bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of secondary bile acids in neoplastic development in the oesophagus
Authors: Cronin James , Williams Lisa , McAdam Elizabeth , Eltahir Zak , Griffiths Paul , Baxter John , Jenkins Gareth
Published: March 2010

Bile acids have been demonstrated, through the use of animal models and clinical association studies, to play a role in neoplastic development in Barrett's metaplasia. How specific bile acids promote neoplasia is as yet unknown, as are the exact identities of the important bile acid subtypes. The combination of bile subtype with appropriate pH is critical, as pH alters bile acid activity enormously. Hence glycine-conjugated bile acids are involved in neoplastic development at acidic pH (pH ~4), and unconjugated bile acids are involved in neoplastic development at more neutral pH (~6). Bile acids (at the appropriate pH) are potent DNA-damaging agents, due to the induction of ROS (reactive oxygen species), which are mainly induced by bile-induced damage to mitochondrial membranes, allowing leakage of ROS into the cytosol. These ROS also induce pro-survival signalling pathways [e.g. via PKC (protein kinase C)-dependent NF-κB (nuclear factor κB) activity]. Interestingly, NOS (nitric oxide synthase), through induction of NO may exacerbate this NF-κB activity and form a positive-feedback loop to amplify the activation of NF-κB by deoxycholic acid in particular. This combination of induced DNA damage and cell survival by bile acids is of major importance in neoplasia. Antioxidants and the tertiary bile acid UDCA (ursodeoxycholic acid) can block bile-induced DNA damage and bile-induced NF-κB activity, and should be considered in chemopreventative strategies.
The role of acid and bile reflux in oesophagitis and Barrett's metaplasia
Authors: Souza Rhonda F.
Published: March 2010

The precise mechanisms whereby gastro-oesophageal reflux disease causes reflux oesophagitis and Barrett's oesophagus are not clear, even though these diseases have been known to be linked for many years. Recent studies indicate a role for the reflux-induced inflammatory response of oesophageal squamous epithelial cells and the immune cells in the pathogenesis of reflux oesophagitis. Although reflux oesophagitis commonly heals with oesophageal squamous cell regeneration, in some individuals the oesophagus heals through the process of metaplasia, a condition termed Barrett's oesophagus. Recent studies indicate that individual differences in the reflux-mediated response of oesophageal squamous epithelial cells in the type of immune response and/or in signalling pathways that regulate cell proliferation or cell phenotype may determine whether the oesophagus heals with the regeneration of squamous cells or through Barrett's metaplasia.
The interaction of four-way DNA junctions with resolving enzymes
Authors: Lilley David M.J.
Published: March 2010

Four-way DNA (Holliday) junctions are resolved into duplex species by the action of the junction-resolving enzymes, nucleases selective for the structure of helical branchpoints. These have been isolated from bacteria and their phages, archaea, yeasts and mammals, including humans. They are all dimeric proteins that bind with high selectivity to DNA junctions and generate bilateral cleavage within the lifetime of the DNA–protein complex. Recent success in obtaining X-ray crystal structures of resolving enzymes bound to DNA junctions has revealed how the structural selectivity of these enzymes is achieved.
Ancient machinery embedded in the contemporary ribosome
Authors: Belousoff Matthew J. , Davidovich Chen , Zimmerman Ella , Caspi Yaron , Wekselman Itai , Rozenszajn Lin , Shapira Tal , Sade-Falk Ofir , Taha Leena , Bashan Anat , Weiss Manfred S. , Yonath Ada
Published: March 2010

Structural analysis, supported by biochemical, mutagenesis and computational evidence, indicates that the peptidyltransferase centre of the contemporary ribosome is a universal symmetrical pocket composed solely of rRNA. This pocket seems to be a relic of the proto-ribosome, an ancient ribozyme, which was a dimeric RNA assembly formed from self-folded RNA chains of identical, similar or different sequences. This could have occurred spontaneously by gene duplication or gene fusion. This pocket-like entity was capable of autonomously catalysing various reactions, including peptide bond formation and non-coded or semi-coded amino acid polymerization. Efforts toward the structural definition of the early entity capable of genetic decoding involve the crystallization of the small ribosomal subunit of a bacterial organism harbouring a single functional rRNA operon.
Nanomechanical constraints acting on the catalytic site of cellular RNA polymerases
Authors: Weinzierl Robert O.J.
Published: March 2010

RNAPs (RNA polymerases) are complex molecular machines containing structural domains that co-ordinate the movement of nucleic acid and nucleotide substrates through the catalytic site. X-ray images of bacterial, archaeal and eukaryotic RNAPs have provided a wealth of structural detail over the last decade, but many mechanistic features can only be derived indirectly from such structures. We have therefore implemented a robotic high-throughput structure–function experimental system based on the automatic generation and assaying of hundreds of site-directed mutants in the archaeal RNAP from Methanocaldococcus jannaschii. In the present paper, I focus on recent insights obtained from applying this experimental strategy to the bridge–helix domain. Our work demonstrates that the bridge–helix undergoes substantial conformational changes within a narrowly confined region (mjA′ Ala822-Gln823-Ser824) during the nucleotide-addition cycle. Naturally occurring radical sequence variations in plant RNAP IV and V enzymes map to this region. In addition, many mutations within this domain cause a substantial increase in the RNAP catalytic activity (‘superactivity’), suggesting that the RNAP active site is conformationally constrained.
The role of ATP in the reactions of type II DNA topoisomerases
Authors: Bates Andrew D. , Maxwell Anthony
Published: March 2010

Type II DNA topoisomerases catalyse changes in DNA topology in reactions coupled to the hydrolysis of ATP. In the case of DNA gyrase, which can introduce supercoils into DNA, the requirement for free energy is clear. However, the non-supercoiling type II enzymes carry out reactions that are apparently energetically favourable, so their requirement for ATP hydrolysis is not so obvious. It has been shown that many of these enzymes (the type IIA family) can simplify the topology of their DNA substrates to a level beyond that expected at equilibrium. Although this seems to explain their usage of ATP, we show that the free energies involved in topology simplification are very small (<0.2% of that available from ATP) and we argue that topology simplification may simply be an evolutionary relic.
Stochastic aspects of transmitter release and bioenergetic dysfunction in isolated nerve terminals
Authors: Nicholls David G.
Published: March 2010

Synaptosomes (isolated nerve terminals) have been studied for more than 40 years. The preparation allows aspects of transmitter metabolism and release to be studied ex vivo from specific brain regions of animals of any age. Conditions can be devised to enable the terminals to fire spontaneous action potentials, allowing the presynaptic control of glutamate exocytosis to be studied. Recent developments have greatly increased the sensitivity with which the bioenergetics of the intra-synaptosomal mitochondria can be investigated.
Reactive hypertrophy of synaptic varicosities within the hippocampus of prion-infected mice
Authors: Sisková Zuzana , Sanyal Nik K. , Orban Adam , O'Connor Vincent , Perry V. Hugh
Published: March 2010

Prion diseases are characteristically accompanied by extensive synaptic pathology that can occur during the preclinical phase of the disease and, in animal models, correlates with the first decline of hippocampus-dependent cognitive functions. This pathology is defined by abnormally shaped synapses in which the postsynaptic membrane modifies its curvature and potentially engulfs the juxtaposed presynaptic membrane. Using the intrahippocampally injected ME7 prion model, we further detailed the structural alterations of the population of ostensibly intact synaptic compartments within the hippocampus during this period of extensive synaptic loss. A disease stage-dependent increase in the average PSD (postsynaptic density) area, the average length of the active zone and the average number of synaptic vesicles indicated that the synapses that were visualized as the animal progressed to end-stage disease were undergoing hypertrophy. Similar findings in samples from AD (Alzheimer's disease) patients, aged and senile individuals, and animal models of neurodegenerative diseases suggest synaptic swelling as synaptic loss is initiated and/or compensatory reaction to counteract the synaptic loss.
Synapse elimination during development and disease: immune molecules take centre stage
Authors: Schafer Dorothy P. , Stevens Beth
Published: March 2010

Synapse elimination is a normal developmental process occurring throughout the central and peripheral nervous systems. Meanwhile, gradual and early loss of synapses is a characteristic that is common to several neurodegenerative disease states. Recent evidence has emerged implicating molecules canonically involved in the immune system and inflammation accompanying neurodegeneration (e.g. classical complement cascade) as important players in the normal elimination of synapses in the developing nervous system. As a result, a question has emerged as to whether mechanisms underlying elimination of synapses during normal development are recapitulated and contribute to early synapse loss and nervous system dysfunction during neurodegenerative disease. The present review explores this possibility and provides a description of many neuroimmune proteins that may participate in the elimination of synapses and synaptic dysfunction in the developing and diseased brain.
Dysfunction and recovery of synapses in prion disease: implications for neurodegeneration
Authors: Moreno Julie A. , Mallucci Giovanna R.
Published: March 2010

Synaptic dysfunction is a key early process in many neurodegenerative diseases, but how this ultimately leads to neuronal loss is not clear. In health, there is ongoing remodelling of synapses and spines in the adult brain: their elimination and formation are continual physiological processes fundamental to learning and memory. But in neurodegenerative disease, including prion disease, lost synapses are not replaced, and their loss is followed by neuronal death. These two processes are separately regulated, with mechanistic, spatial and temporal segregation of the respective death routines of synapses and cell bodies. Mice with prion disease can be cured at the stage of early synaptic dysfunction, when they have reversible impairments at neurophysiological, behavioural and morphological levels. Critically, reversing synaptic dysfunction at this stage of disease rescues neurons, preventing its otherwise inevitable progression to synapse loss and cell death. These findings call for a deeper analysis of the mechanisms underlying neurotoxicity at the synapse, and have important implications for the therapy of prion and other neurodegenerative disorders.
Synaptic dysfunction in Parkinson's disease
Authors: Bagetta Vincenza , Ghiglieri Veronica , Sgobio Carmelo , Calabresi Paolo , Picconi Barbara
Published: March 2010

In neuronal circuits, memory storage depends on activity-dependent modifications in synaptic efficacy, such as LTD (long-term depression) and LTP (long-term potentiation), the two main forms of synaptic plasticity in the brain. In the nucleus striatum, LTD and LTP represent key cellular substrates for adaptive motor control and procedural memory. It has been suggested that their impairment could account for the onset and progression of motor symptoms of PD (Parkinson's disease), a neurodegenerative disorder characterized by the massive degeneration of dopaminergic neurons projecting to the striatum. In fact, a peculiar aspect of striatal plasticity is the modulation exerted by DA (dopamine) on LTP and LTD. Our understanding of these maladaptive forms of plasticity has mostly come from the electrophysiological, molecular and behavioural analyses of experimental animal models of PD. In PD, a host of cellular and synaptic changes occur in the striatum in response to the massive loss of DA innervation. Chronic L-dopa therapy restores physiological synaptic plasticity and behaviour in treated PD animals, but most of them, similarly to patients, exhibit a reduction in the efficacy of the drug and disabling AIMs (abnormal involuntary movements) defined, as a whole, as L-dopa-induced dyskinesia. In those animals experiencing AIMs, synaptic plasticity is altered and is paralleled by modifications in the postsynaptic compartment. In particular, dysfunctions in trafficking and subunit composition of NMDARs [NMDA (N-methyl-D-aspartate) receptors] on striatal efferent neurons result from chronic non-physiological dopaminergic stimulation and contribute to the pathogenesis of dyskinesias. According to these pathophysiological concepts, therapeutic strategies targeting signalling proteins coupled to NMDARs within striatal spiny neurons could represent new pharmaceutical interventions for PD and L-dopa-induced dyskinesia.
Reversibility of functional deficits in experimental models of Rett syndrome
Authors: Cobb Stuart , Guy Jacky , Bird Adrian
Published: March 2010

Mutations in the X-linked MECP2 gene are the primary cause of the severe autism spectrum disorder RTT (Rett syndrome). Deletion of Mecp2 in mice recapitulates many of the overt neurological features seen in humans, and the delayed onset of symptoms is accompanied by deficits in neuronal morphology and synaptic physiology. Recent evidence suggests that reactivation of endogenous Mecp2 in young and adult mice can reverse aspects of RTT-like pathology. In the current perspective, we discuss these findings as well as other genetic, pharmacological and environmental interventions that attempt phenotypic rescue in RTT. We believe these studies provide valuable insights into the tractability of RTT and related conditions and are useful pointers for the development of future therapeutic strategies.
The anti-allodynic α2δ ligand pregabalin inhibits the trafficking of the calcium channel α2δ-1 subunit to presynaptic terminals in vivo
Authors: Bauer Claudia S. , Rahman Wahida , Tran-Van-Minh Alexandra , Lujan Rafael , Dickenson Anthony H. , Dolphin Annette C.
Published: March 2010

Neuropathic pain is caused by lesion or dysfunction of the peripheral sensory nervous system. Up-regulation of the voltage-gated Ca2+ channel subunit α2δ-1 in DRG (dorsal root ganglion) neurons and the spinal cord correlates with the onset of neuropathic pain symptoms such as allodynia in several animal models of neuropathic pain. The clinically important anti-allodynic drugs gabapentin and pregabalin are α2δ-1 ligands, but how these drugs alleviate neuropathic pain is poorly understood. In the present paper, we review recent advances in our understanding of their molecular mechanisms.
Change in tau phosphorylation associated with neurodegeneration in the ME7 model of prion disease
Authors: Asuni Ayodeji A. , Perry V. Hugh , O'Connor Vincent
Published: March 2010

Hyperphosphorylation of the microtubule-associated protein tau is a significant determinant in AD (Alzheimer's disease), where it is associated with disrupted axonal transport and probably causes synaptic dysfunction. Although less well studied, hyperphosphorylation has been observed in prion disease. We have investigated the expression of hyperphosphorylated tau in the hippocampus of mice infected with the ME7 prion agent. In ME7-infected animals, there is a selective loss of CA1 synapse, first discernable at 13 weeks of disease. There is a potential that dysfunctional axonal transport contributes to this synaptopathy. Thus investigating hyperphosphorylated tau that is dysfunctional in AD could illuminate whether and how they are significant in prion disease. We observed no differences in the levels of phosphorylated tau (using MC1, PHF-1 and CP13 antibodies) in detergent-soluble and detergent-insoluble fractions extracted from ME7- and NBH- (normal brain homogenate) treated animals across disease. In contrast, we observed an increase in phospho-tau staining for several epitopes using immunohistochemistry in ME7-infected hippocampal sections. Although the changes were not of the magnitude seen in AD tissue, clear differences for several phospho-tau species were seen in the CA1 and CA3 of ME7-treated animals (pSer199−202>pSer214>PHF-1 antibody). Temporally, these changes were restricted to animals at 20 weeks and none of the disease-related staining was associated with the axons or dendrites that hold CA1 synapses. These findings suggest that phosphorylation of tau at the epitopes examined does not underpin the early synaptic dysfunction. These data suggest that the changes in tau phosphorylation recorded here and observed by others relate to end-stage prion pathology when early dysfunctions have progressed to overt neuronal loss.
Metallothioneins and copper metabolism are candidate therapeutic targets in Huntington's disease
Authors: Hands Sarah L. , Mason Robert , Sajjad M. Umar , Giorgini Flaviano , Wyttenbach Andreas
Published: March 2010

HD (Huntington's disease) is caused by a polyQ (polyglutamine) expansion in the huntingtin protein, which leads to protein misfolding and aggregation of this protein. Abnormal copper accumulation in the HD brain was first reported more than 15 years ago. Recent findings show that copper-regulatory genes are induced during HD and copper binds to an N-terminal fragment of huntingtin, supporting the involvement of abnormal copper metabolism in HD. We have demonstrated that in vitro copper accelerates the fibrillization of an N-terminal fragment of huntingtin with an expanded polyQ stretch (httExon1). As we found that copper also increases polyQ aggregation and toxicity in mammalian cells expressing httExon1, we investigated further whether overexpression of genes involved in copper metabolism, notably MTs (metallothioneins) known to bind copper, protect against httExon1 toxicity. Using a yeast model of HD, we have shown that overexpression of several genes involved in copper metabolism reduces polyQ-mediated toxicity. Overexpression of MT-3 in mammalian cells significantly reduced polyQ aggregation and toxicity. We propose that copper-binding and/or -chaperoning proteins, especially MTs, are potential therapeutic targets for HD.
Sporophytic control of pollen tube growth and guidance in grasses
Authors: Lausser Andreas , Dresselhaus Thomas
Published: March 2010

Pollen tube growth and guidance in the female tissues of flowering plants is a long-studied and anatomically well-described process. A large number of gene products and chemical compounds involved have been identified in the last 20 years, and some underlying molecular mechanisms including self-incompatibility in the Brassicaceae, Solanaceae and Papaveraceae are now well understood. However, the largest part of the pollen tube pathway inside the transmitting tract towards the ovule harbouring the female gametophyte still requires intensive investigations. Especially in the economically most import plant family, the Poaceae or grasses, progamic pollen tube development is barely understood. Using maize as a model, we propose to divide pollen tube germination, growth and guidance towards the female gametophyte into five distinct phases. The model is adapted from Arabidopsis thaliana, taking anatomical differences and novel genetic and cellular studies into consideration. With the exception of Phase V, all phases seem to be under sporophytic control in grasses.
The role of chemical dynamics in plant morphogenesis
Authors: Holloway David M.
Published: March 2010

In biological development, the generation of shape is preceded by the spatial localization of growth factors. Localization, and how it is maintained or changed during the process of growth, determines the shapes produced. Mathematical models have been developed to investigate the chemical, mechanical and transport properties involved in plant morphogenesis. These synthesize biochemical and biophysical data, revealing underlying principles, especially the importance of dynamics in generating form. Chemical kinetics has been used to understand the constraints on reaction and transport rates to produce localized concentration patterns. This approach is well developed for understanding de novo pattern formation, pattern spacing and transitions from one pattern to another. For plants, growth is continual, and a key use of the theory is in understanding the feedback between patterning and growth, especially for morphogenetic events which break symmetry, such as tip branching. Within the context of morphogenetic modelling in general, the present review gives a brief history of chemical patterning research and its particular application to shape generation in plant development.
Regulation of plant light harvesting by thermal dissipation of excess energy
Authors: de Bianchi Silvia , Ballottari Matteo , Dall’Osto Luca , Bassi Roberto
Published: March 2010

Elucidating the molecular details of qE (energy quenching) induction in higher plants has proven to be a major challenge. Identification of qE mutants has provided initial information on functional elements involved in the qE mechanism; furthermore, investigations on isolated pigment–protein complexes and analysis in vivo and in vitro by sophisticated spectroscopic methods have been used for the elucidation of mechanisms involved. The aim of the present review is to summarize the current knowledge of the phenotype of npq (non-photochemical quenching)-knockout mutants, the role of gene products involved in the qE process and compare the molecular models proposed for this process.
Nucleolar RNPs: from genes to functional snoRNAs in plants
Authors: Rodor Julie , Letelier Ingrid , Holuigue Loreto , Echeverria Manuel
Published: March 2010

The snoRNAs (small nucleolar RNAs) and related scaRNAs (small RNAs in the Cajal bodies) represent a major class of nuclear RNAs that guide 2′-O-ribose methylation and pseudouridylation of rRNAs, snRNAs (small nuclear RNAs) and other RNA targets. In vivo, all snoRNAs associate with a set of four highly conserved nucleolar proteins, forming the functional snoRNPs (small nucleolar ribonucleoproteins). The core structure of these mature snoRNPs has now been well described in eukaryotes, but less is known of their biogenesis. Recent data in animals and yeast reveal that assembly of the snoRNPs is a complex process that implicates several auxiliary proteins and transient protein–protein interactions. This new level of snoRNP regulation is now beginning to be unravelled in animals and yeast, but remains unexplored in plants. In the present paper, we review recent data from genomic and functional analysis allowing the identification and study of factors controlling the biogenesis of plant snoRNPs and their impact on plant development.
Recycling domains in plant cell morphogenesis: small GTPase effectors, plasma membrane signalling and the exocyst
Authors: Žárský Viktor , Potocký Martin
Published: March 2010

The Rho/Rop small GTPase regulatory module is central for initiating exocytotically ACDs (active cortical domains) in plant cell cortex, and a growing array of Rop regulators and effectors are being discovered in plants. Structural membrane phospholipids are important constituents of cells as well as signals, and phospholipid-modifying enzymes are well known effectors of small GTPases. We have shown that PLDs (phospholipases D) and their product, PA (phosphatidic acid), belong to the regulators of the secretory pathway in plants. We have also shown that specific NOXs (NADPH oxidases) producing ROS (reactive oxygen species) are involved in cell growth as exemplified by pollen tubes and root hairs. Most plant cells exhibit several distinct plasma membrane domains (ACDs), established and maintained by endocytosis/exocytosis-driven membrane protein recycling. We proposed recently the concept of a ‘recycling domain’ (RD), uniting the ACD and the connected endosomal recycling compartment (endosome), as a dynamic spatiotemporal entity. We have described a putative GTPase–effector complex exocyst involved in exocytic vesicle tethering in plants. Owing to the multiplicity of its Exo70 subunits, this complex, along with many RabA GTPases (putative recycling endosome organizers), may belong to core regulators of RD organization in plants.
Clients' understanding of the role of nurse practitioners
Authors: Allnutt Jane , Allnutt Nissa , McMaster Rose , O'Connell Jane , Middleton Sandy , Hillege Sharon , Della Phillip R. , Gardner Glenn E. , Gardner Anne
Published: March 2010

Nurse practitioners (NPs) have an emerging role in the Australian health care system. However, there remains a dearth of data about public understanding of the NP role. The aim of this study was to evaluate clients’ understanding of the role of the NP and their satisfaction with education received, quality of care and NP knowledge and skill. All authorised NPs working in a designated NP position in Western Australia and those working in three area health services in New South Wales were invited to recruit five consecutive clients to complete the self-administered survey.
Thirty-two NPs (NP response rate 93%) recruited 129 clients (client response rate 90%). Two-thirds of clients (63%) were aware they were consulting an NP. The majority rated the following NP-related outcomes as ‘excellent’ or ‘very good’: education provided (89%); quality of care (95%); and knowledge and skill (93%). Less than half reported an understanding that NPs could prescribe medications (40.5%) or interpret X-rays (33.6%). Clients of NPs practising in a rural or remote setting were more likely than those in an urban setting to have previously consulted an NP (P = 0.005), and where applicable would to prefer to see an NP rather than a doctor (P = 0.022). Successful implementation and expansion of the NP role requires NP visibility in the community. Despite high levels of satisfaction, more awareness of the scope of the NP role is required.
What is known about the topic?The role of nurse practitioners (NPs) in Australian health care is diverse and evolving. There is a dearth of research focusing on NPs, particularly looking at the client perception of their role.
What does this paper add?This study investigates the client’s perception of the role of nurse practitioners and levels of confidence and satisfaction through the use of a self-administered questionnaire.
What are the implications for practitioners?The results suggest that clients have a moderate awareness of the nurse practitioner role. Despite this, clients appear to have high levels of confidence and satisfaction after consultations with nurse practitioners. These results suggest that greater community awareness of the role may help maximise their positive contribution to health care in Australia.
Non-invasive genetic sampling of faecal material and hair from the grey-headed flying-fox (Pteropus poliocephalus)
Authors: Baldwin Heather J. , Hoggard Stephen J. , Snoyman Stephanie T. , Stow Adam J. , Brown Culum
Published: March 2010

Remote-sampling DNA from animals offers obvious benefits for species that are difficult to sample directly and is less disruptive for species of conservation concern. Here we report the results of a pilot study investigating non-invasive DNA sampling of the grey-headed flying-fox (Pteropus poliocephalus), a threatened species that is restricted to the east coast of Australia. We successfully extracted DNA from fresh scats and hair, each of which was of sufficient quality for amplifying mitochondrial DNA markers and microsatellites. A single-locus multitube approach was used to investigate amplification success and genotyping reliability. Faecal samples yielded a higher proportion of successful amplifications and consensus genotype assignments than hair samples. We outline measures that may be utilised to minimise microsatellite genotyping error for future studies. These indirect approaches to obtaining genetic data show much promise given the difficult nature of directly sampling flying-foxes and related species.
Phylogeny of the rock wallabies, Petrogale (Marsupialia: Macropodidae). Part II: Detection of hybridisation among macropodines
Authors: Kirsch John A. W. , Gauthier Olivier , Campeau-Péloquin Antoine , Eldridge Mark D. B. , Lapointe François-Joseph
Published: March 2010

Phylogenetic relationships among rock-wallabies, Petrogale (Marsupialia: Macropodidae), have proven difficult to resolve. Given the documented interspecific hybridisation in the wild and the ease with which hybrids can be bred in captivity, introgression and hybrid speciation are likely explanations for these difficulties. In this paper, an attempt is made at using a phylogenetic approach to identify Petrogale hybrids of known origin. The Hybrid Detection Criterion (HDC) test is applied to DNA–DNA hybridisation data for 15 full species, two natural yard-bred hybrids, and two artificial hybrids from the same pairs of parental species. While the yard-bred hybrids elude detection with this technique, the artificial hybrids, consisting of equimolar mixture of parental extracts, are easily identified. Moreover, splitsgraphs constructed from five pairs of natural and artificial hybrids, including those evaluated with HDC, and their parents show that, in all cases but one, these two kinds of hybrids do not group together. Because the HDC assumes an intermediate phylogenetic position of the hybrid between its postulated parents, it is likely that unequal crossing-over, or another recombination event, affects the results of the test. These conclusions cast some doubt on the possibility of accurately detecting Petrogale hybrids with a phylogenetic approach.
Capturing genetic information using non-target species markers in a species that has undergone a population crash
Authors: Pacioni Carlo , Spencer Peter B. S.
Published: March 2010

Species conservation has relied on the enormous potential of information that arises from field, laboratory and other tools. When using molecular-based tools, the technology involves a considerable effort to develop, both in resources and time. A long-held practice has been to utilise pre-existing primers developed for other closely related species to evaluate conservation questions. In this study, we present a practical approach on how to utilise pre-existing microsatellite markers in bettong and potoroo species. This information is relevant before, during and after a species crash and the approach we describe could be particularly appropriate when there is an immediate need to retrieve a knowledge-base in order to support management decisions. We determined that cross-species amplification success of microsatellite markers is inversely related to evolutionary distance of the source species although their polymorphism is not. A ‘priority-list’ of potential markers for potoroids is given for future conservation genetic studies.
A descriptive study of e‐counsellor attitudes, ethics, and practice
Authors: Finn Jerry , Barak Azy
Published: March 2010

Introduction: The purpose of this study was to examine questions related to the process, perceived outcomes, and ethics of therapists who provide counselling and therapy online. Method: An online survey was conducted (N=93) with identified e‐counsellors with at least a Master's Degree. Questions included demographic information and Likert‐type scales related to extent of practice, theoretical orientation, training and supervision, attitudes about appropriate practice, referral, legal and ethical issues, practice difficulties, and therapist satisfaction. Results: Overall, e‐counsellors are satisfied with their practice and believe it is effective. They generally do not have formal training or supervision in online practice. Current e‐counselling appears to be a part‐time, supplemental practice with little overlap to FTF practice. There was little agreement among respondents on attitudes, practice, ethical issues, and knowledge of regulations related to e‐counselling. Discussion: Lack of consensus about ethical obligations and practice suggest the need for formal training in e‐counselling by professional programmes and international cooperation in formulating practice ethics. Areas for further research are discussed.
Value Authenticity: Unfolding Spirit in The Workplace
Authors: Howell Andrea
Published: March 2010

This paper suggests unfolding spirit within organisations begins with acknowledging spirit is within organisational members. Unfolding spirit within people and within the organisation occurs on two levels—below the line where the underlying belief system lies, and above the line,
where there is recognition that workplaces are environments were people seek meaning and purpose. When the organisation recognises the importance of spirit at work—insight—it may be possible for members to work together—integration—to make spirit comfortably
visible—inspired action.
Conscientious or Unconscious: The Converging Roles of Management Gurus and Corporate Chaplains
Authors: Kahne Bruno , Chaloner Brian
Published: March 2010

This paper provides a reflection on whether business managers are conscientiously bringing religious values into the workplace or whether they are doing this unconsciously through consultants who think that spirituality might be the ultimate tool of motivation.
Multidrug Resistance among Gram-Negative Pathogens That Caused
Healthcare-Associated Infections Reported to the National Healthcare Safety
Network, 2006–2008
Authors: Kallen Alexander J. , Hidron Alicia I. , Patel Jean , Srinivasan Arjun
Published: March 2010

We evaluated isolates of Klebsiella pneumoniae, Pseudomonas
aeruginosa, and Acinetobacter
baumannii that were reported to the National Healthcare Safety
Network from January 2006 through December 2008 to determine the proportion that
represented multidrug-resistant phenotypes. The pooled mean percentage of
resistance varied by the definition used; however, multidrug resistance was
relatively common and widespread.
Inside-Out Regulation of L1 Conformation, Integrin Binding, Proteolysis, and Concomitant Cell Migration
Authors: Chen Maxine M. , Lee Chia-Yao , Leland Hyuma A. , Lin Grace Y. , Montgomery Anthony M. , Silletti Steve
Published: March 2010

Previous reports on the expression of the cell adhesion molecule L1 in pancreatic ductal adenocarcinoma (PDAC) cells range from absent to high. Our data demonstrate that L1 is expressed in poorly differentiated PDAC cells in situ and that threonine-1172 (T1172) in the L1 cytoplasmic domain exhibits steady-state saturated phosphorylation in PDAC cells in vitro and in situ. In vitro studies support roles for casein kinase II and PKC in this modification, consistent with our prior studies using recombinant proteins. Importantly, T1172 phosphorylation drives, or is associated with, a change in the extracellular structure of L1, consistent with a potential role in regulating the shift between the closed conformation and the open, multimerized conformation of L1. We further demonstrate that these distinct conformations exhibit differential binding to integrins αvβ3 and αvβ5 and that T1172 regulates cell migration in a matrix-specific manner and is required for a disintegrin and metalloproteinase-mediated shedding of the L1 ectodomain that has been shown to regulate cell migration. These data define a specific role for T1172 of L1 in regulating aspects of pancreatic adenocarcinoma cell phenotype and suggest the need for further studies to elucidate the specific ramifications of L1 expression and T1172 phosphorylation in the pathobiology of pancreatic cancer.
ProBiS algorithm for detection of structurally similar protein binding sites by local structural alignment
Authors: Konc Janez , Janežič Dušanka
Published: March 2010

Motivation: Exploitation of locally similar 3D patterns of physicochemical properties on the surface of a protein for detection of binding sites that may lack sequence and global structural conservation.

Results: An algorithm, ProBiS is described that detects structurally similar sites on protein surfaces by local surface structure alignment. It compares the query protein to members of a database of protein 3D structures and detects with sub-residue precision, structurally similar sites as patterns of physicochemical properties on the protein surface. Using an efficient maximum clique algorithm, the program identifies proteins that share local structural similarities with the query protein and generates structure-based alignments of these proteins with the query. Structural similarity scores are calculated for the query protein's surface residues, and are expressed as different colors on the query protein surface. The algorithm has been used successfully for the detection of protein–protein, protein–small ligand and protein–DNA binding sites.

Availability: The software is available, as a web tool, free of charge for academic users at http://probis.cmm.ki.si

Contact:  dusa@cmm.ki.si

Supplementary information:  Supplementary data are available at Bioinformatics online.
Identification of genetic network dynamics with unate structure
Authors: Porreca Riccardo , Cinquemani Eugenio , Lygeros John , Ferrari-Trecate Giancarlo
Published: March 2010

Motivation: Modern experimental techniques for time course measurement of gene expression enable the identification of dynamical models of genetic regulatory networks. In general, identification involves fitting appropriate network structures and parameters to the data. For a given set of genes, exploring all possible network structures is clearly prohibitive. Modelling and identification methods for the a priori selection of network structures compatible with biological knowledge and experimental data are necessary to make the identification problem tractable.

Results: We propose a differential equation modelling framework where the regulatory interactions among genes are expressed in terms of unate functions, a class of gene activation rules commonly encountered in Boolean network modelling. We establish analytical properties of the models in the class and exploit them to devise a two-step procedure for gene network reconstruction from product concentration and synthesis rate time series. The first step isolates a family of model structures compatible with the data from a set of most relevant biological hypotheses. The second step explores this family and returns a pool of best fitting models along with estimates of their parameters. The method is tested on a simulated network and compared with state-of-the-art network inference methods on the benchmark synthetic network IRMA.

Contact:  eugenio.cinquemani@inria.fr

Supplementary information:  Supplementary data are available at Bioinformatics online.
CoP: a database for characterizing co-expressed gene modules with biological information in plants
Authors: Ogata Yoshiyuki , Suzuki Hideyuki , Sakurai Nozomu , Shibata Daisuke
Published: March 2010

Summary: Using a large dataset (10 022 assays) obtained from public plant microarray databases, we developed the CoP database for associating co-expressed gene modules with biological information such as gene ontology terms and, if available, metabolic pathway names. The Confeito algorithm developed previously in our laboratory, which is suitable to calculate the interconnectivity between genes in co-expressed gene network, was applied to extract co-expressed gene modules. The database includes the gene modules for Arabidopsis thaliana (thale cress) and seven crops, Glycine max (soybean), Hordeum vulgare (barley), Oryza sativa (rice), Populus trichocarpa (poplar), Triticum aestivum (wheat), Vitis vinifera (grape) and Zea mays (maize).

Availability: The CoP database is available at: http://webs2.kazusa.or.jp/kagiana/cop0911/

Contact:  shibata@kazusa.or.jp
LOTUS, a new domain associated with small RNA pathways in the germline
Authors: Callebaut Isabelle , Mornon Jean-Paul
Published: March 2010

We describe here LOTUS, a hitherto uncharacterized small globular domain, which was identified using sensitive sequence profile analysis. The LOTUS domain is found in germline-specific proteins that are present in the nuage/polar granules of germ cells. TDRD5 and TDRD7, two mammalian members of the germline Tudor group, possess three copies of the LOTUS domain in their extreme N-termini. The Tudor domains of these proteins bind symmetric dimethyl arginines present on the germ cell-specific Piwi proteins, which form a particular clade of Argonaute proteins. Piwi proteins interact with a specific class of non-coding RNAs [piwi-interacting RNAs (piRNAs)] and play a key role in the repression (silencing) of transposons and possibly other germline-specific functions. A LOTUS domain is also present in the Oskar protein, a critical component of the pole plasm in the Drosophila oocyte, which is required for germ cell formation. LOTUS domains are found in various proteins from metazoans and plants, are often associated with RNA-specific modules and are likely to adopt a winged helix fold. This suggests a germline-specific role in the mRNA localization and/or translation or a specific function toward piRNAs.

Contact:  isabelle.callebaut@impmc.upmc.fr

Supplementary information:  Supplementary data are available at Bioinformatics online.
Advanced heart failure and nocturnal hypoxaemia due to central sleep apnoea are associated with increased serum erythropoietin
Authors: Calvin Andrew D. , Somers Virend K. , Steensma David P. , Rio Perez Jose A. , van der Walt Christelle , Fitz‐Gibbon Jennifer M. , Scott Christopher G. , Olson Lyle J.
Published: March 2010

Aims

Central sleep apnoea (CSA) and increased serum erythropoietin (EPO) concentration have each been associated with adverse prognosis in heart failure (HF) patients. The aim of this study was to examine the relationship between nocturnal hypoxaemia due to CSA and the serum EPO concentration in patients with HF.

Methods and results

Heart failure subjects (n = 33) and healthy controls (n = 18) underwent polysomnography (PSG) for diagnosis of CSA and identification and quantification of hypoxaemia. Blood collection for measurement of EPO was performed immediately post‐PSG. For the analysis, HF subjects were dichotomized into subgroups defined by the presence or absence of CSA and by HF severity. Multivariate analyses were performed to evaluate the relationships of hypoxaemia and advanced HF to EPO concentration. Mean EPO concentration was 62% higher for HF subjects with CSA than for healthy controls (P = 0.004). The magnitude of nocturnal hypoxaemia was significantly and positively related to EPO concentration (r = 0.45, P = 0.02). Advanced HF was also significantly and positively related to EPO concentration (r = 0.43, P = 0.02). On multivariate analysis, the presence of combined nocturnal hypoxaemia and advanced HF yielded greater correlation to EPO concentration than either factor alone (r = 0.57, P = 0.04 and P = 0.05, respectively). Linear regression demonstrated that the combination of New York Heart Association Class and CSA was strongly associated with EPO concentration (P < 0.0001).

Conclusion

In non‐anaemic HF patients, advanced HF and hypoxaemia due to CSA may each be independently associated with increased serum EPO concentration.
Anaemia is associated with shorter leucocyte telomere length in patients with chronic heart failure
Authors: Wong Liza S.M. , Huzen Jardi , van der Harst Pim , de Boer Rudolf A. , Codd Veryan , Daan Westenbrink B. , Benus Germaine F.J.D. , Voors Adriaan A. , van Gilst Wiek H. , Samani Nilesh J. , Jaarsma Tiny , van Veldhuisen Dirk J.
Published: March 2010

Aims

Anaemia is highly prevalent and associated with poor prognosis in patients with chronic heart failure (CHF). Reduced erythroid proliferation capacity of haematopoietic progenitor cells is associated with reduced telomere length, a marker of cellular ageing. We hypothesize that short telomere length contributes to the susceptibility to develop anaemia in patients with CHF.

Methods and results

We studied 875 CHF patients, of whom 254 (29%) fulfilled the WHO criteria of anaemia. Telomere length in DNA from peripheral leucocytes was measured with real‐time quantitative polymerase chain reaction. Age, gender, and baseline differences adjusted telomere length was correlated with haemoglobin levels (partial r = 0.130; P = 0.011). One standard deviation shorter telomere length was associated with an increased risk of having anaemia [odds ratio (OR), 1.31; 95% confidence interval (CI), 1.12–1.53; P = 0.001]. This observation was not affected by adjustment for potential confounders (OR, 1.38; 95% CI, 1.05–1.81; P = 0.021 after adjustment for age, gender, erythropoietin levels, renal function, left ventricular ejection fraction, age of CHF onset, blood pressure, history of stroke, diabetes, and B‐type natriuretic peptide levels).

Conclusion

Shorter telomere length increases the odds of having anaemia in CHF patients. This finding supports the hypothesis that cellular ageing in CHF contributes to the susceptibility to develop anaemia.
Exercise training improves cardiac function in infarcted rabbits: involvement of autophagic function and fatty acid utilization
Authors: Chen Ching‐Yi , Hsu Hsiu‐Ching , Lee Bai‐Chin , Lin Hung‐Ju , Chen Ying‐Hsien , Huang Hui‐Chun , Ho Yi‐Lwun , Chen Ming‐Fong
Published: March 2010

Aims

To explore whether exercise can improve cardiac function in a post‐myocardial infarction (MI) rabbit model and to determine contributing factors in the left ventricle (LV).

Methods and results

Adult male New Zealand White rabbits (2.5–3 kg) underwent MI by ligation of the left anterior descending coronary artery. For 8 weeks after surgery, sham‐operated, and post‐MI rabbits were housed under sedentary conditions or assigned to a 4‐week treadmill exercise protocol at a speed of 1.0 km/h for 30 min 5 days per week, then sacrificed. The non‐infarcted region of the LV was harvested for further analysis. MI decreased left ventricular ejection fraction (LVEF) and increased thiobarbituric acid reactive substances (TBARS) generation in the LV. Exercise improved the cardiac function of MI rabbits. Left ventricular LC3II/LC3I (microtubule‐associated protein light chain 3) in the MI group was 2.1‐fold higher than that of the sham group, exercise significantly decreased LC3II/LC3I in the MI group. MI down‐regulated the expression of heart‐type fatty acid binding protein (h‐FABP), and exercise up‐regulated h‐FABP. In addition, LVEF had a significantly positive correlation with h‐FABP and a negative correlation with LC3II/LC3I.

Conclusion

Exercise induced change in autophagic function and fatty acid utilization may contribute to the improvement in ventricular function in the infarcted heart.