bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in the chemical and dynamic properties of cardiac troponin T cause discrete cardiomyopathies in transgenic mice
Authors: Ertz-Berger Briar R. , He Huamei , Dowell Candice , Factor Stephen M. , Haim Todd E. , Nunez Sara , Schwartz Steven D. , Ingwall Joanne S. , Tardiff Jil C.
Published: December 2005

Cardiac troponin T (cTnT) is a central component of the regulatory thin filament. Mutations in cTnT have been linked to severe forms of familial hypertrophic cardiomyopathy. A mutational “hotspot” that leads to distinct clinical phenotypes has been identified at codon 92. Although the basic functional and structural roles of cTnT in modulating contractility are relatively well understood, the mechanisms that link point mutations in cTnT to the development of this complex cardiomyopathy are unknown. To address this question, we have taken a highly interdisciplinary approach by first determining the effects of the residue 92 mutations on the molecular flexibility and stability of cTnT by means of molecular dynamics simulations. To test whether the predicted alterations in thin filament structure could lead to distinct cardiomyopathies
in vivo
, we developed transgenic mouse models expressing either the Arg-92-Trp or Arg-92-Leu cTnT proteins in the heart. Characterization of these models at the cellular and whole-heart levels has revealed mutation-specific early alterations in transcriptional activation that result in distinct pathways of ventricular remodeling and contractile performance. Thus, our computational and experimental results show that changes in thin filament structure caused by single amino acid substitutions lead to differences in the biophysical properties of cTnT and alter disease pathogenesis.
Comparative nutrition and metabolism: Explication of open questions with emphasis on protein and amino acids
Authors: Baker David H.
Published: December 2005

The 20th century saw numerous important discoveries in the nutritional sciences. Nonetheless, many unresolved questions still remain. Fifteen questions dealing with amino acid nutrition and metabolism are posed in this review. The first six deal with the functionality of sulfur amino acids (methionine and cysteine) and related compounds. Other unresolved problems that are discussed include priorities of use for amino acids having multiple functions; interactions among lysine, niacin and tryptophan; amino acid contributions to requirements from gut biosynthesis; the potential for gluconeogenesis to divert amino acids away from protein synthesis; the unique nutritional and metabolic idiosyncrasies of feline species, with emphasis on arginine; controversies surrounding human amino acid requirements; and the potential for maternal diet to influence sex ratio of offspring.
The development and overwintering survival of free-living larvae of Haemonchus contortus in Sweden
Authors: Troell K. , Waller P. , Höglund J.
Published: December 2005

Five complimentary studies were undertaken with the overall aim to examine the ability of free-living stages of Haemonchus contortus to over-winter and tolerate cold stress. Two studies deal with the development and long-term survival of eggs and infective larvae of two geographically different isolates (Kenya and Sweden). Eggs and larvae were monitored in climatic chambers at temperatures that fluctuated daily between −1°C and 15°C, or at constant temperatures of 5°C and 15°C. The development from egg to larvae was dependent on temperatures over 5°C. The long time survival was favoured at lower temperatures. Furthermore, the overwintering capacity of the free-living stages of these isolates was estimated under Swedish field conditions. Two groups of lambs were experimentally infected with different isolates, and kept separated on previously ungrazed plots. In early May the following year, two parasite-naive tracer lambs were turned out on each of the plots to estimate the pick up of overwintered larvae. This experiment was replicated in central and southern Sweden. In addition, two experiments were performed in 2003 on pasture previously grazed by naturally infected sheep. One trial was on a pasture in southern Sweden grazed by a commercial flock, where extreme numbers of H. contortus were found towards the end of the grazing season 2002. The other study was on a pasture plot in central Sweden grazed by a hobby flock in 2002, where three of six lambs died due to haemonchiasis. Overwintered H. contortus was recorded on three of four experimental sites. Worm burdens were in all instances extremely low. No differences in development and survival were found between the isolates. Consequently, overwintering on pasture is of no practical significance in the transmission of H. contortus between grazing-seasons in Sweden.
Population and seasonal distribution of Procamallanus daccai in Eutropiichthys vacha in Kaptai Lake, Chittagong, Bangladesh
Authors: Hafizuddin A.K.M. , Bashirullah A.K.
Published: December 2005

The population and seasonal distribution of Procamallanus daccai (Nematoda: Procamallanidae) in Eutropiichthys vacha (Siluridae) from the Kaptai Lake were studied for a period of 20 months during 1986–1987. A total of 208 fish were necropsied and 5652 worms were recovered, of which 2392 were from 87 infected male fish and 3260 were from 89 infected female fish. Prevalence values varied from 50% to 95%. The intensity and abundance of nematodes fluctuated over the study period and are statistically significant (F=14.87, P<0.0001), and showed a seasonal preference for the summer period (F=33.39, P<0.05). The mean intensity was the highest in the smallest size group at 66.3±12.7 which gradually decreased to 4±1.89 in the largest size group. No significant differences were found between parasites from male and female hosts, except in the summer. Male parasites were less abundant in the population. Female worms were grouped into immature, maturing and gravid and all these stages were present throughout the year. The highest occurrence of both immature and gravid P. daccai was found during the months of February to April each year. Peak recruitment seems to occur during this period due to the presence of high quantities of immature worms.
Molecular characterization of Anisakis pegreffii larvae in Pacific cod in Japan
Authors: Abe N. , Ohya N. , Yanagiguchi R.
Published: December 2005

It is now recognized that the morphospecies Anisakis simplex is not a single species but a complex composed of three sibling species, A. simplex sensu stricto, A. pegreffii and A. simplex C. In Japan, A. simplex-like larvae have been isolated from a variety of fish and humans, but the larvae collected have been identified as A. simplex by only light microscopy. Therefore, the epidemiology of the A. simplex complex, composed of three sibling species, is still unclear in Japan. In the present study, 26 A. simplex-like larval isolates were obtained from two Pacific cod landed in Hokkaido, Japan, and examined genetically by PCR–RFLP and direct sequencing of the ITS region of rDNA. Among the 26 isolates, 24 were identified as A. simplex sensu stricto, the other two as A. pegreffii. The present study is the first to confirm the distribution of A. pegreffii in Japan, and to detect A. pegreffii larvae in Pacific cod.
Biological variation between two Brazilian geographical isolates of Echinostoma paraensei
Authors: Júnior A. Maldonado , Zeitone B.K. , Amado L.A. , Amado I.F. , Machado-Silva J.R. , Lanfredi R.M.
Published: December 2005

The biological behaviour and morphometric data from two allopatric isolates of Echinostoma paraensei (Rio Bonito – RB and Sumidouro – SU) collected from naturally infected Nectomys squamipes from two secluded Atlantic Forest fragments were studied. Mice that had been experimentally infected with ten encysted metacercariae of each isolate were monitored weekly in two trials to analyse worm burden and the kinetics of worm distribution along the intestine. The total number of uterine eggs, wet weights and measurements of the worms and body, acetabulum, testes and ovaries were also analysed. The RB isolate showed a higher worm burden, 7.7±0.8, and a longer life span, 16 weeks, compared to a worm burden of 5.8±1.1 and life span of 9 weeks for the SU isolate. Worms of the RB isolate were clustered in the duodenum and in the bile duct while the SU isolate worms were dispersed along the small intestine of infected mice. Both isolates developed similarly as regards morphometric data and wet weight, although the total number of uterine eggs was greater in RB. The degree of intraspecific variation observed in the worm distribution along the intestine, worm burden and life span raises questions regarding the use of these criteria for species differentiation. These findings suggest that variation in biological parameters found between the E. paraensei isolates could result from geographical isolation and, in particular, the environmental conditions of transmission. Further studies on E. paraensei polulations from different forest fragments will contribute towards an understanding of the speciation of this parasite.
Compatibility of entomopathogenic nematodes with fipronil
Authors: García del Pino F. , Jové M.
Published: December 2005

The survival and infectivity of infective juveniles (IJs) of three species of entomopathogenic nematodes, Steinernema carpocapsae Weiser, S. arenarium (Artyukhovsky) (Rhabditida: Steinernematidae) and Heterorhabditis bacteriophora Poinar (Rhabditida: Heterorhabditidae), were determined after exposure to different concentrations (250, 500, 1000 and 2000 ppm) of fipronil, an insecticide acting on the GABA receptors to block the chloride channel. Heterorhabditis bacteriophora was very tolerant to all concentrations of fipronil, with the highest mortality of 17% being observed at 2000 ppm of fipronil after 72 h exposure. Steinernema carpocapsae showed a similar response, with the highest mortality of 11.25% of IJs being observed after 72 h exposure to 2000 ppm of fipronil. Steinernema arenarium was, however, more sensitive to fipronil, and at 2000 ppm mortality rates of 94.6% and 100% were observed after 24 and 72 h, respectively. Fipronil had negligible effects on the infectivity of the three nematode species tested. The IJs which survive exposure to all concentrations of fipronil tested can infect and reproduce in Galleria larvae. The moderate effects on entomopathogenic nematodes of a lower fipronil concentration (250 ppm) and the field rates (12–60 ppm) of fipronil used as insecticide, suggest that direct mixing of entomopathogenic nematodes and fipronil at field rates is a viable integrated pest management option.
Field and experimental studies on Dicrocoelium dendriticum and dicrocoeliasis in northern Spain
Authors: Manga-González M.Y. , González-Lanza C.
Published: December 2005

The transmission, control and the relationship between Dicrocoelium dendriticum and its definitive (sheep and cattle) and intermediate (molluscs and ants) hosts under natural and experimental conditions are described. Eleven species of molluscs and four of ants were found infected with larval D. dendriticum in León province, north-west Spain. Infected ants were observed between April and November and in tetania at 7.5–26.9°C. The highest shedding of eggs by sheep and cattle was detected in winter. Two treatments applied in November and January were the most effective. In experimentally infected molluscs, the parasite was not visible under the stereomicroscope, at least until 50 days post-infection (p.i.). The prepatent period in experimentally infected lambs was 49–79 days p.i. The number of eggs per gram increased with the days p.i. and the parasite burden. The aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, leukocyte and neutrophil values of infected lambs increased, but those of lymphocytes decreased. Using the enzyme-linked immunosorbert assay technique, the IgG antibody response to excretory–secretory and somatic antigens of D. dendriticum was positive from day 30 p.i., although the maximum antibody levels were observed on day 60 p.i. The number of worms per lamb ranged between 30 and 2063. Cholangitis and cholangiectasia of the septal bile and hepatic ducts were observed. The best enzymatic systems for adult and larval D. dendriticum characterization were lactate dehydrogenase, glucose phosphate isomerase and phosphoglucomutase. Genetic variability of adult D. dendriticum was high using the random amplified polymorphic DNA technique.
The Temperature-Dependent Change in Methylation of theAntirrhinumTransposon Tam3 Is Controlled by the Activity of Its Transposase
Authors: Hashida Shin-Nosuke , Uchiyama Takako , Martin Cathie , Kishima Yuji , Sano Yoshio , Mikami Tetsuo
Published: December 2005

The Antirrhinum majus transposon Tam3 undergoes low temperature–dependent transposition (LTDT). Growth at 15°C permits transposition, whereas growth at 25°C strongly suppresses it. The degree of Tam3 DNA methylation is altered somatically and positively correlated with growth temperature, an exceptional epigenetic system in plants. Using a Tam3-inactive line, we show that methylation change depends on Tam3 activity. Random binding site selection analysis and electrophoretic mobility shift assays revealed that the Tam3 transposase (TPase) binds to the major repeat in the subterminal regions of Tam3, the site showing the biggest temperature-dependent change in methylation state. Methylcytosines in the motif impair the binding ability of the TPase. Proteins in a nuclear extract from plants grown at 15°C but not 25°C bind to this motif in Tam3. The decrease in Tam3 DNA methylation at low temperature also requires cell division. Thus, TPase binding to Tam3 occurs only during growth at low temperature and immediately after DNA replication, resulting in a Tam3-specific decrease in methylation of transposon DNA. Consequently, the Tam3 methylation level in LTDT is regulated by Tam3 activity, which is dependent on the ability of its TPase to bind DNA and affected by growth temperature. Thus, the methylation/demethylation of Tam3 is the consequence, not the cause, of LTDT.
Volutrauma activates the clotting cascade in the newborn but not adult rat
Authors: Chan Anthony , Jayasuriya Kusala , Berry Leslie , Roth-Kleiner Matthias , Post Martin , Belik Jaques
Published: December 2005

Coagulopathy and alveolar fibrin deposition are common in sick neonates and attributed to the primary disease, as opposed to their ventilatory support. Hypothesizing that high tidal volume ventilation activates the extrinsic coagulation pathway, we air ventilated newborn and adult rats at low (10 ml/kg) or high (30 ml/kg) tidal volume and compared them with age-matched nonventilated controls. Blood was collected at the end of the experiment for measurement of clot time, tissue factor, and other coagulation factor content. Similar measurements were obtained from lung lavage material. The newborn clot time (44 ± 1) was lower and plasma tissue factor content higher (103.4 ± 0.4) than adults (88 ± 4 s and 26.6 ± 1.4 units; P < 0.01). High, but not low, tidal volume ventilation of newborns for as little as 15 min significantly reduced clot time and increased plasma tissue factor content ( P < 0.01). High volume ventilation increased plasma factor Xa (0.1 ± 0.1 to 1.6 ± 0.4 nM; P < 0.01) and thrombin (1.3 ± 0.2 to 2.2 ± 0.4 nM; P < 0.05) and decreased antithrombin (0.12 ± 0.01 to 0.05 ± 0.01; P < 0.01) in the newborn. Lung lavage material of high volume-ventilated newborns showed increased ( P < 0.01) factor Xa and thrombin. No changes in these parameters were observed in adult rats that were high volume ventilated for up to 90 min. Compared with adults, newborn rats have a greater propensity for volutrauma-activated intravascular coagulation. These data suggest that mechanical ventilation promotes neonatal thrombosis via lung tissue factor release.
Nitric oxide sensitivity in pulmonary artery and airway smooth muscle: a possible role for cGMP responsiveness
Authors: Taniguchi Miwa , Kwak Young Lan , Jones Keith A. , Warner David O. , Perkins William J.
Published: December 2005

We aimed to assess intrinsic smooth muscle mechanisms contributing to greater nitric oxide (NO) responsiveness in pulmonary vascular vs. airway smooth muscle. Porcine pulmonary artery smooth muscle (PASM) and tracheal smooth muscle (TSM) strips were used in concentration-response studies to the NO donor ( Z)-1-[ N-2-aminoethyl- N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO). PASM consistently exhibited greater relaxation at a given DETA-NO concentration (NO responsiveness) than TSM NO responsiveness, with DETA-NO log EC50being −6.55 ± 0.11 and −5.37 ± 0.13 for PASM and TSM, respectively ( P < 0.01). We determined relationships between tissue cGMP concentration ([cGMP]i) and relaxation using the particulate guanylyl cyclase agonist atrial natriuretic peptide. Atrial natriuretic peptide resulted in nearly complete relaxation, with no detectable increase in [cGMP]iin PASM and only 20% relaxation (10-fold increase in [cGMP]i) in TSM, indicating that TSM is less cGMP responsive than PASM. Total cGMP-dependent protein kinase I (cGKI) mRNA expression was greater in PASM than in TSM (2.23 ± 0.36 vs. 0.93 ± 0.31 amol mRNA/μg total RNA, respectively; P < 0.01), but total cGKI protein expression was not significantly different (0.56 ± 0.07 and 0.49 ± 0.04 ng cGKI/μg protein, respectively). The phosphotransferase assay for the soluble fraction of tissue homogenates demonstrated no difference in the cGMP EC50between PASM and TSM. The maximal phosphotransferase activity indexed to the amount of total cGKI in the homogenate differed significantly between PASM and TSM (1.61 ± 0.15 and 1.04 ± pmol·min−1·ng cGKI−1, respectively; P < 0.05), suggesting that cGKI may be regulated differently in the two tissues. A novel intrinsic smooth muscle mechanism accounting for greater NO responsiveness in PASM vs. TSM is thus greater cGMP responsiveness from increased cGKI-specific activity in PASM.
Conceptual Representations of Action in the Lateral Temporal Cortex
Authors: Kable Joseph W. , Kan Irene P. , Wilson Ashley , Thompson-Schill Sharon L. , Chatterjee Anjan
Published: December 2005

Retrieval of conceptual information from action pictures causes greater activation than from object pictures bilaterally in human motion areas (MT/MST) and nearby temporal regions. By contrast, retrieval of conceptual information from action words causes greater activation in left middle and superior temporal gyri, anterior and dorsal to the MT/MST. We performed two fMRI experiments to replicate and extend these findings regarding action words. In the first experiment, subjects performed conceptual judgments of action and object words under conditions that stressed visual semantic information. Under these conditions, action words again activated posterior temporal regions close to, but not identical with, the MT/MST. In the second experiment, we included conceptual judgments of manipulable object words in addition to judgments of action and animal words. Both action and manipulable object judgments caused greater activity than animal judgments in the posterior middle temporal gyrus. Both of these experiments support the hypothesis that middle temporal gyrus activation is related to accessing conceptual information about motion attributes, rather than alternative accounts on the basis of lexical or grammatical factors. Furthermore, these experiments provide additional support for the notion of a concrete to abstract gradient of motion representations with the lateral occipito-temporal cortex, extending anterior and dorsal from the MT/MST towards the peri-sylvian cortex.
An Effect of Dopamine Depletion on Decision-making: The Temporal Coupling of Deliberation and Execution
Authors: Pessiglione Mathias , Czernecki Virginie , Pillon Bernard , Dubois Bruno , Schüpbach Michael , Agid Yves , Tremblay Léon
Published: December 2005

When a decision between alternative actions has to be made, the primate brain is able to uncouple motor execution from mental deliberation, providing time for higher cognitive processes such as remembering and reasoning. The mental deliberation leading to the decision and the motor execution applying the decision are likely to involve different neuronal circuits linking the basal ganglia and the frontal cortex. Behavioral and physiological studies in monkeys indicate that dopamine depletion may result in a loss of functional segregation between these circuits, hence, in interference between the deliberation and execution processes. To test this hypothesis in humans, we analyzed the movements of parkinsonian patients in a go/no-go task, contrasting periods of uncertainty with periods of knowledge about the rule to be applied. Two groups of patients were compared to healthy subjects: one group was treated with dopaminergic medication and the other with deep brain stimulation; both groups were also tested without any treatment. In healthy subjects, the movement time was unaffected by uncertainty. In untreated patients, the movement time increased with uncertainty, reflecting interference between deliberation and execution processes. This interference was fully corrected with dopaminergic medication but was unchanged with deep brain stimulation. Moreover, decision-related hesitations were detectable in the movements of dopamine-depleted patients, revealing a temporal coupling of deliberation and execution. We suggest that such coupling may be related to the loss of dopamine-mediated functional segregation between basal ganglia circuits processing different stages of goal-directed behavior.
Graded Visual Attention Modulates Brain Responses Evoked by Task-irrelevant Auditory Pitch Changes
Authors: Yucel Gunes , Petty Christopher , McCarthy Gregory , Belger Aysenil
Published: December 2005

Previous studies suggested that auditory change-specific neural responses are attention-independent and reflect central auditory processing. The automaticity of the brain's response to infrequent changes in pitch within a series of auditory tone pips was examined in parallel functional magnetic resonance imaging (fMRI) and event-related potential (ERP) studies. Subjects performed a continuous perceptual-motor visual tracking task at two levels of difficulty while simultaneously hearing a series of task-irrelevant standard tone pips and infrequent pitch-deviant tones. fMRI results revealed that the unattended pitch-deviant tones strongly activated superior temporal and frontal cortical regions. These activations were significantly modulated by the tracking difficulty of the primary task. ERP results revealed that the amplitude of the scalp-negative component evoked by deviant tones (MMN) was attenuated during the more difficult tracking task. Our results demonstrate that the brain's response to task-irrelevant sensory changes is strongly influenced by intermodal attentional demands.
Phase Synchronization Analysis of EEG during Attentional Blink
Authors: Nakatani Chie , Ito Junji , Nikolaev Andrey R. , Gong Pulin , Leeuwen Cees van
Published: December 2005

The attentional blink (AB) phenomenon occurs when perceivers must report two targets embedded in a sequence of distracters; if the first target precedes the second by 200-600 msec, the second one is often missed. We investigated AB by measuring dynamic cross-lag phase synchronization for 565 electrode pairs in 40-Hz-range EEG. Phase synchrony, on average, was higher in experimental conditions, where two targets are reported, than in control conditions, where only the second target is reported. The effect occurred in electrode pairs covering the whole head. Timing of the synchrony was crucial: Brief episodes of enhanced synchrony occurred 100-500 msec before expected target onset in AB conditions where the second target was correctly reported. These results show that intrinsic brain dynamics produce anticipatory synchronization in transient assemblies of cortical areas. Enhanced levels of anticipatory synchronization occur in response to the demands of the task in conditions where the system's limited capacity is under strain.
The Effect of Globalization on National Income Inequality
Authors: Bussmann Margit , Oneal John , de Soysa Indra
Published: December 2005

We assess the effect of globalization on income inequality within countries, focusing on the influence of accumulated foreign direct investment stocks. We analyze data on inequality and foreign investment for 72 countries, 1970-90, incorporating in our tests the Kuznets (1955) curve, the character of political institutions, and various other aspects of the economy and society emphasized in previous research. Our results indicate that globalization does not increase national income inequality. The ratio of foreign direct investment to gross domestic product is unrelated to the distribution of incomes in both developing and developed countries. The share of income received by the poorest 20% of society also is unaffected by foreign investment. Nor are alternative measures of economic openness – the trade-to-GDP ratio and Sachs and Warner's (1995) measure of free trading policies – associated with greater income inequality. If foreign investment increases average incomes in developing countries, as recent research indicates, and does not increase inequality, it must benefit all strata of these societies, including the poor.
Tolerance of Civil Liberties in a New Democracy
Authors: Marsh Robert
Published: December 2005

How tolerant of the civil liberties of people who advocated various unpopular political stances were the citizens of Taiwan, a new democracy in the late 1980s? Are the reasons some Taiwanese were more tolerant than others the same as in other societies? A 1992 survey of a representative sample of the population of Taiwan (N = 1,408) is used to answer these questions. Of the four political stances studied, communism and Taiwan's independence from China were perceived as "more harmful to Taiwan" than the immediate unification of Taiwan with China and the restoration of martial law.Of the hypotheses tested in multivariate analysis, two were largely confirmed: (1) the more one subscribes to the value of democracy as the correct political system for Taiwan, the more tolerant one is of the civil liberties of the "harmful" target groups, but (2) the greater the perceived threat of the harmful political stance, the more intolerant one is of the civil liberties of those advocating the stance. The remaining hypotheses concern the effects of sex, age, ethnicity, education, occupation and income on tolerance.I contextualize the theoretical causal model by reviewing the political history of Taiwan as it changed from an authoritarian one-party state into a democracy. In conclusion, I suggest that the reason the level of intolerance in Taiwan in 1992 has not lead to a diminution of democracy and civil rights between 1992 and the present may be due to "pluralistic intolerance," i.e., the public does not agree on which group to target for intolerance.
Parish Priest and Community in 18th-century Malta: Patterns of Conflict
Authors: Ciappara Frans
Published: December 2005

This essay explores the relations between parish priests and their parishioners in eighteenth-century Malta. It argues that pastors did not succeed in governing the community and controlling local religious life. Generally, they were outsiders. This was a great liability since rivalry between villages was intense and the inhabitants were reluctant to admit new people, to whom they were often hostile. But the main reason for the rivalry between the faithful and the pastor was that the people themselves took an active role in the parish. They regarded the office of parish priest as a subservient one for which service they paid the priest handsomely, and provided him with a livelihood. Pastors were to concern themselves only with vital religious services and leave the administration of the parish to the parishioners. The essay also emphasizes that in the struggle with their parish priest the people found the support from the assistant clergy.
Biominerals
Authors: Skinner H. C. W.
Published: December 2005

Biominerals are a subset of the mineral kingdom, those created by living creatures. In spite of usually fine grain size and intimate association with organic materials, biominerals are readily identified as common mineral species. Iron hydroxides and oxyhydroxides, calcium carbonates and calcium phosphates from uni- and multi-cellular species are presented as examples of biominerals, and biomineralization processes. Their special morphological, and crystal chemical, characteristics provide unique structural contributions to the life forms that create them. Investigations of novel habitats should present opportunities to expand the number of biominerals and their potential for industrial applications.
Simultaneous high throughput and quantitative analysis of MTBE and BTEX by P&T-GCMS using a Precept® autosampler
Authors: Houghton S. L. , Hall S.
Published: December 2005

Fuel-oil contamination of groundwater and waterways is common throughout the world. The fuel components methyl-tert-butyl ether (MTBE) and benzene, toluene, ethylbenzene and o-, p- and m-xylenes (BTEX) compounds are most likely to reach a borehole after a contamination event, and also those that pose the greatest risk.

Various gas chromatography-mass spectrometry (GCMS) methods are available for the analysis of volatile organic compounds (VOCs) but many of these are not suitable for rapid and combined analysis of MTBE and BTEX. Here we describe and validate a simple and reliable method that fulfils these requirements. The method is quick: 48 samples can be analysed in a 24 hour period using the Precept II® autosampler and therefore is suitable for high throughput work. Validation of our experiments is presented in the form of linearity, precision and intra-day repeatability of standards as well as limits of detection and limits of quantification for the range 1—20 μg/l.

This MTBE/BTEX analytical method developed was used to study the optimization of a modular post-abstraction remediation system incorporating air-stripping and granular activated carbon (GAC) technologies (Hall, 2004), from which a selection of sample data is presented.
Preliminary observations on the release of arsenic to groundwater in the presence of hydrocarbon contaminants in UK aquifers
Authors: Burgess W. G. , Pinto L.
Published: December 2005

Degradation of contaminant hydrocarbons in groundwater by microbially mediated oxidation, linked to the reduction of electron acceptors, is fundamental to the strategy of ‘monitored natural attenuation’ (MNA) for oxidizable hydrocarbons, which is increasingly being adopted at polluted aquifer sites throughout Europe and North America. Commonly, oxygen is depleted and following the reduction of nitrate, solid-phase Fe oxides become the dominant electron acceptors. Arsenic, associated with Fe and Mn oxides in soils and sediments, may therefore be mobilized to groundwater and pose an additional threat to environmental receptors. In a pilot study of three aquifers in England, we have examined the extent to which arsenic is released to groundwater under Fe(III)-reducing conditions imposed by contaminant hydrocarbons. Results show that arsenic is locally mobilized in the Chalk to <10 μg/1, in Quaternary gravels to 70 μg/1 and in the Triassic sandstones to 160 μg/1. At the Chalk and Quaternary gravels sites arsenic mobilization is demonstrably linked to reduction of Fe- and Mn-oxides. This is not so at the Triassic sandstone site, where release of arsenic is related to elevated bicarbonate alkalinity. Redox-driven arsenic mobilization at other Triassic sandstone locations is possible. Further work is required on the solid-phase sources of arsenic in the aquifers, and to relate the hydrochemical observations to groundwater hydraulic conditions.
Overview of BITS2005, the Second Annual Meeting of the Italian Bioinformatics Society
Authors: Helmer-Citterich Manuela , Casadio Rita , Guffanti Alessandro , Mauri Giancarlo , Milanesi Luciano , Pesole Graziano , Valle Giorgio , Saccone Cecilia
Published: December 2005

The BITS2005 Conference brought together about 200 Italian scientists working in the field of Bioinformatics, students in Biology, Computer Science and Bioinformatics on March 17–19 2005, in Milan. This Editorial provides a brief overview of the Conference topics and introduces the peer-reviewed manuscripts accepted for publication in this Supplement.
Modelling the interaction of steroid receptors with endocrine disrupting chemicals
Authors: D'Ursi Pasqualina , Salvi Erika , Fossa Paola , Milanesi Luciano , Rovida Ermanna
Published: December 2005

Background

The organic polychlorinated compounds like dichlorodiphenyltrichloroethane with its metabolites and polychlorinated biphenyls are a class of highly persistent environmental contaminants. They have been recognized to have detrimental health effects both on wildlife and humans acting as endocrine disrupters due to their ability of mimicking the action of the steroid hormones, and thus interfering with hormone response. There are several experimental evidences that they bind and activate human steroid receptors. However, despite the growing concern about the toxicological activity of endocrine disrupters, molecular data of the interaction of these compounds with biological targets are still lacking.

Results

We have used a flexible docking approach to characterize the molecular interaction of seven endocrine disrupting chemicals with estrogen, progesterone and androgen receptors in the ligand-binding domain. All ligands docked in the buried hydrophobic cavity corresponding to the hormone steroid pocket. The interaction was characterized by multiple hydrophobic contacts involving a different number of residues facing the binding pocket, depending on ligands orientation. The EDC ligands did not display a unique binding mode, probably due to their lipophilicity and flexibility, which conferred them a great adaptability into the hydrophobic and large binding pocket of steroid receptors.

Conclusion

Our results are in agreement with toxicological data on binding and allow to describe a pattern of interactions for a group of ECD to steroid receptors suggesting the requirement of a hydrophobic cavity to accommodate these chlorine carrying compounds. Although the affinity is lower than for hormones, their action can be brought about by a possible synergistic effect.
A quantization method based on threshold optimization for microarray short time series
Authors: Di Camillo Barbara , Sanchez-Cabo Fatima , Toffolo Gianna , Nair Sreekumaran K , Trajanoski Zlatko , Cobelli Claudio
Published: December 2005

Background

Reconstructing regulatory networks from gene expression profiles is a challenging problem of functional genomics. In microarray studies the number of samples is often very limited compared to the number of genes, thus the use of discrete data may help reducing the probability of finding random associations between genes.

Results

A quantization method, based on a model of the experimental error and on a significance level able to compromise between false positive and false negative classifications, is presented, which can be used as a preliminary step in discrete reverse engineering methods. The method is tested on continuous synthetic data with two discrete reverse engineering methods: Reveal and Dynamic Bayesian Networks.

Conclusion

The quantization method, evaluated in comparison with two standard methods, 5% threshold based on experimental error and rank sorting, improves the ability of Reveal and Dynamic Bayesian Networks to identify relations among genes.
A neural strategy for the inference of SH3 domain-peptide interaction specificity
Authors: Ferraro Enrico , Via Allegra , Ausiello Gabriele , Helmer-Citterich Manuela
Published: December 2005

Background

The SH3 domain family is one of the most representative and widely studied cases of so-called Peptide Recognition Modules (PRM). The polyproline II motif PxxP that generally characterizes its ligands does not reflect the complex interaction spectrum of the over 1500 different SH3 domains, and the requirement of a more refined knowledge of their specificity implies the setting up of appropriate experimental and theoretical strategies. Due to the limitations of the current technology for peptide synthesis, several experimental high-throughput approaches have been devised to elucidate protein-protein interaction mechanisms. Such approaches can rely on and take advantage of computational techniques, such as regular expressions or position specific scoring matrices (PSSMs) to pre-process entire proteomes in the search for putative SH3 targets.

In this regard, a reliable inference methodology to be used for reducing the sequence space of putative binding peptides represents a valuable support for molecular and cellular biologists.

Results

Using as benchmark the peptide sequences obtained from in vitro binding experiments, we set up a neural network model that performs better than PSSM in the detection of SH3 domain interactors. In particular our model is more precise in its predictions, even if its performance can vary among different SH3 domains and is strongly dependent on the number of binding peptides in the benchmark.

Conclusion

We show that a neural network can be more effective than standard methods in SH3 domain specificity detection. Neural classifiers identify general SH3 domain binders and domain-specific interactors from a PxxP peptide population, provided that there are a sufficient proportion of true positives in the training sets. This capability can also improve peptide selection for library definition in array experiments. Further advances can be achieved, including properly encoded domain sequences and structural information as input for a global neural network.
Browsing Isolated Population Data
Authors: Mancosu Gianmaria , Cosso Massimiliano , Marras Francesca , Borlino Cesare Cappio , Ledda Giuseppe , Manias Teresa , Adamo Mauro , Serra Donatella , Melis Paola , Pirastu Mario
Published: December 2005

Background

In our studies of genetically isolated populations in a remote mountain area in the center of Sardinia (Italy), we found that 80–85% of the inhabitants of each village belong to a single huge pedigree with families strictly connected to each other through hundreds of loops. Moreover, intermarriages between villages join pedigrees of different villages through links that make family trees even more complicated. Unfortunately, none of the commonly used pedigree drawing tools are able to draw the complete pedigree, whereas it is commonly accepted that the visual representation of families is very important as it helps researchers in identifying clusters of inherited traits and genotypes. We had a representation issue that compels researchers to work with subsets extracted from the overall genealogy, causing a serious loss of information on familiar relationships.

To visually explore such complex pedigrees, we developed PedNavigator, a browser for genealogical databases properly suited for genetic studies.

Results

The PedNavigator is useful for genealogical research due to its capacity to represent family relations between persons and to make a visual verification of the links during family history reconstruction. As for genetic studies, it is helpful to follow propagation of a specific set of genetic markers (haplotype), or to select people for linkage analysis, showing relations between various branch of a family tree of affected subjects.

Availability

PedNavigator is an application integrated into a Framework designed to handle data for human genetic studies based on the Oracle platform. To allow the use of PedNavigator also to people not owning the same required informatics infrastructure or systems, we developed PedNavigator Lite with mainly the same features of the integrated one, based on MySQL database server. This version is free for academic users, and it is available for download from our site http://www.shardna.com.
Inherited disorder phenotypes: controlled annotation and statistical analysis for knowledge mining from gene lists
Authors: Masseroli Marco , Galati Osvaldo , Manzotti Mauro , Gibert Karina , Pinciroli Francesco
Published: December 2005

Background

Analysis of inherited diseases and their associated phenotypes is of great importance to gain knowledge of underlying genetic interactions and could ultimately give clinically useful insights into disease processes, including complex diseases influenced by multiple genetic loci. Nevertheless, to date few computational contributions have been proposed for this purpose, mainly due to lack of controlled clinical information easily accessible and structured for computational genome-wise analyses. To allow performing phenotype analyses of inherited disorder related genes we implemented new original modules withinGFINDerhttp://www.bioinformatics.polimi.it/GFINDer/, a Web system we previously developed that dynamically aggregates functional annotations of user uploaded gene lists and allows performing their statistical analysis and mining.

Results

NewGFINDermodules allow annotating large numbers of user classified biomolecular sequence identifiers with morbidity and clinical information, classifying them according to genetic disease phenotypes and their locations of occurrence, and statistically analyzing the obtained classifications. To achieve this we exploited, normalized and structured the information present in textual form in the Clinical Synopsis sections of the Online Mendelian Inheritance in Man (OMIM) databank. Such valuable information delineates numerous signs and symptoms accompanying many genetic diseases and it is divided into phenotype location categories, either by organ system or type of finding.

Conclusion

Supporting phenotype analyses of inherited diseases and biomolecular functional evaluations,GFINDerfacilitates a genomic approach to the understanding of fundamental biological processes and complex cellular mechanisms underlying patho-physiological phenotypes.
Regularized Least Squares Cancer Classifiers from DNA microarray data
Authors: Ancona Nicola , Maglietta Rosalia , D'Addabbo Annarita , Liuni Sabino , Pesole Graziano
Published: December 2005

Background

The advent of the technology of DNA microarrays constitutes an epochal change in the classification and discovery of different types of cancer because the information provided by DNA microarrays allows an approach to the problem of cancer analysis from a quantitative rather than qualitative point of view. Cancer classification requires well founded mathematical methods which are able to predict the status of new specimens with high significance levels starting from a limited number of data. In this paper we assess the performances of Regularized Least Squares (RLS) classifiers, originally proposed in regularization theory, by comparing them with Support Vector Machines (SVM), the state-of-the-art supervised learning technique for cancer classification by DNA microarray data. The performances of both approaches have been also investigated with respect to the number of selected genes and different gene selection strategies.

Results

We show that RLS classifiers have performances comparable to those of SVM classifiers as the Leave-One-Out (LOO) error evaluated on three different data sets shows. The main advantage of RLS machines is that for solving a classification problem they use a linear system of order equal to either the number of features or the number of training examples. Moreover, RLS machines allow to get an exact measure of the LOO error with just one training.

Conclusion

RLS classifiers are a valuable alternative to SVM classifiers for the problem of cancer classification by gene expression data, due to their simplicity and low computational complexity. Moreover, RLS classifiers show generalization ability comparable to the ones of SVM classifiers also in the case the classification of new specimens involves very few gene expression levels.
NemaFootPrinter: a web based software for the identification of conserved non-coding genome sequence regions between C. elegans and C. briggsae
Authors: Rambaldi Davide , Guffanti Alessandro , Morandi Paolo , Cassata Giuseppe
Published: December 2005

Background

NemaFootPrinter (Nematode Transcription Factor Scan Through Philogenetic Footprinting) is a web-based software for interactive identification of conserved, non-exonic DNA segments in the genomes of C. elegans and C. briggsae. It has been implemented according to the following project specifications:

a) Automated identification of orthologous gene pairs.

b) Interactive selection of the boundaries of the genes to be compared.

c) Pairwise sequence comparison with a range of different methods.

d) Identification of putative transcription factor binding sites on conserved, non-exonic DNA segments.

Results

Starting from a C. elegans or C. briggsae gene name or identifier, the software identifies the putative ortholog (if any), based on information derived from public nematode genome annotation databases. The investigator can then retrieve the genome DNA sequences of the two orthologous genes; visualize graphically the genes' intron/exon structure and the surrounding DNA regions; select, through an interactive graphical user interface, subsequences of the two gene regions. Using a bioinformatics toolbox (Blast2seq, Dotmatcher, Ssearch and connection to the rVista database) the investigator is able at the end of the procedure to identify and analyze significant sequences similarities, detecting the presence of transcription factor binding sites corresponding to the conserved segments. The software automatically masks exons.

Discussion

This software is intended as a practical and intuitive tool for the researchers interested in the identification of non-exonic conserved sequence segments between C. elegans and C. briggsae. These sequences may contain regulatory transcriptional elements since they are conserved between two related, but rapidly evolving genomes. This software also highlights the power of genome annotation databases when they are conceived as an open resource and the possibilities offered by seamless integration of different web services via the http protocol.

Availability: the program is freely available at http://bio.ifom-firc.it/NTFootPrinter
Web services and workflow management for biological resources
Authors: Romano Paolo , Marra Domenico , Milanesi Luciano
Published: December 2005

Backgorund

The completion of the Human Genome Project has resulted in large quantities of biological data which are proving difficult to manage and integrate effectively. There is a need for a system that is able to automate accesses to remote sites and to "understand" the information that it is managing in order to link data properly. Workflow management systems combined with Web Services are promising Information and Communication Technologies (ICT) tools. Some have already been proposed and are being increasingly applied to the biomedical domain, especially as many biology-related Web Services are now becoming available. Information on biological resources and on genomic sequences mutations are two examples of very specialized datasets that are useful for specific research domains.

Results

The architecture of a system that is able to access and execute predefined workflows is presented in this paper. Web Services allowing access to the IARC TP53 Mutation Database and CABRI catalogues of biological resources have been implemented and are available on-line. Example workflows which retrieve data from these Web Services have also been created and are available on-line.

Conclusion

We present a general architecture and some building blocks for the implementation of a system that is able to remotely execute workflows of biomedical interest and show how this approach can effectively produce useful outputs. The further development and implementation of Web Services allowing access to an exhaustive set of biomedical databases and the creation of effective and useful workflows will improve the automation of in-silico analysis.