bluuebunny/crossref_metadata_2025 huggingface dataset:
A multivariate regression approach to association analysis of a quantitative trait network
Authors: Kim Seyoung , Sohn Kyung-Ah , Xing Eric P.
Published: May 2009

Motivation: Many complex disease syndromes such as asthma consist of a large number of highly related, rather than independent, clinical phenotypes, raising a new technical challenge in identifying genetic variations associated simultaneously with correlated traits. Although a causal genetic variation may influence a group of highly correlated traits jointly, most of the previous association analyses considered each phenotype separately, or combined results from a set of single-phenotype analyses.

Results: We propose a new statistical framework called graph-guided fused lasso to address this issue in a principled way. Our approach represents the dependency structure among the quantitative traits explicitly as a network, and leverages this trait network to encode structured regularizations in a multivariate regression model over the genotypes and traits, so that the genetic markers that jointly influence subgroups of highly correlated traits can be detected with high sensitivity and specificity. While most of the traditional methods examined each phenotype independently, our approach analyzes all of the traits jointly in a single statistical method to discover the genetic markers that perturb a subset of correlated triats jointly rather than a single trait. Using simulated datasets based on the HapMap consortium data and an asthma dataset, we compare the performance of our method with the single-marker analysis, and other sparse regression methods that do not use any structural information in the traits. Our results show that there is a significant advantage in detecting the true causal single nucleotide polymorphisms when we incorporate the correlation pattern in traits using our proposed methods.

Availability: Software for GFlasso is available at http://www.sailing.cs.cmu.edu/gflasso.html

Contact:  sssykim@cs.cmu.edu; ksohn@cs.cmu.edu;
E-zyme: predicting potential EC numbers from the chemical transformation pattern of substrate-product pairs
Authors: Yamanishi Yoshihiro , Hattori Masahiro , Kotera Masaaki , Goto Susumu , Kanehisa Minoru
Published: May 2009

Motivation: The IUBMB's Enzyme Nomenclature system, commonly known as the Enzyme Commission (EC) numbers, plays key roles in classifying enzymatic reactions and in linking the enzyme genes or proteins to reactions in metabolic pathways. There are numerous reactions known to be present in various pathways but without any official EC numbers, most of which have no hope to be given ones because of the lack of the published articles on enzyme assays.

Results: In this article we propose a new method to predict the potential EC numbers to given reactant pairs (substrates and products) or uncharacterized reactions, and a web-server named E-zyme as an application. This technology is based on our original biochemical transformation pattern which we call an ‘RDM pattern’, and consists of three steps: (i) graph alignment of a query reactant pair (substrates and products) for computing the query RDM pattern, (ii) multi-layered partial template matching by comparing the query RDM pattern with template patterns related with known EC numbers and (iii) weighted major voting scheme for selecting appropriate EC numbers. As the result, cross-validation experiments show that the proposed method achieves both high coverage and high prediction accuracy at a practical level, and consistently outperforms the previous method.

Availability: The E-zyme system is available at http://www.genome.jp/tools/e-zyme/

Contact:  kanehisa@kuicr.kyoto-u.ac.jp
Joint estimation of gene conversion rates and mean conversion tract lengths from population SNP data
Authors: Yin Junming , Jordan Michael I. , Song Yun S.
Published: May 2009

Motivation: Two known types of meiotic recombination are crossovers and gene conversions. Although they leave behind different footprints in the genome, it is a challenging task to tease apart their relative contributions to the observed genetic variation. In particular, for a given population SNP dataset, the joint estimation of the crossover rate, the gene conversion rate and the mean conversion tract length is widely viewed as a very difficult problem.

Results: In this article, we devise a likelihood-based method using an interleaved hidden Markov model (HMM) that can jointly estimate the aforementioned three parameters fundamental to recombination. Our method significantly improves upon a recently proposed method based on a factorial HMM. We show that modeling overlapping gene conversions is crucial for improving the joint estimation of the gene conversion rate and the mean conversion tract length. We test the performance of our method on simulated data. We then apply our method to analyze real biological data from the telomere of the X chromosome of Drosophila melanogaster, and show that the ratio of the gene conversion rate to the crossover rate for the region may not be nearly as high as previously claimed.

Availability: A software implementation of the algorithms discussed in this article is available at http://www.cs.berkeley.edu/∼yss/software.html.

Contact:  yss@eecs.berkeley.edu
REPETITA: detection and discrimination of the periodicity of protein solenoid repeats by discrete Fourier transform
Authors: Marsella Luca , Sirocco Francesco , Trovato Antonio , Seno Flavio , Tosatto Silvio C.E.
Published: May 2009

Motivation: Proteins with solenoid repeats evolve more quickly than non-repetitive ones and their periodicity may be rapidly hidden at sequence level, while still evident in structure. In order to identify these repeats, we propose here a novel method based on a metric characterizing amino-acid properties (polarity, secondary structure, molecular volume, codon diversity, electric charge) using five previously derived numerical functions.

Results: The five spectra of the candidate sequences coding for structural repeats, obtained by Discrete Fourier Transform (DFT), show common features allowing determination of repeat periodicity with excellent results. Moreover it is possible to introduce a phase space parameterized by two quantities related to the Fourier spectra which allow for a clear distinction between a non-homologous set of globular proteins and proteins with solenoid repeats. The DFT method is shown to be competitive with other state of the art methods in the detection of solenoid structures, while improving its performance especially in the identification of periodicities, since it is able to recognize the actual repeat length in most cases. Moreover it highlights the relevance of local structural propensities in determining solenoid repeats.

Availability: A web tool implementing the algorithm presented in the article (REPETITA) is available with additional details on the data sets at the URL: http://protein.bio.unipd.it/repetita/.

Contact:  silvio.tosatto@unipd.it
Meta‐Analysis of the Related Nutritional Supplements Dimethyl Sulfoxide and Methylsulfonylmethane in the Treatment of Osteoarthritis of the Knee
Authors: Brien Sarah , Prescott Phil , Lewith George
Published: May 2009

Dimethyl sulphoxide and methylsulfonylmethane are two related nutritional supplements used for symptomatic relief of osteoarthritis (OA). We conducted a meta‐analysis to evaluate their efficacy in reducing pain associated with OA. Randomized or quasi‐randomized controlled trials (RCTs), identified by systematic electronic searches, citation tracking and searches of clinical trial registries, assessing these supplements in osteoarthritis of any joint were considered for inclusion. Meta‐analysis, based on difference in mean pain related outcomes between treatment and comparator groups, was carried out based on a random effect model. Seven potential trials were identified of which three RCTs, two DMSO and one MSM (total N = 326 patients) were eligible for inclusion. All three trials were considered high methodological quality. A significant degree of heterogeneity (χ2 = 6.28,
P = .043) was revealed. Two studies demonstrated statistically significant (but not clinically relevant) reduction in pain compared with controls; with one showing no group difference. The meta‐analysis confirmed a non significant reduction of pain on visual analogue scale of 6.34 mm (SE = 3.49, 95% CI, −0.49, 13.17). The overall effect size of 1.82 was neither statistically nor clinically significant. Current evidence suggests DMSO and MSM are not clinically effective in the reduction of pain in the treatment of OA. No definitive conclusions can currently be drawn from the data due to the mixed findings and the use of inadequate dosing periods.
Towards a quantitative understanding of the within-host dynamics of influenza A infections
Authors: Handel Andreas , Longini Ira M. , Antia Rustom
Published: May 2009

Although the influenza A virus has been extensively studied, a quantitative understanding of the infection dynamics is still lacking. To make progress in this direction, we designed several mathematical models and compared them with data from influenza A infections of mice. We find that the immune response (IR) plays an important part in the infection dynamics. Both an innate and an adaptive IR are required to provide adequate explanation of the data. In contrast, regrowth of epithelial cells did not seem to be an important mechanism on the time scale of the infection. We also find that different model variants for both innate and adaptive responses fit the data well, indicating the need for additional data to allow further model discrimination.
Spine-shaped gold protrusions improve the adherence and electrical coupling of neurons with the surface of micro-electronic devices
Authors: Hai Aviad , Dormann Ada , Shappir Joseph , Yitzchaik Shlomo , Bartic Carmen , Borghs Gustaaf , Langedijk J. P. M. , Spira Micha E.
Published: May 2009

Interfacing neurons with micro- and nano-electronic devices has been a subject of intense study over the last decade. One of the major problems in assembling efficient neuro-electronic hybrid systems is the weak electrical coupling between the components. This is mainly attributed to the fundamental property of living cells to form and maintain an extracellular cleft between the plasma membrane and any substrate to which they adhere. This cleft shunts the current generated by propagating action potentials and thus reduces the signal-to-noise ratio. Reducing the cleft thickness, and thereby increasing the seal resistance formed between the neurons and the sensing surface, is thus a challenge and could improve the electrical coupling coefficient. Using electron microscopic analysis and field potential recordings, we examined here the use of gold micro-structures that mimic dendritic spines in their shape and dimensions to improve the adhesion and electrical coupling between neurons and micro-electronic devices. We found that neurons cultured on a gold-spine matrix, functionalized by a cysteine-terminated peptide with a number of RGD repeats, readily engulf the spines, forming tight apposition. The recorded field potentials of cultured
Aplysia
neurons are significantly larger using gold-spine electrodes in comparison with flat electrodes.
Use of adipose stem cells and polylactide discs for tissue engineering of the temporomandibular joint disc
Authors: Mäenpää Katja , Ellä Ville , Mauno Jari , Kellomäki Minna , Suuronen Riitta , Ylikomi Timo , Miettinen Susanna
Published: May 2009

There is currently no suitable replacement for damaged temporomandibular joint (TMJ) discs after discectomy. In the present study, we fabricated bilayer biodegradable polylactide (PLA) discs comprising a non-woven mat of poly(L/D)lactide (P(L/D)LA) 96/4 and a P(L/DL)LA 70/30 membrane plate. The PLA disc was examined in combination with adipose stem cells (ASCs) for tissue engineering of the fibrocartilaginous TMJ disc
in vitro
. ASCs were cultured in parallel in control and chondrogenic medium for a maximum of six weeks. Relative expression of the genes, aggrecan, type I collagen and type II collagen present in the TMJ disc extracellular matrix increased in the ASC-seeded PLA discs in the chondrogenic medium. The hypertrophic marker, type X collagen, was moderately induced. Alcian blue staining showed accumulation of sulphated glycosaminoglycans. ASC differentiation in the PLA discs was close to that observed in pellet cultures. Comparison of the mRNA levels revealed that the degree of ASC differentiation was lower than that in TMJ disc-derived cells and tissue. The pellet format supported the phenotype of the TMJ disc-derived cells under chondrogenic conditions and also enhanced their hyalinization potential, which is considered part of the TMJ disc degeneration process. Accordingly, the combination of ASCs and PLA discs has potential for the development of a tissue-engineered TMJ disc replacement.
Evidence for intermittency and a truncated power law from highly resolved aphid movement data
Authors: Mashanova Alla , Oliver Tom H. , Jansen Vincent A. A.
Published: May 2009

Power laws are increasingly used to describe animal movement. Despite this, the use of power laws has been criticized on both empirical and theoretical grounds, and alternative models based on extensions of conventional random walk theory (Brownian motion) have been suggested. In this paper, we analyse a large volume of data of aphid walking behaviour (65 068 data points), which provides a highly resolved dataset to investigate the pattern of movement. We show that aphid movement is intermittent—with alternations of a slow movement with frequent change of direction and a fast, relatively directed movement—and that the fast movement consists of two phases—a strongly directed phase that gradually changes into an uncorrelated random walk. By measuring the mean-squared displacement and the duration of non-stop movement episodes we found that both spatial and temporal aspects of aphid movement are best described using a truncated power law approach. We suggest that the observed spatial pattern arises from the duration of non-stop movement phases rather than from correlations in turning angles. We discuss the implications of these findings for interpreting movement data, such as distinguishing between movement and non-movement, and the effect of the range of data used in the analysis on the conclusions.
Time-dependent lateral transmission of force in skeletal muscle
Authors: Gao Yingxin , Wineman Alan S. , Waas Anthony M.
Published: May 2009

There is experimental evidence to suggest that extensible connective tissues are mechanically time-dependent. In view of this, the mechanics of time-dependent lateral stress transfer in skeletal muscle is investigated by employing a viscoelastic shear lag model for the transfer of tensile stress between muscle fibres and the surrounding extracellular matrix (ECM) by means of shear stresses at the interface between the muscle fibre and the ECM. The model allows for both mechanical strains in the muscle as well as the strain owing to muscle contraction. Both the ECM and the muscle fibre are modelled as viscoelastic solids. As a result, time-dependent lateral stress transfer can be studied under a variety of loading and muscle stimulation conditions. The results show that the larger the muscle fibre creep time relative to the ECM relaxation time, the longer it takes for the muscle fibre stress to relax. It also shows that the response of the muscle–ECM composite system also depends on the characteristic time of a strain history relative to the characteristic relaxation time of the ECM. The results from the present model provide significant insight into the role of the parameters that characterize the response of the muscle composite system.
Individual and social discounting in a viscous population
Authors: Sozou Peter D.
Published: May 2009

Social discounting in economics involves applying a diminishing weight to community-wide benefits or costs into the future. It impacts on public policy decisions involving future positive or negative effects, but there is no consensus on the correct basis for determining the social discount rate. This study presents an evolutionary biological framework for social discounting. How an organism should value future benefits to its local community is governed by the extent to which members of the community in the future are likely to be its kin. Trade-offs between immediate and delayed benefits to an individual or to its community are analysed for a modelled patch-structured iteroparous population with limited dispersal. It is shown that the social discount rate is generally lower than the individual (private) discount rate. The difference in the two rates is most pronounced, in ratio terms, when the dispersal level is low and the hazard rate for patch destruction is much smaller than the individual mortality rate. When decisions involve enforced collective action rather than individuals acting independently, social investment increases but the social discount rate remains the same.
Heterozygosity-based assortative mating in blue tits (Cyanistes caeruleus): implications for the evolution of mate choice
Authors: García-Navas Vicente , Ortego Joaquín , Sanz Juan José
Published: May 2009

The general hypothesis of mate choice based on non-additive genetic traits suggests that individuals would gain important benefits by choosing genetically dissimilar mates (compatible mate hypothesis) and/or more heterozygous mates (heterozygous mate hypothesis). In this study, we test these hypotheses in a socially monogamous bird, the blue tit (Cyanistes caeruleus). We found no evidence for a relatedness-based mating pattern, but heterozygosity was positively correlated between social mates, suggesting that blue tits may base their mating preferences on partner's heterozygosity. We found evidence that the observed heterozygosity-based assortative mating could be maintained by both direct and indirect benefits. Heterozygosity reflected individual quality in both sexes: egg production and quality increased with female heterozygosity while more heterozygous males showed higher feeding rates during the brood-rearing period. Further, estimated offspring heterozygosity correlated with both paternal and maternal heterozygosity, suggesting that mating with heterozygous individuals can increase offspring genetic quality. Finally, plumage crown coloration was associated with male heterozygosity, and this could explain unanimous mate preferences for highly heterozygous and more ornamented individuals. Overall, this study suggests that non-additive genetic traits may play an important role in the evolution of mating preferences and offers empirical support to the resolution of the lek paradox from the perspective of the heterozygous mate hypothesis.
Change in maternal environment induced by cross-fostering alters genetic and epigenetic effects on complex traits in mice
Authors: Hager Reinmar , Cheverud James M. , Wolf Jason B.
Published: May 2009

The interaction between maternally provided environment and offspring genotype is a major determinant of offspring development and fitness in many organisms. Recent research has demonstrated that not only genetic effects, but also epigenetic effects may be subject to modifications by the maternal environment. Genomic imprinting resulting in parent-of-origin-dependent gene expression is among the best studied of epigenetic effects. However, very little is known about the degree to which genomic imprinting effects can be modulated by the maternally provided environment, which has important implications for phenotypic plasticity. In this study, we investigated this unresolved question using a cross-fostering design in which mouse pups were nursed by either their own or an unrelated mother. We scanned the entire genome to search for quantitative trait loci whose effects depend on cross-fostering and detected 10 of such loci. Of the 10 loci, 4 showed imprinting by cross-foster interactions. In most cases, the interaction effect was due to the presence of an effect in either cross-fostered or non-cross-fostered animals. Our results demonstrate that genomic imprinting effects may often be modified by the maternal environment and that such interactions can impact key fitness-related traits suggesting a greater plasticity of genomic imprinting than previously assumed.
Interannual variability in species composition explained as seasonally entrained chaos
Authors: Dakos Vasilis , Benincà Elisa , van Nes Egbert H. , Philippart Catharina J. M. , Scheffer Marten , Huisman Jef
Published: May 2009

The species composition of plankton, insect and annual plant communities may vary markedly from year to year. Such interannual variability is usually thought to be driven by year-to-year variation in weather conditions. Here we examine an alternative explanation. We studied the effects of regular seasonal forcing on a multi-species predator–prey model consisting of phytoplankton and zooplankton species. The model predicts that interannual variability in species composition can easily arise without interannual variability in external conditions. Seasonal forcing increased the probability of chaos in our model communities, but squeezed these irregular species dynamics within the seasonal cycle. As a result, the population dynamics had a peculiar character. Consistent with long-term time series of natural plankton communities, seasonal variation led to a distinct seasonal succession of species, yet the species composition varied from year to year in an irregular fashion. Our results suggest that interannual variability in species composition is an intrinsic property of multi-species communities in seasonal environments.
Fine-Tuning of the Cytoplasmic Ca2+ Concentration Is Essential for Pollen Tube Growth
Authors: Iwano Megumi , Entani Tetsuyuki , Shiba Hiroshi , Kakita Mituru , Nagai Takeharu , Mizuno Hideaki , Miyawaki Atsushi , Shoji Tsubasa , Kubo Kenichi , Isogai Akira , Takayama Seiji
Published: May 2009

Pollen tube growth is crucial for the delivery of sperm cells to the ovule during flowering plant reproduction. Previous in vitro imaging of Lilium longiflorum and Nicotiana tabacum has shown that growing pollen tubes exhibit a tip-focused Ca2+ concentration ([Ca2+]) gradient and regular oscillations of the cytosolic [Ca2+] ([Ca2+]cyt) in the tip region. Whether this [Ca2+] gradient and/or [Ca2+]cyt oscillations are present as the tube grows through the stigma (in vivo condition), however, is still not clear. We monitored [Ca2+]cyt dynamics in pollen tubes under various conditions using Arabidopsis (Arabidopsis thaliana) and N. tabacum expressing yellow cameleon 3.60, a fluorescent calcium indicator with a large dynamic range. The tip-focused [Ca2+]cyt gradient was always observed in growing pollen tubes. Regular oscillations of the [Ca2+]cyt, however, were rarely identified in Arabidopsis or N. tabacum pollen tubes grown under the in vivo condition or in those placed in germination medium just after they had grown through a style (semi-in vivo condition). On the other hand, regular oscillations were observed in vitro in both growing and nongrowing pollen tubes, although the oscillation amplitude was 5-fold greater in the nongrowing pollen tubes compared with growing pollen tubes. These results suggested that a submicromolar [Ca2+]cyt in the tip region is essential for pollen tube growth, whereas a regular [Ca2+] oscillation is not. Next, we monitored [Ca2+] dynamics in the endoplasmic reticulum ([Ca2+]ER) in relation to Arabidopsis pollen tube growth using yellow cameleon 4.60, which has a lower affinity for Ca2+ compared with yellow cameleon 3.60. The [Ca2+]ER in pollen tubes grown under the semi-in vivo condition was between 100 and 500 μ  m. In addition, cyclopiazonic acid, an inhibitor of ER-type Ca2+-ATPases, inhibited growth and decreased the [Ca2+]ER. Our observations suggest that the ER serves as one of the Ca2+ stores in the pollen tube and cyclopiazonic acid-sensitive Ca2+-ATPases in the ER are required for pollen tube growth.
The RNA Hydrolysis and the Cytokinin Binding Activities of PR-10 Proteins Are Differently Performed by Two Isoforms of the Pru p 1 Peach Major Allergen and Are Possibly Functionally Related
Authors: Zubini Paola , Zambelli Barbara , Musiani Francesco , Ciurli Stefano , Bertolini Paolo , Baraldi Elena
Published: May 2009

PR-10 proteins are a family of pathogenesis-related (PR) allergenic proteins playing multifunctional roles. The peach (Prunus persica) major allergen, Pru p 1.01, and its isoform, Pru p 1.06D, were found highly expressed in the fruit skin at the pit hardening stage, when fruits transiently lose their susceptibility to the fungal pathogen Monilinia spp. To investigate the possible role of the two Pru p 1 isoforms in plant defense, the recombinant proteins were expressed in Escherichia coli and purified. Light scattering experiments and circular dichroism spectroscopy showed that both proteins are monomers in solution with secondary structures typical of PR-10 proteins. Even though the proteins do not display direct antimicrobial activity, they both act as RNases, a function possibly related to defense. The RNase activity is different for the two proteins, and only that of Pru p 1.01 is affected in the presence of the cytokinin zeatin, suggesting a physiological correlation between Pru p 1.01 ligand binding and enzymatic activity. The binding of zeatin to Pru p 1.01 was evaluated using isothermal titration calorimetry, which provided information on the stoichiometry and on the thermodynamic parameters of the interaction. The structural architecture of Pru p 1.01 and Pru p 1.06D was obtained by homology modeling, and the differences in the binding pockets, possibly accounting for the observed difference in binding activity, were evaluated.
Constitutive activation of nuclear factor‐κB is preferentially involved in the proliferation of basal‐like subtype breast cancer cell lines
Authors: Yamaguchi Noritaka , Ito Taku , Azuma Sakura , Ito Emi , Honma Reiko , Yanagisawa Yuka , Nishikawa Akira , Kawamura Mika , Imai Jun‐ichi , Watanabe Shinya , Semba Kentaro , Inoue Jun‐ichiro
Published: May 2009

Constitutive nuclear factor (NF)‐κB activation is thought to be involved in survival, invasion, and metastasis in various types of cancers. However, neither the subtypes of breast cancer cells with constitutive NF‐κB activation nor the molecular mechanisms leading to its constitutive activation have been clearly defined. Here, we quantitatively analyzed basal NF‐κB activity in 35 human breast cancer cell lines and found that most of the cell lines with high constitutive NF‐κB activation were categorized in the estrogen receptor negative, progesterone receptor negative, ERBB2 negative basal‐like subtype, which is the most malignant form of breast cancer. Inhibition of constitutive NF‐κB activation by expression of IκBα super‐repressor reduced proliferation of the basal‐like subtype cell lines. Expression levels of mRNA encoding NF‐κB‐inducing kinase (NIK) were elevated in several breast cancer cell lines, and RNA interference‐mediated knockdown of NIK reduced NF‐κB activation in a subset of the basal‐like subtype cell lines with upregulated NIK expression. Taken together, these results suggest that constitutive NF‐κB activation, partially dependent on NIK, is preferentially involved in proliferation of basal‐like subtype breast cancer cells and may be a useful therapeutic target for this subtype of cancer. (Cancer Sci 2009; 100: 1668–1674)
Genetic variants in the Runt‐related transcription factor 3 gene contribute to gastric cancer risk in a Chinese population
Authors: Wu Dongmei , Tian Yuanyuan , Gong Weida , Zhu Haixia , Zhang Zhizhong , Wang Meilin , Wang Shizhi , Tan Ming , Wu Haorong , Zhang Zhengdong
Published: May 2009

Runt‐related transcription factor 3 (RUNX3) is a well known gene for its functions in gastric cancer suppression, but the effect of its genetic variations on the risk of gastric cancer remains unclear. In this study, ten tagging single nucleotide polymorphisms (tSNPs) of the RUNX3 gene were selected and genotyped in a hospital‐based case‐control study of 312 gastric cancer patients and 329 cancer‐free controls in a Chinese population. In the single‐locus analysis, three RUNX3 intronic tSNPs associated with significantly increased risk of gastric cancer were observed: the SNP3 rs11249206 CC genotype (adjusted odds ratio [OR] = 1.75, 95% confidence interval [CI] = 1.03–2.99), compared with the TT genotype; the SNP7 rs760805 AA genotype (adjusted OR = 1.82, 95% CI = 1.14–2.92), compared with the TT genotype; and the SNP8 rs2236852 GG genotype (adjusted OR = 1.69, 95% CI = 1.05–2.72), compared with the AA genotype. In the combined analyses of these three tSNPs, we found that the combined genotypes with four to six variant (risk) alleles (i.e. SNP3 C, SNP7 A, and SNP8 G alleles) were associated with an increased risk of gastric cancer compared with those with one to three variant (risk) alleles (adjusted OR = 2.00, 95% CI = 1.41–2.85), and this increased risk was more pronounced among subgroups of age ≥65 years, never smokers, and never drinkers. However, no significant association was observed in the clinicopathological features analyses. In conclusion, the RUNX3 genetic variants may modulate the risk of gastric cancer in a Chinese population. Further larger and functional studies are warranted to validate the findings. (Cancer Sci 2009; 100: 1688–1694)
A 7‐year experience with low blood TSH cutoff levels for neonatal screening reveals an unsuspected frequency of congenital hypothyroidism (CH)
Authors: Corbetta Carlo , Weber Giovanna , Cortinovis Francesca , Calebiro Davide , Passoni Arianna , Vigone Maria C. , Beck‐Peccoz Paolo , Chiumello Giuseppe , Persani Luca
Published: May 2009

Context  The guidelines of the National Academy of Clinical Biochemistry advocated the use of low bloodspot TSH (b‐TSH) threshold for newborn screening of congenital hypothyroidism (CH). The impact generated by the application of this indication is largely unknown.

Objective  To determine the impact on CH epidemiology and classification generated by the introduction of low b‐TSH cutoff.

Design  Retrospective study of 629,042 newborns screened with b‐TSH cutoffs of 12 (years 1999–2002) or 10 mU/l (2003–2005).

Measurements  Congenital hypothyroidism incidence and classification. Results were compared with those virtually obtained with the previous cutoff (20 mU/l). Clinical re‐evaluation after L‐T4 withdrawal of a representative group of 140 CH children at 3–5 years.

Results  Low b‐TSH cutoffs allowed the detection of 435 newborns with confirmed CH (incidence 1:1446). Forty‐five percent of CH infants, including 12/141 dysgenesis, would have been missed using the 20 mU/l cutoff. In contrast to current classification, 32% CH newborns had thyroid dysgenesis and 68% had a gland in situ (GIS). Premature birth was present in 20% of cases being associated with a 3–5 fold increased risk of GIS CH. Re‐evaluation at 3–5 years showed a permanent thyroid dysfunction in 78% of 59 CH toddlers with GIS.

Conclusions  The use of low b‐TSH cutoff allowed the detection of an unsuspected number of children with neonatal hypothyroidism, evolving in mild permanent thyroid dysfunction later in life. The incidence of CH in this Italian population appears to be double than previously thought with a clear‐cut prevalence of functional defects over dysgenetic ones.
Macroprolactinaemia: prevalence and aetiologies in a large group of hospital workers
Authors: Hattori Naoki , Ishihara Takashi , Saiki Yasuhiko
Published: May 2009

Objective  Macroprolactinaemia is one of the causes of hyperprolactinaemia and often leads to misdiagnosis and inappropriate treatment, but the aetiologies are unclear. The objective of the study was to determine the prevalence of macroprolactinaemia in a healthy population and to investigate the mechanisms underlying the development of macroprolactin.

Design  Observational study of the prevalence, causes, mechanisms and diagnosis of disease using excess sera after hepatitis B virus screening tests at a hospital in Japan.

Participants  A total of 1330 hospital workers (1010 women and 320 men) participated in this study.

Measurements  Macroprolactinaemia was screened using the polyethylene glycol (PEG) precipitation method. Sera containing macroprolactin were further examined by binding studies for possible aetiologies.

Results  Of the 1330 subjects, 49 (3·68%) were diagnosed with macroprolactinaemia. The frequency of hyperprolactinaemia in untreated samples in subjects with macroprolactinaemia (30·6%) was significantly higher than in individuals without macroprolactinaemia (2·26%). Of the 49 subjects with macroprolactinaemia, all had a normal monomeric PRL concentration following PEG removal of macroprolactin. Of 44 hyperprolactinaemias found, 15 (34·1%) had macroprolactinaemia. IgG‐bound prolactin was detected in all sera containing macroprolactin. The levels of IgG‐bound prolactin positively correlated with those of macroprolactin, suggesting that IgG‐bound prolactin forms macroprolactin. Approximately three quarters of the subjects with macroprolactinaemia had anti‐prolactin autoantibodies. Glycosylation, aggregation and covalent/noncovalent binding were also involved in the formation of macroprolactin.

Conclusions  Macroprolactinaemia is a common disorder and causes hyperprolactinaemia in a healthy population. The major aetiology of macroprolactin in our subjects was complexes of prolactin–IgG comprising mainly anti‐prolactin autoantibodies, and other minor complex prolactin species.
Incorporating thermal regimes into environmental flows assessments: modifying dam operations to restore freshwater ecosystem integrity
Authors: OLDEN JULIAN D. , NAIMAN ROBERT J.
Published: May 2009

1. Despite escalating conflict over fresh water, recent years have witnessed a growing realisation that human society must modify its behaviour to ensure long‐term ecological vitality of riverine ecosystems. In response, ecologists have been increasingly asked to guide instream flow management by providing ‘environmental flow’ prescriptions for sustaining the ecological integrity of riverine systems.

2. Environmental flows are typically discussed in the context of water releases from dams and water allocation for extraction (such as for urban use or irrigation), where there is general agreement that rivers need to exhibit some resemblance of natural flow variability necessary to support a functioning ecosystem. Although productive dialogue continues on how best to define environmental flows, these discussions have been focused primarily on water quantity without explicit consideration of many components of water quality, including water temperature – a fundamental ecological variable.

3.Many human activities on the landscape have modified riverine thermal regimes. In particular, many dams have modified thermal regimes by selectively releasing hypolimnetic (cold) or epilimnetic (warm) water from thermally stratified reservoirs to the detriment of entire assemblages of native organisms. Despite the global scope of thermal alteration by dams, the prevention or mitigation of thermal degradation has not entered the conversation when environmental flows are discussed.

4.Here, we propose that a river’s thermal regime is a key, yet poorly acknowledged, component of environmental flows. This study explores the concept of the natural thermal regime, reviews how dam operations modify thermal regimes, and discusses the ecological implications of thermal alteration for freshwater ecosystems. We identify five major challenges for incorporating water temperatures into environmental flow assessments, and describe future research opportunities and some alternative approaches for confronting those challenges.

5. We encourage ecologists and water managers to broaden their perspective on environmental flows to include both water quantity and quality with respect to restoring natural thermal regimes. We suggest that scientific research should focus on the comprehensive characterisation of seasonality and variability in stream temperatures, quantification of the temporal and spatial impacts of dam operations on thermal regimes and clearer elucidation of the relative roles of altered flow and temperature in shaping ecological patterns and processes in riverine ecosystems. Future investigations should also concentrate on using this acquired knowledge to identify the ‘manageable’ components of the thermal regime, and develop optimisation models that evaluate management trade‐offs and provide a range of optimal environmental flows that meet both ecosystem and human needs for fresh water.
Water inputs across a tropical montane landscape in Veracruz, Mexico: synergistic effects of land cover, rain and fog seasonality, and interannual precipitation variability
Authors: PONETTE‐GONZÁLEZ ALEXANDRA G. , WEATHERS KATHLEEN C. , CURRAN LISA M.
Published: May 2009

Land‐cover change can alter the spatiotemporal distribution of water inputs to mountain ecosystems, an important control on land‐surface and land‐atmosphere hydrologic fluxes. In eastern Mexico, we examined the influence of three widespread land‐cover types, montane cloud forest, coffee agroforestry, and cleared areas, on total and net water inputs to soil. Stand structural characteristics, as well as rain, fog, stemflow, and throughfall (water that falls through the canopy) water fluxes were measured across 11 sites during wet and dry seasons from 2005 to 2008. Land‐cover type had a significant effect on annual and seasonal net throughfall (NTF <0=canopy water retention plus canopy evaporation; NTF >0=fog water deposition). Forest canopies retained and/or lost to evaporation (i.e. NTF<0) five‐ to 11‐fold more water than coffee agroforests. Moreover, stemflow was fourfold higher under coffee shade than forest trees. Precipitation seasonality and phenological patterns determined the magnitude of these land‐cover differences, as well as their implications for the hydrologic cycle. Significant negative relationships were found between NTF and tree leaf area index (R2=0.38,P<0.002), NTF and stand basal area (R2=0.664,P<0.002), and stemflow and epiphyte loading (R2=0.414,P<0.001). These findings indicate that leaf and epiphyte surface area reductions associated with forest conversion decrease canopy water retention/evaporation, thereby increasing throughfall and stemflow inputs to soil. Interannual precipitation variability also altered patterns of water redistribution across this landscape. Storms and hurricanes resulted in little difference in forest‐coffee wet season NTF, while El Niño Southern Oscillation was associated with a twofold increase in dry season rain and fog throughfall water deposition. In montane headwater regions, changes in water delivery to canopies and soils may affect infiltration, runoff, and evapotranspiration, with implications for provisioning (e.g. water supply) and regulating (e.g. flood mitigation) ecosystem services.
Influence of large South American rivers of the Plata Basin on distributional patterns of tropical snakes: a panbiogeographical analysis
Authors: Arzamendia Vanesa , Giraudo Alejandro R.
Published: May 2009

Aim  The main drainages of the Plata Basin – the Paraná, Paraguay and Uruguay rivers – begin in tropical latitudes and run in a north–south direction into subtropical–temperate latitudes. Consequently, the biota of these rivers has tropical elements that contrast with temperate biomes through which the rivers run. We apply a panbiogeographical approach, to test whether the large rivers of the Plata Basin have a differential influence on distributional patterns of tropical snakes in subtropical and temperate latitudes of South America.

Location  Subtropical and temperate sections of the major Plata Basin rivers, South America.

Methods  We compared the individual tracks of 94 snake taxa. The track analysis consisted of: (1) plotting the localities of each taxon on maps, (2) connecting the localities of each taxon using a minimal geographical proximity determinant of the ‘individual tracks’, and (3) superimposing the individual tracks to determine generalized tracks. To detect tropical snakes that reach higher latitudes through the rivers we used the preferential direction of distribution concept. For each taxon we measured the angular deviations between the line of its individual track and the course of the rivers in a 100 × 100 km scaled grid. Average angular values < 45° indicated a positive association with the rivers.

Results  Thirty‐five of 94 taxa showed distributions associated with the major rivers of the Plata Basin, including fauna from distinct biogeographical lineages, supported by the occurrence of five generalized tracks as follows: (1) the Paraguay–Middle Paraná, (2) the Paraguay–Paraná fluvial axis, Upper Paraná and Middle Paraná to Upper Delta, (3) the Lower Paraguay, Paraná and Uruguay rivers, excluding the sectors High Paraná and High Uruguay, (4) the Uruguay River and Upper Paraná, and (5) the High Paraná. The Atlantic species occurred with significantly higher frequency in the Uruguay River and High Paraná river sections, the Amazon species were found with significantly higher frequency in the Paraguay and Middle Paraná sections, and the species with a Pantanal distribution were found in all sections.

Main conclusions  The observed distributional patterns may be explained by the interaction of ecological, geographical and historical factors. Previous authors have developed ecological (hydrological or environmental similarity) or dispersalist (effect of rivers as migration routes) explanations. The coincidence between generalized tracks and past geomorphological events that caused displacements and changed relationships between the Paraguay, Paraná and Uruguay river sections supports hypotheses involving the strong influence of historical factors in the present configuration of tropical snake distribution in temperate latitudes.
Soybean meal alters autochthonous microbial populations, microvilli morphology and compromises intestinal enterocyte integrity of rainbow trout, Oncorhynchus mykiss (Walbaum)
Authors: Merrifield D L , Dimitroglou A , Bradley G , Baker R T M , Davies S J
Published: May 2009

Rainbow trout were fed either a diet containing fishmeal (FM) as the crude protein source or a diet containing 50% replacement with soybean meal (SBM) for 16 weeks. An enteritis‐like effect was observed in the SBM group; villi, enterocytes and microvilli were noticeably damaged compared with the FM group. The posterior intestine microvilli of SBM‐fed fish were significantly shorter and the anterior intestine microvilli significantly less dense than the FM‐fed fish. Electron microscopy confirmed the presence of autochthonous bacterial populations associated with microvilli of both fish groups. Reduced density of microvilli consequently led to increased exposure of enterocyte tight junctions, which combined with necrotic enterocytes is likely to diminish the protective barrier of the intestinal epithelium. No significant differences in total viable counts of culturable microbial populations were found between the groups in any of the intestinal regions. A total of 1500 isolates were tentatively placed into groups or genera, according to standard methods. Subsequent partial 16S rRNA sequencing revealed species that have not been identified from the rainbow trout intestine previously. Compared with the FM group levels of Psychrobacter spp. and yeast were considerably higher in the SBM group; a reduction of Aeromonas spp. was also observed.
The effect of tooth clenching on the sensory and pain perception in the oro‐facial region of symptom‐free men and women
Authors: OKAYASU I. , OI K. , DE LAAT A.
Published: May 2009

Summary  The aim of this study was (i) to examine the effect of light tooth contact as in diurnal tooth clenching on the tactile detection threshold (TDT), the filament‐prick pain detection threshold (FPT) and the pressure pain threshold (PPT) in the oro‐facial region and (ii) to examine the possible gender difference in this effect on the tactile and pain perception. Twenty healthy volunteers participated. The TDT and the FPT were measured by means of Semmes‐Weinstein monofilaments, on the cheek skin (CS) overlying the masseter muscles (MM) and on the skin overlying the palm side of the thenar skin (TS). The PPT was measured at the central part of the MM using a pressure algometer. Each parameter was measured before and after keeping light tooth contact for 5 min (session 1) and after keeping the jaw relaxed for 5 min (session 2) as a control. Although there were no significant session effects on any of the parameters, there were significant effects of experimental condition on the TDT in both men and women (P < 0·001). Men had a significant higher FPT of the left CS (P < 0·05) and TS (P < 0·01) and a significant higher PPT of the MM than women (P < 0·001). These results illustrate that sensitivity to pain (FPT, PPT) was higher in women than in men. Although there were no significant gender differences in habituation of sensory perception, the increase of TDT after clenching/no clenching was larger in women, which warrants further study.
A randomized prospective long‐term study of two oral appliances for sleep apnoea treatment
Authors: GHAZAL AKSSAM , SORICHTER STEFAN , JONAS IRMTRUD , ROSE EDMUND C.
Published: May 2009

Various types of mandibular protrusive appliances have revealed different treatment success in mild‐to‐moderate obstructive sleep apnoea (OSA). The present study compared the long‐term effect of two different appliances in the treatment of OSA. A total of 103 patients with OSA were randomized and treated with an IST® or Thornton Anterior Positioner (TAP™) appliance. They were followed‐up after a short‐term treatment period of 6 months and long‐term treatment period of over 24 months. Sleep studies in the sleep laboratory were conducted with and without the appliances, and various questionnaires assessing subjective daytime sleepiness, sleep quality, quality of life and symptom scores were administered at each time interval. Quality of life, sleep quality, sleepiness, symptoms and sleep outcome showed significant improvement in the short‐term evaluation with both appliances, but the TAP™ appliance revealed a significantly greater effect. After more than 2 years of treatment, sleep outcomes revealed an equal effect with both appliances. The subjective benefits achieved initially lessened significantly. This study illustrates that both the IST® and the TAP™ appliances are effective therapeutic devices for OSA after a period of over 24 months. Lack of compliance may be due to insufficient improvement in anticipated subjective symptoms and/or a recurrence of symptoms over time.
MULTIPOLAR SPINDLE 1 (MPS1), a novel coiled‐coil protein of Arabidopsis thaliana, is required for meiotic spindle organization
Authors: Jiang Hua , Wang Fen‐Fei , Wu Yu‐Ting , Zhou Xi , Huang Xue‐Yong , Zhu Jun , Gao Ju‐Fang , Dong Rui‐Bin , Cao Kai‐Ming , Yang Zhong‐Nan
Published: May 2009

The spindle is essential for chromosome segregation during meiosis, but the molecular mechanism of meiotic spindle organization in higher plants is still not well understood. Here, we report on the identification and characterization of a plant‐specific protein, MULTIPOLAR SPINDLE 1 (MPS1), which is involved in spindle organization in meiocytes of Arabidopsis thaliana. The homozygous mps1 mutant exhibits male and female sterility. Light microscopy showed that mps1 mutants produced multiple uneven spores during anther development, most of which aborted in later stages. Cytological analysis showed that chromosome segregation was abnormal in mps1 meiocytes. Immunolocalization showed unequal bipolar or multipolar spindles in mps1 meiocytes, which indicated that aberrant spindles resulted in disordered chromosome segregation. MPS1 encodes a 377‐amino‐acid protein with putative coiled‐coil motifs. In situ hybridization analysis showed that MPS1 is strongly expressed in meiocytes.