inactivation nor afterpotential C) p174, which consists of fused protein kinase and myosin domains, and a PDZ (postsynaptic density-95/Discs Large/zona occludens-1) scaffold protein, INAD (inactivation no afterpotential D). Here, we describe a mutation affecting a poorly characterized but evolutionarily conserved protein, Retinophilin (Retin), which is expressed primarily in the phototransducing compartment of photoreceptor cells, the rhabdomeres. Retin and NINAC formed a complex and were mutually dependent on each other for expression. Loss ofretinresulted in an age-dependent impairment in termination of phototransduction. Mutations that affect termination of the photoresponse typically lead to a reduction in levels of the major rhodopsin (Rh1) to attenuate signaling. Consistent with the slower termination inretin1, the mutant photoreceptor cells exhibited increased endocytosis of Rh1 and a decline in Rh1 protein. The slower termination inretin1was a consequence of a cascade of defects, which began with the reduction in NINAC p174 levels. The diminished p174 concentration caused a decrease in INAD. Because PKC requires interaction with INAD for protein stability, this leads to reduction in PKC levels. The decline in PKC was age dependent and paralleled the onset of the termination phenotype inretin1mutant flies. We conclude that the slower termination of the photoresponse inretin1resulted from a requirement for the Retin/NINAC complex for stability of INAD and PKC.
Transcranial Electric Stimulation Entrains Cortical Neuronal Populations in Rats
Authors: Ozen Simal , Sirota Anton , Belluscio Mariano A. , Anastassiou Costas A. , Stark Eran , Koch Christof , Buzsáki György
Published: August 2010

Low intensity electric fields have been suggested to affect the ongoing neuronal activityin vitroand in human studies. However, the physiological mechanism of how weak electrical fields affect and interact with intact brain activity is not well understood. We performedin vivoextracellular and intracellular recordings from the neocortex and hippocampus of anesthetized rats and extracellular recordings in behaving rats. Electric fields were generated by sinusoid patterns at slow frequency (0.8, 1.25 or 1.7 Hz) via electrodes placed on the surface of the skull or the dura. Transcranial electric stimulation (TES) reliably entrained neurons in widespread cortical areas, including the hippocampus. The percentage of TES phase-locked neurons increased with stimulus intensity and depended on the behavioral state of the animal. TES-induced voltage gradient, as low as 1 mV/mm at the recording sites, was sufficient to phase-bias neuronal spiking. Intracellular recordings showed that both spiking and subthreshold activity were under the combined influence of TES forced fields and network activity. We suggest that TES in chronic preparations may be used for experimental and therapeutic control of brain activity.
Beta-Band Activity during Motor Planning Reflects Response Uncertainty
Authors: Tzagarakis Charidimos , Ince Nuri F. , Leuthold Arthur C. , Pellizzer Giuseppe
Published: August 2010

It has been known for many years that the power of beta-band oscillatory activity in motor-related brain regions decreases during the preparation and execution of voluntary movements. However, it is not clear yet whether the amplitude of this desynchronization is modulated by any parameter of the motor task. Here, we examined whether the degree of uncertainty about the upcoming movement direction modulated beta-band desynchronization during motor preparation. To this end, we recorded whole-head neuromagnetic signals while human subjects performed an instructed-delay reaching task with one, two, or three possible target directions. We found that the reduction of power of beta-band activity (16–28 Hz) during motor preparation was scaled relative to directional uncertainty. Furthermore, we show that the change of beta-band power correlates with the change of latency of response associated with response uncertainty. Finally, we show that the main source of beta-band desynchronization was located in the peri-Rolandic region. The results establish directional uncertainty as an important determinant of beta-band power during motor preparation and indicate that neural activity in the sensorimotor cortex during motor preparation covaries with directional uncertainty.
Genetic Targeting of ERK1 Suggests a Predominant Role for ERK2 in Murine Pain Models
Authors: Alter Benedict J. , Zhao Chengshui , Karim Farzana , Landreth Gary E. , Gereau Robert W.
Published: August 2010

The extracellular signal-regulated kinase (ERK) isoforms, ERK1 and ERK2, are believed to be key signaling molecules in nociception and nociceptive sensitization. Studies using inhibitors targeting the shared ERK1/2 upstream activator, mitogen-activated protein kinase kinase (MEK), and transgenic mice expressing a dominant-negative form of MEK have established the importance of ERK1/2 signaling. However, these techniques do not discriminate between ERK1 and ERK2. To dissect the function of each isoform in pain, we used mice with a targeted genetic deletion of ERK1 [ERK1 knock-out (KO)] to test the hypothesis that ERK1 is required for behavioral sensitization in rodent pain models. Despite activation (phosphorylation) of ERK1 after acute noxious stimulation and in models of chronic pain, we found that ERK1 was not required for formalin-induced spontaneous behaviors, complete Freund's adjuvant-induced heat and mechanical hypersensitivity, and spared nerve injury-induced mechanical hypersensitivity. However, ERK1 deletion did delay formalin-induced long-term heat hypersensitivity, without affecting formalin-induced mechanical hypersensitivity, suggesting that ERK1 partially shapes long-term responses to formalin. Interestingly, ERK1 deletion resulted in elevated basal ERK2 phosphorylation. However, this did not appear to influence nociceptive processing, since inflammation-induced ERK2 phosphorylation and pERK1/2 immunoreactivity in spinal cord were not elevated in ERK1 KO mice. Additionally, systemic MEK inhibition with SL327 (α-[amino[(4-aminophenyl)thio]methylene]-2-(trifluoromethyl)benzeneacetonitrile) attenuated formalin-induced spontaneous behaviors similarly in wild-type and ERK1 KO mice, indicating that unrelated signaling pathways do not functionally compensate for the loss of ERK1. Together, these results suggest that ERK1 plays a limited role in nociceptive sensitization and support a predominant role for ERK2 in these processes.
Sebastiãosalgado, Behind the Lens
Authors: Singer Audrey
Published: August 2010

Brazilian-born documentary photographer and one-time economist Sebastião Salgado has made his reputation with in-depth projects delving into social issues such as inequality, development, urbanization, labor, migration, and globalization.
Neighborhood Communities, Remixed for 2010
Authors: Pace Jennifer
Published: August 2010

Picture it: it's early morning, and you step out onto your front yard, covered in flannel and fuzzy slippers, to retrieve the paper. You reach down, snatch the news from its regular spot in the mud puddle (darn paperboy…) and look up. What's that? Across the street? A moving truck. Your brows furrow, lips purse, and you let out a slight groan. “Well, herewe go again…Who is it this time? Do they mow their lawn? Speed? Blast loud music? Are they friendly? Are they trouble?” And most importantly, “Hmm… I wonder if they're renters.”