bluuebunny/crossref_metadata_2025 huggingface dataset:
The genetics of serum lipid responsiveness to dietary interventions
Authors: Ordovas Jose M.
Published: July 2005

CHD is a multifactorial disease that is associated with non-modifiable risk factors, such as age, gender and genetic background, and with modifiable risk factors, including elevated total cholesterol and LDL-cholesterol levels. Lifestyle modification should be the primary treatment for lowering cholesterol values. The modifications recommended include dietary changes, regular aerobic exercise, and normalization of body weight. The recommended dietary changes include restriction in the amount of total fat, saturated fat and cholesterol together with an increase in the consumption of complex carbohydrate and dietary fibre, especially water-soluble fibre. However, nutrition scientists continue to question the value of these universal concepts and the public health benefits of low-fat diets, and an intense debate has been conducted in the literature on whether to focus on reduction of total fat or to aim efforts primarily towards reducing the consumption of saturated andtransfats. Moreover, it is well known that there is a striking variability between subjects in the response of serum cholesterol to diet. Multiple studies have examined the genediet interactions in the response of plasma lipid concentrations to changes in dietary fat and/or cholesterol. These studies have focused on candidate genes known to play key roles in lipoprotein metabolism. Among the gene loci examined, APOE has been the most studied, and the current evidence suggests that this locus might be responsible for some of the inter-individual variability in dietary response. Other loci, including APOA4, APOA1, APOB, APOC3, LPL and CETP have also been found to account for some of the variability in the fasting and fed states.
Phyto-oestrogens: A potential role in the prevention of CHD?
Authors: Cassidy Aedin , Griffin Bruce
Published: July 2005

CHD is a major cause of morbidity and mortality in women. The incidence of CHD in premenopausal women is low but increases substantially after the menopause, and this difference suggests that endogenous oestrogens are cardioprotective. Observational prospective studies have consistently shown that exogenous oestrogens also lower CHD risk. The biological mechanisms by which endogenous and exogenous oestrogens exert their protective effect are multifactorial, affecting lipids, carbohydrate metabolism, body fat distribution and blood pressure. The prevention of CHD with oestrogen therapy is therefore aimed both at correction of the traditional risk factors and at direct control of vessel structure and function. The wide international variation in rates of CHD together with the lower mortality in sub-groups of the population suggests that a considerable proportion of CHD may be prevented by dietary modification. Since phyto-oestrogens are structually similar to oestrogen, they have the potential to mimic its effectsin vivo. The hypocholesterolaemic effects of soyabean protein (rich in phyto-oestrogen precursors) are well established, but the underlying mechanism and atherogenic potential of these changes are unknown. One isoflavone, genistein, has been shownin vitroto exert effects which may slow the development of atherosclerotic disease. However, further studies are required to determine the dose-related changes induced by phyto-oestrogens on serum lipoproteins, haemostasis and vascular function.
Familiarity seekers are fast and novelty seekers are slow
Authors: Christie John
Published: July 2005

Christie and Klein (1995) demonstrated that a familiar item (word) rapidly attracts attention when presented simultaneously with an unfamiliar item (nonword). However, this finding has never been replicated. The current study is an attempt at such a replication. Participants were presented a familiar word and unfamiliar nonword in the experimental condition. At varying times after stimulus onset one of the items moved, and the participant reported the direction of the movement. A replication of Christie and Klein would be obtained if performance was better for movement discrimination of the familiar item shortly after onset but not at later intervals. The original finding was replicated in fast participants while slower participants show a different effect. A potential individual difference variable is suggested to explain this difference between the fast and slow participants.
Simon congruency effects based on stimulus and response numerosity
Authors: Miller Jeff
Published: July 2005

Three choice reaction time experiments documented a Simon-type congruence effect involving the numbers of stimuli and responses. In Experiment 1 the stimulus consisted of one or two high- or low-pitch tones, and participants were required to respond with one or two taps of a response key depending on stimulus pitch. Responses were faster when the number of tones matched the required number of response taps than when these numbers mismatched. Experiment 2 showed that a weaker version of this effect can also be obtained using visual stimuli, and Experiment 3 showed that the analogous effect can even be obtained, albeit very weakly, with bimodal stimuli. There was also evidence that the number of stimuli affected the rate of emitting the two-tap response. These results indicate that stimulus numerosity is processed automatically to the level at which it can affect the selection and possibly the execution of a varying number of responses.
Negative priming is stronger for task-relevant dimensions: Evidence of flexibility in the selective ignoring of distractor information
Authors: Frings Christian , Wentura Dirk
Published: July 2005

The finding that in selective attention tasks responses to previously ignored stimuli are usually retarded is known as negative priming (NP). In previous studies it has been suggested that NP can depend on behavioural goals—that is, NP was observed only for task-relevant object dimensions. We extend these findings with two experiments demonstrating that stronger NP can be observed for task-relevant dimensions than for task-irrelevant dimensions (a) even if participants' tasks vary blockwise within an experiment and (b) if behavioural goals vary from trial to trial. These results suggest that selective NP is a much more flexible process than previously assumed.
Successful differential evaluative conditioning using simultaneous and trace conditioning procedures in the picture–picture paradigm
Authors: Lascelles Kristy R. R. , Davey Graham C. L.
Published: July 2005

This paper describes a study designed to investigate the efficacy of two traditional classical conditioning procedures in generating evaluative conditioning (EC) in the picture–picture paradigm in human participants. Differential EC was found using both simultaneous and trace conditioning procedures. In addition, the use of a block–subblock (BSB) nonpaired control condition and full counterbalancing of conditioned stimulus–unconditioned stimulus (CS–UCS) pairings across participants indicated that the observed EC effects were the result of associative learning. Examination of whether successful conditioning could take place with or without conscious awareness of CS–UCS contingencies was inconclusive. The results provide evidence for EC as an associative process and also provide some insight into the possible conditioning parameters that might successfully generate EC.
Why are artificial polymorphous concepts so hard for birds to learn?
Authors: Lea Stephen E. G. , Wills A. J. , Ryan Catriona M. E.
Published: July 2005

Stimulus sets defined in terms of artificial polymorphous concepts have frequently been used in experiments to investigate the mechanisms of discrimination of natural concepts, both in humans and in other animals. However, such stimulus sets are frequently difficult for either animals or humans to discriminate. Properties of artificial polymorphous stimulus sets that might explain this difficulty include the complexity of the individual stimuli, the unreliable reinforcement of individual positive features, attentional load, difficulties in discriminating some stimulus dimensions, memory load, and a lack of the correlation between features that characterizes natural concepts. An experiment using chickens as subjects and complex artificial visual stimulus sets investigated these hypotheses by training the birds in discriminations that were not polymorphous but did have some of the properties listed above. Discriminations that involved unreliable reinforcement or high attentional load were found to approach the difficulty of polymorphous concept discriminations, and these two factors together were sufficient to account for the entire difficulty. The usual kind of artificial polymorphous concept may not be a good model for natural concepts as they are perceived and discriminated by birds. A RULEX account of natural concept learning may be preferable.
Integration of metabolic networks and gene expression in virtual reality
Authors: Yang Yuting , Engin Levent , Wurtele Eve Syrkin , Cruz-Neira Carolina , Dickerson Julie A.
Published: July 2005

Motivation: Metabolic networks combine metabolism and regulation. These complex networks are difficult to understand and visualize due to the amount and diverse types of information that need to be represented. For example, pathway information gives indications of interactions. Experimental data, such as transcriptomics, proteomics and metabolomics data, give snapshots of the system state. Stereoscopic virtual environments provide a true three-dimensional representation of metabolic networks, which can be intuitively manipulated, and may help to manage the data complexity.

Results: MetNet3D, a 3D virtual reality system, allows a user to explore gene expression and metabolic pathway data simultaneously. Normalized gene expression data are processed in R and visualized as a 3D plot. Users can find a particular gene of interest or a cluster of genes that behave similarly and see how these genes function in metabolic networks from MetNetDB, a database of Arabidopsis metabolic networks, using animated network graphs. Interactive virtual reality, with its enhanced ability to display more information, makes such integration more effective by abstracting key relationships.

Availability: MetNet3D and some sample datasets are available at http://www.vrac.iastate.edu/research/sites/metnet/Download/Download.htm

Contact:  julied@iastate.edu

Supplementary information: Color snapshots and movies are available at http://www.vrac.iastate.edu/research/sites/metnet/Bioinformatics/SupplementaryInformation.htm
simuPOP: a forward-time population genetics simulation environment
Authors: Peng Bo , Kimmel Marek
Published: July 2005

Summary: simuPOP is a forward-time population genetics simulation environment. The core of simuPOP is a scripting language (Python) that provides a large number of objects and functions to manipulate populations, and a mechanism to evolve populations forward in time. Using this R/Splus-like environment, users can create, manipulate and evolve populations interactively, or write a script and run it as a batch file. Owing to its flexible and extensible design, simuPOP can simulate large and complex evolutionary processes with ease. At a more user-friendly level, simuPOP provides an increasing number of built-in scripts that perform simulations ranging from implementation of basic population genetics models to generating datasets under complex evolutionary scenarios.

Availability: simuPOP is freely available at http://simupop.sourceforge.net, distributed under GPL license.

Contact:  bpeng@rice.edu
Distinct roles for the RSC and Swi/Snf ATP-dependent chromatin remodelers in DNA double-strand break repair
Authors: Chai Bob , Huang Jian , Cairns Bradley R. , Laurent Brehon C.
Published: July 2005

The failure of cells to repair damaged DNA can result in genomic instability and cancer. To efficiently repair chromosomal DNA lesions, the repair machinery must gain access to the damaged DNA in the context of chromatin. Here we report that both the RSC and Swi/Snf ATP-dependent chromatin-remodeling complexes play key roles in double-strand break (DSB) repair, specifically by homologous recombination (HR). RSC and Swi/Snf are each recruited to an in vivo DSB site but with distinct kinetics. We show that Swi/Snf is required earlier, at or preceding the strand invasion step of HR, while RSC is required following synapsis for completion of the recombinational repair event.
The human PAF complex coordinates transcription with events downstream of RNA synthesis
Authors: Zhu Bing , Mandal Subhrangsu S. , Pham Anh-Dung , Zheng Yong , Erdjument-Bromage Hediye , Batra Surinder K. , Tempst Paul , Reinberg Danny
Published: July 2005

The yeast PAF (yPAF) complex interacts with RNA polymerase II and coordinates the setting of histone marks associated with active transcription. We report the isolation and functional characterization of the human PAF (hPAF) complex. hPAF shares four subunits with yPAF (hCtr9, hPaf1, hLeo1, and hCdc73), but contains a novel higher eukaryotic-specific subunit, hSki8. RNAi against hSki8 or hCtr9 reduces the cellular levels of other hPAF subunits and of mono- and trimethylated H3-Lys 4 and dimethylated H3-Lys 79. The hSki8 subunit is also a component of the human SKI (hSKI) complex. Yeast SKI complex is cytoplasmic and together with Exosome mediates 3′–5′ mRNA degradation. However, hSKI complex localizes to both nucleus and cytoplasm. Immunoprecipitation experiments revealed that hPAF and hSKI complexes interact, and ChIP experiments demonstrated that hSKI associates with transcriptionally active genes dependent on the presence of hPAF. Thus, in addition to coordinating events during transcription (initiation, promoter clearance, and elongation), hPAF also coordinates events in RNA quality control.
Drosophila argonaute-2 is required early in embryogenesis for the assembly of centric/centromeric heterochromatin, nuclear division, nuclear migration, and germ-cell formation
Authors: Deshpande Girish , Calhoun Gretchen , Schedl Paul
Published: July 2005

The RNA-induced silencing complex (RISC) or the RISC complex mediates RNAi and is comprised of proteins belonging to the dicer and Argonaute family proteins. Here we show that Argonaute-2 (ago-2) is required for proper nuclear migration, pole cell formation, and cellularization during the early stages of embryonic development in Drosophila. We have traced these defects back to the nuclear division cycles. Unlike wild type, nuclear division is asynchronous in ago-2 embryos and there are defects in chromosome condensation, nuclear kinesis, and assembly of spindle apparatus. The aberrations in the nuclear division cycle are correlated with defects in the formation of centric/centromeric heterochromatin and point to a failure in the assembly of functional centromeres.
Runx1 prevents wasting, myofibrillar disorganization, and autophagy of skeletal muscle
Authors: Wang Xiaoxia , Blagden Chris , Fan Jihua , Nowak Scott J. , Taniuchi Ichiro , Littman Dan R. , Burden Steven J.
Published: July 2005

Disruptions in the use of skeletal muscle lead to muscle atrophy. After short periods of disuse, muscle atrophy is reversible, and even after prolonged periods of inactivity, myofiber degeneration is uncommon. The pathways that regulate atrophy, initiated either by peripheral nerve damage, immobilization, aging, catabolic steroids, or cancer cachexia, however, are poorly understood. Previously, we found that Runx1 (AML1), a DNA-binding protein that is homologous to Drosophila Runt and has critical roles in hematopoiesis and leukemogenesis, is poorly expressed in innervated muscle, but strongly induced in muscle shortly after denervation. To determine the function of Runx1 in skeletal muscle, we generated mice in which Runx1 was selectively inactivated in muscle. Here, we show that Runx1 is required to sustain muscle by preventing denervated myofibers from undergoing myofibrillar disorganization and autophagy, structural defects found in a variety of congenital myopathies. We find that only 29 genes, encoding ion channels, signaling molecules, and muscle structural proteins, depend upon Runx1 expression, suggesting that their misregulation causes the dramatic muscle wasting. These findings demonstrate an unexpected role for electrical activity in regulating muscle wasting, and indicate that muscle disuse induces compensatory mechanisms that limit myofiber atrophy. Moreover, these results suggest that reduced muscle activity could cause or contribute to congenital myopathies if Runx1 or its target genes were compromised.
Influences of the vegetation mosaic on riparian and stream environments in a mixed forest‐grassland landscape in “Mediterranean” northwestern California
Authors: Welsh, Jr Hartwell H. , Hodgson Garth R. , Karraker Nancy E.
Published: July 2005

We examined differences in riparian and aquatic environments within the three dominant vegetation patch types of the Mattole River watershed, a 789‐km2 mixed conifer‐deciduous (hardwood) forest and grassland‐dominated landscape in northwestern California, USA. Riparian and aquatic environments, and particularly microclimates therein, influence the distributions of many vertebrate species, particularly the physiologically‐restricted ectotherms – reptiles and amphibians (herpetofauna), and fishes. In addition to being a significant portion of the native biodiversity of a landscape, the presence and relative numbers of these more tractable small vertebrates can serve as useful metrics of its “ecological health.” Our primary objective was to determine the range of available riparian and aquatic microclimatic regimes, and discern how these regimes relate to the dominant vegetations that comprise the landscape mosaic. A second objective, reported in a companion paper, was to examine relationships between available microclimatic regimes and herpetofaunal distributions. Here we examined differences in the composition, structure, and related environmental attributes of the three dominant vegetation types, both adjacent to and within the riparian corridors along 49 tributaries. Using automated dataloggers, we recorded hourly water and air temperatures and relative humidity throughout the summer at a representative subset of streams; providing us with daily means and amplitudes for these variables within riparian environments during the hottest period. Although the three vegetation types that dominate this landscape each had unique structural attributes, the overlap in plant species composition indicates that they represent a seral continuum. None‐the‐less, we found distinct microclimates in each type. Only riparian within late‐seral forests contained summer water temperatures that could support cold‐water‐adapted species. We evaluated landscape‐level variables to determine the best predictors of water temperature as represented by the maximum weekly maximum temperature (MWMT). The best model for predicting MWMT (adj. R2=0.69) consisted of catchment area, aspect, and the proportion of non‐forested (grassland) patches. Our model provides a useful tool for management of cold‐water fauna (e.g. salmonids, stream amphibians) throughout California's “Mediterranean” climate zone.
Genetic structure of Euphrasia stricta on the Baltic island of Gotland, Sweden
Authors: Kolseth Anna‐Karin , Lönn Mikael
Published: July 2005

Genetic differentiation between and within five varieties of Euphrasia stricta (var. brevipila, var. gotlandica, var. stricta, var. suecica and var. tenuis) on Gotland was investigated, using amplified fragment length polymorphism, AFLP. The varieties are described in the literature by morphology and association to habitat type. We wanted to investigate whether the varieties are locally adapted populations to the typical habitat type for each variety or if they are preadapted to certain habitat types and have colonized Gotland in their present form.

A constrained principal coordinate analysis revealed three genetically differentiated subunits within the species. The two early‐flowering varieties suecica and tenuis each formed a distinct group, while the three late‐flowering varieties brevipila, gotlandica and stricta together formed the third group. A phylogenetic tree confirms the partitioning into three groups. Within the group containing the late‐flowering varieties there are populations that pair as each other's closest relatives, but belong to different varieties. These pairs are also geographically adjacent.

The phylogenetic tree had a “star‐like” appearance indicating a stronger divergence between populations than between varieties. The same pattern was seen in the partitioning of genetic diversity, with a lower amount of genetic variation occurring between varieties, FST=0.14, than between populations within the varieties, FST ranging from 0.26 to 0.60.

In Euphrasia stricta the varieties suecica and tenuis and the group containing the varieties stricta/gotlandica/brevipila are likely to have a phylogeographical history outside Gotland, or an ancient and concealed local origin on the island. Within the group stricta/gotlandica/brevipila local evolutionary events seem to determine the variety identity, probably through local adaptation.
Variable dependence on detrital and grazing food webs by generalist predators: aerial insects and web spiders
Authors: Shimazaki Aya , Miyashita Tadashi
Published: July 2005

Recent studies have shown that organisms from the detritus food web subsidize generalist predators in aboveground food webs, but its significance in space and time is largely unknown. Here we report seasonal dynamics of aerial insects from grazing and detritus food webs in both forest and grassland habitats, and show how these patterns influence the dependence of web spiders on the detritus food web. Detrital insects were more abundant in spring, decreased in summer, and then increased slightly in autumn. This pattern was most conspicuous in Nematocera. Due to different seasonal activity patterns of grazing and detrital insects, the proportion of detrital insects was greater in spring and autumn. Detrital insects were relatively more abundant in the forest than in the grassland. Prey captured by web spiders generally reflected seasonal and spatial patterns of aerial insect abundance. In particular, Leucauge spiders reversed their dependence on the two food webs seasonally. Body size of spiders was negatively correlated with the proportion of detrital prey, suggesting that the detrital subsidy is essential for relatively small predators. This size effect probably resulted from interaction of the following two factors: 1) the maximum body size of prey that can be caught increased with spider body size, 2) larger body size classes of aerial insects included a higher proportion of insects from the grazing food web.
Effects of plant diversity, plant productivity and habitat parameters on arthropod abundance in montane European grasslands
Authors: Perner Jörg , Wytrykush Carla , Kahmen Ansgar , Buchmann Nina , Egerer Ilka , Creutzburg Sylvia , Odat Nidal , Audorff Volker , Weisser Wolfgang W.
Published: July 2005

Arthropod abundance has been hypothesized to be correlated with plant diversity but the results of previous studies have been equivocal. In contrast, plant productivity, vegetation structure, abiotic site conditions, and the physical disturbance of habitats, are factors that interact with plant diversity, and that have been shown to influence arthropod abundance. We studied the combined effect of plant species diversity, productivity and site characteristics on arthropod abundance in 71 managed grasslands in central Germany using multivariate statistics. For each site we determined plant species cover, plant community biomass (productivity), macro‐ and micronutrients in the soil, and characterized the location of sites with respect to orographic parameters as well as the current and historic management regimes. Arthropods were sampled using a suction sampler and classified a priori into functional groups (FGs). We found that arthropod abundance was not correlated with plant species richness, effective diversity or Camargo's evenness, even when influences of environmental variables were taken into account. In contrast, plant community composition was highly correlated with arthropod abundances. Plant community productivity influenced arthropod abundance but explained only a small proportion of the variance. The abundances of the different arthropod FGs were influenced differentially by agricultural management, soil characteristics, vegetation structure and by interactions between different FGs of arthropods. Herbivores, carnivores and detritivores reacted differently to variation in environmental variables in a manner consistent with their feeding mode. Our results show that in natural grassland systems arthropod abundance is not a simple function of plant species richness, and they emphasize the important role of plant community composition for the abundance patterns of the arthropod assemblages.
Abundance patterns and coexistence processes in communities of fleas parasitic on small mammals
Authors: Krasnov Boris R. , Mouillot David , Shenbrot Georgy I. , Khokhlova Irina S. , Poulin Robert
Published: July 2005

The abundance of a given species in a community is likely to depend on both the total abundance and diversity of other species making up that community. A large number of co‐occurring individuals or co‐occurring species may decrease the abundance of any given species via diffuse competition; however, indirect interactions among many co‐occurring species can have positive effects on a focal species. The existence of diffuse competition and facilitation remain difficult to demonstrate in natural communities. Here, we use data on communities of fleas ectoparasitic on small mammals from 27 distinct geographical regions to test whether the abundance of any given flea species in a community is affected by either the total abundance of all other co‐occurring flea species, or the species richness and/or taxonomic diversity of the flea community. At all scales of analysis, i.e. whether we compared the same flea species on different host species, or different flea species, two consistent results emerged. First, the abundance of a given flea species correlates positively with the total abundance of all other co‐occurring flea species in the community. Second, the abundance of any given flea species correlates negatively with either the species richness or taxonomic diversity of the flea community. The results do not support the existence of diffuse competition in these assemblages, because the more individuals of other flea species are present on a host population, the more individuals of the focal species are there as well. Instead, we propose explanations involving either apparent facilitation among flea species via suppression of host immune defenses, or niche filtering processes acting to restrict the taxonomic composition and abundance of flea assemblages.
Relative importance of resource quantity, isolation and habitat quality for landscape distribution of a monophagous butterfly
Authors: Krauss Jochen , Steffan‐Dewenter Ingolf , Müller Christine B. , Tscharntke Teja
Published: July 2005

Fragmentation of food resources is a major cause of species extinction. We tested the effects of habitat area, isolation and quality for the occurrence and population density of the endangered butterfly Polyommatus coridon. Polyommatus coridon larvae are monophagous on the plant Hippocrepis comosa, and both species are specialised on calcareous grassland, which is an endangered and highly fragmented habitat type in Germany.

In 2001 we surveyed all known calcareous grasslands (n=298) around the city of Göttingen (Germany) to map the population size of H. comosa in these habitats. Further, habitat isolation (between‐patch distance: 70–7220 m) and habitat quality (cover of flowering plants, height of herb layer, percent bare ground, cover of shrub layer, wind protection, inclination) were quantified. Hippocrepis comosa occurred on only 124 fragments, which were then surveyed by 20 min transect counts for adult P. coridon in 2001 and 2002.

Occurrence and population density of P. coridon were largely determined by the population size of its larval food plant, which was correlated with grassland area. Effects of habitat isolation and habitat quality on P. coridon populations contributed only little to the explanation.

In conclusion, this monophagous habitat specialist depended on large habitats with large food plant populations to exist in viable populations. Habitat isolation and quality appear to contribute to occurrence and density patterns only in landscapes where these factors shift towards extremes, therefore general recommendations for conservation programs are difficult as they depend on regional distinctions.
Pituitary and autonomic responses to cold exposures in man
Authors: Leppäluoto J. , Pääkkönen T. , Korhonen I. , Hassi J.
Published: July 2005

This review presents hormonal responses to various cold exposures and their calorigenic effects in man and some animals. Previous studies in rats have shown that cold exposures activate the hypothalamic‐pituitary‐thyroid axis. Increased thyroid hormone concentrations lead to heat production via general stimulation of metabolism (obligatory thermogenesis) and possibly via activation of thyroid hormone receptors and uncoupling protein 1 (UCP 1) and deiodinase enzyme genes in the brown adipose tissue (BAT). In human subjects long‐term cold exposures do not seem to activate the pituitary‐thyroid axis, but rather accelerate the elimination of triiodothyronine (T3), leading to low serum concentrations of free T3 hormone. In corollary to this a hypothyreotic condition with increased serum thyroid‐stimulating hormone and impaired mood and cognitive performance can be observed after long‐term cold exposures such as wintering. During cold exposures the sympathetic nerve system is activated and noradrenaline is released to blood circulation and to BAT, where it leads to production of cAMP, lipolysis and free fatty acids. Free fatty acids open the mitochondrial proton channel protein in BAT. Protons enter the mitochondria and inhibit ATP synthesis (uncoupling). By this way energy is transformed into heat (facultatory or adaptive thermogenesis). In adult human subjects the amount of BAT is small and adaptive thermogenesis (non‐shivering thermogenesis) has a smaller role. UCP 1 with other uncoupling proteins may have other functions in the control of body weight, sugar balance and formation of reactive oxygen species.
Fuel selection in shivering humans
Authors: Weber J.‐M. , Haman F.
Published: July 2005

Heat exchange has been thoroughly studied in cold‐exposed humans, but the metabolic substrates used for thermogenesis have received less attention. This review deals with oxidative fuel selection in shivering humans. Lipids provide most of the heat during low‐intensity shivering, whereas carbohydrates become dominant under more extreme cold conditions. The contribution from plasma glucose always remains minor, but muscle glycogen plays an important role during intense shivering. Whether the size of muscle glycogen stores influences endurance in the cold remains to be demonstrated. The fuel selection patterns of shivering and exercise are different, but the mechanisms underlying this difference have not been investigated. The simultaneous measurement of metabolic substrate oxidation and muscle fibre recruitment has allowed to characterize two different mechanisms of fuel selection in shivering humans: the recruitment of different pathways within the same fibres and of different fuel‐specific fibres within the same muscles. This suggests that muscle fibre composition of each individual may affect survival. Future research promises to provide a combination of theoretical advances on fundamental principles of fuel selection and applied strategies to manipulate fibre composition (through training) or fuel metabolism (through diet) to prolong human survival in cold environments.
A role for suppressed skeletal muscle thermogenesis in pathways from weight fluctuations to the insulin resistance syndrome
Authors: Dulloo A. G.
Published: July 2005

An impressive body of epidemiological evidence suggests that a history of large perturbations in body weight earlier in life, independently of excess weight, is a risk factor for later development of insulin‐related complications, namely central obesity, type 2 diabetes and cardiovascular disease. Such an increased risk has been reported in men and women who in young adulthood experienced weight fluctuations that involved weight recovery after weight loss caused by disease, famine or voluntary ‘yoyo’ dieting, and is particularly strong when the weight fluctuations occurred much earlier in life and are characterized by catch‐up growth after foetal and/or neonatal growth retardation. As the phase of weight recovery/catch‐up growth is associated with both hyperinsulinaemia and an accelerated rate for recovering fat mass (i.e. catch‐up fat), the questions arise as to whether, why and how processes that regulate catch‐up fat might predispose to hyperinsulinaemia and to insulin‐related diseases. In addressing these issues, this paper first reviews evidence for the existence of an adipose‐specific control of thermogenesis, whose suppression contributes to the phenomenon of catch‐up fat during weight recovery/catch‐up growth. It subsequently concentrates upon recent findings suggesting that: (i) such suppression of thermogenesis directed at catch‐up fat is accompanied by a redistribution of glucose from skeletal muscle to white adipose tissue, and (ii) substrate cycling between de novo lipogenesis and lipid oxidation can operate as a thermogenic effector in skeletal muscle in response to signalling interactions between leptin and insulin – two key ‘adiposity’ hormones implicated in the peripheral control of substrate metabolism. These new findings are integrated into the proposal that, in its ‘evolutionary adaptive’ role to spare glucose for rapid rebuilding of the fat stores, suppressed thermogenesis in skeletal muscle – via inhibition of substrate cycling between de novo lipogenesis and lipid oxidation – confers to the phase of weight recovery/catch‐up growth its high sensitivity towards the development of insulin resistance and hyperinsulinaemia, and hence towards diseases that are clustered around the insulin resistance syndrome.
Endocrine and signalling role of adipose tissue: new perspectives on fat
Authors: Trayhurn P.
Published: July 2005

White adipose tissue (WAT) is now recognized as a major endocrine and secretory organ, releasing a wide range of protein factors and signals termed adipokines – in addition to fatty acids and other lipid moieties. A paradigm shift came with the discovery of leptin, a pleiotropic hormone which is a critical signal to the hypothalamus in the control of appetite and energy balance. A number of adipokines, including adiponectin, tumour necrosis factor‐alpha, interleukin (IL)‐1β, IL‐6, IL‐8, IL‐10, monocyte chemoattractant protein‐1, macrophage migration inhibitory factor, nerve growth factor, vascular endothelial growth factor, plasminogen activator inhibitor‐1 and haptoglobin, are linked to inflammation and the inflammatory response. Obesity is characterized by a state of mild inflammation, and the expression and release of inflammation‐related adipokines generally rises as adipose tissue expands; a notable exception is adiponectin, with its anti‐inflammatory action, the levels of which fall. WAT may be the main site of inflammation in obesity, increased circulating levels of inflammatory markers reflecting spillover from an ‘inflamed’ tissue, leading to the obesity‐associated pathologies of type 2 diabetes and the metabolic syndrome. From the wide range of adipokines now identified, it is evident that WAT is highly integrated into overall physiological regulation, involving extensive crosstalk with other organs and multiple metabolic systems. Whether major changes in adipokine production in obesity, particularly of those factors linked to inflammation, are unique to this condition, or are a feature of all situations in which there are substantial increases in adipose mass (such as pregnancy, and pre‐hibernatory and pre‐migratory fattening) requires consideration.
Effect of atorvastatin and fluvastatin on the metabolism of midazolam by cytochrome P450 in vitro*
Authors: Mc Donnell C. G. , Shorten G. , Van Pelt F. N. A. M.
Published: July 2005

We have investigated the effects of the statins atorvastatin and fluvastatin on the cytochrome P450 3A4 enzyme (CYP 3A4)‐mediated metabolism of midazolam in vitro, using pooled human liver microsomes. Midazolam was metabolised by human hepatic microsomes with a Michaelis–Menten constant (Km) of 5.25 (SD 1.2) μmol.l−1. Atorvastatin was a moderate competitive inhibitor of CYP 3A4 with an inhibitory constant (Ki) of 12.4 (95% CI 4.65–20.06) μmol.l−1. Fluvastatin was a weak non‐competitive inhibitor of CYP 3A4 with a Ki of 94.3 (95% CI 55.01–133.5) μmol.l−1. Both atorvastatin and fluvastatin inhibit the CYP 3A4‐mediated metabolism of midazolam in vitro.
Lung recruitment during mechanical positive pressure ventilation in the PICU: what can be learned from the literature?
Authors: Halbertsma F. J. J. , Van Der Hoeven J. G.
Published: July 2005

A literature review was conducted to assess the evidence for recruitment manoeuvres used in conventional mechanical positive pressure ventilation. A total of 61 studies on recruitment manoeuvres were identified: 13 experimental, 31 ICU, 6 PICU and 12 anaesthesia studies. Recruitment appears to be a continuous process during inspiration and expiration and is determined by peak inspiratory pressure (PIP) and positive end expiratory pressure (PEEP). Single or repeated recruitment manoeuvres may result in a statistically significant increase in oxygenation; however, this is short lasting and clinically irrelevant, especially in late ARDS and pneumonia. Temporary PIP elevation may be effective but only after PEEP loss (for example disconnection and tracheal suctioning). Continuous PEEP elevation and prone positioning can increasePao2significantly. Adverse haemodynamic or barotrauma effects are reported in various studies. No data exist on the effect of recruitment manoeuvres on mortality, morbidity, length of stay or duration of mechanical ventilation. Although recruitment manoeuvres can improve oxygenation, they can potentially increase lung injury, which eventually determines outcome. Based on the presently available literature, prone position and sufficient PEEP as part of a lung protective ventilation strategy seem to be the safest and most effective recruitment manoeuvres. As paediatric physiology is essentially different from adult, paediatric studies are needed to determine the role of recruitment manoeuvres in the PICU.
Differences between brain and rectal temperatures during routine critical care of patients with severe traumatic brain injury*
Authors: Childs C. , Vail A. , Protheroe R. , King A. T. , Dark P. M.
Published: July 2005

Theoretical models suggest that small differences only exist between brain and body temperature in health. Once the brain is injured, brain temperature is generally regarded to rise above body temperature. However, since reports of the magnitude of the temperature gradient between brain and body vary, it is still not clear whether conventional body temperature monitoring accurately predicts brain temperature at all times. In this prospective, descriptive study, 20 adults with severe primary brain trauma were studied during their stay in the neurointensive care unit. Brain temperature ranged from 33.4 to 39.9 °C. Comparisons between paired brain and rectal temperature measurements revealed no evidence of a systematic difference [mean difference −0.04 °C (range −0.13 to 0.05 °C, 95% CI), p = 0.39]. Contrary to popular belief, brain temperature did not exceed systemic temperature in this relatively homogeneous patient series. The mean values masked inconsistent and unpredictable individual brain–rectal temperature differences (range 1.8 to −2.9 °C) and reversal of the brain‐body temperature gradient occurred in some patients. Brain temperature could not be predicted from body temperature at all times.
Fatal exacerbation of peripheral neuropathy during lamivudine therapy: evidence for iatrogenic mitochondrial damage
Authors: Fodale V. , Mazzeo A. , Praticò C. , Aguennouz M. , Toscano A. , Santamaria L. B. , Vita G.
Published: July 2005

A 57‐year‐old man with mild neuropathy who was positive for hepatitis B and C viruses was treated with lamivudine 300 mg.day−1. After 3 months he presented with dysphonia and progressive muscle weakness. Subsequently, he developed tetraparesis followed by acute respiratory failure requiring mechanical ventilation, which was complicated by sudden cardiac arrest. After lamivudine was stopped, the neuropathy improved and respiratory capacity improved. Unfortunately, the patient died suddenly in spite of haemodynamic, ventilatory and metabolic support. Electrophysiological studies showed evidence of a sensory‐motor axonal neuropathy. Nerve biopsy, muscle biopsy, biochemistry and mitochondrial DNA molecular genetics suggested possible widespread iatrogenic mitochondrial damage. Mitochondrial DNA dysfunction could be a potential cause of the sudden cardiac arrest. Stopping lamivudine treatment sooner after the onset of peripheral neuropathy or its exacerbation is important as continued therapy could lead to acute respiratory failure requiring mechanical ventilation and intensive care unit admission.
Prophylactic percutaneous transtracheal catheterisation in the management of patients with anticipated difficult airways: a case series*
Authors: Gerig H. J. , Schnider T. , Heidegger T.
Published: July 2005

Primary tracheostomy under local anaesthesia is indicated in the management of an anticipated difficult airway in patients in whom less invasive procedures are expected to fail or have already failed. However, primary tracheostomy is a relatively complex procedure and places not inconsiderable stress on the patient. In a prospective study in our hospital over a period of 22 months, we were able to avoid primary tracheostomy in 11 patients with very difficult airways. All 11 patients were managed with prophylactically inserted transtracheal catheters and jet ventilation of the lungs. This ensured an adequate oxygen supply during tracheal intubation, and made overall patient management much easier. This method has established itself as a standard procedure in our hospital.
Large venous air embolism in the sitting position despite monitoring with transoesophageal echocardiography
Authors: Wong A. Y. C. , Irwin M. G.
Published: July 2005

A 49‐year‐old male with neurofibromatosis type II was scheduled for posterior fossa craniotomy and excision of a right acoustic neuroma and placement of an auditory brainstem implant in the sitting position. Intra‐operatively, the patient was monitored with transoesophageal echocardiography which detected two major episodes of venous air embolism. Despite immediate treatment the patient's gas exchange progressively worsened during surgery and a chest X‐ray showed extensive bilateral pulmonary infiltrates. The patient developed acute respiratory distress syndrome and required inotropic support in the intensive care unit. Although transoesophageal echocardiography allowed rapid detection of venous air embolism, there was no evidence of therapeutic benefit.
Cardiovascular responses following laryngoscope assisted, fibreoptic orotracheal intubation
Authors: Tong J. L. , Ashworth D. R. , Smith J. E.
Published: July 2005

The Macintosh laryngoscope has recently been used successfully as an airway clearance device during fibreoptic intubation in patients who presented difficult intubation, but it is not known whether this approach will increase the pressor response to intubation. The aim of this investigation was to compare the cardiovascular responses of this method of facilitating airway clearance with the lingual traction plus jaw thrust method. 40 ASA I or II adult patients were given a standardised general anaesthetic and were randomly allocated to receive either lingual traction with jaw thrust (lingual traction group) or direct laryngoscopy with a Macintosh laryngoscope (laryngoscopy group) as the airway clearance manoeuvre prior to fibreoptic orotracheal intubation. Following intubation there was a significant rise in arterial pressure above pre‐induction levels in both groups (p < 0.05); however, the arterial pressure in the laryngoscopy group was significantly greater than that in the lingual traction group (systolic: p = 0.031, diastolic: p = 0.002). It appears therefore that the mechanical stimulus of the Macintosh laryngoscopy evokes a greater pressor response than that of lingual traction plus jaw thrust when these interventions are followed by fibreoptic intubation.
Tramadol‐induced hyponatraemia following unicompartmental knee replacement surgery
Authors: Udy A. , Deacy N. , Barnes D. , Sigston P.
Published: July 2005

We report a case of postoperative hyponatraemia following routine knee surgery, followed by a subsequent, less severe, episode after identical surgery on the contralateral knee. On each occasion the patient had been given the weak opioid tramadol for postoperative pain relief. Through its effects on serotonergic neurotransmission in the central nervous system, we hypothesise that tramadol may have been directly involved in this patient's biochemical disorder.
An evaluation of the Cobra Perilaryngeal Airway™: study halted after two cases of pulmonary aspiration*
Authors: Cook T. M. , Lowe J. M.
Published: July 2005

The Cobra Perilaryngeal Airway™ (Engineered Medical Systems, Indianapolis, IN) is a new supraglottic airway designed for spontaneous and controlled ventilation. It is not yet commercially available in the UK. Our aim was to evaluate the performance of the Cobra Perilaryngeal Airway™ in a cohort study and in a randomised, controlled, crossover comparison study with the Classic Laryngeal Mask Airway™. After studying 29 patients, both studies were suspended and later stopped after two cases of significant pulmonary aspiration had occurred in patients whilst using the Cobra Perilaryngeal Airway™. These cases raised concern about both the design and the safety of the Cobra Perilaryngeal Airway™, particularly during controlled ventilation. We suggest that the Cobra Perilaryngeal Airway™ should not be marketed for controlled ventilation until more safety data are available.
A set of testis‐specific novel genes collected from a collection of Korean Native Chicken ESTs
Authors: Shin J. H. , Kim H. , Song K. D. , Han B. K. , Park T. S. , Kim D. K. , Han J. Y.
Published: July 2005

We report a set of testis‐specific novel genes by comparing the The Institute for Genomic Research (TIGR) chicken gene index with the 13 132 expressed sequence tag (EST) collection from Korean Native Chicken (KNC). A total of 553 novel transcripts have resulted after comparison of our EST contigs and singlets against the chicken gene index and chicken genome sequences. Interestingly, 76% of the new genes were from testis‐specific EST contigs or singlet and analysis of exon/intron structure showed that a significant number of the contigs have intronless coding regions. A large portion of the testis‐specific transcripts have intronless coding region indicating that the testis‐specific expression pattern is related to a group of single exon genes in the chicken. The chicken EST data that are described in this paper have been submitted to the NCBI dbEST under accession numbers CO759017–CO764274, CO765331–CO768903 and CO769672‐CO773972.