Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Les Glyceraldehyde-3-phosphate deshydrogenases de deux bactéries : Clostridium pasteurianum et bacillus stearothermophilus : séquence de leur gène et expression chez escherichia coli : étude phylogénétique de la glyceraldehyde-3-phosphate deshydrogénase

Non disponible / Not availableClonage et séquençage des gènes codant pour la glycéraldéhyde-3-phosphate déshydrogénase de clostridium pasteurianum et de bacillus stearothermophilus. Etude des signaux de régulation de la transcription et de la traduction de ces gènes. Expression de ces gènes dans Escherichia coli. Etude phylogénétique de cette enzyme par comparaison avec 20 structures primaires connues

Validation fonctionnelle d'approches nutritionnelles à allégation "Bien veillir", capables de prévenir le vieillissement cérébral et les maladies neurodégénératives

La maladie d'Alzheimer (MA) est une démence neurodégénérative caractérisée par des pertes de la mémoire et des troubles cognitifs. La toxicité des oligomères solubles du peptide [bêta]-amyloïde (A[bêta]Os) est centrale dans la phase précoce de la maladie. L'absence de traitements curatifs, l'aspect chronique des mécanismes pathogéniques et le partage de facteurs de risque communs avec les pathologies cardiovasculaires, notamment les paramètres alimentaires et le métabolisme lipidique, doivent inciter à considérer l'intérêt de méthodes préventives permettant d'empêcher l'apparition de la maladie. Dès lors, l'approche nutritionnelle apparaît comme une stratégie capable de limiter sa prévalence. Une souris modèle des stades précoces de MA nous a permit d'évaluer le potentiel préventif d'une alimentation enrichie en acide docosahexaénoïque (DHA, C22:6, n-3). Les résultats obtenus montrent qu'un apport alimentaire suffisant en DHA conduit à en enrichir les membranes dans les différentes structures cérébrales. En conséquence, les fonctions synaptiques sont préservées, même après exposition aigüe aux A[bêta]Os, ce qui maintient les capacités cognitives des souris exposées. Nous avons ensuite développé des stratégies nutritionnelles permettant d'évaluer les effets bénéfiques de DHA contre la dyslipidémie induite par l'alimentation et les déficits cognitifs associés au vieillissement normal ou pathologique. Les résultats obtenus à l'issue de notre étude révèlent qu'un apport alimentaire en DHA est capable de prévenir la dyslipidémie provoquée par un régime riche en lipides et de retarder le déclin cognitif lié au vieillissement cérébral normal ou pathologiqueAlzheimer's disease is a neurodegenerative aging-related dementia that is characterized by loss of memory and cognitive disorders. Toxicity of soluble oligomers of [beta]-amyloid peptide (sOA[beta]) is a key element in early stages of the disease. Absence of curative therapies, chronic aspects of the pathogenic mechanisms implicated and influence of common risk factors shared with the cardiovascular diseases, including dietary parameters and lipid metabolism, should widely encourage considering the interest of preventive interventions allowing slowing the progression and delaying the clinical onset of Alzheimer's-related troubles. Therefore, nutritional approaches could appear as a strategy able to reduce the prevalence of this disease. Early Alzheimer's mouse model allowed us to assess the preventive potential of diets supplemented in docosahexaenoic acid (DHA, C22:6 n-3). Our results show that adequate dietary intake of DHA lead to increased levels in different brain structures. Consequently, hippocampal and cortical synaptic functions were preserved, even upon acute exposure to A[beta] oligomers, maintaining or improving the cognitive capacities of A[beta]-exposed mice. These improvements were positively correlated with DHA-enrichment associated in hippocampus and with preserved synaptic integrity. We also designed nutritional strategies in order to evaluate the beneficial effects of DHA on diet-induced dyslipidemia as well as on cognitive impairment and neurodegenerative processes associated with normal or pathologic aging. Our results show that dietary DHA can prevent high-fat diet-induced dyslipidemia and delay cognitive decline related with normal or pathological agingMETZ-SCD (574632105) / SudocNANCY1-Bib. numérique (543959902) / SudocNANCY2-Bibliotheque electronique (543959901) / SudocNANCY-INPL-Bib. électronique (545479901) / SudocSudocFranceF

Etude épidémiologique et moléculaire des voies métaboliques associées au glutathion dans le cancer du sein

NANCY1-SCD Medecine (545472101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Les enzymes de biotransformation des xénobiotiques chez Helix aspersa (escargot) et Pleurozium schreberi (mousse) (biomarqueurs potentiels de la pollution atmosphérique par des hydrocarbures aromatiques polycycliques)

L'objectif de ce travail était d'apprécier la valeur potentielle, en tant que biomarqueurs de la pollution atmosphérique par les hydrocarbures aromatiques polycycliques (HAP), des activités enzymatiques de phase I (7-éthoxyrésorufineO-dééthylase, EROD et 7-éthoxycoumarineO-dééthylase, ECOD) et associées au glutathion (glutathion S-transférases, GST avec le 1-chloro-2,4-dinitrobenzène et le 4-nitroquinoline-1-oxyde comme substrats, la glutathion réductase et les glutathion peroxydases) dans trois organes d'un escargot (Helix aspersa), mais également des activités associées au glutathion et antioxydantes (ascorbate peroxydase et catalase) chez une mousse (Pleurozium schreberi). Dans un premier temps, H. aspersa et P. schreberi ont été exposés durant 3 jours à une ambiance saturée en naphtalène. Alors que les paramètres biochimiques explorés chez P. schreberi n'ont pas été variées, une réponse organo-spécifique a été observée chez H. aspersa. Chez ce dernier les activités EROD et ECOD n'ont pas été modifiées dans le toit de la cavité palléale (TCP) alors qu'elles ont été diminuées dans le rein (R) et augmentées dans la glande digestive (GD). Dans une seconde phase, ces organismes ont été exposés 8 heures à une atmosphère de travail chargée principalement en HAP. Chez P. schreberi, aucune modification des activités enzymatiques n'a été mesurée. A l'inverse, une réponse non dose-dépendante a été observée chez H. aspersa. Si les activités EROD et ECOD ont été augmentées dans ses trois organes, les activités GST mesurées avec le chloro-dinitrobenzène comme substrat l'ont été uniquement dans la GD. La dernière étape, les organismes ont été implantées plusieurs semaines sur différents sites urbains. Dans la GD, les activités GST mesurées avec les deux substrats ont été corrélées positivement aux oxydes d'azote. Ces dernières, ainsi que les activités CYP dans le rein paraissent prometteuses pour une utilisation en tant que biomarqueurs de la pollution atmosphérique par les HAP.[Résumé anglais]METZ-SCD (574632105) / SudocSudocFranceF

Regulation of the expression of hepatic lipolysis stimulated lipoprotein receptor (roles of docosahexaenoic acid and peroxisome proliferator-activated receptor alpha)

Le récepteur LSR est un acteur important du métabolisme hépatique, puisqu'il joue un rôle dans la clairance des lipoprotéines à ApoB/ApoE riches en triglycérides durant la période postprandiale. Dans cette étude, nous avons montré qu'un traitement in vitro par DHA peut augmenter les niveaux de protéine et d'activité LSR dans les cellules d'hépatome de souris Hepa 1-6. En toute cohérence, un régime supplémenté en DHA a conduit à élever les niveaux de protéine LSR hépatique chez la souris. Mais aucune de ces deux études n'a montré de changement au niveau des ARNm. Ceci suggère que l'enrichissement en DHA influe positivement sur le microenvironnement de LSR et son ancrage à la surface de la cellule. Nous avons ensuite étudié le rôle du récepteur PPAR[alpha] dans la régulation du gène lsr. Une analyse in silico nous a permis d'identifier des éléments PPRE dans la région 5' régulatrice du gène humain et de ses homologues de souris et de rat. Des traitements pharmacologiques par des agoniste et antagoniste spécifiques de PPAR[alpha] ont montré que ce récepteur est impliqué dans la régulation transcriptionnelle de l'expression du LSR dans les cellules Hepa 1 6. Enfin, une analyse transcriptomique a révélé une diminution de l'expression de PPAR[alpha] et d'autres gènes impliqués dans le métabolisme lipidique hépatique chez la souris LSR+/- sous régime standard ou riche en graisses. En conclusion, toutes ces études indiquent que l'activité LSR hépatique est sous le contrôle de facteurs nutritionnels capables d'activer divers mécanismes de régulation, faisant du LSR une cible d'intérêt potentiel pour des stratégies nutritionnelles ou thérapeutiques destinées à prévenir ou traiter les dyslipidémiesLipolysis stimulated lipoprotein receptor (LSR) plays an important role in the clearance of ApoB/ApoE containing triglyceride-rich lipoproteins during postprandial phase. In this study, we demonstrated that in vitro treatment of mouse hepatoma cells, Hepa 1-6, with docosahexaenoic acid (DHA) led to an increase in LSR protein levels as well as its activity. Furthermore, the mice placed on the diet supplemented with DHA showed an increase in hepatic LSR protein. However, the mRNA levels remained unchanged in both in vitro and in vivo studies, suggesting that DHA enrichment may result in changes in LSR microenvironment that could affect its anchorage at the surface of cell membrane. Specific peroxisome proliferator response elements were identified in the upstream region of human, mouse and rat lsr gene by in silico analysis. We therefore sought to determine the role of the transcription factor, peroxisome proliferator-activated receptor (PPAR[alpha]), in LSR regulation. In vitro pharmacological studies using PPAR[alpha]-selective agonist and antagonist agents demonstrated that PPAR[alpha] is indeed involved in the transcriptional regulation of LSR expression. Furthermore, qPCR array analysis revealed the downregulation of PPAR[alpha] and various genes involved in hepatic lipid metabolism in LSR+/- mice on standard and high-fat diets. In conclusion, these studies show that the hepatic LSR activity is controlled by dietary factors that can activate various pathways involved in regulating lipid homeostasis, therefore representing LSR as a potential target for either nutritional or therapeutic strategies towards the prevention or treatment of dyslipidemiaNANCY-INPL-Bib. électronique (545479901) / SudocSudocFranceF

Neuroprotective effects of DHA in Alzheimer’s disease models

Alzheimer’s disease (AD) is a major public health concern in all developped countries. Although the precise cause of AD is still unknown, a growing body of evidence supports the notion that soluble oligomers of amyloid b-peptide (Aβ) may be the proximate effectors of synaptic injuries and neuronal death in the early stages of AD. AD patients display lower levels of docosahexaenoic acid (DHA, C22:6; n-3) in plasma and brain tissues as compared to control subjects of same age. Furthermore, epidemiological studies suggest that high DHA intake might have protective properties against neurodegenerative diseases. These observations are supported by in vivo studies showing that DHA-rich diets limit the synaptic loss and cognitive defects induced by Aβ peptide. Although the molecular basis underlying these neuroprotective effects remains unknown, several mechanisms have been proposed such as (i) regulation of the expression of potentially protective genes, (ii) activation of antiinflammatory pathways, (iii) modulation of functional properties of the synaptic membranes along with changes in their physicochemical and structural features. We recently demonstrated that DHA protects neurons from soluble Aβ oligomer-induced apoptosis. Indeed, DHA pretreatment was observed to significantly increase neuronal survival upon Aβ treatment by preventing cytoskeleton perturbations, caspase activation and apoptosis, as well as by promoting ERK-related survival pathways. These data suggest that DHA enrichment most likely induces changes in neuronal membrane properties with functional outcomes, thereby increasing protection from soluble Aβ oligomers. Such neuroprotective effects could be of major interest in the prevention of AD and other neurodegenerative diseases

Neuroprotective effects of DHA in Alzheimer’s disease models

Alzheimer’s disease (AD) is a major public health concern in all developped countries. Although the precise cause of AD is still unknown, a growing body of evidence supports the notion that soluble oligomers of amyloid b-peptide (Aβ) may be the proximate effectors of synaptic injuries and neuronal death in the early stages of AD. AD patients display lower levels of docosahexaenoic acid (DHA, C22:6; n-3) in plasma and brain tissues as compared to control subjects of same age. Furthermore, epidemiological studies suggest that high DHA intake might have protective properties against neurodegenerative diseases. These observations are supported by in vivo studies showing that DHA-rich diets limit the synaptic loss and cognitive defects induced by Aβ peptide. Although the molecular basis underlying these neuroprotective effects remains unknown, several mechanisms have been proposed such as (i) regulation of the expression of potentially protective genes, (ii) activation of antiinflammatory pathways, (iii) modulation of functional properties of the synaptic membranes along with changes in their physicochemical and structural features. We recently demonstrated that DHA protects neurons from soluble Aβ oligomer-induced apoptosis. Indeed, DHA pretreatment was observed to significantly increase neuronal survival upon Aβ treatment by preventing cytoskeleton perturbations, caspase activation and apoptosis, as well as by promoting ERK-related survival pathways. These data suggest that DHA enrichment most likely induces changes in neuronal membrane properties with functional outcomes, thereby increasing protection from soluble Aβ oligomers. Such neuroprotective effects could be of major interest in the prevention of AD and other neurodegenerative diseases

Neuroprotective effects of DHA in Alzheimer’s disease models

Alzheimer’s disease (AD) is a major public health concern in all developped countries. Although the precise cause of AD is still unknown, a growing body of evidence supports the notion that soluble oligomers of amyloid b-peptide (Aβ) may be the proximate effectors of synaptic injuries and neuronal death in the early stages of AD. AD patients display lower levels of docosahexaenoic acid (DHA, C22:6; n-3) in plasma and brain tissues as compared to control subjects of same age. Furthermore, epidemiological studies suggest that high DHA intake might have protective properties against neurodegenerative diseases. These observations are supported by in vivo studies showing that DHA-rich diets limit the synaptic loss and cognitive defects induced by Aβ peptide. Although the molecular basis underlying these neuroprotective effects remains unknown, several mechanisms have been proposed such as (i) regulation of the expression of potentially protective genes, (ii) activation of antiinflammatory pathways, (iii) modulation of functional properties of the synaptic membranes along with changes in their physicochemical and structural features. We recently demonstrated that DHA protects neurons from soluble Aβ oligomer-induced apoptosis. Indeed, DHA pretreatment was observed to significantly increase neuronal survival upon Aβ treatment by preventing cytoskeleton perturbations, caspase activation and apoptosis, as well as by promoting ERK-related survival pathways. These data suggest that DHA enrichment most likely induces changes in neuronal membrane properties with functional outcomes, thereby increasing protection from soluble Aβ oligomers. Such neuroprotective effects could be of major interest in the prevention of AD and other neurodegenerative diseases

Acide docosahexaénoïque et maladie d’Alzheimer : des raisons d’espérer ?

Alzheimer’s disease is a major public health concern in all developped countries. Although the precise cause of Alzheimer’s disease is still unknown, soluble oligomers of the neurotoxic hydrophobic amyloid-β (Aβ) peptide are known to play a critical role. Aging is associated with a loss of docosahexaenoic acid (DHA) in brain tissues in which it is the main polyunsaturated fatty acid. Epidemiological studies on human populations suggested that diets enriched in ω3 fatty acids are associated with reduced risk of Alzheimer’s disease. Furthermore, patients affected by Alzheimer’s disease display lower levels of DHA in plasma and brain tissues as compared to control subjects of same age. Studies on animals showed that diets enriched with DHA limit the synaptic loss and cognitive defects induced by the Aβ peptide. Several mechanisms have been proposed for this protective effects. DHA can induce the expression of potentially protective genes. Conversion of DHA into neuroprotectins has been shown to be alternatively involved in the protection against the Aβ peptide. Eventually, results have been provided suggesting that particular membrane microdomains could be remodelled and subsequently be involved in the neuroprotective process induced by DHA