bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why jackknifing yields good latency estimates
Authors: Miller Jeff , Ulrich Rolf , Schwarz Wolfgang 
Published: January 2009

AbstractWe compared individual‐participant and jackknife‐based methods for scoring the onset latencies of event‐related potential (ERP) components using a diffusion process as a model for an ERP. We studied “ramp‐like” components in which the true ERP increases or decreases monotonically, except for noise. If the growth rates of such components vary across participants, the jackknife‐based measure can easily have only 10%–20% as much error variance as the traditional method, and this advantage is magnified with more participants. We also studied ∩‐shaped or “bump‐like” components. Jackknifing generally yielded smaller error variances with these components too, especially when the component's peak amplitude varied across participants, but less so if the component's peak latency varied. These results help illuminate the reasons for the superiority of jackknife‐based onset latency measures over traditional measures in recent simulations.
Precues enable multiple response preprogramming: Evidence from startle
Authors: Carlsen Anthony N. , Chua Romeo , Summers Jeffrey J. , Inglis J. Timothy , Sanderson David J. , Franks Ian M. 
Published: January 2009

AbstractWhen one or more response dimensions in a choice reaction time (RT) task are provided beforehand (or precued), RT decreases, indicating that the precued part of a response was prepared in advance. In this study, a startling acoustic stimulus was used to investigate the amount of preprogramming that occurs when part of the response is precued because a startling stimulus has been shown to directly trigger preprogrammed responses. Participants performed wrist flexion/extension movements in a precued one to four choice RT paradigm. A control auditory stimulus (82 dB) or a startling acoustic stimulus (124 dB) accompanied the visual “go” signal on each trial. Although RT latencies were significantly reduced by the startle, many more errors were observed in the startled conditions. Importantly, the errors seen at short RT latencies largely reflected multiple movements to the cued response alternatives, suggesting that multiple responses were preprogrammed.
Sensory detection thresholds are modulated across the cardiac cycle: Evidence that cutaneous sensibility is greatest for systolic stimulation
Authors: Edwards L. , Ring C. , McIntyre D. , Winer J. B. , Martin U. 
Published: January 2009

AbstractThe visceral afferent feedback hypothesis proposes that sensorimotor function is impaired by cortical inhibition associated with increased baroreceptor activation. This study is the first to examine the effects of naturally occurring variations in baroreceptor activity across the cardiac cycle on cutaneous sensory detection thresholds. In each trial, an electrocutaneous stimulus was delivered to the index finger at one of three intervals (0, 300, 600 ms) after the R‐wave of the electrocardiogram. Separate interleaving up‐down staircases were used to determine the 50% detection threshold for each R‐wave to stimulation interval. Cutaneous sensory detection thresholds were lower for stimuli presented at R+300 ms than R+0 ms or R+600 ms. The finding that cutaneous sensibility was greater when stimulated during systole than diastole may be accounted for by a modified afferent feedback hypothesis.
Developmental co‐ordination disorder (DCD) in adolescents and adults in further and higher education
Authors: Kirby Amanda , Sugden David , Beveridge Sally , Edwards Lisa 
Published: January 2009

Few studies have looked at the strengths and weaknesses and needs of students with developmenal co‐ordination disorder (DCD). This paper describes a cohort of 93 UK students currently studying at further or higher education and who have reported motor difficulties present since childhood. The study group consisted of 21 reporting to have DCD only, 38 with DCD plus another diagnosis (a combination of any of the following: dyslexia, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), learning difficulties); 23 subjects reporting dyslexia only, and 11 students who have not been formally diagnosed.The aim of this study was to first ascertain the similarities and differences between the students in the type of support received in childhood and while at university. The second goal was to examine the reported strengths and difficulties and see how they vary for each subgroup.The DCD group reported higher levels of motor‐related difficulties such as handwriting and also executive functioning difficulties. They also had higher levels of professional support given in childhood and were also more likely to be living at home with parents compared with the dyslexia group. Despite different types of difficulties reported in the DCD group, the range of student support given across all groups was similar. Significantly more of the dyslexia group were reported to be in receipt of disability student allowance than the DCD group. The DCD and other disorders group were seen to be an intermediary group in most of the areas studied.
Chronic copper exposure exacerbates both amyloid and tau pathology and selectively dysregulates cdk5 in a mouse model of AD
Authors: Kitazawa Masashi , Cheng David , LaFerla Frank M. 
Published: January 2009

AbstractExcess copper exposure is thought to be linked to the development of Alzheimer’s disease (AD) neuropathology. However, the mechanism by which copper affects the CNS remains unclear. To investigate the effect of chronic copper exposure on both beta‐amyloid and tau pathologies, we treated young triple transgenic (3×Tg‐AD) mice with 250 ppm copper‐containing water for a period of 3 or 9 months. Copper exposure resulted in altered amyloid precursor protein processing; increased accumulation of the amyloid precursor protein and its proteolytic product, C99 fragment, along with increased generation of amyloid‐beta peptides and oligomers. These changes were found to be mediated via up‐regulation of BACE1 as significant increases in BACE1 levels and deposits were detected around plaques in mice following copper exposure. Furthermore, tau pathology within hippocampal neurons was exacerbated in copper‐exposed 3×Tg‐AD group. Increased tau phosphorylation was closely correlated with aberrant cdk5/p25 activation, suggesting a role for this kinase in the development of copper‐induced tau pathology. Taken together, our data suggest that chronic copper exposure accelerates not only amyloid pathology but also tau pathology in a mouse model of AD.
Lithium enhances the neuronal differentiation of neural progenitor cellsin vitroand after transplantation into the avulsed ventral horn of adult rats through the secretion of brain‐derived neurotrophic factor
Authors: Su Huanxing , Zhang Wenming , Guo Jiasong , Guo Anchen , Yuan Qiuju , Wu Wutian 
Published: January 2009

AbstractThis study was undertaken to elucidate the molecular mechanisms by which lithium regulates the development of spinal cord‐derived neural progenitor cells (NPCs)in vitroand after transplantedin vivo. Our results show that lithium at the therapeutic concentration significantly increases the proliferation and neuronal differentiation of NPCsin vitro.Specific ELISAs, western blotting, and quantitative real‐time RT‐PCR assays demonstrate that lithium treatment significantly elevates the expression and production of brain‐derived neurotrophic factor (BDNF) by NPCs in culture. Application of a BDNF neutralizing antibody in culture leads to a marked reduction in the neurogenesis of lithium‐treated NPCs to the control level. However, it shows no effects on the proliferation of lithium‐treated NPCs. These findings suggest that the BDNF pathway is possibly involved in the supportive role of lithium in inducing NPC neurogenesis but not proliferation. This study also provides evidence that lithium is able to elevate the neuronal generation and BDNF production of NPCs after transplantation into the adult rat ventral horn with motoneuron degeneration because of spinal root avulsion, which highlights the therapeutic potential of lithium in cell replacement strategies for spinal cord injury because of its ability to promote neuronal differentiation and BDNF production of grafted NPCs in the injured spinal cord.
U18666A, a cholesterol‐inhibition agent, modulates human neuronal nicotinic acetylcholine receptors heterologously expressed in SH‐EP1 cell line
Authors: Zheng Chao , Wang Meng‐Ya , Liu Qiang , Wakui Makoto , Whiteaker Paul , Lukas Ronald J. , Wu Jie 
Published: January 2009

AbstractIn this study, we evaluate the effects of (3β)‐3‐[2‐(diethylamino)ethoxy]androst‐5‐en‐17‐one dihydrochloride (U18666A), a cholesterol synthesis/transporter inhibitor, on selected human neuronal nicotinic acetylcholine receptors (nAChRs) heterologously expressed in the SH‐EP1 cell line using whole‐cell patch‐clamp recordings. The results indicate that with 2‐min pretreatment, U18666A inhibited different nAChR subtypes with a rank‐order of potency (IC50of whole‐cell peak current): α4β2 (8.0 ± 3.0 nM) > α3β2 (1.7 ± 0.4 μM) > α4β4 (26 ± 7.2 μM) > α7 (> 100 μM), suggesting this compound is more selective to α4β2‐nAChRs. Thus, the pharmacological profiles and mechanisms of U18666A acting on α4β2‐nAChRs were investigated in detail. U18666A suppresses both peak and steady state components of whole‐cell currents mediated by human α4β2‐nAChRs in response to nicotine. In nicotine‐induced concentration–response curves, U18666A reduces nicotine‐induced current at maximally effective agonist concentrations without influencing nicotine’s EC50value, suggesting a non‐competitive inhibition. U18666A‐induced inhibition of nAChR function is concentration‐, voltage‐, and use‐dependent, suggesting an open channel block. Taken into consideration of ∼10 000‐fold enhancement of the potency of U18666A after 2‐min pre‐treatment, this compound also likely inhibits α4β2‐nAChRs through a close channel block. In addition, the U18666A‐induced inhibition in α4β2‐nAChRs is not mediated by either increased receptor endocytosis or altered cell cholesterol. These data indicate that U18666A is a potent antagonist of α4β2‐nAChRs and may be useful as a tool in the functional characterization and pharmacological profiling of nAChRs, as well as a potential candidate for smoking cessation.
Lithium induces clearance of protease resistant prion protein in prion‐infected cells by induction of autophagy
Authors: Heiseke Andreas , Aguib Yasmine , Riemer Constanze , Baier Michael , Schätzl Hermann M. 
Published: January 2009

AbstractLithium is used for several decades to treat manic‐depressive illness (bipolar affective disorder). Recently, it was found that lithium induces autophagy, thereby promoting the clearance of mutant huntingtin and α‐synucleins in experimental systems. We show here for the first time that lithium significantly reduces the amount of pathological prion protein (PrPSc) in prion‐infected neuronal and non‐neuronal cultured cells by inducing autophagy. Treatment of prion‐infected cells with 3‐methyladenine, a potent inhibitor of autophagy, counteracted the anti‐prion effect of lithium, demonstrating that induction of autophagy mediates degradation of PrPSc. Co‐treatment with lithium and rapamycin, a drug widely used to induce autophagy, had an additive effect on PrPSc clearance compared to treatment with either drug alone. In addition, we provide evidence that the ability to reduce PrPSc and to induce autophagy is common for diverse lithium compounds, not only for the drug lithium chloride, usually administered in clinical therapy. Furthermore, we show here that besides reduction of PrPSc‐aggregates, lithium‐induced autophagy also slightly reduces the levels of cellular prion protein. Limiting the substrate available for conversion of cellular prion protein into PrPSc may provide an additional mechanism for reduction of PrPSc by lithium‐induced autophagy.
Rapid substrate‐induced down‐regulation in function and surface localization of dopamine transporters: rat dorsal striatum versus nucleus accumbens
Authors: Richards Toni L. , Zahniser Nancy R. 
Published: January 2009

AbstractThe dopamine transporter (DAT) substrates dopamine, d‐amphetamine (AMPH), and methamphetamine are known to rapidly and transiently reduce DAT activity and/or surface expression in dorsal striatum and heterologous expression systems. We sought to determine if similar substrate‐induced regulation of DATs occurs in rat nucleus accumbens. In dorsal striatum synaptosomes, brief (15‐min)in vitrosubstrate pre‐exposure markedly decreased maximal [3H]dopamine uptake velocity whereas identical substrate pre‐exposure in nucleus accumbens synaptosomes produced a smaller, non‐significant reduction. However, 45 min after systemic AMPH administration, maximalex vivo[3H]dopamine uptake velocity was significantly reduced in both brain regions. Protein kinase C inhibition blocked AMPH’s down‐regulation of DAT activity. DAT synaptosomal surface expression was not modified following either the briefin vitroorin vivoAMPH pre‐exposure but was reduced after a longer (1‐h)in vitropre‐exposure in both brain regions. Together, our findings suggest that relatively brief substrate exposure results in greater down‐regulation of DAT activity in dorsal striatum than in nucleus accumbens. Moreover, exposure to AMPH appears to regulate striatal DATs in a biphasic manner, with an initial protein kinase C‐dependent decrease in DAT‐mediated uptake velocity and then, with longer exposure, a reduction in DAT surface expression.
Proteomic analysis reveals novel binding partners of metabotropic glutamate receptor 1
Authors: Francesconi Anna , Kumari Ranju , Suzanne Zukin R. 
Published: January 2009

AbstractRegulated trafficking of neurotransmitter receptors is critical to normal neurodevelopment and neuronal signaling. Group I mGluRs (mGluR1/5 and their splice variants) are G protein‐coupled receptors enriched at excitatory synapses, where they serve to modulate glutamatergic transmission. The mGluR1 splice variants mGluR1a and mGluR1b are broadly expressed in the central nervous system and differ in their signaling and trafficking properties. Several proteins have been identified that selectively interact with mGluR1a and participate in receptor trafficking but no proteins interacting with mGluR1b have thus far been reported. We have used a proteomic strategy to isolate and identify proteins that co‐purify with mGluR1b in Madin‐Darby Canine Kidney (MDCK) cells, an established model system for trafficking studies. Here, we report the identification of 10 novel candidate mGluR1b‐interacting proteins. Several of the identified proteins are structural components of the cell cytoskeleton, while others serve as cytoskeleton‐associated adaptors and motors or endoplasmic reticulum‐associated chaperones. Findings from this work will help unravel the complex cellular mechanisms underlying mGluR trafficking under physiological and pathological conditions.
A Pilot Trial of the Alpha‐1 Adrenergic Antagonist, Prazosin, for Alcohol Dependence
Authors: Simpson Tracy L. , Saxon Andrew J. , Meredith Charles W. , Malte Carol A. , McBride Brittney , Ferguson Laura C. , Gross Christopher A. , Hart Kim L. , Raskind Murray 
Published: January 2009

Background:  Current medications for alcohol dependence (AD) show only modest efficacy. None target brain noradrenergic pathways. Theory and preclinical evidence suggest that noradrenergic circuits may be involved in alcohol reinforcement and relapse. We therefore tested the α‐1 adrenergic receptor antagonist, prazosin, as a pharmacotherapy for AD.Methods:  We randomized 24 participants with AD but without posttraumatic stress disorder to receive either prazosin or placebo in a 6‐week, double‐blind pilot study. Medication was titrated to a target dose of 4 mg QAM, 4 mg QPM, and 8 mg QHS by the end of week 2. Participants received 5 medical management treatment sessions. Participants were reminded 3 times each day via a text pager to take medications and to call a telephone monitoring system once daily to provide self‐reports of alcohol consumption and craving, the primary outcome measures. Results were analyzed using mixed linear regression adjusted for drinking days per week at baseline and week number.Results:  Twenty of the 24 (83%) subjects completed. Among the completers, the prazosin group reported fewer drinking days per week than the placebo group during the final 3 weeks of the study. Since only 1 woman was randomized to placebo and only three women completed the trial, the following results focus on the 17 male completers. The prazosin group reported fewer drinking days per week and fewer drinks per week during the final 3 weeks of the study; average total number of drinking days for the placebo group 5.7 (SEM 1.9) versus 0.9 (SEM 0.5) for the prazosin group, and average total number of drinks 20.8 (SEM 6.5) for the placebo group versus 2.6 (SEM 1.3) for the prazosin group. Rates of adverse events were equivalent across conditions.Conclusions:  Prazosin holds promise as a pharmacologic treatment for AD and deserves further evaluation in a larger controlled trial.
Patterns of Ethanol Intake in Preadolescent, Adolescent, and Adult Wistar Rats Under Acquisition, Maintenance, and Relapse‐Like Conditions
Authors: García‐Burgos David , González Felisa , Manrique Tatiana , Gallo Milagros 
Published: January 2009

Background:  Animal behavioral models of voluntary ethanol consumption represent a valuable tool to investigate the relationship between age and propensity to consume alcohol using an experimental methodology. Although adolescence has been considered as a critical age, few are the studies that consider the preadolescence age. This study examines the ethanol consumption/preference and the propensity to show an alcohol deprivation effect (ADE) after a short voluntary ethanol exposure from a developmental perspective.Methods:  Three groups of heterogeneous Wistar rats of both sexes with ad libitum food and water were exposed for 10 days to 3 ethanol solutions at 3 different ontogenetic periods: preadolescence (PN19), adolescence (PN28), and adulthood (PN90). Ethanol intake (including circadian rhythm), ethanol preference, water and food consumption, and ADE were measured.Results:  During the exposure, the 3 groups differed in their ethanol intake; the greatest amount of alcohol (g/kg) was consumed by the preadolescent rats while the adolescents showed a progressive decrease in alcohol consumption as they approached the lowest adult levels by the end of the assessed period. The pattern of ethanol consumption was not fully explained in terms of hyperphagia and/or hyperdipsia at early ages, and showed a wholly circadian rhythm in adolescent rats. After an abstinence period of 7 days, adult rats showed an ADE measured both as an increment in ethanol consumption and preference, whereas adolescent rats only showed an increment in ethanol preference. Preadolescent rats decreased their consumption and their preference remained unchanged.Conclusions:  In summary, using a short period of ethanol exposure and a brief deprivation period the results revealed a direct relationship between chronological age and propensity to consume alcohol, being the adolescence a transition period from the infant to the adult pattern of alcohol consumption. Preadolescent animals showed the highest ethanol consumption level. The ADE was only found in adult animals for both alcohol consumption and preference, whereas adolescents showed an ADE only for preference. No effect of sex was detected in any phase of the experiment.
Improved wound stability with a modified minimally invasive surgical technique in the regenerative treatment of isolated interdental intrabony defects
Authors: Cortellini Pierpaolo , Tonetti Maurizio S. 
Published: January 2009

AbstractAims: This paper describes a modified surgical approach of the minimally invasive surgical technique (modified minimally invasive surgical technique, M‐MIST) and preliminarily evaluates its applicability and clinical performances in the treatment of isolated deep intrabony defects in combination with amelogenins.Material and Methods: Twenty deep isolated intrabony defects in 20 patients were studied. Fifteen were surgically accessed with the M‐MIST, while in five sites, which presented a lingual intrabony component, the conventional MIST had to be applied. The M‐MIST consisted of a buccal incision of the defect‐associated papilla, according to the principles of the papilla preservation techniques. Only a buccal flap was raised while the interdental papilla was left in situ. The granulation tissue filling the defect was dissected and removed, leaving the interdental and palatal tissues untouched. Root instrumentation and application of the regenerative material were performed before suturing. Primary closure of the flaps was attained with a single internal modified mattress suture. Surgery was performed with the aid of an operating microscope and microsurgical instruments.Results: The surgical chair‐time of the M‐MIST‐treated sites (N=15) was 56±8.64 min. Early wound healing was uneventful: primary wound closure was attained and maintained in all sites. No oedema or haematoma was noted. Patients did not report pain or discomfort. The 1‐year clinical attachment level (CAL) gain was 4.5±1.4 mm in defects 6±1.5 mm deep. Residual probing depths (PDs) were 3.1±0.6 mm. A minimal increase of 0.1±0.3 mm in gingival recession between baseline and 1 year was observed.Conclusions: M‐MIST was applicable on 15 isolated interproximal defects out of 20 selected ones. It resulted in very limited patient morbidity and excellent clinical improvements. These outcomes should be confirmed in a larger study.
Implants placed in combination with an internal sinus lift without graft material: an analysis of short‐term failure
Authors: Gabbert Olaf , Koob Andreas , Schmitter Marc , Rammelsberg Peter 
Published: January 2009

AbstractAim: Investigation of the short‐term survival of implants placed in combination with an internal sinus lift (ISL) without graft material.Material and Methods: Thirty‐six patients received 92 screw‐shaped dental implants in combination with an ISL. No bone grafts or bone substitutes were used. Forty‐four patients with 77 implants in the native posterior maxilla served as controls. X‐rays taken after implant placement and 6 months later were evaluated for the presence of bone gain at the apical aspect of the implants. Kaplan–Meier survival curves and Cox regression analysis were used to estimate survival curves and to isolate risk factors for implant failures.Results: Within a mean observation period of 1.2 years (minimum 9 months; maximum 3.7 years), four failures were recorded in the experimental group and two in the controls. The probability of survival was above 94% for both groups. Six–nine months after surgery, bone gain was observed in 29 out of 92 implants. Comparison of the experimental group and controls revealed no effect of ISL and membrane perforation on the probability of survival.Conclusions: Promising short‐term outcomes were observed for implants with ISL without graft material; for a substantial proportion of implants, apical bone gain was observed in the first 6–9 months.