Seismic detection and characterization of landslides and other mass movements

Seismic methods used in the study of snow avalanches may be employed to detect and characterize landslides and other mass movements, using standard spectrogram/sonogram analysis. For snow avalanches, the spectrogram for a station that is approached by a sliding mass exhibits a triangular time/frequency signature due to an increase over time in the higher-frequency constituents. Recognition of this characteristic footprint in a spectrogram suggests a useful metric for identifying other mass-movement events such as landslides. The 1 June 2005 slide at Laguna Beach, California is examined using data obtained from the Caltech/USGS Regional Seismic Network. This event exhibits the same general spectrogram features observed in studies of Alpine snow avalanches. We propose that these features are due to the systematic relative increase in high-frequency energy transmitted to a seismometer in the path of a mass slide owing to a reduction of distance from the source signal. This phenomenon is related to the path of the waves whose high frequencies are less attenuated as they traverse shorter source-receiver paths. Entrainment of material in the course of the slide may also contribute to the triangular time/frequency signature as a consequence of the increase in the energy involved in the process; in this case the contribution would be a source effect. By applying this commonly observed characteristic to routine monitoring algorithms, along with custom adjustments for local site effects, we seek to contribute to the improvement in automatic detection and monitoring methods of landslides and other mass movements.

Detecting and measuring deprivation in primary care: development, validity and reliability of a self-reported questionnaire - the DiPCare-Q

Background: General practitioners play a central role in taking deprivation into consideration when caring for patients in primary care. Validated questions to identify deprivation in primary-care practices are still lacking. For both clinical and research purposes, this study therefore aims to develop and validate a standardized instrument measuring both material and social deprivation at an individual level. Methods: The Deprivation in Primary Care Questionnaire (DiPCare-Q) was developed using qualitative and quantitative approaches between 2008 and 2011. A systematic review identified 199 questions related to deprivation. Using judgmental item quality, these were reduced to 38 questions. Two focus groups (primary-care physicians, and primary-care researchers), structured interviews (10 laymen), and think aloud interviews (eight cleaning staff) assured face validity. Item response theory analysis was then used to derive the DiPCare-Q index using data obtained from a random sample of 200 patients who were to complete the questionnaire a second time over the phone. For construct and criterion validity, the final 16 questions were administered to a random sample of 1,898 patients attending one of 47 different private primary-care practices in western Switzerland (validation set) along with questions on subjective social status (subjective SES ladder), education, source of income, welfare status, and subjective poverty. Results: Deprivation was defined in three distinct dimensions (table); material deprivation (eight items), social deprivation (five items) and health deprivation (three items). Item consistency was high in both the derivation (KR20 = 0.827) and the validation set (KR20 = 0.778). The DiPCare-Q index was reliable (ICC = 0.847). For construct validity, we showed the DiPCare-Q index to be correlated to patients' estimation of their position on the subjective SES ladder (rs = 0.539). This position was correlated to both material and social deprivation independently suggesting two separate mechanisms enhancing the feeling of deprivation. Conclusion: The DiPCare-Q is a rapid, reliable and validated instrument useful for measuring both material and social deprivation in primary care. Questions from the DiPCare-Q are easy to use when investigating patients' social history and could improve clinicians' ability to detect underlying social distress related to deprivation.

Activity of beta-glucosidase and levels of isoflavone glucosides in soybean cultivars affected by the environment

The enzyme beta-glucosidase hydrolyses the isoflavone glucosides developing aglycones, which are compounds with anticancer effects, that are also related with the astringency observed in soybean flavor. Due to the importance of this enzyme, a study was carried out to determine beta-glucosidase activity in soybean (Glycine max (L.) Merrill) cultivars with different contents of isoflavone glucosides (enzyme substrate). The enzyme activity was determined in 51 soybean cultivars sowed in Londrina (latitude 23ºS), in Paraná State, Brazil, and in the cultivar IAS 5 from soybean production regions of different Brazilian states. Among the cultivars, a range of variability of 176.1 to 96.3 units of enzyme activity (cultivars IAC-2 and Embrapa 2, respectively) was observed. A significant variability among cultivars could suggest genetic differences. In the states of Rio Grande do Sul, Paraná and Mato Grosso do Sul, the cultivar IAS 5 presented similar average of beta-glucosidase activity: 132.1, 131.9 and 132.5 units, respectively. Among locations in the states, the cultivar IAS 5 presented a variability for enzyme activity from 138.8 to 124.8 units, which were statistically different. In spite of statistics, the numerical values were not too different to assume that environmental conditions affected enzyme activity. A non-significative correlation for isoflavone glucoside concentrations and enzyme activity was observed among cultivars.

Tire traces: discrimination and classification of pyrolysis-GC/MS profiles

Tire traces can be observed on several crime scenes as vehicles are often used by criminals. The tread abrasion on the road, while braking or skidding, leads to the production of small rubber particles which can be collected for comparison purposes. This research focused on the statistical comparison of Py-GC/MS profiles of tire traces and tire treads. The optimisation of the analytical method was carried out using experimental designs. The aim was to determine the best pyrolysis parameters regarding the repeatability of the results. Thus, the pyrolysis factor effect could also be calculated. The pyrolysis temperature was found to be five time more important than time. Finally, a pyrolysis at 650 °C during 15 s was selected. Ten tires of different manufacturers and models were used for this study. Several samples were collected on each tire, and several replicates were carried out to study the variability within each tire (intravariability). More than eighty compounds were integrated for each analysis and the variability study showed that more than 75% presented a relative standard deviation (RSD) below 5% for the ten tires, thus supporting a low intravariability. The variability between the ten tires (intervariability) presented higher values and the ten most variant compounds had a RSD value above 13%, supporting their high potential of discrimination between the tires tested. Principal Component Analysis (PCA) was able to fully discriminate the ten tires with the help of the first three principal components. The ten tires were finally used to perform braking tests on a racetrack with a vehicle equipped with an anti-lock braking system. The resulting tire traces were adequately collected using sheets of white gelatine. As for tires, the intravariability for the traces was found to be lower than the intervariability. Clustering methods were carried out and the Ward's method based on the squared Euclidean distance was able to correctly group all of the tire traces replicates in the same cluster than the replicates of their corresponding tire. Blind tests on traces were performed and were correctly assigned to their tire source. These results support the hypothesis that the tested tires, of different manufacturers and models, can be discriminated by a statistical comparison of their chemical profiles. The traces were found to be not differentiable from their source but differentiable from all the other tires present in the subset. The results are promising and will be extended on a larger sample set.

Owl pellets as a source of DNA for genetic studies of small mammals.

Owl pellets contain a good skeletal record of the small mammals consumed, and correspond to the undigested portions of prey which are regurgitated. These pellets are easy to find at the roosting site of owls. As it has been demonstrated that amplifiable DNA can be isolated from ancient bone remains, the possibility of using owl pellets as a source of DNA for small mammal genetics studies via the polymerase chain reaction has been investigated. The main uncertainties when isolating DNA from such a material are firstly the possibility that the extracted DNA would be too degraded during the digestion in the stomach of the owl, and secondly that extensive cross-contaminations could occur among the different prey consumed. The results obtained clearly demonstrate that cross-contamination does not occur, and that mitochondrial and nuclear DNA can be amplified using skulls of small mammals found in owl pellets as a source of DNA. The relative efficiency of two methods of DNA extraction is estimated and discussed. Thus, owl pellets represent a non-invasive sampling technique which provides a valuable source of DNA for studying population genetics of small mammals.

Automatic filtering and substantiation of drug safety signals

Drug safety issues pose serious health threats to the population and constitute a major cause of mortality worldwide. Due to the prominent implications to both public health and the pharmaceutical industry, it is of great importance to unravel the molecular mechanisms by which an adverse drug reaction can be potentially elicited. These mechanisms can be investigated by placing the pharmaco-epidemiologically detected adverse drug reaction in an information-rich context and by exploiting all currently available biomedical knowledge to substantiate it. We present a computational framework for the biological annotation of potential adverse drug reactions. First, the proposed framework investigates previous evidences on the drug-event association in the context of biomedical literature (signal filtering). Then, it seeks to provide a biological explanation (signal substantiation) by exploring mechanistic connections that might explain why a drug produces a specific adverse reaction. The mechanistic connections include the activity of the drug, related compounds and drug metabolites on protein targets, the association of protein targets to clinical events, and the annotation of proteins (both protein targets and proteins associated with clinical events) to biological pathways. Hence, the workflows for signal filtering and substantiation integrate modules for literature and database mining, in silico drug-target profiling, and analyses based on gene-disease networks and biological pathways. Application examples of these workflows carried out on selected cases of drug safety signals are discussed. The methodology and workflows presented offer a novel approach to explore the molecular mechanisms underlying adverse drug reactions

The origins and impact of primate segmental duplications

Duplicated sequences are substrates for the emergence of new genes and are an important source of genetic instability associated with rare and common diseases. Analyses of primate genomes have shown an increase in the proportion of interspersed segmental duplications (SDs) within the genomes of humans and great apes. This contrasts with other mammalian genomes that seem to have their recently duplicated sequences organized in a tandem configuration. In this review, we focus on the mechanistic origin and impact of this difference with respect to evolution, genetic diversity and primate phenotype. Although many genomes will be sequenced in the future, resolution of this aspect of genomic architecture still requires high quality sequences and detailed analyses.

Macropropagation and micropropagation of Ziziphus spina-christi

Christ's thorn (Ziziphus spina-christi (L.) Desf.) is a cross-pollinated plant with a wide range of genetic variability in nature and, for this reason, vegetative propagation assumes importance for improvement programs. The objective of this work was to evaluate cutting, T budding and tissue culture methods for this species. Shoots of 22-25 cm length were treated by two culture media and three shoot diameters for cutting trial. The T budding treatments consisted of three and five collection dates in spring and autumn, respectively. Tissue culture nodal segments bearing axillary buds were removed from shoots of mature trees at different seasons. Experiments to determine the best disinfectant chemical, appropriate conditions and materials to prevent phenolic compound exudation, explant characteristics, media type and cytokinin-auxin ratios were carried out. Successful rooting happened only on the sand beds and with cuttings greater than 8 mm diameter. The effects of T budding seasons on budtake percentage were significantly different. The best time for explant harvesting was mid of summer. Amount of rooting on media containing IBA as well as activated charcoal and disinfection with Ca(OCl)2 at concentration of 5% for 20 minutes were the best treatments.

Late Cretaceous to Eocene geology of the South Central American forearc area (southern Costa Rica and western Panama) : initiation and evolution of an intra-oceanic convergent margin

Résumé : L'arc volcanique du sud de l'Amérique Centrale se situe sur la marge SW de la Plaque Caraïbe, au-dessus des plaques subduites de Cocos et Nazca. Il s'agit de l'un des arcs intra-océaniques les plus étudiés au monde, qui est généralement considéré comme s'étant développé à la fin du Crétacé le long d'un plateau océanique (le Plateau Caraïbe ou CLIP) et se trouvant actuellement dans un régime de subduction érosive. Au cours des dernières décennies, des efforts particuliers ont été faits pour comprendre les processus liés à la subduction sur la base d'études géophysiques et géochimiques. Au sud du Costa Rica et à l'ouest du Panama, des complexes d'accrétions et structures à la base de l'arc volcanique ont été exposés grâce à la subduction de rides asismiques et de failles transformantes. Des affleurements, situés jusqu'à seulement 15 km de la fosse, offrent une possibilité unique de mieux comprendre quelques uns des processus ayant lieu le long de la zone de subduction. Nous présentons de nouvelles contraintes sur l'origine de ces affleurements en alliant une étude de terrain poussée, de nouvelles données géochimiques, sédimentaires et paléontologiques, ainsi que des observations structurales effectuées en télédétection. Une nouvelle stratigraphie tectonique entre le Campanien et l'Éocène est définie pour la région d'avant-arc située entre la Péninsule d'Osa (Costa Rica) et la Péninsule d'Azuero (Panama). Nos résultats montrent que la partie externe de la marge est composée d'un arrangement complexe de roches ignées et de séquences sédimentaires de recouvrement qui comprennent principalement le socle de l'arc, des roches d'arc primitif, des fragments de monts sous-marins accrétés et des mélanges d'accrétion. Des preuves sont données pour le développement de l'arc volcanique du sud de l'Amérique Centrale sur un plateau océanique. Le début de la subduction le long de la marge SW de la Plaque Caraïbe a eu lieu au Campanien et a généré des roches d'arc primitif caractérisées par des affinités géochimiques particulières, globalement intermédiaires entre des affinités de plateau et d'arc insulaire. L'arc était mature au Maastrichtien et formait un isthme essentiellement continu entre l'Amérique du Nord et l'Amérique du Sud. Ceci a permis la migration de faunes terrestres entre les Amériques et pourrait avoir contribué à la crise fin Crétacé -Tertiaire en réduisant les courants océaniques subéquatoriaux entre le Pacifique et l'Atlantique. Plusieurs unités composées de fragments de monts sous-marins accrétés sont définies. La nature et l'arrangement structural de ces unités définissent de nouvelles contraintes sur les modes d'accrétion des monts sous-marins/îles océaniques et sur l'évolution de la marge depuis la formation de la zone de subduction. Entre la fin du Crétacé et l'Éocène moyen, la marge a enregistré plusieurs épisodes ponctuels d'accrétion de monts sous-marins alternant avec de la subduction érosive. A l'Éocène moyen, un événement tectonique régional pourrait avoir causé un fort couplage entre les plaques supérieure et inférieure, menant à des taux plus important d'accrétion de monts sous-marins. Durant cette période, la situation le long de la marge était très semblable à la situation actuelle et caractérisée par la présence de monts sous-marins subductants et l'absence d'accrétion de sédiments. L'enregistrement géologique montre qu'il n'est pas possible d'attribuer une nature érosive ou accrétionnaire à la marge dans le passé ou -par analogie- aujourd'hui, parce que (1) les processus d'accrétion et érosifs varient fortement spatialement et temporellement et (2) il est impossible d'évaluer la quantité exacte de matériel tectoniquement enlevé à la marge depuis le début de la subduction. Au sud du Costa Rica, certains fragments de monts sous-marins accrétés sont représentatifs d'une interaction entre une ride et un point chaud dans le Pacifique au Crétacé terminal/Paléocène. L'existence de ces fragments de monts sous-marins et la morphologie du fond de l'Océan Pacifique indiquent que la formation de la ride de Cocos-Nazca s'est formée au moins ~40 Ma avant l'âge proposé par les modèles tectoniques actuels. Au Panama, nous avons identifié une île océanique d'âge début Éocène qui a été accrétée à l'Éocène moyen. L'accrétion a eu lieu à très faible profondeur par détachement de l'île dans la fosse, et a mené à une exceptionnelle préservation des structures volcaniques. Des affleurement comprenant aussi bien des parties basses et hautes de l'édifice volcanique on été étudiées, depuis la phase sous-marine bouclier jusqu'à la phase subaérienne post-bouclier. La stratigraphie nous a permis de différencier les laves de la phase sous-marine de celles de la phase subaérienne. La composition des laves indique une diminution progressive de l'intensité de la fusion partielle de la source et une diminution de la température des laves produites durant les derniers stades de l'activité volcanique. Nous interprétons ces changements comme étant liés à l'éloignement progressif de l'île océanique de la zone de fusion ou point chaud. Abstract The southern Central American volcanic front lies on the SW edge of the Caribbean Plate, inboard of the subducting Cocos and Nazca Plates. It is one of the most studied intra-oceanic convergent margins around the world, which is generally interpreted to have developed in the late Cretaceous along an oceanic plateau (the Caribbean Large Igneous Province or CLIP) and to be currently undergoing a regime of subduction erosion. In the last decades a particular effort has been made to understand subduction-related processes on the basis of geophysical and geochemical studies. In southern Costa Rica and western Panama accretionary complexes and structures at the base of the volcanic front have been exposed in response to subduction of aseismic ridges and transforms. Onland exposures are located as close as to 15 km from the trench and provide a unique opportunity to better understand some of the processes occurring along the subduction zone. We provide new constraints on the origins of these exposures by integrating a comprehensive field work, new geochemical, sedimentary and paleontological data, as well as structural observations based on remote imaging. A new Campanian to Eocene tectonostratigraphy is defined for the forearc area located between the Osa Peninsula (Costa Rica) and the Azuero Peninsula (Panama). Our results show that the outer margin is composed of a complicated arrangement of igneous complexes and overlapping sedimentary sequences that essentially comprise an arc basement, primitive island-arc rocks, accreted seamount fragments and accretionary mélanges. Evidences are provided for the development of the southern Central American arc on the top an oceanic plateau. The subduction initiation along the SW edge of the Caribbean Plate occurred in the Campanian and led to formation of primitive island-arc rocks characterized by unusual geochemical affinities broadly intermediate between plateau and arc affinities. The arc was mature in the Maastrichtian and was forming a predominantly continuous landbridge between the North and South Americas. This allowed migration of terrestrial fauna between the Americas and may have contributed to the Cretaceous-Tertiary crisis by limiting trans-equatorial oceanic currents between the Pacific and the Atlantic. Several units composed of accreted seamount fragments are defined. The nature of the units and their structural arrangement provide new constraints on the modes of accretion of seamounts/oceanic islands and on the evolution of the margin since subduction initiation. Between the late Cretaceous and the middle Eocene, the margin recorded several local episodes of seamount accretion alternating with tectonic erosion. In the middle Eocene a regional tectonic event may have triggered strong coupling between the overriding and subducting plates, leading to higher rates of seamount accretion. During this period the situation along the margin was very similar to the present and characterized by subducting seamounts and absence of sediment accretion. The geological record shows that it is not possible to ascribe an overall erosive or accretionary nature to the margin in the past and, by analogy, today, because (1) accretionary and erosive processes exhibit significant lateral and temporal variations and (2) it is impossible to estimate the exact amount of material tectonically eroded from the margin since subduction initiation. In southern Costa Rica, accreted seamount fragments point toward a plume-ridge interaction in the Pacific in the late Cretaceous/Paleocene. This occurrence of accreted seamount fragments and morphology of the Pacific Ocean floor is indicative of the formation of the Cocos-Nazca spreading system at least ~40 Ma prior to the age proposed in current tectonic models. In Panama, we identified a remarkably-well preserved early Eocene oceanic island that accreted in the middle Eocene. The accretion probably occurred at very shallow depth by detachment of the island in the trench and led to an exceptional preservation of the volcanic structures. Exposures of both deep and superficial parts of the volcanic edifice have been studied, from the submarine-shield to subaerial-postshield stages. The stratigraphy allowed us to distinguish lavas produced during the submarine and subaerial stages. The lava compositions likely define a progressive diminution of source melting and a decrease in the temperature of erupted melts in the latest stages of volcanic activity. We interpret these changes to primarily reflect the progressive migration of the oceanic island out of the melting region or hotspot.

Determination and Evaluation of Alternate Methods for Managing and Controlling Highway-Related Dust, TR-449, 2002

Road dust is caused by wind entraining fine material from the roadway surface and the main source of Iowa road dust is attrition of carbonate rock used as aggregate. The mechanisms of dust suppression can be considered as two processes: increasing particle size of the surface fines by agglomeration and inhibiting degradation of the coarse material. Agglomeration may occur by capillary tension in the pore water, surfactants that increase bonding between clay particles, and cements that bind the mineral matter together. Hygroscopic dust suppressants such as calcium chloride have short durations of effectiveness because capillary tension is the primary agglomeration mechanism. Somewhat more permanent methods of agglomeration result from chemicals that cement smaller particles into a mat or larger particles. The cements include lignosulfonates, resins, and asphalt products. The duration of the cements depend on their solubility and the climate. The only dust palliative that decreases aggregate degradation is shredded shingles that act as cushions between aggregate particles. It is likely that synthetic polymers also provide some protection against coarse aggregate attrition. Calcium chloride and lignosulfonates are widely used in Iowa. Both palliatives have a useful duration of about 6 months. Calcium chloride is effective with surface soils of moderate fine content and plasticity whereas lignin works best with materials that have high fine content and high plasticity indices. Bentonite appears to be effective for up to two years and works well with surface materials having low fines and plasticity and works well with limestone aggregate. Selection of appropriate dust suppressants should be based on characterization of the road surface material. Estimation of dosage rates for potential palliatives can be based on data from this report, from technical reports, information from reliable vendors, or laboratory screening tests. The selection should include economic analysis of construction and maintenance costs. The effectiveness of the treatment should be evaluated by any of the field performance measuring techniques discussed in this report. Novel dust control agents that need research for potential application in Iowa include; acidulated soybean oil (soapstock), soybean oil, ground up asphalt shingles, and foamed asphalt. New laboratory evaluation protocols to screen additives for potential effectiveness and determine dosage are needed. A modification of ASTM D 560 to estimate the freeze-thaw and wet-dry durability of Portland cement stabilized soils would be a starting point for improved laboratory testing of dust palliatives.

Two cases of interferon-alpha-induced sarcoidosis koebnerized along venous drainage lines : new pathogenic insights and review of the literature of interferon-induced sarcoidosis

La sarcoïdose est une affection inflammatoire granuiomateuse systémique d'origine inconnue touchant le plus fréquemment les poumons, le système lymphoïde, le foie, les yeux et la peau. Dans cet article, nous rapportons deux cas de sarcoïdose cutanée touchant les avant-bras de deux patients anciens toxicomanes traités par interféron-a et ribavirine pour une hépatite C chronique. Nous procédons à une revue de la littérature de la sarcoïdose induite par l'interféron et élaborons une nouvelle hypothèse pathogénique de l'effet Koebner dans la sarcoïdose cutanée. Dans le cas des deux patients que nous décrivons, la distribution des lésions cutanées coïncide avec les anciens sites d'injection d'héroïne le long des trajets veineux des deux avant- bras. Cette distribution unique de l'atteinte cutanée suggère que les dommages tissulaires induits par la répétition d'injections percutanées puissent représenter un terrain favorisant au développement local d'une sarcoïdose cutanée. Fait intéressant, il a été récemment démontré que les cellules dendritiques plasmacytoïdes - sous-type de cellules dendritiques généralement absent de la peau - infiltrent rapidement les sites de peau lésée. Ces cellules sont la source d'une production endogène d'interféron-a, cytokine connue pour promouvoir le processus de cicatrisation, mais également pour favoriser le développement de sarcoïdose chez des individus prédisposés. Ainsi, nous postulons que les lésions de sarcoïdose cutanée limitées le long des trajets veineux - sites préalables d'injection percutanée de drogues - peuvent résulter d'une expression locale supplémentaire d'interféron-a. Celle-ci serait en outre favorisée par le traitement de ribavirine dans le cadre de l'hépatite C, connu pour renforcer la production endogène d'interféron-a. L'identification de nombreuses cellules dendritiques plasmacytoïdes circonscrivant l'inflammation granuiomateuse sur la biopsie cutanée de l'un de nos patients semble être un argument dans ce sens, conforté par l'absence de corps étranger détecté en microscopie par lumière polarisée. Cette observation semble pouvoir représenter un point crucial dans la compréhension des mécanismes physiopathologiques à la base de l'infiltration des cicatrices cutanées par la sarcoïdose. Des investigations supplémentaires doivent encore être effectuées afin de confirmer cette hypothèse.

Dietary n-6- or n-3-rich vegetable fats and antioxidants: effects on fatty acid composition and stability of rabbit plasma, liver and meat

We supplemented diets with a-tocopheryl acetate (100 mg/kg) and replaced beef tallow (BT) in feeds with increasing doses of n-6- or n-3-rich vegetable fat sources (linseed and sunflower oil), and studied the effects on the fatty acid (FA) composition, the a-tocopherol (aT) content and the oxidative stability of rabbit plasma and liver. These effects were compared with those observed in a previous study in rabbit meat. As in meat, the content of saturated, monounsaturated and trans FA in plasma and liver mainly reflected feed FA profile, except stearic acid in liver, which increased as feeds contained higher doses of vegetable fat, which could be related to an inhibition of the activity of the stearoyl-CoA-desaturase. As linseed oil increased in feeds, the n-6/n-3 FA ratio was decreased in plasma and liver as a result of the incorporation of FA from diets and also, due to the different performance and selectivity of desaturase enzymes. However, an increase in the dose of vegetable fat in feeds led to a significant reduction in the aT content of plasma and liver, which was greater when the fat source was linseed oil. Increasing the dose of vegetable fat in feeds also led to an increase in the susceptibility to oxidation (lipid hydroperoxide (LHP) value) of rabbit plasma, liver and meat and on the thiobarbituric acid (TBA) values of meat. Although the dietary supplementation with a-tocopheryl acetate increased the aT content in plasma and liver, it did not modify significantly their TBA or LHP values. In meat however, both TBA and LHP values were reduced by the dietary supplementation with a-tocopheryl acetate. The plasma aT content reflected the aT content in tissues, and correlated negatively with tissue oxidability. From the studied diets, those containing 1.5% linseed oil plus 1.5% BT and 100 mg of a-tocopheryl acetate/kg most improved the FA composition and the oxidative stability of rabbit tissues.

N-myc controls proliferation, morphogenesis, and patterning of the inner ear

Myc family members play crucial roles in regulating cell proliferation, size, and differentiation during organogenesis. Both N-myc and c-myc are expressed throughout inner ear development. To address their function in the mouse inner ear, we generated mice with conditional deletions in either N-myc or c-myc. Loss of c-myc in the inner ear causes no apparent defects, whereas inactivation of N-myc results in reduced growth caused by a lack of proliferation. Reciprocally, the misexpression of N-myc in the inner ear increases proliferation. Morphogenesis of the inner ear in N-myc mouse mutants is severely disturbed, including loss of the lateral canal, fusion of the cochlea with the sacculus and utriculus, and stunted outgrowth of the cochlea. Mutant cochleas are characterized by an increased number of cells exiting the cell cycle that express the cyclin-dependent kinase inhibitor p27Kip1 and lack cyclin D1, both of which control the postmitotic state of hair cells. Analysis of different molecular markers in N-myc mutant ears reveals the development of a rudimentary organ of Corti containing hair cells and the underlying supporting cells. Differentiated cells, however, fail to form the highly ordered structure characteristic for the organ of Corti but appear as rows or clusters with an excess number of hair cells. The Kölliker's organ, a transient structure neighboring the organ of Corti and a potential source of ectopic hair cells, is absent in the mutant ears. Collectively, our data suggest that N-myc regulates growth, morphogenesis, and pattern formation during the development of the inner ear.

Body mass index and risk of head and neck cancer in a pooled analysis of case-control studies in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium.

BACKGROUND: Head and neck cancer (HNC) risk is elevated among lean people and reduced among overweight or obese people in some studies; however, it is unknown whether these associations differ for certain subgroups or are influenced by residual confounding from the effects of alcohol and tobacco use or by other sources of biases. METHODS: We pooled data from 17 case-control studies including 12 716 cases and the 17 438 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between body mass index (BMI) at different ages and HNC risk, adjusted for age, sex, centre, race, education, tobacco smoking and alcohol consumption. RESULTS: Adjusted ORs (95% CIs) were elevated for people with BMI at reference (date of diagnosis for cases and date of selection for controls) 25.0-30.0 kg/m(2) (0.52, 0.44-0.60) and BMI >/=30 kg/m(2) (0.43, 0.33-0.57), compared with BMI >18.5-25.0 kg/m(2). These associations did not differ by age, sex, tumour site or control source. Although the increased risk among people with BMI 25 kg/m(2) was present only in smokers and drinkers. CONCLUSIONS: In our large pooled analysis, leanness was associated with increased HNC risk regardless of smoking and drinking status, although reverse causality cannot be excluded. The reduced risk among overweight or obese people may indicate body size is a modifier of the risk associated with smoking and drinking. Further clarification may be provided by analyses of prospective cohort and mechanistic studies.

Bone marrow-derived cells are implicated as a source of lymphatic endothelial progenitors in human breast cancer.

Bone marrow-derived endothelial progenitor cells (EPCs) infiltrate into sites of neovascularization in adult tissues and mature into functional blood endothelial cells (BECs) during a process called vasculogenesis. Human marrow-derived EPCs have recently been reported to display a mixed myeloid and lymphatic endothelial cell (LEC) phenotype during inflammation-induced angiogenesis; however, their role in cancer remains poorly understood. We report the in vitro differentiation of human cord blood CD133(+)CD34(+) progenitors into podoplanin(+) cells expressing both myeloid markers (CD11b, CD14) and the canonical LEC markers vascular endothelium growth factor receptor 3 (VEGFR-3), lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), and prospero homeobox 1 (PROX-1). These podoplanin(+) cells displayed sprouting behavior comparable to that of LECs in vitro and a dual hemangiogenic and lymphangiogenic activity in vivo in an endothelial cell sprouting assay and corneal vascularization assay, respectively. Furthermore, these cells expressed vascular endothelium growth factor (VEGF) family members A, -C, and -D. Thus, bone-marrow derived EPCs stimulate hemangiogenesis and lymphangiogenesis through their ability to differentiate into LECs and to produce angiogenic factors. Importantly, plasma from patients with breast cancer induced differentiation of CD34(+) cord blood progenitors into hemangiogenic and lymphangiogenic CD11b(+) myeloid cells, whereas plasma from healthy women did not have this effect. Consistent with these findings, circulating CD11b(+) cells from breast cancer patients, but not from healthy women, displayed a similar dual angiogenic activity. Taken together, our results show that marrow-derived EPCs become hemangiogenic and lymphangiogenic upon exposure to cancer plasma. These newly identified functions of bone-marrow derived EPCs are expected to influence the diagnosis and treatment of breast cancer.