bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential transcript expression between the microfilariae of the filarial nematodes, Brugia malayi and B. pahangi
Authors: Kariuki Michael M , Hearne Leonard B , Beerntsen Brenda T
Published: April 2010

Background

Brugia malayi and B. pahangi are two closely related nematodes that cause filariasis in humans and animals. However, B. pahangi microfilariae are able to develop in and be transmitted by the mosquito, Armigeres subalbatus, whereas most B. malayi are rapidly melanized and destroyed within the mosquito hemocoel. A cross-species microarray analysis employing the B. malayi V2 array was carried out to determine the transcriptional differences between B. malayi and B. pahangi microfilariae with similar age distribution.

Results

Following microarray data analysis, a list of preferentially expressed genes in both microfilariae species was generated with a false discovery rate estimate of 5% and a signal intensity ratio of 2 or higher in either species. A total of 308 probes were preferentially expressed in both species with 149 probes, representing 123 genes, in B. pahangi microfilariae and 159 probes, representing 107 genes, in B. malayi microfilariae. In B. pahangi, there were 76 (62%) up-regulated transcripts that coded for known proteins that mapped into the KEGG pathway compared to 61 (57%) transcripts in B. malayi microfilariae. The remaining 47 (38%) transcripts in B. pahangi and 46 (43%) transcripts in B. malayi microfilariae were comprised almost entirely of hypothetical genes of unknown function. Twenty-seven of the transcripts in B. pahangi microfilariae coded for proteins that associate with the secretory pathway compared to thirty-nine in B. malayi microfilariae. The data obtained from real-time PCR analysis of ten genes selected from the microarray list of preferentially expressed genes showed good concordance with the microarray data, indicating that the microarray data were reproducible.

Conclusion

In this study, we identified gene transcripts that were preferentially expressed in the microfilariae of B. pahangi and B. malayi, some of which coded for known immunomodulatory proteins. These comparative transcriptome data will be of interest to researchers keen on understanding the inherent differences, at the molecular level, between B. malayi and B. pahangi microfilariae especially because these microfilariae are capable of surviving in the same vertebrate host but elicit different immune response outcomes in the mosquito, Ar. subalbatus.
The analysis of oral microbial communities of wild-type and toll-like receptor 2-deficient mice using a 454 GS FLX Titanium pyrosequencer
Authors: Chun Jongsik , Kim Kap Y , Lee Jae-Hak , Choi Youngnim
Published: April 2010

Background

Although mice have long served as an animal model for periodontitis, information on the composition of their indigenous oral microbiota is limited. The aim of the current study was to characterize mouse oral bacterial flora by applying extensive parallel pyrosequencing using the latest model pyrosequencer, a Roche/454 Genome Sequencer FLX Titanium. In addition, the effect of Toll-like receptor (TLR) 2 deficiency on oral microbiota was evaluated.

Results

Eight oral bacterial communities of wild-type (n = 4) and TLR2 knock-out (n = 4) C57BL/6 mice were characterized by analyzing 80,046 reads of 16S rRNA genes obtained by pyrosequencing. Excluding the PCR primers, the average length of each sequencing product was 443 bp. The average species richness of the murine oral bacterial communities was estimated to be about 200, but the communities were dominated by only two main phyla and several species. Therefore, the bacterial communities were relatively simple. The bacterial composition of the murine oral microbiota was significantly different from that of humans, and the lack of TLR2 had a negligible effect on the murine oral microbiota.

Conclusion

Pyrosequencing using the Roche/454 FLX Titanium successfully characterized mouse oral bacterial communities. The relatively simple oral bacterial communities of mice were not affected by TLR2 deficiency. These findings will provide a basis for future studies on the role of periodontal pathogens in the murine model of periodontitis.
Estimation of HIV-1 incidence among five focal populations in Dehong, Yunnan: a hard hit area along a major drug trafficking route
Authors: Duan Song , Shen Sheng , Bulterys Marc , Jia Yujiang , Yang Yuecheng , Xiang Lifeng , Tian Fei , Lu Lin , Xiao Yao , Wang Minjie , Jia Manhong , Jiang Huazhou , Vermund Sten H , Jiang Yan
Published: April 2010

Background

Since 1989 when the first 146 HIV positives in China were identified, Dehong Prefecture had been one of the areas hardest-hit by HIV in China. The local and national governments have put substantial financial resources into tackling the HIV epidemic in Dehong from 2004. The objective of this study was to track dynamic changes in HIV-1 prevalence and incidence among five focal populations in Dehong and to assess the impact of HIV prevention and control efforts.

Methods

Consecutive cross-sectional surveys conducted in five focal populations between 2004 and 2008. Specimens seropositive for HIV were tested with the BED IgG capture enzyme immunoassay to identify recent seroconversions (median, 155 days) using normalized optical density of 0.8 and adjustments.

Results

From 2004 to 2008, estimated annual HIV incidence among injecting drug users (IDUs) decreased significantly [from 15.0% (95% CI = 11.4%-18.5%) in 2004 to 4.3% (95% CI = 2.4%-6.2%) in 2008; trend test P < 0.0001]. The incidence among other focal populations, such as HIV discordant couples (varying from 5.5% to 4.7%), female sex workers (varying from 1.4% to 1.3%), pregnant women (0.1%), and pre-marital couples (0.2 to 0.1%) remained stable. Overall, the proportion of recent HIV-1 infections was higher among females than males (P < 0.0001).

Conclusions

The HIV epidemic in Dehong continued to expand during a five-year period but at a slowing rate among IDUs, and HIV incidence remains high among IDUs and discordant couples. Intensive prevention measures should target sub-groups at highest risk to further slow the epidemic and control the migration of HIV to other areas of China, and multivariate analysis is needed to explore which measures are more effective for different populations.
Prolyl oligopeptidase is inhibited in relapsing-remitting multiple sclerosis
Authors: Tenorio-Laranga Jofre , Coret-Ferrer Francisco , Casanova-Estruch Buenaventura , Burgal María , García-Horsman J Arturo
Published: April 2010

Background

Multiple sclerosis (MS) is a complex, inflammatory and neurodegenerative disease of the central nervous system leading to long-term disability. Recent studies indicate a close association between inflammation and neurodegeneration in all lesions and disease stages of MS. Prolyl oligopeptidase (POP) is a proline-specific serine protease that cleaves several neuroactive peptides. This peptidase has been implicated in neurodegeneration, as well as in the modulation of the inflammatory response.

Methods

We examined plasma POP and the levels of an endogenous POP inhibitor from relapsing remitting MS patients and compared these with healthy controls, by monitoring the fluorescent changes due to standard fluorescently labelled substrate cleavage. We analysed the data in relationship to patient age and disease disability status.

Results

We observed a significant decrease in POP activity in plasma of relapsing remitting MS patients relative to healthy controls, coupled with an increase of POP endogenous inhibitor. The POP activity was also correlated with patient age and disability status. The lowered POP activity from plasma of MS patients could be rescued by reductants

Conclusions

The decrease in circulating POP activity measured in MS is reverted by reductants. This suggests that POP inactivation in MS might be a result of the oxidative conditions prevailing in the plasma of the diseased patients. Plasma levels of POP activity as well as those of their endogenous inhibitor are suggested as biomarkers of inflammation and oxidative stress in MS.
Identification and Characterization of a Promoter Cassette Conferring Adipocyte-Specific Gene Expression
Authors: Wang Zhao V. , Deng Yingfeng , Wang Qiong A. , Sun Kai , Scherer Philipp E.
Published: April 2010

The adipocyte-specific secretory molecule adiponectin has found widespread acceptance as a systemic marker that effectively integrates a number of signals associated with metabolic dysfunction at the level of adipose tissue. The widely used aP2 promoter cassette, which is frequently chosen to achieve adipocyte-specific expression of transgenes, conveys transcription in cell types other than adipocytes, such as macrophages and cardiomyocytes. To improve our ability to drive transgene expression in a more adipocyte-specific way, we aimed to define the minimal promoter segment from the adiponectin genomic locus. We generated a series of transgenic animals in which the expression of reporter genes and Cre recombinase was driven by 2, 4.9, and 5.4 kb of adiponectin promoter sequences. We found that the 5.4-kb adiponectin promoter fragment is the most effective cassette conveying adipocyte-specific expression of target genes. We therefore define a novel promoter cassette that ensures adipocyte-specific expression of passenger genes and may be used in the generation of transgenic mouse models to study gene function in vivo.
Utility of Glycated Hemoglobin in Diagnosing Type 2 Diabetes Mellitus: A Community-Based Study
Authors: Kumar Padala Ravi , Bhansali Anil , Ravikiran Muthuswamy , Bhansali Shobhit , Dutta Pinaki , Thakur J. S. , Sachdeva Naresh , Bhadada Sanjay Kumar , Walia Rama
Published: April 2010

Context: Although glycated hemoglobin (HbA1c) has recently been incorporated as a diagnostic test by the American Diabetes Association, its validity needs to be established in Asian Indians in a community setting.

Objective: The objective of the study was to assess the validity of HbA1c as a screening and diagnostic test in individuals with newly detected diabetes mellitus.

Design and Setting: Community based randomized cross sectional study in urban Chandigarh, a city in north India, from April 2008 to August 2009.

Subjects: Subjects included 1972 subjects aged 20 yr or older.

Intervention: Intervention included an oral glucose tolerance test and glycated hemoglobin in all the subjects.

Main Outcome Measures: Utility of HbA1c as a diagnostic method in newly detected diabetes mellitus subjects was evaluated.

Results: Using World Health Organization criteria for diagnosis of diabetes mellitus, 134 (6.7%) had newly detected diabetes mellitus, 192 (9.7%) known diabetes mellitus, 329 (16.6%) prediabetes, and 1317 (69.4%) were normal of 1972 people screened. Using only the ADA criteria, 38% people were underdiagnosed. An HbA1c level of 6.1% had an optimal sensitivity and specificity of 81% for diagnosing diabetes. A HbA1c level of 6.5% (±2 sd) and 7% (±2.7 sd) had sensitivity and specificity of 65 and 88% and 42 and 92%, respectively, with corresponding positive predictive value and negative predictive value of 75.2 and 96.5% and 90.4and 94.4%, respectively, for diagnosis of newly detected diabetes mellitus.

Conclusion: A HbA1c cut point of 6.1% has an optimal sensitivity and specificity of 81% and can be used as a screening test, and a cut point of 6.5% has optimal specificity of 88% for diagnosis of diabetes.
Vandetanib (100 mg) in Patients with Locally Advanced or Metastatic Hereditary Medullary Thyroid Cancer
Authors: Robinson Bruce G. , Paz-Ares Luis , Krebs Annetta , Vasselli James , Haddad Robert
Published: April 2010

Purpose: Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinases that also inhibits rearranged during transfection kinase activity. Vandetanib (300 mg/d) has previously demonstrated antitumor activity in patients with advanced hereditary medullary thyroid cancer (MTC). This study investigated the efficacy and safety of 100 mg/d vandetanib in patients with advanced hereditary MTC.

Patients and Methods: Eligible patients with unresectable, measurable, locally advanced, or metastatic hereditary MTC received 100 mg/d vandetanib. Upon disease progression, eligible patients could enter postprogression treatment with 300 mg/d vandetanib until a withdrawal criterion was met. The primary objective was to assess the objective response rate by response evaluation criteria in solid tumors.

Results: The study comprised 19 patients (13 males, six females; mean age 45 yr). Confirmed objective partial responses were observed in three patients, yielding an objective response rate of 16% (95% confidence interval 3.4–39.6). Stable disease lasting 24 wk or longer was reported in a further 10 patients (53%); the disease control rate was therefore 68% (95% confidence interval 43.4–87.4). Serum levels of calcitonin and carcinoembryonic antigen showed a sustained 50% or greater decrease from baseline in 16% (three of 19) and 5% (one of 19) of patients, respectively. Adverse events were predominantly grade 1 or 2 and consistent with previous vandetanib monotherapy studies.

Conclusions: Vandetanib at a once-daily dose of 100 mg has clinically relevant antitumor activity in patients with locally advanced or metastatic hereditary MTC and an overall acceptable safety profile.
Preparation of High-molecular-weight Phenolic Resins by means of a Phase-separation Reaction System
Authors: Wang Pengfei , Ogoshi Tomoki , Yamagishi Tada-Aki , Nakamoto Yoshiaki
Published: April 2010

High-molecular-weight o-cresol resins with narrow-molecular-weight distribution were prepared using a phase-separation reaction system. The prepared o-cresol resins included a trace of monomer, so that the molecular-weight distribution was narrow. In high molecular weight o-cresol resin, the fractions of ortho–ortho′, ortho–para′, and para–para′ methylene linkages were close to 25%, 50%, and 25%, respectively. This indicated that the reactivity of the ortho position was equal to that of the para position. It was found that the o-cresol ring was highly activated in phase separation reaction system using H2SO4/acetic acid.
Microwave-assisted One-pot Synthesis of Luminescent Organic–Inorganic Hybrids via Simultaneous Process of Sol–Gel and Suzuki–Miyaura Coupling Reactions
Authors: Kajiwara Yuichi , Nagai Atsushi , Chujo Yoshiki
Published: April 2010

In order to disperse luminescent compounds with low solubility or high crystallinity into silica matrices, we demonstrate here facile one-pot synthesis of organic–inorganic luminescent hybrids via simultaneous process of sol–gel reaction of 3-(chloropropyl)trimethoxysilane (CPTMS) and the Suzuki–Miyaura homocoupling of 1-pyreneboronic acid under microwave irradiation. Highly luminescent hybrid without aggregates of the pyrene dimer, which was efficiently generated in situ, was obtained by microwave irradiation due to rapid formation of silica matrices, whereas huge aggregates were observed in the hybrid prepared under conventional heating.
Color Tunable Novel Amphotropic Liquid Crystalline Acrylate End-capped with a Cholesteryl Group
Authors: Hsieh Feng-Min , Fang Hau , Liu Jui-Hsiang
Published: April 2010

We report a novel, monomeric, lyotropic, cholesteric liquid crystal revealing selective reflection in the visible light region and having photochromic properties in the lyotropic liquid crystal phase. Monomer (+)-cholesteryl (6-acryloyloxyhexyloxy)-4-cinnamate was synthesized. Liquid crystal phases of M1 were identified using polarized optical microscopic and X-ray diffraction methods. Reflection light spectra were analyzed using an optical fiber system.
To Wait or Not to Wait—And Who Goes First? Delay Management with Priority Decisions
Authors: Schachtebeck Michael , Schöbel Anita
Published: April 2010

Delay management is an important issue in the daily operations of any railway company. The task is to update the planned timetable to a disposition timetable in such a way that the inconvenience for the passengers is as small as possible. The two main decisions that have to be made in this respect are the wait-depart decisions, to decide which connections should be maintained in case of delays, and the priority decisions, which determine the order in which trains are allowed to pass a specific piece of track. The latter are necessary to take the limited capacity of the track system into account. While the wait-depart decisions have been intensively studied in the literature, the priority decisions in the capacitated case have been neglected so far in delay management optimization models.

In the current paper, we add the priority decisions to the integer programming formulation of the delay management problem and are hence able to deal with the capacitated case. The corresponding constraints are disjunctive constraints leading to cycles in the resulting event-activity network. Nevertheless, we are able to derive reduction techniques for the network that enable us to extend the formulation of the never-meet property from the uncapacitated delay management problem to the capacitated case. We then use our results to derive exact and heuristic solution procedures for solving the delay management problem.

The results of the algorithms are evaluated both from a theoretical and a numerical point of view. The latter has been done within a case study using the railway network in the region of Harz, Germany.
Dexlansoprazole in the Treatment of Esophagitis and Gastroesophageal Reflux Disease
Authors: Abel Cheryl , Desilets Alicia R , Willett Kristine
Published: April 2010

OBJECTIVE:

To describe the pharmacology, pharmacokinetics, and efficacy of dexlansoprazole in the treatment of heartburn associated with nonerosive gastroesophageal reflux disease (GERD) and healing and maintenance of healing of all grades of erosive esophagitis (EE).

DATA SOURCES:

Literature searches were conducted using MEDLINE Ovid (1950-December 2009, week 4) and EMBASE (1980-2009, week 53) using the term dexlansoprazole. References from articles obtained from the search were evaluated for other relevant citations.

STUDY SELECTION AND DATA EXTRACTION:

All articles published in English evaluating the pharmacology, pharmacokinetics, efficacy, and adverse effect profile of dexlansoprazole were selected for inclusion.

DATA SYNTHESIS:

Dexlansoprazole is the newest addition to the proton pump inhibitor (PPI) class and is approved for the treatment of heartburn associated with nonerosive GERD, healing of all grades of EE, as well as maintenance of healing of EE. Dexlansoprazole has a unique dual delayed-release formulation, which releases drug at 2 points in time; the first peak occurs 1-2 hours after administration and the second occurs within 4-5 hours after administration. In Phase 3 trials conducted in adults, researchers found that dexlansoprazole increases rates of healing of EE, as well as the maintenance of healing, compared to lansoprazole. Relief of heartburn symptoms was comparable among the dexlansoprazole and lansoprazole treatment groups. Common adverse effects of dexlansoprazole are similar to those of the other PPIs, including diarrhea, abdominal pain, nausea, upper respiratory infection, vomiting, and flatulence.

CONCLUSIONS:

Dexlansoprazole provides another treatment option for the management of EE and symptoms of heartburn. Considering that the cost of dexlansoprazole is not favorable, further studies evaluating potential advantages over other agents are necessary to define the role of dexlansoprazole in the treatment of these conditions.
Do Pharmacists Know Which Patients with Bowel Symptoms Should Seek Further Medical Advice? A Survey of Pharmacists Practicing in Community Pharmacy in Western Australia
Authors: Jiwa Moyez , Spilsbury Katrina , Duke Janine
Published: April 2010

BACKGROUND:

Pharmacists in Australia are routinely asked to advise people with lower bowel symptoms. Clinical, demographic, and working environment parameters may affect whether appropriate referral for advanced care is advised by pharmacists.

OBJECTIVE:

To characterize how selected clinical, demographic, and working environment variables affect the likelihood of a pharmacist providing a referral for patients with lower bowel symptoms to consult a general practitioner, and to investigate factors associated with agreement with an expert panel and colorectal cancer guidelines.

METHODS:

Self-administered questionnaires were distributed to a random sample of 300 pharmacists in Western Australia. Vignettes were constructed around 6 clinical variables and pharmacists were asked to describe a referral pathway. Logistic regression was used to identify factors associated with odds of referral and agreement with an expert panel.

RESULTS:

One hundred sixty-seven completed surveys were returned, giving a response rate of 56%. The odds of referral to a general practitioner were mostly associated with presenting symptoms, although lower odds of referral were observed with increasing volumes of weekly prescriptions. The odds of pharmacists agreeing with the expert panel for an urgent referral were 70% (95% CI 50 to 80) lower for weight loss as the presenting symptom compared to rectal bleeding. The expert panel considered weight loss or rectal bleeding of 4 weeks' duration as meriting an urgent referral, but 63% and 30% of pharmacists, respectively, disagreed. In contrast to cancer guidelines, over 60% of respondents did not consider persistent diarrhea in a 65-year-old patient as a likely symptom of significant bowel pathology.

CONCLUSIONS:

In general, pharmacists' patterns of referral were influenced by clinical symptoms and not by demographic or working environment variables. They over-referred patients with diarrhea but under-referred those with weight loss and rectal bleeding, according to the expert panel. This is a cause for concern because any unexplained rectal bleeding should be referred for further investigation.
Propuesta metodológica para la redistritación electoral en México: El Caso de Michoacán
Authors: Caballero Graciela Martínez
Published: April 2010

This paper presents a methodological proposal of electoral districting where the population imbalance between the electoral districts is minimized during the period of territorial reorganization. The initial context is the process of federal electoral redistricting in Mexico made in 2004–2005, modified and applied to the state of Michoacán. The work places special emphasis on indicators such as migration and density of the population over eighteen years of age.
Neural Timing Is Linked to Speech Perception in Noise
Authors: Anderson Samira , Skoe Erika , Chandrasekaran Bharath , Kraus Nina
Published: April 2010

Understanding speech in background noise is challenging for every listener, including those with normal peripheral hearing. This difficulty is attributable in part to the disruptive effects of noise on neural synchrony, resulting in degraded representation of speech at cortical and subcortical levels as reflected by electrophysiological responses. These problems are especially pronounced in clinical populations such as children with learning impairments. Given the established effects of noise on evoked responses, we hypothesized that listening-in-noise problems are associated with degraded processing of timing information at the brainstem level. Participants (66 children; ages, 8–14 years; 22 females) were divided into groups based on their performance on clinical measures of speech-in-noise (SIN) perception and reading. We compared brainstem responses to speech syllables between top and bottom SIN and reading groups in the presence and absence of competing multitalker babble. In the quiet condition, neural response timing was equivalent between groups. In noise, however, the bottom groups exhibited greater neural delays relative to the top groups. Group-specific timing delays occurred exclusively in response to the noise-vulnerable formant transition, not to the more perceptually robust, steady-state portion of the stimulus. These results demonstrate that neural timing is disrupted by background noise and that greater disruptions are associated with the inability to perceive speech in challenging listening conditions.
Spinal Processing of Noxious and Innocuous Cold Information: Differential Modulation by the Periaqueductal Gray
Authors: Leith J. Lianne , Koutsikou Stella , Lumb Bridget M. , Apps Richard
Published: April 2010

In addition to cold being an important behavioral drive, altered cold sensation frequently accompanies pathological pain states. However, in contrast to peripheral mechanisms, central processing of cold sensory input has received relatively little attention. The present study characterized spinal responses to noxious and innocuous intensities of cold stimulationin vivoand established the extent to which they are modulated by descending control originating from the periaqueductal gray (PAG), a major determinant of acute and chronic pain. In lightly anesthetized rats, hindpaw cooling with ethyl chloride, but not acetone, was sufficiently noxious to evoke withdrawal reflexes, which were powerfully inhibited by ventrolateral (VL)-PAG stimulation. In a second series of experiments, subsets of spinal dorsal horn neurons were found to respond to innocuous and/or noxious cold. Descending control from the VL-PAG distinguished between activity in nociceptive versus non-nociceptive spinal circuits in that innocuous cold information transmitted by non-nociceptive class 1 and wide-dynamic-range class 2 neurons remained unaltered. In contrast, noxious cold information transmitted by class 2 neurons and all cold-evoked activity in nociceptive-specific class 3 neurons was significantly depressed. We therefore demonstrate that spinal responses to cold can be powerfully modulated by descending control systems originating in the PAG, and that this control selectively modulates transmission of noxious versus innocuous information. This has important implications for central processing of cold somatosensation and, given that chronic pain states are dependent on dynamic alterations in descending control, will help elucidate mechanisms underlying aberrant cold sensations that accompany pathological pain states.
Top-Down and Bottom-Up Attention to Memory Are Dissociated in Posterior Parietal Cortex: Neuroimaging and Neuropsychological Evidence
Authors: Ciaramelli Elisa , Grady Cheryl , Levine Brian , Ween Jon , Moscovitch Morris
Published: April 2010

Posterior parietal cortex is active during episodic memory retrieval, yet its role remains unclear. According to a recent proposal, dorsal parietal cortex (DPC) allocates top-down attention to memory retrieval, whereas ventral parietal cortex (VPC) mediates the bottom-up attentional capture by retrieved contents, i.e., the Attention-to-Memory (AtoM) hypothesis. Here, for the first time, functional magnetic resonance imaging (fMRI) and lesion techniques were combined in a single study to test the role of parietal cortex in episodic retrieval. Participants studied word pairs and then detected studied (target) words among new words. In some conditions, a studied word cued the upcoming target word, facilitating recognition performance. In line with the AtoM hypothesis, left DPC was engaged when participants searched for/anticipated memory targets upon presentation of relevant memory cues and predicted the ensuing behavioral advantage. In contrast, left VPC predicted efficacy and speed of target detection on noncued trials and was largest for memory targets that were invalidly cued. Consistent with fMRI evidence, patients with lesions in DPC did not benefit from memory cueing, whereas patients with lesions in VPC had problems recognizing unexpected memory targets. These results support the AtoM hypothesis that DPC and VPC mediate top-down and bottom-up attention to memory retrieval, respectively.
LEF1/β-Catenin Complex Regulates Transcription of the Cav3.1 Calcium Channel Gene (Cacna1g) in Thalamic Neurons of the Adult Brain
Authors: Wisniewska Marta B. , Misztal Katarzyna , Michowski Wojciech , Szczot Marcin , Purta Elzbieta , Lesniak Wieslawa , Klejman Monika E. , Dabrowski Michal , Filipkowski Robert K. , Nagalski Andrzej , Mozrzymas Jerzy W. , Kuznicki Jacek
Published: April 2010

β-Catenin, together with LEF1/TCF transcription factors, activates genes involved in the proliferation and differentiation of neuronal precursor cells. In mature neurons, β-catenin participates in dendritogenesis and synaptic function as a component of the cadherin cell adhesion complex. However, the transcriptional activity of β-catenin in these cells remains elusive. In the present study, we found that in the adult mouse brain, β-catenin and LEF1 accumulate in the nuclei of neurons specifically in the thalamus. The particular electrophysiological properties of thalamic neurons depend on T-type calcium channels. Cav3.1 is the predominant T-type channel subunit in the thalamus, and we hypothesized that theCacna1ggene encoding Cav3.1 is a target of the LEF1/β-catenin complex. We demonstrated that the expression ofCacna1gis high in the thalamus and is further increased in thalamic neurons treatedin vitrowith LiCl or WNT3A, activators of β-catenin. Luciferase reporter assays confirmed that theCacna1Gpromoter is activated by LEF1 and β-catenin, and footprinting analysis revealed four LEF1 binding sites in the proximal region of this promoter. Chromatin immunoprecipitation demonstrated that theCacna1gproximal promoter is occupied by β-cateninin vivoin the thalamus, but not in the hippocampus. Moreover, WNT3A stimulation enhanced T-type current in cultured thalamic neurons. Together, our data indicate that the LEF1/β-catenin complex regulates transcription ofCacna1gand uncover a novel function for β-catenin in mature neurons. We propose that β-catenin contributes to neuronal excitability not only by a local action at the synapse but also by activating gene expression in thalamic neurons.
Adaptive Reweighting of Auditory Localization Cues in Response to Chronic Unilateral Earplugging in Humans
Authors: Kumpik Daniel P. , Kacelnik Oliver , King Andrew J.
Published: April 2010

Localizing a sound source involves the detection and integration of various spatial cues present in the sound waves at each ear. Previous studies indicate that the brain circuits underlying sound localization are calibrated by experience of the cues available to each individual. Plasticity in spatial hearing is most pronounced during development but can also be demonstrated during adulthood under certain circumstances. Investigations into whether adult humans can adjust to reduced input in one ear and learn a new correspondence between interaural differences cues and directions in space have produced conflicting results. Here we show that humans of both sexes can relearn to localize broadband sounds with a flat spectrum in the horizontal plane after altering the spatial cues available by plugging one ear. In subjects who received daily training, localization accuracy progressively shifted back toward their pre-plug performance after 1 week of earplugging, whereas no improvement was seen if all trials were performed on the same day. However, localization performance did not improve on a task that used stimuli in which the source spectrum was randomized from trial to trial, indicating that monaural spectral cues are needed for plasticity. We also characterized the effects of the earplug on sensitivity to interaural time and level differences and found no clear evidence for adaptation to these cues as the free-field localization performance improved. These findings suggest that the mature auditory system can accommodate abnormal inputs and maintain a stable spatial percept by reweighting different cues according to how informative they are.
Initiating the Development of Multisensory Integration by Manipulating Sensory Experience
Authors: Yu Liping , Rowland Benjamin A. , Stein Barry E.
Published: April 2010

The multisensory integration capabilities of superior colliculus neurons emerge gradually during early postnatal life as a consequence of experience with cross-modal stimuli. Without such experience neurons become responsive to multiple sensory modalities but are unable to integrate their inputs. The present study demonstrates that neurons retain sensitivity to cross-modal experience well past the normal developmental period for acquiring multisensory integration capabilities. Experience surprisingly late in life was found to rapidly initiate the development of multisensory integration, even more rapidly than expected based on its normal developmental time course. Furthermore, the requisite experience was acquired by the anesthetized brain and in the absence of any of the stimulus–response contingencies generally associated with learning. The key experiential factor was repeated exposure to the relevant stimuli, and this required that the multiple receptive fields of a multisensory neuron encompassed the cross-modal exposure site. Simple exposure to the individual components of a cross-modal stimulus was ineffective in this regard. Furthermore, once a neuron acquired multisensory integration capabilities at the exposure site, it generalized this experience to other locations, albeit with lowered effectiveness. These observations suggest that the prolonged period during which multisensory integration normally appears is due to developmental factors in neural circuitry in addition to those required for incorporating the statistics of cross-modal events; that neurons learn a multisensory principle based on the specifics of experience and can then apply it to other stimulus conditions; and that the incorporation of this multisensory information does not depend on an alert brain.
Functional Differences between and across Different Regions of the Apical Branch of Hippocampal CA1 Dendrites with Respect to Long-Term Depression Induction and Synaptic Cross-Tagging
Authors: Parvez Suhel , Ramachandran Binu , Frey Julietta U.
Published: April 2010

The hippocampus is an ideal system to study synaptic plasticity in the context of learning and memory. The induction, expression, and interaction of long-term potentiation (LTP) as well as long-term depression (LTD) are essential elements for the functioning of complex networks in information processing and storage. Here we investigated whether different loci at the apical dendritic branch of CA1 pyramidal neurons are characterized by different capabilities to induce, express, and interact with LTP and LTD in hippocampal slicesin vitro. We found that high-frequency stimulation resulted in longer-lasting forms of LTP in proximal and distal parts of the apical dendrites, whereas low-frequency stimulation induced longer-lasting LTD in distal but not at proximal parts. Interestingly, processes of “synaptic cross-tagging” could be described for any form of LTP transformation from early-stage LTP (E-LTP) into late-phase LTP (L-LTP) in distal and proximal parts, but for LTD, only at the distal part but not for the proximal part, although low-frequency stimulation at the proximal input, which resulted here only in a short-term depression, was paradoxically able to reinforce E-LTP into L-LTP at distal parts. We have identified protein kinase Mzeta (PKMzeta) as the LTP-specific, synthesized plasticity-related protein transforming E-LTP into L-LTP by strong low-frequency stimulation in the apical CA dendrite by cross-tagging mechanisms.
Dissociation of within- and between-Session Extinction of Conditioned Fear
Authors: Plendl Wolfgang , Wotjak Carsten T.
Published: April 2010

Recent findings obtained in patients with phobias or trauma-related anxiety disorders raise doubts concerning the interrelation between acute fear relief during an exposure-based therapeutic session and beneficial treatment progress. In a mouse model explicit for exposure therapy, we challenge the view that within-session fear reduction is the turning point for relearning of a stimulus-threat association. Even though within-session extinction of auditory-cued fear memory was identical for prolonged and spaced tone presentations, only the latter caused between-session extinction. Furthermore, spaced tone presentations led to between-session extinction even in the complete absence of within-session extinction, as observed for remote fear memories and in case of abolished cannabinoid receptor type 1 signaling. Induction of between-session extinction was accompanied by an increase in the number of c-Fos-positive neurons within the basolateral amygdala, the cingulate cortex, and the dentate gyrus, independent of the level of within-session extinction. Together, our findings demonstrate that within-session extinction is neither sufficient nor essential for between-session extinction, thus calling for a reconsideration of current concepts underlying exposure-based therapies.
Equilibrative Nucleoside Transporter 2 Regulates Associative Learning and Synaptic Function inDrosophila
Authors: Knight David , Harvey Philip J. , Iliadi Konstantin G. , Klose Markus K. , Iliadi Natalia , Dolezelova Eva , Charlton Milton P. , Zurovec Michal , Boulianne Gabrielle L.
Published: April 2010

Nucleoside transporters are evolutionarily conserved proteins that are essential for normal cellular function. In the present study, we examined the role of equilibrative nucleoside transporter 2 (ent2) inDrosophila. Null mutants ofent2are lethal during late larval/early pupal stages, indicating thatent2is essential for normal development. Hypomorphic mutant alleles ofent2, however, are viable and exhibit reduced associative learning. We additionally used RNA interference to knock downent2expression in specific regions of the CNS and show thatent2is required in the α/β lobes of the mushroom bodies and the antennal lobes. To determine whether the observed behavioral defects are attributable to defects in synaptic transmission, we examined transmitter release at the larval neuromuscular junction (NMJ). Excitatory junction potentials were significantly elevated inent2mutants, whereas paired-pulse plasticity was reduced. We also observed an increase in stimulus dependent calcium influx in the presynaptic terminal. The defects observed in calcium influx and transmitter release probability at the NMJ were rescued by introducing an adenosine receptor mutant allele (AdoR1) into theent2mutant background. The results of the present study provide the first evidence of a role forent2function inDrosophilaand suggest that the observed defects in associative learning and synaptic function may be attributable to changes in adenosine receptor activation.
A novel homozygous splice acceptor site mutation of KISS1R in two siblings with normosmic isolated hypogonadotropic hypogonadism
Authors: Teles M G , Trarbach E B , Noel S D , Guerra-Junior G , Jorge A , Beneduzzi D , Bianco S D , Mukherjee A , Baptista M T , Costa E M , De Castro M , Mendonça B B , Kaiser U B , Latronico A C
Published: April 2010

Context

Loss-of-function mutations of the kisspeptin-1 receptor gene, KISS1R, have been identified in patients with normosmic isolated hypogonadotropic hypogonadism (nIHH).

Objective

To investigate KISS1R defects in patients with absent or delayed puberty.

Patients

We investigated KISS1R gene defects in a cohort of 99 Brazilian patients with nIHH or constitutional delay of puberty (CDP).

Methods

The entire coding region of KISS1R was amplified by PCR followed by automatic sequencing. In addition, screening for KISS1R exonic deletions was performed by multiplex ligation-dependent probe amplification.

Results

One novel homozygous KISS1R mutation was identified in two siblings with nIHH. This variant was an insertion/deletion (indel) mutation characterized by the deletion of three nucleotides (GCA) at position −2 to −4, and by the insertion of seven nucleotides (ACCGGCT) at the same position, within the 3′ splice acceptor site of intron 2 of KISS1R. The brothers who carried this KISS1R mutation had no clinical evidence of pubertal development at the ages of 14 and 20 years. Computational analysis of this indel mutation predicted the generation of an abnormal protein. In addition, a new heterozygous KISS1R variant (p.E252Q) was identified in a male patient with sporadic nIHH. However, in vitro studies of this variant did not demonstrate functional impairment. Only known polymorphisms were identified in patients with CDP.

Conclusion

Loss-of-function mutations of KISS1R represents a rare cause of nIHH, and was absent in patients with CDP. We have described a novel KISS1R homozygous splice acceptor site mutation in the familial form of nIHH.
Ethical Questions in Forensic Linguistics: Introduction to Papers from a Linguistic Society of America Panel Presentation, San Francisco, California, January 9, 2009
Authors: Shuy Roger
Published: April 2010

With seemingly greater frequency, linguists today are working as consultants in “forensic” linguistics, employed by attorneys to prepare reports and testimony based on their linguistic research. Their work is generally beneficial to the side (litigant; prosecutor or defender) that employs them.
Linguistic research that is conducted for purposes other than academic publishing raises a number of serious ethical issues. This introduction addresses a number of ethical questions within the framework of forensic linguistics.
1. To what extent should a scholar disclose the relationship between forensic linguistic case-driven research and later scholarly publication?
2. What are the implications of the adversarial nature of legal proceedings vis-à-vis (a) the scholar's supposed devotion to "truth" and (b) the legal requirement of telling not only the truth and nothing but the truth, but also the whole truth.
3. What are the appropriate scholarly credentials for forensic linguistic consulting? To what extent can proper credentialing be enforced? By what authority?
4. Should organizations such as the Linguistic Society of America and the International Association of Forensic Linguists take an official position on any of these issues?
5. What does an attorney expect of a linguistic expert? What sort of training would the legal profession find especially helpful?
Scottish indie music and BBC radio’s 'Beat Patrol' (1995–2000)
Authors: Percival J.
Published: April 2010

This essay investigates music radio consumption and how it relates to local popular music production. The study focuses on one specialist weekly music programme, Beat Patrol, presented in several formats by Peter Easton at BBC Radio Scotland from 1984 to 2000, and the ways in which a very specific segment of that show’s audience (in this case, indie musicians) make sense of that show. Firstly, it offered an independent measurement of the bands’ critical success and status in relation to local, regional and national music scenes. The show therefore contributed directly to the acquisition of cultural and social capital for musicians at an early stage of their careers. Secondly, Beat Patrol provided a powerful tool with which bands were able to evaluate both the technical and aesthetic qualities of their recordings in relation to their peers and to artists whose work they admired. The use of this comparative tool suggests that specialist music radio was central to the development of indie musicians’ notions of good’ and ‘bad’ creative and technical characteristics of their own music.
Discovering authenticity?
Authors: Crutchfield Rory
Published: April 2010

In 1952 the anthropologist, archivist, and artist Harry Smith finally released the three albums of folk music collected from commercial recordings from the 1920’s and 30’s on Moses Asch’s Folkways label. This article will discuss the gradual development of the notion of ‘authenticity’ through the most eminent direct or indirect participants in the Anthology, and in what ways they were complicit in the construction of such a concept. It will trace the lineage of the music of the Anthology, and exhibit the connections between these disparate creative elements, in an attempt to present a comprehensive picture of how ‘authenticity’ is fabricated in this case. It will also explore the apparent distinction between folk and pop culture and the way in which they are separated further through being branded ‘authentic’ or ‘inauthentic’. The aim is to demonstrate that everyone involved in whatever capacity in the Anthology was discovering the same idea of ‘authenticity’, vulnerable to the same marketed ‘authenticity’, and complicit in the same fabrication of ‘authenticity’.
The vegetables turned
Authors: Carter Dale
Published: April 2010

This article offers a comparative analysis of aspects of the careers of two celebrated 1960s popular musicians, Brian Wilson of The Beach Boys and Syd Barrett of Pink Floyd. Through formal and contextual readings of selected songs, it argues that during 1967, in the hands of Barrett, Wilson and his lyricist Van Dyke Parks, the incongruous, semantically complex figure of the vegetable came to illuminate aspects of psychedelic consciousness and – part by design, part by accident – the link between LSD and Anglo-American popular music. It threw light, too, on the scope and limits of changes in the relationship between creative artists and the Anglo-American popular music industry in the mid-1960s. Finally, and in retrospect, the figure of the vegetable cast into relief the counter-culture’s utopian and dystopian dynamics as manifested in these song-writers’ personal lives, now rendered as contemporary counter-cultural myth.
Gordon Stretton
Authors: Daniels Jeff , Rye Howard
Published: April 2010

A Liverpudlian of mixed Jamaican and Irish ancestry, William Masters, born in 1887, provides a fascinating study of a member of the African diaspora seeking and finding an artistic identity. After membership of a Lancashire clog-dancing troupe, he adopted a stage name, Gordon Stretton, in tribute to an Edwardian music-hall artist, then learnt to be a jazz drummer under the tutelage of visiting African-American musician Billy Dorsey. Stretton’s varied career subsequently took him to France and Argentina. He exemplifies the manner in which members of the African diaspora of very varied backgrounds were sucked into currently prestigious North American idioms.
Resource notes
Authors: Lineham Andy
Published: April 2010

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The Self Possessed: Deity and Spirit Possession in South Asian Literature and Civilization, by Frederick M. Smith
Authors: Taylor Kathleen
Published: April 2010

The Self Possessed: Deity and Spirit Possession in South Asian Literature and Civilization, by Frederick M. Smith. New York: Columbia University Press, 2006. xxvii + 701pp. ISBN 0-231-13748-6 (hb), 0-231-51065-9 (electronic).
Depressão no período gestacional e baixo peso ao nascer: uma revisão sistemática da literatura
Authors: Araujo Daniele Marano Rocha , Vilarim Marina Machado , Sabroza Adriane Reis , Nardi Antonio Egidio
Published: April 2010

Realizou-se uma revisão sistemática enfocando o efeito da depressão no período gestacional sobre o maior risco do baixo peso ao nascer. A revisão consistiu na busca de artigos publicados nas bases de dados PubMed, SciELO e ISIWEB utilizando-se as palavras-chave: "depression", "pregnancy", "low birth weight" e "birth weight". Foram localizados noventa e nove estudos, no entanto após a leitura dos resumos foram selecionados dez artigos. Segundo o critério de Downs & Black, utilizado para aferir a qualidade dos estudos selecionados, apenas um foi considerado de excelente qualidade, pois alcançou a pontuação máxima de 20 pontos. A depressão na gestação foi associada ao baixo peso ao nascer em sete estudos. Contradições nos achados devem-se às diferenças nas escalas utilizadas para mensurar a depressão, tamanho amostral e controle insuficiente de importantes fatores limitantes de avaliação dos resultados. Por estes motivos, são necessários estudos cuidadosamente desenhados para esclarecer a associação entre depressão durante o período gestacional e baixo peso ao nascer.