bluuebunny/crossref_metadata_2025 huggingface dataset:
Interannual Variations of East Asian Trough Axis at 500 hPa and its Association with the East Asian Winter Monsoon Pathway
Authors: Wang Lin , Chen Wen , Zhou Wen , Huang Ronghui
Published: August 2008

Interannual variations of the East Asian trough (EAT) axis at 500 hPa are studied with the European Centre for Medium-Range Weather Forecasts 40-yr reanalysis data. The associated circulation pattern and pathway of the East Asian winter monsoon (EAWM) with the EAT axis tilt are specially investigated with a trough axis index, which is closely related to the midlatitude baroclinic process and mainly represents the intensity of the eddy-driven jet over the East Asia–North Pacific sector. When the tilt of EAT is smaller than normal, the EAWM prefers to take the southern pathway and less cold air moves to the central North Pacific. However, the EAWM prefers the eastern pathway and brings more cold air to the North Pacific when the tilt of EAT is larger than normal. These differences induce pronounced changes in both the precipitation and the surface air temperature over East and Southeast Asia. Furthermore, the tilt status of the EAT has a significant modulation effect on the regional climate anomalies related to the intensity of the EAWM. The findings suggest an increase in the temperature anomaly associated with the EAWM intensity and a clear northward–southward shift in its pattern in anomalous tilt phase of the EAT. In addition, the modulation tends to be confined mainly to East Asia and expanded to a larger area during the weak and the strong EAWM winters, respectively. The possible reasons for interannual variations of the EAT tilt are discussed, and it is speculated that the midlatitude air–sea interaction in the North Pacific plays a dominant role. This study on the EAT tilt may enrich knowledge of the East Asian winter monsoon beyond the conventional intensity index and may be helpful to improve regional climate prediction in East Asia.
Quality Control of Large Argo Datasets
Authors: Gaillard Fabienne , Autret Emmanuelle , Thierry Virginie , Galaup Philippe , Coatanoan Christine , Loubrieu Thomas
Published: August 2008

Argo floats have significantly improved the observation of the global ocean interior, but as the size of the database increases, so does the need for efficient tools to perform reliable quality control. It is shown here how the classical method of optimal analysis can be used to validate very large datasets before operational or scientific use. The analysis system employed is the one implemented at the Coriolis data center to produce the weekly fields of temperature and salinity, and the key data are the analysis residuals. The impacts of the various sensor errors are evaluated and twin experiments are performed to measure the system capacity in identifying these errors. It appears that for a typical data distribution, the analysis residuals extract 2/3 of the sensor error after a single analysis. The method has been applied on the full Argo Atlantic real-time dataset for the 2000–04 period (482 floats) and 15% of the floats were detected as having salinity drifts or offset. A second test was performed on the delayed mode dataset (120 floats) to check the overall consistency, and except for a few isolated anomalous profiles, the corrected datasets were found to be globally good. The last experiment performed on the Coriolis real-time products takes into account the recently discovered problem in the pressure labeling. For this experiment, a sample of 36 floats, mixing well-behaved and anomalous instruments of the 2003–06 period, was considered and the simple test designed to detect the most common systematic anomalies successfully identified the deficient floats.
Food Palatability, Rheology, and Meal Patterning
Authors: Mattes Richard D.
Published: August 2008

Background: Overweight and obesity are largely of dietary origin and reflect food choice. Food palatability, eating patterns, and food form are important determinants of choice and energy balance. Methods: A review of the literature provides a characterization of the roles of these determinants of feeding. Results: Food palatability is the strongest predictor of intake where availability is not limiting. Whether the rewarding properties of palatable items lead to nonhomeostatic feeding and weight gain warrants further study. Positive energy balance is attributed to greater energy intake within eating events but also to a greater extent, increased eating frequency. Although the size and frequency of eating events may compensate for each other, interventions aimed at limiting the latter may be especially productive. One of the most marked dietary trends is an increase of energy derived from beverages. The weak dietary compensation that energy‐yielding beverages elicit leads to positive energy balance. This, too, is a promising target for moderating energy intake. Conclusions: A better understanding of dietary factors promoting positive energy balance should reveal strategies for weight management.
Dietary Management of Obesity
Authors: Astrup Arne
Published: August 2008

Background: The optimal diet for prevention of weight gain, obesity, metabolic syndrome, and type 2 diabetes is fat‐reduced, fiber‐rich, high in low‐energy density carbohydrates (fruit, vegetables, and whole grain products), and intake of energy‐containing drinks is restricted. Results on dietary fat: The reduction of the total fat content of ad libitum diets produces weight loss in both the short term and over periods as long as 7 years. A fat‐reduced diet, combined with physical activity, reduces almost all risk factors for cardiovascular disease and reduces the incidence of type 2 diabetes. The combination of reduction of dietary fat and energy, and increased physical activity has been shown to reduce the incidence of diabetes by 58% in 2 major trials. In post hoc analyses, the reduction in dietary fat (energy density) and increase in fiber were the strongest predictors of weight loss and diabetes‐protective effects. Low‐glycemic index and high‐protein diets: It remains to be shown whether a low‐glycemic index diet provides any benefit to weight control beyond this. Low‐carbohydrate diets may be an option for inducing weight loss in obese patients, but a very low intake of carbohydrate‐rich foods is not commensurate with a healthy and palatable diet in the long term. However, there is evidence that increasing the protein content of the diet from 15% up to 20%‐30%, at the expense of carbohydrates, increases the satiating effect of the diet, and induces a spontaneous weight loss, and this could turn out to be a preferred option for patients with metabolic syndrome and type 2 diabetes.
Nutrition Therapy in Critically Ill Infants and Children
Authors: Skillman Heather E. , Wischmeyer Paul E.
Published: August 2008

Infants and children are susceptible to the profound metabolic effects of critical illness. In addition, preexisting malnutrition and obesity have adverse consequences during the intensive care unit stay. Early enteral and parenteral feeding can improve nutrition deficits, but neither has been sufficiently studied to show an effect on clinical outcomes in pediatric critical care. Indirect calorimetry is a useful technique that identifies patients receiving inadequate or excessive nutrition, but this technique is underused.
Addressing circadian rhythm disturbances in depressed patients
Authors: Lam RW
Published: August 2008

Abstract

Desynchronisation of normal circadian rhythms, including the sleep–wake rhythm, is common in major depressive disorder (MDD). The association between sleep disturbances and depression has long been recognised. Disturbed sleep is a diagnostic criterion for MDD, and insomnia commonly precedes the onset of symptomatic mood disorders. Disruptions of the sleep–wake cycle (sleep architecture and timing) are residual symptoms that may prevent the attainment of high-quality remission and delay recovery from MDD. Therefore, early recognition and treatment of sleep disturbances may be important for the treatment and prevention of recurrent depression. Evidence suggests that melatonergic (MT1 and MT2) and the 5-HT2C serotonergic receptor subtypes are important modulators of circadian rhythmicity. Agomelatine is the first melatonergic antidepressant; an agonist of melatonin MT1 and MT2 receptors, with additional antagonist properties at the 5-HT2C receptors. Agomelatine combines antidepressant efficacy including quality and efficiency of sleep, with a more favourable side-effect profile than current antidepressant treatments, including neutral effects on sexual function, bodyweight and the absence of discontinuation symptoms. These positive features provide a novel approach to the treatment of depression and the attainment of high-quality remission in MDD.
Caregiver Responsiveness and Social Interaction Behaviors of Young Children With Autism
Authors: Ruble Lisa , McDuffie Andrea , King Andrea S. , Lorenz Doug
Published: August 2008

Although it is documented that parent interaction influences children's development, few studies have focused on methods for reliably assessing molar-level caregiver-child interactions that are used regularly in treatment evaluations in community-based settings, and none have targeted children with autism spectrum disorders. Thirty-five children and their caregivers participated in an outpatient evaluation for therapeutic treatment planning for children with autism spectrum disorders. Parent-child interactions (part of the routine evaluation) were coded immediately after a 10-minute free-play activity. Analyses indicated that molar-level caregiver interaction behaviors could be evaluated with good reliability. Correlational analysis of parent and child demographics with the quality of interactions revealed no significant relationships, consistent with previous research. However, an expected and significant concurrent association was observed between parent responsiveness, measured using the observational rating scale, and parents' reports of children's ability to initiate interactions with adults. Research on reliable, ecologically feasible methods of parent-child interaction assessment conducted in community-based settings may help translate evidence-based practices into real-world settings.
Arthroscopic Treatment of Chronic Osteochondral Lesions of the Talus
Authors: Ferkel Richard D. , Zanotti Robert M. , Komenda Gregory A. , Sgaglione Nicholas A. , Cheng Margaret S. , Applegate Gregory R. , Dopirak Ryan M.
Published: August 2008

Background

Osteochondral lesions of the talus are relatively uncommon but may be a cause of significant pain and disability in symptomatic patients.

Hypothesis

Arthroscopic treatment of osteochondral lesions of the talus will result in good long-term clinical outcomes in the majority of patients.

Study Design

Case series; Level of evidence, 4.

Methods

Fifty patients with chronic osteochondral lesions of the talus underwent arthroscopic treatment. Average age was 32 years (range, 12-72 years). Average follow-up was 71 months (range, 24-152 months). Treatment consisted of either drilling of the osteochondral lesions of the talus in situ (n = 4), excision of the osteochondral lesions of the talus and abrasion arthroplasty (n = 6), or excision of the osteochondral lesions of the talus and drilling (n = 40). Preoperative and intraoperative staging of the osteochondral lesions of the talus was performed. Follow-up evaluation included 3 clinical rating systems: Alexander, modified Weber, and American Orthopaedic Foot and Ankle Society Ankle/Hindfoot scores.

Results

There were 72% excellent/good, 20% fair, and 8% poor results on the Alexander scale. According to the modified Weber scale, there were 64% excellent/good, 30% fair, and 6% poor results. The average American Orthopaedic Foot and Ankle Society Ankle/Hindfoot score was 84 (range, 34-100). We found no correlation between plain radiographs, computed tomography, or magnetic resonance imaging staging and clinical results. However, there was significant correlation between arthroscopic stage and clinical outcome. Seventeen patients had been seen 5 years previously and evaluated using the same criteria; 35% demonstrated a deterioration in their result over time.

Conclusion

Arthroscopic treatment of chronic symptomatic osteochondral lesions of the talus results in good clinical outcomes in the majority of patients. However, pain and functional limitation may persist in some patients, especially those noted to have unstable osteochondral defects at the time of arthroscopy.
Arthroscopic versus Mini-Open Rotator Cuff Repair
Authors: Morse Kenneth , Davis A. David , Afra Robert , Kaye Elizabeth Krall , Schepsis Anthony , Voloshin Ilya
Published: August 2008

Background

Controversy remains regarding the results of all arthroscopic rotator cuff repairs compared with the mini-open approach. The purpose of this study was to perform a comprehensive literature search and meta-analysis of clinical trials comparing the results of arthroscopic rotator cuff repairs and mini-open rotator cuff repairs.

Hypothesis

There is no difference between the clinical results obtained from all arthroscopic rotator cuff repairs compared with mini-open repairs.

Study Design

Meta-analysis.

Methods

A computerized search of articles published between 1966 and July 2006 was performed using MEDLINE and PubMed. Additionally, a search of abstracts from 4 major annual meetings each held between 2000 and 2005 was performed to identify Level I to III studies comparing the results of arthroscopic rotator cuff repair and mini-open repair. Studies that included follow-up of an average of over 2 years and a minimum of 1 year and included the use of 1 of 4 validated functional outcome scores used to study shoulder injuries were included in the present meta-analysis. All outcome scores were converted to a 100-point scale to allow for outcome comparison.

Results

Five studies that met the inclusion criteria were identified. There was no difference in functional outcome scores or complications between the arthroscopic and mini-open repair groups.

Conclusion

Based on current literature, there was no difference in outcomes between the arthroscopic and mini-open rotator cuff repair techniques.
Weak-Form Efficiency of Foreign Exchange Markets of Developing Economies
Authors: Wickremasinghe Guneratne B , Kim Jae H
Published: August 2008

This study examines the empirical validity of the weak-form Efficient Market Hypothesis (EMH) for the foreign exchange market of Sri Lanka, using a battery of (univariate and panel) unit root tests, including those that allow for structural breaks. Monthly exchange rates for four major currencies (Indian rupee, UK pound, US dollar and Japanese yen) vis–à–vis the Sri Lankan rupee are considered in the empirical analysis. The results indicate that the four exchange rates studied follow a random walk, thus supporting the validity of the weak-form EMH. These results have strong implications for the participants of the foreign exchange market of Sri Lanka and government policy makers.
Measuring Several Aspects of Attention in One Test
Authors: Egeland Jens , Kovalik-Gran Iwona
Published: August 2008

Objective: Continuous performance tests are known to typically measure sustained attention but usually also yield parameters that potentially measure other subprocesses of attention. The aim of the present study was to test the factor structure of the Conners’s Continuous Performance Test (CCPT) in a heterogeneous clinical sample consisting of subjects considered to fail in different subfunctions of attention. Method and Results: CCPT records from 376 patients were factor analyzed, yielding five factors indicating a differentiation between focused attention, hyperactivity—impulsivity, sustained attention, vigilance, and change in control. Conclusion: The study warns against reducing CCPT performance to one overall score of attention. The study further emphasizes the need to reserve the concept of sustained attention for measures of change as a function of time on task. The differentiation between sustained attention and vigilance and the concept of change in mental control during the test are possible methodological contributions of the study. (J. of Att. Dis. 2010; 13(4) 339-357)
Telomerase activity of HIV-1–specific CD8+ T cells: constitutive up-regulation in controllers and selective increase by blockade of PD ligand 1 in progressors
Authors: Lichterfeld Mathias , Mou Danlei , Cung Thai Duong Hong , Williams Katie L. , Waring Michael T. , Huang Jinghe , Pereyra Florencia , Trocha Alicja , Freeman Gordon J. , Rosenberg Eric S. , Walker Bruce D. , Yu Xu G.
Published: August 2008

Exhaustion of virus-specific T cells may play an important role in the pathophysiology of chronic viral infections. Here, we analyzed telomere length and telomerase activity in HIV-1–specific CD8+ T cells from progressors or controllers to determine underlying molecular pathways of T-cell exhaustion and senescence. Telomere lengths of HIV-1–specific CD8+ T cells from progressors were significantly shorter compared with autologous cytomegalovirus (CMV)/Epstein-Barr virus (EBV)–specific CD8+ T cells or bulk CD8+ T cells, while telomere lengths from controllers significantly exceeded those of autologous bulk CD8+ T cells and reached a similar level as HIV-1–specific CD8+ T cells collected during primary HIV-1 infection. Telomere length stabilization in controllers corresponded to high levels of constitutive telomerase activity, which was associated with preservation of cytotoxic and proliferative properties. Conversely, limited constitutive telomerase activity was observed in HIV-1–specific CD8+ T cells from progressors, although an increase in both telomere length and telomerase activity was achieved in antigenic-peptide–stimulated cells from progressors after blocking the PD-1/PD ligand 1 (PD-L1) pathway. Collectively, these data suggest a causal role of telomere shortening for the functional deficiencies of HIV-1–specific CD8+ T cells in chronic progressive infection, while high constitutive telomerase activities appears to contribute to maintenance of polyfunctional HIV-1–specific CD8+ T cells from HIV-1 controllers.
Alignment of protein structures in the presence of domain motions
Authors: Mosca Roberto , Brannetti Barbara , Schneider Thomas R
Published: August 2008

Background

Structural alignment is an important step in protein comparison. Well-established methods exist for solving this problem under the assumption that the structures under comparison are considered as rigid bodies. However, proteins are flexible entities often undergoing movements that alter the positions of domains or subdomains with respect to each other. Such movements can impede the identification of structural equivalences when rigid aligners are used.

Results

We introduce a new method called RAPIDO (R apid A lignment of P roteins i n terms of Do mains) for the three-dimensional alignment of protein structures in the presence of conformational changes. The flexible aligner is coupled to a genetic algorithm for the identification of structurally conserved regions. RAPIDO is capable of aligning protein structures in the presence of large conformational changes. Structurally conserved regions are reliably detected even if they are discontinuous in sequence but continuous in space and can be used for superpositions revealing subtle differences.

Conclusion

RAPIDO is more sensitive than other flexible aligners when applied to cases of closely homologues proteins undergoing large conformational changes. When applied to a set of kinase structures it is able to detect similarities that are missed by other alignment algorithms. The algorithm is sufficiently fast to be applied to the comparison of large sets of protein structures.
Identification and correction of abnormal, incomplete and mispredicted proteins in public databases
Authors: Nagy Alinda , Hegyi Hédi , Farkas Krisztina , Tordai Hedvig , Kozma Evelin , Bányai László , Patthy László
Published: August 2008

Background

Despite significant improvements in computational annotation of genomes, sequences of abnormal, incomplete or incorrectly predicted genes and proteins remain abundant in public databases. Since the majority of incomplete, abnormal or mispredicted entries are not annotated as such, these errors seriously affect the reliability of these databases. Here we describe the MisPred approach that may provide an efficient means for the quality control of databases. The current version of the MisPred approach uses five distinct routines for identifying abnormal, incomplete or mispredicted entries based on the principle that a sequence is likely to be incorrect if some of its features conflict with our current knowledge about protein-coding genes and proteins: (i) conflict between the predicted subcellular localization of proteins and the absence of the corresponding sequence signals; (ii) presence of extracellular and cytoplasmic domains and the absence of transmembrane segments; (iii) co-occurrence of extracellular and nuclear domains; (iv) violation of domain integrity; (v) chimeras encoded by two or more genes located on different chromosomes.

Results

Analyses of predicted EnsEMBL protein sequences of nine deuterostome (Homo sapiens, Mus musculus, Rattus norvegicus, Monodelphis domestica, Gallus gallus, Xenopus tropicalis, Fugu rubripes, Danio rerio and Ciona intestinalis) and two protostome species (Caenorhabditis elegans and Drosophila melanogaster) have revealed that the absence of expected signal peptides and violation of domain integrity account for the majority of mispredictions. Analyses of sequences predicted by NCBI's GNOMON annotation pipeline show that the rates of mispredictions are comparable to those of EnsEMBL. Interestingly, even the manually curated UniProtKB/Swiss-Prot dataset is contaminated with mispredicted or abnormal proteins, although to a much lesser extent than UniProtKB/TrEMBL or the EnsEMBL or GNOMON-predicted entries.

Conclusion

MisPred works efficiently in identifying errors in predictions generated by the most reliable gene prediction tools such as the EnsEMBL and NCBI's GNOMON pipelines and also guides the correction of errors. We suggest that application of the MisPred approach will significantly improve the quality of gene predictions and the associated databases.
A high throughput live transparent animal bioassay to identify non-toxic small molecules or genes that regulate vertebrate fat metabolism for obesity drug development
Authors: Jones Kevin S , Alimov Alexander P , Rilo Horacio L , Jandacek Ronald J , Woollett Laura A , Penberthy W Todd
Published: August 2008

Background

The alarming rise in the obesity epidemic and growing concern for the pathologic consequences of the metabolic syndrome warrant great need for development of obesity-related pharmacotherapeutics. The search for such therapeutics is severely limited by the slow throughput of animal models of obesity. Amenable to placement into a 96 well plate, zebrafish larvae have emerged as one of the highest throughput vertebrate model organisms for performing small molecule screens. A method for visually identifying non-toxic molecular effectors of fat metabolism using a live transparent vertebrate was developed. Given that increased levels of nicotinamide adenine dinucleotide (NAD) via deletion of CD38 have been shown to prevent high fat diet induced obesity in mice in a SIRT-1 dependent fashion we explored the possibility of directly applying NAD to zebrafish.

Methods

Zebrafish larvae were incubated with daily refreshing of nile red containing media starting from a developmental stage of equivalent fat content among siblings (3 days post-fertilization, dpf) and continuing with daily refreshing until 7 dpf.

Results

PPAR activators, beta-adrenergic agonists, SIRT-1 activators, and nicotinic acid treatment all caused predicted changes in fat, cholesterol, and gene expression consistent with a high degree of evolutionary conservation of fat metabolism signal transduction extending from man to zebrafish larvae. All changes in fat content were visually quantifiable in a relative fashion using live zebrafish larvae nile red fluorescence microscopy. Resveratrol treatment caused the greatest and most consistent loss of fat content. The resveratrol tetramer Vaticanol B caused loss of fat equivalent in potency to resveratrol alone. Significantly, the direct administration of NAD decreased fat content in zebrafish. Results from knockdown of a zebrafish G-PCR ortholog previously determined to decrease fat content in C. elegans support that future GPR142 antagonists may be effective non-toxic anti-obesity therapeutics.

Conclusion

Owing to the apparently high level of evolutionary conservation of signal transduction pathways regulating lipid metabolism, the zebrafish can be useful for identifying non-toxic small molecules or pharmacological target gene products for developing molecular therapeutics for treating clinical obesity. Our results support the promising potential in applying NAD or resveratrol where the underlying target protein likely involves Sirtuin family member proteins. Furthermore data supports future studies focused on determining whether there is a high concentration window for resveratrol that is effective and non-toxic in high fat obesity murine models.
Knowledge transfer in Tehran University of Medical Sciences: an academic example of a developing country
Authors: Nedjat Saharnaz , Majdzadeh Reza , Gholami Jaleh , Nedjat Sima , Maleki Katayoun , Qorbani Mostafa , Shokoohi Mostafa , Ashoorkhani Mahnaz
Published: August 2008

Background

In the past two decades, scientific publications in Iran have considerably increased their medical science content, and the number of articles published in ISI journals has doubled between 1997 and 2001. The aim of the present study was to determine how frequently knowledge transfer strategies were applied in Tehran University of Medical Sciences (TUMS). We were also interested in studying the determining factors leading to the type of strategy selected.

Methodology

All TUMS research projects that had received grants from inside and outside the university in 2004, and were completed by the end of 2006, were included in the study. In total, 301 projects were examined, and data on each of the projects were collected by the research team using a standardized questionnaire. The projects' principle investigators filled out a second questionnaire. In all, 208 questionnaires were collected.

Results

Researchers stated being more engaged in the passive strategies of knowledge transfer, especially those publishing in peer-reviewed journals. The mean score for the researchers' performance in passive and active strategies were 22% and 9% of the total score, respectively. Linear regression analysis showed that the passive strategy score decreased with the increase in the number of years working as a professional (p = 0.01) and personal interest as the only reason for choosing the research topic (p = 0.01). Regarding the active strategies of knowledge transfer, health system research studies significantly raised the score (p = 0.02) and 'executive responsibility' significantly lowered it (p = 0.03).

Conclusion

As a study carried out in a Middle Eastern developing country, we see that, like many other universities in the world, many academicians still do not give priority to active strategies of knowledge transfer. Therefore, if 'linking knowledge to action' is necessary, it may also be necessary to introduce considerable changes in academic procedures and encouragement policies (e.g., employment and promotion criteria of academic members).
Spontaeneous subacute portomesenteric venous thrombosis: a case report
Authors: Mushtaque Muhammed , Cahill Ronan A , Sheehan John J , Stephens Richard B
Published: August 2008

Although uncommon and often asymptomatic, portal venous thrombosis can have catastrophic consequences for the individual it afflicts, particularly when the process propagates to involve the superior mesenteric vein. Familiarity with the condition's pathogenesis and presentation however permits early diagnosis and allows aggressive conservative management to achieve a successful outcome. Here we describe the successful outcome of such management for a 42-year-old male patient who developed this condition spontaneously.
Association Studies of Common Variants in 10 Hypogonadotropic Hypogonadism Genes with Age at Menarche
Authors: Gajdos Zofia K. Z. , Butler Johannah L. , Henderson Katherine DeLellis , He Chunyan , Supelak Pamela J. , Egyud Matthew , Price Alkes , Reich David , Clayton Peter E. , Le Marchand Loic , Hunter David J. , Henderson Brian E. , Palmert Mark R. , Hirschhorn Joel N.
Published: August 2008

Context: Although the timing of puberty is a highly heritable trait, little is known about the genes that regulate pubertal timing in the general population. Several genes have been identified that, when mutated, cause disorders of delayed or absent puberty such as hypogonadotropic hypogonadism (HH).

Objective: Because severe variants in HH-related genes cause a severe puberty phenotype, we hypothesized that common subtle variation in these genes could contribute to the population variation in pubertal timing.

Design: We assessed common genetic variation in 10 HH-related genes in 1801 women from the Hawaii and Los Angeles Multiethnic Cohort with either early (age < 11 yr) or late (age > 14 yr) menarche and in other replication samples. In addition to these common variants, we also studied the most frequently reported HH mutations to assess their role in the population variation in pubertal timing.

Setting and Patients/Other Participants: Within the general community, 1801 women from the Hawaii and Los Angeles Multiethnic Cohort participated.

Main Outcome Measures: We assessed the association of genetic variation with age at menarche.

Results: We found no significant association between any of the variants tested and age at menarche, although we cannot rule out modest effects of these variants or of other variants at long distances from the coding region. In several self-reported racial/ethnic groups represented in our study, we observed an association between estimated genetic ancestry and age at menarche.

Conclusions: Our results suggest that common variants near 10 HH-related loci do not play a substantial role in the regulation of age at menarche in the general population.
Intermittent severe, symptomatic hyponatraemia due to the nephrogenic syndrome of inappropriate antidiuresis
Authors: Soule Steven , Florkowski Chris , Potter Howard , Pattison David , Swan Martin , Hunt Penny , George Peter
Published: August 2008

A 20-year-old fit male soldier presented on two separate occasions 16 months apart with severe, symptomatic hyponatraemia and a clinical and biochemical picture consistent with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). In the intervening period, repeated plasma sodium values were in the reference range. Intensive investigation failed to reveal a cause for SIADH that was initially considered idiopathic. The description of a family comprising several adults with intermittent or water load induced-hyponatraemia associated with an activating mutation in the arginine vasopressin (AVP) receptor type 2 (AVPR2) raised the question of whether our patient could have a similar ‘nephrogenic syndrome of inappropriate antidiuresis’. Mutational screening of AVPR2 in our patient revealed a single missense mutation (R137C) in the second intracellular loop, which has been associated with constitutive activation of the AVPR2. In conclusion, adults with intermittent, severe hyponatraemia may have a constitutively activating mutation in the AVPR2 with resultant nephrogenic syndrome of inappropriate antidiuresis. Patients with idiopathic SIADH, particularly those with unmeasurable circulating AVP concentrations, should be considered for mutational screening of AVPR2.
Low adiponectin state is associated with metabolic abnormalities in obese children, particularly depending on apolipoprotein E phenotype
Authors: Wardaningsih Elfi , Miida Takashi , Seino Utako , Fueki Yuriko , Ito Masayuki , Nagasaki Keisuke , Kikuchi Toru , Uchiyama Makoto , Hirayama Satoshi , Hanyu Osamu , Miyake Kazunori , Okada Masahiko
Published: August 2008

Background

Adiponectin links obesity with insulin resistance, which causes various metabolic abnormalities including dyslipidaemia. Apolipoprotein E (apoE) phenotypes also affect lipoprotein profiles. We aimed to determine whether low adiponectin concentrations are associated with insulin resistance and downstream metabolic abnormalities in obese children.

Methods

We measured fasting concentrations of lipids, apoE, glucose, insulin and adiponectin, as well as anthropometric parameters, in 191 obese children aged 6–15 years. ApoE phenotypes were determined by isoelectric focusing. Boys ( n = 79) and girls ( n = 39) with apoE3/3 were classified into tertiles according to their adiponectin concentrations. Metabolic parameters, were compared among these three groups in boys and girls separately.

Results

The low adiponectin groups had higher median homeostasis model assessment of insulin resistance (HOMA-IR) than the middle and high adiponectin groups in both boys [5.3 (low) versus 3.1 (middle; P < 0.05) and 3.5 (high; P < 0.05)] and girls [5.0 (low) versus 4.4 (middle) and 3.0 (high; P < 0.05)]. However, only boys who were in the low adiponectin group exhibited significantly higher concentrations of blood pressure, triglycerides, LDL-cholesterol, and remnant-like particle-cholesterol, and lower concentrations of HDL-cholesterol compared with the middle or high adiponectin groups.

Conclusion

Low adiponectin concentration is associated with insulin resistance in obese children. Furthermore, decreased adiponectin with E3/3 exhibited more prominent downstream metabolic abnormalities in obese boys than in obese girls.
Assay validation and biological variation of serum receptor for advanced glycation end-products
Authors: Brown Louise F , Fraser Callum G
Published: August 2008

Background

The analytical performance characteristics of an enzyme-linked immunosorbent assay for the receptor for advanced glycation end-products (RAGE) were evaluated. The within- and between-subject components of biological variation were also estimated.

Methods

Blood was sampled from healthy volunteers into K2-ethylenediamine tetraacetic acid (EDTA) and serum separator tubes (SST) and the stability of RAGE in whole blood, plasma and serum examined. Performance characteristics of the assay were assessed using quality control materials. Three samples were obtained from each of 21 healthy volunteers one-week apart, RAGE measured and components of biological variation estimated.

Results

RAGE concentrations in blood specimens collected into K2-EDTA and SST were stable for at least 6 hours and, after centrifugation, both plasma and serum were stable for at least 24 hours. The RAGE assay had the following characteristics: inter-assay imprecision: coefficient of variation ≤7.3%, working range: 26–5000 ng/L, linearity: r = 0.9977 and detection limit: 26 ng/L. Overall within- and between-subject biological variations were 14.6% and 56.5%, the index of individuality was 0.31 and the reference change value was 49.0% at P < 0.05.

Conclusion

Samples for RAGE analyses in serum or plasma can be collected without significant difficulties with the assay showing acceptable analytical performance characteristics. Conventional population-based reference values are of limited utility in diagnosis, indicating that RAGE is likely to be more useful in monitoring disease.
Newsvendor “Pull-to-Center” Effect: Adaptive Learning in a Laboratory Experiment
Authors: Bostian AJ A. , Holt Charles A. , Smith Angela M.
Published: August 2008

In the newsvendor game, the expected-profit-maximizing order quantity is higher in the demand interval when the per-unit profit margin is high and lower in the demand interval when the per-unit profit margin is low. However, laboratory experiments show a “pull-to-center” effect: average order quantities are too low when they should be high and vice versa. We replicate this pull-to-center effect in laboratory experiments and construct an adaptive learning model that incorporates memory, reinforcement, and probabilistic choice to explain individual decisions. The intuition underlying the model's prediction is that the most recent demand observation is more likely to have been greater than the optimal order quantity if the optimal order quantity is low, in which case a recency bias tends to pull the order quantity upward. A countervailing downward pull exists if the optimal order quantity is high. The recency effect may be augmented by a reinforcement bias, which causes subjects to focus more on the profitability of decisions they actually make and less on counterfactual payoffs that would have resulted from other order quantities. The predictions of this model track the observed data patterns across treatments. A pull-to-center pattern is also observed in designs involving doubled payoffs and reduced order frequency.
TARP Redundancy Is Critical for Maintaining AMPA Receptor Function
Authors: Menuz Karen , O'Brien Jessica L. , Karmizadegan Siavash , Bredt David S. , Nicoll Roger A.
Published: August 2008

Transmembrane AMPA receptor regulatory proteins (TARPs) are AMPA receptor auxiliary subunits that influence diverse aspects of receptor function. However, the full complement of physiological roles for TARPsin vivoremains poorly understood. Here we find that double knock-out mice lacking TARPs γ-2 and γ-3 are profoundly ataxic and fail to thrive. We demonstrate that these TARPs are critical for the synaptic targeting and kinetics of AMPA receptors in cerebellar Golgi cells, but that either alone is sufficient to fully preserve function. By analyzing the few remaining synaptic AMPA receptors in the γ-2, γ-3 double knock-out mice, we unexpectedly find that these TARPs specify AMPA receptor subunit composition. This study establishes a new role for TARPs in regulating AMPA receptor assembly and suggests that TARPs are necessary for proper AMPA receptor localization and function in most, if not all, neurons of the CNS.
A Role for TASK-1 (KCNK3) Channels in the Chemosensory Control of Breathing
Authors: Trapp Stefan , Isabel Aller M. , Wisden William , Gourine Alexander V.
Published: August 2008

Acid-sensitive K+channels of the tandem P-domain K+-channel family (TASK-1 and TASK-3) have been implicated in peripheral and central respiratory chemosensitivity; however, because of the lack of decisive pharmacological agents, the final proof of the role of the TASK channel in the chemosensory control of breathing has been missing. In the mouse, TASK-1 and TASK-3 channels are dispensable for central respiratory chemosensitivity (Mulkey et al., 2007). Here, we have used knock-out animals to determine whether TASK-1 and TASK-3 channels play a role in the carotid body function and chemosensory control of breathing exerted by the carotid body chemoreceptors. Ventilatory responses to hypoxia (10% O2in inspired air) and moderate normoxic hypercapnia (3–6% CO2in inspired air) were significantly reduced in TASK-1 knock-out mice. In contrast, TASK-3-deficient mice showed responses to both stimuli that were similar to those developed by their wild-type counterparts. TASK-1 channel deficiency resulted in a marked reduction of the hypoxia (by 49%)- and CO2(by 68%)-evoked increases in the carotid sinus nerve chemoafferent discharge recorded in thein vitrosuperfused carotid body/carotid sinus nerve preparations. Deficiency in both TASK-1 and TASK-3 channels increased baseline chemoafferent activity but did not cause a further reduction of the carotid body chemosensory responses. These observations provide direct evidence that TASK-1 channels contribute significantly to the increases in the carotid body chemoafferent discharge in response to a decrease in arterial PO2or an increase in PCO2/[H+]. TASK-1 channels therefore play a key role in the control of ventilation by peripheral chemoreceptors.
BRI2 Inhibits Amyloid β-Peptide Precursor Protein Processing by Interfering with the Docking of Secretases to the Substrate
Authors: Matsuda Shuji , Giliberto Luca , Matsuda Yukiko , McGowan Eileen M. , D'Adamio Luciano
Published: August 2008

Genetic alterations of amyloid β-peptide (Aβ) production caused by mutations in the Aβ precursor protein (APP) cause familial Alzheimer's disease (AD). Mutations inBRI2, a gene of undefined function, are linked to familial British and Danish dementias, which are pathologically and clinically similar to Alzheimer's disease. We report that BRI2 is a physiological suppressor of Aβ production. BRI2 restrict docking of γ-secretase to APP and access of α- and β-secretases to their cleavage APP sequences. Alterations of BRI2 by gene targeting or transgenic expression regulate Aβ levels and AD pathology in mouse models of AD. Competitive inhibition of APP processing by BRI2 may provide a new approach to AD therapy and prevention.
Preferential Enhancement of Dopamine Transmission within the Nucleus Accumbens Shell by Cocaine Is Attributable to a Direct Increase in Phasic Dopamine Release Events
Authors: Aragona Brandon J. , Cleaveland Nathan A. , Stuber Garret D. , Day Jeremy J. , Carelli Regina M. , Wightman R. Mark
Published: August 2008

Preferential enhancement of dopamine transmission within the nucleus accumbens (NAc) shell is a fundamental aspect of the neural regulation of cocaine reward. Despite its importance, the nature of this effect is poorly understood. Here, we used fast-scan cyclic voltammetry to examine specific transmission processes underlying cocaine-evoked increases in dopamine transmission within the NAc core and shell. Initially, we examined altered terminal dopamine concentrations after global autoreceptor blockade. This was the first examination of autoreceptor regulation of naturally occurring phasic dopamine transmission and provided a novel characterization of specific components of dopamine neurotransmission. Comparison of increased dopamine signaling evoked by autoreceptor blockade and cocaine administration allowed robust resolution between increased frequency, concentration, and duration of phasic dopamine release events after cocaine delivery. Cocaine increased dopamine transmission by slowed uptake and increased concentration of dopamine released in the core and shell. However, an additional increase in the number phasic release events occurred only within the NAc shell, and this increase was eliminated by inactivation of midbrain dopaminergic neurons. This represents the first evidence that cocaine directly increases the frequency of dopamine release events and reveals that this is responsible for preferentially increased dopamine transmission within the NAc shell after cocaine administration. Additionally, cocaine administration resulted in a synergistic increase in dopamine concentration, and subregion differences were abolished when cocaine was administered in the absence of autoregulation. Together, these results demonstrate that cocaine administration results in a temporally and regionally specific increase in phasic dopamine release that is significantly regulated by dopamine autoreceptors.
Altered Molecular Regionalization and Normal Thalamocortical Connections in Cortex-SpecificPax6Knock-Out Mice
Authors: Piñon Maria Carmen , Tuoc Tran Cong , Ashery-Padan Ruth , Molnár Zoltán , Stoykova Anastassia
Published: August 2008

Transcription factor Pax6 exerts a prominent rostrolateralhighto caudomediallowexpression gradient in the cortical progenitors and have been implicated in regulation of area identity in the mammalian cortex. Herein, we analyzed the role of Pax6 in molecular arealization and development of thalamocortical connections in the juvenile cortex-specific conditionalPax6knock-out mice (Pax6cKO). Using a set of molecular markers of positional identity (Id2,Cadherin6,COUP-TF1,RZRβ, andEphA7), we show that, in the juvenilePax6cKO, the relative size of caudal cortical areas (putative visual and somatosensory) are mildly enlarged, whereas the rostral domain (putative motor) is severely reduced. Despite the rostral shift of graded expression of areal markers, the distribution of area-specific thalamocortical and corticofugal projections appear normal in thePax6cKO. This indicates that change of the size of cortical areas is not accompanied by a change in cortical identity. We show furthermore that, despite a severe depletion of supragranular cortical layers and accumulation of cells along the pallial–subpallial boundary, thalamocortical fibers establish a periphery-related pattern of the somatosensory cortex in normal position inPax6cKO.Our findings indicate that Pax6 expression gradients in cortical progenitors do not directly impart thalamocortical or corticofugal areal identity.
Developmental Excitation of Corticothalamic Neurons by Nicotinic Acetylcholine Receptors
Authors: Kassam Sameera M. , Herman Patrick M. , Goodfellow Nathalie M. , Alves Nyresa C. , Lambe Evelyn K.
Published: August 2008

In this study, we show robust nicotinic excitation of pyramidal neurons in layer VI of prefrontal cortex. This layer contains the corticothalamic neurons, which gate thalamic activity and play a critical role in attention. Our experiments tested nicotinic excitation across postnatal development, using whole-cell recordings in prefrontal brain slices from rats. These experiments showed that layer VI neurons have peak nicotinic currents during the first postnatal month, a time period of intensive cortical development in rodents. We demonstrate that these currents are mediated directly by postsynaptic nicotinic receptors and can be suppressed by a competitive antagonist of α4β2* nicotinic receptors. To record from identified corticothalamic neurons, we performed stereotaxic surgery to label the neurons projecting to medial dorsal thalamus. As hypothesized, recordings from these retrogradely labeled neurons in layer VI showed prominent nicotinic currents. Finally, we examined the effects of the drug nicotine on layer VI neurons and probed for the potential involvement of the accessory subunit, α5, in their receptors. A level of nicotine similar to that found in the blood of smokers elicits a stable inward current in layer VI neurons, yet this exposure desensitizes ∼50% of the subsequent current elicited by acetylcholine. An allosteric modulator of α4β2α5receptors resulted in a 2.5-fold potentiation of submaximal nicotinic currents. This result is consistent with the expression of the relatively rare α5nicotinic subunit in layer VI. In summary, we show that layer VI corticothalamic neurons can be strongly excited during development by an unusual subtype of nicotinic receptor.