Sample records for developmental instability di
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ERIC Educational Resources Information Center
Thoma, Robert J.; Yeo, Ronald A.; Gangestad, Steven W.; Halgren, Eric; Sanchez, Natalie M.; Lewine, Jeffrey D.
2005-01-01
Measures of developmental instability (DI) reflect developmental disruptions due to genetic and environmental perturbations during normal development. DI might be expected to influence the developmental course of brain development and hence intelligence, and several studies indicate this to be the case. The factors that mediate this relationship…
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Hoover, Kara C; Matsumura, Hirofumi
2008-12-01
We examined nutritional and developmental instability in prehistoric Japan, using data from 49 individuals across 13 archaeological sites. Hypoplasia incidence was used as a measure of nutritional stress, and fluctuating asymmetry (of upper facial breath, orbital breadth, and orbital height) as an indirect assessment of developmental instability. Abundant resources due to a stable climate during the Middle Jomon (5,000-3,000 BP) encouraged population growth, which led to regional cultural homogeneity and complexity. A population crash on Honshu in the Late/Final Jomon (roughly 4,000-2,000 BP) led to regionally divergent subsistence economies and settlement patterns. We find that the nutritional stress was consistent between periods, but developmental instability (DI) decreased in the Late/Final Jomon. While the DI values were not statistically significant, the higher values for Middle Jomon may result from sedentism, social stratification, and differential access to resources. On Hokkaido, Jomon culture persisted until the Okhotsk period (1,000-600 BP), marked by the arrival of immigrants from Sakhalin. Nutritional stress was consistent between Middle and Late/Final Jomon, but DI increased in the Late/Final. Nutritional and developmental instability decreased from Late/Final to Okhotsk, suggesting a positive immigrant effect. We expected to find an association between stress markers due to the synergistic relationship between nutrition and pathology. The data support this hypothesis, but only one finding was statistically significant. While high critical values from small sample sizes place limits on the significance of our results, we find that the impact of environmental and cultural change to prehistoric Japanese populations was minimal. (c) 2008 Wiley-Liss, Inc.
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Alados, C.L.; Escos, J.; Emlen, J.M.
1994-01-01
Developmental lnstability (DI) has been proposed as an inexpensive, quickly applied, and sensitive indicator of stress that can be utilized in early warning and in monitoring anthropogenic impacts on fish and other animals and plants. A problem arises, however, to the extent that natural stressors confound the effects of human-induced disturbances. Our objective in this work was to investigate whether a natural stressor, in the form of EI Nino conditions, contributed to DI in the Pacific hake. Right-left (fluctuating> asymmetry of otolith length, width, growth rate, and weight, as well as right-left otolith shape differences, were used as measures of DI. Results show that indeed EI Nino disrupts development, indicating stress. This outcome suggests that DI, as an early warning and monitoring tool for stress, must be used with caution.
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Dongen, S V
2006-11-01
The role of developmental instability (DI), as measured by fluctuating asymmetry (FA), in evolutionary biology has been the focus of a wealth of research for more than half a century. In spite of this long period and many published papers, our current state of knowledge reviewed here only allows us to conclude that patterns are heterogeneous and that very little is known about the underlying causes of this heterogeneity. In addition, the statistical properties of FA as a measure of DI are only poorly grasped because of a general lack of understanding of the underlying mechanisms that drive DI. If we want to avoid that this area of research becomes abandoned, more efforts should be made to understand the observed heterogeneity, and attempts should be made to develop a unifying statistical protocol. More specifically, and perhaps most importantly, it is argued here that more attention should be paid to the usefulness of FA as a measure of DI since many factors might blur this relationship. Furthermore, the genetic architecture, associations with fitness and the importance of compensatory growth should be investigated under a variety of stress situations. In addition, more focus should be directed to the underlying mechanisms of DI as well as how these processes map to the observable phenotype. These insights could yield more efficient statistical models and a unified approach to the analysis of patterns in FA and DI. The study of both DI and canalization is indispensable to obtain better insights in their possible common origin, especially because both have been suggested to play a role in both micro- and macro-evolutionary processes.
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Characterization of branch complexity by fractal analyses and detect plant functional adaptations
Alados, C.L.; Escos, J.; Emlen, J.M.; Freeman, D.C.
1999-01-01
The comparison between complexity in the sense of space occupancy (box-counting fractal dimension Dc and information dimension DI ) and heterogeneity in the sense of space distribution (average evenness index and evenness variation coefficient JCV) were investigated in mathematical fractal objects and natural branch ¯ J structures. In general, increased fractal dimension was paired with low heterogeneity. Comparisons between branch architecture in Anthyllis cytisoides under different slope exposure and grazing impact revealed that branches were more complex and more homogeneously distributed for plants on northern exposures than southern, while grazing had no impact during a wet year. Developmental instability was also investigated by the statistical noise of the allometric relation between internode length and node order. In conclusion, our study demonstrated that fractal dimension of branch structure can be used to analyze the structural organization of plants, especially if we consider not only fractal dimension but also shoot distribution within the canopy (lacunarity). These indexes together with developmental instability analyses are good indicators of growth responses to the environment.
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Developmental instability of gynodioecious Teucrium lusitanicum
Alados, C.L.; Navarro, T.; Cabezudo, B.; Emlen, J.M.; Freeman, C.
1998-01-01
Developmental instability was assessed in two geographical races of Teucrium lusitanicum using morphometric measures of vegetative and reproductive structures. T. lusitanicum is a gynodioecious species. Male sterile (female) individuals showed greater developmental instability at all sites. Plants located inland had higher developmental instability of vegetative characters and lower developmental instability of reproductive characters than coastal plants. These results support the contentions that (1) developmental instability is affected more by the disruption of co-adapted gene complexes than by lower heterozygosity, and (2) different habitat characteristics result in the differential response of vegetative and reproductive structures.
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The Theory behind the Theory in DCT and SCDT: A Response to Rigazio-DiGilio.
ERIC Educational Resources Information Center
Terry, Linda L.
1994-01-01
Responds to previous article by Rigazio-DiGilio on Developmental Counseling and Therapy and Systemic Cognitive-Developmental Therapy as two integrative models that unify individual, family, and network treatment within coconstructive-developmental framework. Discusses hidden complexities in cognitive-developmental ecosystemic integration and…
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Freeman, D.C.; Brown, M.L.; Duda, J.J.; Graraham, J.H.; Emlen, J.M.; Krzysik, A.J.; Balbach, H.; Kovacic, D.A.; Zak, J.C.
2005-01-01
We studied Cnidoscolus stimulosus and Ipomoea pandurata, two common herbs of the Fall Line Sandhills to assess their potential as ecosystem level stress indicators. We focused on plants because they are among the most persistent organisms in terrestrial ecosystems. We used developmental instability as an indicator of plant population stress. Developmental instability is usually measured as deviations from symmetry, in traits that normally develop symmetrically. Thus, symmetry represents an idealized a priori phenotype. Stress presumably causes perturbations during development that may exceed the capacity of the organism to buffer or correct, resulting in developmental instability, and hence deviations from this ideal. Soil disturbance imposed by different land use patterns at Fort Benning, Georgia provided a gradient of soil disturbance. In 2000-2002 we collected plants from nine different sites representing three levels of disturbance. In addition, in 2002 we collected microhabitat data in 1 m quadrats surrounding each plant whose developmental stability we also assessed. The developmental instability of both species was influenced by land use patterns, whether or not the sites had been previously burned, and microhabitat variables. Developmental instability increased with soil disturbance, burning in the prior year, and as the percentage of bare ground increased around the target individual. To some extent, favorable microhabitat conditions reduced developmental instability in sites with medium and high soil disturbance, whereas unfavorable conditions at low soil disturbance sites increased developmental instability. As an indicator of community level stress, developmental instability is best used in conjunction with other indices of environmental quality. ?? Published by Elsevier Ltd.
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Campbell, W.B.; Emlen, J.M.
1997-01-01
Stress in organisms results in energy dissipation, making developmental pathways less stable. Effects of chronic stress, manifested as small random departures from phenotypic symmetry, reflect developmental instability, are considered to be epigenetic and an effect produced by compromised fitness. Instability is detectable and effectively interpreted among sites or populations if samples are collected randomly, the stressor is present throughout character development, characters are identified accurately and excessive mortality does not erase the existence of developmental instability. Bacterial kidney disease (BKD) is a chronic systemic disease in salmonids that, after vertical transmission from parent to egg, persists and spreads throughout ontogeny, potentially affecting developmental processes. Because levels of progeny infection reflect parental infection levels, groups of offspring from parents with high and low levels of BKD infection can be compared to assess the effects of disease-mediated developmental stress. Analyses of fluctuating asymmetry in five bilateral characters were inconclusive, but significant reductions in the proportion of unusable scales, in the number of circulus errors, and in the directional asymmetry of branchiostegal rays were observed in fish from the high-BKD group. This group also contained individuals of significantly larger size. These results are opposite to those expected from traditional developmental instability theory in suggesting that surviving high-BKD fish have greater developmental stability. This reversal appears to be produced by selective mortality having a greater effect than sublethal stress in altering developmental instability patterns. These results are discussed with respect to size selectivity, heterosis and the assumptions supporting developmental instability as a tool for detecting chronic sublethal stress.
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Scheiner, Samuel M
2014-02-01
One potential evolutionary response to environmental heterogeneity is the production of randomly variable offspring through developmental instability, a type of bet-hedging. I used an individual-based, genetically explicit model to examine the evolution of developmental instability. The model considered both temporal and spatial heterogeneity alone and in combination, the effect of migration pattern (stepping stone vs. island), and life-history strategy. I confirmed that temporal heterogeneity alone requires a threshold amount of variation to select for a substantial amount of developmental instability. For spatial heterogeneity only, the response to selection on developmental instability depended on the life-history strategy and the form and pattern of dispersal with the greatest response for island migration when selection occurred before dispersal. Both spatial and temporal variation alone select for similar amounts of instability, but in combination resulted in substantially more instability than either alone. Local adaptation traded off against bet-hedging, but not in a simple linear fashion. I found higher-order interactions between life-history patterns, dispersal rates, dispersal patterns, and environmental heterogeneity that are not explainable by simple intuition. We need additional modeling efforts to understand these interactions and empirical tests that explicitly account for all of these factors.
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Trisomy 21 and facial developmental instability.
Starbuck, John M; Cole, Theodore M; Reeves, Roger H; Richtsmeier, Joan T
2013-05-01
The most common live-born human aneuploidy is trisomy 21, which causes Down syndrome (DS). Dosage imbalance of genes on chromosome 21 (Hsa21) affects complex gene-regulatory interactions and alters development to produce a wide range of phenotypes, including characteristic facial dysmorphology. Little is known about how trisomy 21 alters craniofacial morphogenesis to create this characteristic appearance. Proponents of the "amplified developmental instability" hypothesis argue that trisomy 21 causes a generalized genetic imbalance that disrupts evolutionarily conserved developmental pathways by decreasing developmental homeostasis and precision throughout development. Based on this model, we test the hypothesis that DS faces exhibit increased developmental instability relative to euploid individuals. Developmental instability was assessed by a statistical analysis of fluctuating asymmetry. We compared the magnitude and patterns of fluctuating asymmetry among siblings using three-dimensional coordinate locations of 20 anatomic landmarks collected from facial surface reconstructions in four age-matched samples ranging from 4 to 12 years: (1) DS individuals (n = 55); (2) biological siblings of DS individuals (n = 55); 3) and 4) two samples of typically developing individuals (n = 55 for each sample), who are euploid siblings and age-matched to the DS individuals and their euploid siblings (samples 1 and 2). Identification in the DS sample of facial prominences exhibiting increased fluctuating asymmetry during facial morphogenesis provides evidence for increased developmental instability in DS faces. We found the highest developmental instability in facial structures derived from the mandibular prominence and lowest in facial regions derived from the frontal prominence. Copyright © 2013 Wiley Periodicals, Inc.
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DEVELOPMENTAL TOXICITY OF DI- AND TETRACHLOROETHANE AND DICHLOROPROPANE IN EMBRYO CULTURE
DEVELOPMENTAL TOXICITY OF DI- AND TETRACHLOROETHANE AND DICHLOROPROPANE IN EMBRYO CULTURE. JE Andrews, H Nichols, and ES Hunter. Reproductive Toxicology Division, NHEERL, USEPA, RTP, NC.
Disinfection of drinking water with chlorine results in numerous chlorinated byprodu... -
Alados, C.L.; Emlen, J.M.; Wachocki, B.; Freeman, D.C.
1998-01-01
Developmental instability has been used to monitor the well-being of natural populations exposed to physical, chemical and biological stressors. Here, we use developmental instability to assess the impact of grazing on Chrysothamnus greenii and Seriphidium novumshrubs, and Oryzopsis hymenoidesgrass, common in the arid intermountain west of the U.S.A. Statistical noise in allometric relations was used as an indicator of developmental instability arising from grazing-induced stress. Unpalatable species that are not grazed (Chrysothamnus greenii) or species that are dormant during the winter–spring grazing period (Oryzopsis hymenoides) show lower allometric variability under high grazing pressure. Palatable species (Seriphidium novum) exhibit high developmental instability under low and high grazing pressure. Grazing pressure imposed by presumably co-adapted wild herbivores enhances developmental stability in species habituated to moderate grazing, likeOryzopsis hymenoides, but stresses plants such as Chrysothamnus greenii that prefer disturbed environments. These grazing effects are probably due to the impact grazing has on competitive relationships and not to the direct action of the herbivore on the plants.
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Trisomy 21 and Facial Developmental Instability
Starbuck, John M.; Cole, Theodore M.; Reeves, Roger H.; Richtsmeier, Joan T.
2013-01-01
The most common live-born human aneuploidy is trisomy 21, which causes Down syndrome (DS). Dosage imbalance of genes on chromosome 21 (Hsa21) affects complex gene-regulatory interactions and alters development to produce a wide range of phenotypes, including characteristic facial dysmorphology. Little is known about how trisomy 21 alters craniofacial morphogenesis to create this characteristic appearance. Proponents of the “amplified developmental instability” hypothesis argue that trisomy 21 causes a generalized genetic imbalance that disrupts evolutionarily conserved developmental pathways by decreasing developmental homeostasis and precision throughout development. Based on this model, we test the hypothesis that DS faces exhibit increased developmental instability relative to euploid individuals. Developmental instability was assessed by a statistical analysis of fluctuating asymmetry. We compared the magnitude and patterns of fluctuating asymmetry among siblings using three-dimensional coordinate locations of 20 anatomic landmarks collected from facial surface reconstructions in four age-matched samples ranging from 4 to 12 years: 1) DS individuals (n=55); 2) biological siblings of DS individuals (n=55); 3) and 4) two samples of typically developing individuals (n=55 for each sample), who are euploid siblings and age-matched to the DS individuals and their euploid siblings (samples 1 and 2). Identification in the DS sample of facial prominences exhibiting increased fluctuating asymmetry during facial morphogenesis provides evidence for increased developmental instability in DS faces. We found the highest developmental instability in facial structures derived from the mandibular prominence and lowest in facial regions derived from the frontal prominence. PMID:23505010
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URINARY BIOMARKERS OF DI-ISONONYL PHTHALATE IN RATS
Commercial di-isononyl phthalate (DiNP) is a mixture of various branched-chain dialkyl phthalates mainly containing ninecarbon alkyl isomers. At high doses in rodents, DiNP is a carcinogen, and a developmental toxicant. After exposure, the diester isomers are de-esterified to for...
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Developmental instability and fitness in Periploca laevigata experiencing grazing disturbance
Alados, C.L.; Giner, M.L.; Dehesa, L.; Escos, J.; Barroso, F.; Emlen, J.M.; Freeman, D.C.
2002-01-01
We investigated the sensitivity of developmental instability measurements (leaf fluctuating asymmetry, floral radial asymmetry, and shoot translational asymmetry) to a long‐standing natural stress (grazing) in a palatable tannin‐producing shrub (Periploca laevigata Aiton). We also assessed the relationship between these measures of developmental instability and fitness components (growth and floral production). Developmental instability, measured by translational asymmetry, was the most accurate estimator of a plant’s condition and, consequently, environmental stress. Plants with less translational asymmetry grew more and produced more flowers. Plants from the medium‐grazed population were developmentally more stable, as estimated by translational and floral asymmetry, than either more heavily or more lightly grazed populations. Leaf fluctuating asymmetry was positively correlated with tannin concentration. The pattern of internode growth also responded to grazing impact. Plants under medium to heavy grazing pressure accelerated early growth and consequently escaped herbivory later in the season, i.e., at the beginning of the spring, when grazing activity was concentrated in herbaceous plants. Periploca laevigata accelerated growth and finished growing sooner than in the other grazing treatment. Thus, its annual growth was more mature and less palatable later in the season when grazers typically concentrate on shrubs. The reduction of developmental instability under medium grazing is interpreted as a direct effect of grazing and not as the release from competition.
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ERIC Educational Resources Information Center
Flores, Margaret M.; Nelson, Cynthia; Hinton, Vanessa; Franklin, Toni M.; Strozier, Shaunita D.; Terry, LaTonya; Franklin, Susan
2013-01-01
There is limited research demonstrating Direct Instruction (DI) as an effective reading comprehension intervention for students with autism spectrum disorders (ASD) and developmental disabilities (DD). Previous research has shown that DI, when portions of the program were implemented, resulted in increased skills (Flores & Ganz, 2007; Flores…
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ERIC Educational Resources Information Center
Mandy, William; Clarke, Kiri; McKenner, Michele; Strydom, Andre; Crabtree, Jason; Lai, Meng-Chuan; Allison, Carrie; Baron-Cohen, Simon; Skuse, David
2018-01-01
We developed a brief, informant-report interview for assessing autism spectrum conditions (ASC) in adults, called the Developmental, Dimensional and Diagnostic Interview-Adult Version (3Di-Adult); and completed a preliminary evaluation. Informant reports were collected for participants with ASC (n = 39), a non-clinical comparison group (n = 29)…
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ERIC Educational Resources Information Center
Chuthapisith, Jariya; Taycharpipranai, Pasinee; Ruangdaraganon, Nichara; Warrington, Richard; Skuse, David
2012-01-01
This study aimed to examine the effectiveness of a translated version of the short version of the Developmental, Dimensional and Diagnostic Interview (3Di) in discriminating children with autism spectrum disorders (ASDs) from typically developing children. Two groups, comprising 63 children with clinically ascertained ASDs and 67 typically…
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ERIC Educational Resources Information Center
Flores, Margaret M.; Schweck, Kelly B.; Hinton, Vanessa
2016-01-01
Language intervention using Direct Instruction (DI) has shown positive results. There is a growing body of investigation of Language for Learning (LL), a DI program, on the performance of students with autism spectrum disorders (ASD) and students with developmental delays (DD). There is need for replication and extension of research to include…
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ERIC Educational Resources Information Center
Lai, Kelly Y. C.; Leung, Patrick W. L.; Mo, Flora Y. M.; Lee, Marshall M. C.; Shea, Caroline K. S.; Chan, Grace F. C.; Che, Kiti K. I.; Luk, Ernest S. L.; Mak, Arthur D. P.; Warrington, Richard; Skuse, David
2015-01-01
Autism spectrum disorder (ASD) is a disorder with high levels of co-morbidities. The Developmental, Dimensional and Diagnostic Interview (3Di) is a relatively new instrument designed to provide dimensional as well as categorical assessment of autistic behaviours among children with normal intelligence. Its sound psychometric properties and…
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Hopkins, William D.; Dahl, Jeremy F.; Pilcher, Dawn
2007-01-01
Genetic mechanisms have been proposed to explain the pervasive representation of right-handedness in humans, whereas random, nongenetic factors have been posited to explain the lack of population-level right-handedness in nonhuman primates. We report evidence that hand preferences in chimpanzees are heritable, even among related individuals raised in different environments. Furthermore, we report that the degree of heritability is modified by factors associated with developmental instability, notably, offspring parity. The data are interpreted to reconcile both genetic models for handedness and hypotheses suggesting that developmental instability influences variation in handedness. PMID:11476096
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Chen, Chien-Min; Chen, Chia-Ling; Hou, Jia-Woei; Hsu, Hung-Chih; Chung, Chia-Ying; Chou, Shih-Wei; Lin, Chu-Hsu; Chen, Kai-Hua
2010-01-01
A majority of the children with Prader-Willi syndrome (PWS) have global developmental delay and mental delay. The aim of this study was to investigate the developmental profiles and mental assessments among preschool children with PWS. Ten children with PWS between the ages of 15 months to 6 years, and 11 children with typical development were enrolled. Developmental profiles in terms of their developmental quotient (DQ) for the eight domains of the Chinese Children Developmental Inventory (CCDI) and mental assessments in terms of intelligence quotient (IQ) and developmental index (DI) were carried out for all children. The DQs of all eight domains, including gross motor, fine motor, expressive language, concept comprehension, situation comprehension, self help, personal- social and general development, in the PWS group were lower than the DQs of the children from the typical development group (p < 0.01). Children with PWS had better DQs in the fine motor domain than in the gross motor domain and in the receptive language domain than in the expressive language domain. Furthermore, their verbal IQ were better than their performance IQ and their mental DI was better than their psychomotor DI. These findings suggest that the children with PWS show an uneven global developmental delay together with an uneven mental delay. The results of this study should allow clinicians to better understand the developmental functioning of children with PWS and this will help with the planning of treatment strategies.
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ERIC Educational Resources Information Center
Cortés, Maria José; Orejuela, Carmen; Castellví, Gemma; Folch, Annabel; Rovira, Lluís; Salvador-Carulla, Luis; Irazábal, Marcia; Muñoz, Silvia; Haro, Josep Maria; Vilella, Elisabet; Martínez-Leal, Rafael
2018-01-01
Strategies for the early detection of autism spectrum disorders (ASD) in people with intellectual developmental disorder (IDD) are urgently needed, but few specific tools have been developed. The present study examines the psychometric properties of the EVTEA-DI, a Spanish adaptation of the PDD-MRS, in a large randomized sample of 979 adults with…
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Haney-Caron, Emily; Goldstein, Naomi E. S.; Giallella, Christy L.; Kemp, Kathleen; Romaine, Christina Riggs
2016-01-01
Developmental immaturity (DI) may help explain some of the variability in aspects of academic achievement among girls in the juvenile justice system, a population with high rates of truancy, dropout, and school failure. This study examined the relationships among the decision making and independent functioning components of DI, verbal intelligence, and academic achievement within this population. Using data from 60 girls in residential juvenile justice facilities, multiple regression analyses indicated that verbal IQ moderated the relationship between the DI construct of decision making and academic achievement. Self-reported school attendance and number of previous arrests did not significantly mediate the relationship between DI and academic achievement. These results may indicate that the decision-making factor of DI may be particularly important, and, if results are replicated, future intervention efforts could focus more on improving this skill within this juvenile justice population. Additionally, the overall importance of the full DI construct is an important area of future study. PMID:28082833
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Duda, J.J.; Freeman, D.C.; Brown, M.L.; Graham, J.H.; Krzysik, A.J.; Emlen, J.M.; Zak, J.C.; Kovacic, D.A.
2004-01-01
We used developmental instability, water potential, and variable fluorescence to determine if populations of winged sumac (Rhus copallinum) were being negatively effected by military training disturbance. We established nine sites that represented a land-use disturbance gradient with three impact levels (low, medium, and high), the effects mostly due to mechanized infantry training maneuvers. Although mean values of developmental instability, water potential, and variable fluorescence differed significantly among sites, the patterns did not consistently differentiate sites relative to the disturbance gradient. At the population level, some measures of developmental instability and variable fluorescence were positively correlated. All nine sites consisted of habitat mosaics, with the abundance of higher quality habitat patches and canopy gaps closely related to habitat impacts. It may be that R. copallinum is selecting similar micro-environments at all sites and therefore minimizing inter-site variation in stress measures, despite large differences in overall habitat condition. Our results call for caution in developing ecological indicators using the response of physiological and morphological measures from a single plant species. ?? 2003 Elsevier Ltd. All rights reserved.
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Developmental instability in Rhus copallinum L.: multiple stressors, years, and responses
Freeman, D. Carl; Brown, Michelle L.; Duda, Jeffrey J.; Graham, John H.; Emlen, John M.; Krzysik, Anthony J.; Balbach, Harold E.; Kovacic, Dave A.; Zak, John C.
2004-01-01
Developmental instability, as assessed by leaf fluctuating asymmetry and stem internode allometry, was examined at nine sites, representing three levels of disturbance, over multiple years. Site selection was based on land‐use disturbance classes related to training of mechanized infantry and other land management activities at Fort Benning, Georgia. Developmental instability varied among sites and years, and there was a strong site‐by‐year interaction for many traits. Indeed, depending on the year, the same site could be ranked as having the greatest and least amount of leaf fluctuating asymmetry. Burning a site the year prior to collecting the leaves profoundly influenced measures of leaf fluctuating asymmetry. In the absence of recent burning, leaf fluctuating asymmetry declined with increasing disturbance, but burning the year prior to collecting the leaves reversed this trend. Total plant cover, proportion of bare ground, and amount of plant litter influenced the amount of leaf asymmetry in a site‐dependent manner. Overall, burning influenced the levels of developmental instability more than either disturbance or microhabitat variables such as total plant cover, which should reflect competition in a plant’s immediate neighborhood.
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John H. Graham; Jeffrey J. Duda; Michelle L. Brown; Stanley Kitchen; John M. Emlen; Jagadish Malol; Elizabeth Bankstahl; Anthony J. Krzysik; Harold Balbach; D. Carl Freeman
2012-01-01
Ecological indicators provide early warning of adverse environmental change, helping land managers adaptively manage their resources while minimizing costly remediation. In 1999 and 2000, we studied two such indicators, growth and developmental instability, of loblolly pine (Pinus taeda L.) influenced by mechanized infantry training at Fort Benning, Georgia. Disturbed...
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Potential of DCT/SCDT in Addressing Two Elusive Themes of Mental Health Counseling.
ERIC Educational Resources Information Center
Borders, L. DiAnne
1994-01-01
Responds to previous article by Rigazio-DiGilio on Developmental Counseling and Therapy and Systemic Cognitive-Developmental Therapy as two integrative models that unify individual, family, and network treatment within coconstructive-developmental framework. Considers extent to which model breaks impasse in integrating development into counseling…
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ERIC Educational Resources Information Center
Slappendel, Geerte; Mandy, William; van der Ende, Jan; Verhulst, Frank C.; van der Sijde, Ad; Duvekot, Jorieke; Skuse, David; Greaves-Lord, Kirstin
2016-01-01
The Developmental Diagnostic Dimensional Interview-short version (3Di-sv) provides a brief standardized parental interview for diagnosing autism spectrum disorder (ASD). This study explored its validity, and compatibility with DSM-5 ASD. 3Di-sv classifications showed good sensitivity but low specificity when compared to ADOS-2-confirmed clinical…
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Graham, John H.; Duda, Jeffrey J.; Brown, Michelle L.; Kitchen, Stanley G.; Emlen, John M.; Malol, Jagadish; Bankstahl, Elizabeth; Krzysik, Anthony J.; Balbach, Harold E.; Freeman, D. Carl
2012-01-01
Ecological indicators provide early warning of adverse environmental change, helping land managers adaptively manage their resources while minimizing costly remediation. In 1999 and 2000, we studied two such indicators, growth and developmental instability, of loblolly pine (Pinus taeda L.) influenced by mechanized infantry training at Fort Benning, Georgia. Disturbed areas were used for military training; tracked and wheeled vehicles damaged vegetation and soils. Highly disturbed sites had fewer trees, diminished ground cover, warmer soils in the summer, and more compacted soils with a shallower A-horizon. We hypothesized that disturbance would decrease the growth of needles, branches, and tree rings, increase the complexity of tree rings, and increase the developmental instability of needles. Contrary to our expectations, however, disturbance enhanced growth in the first year of the study, possibly by reducing competition. In the second year, a drought reduced growth of branches and needles, eliminating the stimulatory effect of disturbance. Growth-ring widths increased with growing-season precipitation, and decreased with growing-season temperature over the last 40 years. Disturbance had no effect on tree-ring complexity, as measured by the Hurst exponent. Within-fascicle variation of current-year needle length, a measure of developmental instability, differed among the study populations, but appeared unrelated to mechanical disturbance or drought.
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Revision Surgery in Permanent Patellar Dislocation in DiGeorge Syndrome
Berruto, Massimo; Parente, Andrea; Ferrua, Paolo; Pasqualotto, Stefano; Uboldi, Francesco; Usellini, Eva
2015-01-01
A 29-year-old patient, suffering from DiGeorge syndrome, came to our attention with a history of persistent pain and patellar instability in the left knee after failure of arthroscopic lateral release and Elmslie-Trillat procedure. The patient was unable to walk without crutches and severely limited in daily living activities. Because of arthritic changes of the patellofemoral joint and the failure of previous surgeries it was decided to perform only an open lateral release and medial patellofemoral ligament (MPFL) reconstruction using a biosynthetic ligament in order to obtain patellofemoral stability. At one year post-op range of motion (ROM) was 0–120 with a firm end point at medial patellar mobilization; patella was stable throughout the entire ROM. All the scores improved and she could be able to perform daily activity without sensation of instability. Bilateral patellar subluxation and systemic hyperlaxity are characteristics of syndromic patients and according to literature can be also present in DiGeorge syndrome. MPFL reconstruction with lateral release was demonstrated to be the correct solution in the treatment of patellar instability in this complex case. The choice of an artificial ligament to reconstruct the MPFL was useful in this specific patient with important tissue laxity due to her congenital syndrome. PMID:26783479
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ERIC Educational Resources Information Center
Duvekot, Jorieke; van der Ende, Jan; Verhulst, Frank C.; Greaves-Lord, Kirstin
2015-01-01
The screening accuracy of the parent and teacher-reported Social Responsiveness Scale (SRS) was compared with an autism spectrum disorder (ASD) classification according to (1) the Developmental, Dimensional, and Diagnostic Interview (3Di), (2) the Autism Diagnostic Observation Schedule (ADOS), (3) both the 3Di and ADOS, in 186 children referred to…
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Perceived Instability in Emerging Adulthood: The Protective Role of Identity Capital
ERIC Educational Resources Information Center
Luyckx, Koen; De Witte, Hans; Goossens, Luc
2011-01-01
Developmental instability characterizes the late teens and twenties in today's late-modern society. The present study (a) focused on the link between instability and both general (i.e., self-esteem and depressive symptoms) and work-related outcomes (i.e., work engagement and burnout) and (b) investigated the possible moderating role of identity…
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DEVELOPMENTAL EXPOSURE TO DI-N-BUTYLTIN DICHLORIDE (DBTC): IMMUNOTOXIC AND NEUROTOXIC EVALUATION
Organotins are incorporated as stabilizers in PVC water supply pipe. Particularly when new, mono- and di-substituted methyl- and butyltins leach from the pipe and are thus of regulatory concern to EPA. These contaminants have adverse effects on both the immune and nervous systems...
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Effect of thermal cycling. Final report, April 1985-January 1987
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jacobs, S.F.
The objective of this effort is to evaluate the stability of low expansion Zerodur, developmental Zerodur, ULE, and Cer-Vit as possible substrate materials for high energy laser mirrors. This effort will determine whether there is instability in developmental Zerodur, ULE and Cer-Vit over operating temperatures and coating temperatures (300-475K). Zerodur has already been shown to exhibit instability. Thermal cycling will be investigated as a possible approach to eliminate or reduce hysteresis. The effect of polishing on hysteresis will also be investigated.
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NASA Astrophysics Data System (ADS)
Jacobs, Stephen F.
1988-05-01
The objective of this effort is to evaluate the stability of low expansion Zerodur, developmental Zerodur, ULE, and Cer-Vit as possible substrate materials for high energy laser mirrors. This effort will determine whether there is instability in developmental Zerodur, ULE and Cer-Vit over operating temperatures and coating temperatures (300 to 475 K). Zerodur has already been shown to exhibit instability. Thermal cycling will be investigated as a possible approach to eliminate or reduce hysteresis. The effect of polishing on hysteresis will also be investigated.
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Imaging of shoulder instability
Martínez Martínez, Alberto; Tomás Muñoz, Pablo; Pozo Sánchez, José; Zarza Pérez, Antonio
2017-01-01
This extended review tries to cover the imaging findings of the wide range of shoulder injuries secondary to shoulder joint instability. Usefulness of the different imaging methods is stressed, including radiography, computed tomography (CT) and magnetic resonance. The main topics to be covered include traumatic, atraumatic and minor instability syndromes. Radiography may show bone abnormalities associated to instability, including developmental and post-traumatic changes. CT is the best technique depicting and quantifying skeletal changes. MR-arthrography is the main tool in diagnosing the shoulder instability injuries. PMID:28932699
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Developmental instability: measures of resistance and resilience using pumpkin (Cucurbita pepo L.)
Freeman, D. Carl; Brown, Michelle L.; Dobson, Melissa; Jordan, Yolanda; Kizy, Anne; Micallef, Chris; Hancock, Leandria C.; Graham, John H.; Emlen, John M.
2003-01-01
Fluctuating asymmetry measures random deviations from bilateral symmetry, and thus estimates developmental instability, the loss of ability by an organism to regulate its development. There have been few rigorous tests of this proposition. Regulation of bilateral symmetry must involve either feedback between the sides or independent regulation toward a symmetric set point. Either kind of regulation should decrease asymmetry over time, but only right–left feedback produces compensatory growth across sides, seen as antipersistent growth following perturbation. Here, we describe the developmental trajectories of perturbed and unperturbed leaves of pumpkin, Cucurbita pepoL., grown at three densities. Covering one side of a leaf with aluminium foil for 24 h perturbed leaf growth. Reduced growth on the perturbed side caused leaves to become more asymmetrical than unperturbed controls. After the treatment the size-corrected asymmetry decreased over time. In addition, rescaled range analysis showed that asymmetry was antipersistent rather than random, i.e. fluctuation in one direction was likely to be followed by fluctuations in the opposite direction. Development involves right–left feedback. This feedback reduced size-corrected asymmetry over time most strongly in the lowest density treatment suggesting that developmental instability results from a lack of resilience rather than resistance.
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New insights into the mechanism of phthalate-induced developmental effects.
Mu, Xiyan; Huang, Ying; Li, Jia; Yang, Ke; Yang, Wenbo; Shen, Gongming; Li, Xuxing; Lei, Yunlei; Pang, Sen; Wang, Chengju; Li, Xuefeng; Li, Yingren
2018-06-11
To investigate the biological pathways involved in phthalate-induced developmental effects, zebrafish embryos were exposed to different concentrations of di-(2-ethylhexyl) (DEHP) and di-butyl phthalate (DBP) for 96 h. Embryonic exposure to DEHP and DBP induced body length decrease, yolk sac abnormities, and immune responses (up-regulation of immune proteins and genes). The lipidomic results showed that at a concentration of 50 μg/L, DEHP and DBP significantly reduced the levels of fatty acids, triglycerides, diacylglycerol, and cholesterol. These effects are partly explained by biological pathway enrichment based on data from the transcriptional and proteomic profiles. Co-exposure to DBP and ER antagonist did not significantly relieve the toxic symptoms compared with exposure to DBP alone. This indicates that phthalate-induced developmental abnormities in zebrafish might not be mediated by the ER pathway. In conclusion, we identified the possible biological pathways that mediate phthalate-induced developmental effects and found that these effects may not be driven by estrogenic activation. Copyright © 2018 Elsevier Ltd. All rights reserved.
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ERIC Educational Resources Information Center
Flores, Margaret M.; Ganz, Jennifer B.
2014-01-01
There is limited research demonstrating direct instruction (DI) as an effective language intervention for students with autism spectrum disorders (ASD) and developmental disabilities (DD). Existing research has shown that instruction using partial implementation of DI programs resulted in student learning (Ganz, 2007) and instruction using whole…
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Ostberg, C.O.; Duda, J.J.; Graham, J.H.; Zhang, S.; Haywood, K. P.; Miller, B.; Lerud, T.L.
2011-01-01
Hybridization of cutthroat trout Oncorhynchus clarkii with nonindigenous rainbow trout O. mykiss contributes to the decline of cutthroat trout subspecies throughout their native range. Introgression by rainbow trout can swamp the gene pools of cutthroat trout populations, especially if there is little selection against hybrids. We used rainbow trout, Yellowstone cutthroat trout O. clarkii bouvieri, and rainbow trout × Yellowstone cutthroat trout F1 hybrids as parents to construct seven different line crosses: F1 hybrids (both reciprocal crosses), F2 hybrids, first-generation backcrosses (both rainbow trout and Yellowstone cutthroat trout), and both parental taxa. We compared growth, morphology, and developmental instability among these seven crosses reared at two different temperatures. Growth was related to the proportion of rainbow trout genome present within the crosses. Meristic traits were influenced by maternal, additive, dominant, overdominant, and (probably) epistatic genetic effects. Developmental stability, however, was not disturbed in F1 hybrids, F2 hybrids, or backcrosses. Backcrosses were morphologically similar to their recurrent parent. The lack of developmental instability in hybrids suggests that there are few genetic incompatibilities preventing introgression. Our findings suggest that hybrids are not equal: that is, growth, development, character traits, and morphology differ depending on the genomic contribution from each parental species as well as the hybrid generation.
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NASA Astrophysics Data System (ADS)
Francioso, R.; Sdao, F.; Tropeano, M.
2003-04-01
The Italian Ministry of Education, University and Research financed a research project about the study and the control of hydrogeological hazard of some sites belonging to the "Parco Archeologico Storico Naturale delle Chiese Rupestri del Materano"; the Park and the old city of Matera ("Sassi di Matera") was inserted in the UNESCO World Heritage list since 1993. The studied sites ("Belvedere Chiese Rupestri" and "Iazzo dell'Ofra" localities) are located along the top of the walls of the deep canyon (locally called "Gravina di Matera" and deeper than 100 m) which characterizes the area. Several valuable medieval rupestrian hand-hewn rock churches and sanctuaries are present along the canyon walls. The canyon cut weak rocks (Plio-Pleistocene calcarenites, in which churches and sanctuaries are excavated) and the underlying well-stratified limestones (Cretaceous calcilutites). Both rocks are abundantly and strongly fractured and disjointed by several different joint sets, and, on the left wall of the "Gravina di Matera" canyon, they are characterized by a mainly dipping-slope attitude. Consequently, rock blocks of different sizes formed (up to some tens of m^3 in volume), and are characterized by low stability condition. The considerable acclivity of the walls and the defects and intense fracturing state of rocks, especially along the edge, cause rapid falls, topples and rockslides of the blocks. This geomorphological fragility, confirmed by wide-spread signs of potential instability and by several rock blocks fell in the stream, causes the diffuse and significant structural-failures processes that involve most of the very fine rupestrian heritages. Our study, after the geological and geomorphological description of the sites and the editing of thematic maps, concentrates on the determination the present-day slope instability conditions. Moreover, the study demonstrated the notable genetic relationship between jointing, slope instability and failure type of carbonate blocks. The main results of this geological and geomorphological studies and thematic maps will be reported and discussed.
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Growing Pains: A Theory of Stress and Moral Conflict.
ERIC Educational Resources Information Center
Blakeney, Ronnie Ann; Blakeney, Charles David
1992-01-01
Outlines relationship between crises that create stress in one's life and periods of instability in moral development. Suggests that stressful issues are more difficult to resolve during periods of developmental instability and that, when problems are most stressful, people often experience impact of stress physiologically. Reconstructs stress and…
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Slappendel, Geerte; Mandy, William; van der Ende, Jan; Verhulst, Frank C; van der Sijde, Ad; Duvekot, Jorieke; Skuse, David; Greaves-Lord, Kirstin
2016-05-01
The Developmental Diagnostic Dimensional Interview-short version (3Di-sv) provides a brief standardized parental interview for diagnosing autism spectrum disorder (ASD). This study explored its validity, and compatibility with DSM-5 ASD. 3Di-sv classifications showed good sensitivity but low specificity when compared to ADOS-2-confirmed clinical diagnosis. Confirmatory factor analyses found a better fit against a DSM-5 model than a DSM-IV-TR model of ASD. Exploration of the content validity of the 3Di-sv for the DSM-5 revealed some construct underrepresentation, therefore we obtained data from a panel of 3Di-trained clinicians from ASD-specialized centers to recommend items to fill these gaps. Taken together, the 3Di-sv provides a solid basis to create a similar instrument suitable for DSM-5. Concrete recommendations are provided to improve DSM-5 compatibility.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Lipson, A.; Sholler, G.; Issacs, D.
We report on a female with a interstitial deletion of 10p13 and a phenotype similar to that seen with the 22q deletion syndromes (DiGeorge/velo-cardio-facial). She had a posterior cleft palate, perimembranous ventricular septal defect, dyscoordinate swallowing, T-cell subset abnormalities, small ears, maxillary and mandibular hypoplasia, broad nasal bridge, deficient alae nasi, contractures of fingers and developmental delay. This could indicate homology of some developmental genes at 22q and 10p so that patients with the velocardiofacial phenotype who do not prove to be deleted on 22q are candidates for a 10p deletion. 58 refs., 3 figs.
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Duvekot, Jorieke; van der Ende, Jan; Verhulst, Frank C; Greaves-Lord, Kirstin
2015-06-01
The screening accuracy of the parent and teacher-reported Social Responsiveness Scale (SRS) was compared with an autism spectrum disorder (ASD) classification according to (1) the Developmental, Dimensional, and Diagnostic Interview (3 Di), (2) the Autism Diagnostic Observation Schedule (ADOS), (3) both the 3 Di and ADOS, in 186 children referred to six mental health centers. The parent report showed excellent correspondence to an ASD classification according to the 3 Di and both the 3 Di and ADOS. The teacher report added significantly to the screening accuracy over and above the parent report when compared with the ADOS classification. Findings support the screening utility of the parent-reported SRS among clinically referred children and indicate that different informants may provide unique information relevant for ASD assessment.
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Escos, J.; Alados, C.L.; Pugnaire, F. I.; Puigdefábregas, J.; Emlen, J.
2000-01-01
This paper investigates allocation of energy to mechanisms that generate and preserve architectural forms (i.e. developmental stability, complexity of branching patterns) and productivity (growth and reproduction) in response to environmental disturbances (i.e. grazing and resource availability). The statistical error in translational symmetry was used to detect random intra-individual variability during development. This can be thought of as a measure of developmental instability caused by stress. Additionally, we use changes in fractal complexity and shoot distribution of branch structures as an alternate indicator of stress. These methods were applied to Anthyllis cytisoides L., a semi-arid environment shrub, to ascertain the effect of grazing and slope exposure on developmental traits in a 2×2 factorial design. The results show that A. cytisoidesmaintains developmental stability at the expense of productivity. Anthyllis cytisoides was developmentally more stable when grazed and when on south-facing, as opposed to north-facing slopes. On the contrary, shoot length, leaf area, fractal dimension and reproductive-to-vegetative allocation ratio were larger in north- than in south-facing slopes. As a consequence, under extreme xeric conditions, shrub mortality increased in north-facing slopes, especially when not grazed. The removal of transpiring area and the reduction of plant competition favoured developmental stability and survival in grazed plants. Differences between grazed and ungrazed plants were most evident in more mesic (north-facing) areas.
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Systems Characterization of Combustor Instabilities With Controls Design Emphasis
NASA Technical Reports Server (NTRS)
Kopasakis, George
2004-01-01
This effort performed test data analysis in order to characterize the general behavior of combustor instabilities with emphasis on controls design. The analysis is performed on data obtained from two configurations of a laboratory combustor rig and from a developmental aero-engine combustor. The study has characterized several dynamic behaviors associated with combustor instabilities. These are: frequency and phase randomness, amplitude modulations, net random phase walks, random noise, exponential growth and intra-harmonic couplings. Finally, the very cause of combustor instabilities was explored and it could be attributed to a more general source-load type impedance interaction that includes the thermo-acoustic coupling. Performing these characterizations on different combustors allows for more accurate identification of the cause of these phenomena and their effect on instability.
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Fluctuating Asymmetry and General Intelligence: No Genetic or Phenotypic Association
ERIC Educational Resources Information Center
Johnson, Wendy; Segal, Nancy L.; Bouchard, Thomas J., Jr.
2008-01-01
Fluctuating asymmetry (FA) is the non-pathological left-right asymmetry of body traits that are usually left-right symmetrical, such as eye breadths and elbow to wrist lengths in humans, but which can be affected by developmental stressors. It is generally considered throughout biology to be an indicator of developmental instability and thus of…
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Marsee, Kevin; Woodruff, Tracey J.; Axelrad, Daniel A.; Calafat, Antonia M.; Swan, Shanna H.
2006-01-01
Phthalate diesters have been shown to be developmental and reproductive toxicants in animal studies. A recent epidemiologic study showed certain phthalates to be significantly associated with reduced anogenital distance in human male infants, the first evidence of subtle developmental effects in human male infants exposed prenatally to phthalates. We used two previously published methods to estimate the daily phthalate exposures for the four phthalates whose urinary metabolites were statistically significantly associated with developmental effects in the 214 mother–infant pairs [di-n-butyl phthalate (DnBP), diethyl phthalate (DEP), butylbenzyl phthalate (BBzP), diisobutyl phthalate (DiBP)] and for another important phthalate [di-2-ethylhexyl phthalate (DEHP)]. We estimated the median and 95th percentile of daily exposures to DBP to be 0.99 and 2.68 μg/kg/day, respectively; for DEP, 6.64 and 112.3 μg/kg/day; for BBzP, 0.50 and 2.47 μg/kg/day; and for DEHP, 1.32 and 9.32 μg/kg/day. The U.S. Environmental Protection Agency (EPA) reference doses for these chemicals are 100 (DBP), 800 (DEP), 200 (BBzP), and 20 (DEHP) μg/kg/day. The median and 95th percentile exposure estimates for the phthalates associated with reduced anogenital distance in the study population are substantially lower than current U.S. EPA reference doses for these chemicals and could be informative to any updates of the hazard assessments and risk assessments for these chemicals. PMID:16759976
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Thiffault, Isabelle; Saunders, Carol; Jenkins, Janda; Raje, Nikita; Canty, Kristi; Sharma, Mukta; Grote, Lauren; Welsh, Holly I; Farrow, Emily; Twist, Greyson; Miller, Neil; Zwick, David; Zellmer, Lee; Kingsmore, Stephen F; Safina, Nicole P
2015-05-07
Chromosome instability syndromes are a group of inherited conditions associated with chromosomal instability and breakage, often leading to immunodeficiency, growth retardation and increased risk of malignancy. We performed exome sequencing on a girl with a suspected chromosome instability syndrome that manifested as growth retardation, microcephaly, developmental delay, dysmorphic features, poikiloderma, immune deficiency with pancytopenia, and myelodysplasia. She was homozygous for a previously reported splice variant, c.4444 + 3A > G in the POLE1 gene, which encodes the catalytic subunit of DNA polymerase E. This is the second family with POLE1-deficency, with the affected individual demonstrating a more severe phenotype than previously described.
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Kubilus, James K.; Zapater i Morales, Carolina; Linsenmayer, Thomas F.
2017-01-01
Purpose During development, the corneal epithelium (CE) and the conjunctiva are derived from the surface ectoderm. Here we have examined how, during development, the cells of these two issues become isolated from each other. Methods Epithelia from the anterior eyes of chicken embryos were labeled with the fluorescent, lipophilic dye, 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI). DiI was placed on the epithelial surface of the developing anterior eye and its diffusion was monitored by fluorescence microscopy. Concomitant morphologic changes in the surface cells of these epithelial were examined by scanning electron microscopy. Immunofluorescence was used to analyze the expression of cytokeratin K3, ZO-1, N-cadherin and Connexin-43 and the function of gap junctions was analyzed using a cut-loading with the fluorescent dye rhodamine-dextran. Results Prior to embryonic day 8 (E8), DiI placed on the surface of the CE spreads throughout all the epithelial cells of the anterior eye. When older eyes were similarly labeled, dye diffusion was restricted to the CE. Similarly, diffusion of DiI placed on the conjunctival surface after E8 was restricted to the conjunctiva. Scanning electron microscopy showed that developmentally (1) physical separations progressively form between the cells of the CE and those of the conjunctiva, and (2) by E8 these separations form a ring that completely encompasses the cornea. The functional restriction of gap junctions between these tissues did not occur until E14. Conclusions During ocular development, a barrier to the diffusion of DiI forms between the contiguous CE and conjunctiva prior to the differential expression of gap junctions within these tissues. PMID:28319640
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Toward a definition of affective instability.
Renaud, Suzane M; Zacchia, Camillo
2012-01-01
Affective instability is a psychophysiological symptom observed in some psychopathologies. It is a complex construct that encompasses (1) primary emotions, or affects, and secondary emotions, with each category having its own characteristics, amplitude, and duration, (2) rapid shifting from neutral or valenced affect to intense affect, and (3) dysfunctional modulation of emotions. Affective instability is often confused with mood lability, as in bipolar disorders, as well as with other terms. To clarify the concept, we searched databases for the term affective instability and read related articles on the topic. In this article we situate the term within the current affective nomenclature and human emotional experience, explore its psychophysiological features, and place it within the context of psychopathology. We explain why the term can potentially be confused with mood pathology and then define affective instability as an inherited temperamental trait modulated by developmental experience.
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Bacterial Signal Transduction by Cyclic Di-GMP and Other Nucleotide Second Messengers
Gründling, Angelika; Jenal, Urs; Ryan, Robert; Yildiz, Fitnat
2015-01-01
The first International Symposium on c-Di-GMP Signaling in Bacteria (22 to 25 March 2015, Harnack-Haus, Berlin, Germany) brought together 131 molecular microbiologists from 17 countries to discuss recent progress in our knowledge of bacterial nucleotide second messenger signaling. While the focus was on signal input, synthesis, degradation, and the striking diversity of the modes of action of the current second messenger paradigm, i.e., cyclic di-GMP (c-di-GMP), “classics” like cAMP and (p)ppGpp were also presented, in novel facets, and more recent “newcomers,” such as c-di-AMP and c-AMP-GMP, made an impressive appearance. A number of clear trends emerged during the 30 talks, on the 71 posters, and in the lively discussions, including (i) c-di-GMP control of the activities of various ATPases and phosphorylation cascades, (ii) extensive cross talk between c-di-GMP and other nucleotide second messenger signaling pathways, and (iii) a stunning number of novel effectors for nucleotide second messengers that surprisingly include some long-known master regulators of developmental pathways. Overall, the conference made it amply clear that second messenger signaling is currently one of the most dynamic fields within molecular microbiology, with major impacts in research fields ranging from human health to microbial ecology. PMID:26055111
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Distinguishing mechanisms for alternans in cardiac cells using constant-diastolic-interval pacing
NASA Astrophysics Data System (ADS)
Cherry, Elizabeth M.
2017-09-01
Alternans, a proarrhythmic dynamical state in which cardiac action potentials alternate between long and short durations despite a constant pacing period, traditionally has been explained at the cellular level using nonlinear dynamics principles under the assumption that the action potential duration (APD) is determined solely by the time elapsed since the end of the previous action potential, called the diastolic interval (DI). In this scenario, APDs at a steady state should be the same provided that the preceding DIs are the same. Nevertheless, experiments attempting to eliminate alternans by dynamically adjusting the timing of pacing stimuli to keep the DI constant showed that alternans persisted, contradicting the traditional theory. It is now widely known that alternans also can arise from a different mechanism associated with intracellular calcium cycling. Our goal is to determine whether intracellular calcium dynamics can explain the experimental findings regarding the persistence of alternans despite a constant DI. For this, we use mathematical models capable of producing alternans through both voltage- and calcium-mediated mechanisms. We show that for voltage-driven alternans, action potentials elicited from a constant-DI protocol are always the same. However, in the case of calcium-driven alternans, the constant-DI protocol can result in alternans. Reducing the strength of the calcium instability progressively reduces and finally eliminates constant-DI alternans. Our findings suggest that screening for the presence of alternans using a constant-DI protocol has the potential for differentiating between voltage-driven and calcium-driven alternans.
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Leite, Ana Julia Cunha; Pinto, Irene Plaza; Cunha, Damiana Mirian da Cruz e; Ribeiro, Cristiano Luiz; da Silva, Claudio Carlos; da Cruz, Aparecido Divino; Minasi, Lysa Bernardes
2016-01-01
The chromosome 22q11.2 region has long been implicated in genomic diseases. Some genomic regions exhibit numerous low copy repeats with high identity in which they provide increased genomic instability and mediate deletions and duplications in many disorders. DiGeorge Syndrome is the most common deletion syndrome and reciprocal duplications could be occurring in half of the frequency of microdeletions. We described five patients with phenotypic variability that carries deletions or reciprocal duplications at 22q11.2 detected by Chromosomal Microarray Analysis. The CytoScan HD technology was used to detect changes in the genome copy number variation of patients who had clinical indication to global developmental delay and a normal karyotype. We observed in our study three microdeletions and two microduplications in 22q11.2 region with variable intervals containing known genes and unstudied transcripts as well as the LCRs that are often flanking and within this genomic rearrangement. The identification of these variants is of particular interest because it may provide insight into genes or genomic regions that are crucial for specific phenotypic manifestations and are useful to assist in the quest for understanding the mechanisms subjacent to genomic deletions and duplications. PMID:27123452
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Experimental Replication of an Aeroengine Combustion Instability
NASA Technical Reports Server (NTRS)
Cohen, J. M.; Hibshman, J. R.; Proscia, W.; Rosfjord, T. J.; Wake, B. E.; McVey, J. B.; Lovett, J.; Ondas, M.; DeLaat, J.; Breisacher, K.
2000-01-01
Combustion instabilities in gas turbine engines are most frequently encountered during the late phases of engine development, at which point they are difficult and expensive to fix. The ability to replicate an engine-traceable combustion instability in a laboratory-scale experiment offers the opportunity to economically diagnose the problem (to determine the root cause), and to investigate solutions to the problem, such as active control. The development and validation of active combustion instability control requires that the causal dynamic processes be reproduced in experimental test facilities which can be used as a test bed for control system evaluation. This paper discusses the process through which a laboratory-scale experiment was designed to replicate an instability observed in a developmental engine. The scaling process used physically-based analyses to preserve the relevant geometric, acoustic and thermo-fluid features. The process increases the probability that results achieved in the single-nozzle experiment will be scalable to the engine.
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The purpose of the Center is to provide timely, unbiased, scientifically sound evaluations of human and experimental evidence for adverse effects on reproduction and development caused by agents to which humans may be exposed.
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Lung, For-Wey; Chen, Po-Fei; Shu, Bih-Ching
2012-08-01
This study aimed to investigate the concurrent validity of the parent-report Taiwan Birth Cohort Study Developmental Instrument (TBCS-DI) with the Bayley Scales of Infant Development-Second Edition (BSID-II) and the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R) at 6, 18, 36, and 60 months. 100 children were recruited at 6 months, 88 children followed-up at 18 months, 71 at 36 months, and 53 at 60 months. Longitudinally, the parent-report TBCS-DI, with the professional psychological assessments of the BSID-II and the WPPSI-R showed predictive validity. Looking at each time point in cross section, at 6 and 18 months the TBCS-DI had good concurrent validity with the BSID-II, and at 36 and 60 months the TBCS-DI was correlated only with the motor and performance domains of the BSID-II and WPPSI-R. With further investigation, the TBCS-DI may be used both in research and in clinical settings.
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IMMUNE FUNCTION IN RATS DEVELOPMENTALLY EXPOSED TO DIBUTYLTIN DICHLORIDE
Organotins are used commercially as pesticides, antifouling agents and stabilizers for polyvinyl chloride (PVC) pipe. Mono- and di-substituted methyl and butyltins, used in PVC pipe production, are of concern to the USEPA as they leach from supply pipes into drinking water and ha...
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Effectiveness of Four Instructional Programs Designed to Serve English Learners
ERIC Educational Resources Information Center
Valentino, Rachel A.; Reardon, Sean F.
2015-01-01
This article investigates the differences in academic achievement trajectories from elementary through middle school among English Learner (EL) students in four different instructional programs: English Immersion (EI), Transitional Bilingual (TB), Developmental Bilingual (DB), and Dual Immersion (DI). Comparing students with the same parental…
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Developmental instability and schizotypy.
Rosa, A; van Os, J; Fañanás, L; Barrantes, N; Caparrós, B; Gutiérrez, B; Obiols, J
2000-06-16
It has been suggested that evidence of developmental disturbance of cognition and lateralisation in schizophrenia can be best understood from the perspective of developmental stability (DS), an indicator of the extent to which an individual develops according to a specified ontogenic programme in the presence of environmental noise. Higher levels of fluctuating asymmetry (FA; the difference between right and left side of a quantitative morphological trait such as dermatoglyphics) are thought to reflect less DS. We examined this issue for dimensions of schizotypy. Associations between FA, measures of laterality and cognitive function on the one hand, and negative and positive dimensions of schizotypy on the other, were examined in a sample of 260 healthy adolescents aged 11.9-15.6years. FA was measured as a-b ridge count right-left differences. Neuropsychological measures yielded a general cognitive ability score and a frontal function score. Laterality was assessed with the Annett scale. Measures of psychosis proneness were normally distributed. Negative schizotypy was associated with more FA and lower general cognitive ability in a dose-response fashion. The association with FA was more apparent in boys. No associations existed with laterality or frontal function. The negative dimension of schizotypy may be associated with early developmental instability, resembling the pattern seen in the negative symptom dimension of schizophrenia. Measures of fluctuating asymmetry may be more sensitive with regard to the schizotypy phenotype than measures of laterality.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Gilardi, E.; Cimorelli, L.
1963-07-01
The dynamic behavior of an integrated, pressurizedwater reactor with natural circulation was investigated both by analog computer techniques and a simplified analytical approach. Hydraulic instabilities due to the core or riser were considered, as well as overall stability and problems arising from heavy sea conditions. (auth)
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Fast instability caused by electron cloud in combined function magnets
Antipov, S. A.; Adamson, P.; Burov, A.; ...
2017-04-10
One of the factors which may limit the intensity in the Fermilab Recycler is a fast transverse instability. It develops within a hundred turns and, in certain conditions, may lead to a beam loss. The high rate of the instability suggest that its cause is electron cloud. Here, we studied the phenomena by observing the dynamics of stable and unstable beam, simulating numerically the build-up of the electron cloud, and developed an analytical model of an electron cloud driven instability with the electrons trapped in combined function di-poles. We also found that beam motion can be stabilized by a clearingmore » bunch, which confirms the electron cloud nature of the instability. The clearing suggest electron cloud trapping in Recycler combined function mag-nets. Numerical simulations show that up to 1% of the particles can be trapped by the magnetic field. Since the process of electron cloud build-up is exponential, once trapped this amount of electrons significantly increases the density of the cloud on the next revolution. Furthermore, in a Recycler combined function dipole this multi-turn accumulation allows the electron cloud reaching final intensities orders of magnitude greater than in a pure dipole. The estimated resulting instability growth rate of about 30 revolutions and the mode fre-quency of 0.4 MHz are consistent with experimental observations and agree with the simulation in the PEI code. The created instability model allows investigating the beam stability for the future intensity upgrades.« less
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Fast instability caused by electron cloud in combined function magnets
DOE Office of Scientific and Technical Information (OSTI.GOV)
Antipov, S. A.; Adamson, P.; Burov, A.
One of the factors which may limit the intensity in the Fermilab Recycler is a fast transverse instability. It develops within a hundred turns and, in certain conditions, may lead to a beam loss. The high rate of the instability suggest that its cause is electron cloud. Here, we studied the phenomena by observing the dynamics of stable and unstable beam, simulating numerically the build-up of the electron cloud, and developed an analytical model of an electron cloud driven instability with the electrons trapped in combined function di-poles. We also found that beam motion can be stabilized by a clearingmore » bunch, which confirms the electron cloud nature of the instability. The clearing suggest electron cloud trapping in Recycler combined function mag-nets. Numerical simulations show that up to 1% of the particles can be trapped by the magnetic field. Since the process of electron cloud build-up is exponential, once trapped this amount of electrons significantly increases the density of the cloud on the next revolution. Furthermore, in a Recycler combined function dipole this multi-turn accumulation allows the electron cloud reaching final intensities orders of magnitude greater than in a pure dipole. The estimated resulting instability growth rate of about 30 revolutions and the mode fre-quency of 0.4 MHz are consistent with experimental observations and agree with the simulation in the PEI code. The created instability model allows investigating the beam stability for the future intensity upgrades.« less
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Campbell, W.B.; Emlen, J.M.; Hershberger, W.K.
1998-01-01
Developmental stability, or homeostasis, facilitates the production of consistent phenotypes by buffering against stress. Fluctuating asymmetry is produced by developmental instability and is manifested as small random departures from bilateral symmetry. Increased fluctuating asymmetry is thought to parallel compromised fitness, in part, because stress promotes energy dissipation. Compensatory energy expenditures within the organism are required to complete development, thus promoting instability through reductions in homeostasis. Increased heterozygosity may enhance developmental stability by reducing energy dissipation from stress through increased metabolic efficiency, possibly by providing greater flexibility in metabolic pathways. Traditionally, fluctuating asymmetry has been used as a bioindicator of chronic stress, provided that selective mortality of less fit individuals did not reduce stress-mediated increases in fluctuating asymmetry to background levels produced by natural developmental error, or create data inconsistencies such as higher asymmetry in groups exposed to lower stress. Unfortunately, absence of selective mortality and its effects, while often assumed, can be difficult to substantiate. We integrated measures of early growth, mortality, fluctuating asymmetry (mandibular pores, pectoral finrays, pelvic finrays, and gillrakers on the upper and lower arms of the first branchial arch) and directional asymmetry (branchiostegal rays) to assess chronic thermal stress (fluctuating temperatures as opposed to ambient temperatures) in developing eggs from two different coho salmon (Oncorhynchus kisutch) stocks and their reciprocal hybrids. Hybridization provided insight on the capacity of heterozygosity to reduce stress during development. Although egg losses were consistently higher in crosses exposed to fluctuating temperatures, egg mortality was predominantly a function of maternal stock of origin. Post-hatch losses were higher in crosses exposed to ambient temperatures than in crosses exposed to fluctuating temperatures during embryogenesis. Observed patterns of early growth revealed no heterosis, but instead reflected maternal effects, with some crosses slowing growth and yolk utilization when exposed to fluctuating temperatures. Analyses of fluctuating asymmetry also showed no effects from heterosis. While analyses of composite asymmetry scores and branchiostegal rays were inconclusive, analyses of individual characters showed significantly higher fluctuating asymmetry in pelvic finray counts and a marginal change in the numbers of fish asymmetric for this character in crosses exposed to chronic thermal stress. In contrast, the fluctuating asymmetry in lower gillraker counts was significantly higher in crosses exposed to ambient temperatures and there were significantly more fish asymmetric for this character. Data on mortalities and fluctuating asymmetry indicate pelvic finray development was thermally stressed, while the heightened fluctuating asymmetry in lower gillraker counts under ambient temperatures was due to a greater frequency of less fit fish that had not been culled by thermal stress. Changes in early growth patterns in response to developmental stress yielded no parallel responses in meristic characters. We conclude that chronic thermal stress produced both selectively lethal and sublethal effects that directly shaped fluctuating asymmetry and fitness profiles in these crosses. Implicit in this conclusion is that developmental instability analyses can detect more than just chronic sublethal stress, thus providing substantial credence for using instability studies as proactive bioassessment methodologies.
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MYSTERIES OF THE HUMAN FETUS REVEALED
SANDMAN, CURT A
2015-01-01
The impressive program of research from the DiPietro laboratory succeeds in its aim to document the ontogeny of human fetal neurobehavioral development. From studies of great depth and breadth, and wielding creative methods of assessment, DiPietro et al open a window into the largely inaccessible developing human fetal brain. This commentary, with reference to the seminal cardiovascular studies of the Lacey's, supports the measures of the fetal heart to index fetal well-being and to provide evidence of stimulus processing. A separate case is made that the DiPietro program provides unique and invaluable information for assessing the influential Developmental Origins of Health and Disease or Fetal Programming Models. The goal of these models, to predict or understand the influences of early experience or response patterns on later postnatal life, is identical to the ultimate goal of the DiPietro program. Because human fetal behavior is uncontaminated by socialization or parenting or peers, it may be the best reflection of fetal exposures. The remarkable neurobehavioral profiles generated by the DiPietro program can make a critical contribution to the Fetal Programming Model in terms of sensitive and critical periods of nervous system vulnerability and to specify gestational periods of neurobehavioral risk.. PMID:26303720
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Hip instability: a review of hip dysplasia and other contributing factors
Kraeutler, Matthew J.; Garabekyan, Tigran; Pascual-Garrido, Cecilia; Mei-Dan, Omer
2016-01-01
Summary Background Hip instability has classically been associated with developmental dysplasia of the hip (DDH) in newborns and children. However, numerous factors may contribute to hip instability in children, adolescents, and adults. Purpose This review aims to concisely present the literature on hip instability in patients of all ages in order to guide health care professionals in the appropriate diagnosis and treatment of the various disorders which may contribute to an unstable hip. Methods We reviewed the literature on the diagnosis and surgical management of hip dysplasia and other causes of hip instability. Conclusions Multiple intra- and extra-articular variables may contribute to hip instability, including acetabular bony coverage, femoral torsion, femoroacetabular impingement, and soft tissue laxity. Physical examination and advanced imaging studies are essential to accurately diagnose the pathology contributing to a patient’s unstable hip. Conservative management, including activity modification and physical therapy, may be used as a first-line treatment in patients with intra-articular hip pathology. Patients who continue to experience symptoms of pain or instability should proceed with arthroscopic or open surgical treatment aimed at correcting the underlying pathology. Level of evidence V. PMID:28066739
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Characterization of a developmental toxicity dose-response model.
Faustman, E M; Wellington, D G; Smith, W P; Kimmel, C A
1989-01-01
The Rai and Van Ryzin dose-response model proposed for teratology experiments has been characterized for its appropriateness and applicability in modeling the dichotomous response data from developmental toxicity studies. Modifications were made in the initial probability statements to reflect more accurately biological events underlying developmental toxicity. Data sets used for the evaluation were obtained from the National Toxicology Program and U.S. EPA laboratories. The studies included developmental evaluations of ethylene glycol, diethylhexyl phthalate, di- and triethylene glycol dimethyl ethers, and nitrofen in rats, mice, or rabbits. Graphic examination and statistical evaluation demonstrate that this model is sensitive to the data when compared to directly measured experimental outcomes. The model was used to interpolate to low-risk dose levels, and comparisons were made between the values obtained and the no-observed-adverse-effect levels (NOAELs) divided by an uncertainty factor. Our investigation suggests that the Rai and Van Ryzin model is sensitive to the developmental toxicity end points, prenatal deaths, and malformations, and appears to model closely their relationship to dose. PMID:2707204
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Novel Spoken Word Learning in Adults with Developmental Dyslexia
ERIC Educational Resources Information Center
Conner, Peggy S.
2013-01-01
A high percentage of individuals with dyslexia struggle to learn unfamiliar spoken words, creating a significant obstacle to foreign language learning after early childhood. The origin of spoken-word learning difficulties in this population, generally thought to be related to the underlying literacy deficit, is not well defined (e.g., Di Betta…
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Dose Range-Finding Developmental Toxicity (Segment II) Study of WR242511 in Rabbits
1994-07-26
NA = Not applicable R = Right NK = Neck PT = Protruded tongue CP = Cleft palate N = No visible L = Left HL = Hind limb SB = Spina bifida CL = Cleft ... lip abnormalities M = Male FL = Fore limb SUBQ = Subcutaneous HT = Hematoma A = Alive F = Female DI = Digit P = Petechial EX = Exophthalmos D
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DEHP, dibutyl (DBP)-, and benzyl butyl (BBP)- phthalate are plasticizers that cause adverse developmental reproductive effects in laboratory animals. They alter sexual differentiation in the rat by reducing fetal Leydig cell testosterone synthesis and insl3 mRNA levels, which in ...
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ERIC Educational Resources Information Center
DeVries, Rheta; And Others
This study examined the interactions between teachers and children in three kindergarten classrooms. Programs used in the classrooms were: a direct-instruction (DI) program, representing a cultural transmission paradigm; a contructivist program (CON), representing the cognitive-developmental paradigm; and an eclectic program (ECL), combining…
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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...
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Fluctuating asymmetry and stress in a medieval Nubian population.
Deleon, Valerie B
2007-04-01
Fluctuating asymmetry is commonly used as a bioindicator of developmental stress. This study addresses asymmetry under nutritional/systemic stress in the human craniofacial skeleton and its utility as an indicator of developmental instability. Crania from the diachronic Christian cemeteries at Kulubnarti (Sudanese Nubia) were chosen as a model for nutrition/systemic stress. Previous studies indicate that individuals from the Early Christian cemetery were subjected to greater developmental stress when compared with individuals from the Late Christian cemetery. Therefore, crania from the Early Christian cemetery should display a greater magnitude of fluctuating asymmetry than crania from the Late Christian cemetery. Thirty adult crania of comparable age and sex were selected from each population. Landmark coordinates were digitized in two separate trials and averaged to minimize error. Euclidean distance matrix analysis (EDMA) was used to measure and compare the magnitude of fluctuating asymmetry in each sample. Results indicate that crania from the Early Christian cemetery display greater amounts of fluctuating asymmetry than those from the Late Christian cemetery, as predicted. The degree of fluctuating asymmetry for each linear distance is highly correlated between the cemeteries, suggesting that all humans may share common patterns of fluctuating asymmetry in the skull. In contrast, there is little correlation between magnitude of fluctuating asymmetry and length of linear distance, between-subject variability, or measurement error. These results support the hypothesis that poor nutrition/systemic stress increases developmental instability in the human skull and that increased fluctuating asymmetry constitutes morphological evidence of this stress.
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Robust and irreversible development in cell society as a general consequence of intra-inter dynamics
NASA Astrophysics Data System (ADS)
Kaneko, Kunihiko; Furusawa, Chikara
2000-05-01
A dynamical systems scenario for developmental cell biology is proposed, based on numerical studies of a system with interacting units with internal dynamics and reproduction. Diversification, formation of discrete and recursive types, and rules for differentiation are found as a natural consequence of such a system. “Stem cells” that either proliferate or differentiate to different types stochastically are found to appear when intra-cellular dynamics are chaotic. Robustness of the developmental process against microscopic and macroscopic perturbations is shown to be a natural consequence of such intra-inter dynamics, while irreversibility in developmental process is discussed in terms of the gain of stability, loss of diversity and chaotic instability.
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Anelastic and Compressible Simulation of Moist Dynamics at Planetary Scales
NASA Astrophysics Data System (ADS)
Kurowski, M.; Smolarkiewicz, P. K.; Grabowski, W.
2015-12-01
Moist anelastic and compressible numerical solutions to the planetary baroclinic instability and climate benchmarks are compared. The solutions are obtained applying a consistent numerical framework for dis- crete integrations of the various nonhydrostatic flow equations. Moist extension of the baroclinic instability benchmark is formulated as an analog of the dry case. Flow patterns, surface vertical vorticity and pressure, total kinetic energy, power spectra, and total amount of condensed water are analyzed. The climate bench- mark extends the baroclinic instability study by addressing long-term statistics of an idealized planetary equilibrium and associated meridional transports. Short-term deterministic anelastic and compressible so- lutions differ significantly. In particular, anelastic baroclinic eddies propagate faster and develop slower owing to, respectively, modified dispersion relation and abbreviated baroclinic vorticity production. These eddies also carry less kinetic energy, and the onset of their rapid growth occurs later than for the compressible solutions. The observed differences between the two solutions are sensitive to initial conditions as they di- minish for large-amplitude excitations of the instability. In particular, on the climatic time scales, the anelastic and compressible solutions evince similar zonally averaged flow patterns with the matching meridional transports of entropy, momentum, and moisture.
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Characterization of branch complexity by fractal analyses
Alados, C.L.; Escos, J.; Emlen, J.M.; Freeman, D.C.
1999-01-01
The comparison between complexity in the sense of space occupancy (box-counting fractal dimension D(c) and information dimension D1) and heterogeneity in the sense of space distribution (average evenness index f and evenness variation coefficient J(cv)) were investigated in mathematical fractal objects and natural branch structures. In general, increased fractal dimension was paired with low heterogeneity. Comparisons between branch architecture in Anthyllis cytisoides under different slope exposure and grazing impact revealed that branches were more complex and more homogeneously distributed for plants on northern exposures than southern, while grazing had no impact during a wet year. Developmental instability was also investigated by the statistical noise of the allometric relation between internode length and node order. In conclusion, our study demonstrated that fractal dimension of branch structure can be used to analyze the structural organization of plants, especially if we consider not only fractal dimension but also shoot distribution within the canopy (lacunarity). These indexes together with developmental instability analyses are good indicators of growth responses to the environment.
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Demonstration of Active Combustion Control
NASA Technical Reports Server (NTRS)
Lovett, Jeffrey A.; Teerlinck, Karen A.; Cohen, Jeffrey M.
2008-01-01
The primary objective of this effort was to demonstrate active control of combustion instabilities in a direct-injection gas turbine combustor that accurately simulates engine operating conditions and reproduces an engine-type instability. This report documents the second phase of a two-phase effort. The first phase involved the analysis of an instability observed in a developmental aeroengine and the design of a single-nozzle test rig to replicate that phenomenon. This was successfully completed in 2001 and is documented in the Phase I report. This second phase was directed toward demonstration of active control strategies to mitigate this instability and thereby demonstrate the viability of active control for aircraft engine combustors. This involved development of high-speed actuator technology, testing and analysis of how the actuation system was integrated with the combustion system, control algorithm development, and demonstration testing in the single-nozzle test rig. A 30 percent reduction in the amplitude of the high-frequency (570 Hz) instability was achieved using actuation systems and control algorithms developed within this effort. Even larger reductions were shown with a low-frequency (270 Hz) instability. This represents a unique achievement in the development and practical demonstration of active combustion control systems for gas turbine applications.
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Risk and Protective Processes Predicting Rural African American Young Men's Substance Abuse.
Cho, Junhan; Kogan, Steven M
2016-12-01
Informed by a life course perspective, this study tested a cascade model linking harsh, unresponsive parenting during childhood to young African American men's substance abuse via precocious transitions, economic instability, and future orientation. The moderating influence of community disadvantage and romantic partner support on the hypothesized pathways was also examined. At the baseline, the sample included 505 African American men between ages 19 and 22 years from high-poverty rural communities. Follow-up data were collected 18 months after baseline. Using structural equation modeling, we identified harsh, unresponsive parenting influenced precocious transitions in adolescence, which in turn increased economic instability during young adulthood. Economic instability was associated with a reduction in future orientation, a proximal influence on increases in substance abuse. Also, residence in a disadvantaged community amplified the influence of precocious transitions on economic instability and the influence of economic instability on future orientation. Involvement with supportive romantic partnership evinced a protective effect, attenuating the influence of precocious transitions on economic instability and the influence of economic instability on a future orientation. This study expands understanding of young adults' substance abuse by demonstrating the risk and protective processes linking substance abuse to developmental factors across childhood, adolescence, and young adulthood. © Society for Community Research and Action 2016.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Tonk, Elisa C.M., E-mail: ilse.tonk@rivm.nl; Laboratory for Health Protection Research, National Institute for Public Health and the Environment; Verhoef, Aart
The developing immune system displays a relatively high sensitivity as compared to both general toxicity parameters and to the adult immune system. In this study we have performed such comparisons using di(2-ethylhexyl) phthalate (DEHP) as a model compound. DEHP is the most abundant phthalate in the environment and perinatal exposure to DEHP has been shown to disrupt male sexual differentiation. In addition, phthalate exposure has been associated with immune dysfunction as evidenced by effects on the expression of allergy. Male wistar rats were dosed with corn oil or DEHP by gavage from postnatal day (PND) 10–50 or PND 50–90 atmore » doses between 1 and 1000 mg/kg/day. Androgen-dependent organ weights showed effects at lower dose levels in juvenile versus adult animals. Immune parameters affected included TDAR parameters in both age groups, NK activity in juvenile animals and TNF-α production by adherent splenocytes in adult animals. Immune parameters were affected at lower dose levels compared to developmental parameters. Overall, more immune parameters were affected in juvenile animals compared to adult animals and effects were observed at lower dose levels. The results of this study show a relatively higher sensitivity of juvenile versus adult rats. Furthermore, they illustrate the relative sensitivity of the developing immune system in juvenile animals as compared to general toxicity and developmental parameters. This study therefore provides further argumentation for performing dedicated developmental immune toxicity testing as a default in regulatory toxicology. -- Highlights: ► In this study we evaluate the relative sensitivities for DEHP induced effects. ► Results of this study demonstrate the age-dependency of DEHP toxicity. ► Functional immune parameters were more sensitive than structural immune parameters. ► Immune parameters were affected at lower dose levels than developmental parameters. ► Findings demonstrate the susceptibility of the developing immune system for DEHP.« less
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MYSTERIES OF THE HUMAN FETUS REVEALED.
Sandman, Curt A
2015-09-01
The impressive program of research from the DiPietro laboratory succeeds in its aim to document the ontogeny of human fetal neurobehavioral development. From studies of great depth and breadth, and wielding creative methods of assessment, DiPietro et al. open a window into the largely inaccessible developing human fetal brain. This commentary, with reference to the seminal cardiovascular studies of the Laceys, supports the measures of the fetal heart to index fetal well-being and to provide evidence of stimulus processing. A separate case is made that the DiPietro program provides unique and invaluable information for assessing the influential Developmental Origins of Health and Disease or Fetal Programming Models. The goal of these models, to predict or understand the influences of early experience or response patterns on later postnatal life, is identical to the ultimate goal of the DiPietro program. Because human fetal behavior is uncontaminated by socialization or parenting or peers, it may be the best reflection of fetal exposures. The remarkable neurobehavioral profiles generated by the DiPietro program can make a critical contribution to the Fetal Programming Model in terms of sensitive and critical periods of nervous system vulnerability and to specify gestational periods of neurobehavioral risk. © 2015 The Society for Research in Child Development, Inc.
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Genomic Instability at Premalignant and Early Stages of Breast Cancer Development
1999-08-01
by routine DNA flow cytometry vation. ERBB2 expression was detected with a to determine DNA index (DI). commercially available antibody (Oncogene Sci...supplements the information gained from ic microsatellite primers. We observed that the ploidy analysis by DNA flow cytometry alone. In DNA so obtained...preserved the proportionality of many cases where flow cytometry could not be per- the different alleles as found in the original sample. formed because the
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Discovery of Genomic Breakpoints Affecting Breast Cancer Progression and Prognosis
2010-10-01
mutations compared to those detected by the 5Kbp method alone. Fosmid diTag method also reveals much higher proportion of gene fusions and truncations...observed highly similar structural mutational spectra affecting different sets of genes , pointing to similar histories of genomic instability against... mutations have been identified in non-BRCA1/2 multiethnic breast cancer cases (45,46), no truncating mutation of the RAP80 gene in breast cancer has
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Organotins are used commercially as pesticides, antifouling agents and stabilizers for polyvinyl chloride (PVC) pipe. Mono- and di-substituted methyl and butyltins, used in PVC pipe production, are of concern to the U.S. EPA as they leach from supply pipes into drinking water an...
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Family Instability and Child Well-Being
ERIC Educational Resources Information Center
Fomby, Paula; Cherlin, Andrew J.
2007-01-01
Children who experience multiple transitions in family structure may face worse developmental outcomes than children raised in stable, two-parent families, and perhaps even worse than children raised in stable, single-parent families--a point denoted in much prior research. Multiple transitions and negative child outcomes, however, may be…
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The quest for four-dimensional imaging in plant cell biology: it's just a matter of time
Domozych, David S.
2012-01-01
Background Analysis of plant cell dynamics over time, or four-dimensional imaging (4-DI), represents a major goal of plant science. The ability to resolve structures in the third dimension within the cell or tissue during developmental events or in response to environmental or experimental stresses (i.e. 4-DI) is critical to our understanding of gene expression, post-expression modulations of macromolecules and sub-cellular system interactions. Scope Microscopy-based technologies have been profoundly integral to this type of investigation, and new and refined microscopy technologies now allow for the visualization of cell dynamics with unprecedented resolution, contrast and experimental versatility. However, certain realities of light and electron microscopy, choice of specimen and specimen preparation techniques limit the scope of readily attaining 4-DI. Today, the plant microscopist must use a combinatorial strategy whereby multiple microscopy-based investigations are used. Modern fluorescence, confocal laser scanning, transmission electron and scanning electron microscopy provide effective conduits for synthesizing data detailing live cell dynamics and highly resolved snapshots of specific cell structures that will ultimately lead to 4-DI. This review provides a synopsis of such technologies available. PMID:22628381
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ERIC Educational Resources Information Center
Henry, Sara Kathleen
2010-01-01
Postsecondary education marks a transitional time in the lives of young adults. During this time, traditional-aged college students confront a substantial number of developmental challenges that are extraordinarily diverse and complex (Evans, Forney, & Guido-DiBrito, 1998). Erikson's (1968) theory of psychosocial development posited that the major…
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ERIC Educational Resources Information Center
Tyler, Catherine L.; Tyler, J. Michael
2006-01-01
Although there is widespread agreement on the importance of ethics instruction in business education, there is not agreement on the best approach or timing of instruction. This article uses J. O. Prochaska and DiClemente's transtheoretical model of change as the basis for a developmental model of student readiness for learning about ethics. By…
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Cryptorchidism is a fairly common human malformation, being displayed in 1-3 males per 100 at birth. Since only a small percentage of these lesions can be linked to known genetic defects, developmental exposure to man-made chemicals has been implicated in the increase in thisrepr...
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Harris, B Z; Kaiser, D; Singer, M
1998-04-01
Guanosine 3'-di-5'-(tri)di-phosphate nucleotides [(p)ppGpp], synthesized in response to amino acid limitation, induce early gene expression leading to multicellular fruiting body formation in Myxococcus xanthus. A mutant (DK527) that fails to accumulate (p)ppGpp in response to starvation was found to be blocked in development prior to aggregation. By use of a series of developmentally regulated Tn5lac transcriptional fusion reporters, the time of developmental arrest in DK527 was narrowed to within the few hours of development, the period of starvation recognition. The mutant is also defective in the production of A-factor, an early extracellular cell-density signal. The relA gene from Escherichia coli, which encodes a ribosome-dependent (p)ppGpp synthetase, rescues this mutant. We also demonstrate that inactivation of the M. xanthus relA homolog blocks development and the accumulation of (p)ppGpp. Moreover, the wild-type allele of Myxococcus relA rescues DK527. These observations support a model in which accumulation of (p)ppGpp, in response to starvation, initiates the program of fruiting body development, including the production of A-factor.
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Tanaka, Miho J
2018-06-01
Trochlear dysplasia and patella alta are known risk factors for patellar instability, yet the relation between the two has not been well understood. Morphologic abnormalities such as trochlear dysplasia and patella alta are known to alter patellofemoral kinematics, whereas altered contact pressures, in turn, have been associated with the development of trochlear dysplasia. As our current treatments aim to correct these deformities through increasingly complex procedures such as trochleoplasty and tuberosity distalization, we should consider this relation and the potential for changing the course of developing such morphologic abnormalities earlier in life. Further studies on the developmental cause of this disorder may help guide future treatments in the management of patellar instability. Copyright © 2018 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.
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NASA Technical Reports Server (NTRS)
Morgan, C. J.; Hulka, J. R.; Casiano, M. J.; Kenny, R. J.; Hinerman, T. D.; Scholten, N.
2015-01-01
The J-2X engine, a liquid oxygen/liquid hydrogen propellant rocket engine available for future use on the upper stage of the Space Launch System vehicle, has completed testing of three developmental engines at NASA Stennis Space Center. Twenty-one tests of engine E10001 were conducted from June 2011 through September 2012, thirteen tests of the engine E10002 were conducted from February 2013 through September 2013, and twelve tests of engine E10003 were conducted from November 2013 to April 2014. Verification of combustion stability of the thrust chamber assembly was conducted by perturbing each of the three developmental engines. The primary mechanism for combustion stability verification was examining the response caused by an artificial perturbation (bomb) in the main combustion chamber, i.e., dynamic combustion stability rating. No dynamic instabilities were observed in the TCA, although a few conditions were not bombed. Additional requirements, included to guard against spontaneous instability or rough combustion, were also investigated. Under certain conditions, discrete responses were observed in the dynamic pressure data. The discrete responses were of low amplitude and posed minimal risk to safe engine operability. Rough combustion analyses showed that all three engines met requirements for broad-banded frequency oscillations. Start and shutdown transient chug oscillations were also examined to assess the overall stability characteristics, with no major issues observed.
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ERIC Educational Resources Information Center
Benner, Aprile D.; Kim, Su Yeong
2010-01-01
In this brief report, we investigated whether the Family Stress Model could be replicated with a sample of Chinese American families. Path analyses with 444 adolescents and their parents provided support for the model's generalizability. Specifically, mothers' and fathers' reports of economic status (i.e., income, financial, and job instability)…
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Developmental Stability Covaries with Genome-Wide and Single-Locus Heterozygosity in House Sparrows
Vangestel, Carl; Mergeay, Joachim; Dawson, Deborah A.; Vandomme, Viki; Lens, Luc
2011-01-01
Fluctuating asymmetry (FA), a measure of developmental instability, has been hypothesized to increase with genetic stress. Despite numerous studies providing empirical evidence for associations between FA and genome-wide properties such as multi-locus heterozygosity, support for single-locus effects remains scant. Here we test if, and to what extent, FA co-varies with single- and multilocus markers of genetic diversity in house sparrow (Passer domesticus) populations along an urban gradient. In line with theoretical expectations, FA was inversely correlated with genetic diversity estimated at genome level. However, this relationship was largely driven by variation at a single key locus. Contrary to our expectations, relationships between FA and genetic diversity were not stronger in individuals from urban populations that experience higher nutritional stress. We conclude that loss of genetic diversity adversely affects developmental stability in P. domesticus, and more generally, that the molecular basis of developmental stability may involve complex interactions between local and genome-wide effects. Further study on the relative effects of single-locus and genome-wide effects on the developmental stability of populations with different genetic properties is therefore needed. PMID:21747940
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2003-04-01
TThe National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for di-n-butyl phthalate (DBP) to cause adverse effects on reproduction and development in humans. DBP is one of 7 phthalate chemicals evaluated by the NTP CERHR Phthalates Expert Panel. These phthalates were selected for evaluation because of high production volume, extent of human exposures, use in children's products, and/or published evidence of reproductive or developmental toxicity. Unlike many phthalates, DBP is not currently used as a plasticizer in polyvinyl chloride plastics. DBP is a component of latex adhesives and is used in cosmetics and other personal care products, as a plasticizer in cellulose plastics, and as a solvent for dyes. The results of this evaluation on DBP are published in a NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Di-n-Butyl Phthalate, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to DBP on human development and reproduction. First, although DBP could possibly affect human reproduction and development if exposures are sufficiently high, the NTP concludes that there is negligible concern for reproductive toxicity in exposed adults. Second, the NTP concludes that there is minimal concern for developmental effects when pregnant women are exposed to DBP levels estimated by the panel (2-10 mug/kg body weight/day). There is no direct evidence that exposure of people to DBP adversely affects reproduction or development, but studies reviewed by the expert panel show that oral exposure to high doses of DBP (>/=100 mg/kg body weight/day) may adversely affect the prenatal and early postnatal development in rodents. Finally, based on exposure estimates in women of reproductive age, the NTP concludes that there is some concern for DBP causing adverse effects to human development, particularly development of the male reproductive system. NTP-CERHR monographs are transmitted to federal and state agencies, interested parties, and the public and are available electronically in PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919-316-4511).
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Molenaar, Peter C M
2008-01-01
It is argued that general mathematical-statistical theorems imply that standard statistical analysis techniques of inter-individual variation are invalid to investigate developmental processes. Developmental processes have to be analyzed at the level of individual subjects, using time series data characterizing the patterns of intra-individual variation. It is shown that standard statistical techniques based on the analysis of inter-individual variation appear to be insensitive to the presence of arbitrary large degrees of inter-individual heterogeneity in the population. An important class of nonlinear epigenetic models of neural growth is described which can explain the occurrence of such heterogeneity in brain structures and behavior. Links with models of developmental instability are discussed. A simulation study based on a chaotic growth model illustrates the invalidity of standard analysis of inter-individual variation, whereas time series analysis of intra-individual variation is able to recover the true state of affairs. (c) 2007 Wiley Periodicals, Inc.
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Turtle Carapace Anomalies: The Roles of Genetic Diversity and Environment
Velo-Antón, Guillermo; Becker, C. Guilherme; Cordero-Rivera, Adolfo
2011-01-01
Background Phenotypic anomalies are common in wild populations and multiple genetic, biotic and abiotic factors might contribute to their formation. Turtles are excellent models for the study of developmental instability because anomalies are easily detected in the form of malformations, additions, or reductions in the number of scutes or scales. Methodology/Principal Findings In this study, we integrated field observations, manipulative experiments, and climatic and genetic approaches to investigate the origin of carapace scute anomalies across Iberian populations of the European pond turtle, Emys orbicularis. The proportion of anomalous individuals varied from 3% to 69% in local populations, with increasing frequency of anomalies in northern regions. We found no significant effect of climatic and soil moisture, or climatic temperature on the occurrence of anomalies. However, lower genetic diversity and inbreeding were good predictors of the prevalence of scute anomalies among populations. Both decreasing genetic diversity and increasing proportion of anomalous individuals in northern parts of the Iberian distribution may be linked to recolonization events from the Southern Pleistocene refugium. Conclusions/Significance Overall, our results suggest that developmental instability in turtle carapace formation might be caused, at least in part, by genetic factors, although the influence of environmental factors affecting the developmental stability of turtle carapace cannot be ruled out. Further studies of the effects of environmental factors, pollutants and heritability of anomalies would be useful to better understand the complex origin of anomalies in natural populations. PMID:21533278
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NASA Astrophysics Data System (ADS)
Isola, Ilaria; Fornaciai, Alessandro; Favalli, Massimiliano; Gigli, Giovanni; Nannipieri, Luca; Mucchi, Lorenzo; Intrieri, Emanuele; Pizziolo, Marco; Bertolini, Giovanni; Trippi, Federico; Casagli, Nicola; Schina, Rosa; Carnevale, Ennio
2017-04-01
High-resolution topographic data has been collected over the Lavina di Roncovetro active landslide (Reggio Emilia, Italy) for about 3 years by using various methods and technologies. Tha Lavina di Roncovetro landslide can be considered as a fluid-viscous mudflow, which can reach a down flow maximum rate of 10 m/day. The landslide started between the middle and the end of the XIX century and since then it has had a rapid evolution mainly characterized by the rapid retrogression of the crown to the extent that now reaches the top of Mount Staffola. In the frame of EU Wireless Sensor Network for Ground Instability Monitoring - Wi-GIM project (LIFE12ENV/IT/001033) the Lavina di Roncovetro landslide has been periodically tracked using technologies that span from the LiDAR, both terrestrial and aerial, to the Structure from Motion (SfM) photogrammetry method based on Unmanned Aerial Vehicle (UAV) and aerial survey. These data are used to create six high-resolution Digital Terrain Models (DEMs), which imaged the landslide surface on March 2014, October 2014, June 2015, July 2015, January 2016 and December 2016. Multi-temporal high-resolution topographic data have been used for qualitative and quantitative morphometric analysis and topographic change detection of the landslide with the aim to estimate and map the volume of removed and/or accumulated material, the average rates of vertical and horizontal displacement and the deformation structures affecting the landslide over the investigated period.
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Kuznetsova, G D; Gabova, A V; Lazarev, I E; Obukhov, Iu V; Obukhov, K Iu; Morozov, A A; Kulikov, M A; Shchatskova, A B; Vasil'eva, O N; Tomilovskaia, E S
2015-01-01
Frequency-temporal electroencephalogram (EEG) reactions to hypogravity were studied in 7 male subjects at the age of 20 to 27 years. The experiment was conducted using dry immersion (DI) as the best known method of simulating the space microgravity effects on the Earth. This hypogravity model reproduces hypokinesia, i.e. the weight-bearing and mechanic load removal, which is typical of microgravity. EEG was recorded by Neuroscan-2 (Compumedics) before the experiment (baseline data) and at the end of day 2 in DI. Comparative analysis of the EEG frequency-temporal structure was performed with the use of 2 techniques: Fourier transform and modified wavelet analysis. The Fourier transform elicited that after 2 days in DI the main shifts occurring to the EEG spectral composition are a decline in the alpha power and a slight though reliable growth of theta power. Similar frequency shifts were detected in the same records analyzed using the wavelet transform. According to wavelet analysis, during DI shifts in EEG frequency spectrum are accompanied by frequency desorganization of the EEG dominant rhythm and gross impairment of total stability of the electrical activity with time. Wavelet transform provides an opportunity to quantify changes in the frequency-temporal structure of the electrical activity of the brain. Quantitative evidence of frequency desorganization and temporal instability of EEG wavelet spectrograms may be the key to the understanding of mechanisms that drive functional disorders in the brain cortex in the conditions of hypogravity.
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Mitotic Mysteries: The Case of HP1.
Higgins, Jonathan M G; Prendergast, Lisa
2016-03-07
The role of Heterochromatin Protein-1 (HP1) during mitosis has been controversial. Two recent studies in Science and Developmental Cell, from Tanno et al. (2015) and Abe et al. (2016), suggest that the means of HP1 localization and its function at inner centromeres are altered in cancer cells with chromosomal instability. Copyright © 2016 Elsevier Inc. All rights reserved.
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Fractal structures and fractal functions as disease indicators
Escos, J.M; Alados, C.L.; Emlen, J.M.
1995-01-01
Developmental instability is an early indicator of stress, and has been used to monitor the impacts of human disturbance on natural ecosystems. Here we investigate the use of different measures of developmental instability on two species, green peppers (Capsicum annuum), a plant, and Spanish ibex (Capra pyrenaica), an animal. For green peppers we compared the variance in allometric relationship between control plants, and a treatment group infected with the tomato spotted wilt virus. The results show that infected plants have a greater variance about the allometric regression line than the control plants. We also observed a reduction in complexity of branch structure in green pepper with a viral infection. Box-counting fractal dimension of branch architecture declined under stress infection. We also tested the reduction in complexity of behavioral patterns under stress situations in Spanish ibex (Capra pyrenaica). Fractal dimension of head-lift frequency distribution measures predator detection efficiency. This dimension decreased under stressful conditions, such as advanced pregnancy and parasitic infection. Feeding distribution activities reflect food searching efficiency. Power spectral analysis proves to be the most powerful tool for character- izing fractal behavior, revealing a reduction in complexity of time distribution activity under parasitic infection.
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Convolute laminations — a theoretical analysis: example of a Pennsylvanian sandstone
NASA Astrophysics Data System (ADS)
Visher, Glenn S.; Cunningham, Russ D.
1981-03-01
Data from an outcropping laminated interval were collected and analyzed to test the applicability of a theoretical model describing instability of layered systems. Rayleigh—Taylor wave perturbations result at the interface between fluids of contrasting density, viscosity, and thickness. In the special case where reverse density and viscosity interlaminations are developed, the deformation response produces a single wave with predictable amplitudes, wavelengths, and amplification rates. Physical measurements from both the outcropping section and modern sediments suggest the usefulness of the model for the interpretation of convolute laminations. Internal characteristics of the stratigraphic interval, and the developmental sequence of convoluted beds, are used to document the developmental history of these structures.
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Di-Isobutyl Phthalate (DIBP) Hazard Identification [Abstract ...
The hazard potential for DIBP is being evaluated as part of EPA’s Integrated Risk Information System (IRIS) Toxicological Review. DIBP is a plasticizer that confers flexibility and durability in industrial and consumer products. A literature search identified a relatively small epidemiology and animal toxicology database for DIBP. The epidemiological database includes studies that assessed the relationship between urinary concentrations of the DIBP metabolite mono-isobutyl phthalate (MIBP)and developmental, neurodevelopmental, immunological or breast cancer outcomes. There is limited support for associations between MIBP and inflammatory biomarker levels and decreased masculine play behavior. The animal toxicological database includes studies that assessed “phthalate syndrome” male reproductive developmental endpoints after in utero DIBP exposure. Data from the largest developmental study, Saillenfait et al. (2008), shows changes in anogenital distance, male reproductive organ weights, and litter incidence of phthalate syndrome endpoints in the lower dose range after early gestational exposure. Other studies observed increased fetal mortality, male postnatal and adult growth decrements, decreased fetal testicular testosterone and changes in expression of genes in androgen production pathways. The developmental reproductive effects observed in animal studies are consistent with the reduced testicular testosterone mode of action that is well-characterize
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Fluctuating asymmetry and psychometric intelligence.
Furlow, F B; Armijo-Prewitt, T; Gangestad, S W; Thornhill, R
1997-01-01
Little is known about the genetic nature of human psychometric intelligence (IQ), but it is widely assumed that IQ's heritability is at loci for intelligence per se. We present evidence consistent with a hypothesis that interindividual IQ differences are partly due to heritable vulnerabilities to environmental sources of developmental stress, an indirect genetic mechanism for the heritability of IQ. Using fluctuating asymmetry (FA) of the body (the asymmetry resulting from errors in the development of normally symmetrical bilateral traits under stressful conditions), we estimated the relative developmental instability of 112 undergraduates and administered to them Cattell's culture fair intelligence test (CFIT). A subsequent replication on 128 students was performed. In both samples, FA correlated negatively and significantly with CFIT scores. We propose two non-mutually exclusive physiological explanations for this correlation. First, external body FA may correlate negatively with the developmental integrity of the brain. Second, individual energy budget allocations and/or low metabolic efficiency in high-FA individuals may lower IQ scores. We review the data on IQ in light of our findings and conclude that improving developmental quality may increase average IQ in future generations. PMID:9265189
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Leonard, Thomas J.; Dick, Stanley; Gaber, Richard F.
1978-01-01
A series of hemi-compatible dikaryon x monokaryon (di-mon) matings was designed to determine whether there was any genetic interaction between the dikaryotic nuclei. One of the nuclei in each dikaryon was known to carry a recessive gene (mnd) that promoted the development of an abnormal growth form, mound. Dikaryons containing both mnd + and mnd nuclei produced mosaic colonies that consisted of three distinct kinds of hyphae: mound, fruiting body, and vegetative (devoid of any multihyphal structure). When dikaryotic hyphae from each of these morphological regions were used in di-mon matings, the genetic and developmental characteristics of the selected nuclear types were examined in the resulting derived dikaryons. The results showed that fruiting-body and vegetative cells contained the expected mnd and mnd+ nuclei. Dikaryotic mound hyphae, however, contained only mnd nuclei. In a manner as yet unresolved, but clearly dependent on the presence of the mnd allele, the mnd + allele of a wild nucleus was altered to, or acquired, the mnd allele. A number of hypotheses were considered to explain the genetic event(s) that generates [mnd + mnd*] dikaryotic cells from [mnd+ + mnd] cells, but none was found to be entirely satisfactory. PMID:17248788
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The measurement and prevalence of an ideational model of family and economic development in Nepal.
Thornton, Arland; Ghimire, Dirgha J; Mitchell, Colter
2012-11-01
Developmental idealism (DI) is a system of beliefs and values that endorses modern societies and families and sees them as occurring together, with modern families as causes and consequences of societal development. This study was motivated by the belief that the population of Nepal has absorbed these ideas and that the ideas affect their family behaviour. We use data collected in Nepal in 2003 to show that Nepalis discuss ideas about development and its relationship to family life and that DI has been widely accepted. It is related in predictable ways to education, paid employment, rural-urban residence, and mass media exposure. Although it would be useful to know its influence on demographic decision-making and behaviour, we cannot evaluate this with our one-time cross-sectional survey. Our data and theory suggest that this influence may be substantial.
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Schlüter, Nils
2016-01-01
The Late Cretaceous echinoid genus Micraster (irregular echinoids, Spatangoida) is one of the most famous examples of a continuous evolutionary lineage in invertebrate palaeontology. The influence of the environment on the phenotype, however, was not tested so far. This study analyses differences in phenotypical variations within three populations of Micraster (Gibbaster) brevis from the early Coniacian, two from the Münsterland Cretaceous Basin (Germany) and one from the North Cantabrian Basin (Spain). The environments of the Spanish and the German sites differed by their sedimentary characteristics, which are generally a crucial factor for morphological adaptations in echinoids. Most of the major phenotypical variations (position of the ambitus, periproct and development of the subanal fasciole) among the populations can be linked to differences in their host sediments. These phenotypic variations are presumed to be an expression of phenotpic plasticiy, which has not been considered in Micraster in previous studies. Two populations (Erwitte area, Germany; Liencres area, Spain) were tested for stochastic variation (fluctuating asymmetry) due to developmental instability, which was present in all studied traits. However, differences in the amount of fluctuating asymmetry between both populations were recognised only in one trait (amount of pore pairs in the anterior paired petals). The results strengthen previous assumptions on ecophenotypic variations in Micraster. PMID:26849648
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Fowler, Patrick J; Henry, David B; Schoeny, Michael; Taylor, Jeremy; Chavira, Dina
2014-02-01
This longitudinal study tested whether developmental timing of exposure to housing mobility exacerbates behavior problems in an at-risk sample of youth. Participants were 2,442 youth 4 to 16 years old at risk for child maltreatment followed at 3 time points over a 36-month follow-up. Caregivers reported on youth externalizing behaviors at each assessment. Latent growth models examined the effect of housing mobility on behavior problems after accounting for change in cognitive development, family instability, child gender, ethnicity, family income, and caregiver mental health at baseline. Findings suggested increased housing mobility predicted greater behavior problems when children were exposed at key developmental periods. Preschoolers exhibited significantly higher rates of behavior problems that remained stable across the 3-year follow-up. Likewise, adolescents exposed to more mobility became relatively more disruptive over time. No effects were found for school-age children. Children who moved frequently during infancy and more recently demonstrated significantly worse behavior over time. The developmental timing of housing mobility affects child behavioral outcomes. Youth in developmental transition at the time of mobility are at greatest risk for disturbances to residential contexts. Assessing housing history represents an important component of interventions with at-risk families. Copyright © 2014 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.
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Shadrina, E G; Vol'pert, Ia L
2014-01-01
The value of fluctuating asymmetry is considered to be an indicator of the developmental instability of the organism. The consequences of activities of the mining industry plants, which are characterized by alienation and transformation of large areas of natural landscapes, are analyzed as an anthropogenic factor. The objects of study were small mammals (northern red-backed (Clethrionomys rutilus) and gray red-backed (Clethrionomys rufocanus) voles, tundra vole (Microtus oeconomus), Laxmann's (Sorex caecutiens) and tundra (S. tundrensis) shrews) and trees (Japanese white birch (Betula platyphylla), Betula divaricate, Betula exilis, Duschekiafruticosa, and common osier (Salix viminalis)). In total, 3500 skulls and approximately 30000 leaves collected in the taiga zone of Yakutia were studied. The index offluctuating asymmetry, as well as population parameters and composition of small mammal communities, were analyzed. The data on the value of the fluctuating asymmetry in the studied species in natural habitats are given. It is shown that, in natural conditions, this parameter can rise with deterioration in living conditions, particularly at the ecological periphery of the range. Anthropogenic transformation of natural landscapes creates an "anthropogenic periphery" and causes changes similar to the adaptive responses at the northern limit of the distribution of species. It was found that, through pollution and disruption of ecosystems, the mining industry affects all levels of organization of the living matter, but the population and cenotic parameters give an unambiguous response only at macroanthropogenic transformations. Increase in the level of fluctuating asymmetry is the most sensitive indicator of anthropogenic impact and it should also be taken into account that disruptions in the developmental stability of an organism reflect the destructive processes occurring in the population and community.
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Hard to Swallow: Developmental Biological Insights into Pediatric Dysphagia
LaMantia, Anthony-Samuel; Moody, Sally A.; Maynard, Thomas M.; Karpinski, Beverly A.; Zohn, Irene E.; Mendelowitz, David; Lee, Norman H.; Popratiloff, Anastas
2015-01-01
Pediatric dysphagia—feeding and swallowing difficulties that begin at birth, last throughout childhood, and continue into maturity—is one of the most common, least understood complications in children with developmental disorders. We argue that a major cause of pediatric dysphagia is altered hindbrain patterning during pre-natal development. Such changes can compromise craniofacial structures including oropharyngeal muscles and skeletal elements as well as motor and sensory circuits necessary for normal feeding and swallowing. Animal models of developmental disorders that include pediatric dysphagia in their phenotypic spectrum can provide mechanistic insight into pathogenesis of feeding and swallowing difficulties. A fairly common human genetic developmental disorder, DiGeorge/22q11.2 Deletion Syndrome (22q11DS) includes a substantial incidence of pediatric dysphagia in its phenotypic spectrum. Infant mice carrying a parallel deletion to 22q11DS patients have feeding and swallowing difficulties. Altered hindbrain patterning, neural crest migration, craniofacial malformations, and changes in cranial nerve growth prefigure these difficulties. Thus, in addition to craniofacial and pharyngeal anomalies that arise independently of altered neural development, pediatric dysphagia may reflect disrupted hindbrain patterning and its impact on neural circuit development critical for feeding and swallowing. The mechanisms that disrupt hindbrain patterning and circuitry may provide a foundation to develop novel therapeutic approaches for improved clinical management of pediatric dysphagia. PMID:26554723
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Cysarz, Dirk; Linhard, Maijana; Seifert, Georg; Edelhäuser, Friedrich
2018-01-01
The electrocardiogram-based cardiopulmonary coupling (CPC) technique may be used to track sleep instabilities. With progressing age, maturational changes during childhood and adolescence affect sleep. The objective was to assess developmental changes in sleep instabilities in a natural setting. ECGs during nighttime sleep on regular school days were recorded from 363 subjects aged 4 to 22 years (204 females). The estimated total sleep time (ETST) decreased from 598 to 445 min during childhood and adolescence. Stable sleep linearly decreased with progressing age (high frequency coupling (HFC): 70-48% ETST). Unstable sleep [low frequency coupling (LFC): 9-19% ETST], sleep fragmentation or disordered breathing (elevated LFC: 4-12% ETST), and wake/REM states [very low frequency coupling (VLFC): 20-32% ETST] linearly increased with age. Hence, with progressing age the sleep of children and adolescents shortens, becomes more unstable and is more often affected by fragmentation or sleep disordered breathing, especially in the age group >13 years. It remains to be clarified whether some of the changes are caused by a social jetlag, i.e., the misalignment of body clock and social time especially in adolescents.
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Monitoring and Early Warning of the 2012 Preonzo Catastrophic Rockslope Failure
NASA Astrophysics Data System (ADS)
Loew, Simon; Gschwind, Sophie; Keller-Signer, Alexandra; Valenti, Giorgio
2015-04-01
In this contribution we describe the accelerated creep stage and early warning system of a 210'000 m3 rock slope failure that occurred in May 2012 above the village of Preonzo (Swiss Alps). The very rapid failure occurred from a larger and retrogressive instability in high-grade metamorphic ortho-gneisses and amphibolites with a total volume of about 350'000 m3 located at an alpine meadow called Alpe di Roscioro. This instability showed clearly visible signs of movements since 1989 and accelerated creep with significant hydro-mechanical forcing since about 1999. Because the instability at Preonzo threatened a large industrial facility and important transport routes a cost-effective early warning system was installed in 2010. The alarm thresholds for pre-alarm, general public alarm and evacuation were derived from 10 years of continuous displacement monitoring with crack extensometers and an automated total station. These thresholds were successfully applied to evacuate the industrial facility and close important roads a few days before the catastrophic slope failure of May 15th, 2012. The rock slope failure occurred in two events, exposing a planar rupture plane dipping 42° and generating deposits in the mid-slope portion with a travel angle of 38°. Two hours after the second rockslide, the fresh colluvial deposits became reactivated in a devastating de-bris avalanche reaching the foot of the slope.
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D’Souza, Fiona; Pudakalakatti, Shivanand M.; Uppangala, Shubhashree; Honguntikar, Sachin; Salian, Sujith Raj; Kalthur, Guruprasad; Pasricha, Renu; Appajigowda, Divya; Atreya, Hanudatta S.; Adiga, Satish Kumar
2016-01-01
Early development of certain mammalian embryos is protected by complex checkpoint systems to maintain the genomic integrity. Several metabolic pathways are modulated in response to genetic insults in mammalian cells. The present study investigated the relationship between the genetic integrity, embryo metabolites and developmental competence in preimplantation stage mouse embryos with the aim to identify early biomarkers which can predict embryonic genetic integrity using spent medium profiling by NMR spectroscopy. Embryos carrying induced DNA lesions (IDL) developed normally for the first 2.5 days, but began to exhibit a developmental delay at embryonic day 3.5(E3.5) though they were morphologically indistinguishable from control embryos. Analysis of metabolites in the spent medium on E3.5 revealed a significant association between pyruvate, lactate, glucose, proline, lysine, alanine, valine, isoleucine and thymine and the extent of genetic instability observed in the embryos on E4.5. Further analysis revealed an association of apoptosis and micronuclei frequency with P53 and Bax transcripts in IDL embryos on the E4.5 owing to delayed induction of chromosome instability. We conclude that estimation of metabolites on E3.5 in spent medium may serve as a biomarker to predict the genetic integrity in pre-implantation stage embryos which opens up new avenues to improve outcomes in clinical IVF programs. PMID:27853269
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Rein, Katrin; Yanez, Diana A.; Terré, Berta; Palenzuela, Lluís; Aivio, Suvi; Wei, Kaichun; Edelmann, Winfried; Stark, Jeremy M.; Stracker, Travis H.
2015-01-01
The maintenance of genome stability is critical for the suppression of diverse human pathologies that include developmental disorders, premature aging, infertility and predisposition to cancer. The DNA damage response (DDR) orchestrates the appropriate cellular responses following the detection of lesions to prevent genomic instability. The MRE11 complex is a sensor of DNA double strand breaks (DSBs) and plays key roles in multiple aspects of the DDR, including DNA end resection that is critical for signaling and DNA repair. The MRE11 complex has been shown to function both upstream and in concert with the 5′-3′ exonuclease EXO1 in DNA resection, but it remains unclear to what extent EXO1 influences DSB responses independently of the MRE11 complex. Here we examine the genetic relationship of the MRE11 complex and EXO1 during mammalian development and in response to DNA damage. Deletion of Exo1 in mice expressing a hypomorphic allele of Nbs1 leads to severe developmental impairment, embryonic death and chromosomal instability. While EXO1 plays a minimal role in normal cells, its loss strongly influences DNA replication, DNA repair, checkpoint signaling and damage sensitivity in NBS1 hypomorphic cells. Collectively, our results establish a key role for EXO1 in modulating the severity of hypomorphic MRE11 complex mutations. PMID:26160886
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Evaluation and Referral for Developmental Dysplasia of the Hip in Infants.
Shaw, Brian A; Segal, Lee S
2016-12-01
Developmental dysplasia of the hip (DDH) encompasses a wide spectrum of clinical severity, from mild developmental abnormalities to frank dislocation. Clinical hip instability occurs in 1% to 2% of full-term infants, and up to 15% have hip instability or hip immaturity detectable by imaging studies. Hip dysplasia is the most common cause of hip arthritis in women younger than 40 years and accounts for 5% to 10% of all total hip replacements in the United States. Newborn and periodic screening have been practiced for decades, because DDH is clinically silent during the first year of life, can be treated more effectively if detected early, and can have severe consequences if left untreated. However, screening programs and techniques are not uniform, and there is little evidence-based literature to support current practice, leading to controversy. Recent literature shows that many mild forms of DDH resolve without treatment, and there is a lack of agreement on ultrasonographic diagnostic criteria for DDH as a disease versus developmental variations. The American Academy of Pediatrics has not published any policy statements on DDH since its 2000 clinical practice guideline and accompanying technical report. Developments since then include a controversial US Preventive Services Task Force "inconclusive" determination regarding usefulness of DDH screening, several prospective studies supporting observation over treatment of minor ultrasonographic hip variations, and a recent evidence-based clinical practice guideline from the American Academy of Orthopaedic Surgeons on the detection and management of DDH in infants 0 to 6 months of age. The purpose of this clinical report was to provide literature-based updated direction for the clinician in screening and referral for DDH, with the primary goal of preventing and/or detecting a dislocated hip by 6 to 12 months of age in an otherwise healthy child, understanding that no screening program has eliminated late development or presentation of a dislocated hip and that the diagnosis and treatment of milder forms of hip dysplasia remain controversial. Copyright © 2016 by the American Academy of Pediatrics.
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Okegbe, Chinweike; Fields, Blanche L.; Cole, Stephanie J.; Beierschmitt, Christopher; Morgan, Chase J.; Price-Whelan, Alexa; Stewart, Richard C.; Lee, Vincent T.; Dietrich, Lars E. P.
2017-01-01
Diverse organisms secrete redox-active antibiotics, which can be used as extracellular electron shuttles by resistant microbes. Shuttle-mediated metabolism can support survival when substrates are available not locally but rather at a distance. Such conditions arise in multicellular communities, where the formation of chemical gradients leads to resource limitation for cells at depth. In the pathogenic bacterium Pseudomonas aeruginosa PA14, antibiotics called phenazines act as oxidants to balance the intracellular redox state of cells in anoxic biofilm subzones. PA14 colony biofilms show a profound morphogenic response to phenazines resulting from electron acceptor-dependent inhibition of ECM production. This effect is reminiscent of the developmental responses of some eukaryotic systems to redox control, but for bacterial systems its mechanistic basis has not been well defined. Here, we identify the regulatory protein RmcA and show that it links redox conditions to PA14 colony morphogenesis by modulating levels of bis-(3′,5′)-cyclic-dimeric-guanosine (c-di-GMP), a second messenger that stimulates matrix production, in response to phenazine availability. RmcA contains four Per-Arnt-Sim (PAS) domains and domains with the potential to catalyze the synthesis and degradation of c-di-GMP. Our results suggest that phenazine production modulates RmcA activity such that the protein degrades c-di-GMP and thereby inhibits matrix production during oxidizing conditions. RmcA thus forms a mechanistic link between cellular redox sensing and community morphogenesis analogous to the functions performed by PAS-domain–containing regulatory proteins found in complex eukaryotes. PMID:28607054
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Yoneshima, Yasuto; Abolhassani, Nona; Iyama, Teruaki; Sakumi, Kunihiko; Shiomi, Naoko; Mori, Masahiko; Shiomi, Tadahiro; Noda, Tetsuo; Tsuchimoto, Daisuke; Nakabeppu, Yusaku
2016-01-01
Deoxyinosine (dI) occurs in DNA either by oxidative deamination of a previously incorporated deoxyadenosine residue or by misincorporation of deoxyinosine triphosphate (dITP) from the nucleotide pool during replication. To exclude dITP from the pool, mammals possess specific hydrolysing enzymes, such as inosine triphosphatase (ITPA). Previous studies have shown that deficiency in ITPA results in cell growth suppression and DNA instability. To explore the mechanisms of these phenotypes, we analysed ITPA-deficient human and mouse cells. We found that both growth suppression and accumulation of single-strand breaks in nuclear DNA of ITPA-deficient cells depended on MLH1/PMS2. The cell growth suppression of ITPA-deficient cells also depended on p53, but not on MPG, ENDOV or MSH2. ITPA deficiency significantly increased the levels of p53 protein and p21 mRNA/protein, a well-known target of p53, in an MLH1-dependent manner. Furthermore, MLH1 may also contribute to cell growth arrest by increasing the basal level of p53 activity. PMID:27618981
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Housing Mobility and Cognitive Development: Change in Verbal and Nonverbal Abilities
Fowler, Patrick J.; McGrath, Lauren M.; Henry, David B.; Schoeny, Michael; Chavira, Dina; Taylor, Jeremy J.; Day, Orin
2015-01-01
This study investigates the influence of housing instability on verbal and nonverbal cognitive development among at-risk children and adolescents involved in the child welfare system. Frequent residential changes threaten child mental health, especially among low-income families. Little is known regarding disruptions to cognitive growth, specifically the impact on verbal and nonverbal abilities. The study tests whether developmental timing of housing mobility affects cognitive development beyond individual and family risks. A nationally representative study of families (n = 2,442) susceptible to housing and family instability tracked children and adolescents aged four to 14 years (M = 8.95 years) over 36 months following investigation by the child welfare system. Youth completed standardized cognitive assessments while caregivers reported on behavior problems and family risk at three time points. Latent growth models examined change in cognitive abilities over time. Housing mobility in the 12 months prior to baseline predicts lower verbal cognitive abilities that improve marginally. Similar effects emerge for all age groups; however, frequent moves in infancy diminish the influence of subsequent housing mobility on verbal tasks. Housing instability threatened cognitive development beyond child maltreatment, family changes, poverty, and other risks. Findings inform emerging research on environmental influences on neurocognitive development, as well as identify targets for early intervention. Systematic assessment of family housing problems, including through the child welfare system, provides opportunities for coordinated responses to prevent instability and cognitive threats. PMID:26184055
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Lindsay, E.A.; Halford, S.; Wadey, R.
1993-08-01
DiGeorge syndrome (DGS) is a developmental defect characterized by cardiac defects, facial dysmorphism, and mental retardation. Several studies have described a critical region for DGS at 22q11, within which the majority of DGS patients have deletions. The authors have isolated nine cosmid and three YAC clones using previously described and newly isolated probes that have been shown to be deleted in many DGS patients. Using fluorescence in situ hybridization and digital imaging, they have mapped and ordered these clones relative to the breakpoints of two balanced translocations at 22q11 (one in a DGS patient and one in the unaffected parentmore » of a DGS child). The data indicate that the breakpoint in the unaffected individual distally limits the DGS critical region (defined as the smallest region of overlap), while proximally the region is limited by repeat-rich DNA. The critical region includes the balanced translocation breakpoint of the DGS patient that presumably disrupts the gene causing this syndrome.« less
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Albuixech-Crespo, Beatriz; López-Blanch, Laura; Burguera, Demian; Maeso, Ignacio; Sánchez-Arrones, Luisa; Moreno-Bravo, Juan Antonio; Somorjai, Ildiko; Pascual-Anaya, Juan; Puelles, Eduardo; Bovolenta, Paola; Garcia-Fernàndez, Jordi; Puelles, Luis; Irimia, Manuel; Ferran, José Luis
2017-04-01
All vertebrate brains develop following a common Bauplan defined by anteroposterior (AP) and dorsoventral (DV) subdivisions, characterized by largely conserved differential expression of gene markers. However, it is still unclear how this Bauplan originated during evolution. We studied the relative expression of 48 genes with key roles in vertebrate neural patterning in a representative amphioxus embryonic stage. Unlike nonchordates, amphioxus develops its central nervous system (CNS) from a neural plate that is homologous to that of vertebrates, allowing direct topological comparisons. The resulting genoarchitectonic model revealed that the amphioxus incipient neural tube is unexpectedly complex, consisting of several AP and DV molecular partitions. Strikingly, comparison with vertebrates indicates that the vertebrate thalamus, pretectum, and midbrain domains jointly correspond to a single amphioxus region, which we termed Di-Mesencephalic primordium (DiMes). This suggests that these domains have a common developmental and evolutionary origin, as supported by functional experiments manipulating secondary organizers in zebrafish and mice.
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Albuixech-Crespo, Beatriz; Maeso, Ignacio; Sánchez-Arrones, Luisa; Moreno-Bravo, Juan Antonio; Somorjai, Ildiko; Pascual-Anaya, Juan; Puelles, Eduardo; Bovolenta, Paola; Garcia-Fernàndez, Jordi; Puelles, Luis; Ferran, José Luis
2017-01-01
All vertebrate brains develop following a common Bauplan defined by anteroposterior (AP) and dorsoventral (DV) subdivisions, characterized by largely conserved differential expression of gene markers. However, it is still unclear how this Bauplan originated during evolution. We studied the relative expression of 48 genes with key roles in vertebrate neural patterning in a representative amphioxus embryonic stage. Unlike nonchordates, amphioxus develops its central nervous system (CNS) from a neural plate that is homologous to that of vertebrates, allowing direct topological comparisons. The resulting genoarchitectonic model revealed that the amphioxus incipient neural tube is unexpectedly complex, consisting of several AP and DV molecular partitions. Strikingly, comparison with vertebrates indicates that the vertebrate thalamus, pretectum, and midbrain domains jointly correspond to a single amphioxus region, which we termed Di-Mesencephalic primordium (DiMes). This suggests that these domains have a common developmental and evolutionary origin, as supported by functional experiments manipulating secondary organizers in zebrafish and mice. PMID:28422959
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Do, Kim Q.; Cuenod, Michel; Hensch, Takao K.
2015-01-01
Schizophrenia is a neurodevelopmental disorder reflecting a convergence of genetic risk and early life stress. The slow progression to first psychotic episode represents both a window of vulnerability as well as opportunity for therapeutic intervention. Here, we consider recent neurobiological insight into the cellular and molecular components of developmental critical periods and their vulnerability to redox dysregulation. In particular, the consistent loss of parvalbumin-positive interneuron (PVI) function and their surrounding perineuronal nets (PNNs) as well as myelination in patient brains is consistent with a delayed or extended period of circuit instability. This linkage to critical period triggers (PVI) and brakes (PNN, myelin) implicates mistimed trajectories of brain development in mental illness. Strategically introduced antioxidant treatment or later reinforcement of molecular brakes may then offer a novel prophylactic psychiatry. PMID:26032508
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Tessadori, Federico; Giltay, Jacques C; Hurst, Jane A; Massink, Maarten P; Duran, Karen; Vos, Harmjan R; van Es, Robert M; Scott, Richard H; van Gassen, Koen L I; Bakkers, Jeroen; van Haaften, Gijs
2017-11-01
Covalent modifications of histones have an established role as chromatin effectors, as they control processes such as DNA replication and transcription, and repair or regulate nucleosomal structure. Loss of modifications on histone N tails, whether due to mutations in genes belonging to histone-modifying complexes or mutations directly affecting the histone tails, causes developmental disorders or has a role in tumorigenesis. More recently, modifications affecting the globular histone core have been uncovered as being crucial for DNA repair, pluripotency and oncogenesis. Here we report monoallelic missense mutations affecting lysine 91 in the histone H4 core (H4K91) in three individuals with a syndrome of growth delay, microcephaly and intellectual disability. Expression of the histone H4 mutants in zebrafish embryos recapitulates the developmental anomalies seen in the patients. We show that the histone H4 alterations cause genomic instability, resulting in increased apoptosis and cell cycle progression anomalies during early development. Mechanistically, our findings indicate an important role for the ubiquitination of H4K91 in genomic stability during embryonic development.
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Comprehensive analysis of titin protein isoform and alternative splicing in normal and mutant rats.
Li, Shijun; Guo, Wei; Schmitt, Benjamin M; Greaser, Marion L
2012-04-01
Titin is a giant protein with multiple functions in cardiac and skeletal muscles. Rat cardiac titin undergoes developmental isoform transition from the neonatal 3.7 MDa N2BA isoform to primarily the adult 2.97 MDa N2B isoform. An autosomal dominant mutation dramatically altered this transformation. Titins from eight skeletal muscles: Tibialis Anterior (TA), Longissimus Dorsi (LD) and Gastrocnemius (GA), Extensor Digitorum Longus (ED), Soleus (SO), Psoas (PS), Extensor Oblique (EO), and Diaphram (DI) were characterized in wild type and in homozygous mutant (Hm) rats with a titin splicing defect. Results showed that the developmental reduction in titin size is eliminated in the mutant rat so that the titins in all investigated skeletal muscles remain large in the adult. The alternative splicing of titin mRNA was found repressed by this mutation, a result consistent with the large titin isoform in the mutant. The developmental pattern of titin mRNA alternative splicing differs between heart and skeletal muscles. The retention of intron 49 reveals a possible mechanism for the absence of the N2B unique region in the expressed titin protein of skeletal muscle. © 2011 Wiley Periodicals, Inc.
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Lazić, Marko M; Carretero, Miguel A; Crnobrnja-Isailović, Jelka; Kaliontzopoulou, Antigoni
2015-01-01
When populations experience suboptimal conditions, the mechanisms involved in the regulation of phenotypic variation can be challenged, resulting in increased phenotypic variance. This kind of disturbance can be diagnosed by using morphometric tools to study morphological patterns at different hierarchical levels and evaluate canalization, developmental stability, integration, modularity, and allometry. We assess the effect of urbanization on phenotypic variation in the common wall lizard (Podarcis muralis) by using geometric morphometrics to assess disturbance to head shape development. The head shapes of urban lizards were more variable and less symmetric, suggesting that urban living is more likely to disturb development. Head shape variation was congruent within and across individuals, which indicated that canalization and developmental stability are two related phenomena in these organisms. Furthermore, urban lizards exhibited smaller mean head sizes, divergent size-shape allometries, and increased deviation from within-group allometric lines. This suggests that mechanisms regulating head shape allometry may also be disrupted. The integrated evaluation of several measures of developmental instability at different hierarchical levels, which provided in this case congruent results, can be a powerful methodological guide for future studies, as it enhances the detection of environmental disturbances on phenotypic variation and aids biological interpretation of the results.
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Akhter, Shamima; Lam, Yung C.; Chang, Sandy; Legerski, Randy J.
2013-01-01
Summary Conserved metallo β-Lactamase and β-CASP (CPSF-Artemis-Snm1-Pso2) domain nuclease family member SNM1B/Apollo is a shelterin-associated protein that localizes to telomeres through its interaction with TRF2. To study its in vivo role, we generated a knockout of SNM1B/Apollo in a mouse model. Snm1B/Apollo homozygous null mice die at birth with developmental delay and defects in multiple organ systems. Cell proliferation defects were observed in Snm1B/Apollo mutant mouse embryonic fibroblasts (MEFs) owing to high levels of telomeric end-to-end fusions. Deficiency of the nonhomologous end-joining (NHEJ) factor Ku70, but not p53, rescued the developmental defects and lethality observed in Snm1B/Apollo mutant mice as well as the impaired proliferation of Snm1B/Apollo-deficient MEFs. These findings demonstrate that SNM1B/Apollo is required to protect telomeres against NHEJ-mediated repair, which results in genomic instability and the consequent multi-organ developmental failure. Although Snm1B/Apollo-deficient MEFs exhibited high levels of apoptosis, abrogation of p53-dependent programmed cell death did not rescue the multi-organ developmental failure in the mice. PMID:20854421
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Fluctuating asymmetry as risk marker for stress and structural defects in a toxicologic experiment.
Breno, Matteo; Bots, Jessica; De Schaepdrijver, Luc; Van Dongen, Stefan
2013-08-01
Fluctuating asymmetry (the directionally random asymmetry of bilateral structures, FA) is commonly used as a measure of developmental instability, and may increase with stress. As several studies reported a relation between FA and developmental abnormalities, we investigate whether FA could be an additional perhaps more sensitive marker of developmental toxicity. The aim of this work is analyzing patterns of FA in multiple traits in a large dataset of rabbit fetuses, which were prenatally exposed to a toxic compound and sacrificed just before natural delivery. Gravid females were exposed to three doses of this compound, inducing abnormalities in the fetuses at the high dose only. The average FA, however, was already higher than control in rabbit fetuses of the low-dose group but did not further increase with higher concentrations. Moreover, the increase in FA differed between traits, with the hindlimbs showing the strongest response. In addition, we did not find any association between FA and the presence of fetal abnormalities at the individual level. Although these results suggest that FA may act as "an early warning system," we did not find a dose-response relationship with increasing stress and effects were trait-specific. Further testing is needed before FA may be considered as a sensitive marker in developmental toxicity studies. © 2013 Wiley Periodicals, Inc.
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Le Guen, Tangui; Jullien, Laurent; Touzot, Fabien; Schertzer, Michael; Gaillard, Laetitia; Perderiset, Mylène; Carpentier, Wassila; Nitschke, Patrick; Picard, Capucine; Couillault, Gérard; Soulier, Jean; Fischer, Alain; Callebaut, Isabelle; Jabado, Nada; Londono-Vallejo, Arturo; de Villartay, Jean-Pierre; Revy, Patrick
2013-08-15
Hoyeraal-Hreidarsson syndrome (HHS), a severe variant of dyskeratosis congenita (DC), is characterized by early onset bone marrow failure, immunodeficiency and developmental defects. Several factors involved in telomere length maintenance and/or protection are defective in HHS/DC, underlining the relationship between telomere dysfunction and these diseases. By combining whole-genome linkage analysis and exome sequencing, we identified compound heterozygous RTEL1 (regulator of telomere elongation helicase 1) mutations in three patients with HHS from two unrelated families. RTEL1 is a DNA helicase that participates in DNA replication, DNA repair and telomere integrity. We show that, in addition to short telomeres, RTEL1-deficient cells from patients exhibit hallmarks of genome instability, including spontaneous DNA damage, anaphase bridges and telomeric aberrations. Collectively, these results identify RTEL1 as a novel HHS-causing gene and highlight its role as a genomic caretaker in humans.
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Loss of Nucleotide Excision Repair as a Source of Genomic Instability in Breast Cancer
2005-06-01
prone syndrome xeroderma pigmentosum (XP), and reminiscent of p48 deficiency in XP-E cells, and we have in result in the developmental and...photoproduct; UV-DDB, UV-damaged DNA binding factor; wt, wild-type; well as damaged DNA itself, thus suggesting that it may act as XP, xeroderma pigmentosum . a...the potential for mutagenesis. If UV-DDB is a chromatin the classification of five cell strains of xeroderma pigmentosum group E remodeling factor
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Developmental Idealism, Body Weight and Shape, and Marriage Entry in Transitional China.
Xu, Hongwei
2016-04-01
New trends toward later and less marriage are emerging in post-reform China. Previous research has examined the changing individual-level socioeconomic and demographic characteristics shaping marriage entry in Chinese adults. Employing a cultural model known as developmental idealism (DI), this study argues that a new worldview specifying an ideal body type has become popular in the West and that this new worldview has been exported to China. This new part of the DI package is likely stratified by gender, has a stronger impact on women than on men, and has likely penetrated urban areas more than rural areas. Drawing on the 1991-2009 longitudinal data from the China Health and Nutrition Survey, this study employs discrete-time logit models to estimate the relationships between various body types and transition to first marriage in Chinese young adults 18-30 years old. Body weight status and body shape are measured by body mass index (BMI) and waist-to-hip ratio (WHR), respectively, and further divided into categories of underweight, normal, and obese. Regression results indicate that larger values of BMI and WHR were associated with delayed entry into first marriage in urban women, whereas being overweight or obese was associated with accelerated transition to first marriage in rural men. Not only were these associations statistically significant, but their strengths were substantively remarkable. Findings from this study suggest that both body weight and body shape have important implications for marital success, independent of individual-level socioeconomic and demographic characteristics, and contribute to evolving gender and rural-urban disparities, as China is undergoing a rapid nutrition transition.
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Gabriele, Mark L.; Shahmoradian, Sarah H.; French, Christopher C.; Henkel, Craig K.we; McHaffie, John G.
2007-01-01
The central nucleus of the inferior colliculus (IC) is a laminated structure that receives multiple converging afferent projections. These projections terminate in a layered arrangement and are aligned with dendritic arbors of the predominant disc-shaped neurons, forming fibrodendritic laminae. Within this structural framework, inputs terminate in a precise manner, establishing a mosaic of partially overlapping domains that likely define functional compartments. Although several of these patterned inputs have been described in the adult, relatively little is known about their organization prior to hearing onset. The present study used the lipophilic carbocyanine dyes DiI and DiD to examine the ipsilateral and contralateral projections from the lateral superior olivary (LSO) nucleus to the IC in a developmental series of paraformaldehyde-fixed kitten tissue. By birth, the crossed and uncrossed projections had reached the IC and were distributed across the frequency axis of the central nucleus. At this earliest postnatal stage, projections already exhibited a characteristic banded arrangement similar to that described in the adult. The heaviest terminal fields of the two inputs were always complementary in nature, with the ipsilateral input appearing slightly denser. This early arrangement of interdigitating ipsilateral and contralateral LSO axonal bands that occupy adjacent sublayers supports the idea that the initial establishment of this highly organized mosaic of inputs that defines distinct synaptic domains within the IC occurs largely in the absence of auditory experience. Potential developmental mechanisms that may shape these highly ordered inputs prior to hearing onset are discussed. PMID:17850770
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Developmental Idealism, Body Weight and Shape, and Marriage Entry in Transitional China
Xu, Hongwei
2016-01-01
New trends toward later and less marriage are emerging in post-reform China. Previous research has examined the changing individual-level socioeconomic and demographic characteristics shaping marriage entry in Chinese adults. Employing a cultural model known as developmental idealism (DI), this study argues that a new worldview specifying an ideal body type has become popular in the West and that this new worldview has been exported to China. This new part of the DI package is likely stratified by gender, has a stronger impact on women than on men, and has likely penetrated urban areas more than rural areas. Drawing on the 1991-2009 longitudinal data from the China Health and Nutrition Survey, this study employs discrete-time logit models to estimate the relationships between various body types and transition to first marriage in Chinese young adults 18-30 years old. Body weight status and body shape are measured by body mass index (BMI) and waist-to-hip ratio (WHR), respectively, and further divided into categories of underweight, normal, and obese. Regression results indicate that larger values of BMI and WHR were associated with delayed entry into first marriage in urban women, whereas being overweight or obese was associated with accelerated transition to first marriage in rural men. Not only were these associations statistically significant, but their strengths were substantively remarkable. Findings from this study suggest that both body weight and body shape have important implications for marital success, independent of individual-level socioeconomic and demographic characteristics, and contribute to evolving gender and rural-urban disparities, as China is undergoing a rapid nutrition transition. PMID:27909585
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DOE Office of Scientific and Technical Information (OSTI.GOV)
J Squire, A Bhattacharjee
We study the magnetorotational instability (MRI) (Balbus & Hawley 1998) using non-modal stability techniques.Despite the spectral instability of many forms of the MRI, this proves to be a natural method of analysis that is well-suited to deal with the non-self-adjoint nature of the linear MRI equations. We find that the fastest growing linear MRI structures on both local and global domains can look very diff erent to the eigenmodes, invariably resembling waves shearing with the background flow (shear waves). In addition, such structures can grow many times faster than the least stable eigenmode over long time periods, and be localizedmore » in a completely di fferent region of space. These ideas lead – for both axisymmetric and non-axisymmetric modes – to a natural connection between the global MRI and the local shearing box approximation. By illustrating that the fastest growing global structure is well described by the ordinary diff erential equations (ODEs) governing a single shear wave, we find that the shearing box is a very sensible approximation for the linear MRI, contrary to many previous claims. Since the shear wave ODEs are most naturally understood using non-modal analysis techniques, we conclude by analyzing local MRI growth over finite time-scales using these methods. The strong growth over a wide range of wave-numbers suggests that non-modal linear physics could be of fundamental importance in MRI turbulence (Squire & Bhattacharjee 2014).« less
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Genetic Drivers of Kidney Defects in the DiGeorge Syndrome.
Lopez-Rivera, Esther; Liu, Yangfan P; Verbitsky, Miguel; Anderson, Blair R; Capone, Valentina P; Otto, Edgar A; Yan, Zhonghai; Mitrotti, Adele; Martino, Jeremiah; Steers, Nicholas J; Fasel, David A; Vukojevic, Katarina; Deng, Rong; Racedo, Silvia E; Liu, Qingxue; Werth, Max; Westland, Rik; Vivante, Asaf; Makar, Gabriel S; Bodria, Monica; Sampson, Matthew G; Gillies, Christopher E; Vega-Warner, Virginia; Maiorana, Mariarosa; Petrey, Donald S; Honig, Barry; Lozanovski, Vladimir J; Salomon, Rémi; Heidet, Laurence; Carpentier, Wassila; Gaillard, Dominique; Carrea, Alba; Gesualdo, Loreto; Cusi, Daniele; Izzi, Claudia; Scolari, Francesco; van Wijk, Joanna A E; Arapovic, Adela; Saraga-Babic, Mirna; Saraga, Marijan; Kunac, Nenad; Samii, Ali; McDonald-McGinn, Donna M; Crowley, Terrence B; Zackai, Elaine H; Drozdz, Dorota; Miklaszewska, Monika; Tkaczyk, Marcin; Sikora, Przemyslaw; Szczepanska, Maria; Mizerska-Wasiak, Malgorzata; Krzemien, Grazyna; Szmigielska, Agnieszka; Zaniew, Marcin; Darlow, John M; Puri, Prem; Barton, David; Casolari, Emilio; Furth, Susan L; Warady, Bradley A; Gucev, Zoran; Hakonarson, Hakon; Flogelova, Hana; Tasic, Velibor; Latos-Bielenska, Anna; Materna-Kiryluk, Anna; Allegri, Landino; Wong, Craig S; Drummond, Iain A; D'Agati, Vivette; Imamoto, Akira; Barasch, Jonathan M; Hildebrandt, Friedhelm; Kiryluk, Krzysztof; Lifton, Richard P; Morrow, Bernice E; Jeanpierre, Cecile; Papaioannou, Virginia E; Ghiggeri, Gian Marco; Gharavi, Ali G; Katsanis, Nicholas; Sanna-Cherchi, Simone
2017-02-23
The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5×10 -14 ). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.).
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Bergeron, Lise; Berthiaume, Claude; St-Georges, Marie; Piché, Geneviève; Smolla, Nicole
2013-08-01
As no single informant can be considered the gold standard of child psychopathology, interviewing of children regarding their own symptoms is necessary. Our study focused on the reliability, validity, and clinical use of the Dominic Interactive (DI), a multimedia self-report screen to assess symptoms for the most frequent Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, mental disorders in school-aged children. A sample of 585 children aged 6 to 11 years from the community and psychiatric clinics was used to analyze the internal consistency, the test-retest estimate of reliability, and the criterion-related validity of the DI against the referral status. In addition, cross-informant correlation coefficients between this instrument (child report) and the Child Symptom Inventory (parent report) were explored in a subsample of 292 participants. For the total sample, Cronbach alpha coefficients ranged from 0.63 to 0.91. Test-retest kappas varied from 0.42 to 0.62 for categories based on cut-off points, except for specific phobias. Intraclass correlation coefficients ranged from 0.70 to 0.81 for symptom scales. The DI discriminated between referred and non-referred children in psychiatric clinics for all symptom scales. Significant cross-informant correlation coefficients were higher for the externalizing symptoms (0.35 to 0.48) than the internalizing symptoms (0.14 to 0.27). Findings of our study reasonably support adequate psychometric properties of the DI. This instrument offers a developmentally sensitive screening method to obtain unique information from young children about their mental health problems in front-line services, psychiatric clinics, and research settings.
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Pan, Guowei; Hanaoka, Tomoyuki; Yoshimura, Mariko; Zhang, Shujuan; Wang, Ping; Tsukino, Hiromasa; Inoue, Koichi; Nakazawa, Hiroyuki; Tsugane, Shoichiro; Takahashi, Ken
2006-11-01
Observations of adverse developmental and reproductive effects in laboratory animals and wildlife have fueled increasing public concern regarding the potential for various chemicals to impair human fertility. Our objective in this study was to assess the effect of occupational exposure to high levels of phthalate esters on the balance of gonadotropin and gonadal hormones including luteinizing hormone, follicle-stimulating hormone, free testosterone (fT), and estradiol. We examined urine and blood samples of 74 male workers at a factory producing unfoamed polyvinyl chloride flooring exposed to di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) and compared them with samples from 63 male workers from a construction company, group matched for age and smoking status. Compared to the unexposed workers, the exposed workers had substantially and significantly elevated concentrations of mono-n-butyl phthalate (MBP; 644.3 vs. 129.6 microg/g creatinine, p < 0.001) and mono-2-ethylhexyl phthalate (MEHP; 565.7 vs. 5.7 microg/g creatinine, p < 0.001). fT was significantly lower (8.4 vs. 9.7 microg/g creatinine, p = 0.019) in exposed workers than in unexposed workers. fT was negatively correlated to MBP (r = -0.25, p = 0.03) and MEHP (r = -0.19, p = 0.095) in the exposed worker group. Regression analyses revealed that fT decreases significantly with increasing total phthalate ester score (the sum of quartiles of MBP and MEHP; r = -0.26, p = 0.002). We observed a modest and significant reduction of serum fT in workers with higher levels of urinary MBP and MEHP compared with unexposed workers.
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Pan, Guowei; Hanaoka, Tomoyuki; Yoshimura, Mariko; Zhang, Shujuan; Wang, Ping; Tsukino, Hiromasa; Inoue, Koichi; Nakazawa, Hiroyuki; Tsugane, Shoichiro; Takahashi, Ken
2006-01-01
Background Observations of adverse developmental and reproductive effects in laboratory animals and wildlife have fueled increasing public concern regarding the potential for various chemicals to impair human fertility. Objective Our objective in this study was to assess the effect of occupational exposure to high levels of phthalate esters on the balance of gonadotropin and gonadal hormones including luteinizing hormone, follicle-stimulating hormone, free testosterone (fT), and estradiol. Methods We examined urine and blood samples of 74 male workers at a factory producing unfoamed polyvinyl chloride flooring exposed to di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) and compared them with samples from 63 male workers from a construction company, group matched for age and smoking status. Results Compared to the unexposed workers, the exposed workers had substantially and significantly elevated concentrations of mono-n-butyl phthalate (MBP; 644.3 vs. 129.6 μg/g creatinine, p < 0.001) and mono-2-ethylhexyl phthalate (MEHP; 565.7 vs. 5.7 μg/g creatinine, p < 0.001). fT was significantly lower (8.4 vs. 9.7 μg/g creatinine, p = 0.019) in exposed workers than in unexposed workers. fT was negatively correlated to MBP (r = −0.25, p = 0.03) and MEHP (r = −0.19, p = 0.095) in the exposed worker group. Regression analyses revealed that fT decreases significantly with increasing total phthalate ester score (the sum of quartiles of MBP and MEHP; r = −0.26, p = 0.002). Conclusion We observed a modest and significant reduction of serum fT in workers with higher levels of urinary MBP and MEHP compared with unexposed workers. PMID:17107847
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[Toxicity effects of phthalate substitute plasticizers used in toys].
Hirata-Koizumi, Mutsuko; Takahashi, Mika; Matsumoto, Mariko; Kawamura, Tomoko; Ono, Atsushi; Hirose, Akihiko
2012-01-01
Phthalate esters are widely used as plasticizers in polyvinyl chloride products. Because of human health concerns, regulatory authorities in Japan, US, Europe and other countries control the use of di(2-ethylhexyl) phthalate, diisononyl phthalate, di-n-butyl phthalate, butylbenzyl phthalate, diisodecyl phthalate and di-n-octyl phthalate for the toys that can be put directly in infants' mouths. While these regulatory actions will likely reduce the usage of phthalate esters, there is concern that other plasticizers that have not been sufficiently evaluated for safety will be used more frequently. We therefore collected and evaluated the toxicological information on di(2-ethylhexyl) terephthalate (DEHT), 1,2-cyclohexanedicarboxylic acid, diisononyl ester (DINCH), diisononyl adipate (DINA), 2,2,4-trimetyl-1,3-pentanediol diisobutyrate (TXIB), tri-n-butyl citrate (TBC) and acetyl tri-n-butyl citrate (ATBC) which were detected at a relatively high frequency in toys. The collected data have shown that chronic exposure to DEHT affects the eye and nasal turbinate, and DINCH exerts effects on the thyroid and kidney in rats. DINA and TXIB have been reported to have hepatic and renal effects in dogs or rats, and ATBC slightly affected the liver in rats. The NOAELs for repeated dose toxicity are relatively low for DINCH (40 mg/kg bw/day) and TXIB (30 mg/kg bw/day) compared with DEHT, DINA and ATBC. DEHT, TXIB and ATBC have been reported to have reproductive/developmental effects at relatively high doses in rats. For DINA and TBC, available data are insufficient for assessing the hazards, and therefore, adequate toxicity studies should be conducted. In the present review, the toxicity information on 6 alternatives to phthalate plasticizers is summarized, focusing on the effects after oral exposure, which is the route of most concern.
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Freeman, D. Carl; Brown, Michelle L.; Duda, Jeffrey J.; Graham, John H.; Emlen, John M.; Krzysik, Anthony J.; Balbach, Harold E.; Kovacic, David A.; Zak, John C.
2004-01-01
We examined net photosynthesis, transpiration, stomatal conductance, and leaf fluctuating asymmetry on two species (Rhus copallinum and Ipomoea pandurata) as indicators of stress at nine sites across a gradient of soil disturbance at Fort Benning, Georgia. There were three sites for each of three disturbance levels. Physical habitat disturbance was caused by activities associated with infantry training, including mechanized elements (tanks and personnel carriers) and foot soldiers. In addition, we examined the influence of prescribed burns and microhabitat effects (within meter‐square quadrats centered about the plant) on these measures of plant stress. Net photosynthesis declined with increasing disturbance in the absence of burning for both species. However, when sites were burned the previous year, net photosynthesis increased with increasing disturbance. Developmental instability in Rhus, as measured by fluctuating asymmetry, also declined with increasing disturbance in the absence of burning but increased with disturbance if sites were burned the previous year. Developmental instability was much less sensitive to burning in Ipomoea and in general was lowest at intermediate disturbance sites. Microenvironmental and microhabitat effects were weakly correlated with measures of plant stress when all sites were combined. However, higher correlations were obtained within site categories, especially when the recent history of prescribed burning was used as a category. Finally, using all of the combined data in a discriminant function analysis allowed us to correctly predict the disturbance level of more than 80% of the plants. Plant stress is responsive to both large‐scale perturbations, such as burning, and microhabitat parameters. Because of this, it is important to include macro‐ and microhabitat parameters when assessing stress. Similarly, we found a combination of developmental and physiological indicators of stress was superior to using them separately.
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Knopper, Loren D; Mineau, Pierre
2004-06-01
This is the second of two articles reporting the results of a nonlethal biomonitoring study that quantified the effects of pesticide exposure on meadow voles (Microtus pennsylvanicus) living in golf course ecosystems of the Ottawa/Gatineau region (ON and PQ, Canada, respectively). In the present article, we describe results of measurements regarding developmental instability (e.g., fluctuating asymmetry), congenital birth defects (e.g., skeletal terata), clinical hematology (e.g., differential counts), general body condition (e.g., body mass-length relationships), and blood parasite load (Trypanosoma sp. and Bartonella spp.). Voles were captured during the year 2001 to 2003 at six golf courses and two reference sites. Once voles were fully sedated using isoflurane, blood was collected, radiographs taken, and morphometric measurements recorded. Three animals from each course were euthanized to determine body burdens of historically used organochlorine (OC) and metal-based pesticides. Exposure to in-use pesticides was determined from detailed golf course pesticide-use records. None of the endpoints measured was significantly related to body burdens of OC pesticides and metals historically used, nor did any endpoint significantly vary among capture sites in relation to total pesticide application to the capture site or to the number of days since the last application of pesticide. Based on these findings, it appears that voles from golf courses were no less healthy than their conspecifics from reference sites.
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Rein, Katrin; Yanez, Diana A; Terré, Berta; Palenzuela, Lluís; Aivio, Suvi; Wei, Kaichun; Edelmann, Winfried; Stark, Jeremy M; Stracker, Travis H
2015-09-03
The maintenance of genome stability is critical for the suppression of diverse human pathologies that include developmental disorders, premature aging, infertility and predisposition to cancer. The DNA damage response (DDR) orchestrates the appropriate cellular responses following the detection of lesions to prevent genomic instability. The MRE11 complex is a sensor of DNA double strand breaks (DSBs) and plays key roles in multiple aspects of the DDR, including DNA end resection that is critical for signaling and DNA repair. The MRE11 complex has been shown to function both upstream and in concert with the 5'-3' exonuclease EXO1 in DNA resection, but it remains unclear to what extent EXO1 influences DSB responses independently of the MRE11 complex. Here we examine the genetic relationship of the MRE11 complex and EXO1 during mammalian development and in response to DNA damage. Deletion of Exo1 in mice expressing a hypomorphic allele of Nbs1 leads to severe developmental impairment, embryonic death and chromosomal instability. While EXO1 plays a minimal role in normal cells, its loss strongly influences DNA replication, DNA repair, checkpoint signaling and damage sensitivity in NBS1 hypomorphic cells. Collectively, our results establish a key role for EXO1 in modulating the severity of hypomorphic MRE11 complex mutations. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.
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Housing mobility and cognitive development: Change in verbal and nonverbal abilities.
Fowler, Patrick J; McGrath, Lauren M; Henry, David B; Schoeny, Michael; Chavira, Dina; Taylor, Jeremy J; Day, Orin
2015-10-01
This study investigates the influence of housing instability on verbal and nonverbal cognitive development among at-risk children and adolescents involved in the child welfare system. Frequent residential changes threaten child mental health, especially among low-income families. Little is known regarding disruptions to cognitive growth, specifically the impact on verbal and nonverbal abilities. The study tests whether developmental timing of housing mobility affects cognitive development beyond individual and family risks. A nationally representative study of families (n=2,442) susceptible to housing and family instability tracked children and adolescents aged 4-14 years (M=8.95 years) over 36 months following investigation by the child welfare system. Youth completed standardized cognitive assessments while caregivers reported on behavior problems and family risk at three time points. Latent growth models examined change in cognitive abilities over time. Housing mobility in the 12 months prior to baseline predicts lower verbal cognitive abilities that improve marginally. Similar effects emerge for all age groups; however, frequent moves in infancy diminish the influence of subsequent housing mobility on verbal tasks. Housing instability threatened cognitive development beyond child maltreatment, family changes, poverty, and other risks. Findings inform emerging research on environmental influences on neurocognitive development, as well as identify targets for early intervention. Systematic assessment of family housing problems, including through the child welfare system, provides opportunities for coordinated responses to prevent instability and cognitive threats. Copyright © 2015 Elsevier Ltd. All rights reserved.
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How many breaks do we need to CATCH on 22q11?
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dallapiccola, B.; Pizzuti, A.; Novelli, G.
1996-07-01
The major clinical manifestations of DiGeorge syndrome (DGS; MIM 188400), which reflect developmental abnormalities of the 3d and 4th pharyngeal pouch derivatives, include thymus- and parathyroid-gland aplasia or hypoplasia and conotruncal cardiac malformations. The additional dysmorphic facial features, such as hypertelorism, cleft lip and palate, bifid uvula, and small/low-set ears, which are also common, presumably reflect the same defect. The DGS phenotype has been associated with chromosome abnormalities and, sometimes, is the effect of teratogenic agents such as retinoic acid and alcohol. 53 refs., 1 fig.
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Directional measures of postural sway as predictors of balance instability and accidental falls
Janusz, Błaszczyk W.; Beck, Monika; Szczepańska, Justyna; Sadowska, Dorota; Bacik, Bogdan; Juras, Grzegorz
2016-01-01
Abstract Despite the obvious advantages and popularity of static posturography, universal standards for posturographic tests have not been developed thus far. Most of the center-of-foot pressure (COP) indices are strongly dependent on an individual experimental design, and are susceptible to distortions, which makes results of their analysis incomparable. In this research, we present a novel approach to the analysis of the COP trajectory based on the directional features of postural sway. Our novel output measures: the sway directional indices (DI) and sway vector (SV) were applied to assess the postural stability in the group of young able-bodied subjects. Towards this aim, the COP trajectories were recorded in 100 students standing still for 60 s, with eyes open (EO) and then, with eyes closed (EC). Each record was subdivided then into 20, 30 and 60 s samples. Interclass correlation coefficients were calculated from the samples. The controlled variables (visual conditions) uniquely affected the output measures, but only in case of proper signal pretreatment (low-pass filtering). In filtering below 6 Hz, the DI and SV provided a unique set of descriptors for postural control. Both sway measures were highly independent of the trial length and the sampling frequency, and were unaffected by the sampling noise. Directional indices of COP filtered at 6 Hz showed high to very high reliability, with ICC range of 0.7-0.9. Results of a single 60 s trial are sufficient to reach acceptable reliability for both DI and SV. In conclusion, the directional sway measures may be recommended as the primary standard in static posturography. PMID:28149395
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Pharyngeal mesoderm regulatory network controls cardiac and head muscle morphogenesis.
Harel, Itamar; Maezawa, Yoshiro; Avraham, Roi; Rinon, Ariel; Ma, Hsiao-Yen; Cross, Joe W; Leviatan, Noam; Hegesh, Julius; Roy, Achira; Jacob-Hirsch, Jasmine; Rechavi, Gideon; Carvajal, Jaime; Tole, Shubha; Kioussi, Chrissa; Quaggin, Susan; Tzahor, Eldad
2012-11-13
The search for developmental mechanisms driving vertebrate organogenesis has paved the way toward a deeper understanding of birth defects. During embryogenesis, parts of the heart and craniofacial muscles arise from pharyngeal mesoderm (PM) progenitors. Here, we reveal a hierarchical regulatory network of a set of transcription factors expressed in the PM that initiates heart and craniofacial organogenesis. Genetic perturbation of this network in mice resulted in heart and craniofacial muscle defects, revealing robust cross-regulation between its members. We identified Lhx2 as a previously undescribed player during cardiac and pharyngeal muscle development. Lhx2 and Tcf21 genetically interact with Tbx1, the major determinant in the etiology of DiGeorge/velo-cardio-facial/22q11.2 deletion syndrome. Furthermore, knockout of these genes in the mouse recapitulates specific cardiac features of this syndrome. We suggest that PM-derived cardiogenesis and myogenesis are network properties rather than properties specific to individual PM members. These findings shed new light on the developmental underpinnings of congenital defects.
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Akhter, Shamima; Lam, Yung C; Chang, Sandy; Legerski, Randy J
2010-12-01
Conserved metallo β-Lactamase and β-CASP (CPSF-Artemis-Snm1-Pso2) domain nuclease family member SNM1B/Apollo is a shelterin-associated protein that localizes to telomeres through its interaction with TRF2. To study its in vivo role, we generated a knockout of SNM1B/Apollo in a mouse model. Snm1B/Apollo homozygous null mice die at birth with developmental delay and defects in multiple organ systems. Cell proliferation defects were observed in Snm1B/Apollo mutant mouse embryonic fibroblasts (MEFs) owing to high levels of telomeric end-to-end fusions. Deficiency of the nonhomologous end-joining (NHEJ) factor Ku70, but not p53, rescued the developmental defects and lethality observed in Snm1B/Apollo mutant mice as well as the impaired proliferation of Snm1B/Apollo-deficient MEFs. These findings demonstrate that SNM1B/Apollo is required to protect telomeres against NHEJ-mediated repair, which results in genomic instability and the consequent multi-organ developmental failure. Although Snm1B/Apollo-deficient MEFs exhibited high levels of apoptosis, abrogation of p53-dependent programmed cell death did not rescue the multi-organ developmental failure in the mice. © 2010 The Authors. Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.
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Shen, Ru; Zhao, Ling-Li; Yu, Zhen; Zhang, Cheng; Chen, Yuan-Hua; Wang, Hua; Zhang, Zhi-Hui; Xu, De-Xiang
2017-01-01
Di (2-ethylhexyl) phthalate (DEHP) is male developmental toxicant that impairs testis development with reduced anogenital distance. The present study aimed to investigate whether maternal DEHP exposure during pregnancy causes intrauterine growth restriction (IUGR) in a gender-specific manner and to identify the critical window of DEHP-induced fetal IUGR. Pregnant mice were administered with DEHP (0, 50 or 200mg/kg) by gavage. Fetal IUGR was observed not only in males but also in females when litters were exposed to DEHP on gestational day (GD)0-GD17. Interestingly, fetal weight and crown-rump length were reduced, markedly in dams with DEHP on GD13-GD17, slightly in dams with on GD7-GD12, but not in dams with on GD0-GD6. Further analysis showed that maternal DEHP exposure on GD7-GD12 inhibited cell proliferation, lowered placental weight, and reduced blood sinusoid area in placental labyrinth layer. These results suggest that maternal DEHP exposure induces IUGR in a stage-specific but gender-independent manner. Copyright © 2016 Elsevier Inc. All rights reserved.
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Gu, Yi-Hua; Liu, Miao; Xu, Yan; Yuan, Yao; Sun, Fei; Zhang, Hui-Qin; Shi, Hui-Juan
2012-01-01
The present study was undertaken to determine the reproductive hazards of Di-(2-ethylhexyl)-phthalate (DEHP) on mouse spermatozoa and embryos in vitro and genomic changes in vivo. Direct low-level DEHP exposure (1 μg/ml) on spermatozoa and embryos was investigated by in vitro fertilization (IVF) process, culture of preimplanted embryos in DEHP-supplemented medium and embryo transfer to achieve full term development. Big Blue® transgenic mouse model was employed to evaluate the mutagenesis of testicular genome with in vivo exposure concentration of DEHP (500 mg/kg/day). Generally, DEHP-treated spermatozoa (1 μg/ml, 30 min) presented reduced fertilization ability (P<0.05) and the resultant embryos had decreased developmental potential compared to DMSO controls (P<0.05). Meanwhile, the transferred 2-cell stage embryos derived from treated spermatozoa also exhibited decreased birth rate than that of control (P<0.05). When fertilized oocytes or 2-cell stage embryos were recovered by in vivo fertilization (without treatment) and then exposed to DEHP, the subsequent development proceed to blastocysts was different, fertilized oocytes were significantly affected (P<0.05) whereas developmental progression of 2-cell stage embryos was similar to controls (P>0.05). Testes of the Big Blue® transgenic mice treated with DEHP for 4 weeks indicated an approximately 3-fold increase in genomic DNA mutation frequency compared with controls (P<0.05). These findings unveiled the hazardous effects of direct low-level exposure of DEHP on spermatozoa's fertilization ability as well as embryonic development, and proved that in vivo DEHP exposure posed mutagenic risks in the reproductive organ – at least in testes, are of great concern to human male reproductive health. PMID:23226291
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Schaedlich, Kristina; Schmidt, Juliane-Susanne; Kwong, Wing Yee; Sinclair, Kevin D; Kurz, Randy; Jahnke, Heinz-Georg; Fischer, Bernd
2015-07-01
Di(2-ethylhexyl)phthalate (DEHP) is the most common plasticizer in plastic devices of everyday use. It is a ubiquitous environmental contaminant and primarily known to impair male gonadal development and fertility. Studies concerning the long-term effects of prenatal DEHP exposure on certain diseases [The Developmental Origins of Health and Disease paradigm (DOHaD) hypothesis] are scarce although it is proven that DEHP crosses the placenta. Rising environmental pollution during the last centuries coincides with an increasing prevalence of cardiovascular and metabolic diseases. We have investigated the effects of an early embryonic DEHP exposure at different developmental stages on cardiomyogenesis. We used an in-vitro model, the murine P19 embryonic carcinoma cell line (P19 ECC), mimicking early embryonic stages up to differentiated beating cardiomyocytes. P19 ECC were exposed to DEHP (5, 50, 100 µg ml(-1)) at the undifferentiated stage for 5 days and subsequently differentiated to beating cardiomyocytes. We analyzed the expression of metabolic (Pparg1, Fabp4 and Glut4), cardiac (Myh6, Gja1) and methylation (Dnmt1, Dnmt3a) marker genes by quantitative real-time PCR (qRT-PCR), beating rate and the differentiation velocity of the cells. The methylation status of Pparg1, Ppara and Glut4 was investigated by pyrosequencing. DEHP significantly altered the expression of all investigated genes. The beating rate and differentiation velocity were accelerated. Exposure to DEHP led to small but statistically significant increases in methylation of specific CpGs within Ppara and Pparg1, which otherwise were generally hypomethylated, but methylation of Glut4 was unaltered. Early DEHP exposure of P19 ECC alters the expression of genes associated with cellular metabolism and the functional features of cardiomyocytes. Copyright © 2014 John Wiley & Sons, Ltd.
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Triggering autophagic cell death with a di-manganese(II) developmental therapeutic.
Slator, Creina; Molphy, Zara; McKee, Vickie; Kellett, Andrew
2017-08-01
There is an unmet need for novel metal-based chemotherapeutics with alternative modes of action compared to clinical agents such as cisplatin and metallo-bleomycin. Recent attention in this field has focused on designing intracellular ROS-mediators as powerful cytotoxins of human cancers and identifying potentially unique toxic mechanisms underpinning their utility. Herein, we report the developmental di-manganese(II) therapeutic [Mn 2 (μ-oda)(phen) 4 (H 2 O) 2 ][Mn 2 (μ-oda)(phen) 4 (oda) 2 ]·4H 2 O (Mn-Oda) induces autophagy-promoted apoptosis in human ovarian cancer cells (SKOV3). The complex was initially identified to intercalate DNA by topoisomerase I unwinding and circular dichroism spectroscopy. Intracellular DNA damage, detected by γH2AX and the COMET assay, however, is not linked to direct Mn-Oda free radical generation, but is instead mediated through the promotion of intracellular reactive oxygen species (ROS) leading to autophagic vacuole formation and downstream nuclear degradation. To elucidate the cytotoxic profile of Mn-Oda, a wide range of biomarkers specific to apoptosis and autophagy including caspase release, mitochondrial membrane integrity, fluorogenic probe localisation, and cell cycle analysis were employed. Through these techniques, the activity of Mn-Oda was compared directly to i.) the pro-apoptotic clinical anticancer drug doxorubicin, ii.) the multimodal histone deacetylase inhibitor suberoyanilide hydroxamic acid, and iii.) the autophagy inducer rapamycin. In conjunction with ROS-specific trapping agents and established inhibitors of autophagy, we have identified autophagy-induction linked to mitochondrial superoxide production, with confocal image analysis of SKOV3 cells further supporting autophagosome formation. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
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Huang, Xue-Feng; Li, Yan; Gu, Yi-Hua; Liu, Miao; Xu, Yan; Yuan, Yao; Sun, Fei; Zhang, Hui-Qin; Shi, Hui-Juan
2012-01-01
The present study was undertaken to determine the reproductive hazards of Di-(2-ethylhexyl)-phthalate (DEHP) on mouse spermatozoa and embryos in vitro and genomic changes in vivo. Direct low-level DEHP exposure (1 μg/ml) on spermatozoa and embryos was investigated by in vitro fertilization (IVF) process, culture of preimplanted embryos in DEHP-supplemented medium and embryo transfer to achieve full term development. Big Blue® transgenic mouse model was employed to evaluate the mutagenesis of testicular genome with in vivo exposure concentration of DEHP (500 mg/kg/day). Generally, DEHP-treated spermatozoa (1 μg/ml, 30 min) presented reduced fertilization ability (P<0.05) and the resultant embryos had decreased developmental potential compared to DMSO controls (P<0.05). Meanwhile, the transferred 2-cell stage embryos derived from treated spermatozoa also exhibited decreased birth rate than that of control (P<0.05). When fertilized oocytes or 2-cell stage embryos were recovered by in vivo fertilization (without treatment) and then exposed to DEHP, the subsequent development proceed to blastocysts was different, fertilized oocytes were significantly affected (P<0.05) whereas developmental progression of 2-cell stage embryos was similar to controls (P>0.05). Testes of the Big Blue® transgenic mice treated with DEHP for 4 weeks indicated an approximately 3-fold increase in genomic DNA mutation frequency compared with controls (P<0.05). These findings unveiled the hazardous effects of direct low-level exposure of DEHP on spermatozoa's fertilization ability as well as embryonic development, and proved that in vivo DEHP exposure posed mutagenic risks in the reproductive organ - at least in testes, are of great concern to human male reproductive health.
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Lehoux, Pascale M; Howe, Nina
2007-03-01
The role of perceived non-shared environmental influences and personality traits in the risk of developing bulimia nervosa (BN) was compared in 40 women with BN and their non-eating disordered sisters. The two sisters were compared for (a) eating pathology, (b) perceived non-shared environmental factors (differential family relationships, developmental teasing, traumatic experiences), (c) personality traits (impulsivity, affective instability, narcissism), and (d) psychopathology (anxiety, depression). Specific perceived non-shared risk factors (e.g. perceptions of teasing), nonspecific non-shared risk factors (e.g. insecure paternal attachment) and personality traits (e.g. narcissism) distinguished women with BN from sisters. In the final logistic regression, insecure paternal attachment predicted the risk for BN, while trends were apparent for narcissism and developmental teasing after controlling for psychopathology. Our correlational cross-sectional design does not allow for investigation of direction of effects. However, it is an important first step in identifying possible perceived non-shared environmental influences and personality traits that may constitute vulnerability factors predisposing individuals to the development of BN. Findings are discussed in the light of existing models of risk factors for the etiology of BN.
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May, Emily M; Azar, Sandra T; Matthews, Stephen A
2018-03-01
Living in a disadvantaged neighborhood is associated with heightened risk for poor school readiness and health outcomes in early childhood, and the home environment is thought to be a primary mechanism by which neighborhood context impacts preschoolers. This study examined the effects of neighborhood concentrated disadvantage and neighborhood residential instability on the home physical environment and home learning environment for preschoolers in economically disadvantaged families (N = 187). Using structural equation modeling, mothers' perceived neighborhood disorder and depressive symptoms were examined as mechanisms by which neighborhood context "comes through the door." Mothers' neighborhood social embeddedness was also explored as a protective factor. Results showed that concentrated disadvantage was negatively associated with the quality of the home physical environment, and residential instability was negatively associated with the quality of the home learning environment. Concentrated disadvantage had an indirect effect on the home learning environment through mothers' perceived neighborhood disorder and depressive symptoms. The effects of concentrated disadvantage on the home environment were buffered by mothers' neighborhood social embeddedness. Study findings advance understanding of socioeconomic- and place-based disparities in developmental outcomes and identify potential targets for interventions aimed at lessening effects of neighborhood disadvantage on families with young children. © Society for Community Research and Action 2018.
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Morrissey, Mark D; Mathews, Iva Z; McCormick, Cheryl M
2011-01-01
Adolescence is a time of developmental changes and reorganization in the brain and stress systems, thus, adolescents may be more vulnerable than adults to the effects of chronic mild stressors. Most studies, however, have not directly compared stress experienced in adolescence to the same stress experience in adulthood. In the present study, adolescent (n=46) and adult (n=48) male rats underwent 16 days of social instability stress (daily 1h isolation and change of cage partners) or were non-stress controls. Rats were then tested on the strength of acquired contextual and cued fear conditioning, as well as extinction learning, beginning either the day after the stress procedure or 3 weeks later. No difference was found among the groups during the Training Phase of conditioning. Irrespective of the time between the social stress experience and fear conditioning, rats stressed in adolescence had decreased context and cue memory, and cue generalization compared to control rats, as measured by the percentage of time spent freezing in tests. Social instability stress in adulthood had no effect on any measure of fear conditioning. The results support the hypothesis that adolescence is a time of heightened vulnerability to stressors. Copyright © 2010 Elsevier Inc. All rights reserved.
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Design study of a re-bunching RFQ for the SPES project
NASA Astrophysics Data System (ADS)
Shin, Seung Wook; Palmieri, A.; Comunian, M.; Grespan, F.; Chai, Jong Seo
2014-05-01
An upgrade to the 2nd generation of the selective production of exotic species (SPES) to produce a radioactive ion beam (RIB) has been studied at the istituto nazionale di fisica nucleare — laboratory nazionali di Legnaro (INFN-LNL). Due to the long distance between the isotope separator online (ISOL) facility and the superconducting quarter wave resonator (QWR) cavity acceleratore lineare per ioni (ALPI), a new re-buncher cavity must be introduced to maintain the high beam quality during the beam transport. A particular radio frequency quadrupole (RFQ) structure has been suggested to meet the requirements of this project. A window-type RFQ, which has a high mode separation, less power dissipation and compact size compared to the conventional normal 4-vane RFQ, has been introduced. The RF design has been studied considering the requirements of the re-bunching machine for high figures of merit such as a proper operation frequency, a high shunt impedance, a high quality factor, a low power dissipation, etc. A sensitivity analysis of the fabrication and the misalignment error has been conducted. A micro-movement slug tuner has been introduced to compensate for the frequency variations that may occur due to the beam loading, the thermal instability, the microphonic effect, etc.
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Shtasel-Gottlieb, Zoë; Palakshappa, Deepak; Yang, Fanyu; Goodman, Elizabeth
2015-02-01
To explore the association between developmental assets (characteristics, experiences, and relationships that shape healthy development) and food insecurity among adolescents from a low-income urban community. This mixed-methods study occurred in two phases. In phase 1, using a census approach, 2,350 6th to 12th graders from the public school district completed an anonymous survey that included the developmental assets profile (DAP), the youth self-report form of the Core Food Security Module, and demographic questions. Logistic and multinomial regression analyses determined independent associations between developmental assets and food security adjusting for demographics. In phase 2, 20 adult key informant interviews and four semistructured student focus groups were performed to explain findings from phase 1. On average, DAP scores were consistent with national norms. Food insecurity was prevalent; 14.9% reported low food security and 8.6% very low food security (VLFS). Logistic regression revealed that higher DAP was associated with lower odds of food insecurity (odds ratio [OR], .96; 95% confidence interval [CI], .95-.97); family assets drove this association (OR, .93; 95% CI, .91-.95). In multinomial regression modeling, these associations persisted, and paradoxically, higher community assets were also associated with VLFS (ORVLFS, 1.08; 95% CI, 1.04-1.13). Qualitative analyses suggested that greater need among VLFS youth led to increased connections to community resources despite barriers to access such as stigma, home instability, and cultural differences. Food insecurity is a pervasive problem among adolescents from low-income communities and is associated with lower developmental assets, particularly family assets. The fact that community assets were higher among VLFS youth underscores the importance of community-level resources in struggling areas. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.
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Vasil'ev, A G; Bol'shakov, V N; Vasil'eva, I A; Evdokimov, N G; Sineva, N V
2018-01-01
Geometric morphometry has been used to reveal transformations of mandible morphogenesis in the offspring of mole voles resettled to the northern part of the species range from a southern population. The transformations were new compared to both the original (southern) and the aboriginal (northern) populations. A significant increase in the intragroup morphological disparity estimated by the mean nearest neighbor distance (MNND) in the resettled animals compared to both aboriginal populations is an indirect indication of an increased developmental instability in the resettled animals exposed to new climatic conditions.
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Miller, Laurence; Miller, Halle B; Bjorklund, David
2010-01-01
Military deployment of a parent carries with it a number of stresses for children, all centering around uncertainty, instability and unpredictability. This article conceptualizes military deployment and relocation stress in the context of attachment theory, and describes the types of adverse outcomes that can occur as the result of impaired attachment. It then presents a set of practical recommendations for mental health clinicians and counselors for helping children and families cope productively and negotiate the developmental hurdles associated with maintaining healthy attachment and family stability in the face of military deployment.
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Spontaneous Symmetry Breaking Turing-Type Pattern Formation in a Confined Dictyostelium Cell Mass
NASA Astrophysics Data System (ADS)
Sawai, Satoshi; Maeda, Yasuo; Sawada, Yasuji
2000-09-01
We have discovered a new type of patterning which occurs in a two-dimensionally confined cell mass of the cellular slime mold Dictyostelium discoideum. Besides the longitudinal structure reported earlier, we observed a spontaneous symmetry breaking spot pattern whose wavelength shows similar strain dependency to that of the longitudinal pattern. We propose that these structures are due to a reaction-diffusion Turing instability similar to the one which has been exemplified by CIMA (chlorite-iodide-malonic acid) reaction. The present finding may exhibit the first biochemical Turing structure in a developmental system with a controllable boundary condition.
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Genetic Drivers of Kidney Defects in the DiGeorge Syndrome
Lopez-Rivera, E.; Liu, Y.P.; Verbitsky, M.; Anderson, B.R.; Capone, V.P.; Otto, E.A.; Yan, Z.; Mitrotti, A.; Martino, J.; Steers, N.J.; Fasel, D.A.; Vukojevic, K.; Deng, R.; Racedo, S.E.; Liu, Q.; Werth, M.; Westland, R.; Vivante, A.; Makar, G.S.; Bodria, M.; Sampson, M.G.; Gillies, C.E.; Vega-Warner, V.; Maiorana, M.; Petrey, D.S.; Honig, B.; Lozanovski, V.J.; Salomon, R.; Heidet, L.; Carpentier, W.; Gaillard, D.; Carrea, A.; Gesualdo, L.; Cusi, D.; Izzi, C.; Scolari, F.; van Wijk, J.A.E.; Arapovic, A.; Saraga-Babic, M.; Saraga, M.; Kunac, N.; Samii, A.; McDonald-McGinn, D.M.; Crowley, T.B.; Zackai, E.H.; Drozdz, D.; Miklaszewska, M.; Tkaczyk, M.; Sikora, P.; Szczepanska, M.; Mizerska-Wasiak, M.; Krzemien, G.; Szmigielska, A.; Zaniew, M.; Darlow, J.M.; Puri, P.; Barton, D.; Casolari, E.; Furth, S.L.; Warady, B.A.; Gucev, Z.; Hakonarson, H.; Flogelova, H.; Tasic, V.; Latos-Bielenska, A.; Materna-Kiryluk, A.; Allegri, L.; Wong, C.S.; Drummond, I.A.; D’Agati, V.; Imamoto, A.; Barasch, J.M.; Hildebrandt, F.; Kiryluk, K.; Lifton, R.P.; Morrow, B.E.; Jeanpierre, C.; Papaioannou, V.E.; Ghiggeri, G.M.; Gharavi, A.G.; Katsanis, N.; Sanna-Cherchi, S.
2017-01-01
BACKGROUND The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. METHODS We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. RESULTS We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5×10−14). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. CONCLUSIONS We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.) PMID:28121514
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Glotzbecker, Michael P; Wasser, Aubrey M; Troy, Michael J; Proctor, Mark; Emans, John B
2015-06-01
Vertebral osteomyelitis of the upper cervical spine requiring surgical treatment in children is rare. Surgical treatment of the immature spine is commonly associated with certain risks and complications. We describe a unique treatment approach for a young child that required emergent stabilization of the upper cervical spine due to progressive instability caused by osteomyelitis. A 3-month-old infant with neurological decline from progressive instability of the occiput C1 and C2 was admitted for surgical treatment after failed bracing. The patient had reduction and occiput to C2 posterior fusion and segmental instrumentation, with nonsegmental instrumentation extending in the soft tissues from C2 to T4 with the intent of providing stabilization without fusion and permitting further growth. The implants were removed 1 year after the original procedure. At 2 years following implant removal, he continued to have mild global developmental delay but was progressing well and was able to navigate independently with a posterior walker, using AFOs for support. Subaxial cervical motion and x-ray appearance were normal. The technique used here to overcome the difficulty of providing secure immobilization of the craniocervical junction while not creating inadvertent fusion of the subaxial cervical spine may have application in other clinical situations. Level V.
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Parental divorce and developmental progression: an inquiry into their relationship.
Wallerstein, J; Resnikoff, D
1997-02-01
The authors argue that the patterning of conscious and unconscious needs, wishes, and expectations that parents and children bring to each other is often profoundly altered under the impact of divorce and the parents' subsequent adult relationships. These changes, which are inherent in the divorce experience, have the power to modify significantly or derail the young child's developmental course. Clinical observations from an ongoing longitudinal research project show striking changes in the child's image of his parents, as portrayed here in the vivid play and fantasy of a psychologically sturdy child, concurrent with psychological changes in both parents and in their parenting. A follow-up, twelve years later, is reported. The authors suggest that the stable parenting of this child's first three years represented an internalised template of good relationships, which enabled him, despite the father's subsequent abandonment, the mother's grave acting out and the stepfather's rejection, to turn away from his disappointment in his parents, to wrest what was available from school, friends and others, and to propel himself forward at each point to the next developmental stage, moving increasingly away from his family towards independence and competence. The consistency of the child's inner life and integrity is contrasted with the depression of his parents and the instability of their parenting.
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Cukras, Catherine; Gaasterland, Terry; Lee, Pauline; Gudiseva, Harini V; Chavali, Venkata R M; Pullakhandam, Raghu; Maranhao, Bruno; Edsall, Lee; Soares, Sandra; Reddy, G Bhanuprakash; Sieving, Paul A; Ayyagari, Radha
2012-01-01
Retinitis Pigmentosa (RP) is a common form of retinal degeneration characterized by photoreceptor degeneration and retinal pigment epithelium (RPE) atrophy causing loss of visual field and acuities. Exome sequencing identified a novel homozygous splice site variant (c.111+1G>A) in the gene encoding retinol binding protein 4 (RBP4). This change segregated with early onset, progressive, and severe autosomal recessive retinitis pigmentosa (arRP) in an eight member consanguineous pedigree of European ancestry. Additionally, one patient exhibited developmental abnormalities including patent ductus arteriosus and chorioretinal and iris colobomas. The second patient developed acne from young age and extending into the 5(th) decade. Both patients had undetectable levels of RBP4 in the serum suggesting that this mutation led to either mRNA or protein instability resulting in a null phenotype. In addition, the patients exhibited severe vitamin A deficiency, and diminished serum retinol levels. Circulating transthyretin levels were normal. This study identifies the RBP4 splice site change as the cause of RP in this pedigree. The presence of developmental abnormalities and severe acne in patients with retinal degeneration may indicate the involvement of genes that regulate vitamin A absorption, transport and metabolism.
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Cukras, Catherine; Gaasterland, Terry; Lee, Pauline; Gudiseva, Harini V.; Chavali, Venkata R. M.; Pullakhandam, Raghu; Maranhao, Bruno; Edsall, Lee; Soares, Sandra; Reddy, G. Bhanuprakash; Sieving, Paul A.; Ayyagari, Radha
2012-01-01
Retinitis Pigmentosa (RP) is a common form of retinal degeneration characterized by photoreceptor degeneration and retinal pigment epithelium (RPE) atrophy causing loss of visual field and acuities. Exome sequencing identified a novel homozygous splice site variant (c.111+1G>A) in the gene encoding retinol binding protein 4 (RBP4). This change segregated with early onset, progressive, and severe autosomal recessive retinitis pigmentosa (arRP) in an eight member consanguineous pedigree of European ancestry. Additionally, one patient exhibited developmental abnormalities including patent ductus arteriosus and chorioretinal and iris colobomas. The second patient developed acne from young age and extending into the 5th decade. Both patients had undetectable levels of RBP4 in the serum suggesting that this mutation led to either mRNA or protein instability resulting in a null phenotype. In addition, the patients exhibited severe vitamin A deficiency, and diminished serum retinol levels. Circulating transthyretin levels were normal. This study identifies the RBP4 splice site change as the cause of RP in this pedigree. The presence of developmental abnormalities and severe acne in patients with retinal degeneration may indicate the involvement of genes that regulate vitamin A absorption, transport and metabolism. PMID:23189188
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Effects of In Utero Exposure to Di-n-Butyl Phthalate on Testicular Development in Rat
Ma, Tan; Yin, Xiaoqin; Han, Ruitong; Ding, Jie; Zhang, Huan; Han, Xiaodong
2017-01-01
Humans are inevitably exposed to ubiquitous phthalate esters (PAEs). In utero exposure to di-n-butyl phthalate (DBP) induces abnormal development of the testis and reproductive tract in male offspring, which correspond closely with the human condition of testicular dysgenesis syndrome (TDS)-like syndrome. However, the underlying mechanisms have not been elucidated in detail. In this study, pregnant rats were orally exposed to either corn oil (controls) or DBP at three different doses by gavage during Gestational Days 12.5–21.5. Pathological examinations were performed for toxicity evaluation. Proliferation and apoptosis related proteins (ras related dexamethasone induced 1 (Rasd1), mitogen-activated protein kinase kinases1/2 (MEK1/2), Bcl-2, and Bax) were measured for mechanisms exploration. The results showed that different doses of DBP caused male developmental and reproductive toxicity in rats, including the decrease of anogenital distance (AGD), the histological damage of testis, and apoptosis of seminiferous tubule cells. Our data suggested that DBP played chronic and continuous toxic roles on male reproductive system by disrupting expression of Rasd1 and MEK1/2 as well as Bcl-2/Bax ratio. Further research is warranted. PMID:29064414
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Barlow, Norman J; McIntyre, Barry S; Foster, Paul M D
2004-01-01
In utero exposure of male rats to the antiandrogen di(n-butyl) phthalate (DBP) leads to decreased anogenital distance (AGD) on postnatal day (PND) 1, increased areolae retention on PND 13, malformations in the male reproductive tract, and histologic testicular lesions including marked seminiferous epithelial degeneration and a low incidence of Leydig cell (LC) adenomas on PND 90. One objective of this study was to determine the incidence and persistence of decreased AGD, increased areolae retention, and LC adenomas in adult rats following in utero DBP exposure. A second objective was to determine whether AGD and areolae retention during the early postnatal period are associated with lesions in the male reproductive tract. Pregnant Crl:CD(SD)BR rats were gavaged with corn oil or DBP at 100 or 500 mg/kg/day, 10 dams per group. Three replicates of rats (n = 30 rats per replicate) were exposed from gestation day 12 to 21 and the male offspring allowed to mature to 6, 12, or 18 months of age. Gross malformations in the male reproductive tract and histologic lesions in the testes were similar to those previously described. However, testicular dysgenesis, a lesion of proliferating LCs and aberrant tubules that has not been previously described in DBP-exposed testes, was diagnosed. The incidence of this lesion was approximately 20% unilateral and 7-18% bilateral in the high-dose group and was similar among all ages examined, implicating a developmental alteration rather than an age-related change. AGD and areolae retention were found to be permanent changes following in utero exposure to 500 mg/kg/day of DBP. Decreased AGD was a sensitive predictor of lesions in the male reproductive tract, relatively small changes in AGD were associated with a significant incidence of male reproductive malformations. In utero DBP exposure induced proliferative developmental lesions, some of which would have been diagnosed as LC adenomas by the morphological criteria set forth by the Society of Toxicologic Pathology. However, these lesions were dissimilar to traditional LC adenomas as the LCs were poorly differentiated and the lesions contained aberrant seminiferous tubules. While the morphology and incidence of this DBP-induced testicular developmental lesion has been fully characterized by this study, the detailed pathogenesis warrants further investigation.
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Phthalates and heavy metals as endocrine disruptors in food: A study on pre-packed coffee products.
De Toni, Luca; Tisato, Francesco; Seraglia, Roberta; Roverso, Marco; Gandin, Valentina; Marzano, Cristina; Padrini, Roberto; Foresta, Carlo
2017-01-01
Phthalate plasticizers and heavy metals are widely recognized to be pollutants that interfere with key developmental processes such as masculinization. We investigated the release of phthalates and heavy metals in coffee brewed from coffee packed in single-serve coffee containers made from different types of materials: metal, biodegradable and plastics. We detected with GC-MS small amounts phthalates, below the tolerated daily risks levels, in all the coffees prepared from the different types of capsules. Specifically, Di (2-ethyl-hexyl)-phthalate and DiBP: Diisobuthyl-pthalate were ubiquitously present despite the high variability among the samples (respective range 0.16-1.87 μg/mL and 0.01-0.36 μg/mL). Whereas, diethyl-phthalate (range 0.20-0.26 μg/mL) and di- n -buthyl-phthalate (range 0.02-0.14 μg/mL) were detected respectively in one and three out of the four types of capsule tested. In contrast, we detected by atomic mass spectrometry on mineralized samples heavy metals lead (Pb) and nickel (Ni), in all coffee tested. PB levels (respective range 0.32-211.57 μg/dose) accounted for 42-79%, whereas Ni levels (respective range 166.25-1950.26 μg/dose) accounted for >100% of the tolerable daily intake. These results add to the already present concerns related to the multiple pathways of human exposure and the ubiquitous presence of these pollutants in consumer products and their long-term effect on human health.
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How to Make a Neurocrystal: Modeling the developmental patterning of the fly's retina
NASA Astrophysics Data System (ADS)
Lubensky, David
2005-03-01
Animals' ability to create the complex patterns found in many organisms is an enduring source of wonder and a topic that has long drawn the interest of scientists of all stripes. Famously, it was an attempt to model developmental patterning that led to the discovery of the Turing instability. Here, we study one of the most remarkable and best-characterized examples of such pattern formation, the development of the fruit fly's compound eye. In the fly larva, a front of differentiation moves across the sheet of tissue that will become the adult retina. It leaves behind it a striking hexagonal array of cells marked by high levels of the protein Atonal. It has previously been noted that a standard activator-inhibitor model might explain this process [Meinhardt, 1992], but only recently has the basic genetic logic governing photoreceptor specification been deciphered [e.g. Frankfort and Mardon, 2002]. We build on these advances with the first model of retinal patterning based on experimentally verified interactions. Surprisingly, we conclude that a Turing-instability-based mechanism alone cannot reproduce the observed behavior. Instead, we propose that the pattern is generated primarily by a novel ``epitaxial'' process in which, as the front progresses, each newly-created row of unit cells acts as a template for the next one. A clear prediction of this model is that if the communication between successive rows is broken, even transiently, a striped pattern will appear. Preliminary experimental tests suggest that just such a phenomenon occurs in some mutants. Related patterning processes have been observed in systems as diverse as chick feather buds and vertebrate retinal ganglion cells [Pichaud, Treisman, and Desplan, 2001]; our model may thus describe an evolutionarily conserved module.
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RPAS application for estimating road exposition to rockfall
NASA Astrophysics Data System (ADS)
Santangelo, Michele; Alvioli, Massimiliano; Baldo, Marco; Giordan, Daniele; Guzzetti, Fausto; Marchesini, Ivan; Reichenbach, Paola
2017-04-01
The use of Remotely Piloted Aircraft Systems (RPASs) for landslide analysis and characterization is often aimed at the acquisition of DSMs and orthpohotos. One of the most interesting utilizations of RPASs to landslide studies consists in the production of data for rockfall risk assessment. A typical approach to study rockfalls consists in the application of numerical or stochastic models for the definition of possible trajectories of rock blocks to accurate DTMs of the source and runout areas. In this work, the case study of the rockfall of Vinnanova di Accumoli (Marche Region, central Italy) is presented and discussed. In this area, the earthquakes of the seismic sequence started on 24 August 2016 that struck central Italy caused several rockfalls that, in some cases damaged roads, and represented a threat to the population. In particular, the provincial road SP18 near Villanova di Accumoli was closed due to a 1 m3 rock block that fell down from the slope and crossed the SP20, partially damaging it. During the emergency, it was decided to apply a numerical model to estimate the trajectories of the remaining instable rock masses and to define the possible places where to set up protection measures to safely re-open the road. Therefore, a survey with a multicopter was carried out to obtain (i) an accurate DSM of the source area and the slope (ii) the identification and characterization of other instable blocks possibly not visible in the field. The 6,500 m2 area was covered by a total 161 photograms by a 34 Mpixel camera, obtaining a 1.5 cm/pixel Ground Sampling Distance (GSD). The final orthophoto has a resolution of 2.5 cm, whereas the DSM has a resolution of 20 cm. The DSM was then filtered by a three-step procedure including manual removal of sparse vegetation cover. In area covered by dense vegetation (the lower part of the slope) the DSM could not be manually filtered, which hampered to run the numerical model. This problem was addressed by a GPS RTK survey of the most vegetated area. A total of 73 points with less than 1m error were acquired and integrated in the DTM. The resulting integrated DTM has a resolution of 25 cm. The numerical model STONE was then applied to the source areas mapped in the field and by photo-interpretation of the RPAS orthophoto to get a 1m raster showing the potential trajectories of the mapped instable rock masses. Results showed that only the part of the road hit by the rockfall was actually exposed to rockfall trajectories. Therefore only limited protection measures were suggested to reduce the exposition of the road.
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Matsui, Daisuke; Okazaki, Seiji; Matsuda, Motoki; Asano, Yasuhisa
2015-02-20
Microbial NAD(+)-dependent L-tryptophan dehydrogenase (TrpDH, EC1.4.1.19), which catalyzes the reversible oxidative deamination and the reductive amination between L-tryptophan and indole-3-pyruvic acid, was found in the scytonemin biosynthetic pathway of Nostoc punctiforme ATCC29133. The TrpDH exhibited high specificity toward L-tryptophan, but its instability was a drawback for L-tryptophan determination. The mutant enzyme TrpDH L59F/D168G/A234D/I296N with thermal stability was obtained by screening of Escherichia coli transformants harboring various mutant genes, which were generated by error-prone PCR using complementation in an L-tryptophan auxotroph of E. coli. The specific activity and stability of this mutant enzyme were higher than those of the wild type enzyme. We also revealed here that in these four mutation points, the two amino acid residues Asp168 and Ile296 contributed to increase the enzyme stability, and the Leu59, Ala234 residues to increase its specific activity. Growth of the strain harboring the gene of above 4 point mutated enzyme was accelerated by the enhanced performance. In the present study, we demonstrated that TrpDH L59F/D168G/A234D/I296N was available for determination of L-tryptophan in human plasma. Copyright © 2015 Elsevier B.V. All rights reserved.
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Frazier, Brenda A.; Wolczanski, Peter T.; Keresztes, Ivan; DeBeer, Serena; Lobkovsky, Emil B.; Pierpont, Aaron W.; Cundari, Thomas R.
2012-01-01
Attempted syntheses of (smif)2Ti (smif = 1,3-di-(2-pyridyl)-2-azaallyl) based on metatheses of TiClnLm (n = 2–4) with M(smif) (M = Li, Na), in the presence of a reducing agent (Na/Hg) when necessary, failed, but several apparent Ti(II) species were identified by X-ray crystallography and multidimensional NMR spectroscopy: (smif){Li(smif-smif)}Ti (1, X-ray), [(smif)Ti]2(μ-κ3,κ3-N,N(py)2-smif,smif) (2), (smif)Ti(κ3-N,N(py)2-smif,(smif)H) (3), and (smif)Ti(dpma) (4). NMR spectroscopy and K-edge XAS showed that each compound possesses ligands that are redox non-innnocent, such that d1 Ti(III) centers AF-couple to ligand radicals: (smif){Li(smif-smif)2−}TiIII (1), [(smif2−)TiIII]2(μ-κ3,κ3-N,N(py)2-smif,smif) (2), [(smif2−)TiIII](κ3-N,N(py)2-smif,(smif)H) (3), and (smif2−)TiIII(dpma) (4). The instability of the (smif)2Ti relative to its C-C coupled dimer, 2, is rationalized via the complementary nature of the amide and smif radical anion ligands, which are also common to 3 and 4. Calculations support this contention. PMID:22830452
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Koi, Minoru; Tseng-Rogenski, Stephanie S; Carethers, John M
2018-01-15
Microsatellite alterations within genomic DNA frameshift as a result of defective DNA mismatch repair (MMR). About 15% of sporadic colorectal cancers (CRCs) manifest hypermethylation of the DNA MMR gene MLH1 , resulting in mono- and di-nucleotide frameshifts to classify it as microsatellite instability-high (MSI-H) and hypermutated, and due to frameshifts at coding microsatellites generating neo-antigens, produce a robust protective immune response that can be enhanced with immune checkpoint blockade. More commonly, approximately 50% of sporadic non-MSI-H CRCs demonstrate frameshifts at di- and tetra-nucleotide microsatellites to classify it as MSI-low/elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) as a result of functional somatic inactivation of the DNA MMR protein MSH3 via a nuclear-to-cytosolic displacement. The trigger for MSH3 displacement appears to be inflammation and/or oxidative stress, and unlike MSI-H CRC patients, patients with MSI-L/EMAST CRCs show poor prognosis. These inflammatory-associated microsatellite alterations are a consequence of the local tumor microenvironment, and in theory, if the microenvironment is manipulated to lower inflammation, the microsatellite alterations and MSH3 dysfunction should be corrected. Here we describe the mechanisms and significance of inflammatory-associated microsatellite alterations, and propose three areas to deeply explore the consequences and prevention of inflammation's effect upon the DNA MMR system.
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Koi, Minoru; Tseng-Rogenski, Stephanie S; Carethers, John M
2018-01-01
Microsatellite alterations within genomic DNA frameshift as a result of defective DNA mismatch repair (MMR). About 15% of sporadic colorectal cancers (CRCs) manifest hypermethylation of the DNA MMR gene MLH1, resulting in mono- and di-nucleotide frameshifts to classify it as microsatellite instability-high (MSI-H) and hypermutated, and due to frameshifts at coding microsatellites generating neo-antigens, produce a robust protective immune response that can be enhanced with immune checkpoint blockade. More commonly, approximately 50% of sporadic non-MSI-H CRCs demonstrate frameshifts at di- and tetra-nucleotide microsatellites to classify it as MSI-low/elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) as a result of functional somatic inactivation of the DNA MMR protein MSH3 via a nuclear-to-cytosolic displacement. The trigger for MSH3 displacement appears to be inflammation and/or oxidative stress, and unlike MSI-H CRC patients, patients with MSI-L/EMAST CRCs show poor prognosis. These inflammatory-associated microsatellite alterations are a consequence of the local tumor microenvironment, and in theory, if the microenvironment is manipulated to lower inflammation, the microsatellite alterations and MSH3 dysfunction should be corrected. Here we describe the mechanisms and significance of inflammatory-associated microsatellite alterations, and propose three areas to deeply explore the consequences and prevention of inflammation’s effect upon the DNA MMR system. PMID:29375743
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Kinch, Cassandra D; Kurrasch, Deborah M; Habibi, Hamid R
2016-06-01
Exposure to environmental contaminants has been linked to developmental and reproductive abnormalities leading to infertility, spontaneous abortion, reduced number of offspring, and metabolic disorders. In addition, there is evidence linking environmental contaminants and endocrine disruption to abnormal developmental rate, defects in heart and eye morphology, and alterations in behavior. Notably, these effects could not be explained by interaction with a single hormone receptor. Here, using a whole-organism approach, we investigated morphological changes to developing zebrafish caused by exposure to a number of environmental contaminants, including bisphenol A (BPA), di(2-ethylhexyl)phthalate (DEHP), nonylphenol, and fucosterol at concentrations measured in a local water body (Oldman River, AB), individually and in mixture. Exposure to nanomolar contaminant concentrations resulted in abnormal morphological development, including changes to body length, pericardia (heart), and the head. We also characterize the spatiotemporal expression profiles of estrogen, androgen, and thyroid hormone receptors to demonstrate that localization of these receptors might be mediating contaminant effects on development. Finally, we examined the effects of contaminants singly and in mixture. Combined, our results support the hypothesis that adverse effects of contaminants are not mediated by single hormone receptor signaling, and adversity of contaminants in mixture could not be predicted by simple additive effect of contaminants. The findings provide a framework for better understanding of developmental toxicity of environmental contaminants in zebrafish and other vertebrate species. Copyright © 2016 Elsevier B.V. All rights reserved.
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Metabolomic Profiling of Amino Acids and β-Cell Function Relative to Insulin Sensitivity in Youth
Michaliszyn, Sara F.; Sjaarda, Lindsey A.; Mihalik, Stephanie J.; Lee, SoJung; Bacha, Fida; Chace, Donald H.; De Jesus, Victor R.; Vockley, Jerry
2012-01-01
Context: In longitudinal studies of adults, elevated amino acid (AA) concentrations predicted future type 2 diabetes mellitus (T2DM). Objective: The aim of the present investigation was to examine whether increased plasma AA concentrations are associated with impaired β-cell function relative to insulin sensitivity [i.e. disposition index (DI)], a predictor of T2DM development. Design, Setting, and Participants: Metabolomic analysis for fasting plasma AAs was performed by tandem mass spectrometry in 139 normal-weight and obese adolescents with and without dysglycemia. First-phase insulin secretion was evaluated by a hyperglycemic (∼225 mg/dl) clamp and insulin sensitivity by a hyperinsulinemic-euglycemic clamp. DI was calculated as the product of first-phase insulin and insulin sensitivity. Results: DI was positively associated with branched-chain AAs (leucine/isoleucine and valine; r = 0.27 and 0.29, P = 0.001), neutrally transported AAs (phenylalanine and methionine; r = 0.30 and 0.35, P < 0.001), basic AAs (histidine and arginine; r = 0.28 and 0.23, P ≤ 0.007), serine (r = 0.35, P < 0.001), glycine (r = 0.26, P = 0.002), and branched-chain AAs-derived intermediates C3, C4, and C5 acylcarnitine (range r = 0.18–0.19, P ≤ 0.04). Conclusion: In youth, increased plasma AA concentrations are not associated with a heightened metabolic risk profile for T2DM; rather, they are positively associated with β-cell function relative to insulin sensitivity. These contrasting observations between adults and youth may be a reflection of developmental differences along the lifespan dependent on the combined impact of the aging process together with the impact of progressive obesity. PMID:22977272
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Noonan like appearance and familial deletion of the 22q11 Shprintzen-DiGeorge critical region
DOE Office of Scientific and Technical Information (OSTI.GOV)
Piussan, C.; Mathieu, M.; Boudailliez, B.
1994-09-01
Shprintzen velocardiofacial syndrome (VCFS) and reported cases of autosomal dominant DiGeorge sequence (DGS) both belong to a heterogeneous developmental field defect due to the familial segregation of a 22q11 deletion. Two sisters present with mental retardation, dysmorphia and multiple congenital anomalies. The eldest has a Noonan-like appearance; short stature, short webbed neck, low posterior hairline, widely spaced nipples, hemivertebrae, speech disability and mild hypoparathyroidism. Her younger sister has prominent eyes, floppy ears, pulmonary valvular stenosis, hypoplastic right kidney, left multicystic kidney, hypoparathyroidism and renal failure causing death at age 3. Their retarded mother has a typical Shprintzen phenotype and nomore » hypoparathyroidism. A deletion of the critical DiGeorge-Shprintzen conotruncal malformation region was found by FISH in the mother and her Noonan-like daughter. In the mother`s family exist 3 cleft palates, an imperforate anus, a stillbirth and one infant died at age 3 months because of heart malformation. To our knowledge, another case of Noonan-like appearance in a DG patient affected with monosomy 22q11 has been reported in 1992 by Wilson et al. Whether resulting from the hemizygosity of a gene or from the deletion of contiguous genes, the wide DGS-VCFS spectrum encompasses quite variable phenotypes, discordant for palatal and conotruncal defects as well as for hypoparathyroidism, dysmorphic features and multiple congenital anomalies. Physical mapping of both the large 22q11 region commonly lost and the smallest deletion sufficient to produce DGS has been done and may account for the broadening spectrum, the variable expression and the frequently delayed diagnosis of this syndrome.« less
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Polε Instability Drives Replication Stress, Abnormal Development, and Tumorigenesis.
Bellelli, Roberto; Borel, Valerie; Logan, Clare; Svendsen, Jennifer; Cox, Danielle E; Nye, Emma; Metcalfe, Kay; O'Connell, Susan M; Stamp, Gordon; Flynn, Helen R; Snijders, Ambrosius P; Lassailly, François; Jackson, Andrew; Boulton, Simon J
2018-05-17
DNA polymerase ε (POLE) is a four-subunit complex and the major leading strand polymerase in eukaryotes. Budding yeast orthologs of POLE3 and POLE4 promote Polε processivity in vitro but are dispensable for viability in vivo. Here, we report that POLE4 deficiency in mice destabilizes the entire Polε complex, leading to embryonic lethality in inbred strains and extensive developmental abnormalities, leukopenia, and tumor predisposition in outbred strains. Comparable phenotypes of growth retardation and immunodeficiency are also observed in human patients harboring destabilizing mutations in POLE1. In both Pole4 -/- mouse and POLE1 mutant human cells, Polε hypomorphy is associated with replication stress and p53 activation, which we attribute to inefficient replication origin firing. Strikingly, removing p53 is sufficient to rescue embryonic lethality and all developmental abnormalities in Pole4 null mice. However, Pole4 -/- p53 +/- mice exhibit accelerated tumorigenesis, revealing an important role for controlled CMG and origin activation in normal development and tumor prevention. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.
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25-KVA Amorphous Metal-Core Transformer Developmental Test Report
1989-08-01
N-1801 August 1989 By G.V. Urata and J.O. Franchi Sponsored By Naval Facilites Engineering Command Technical Note and Office of Naval Research 25-kVA...wt’c.i,,., di.shtr tlion iswilm ihed 89 11 1.3 108 C4C E .0>. .4) C L ’TU m ’D ’s n C w o o en o’ 0. 1 0 4 = ~ E 0 0 -~CI u 0 44 E N N M Cn E E E~ E EE...REPRODUCE LEGIBLY. REPORT DOCUMENTATION PAGE OM No. o70-o , Pub €ic r o t r b e to jhm, t o ,im io n of Anf rflut,O . m e, o .e, *. du .a. e o ., nte tve
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Maharasingam, M; Ostman-Smith, I; Pike, M G
2003-01-01
To examine whether the learning difficulties seen in a proportion of children with DGS are secondary to cardiac pathology and treatment, or a feature of the DGS phenotype. Cohort study of all patients with DGS and coexisting cardiac lesions within a region. Ten children with 22q11 deletion were assigned two controls each, matched for age, sex, cardiac lesion, and preoperative hemodynamic status but without DGS. The neurodevelopmental status was evaluated with the Ruth Griffiths test for babies and young children. Children with the 22q11 deletion showed a wide range of developmental quotient (DQ; mean 71, 95% CI 47 to 95) and subscale scores, but these as a group were significantly lower than those of the control group (DQ 113, 95% CI 108 to 118). Four of the DGS children had DQs below 60. Hypocalcaemia, prolonged postoperative ventilation, and abnormal neurology perioperatively were associated with a low DQ. A proportion of children with DGS have a very poor developmental outcome following cardiac surgery. This outcome is not attributable to the cardiac condition and its treatment alone, but represents either a pre-existing component of the syndrome or an interaction between the syndrome and its treatment.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, M.; Zackai, E.H.; Kaplan, P.
1996-10-16
Kabuki syndrome (KS) or Niikawa-Kuroki syndrome is a sporadic disorder characterized by postnatal growth retardation, developmental delay, mild to moderate retardation, and a characteristic facial appearance. Cardiovascular defects, clefts of the lip, palate, or both, and musculoskeletal abnormalities occur in about 50% of patients with KS. The cause of this multiple congenital anomaly syndrome is unknown, and investigators have speculated that KS is a contiguous gene-deletion syndrome. Based on the presence of congenital heart defects in patients with KS, it was suggested that this disorder might share a common cause with the 22q11 deletion syndromes. A preliminary study of 2more » patients with KS failed to detect a deletion within 22q11. We report the results of fluorescence in situ hybridization with cosmid probes for loci D22S75 (N25) and D22S259 (1132) within the DiGeorge chromosomal region (DGCR) on metaphase spreads from an additional 5 patients, 2 non-Japanese and 3 Japanese, with KS. None of the 5 had deletions at either locus. It is unlikely that KS is caused by a deletion within 22q11. 16 refs.« less
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Zuo, Yayun; Peng, Xiong; Wang, Kang; Lin, Fangfei; Li, Yuting; Chen, Maohua
2016-07-21
The voltage-gated sodium channel (VGSC) is the target of sodium-channel-blocking insecticides. Traditionally, animals were thought to have only one VGSC gene comprising a α-subunit with four homologous domains (DI-DIV). The present study showed that Rhopalosiphum padi, an economically important crop pest, owned a unique heterodimeric VGSC (H1 and H2 subunits) encoded by two genes (Rpvgsc1 and Rpvgsc2), which is unusual in insects and other animals. The open reading frame (ORF) of Rpvgsc1 consisted 1150 amino acids, and the ORF of Rpvgsc2 had 957 amino acids. Rpvgsc1 showed 64.1% amino acid identity to DI-DII of Drosophila melanogaster VGSC and Rpvgsc2 showed 64.0% amino acid identity to DIII-DIV of D. melanogaster VGSC. A M918L mutation previously reported in pyrethroids-resistant strains of other insects was found in the IIS4-S6 region of R. padi field sample. The two R. padi VGSC genes were expressed at all developmental stages and showed similar expression patterns after treatment with beta-cypermethrin. Knockdown of Rpvgsc1 or Rpvgsc2 caused significant reduction in mortality rate of R. padi after exposure to beta-cypermethrin. These findings suggest that the two R. padi VGSC genes are both functional genes.
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NASA Astrophysics Data System (ADS)
Zuo, Yayun; Peng, Xiong; Wang, Kang; Lin, Fangfei; Li, Yuting; Chen, Maohua
2016-07-01
The voltage-gated sodium channel (VGSC) is the target of sodium-channel-blocking insecticides. Traditionally, animals were thought to have only one VGSC gene comprising a α-subunit with four homologous domains (DI-DIV). The present study showed that Rhopalosiphum padi, an economically important crop pest, owned a unique heterodimeric VGSC (H1 and H2 subunits) encoded by two genes (Rpvgsc1 and Rpvgsc2), which is unusual in insects and other animals. The open reading frame (ORF) of Rpvgsc1 consisted 1150 amino acids, and the ORF of Rpvgsc2 had 957 amino acids. Rpvgsc1 showed 64.1% amino acid identity to DI-DII of Drosophila melanogaster VGSC and Rpvgsc2 showed 64.0% amino acid identity to DIII-DIV of D. melanogaster VGSC. A M918L mutation previously reported in pyrethroids-resistant strains of other insects was found in the IIS4-S6 region of R. padi field sample. The two R. padi VGSC genes were expressed at all developmental stages and showed similar expression patterns after treatment with beta-cypermethrin. Knockdown of Rpvgsc1 or Rpvgsc2 caused significant reduction in mortality rate of R. padi after exposure to beta-cypermethrin. These findings suggest that the two R. padi VGSC genes are both functional genes.
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Shtasel-Gottlieb, Zoë; Palakshappa, Deepak; Yang, Fanyu; Goodman, Elizabeth
2014-01-01
Purpose To explore the association between developmental assets (characteristics, experiences, and relationships that shape healthy development) and food insecurity among adolescents from a low-income, urban community. Methods This mixed methods study occurred in two phases. In Phase 1, using a census approach, 2350 6-12th graders from the public school district completed an anonymous survey that included the Development Assets Profile (DAP), youth self-report form of the Core Food Security Module, and demographic questions. Logistic and multinomial regression analyses determined independent associations between developmental assets and food security adjusting for demographics. In Phase 2, 20 adult key informant interviews and four semi-structured student focus groups were performed to explain findings from Phase 1. Results On average, DAP scores were consistent with national norms. Food insecurity was prevalent; 14.9% reported low food security and 8.6% very low food security (VLFS). Logistic regression revealed that higher DAP was associated with lower odds of food insecurity (OR=.96, 95% CI=.95-.97); family assets drove this association(OR=.93, 95% CI=.91-.95). In multinomial regression modeling, these associations persisted and, paradoxically, higher community assets were also associated with VLFS (ORVLFS=1.08, 95% CI=1.04-1.13). Qualitative analyses suggested that greater need among VLFS youth led to increased connections to community resources despite barriers to access such as stigma, home instability, and cultural differences. Conclusion Food insecurity is a pervasive problem among adolescents from low-income communities and is associated with lower developmental assets, particularly family assets. That community assets were higher among VLFS youth underscores the importance of community-level resources in struggling areas. PMID:25620305
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Electrostatic instability of ring current protons beyond the plasmapause during injection events
NASA Technical Reports Server (NTRS)
Coroniti, F. V.; Fredricks, R. W.; White, R.
1972-01-01
The stability of ring current protons with an injection spectrum modeled by an m = 2 mirror distribution function was examined for typical ring current parameters. It was found that the high frequency loss cone mode can be excited at wave numbers K lambda sub Di about = to 0.1 to 0.5, at frequencies omega about = to (0.2 to 0.6) omega sub pi and with growth rates up to gamma/omega about = to 0.03. These waves interact with the main body of the proton distribution and propagate nearly perpendicular to the local magnetic field. Cold particle partial densities tend to reduce the growth rate so that the waves are quenched at or near to the plasmapause boundary. Wave e-folding lengths are comparable to 0.1 R sub e, compared to the value of about 4 R sub e found for ion cyclotron waves at the same plasma conditions.
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Birth order and fluctuating asymmetry: a first look.
Lalumière, M L; Harris, G T; Rice, M E
1999-01-01
We investigated the hypothesis that maternal immunoreactivity to male-specific features of the foetus can increase developmental instability. We predicted that the participants' number of older brothers would be positively related to the fluctuating asymmetry of ten bilateral morphological traits. The participants were 40 adult male psychiatric patients and 31 adult male hospital employees. Consistent with the hypothesis, the participants' number of older brothers--but not number of older sisters, younger brothers or younger sisters--was positively associated with fluctuating asymmetry. The patients had significantly larger fluctuating asymmetry scores and tended to have more older brothers than the employees, but the positive relationship between the number of older brothers and fluctuating asymmetry was observed in both groups. PMID:10643079
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Tubbs, R S; Kelly, D R; Mroczek-Musulman, E C; Braune, K; Reddy, A; Georgeson, K; Grabb, P A; Oakes, W J
2005-03-01
The authors present a case of a child with dwarfism that was noted to be developmentally delayed. Imaging revealed atlantoaxial instability, occult spinal dysraphism, and a presacral mass. Histopathology of the presacral lesion was that of a myxopapillary ependymoma with epidermoid cyst. We believe this to be the first report in the extant medical literature of this constellation of findings in the same patient. However, there are rare reports indicating a possible association of occult spinal dysraphism and the simultaneous occurrence of spinal ependymomas. Further case reports are necessary to discern whether these pathological entities are true low rate associations that the clinician should consider in their evaluation of these patients.
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NASA Astrophysics Data System (ADS)
Nan, Lijun; Li, Yashan; Cui, Changwei; Ning, Na; Huang, Jing; Xu, Chengdong; Zhang, Xiaofang; Yang, Ruiqun; Zhong, Yingxue
2018-04-01
The stability of wine is an important feature during the wine aging, which is mainly reflected in the balance of color, taste and aroma during the wine aging. During the wine fermentation, the role of microbes and enzymes including the interaction between them caused the mutual penetration, combination, decomposition and transformation among the substances in connection with color, aroma and taste in wine, which led to the instability of wine. After the fermentation of wine, the long aging period could just stabilize the wine. Still, the quality of wine had changed a lot. Based on the indicative changes in wine, such as microbiological interactions, biochemical reactions as well as interactions between the microorganism and biochemical reactions, the impact of changes of the basic biochemical and physicochemical indices on the stability of red wine were reviewed, and developmental suggestions in the future were also put forward in this paper, in order to reveal the mechanism of instability through the effect of dynamic change on the stability of red wine and analyze the unstable root of the red wine, which could lay a foundation for further research, and provide help for actual production.
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Opitz, J M; Lewin, S O
1987-01-01
Identical anomalies produced by different causes such as aneuploidy, gene mutation, teratogenic chemicals, and certain surgical procedures are a clear indication that embryonic primordia respond as units in the production of developmental anomalies of anatomic structure. Hence, they must also act as units during normal ontogeny. The presence of identical malformations in different mammalian species identifies developmental and anatomic homology by virtue of descent from a common ancestor. These dys- and orthomorphogenetically reactive units are the equivalents of the classic experimental embryologist's epimorphic fields, which are those units of the embryo in which the development of complex structures appropriate to the species is determined and controlled in a spatially coordinated, temporarily synchronous, and epimorphically hierarchical manner that expresses both species-nonspecific (that is, phylogenetic) and species-specific genetically coded developmental information. Thus, it is as important for pathologists as it is for clinical geneticists to steep themselves in the art and science of phenotype analysis and to be able to do all of those studies, including anthropometry, dermatoglyphics, and growth analysis, that are required to arrive at inferences of cause and pathogenesis from the phenotype. There is probably one other incentive besides the ethical and intellectual ones to do this and to do it as well as possible, namely, the medico-legal consequences. If pathologists fail to illuminate the causal genesis of a given case to aid in preventing recurrence, then, in short order, they might be held equally as liable as clinicians for missing high recurrence risk genetic diagnoses. These depressing considerations aside, it is important to close on a positive note. As at the outset, we want to emphasize once more that, without question, this is the most exciting time to be working in the field of developmental pathology. In this specialty a marriage is occurring of several types of investigational methods, ranging from humble morphologic studies to metabolic analysis to the most sophisticated designs of molecular biology, to produce new interdisciplinary approaches to the solution of the oldest intellectual problem confronting medicine--how does the "fabric of the human body" (in the immortal words of Vesalius) come about?(ABSTRACT TRUNCATED AT 250 WORDS)
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Hunt, Jennifer L
2006-01-01
Warthin tumors are controversial entities with a poorly understood etiology. Although some investigators have suggested a neoplastic origin, others have supported a developmental anomaly. A recent study described the absence of staining for hMLH1 and hMSH2 proteins in the epithelial component of Warthin tumors, suggesting that they arise secondary to defects in the DNA mismatch repair system. To determine if Warthin tumors exhibit evidence of DNA mismatch repair defects. Immunostains for hMLH1 and hMSH2 were performed using a standard approach. Microdissection of the epithelial component was followed by DNA extraction from the tissue fragments. Polymerase chain reaction and capillary electrophoresis analyses were performed for the following 5 National Cancer Institute-recommended microsatellites: D2s123, D5s346, D17s250, BAT25, and BAT26. Twelve patients with Warthin tumors were included. The immunostains for hMLH1 and hMSH2 showed preserved expression in the nuclei of the epithelial component of all Warthin tumors. No microsatellite instability was detected, and no loss of heterozygosity was seen. These results are not concordant with previously reported results showing loss of expression of the hMLH1 and hMSH2 DNA mismatch repair enzymes in the epithelial component of Warthin tumors. Furthermore, no microsatellite instability was detected in the 5 loci tested for each tumor in this series. These data demonstrate that Warthin tumors do not have evidence of DNA mismatch repair defects at the genomic or protein expression level.
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Balmus, Gabriel; Zhu, Min; Mukherjee, Sucheta; Lyndaker, Amy M.; Hume, Kelly R.; Lee, Jaesung; Riccio, Mark L.; Reeves, Anthony P.; Sutter, Nathan B.; Noden, Drew M.; Peters, Rachel M.; Weiss, Robert S.
2012-01-01
The human genomic instability syndrome ataxia telangiectasia (A-T), caused by mutations in the gene encoding the DNA damage checkpoint kinase ATM, is characterized by multisystem defects including neurodegeneration, immunodeficiency and increased cancer predisposition. ATM is central to a pathway that responds to double-strand DNA breaks, whereas the related kinase ATR leads a parallel signaling cascade that is activated by replication stress. To dissect the physiological relationship between the ATM and ATR pathways, we generated mice defective for both. Because complete ATR pathway inactivation causes embryonic lethality, we weakened the ATR mechanism to different degrees by impairing HUS1, a member of the 911 complex that is required for efficient ATR signaling. Notably, simultaneous ATM and HUS1 defects caused synthetic lethality. Atm/Hus1 double-mutant embryos showed widespread apoptosis and died mid-gestationally. Despite the underlying DNA damage checkpoint defects, increased DNA damage signaling was observed, as evidenced by H2AX phosphorylation and p53 accumulation. A less severe Hus1 defect together with Atm loss resulted in partial embryonic lethality, with the surviving double-mutant mice showing synergistic increases in genomic instability and specific developmental defects, including dwarfism, craniofacial abnormalities and brachymesophalangy, phenotypes that are observed in several human genomic instability disorders. In addition to identifying tissue-specific consequences of checkpoint dysfunction, these data highlight a robust, cooperative configuration for the mammalian DNA damage response network and further suggest HUS1 and related genes in the ATR pathway as candidate modifiers of disease severity in A-T patients. PMID:22575700
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NASA Astrophysics Data System (ADS)
Bombaci, I.; Covello, A.; Marcucci, L. E.; Rosati, S.
2009-07-01
Armani Paolo (Università di Trento) Benhar Omar (INFN Roma) Bombaci Ignazio (Università di Pisa) Bonanno Luca (Università di Ferrara) Catara Francesco (Università di Catania) Cò Giampaolo (Università di Lecce) Colonna Maria (Laboratori Nazionali del Sud, INFN Catania) Colonna Nicola (INFN Bari) Conti Francesco (Università di Pavia) Coraggio Luigi (INFN Napoli) Covello Aldo (Università di Napoli) Cristoforetti Marco (Technische Universität München, Germania) Cuofano Carmine (Università di Ferrara) Di Toro Massimo (Università di Catania) Drago Alessandro (Università di Ferrara) Faccioli Pietro (Università di Trento) Farina Nicola (INFN Roma) Finelli Paolo (Università di Bologna) Fiorentini Giovanni (Università di Ferrara) Fortunato Lorenzo (Università di Padova) Gambacurta Danilo (Università di Catania) Gandolfi Stefano (Università di Trento) Gargano Angela (INFN Napoli) Giannini Mauro (Università di Genova) Girlanda Luca (INFN Pisa) Giusti Carlotta (INFN Pavia) Illarionov Alexei (SISSA Trieste) Itaco Nunzio (Università di Napoli) Kievsky Alejandro (INFN Pisa) Lanza Edoardo (INFN Catania) Leidemann Winfried (Università di Trento) Lenzi Silvia (Università di Padova) Lipparini Enrico (Università di Trento) Lissia Marcello (Università di Cagliari) Lo Iudice Nicola (Università di Napoli) Maieron Chiara (Università di Lecce) Marcucci Laura Elisa (Università di Pisa) Matera Francesco (Università di Firenze) Millo Raffaele (Università di Trento) Orlandini Giuseppina (Università di Trento) Pacati Franco (Università di Pavia) Pastore Alessandro (Univeristy of Jyväskylä, Finlandia) Pederiva Francesco (Università di Trento) Pisent Gualtiero (Università di Padova) Prete Gianfranco (INFN Laboratori Nazionali di Legnaro) Quarati Piero (Politecnico di Torino) Rosati Sergio (Università di Pisa) Salmè Giovanni (INFN Roma) Santopinto Elena (INFN Genova) Traini Marco (Università di Trento) Vigezzi Enrico (INFN Milano) Vitturi Andrea (Università di Padova) Viviani Michele (INFN Pisa)
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Chester, N; Kuo, F; Kozak, C; O'Hara, C D; Leder, P
1998-11-01
Bloom's syndrome is a human autosomal genetic disorder characterized at the cellular level by genome instability and increased sister chomatid exchanges (SCEs). Clinical features of the disease include proportional dwarfism and a predisposition to develop a wide variety of malignancies. The human BLM gene has been cloned recently and encodes a DNA helicase. Mouse embryos homozygous for a targeted mutation in the murine Bloom's syndrome gene (Blm) are developmentally delayed and die by embryonic day 13.5. The fact that the interrupted gene is the homolog of the human BLM gene was confirmed by its homologous sequence, its chromosomal location, and by demonstrating high numbers of SCEs in cultured murine Blm-/- fibroblasts. The proportional dwarfism seen in the human is consistent with the small size and developmental delay (12-24 hr) seen during mid-gestation in murine Blm-/- embryos. Interestingly, the growth retardation in mutant embryos can be accounted for by a wave of increased apoptosis in the epiblast restricted to early post-implantation embryogenesis. Mutant embryos do not survive past day 13.5, and at this time exhibit severe anemia. Red blood cells and their precursors from Blm-/- embryos are heterogeneous in appearance and have increased numbers of macrocytes and micronuclei. Both the apoptotic wave and the appearance of micronuclei in red blood cells are likely cellular consequences of damaged DNA caused by effects on replicating or segregating chromosomes.
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Comparative analysis of recent satellite missions for multi-temporal SAR interferometry
NASA Astrophysics Data System (ADS)
Bovenga, Fabio; Refice, Alberto; Belmonte, Antonella; Pasquariello, Guido
2016-10-01
Multi-temporal InSAR (MTI) applications pose challenges related to the availability of coherent scattering from the ground surface, the complexity of the ground deformations, the atmospheric artifacts, the visibility problems related to the ground elevation. Nowadays, several satellite missions are available providing interferometric SAR data at different wavelengths, spatial resolutions, and revisit time. A new interesting opportunity is provided by Sentinel-1 mission, which has a spatial resolution comparable to previous ESA C-band missions, and revisit times reduced to up to 6 days. It is envisioned that, by offering regular, global-scale coverage, improved temporal resolution and freely available imagery, Sentinel-1 will guarantee an increasing use of MTI for ground displacement investigations. According to these different SAR space-borne missions, the present work discusses current and future opportunities of MTI applications to ground instability monitoring. Issues related to coherent target detection and mean velocity precision will be addressed through a simple theoretical model assuming backscattering mechanisms related to point scatterers. The paper also presents an example of multi-sensor ground instability investigation over the site of Marina di Lesina, Southern Italy, a village lying over a gypsum diapir, where a hydration process, involving the underlying anhydride, causes a smooth uplift pattern affecting the entire village area, and the formation of scattered sinkholes. More than 20 years of MTI SAR data have been used, coming from both legacy ERS and ENVISAT missions, and last-generation Radarsat-2, COSMO-SkyMed, and Sentinel-1A sensors.
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NASA Astrophysics Data System (ADS)
2014-07-01
Alba Paolo (Università di Torino) Becattini Francesco (Università di Firenze) Bombaci Ignazio (Università di Pisa) Bonaccorso Angela (INFN Pisa) Colonna Maria (INFN-LNS Catania) Coraggio Luigi (INFN Napoli) Covello Aldo (Università di Napoli) Di Toro Massimo (Università di Catania) De Angelis Giacomo (INFN-LNL Legnaro) Gargano Angela (INFN Napoli) Gattobigio Mario (INLN, Université de Nice-Sophia Antipolis, CNRS, France) Gensini Paolo (INFN Lecce) Giannini Mauro (Università di Genova) Girlanda Luca (Università del Salento) Giusti Carlotta (Università di Pavia) Greco Vincenzo (Università di Catania) Grossi Eduardo (Università di Firenze) Itaco Nunzio (Università di Napoli) Kievsky Alejandro (INFN Pisa) Lanza Edoardo (INFN Catania) Lavagno Andrea (Politecnico di Torino) Logoteta Domenico (Universidade de Coimbra, Coimbra, Portugal) Lo Iudice Nicola (Università di Napoli) Lombardo Maria Paola (INFN-LNF Frascati) Lo Meo Sergio (ENEA Bologna) Mannarelli Massimo (INFN-LNGS Assergi) Marcucci Laura Elisa (Università di Pisa) Matera Francesco (Università di Firenze) Orlandini Giuseppina (Università di Trento) Pacati Franco (Università di Pavia) Pederiva Francesco (Università di Trento) Pirrone Sara (INFN Catania) Puglisi Armando (Università di Catania) Radici Marco (INFN Pavia) Rinaldi Matteo (Università di Perugia) Roggero Alessandro (Università di Trento) Rolando Valentina (Università di Ferrara) Rosati Sergio (Università di Pisa) Ruggieri Marco (Università di Catania) Salmè Gianni (INFN Roma) Santopinto Elena (INFN Genova) Scopetta Sergio (Università di Perugia) Taiuti Mauro (Università di Genova) Vigezzi Enrico (INFN Milano) Viviani Michele (INFN Pisa) Vorabbi Matteo (Università di Pavia)
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Preterm birth and developmental problems in the preschool age. Part I: minor motor problems.
Ferrari, Fabrizio; Gallo, Claudio; Pugliese, Marisa; Guidotti, Isotta; Gavioli, Sara; Coccolini, Elena; Zagni, Paola; Della Casa, Elisa; Rossi, Cecilia; Lugli, Licia; Todeschini, Alessandra; Ori, Luca; Bertoncelli, Natascia
2012-11-01
Nearly half of very preterm (VP) and extremely preterm (EP) infants suffers from minor disabilities. The paper overviews the literature dealing with motor problems other than cerebral palsy (CP) during infancy and preschool age. The term "minor motor problems" indicates a wide spectrum of motor disorders other than CP; "minor" does not mean "minimal", as a relevant proportion of the preterm infants will develop academic and behavioural problems at school age. Early onset disorders consist of abnormal general movements (GMs), transient dystonia and postural instability; these conditions usually fade during the first months. They were underestimated in the past; recently, qualitative assessment of GMs using Prechtl's method has become a major item of the neurological examination. Late onset disorders include developmental coordination disorder (DCD) and/or minor neurological dysfunction (MND): both terms cover partly overlapping problems. Simple MND (MND-1) and complex MND (MND-2) can be identified and MND-2 gives a higher risk for learning and behavioural disorders. A relationship between the quality of GMs and MND in childhood has been recently described. The Touwen infant neurological examination (TINE) can reliably detect neurological signs of MND even in infancy. However, the prognostic value of these disorders requires further investigations.
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Chen, Kevin G; Mallon, Barbara S; Johnson, Kory R; Hamilton, Rebecca S; McKay, Ronald D G; Robey, Pamela G
2014-05-01
Human pluripotent stem cells (hPSCs) have two potentially attractive applications: cell replacement-based therapies and drug discovery. Both require the efficient generation of large quantities of clinical-grade stem cells that are free from harmful genomic alterations. The currently employed colony-type culture methods often result in low cell yields, unavoidably heterogeneous cell populations, and substantial chromosomal abnormalities. Here, we shed light on the structural relationship between hPSC colonies/embryoid bodies and early-stage embryos in order to optimize current culture methods based on the insights from developmental biology. We further highlight core signaling pathways that underlie multiple epithelial-to-mesenchymal transitions (EMTs), cellular heterogeneity, and chromosomal instability in hPSCs. We also analyze emerging methods such as non-colony type monolayer (NCM) and suspension culture, which provide alternative growth models for hPSC expansion and differentiation. Furthermore, based on the influence of cell-cell interactions and signaling pathways, we propose concepts, strategies, and solutions for production of clinical-grade hPSCs, stem cell precursors, and miniorganoids, which are pivotal steps needed for future clinical applications. Published by Elsevier B.V.
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SAPHO osteomyelitis and sarcoid dermatitis in a patient with DiGeorge syndrome.
Jyonouchi, Harumi; Lien, Kenneth W; Aguila, Helen; Spinnato, Gaetano G; Sabharwal, Sanjeev; Pletcher, Beth A
2006-06-01
We report the development and spontaneous resolution of annular erythematous skin lesions consistent with sarcoid dermatitis in a child with DiGeorge syndrome (DGS) carrying the 22q11.2 microdeletion. The skin lesion developed after she was treated with isoniazid (INH) following exposure to active tuberculosis (TB). After resolution of the skin lesions, this child developed sterile hyperplastic osteomyelitis consistent with SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) osteomyelitis in her right mandible triggered by an odontogenic infection. This child had congenital heart disease, dysmorphic facies, recurrent sinopulmonary infection, gastroesophageal reflux disease, scoliosis, reactive periostitis, and developmental delay. She had a low CD4 and CD8 T cell count with a normal 4/8 ratio, but normal cell proliferation and T cell cytokine production in response to mitogens. When she was presented with sterile osteomyelitis of right mandible, she revealed polyclonal hypergammaglobulinemia with elevated erythrocyte sedimentation rate (ESR)/angiotensin converting enzyme (ACE) levels, but negative CRP. Autoimmune and sarcoidosis workup was negative. Inflammatory parameters gradually normalized following resolution of odontogenic infection and with the use of non-steroidal anti-inflammatory drugs (NSAIDs). The broad clinical spectrum of DGS is further expanded with the development of autoimmune and inflammatory complications later in life. This case suggests that patients with the DGS can present with unusual sterile inflammatory lesions triggered by environmental factors, further broadening the clinical spectrum of this syndrome.
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Enamel-free teeth: Tbx1 deletion affects amelogenesis in rodent incisors.
Catón, Javier; Luder, Hans-Ulrich; Zoupa, Maria; Bradman, Matthew; Bluteau, Gilles; Tucker, Abigail S; Klein, Ophir; Mitsiadis, Thimios A
2009-04-15
TBX1 is a principal candidate gene for DiGeorge syndrome, a developmental anomaly that affects the heart, thymus, parathyroid, face, and teeth. A mouse model carrying a deletion in a functional region of the Tbx1 gene has been extensively used to study anomalies related to this syndrome. We have used the Tbx1 null mouse to understand the tooth phenotype reported in patients afflicted by DiGeorge syndrome. Because of the early lethality of the Tbx1-/- mice, we used long-term culture techniques that allow the unharmed growth of incisors until their full maturity. All cultured incisors of Tbx1-/- mice were hypoplastic and lacked enamel, while thorough histological examinations demonstrated the complete absence of ameloblasts. The absence of enamel is preceded by a decrease in proliferation of the ameloblast precursor cells and a reduction in amelogenin gene expression. The cervical loop area of the incisor, which contains the niche for the epithelial stem cells, was either severely reduced or completely missing in mutant incisors. In contrast, ectopic expression of Tbx1 was observed in incisors from mice with upregulated Fibroblast Growth Factor signalling and was closely linked to ectopic enamel formation and deposition in these incisors. These results demonstrate that Tbx1 is essential for the maintenance of ameloblast progenitor cells in rodent incisors and that its deletion results in the absence of enamel formation.
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Enamel-free teeth: Tbx1 deletion affects amelogenesis in rodent incisors
Catón, Javier; Luder, Hans-Ulrich; Zoupa, Maria; Bradman, Matthew; Bluteau, Gilles; Tucker, Abigail S.; Klein, Ophir; Mitsiadis, Thimios A.
2010-01-01
TBX1 is a principal candidate gene for DiGeorge syndrome, a developmental anomaly that affects the heart, thymus, parathyroid, face, and teeth. A mouse model carrying a deletion in a functional region of the Tbx1 gene has been extensively used to study anomalies related to this syndrome. We have used the Tbx1 null mouse to understand the tooth phenotype reported in patients afflicted by DiGeorge syndrome. Because of the early lethality of the Tbx1−/− mice, we used long-term culture techniques that allow the unharmed growth of incisors until their full maturity. All cultured incisors of Tbx1−/− mice were hypoplastic and lacked enamel, while thorough histological examinations demonstrated the complete absence of ameloblasts. The absence of enamel is preceded by a decrease in proliferation of the ameloblast precursor cells and a reduction in amelogenin gene expression. The cervical loop area of the incisor, which contains the niche for the epithelial stem cells, was either severely reduced or completely missing in mutant incisors. In contrast, ectopic expression of Tbx1 was observed in incisors from mice with upregulated Fibroblast Growth Factor signalling and was closely linked to ectopic enamel formation and deposition in these incisors. These results demonstrate that Tbx1 is essential for the maintenance of ameloblast progenitor cells in rodent incisors and that its deletion results in the absence of enamel formation. PMID:19233155
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Bhat, Virunya S; Durham, Jennifer L; English, J Caroline
2014-10-01
Di-(2-propylheptyl) phthalate (DPHP) is a high molecular weight polyvinyl chloride plasticizer. Since increasing production volume and broad utility may result in human exposure, an oral reference dose (RfD) was derived from laboratory animal data due to the lack of human data. In addition to liver and kidney, target organs were the thyroid, pituitary and adrenal glands in rats, recognizing that reproductive performance was not altered in two successive generations of DPHP-exposed rats. DPHP caused a reduction in pup and maternal body weights but not developmental or testicular effects typical of "phthalate syndrome." DPHP was not genotoxic. Due to the lack of carcinogenicity data, there is inadequate information to assess carcinogenic potential. The RfD of 0.1mg/kg-day was derived from the human equivalent BMDL10 of 10mg/kg-day for thyroid hypertrophy/hyperplasia in male F1 adults from the two-generation study. While in utero exposure did not alter sensitivity to thyroid lesions compared to subchronic exposures beginning at 6weeks of age, F1 adult males were the longest-term exposed population. The total uncertainty factor of 100x was comprised of intraspecies (10x), study duration (3x), and database (3x) factors but not an interspecies factor since rodents are more sensitive than humans to thyroid gland effects. Copyright © 2014 Elsevier Inc. All rights reserved.
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Sawado, Tomoyuki; Halow, Jessica; Im, Hogune; Ragoczy, Tobias; Bresnick, Emery H; Bender, M A; Groudine, Mark
2008-07-15
Genome-wide analyses of the relationship between H3 K79 dimethylation and transcription have revealed contradictory results. To clarify this relationship at a single locus, we analyzed expression and H3 K79 modification levels of wild-type (WT) and transcriptionally impaired beta-globin mutant genes during erythroid differentiation. Analysis of fractionated erythroid cells derived from WT/Delta locus control region (LCR) heterozygous mice reveals no significant H3 K79 dimethylation of the beta-globin gene on either allele prior to activation of transcription. Upon transcriptional activation, H3 K79 di-methylation is observed along both WT and DeltaLCR alleles, and both alleles are located in proximity to H3 K79 dimethylation nuclear foci. However, H3 K79 di-methylation is significantly increased along the DeltaLCR allele compared with the WT allele. In addition, analysis of a partial LCR deletion mutant reveals that H3 K79 dimethylation is inversely correlated with beta-globin gene expression levels. Thus, while our results support a link between H3 K79 dimethylation and gene expression, high levels of this mark are not essential for high level beta-globin gene transcription. We propose that H3 K79 dimethylation is destabilized on a highly transcribed template.
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Case report of 5 siblings: malnutrition? Rickets? DiGeorge syndrome? Developmental delay?
Cundiff, David K; Harris, William
2006-01-16
Parents of six children are facing a trial on charges of aggravated manslaughter in the care a 5 1/2 month old infant who died suddenly and neglect of their four older children for causing them to be malnourished by feeding them all an exclusively raw foods vegan diet. Both parents declined plea bargains and plan to defend themselves in court. The fifth child born to a married couple was breast-fed until 2 1/2 months. Subsequently, the parents fed the baby an exclusively raw foods diet prepared in a blender at home. The four older children, ages 18 months-6 1/2 years also ate an exclusively raw foods vegan diet. None of the four older children had significant previous injuries or serious illnesses. At autopsy, the infant weighed 3180 mg (6.99 pounds) and appeared emaciated. The thymus gland was absent and parathyroid glands were not located. The lungs were "congested." DiGeorge anomaly cannot be ruled out from these findings. Although, the coroner ruled that "malnutrition" was the sole cause of death, malnutrition, according to the World Health Organization definition, cannot be diagnosed in this infant. Compared with standard growth charts, the older children fell 2.1-4.1 standard deviations below the mean for North American children in height and weight. Labs were normal except for a low cholesterol level in all and a low prealbumin in one of three children tested. Therefore, malnutrition cannot be diagnosed in these children. The pediatrician diagnosed rickets in the four-year-old. However, chest x-rays were normal in all and long bone x-rays showed minimal changes in one child--no sign of rickets. The clinical diagnosis of rickets was not confirmed by the Center for Disease Control's criteria. A psychologist diagnosed the 18-month-old as developmentally delayed to the level of a 15-month-old, but this diagnosis is questionable. The raw foods vegan diet and possibly inherited small stature from the father's side account for their relatively low heights and weights. Catch-up growth will probably occur on the standard American diet but would have also been expected if they had remained on a vegan diet.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Pocar, Paola, E-mail: paola.pocar@unimi.it; Fianda
Endocrine disruptors (EDs) are compounds known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. This study was designed to establish whether gestational and lactational exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) at environmental doses promotes transgenerational effects on reproductive health in female offspring, as adults, over three generations in the mouse. Gestating F0 mouse dams were exposed to 0, 0.05, 5 mg/kg/day DEHP in the diet from gestational day 0.5 until the end of lactation. The incidence of adult-onset disease in reproductive function was recorded in F1, F2 and F3 female offspring.more » In adult F1 females, DEHP exposure induced reproductive adverse effects with: i) altered ovarian follicular dynamics with reduced primordial follicular reserve and a larger growing pre-antral follicle population, suggesting accelerated follicular recruitment; ii) reduced oocyte quality and embryonic developmental competence; iii) dysregulation of the expression profile of a panel of selected ovarian and pre-implantation embryonic genes. F2 and F3 female offspring displayed the same altered reproductive morphological phenotype and gene expression profiles as F1, thus showing transgenerational transmission of reproductive adverse effects along the female lineage. These findings indicate that in mice exposure to DEHP at doses relevant to human exposure during gonadal sex determination significantly perturbs the reproductive indices of female adult offspring and subsequent generations. Evidence of transgenerational transmission has important implications for the reproductive health and fertility of animals and humans, significantly increasing the potential biohazards of this toxicant. - Highlights: • Maternal exposure to DEHP transgenerationally affects female reproductive health. • DEHP reduced ovarian follicular reserve up to the third generation. • DEHP reduced oocyte and blastocyst developmental competence up to F3. • DEHP altered expression levels for key genes in ovary and blastocysts up to F4. • DEHP's adverse effects were observed at doses relevant for human exposure.« less
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Variation in vocal-motor development in infant siblings of children with autism.
Iverson, Jana M; Wozniak, Robert H
2007-01-01
In this study we examined early motor, vocal, and communicative development in a group of younger siblings of children diagnosed with autism (Infant Siblings). Infant Siblings and no-risk comparison later-born infants were videotaped at home with a primary caregiver each month from 5 to 14 months, with follow-up at 18 months. As a group, Infant Siblings were delayed in the onset of early developmental milestones and spent significantly less time in a greater number of postures, suggestive of relative postural instability. In addition, they demonstrated attenuated patterns of change in rhythmic arm activity around the time of reduplicated babble onset; and they were highly likely to exhibit delayed language development at 18 months.
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Simons, Ronald L.; Simons, Leslie Gordon; Lei, Man Kit; Landor, Antoinette
2011-01-01
The present study tests a developmental model designed to explain the romantic relationship difficulties and reluctance to marry often reported for African Americans. Using longitudinal data from a sample of approximately 400 African American young adults, we examine the manner in which race-related adverse experiences during late childhood and early adolescence give rise to the cynical view of romantic partners and marriage held by many young African Americans. Our results indicate that adverse circumstances disproportionately suffered by African American youth (viz., harsh parenting, family instability, discrimination, criminal victimization, and financial hardship) promote distrustful relational schemas that lead to troubled dating relationships, and that these negative relationship experiences, in turn, encourage a less positive view of marriage. PMID:22328799
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Giuliani, Jacopo; Bonetti, Andrea
2017-12-01
Riassunto. L'analisi è stata condotta al fine di valutare l'effetto sia sulla sopravvivenza globale (OS) sia sulla sopravvivenza libera da progressione di malattia (PFS) della chemioterapia di combinazione in prima linea per il carcinoma pancreatico in fase avanzata di malattia. La presente analisi è limitata agli studi randomizzati controllati (RCT) di fase III. Successivamente è stata applicata la European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) agli RCT di fase III analizzati per ricavare uno score relativo all'entità del beneficio clinico ottenuto per ciascun RCT. Sono state calcolate inoltre le differenze in termini di PFS tra i diversi bracci di trattamento rapportandole con i costi dei farmaci necessari per ottenere il beneficio di PFS. La nostra analisi ha valutato 11 RCT di fase III, per un totale di 4572 pazienti. Combinando i costi della terapia con la misura dell'efficacia espressa dalla PFS, è stato ottenuto un costo di 74,12 euro (€) per mese di vita guadagnato in termini di PFS con la combinazione di 5-fluorouracil, leucovorin, irinotecan e oxaliplatino (FOLFIRINOX), 90,14 € per la combinazione di gemcitabina e oxaliplatino (GEMOX) e 4708,7 € per la combinazione di nab-paclitaxel e gemcitabina. Da questo punto di vista riteniamo che l'utilizzo delle "vecche chemioterapie di combinazione" (per es., GEMOX) non dovrebbe essere completamente abbandonato, ma valutato sul singolo paziente, sulla base di diversi fattori (età, ECOG PS, comorbilità, carico di malattia), al fine di ottenere una reale "tailored therapy".
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Molecular analysis of DiGeorge Syndrome-related translocation breakpoints in 22q11.2
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chieffo, C.; Barnoski, B.L.; Emanuel, B.S.
1994-09-01
22q11 demonstrates a high frequency of disease-specific rearrangements. Several of the rearrangements are associated with developmental abnormalities such as DiGeorge Syndrome (DGS), Velocardiofacial Syndrome (VCFS), Cat Eye Syndrome (CES) and Supernumerary der(22)t(11;22) Syndrome. DGS and VCFS involve deletions of 22q11.2 resulting from unbalanced translocations or microdeletions. In contrast, CES and Supernumerary der(22)t(11;22) Syndrome result from duplications of this region via inter- or intra- chromosomal exchange. Although the molecular mechanism giving rise to these rearrangements has yet to be elucidated, the presence of known 22q11 repetitive elements are likely to be involved. GM5878 is a 46,XY,t(10;22) cell line from a balancedmore » translocation carrier father of an unbalanced DGS patient. GM0980 is a cell line from a patient with features of DGS/VCFS with an unbalanced karyotype. Using FISH cosmids, we have localized these translocation breakpoints near pH160b (D22S66) which maps to the center of the DiGeorge chromosomal region (DGCR). To further localize the breakpoint of GM5878, overlapping cosmids spanning this region were used as probes for FISH. Use of additional overlapping cosmids allowed the sublocalization of the breakpoint to a 10kb region. A 4.8 kb BglII fragment predicted to cross the breakpoint was isolated. When this fragment was used as a probe to normal and GM5878 DNA, novel bands were detected in GM5878 DNA digested with EcoRI and BglII. Similar analysis of the GM0980 breakpoint is being pursued. Full molecular characterization of these translocations is in progress using inverse PCR to clone the junctional fragments for sequencing. Detailed analysis of the region may reveal molecular features which make this a rearrangement prone area of the genome and help elucidate its relationship to human cytogenetic disease.« less
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Pereira, José; Araújo, Rui; Farias, Cláudio; Bessa, Cristiana; Mesquita, Isabel
2016-01-01
This study conducted a comparative analysis of students’ knowledge development on athletics in Sport Education and in a Direct Instruction unit taking into account sex and initial skill level. The participants were an experienced Physical Education teacher and two sixth-grade classes totaling 47 students (25 boys and 22 girls). Each class was randomly placed in either Sport Education or Direct Instruction classes and participated in 20, 45-minutes lessons focused on shot put, hurdles and triple jump. Knowledge on athletics was assessed through a 25-items written and video-based test. The inter-group differences and improvements across time in the knowledge test were analyzed through the Mann-Whitney and Wilcoxon tests, respectively. There were significant knowledge improvements in both instructional approaches irrespective of students’ gender and skill level. In Direct Instruction, the type of task organization, the high rates of repetition of movement patterns and feedback by the teacher were beneficial to student learning. In Sport Education, the autonomy granted to students in the control of the pace of task transitions by making on-going judgments on achievement of performance criteria, implicated students affectively and cognitively with the learning content. It was further supported that several models and teaching strategies should be taken into consideration when teaching Physical Education. Different approaches should be perceived as alternatives and teachers should retain the best in each according with the moment in the unit, student developmental stage, and the specific learning objectives in the task. Key points The results in this study showed that regardless of students’ sex, both DI and SE were efficient in the promotion of improvements in students’ content knowledge of athletics. Both boys and girls improved from the pre-test to the post-test in SE and DI. SE was particularly beneficial to lower skill-level. On the contrary, in the DI unit, both higher and lower skill-level students showed knowledge improvements. PMID:27928201
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Panlilio, Carlomagno C; Jones Harden, Brenda; Harring, Jeffrey
2018-01-01
Guided by bio-ecological theory, this study aimed to: (1) identify heterogeneity in the developmental patterns of emotion regulation for maltreated preschool-aged children; (2) examine the role of gender, language, placement instability, cognitive stimulation, and emotional support on patterns of stability and change of emotion regulation over time; and (3) elucidate the role of emotion regulation/dysregulation patterns on later academic achievement. This study utilized data from the first cohort of the National Survey of Child and Adolescent Well-Being. Results using LCA and LTA models indicated stability and change in emotionally regulated vs. emotionally dysregulated latent classes across 4, 5, and 6 ½ years of age. Placement instability significantly increased the likelihood of being classified as emotionally dysregulated at wave 1. Moreover, children classified as emotionally dysregulated by age 6 ½ scored significantly lower than children who were classified as emotionally regulated on measures of reading and math achievement by age 10. Based on these findings, placement stability at first contact with CPS should be promoted in order to prevent cascading negative effects on emotion regulation. Additionally, children who are more emotionally dysregulated by the time they transition to formal schooling should receive increased socioemotional and socioemotional learning supports. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Grein, K A; Glidden, L M
2015-07-01
Well-being outcomes for parents of children with intellectual and developmental disabilities (IDD) may vary from positive to negative at different times and for different measures of well-being. Predicting and explaining this variability has been a major focus of family research for reasons that have both theoretical and applied implications. The current study used data from a 23-year longitudinal investigation of adoptive and birth parents of children with IDD to determine which early child, mother and family characteristics would predict the variance in maternal outcomes 20 years after their original measurement. Using hierarchical regression analyses, we tested the predictive power of variables measured when children were 7 years old on outcomes of maternal well-being when children were 26 years old. Outcome variables included maternal self-report measures of depression and well-being. Final models of well-being accounted for 20% to 34% of variance. For most outcomes, Family Accord and/or the personality variable of Neuroticism (emotional stability/instability) were significant predictors, but some variables demonstrated a different pattern. These findings confirm that (1) characteristics of the child, mother and family during childhood can predict outcomes of maternal well-being 20 years later; and (2) different predictor-outcome relationships can vary substantially, highlighting the importance of using multiple measures to gain a more comprehensive understanding of maternal well-being. These results have implications for refining prognoses for parents and for tailoring service delivery to individual child, parent and family characteristics. © 2014 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.
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Hong, Seonghwan; Park, Sung Pyo; Kim, Yeong-Gyu; Kang, Byung Ha; Na, Jae Won; Kim, Hyun Jae
2017-11-24
We report low-temperature solution processing of hafnium oxide (HfO 2 ) passivation layers for amorphous indium-gallium-zinc oxide (a-IGZO) thin-film transistors (TFTs). At 150 °C, the hafnium chloride (HfCl 4 ) precursor readily hydrolyzed in deionized (DI) water and transformed into an HfO 2 film. The fabricated HfO 2 passivation layer prevented any interaction between the back surface of an a-IGZO TFT and ambient gas. Moreover, diffused Hf 4+ in the back-channel layer of the a-IGZO TFT reduced the oxygen vacancy, which is the origin of the electrical instability in a-IGZO TFTs. Consequently, the a-IGZO TFT with the HfO 2 passivation layer exhibited improved stability, showing a decrease in the threshold voltage shift from 4.83 to 1.68 V under a positive bias stress test conducted over 10,000 s.
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CONFERENCE DESCRIPTION Theory of Fusion Plasmas: Varenna-Lausanne International Workshop
NASA Astrophysics Data System (ADS)
Garbet, X.; Sauter, O.
2010-12-01
The Joint Varenna-Lausanne international workshop on Theory of Fusion Plasmas takes place every other year in a place particularly favourable for informal and in-depth discussions. Invited and contributed papers present state-of-the-art research in theoretical plasma physics, covering all domains relevant to fusion plasmas. This workshop always welcomes a fruitful mix of experienced researchers and students, to allow a better understanding of the key theoretical physics models and applications. Theoretical issues related to burning plasmas Anomalous Transport (Turbulence, Coherent Structures, Microinstabilities) RF Heating and Current Drive Macroinstabilities Plasma-Edge Physics and Divertors Fast particles instabilities Further details: http://Varenna-Lausanne.epfl.ch The conference is organized by: Centre de Recherches en Physique des Plasmas, Ecole Polytechnique Fédérale de Lausanne, Association EURATOM - Confédération Suisse 'Piero Caldirola' International Centre for the Promotion of Science and International School of Plasma Physics Istituto di Fisica del Plasma del CNR, Milano Editors: X Garbet (CEA, Cadarache, France) and O Sauter (CRPP-EPFL, Lausanne, Switzerland)
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Sub-ion scale plasmoids during collisionless reconnection on TREX
NASA Astrophysics Data System (ADS)
Olson, Joseph; Egedal, Jan; Myers, Rachel; Greess, Sam; Clark, Mike; Wallace, John; Forest, Cary; Wisconsin Plasma Astrophysics Laboratory Collaboration
2016-10-01
The Terrestrial Reconnection Experiment (TREX), operating at the Wisconsin Plasma Astrophysics Laboratory, is able to explore a collisionless regime inaccessible to previous reconnection experiments. To date, TREX has already achieved Lundquist numbers up to 104 where kinetic effects, such as electron pressure anisotropy, become important to the reconnection dynamics. During a recent run campaign in this collisionless regime, the spontaneous formation of magnetic islands (plasmoids) inside the ion diffusion region was observed. It is known that long current layers are susceptible to tearing, leading to the formation of plasmoids, and that these plasmoids have strong effects on the reconnection rate and particle energization. However, contrary to theoretical and numerical predictions, the TREX experiments show that the plasmoid instability is active even when the current layer is less than one di long. Analysis of these events shows that smaller plasmoids occur at a higher rate than larger ones, suggesting that magnetic islands could be seeded in plasmas more effectively than previously thought.
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Properties of Alfven Eigenmodes in the TAE range on the National Spherical Torus Experiment-Upgrade
DOE Office of Scientific and Technical Information (OSTI.GOV)
None
2013-04-24
A second Neutral Beam (NB) injection line is being installed on the NSTX Upgrade device, resulting in six NB sources with di erent tangency radii that will be available for heating and current drive. This work explores the properties of instabilities in the frequency range of the Toroidal Alfv en Eigenmode (TAE) for NSTX-U scenarios with various NB injection geometries, from more perpendicular to more tangential, and with increased toroidal magnetic eld with respect to previous NSTX scenarios. Predictions are based on analysis through the ideal MHD code NOVA-K. For the scenarios considered in this work, modi cations of themore » Alfv en continuum result in a frequency upshift and a broadening of the radial mode structure. The latter e ect may have consequences for fast ion transport and loss. Preliminary stability considerations indicate that TAEs are potentially unstable, with ion Landau damping representing the dominant damping mechanism« less
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Reijns, Martin A.M.; Rabe, Björn; Rigby, Rachel E.; Mill, Pleasantine; Astell, Katy R.; Lettice, Laura A.; Boyle, Shelagh; Leitch, Andrea; Keighren, Margaret; Kilanowski, Fiona; Devenney, Paul S.; Sexton, David; Grimes, Graeme; Holt, Ian J.; Hill, Robert E.; Taylor, Martin S.; Lawson, Kirstie A.; Dorin, Julia R.; Jackson, Andrew P.
2012-01-01
Summary The presence of ribonucleotides in genomic DNA is undesirable given their increased susceptibility to hydrolysis. Ribonuclease (RNase) H enzymes that recognize and process such embedded ribonucleotides are present in all domains of life. However, in unicellular organisms such as budding yeast, they are not required for viability or even efficient cellular proliferation, while in humans, RNase H2 hypomorphic mutations cause the neuroinflammatory disorder Aicardi-Goutières syndrome. Here, we report that RNase H2 is an essential enzyme in mice, required for embryonic growth from gastrulation onward. RNase H2 null embryos accumulate large numbers of single (or di-) ribonucleotides embedded in their genomic DNA (>1,000,000 per cell), resulting in genome instability and a p53-dependent DNA-damage response. Our findings establish RNase H2 as a key mammalian genome surveillance enzyme required for ribonucleotide removal and demonstrate that ribonucleotides are the most commonly occurring endogenous nucleotide base lesion in replicating cells. PMID:22579044
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Bonsignore, Maria; Andolfi, Nunzia; Quinci, Enza Maria; Madeddu, Anselmo; Tisano, Francesco; Ingallinella, Vincenzo; Castorina, Maria; Sprovieri, Mario
2016-01-01
OBIETTIVI: valutare e quantificare l'esposizione umana al mercurio (Hg) ed esplorare i fattori chiave che influenzano la contaminazione nelle popolazioni residenti in prossimità della Rada di Augusta, un'area a elevato rischio ambientale a causa degli effetti degli sversamenti incontrollati di Hg da parte di uno dei più grandi impianti cloro-soda d'Europa. DISEGNO: un campione di residenti nei comuni di Augusta, Priolo e Melilli (Sicilia orientale) è stato selezionato per lo studio di biomonitoraggio umano. Un questionario dettagliato è stato somministrato a ogni partecipante per raccogliere informazioni anagrafiche sulle abitudini di vita e alimentari. I livelli di Hg in sangue e capelli, usati come traccianti di esposizione a metilmercurio, sono stati messi in relazione al consumo di pesce locale. Il contenuto di Hg nelle urine è stato utilizzato per esplorare eventuali esposizioni atmosferiche a Hg inorganico. Una regressione lineare multivariata è stata applicata con l'obiettivo di esplorare i fattori che influenzano l'esposizione umana al Hg. L'approccio tossicocinetico è stato impiegato al fine di calcolare la dose settimanale provvisoria tollerabile ( provisional tolerable weekly intake, PTWI) e di predire le concentrazioni di Hg attese nel sangue degli individui con una dieta alimentare basata esclusivamente su pesce locale. 224 individui residenti nei comuni di Augusta, Melilli e Priolo. RISULTATI: eccessi di Hg sono stati misurati nel sangue e nei capelli del campione considerato. I più alti livelli sono stati rilevati ad Augusta, dove anche il consumo di pesce locale risulta maggiore. I valori di dose settimanale tollerabile provvisoria (PTWI) calcolati eccedono, nella maggior parte dei casi, le raccomandazioni internazionali, specialmente nei residenti ad Augusta. CONCLUSIONI: gli elevati livelli di Hg registrati nei campioni di sangue e capelli derivano, con ogni probabilità, dal consumo di pesce locale. Rispetto ad Augusta, gli individui di Priolo e Melilli subiscono un impatto più limitato. L'esposizione a Hg inorganico può essere considerata trascurabile.
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Creative thinking and Big Five factors of personality measured in Italian schoolchildren.
De Caroli, Maria Elvira; Sagone, Elisabetta
2009-12-01
This study examined the relations of creative thinking with Big Five factors of personality and the differences by sex and age on creativity. A sample of Italian schoolchildren (56 boys, 56 girls), between 8 to 10 years of age, completed the Test of Creative Thinking and the Big Five Questionnaire for Children. Analysis of results indicated that older children obtained significantly higher scores than the younger ones on Elaboration and Production of titles. Girls obtained significantly higher scores than boys on Originality and Elaboration. The results suggested a modest and negative relation of Flexibility with Conscientiousness and Production of titles with Emotional instability. These findings support the need to explore the connection between creativity and personality with developmental age by means of multiple tasks for evaluating creative thinking.
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Plaschke, Jens; Preußler, Mark; Ziegler, Andreas; Schackert, Hans K
2012-07-01
High level of microsatellite instability (MSI-H) in colorectal cancer (CRC) is caused by the inactivation of mismatch repair (MMR) genes; however, it is unknown for tumors with low level MSI (MSI-L). The protein complex involving MSH3 preferentially recognizes insertion/deletion loops (IDLs) of two to eight bases and di- and tetranucleotide repeats are affected in the majority of MSI-L CRC. We selected 10 and eight MSI-L CRCs from 228 and 204 patients with sporadic and hereditary disease, respectively. The tumors were analyzed for protein expression of MSH3, MSH2, MSH6, MLH1, and PMS2, and for mutations and loss of heterozygosity (LOH) in MSH3. Four tumors showed a markedly reduced MSH3 expression, whereas all 18 tumors had normal expression of the remaining MMR proteins. Twenty-five different sequence variants were identified. None of these results in a truncated protein, though L902W represents the first constitutional missense mutation in MSH3 predicted to be functional based on conservation among mutS homologues. All variants have also been found in normal DNA of the patients and in controls. LOH intragenic to MSH3 was evident for 12 of 16 (75%) informative tumors. Occurrence of sequence variants in normal DNA of the patients and in controls excludes somatic mutations and mutations specific to the CRC patient population, respectively. In contrast, the high frequency of LOH as well as the aberrant protein expression in some tumors indicates an involvement of MSH3 impairment in MSI-L CRC.
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NASA Astrophysics Data System (ADS)
Ha, Minseok; Graham, Samuel
2017-08-01
Experimental studies have shown that microporous surfaces induce one of the highest enhancements in critical heat flux (CHF) during pool boiling. However, microporous surfaces may also induce a very large surface superheat (>100 °C) which is not desirable for applications such as microelectronics cooling. While the understanding of the CHF mechanism is the key to enhancing boiling heat transfer, a comprehensive understanding is not yet available. So far, three different theories for the CHF of microporous surfaces have been suggested: viscous-capillary model, hydrodynamic instability model, and dryout of the porous coatings. In general, all three theories account for some aspects of boiling phenomena. In this study, the theories are examined through their correlations with experimental data on microporous surfaces during pool boiling using deionized (DI) water. It was found that the modulation of the vapor-jet through the pore network enables a higher CHF than that of a flat surface based on the hydrodynamic instability theory. In addition, it was found that as the heat flux increases, a vapor layer grows in the porous coatings described by a simple thermal resistance model which is responsible for the large surface superheat. Once the vapor layer grows to fill the microporous structure, transition to film boiling occurs and CHF is reached. By disrupting the formation of this vapor layer through the fabrication of channels to allow vapor escape, an enhancement in the CHF and heat transfer coefficient was observed, allowing CHF greater than 3500 kW/m2 at a superheat less than 50 °C.
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Calorimetria nucleare in collisioni tra ioni pesanti ad energie intermedie
NASA Astrophysics Data System (ADS)
Spezzi, L.
2002-07-01
Nel presente lavoro di tesi ci si e' occupati di uno studio sistematico di misure di temperatura ed energia di eccitazione in sistemi nucleari formati in reazioni tra ioni pesanti ad energie intermedie. La temperatura a stata misurata tramite due diversi metodi: rapporto tra le rese di isotopi che differiscono di uno stesso numero di nucleoni ( d/t-3He/4He , 3He/4He -6Li/7Li) - temperatura isotopica -, e rapporto tra le popolazioni degli stati eccitati in frammenti instabili (5Li e 6Li) che decadono in particelle leggere in coincidenza - temperatura di emissione. Le misure in esame sono state effettuate presso i Laboratori Nazionali del Sud per i sistemi 93Nb+93Nb, 93Nb+116,124Sn, 116,120Sn+116,124Sn e 116Sn+93Nb ad energie comprese tra 17 e 40 A MeV. L'apparato di rivelazione era costituito da un odoscopio ad alta granularite (96 telescopi Si (50micron)-Si(300micron)-CsI(Tl) ) e basse soglie di rivelazione, utilizzato sia per identificare risonanze in frammenti eccitati che per misure di rese di isotopi di frammenti con 2<=Z<=6, e dal multirivelatore FIASCO che, grazie alla misura contemporanea di posizione e tempo di volo dei frammenti provenienti dal proiettile (PLF - Projectile Like Fragments) e dal bersaglio (TLF - Target Like Fragment), e' stato utilizzato per misurare direttamente l'energia di eccitazione del sistema in studio. Analisi precedenti, condotte nell'ambito di varie collaborazioni, hanno messo in evidenza la possible esistenza di una transizione di fase liquido-gas del primo ordine nella materia nucleare. In tale contesto, ci siamo occupati di una verifica della curva calorica nucleare, ovvero della correlazione esistente fra temperatura ed energia di eccitazione del sistema, indagando, nel contempo, sulla sua dipendenza dalla massa del sistema che si frammenta. Si e' effettuato, inoltre, un confronto fra i due diversi metodi di misura della temperatura (temperatura isotopica e di emissione): l'andamento plateau-like della curva calorica e' stato confermato sia dalle temperature isotopiche che dalle temperature di emissione. Le "temperature limite", ovvero quelle relative all'andamento plateau-like della curva calorica, misurate per i vari sistemi studiati, sono state confrontate con quelle attualmente disponibili in letteratura, confermando la dipendenza dalla massa del sistema di tale grandezza.
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Bena, Antonella; Chiusolo, Monica; Orengia, Manuela; Cadum, Ennio; Farina, Elena; Musmeci, Loredana; Procopio, Enrico; Salamina, Giuseppe
2016-01-01
Si intende qui descrivere il sistema di sorveglianza sugli effetti sulla salute (SpoTT) dell'inquinamento ambientale nelle aree circostanti l'inceneritore di Torino. SPoTT ha 3 linee di attività: 1. monitoraggio epidemiologico degli effetti a breve termine attraverso analisi temporali e misura della correlazione tra livelli giornalieri di emissioni dell'impianto e andamento degli eventi individuati dagli archivi dei dimessi (SDO), di pronto soccorso e di mortalità; sono coinvolti coloro che nel 2013-2018 risiedevano nell'area di ricaduta delle emissioni; 2. sorveglianza epidemiologica degli effetti a lungo termine, stimando tassi standardizzati di mortalità e morbosità; a ogni soggetto è attribuito il valore stimato di esposizione cumulato nel tempo caratteristico della residenza anagrafica; le informazioni sulla salute sono reperite dagli archivi SDO, di mortalità e dai certificati di assistenza al parto; sono studiati due decenni pre-post l'avvio dell'impianto: 2003-2012 e 2013-2022; 3. monitoraggio biologico con misurazione pre-post di metalli, PCDD/F, PCB, OH-IPA; sono coinvolti 196 residenti esposti e 196 di controllo di 35-69 anni, campionati a caso dalle anagrafi comunali; sono effettuate misure di funzionalità endocrina e respiratoria, pressione arteriosa, rischio cardiovascolare; l'esposizione cumulativa sarà stimata per ciascuna persona campionata integrando l'indirizzo di residenza, il tempo di permanenza in ciascun indirizzo e i dati ricavati dai modelli di ricaduta; sarà costituita una biobanca per future indagini di laboratorio; sono coinvolti anche 20 allevatori e i lavoratori dell'impianto. Una quarta linea di attività, non descritta in questo articolo, riguarda il monitoraggio della salute dei lavoratori addetti all'impianto. SPoTT è il primo studio in Italia su inceneritori e salute che adotta un disegno di studio longitudinale di adeguata potenza sia per i residenti sia per i lavoratori. I primi risultati sono attesi nel corso del 2016.
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Guerriero, Chiara; Verdina, Federico; Ferri, Chiara; Pizzaguerra, Martina; Silvestri, Silvia; Tober, Nastassja; Ristagno, Quenya; Costa, Alessandro; Cerasuolo, Michele; Faggiano, Fabrizio; Allara, Elias
2016-01-01
INTRODUZIONE: gli incidenti stradali sono l'ottava causa di morte al mondo e la prima tra i giovani di 15-29 anni. In Italia il Piano nazionale sicurezza stradale raccomanda l'educazione scolastica per la prevenzione degli incidenti stradali; ad oggi non esistono documenti che raccolgano evidenze di efficacia sugli interventi educativi stradali e le rapportino al contesto italiano. OBIETTIVI: riassumere e discutere ciò che è noto in letteratura riguardo agli interventi scolastici per la prevenzione degli incidenti stradali. METODI: sono state ricercate linee guida e revisioni sistematiche usando i seguenti criteri di inclusione: popolazione di età inferiore ai 25 anni di entrambi i sessi; interventi scolastici di educazione stradale; effetti su indicatori primari di esito come riduzione degli incidenti stradali, astinenza dalla guida sotto l'effetto di alcol e dall'accettare passaggi in macchina da guidatori che sono sotto l'effetto di alcol; effetti su indicatori secondari di esito come conoscenze e competenze sui comportamenti di guida sicura. RISULTATI: sono state identificate due revisioni sistematiche. L'educazione stradale nelle scuole non mostra evidenza di efficacia (rischio relativo 1,03; IC95% 0,98-1,08) nel ridurre gli incidenti. Programmi scolastici più specifici mostrano risultati solo in parte convincenti per l'adozione di comportamenti sicuri come l'astinenza dal guidare sotto l'effetto di alcol e dall'accettare passaggi in macchina da guidatori che sono sotto l'effetto di alcol. DISCUSSIONE: le revisioni incluse non hanno trovato programmi efficaci nella riduzione degli incidenti stradali o dei fattori che possano determinarli. Nell'attesa di studi più recenti, appare opportuno promuovere l'implementazione di interventi misti, scolastici e di comunità, che hanno mostrato maggiori prove di efficacia.
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[National epidemiological surveillance systems of mesothelioma cases].
Ferrante, Pierpaolo; Binazzi, Alessandra; Branchi, Claudia; Marinaccio, Alessandro
2016-01-01
INTRODUZIONE: sebbene la relazione causale tra esposizione ad amianto e malattie neoplastiche sia ben nota, in molti Paesi il consumo del materiale è ancora rilevante e crescente. A causa della lunga latenza, nei Paesi dove è stato bandito (come in Italia) è oggi in corso un'epidemia di malattie correlate ad amianto. OBIETTIVI: descrivere i sistemi di sorveglianza dei mesoteliomi attivi nel mondo mediante un'analisi comparativa. è stata condotta una revisione bibliografica della letteratura disponibile sui sistemi di sorveglianza epidemiologica dei mesoteliomi attivi nel mondo, comparando metodi e risultati disponibili. RISULTATI: sistemi di ricerca dei casi incidenti e di analisi anamnestica dei soggetti ammalati sono attivi solo in Italia, Francia e Corea del Sud. I Paesi presso i quali sono attivi sistemi di rilevazione e controllo dei casi incidenti di mesotelioma sono quelli in cui vige il bando dell'amianto e che hanno sperimentato consumi rilevanti in passato. Non sono stati istituiti sistemi epidemiologici di sorveglianza in molti Paesi dove il consumo di amianto è ancora importante (inclusi Russia, Cina, India e Brasile). CONCLUSIONI: si conferma l'importanza dei sistemi di sorveglianza epidemiologica dei mesoteliomi per la sanità pubblica, il sostegno alle politiche di welfare e la prevenzione dei rischi. Lo sviluppo di progetti per tendere a una maggiore uniformità nei metodi di ricerca dei casi, di classificazione delle diagnosi e dell'esposizione e nelle tecniche di analisi dei dati potrebbe consentire una maggiore fruibilità dei dati aggregati. La disponibilità di dati internazionali confrontabili può essere di stimolo all'adozione di provvedimenti di bando internazionale.
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NASA Astrophysics Data System (ADS)
Cavenago, Dario; Mezzanzanica, Mario
I servizi sono oramai centrali nella vita sociale di ogni Paese. L'aspettativa di ogni attore sociale, sia esso cittadino/utente e/o istituzione, è quella di ricevere da uno scambio che ha alla base un servizio un contributo che si caratterizza per una qualità intrinseca. Il mantenimento di tale promessa richiede all'azienda erogatrice un forte coinvolgimento, nel disegno del servizio, degli utenti ed una capacità di gestione della conoscenza; ciò è particolarmente significativo per quei servizi che si caratterizzano per una forte personalizzazione o complessità progettuale. Disegnare un servizio, metterlo in produzione e gestirne l'erogazione ha una complessità variabile in base al grado di coinvolgimento dei destinati ed alle dimensioni critiche che esprimono le condizioni di fattibilità di un servizio di qualità appropriato alle attese degli utilizzatori. Ugualmente la globalizzazione dell'economia e la scarsità delle risorse ha portato l'attenzione, ai fini della sostenibilità delle condizioni sopra richiamate, di una ricerca di modelli e strumenti che permettano una valutazione e una standardizzazione dei processi di produzione ed erogazione secondo condizioni di economicità. Tali primi e sintetici elementi hanno condotto diversi attori istituzionali, grandi imprese ed università attraverso i loro centri di ricerca, ad una azione di riflessione sul grado di "ingegnerizzazione" dei processi sottesi alla erogazione dei servizi ed in particolare ai servizi che attuano le politiche dei grandi settori di base dell'economia di una Nazione: educazione, sanità, sociale, sviluppo infrastrutture ecc.
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NASA Astrophysics Data System (ADS)
Osezua Aikhuele, Daniel; Mohd Turan, Faiz
2016-02-01
The instability in today's market and the emerging demands for mass customized products by customers, are driving companies to seek for cost effective and time efficient improvements in their production system and this have led to real pressure for the adaptation of new developmental architecture and operational parameters to remain competitive in the market. Among such developmental architecture adopted, is the integration of lean thinking in the product development process. However, due to lack of clear understanding of the lean performance and its measurements, many companies are unable to implement and fully integrate the lean principle into their product development process and without a proper performance measurement, the performance level of the organizational value stream will be unknown and the specific area of improvement as it relates to the LPD program cannot be tracked. Hence, it will result in poor decision making in the LPD implementation. This paper therefore seeks to present a conceptual model for evaluation of LPD performances by identifying and analysing the core existing LPD enabler (Chief Engineer, Cross-functional teams, Set-based engineering, Poka-yoke (mistakeproofing), Knowledge-based environment, Value-focused planning and development, Top management support, Technology, Supplier integration, Workforce commitment and Continuous improvement culture) for assessing the LPD performance.
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Wong, Carolyn F; Schrager, Sheree M; Chou, Chih-Ping; Weiss, George; Kipke, Michele D
2013-06-01
Emerging adulthood is a transitional time often marked by instability in many areas of life, including residential status, work, school, and romantic relationships. The purpose of this study is to examine transitions in HIV-risk related behaviors among a cohort of ethnically-diverse young men who have sex with men (YMSM) and to reveal how changes in developmental contexts during emerging adulthood might be associated with these behavioral changes. Hidden Markov models were used to examine movement across different stages of behavioral risk-taking over time. Semi-annual surveys were administered across 2 years; analyses included those with at least three of the five waves of data. Results indicated substantial movement at the individual-level transitions. Additionally, high variability in sexual risk, alcohol misuse, and illicit drug-risk behaviors was predicted by age, ethnicity, and correlates of emerging adulthood, such as residential status, work, post-secondary school enrollment, and primary-relationship status. Findings provide evidence of great change in risky behaviors among YMSM during this pivotal time, particularly among those who actively experiment in varying levels of risk-taking. In order to prevent experimental behaviors from evolving into more serious risk, interventions must consider ways to assist YMSM to adjust to life changes brought on by emerging adulthood.
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Bitar, KM; Ferdhany, ME; Saw, A
2016-01-01
Introduction: Hip spica casting is an important component of treatment for developmental dysplasia of the hip (DDH) and popular treatment method for femur fractures in children. Breakage at the hip region is a relatively common problem of this cast. We have developed a three-slab technique of hip spica application using fibreglass as the cast material. The purpose of this review was to evaluate the physical durability of the spica cast and skin complications with its use. Methodology: A retrospective review of children with various conditions requiring hip spica immobilisation which was applied using our method. Study duration was from 1st of January 2014 until 31st December 2015. Our main outcomes were cast breakage and skin complications. For children with hip instability, the first cast would be changed after one month, and the second cast about two months later. Results: Twenty-one children were included, with an average age of 2.2 years. The most common indication for spica immobilisation was developmental dysplasia of the hip. One child had skin irritation after spica application. No spica breakage was noted. Conclusion: This study showed that the three-slab method of hip spica cast application using fibreglass material was durable and safe with low risk of skin complications. PMID:28553442
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Starkey, Jessica D.; Yamamoto, Masakazu; Yamamoto, Shoko; Goldhamer, David J.
2011-01-01
The developmental potential of skeletal muscle stem cells (satellite cells) remains controversial. The authors investigated satellite cell developmental potential in single fiber and clonal cultures derived from MyoDiCre/+;R26REYFP/+ muscle, in which essentially all satellite cells are permanently labeled. Approximately 60% of the clones derived from cells that co-purified with muscle fibers spontaneously underwent adipogenic differentiation. These adipocytes stained with Oil-Red-O and expressed the terminal differentiation markers, adipsin and fatty acid binding protein 4, but did not express EYFP and were therefore not of satellite cell origin. Satellite cells mutant for either MyoD or Myf-5 also maintained myogenic programming in culture and did not adopt an adipogenic fate. Incorporation of additional wash steps prior to muscle fiber plating virtually eliminated the non-myogenic cells but did not reduce the number of adherent Pax7+ satellite cells. More than half of the adipocytes observed in cultures from Tie2-Cre mice were recombined, further demonstrating a non-satellite cell origin. Under adipogenesis-inducing conditions, satellite cells accumulated cytoplasmic lipid but maintained myogenic protein expression and did not fully execute the adipogenic differentiation program, distinguishing them from adipocytes observed in muscle fiber cultures. The authors conclude that skeletal muscle satellite cells are committed to myogenesis and do not spontaneously adopt an adipogenic fate. PMID:21339173
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Carethers, John M; Koi, Minoru; Tseng-Rogenski, Stephanie S
2015-03-31
DNA mismatch repair (MMR) function is critical for correcting errors coincident with polymerase-driven DNA replication, and its proteins are frequent targets for inactivation (germline or somatic), generating a hypermutable tumor that drives cancer progression. The biomarker for defective DNA MMR is microsatellite instability-high (MSI-H), observed in ~15% of colorectal cancers, and defined by mono- and dinucleotide microsatellite frameshift mutations. MSI-H is highly correlated with loss of MMR protein expression, is commonly diploid, is often located in the right side of the colon, prognosticates good patient outcome, and predicts poor efficacy with 5-fluorouracil treatment. Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) is another form of MSI at tetranucleotide repeats that has been observed in multiple cancers, but its etiology and clinical relevance to patient care has only been recently illuminated. Specifically, EMAST is an acquired somatic defect observed in up to 60% of colorectal cancers and caused by unique dysfunction of the DNA MMR protein MSH3 (and its DNA MMR complex MutSβ, a heterodimer of MSH2-MSH3), and in particular a loss-of-function phenotype due to a reversible shift from its normal nuclear location into the cytosol in response to oxidative stress and the pro-inflammatory cytokine interleukin-6. Tumor hypoxia may also be a contributor. Patients with EMAST colorectal cancers show diminished prognosis compared to patients without the presence of EMAST in their cancer. In addition to defective DNA MMR recognized by tetranucleotide (and di- and tri-nucleotide) frameshifts, loss of MSH3 also contributes to homologous recombination-mediated repair of DNA double stranded breaks, indicating the MSH3 dysfunction is a complex defect for cancer cells that generates not only EMAST but also may contribute to chromosomal instability and aneuploidy. Areas for future investigation for this most common DNA MMR defect among colorectal cancers include relationships between EMAST and chemotherapy response, patient outcome with aneuploid changes in colorectal cancers, target gene mutation analysis, and mechanisms related to inflammation-induced compartmentalization and inactivation for MSH3.
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Carethers, John M.; Koi, Minoru; Tseng-Rogenski, Stephanie S.
2015-01-01
DNA mismatch repair (MMR) function is critical for correcting errors coincident with polymerase-driven DNA replication, and its proteins are frequent targets for inactivation (germline or somatic), generating a hypermutable tumor that drives cancer progression. The biomarker for defective DNA MMR is microsatellite instability-high (MSI-H), observed in ~15% of colorectal cancers, and defined by mono- and dinucleotide microsatellite frameshift mutations. MSI-H is highly correlated with loss of MMR protein expression, is commonly diploid, is often located in the right side of the colon, prognosticates good patient outcome, and predicts poor efficacy with 5-fluorouracil treatment. Elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) is another form of MSI at tetranucleotide repeats that has been observed in multiple cancers, but its etiology and clinical relevance to patient care has only been recently illuminated. Specifically, EMAST is an acquired somatic defect observed in up to 60% of colorectal cancers and caused by unique dysfunction of the DNA MMR protein MSH3 (and its DNA MMR complex MutSβ, a heterodimer of MSH2-MSH3), and in particular a loss-of-function phenotype due to a reversible shift from its normal nuclear location into the cytosol in response to oxidative stress and the pro-inflammatory cytokine interleukin-6. Tumor hypoxia may also be a contributor. Patients with EMAST colorectal cancers show diminished prognosis compared to patients without the presence of EMAST in their cancer. In addition to defective DNA MMR recognized by tetranucleotide (and di- and tri-nucleotide) frameshifts, loss of MSH3 also contributes to homologous recombination-mediated repair of DNA double stranded breaks, indicating the MSH3 dysfunction is a complex defect for cancer cells that generates not only EMAST but also may contribute to chromosomal instability and aneuploidy. Areas for future investigation for this most common DNA MMR defect among colorectal cancers include relationships between EMAST and chemotherapy response, patient outcome with aneuploid changes in colorectal cancers, target gene mutation analysis, and mechanisms related to inflammation-induced compartmentalization and inactivation for MSH3. PMID:25836926
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[Linee guida italiane per il trattamento dell'alcolismo].
Ceccanti, Mauro; Iannitelli, Angela; Fiore, Marco
2018-01-01
RIASSUNTO. L'Europa è la regione con il più forte consumo di alcol al mondo, con la più elevata percentuale di malattie totali e morti premature alcol-correlate. In Italia, questo fenomeno coinvolge circa il 13% della popolazione oltre i 18 anni e oltre il 25% dei pazienti ospedalizzati. Sfortunatamente, solo il 5% di questi pazienti vengono riconosciuti come persone affette da disturbo da uso di alcol (DUA). Una scarsa conoscenza della malattia, la mancanza di accesso alle cure e le poche risorse messe a disposizione nella gestione del problema sono tra le principali cause di ritardo nella diagnosi, alla fine con conseguenze cliniche molto più importanti e costose da gestire. Alla luce di ciò, abbiamo deciso di dedicare questo numero speciale della Rivista di psichiatria a una serie di articoli riguardanti le linee guida italiane per il trattamento della dipendenza da alcol. Realizzate in collaborazione con numerosi esperti e importanti società scientifiche italiane come il Centro di Riferimento Alcologico della Regione Lazio (CRARL), la Società Italiana Tossicodipendenze (SITD), la Società italiana per il Trattamento dell'Alcolismo e le sue Complicanze (SITAC), la Società Italiana Psichiatria delle Dipendenze (SIPDip), la Società Italiana Patologie da Dipendenza (SIPaD) e l'Istituto di Biologia Cellulare e Neurobiologia (IBCN-CNR), queste linee guida forniscono agli operatori una serie di raccomandazioni basate su prove di efficacia volte ad aumentare la conoscenza e un uso appropriato dei farmaci per le persone affette da DUA. Con la possibilità di un continuo aggiornamento, l'obiettivo principale di queste linee guida sarà quello di garantire l'omogeneità dei trattamenti e un incremento qualitativo nell'assistenza dei pazienti affetti da DUA, così da ridurre le conseguenze psicosociali e sulla salute pubblica di questa importante malattia psichiatrica.
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Plasticizers and BPA Residues in Tunisian and Italian Culinary Herbs and Spices.
Di Bella, Giuseppa; Ben Mansour, Hedi; Ben Tekaya, Asma; Beltifa, Asma; Potortì, Angela Giorgia; Saiya, Emanuele; Bartolomeo, Giovanni; Dugo, Giacomo; Lo Turco, Vincenzo
2018-06-01
In the present study, 18 plasticizers and residues in 10 different Tunisian and Italian culinary herbs and spices (black pepper, mint, caraway, coriander, oregano, rosemary, thyme, fennel, verbena, and laurel) were determined by GC/MS. Di-methylphthalate, di-(2-methylpropyl)adipate, di-n-butyladipate, di-propylphthalate, benzylbenzoate, di-phenylphthalate, and bisphenol A were lower than their LOQ in all 118 samples. Among the Tunisian samples, di-(2-ethylhexyl)phthalate was found in all types of samples and di-butylphthalate in 50% of types; all other phthalates were rarely dectected. Among the adipates, only di-methyladipate was found in 90% of types; di-ethyladipate was seldom found and di-(2-ethylhexyl)adipate only in samples of caraway. Di-(2-ethylhexyl)terephthalate was found in all types of samples; di-(2-ethylhexyl)sebacate was detected rarely but with high values. Among the Sicilian samples, di-ethylphthalate and di-(2-methylpropyl)phthalate were detected only in samples of mint; di-methyladipate, di-butylphthalate, and benzylbutylphthalate were identified in oregano and laurel; di-(2-ethylhexyl)terephthalate and di-(2-ethylhexyl)sebacate only in oregano. In any case, the results suggested that intake of these contaminants through spices and herbs is not a dangerous risk to the consumers. Probably, as already observed for the other food, these contaminants could result from pollution of the environment (air, water, and/or soil) and/or farming methods. Plasticizers and BPA in Tunisian and Italian spices were determined by GC/MS. Tunisian spices seem to contain more residues than Italian samples. Intake of these contaminants by spices is not a dangerous risk to the consumers. These pollutants could result from environmental pollution or agricultural practices. © 2018 Institute of Food Technologists®.
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Melero-Jiménez, Ignacio J.; Salvo, A. Enrique; Báez, José C.; Bañares-España, Elena; Reul, Andreas
2017-01-01
The canopy-forming, intertidal brown (Phaeophyceae) seaweed Fucus guiryi is distributed along the cold-temperate and warm-temperate coasts of Europe and North Africa. Curiously, an isolated population develops at Punta Calaburras (Alboran Sea, Western Mediterranean) but thalli are not present in midsummer every year, unlike the closest (ca. 80 km), perennial populations at the Strait of Gibraltar. The persistence of the alga at Punta Calaburras could be due to the growth of resilient, microscopic stages as well as the arrival of few–celled stages originating from neighbouring localities, and transported by the permanent Atlantic Jet flowing from the Atlantic Ocean into the Mediterranean. A twenty-six year time series (from 1990 to 2015) of midsummer occurrence of F. guiryi thalli at Punta Calaburras has been analysed by correlating with oceanographic (sea surface temperature, an estimator of the Atlantic Jet power) and climatic factors (air temperature, rainfall, and North Atlantic Oscillation –NAO-, and Arctic Oscillation –AO- indexes). The midsummer occurrence of thalli clustered from 1990–1994 and 1999–2004, with sporadic occurrences in 2006 and 2011. Binary logistic regression showed that the occurrence of thalli at Punta Calaburras in midsummer is favoured under positive NAO index from April to June. It has been hypothesized that isolated population of F. guiryi should show greater stress than their congeners of permanent populations, and to this end, two approaches were used to evaluate stress: one based on the integrated response during ontogeny (developmental instability, based on measurements of the fractal branching pattern of algal thalli) and another based on the photosynthetic response. Although significant differences were detected in photosynthetic quantum yield and water loss under emersion conditions, with thalli from Punta Calaburras being more affected by emersion than those from Tarifa, the developmental instability showed that the population from Tarifa suffers higher stress during ontogeny than that from Punta Calaburras. In conclusion, this study demonstrates the teleconnection between atmospheric oscillations and survival and proliferation of marine macroalgae. PMID:29158980
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Nattero, Julieta; Dujardin, Jean-Pierre; Del Pilar Fernández, María; Gürtler, Ricardo E
2015-12-01
Fluctuating asymmetry (FA), a slight and random departure from bilateral symmetry that is normally distributed around a 0 mean, has been widely used to infer developmental instability. We investigated whether habitats (ecotopes) and host-feeding sources influenced wing FA of the hematophagous bug Triatoma infestans. Because bug populations occupying distinct habitats differed substantially and consistently in various aspects such as feeding rates, engorgement status and the proportion of gravid females, we predicted that bugs from more open peridomestic habitats (i.e., goat corrals) were more likely to exhibit higher FA than bugs from domiciles. We examined patterns of asymmetry and the amount of wing size and shape FA in 196 adult T. infestans collected across a gradient of habitat suitability and stability that decreased from domiciles, storerooms, kitchens, chicken coops, pig corrals, to goat corrals in a well-defined area of Figueroa, northwestern Argentina. The bugs had unmixed blood meals on human, chicken, pig and goat depending on the bug collection ecotope. We documented the occurrence of FA in wing shape for bugs fed on all host-feeding sources and in all ecotopes except for females from domiciles or fed on humans. FA indices for wing shape differed significantly among host-feeding sources, ecotopes and sexes. The patterns of wing asymmetry in females from domiciles and from goat corrals were significantly different; differences in male FA were congruent with evidence showing that they had higher mobility than females across habitats. The host-feeding sources and habitats of T. infestans affected wing developmental stability depending on sex. Copyright © 2015 Elsevier B.V. All rights reserved.
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Alcohol-Induced Developmental Origins of Adult-Onset Diseases
Lunde, Emilie R.; Washburn, Shannon E.; Golding, Michael C.; Bake, Shameena; Miranda, Rajesh C.; Ramadoss, Jayanth
2016-01-01
Fetal alcohol exposure may impair growth, development, and function of multiple organ systems, and is encompassed by the term Fetal Alcohol Spectrum Disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker’s hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult-development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psycho-behavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult-onset of neuro-behavioral deficits, cardiovascular disease, endocrine dysfunction, nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation is a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter-relation are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD. PMID:27254466
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Alcohol-Induced Developmental Origins of Adult-Onset Diseases.
Lunde, Emilie R; Washburn, Shannon E; Golding, Michael C; Bake, Shameena; Miranda, Rajesh C; Ramadoss, Jayanth
2016-07-01
Fetal alcohol exposure may impair growth, development, and function of multiple organ systems and is encompassed by the term fetal alcohol spectrum disorders (FASD). Research has so far focused on the mechanisms, prevention, and diagnosis of FASD, while the risk for adult-onset chronic diseases in individuals exposed to alcohol in utero is not well explored. David Barker's hypothesis on Developmental Origins of Health and Disease (DOHaD) suggests that insults to the milieu of the developing fetus program it for adult development of chronic diseases. In the 25 years since the introduction of this hypothesis, epidemiological and animal model studies have made significant advancements in identifying in utero developmental origins of chronic adult-onset diseases affecting cardiovascular, endocrine, musculoskeletal, and psychobehavioral systems. Teratogen exposure is an established programming agent for adult diseases, and recent studies suggest that prenatal alcohol exposure correlates with adult onset of neurobehavioral deficits, cardiovascular disease, endocrine dysfunction, and nutrient homeostasis instability, warranting additional investigation of alcohol-induced DOHaD, as well as patient follow-up well into adulthood for affected individuals. In utero epigenetic alterations during critical periods of methylation are a key potential mechanism for programming and susceptibility of adult-onset chronic diseases, with imprinted genes affecting metabolism being critical targets. Additional studies in epidemiology, phenotypic characterization in response to timing, dose, and duration of exposure, as well as elucidation of mechanisms underlying FASD-DOHaD inter relation, are thus needed to clinically define chronic disease associated with prenatal alcohol exposure. These studies are critical to establish interventional strategies that decrease incidence of these adult-onset diseases and promote healthier aging among individuals affected with FASD. Copyright © 2016 by the Research Society on Alcoholism.
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Esposito, Mauro; Cavallo, Stefania; Rosato, Guido; Chiaravalle, Eugenio; Miedico, Oto; Pellicanò, Roberta; Soprano, Vittorio; Baldi, Loredana
2016-01-01
INTRODUZIONE: una vasta area compresa tra le province di Napoli e Caserta nella regione Campania ha negli ultimi anni attirato l'attenzione dei mass media a causa degli interramenti illeciti di rifiuti di varia origine nei campi o del loro abbandono lungo le strade. A tali pratiche illecite si aggiunge il fenomeno dei roghi incontrollati di questo materiale, motivo per il quale la zona è stata soprannominata "Terra dei fuochi". OBIETTIVI: ricerca di elementi in tracce presenti nei prodotti alimentari di origine vegetale prodotti nella Terra dei fuochi. DISEGNO E SETTING: piano di monitoraggio per il rilevamento dei livelli di alcuni metalli tossici ed essenziali nei vegetali coltivati in Campania nella Terra dei fuochi. La determinazione dei microelementi è stata effettuata dopo mineralizzazione della sostanza organica mediante microonde, utilizzando la spettrometria di massa a plasma induttivamente accoppiato (ICP-MS). RISULTATI: durante l'attività di monitoraggio sono stati raccolti 65 campioni di ortaggi e 49 campioni di frutta in 43 comuni rientranti nella Terra dei fuochi. Il contenuto medio di metalli tossici, cadmio e piombo nei prodotti ortofrutticoli è risultato ben lontano dai limiti massimi fissati dalla normativa europea. I valori delle concentrazioni sono significativamente inferiori rispetto a quanto riscontrato in zone ad alto impatto ambientale a causa della presenza di impianti industriali. CONCLUSIONI: la presenza di elementi tossici o potenzialmente tali nei campioni vegetali prodotti nella Terra dei fuochi è attribuibile a una varietà di fattori ambientali rilevanti (caratteristiche geologiche dell'area, inquinamento del suolo, dell'atmosfera e delle acque di irrigazione, pratiche illecite di smaltimento dei rifiuti industriali); non sembra, tuttavia, sussistere un rischio per la salute dei consumatori. Resta comunque l'allerta per la loro presenza nell'ambiente e la necessità che le attività di monitoraggio continuino.
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Mass Spectrometry of Large, Fragile, and Involatile Molecules.
ERIC Educational Resources Information Center
Busch, Kenneth L.; Cooks, R. Graham
1982-01-01
Desorption ionization (DI) is used to obtain mass spectra of molecules whose vaporization by heating may lead to thermal degradation. Discusses DI techniques, characteristics of DI mass spectra, ion production, current applications of DI in mass spectroscopy, developments in DI, and prospects for future evolution of new DI techniques. (Author/JN)
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Borderline intellectual functioning and sleep: the role of cyclic alternating pattern.
Esposito, Maria; Carotenuto, Marco
2010-11-19
In the clinical literature there are few specific studies about the relationship between cognition processes and sleep during childhood. In addition, milder deficits in general intellectual capacity have received less attention relative to major cognitive dysfunctions (such as the genetic or environmental basis of mental retardation), especially concerning the low normal and borderline status. Sleep could play a key role in multiple intellectual abilities such as memory, executive functions, and school performances. Aim of our study is to assess the sleep macrostructure and NREM instability (cyclic alternating pattern) and their relationship with IQ in a sample of subjects with borderline intellectual functioning (BIF). The DSM-IV defines BIF as a total intelligence quotient (TIQ) ranging between 71 and 84. Intellective functioning was assessed using the Italian version of Wechsler Intelligence Scale for Children-Revised (WISC-R), a well validated test for the developmental age between 6 and 16. For this study, 12 BIF and 17 healthy children, matched for sex and age, underwent an overnight PSG recording. Macrostructural sleep and CAP analysis were also performed. To our knowledge, this study represents the first attempt to evaluate sleep architecture and NREM instability organization in children with BIF. Findings from this investigation evidence that BIF presents alterations in both macro- and microstructural sleep architecture, with an interesting statistical significant correlation with IQ. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
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Staffend, Nancy A; Meisel, Robert L
2011-01-01
Fine neuronal morphology, such as dendritic spines, classically has been studied using the Golgi technique; however, Golgi staining is difficult to combine with other histological techniques. With the increasing popularity of fluorescent imaging, a number of fluorescent dyes have been developed that enable the coupling of multiple fluorescent labels in a single preparation. These fluorescent dyes include the lipophilic dialkylcarbocyanine, DiI; traditionally used for anterograde and retrograde neuronal tracing. More recently, DiI labeling has been used in combination with the Gene Gun for "DiOlistic" labeling of neurons in slice preparations. DiI sequesters itself within and diffuses laterally along the neuronal membrane, however once the cell is permeabilized, the DiI begins to leak from the cell membrane. A DiI derivative, Cell Tracker™ CM-DiI, increases dye stability and labeling half-life in permeabilized tissue, however at much greater expense. Here, the DiI and CM-DiI DiOlistic labeling techniques were tested in side-by-side experiments evaluating dye stability within dendritic architecture in medium spiny neurons of the dorsal stratum in both non-permeabilized and permeabilized tissue sections. In tissue sections that were not permeabilized, spine density in DiI labeled sections was higher than in CM-DiI labeling. In contrast, tissue sections that were permeabilized had higher spine densities in CM-DiI labeled neurons. These results suggest that for experiments involving non-permeabilized tissue, traditional DiI will suffice, however for experiments involving permeabilized tissue CM-DiI provides more consistent data. These experiments provide the first quantitative analyses of the impact of methodological permutations on neuronal labeling with DiI.
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Application of real-time PCR and melting curve analysis in rapid Diego blood group genotyping.
Novaretti, M C Z; Ruiz, A S; Dorlhiac-Llacer, P E; Chamone, D A F
2010-01-01
The paucity of appropriate reagents for serologic typing of the Diego blood group antigens has prompted the development of a real-time PCR and melting curve analysis for Diego blood group genotyping. In this study, we phenotyped 4326 donor blood samples for Di(a) using semiautomated equipment. All 157 Di(a+) samples were then genotyped by PCR using sequence-specific primers (PCR-SSP) for DI*02 because of anti-Di(b) scarcity. Of the 4326 samples, we simultaneously tested 160 samples for Di(a) and Di(b) serology, and DI*01 and DI*02 by PCR-SSP and by real-time PCR. We used the same primers for Diego genotyping by real-time PCR and PCR-SSP. Melting curve profiles obtained using the dissociation software of the real-time PCR apparatus enabled the discrimination of Diego alleles. Of the total samples tested, 4169 blood donors, 96.4 percent (95% confidence interval [CI], 95.8-96.9%), were homozygous for DI*02 and 157, 3.6 percent (95% CI, 3.1%-4.2%), were heterozygous DI*01/02. No blood donor was found to be homozygous for DI*01 in this study. The calculated DI*01 and DI*02 allele frequencies were 0.0181 (95% CI, 0.0173-0.0189) and 0.9819 (95% CI, 0.9791-0.9847), respectively, showing a good fit for the Hardy-Weinberg equilibrium. There was full concordance among Diego phenotype results by PCR-SSP and real-time PCR. DI*01 and DI*02 allele determination with SYBR Green I and thermal cycler technology are useful methods for Diego determination. The real-time PCR with SYBR Green I melting temperature protocol can be used as a rapid screening tool for DI*01 and DI*02 blood group genotyping.
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VII Workshop Italiano sulla fisica pp a LHC
NASA Astrophysics Data System (ADS)
LHCpp2016 è la settima edizione dell'incontro nazionale sulla fisica p-p a LHC. Questa serie di incontri è nata a Pisa nel 2003 con lo scopo di stimolare lo scambio di idee tra le comunità sperimentali di ATLAS, CMS e LHCB e la comunità teorica. Caratteristica fondamentale di questi incontri è la preparazione di larga parte dei talk in collaborazione tra i vari esperimenti e la comunità teorica. Largo spazio nella preparazione e presentazione dei talk viene dato ai giovani ricercatori. In questa settima edizione, che si tiene di nuovo a Pisa, vogliamo concentrare l'attenzione sulle potenzialità di scoperta offerte dai dati raccolti durante il runII di LHC.
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Zou, Peng; Chen, Hongwei; Paholak, Hayley J.; Sun, Duxin
2013-01-01
Understanding in vivo drug release kinetics is critical for the development of nanoparticle-based delivery systems. In this study, we developed a fluorescence resonance energy transfer (FRET) imaging approach to noninvasively monitor in vitro and in vivo cargo release from polymeric nanoparticles. The FRET donor dye (DiO or DiD) and acceptor dye (DiI or DiR) were individually encapsulated into poly(ethylene oxide)-b-polystyrene (PEO-PS) nanoparticles. When DiO (donor) nanoparticles and DiI (acceptor) nanoparticles were co-incubated with cancer cells for 2 h, increased FRET signals were observed from cell membranes, suggesting rapid release of DiO and DiI to cell membranes. Similarly, increased FRET ratios were detected in nude mice after intravenous co-administration of DiD (donor) nanoparticles and DiR (acceptor) nanoparticles. In contrast, another group of nude mice i.v. administrated with DiD/DiR co-loaded nanoparticles showed decreased FRET ratios. Based on the difference in FRET ratios between the two groups, in vivo DiD/DiR release half-life from PEO-PS nanoparticles was determined to be 9.2 min. In addition, it was observed that the presence of cell membranes facilitated burst release of lipophilic cargos while incorporation of oleic acid-coated iron oxide into PEO-PS nanoparticles slowed the release of DiD/DiR to cell membranes. The developed in vitro and in vivo FRET imaging techniques can be used to screening stable nano-formulations for lipophilic drug delivery. PMID:24033270
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Picardi, Nicola
2018-01-01
È pleonastico ricordare che ogni individuo raziocinante delle essere responsabile delle sue azioni: deve agire con la coscienza degli scopi che si propone evitando possibili conseguenze negative dei suoi atti. In ambito medico questo tipo di responsabilità è codificata con le norme della "deontologia". Per secoli l'arte terapeutica è stata praticata da individui dotati di una particolare vocazione ed una particolare cultura acquisita da Maestri dell'arte ancor prima che dalla propria esperienza, con nozioni di erboristeria e di elementari conoscenze anatomiche e di fisiologia, circondati da un'aura sacerdotale e da un rispetto derivante dal timore e dall'ammirazione per il coraggio e auspicabilmente dai successi, e facendo riferimento nell'occidente mediterraneo alle regole operative fissate nel Giuramento di Ippocrate, di significato tra il sacro ed il deontologico. Lo sviluppo delle tecniche anestesiologiche a partire dalla seconda metà dell'800 ha determinato l'ampliamento delle iniziative chirurgiche di tipo elettivo, a fianco con gli storici interventi in emergenza per la cura di lesioni traumatiche, ancor prima delle acquisizioni riguardanti le infezioni. Con l'espansione del campo di azione della chirurgia, le possibili complicanze ed i possibili insuccessi hanno fatto da contrappeso ai sentimenti di rispetto e di fiducia nei confronti dei chirurghi, giungendo a far assimilare in tali casi la loro opera quale causa all'origine di danni, provocati rientrando quindi nella categoria dei reati sottoposti alla Legge penale. Così, al termine deontologico di "responsabilità" valido per ogni iniziativa ed ogni professione, per i medici è venuto ad associarsi la qualifica di "professionale", con un significato di presunta colpevolezza. Da una parte le regole deontologiche si sono ampliate, ed hanno coinvolto direttamente il paziente nella fase decisionale delle terapie chirurgiche, formalizzate programmaticamente in moderni codici deontologici ed operativamente nel documento del "consenso informato". Per altro verso le leggi innovative del Codice Civile definito nel 1942, che al posto delle pene del codice penale introduceva il criterio della risarcibilità economica del danno in caso di riconosciuta "responsabilità professionale", ha determinato il coinvolgimento di altre figura professionali, e cioè di avvocati e di medici legali, oltre che delle organizzazioni assicurative, con detrimento alla serenità nell'espletamento delle professioni sanitarie e con l'insorgenza per reazione della cosidetta "medicina difensiva". La concretezza di queste problematiche hanno richiesto l'interessamento attivo della Giurisprudenza con una serie di sentenze, ed una formulazione di decreti e nuove leggi parlamentari, ancora in pieno assestamento nel corso del 2017, lasciano in qualche modo ancora irrisolti alcuni nodi.
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Case report of 5 siblings: malnutrition? Rickets? DiGeorge syndrome? Developmental delay?
Cundiff, David K; Harris, William
2006-01-01
Background Parents of six children are facing a trial on charges of aggravated manslaughter in the care a 5 1/2 month old infant who died suddenly and neglect of their four older children for causing them to be malnourished by feeding them all an exclusively raw foods vegan diet. Both parents declined plea bargains and plan to defend themselves in court. Case presentation The fifth child born to a married couple was breast-fed until 2 1/2 months. Subsequently, the parents fed the baby an exclusively raw foods diet prepared in a blender at home. The four older children, ages 18 months – 6 1/2 years also ate an exclusively raw foods vegan diet. None of the four older children had significant previous injuries or serious illnesses. At autopsy, the infant weighed 3180 mg (6.99 pounds) and appeared emaciated. The thymus gland was absent and parathyroid glands were not located. The lungs were "congested." DiGeorge anomaly cannot be ruled out from these findings. Although, the coroner ruled that "malnutrition" was the sole cause of death, malnutrition, according to the World Health Organization definition, cannot be diagnosed in this infant. Compared with standard growth charts, the older children fell 2.1–4.1 standard deviations below the mean for North American children in height and weight. Labs were normal except for a low cholesterol level in all and a low prealbumin in one of three children tested. Therefore, malnutrition cannot be diagnosed in these children. The pediatrician diagnosed rickets in the four-year-old. However, chest x-rays were normal in all and long bone x-rays showed minimal changes in one child – no sign of rickets. The clinical diagnosis of rickets was not confirmed by the Center for Disease Control's criteria. A psychologist diagnosed the 18-month-old as developmentally delayed to the level of a 15-month-old, but this diagnosis is questionable. Conclusion The raw foods vegan diet and possibly inherited small stature from the father's side account for their relatively low heights and weights. Catch-up growth will probably occur on the standard American diet but would have also been expected if they had remained on a vegan diet. PMID:16412249
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Koester-Eiserfunke, Nora; Fischle, Wolfgang
2011-01-01
MBT domain proteins are involved in developmental processes and tumorigenesis. In vitro binding and mutagenesis studies have shown that individual MBT domains within clustered MBT repeat regions bind mono- and dimethylated histone lysine residues with little to no sequence specificity but discriminate against the tri- and unmethylated states. However, the exact function of promiscuous histone methyl-lysine binding in the biology of MBT domain proteins has not been elucidated. Here, we show that the Caenorhabditis elegans four MBT domain protein LIN-61, in contrast to other MBT repeat factors, specifically interacts with histone H3 when methylated on lysine 9, displaying a strong preference for di- and trimethylated states (H3K9me2/3). Although the fourth MBT repeat is implicated in this interaction, H3K9me2/3 binding minimally requires MBT repeats two to four. Further, mutagenesis of residues conserved with other methyl-lysine binding MBT regions in the fourth MBT repeat does not abolish interaction, implicating a distinct binding mode. In vivo, H3K9me2/3 interaction of LIN-61 is required for C. elegans vulva development within the synMuvB pathway. Mutant LIN-61 proteins deficient in H3K9me2/3 binding fail to rescue lin-61 synMuvB function. Also, previously identified point mutant synMuvB alleles are deficient in H3K9me2/3 interaction although these target residues that are outside of the fourth MBT repeat. Interestingly, lin-61 genetically interacts with two other synMuvB genes, hpl-2, an HP1 homologous H3K9me2/3 binding factor, and met-2, a SETDB1 homologous H3K9 methyl transferase (H3K9MT), in determining C. elegans vulva development and fertility. Besides identifying the first sequence specific and di-/trimethylation binding MBT domain protein, our studies imply complex multi-domain regulation of ligand interaction of MBT domains. Our results also introduce a mechanistic link between LIN-61 function and biology, and they establish interplay of the H3K9me2/3 binding proteins, LIN-61 and HPL-2, as well as the H3K9MT MET-2 in distinct developmental pathways. PMID:21437264
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Central radio galaxies in groups: cavities, bubbles and the history of AGN heating
NASA Astrophysics Data System (ADS)
Giacintucci, S.; Venturi, T.; Raychaudhury, S.; Vrtilek, J.
2008-10-01
E' noto che le regioni centrali degli ammassi e gruppi di galassie costituiscono un ambiente in cui gas caldo e plasma radioemittente proveniente dalle galassie dominanti interagiscono tra loro. In particolare, si pensa che la radioemissione dell'AGN centrale ed i suoi possibili cicli di attivita', siano strettamente legati alla presenza di cavita' e "bubbles" nel gas intergalattico. Si presentera' lo status di un progetto osservativo effettuato con il Giant Metrewave Radio Telescope (GMRT, India) su di un campione di 18 gruppi di galassie, osservati a tre frequenze radio (235 MHz, 325 MHz e 610 MHz). Lo studio della morfologia radio degli AGN centrali e la relativa analisi spettrale permettono di ottenere stime sull'eta' di questi oggetti, e sulla loro energia totale, che a loro volta sono in relazione con le proprieta' X dei gruppi stessi. Per tutti gli oggetti del campione sono disponibili osservazioni Chandra di proprieta'. Per due oggetti del campione, 4C+24.36 (al centro di AWM04) e NGC741 (al centro di RSOG17) verra' presentato uno studio dettagliato.
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[Trattamento della dipendenza da alcol. Alcol e giovani: punto di vista sociale].
Alessandrini, Giovanni; Ciccarelli, Rosaria; Battagliese, Gemma; Lombardo, Giuseppe; De Rosa, Francesca; Messina, Marisa Patrizia; Vitali, Mario; Pisciotta, Fabiola; Nanut, Miriana; Attilia, Maria Luisa; Ceccanti, Mauro
2018-01-01
RIASSUNTO. Gli adolescenti rappresentano la fascia di età più vulnerabile ai danni causati dall'abuso di alcol, in quanto iniziare a bere in giovane età è associato a un aumento del rischio di dipendenza da alcolici in età adulta. I giovani tendono a bere grandi quantità di alcolici al fine di ricercare forti emozioni e nel tentativo di raggiungere il divertimento a ogni costo, tramite le proprietà psicotrope degli alcolici. Le cause che li inducono ad assumere questi comportamenti sono da ricercare nella non conoscenza degli effetti dannosi dell'alcol, nel rito di convivialità sociale (evenienza per la quale si attribuisce all'alcol la funzione di facilitatore dell'aggregazione tra giovani), nella mancanza di interessi personali, nella scarsità dei controlli e nelle abitudini familiari. Le azioni da intraprendere per limitare o arrestare il consumo nocivo di alcol nei giovani si devono basare su interventi finalizzati a ritardare l'età del primo contatto con le bevande alcoliche, mediante la realizzazione di campagne educazionali rivolte ai giovani stessi, ai loro familiari e alla società intera.
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Chelvanayagam, D K; Beazley, L D
1997-03-01
The stain toluidine blue-O (tol blue), applied to sections of neural tissue, is shown to be compatible with the vivid fluorescent lipophilic neural tracers 4-(4-dihexadecylaminostyryl)-N-methylpyridinium iodide (Di-ASP), 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO) and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI). As with other Nissl stains, toluidine blue-O fluoresces in the red end of the spectrum but such fluorescence quenches upon binding with tissue. Moreover, progressive staining occurs at concentrations low enough to minimise any background fluorescence attributable to non-specific residence of the stain. The bright yellow Di-ASP and vivid green DiO signals are spectrally removed from the red fluorescence of toluidine blue-O. With toluidine blue-O counterstaining, Di-ASP generally offers contrast superior to that with DiI, however, the latter is improved by viewing in a polarised green bright field. Visible Di-ASP emission, although broad, peaks at a more film-sensitive region of the spectrum than that for DiI, thus reducing the photographic exposure required.
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Enzymatic Production of c-di-GMP Using a Thermophilic Diguanylate Cyclase.
Venkataramani, Prabhadevi; Liang, Zhao-Xun
2017-01-01
C-di-GMP has emerged as a prevalent bacterial messenger that controls a multitude of bacterial behaviors. Having access to milligram or gram quantities of c-di-GMP is essential for the biochemical and structural characterization of enzymes and effectors involved in c-di-GMP signaling. Although c-di-GMP can be synthesized using chemical methods, diguanylate cyclases (DGC)-based enzymatic synthesis is the most efficient method of preparing c-di-GMP today. Many DGCs are not suitable for c-di-GMP production because of poor protein stability and the presence of a c-di-GMP-binding inhibitory site (I-site) in most DGCs. We have identified and engineered a thermophilic DGC for efficient production of c-di-GMP for characterizing c-di-GMP signaling proteins and riboswitches. Importantly, residue replacement in the inhibitory I-site of the thermophilic DGC drastically relieved product inhibition to enable the production of hundreds of milligrams of c-di-GMP using 5-10 mg of this robust biocatalyst.
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Code of Federal Regulations, 2014 CFR
2014-07-01
... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes, reaction products with 3-(triethoxysilyl)-1-propanamine. 721... Substances § 721.10325 Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes...
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Code of Federal Regulations, 2013 CFR
2013-07-01
... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes, reaction products with 3-(triethoxysilyl)-1-propanamine. 721... Substances § 721.10325 Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes...
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Code of Federal Regulations, 2012 CFR
2012-07-01
... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes, reaction products with 3-(triethoxysilyl)-1-propanamine. 721... Substances § 721.10325 Cyclosilazanes, di-Me, Me hydrogen, polymers with di-Me, Me hydrogen silazanes...
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Regulation of spindle integrity and mitotic fidelity by BCCIP
Huhn, S C; Liu, J; Ye, C; Lu, H; Jiang, X; Feng, X; Ganesan, S; White, E; Shen, Z
2017-01-01
Centrosomes together with the mitotic spindle ensure the faithful distribution of chromosomes between daughter cells, and spindle orientation is a major determinant of cell fate during tissue regeneration. Spindle defects are not only an impetus of chromosome instability but are also a cause of developmental disorders involving defective asymmetric cell division. In this work, we demonstrate BCCIP, especially BCCIPα, as a previously unidentified component of the mitotic spindle pole and the centrosome. We demonstrate that BCCIP localizes proximal to the mother centriole and participates in microtubule organization and then redistributes to the spindle pole to ensure faithful spindle architecture. We find that BCCIP depletion leads to morphological defects, disoriented mitotic spindles, chromosome congression defects and delayed mitotic progression. Our study identifies BCCIP as a novel factor critical for microtubule regulation and explicates a mechanism utilized by BCCIP in tumor suppression. PMID:28394342
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Leventhal, T; Brooks-Gunn, J
2000-03-01
This article provides a comprehensive review of research on the effects of neighborhood residence on child and adolescent well-being. The first section reviews key methodological issues. The following section considers links between neighborhood characteristics and child outcomes and suggests the importance of high socioeconomic status (SES) for achievement and low SES and residential instability for behavioral/emotional outcomes. The third section identifies 3 pathways (institutional resources, relationships, and norms/collective efficacy) through which neighborhoods might influence development, and which represent an extension of models identified by C. Jencks and S. Mayer (1990) and R. J. Sampson (1992). The models provide a theoretical base for studying neighborhood mechanisms and specify different levels (individual, family, school, peer, community) at which processes may operate. Implications for an emerging developmental framework for research on neighborhoods are discussed.
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Screening for developmental dysplasia of the hip.
Desprechins, B; Ernst, C; de Mey, J
2007-01-01
The reported prevalence of established dislocation the hip in an unscreened population varies from 0.7 to 1.6 / 1000 children in European and American white populations. In clinically screened populations neonatal hip instability is reported to occur in 3 to 30 / 1000 newborns while established congenital dislocation has a prevalence of 0.1- 4/1000 of which 1/1000 is judged to be in need for surgery. Early diagnosis of DDH is essential for successful treatment and later prognosis of the disorder. Combined procedure including evaluation of both hip morphology and hip stability is currently recommended. Opinions differ about the need for universal versus selective sonographic screening for diagnosis of DDH. Currently selective screening of those infants with recognised risk factors and those with abnormal physical examination would be cost-effective and the only practicable method for most countries.
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Acute myeloid leukemia and diabetes insipidus with monosomy 7.
Harb, Antoine; Tan, Wei; Wilding, Gregory E; Battiwalla, Minoo; Sait, Sheila N J; Wang, Eunice S; Wetzler, Meir
2009-04-15
The predisposition of monosomy 7 to diabetes insipidus (DI) in acute myeloid leukemia (AML) led us to ask whether AML associated with monosomy 7 and DI will differ from AML associated with other karyotype aberrations and DI and whether the outcome of patients with AML and DI will differ from those without DI. We describe 2 patients from Roswell Park Cancer Institute and discuss 29 additional cases from the literature. AML with monosomy 7 and DI (n = 25) had a trend towards a lower complete remission (p = 0.0936) and worse survival (p = 0.0480) than AML with other karyotype changes and DI (n = 6). Further, AML with monosomy 7 and DI had worse complete remission rate and overall survival than AML with monosomy 7 but without DI. In conclusion, it appears that AML with monosomy 7 and DI is a disease entity with specifically poor outcome.
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IL TRAPIANTO ORTOTOPICO DEL FEGATO
STARZL, THOMAS E.
2010-01-01
E’ormai noto che esiste la possibilità rivoluzionaria di utilizzare il fegato per il trattamento della stadio terminale delle epatopatie. Nel gennaio 1980 si celebra il decimo anna di sopravvivenza con fegato trapiantato (la più lunga della letteratura) di un paziente da noi trattato. Si tratta di uno dei 12 malati sottoposti a trapianto e seguiti per più di 5 anni. La nota positiva di questa tipo di trattamento è rappresentata dall’eccellente tenore di vita che i pazienti conducono e dalla riabilitazione sociale e professionale. La nota negativa è data, invece, dal fatto che i buoni risultati non vengono raggiunti con regolarità e non possono essere previsti con esattezza. In questa breve rassegna considereremo la esperienza da noi fatta presso l’Università di Denver nel Colorado, mettendo in risalto le cause dell’elevata mortalità precoce e le prospettive future di questa mezzo terapeutico. PMID:21572898
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Trasforiiazioni Termoelastiche Finite di Solidi Incomprimibili
NASA Astrophysics Data System (ADS)
Signorini, A.
Queste lezlioni hanno come direttiva una sintesi di quanto si trova sistematicamente sviluppato in una mia Memoria sulle trasformazioni termoelastiche finite di solidi incomprimibili, in corso di stampa negli Annali di Matematica pura e applicata t. XXXIX ( 1955) pp. 147-201 , Verranno anche esposti, come necessaria premessa, alcuni d ei risultati di due precedenti Memorie degli stessi Annali. Invece, per motivo di brevità, non potrò dare neppure un cenno delle ulteriori ricerche svilup pate dal prof. T. Manacorda in tre recentissimi suoi lavori:
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Elaborazione dei dati sperimentali
NASA Astrophysics Data System (ADS)
Dapor, M.; Ropele, M.
L'analisi statistica dei dati sperimentali, la loro elaborazione ed una corretta stima degli errori sono conoscenze necessarie agli studenti di fisica, biologia, chimica, ingegneria e dei corsi di specializzazione tecnico-scientifici in cui a di laboratorio. Chi si occupa di problemi tecnici e di misure, per studio o per lavoro, deve possedere gli strumenti matematici di calcolo e di analisi necessari ad una corretta interpretazione dei dati sperimentali. Il testo fornisce in modo sintetico, chiaro ed esaustivo, tutte le nozioni e le conoscenze utili allo scopo.
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Fahmi, Tazin; Port, Gary C.
2017-01-01
Signal transduction pathways enable organisms to monitor their external environment and adjust gene regulation to appropriately modify their cellular processes. Second messenger nucleotides including cyclic adenosine monophosphate (c-AMP), cyclic guanosine monophosphate (c-GMP), cyclic di-guanosine monophosphate (c-di-GMP), and cyclic di-adenosine monophosphate (c-di-AMP) play key roles in many signal transduction pathways used by prokaryotes and/or eukaryotes. Among the various second messenger nucleotides molecules, c-di-AMP was discovered recently and has since been shown to be involved in cell growth, survival, and regulation of virulence, primarily within Gram-positive bacteria. The cellular level of c-di-AMP is maintained by a family of c-di-AMP synthesizing enzymes, diadenylate cyclases (DACs), and degradation enzymes, phosphodiesterases (PDEs). Genetic manipulation of DACs and PDEs have demonstrated that alteration of c-di-AMP levels impacts both growth and virulence of microorganisms. Unlike other second messenger molecules, c-di-AMP is essential for growth in several bacterial species as many basic cellular functions are regulated by c-di-AMP including cell wall maintenance, potassium ion homeostasis, DNA damage repair, etc. c-di-AMP follows a typical second messenger signaling pathway, beginning with binding to receptor molecules to subsequent regulation of downstream cellular processes. While c-di-AMP binds to specific proteins that regulate pathways in bacterial cells, c-di-AMP also binds to regulatory RNA molecules that control potassium ion channel expression in Bacillus subtilis. c-di-AMP signaling also occurs in eukaryotes, as bacterially produced c-di-AMP stimulates host immune responses during infection through binding of innate immune surveillance proteins. Due to its existence in diverse microorganisms, its involvement in crucial cellular activities, and its stimulating activity in host immune responses, c-di-AMP signaling pathway has become an attractive antimicrobial drug target and therefore has been the focus of intensive study in several important pathogens. PMID:28783096
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Il ruolo svolto dall’attività lavorativa sull’ipertensione arteriosa
Barbini, N.; Gorini, G.; Ferrucci, L.; Biggeri, A.
2009-01-01
RIASSUNTO Introduzione I parametri di pressione arteriosa, sistolica (PAS) o diastolica (PAD) hanno costituito I’oggetto di numerosi studi, alcuni dei quali stabiliscono un’associazione tra I’aumnto di tali parametri e la mortalità, in particolare alle età medie. I fattori di rischio di ipertensione più frequentemente studiati sono il consumo di alcol, il fumo e I’origine etnica in riferimento sia alle differenze genetiche che nella condotta alimentare, mentre i fattori di origine professionale sono stati presi in considerazione più raramente e in maniera poco approfondita, inoltre sono state riferite notevoli differenze nelle pressioni arteriose medie di individui che svolgono professioni diverse. Sembra infatti che i “colletti blu” siano più a rischio dei “colletti bianchi”. Obiettivi Il nostro scopo è valutare se determinati rischi o vincoli connessi con l’attività professionale o determinati stili di vita rappresentano un fattore di rischio per l’ipertensione arteriosa in considerazioni dell’aumentare dell’età. Elementi specifici che rendano conto di questa relazione non sono stati ancora completamente chiariti e soprattutto i dati sulla popolazione italiana sono molto limitati. Metodi La metodologia di ricerca utilizzata è stata quella dell’indagine francese ESTEV (Derriennic, Touranchet, Volkoff) - VISAT (Marquie, Janson), studio epidemiologico longitudinale su oltre 23000 lavoratori attivata in Francia nel 1990 al fine di indagare gli effetti a lungo termine delle condizioni di lavoro, riferite all’intera vita professionale, sia sull’invecchiamento sia sulla salute dei lavoratori. Analoga indagine è stata avviata in Italia, nel 2000, in 6 Regioni, prendendo in esame i lavoratori dipendenti di diversi settori produttivi appartenenti a 5 coorti di età: da 32 a 52 anni con intervallo di 5 anni. Le rilevazioni sono state effettuate dai medici del lavoro di azienda attraverso 3 questionari: 1. sulle condizioni professionali (esposizione a determinati rischi o vincoli); 2. sugli stili di vita e la salute percepita secondo il Nottingham Health Profile; 3. sulle condizioni oggettive di salute. Per il presente lavoro saranno considerati solo alcuni parametri utili all’approfondimento epidemiologico nel settore cardiocircolatorio. Essi riguarderanno: 1) le condizioni di lavoro, 2) la valutazione soggettiva del lavoro, 3) costrizioni specifiche del lavoro vissute come più gravose con l’avanzare dell’età. Relativamente all’ipertensione, sono stati considerati ipertesi i soggetti che presentavano una PAS ≥160 mm/Hg e/o una PAD ≥90 mm/Hg nonché coloro in cura antipertensiva. Risultati I risultati si riferiscono a 1104 lavoratori, di cui 76% uomini e 24% donne. La prevalenza di ipertensione si è dimostrata più elevata nei maschi (33% Vs 22%). Le stime del rischio hanno evidenziato una associazione statisticamente significativa con alcuni fattori lavorativi come mantenere posture difficili (O.R. 1.71), lavorare in presenza di calore (O.R. 1.43), a contatto con agenti chimici (O.R, 1.31). stare a lungo seduti (O.R. 1.48), fare più cose contemporaneamente (O.R. 1.41), essere interrotti nel proprio lavoro (O.R. 1,35). non poter distogilere gli occhi dal lavoro (O.R.1.61). Conclusioni Noi abbiamo osservato che alcune caratteristiche fisiche del lavoro, ma soprattutto quelle di tipo organizzativo sono fortemente associate all’ipertensione arteriosa. Un elemento importante è sembrata la valutazione soggettiva del valore che i lavoratori danno del proprio lavoro: tale elemento è fortemente connesso con I’organizzazione del lavoro, pertanto è un possibile target di prevenzione (fattore di rischio modificabile). PMID:17886759
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[Atmospheric non-methane hydrocarbons near plants of crude oil first treatment].
Bustaffa, Elisa; De Marinis Loiotile, Annamaria; Farella, Genoveffa; Petraccone, Stefania; De Gennaro, Gianluigi; Bianchi, Fabrizio
2016-01-01
La continua espansione delle attività di perforazione ai fini dell'estrazione petrolifera in prossimità di aree abitate ha fatto sì che negli ultimi anni l'attenzione si focalizzasse sull'impatto di questo processo fortemente industrializzato sulla salute pubblica. Le comunità che vivono nei dintorni di impianti di questo tipo devono, infatti, fronteggiare diversi problemi, quali l'inquinamento atmosferico e acustico, la contaminazione del suolo e delle acque sotterranee, il traffico dei camion da e verso il sito, incidenti e malfunzionamenti all'interno dell'impianto. In questo contesto, la valutazione del rischio per la salute è ostacolata dal fatto che l'esposizione alle sostanze chimiche presenti non può essere valutata in via definitiva, poiché non sempre si è a conoscenza di tutti i composti immessi nell'ambiente né delle loro concentrazioni, per non parlare del problema delle coesposizioni ad altri inquinanti. Nonostante l'oramai conclamato e vasto interesse generato da questo argomento, ad oggi esistono pochi studi basati su popolazioni riguardanti gli effetti sulla salute delle comunità che vivono in prossimità dei siti di perforazione ed estrazione; ciò genera la necessità di condurre campagne di monitoraggio mirate e studi epidemiologici che verifichino l'eventuale esistenza e natura di pattern di malattie associati a tali attività. La presente rassegna bibliografica individua, quindi, i principali inquinanti atmosferici presenti in prossimità di un impianto di primo trattamento del greggio e cerca di fornire un quadro generale delle loro potenziali sorgenti e caratteristiche.
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[Cyberstalking among Italian nurses: a large multicentric study].
Comparcini, Dania; Simonetti, Valentina; Lupo, Roberto; Galli, Francesco; Bocij, Paul; Cicolini, Giancarlo
2016-01-01
Determinare la prevalenza di cyberstalking tra gli infermieri italiani e valutare il livello di ansia e depressione nelle vittime. Da aprile a settembre 2014 è stato condotto uno studio multicentrico trasversale in un campione di infermieri italiani (n=997) utilizzando il questionario "Cyberstalking" per analizzare il fenomeno del cyberstalking. Ai partecipanti, che si sono autodefinite vittime di cyberstalking, è stato chiesto anche di compilare gli strumenti "Beck Depression Inventory" e "State-Trait Anxiety Inventory" per valutare, rispettivamente, i livelli di depressione ed ansia. La prevalenza di cyberstalking tra gli infermieri italiani è risultata pari al 23.3%. Il 42.7% ha dovuto cambiare il proprio stile di vita e lavorativo. Il cyberstalker era prevalentemente di sesso maschile (52%) e, nel 49% dei casi, era un paziente. Le vittime hanno riferito moderati livelli di ansia (media=28.4, SD=23.2) e depressione (media=92.7, SD=18.3); i risultati hanno mostrato un aumento dei livelli di depressione negli infermieri esperti nell'utilizzo del computer, gestori di siti web o blog, e una correlazione negativa tra il livello di ansia e gli infermieri esperti (r = -0.264). Il cyberstalking è un fenomeno che si riscontra frequentemente tra gli infermieri. Il rapporto infermiere - paziente gioca un ruolo centrale nello sviluppo del fenomeno e le vittime hanno riferito disordini correlati allo stress che influenzano la vita lavorativa. Questi risultati preliminari potrebbero sensibilizzare, i dirigenti ospedalieri, la politica e i centri antiviolenza al fine di sviluppare strategie risolutiv.
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Theory and simulation of electron beam dynamics in the AWE superswarf magnetically immersed diode
DOE Office of Scientific and Technical Information (OSTI.GOV)
Oliver, B.V.; Welch, D.R.; Olson, C.L.
1999-07-01
Results from numerical simulation and analytic theory of magnetically immersed diode behavior on the United Kingdom's Atomic Weapons Establishment (AWE) Superswarf accelerator are presented. The immersed diode consists of a cylindrical needle point cathode immersed in a strong {approximately}10--20 T solenoidal magnetic field. The anode-cathode (A-K) accelerating gap is held at vacuum and is {approximately}5--10 cm in length, with the anode/target located at the mid-plane of the solenoid. Typical accelerator parameters are 5--6 MeV and 40 kA. Ions emitted from the anode target stream toward the cathode and interact strongly with the electron beam. Collective oscillations between the beam electronsmore » and counter-streaming ions are driven unstable and results in a corkscrew rotation of the beam, yielding a time-integrated spot size substantially larger than that expected from single particle motion. This magnetized ion-hose instability is three dimensional. On the other hand, beam transverse temperature variations, although slightly enhanced in 3D, are primarily due to changes in the effective potential at the cathode (a combination of both the electrostatic and vector potential) and are manifest in 2D. Simulation studies examining spot and dose variation with varying cathode diameter and A-K gap distance are presented and confirm the above mentioned trends. Conclusions are that the diode current is determined by standard di-polar space-charge limited emissions, the minimum beam spot-size is limited by the ion-hose instability saturation amplitude, and the beam transverse temperature at the target is a function of the initial conditions on the cathode. Comparison to existing data will also be presented.« less
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1988-01-01
TASK AREA & WORK UNIT NUMBERS Dipartimento di Matematica -G.--iattelnuoz .’ Universita di Roma "La Sapienze" rlnlRr% Pnmaq (Tt-al’g) I$. CONTROLLING...guaranteed. 3. Adminisrtrative actions The following investigators are working on the contract: (i) Francesco Zirilli Dipartimento di Matematica "G...Castelnuovo" Universiti di Roma "La Sapienza" 00185 Romna (Italy) (ii) Filippo Aluffi-Pentini Dipartimento di Matematica Universiti di Barn 80125 Bari (Italy
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Morishita, Yuki; Nomura, Yusuke; Fukui, Chie; Fujisawa, Ayano; Watanabe, Kayo; Fujimaki, Hideo; Kumada, Hidefumi; Inoue, Kaoru; Morikawa, Tomomi; Takahashi, Miwa; Kawakami, Tsuyoshi; Sakoda, Hideyuki; Mukai, Tomokazu; Yuba, Toshiyasu; Inamura, Ken-Ichi; Tanoue, Akito; Miyazaki, Ken-Ichi; Chung, Ung-Il; Ogawa, Kumiko; Yoshida, Midori; Haishima, Yuji
2018-04-01
Di (2-ethylhexyl) phthalate (DEHP), a typical plasticizer used for polyvinyl chloride (PVC), is eluted from PVC-made blood containers and protects against red blood cell (RBC) hemolysis. However, concerns have arisen regarding the reproductive and developmental risks of DEHP in humans, and the use of alternative plasticizers for medical devices has been recommended worldwide. In this study, we propose that the use of a novel plasticizer, 4-cyclohexene-1,2-dicarboxylic acid dinonyl ester (DL9TH), could help produce more useful and safe blood containers. PVC sheet containing DL9TH and di (2-ethylhexyl) 4-cyclohexene-1,2-dicarboxylate (DOTH) provides comparable or superior protective effects to RBCs relative to PVC sheet containing DEHP or di-isononyl-cyclohexane-1,2-dicarboxylate (DINCH ® , an alternative plasticizer that has been used in PVC sheets for blood containers). The total amount of plasticizer eluted from DOTH/DL9TH-PVC sheets is nearly the same as that eluted from DEHP-PVC sheets. In addition, DOTH/DL9TH-PVC has better cold resistance than DEHP- and DINCH ® -PVC sheets. In vitro and in vivo tests for biological safety based on International Organization for Standardization guidelines (10993 series) suggest that the DOTH/DL9TH-PVC sheet can be used safely. Subchronic toxicity testing of DL9TH in male rats in accordance with the principles of Organisation for Economic Co-operation and Development Test Guideline 408 showed that DL9TH did not induce adverse effects up to the highest dose level tested (717 mg/kg body weight/day). There were no effects on testicular histopathology and sperm counts, and no indications of endocrine effects: testosterone, thyroid-stimulating hormone, follicle-stimulating hormone, and 17β-estradiol were unchanged by the treatment, compared with the control group. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1052-1063, 2018. © 2017 Wiley Periodicals, Inc.
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Analysis of 22q11.2 deletions by FISH in a series of velocardiofacial syndrome patients
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ravnan, J.B.; Golabi, M.; Lebo, R.V.
Deletions in chromosome 22 band q11.2 have been associated with velocardiofacial (VCF or Shprintzen) syndrome and the DiGeorge anomaly. A study of VCF patients evaluated at the UCSF Medical Center was undertaken to correlate disease phenotype with presence or absence of a deletion. Patients referred for this study had at least two of the following: dysmorphic facial features, frequent ear infections or hearing loss, palate abnormalities, thymic hypoplasia, hypocalcemia, congenital heart defect, hypotonia, and growth or language delay. Fluorescence in situ hybridization (FISH) using the DiGeorge critical region probe N25 was used to classify patients according to the presence ormore » absence of a deletion in 22q11.2, and the results were compared to clinical characteristics. We have completed studies on 58 patients with features of VCF. Twenty-one patients (36%) were found to have a deletion in 22q11.2 by FISH. A retrospective study of archived slides from 14 patients originally studied only by prometaphase GTG banding found six patients had a deletion detected by FISH; of these, only two had a microscopically visible chromosome deletion. Our study of 11 sets of parents of children with the deletion found two clinically affected mothers with the deletion, including one with three of three children clinically affected. A few patients who did not fit the classical VCF description had a 22q11.2 deletion detected by FISH. These included one patient with both cleft lip and palate, and another with developmental delay and typical facial features but no cardiac or palate abnormalities. Both patients with the DiGeorge anomaly as part of VCF had the deletion. On the other hand, a number of patients diagnosed clinically with classical VCF did not have a detectable deletion. This raises the question whether they represent a subset of patients with a defect of 22q11.2 not detected by the N25 probe, or whether they represent a phenocopy of VCF.« less
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Diversity of Cyclic Di-GMP-Binding Proteins and Mechanisms
2015-01-01
ABSTRACT Cyclic di-GMP (c-di-GMP) synthetases and hydrolases (GGDEF, EAL, and HD-GYP domains) can be readily identified in bacterial genome sequences by using standard bioinformatic tools. In contrast, identification of c-di-GMP receptors remains a difficult task, and the current list of experimentally characterized c-di-GMP-binding proteins is likely incomplete. Several classes of c-di-GMP-binding proteins have been structurally characterized; for some others, the binding sites have been identified; and for several potential c-di-GMP receptors, the binding sites remain to be determined. We present here a comparative structural analysis of c-di-GMP-protein complexes that aims to discern the common themes in the binding mechanisms that allow c-di-GMP receptors to bind it with (sub)micromolar affinities despite the 1,000-fold excess of GTP. The available structures show that most receptors use their Arg and Asp/Glu residues to bind c-di-GMP monomers, dimers, or tetramers with stacked guanine bases. The only exception is the EAL domains that bind c-di-GMP monomers in an extended conformation. We show that in c-di-GMP-binding signature motifs, Arg residues bind to the O-6 and N-7 atoms at the Hoogsteen edge of the guanine base, while Asp/Glu residues bind the N-1 and N-2 atoms at its Watson-Crick edge. In addition, Arg residues participate in stacking interactions with the guanine bases of c-di-GMP and the aromatic rings of Tyr and Phe residues. This may account for the presence of Arg residues in the active sites of every receptor protein that binds stacked c-di-GMP. We also discuss the implications of these structural data for the improved understanding of the c-di-GMP signaling mechanisms. PMID:26055114
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Montinari, Maria Rosa; Gianicolo, Emilio Antonio Luca; Vigotti, Maria Angela
2016-01-01
OBIETTIVI: valutare l'andamento temporale della mortalità per patologie respiratorie nelle province pugliesi utilizzando dati omogenei per fonte e metodologia di calcolo. DISEGNO: analisi ecologica storica degli andamenti temporali di mortalità per tumori e patologie dell'apparato respiratorio nelle province pugliesi, in Puglia e nelle ripartizioni geografiche italiane dal 1933 al 2010. SETTING E PARTECIPANTI: i dati di mortalità e le popolazioni residenti sono di fonte Istat. Sono state esaminate tutte le cause di decesso, il tumore della laringe, il tumore del polmone, l'insieme dei tumori respiratori, la bronchite, la polmonite e la broncopolmonite considerate congiuntamente, e l'insieme delle patologie respiratorie. Le analisi sono disaggregate per sesso dal 1969. PRINCIPALI MISURE DI OUTCOME: rapporti standardizzati di mortalità (SMR%) in riferimento all'Italia, con intervalli di confidenza al 95%, e tassi di mortalità standardizzati col metodo diretto (TSD ) in riferimento alla popolazione standard europea. RISULTATI: dal 1933 al 2010, i TSD per tumori respiratori e per bronchiti diminuiscono in tutte le aree analizzate. Tuttavia, nelle province di Taranto, Brindisi e Lecce, l'SMR% per tumori respiratori, inferiore al riferimento nazionale fino agli anni Sessanta, si allinea (a Brindisi) e supera (a Lecce e Taranto) il riferimento negli anni successivi. Nelle province di Foggia e Bari il numero dei decessi per tumore del polmone è costantemente inferiore all'atteso. CONCLUSIONI: la ricostruzione storica e l'analisi dei trend temporali di mortalità dal 1933 al 2010 mostrano alcune criticità sanitarie in periodi specifici. L'elaborazione dei dati di mortalità per un arco temporale di circa 80 anni ha messo in evidenza la maggiore rilevanza di queste criticità con l'avvio dello sviluppo industriale.
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Structural Basis of Ligand Binding by a C-di-GMP Riboswitch
DOE Office of Scientific and Technical Information (OSTI.GOV)
Smith, K.; Lipchock, S; Ames, T
2009-01-01
The second messenger signaling molecule bis-(3{prime}-5{prime})-cyclic dimeric guanosine monophosphate (c-di-GMP) regulates many processes in bacteria, including motility, pathogenesis and biofilm formation. c-di-GMP-binding riboswitches are important downstream targets in this signaling pathway. Here we report the crystal structure, at 2.7 {angstrom} resolution, of a c-di-GMP riboswitch aptamer from Vibrio cholerae bound to c-di-GMP, showing that the ligand binds within a three-helix junction that involves base-pairing and extensive base-stacking. The symmetric c-di-GMP is recognized asymmetrically with respect to both the bases and the backbone. A mutant aptamer was engineered that preferentially binds the candidate signaling molecule c-di-AMP over c-di-GMP. Kinetic and structuralmore » data suggest that genetic regulation by the c-di-GMP riboswitch is kinetically controlled and that gene expression is modulated through the stabilization of a previously unidentified P1 helix, illustrating a direct mechanism for c-di-GMP signaling.« less
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Mannino, Gherardo; Guerini, Rossella
2018-01-01
RIASSUNTO. Al fine di comprendere meglio la psicopatologia del disturbo ossessivo-compulsivo (DOC), in anni recenti è stata prestata una crescente attenzione alla cosiddetta "paura di sé" (fear of self), vale a dire la paura che le persone con DOC nutrono di ospitare dentro di sé aspetti inaccettabili. Tuttavia, l'esatta dinamica di questo fenomeno ancora non è chiara: di conseguenza, allo scopo di delucidarla meglio, sarà qui descritto uno specifico processo psicologico denominato Identificazione Retrospettiva delle Motivazioni e delle Inclinazioni (IRMI). Quando un paziente con DOC valuta in qualche modo come inaccettabile una propria esperienza interna (pensieri, emozioni, immagini mentali, ecc.) o un proprio comportamento, identificherà retrospettivamente le presunte motivazioni/inclinazioni negative che sarebbero state all'origine di quell'esperienza o comportamento. L'IRMI non solo aiuta a comprendere meglio il fenomeno della "paura di sé", ma possiede anche importanti implicazioni per la terapia.
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1998-01-01
Parabolic Boundary Control Problem ARIELA BRIANI AND MAURIZIO FALCONE Dipartimento di Matematica Universitä di Pisa Dipartimento di Matematica ...Ministry for University and Scientific Research (MURST Project "Analisi Numerica e Matematica Computazionale"). 50 A Priori Estimates for the...Briani Dipartimento di Matematica Universitä di Pisa Via Buonarroti 2 1-56126 Pisa e-mail:briani@dm.unipi.it Maurizio Falcone Dipartimento di
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X-ray Observations of the Sun: Solar Flares and their Impact on the Geophysical Space
2012-07-01
Michele Piana Universita’ di Genova Dipartimento Di Matematica Via Dodecaneso 35 Genova, Italy 16146 EOARD Grant 09-3050 Report...ORGANIZATION NAME(S) AND ADDRESS(ES) Universita’ di Genova Dipartimento Di Matematica Via Dodecaneso 35 Genova, Italy 16146 8. PERFORMING...Piana, DIpartimento di Matematica , Universita’ di Genova Scientific Report The aim of the present project was to apply computational tools based on
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Steiner, Samuel; Lori, Christian; Boehm, Alex; Jenal, Urs
2013-01-01
In many bacterial pathogens, the second messenger c-di-GMP stimulates the production of an exopolysaccharide (EPS) matrix to shield bacteria from assaults of the immune system. How c-di-GMP induces EPS biogenesis is largely unknown. Here, we show that c-di-GMP allosterically activates the synthesis of poly-β-1,6-N-acetylglucosamine (poly-GlcNAc), a major extracellular matrix component of Escherichia coli biofilms. C-di-GMP binds directly to both PgaC and PgaD, the two inner membrane components of the poly-GlcNAc synthesis machinery to stimulate their glycosyltransferase activity. We demonstrate that the PgaCD machinery is a novel type c-di-GMP receptor, where ligand binding to two proteins stabilizes their interaction and promotes enzyme activity. This is the first example of a c-di-GMP-mediated process that relies on protein–protein interaction. At low c-di-GMP concentrations, PgaD fails to interact with PgaC and is rapidly degraded. Thus, when cells experience a c-di-GMP trough, PgaD turnover facilitates the irreversible inactivation of the Pga machinery, thereby temporarily uncoupling it from c-di-GMP signalling. These data uncover a mechanism of c-di-GMP-mediated EPS control and provide a frame for c-di-GMP signalling specificity in pathogenic bacteria. PMID:23202856
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Dubas, Judith Semon; Baams, Laura; Doornwaard, Suzan M; van Aken, Marcel A G
2017-10-01
Research on how dark personality traits develop and relate to risky behaviors and family relations during adolescence is scarce. This study used a person-oriented approach to examine (a) whether distinct groups of adolescents could be identified based on their developmental profiles of callous-unemotional (CU), grandiose manipulative (GM), and dysfunctional impulsivity (DI) traits and (b) whether these groups differ in their problem behaviors and parent-adolescent relationship quality. Latent class growth analyses on 4-wave data of 1,131 Dutch adolescents revealed 3 personality profiles: (1) a dark impulsive group (13.9%), with high scores on all 3 traits (CU, GM, and DI) that were stable over time; (2) an impulsive group (26.1%), with high and increasing levels of impulsivity and relatively low scores on CU and GM; and (3) and a low risk group (60.0%), with relatively low levels on all 3 personality characteristics, with impulsivity decreasing over time. Compared with adolescents in the low risk group, adolescents in the dark impulsive and impulsive groups reported higher initial levels of substance use, sexual risk behaviors, permissive sexual attitudes, parent-adolescent conflict, and lower parent-adolescent satisfaction, as well as greater increases in sexual risk behavior over time. Compared with adolescents in the impulsive group, those in the dark impulsive group showed the highest levels of risk behaviors. Hence, dark personality traits coupled with impulsivity may be indicative of an earlier and more severe trajectory of problem behaviors that may differ from the trajectory of youth who are only impulsive. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
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McDonald-McGinn, Donna M.; Sullivan, Kathleen E.; Marino, Bruno; Philip, Nicole; Swillen, Ann; Vorstman, Jacob A. S.; Zackai, Elaine H.; Emanuel, Beverly S.; Vermeesch, Joris R.; Morrow, Bernice E.; Scambler, Peter J.; Bassett, Anne S.
2016-01-01
22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder, estimated to result mainly from de novo non-homologous meiotic recombination events occurring in approximately 1 in every 1,000 fetuses. The first description in the English language of the constellation of findings now known to be due to this chromosomal difference was made in the 1960s in children with DiGeorge syndrome, who presented with the clinical triad of immunodeficiency, hypoparathyroidism and congenital heart disease. The syndrome is now known to have a heterogeneous presentation that includes multiple additional congenital anomalies and later-onset conditions, such as palatal, gastrointestinal and renal abnormalities, autoimmune disease, variable cognitive delays, behavioural phenotypes and psychiatric illness — all far extending the original description of DiGeorge syndrome. Management requires a multidisciplinary approach involving paediatrics, general medicine, surgery, psychiatry, psychology, interventional therapies (physical, occupational, speech, language and behavioural) and genetic counselling. Although common, lack of recognition of the condition and/or lack of familiarity with genetic testing methods, together with the wide variability of clinical presentation, delays diagnosis. Early diagnosis, preferably prenatally or neonatally, could improve outcomes, thus stressing the importance of universal screening. Equally important, 22q11.2DS has become a model for understanding rare and frequent congenital anomalies, medical conditions, psychiatric and developmental disorders, and may provide a platform to better understand these disorders while affording opportunities for translational strategies across the lifespan for both patients with 22q11.2DS and those with these associated features in the general population. PMID:27189754
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Pizzuti, A.; Ratti, A.; Penso, D.
DiGeorge syndrome (DGS) is a developmental defect of some of the neural crest derivatives. Most DGS patients show haploinsufficiency due to interstitial deletions of the proximal long arm of chromosome 22. Deletions of 22q11 have also been reported in patients with the velo-cardio-facial syndrome and familial conotruncal heart defects. It has been suggested that the wide phenotype spectrum associated with 22q11 monosomy is a consequence of contiguous-gene deletions. We report the isolation of human cDNAs homologous to the Drosophila dishevelled (dsh) segment-polarity gene. Sequences homologous to the 3{prime} UTR of these transcripts (DVL-22) were positioned within the DGS critical regionmore » and were found to be deleted in DGS patients. Human DVL mRNAs are expressed in several fetal and adult tissues, including the thymus and, at high levels, the heart. Two transcripts, 3.2 and 5 kb, were detected, in Northern blot analysis, with different expression patterns in the surveyed tissues when different cDNAs were used. The isolated cDNAs exhibit high amino acid homology with the mouse and Xenopus Dvl-1 gene, the only other vertebrate dsh homologues so far isolated. The pivotal role of dsh in fly development suggests an analogous key function in vertebrate embryogenesis of its homologue genes. Since DGS may be due to perturbation of differentiation mechanisms at decisive embryological stages, a Dsh-like gene in the small-region overlap (SRO) might be a candidate for the pathogenesis of this disorder. 52 refs., 3 figs.« less
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NASA Astrophysics Data System (ADS)
Sciarra, Marco; Carabba, Luigi; Urbano, Tullio; Calista, Monia
2016-04-01
This work illustrates the studies carried out on a complex landslide phenomenon between the Sangro and Osento River's mouths, near Torino di Sangro village in Southern Abruzzo Region (Italy). Historical activity of this landslide is well-documented since 1916; the activation/reactivation of the movements caused several interruptions of a national railway and the damage of few houses. The Torino di Sangro case study can be regarded as representative of many large landslides distributed along the central Adriatic coast (e.g., Ancona, Ortona, Vasto and Petacciato Landslides) that affect densely populated urban areas with a large amount of man-made infrastructure. The main controlling factors of these large and deep-seated landslides are still debated. From the geological and geomorphological viewpoint, the central Adriatic coast is characterized by a low-relief landscape (mesa) carved on clay-sandstone-conglomerate bedrock belonging to the Upper Pliocene - Lower Pleistocene marine deposits and locally to the Middle Pleistocene marine to continental transitional deposits. This high coast is widely affected by slope instability (rock falls, rotational, complex and shallow landslides) on both active and inactive sea cliffs, the first being mainly affected by wave-cut erosion and the latter influenced by heavy rainfall and changes of pore pressure. The main landslide has the typical characteristics of a deep-seated gravitation deformation. The landslide study was based on a multidisciplinary approach including: 1) definition and GIS mapping of geology and geomorphology factors (slope, aspect, topographic curvature, bedrock lithology, near-surface deposits, deposit thickness and land use), by means of DTM processing, multi-temporal analysis, and large-scale geomorphological field survey; 2) monitoring system in the landslide; 3) application of empiric models for the analysis of unstable sandstone-conglomerate escarpments; 4) slope stability analysis performed using a stress-strain numerical modeling solved by a Finite Difference Method (FLAC 2D). This study suggests that rock falls and shallow landslide are hazardous phenomenal that involve the near-surface cover of a bigger and more complex landslide. The distinction between secondary processes, which appear to be the most hazardous in the short-term, and deep-seated one, demonstrated that accurate multi-approach analysis provide important information that can be supportive for local administration and decision makers, and for the comprehension of the factors controlling large and deep-seated landslide affecting the Adriatic coastal slopes.
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Kalo, Dorit; Hadas, Ron; Furman, Ori; Ben-Ari, Julius; Maor, Yehoshua; Patterson, Donald G.; Tomey, Cynthia; Roth, Zvi
2015-01-01
We examined acute exposure of Holstein cows to di(2-ethylhexyl) phthalate (DEHP) and its carryover effects on ovarian function and oocyte developmental competence. Synchronized cows were tube-fed with water or 100 mg/kg DEHP per day for 3 days. Blood, urine and milk samples were collected before, during and after DEHP exposure to examine its clearance pattern. Ovarian follicular dynamics was monitored through an entire estrous cycle by ultrasonographic scanning. Follicular fluids were aspirated from the preovulatory follicles on days 0 and 29 of the experiment and analyzed for phthalate metabolites and estradiol concentration. The aspirated follicular fluid was used as maturation medium for in-vitro embryo production. Findings revealed that DEHP impairs the pattern of follicular development, with a prominent effect on dominant follicles. The diameter and growth rate of the first- and second-wave dominant follicles were lower (P < 0.05) in the DEHP-treated group. Estradiol concentration in the follicular fluid was lower in the DEHP-treated group than in controls, and associated with a higher number of follicular pathologies (follicle diameter >25 mm). The pattern of growth and regression of the corpus luteum differed between groups, with a lower volume in the DEHP-treated group (P < 0.05). The follicular fluid aspirated from the DEHP-treated group, but not the controls, contained 23 nM mono(2-ethylhexyl) phthalate. Culturing of cumulus oocyte complexes in the follicular fluid aspirated from DEHP-treated cows reduced the proportion of oocytes progressing to the MII stage, and the proportions of 2- to 4-cell-stage embryos (P < 0.04) and 7-day blastocysts (P < 0.06). The results describe the risk associated with acute exposure to DEHP and its deleterious carryover effects on ovarian function, nuclear maturation and oocyte developmental competence. PMID:26154164
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Neonatal intensive care unit phthalate exposure and preterm infant neurobehavioral performance.
Stroustrup, Annemarie; Bragg, Jennifer B; Andra, Syam S; Curtin, Paul C; Spear, Emily A; Sison, Denise B; Just, Allan C; Arora, Manish; Gennings, Chris
2018-01-01
Every year in the United States, more than 300,000 infants are admitted to neonatal intensive care units (NICU) where they are exposed to a chemical-intensive hospital environment during a developmentally vulnerable period. The neurodevelopmental impact of environmental exposure to phthalates during the NICU stay is unknown. As phthalate exposure during the third trimester developmental window has been implicated in neurobehavioral deficits in term-born children that are strikingly similar to a phenotype of neurobehavioral morbidity common among children born premature, the role of early-life phthalate exposure on the neurodevelopmental trajectory of premature infants may be clinically important. In this study, premature newborns with birth weight <1500g were recruited to participate in a prospective environmental health cohort study, NICU-HEALTH (Hospital Exposures and Long-Term Health), part of the DINE (Developmental Impact of NICU Exposures) cohort of the ECHO (Environmental influences on Child Health Outcomes) program. Seventy-six percent of eligible infants enrolled in the study. Sixty-four of 81 infants survived and are included in this analysis. 164 urine specimens were analyzed for phthalate metabolites using high-performance liquid chromatography/tandem mass spectrometry. The NICU Network Neurobehavioral Scale (NNNS) was performed prior to NICU discharge. Linear and weighted quantile sum regression quantified associations between phthalate biomarkers and NNNS performance, and between phthalate biomarkers and intensity of medical intervention. The sum of di(2-ethylhexyl) phthalate metabolites (∑DEHP) was associated with improved performance on the Attention and Regulation scales. Specific mixtures of phthalate biomarkers were also associated with improved NNNS performance. More intense medical intervention was associated with higher ∑DEHP exposure. NICU-based exposure to phthalates mixtures was associated with improved attention and social response. This suggests that the impact of phthalate exposure on neurodevelopment may follow a non-linear trajectory, perhaps accelerating the development of certain neural networks. The long-term neurodevelopmental impact of NICU-based phthalate exposure needs to be evaluated.
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Waveform Diversity and Design for Interoperating Radar Systems
2013-01-01
University Di Pisa Department Di Ingegneria Dell Informazione Elettronica, Informatica , Telecomunicazioni Via Girolamo Caruso 16 Pisa, Italy 56122...NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) University Di Pisa Department Di Ingegneria Dell Informazione Elettronica, Informatica ...DIPARTIMENTO DI INGEGNERIA DELL’INFORMAZIONE ELETTRONICA, INFORMATICA , TELECOMUNICAZIONI WAVEFORM DIVERSITY AND DESIGN FOR INTEROPERATING
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The Italian Army’s Role in Homeland Security
2003-04-07
Operazione “Vespri Siciliani”. Ciclo delle lezioni apprese (Civitavecchia: Scuola di Guerra, Maggio 1998) and Operazione “Forza Paris”. Ciclo delle lezioni...di un Esercito di qualita`.” Rivista Militare 6 (Novembre-Dicembre 2002): II. 61 Scuola di Guerra, Operazione “Vespri Siciliani”. Ciclo delle lezioni...A/2. 64 Scuola di Guerra, Operazione “Vespri Siciliani”. Ciclo delle lezioni apprese, C-13. 65 Scuola di Guerra, Operazione “Forza Paris”. Ciclo
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Mills-Koonce, W Roger; Willoughby, Michael T; Garrett-Peters, Patricia; Wagner, Nicholas; Vernon-Feagans, Lynne
2016-08-01
Child conduct problems (CP) reflect a heterogeneous collection of oppositional, aggressive, norm-violating, and sometimes violent behaviors, whereas child callous-unemotional (CU) behaviors reflect interpersonal styles of interactions reflecting a lack of guilt and empathy as well as uncaring and shallow emotional responses to others. Taken together, high levels of child CP and CU behaviors are thought to identify a relatively homogenous group of children at elevated risk for persistent and more severe problem behaviors across childhood and into adulthood. Although a large body of research has examined the developmental etiology of CP behaviors, only recently has a developmental psychopathology approach been applied to early CU behaviors. The current study examines multiple levels of contextual influences during the first years of life, including family socioeconomic status, household chaos, and parenting behaviors, on CP and CU behaviors assessed during the first-grade year. Whereas previous studies found associations between parenting behaviors and child problem behaviors moderated by household chaos, the current study found no evidence of moderation. However, path analyses suggest that the associations between child CP and CU behaviors and the contextual variables of socioeconomic status (family income and parental education) and household chaos (disorganization and instability) were mediated by maternal sensitive and harsh-intrusive parenting behavior. Analyses are presented, interpreted, and discussed with respect to both bioecological and family stress models of development.
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Schaeffer, Emily K; Study Group, Ihdi; Mulpuri, Kishore
2018-05-07
There is a lack of high quality evidence available to guide clinical practice in the treatment and management of developmental dysplasia of the hip (DDH). Evidence has been limited by persistent confusion on diagnostic and classification terminology, variability in surgeon decision making and a reliance on single centre, retrospective studies with small patient numbers. To address gaps in knowledge regarding screening, diagnosis and management of DDH, the International Hip Dysplasia Institute began a multicentre, international prospective study on infants with hips dislocated at rest. This review discusses the current state of screening, diagnostic and management practices in DDH and addresses important unanswered questions that will be critical in identifying best practices and optimising patient outcomes. There is insufficient evidence to support universal ultrasound screening; instead, selective screening should be performed by 6-8 weeks of age on infants with risk factors of breech presentation, family history, or history of clinical hip instability. Follow-up of infants with risk factors and normal initial screening should be considered to at least 6 months of age. Brace treatment is a sensible first-line treatment for management of dislocated hips at rest in infants < 6 months of age. Early operative reduction may be considered as there is insufficient evidence to support a protective role for the ossific nucleus in the development of avascular necrosis.
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Najdekrova, Lucie; Siroky, Jiri
2012-09-17
Telomeres, as elaborate nucleo-protein complexes, ensure chromosomal stability. When impaired, the ends of linear chromosomes can be recognised by cellular repair mechanisms as double-strand DNA breaks and can be healed by non-homologous-end-joining activities to produce dicentric chromosomes. During cell divisions, particularly during anaphase, dicentrics can break, thus producing naked chromosome tips susceptible to additional unwanted chromosome fusion. Many telomere-building protein complexes are associated with telomeres to ensure their proper capping function. It has been found however, that a number of repair complexes also contribute to telomere stability. We used Arabidopsis thaliana to study the possible functions of the DNA repair subunit, NBS1, in telomere homeostasis using knockout nbs1 mutants. The results showed that although NBS1-deficient plants were viable, lacked any sign of developmental aberration and produced fertile seeds through many generations upon self-fertilisation, plants also missing the functional telomerase (double mutants), rapidly, within three generations, displayed severe developmental defects. Cytogenetic inspection of cycling somatic cells revealed a very early onset of massive genome instability. Molecular methods used for examining the length of telomeres in double homozygous mutants detected much faster telomere shortening than in plants deficient in telomerase gene alone. Our findings suggest that NBS1 acts in concert with telomerase and plays a profound role in plant telomere renewal.
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Endocrine manifestations and management of Prader-Willi syndrome.
Emerick, Jill E; Vogt, Karen S
2013-08-21
Prader-Willi syndrome (PWS) is a complex genetic disorder, caused by lack of expression of genes on the paternally inherited chromosome 15q11.2-q13. In infancy it is characterized by hypotonia with poor suck resulting in failure to thrive. As the child ages, other manifestations such as developmental delay, cognitive disability, and behavior problems become evident. Hypothalamic dysfunction has been implicated in many manifestations of this syndrome including hyperphagia, temperature instability, high pain threshold, sleep disordered breathing, and multiple endocrine abnormalities. These include growth hormone deficiency, central adrenal insufficiency, hypogonadism, hypothyroidism, and complications of obesity such as type 2 diabetes mellitus. This review summarizes the recent literature investigating optimal screening and treatment of endocrine abnormalities associated with PWS, and provides an update on nutrition and food-related behavioral intervention. The standard of care regarding growth hormone therapy and surveillance for potential side effects, the potential for central adrenal insufficiency, evaluation for and treatment of hypogonadism in males and females, and the prevalence and screening recommendations for hypothyroidism and diabetes are covered in detail. PWS is a genetic syndrome in which early diagnosis and careful attention to detail regarding all the potential endocrine and behavioral manifestations can lead to a significant improvement in health and developmental outcomes. Thus, the important role of the provider caring for the child with PWS cannot be overstated.
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Biomedical applications of ferulic acid encapsulated electrospun nanofibers.
Vashisth, Priya; Kumar, Naresh; Sharma, Mohit; Pruthi, Vikas
2015-12-01
Ferulic acid is a ubiquitous phytochemical that holds enormous therapeutic potential but has not gained much consideration in biomedical sector due to its less bioavailability, poor aqueous solubility and physiochemical instability. In present investigation, the shortcomings associated with agro-waste derived ferulic acid were addressed by encapsulating it in electrospun nanofibrous matrix of poly (d,l-lactide-co-glycolide)/polyethylene oxide. Fluorescent microscopic analysis revealed that ferulic acid predominantly resides in the core of PLGA/PEO nanofibers. The average diameters of the PLGA/PEO and ferulic acid encapsulated PLGA/PEO nanofibers were recorded as 125 ± 65.5 nm and 150 ± 79.0 nm, respectively. The physiochemical properties of fabricated nanofibers are elucidated by IR, DSC and NMR studies. Free radical scavenging activity of fabricated nanofibers were estimated using di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium (DPPH) assay. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay confirmed the cytotoxicity of ferulic acid encapsulated nanofibers against hepatocellular carcinoma (HepG2) cells. These ferulic acid encapsulated nanofibers could be potentially explored for therapeutic usage in biomedical sector.
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The role of current sheet formation in driven plasmoid reconnection in laser-produced plasma bubbles
NASA Astrophysics Data System (ADS)
Lezhnin, Kirill; Fox, William; Bhattacharjee, Amitava
2017-10-01
We conduct a multiparametric study of driven magnetic reconnection relevant to recent experiments on colliding magnetized laser produced plasmas using the PIC code PSC. Varying the background plasma density, plasma resistivity, and plasma bubble geometry, the results demonstrate a variety of reconnection behavior and show the coupling between magnetic reconnection and global fluid evolution of the system. We consider both collision of two radially expanding bubbles where reconnection is driven through an X-point, and collision of two parallel fields where reconnection must be initiated by the tearing instability. Under various conditions, we observe transitions between fast, collisionless reconnection to a Sweet-Parker-like slow reconnection to complete stalling of the reconnection. By varying plasma resistivity, we observe the transition between fast and slow reconnection at Lundquist number S 103 . The transition from plasmoid reconnection to a single X-point reconnection also happens around S 103 . We find that the criterion δ /di < 1 is necessary for fast reconnection onset. Finally, at sufficiently high background density, magnetic reconnection can be suppressed, leading to bouncing motion of the magnetized plasma bubbles.
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Marcon, Alessandro; Vaona, Alberto; Rigon, Giulio; Carazzolo, Marco; Del Zotti, Franco; Girotto, Sandro; Marafetti, Claudio
2016-01-01
OBIETTIVI: descrivere, nella ASL 21 di Legnago (VR), l'andamento di alcuni indicatori sanitari tra il 2009, anno precedente all'avvio di un progetto triennale per la gestione integrata dell'assistenza al paziente con diabete mellito di tipo 2, e il 2012, ultimo anno del progetto. DISEGNO: studio longitudinale trasversale ripetuto. SETTING E PARTECIPANTI: tutti i pazienti diabetici di tipo 2 della ASL 21, identificati nei database aziendali (in base a esenzioni per patologia, accessi al servizio diabetologico, consumo di farmaci antidiabetici e strisce per la determinazione della glicemia) e nelle cartelle cliniche dei medici di famiglia. PRINCIPALI MISURE DI OUTCOME: numero di test diagnostici e di follow-up erogati, consumo di farmaci, prestazioni specialistiche, accessi al pronto soccorso, ricoveri e mortalità. RISULTATI: nonostante un calo generalizzato (-3,1%) nei test erogati dalla ASL 21 ai suoi assistititi nel periodo 2009-2012, l'analisi ha documentato un marcato aumento per gli esami previsti nella gestione del diabete, quali curve da carico glicemico (+104,3%), emoglobina glicata (+19,0%) e microalbuminuria (+296,1%). I soggetti identificati come diabetici sono aumentati da 8.084 nel 2009 (5,2%) a 9.221 nel 2012 (5,9%). Sono stati osservati aumenti nella prevalenza di pazienti visitati presso un servizio diabetologico (dal 22,6% al 39,0%), nonché negli utilizzatori di metformina (dal 28,0% al 37,5%), insuline (dal 13,5% al 18,3%) e incretine (dall'1,4% al 9,0%). Il consumo di sulfaniluree è, invece, calato (dal 49,9% al 40,8%), come anche l'erogazione di alcune prestazioni specialistiche, gli accessi al pronto soccorso e i ricoveri, mentre il tasso di mortalità è rimasto stabile (29,6 decessi x1.000/anno). CONCLUSIONE: durante il periodo di implementazione del progetto sembra essersi verificato un aumento della sensibilità diagnostica e una maggiore presa in carico del paziente diabetico. Anche se la natura osservazionale dello studio non consente di dimostrare una relazione causa-effetto, i risultati sembrano supportare l'ipotesi che la gestione integrata della patologia migliori l'appropriatezza dell'assistenza.
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Sviluppi di Ricevitori E di Componentistica Per Banda 3 mm Ad INAF-OA Cagliari
NASA Astrophysics Data System (ADS)
Navarrini, Alessandro
2017-11-01
L'INAF-OA Cagliari (OACa) sta sviluppando un ricevitore criogenico a basso rumore basato su un mixer SSB (Single Side Band) a superconduttore SIS (Superconductor-Insulator-Superconductor) per la banda 3 mm. Il ricevitore, acquistato da IRAM, è stato fortemente modificato per essere adattato al fuoco Gregoriano di SRT (Sardinia Radio Telescope). Lo strumento è caratterizzato da una nuova criogenia a ciclo chiuso 4 K (per evitare l'uso di elio liquido in antenna), da un nuovo oscillatore locale (di tipo ALMA Banda 3) e da un nuovo sistema di controllo e di monitoraggio basato su schede Raspberry ed Arduino sviluppato ad OACa. Verranno presentati i recenti sviluppi sul ricevitore, inclusi i risultati preliminari della misura della temperatura di rumore, che raggiunge un valore pari a Trec=66 K alla frequenza di 86 GHz, nonostante la criogenia non sia ancora ottimizzata. L'INAF-OACa è coinvolto nel progetto AETHRA (Advanced European Technologies for Heterodyne Receivers for Astronomy) nel quadro del programma Radionet/Horizon2020 per il quale sta contribuendo al WP1 (Work Package 1). Lo scopo del WP1 è di sviluppare e costruire un dimostratore di un array di ricevitori a doppia polarizzazione per la banda 3 mm basato su amplificatori criogenici a basso rumore (LNA) in tecnologia a semiconduttore MMIC. Nell'ambito del WP1 l'OACa ha in carico il progetto di un OrthomodeTransducer (OMT) in guida d'onda o in tecnologia planare per la banda 72-116 GHz che sia integrabile con amplificatori MMICs ed adatto all'integrazione in un array da installare nel piano focale di un radiotelescopio. Verranno presentati i design preliminari degli OMT per AETHRA, che sono basati su prototipi sviluppati in passato da OACa.
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Using relative rate methods, rate constants for the gas-phase reactions of OH radicals and Cl atoms with di-n-propyl ether, di-n-propyl ether-d14, di-n-butyl ether and di-n-butyl ether-d18 have been measured at 296 ? 2 K and atmos...
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Worldwide Report, Telecommunications Policy, Research and Development, No. 258
1983-01-28
3379, December 1979. [20] F. Vatalaro: Caratteristiche di un filtro digitale dpplicato al sistema DME di precisione per MLS, F.U.B., Relazione 43...Spring 1980. [8] F. Chiarini, M. Gori: Possibilitä di miglioramento della precisione di un DME in banda L öfferta da u’n sistema di antenne a...Vecchio, G. Pedrini, F. Vatalaro: Rapporto sul programma per la determinazione delta forma d’onda impulsiva ottima per un sistema DME di precisione in
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Pallavicini, Marco
1995-01-01
Oggetto di questa tesi e la misura di alcune caratteristiche fisiche (massa, larghezza, e larghezza parziale in p -more » $$\\bar{p}$$) degli stati 3P 1 e 3P 2 del charmonio, -ovvero del sistema legato di un quark "charm" e del suo antiquark-, nell'amito dell'esperimento E-760, installato nell'accumulatore di antiprotoni del Fermilab.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Paoletti, Riccardo
La produzione di eventi elastici è stata misurata al Collider Tevatron del Fermi National Accelerator Laboratory (Batavia. 11.~ U .S.A.) alla energia nel centro di massa. di √s = 1800 GeV, nell'intervallo 0.06 < I t I< 0.24. Sono forniti dettagli sull'esperimento CDF che ha compiuto la misura e sui criteri di selezione degli eventi.
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2012-01-05
Università degli Studi di Pavia bIstituto di Matematica Applicata e Tecnologie Informatiche “E. Magenes” del CNR, Pavia cDAEIMI, Università degli Studi di...Cassino d Institute for Computational Engineering and Sciences, University of Texas at Austin eDipartimento di Matematica , Università degli Studi di
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INFEZIONI VIRALI CONGENITE, PERINATALI E NEONATALI VIRAL INFECTIONS OF THE FETUS AND NEWBORN INFANT
Tremolada, Sara; Delbue, Serena; Ferrante, Pasquale
2009-01-01
Riassunto Alcuni virus possono essere trasmessi verticalmente da madre a figlio in seguito allo sviluppo, da parte della madre, di un’infezione primaria, ricorrente o cronica. La trasmissione materno-fetale dei virus, che può avvenire in utero (infezione congenita), durante il travaglio del parto (infezione perinatale), oppure attraverso l’allattamento (infezione postnatale), può causare aborto spontaneo, morte fetale, ritardo di crescita intrauterino, anomalie congenite e patologie neonatali o postnatali di diversa entità. Alcuni fattori di rischio sembrano influenzare l’incidenza di trasmissione materno-fetale dei virus, come ad esempio la presenza di altre infezioni virali, la carica virale materna, il tipo di infezione (primaria o ricorrente), la durata della rottura delle membrane, la modalità con cui avviene il parto, le condizioni socio-economiche e l’allattamento. Oggi è possibile prevenire la trasmissione materno-fetale di molti virus grazie all’utilizzo di vaccini, immunizzazione passiva e farmaci antivirali. Il rischio di trasmissione delle infezioni perinatali e postnatali, inoltre, può essere diminuito evitando l’allattamento o ricorrendo ad un parto cesareo. PMID:19216201
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Gonen, Limor D
2017-03-01
To measure the private and social benefits of donor insemination (DI). An empirical model investigates the general public and DI clients' willingness to pay (WTP) for DI, and the willingness of potential donors to become altruistic or paid sperm donors. The general public and DI clients value DI and have a positive WTP for it, whereas willingness to donate, altruistically or for payment, is either low or very low. The general public's and DI clients' WTP for DI is in average above actual cost, so the government should consider funding or subsidizing DI. The government should encourage altruistic gamete donation through information and education of all parties involved directly and indirectly in the process of donation whose ultimate goal is the birth of a child.
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Income poverty, poverty co-factors, and the adjustment of children in elementary school.
Ackerman, Brian P; Brown, Eleanor D
2006-01-01
Since 1990, there have been great advances in how developmental researchers construct poverty. These advances are important because they may help inform social policy at many levels and help frame how American culture constructs poverty for children, both symbolically and in the opportunities children and families get to escape from poverty. Historically, developmental perspectives have embodied social address and main effects models, snapshot views of poverty effects at single points in time, and a rather narrow focus on income as the symbolic marker of the ecology of disadvantage. More recent views, in contrast, emphasize the diverse circumstances of disadvantaged families and diverse outcomes of disadvantaged children, the multiple sources of risk and the multiple determinants of poor outcomes for these children, dynamic aspects of that ecology, and change as well as continuity in outcome trajectories. The advances also consist of more powerful frames for understanding the ecology of disadvantage and the risk it poses for child outcomes. Most developmental researchers still tend to frame causal variables ultimately in terms of the dichotomy between social causation and social selection views, with a primary emphasis on the former. In part, this framing has reflected limitations of sample size and design, because the theoretical and empirical power of reciprocal selection models is clear (Kim et al., 2003). The conceptual advances that prompt such models include widespread acknowledgement of third variable problems in interpreting effects, of the clear need for multivariate approaches, and the need to pursue mechanisms and moderators of the relations between causal candidates and child outcomes. In the context of these advances, one of the core goals of our research program has been to construct robust representations of environmental adversity for disadvantaged families. Most of our research focuses on contextual co-factors at a family level (e.g., maternal relationship instability), which either have not been described by many researchers or have been described in a way that does not fit the ecology of disadvantage (e.g., marital status). We found that income poverty, key contextual co-factors, and endogenous child attributes tend to show independent and selective associations with child academic competence and externalizing behavior, and that co-factor effects tend to be direct rather than mediated by harsh parenting, tend to have effects that are episodic and concurrent, and are easily- and well-represented by multiple risk indexes that bear powerful relations to child problem behaviors. A second core goal has been to better understand the developmental construction of poor outcomes for disadvantaged children, which requires consideration of dynamic aspects of the ecology and the potential importance of the timing of risk experiences. We found that family instability and change in environmental circumstances predict increases in problem behaviors, and that dose of adversity seems to matter for some variables if it is recent, and not for other variables. Through person-centered research, we also are beginning to understand some factors that seem to underlie the convergence of adjustment problems over grade in school. Many of our co-factor findings and many of our developmental findings seem both complex and double-edged. One edge is that they encourage a certain pessimism in showing how environmental adversity progressively constructs poor outcomes for disadvantaged children in school. Overall, for instance, we saw more problems and more multi-dimensional problems in fifth grade than in first grade, and the impact of environmental change was mostly negative. The other edge, however, is more positive in reflecting the possibility of discontinuity in child adjustment problems associated with positive changes in family circumstances. Findings for minimal persistence and for the strength of recent and concurrent effects argue that the possibility of self-righting and emergent competence in school is robust through the fifth grade even for the most problematic disadvantaged children.
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Preference and Frequency of Mobile Phone App Use for Drug Information Among Student Pharmacists
Park, Sharon K.; Purnell, Miriam C.; Freeman, Maisha Kelly; Reese, Racquel V.; Varga, Stefan
2017-01-01
Background: Health care professionals commonly use mobile devices to retrieve drug information (DI) in clinical practice. The preference and frequency of such use by student pharmacists are not well understood. Objective: To investigate the preference and frequency of mobile phone application (app) use for retrieving DI among student pharmacists. Methods: DI specialists from 3 pharmacy schools generated a 13-question survey relating to students’ preference and frequency of DI app use via their mobile phone. The survey was tested and electronically disseminated to all current P1 through P4 students from all 3 schools. Data were collected for student demographics, availability of mobile phone and DI apps, frequency of using DI apps, and whether DI apps were purchased. Data were analyzed descriptively and statistically. Results: About 74% (n = 221) of students reported using their mobile phone apps for retrieving DI. About 95% of the students used 1 to 3 apps for DI purposes and more than 85% used them a few times a week or more. About 17.6% of the students reported purchasing apps for the purpose of finding DI and that purchased apps are more accurate (27.6%), more comprehensive (36.2%), and more current (26.2%), compared with free apps. Conclusions: Student pharmacists used 1 to 3 mobile apps, at least a few times a week for DI. Some students purchased apps for DI use in addition to free subscriptions from their school. Students perceived purchased DI apps being more accurate, more comprehensive, and more up to date than the free apps.
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Afzal, Samina; Wherrett, Diane; Bartels, Ute; Tabori, Uri; Huang, Annie; Stephens, Derek; Bouffet, Eric
2010-05-01
Patients with intracranial germ cell tumor (IGCT) often present with pituitary dysfunction, including diabetes insipidus (DI). Recent protocols have used pre-radiation chemotherapy with combinations of etoposide, carboplatin and/or cisplatin, and ifosfamide. Management of DI in these patients requires monitoring of electrolytes and fluids during chemotherapy and hyperhydration. All consecutive patients treated with chemotherapy for an IGCT during the period 1990-2007 at the Hospital for Sick Children, Toronto were reviewed. Out of 32 patients who received chemotherapy, 21 had DI. Only cycles containing cisplatin and/or ifosfamide and hyperhydration were considered. DI and non-DI patients were compared for each cycle of chemotherapy. Patients were studied for number of days in hospital per chemotherapy course, daily fluid input and output, changes in dose, schedule and route of administration of desmopressin (DDAVP) during chemotherapy, daily variations in sodium level, electrolyte monitoring requirements per day, and complications related to fluid and electrolyte disturbances. Fifty-four cycles of chemotherapy in DI patients were compared to 25 cycles in non DI patients. All 21 patients with DI required daily change in dosage and schedule of DDAVP. Marked variations in daily sodium level were observed in the DI group. Seventeen courses required prolonged admission in the DI group (one in non DI patients) and 6 patients experienced serious complications. In conclusion, DI is a risk factor for complications when cisplatin and/or ifosfamide based protocols are used. The role of these agents in the management of ICGT should be carefully evaluated and guidelines for management of DI established.
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NASA Astrophysics Data System (ADS)
Filacchione, Gianrico
2006-10-01
Nel corso dell’ultimo decennio l’esplorazione planetaria ha potuto beneficiare dei dati prodotti dagli spettrometri ad immagine: grazie a questa nuova classe di strumenti, realizzati per l’osservazione in remoto di superfici ed atmosfere planetarie, è possibile acquisire dati iperspettrali con elevati poteri risolutivi spaziali e spettrali. Il principale vantaggio offerto dagli spettrometri ad immagine, rispetto alle camere ed agli spettrometri puntuali, è rappresentato dalla capacità di misurare, identificare e mappare le unità composizionali delle superfici planetarie; queste informazioni permettono di investigare sia l’evoluzione geochimica delle superfici sia la dinamica e la composizione delle atmosfere. Sebbene i primi spettrometri ad immagine siano stati francesi (Phobos/ISM, Imaging Spectrometer for Mars) e statunitensi (Galileo/NIMS, Near Infrared Mapping Spectrometer), il nostro paese nel corso degli ultimi anni è stato in grado di proporre alla com unità spaziale internazionale degli strumenti dalle elevate prestazioni che sono stati infatti accettati come payload scientifici su diverse missioni interplanetarie: dai canali visibili di VIMS (Visual and Infrared Mapping Spectrometer) su Cassini (Nasa, JPL, ESA, ASI) e di OMEGA (Observatoire pour la Minéralogie, l’Eau, les Glacies et l’Activitè de Mars) su MarsExpress (ESA) ai due VIRTIS (Visible and Infrared Thermal Imaging Spectrometer) su Rosetta (ESA) e VenusExpress (ESA) fino a VIR-MS (Visible and Infrared Mapping Spectrometer) su Dawn (Nasa). In questo momento inoltre altri due spettrometri sono in avanzata fase di studio: JIRAM (Jovian InfraRed Auroral Mapper) su Juno (missione New Discovery Nasa) e VIHI (Visible and Infrared Hyperspectral Imager) integrato nel payload italiano di remote sensing SIMBIO-SYS di BepiColombo (missione cornerstone ESA). La realizzazione di uno spettrometro ad immagini da utilizzare su una missione interplanetaria richiede un’accurata analisi in fase progettuale e realizzativa dei parametri e de lle prestazioni strumentali; in generale infatti non solo sarà necessario mantenere le dimensioni, il peso, i consumi elettrici ed il data-volume entro i requisiti disponibili del satellite ma anche ottimizzare i disegni ottici, meccanici ed elettronici al fine di ottenere le massime prestazioni possibili in funzione della natura del target osservato e dei parametri orbitali della missione. Questa tesi descrive i metodi utilizzati per caratterizzare il funzionamento di spettrometri ad immagine per l’esplorazione planetaria. L’attività svolta ha riguardato sia la misura in laboratorio dei parametri strumentali fondamentali sia l’analisi dei dati in volo su cui verificarne ed eventualmente correggerne la risposta. Il funzionamento degli strumenti e la metodologia di calibrazione vengono descritti nelle due parti principali e nelle appendici di questa tesi per gli esperimenti Cassini-VIMS-V e Rosetta-VIRTIS-M. La prima parte è dedicata all’esperimento VIMS-V sul satellite Cassini, il cui disegno ottico, originariamente proposto da Francis Reininger, verrà successivamente riutilizzato e perfezionato su VIRTIS-M (Reininger et al., 1994; Miller et al., 1996). Il capitolo 1 contiene una descrizione dei parametri ottici, strutturali, termici ed elettronici di VIMS-V mettendone in risalto gli aspetti più innovativi del progetto. Vengono inoltre descritti la collocazione dell’esperimento sul satellite Cassini, il coallineamento con gli altri strumenti di remote sensing, i possibili modi operativi ed il formato dei dati scientifici. Il capitolo 2 riguarda il processo di calibrazione ed analisi dei dati in volo di VIMS-V. La procedura eseguita per calibrare radiometricamente lo strumento utilizzando i dati della superficie della Luna e per stimare il flat-field mediante i dati dell’atmosfera di Venere viene dettagliatamente descritta assieme agli algoritmi utilizzati per la rimozione di diversi effetti strumentali (read-out noise e tilt spettrale); alcuni di questi effetti sono stati caratterizzati e dettagliamente misurati in laboratorio utilizzando il modello spare (flight) di VIMS-V. Parte del capitolo è dedicata alla verifica della procedura di calibrazione su diversi target aventi caratteristiche spettroradiometriche note. Questi algoritmi di processamento sono correntemente utilizzati dal team scientifico di VIMS per calibrare i dati del canale -VIS rilasciati ufficialmente alla comunità scientifica internazionale attraverso il Planetary Data System (PDS) della Nasa. La seconda parte riguarda l’esperimento VIRTIS-M sul satellite Rosetta. Il capitolo 3 contiene la descrizione dello strumento mettendo in risalto l’evoluzione dal precedente progetto VIMS-V ed i problemi tecnologici e costruttivi da questo derivanti. I diversi modi operativi, la sequenza di acquisizione e di processamento dei dati nell’elettronica principale sono ampiament e discussi. Viene inoltre evidenziata la collocazione dello spettrometro sul satellite Rosetta. Nel capitolo 4 viene descritta l’attività di calibrazione effettuata in Galileo Avionica (Campi Bisenzio, FI, Italia) ed allo IAS (Orsay, Francia) subito dopo l’integrazione di VIRTIS ed il conseguente processamento dei dati necessario per ricavare i principali parametri di funzionamento (calibrazioni spettrali e geometriche, flat-field, funzioni di trasferimento, lampade di calibrazione interne). Nel capitolo 5 l’accuratezza di queste grandezze è stata verificata su i primi dati in volo ottenuti da VIRTIS-M durante la fase di commissioning e di cruise del satellite (Terra, Luna e Saturno); queste osservazioni sono inoltre state utilizzate per migliorare e verificare alcuni aspetti della procedura di calibrazione che non erano stati sufficientemente definiti durante i test a terra. L’appendice A riguarda il formato PDS (Planetary Data System) utilizzato per l’archiviazione dei dati e degli housekeepings ingegnerisitici e scientifici delle osservazioni; nell’appendice B è contenuta la descrizione del modello radiometrico teorico di VIRTIS-M utilizzato per stimare il rapporto segnale/rumore; nelle appendici C e D sono infine contenute diverse Tabelle non incluse nel testo delle parti principali a causa della loro lunghezza.
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Identification of Synthetic Fluids Utilizing Pyrolysis Gas Liquid Chromatographic Techniques
1981-09-01
Base Stock No. 6327 Di-isodecyl Azelate II 7 Synthetic Base Stock No. 6318 Di-2-ethylhexyl Azelate I 8 Synthetic Base Stock No. 6323 l)i-2-ethylhexyl...Adipatc 13 9 Synthetic Base Stock No. 6321 Di-2-cthylhexyl Sebacattk 14 10 Synthetic Base Stock No. 6326 Di-tridecyl Azelate 15 11 Synthetic Base...Stock No. 6319 Di-tridecyl Adipate 16 12 Synthetic Base Stock No. 6320 Di-iso-octyl Azelate 17 13 Synthetic Base Stock No. 6516 TMP Triheptanoate 18 14
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Natural history of idiopathic diabetes insipidus.
Richards, Gail E; Thomsett, Michael J; Boston, Bruce A; DiMeglio, Linda A; Shulman, Dorothy I; Draznin, Martin
2011-10-01
To determine what percentage of diabetes insipidus (DI) in childhood is idiopathic and to assess the natural history of idiopathic DI. We conducted a retrospective chart review of 105 patients with DI who were born or had DI diagnosed between 1980-1989 at 3 medical centers. A second cohort of 30 patients from 6 medical centers in whom idiopathic DI was diagnosed after 1990 was evaluated retrospectively for subsequent etiologic diagnoses and additional hypothalamic/pituitary deficiencies and prospectively for quality of life. In the first cohort, 11% of patients had idiopathic DI. In the second cohort, additional hypothalamic/pituitary hormone deficiencies developed in 33%, and 37% received an etiologic diagnosis for DI. Health-related quality of life for all the patients with idiopathic DI was comparable with the healthy reference population. Only a small percentage of patients with DI will remain idiopathic after first examination. Other hormone deficiencies will develop later in one-third of those patients, and slightly more than one-third of those patients will have an etiology for the DI diagnosed. Long-term surveillance is important because tumors have been diagnosed as long as 21 years after the onset of DI. Quality of life for these patients is as good as the reference population. Copyright © 2011 Mosby, Inc. All rights reserved.
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Anticancer Molecular Mechanisms of Resveratrol
Varoni, Elena M.; Lo Faro, Alfredo Fabrizio; Sharifi-Rad, Javad; Iriti, Marcello
2016-01-01
Resveratrol is a pleiotropic phytochemical belonging to the stilbene family. Though it is only significantly present in grape products, a huge amount of preclinical studies investigated its anticancer properties in a plethora of cellular and animal models. Molecular mechanisms of resveratrol involved signaling pathways related to extracellular growth factors and receptor tyrosine kinases; formation of multiprotein complexes and cell metabolism; cell proliferation and genome instability; cytoplasmic tyrosine kinase signaling (cytokine, integrin, and developmental pathways); signal transduction by the transforming growth factor-β super-family; apoptosis and inflammation; and immune surveillance and hormone signaling. Resveratrol also showed a promising role to counteract multidrug resistance: in adjuvant therapy, associated with 5-fluoruracyl and cisplatin, resveratrol had additive and/or synergistic effects increasing the chemosensitization of cancer cells. Resveratrol, by acting on diverse mechanisms simultaneously, has been emphasized as a promising, multi-target, anticancer agent, relevant in both cancer prevention and treatment. PMID:27148534
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Children who murder: a review.
Shumaker, D M; Prinz, R J
2000-06-01
Despite considerable research on juvenile homicide, pre-adolescent homicide offenders have received less attention. This paper reviews the existing literature on preteen murderers in order to characterize the current state of research knowledge about this population, and draws on some of the work on adolescent homicide as well. The analysis of this literature considers historical context, methodological issues, previous attempts to classify youthful homicide offenders, and predictors of preteen homicidal behavior. While there is a high degree of heterogeneity within this population, several developmental similarities emerged across cases that were associated with the perpetration of homicide by preteens. A high percentage of preteen homicide offenders come from homes characterized by physical abuse, domestic violence, poor or absent parenting, and overall instability. Gun availability may have been a facilitating factor. Support for different etiologies of preteen versus adolescent homicide is weak. Recommendations for future research directions are offered.
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Anticancer Molecular Mechanisms of Resveratrol.
Varoni, Elena M; Lo Faro, Alfredo Fabrizio; Sharifi-Rad, Javad; Iriti, Marcello
2016-01-01
Resveratrol is a pleiotropic phytochemical belonging to the stilbene family. Though it is only significantly present in grape products, a huge amount of preclinical studies investigated its anticancer properties in a plethora of cellular and animal models. Molecular mechanisms of resveratrol involved signaling pathways related to extracellular growth factors and receptor tyrosine kinases; formation of multiprotein complexes and cell metabolism; cell proliferation and genome instability; cytoplasmic tyrosine kinase signaling (cytokine, integrin, and developmental pathways); signal transduction by the transforming growth factor-β super-family; apoptosis and inflammation; and immune surveillance and hormone signaling. Resveratrol also showed a promising role to counteract multidrug resistance: in adjuvant therapy, associated with 5-fluoruracyl and cisplatin, resveratrol had additive and/or synergistic effects increasing the chemosensitization of cancer cells. Resveratrol, by acting on diverse mechanisms simultaneously, has been emphasized as a promising, multi-target, anticancer agent, relevant in both cancer prevention and treatment.
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Biological monitoring of environmental quality: The use of developmental instability
Freeman, D.C.; Emlen, J.M.; Graham, J.H.; Hough, R. A.; Bannon, T.A.
1994-01-01
Distributed robustness is thought to influence the buffering of random phenotypic variation through the scale-free topology of gene regulatory, metabolic, and protein-protein interaction networks. If this hypothesis is true, then the phenotypic response to the perturbation of particular nodes in such a network should be proportional to the number of links those nodes make with neighboring nodes. This suggests a probability distribution approximating an inverse power-law of random phenotypic variation. Zero phenotypic variation, however, is impossible, because random molecular and cellular processes are essential to normal development. Consequently, a more realistic distribution should have a y-intercept close to zero in the lower tail, a mode greater than zero, and a long (fat) upper tail. The double Pareto-lognormal (DPLN) distribution is an ideal candidate distribution. It consists of a mixture of a lognormal body and upper and lower power-law tails.
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Oxidative Stress, Bone Marrow Failure, and Genome Instability in Hematopoietic Stem Cells
Richardson, Christine; Yan, Shan; Vestal, C. Greer
2015-01-01
Reactive oxygen species (ROS) can be generated by defective endogenous reduction of oxygen by cellular enzymes or in the mitochondrial respiratory pathway, as well as by exogenous exposure to UV or environmental damaging agents. Regulation of intracellular ROS levels is critical since increases above normal concentrations lead to oxidative stress and DNA damage. A growing body of evidence indicates that the inability to regulate high levels of ROS leading to alteration of cellular homeostasis or defective repair of ROS-induced damage lies at the root of diseases characterized by both neurodegeneration and bone marrow failure as well as cancer. That these diseases may be reflective of the dynamic ability of cells to respond to ROS through developmental stages and aging lies in the similarities between phenotypes at the cellular level. This review summarizes work linking the ability to regulate intracellular ROS to the hematopoietic stem cell phenotype, aging, and disease. PMID:25622253
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Wild brown trout affected by historical mining in the Cévennes National Park, France.
Monna, F; Camizuli, E; Revelli, P; Biville, C; Thomas, C; Losno, R; Scheifler, R; Bruguier, O; Baron, S; Chateau, C; Ploquin, A; Alibert, P
2011-08-15
In the protected area of the Cévennes National Park (Southern France), 114 wild brown trout (Salmo trutta fario) were captured at six locations affected to different extents by historical mining and metallurgy dating from the Iron Age to Modern Times. Cadmium and lead in trout livers and muscles reflect high sediment contamination, although an age-related effect was also detected for hepatic metal concentrations. Lead isotope signatures confirm exposure to drainage from mining and metallurgical waste. Developmental instability, assessed by fluctuating asymmetry, is significantly correlated with cadmium and lead concentrations in trout tissues, suggesting that local contamination may have affected fish development. Nowadays, the area is among the least industrialized in France. However, our results show that 60% of the specimens at one site exceed EU maximum allowed cadmium or lead concentration in foodstuffs. The mining heritage should not be neglected when establishing strategies for long-term environmental management.
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Parladé, Meaghan V.; Iverson, Jana M.
2012-01-01
From a dynamic systems perspective, transition points in development are times of increased instability, during which behavioral patterns are susceptible to temporary decoupling. This study investigated the impact of the vocabulary spurt on existing patterns of communicative coordination. Eighteen typically developing infants were videotaped at home 1 month before, at, and after the vocabulary spurt. Infants were identified as spurters if they underwent a discrete phase transition in vocabulary development (marked by an inflection point), and compared with a group of nonspurters whose word-learning rates followed a trajectory of continuous change. Relative to surrounding sessions, there were significant reductions in overall coordination of communicative behaviors and in words produced in coordination at the vocabulary spurt session for infants who experienced more dramatic vocabulary growth. In contrast, nonspurters demonstrated little change across sessions. Findings underscore the importance of transitions as opportunities for observing processes of developmental change. PMID:21219063
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Advanced Gas Turbine (AGT) powertrain system development for automotive applications
NASA Technical Reports Server (NTRS)
1984-01-01
Rotor dynamic instability investigations were conducted. Forward ball bearing hydraulic mount configurations were tested with little effect. Trial assembly of S/N 002 ceramic engine was initiated. Impeller design activities were completed on the straight line element (SLE) blade definition to address near-net-shape powder metal die forging. Performance characteristics of the Baseline Test 2A impeller were closely preserved. The modified blading design has been released for tooling procurement. Developmental testing of the diffusion flame combustor (DFC) for initial use in the S/N 002 2100 F ceramic structures engine was completed. A natural gas slave preheater was designed and fabricated. Preliminary regenerator static seal rig testing showed a significant reduction in leakage and sensitivity to stack height. Ceramic screening tests were completed and two complete sets of ceramic static structures were qualified for engine testing. Efforts on rotor dynamics development to resolve subsynchronous motion were continued.
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The Epidemiology and Demographics of Hip Dysplasia
Loder, Randall T.; Skopelja, Elaine N.
2011-01-01
The etiology of developmental dysplasia of the hip (DDH) is unknown. There are many insights, however, from epidemiologic/demographic information. A systematic medical literature review regarding DDH was performed. There is a predominance of left-sided (64.0%) and unilateral disease (63.4%). The incidence per 1000 live births ranges from 0.06 in Africans in Africa to 76.1 in Native Americans. There is significant variability in incidence within each racial group by geographic location. The incidence of clinical neonatal hip instability at birth ranges from 0.4 in Africans to 61.7 in Polish Caucasians. Predictors of DDH are breech presentation, positive family history, and gender (female). Children born premature, with low birth weights, or to multifetal pregnancies are somewhat protected from DDH. Certain HLA A, B, and D types demonstrate an increase in DDH. Chromosome 17q21 is strongly associated with DDH. Ligamentous laxity and abnormalities in collagen metabolism, estrogen metabolism, and pregnancy-associated pelvic instability are well-described associations with DDH. Many studies demonstrate an increase of DDH in the winter, both in the northern and southern hemispheres. Swaddling is strongly associated with DDH. Amniocentesis, premature labor, and massive radiation exposure may increase the risk of DDH. Associated conditions are congenital muscular torticollis and congenital foot deformities. The opposite hip is frequently abnormal when using rigorous radiographic assessments. The role of acetabular dysplasia and adult hip osteoarthritis is complex. Archeological studies demonstrate that the epidemiology of DDH may be changing. PMID:24977057
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The Role of NREM Sleep Instability in Child Cognitive Performance
Bruni, Oliviero; Kohler, Mark; Novelli, Luana; Kennedy, Declan; Lushington, Kurt; Martin, James; Ferri, Raffaele
2012-01-01
Study Objectives: Based on recent reports of the involvement of cyclic alternating pattern (CAP) in cognitive functioning in adults, we investigated the association between CAP parameters and cognitive performance in healthy children. Design: Polysomnographic assessment and standardized neurocognitive testing in healthy children. Settings: Sleep laboratory. Participants: Forty-two children aged 7.6 ± 2.7 years, with an even distribution of body mass percentile (58.5 ± 25.5) and SES reflective of national norms. Measurements: Analysis of sleep macrostructure following the R&K criteria and of cyclic alternating pattern (CAP). The neurocognitive tests were the Stanford Binet Intelligence Scale (5th edition) and a Neuropsychological Developmental Assessment (NEPSY) Results: Fluid reasoning ability was positively associated with CAP rate, particularly during SWS and with A1 total index and A1 index in SWS. Regression analysis, controlling for age and SES, showed that CAP rate in SWS and A1 index in SWS were significant predictors of nonverbal fluid reasoning, explaining 24% and 22% of the variance in test scores, respectively. Conclusion: This study shows that CAP analysis provides important insights on the role of EEG slow oscillations (CAP A1) in cognitive performance. Children with higher cognitive efficiency showed an increase of phase A1 in total sleep and in SWS Citation: Bruni O; Kohler M; Novelli L; Kennedy D; Lushington K; Martin J; Ferri R. The role of NREM sleep instability in child cognitive performance. SLEEP 2012;35(5):649-656. PMID:22547891
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2007-10-10
Dipartimento di Meccanica Strutturale, Università degli Studi di Pavia cDipartimento di Matematica , Università degli Studi di Pavia dEuropean Centre...for Training and Research in Earthquake Engineering, Pavia eIstituto di Matematica Applicata e Tecnologie Informatiche del CNR, Pavia “Comparisons
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Meningococco B: controllo di due focolai epidemici mediante vaccinazione
2014-01-01
Riassunto La problematica di un efficace approccio vaccinale nei confronti del Meningococco B (MenB) è stata superata identificando con la metodica della "reverse vaccinology" alcuni antigeni capaci di indurre una risposta verso la maggior parte dei ceppi di MenB circolanti nel mondo. Il nuovo vaccino MenB a 4 componenti (4CMenB) è stato autorizzato in Europa, Australia e Canada, ed è entrato nei calendari di immunizzazione pediatrica internazionali: Australia, Canada, UK. In Italia, le prime regioni che hanno raccomandato la vaccinazione contro il MenB sono state Basilicata e Puglia. La gestione di epidemie/focolai epidemici richiede la messa in atto di una risposta rapida da parte delle autorità sanitarie nei confronti di una emergenza sanitaria ad elevato impatto, anche emotivo, sulla popolazione, come recentemente dimostrato in due università americane. Alla dichiarazione di focolaio epidemico in atto, in entrambi i contesti si è attivata una procedura per l'uso del vaccino 4CMenB non ancora autorizzato negli USA. È stato così possibile organizzare gli interventi di profilassi attiva nei due campus universitari, adottando il primo impiego su larga scala del nuovo vaccino 4CMenB e conseguendo, in tempi relativamente brevi, elevati tassi di copertura vaccinale. A fronte di circa 14000 studenti immunizzati con almeno una dose, non è stata segnalata alcuna problematica di eventi avversi conseguenti all'immunizzazione; ad oggi non si sono verificati casi nei soggetti che hanno ricevuto il vaccino. Come conseguenza dei due focolai descritti, è oggi in corso la valutazione da parte dell'FDA per l'estensione dell'uso del vaccino 4CMenB negli Stati Uniti negli adolescenti e giovani adulti. PMID:25916017
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Clinical Predictors of Diabetes Insipidus After Transcranial Surgery for Pituitary Adenoma.
Wang, Songquan; Li, Deling; Ni, Ming; Jia, Wang; Zhang, Qing; He, Jue; Jia, Guijun
2017-05-01
Diabetes insipidus (DI) is a well-known complication of transsphenoidal pituitary adenoma surgery. However, the risk factors for DI after transcranial surgery have not been clarified. In this study, the clinical parameters for predicting DI after transcranial surgery were investigated. The perioperative records of 90 patients who underwent transcranial (TC) surgery at the authors' institution between November 2011 and March 2013 were chosen from 1657 patients with pituitary adenoma and retrospectively analyzed. The degree of deformation of the third ventricle and hypothalamus were assessed by preoperative magnetic resonance imaging. Immediate postoperative DI was found in 30 patients (33.3%). Persistent DI was noted in 11 patients (12.6%). Compared with patients in the nonpostoperative DI group, those with postoperative DI had a higher degree of deformation of the third ventricle and hypothalamus (P < 0.001). In a binary logistic regression analysis, the degree of deformation of the third ventricle and hypothalamus (odds ratio [OR], 3.079; 95% confidence interval [CI], 1.600-5.925; P = 0.001) had a significant positive correlation with immediate postoperative DI, as well as postoperative hemorrhage (OR, 6.235, 95% CI, 1.457-26.689; P = 0.014). Postoperative hemorrhage (OR, 4.363; 95% CI, 1.021-18.647; P = 0.047) showed a positive correlation with permanent DI, as well as the degree of deformation of the third ventricle and hypothalamus (OR, 2.336; 95% CI, 1.005-5.427; P = 0.049). The degree of deformation of the third ventricle and hypothalamus assessed by preoperative magnetic resonance imaging may help to predict postoperative DI. Postoperative hemorrhage might increase the incidence of postoperative DI, whether it is immediate postoperative DI or permanent DI. Copyright © 2017 Elsevier Inc. All rights reserved.
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Hayashi, Yasuhiko; Aida, Yasuhiro; Sasagawa, Yasuo; Oishi, Masahiro; Kita, Daisuke; Tachibana, Osamu; Ueda, Fumiaki; Nakada, Mitsutoshi
2018-02-01
Diabetes insipidus (DI) is a major complication of transsphenoidal surgery (TSS). DI usually occurs within a couple of days after TSS. Delayed occurrence of postoperative DI is rarely observed and its developing mechanisms remain unknown. Six patients were identified as having postoperative delayed DI, which was defined as DI that first occurred 2 or more weeks after TSS. They consisted of 1 male and 5 females, and their mean age was 38.3 years (range, 10-76 years). Five patients were histologically diagnosed with Rathke cleft cyst (RCC), and one had RCC coexisting with prolactin-secreting adenoma. Sequential T1-weighted magnetic resonance imaging was evaluated for hyperintensity (HI) in the pituitary stalk and the posterior lobe, indicating the location of antidiuretic hormone. No patients had any DI before TSS. Delayed DI occurred 2 weeks to 3 months after TSS and persisted for 2 weeks to 5 months. T1-weighted magnetic resonance imaging showed that the HI in the posterior lobe became faint but did not disappear after DI occurrence, and their intensities increased with recovery from DI. In contrast, the HI in the pituitary stalk was found faintly preoperatively and turned clear postoperatively and decreased with recovery from DI. The morphologic patterns were dependent on DI duration. In the delayed occurrence of DI, it was suggested that preoperative antidiuretic hormone transport was mildly congested yet not completely blocked when DI manifested postoperatively. Gradual spreading of inflammation to the infundibulum after RCC removal was considered as 1 possible mechanism of this delayed DI development. Copyright © 2017 Elsevier Inc. All rights reserved.
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Macatee, Richard J; Cougle, Jesse R
2015-09-01
A growing body of research has linked high distress intolerance (DI) to obsessions, but not other OCD symptom domains. However, existing research is correlational. Experimental studies are needed, but brief methods for reducing DI are lacking. To address these gaps in the literature, a brief, computerized intervention aimed at reducing DI was developed to determine if changing DI affected obsessional phenomena. Individuals reporting high DI were randomized to a treatment or waitlist control group (N = 53). Individuals in the treatment group received the DI treatment (i.e., a 2 h computerized intervention) over two weeks, and then underwent a post-assessment in which DI and obsession-relevant phenomena were measured. Individuals in the control group only received the post-assessment. Analyses revealed a greater reduction in self-reported DI on one measure and smaller decreases in behavioral DI in the intervention condition relative to the waitlist condition, as well as lower in-vivo urges to neutralize an intrusive thought; however, anxious reactivity to the intrusion and neutralization behavior were not affected. Further, bootstrapping analyses revealed that reductions in DI mediated the effect of the intervention on neutralization urges. A clinical sample and placebo control condition were not used. These results provide experimental evidence for the role of DI in obsessional phenomena, specifically in affecting urges to neutralize intrusions, findings consistent with negative reinforcement models of DI. Further, results revealed that DI can be reduced with a brief, computerized intervention, which has important implications for future experimental research and treatment development. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Introduction to Kinetic Model Equations
2011-01-01
application . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 ∗Dipartimento di Matematica del Politecnico di Milano Piazza Leonardo da Vinci 32...NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Dipartimento di Matematica del Politecnico di Milano Piazza Leonardo da Vinci 32, 20133 Milano
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Gianicolo, Emilio Antonio Luca; Mangia, Cristina; Cervino, Marco; Bruni, Antonella; De Marchi, Bruna; Biggeri, Annibale; Porcu, Rosa; Vigotti, Maria Angela
2016-01-01
OBIETTIVI: valutare lo stato di salute della popolazione residente nel comune di Manfredonia dal 1970 al 2013. DISEGNO: analisi descrittiva dell'andamento temporale della mortalità generale, per gruppi di cause, dal 1970 al 2013. SETTING E PARTECIPANTI: i dati di mortalità e le popolazioni residenti sono di fonte Istat. Sono state esaminate 55 cause di decesso. Le analisi sono disaggregate per sesso e periodo. PRINCIPALI MISURE DI OUTCOME: sono stati elaborati i rapporti standardizzati di mortalità (SMR%), con i rispettivi intervalli di confidenza al 90% (IC90%), e i tassi di mortalità standardizzati col metodo diretto (TSD ). RISULTATI: lo stato di salute misurato dal tasso di mortalità per tutte le cause migliora nel tempo: i TSD passano da 92 x10.000 negli anni 1970-1974 a 52 x10.000 nel biennio 2012-2013 negli uomini, da 70 x10.000 a 39 x10.000 nelle donne. Tuttavia, rispetto alla media regionale Manfredonia perde progressivamente il suo vantaggio, passando da -20% a -10% negli uomini, e da -20% a +1,5% nelle donne. Questo andamento è molto evidente per il complesso delle cause cardiovascolari, mentre i tumori maligni sono in generale nella media regionale. Nell'ultimo periodo disponibile per causa di decesso (2006-2011), la mortalità per infarto miocardico è stata più alta della media regionale (uomini: +35%; donne: +54%). I rapporti standardizzati di mortalità (SMR) mostrano tra gli uomini valori in crescita, in particolar modo rispetto al riferimento provinciale, con un eccesso a cominciare dal periodo 2006-2011 (22 decessi/anno e 19 attesi; SMR%: 117,2; IC90% 101,1-135,2; riferimento: provincia di Foggia). Anche tra le donne gli SMR% superano i riferimenti provinciali negli ultimi periodi esaminati (nel 2012-2013: 7 decessi/ anno e 4,2 attesi; SMR%: 116,4; IC90% 97,0-260,7; riferimento: provincia di Foggia). CONCLUSIONI: la mortalità a Manfredonia è diminuita in misura minore rispetto a quella osservata nei riferimenti provinciali e regionali. Il vantaggio che si osservava negli anni Sessanta si è, infatti, ridotto nel tempo, fino ad annullarsi negli ultimi anni. Dal 1970, Manfredonia ha progressivamente perso il vantaggio che aveva. Dagli anni Duemila, la mortalità per infarto del miocardio è in eccesso sulla media regionale e provinciale. Da casi documentati in letteratura si osserva che le popolazioni che sperimentano catastrofi di origine naturale o antropica possono fronteggiare un aumento di patologie cardiovascolari. La mortalità per tumore polmonare mostra un eccesso sulla media regionale, in particolare provinciale, a cominciare dal 2000, coerentemente con i tempi di latenza legati all'esposizione ad arsenico negli anni Settanta.
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Chin, Alvin J.; Saint-Jeannet, Jean-Pierre; Lo, Cecilia W.
2012-01-01
To illustrate the impact developmental biology and genetics have already had on the clinical management of the million infants born worldwide each year with CHD, we have chosen three stories which have had particular relevance for pediatric cardiologists, cardiothoracic surgeons, cardiac anesthesiologists, and cardiac nurses. First, we show how Margaret Kirby’s finding of the unexpected contribution of an ectodermal cell population – the cranial neural crest – to the aortic arch arteries and arterial pole of the embryonic avian heart provided a key impetus to the field of cardiovascular patterning. Recognition that a majority of patients affected by the neurocristopathy DiGeorge syndrome have a chromosome 22q11 deletion, have also spurred tremendous efforts to characterize the molecular mechanisms contributing to this pathology, assigning a major role to the transcription factor Tbx1. Second, synthesizing the work of the last two decades by many laboratories on a wide gamut of metazoans (invertebrates, tunicates, agnathans, teleosts, lungfish, amphibians, and amniotes), we review the >20 major modifications and additions to the ancient circulatory arrangement composed solely of a unicameral (one-chambered), contractile myocardial tube and a short proximal aorta. Two changes will be discussed in detail – the interposition of a second cardiac chamber in the circulation and the septation of the cardiac ventricle. By comparing the developmental genetic data of several model organisms, we can better understand the origin of the various components of the multicameral (multi-chambered) heart seen in humans. Third, Martina Brueckner’s discovery that a faulty axonemal dynein was responsible for the phenotype of the iv/iv mouse (the first mammalian model of human heterotaxy) focused attention on the biology of cilia. We discuss how even the care of the complex cardiac and non-cardiac anomalies seen in heterotaxy syndrome, which have long seemed impervious to advancements in surgical and medical intensive care (Jacobs et al., 2011), may yet yield to strategies grounded in a better understanding of the cilium. The fact that all cardiac defects seen in patients with full-blown heterotaxy can also be seen in patients without obvious laterality defects hints at important roles for ciliary function not only in left-right axis specification but also in cardiovascular morphogenesis. These three developmental biology stories illustrate how the remaining unexplained mortality and morbidity of congenital heart disease can be solved. PMID:22640994
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Diabetes insipidus during pregnancy.
Ananthakrishnan, Sonia
2016-03-01
Diabetes insipidus (DI) in pregnancy is a heterogeneous syndrome, most classically presenting with polyuria and polydipsia that can complicate approximately 1 in 30,000 pregnancies. The presentation can involve exacerbation of central or nephrogenic DI during pregnancy, which may have been either overt or subclinical prior to pregnancy. Women without preexisting DI can also be affected by the actions of placental vasopressinase which increases in activity between the 4th and 38th weeks of gestation, leading to accelerated metabolism of AVP and causing a transient form of DI of pregnancy. This type of DI may be associated with certain complications during pregnancy and delivery, such as preeclampsia. Management of DI of pregnancy depends on the pathophysiology of the disease; forms of DI that lack AVP can be treated with desmopressin (DDAVP), while forms of DI that involve resistance to AVP require evaluation of the underlying causes. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Geng, Yijie; Feng, Bradley
2016-07-01
The emerging models of human embryonic stem cell (hESC) self-organizing organoids provide a valuable in vitro platform for studying self-organizing processes that presumably mimic in vivo human developmental events. Here we report that through a chemical screen, we identified two novel and structurally similar small molecules BIR1 and BIR2 which robustly induced the self-organization of a balloon-shaped three-dimensional structure when applied to two-dimensional adherent hESC cultures in the absence of growth factors. Gene expression analyses and functional assays demonstrated an endothelial identity of this balloon-like structure, while cell surface marker analyses revealed a VE-cadherin(+)CD31(+)CD34(+)KDR(+)CD43(-) putative endothelial progenitor population. Furthermore, molecular marker labeling and morphological examinations characterized several other distinct DiI-Ac-LDL(+) multi-cellular modules and a VEGFR3(+) sprouting structure in the balloon cultures that likely represented intermediate structures of balloon-formation.
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Jackson, S; Gascón, J; Carrera, E; Monte, E; Prat, S
1997-01-01
Differential screening of a potato leaf cDNA library with cDNA probes made from tuberizing and non-tuberizing Solanum demissum plants led to the identification of a clone that is upregulated in leaves and other tissues upon tuberization. This clone was also shown to have a high level of expression in green tomato fruit, its expression falling off as the fruit turns red. No sucrose or hormonal regulation of the expression of this clone was observed and it did not respond to wounding or heat stress. Clone 32B is 532 bp long and contains an open reading frame encoding a small protein of 98 amino acids. The deduced protein sequence has a putative signal peptide for ER transport and a 10 amino acid domain in the C-terminal region of the protein, both of which are also found in the cotton LEA5, Arabidopsis Di21 and the mungbean Arg2 proteins.
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Early onset intellectual disability in chromosome 22q11.2 deletion syndrome.
Cascella, Marco; Muzio, Maria Rosaria
2015-01-01
Chromosome 22q11.2 deletion syndrome, or DiGeorge syndrome, or velocardiofacial syndrome, is one of the most common multiple anomaly syndromes in humans. This syndrome is commonly caused by a microdelection from chromosome 22 at band q11.2. Although this genetic disorder may reflect several clinical abnormalities and different degrees of organ commitment, the clinical features that have driven the greatest amount of attention are behavioral and developmental features, because individuals with 22q11.2 deletion syndrome have a 30-fold risk of developing schizophrenia. There are differing opinions about the cognitive development, and commonly a cognitive decline rather than an early onset intellectual disability has been observed. We report a case of 22q11.2 deletion syndrome with both early assessment of mild intellectual disabilities and tetralogy of Fallot as the only physic manifestation. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.
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Peer review of RELAP5/MOD3 documentation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Craddick, W.G.
1993-12-31
A peer review was performed on a portion of the documentation of the RELAP5/MOD3 computer code. The review was performed in two phases. The first phase was a review of Volume 3, Developmental Assessment problems, and Volume 4, Models and Correlations. The reviewers for this phase were Dr. Peter Griffith, Dr. Yassin Hassan, Dr. Gerald S. Lellouche, Dr. Marino di Marzo and Mr. Mark Wendel. The reviewers recommended a number of improvements, including using a frozen version of the code for assessment guided by a validation plan, better justification for flow regime maps and extension of models beyond their datamore » base. The second phase was a review of Volume 6, Quality Assurance of Numerical Techniques in RELAP5/MOD3. The reviewers for the second phase were Mr. Mark Wendel and Dr. Paul T. Williams. Recommendations included correction of numerous grammatical and typographical errors and better justification for the use of Lax`s Equivalence Theorem.« less
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Fourth International Congress on Industrial and Applied Mathematics. Book of Abstracts
1999-01-01
Dipartimento di Matematica , Universita’ di Pavia, Italy) Logarithmic Sobolev inequalities for kinetic semiconductor equations In this paper we analyze the...terms of Whitney forms. FERNANDES, Paolo (Istituto per la Matematica Applicata del Consiglio Nazionale delle Ricerche, Italy) Dealing with realistic... Matematica dell Universita di Pavia, Italy. PERUGIA, Ilaria (Diaprtimento di Matematica , Universita’ di Pavia - Italy) An adaptive field-based method
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Jones, A; Shepard, S; Dave, J
Purpose: To characterize the distribution of the deviation index (DI) in digital radiography practices across the United States. Methods: DI data was obtained from 10 collaborating institutions in the United States between 2012 and 2015. Each institution complied with the requirements of the Institutional Review Board at their site. DI data from radiographs of the body parts chest, abdomen, pelvis and extremity were analyzed for anteroposterior, posteroanterior, lateral, and decubitus views. The DI data was analyzed both in aggregate and stratified by exposure control method, image receptor technology, patient age, and participating site for each body part and view. Themore » number of exposures with DI falling within previously published control limits for DI and descriptive statistics were calculated. Results: DI data from 505,930 radiographic exposures was analyzed. The number of exposures with DI falling within published control limits for DI varied from 10 to 20% for adult patients and 10 to 23% for pediatric patients for different body parts and views. Mean DI values averaged over other parameters for radiographs of the abdomen, chest, pelvis, and extremities ranged from 0.3 to 1.0, −0.6 to 0.5, 0.8, and −0.9 to 0.5 for the different adult views and ranged from −1.6 to −0.1, −0.3 to 0.5, −0.1, −0.2 to 1.4 for the different pediatric views, respectively (DI data was solicited only for anteroposterior view of pelvis). Standard deviation values of DI from individual sites ranged from 1.3 to 3.6 and 1.3 to 3.0 for the different adult and pediatric views, respectively. Also of interest was that target exposure indicators varied by up to a factor of 6 between sites for certain body parts and views. Conclusion: Previously published DI control limits do not reflect the state of clinical practice in digital radiography. Mean DI and target exposure indicators are targets for quality improvement efforts in radiography.« less
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Signorelli, Carlo; Odone, Anna; Bianco, Daniela; Di Vivo, Natalia; Bevere, Francesco
2016-01-01
Il dato dell'Organizzazione per la cooperazione e lo sviluppo economico (OCSE) del 2012, che indicava l'Italia come il Paese con la più bassa spesa in prevenzione sanitaria, ha dato lo spunto per una raccolta sistematica e un'analisi critica dei flussi disponibili sulla spesa per le attività di prevenzione in Italia. Le statistiche correnti di spesa sanitaria sono raccolte centralmente dall'Agenzia nazionale per i servizi sanitari regionali (Agenas) attraverso i modelli di rilevazione dei costi dei livelli essenziali di assistenza (LEA) delle aziende USL. Le tre macroaree dei LEA sono: assistenza distrettuale, assistenza ospedaliera e assistenza sanitaria collettiva in ambiente di vita e di lavoro. Le spese per la prevenzione rientrano in quest'ultima e sono ripartite nelle seguenti voci: attività di prevenzione rivolte alle persone, igiene degli alimenti e della nutrizione, igiene e sanità pubblica, prevenzione e sicurezza negli ambienti di lavoro, sanità pubblica veterinaria, attività medico-legale per finalità pubblica. Tra il 2006 e il 2013, ultimo dato disponibile, la spesa per le attività di prevenzione del Servizio sanitario nazionale (SSN) è rimasta costante in rapporto alla spesa sanitaria totale (4,2%), pari a 4,9 miliardi nel 2013. Nel periodo di studio considerato (2006-2013) appaiono in aumento le spese per le attività rivolte alle persone (+8,7%), attribuibili soprattutto a vaccinazioni e screening, e in diminuzione le attività di igiene pubblica (-5,7%) e quelle della sanità pubblica veterinaria (-3,8%). I confronti internazionali indicano una spesa per la prevenzione del 2,9% rispetto alla spesa sanitaria totale, costante negli anni e nella media dei Paesi OCSE. Per la prevenzione, l'Italia spende tanto quanto i Paesi che non possiedono un servizio sanitario pubblico; il dato risulta inferiore del 5% rispetto alla programmazione nazionale, con poche eccezioni e molta variabilità regionale all'interno delle componenti delle voci di spesa. In questo contesto si sottolinea l'importanza di investire maggiori risorse nella pianificazione e nell'implementazione di interventi preventivi di provata efficacia e costo-efficacia.
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Occurrence of Cyclic di-GMP-Modulating Output Domains in Cyanobacteria: an Illuminating Perspective
Agostoni, Marco; Koestler, Benjamin J.; Waters, Christopher M.; Williams, Barry L.; Montgomery, Beronda L.
2013-01-01
ABSTRACT Microorganisms use a variety of metabolites to respond to external stimuli, including second messengers that amplify primary signals and elicit biochemical changes in a cell. Levels of the second messenger cyclic dimeric GMP (c-di-GMP) are regulated by a variety of environmental stimuli and play a critical role in regulating cellular processes such as biofilm formation and cellular motility. Cyclic di-GMP signaling systems have been largely characterized in pathogenic bacteria; however, proteins that can impact the synthesis or degradation of c-di-GMP are prominent in cyanobacterial species and yet remain largely underexplored. In cyanobacteria, many putative c-di-GMP synthesis or degradation domains are found in genes that also harbor light-responsive signal input domains, suggesting that light is an important signal for altering c-di-GMP homeostasis. Indeed, c-di-GMP-associated domains are often the second most common output domain in photoreceptors—outnumbered only by a histidine kinase output domain. Cyanobacteria differ from other bacteria regarding the number and types of photoreceptor domains associated with c-di-GMP domains. Due to the widespread distribution of c-di-GMP domains in cyanobacteria, we investigated the evolutionary origin of a subset of genes. Phylogenetic analyses showed that c-di-GMP signaling systems were present early in cyanobacteria and c-di-GMP genes were both vertically and horizontally inherited during their evolution. Finally, we compared intracellular levels of c-di-GMP in two cyanobacterial species under different light qualities, confirming that light is an important factor for regulating this second messenger in vivo. PMID:23943760
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Surface Circulation in the Northeastern Mediterranean (NEMED)
2011-09-30
NEMED) Pierre-Marie Poulain Istituto Nazionale di Oceanografia e di Geofisica Sperimentale Borgo Grotta Gigante, 42/c 34010 Sgonico (Trieste...Istituto Nazionale di Oceanografia e di Geofisica Sperimentale,Borgo Grotta Gigante, 42/c,34010 Sgonico (Trieste), Italy, 8. PERFORMING ORGANIZATION
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Circulation in the Southeastern Mediterranean Sea (EGITTO-NICOP)
2007-09-30
Circulation in the Southeastern Mediterranean Sea (EGITTO-NICOP) Pierre-Marie Poulain Istituto Nazionale di Oceanografia e di Geofisica ...Nazionale di Oceanografia e di Geofisica Sperimentale,Borgo Grotta Gigante, 42/c,34010 Sgonico (Trieste), Italy, , 8. PERFORMING ORGANIZATION REPORT NUMBER
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O'Neal, Lindsey; Ryu, Min-Hyung; Gomelsky, Mark; Alexandre, Gladys
2017-09-15
Bacterial chemotaxis receptors provide the sensory inputs that inform the direction of navigation in changing environments. Recently, we described the bacterial second messenger cyclic di-GMP (c-di-GMP) as a novel regulator of a subclass of chemotaxis receptors. In Azospirillum brasilense , c-di-GMP binds to a chemotaxis receptor, Tlp1, and modulates its signaling function during aerotaxis. Here, we further characterize the role of c-di-GMP in aerotaxis using a novel dichromatic optogenetic system engineered for manipulating intracellular c-di-GMP levels in real time. This system comprises a red/near-infrared-light-regulated diguanylate cyclase and a blue-light-regulated c-di-GMP phosphodiesterase. It allows the generation of transient changes in intracellular c-di-GMP concentrations within seconds of irradiation with appropriate light, which is compatible with the time scale of chemotaxis signaling. We provide experimental evidence that binding of c-di-GMP to the Tlp1 receptor activates its signaling function during aerotaxis, which supports the role of transient changes in c-di-GMP levels as a means of adjusting the response of A. brasilense to oxygen gradients. We also show that intracellular c-di-GMP levels in A. brasilense change with carbon metabolism. Our data support a model whereby c-di-GMP functions to imprint chemotaxis receptors with a record of recent metabolic experience, to adjust their contribution to the signaling output, thus allowing the cells to continually fine-tune chemotaxis sensory perception to their metabolic state. IMPORTANCE Motile bacteria use chemotaxis to change swimming direction in response to changes in environmental conditions. Chemotaxis receptors sense environmental signals and relay sensory information to the chemotaxis machinery, which ultimately controls the swimming pattern of cells. In bacteria studied to date, differential methylation has been known as a mechanism to control the activity of chemotaxis receptors and modulates their contribution to the overall chemotaxis response. Here, we used an optogenetic system to perturb intracellular concentrations of the bacterial second messenger c-di-GMP to show that in some chemotaxis receptors, c-di-GMP functions in a similar feedback loop to connect the metabolic status of the cells to the sensory activity of chemotaxis receptors. Copyright © 2017 American Society for Microbiology.
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O'Neal, Lindsey; Ryu, Min-Hyung; Gomelsky, Mark
2017-01-01
ABSTRACT Bacterial chemotaxis receptors provide the sensory inputs that inform the direction of navigation in changing environments. Recently, we described the bacterial second messenger cyclic di-GMP (c-di-GMP) as a novel regulator of a subclass of chemotaxis receptors. In Azospirillum brasilense, c-di-GMP binds to a chemotaxis receptor, Tlp1, and modulates its signaling function during aerotaxis. Here, we further characterize the role of c-di-GMP in aerotaxis using a novel dichromatic optogenetic system engineered for manipulating intracellular c-di-GMP levels in real time. This system comprises a red/near-infrared-light-regulated diguanylate cyclase and a blue-light-regulated c-di-GMP phosphodiesterase. It allows the generation of transient changes in intracellular c-di-GMP concentrations within seconds of irradiation with appropriate light, which is compatible with the time scale of chemotaxis signaling. We provide experimental evidence that binding of c-di-GMP to the Tlp1 receptor activates its signaling function during aerotaxis, which supports the role of transient changes in c-di-GMP levels as a means of adjusting the response of A. brasilense to oxygen gradients. We also show that intracellular c-di-GMP levels in A. brasilense change with carbon metabolism. Our data support a model whereby c-di-GMP functions to imprint chemotaxis receptors with a record of recent metabolic experience, to adjust their contribution to the signaling output, thus allowing the cells to continually fine-tune chemotaxis sensory perception to their metabolic state. IMPORTANCE Motile bacteria use chemotaxis to change swimming direction in response to changes in environmental conditions. Chemotaxis receptors sense environmental signals and relay sensory information to the chemotaxis machinery, which ultimately controls the swimming pattern of cells. In bacteria studied to date, differential methylation has been known as a mechanism to control the activity of chemotaxis receptors and modulates their contribution to the overall chemotaxis response. Here, we used an optogenetic system to perturb intracellular concentrations of the bacterial second messenger c-di-GMP to show that in some chemotaxis receptors, c-di-GMP functions in a similar feedback loop to connect the metabolic status of the cells to the sensory activity of chemotaxis receptors. PMID:28264994
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Coastal Ocean Circulation Experiment off Senegal (COCES)
2011-09-30
Pierre-Marie Poulain Istituto Nazionale di Oceanografia e di Geofisica Sperimentale Borgo Grotta Gigante, 42/c 34010 Sgonico (Trieste), Italy...ORGANIZATION NAME(S) AND ADDRESS(ES) Istituto Nazionale di Oceanografia e di Geofisica Sperimentale,Borgo Grotta Gigante, 42/c,34010 Sgonico (Trieste
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Coastal Ocean Circulation Experiment off Senegal (COCES)
2009-01-01
Pierre-Marie Poulain Istituto Nazionale di Oceanografia e di Geofisica Sperimentale Borgo Grotta Gigante, 42/c 34010 Sgonico (Trieste), Italy...NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Istituto Nazionale di Oceanografia e di Geofisica Sperimentale,Borgo Grotta Gigante, 42/c
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2017-07-01
spectrum disorder. However, DI-LL has not yet been carefully studied in children with ASD. As in ABA, the DI-LL curriculum incorporates immediate... study of DI-LL in children with ASD and language delay. The purpose of this study is to test the efficacy of DI-LL in a six-month randomized trial in...fading. To date, there is only one small study of DI-LL in children with ASD and language delay. The purpose of this study is to test the efficacy of
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[Analysis of factors predicting early unplanned readmissions].
Di Domenico, Gabriella; Tersigni, Ivan; Federico, Bruno; Leuter, Cinzia
2016-01-01
OBIETTIVI: determinare i fattori associati ai ricoveri ripetuti per identificare i pazienti a rischio di riospedalizzazione entro i 30 giorni dalla dimissione. DISEGNO: analisi retrospettiva delle dimissioni nell'anno 2013 attraverso le schede di dimissione ospedaliera (SDO). 3.900 pazienti ricoverati presso il presidio ospedaliero "Fabrizio Spaziani" di Frosinone. PRINCIPALI MISURE DI OUTCOME: analisi bivariata per l'analisi dell'associazione tra variabili. La regressione logistica è stata utilizzata per identificare i fattori di rischio associati al ricovero ripetuto. RISULTATI: tra i 3.900 pazienti considerati, il 12,8% ha avuto una riammissione non programmata entro un mese dalla dimissione precedente per le stesse categorie diagnostiche principali (MCD). Sono state rilevate differenze statisticamente significative tra i pazienti con e senza ricovero ripetuto per età, durata della degenza, titolo di studio, condizione occupazionale e diagnosi. I fattori che aumentano la probabilità di una riospedalizzazione sono il vivere da solo, la condizione di pensionato o casalinga, una degenza più lunga e alcune diagnosi, fra cui malattie dell'apparato respiratorio, del sistema nervoso e dell'apparato urinario. CONCLUSIONE: alcune caratteristiche sociodemografiche e la diagnosi dei pazienti ospedalizzati sono associate al rischio di riospedalizzazione entro 30 giorni dalla dimissione. I dati disponibili nell'archivio delle SDO possono essere utilizzati per un'identificazione dei pazienti a rischio sui quali definire specifici piani di dimissione.
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Forner-Piquer, Isabel; Maradonna, Francesca; Gioacchini, Giorgia; Santangeli, Stefania; Allarà, Marco; Piscitelli, Fabiana; Habibi, Hamid R; Di Marzo, Vincenzo; Carnevali, Oliana
2017-10-01
Phthalates, used as plasticizers, have become a ubiquitous contaminant and have been reported for their potential to induce toxicity in living organisms. Among them, di-isononyl phthalate (DiNP) has been recently used to replace di(2-ethylhexyl) phthalate (DEHP). Nowadays, there is evidence that DiNP is an endocrine-disrupting chemical; however, little is known about its effects on the endocannabinoid system (ECS) and lipid metabolism. Hence, the aim of our study was to investigate the effects of DiNP on the ECS in zebrafish liver and brain and on hepatic lipid storage. To do so, adult female zebrafish were exposed to three concentrations (0.42 µg/L, 4.2 µg/L, and 42 µg/L) of DiNP via water for 3 weeks. Afterwards, we investigated transcript levels for genes involved in the ECS of the brain and liver as well as liver histology and image analysis, Fourier-transform infrared spectroscopy imaging, and measurement of endocannabinoid levels. Our results demonstrate that DiNP upregulates orexigenic signals and causes hepatosteatosis together with deregulation of the peripheral ECS and lipid metabolism. A decrease in the levels of ECS components at the central level was observed after exposure to the highest DiNP concentration tested. These findings suggest that replacement of DEHP with DiNP should be considered with caution because of observed adverse DiNP effects on aquatic organisms. Copyright © 2017 Endocrine Society.
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Mediterranean diet and 3-year Alzheimer brain biomarker changes in middle-aged adults.
Berti, Valentina; Walters, Michelle; Sterling, Joanna; Quinn, Crystal G; Logue, Michelle; Andrews, Randolph; Matthews, Dawn C; Osorio, Ricardo S; Pupi, Alberto; Vallabhajosula, Shankar; Isaacson, Richard S; de Leon, Mony J; Mosconi, Lisa
2018-05-15
To examine in a 3-year brain imaging study the effects of higher vs lower adherence to a Mediterranean-style diet (MeDi) on Alzheimer disease (AD) biomarker changes (brain β-amyloid load via 11 C-Pittsburgh compound B [PiB] PET and neurodegeneration via 18 F-fluorodeoxyglucose [FDG] PET and structural MRI) in midlife. Seventy 30- to 60-year-old cognitively normal participants with clinical, neuropsychological, and dietary examinations and imaging biomarkers at least 2 years apart were examined. These included 34 participants with higher (MeDi+) and 36 with lower (MeDi-) MeDi adherence. Statistical parametric mapping and volumes of interest were used to compare AD biomarkers between groups at cross section and longitudinally. MeDi groups were comparable for clinical and neuropsychological measures. At baseline, compared to the MeDi+ group, the MeDi- group showed reduced FDG-PET glucose metabolism (CMRglc) and higher PiB-PET deposition in AD-affected regions ( p < 0.001). Longitudinally, the MeDi--group showed CMRglc declines and PiB increases in these regions, which were greater than those in the MeDi+ group ( p interaction < 0.001). No effects were observed on MRI. Higher MeDi adherence was estimated to provide 1.5 to 3.5 years of protection against AD. Lower MeDi adherence was associated with progressive AD biomarker abnormalities in middle-aged adults. These data support further investigation of dietary interventions for protection against brain aging and AD. © 2018 American Academy of Neurology.
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Bronchodilatory effect of deep inspiration in freshly isolated sheep lungs.
Wong, William D; Wang, Lu; Paré, Peter D; Seow, Chun Y
2017-02-01
Taking a big breath is known to reverse bronchoconstriction induced by bronchochallenge in healthy subjects; this bronchodilatory effect of deep inspiration (DI) is diminished in asthmatics. The mechanism underlying the DI effect is not clear. Observations from experiments using isolated airway smooth muscle (ASM) preparations and airway segments suggest that straining of ASM due to DI could lead to bronchodilation, possibly due to strain-induced reduction in ASM contractility. However, factors external to the lung cannot be excluded as potential causes for the DI effect. Neural reflex initiated by stretch receptors in the lung are known to inhibit the broncho-motor tone and enhance vasodilatation; the former directly reduces airway resistance, and the latter facilitates removal of contractile agonists through the bronchial circulation. If the DI effect is solely mediated by factors extrinsic to the lung, the DI effect would be absent in isolated, nonperfused lungs. Here we examined the DI effect in freshly isolated, nonperfused sheep lungs. We found that imposition of DI on isolated lungs resulted in significant bronchodilation, that this DI effect was present only after the lungs were challenged with a contractile agonist (acetylcholine or histamine), and that the effect was independent of the difference in lung volume observed pre- and post-DI. We conclude that a significant portion of the bronchodilatory DI effect stems from factors internal to the lung related to the activation of ASM. Copyright © 2017 the American Physiological Society.
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How changes in nutrition have influenced the development of allergic diseases in childhood
2012-01-01
The increasing prevalence of allergic diseases in childhood in the last decades could be linked to concomitant dietary changes, especially with the modified and lower consumption of fruit, vegetables and minerals. The consumption of these foods by pregnant women and children in the first years of life seems to be associated with a reduced risk of asthma and related symptoms. Foods that can prevent the development of wheezing through their antioxidant effects contain vitamin C and selenium; blood levels of these elements correlate negatively with the risk of wheezing. Intake of vitamin E during pregnancy also appears to be correlated with a reduced risk of wheezing for the unborn child. Similarly, low intake of zinc and carotenoids by pregnant women is associated with an increased risk of wheezing and asthma in childhood. Fiber also has anti-inflammatory properties and protective effects against allergic diseases such as atopic dermatitis and asthma. The consumption of fat influences the development of the airways. Populations in Western countries have increased their consumption of n-6 PUFAs and, in parallel, reduced n-3 PUFAs. This has led to decreased production of PGE2, which is believed to have a protective effect against inflammation of the airways. Conflicting hypotheses also concern vitamin D; both an excess and a deficiency of vitamin D, in fact, have been associated with an increased risk of asthma. Further studies on the role of these substances are necessary before any conclusions can be drawn on a clinical level. Astratto La crescente prevalenza negli ultimi decenni delle malattie allergiche in età pediatrica potrebbe essere legata a concomitanti cambiamenti nella dieta, in particolare alla minore e modificata introduzione di frutta, verdura e minerali. Il consumo di questi alimenti da parte delle donne in gravidanza e dei bambini nei primi anni di vita sembra essere associato ad un ridotto rischio di asma e di sintomi correlati. Gli alimenti che possono prevenire lo sviluppo di respiro sibilante (wheezing) attraverso i loro effetti antiossidanti contengono vitamina C e selenio; i livelli ematici di questi elementi sono correlati negativamente con il rischio di wheezing. Inoltre l'assunzione di vitamina E durante la gravidanza sembra essere correlato con un rischio ridotto di respiro sibilante per il nascituro. Allo stesso modo, basso apporto di zinco e di carotenoidi in donne in gravidanza è associata ad un aumentato rischio di wheezing e asma nell'infanzia. Anche le fibre hanno proprietà anti-infiammatorie ed effetti protettivi contro le malattie allergiche come la dermatite atopica e l’asma. Il consumo di grassi influenza lo sviluppo delle vie aeree. Le popolazioni dei paesi occidentali hanno aumentato il loro consumo di n-6 PUFA e, parallelamente, ridotto n-3 PUFA. Ciò ha portato alla diminuzione della produzione di PGE2, che si ritiene abbia un effetto protettivo contro l'infiammazione delle vie aeree. Ipotesi contrastanti riguardano la vitamina D, sia un eccesso che una carenza di vitamina D, infatti, sono stati associati ad un aumentato rischio di asma. Ulteriori studi sul ruolo di queste sostanze sono necessari prima di trarre conclusioni sul piano clinico. PMID:22651129
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Surface Circulation in the Northeastern Mediterranean (NEMED)
2010-09-30
NEMED) Pierre-Marie Poulain Istituto Nazionale di Oceanografia e di Geofisica Sperimentale Borgo Grotta Gigante, 42/c 34010 Sgonico (Trieste...TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Istituto Nazionale di Oceanografia e di Geofisica Sperimentale
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Coastal Ocean Circulation Experiment off Senegal (COCES)
2010-09-30
Pierre-Marie Poulain Istituto Nazionale di Oceanografia e di Geofisica Sperimentale Borgo Grotta Gigante, 42/c 34010 Sgonico (Trieste), Italy...ORGANIZATION NAME(S) AND ADDRESS(ES) Istituto Nazionale di Oceanografia e di Geofisica Sperimentale,Borgo Grotta Gigante, 42/c,34010 Sgonico (Trieste), Italy
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Diabetes insipidus and pregnancy.
Chanson, Philippe; Salenave, Sylvie
2016-06-01
Diabetes insipidus (DI) is a rare complication of pregnancy. It is usually transient, being due to increased placental production of vasopressinase that inactivates circulating vasopressin. Gestational, transient DI occurs late in pregnancy and disappears few days after delivery. Acquired central DI can also occur during pregnancy, for example in a patient with hypophysitis or neuroinfundibulitis during late pregnancy or postpartum. Finally, pre-existing central or nephrogenic DI may occasionally be unmasked by pregnancy. Treatment with dDAVP (desmopressin, Minirin(®)) is very effective on transient DI of pregnancy and also on pre-existing or acquired central DI. Contrary to vasopressin, dDAVP is not degraded by vasopressinase. Nephrogenic DI is insensitive to dDAVP and is therefore more difficult to treat during pregnancy if fluid intake needs to be restricted. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
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Novel naphthylstyryl-pyridium potentiometric dyes offer advantages for neural network analysis.
Obaid, A L; Loew, L M; Wuskell, J P; Salzberg, B M
2004-04-30
The submucous plexus of the guinea pig intestine is a quasi-two-dimensional mammalian neural network that is particularly amenable to study using multiple site optical recording of transmembrane voltage (MSORTV) [Biol. Bull. 183 (1992) 344; J. Neurosci. 19 (1999) 3073]. For several years the potentiometric dye of choice for monitoring the electrical activity of its individual neurons has been di-8-ANEPPS [Neuron 9 (1992) 393], a naphthylstyryl-pyridinium dye with a propylsulfonate headgroup that provides relatively large fluorescence changes during action potentials and synaptic potentials. Limitations to the use of this dye, however, have been its phototoxicity and its low water solubility which requires the presence of DMSO and Pluronic F-127 in the staining solution. In searching for less toxic and more soluble dyes exhibiting larger fluorescence signals, we first tried the dienylstyryl-pyridinium dye RH795 [J. Neurosci. 14 (1994) 2545] which is highly soluble in water. This dye yielded relatively large signals, but it was internalized quickly by the submucosal neurons resulting in rapid degradation of the signal-to-noise ratio. We decided to synthesize a series of naphthylstyryl-pyridinium dyes (di-n-ANEPPDHQ) having the same chromophore as di-8-ANEPPS and the quaternary ammonium headgroup (DHQ) of RH795 (resulting in two positive charges versus the neutral propylsulfonate-ring nitrogen combination), and we tested the di-methyl (JPW3039), di-ethyl (JPW2081), di-propyl (JPW3031), di-butyl (JPW5029), and di-octyl (JPW5037) analogues, all of them soluble in ethanol. We found that the di-propyl (di-3-ANEPPDHQ) and the di-butyl (di-4-ANEPPDHQ) forms yielded the best combination of signal-to-noise ratio, moderate phototoxicity and absence of dye internalization.
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Scavarda, Valeska Tavares; Pinheiro, Aurelio Carvalho; Costa, Symône Damasceno; de Andrade, Zélia Maria; Carvalhaes, João Tomás de Abreu; Campos, Orlando; Carvalho, Antonio Carlos; Moises, Valdir Ambrosio
2014-10-01
Cardiac disease frequently occurs in children with chronic kidney disease (CKD) undergoing dialysis (DI), but it is not well studied in patients undergoing conservative treatment (CT). The aim of our study was to use echocardiography to analyze and compare the cardiac involvement of children with CKD undergoing DI or CT. Seventy-one children with CKD were included; 41 undergoing DI and 30 undergoing CT. There were 33 controls. Measurements of arterial pressure and structural and functional echocardiographic variables were obtained; the children were followed up for 18 months. Tests of comparison and multiple regression were used; significant if P < 0.05. Arterial hypertension (AH) was present in 37 of 71 (52%) children with CKD: 27 (65.8%) in DI and 10 (33.3%) in CT (X2 = 8.7; P = 0.003). An abnormal left ventricular geometric pattern was present in 37/41 (90.3%) undergoing DI, 33 had left ventricular hypertrophy (LVH), and in 14/30 (46.7%) undergoing CT, 5 had LVH. Ejection fraction was normal in all groups; diastolic function alteration (DFA) occurred in 28/41 (68.3%) children on DI and in 10/30 (33.3%) on CT (X2 = 9.2; P = 0.002). For children with CKD, DI (P = 0.002) and hypertension (P = 0.04) were associated with LVH; among those on DI, only AH was associated with LVH (P = 0.02). During the follow-up, 18 (43.9%) children undergoing DI had at least one cardiovascular event. Children with CKD undergoing CT had less cardiac involvement than those undergoing DI. LVH was associated with DI and AH in all children with CKD and with AH in those on DI.
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A Change Impact Analysis to Characterize Evolving Program Behaviors
NASA Technical Reports Server (NTRS)
Rungta, Neha Shyam; Person, Suzette; Branchaud, Joshua
2012-01-01
Change impact analysis techniques estimate the potential effects of changes made to software. Directed Incremental Symbolic Execution (DiSE) is an intraprocedural technique for characterizing the impact of software changes on program behaviors. DiSE first estimates the impact of the changes on the source code using program slicing techniques, and then uses the impact sets to guide symbolic execution to generate path conditions that characterize impacted program behaviors. DiSE, however, cannot reason about the flow of impact between methods and will fail to generate path conditions for certain impacted program behaviors. In this work, we present iDiSE, an extension to DiSE that performs an interprocedural analysis. iDiSE combines static and dynamic calling context information to efficiently generate impacted program behaviors across calling contexts. Information about impacted program behaviors is useful for testing, verification, and debugging of evolving programs. We present a case-study of our implementation of the iDiSE algorithm to demonstrate its efficiency at computing impacted program behaviors. Traditional notions of coverage are insufficient for characterizing the testing efforts used to validate evolving program behaviors because they do not take into account the impact of changes to the code. In this work we present novel definitions of impacted coverage metrics that are useful for evaluating the testing effort required to test evolving programs. We then describe how the notions of impacted coverage can be used to configure techniques such as DiSE and iDiSE in order to support regression testing related tasks. We also discuss how DiSE and iDiSE can be configured for debugging finding the root cause of errors introduced by changes made to the code. In our empirical evaluation we demonstrate that the configurations of DiSE and iDiSE can be used to support various software maintenance tasks
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NASA Astrophysics Data System (ADS)
Lehmann, Daniel; Zahn, Dietrich R. T.
2009-04-01
A comparison of the electrical characteristics of organic field-effect transistors (OFETs) based on derivatives of the electron-conductor perylene tetracarboxylic diimide (PTCDI) in top-contact configuration is presented. The derivatives used are N,N'-dimethyl-3,4,9,10-perylene-tetracarboxylic-diimide (DiMe-PTCDI), N,N'-diphenyl-3,4,9,10-perylene-tetracarboxylic-diimide (DiPhenyl-PTCDI), N,N'-dimethoxyethyl-3,4,9,10-perylene-tetracarboxylic-diimide (DiMethoxyethyl-PTCDI), N,N'-di(3-pentyl)-3,4,9,10-perylene-tetracarboxylic-diimide (Di3Pentyl-PTCDI), and N,N'-diheptyl-3,4,9,10-perylene-tetracarboxylic-diimide (DiHeptyl-PTCDI). Current/voltage measurements were first performed in situ and later ex situ. Additionally, the effect of annealing and bias stress was probed in situ. A strong influence of the different side groups on the order of magnitude of the electron mobility is revealed, ranging from 4×10-6 cm2/V s for DiMethoxyethyl-PTCDI to 5×10-2 cm2/V s for DiHeptyl-PTCDI. While none of the devices was stable in air after exposition to air, only the DiMe-PTCDI one resumed its functionality after restoring vacuum conditions. The dielectric functions of the derivatives was derived, additionally revealing optical isotropy for all films and varying surface roughness. While DiHeptyl-PTCDI and Di3Pentyl-PTCDI, yielding also the highest electron mobilities, form smooth layers with negligible surface roughness, strong island formation was be observed for DiPhenyl-PTCDI and DiMethoxyethyl-PTCDI, yielding low mobilities. This island growth was also confirmed by atomic force microscopy measurements. Ageing of the samples for several months under ambient conditions leads to increased roughness for the very rough samples. Layers with smooth surface, on the other hand, showed no significant change in the dielectric behavior of the sample.
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Abdolhosseini, Sana; Ghiasvand, Ali Reza; Heidari, Nahid
2018-05-14
A stainless steel fiber was made porous and adhesive by platinization and then coated by nanostructured polypyrrole (PPy), using an appropriate electrophoretic deposition (EPD) method. The morphological surface structure and functional groups of the PPy-coated fiber were studied using SEM (Scanning electron microscope) instrument. The prepared fiber was used for comparison of direct immersion (DI) and electroenhanced direct immersion solid-phase microextraction (EE-DI-SPME) of nicotine in human plasma and urine samples followed by gas chromatography flame ionization detector (GC-FID) determination. The effects of the influential experimental parameters on the efficiency of the DI-SPME and EE-DI-SPME methods, including the pH and ionic strength of the sample solution, applied Direct current (DC) voltage, extraction temperature and time and stirring rate, were optimized. Under the optimal conditions, the calibration curves for the DI-SPME-GC-FID and EE-DI-SPME-GC-FID methods were linear over the ranges of 0.1⁻10.0 μg mL -1 and 0.001⁻10.0 μg mL -1 , respectively. The relative standard deviations (RSDs, n = 6) were found to be 6.1% and 4.6% for the DI and EE strategies, respectively. The LODs (limit of detection) of the DI-SPME-GC-FID and EE-DI-SPME-GC-FID methods were found to be 10 and 0.3 ng mL -1 , respectively. The relative recovery values (for the analysis of 1 µg mL -1 nicotine) were found to be 91⁻110% for EE-DI-SPME and 75⁻105% for DI-SPME. The enrichment factors for DI-SPME and EE-DI-SPME sampling were obtained as 38,734 and 50,597, respectively. The results indicated that EE-SPME was more efficient for quantitation of nicotine in biological fluids. The developed procedure was successfully carried out for the extraction and measurement of nicotine in real plasma and urine samples.
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Shimoda, Masayuki; Noguchi, Hirofumi; Fujita, Yasutaka; Takita, Morihito; Ikemoto, Tetsuya; Chujo, Daisuke; Naziruddin, Bashoo; Levy, Marlon F; Kobayashi, Naoya; Grayburn, Paul A; Matsumoto, Shinichi
2012-01-01
Porcine islets are considered to be a promising resource for xenotransplantation. However, it is difficult to isolate porcine islets because of the marked fragility and rapid dissociation. Endogenous trypsin is one of the main factors to damage islets during the isolation procedure. Recent studies have suggested that trypsin inhibitors during the preservation of pancreas or the collagenase digestion can improve the result of islet isolation. In this study, we examined whether α1-antitrypsin (Aralast™), which inhibits several endogenous proteases and has immunomodulatory properties, can protect islets from the proteases and improve the results of porcine islet isolation. Twelve porcine pancreata were divided into three groups: without Aralast group (standard, n = 5), preserved with Aralast using the ductal injection (DI) method (DI, n = 3), and with Aralast using the DI method and in the collagenase solution (DI+C, n = 4). Efficacy of islet isolation was assessed by islet yields, purity, and viability. The trypsin activity of the preservation and the digestion solution during the isolation procedure was measured. During islet isolation, the trypsin activity in DI+C group was significantly inhibited compared to the standard group, whereas DI group showed less effect than DI+C group. The average of postpurification islet equivalents (IEQ) per pancreas weight in the DI+C group was significantly higher than the standard group (standard: 3516 ± 497 IEQ/g, DI: 4607 ± 1090 IEQ/g, DI+C: 7097 ± 995 IEQ/g; p = 0.017 between standard and DI+C). In the DI+C group, stimulation index was higher than in other groups, although there was no significant difference. The presence of Aralast in both DI solution and collagenase solution markedly inhibited trypsin activity during pancreas digestion procedure and improved the porcine islet isolation. Inhibition of trypsin activity by Aralast could improve porcine islet isolation.
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Coastal Ocean Circulation Experiment Off Senegal (COCES - II)
2012-09-30
II) Pierre-Marie Poulain Istituto Nazionale di Oceanografia e di Geofisica Sperimentale Borgo Grotta Gigante, 42/c 34010 Sgonico (Trieste...NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Istituto Nazionale di Oceanografia e di Geofisica
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Near-Surface Dispersion and Circulation in the Marmara Sea (MARMARA)
2009-01-01
Sea (MARMARA) Pierre-Marie Poulain Istituto Nazionale di Oceanografia e di Geofisica Sperimentale Borgo Grotta Gigante, 42/c 34010 Sgonico...PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Istituto Nazionale di Oceanografia e di Geofisica Sperimentale,Borgo Grotta Gigante, 42/c,34010 Sgonico
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Surface Circulation in the Northeastern Mediterranean (NEMED)
2008-09-30
Nazionale di Oceanografia e di Geofisica Sperimentale Borgo Grotta Gigante, 42/c 34010 Sgonico (Trieste), Italy Phone: +39 040 2140322 Fax: +39 040...NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Istituto Nazionale di Oceanografia e di Geofisica Sperimentale,Borgo Grotta Gigante, 42/c
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Sakano, M; Otsu, K; Fujiwara, N; Fukumoto, S; Yamada, A; Harada, H
2013-04-01
Some clinical cases of hypoplastic tooth root are congenital. Because the formation of Hertwig's epithelial root sheath (HERS) is an important event for root development and growth, we have considered that understanding the HERS developmental mechanism contributes to elucidate the causal factors of the disease. To find integrant factors and phenomenon for HERS development and growth, we studied the proliferation and mobility of the cervical loop (CL). We observed the cell movement of CL by the DiI labeling and organ culture system. To examine cell proliferation, we carried out immunostaining of CL and HERS using anti-Ki67 antibody. Cell motility in CL was observed by tooth germ slice organ culture using green fluorescent protein mouse. We also examined the expression of paxillin associated with cell movement. Imaging using DiI labeling showed that, at the apex of CL, the epithelium elongated in tandem with the growth of outer enamel epithelium (OEE). Cell proliferation assay using Ki67 immunostaining showed that OEE divided more actively than inner enamel epithelium (IEE) at the onset of HERS formation. Live imaging suggested that mobility of the OEE and cells in the apex of CL were more active than in IEE. The expression of paxillin was observed strongly in OEE and the apex of CL. The more active growth and movement of OEE cells contributed to HERS formation after reduction of the growth of IEE. The expression pattern of paxillin was involved in the active movement of OEE and HERS. The results will contribute to understand the HERS formation mechanism and elucidate the cause of anomaly root. © 2012 John Wiley & Sons A/S.
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Spine Formation and Maturation in the Developing Rat Auditory Cortex
Schachtele, Scott J.; Losh, Joe; Dailey, Michael E.; Green, Steven H.
2013-01-01
The rat auditory cortex is organized as a tonotopic map of sound frequency. This map is broadly tuned at birth and is refined during the first 3 weeks postnatal. The structural correlates underlying tonotopic map maturation and reorganization during development are poorly understood. We employed fluorescent dye ballistic labeling (“DiOlistics”) alone, or in conjunction with immunohistochemistry, to quantify synaptogenesis in the auditory cortex of normal hearing rats. We show that the developmental appearance of dendritic protrusions, which include both immature filopodia and mature spines, on layers 2/3, 4, and 5 pyramidal and layer 4 spiny nonpyramidal neurons occurs in three phases: slow addition of dendritic protrusions from postnatal day 4 (P4) to P9, rapid addition of dendritic protrusions from P9 to P19, and a final phase where mature protrusion density is achieved (>P21). Next, we combined DiOlistics with immunohistochemical labeling of bassoon, a presynaptic scaffolding protein, as a novel method to categorize dendritic protrusions as either filopodia or mature spines in cortex fixed in vivo. Using this method we observed an increase in the spine-to-filopodium ratio from P9–P16, indicating a period of rapid spine maturation. Previous studies report mature spines as being shorter in length compared to filopodia. We similarly observed a reduction in protrusion length between P9 and P16, corroborating our immunohistochemical spine maturation data. These studies show that dendritic protrusion formation and spine maturation occur rapidly at a time previously shown to correspond to auditory cortical tonotopic map refinement (P11–P14), providing a structural correlate of physiological maturation. PMID:21800311
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Pocar, Paola; Fiandanese, Nadia; Berrini, Anna; Secchi, Camillo; Borromeo, Vitaliano
2017-05-01
Endocrine disruptors (EDs) are compounds known to promote transgenerational inheritance of adult-onset disease in subsequent generations after maternal exposure during fetal gonadal development. This study was designed to establish whether gestational and lactational exposure to the plasticizer di(2-ethylhexyl)phthalate (DEHP) at environmental doses promotes transgenerational effects on reproductive health in female offspring, as adults, over three generations in the mouse. Gestating F0 mouse dams were exposed to 0, 0.05, 5mg/kg/day DEHP in the diet from gestational day 0.5 until the end of lactation. The incidence of adult-onset disease in reproductive function was recorded in F1, F2 and F3 female offspring. In adult F1 females, DEHP exposure induced reproductive adverse effects with: i) altered ovarian follicular dynamics with reduced primordial follicular reserve and a larger growing pre-antral follicle population, suggesting accelerated follicular recruitment; ii) reduced oocyte quality and embryonic developmental competence; iii) dysregulation of the expression profile of a panel of selected ovarian and pre-implantation embryonic genes. F2 and F3 female offspring displayed the same altered reproductive morphological phenotype and gene expression profiles as F1, thus showing transgenerational transmission of reproductive adverse effects along the female lineage. These findings indicate that in mice exposure to DEHP at doses relevant to human exposure during gonadal sex determination significantly perturbs the reproductive indices of female adult offspring and subsequent generations. Evidence of transgenerational transmission has important implications for the reproductive health and fertility of animals and humans, significantly increasing the potential biohazards of this toxicant. Copyright © 2017 Elsevier Inc. All rights reserved.
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Aydemir, Duygu; Karabulut, Gözde; Şimşek, Gülsu; Gok, Muslum; Barlas, Nurhayat; Ulusu, Nuriye Nuray
2018-04-13
Di(2-ethylhexyl) phthalate (DEHP) is a widely used synthetic polymer in the industry. DEHP may induce reproductive and developmental toxicity, obesity, carcinogenesis and cause abnormal endocrine function in both human and wildlife. The aim of this study was to investigate trace element and mineral levels in relation of kidney and liver damage in DEHP-administered rats. Therefore, prepubertal male rats were dosed with 0, 100, 200, and 400 mg/kg/day of DEHP. At the end of the experiment, trace element and mineral levels, glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6-PGD), glutathione reductase (GR) and glutathione S-transferase (GST) enzyme activities were evaluated in the serum, liver, and kidney samples of rats. Furthermore, serum clinical biochemistry parameters, organ/body weight ratios and histological changes were investigated to evaluate impact of DEHP more detailed. Our data indicated that sodium (Na), calcium (Ca), potassium (K), lithium (Li), rubidium (Rb) and cesium (Cs) levels significantly decreased, however iron (Fe) and selenium (Se) concentrations significantly increased in DEHP-administered groups compared to the control in the serum samples. On the other hand, upon DEHP administration, selenium concentration, G6PD and GR activities were significantly elevated, however 6-PGD activity significantly decreased compared to the control group in the kidney samples. Decreased G6PD activity was the only significant change between anti-oxidant enzyme activities in the liver samples. Upon DEHP administration, aberrant serum biochemical parameters have arisen and abnormal histological changes were observed in the kidney and liver tissue. In conclusion, DEHP may induce liver and kidney damage, also result abnormalities in the trace element and mineral levels.
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Water homeostasis and diabetes insipidus in horses.
Schott, Harold C
2011-04-01
Diabetes insipidus (DI) is a rare disorder of horses characterized by profound polyuria and polydipsia (PU/PD), which can be caused by loss of production of arginine vasopressin (AVP). This condition is termed neurogenic or central DI. DI may also develop with absence or loss of AVP receptors or activity on the basolateral membrane of collecting-duct epithelial cells. This condition is termed nephrogenic DI. Equine clinicians may differentiate true DI from more common causes of PU/PD by a systematic diagnostic approach. DI may not be a correctable disorder, and supportive care of affected horses requires an adequate water source. Copyright © 2011 Elsevier Inc. All rights reserved.
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High-Performance Liquid Chromatography (HPLC)-Based Detection and Quantitation of Cellular c-di-GMP.
Petrova, Olga E; Sauer, Karin
2017-01-01
The modulation of c-di-GMP levels plays a vital role in the regulation of various processes in a wide array of bacterial species. Thus, investigation of c-di-GMP regulation requires reliable methods for the assessment of c-di-GMP levels and turnover. Reversed-phase high-performance liquid chromatography (RP-HPLC) analysis has become a commonly used approach to accomplish these goals. The following describes the extraction and HPLC-based detection and quantification of c-di-GMP from Pseudomonas aeruginosa samples, a procedure that is amenable to modifications for the analysis of c-di-GMP in other bacterial species.
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Lo Gnomone Clementino Astronomia Meridiana in Basilica
NASA Astrophysics Data System (ADS)
Sigismondi, Costantino
2014-05-01
Costruito per chiara volontà del papa 70 anni dopo il caso Galileo, lo Gnomone Clementino è un grande telescopio solare che non fa uso di lenti a 92 anni dall’invenzione del cannocchiale. Queste due caratteristiche basterebbero da sole a giustificare l’interesse verso questo strumento. L’astronomia meridiana è alla base dell’astrometria e dell’astrofisica moderna. Lo Gnomone Clementino sta oggi all’astronomia, come il veliero “Amerigo Vespucci” sta alla Marina Italiana. E’ possibile svolgere ogni genere di osservazione e studio su questo strumento, e dal 2002 vi tengo lezioni teorico-pratiche del corso di Storia dell’Astronomia e La Terra nel Sistema Solare della Sapienza, Università di Roma, Facoltà di Lettere e Filosofia. Questo testo aggiunge alcuni tasselli alla ricerca storica sulla meridiana, appoggiandosi, com’è naturale, sulle spalle di giganti che mi hanno preceduto in questi studi. In particolare la misura dell’azimut della meridiana, ed il suo inquadramento tra gli strumenti simili ed alcuni studi di astrometria sui dati del 1701-1703 di Bianchini, che sono apparsi fin’ora soltanto su riviste specializzate ed in Inglese vengono qui proposti in Italiano e semplificati, per valorizzare sempre più questa straordinaria opera d’arte e di scienza.
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Assessment of skeletal maturation using mandibular second molar maturation stages.
Goyal, S; Goyal, S; Gugnani, N
2014-01-01
To investigate the relationship between cervical vertebrae maturation and mandibular second molar calcification stages. The study was designed as a retrospective, descriptive and crosssectional research project. Pre-treatment lateral cephalograms and panoramic radiographs of 99 males and 110 females in the age range of 7 to 18 years 7 months were evaluated with Demirjian Index (DI) and cervical vertebrae maturation indicators (CVMI) of Hassel and Farman. A null hypothesis was proposed that there is no relation between CVMI and DI. A highly significant association (Pearson's contingency coefficient 0.713 for males and 0.863 for females) was found between DI and CVMI. In males, the DI stage E corresponded to stage 2 of CVMI (pre-peak of pubertal growth spurt) and DI stages F and G corresponded to stages 3 and 4 of CVMI (peak of pubertal growth spurt). DI stage H was associated with stages 5 and 6 of CVMI (end of pubertal growth spurt). In females, the DI stages C, D corresponded to CVMI stages 1, 2; DI stages E, F with CVMI stages 3, 4; DI stages G, H with CVMI stages 5, 6. Mandibular second molar calcification stages can be used as indicators for assessment of skeletal maturity.
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Trier, Xenia; Nielsen, Nikoline Juul; Christensen, Jan H
2011-09-01
In this study, we provide strategies for detecting and quantifying the structural isomers of polyfluorinated di- and tri-alkyl surfactants (PFAS) by mass spectrometry (MS). We specifically investigate polyfluorinated dialkylated phosphate ester surfactants (x:2/y:2 diPAPS, (F(CF(2))( x )CH(2)CH(2)O-P(O)(O)(-)-OCH(2)CH(2)(CF(2))( y )F)) and their thioether analogues (x:2/y:2 S-diPAPS, F(CF(2))( x )CH(2)CH(2)SCH(2)-C[CH(2)O)(2)P(O)(O)(-)]-CH(2)SCH(2)CH(2)(CF(2))( y )F), which are used for industrial applications, such as oil- and water-repellent coatings on paper and board. DiPAPS have been found in human blood and are metabolised to the persistent perfluoroalkyl carboxylic acids (PFCA) in rats. A microwave popcorn bag extract was analysed by ultrahigh-pressure liquid chromatography coupled to a negative electrospray ionisation-quadrupole time-of-flight MS. The extract contained S-diPAPS, diPAPS and trialkylated (triPAPS) impurities. TriPAPS were also present in industrial and synthetic diPAPS standards, and were verified with an 8:2/8:2/8:2 triPAPS standard. The eight elemental compositions (m/z's) of diPAPS in the extract represent 19 precursor ion structures, and the six S-diPAPS m/z's represent at least 13 structures. The diPAPS had [M-H](-) precursor ions of m/z 789, 889,…1,489 and the S-diPAPS of m/z 921, 1,021,…1,421, corresponding to fluorinated chains from C(6-18). Each m/z appeared as one to three chromatographic peaks of structural isomers, where, e.g. m/z 1,189 was present as 10:2/10:2, 8:2/12:2 and 6:2/14:2 diPAPS. The isomers formed different products ions, thus only half of the m/z 1,189 diPAPS concentration was measured with one precursor ion > product ion transition. In general, knowledge about structural isomers of poly-alkylated PFAS is needed for the estimation of types and amounts of perfluorinated degradation products, such as PFCA from diPAPS.
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Solving Kinetic Equations on GPU’s
2011-01-01
7 Acknowledgments 23 8 Appendix: CUDA pseudo-codes 27 ∗Dipartimento di Matematica del Politecnico di Milano Piazza Leonardo da Vinci 32, 20133 Milano...PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Dipartimento di Matematica del Politecnico di Milano Piazza Leonardo da Vinci 32, 20133 Milano, Italy 8
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Santangelo, Philip S; Reinhard, Iris; Koudela-Hamila, Susanne; Bohus, Martin; Holtmann, Jana; Eid, Michael; Ebner-Priemer, Ulrich W
2017-11-01
Borderline personality disorder (BPD) is defined by a pervasive pattern of instability. Although there is ample empirical evidence that unstable self-esteem is associated with a myriad of BPD-like symptoms, self-esteem instability and its temporal dynamics have received little empirical attention in patients with BPD. Even worse, the temporal interplay of affective instability and self-esteem instability has been neglected completely, although it has been hypothesized recently that the lack of specificity of affective instability in association with BPD might be explained by the highly intertwined temporal relationship between affective and self-esteem instability. To investigate self-esteem instability, its temporal interplay with affective instability, and its association with psychopathology, 60 patients with BPD and 60 healthy controls (HCs) completed electronic diaries for 4 consecutive days during their everyday lives. Participants reported their current self-esteem, valence, and tense arousal levels 12 times a day in approximately one-hr intervals. We used multiple state-of-the-art statistical techniques and graphical approaches to reveal patterns of instability, clarify group differences, and examine the temporal interplay of self-esteem instability and affective instability. As hypothesized, instability in both self-esteem and affect was clearly elevated in the patients with BPD. In addition, self-esteem instability and affective instability were highly correlated. Both types of instability were related to general psychopathology. Because self-esteem instability could not fully explain affective instability and vice versa and neither affective instability nor self-esteem instability was able to explain psychopathology completely, our findings suggest that these types of instability represent unique facets of BPD. (PsycINFO Database Record (c) 2017 APA, all rights reserved).
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Parrey, Ashaq Hussain; Ahmad, Fayaz; Ahmad, Mushtaq; Basher, Adil
2018-01-01
Systemic lupus erythematosus (SLE) presenting as diabetes insipidus (DI) is a rare association; there is a case report of neurogenic DI in patients of SLE; however, SLE and nephrogenic DI has not been reported in literature. We present a case of SLE presenting as nephrogenic DI. We report a case who presented with DI (nephrogenic) and fulfilled criteria for SLE and Sjögren's syndrome with renal tubular acidosis.
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Illustrated review of the leaf-mining Nepticulidae of the central Andes (Peru and Bolivia).
Stonis, Jonas R; Diškus, Arūnas; Remeikis, Andrius; Karsholt, Ole; Torres, Nixon Cumbicus
2017-04-24
We review forty-five species of Nepticulidae (Lepidoptera) based on an analysis of samples collected in the central Andean region of Peru and Bolivia. Thirteen of these species are new to science, and are named and described here: Stigmella paracosma Remeikis & Stonis, sp. nov., S. expressa Remeikis & Stonis, sp. nov., S. acalyphae Diškus & Stonis, sp. nov., S. lepida Diškus & Stonis, sp. nov., S. misera Diškus & Stonis, sp. nov., S. inca Diškus & Stonis, sp. nov., S. eiffeli Diškus & Stonis, sp. nov., S. arequipica Remeikis & Stonis, sp. nov., S. coronaria Diškus & Stonis, sp. nov., S. azulella Diškus & Stonis, sp. nov., S. sparsella Diškus & Stonis, sp. nov., Manoneura forcipis Diškus & Stonis, sp. nov., and Acalyptris murex Diškus & Stonis, sp. nov. Some of the central Andean species are recorded here as leaf-miners on Euphorbiaceae (Acalypha), Fabaceae (Collaea), Rosaceae (Polylepis), Malvaceae (Sida), Calceolariaceae (Calceolaria), Lamiaceae (Clinopodium), and Asteraceae (Ageratina and Trixis). We create eleven new species groups based on morphological characters designated in Stigmella and one in Acalyptris. A pictorial key to the species groups and distribution maps are provided. All new species are illustrated with 150 photographs and drawings of the adults and genitalia, and, where known and/or available, photographs of host-plants and leaf-mines.
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Baljuls, Angela; Beck, Matthias; Oenel, Ayla; Robubi, Armin; Kroschewski, Ruth; Hekman, Mirko; Rudel, Thomas; Rapp, Ulf R.
2012-01-01
The maternally imprinted Ras-related tumor suppressor gene DiRas3 is lost or down-regulated in more than 60% of ovarian and breast cancers. The anti-tumorigenic effect of DiRas3 is achieved through several mechanisms, including inhibition of cell proliferation, motility, and invasion, as well as induction of apoptosis and autophagy. Re-expression of DiRas3 in cancer cells interferes with the signaling through Ras/MAPK and PI3K. Despite intensive research, the mode of interference of DiRas3 with the Ras/RAF/MEK/ERK signal transduction is still a matter of speculation. In this study, we show that DiRas3 associates with the H-Ras oncogene and that activation of H-Ras enforces this interaction. Furthermore, while associated with DiRas3, H-Ras is able to bind to its effector protein C-RAF. The resulting multimeric complex consisting of DiRas3, C-RAF, and active H-Ras is more stable than the two protein complexes H-Ras·C-RAF or H-Ras·DiRas3, respectively. The consequence of this complex formation is a DiRas3-mediated recruitment and anchorage of C-RAF to components of the membrane skeleton, suppression of C-RAF/B-RAF heterodimerization, and inhibition of C-RAF kinase activity. PMID:22605333
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Cyclic Di-GMP modulates the disease progression of Erwinia amylovora.
Edmunds, Adam C; Castiblanco, Luisa F; Sundin, George W; Waters, Christopher M
2013-05-01
The second messenger cyclic di-GMP (c-di-GMP) is a nearly ubiquitous intracellular signal molecule known to regulate various cellular processes, including biofilm formation, motility, and virulence. The intracellular concentration of c-di-GMP is inversely governed by diguanylate cyclase (DGC) enzymes and phosphodiesterase (PDE) enzymes, which synthesize and degrade c-di-GMP, respectively. The role of c-di-GMP in the plant pathogen and causal agent of fire blight disease Erwinia amylovora has not been studied previously. Here we demonstrate that three of the five predicted DGC genes in E. amylovora (edc genes, for Erwinia diguanylate cyclase), edcA, edcC, and edcE, are active diguanylate cyclases. We show that c-di-GMP positively regulates the secretion of the main exopolysaccharide in E. amylovora, amylovoran, leading to increased biofilm formation, and negatively regulates flagellar swimming motility. Although amylovoran secretion and biofilm formation are important for the colonization of plant xylem tissues and the development of systemic infections, deletion of the two biofilm-promoting DGCs increased tissue necrosis in an immature-pear infection assay and an apple shoot infection model, suggesting that c-di-GMP negatively regulates virulence. In addition, c-di-GMP inhibited the expression of hrpA, a gene encoding the major structural component of the type III secretion pilus. Our results are the first to describe a role for c-di-GMP in E. amylovora and suggest that downregulation of motility and type III secretion by c-di-GMP during infection plays a key role in the coordination of pathogenesis.
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Cyclic Di-GMP Modulates the Disease Progression of Erwinia amylovora
Edmunds, Adam C.; Castiblanco, Luisa F.; Sundin, George W.
2013-01-01
The second messenger cyclic di-GMP (c-di-GMP) is a nearly ubiquitous intracellular signal molecule known to regulate various cellular processes, including biofilm formation, motility, and virulence. The intracellular concentration of c-di-GMP is inversely governed by diguanylate cyclase (DGC) enzymes and phosphodiesterase (PDE) enzymes, which synthesize and degrade c-di-GMP, respectively. The role of c-di-GMP in the plant pathogen and causal agent of fire blight disease Erwinia amylovora has not been studied previously. Here we demonstrate that three of the five predicted DGC genes in E. amylovora (edc genes, for Erwinia diguanylate cyclase), edcA, edcC, and edcE, are active diguanylate cyclases. We show that c-di-GMP positively regulates the secretion of the main exopolysaccharide in E. amylovora, amylovoran, leading to increased biofilm formation, and negatively regulates flagellar swimming motility. Although amylovoran secretion and biofilm formation are important for the colonization of plant xylem tissues and the development of systemic infections, deletion of the two biofilm-promoting DGCs increased tissue necrosis in an immature-pear infection assay and an apple shoot infection model, suggesting that c-di-GMP negatively regulates virulence. In addition, c-di-GMP inhibited the expression of hrpA, a gene encoding the major structural component of the type III secretion pilus. Our results are the first to describe a role for c-di-GMP in E. amylovora and suggest that downregulation of motility and type III secretion by c-di-GMP during infection plays a key role in the coordination of pathogenesis. PMID:23475975
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Choi, Philip H; Sureka, Kamakshi; Woodward, Joshua J; Tong, Liang
2015-06-01
Cyclic-di-AMP (c-di-AMP) is a broadly conserved bacterial second messenger that is of importance in bacterial physiology. The molecular receptors mediating the cellular responses to the c-di-AMP signal are just beginning to be discovered. PstA is a previously uncharacterized PII -like protein which has been identified as a c-di-AMP receptor. PstA is widely distributed and conserved among Gram-positive bacteria in the phylum Firmicutes. Here, we report the biochemical, structural, and functional characterization of PstA from Listeria monocytogenes. We have determined the crystal structures of PstA in the c-di-AMP-bound and apo forms at 1.6 and 2.9 Å resolution, respectively, which provide the molecular basis for its specific recognition of c-di-AMP. PstA forms a homotrimer structure that has overall similarity to the PII protein family which binds ATP. However, PstA is markedly different from PII proteins in the loop regions, and these structural differences mediate the specific recognition of their respective nucleotide ligand. The residues composing the c-di-AMP binding pocket are conserved, suggesting that c-di-AMP recognition by PstA is of functional importance. Disruption of pstA in L. monocytogenes affected c-di-AMP-mediated alterations in bacterial growth and lysis. Overall, we have defined the PstA family as a conserved and specific c-di-AMP receptor in bacteria. © 2015 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.
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Enhanced healing of full-thickness burn wounds using di-rhamnolipid
Stipcevic, Tamara; Piljac, Ante; Piljac, Goran
2006-01-01
The aim of this study was to investigate the properties of di-rhamnolipid [α-L-rhamnopyranosyl-(1–2)-α-L-rhamnopyranosyl-3-hydroxydecanoyl-3-hydroxydecanoic acid, also referred to as di-rhamnolipid BAC-3] relating to the process of cutaneous wound healing. Di-rhamnolipid was prepared in a eucerin ointment and applied topically on full-thickness burn wounds in normal Sprague–Dawley rats covering 5% of the total body surface area. The rate of wound closure was measured over the period of 45 days. The collagen content was evaluated microscopically, by performing densitometric analysis on Verhoeff’s stained histopathological slides of wound biopsies taken at the end of 45th day of di-rhamnolipid treatment. Di-rhamnolipid toxicity was assessed with the subcutaneous multi-dose study in Swiss–Webster mice. The treatment of full-thickness-burn wounds with topical 0.1% di-rhamnolipid accelerated the closure of wounds on day 21 of the treatment by 32% compared to the control ( p < 0.05). On day 35, the wounds closed in all animals-treated with 0.1% di-rhamnolipid ointment while some rats in the control group had open wounds on days 35 and even 45. Histologic comparisons have shown that di-rhamnolipid significantly decreased collagen content in burn wounds (47.5%, p < 0.05) as compared to the vehicle-treated (control) wounds. Di-rhamnolipid was well-tolerated. The results of this study raise the possibility of potential efficacy of di-rhamnolipid in accelerating normal wound healing and perhaps in overcoming defects associated with healing failure in chronic wounds. PMID:16380213
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Tzeng, W.-P.; Frey, Teryl K.
Rubella virus (RUB) replicons are derivatives of the RUB infectious cDNA clone that retain the nonstructural open reading frame (NS-ORF) that encodes the replicase proteins but not the structural protein ORF (SP-ORF) that encodes the virion proteins. RUB defective interfering (DI) RNAs contain deletions within the SP-ORF and thus resemble replicons. DI RNAs often retain the 5' end of the capsid protein (C) gene that has been shown to modulate virus-specific RNA synthesis. However, when replicons either with or without the C gene were passaged serially in the presence of wt RUB as a source of the virion proteins, itmore » was found that neither replicon was maintained and DI RNAs were generated. The majority DI RNA species contained in-frame deletions in the SP-ORF leading to a fusion between the 5' end of the C gene and the 3' end of the E1 glycoprotein gene. DI infectious cDNA clones were constructed and transcripts from these DI infectious cDNA clones were maintained during serial passage with wt RUB. The C-E1 fusion protein encoded by the DI RNAs was synthesized and was required for maintenance of the DI RNA during serial passage. This is the first report of a functional novel gene product resulting from deletion during DI RNA generation. Thus far, the role of the C-E1 fusion protein in maintenance of DI RNAs during serial passage remained elusive as it was found that the fusion protein diminished rather than enhanced DI RNA synthesis and was not incorporated into virus particles.« less
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Engineering Intern, NREL, Golden, CO, 2013 Featured Publications N. DiOrio, A. Dobos, S. Janzou, A. Nelson and Renewable Energy Laboratory, Golden, CO. N. DiOrio, A. Dobos and S. Janzou. 2015. "Economic Analysis . C. Christensen, J. Maguire, J. Burch, N. DiOrio. "Simplified Solar Water Heater Simulation
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de Vega-Bartol, José J; Santos, Raquen Raissa; Simões, Marta; Miguel, Célia M
2013-05-01
Suitable internal control genes to normalize qPCR data from different stages of embryo development and germination were identified in two representative conifer species. Clonal propagation by somatic embryogenesis has a great application potentiality in conifers. Quantitative PCR (qPCR) is widely used for gene expression analysis during somatic embryogenesis and embryo germination. No single reference gene is universal, so a systematic characterization of endogenous genes for concrete conditions is fundamental for accuracy. We identified suitable internal control genes to normalize qPCR data obtained at different steps of somatic embryogenesis (embryonal mass proliferation, embryo maturation and germination) in two representative conifer species, Pinus pinaster and Picea abies. Candidate genes included endogenous genes commonly used in conifers, genes previously tested in model plants, and genes with a lower variation of the expression along embryo development according to genome-wide transcript profiling studies. Three different algorithms were used to evaluate expression stability. The geometric average of the expression values of elongation factor-1α, α-tubulin and histone 3 in P. pinaster, and elongation factor-1α, α-tubulin, adenosine kinase and CAC in P. abies were adequate for expression studies throughout somatic embryogenesis. However, improved accuracy was achieved when using other gene combinations in experiments with samples at a single developmental stage. The importance of studies selecting reference genes to use in different tissues or developmental stages within one or close species, and the instability of commonly used reference genes, is highlighted.
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Ocular abnormalities in congenital Zika syndrome: a case report, and review of the literature.
Guevara, Jade Gieseke; Agarwal-Sinha, Swati
2018-06-09
As the number of children with Zika virus-related complications grows, the long-term developmental trajectory and its effects on families are unknown. We present the first known case of congenital Zika syndrome seen at our institution with significant fundus findings. A 3-day-old Hispanic baby girl presented with severe microcephaly of 24 cm and temperature instability at birth. Her mother had traveled to Honduras early in pregnancy and testing of amniotic fluid was positive for Zika virus via polymerase chain reaction. A dilated fundus examination was significant for bilateral severe colobomatous chorioretinal atrophy of the macula and pigmentary changes. Neonatal magnetic resonance imaging revealed diffuse lissencephaly with decreased brain volume, atrophic corpus callosum and brainstem, periventricular calcifications, and ventriculomegaly of the lateral ventricles. Our patient, who presented with the first known case of congenital Zika syndrome in Northern Florida, demonstrated profound bilateral colobomatous chorioretinal atrophy of the macula. The ophthalmologic findings along with severe microcephaly emphasize the neurotropism of the Zika virus, and ultimately are indicative of poor developmental and visual prognosis for affected infants. With the increased prevalence of Zika virus, ophthalmologists should be aware of the associated findings and the importance of an eye-screening examination with a dilated fundus examination within 1 month of life of infants in which congenital Zika syndrome is suspected. A multidisciplinary care approach is essential for the care of affected infants and their families.
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Grein, Katherine A.; Glidden, Laraine Masters
2014-01-01
Background Well-being outcomes for parents of children with intellectual and developmental disabilities (IDD) may vary from positive to negative at different times and for different measures of well-being. Predicting and explaining this variability has been a major focus of family research for reasons that have both theoretical and applied implications. Methods The current study used data from a 23-year longitudinal investigation of adoptive and birth parents of children with IDD to determine which early child, mother, and family characteristics would predict the variance in maternal outcomes 20 years after their original measurement. Using hierarchical regression analyses, we tested the predictive power of variables measured when children were 7 years old on outcomes of maternal well-being when children were 26 years old. Outcome variables included maternal self-report measures of depression and well–being. Results Final models of well-being accounted for 20% to 34% of variance. For most outcomes, Family Accord and/or the personality variable of Neuroticism (emotional stability/instability) were significant predictors, but some variables demonstrated a different pattern. Conclusions These findings confirm that 1) Characteristics of the child, mother, and family during childhood can predict outcomes of maternal well-being 20 years later; and 2) Different predictor-outcome relationships can vary substantially, highlighting the importance of using multiple measures to gain a more comprehensive understanding of maternal well-being. These results have implications for refining prognoses for parents and for tailoring service delivery to individual child, parent, and family characteristics. PMID:25185956
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Physical biology of human brain development.
Budday, Silvia; Steinmann, Paul; Kuhl, Ellen
2015-01-01
Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events. Developmental biology and genetics have shaped our understanding of the molecular and cellular mechanisms during neurodevelopment. Recent studies suggest that physical forces play a central role in translating these cellular mechanisms into the complex surface morphology of the human brain. However, the precise impact of neuronal differentiation, migration, and connection on the physical forces during cortical folding remains unknown. Here we review the cellular mechanisms of neurodevelopment with a view toward surface morphogenesis, pattern selection, and evolution of shape. We revisit cortical folding as the instability problem of constrained differential growth in a multi-layered system. To identify the contributing factors of differential growth, we map out the timeline of neurodevelopment in humans and highlight the cellular events associated with extreme radial and tangential expansion. We demonstrate how computational modeling of differential growth can bridge the scales-from phenomena on the cellular level toward form and function on the organ level-to make quantitative, personalized predictions. Physics-based models can quantify cortical stresses, identify critical folding conditions, rationalize pattern selection, and predict gyral wavelengths and gyrification indices. We illustrate that physical forces can explain cortical malformations as emergent properties of developmental disorders. Combining biology and physics holds promise to advance our understanding of human brain development and enable early diagnostics of cortical malformations with the ultimate goal to improve treatment of neurodevelopmental disorders including epilepsy, autism spectrum disorders, and schizophrenia.
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A glossary for dissemination and implementation research in health.
Rabin, Borsika A; Brownson, Ross C; Haire-Joshu, Debra; Kreuter, Matthew W; Weaver, Nancy L
2008-01-01
Dissemination and implementation (D&I) Research is increasingly Recognized as an important function of academia and is a growing priority for major health-related funders. Because D&I Research in the health field has emerged from Research traditions in diverse disciplines Ranging from agriculture to education, there are inconsistencies in the use and meaning of terms and main concepts. This glossary provides definitions for the key concepts and terms of D&I Research in health (in both public health and clinical settings). Definitions are organized under five major sections: (1) foundation concepts; (2) types of Research; (3) models, theories, and frameworks; (4) factors influencing the D&I processes; and (5) measurement/evaluation of the D&I process. The aim of this glossary is to aid in the development of more standardized and established terminology for D&I Research, facilitate the communication across different stakeholders, and ultimately contribute to higher-quality D&I Research.
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[Trattamento farmacologico del disturbo da uso di alcol. Evidenze scientifiche].
Attilia, Fabio; Perciballi, Roberta; Rotondo, Claudia; Capriglione, Ida; Iannuzzi, Silvia; Attilia, Maria Luisa; Vitali, Mario; Alessandrini, Giovanni; Scamporrino, Maria Concetta Marcella; Fiore, Marco; Ceccanti, Mauro
2018-01-01
RIASSUNTO. La terapia farmacologica nei pazienti con disturbo da uso di alcol riveste un ruolo centrale nel progetto terapeutico, altamente contestualizzato in un approccio multidisciplinare. Sebbene i trattamenti non farmacologici per la dipendenza da alcol risultino ben strutturati e in continua evoluzione, dal punto di vista medico le possibilità di intervento sono realmente ristrette, con poche molecole a disposizione approvate per il disturbo da uso di alcol: nello specifico, l'acamprostato, il naltrexone e, più recentemente, il nalmefene tra gli anticraving; il disulfiram tra gli avversivanti. Nuovi approcci sperimentali stanno cercando di ampliare tale gamma attraverso l'utilizzo di farmaci off-label. Evidenze scientifiche devono supportare l'indicazione terapeutica, quest'ultima deve dimostrarsi "cucita" sulle esigenze del paziente e sulle comorbilità presenti tenendo conto del profilo bio-psico-sociale individuale. Fondamentale risulta il follow-up per valutare la ritenzione in trattamento e il monitoraggio degli outcome alcologici.
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Application of the diligence inventory in dental education.
Jasinevicius, T R; Bernard, H; Schuttenberg, E M
1998-04-01
The fifty-five-item Diligence Inventory for Higher Education (DI-HE) was applied to a new subject group--190 dental students. After item and factor analysis, a fifty-item (four subscale) inventory best reflected this group. The DI-HE's split half reliability was 0.81 (p < 0.001), the reliability coefficient for the pre- and post-test was 0.68 (p < 0.01), and the correlation coefficient alpha was 0.90. The DI-HE scores were high, with no statistical differences among the four classes. Overall, significant relationships were found between grade point averages (GPAs) and DI-HE total and subscale scores, with r values as high as 0.44. While female students' DI-HE scores were significantly higher (p = 0.023) than male students' scores, no correlations between DI-HE scores and GPAs for females were found. The results suggest that DI-HE may be useful for assessment purposes in professional education.
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A High-Order Test for Optimality of Bang-Bang Controls.
1983-11-01
Systems * Istituto di Matematica Applicata, Universitl di Padova, ITALY. sponsored by the United States Army under Contract No. DAAG29-80-C-0041...the first order variation at the terminal point of the trajectory lim [x(T,u ) - x(TW)]/E (1.1) Istituto di Matematica Applicata, Universitl di Padova
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40 CFR 721.10261 - Oxime, di-Me silane (generic).
Code of Federal Regulations, 2013 CFR
2013-07-01
... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Oxime, di-Me silane (generic). 721... Substances § 721.10261 Oxime, di-Me silane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as oxime, di-Me silane (PMN P-09-589...
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40 CFR 721.10261 - Oxime, di-Me silane (generic).
Code of Federal Regulations, 2012 CFR
2012-07-01
... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Oxime, di-Me silane (generic). 721... Substances § 721.10261 Oxime, di-Me silane (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as oxime, di-Me silane (PMN P-09-589...
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40 CFR 721.2094 - N,N′-di(alkyl heteromonocycle)amino chlorotriazine.
Code of Federal Regulations, 2011 CFR
2011-07-01
... 40 Protection of Environment 31 2011-07-01 2011-07-01 false N,Nâ²-di(alkyl heteromonocycle)amino... Specific Chemical Substances § 721.2094 N,N′-di(alkyl heteromonocycle)amino chlorotriazine. (a) Chemical... as N,N′-di(alkyl heteromonocycle)amino chlorotriazine (PMN P-93-1369) is subject to reporting under...
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40 CFR 721.2094 - N,N′-di(alkyl heteromonocycle)amino chlorotriazine.
Code of Federal Regulations, 2010 CFR
2010-07-01
... 40 Protection of Environment 30 2010-07-01 2010-07-01 false N,Nâ²-di(alkyl heteromonocycle)amino... Specific Chemical Substances § 721.2094 N,N′-di(alkyl heteromonocycle)amino chlorotriazine. (a) Chemical... as N,N′-di(alkyl heteromonocycle)amino chlorotriazine (PMN P-93-1369) is subject to reporting under...
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Structural Analysis of the GGDEF-EAL Domain-Containing c-di-GMP Receptor FimX
DOE Office of Scientific and Technical Information (OSTI.GOV)
Navarro, M.; De, N; Bae, N
2009-01-01
Bacterial pathogenesis involves social behavior including biofilm formation and swarming, processes that are regulated by the bacterially unique second messenger cyclic di-GMP (c-di-GMP). Diguanylate cyclases containing GGDEF and phosphodiesterases containing EAL domains have been identified as the enzymes controlling cellular c-di-GMP levels, yet less is known regarding signal transmission and the targets of c-di-GMP. FimX, a protein from Pseudomonas aeruginosa that governs twitching motility, belongs to a large subfamily containing both GGDEF and EAL domains. Biochemical and structural analyses reveals its function as a high-affinity receptor for c-di-GMP. A model for full-length FimX was generated combining solution scattering data andmore » crystal structures of the degenerate GGDEF and EAL domains. Although FimX forms a dimer in solution via the N-terminal domains, a crystallographic EAL domain dimer suggests modes for the regulation of FimX by c-di-GMP binding. The results provide the structural basis for c-di-GMP sensing via degenerate phosphodiesterases.« less
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[Trattamento del disturbo da uso di alcol da un punto di vista psicologico].
Coriale, Giovanna; Fiorentino, Daniela; De Rosa, Francesca; Solombrino, Simona; Scalese, Bruna; Ciccarelli, Rosaria; Attilia, Fabio; Vitali, Mario; Musetti, Alessia; Fiore, Marco; Ceccanti, Mauro
2018-01-01
RIASSUNTO. L'elaborazione del piano di trattamento rappresenta un momento molto delicato e complesso del processo terapeutico del disturbo da abuso di alcol (DUA). È la fase in cui le informazioni raccolte da un'équipe di professionisti (medici, psicologi e assistenti sociali) (modello bio-psico-sociale del DUA) vengono messe insieme per decidere il percorso terapeutico più adatto. Per quanto riguarda la parte psicologica, è di notevole importanza scegliere un trattamento clinico in grado di ridurre al minimo la mancata adesione al trattamento e, per i soggetti che rimangono in trattamento, di garantirne l'efficacia. Se da una parte, le tecniche psicoanalitiche e comportamentali hanno fornito le basi della terapia psicologica dell'alcolismo, dall'altra, gli approcci basati sull'evidenza scientifica sono stati elaborati a partire dai principi del colloquio motivazionale e della terapia cognitivo-comportamentale. In questo articolo viene fornita una panoramica dei trattamenti che sono risultati più efficaci nel trattare il DUA e delle modalità temporali più adeguate per monitorare l'efficacia del trattamento.
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c-di-GMP is an Effective Immunomodulator and Vaccine Adjuvant Against Pneumococcal Infection
Ogunniyi, Abiodun D.; Paton, James C.; Kirby, Alun C.; McCullers, Jonathan A.; Cook, Jan; Hyodo, Mamoru; Hayakawa, Yoshihiro; Karaolis, David K. R.
2009-01-01
Cyclic diguanylate (c-di-GMP) is a unique bacterial intracellular signaling molecule capable of stimulating enhanced protective innate immunity against various bacterial infections. The effects of intranasal pretreatment with c-di-GMP, or intraperitoneal coadministration of c-di-GMP with the pneumolysin toxoid (PdB) or PspA before pneumococcal challenge, was investigated in mice. We found that c-di-GMP had no significant direct short-term effect on the growth rate of S. pneumoniae either in vitro or in vivo. However, intranasal pretreatment of mice with c-di-GMP resulted in significant decrease in bacterial load in lungs and blood after serotypes 2 and 3 challenge, and significant decrease in lung titers after serotype 4 challenge. Potential cellular mediators of these enhanced protective responses were identified in lungs and draining lymph nodes. Intraperitoneal coadministration of c-di-GMP with PdB or PspA before challenge resulted in significantly higher antigen-specific antibody titers and increased survival of mice, compared to that obtained with alum adjuvant. These findings demonstrate that local or systemic c-di-GMP administration stimulates innate and adaptive immunity against invasive pneumococcal disease. We propose that c-di-GMP can be used as an effective broad spectrum immunomodulator and vaccine adjuvant to prevent infectious diseases. PMID:18640167
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[Trattamento della dipendenza da alcol. Alcol e persone senza fissa dimora: punto di vista sociale].
Alessandrini, Giovanni; Ciccarelli, Rosaria; Battagliese, Gemma; Cereatti, Federica; Gencarelli, Simona; Messina, Marisa Patrizia; Vitali, Mario; De Rosa, Francesca; Ledda, Roberta; Mancini, Serena; Attilia, Maria Luisa
2018-01-01
RIASSUNTO. Il fenomeno delle persone senza fissa dimora sta assumendo in questi anni una rilevanza sociale devastante, con una prevalenza stimata in USA e in Europa compresa tra il 5,6% e il 13,9%. Queste persone hanno una scarsa qualità di vita, una limitata o assente vita sociale, sono spesso disoccupate o lavorano solo saltuariamente. Sono a rischio di problemi con la legge, sono spesso affette da dipendenza da droghe, da patologie psichiatriche e internistiche. L'alcol spesso non rappresenta la causa della loro condizione sociale, ma solo la conseguenza, contribuendo in questo modo al loro degrado bio-psico-sociale. Nel 2009 lo US Department of Housing and Urban Development's Homelessness Assistance Programs e nel 2010 la European Consensus Conference on Homelessness hanno segnato un grande passo avanti nella riabilitazione sociale di queste persone, utilizzando il concetto del "case management". In particolare lo Standard Case Management si è dimostrato in grado di migliorare la stabilità abitativa, di ridurre l'uso di droghe e di rimuovere le barriere lavorative. L'Assertive Community Treatment si è dimostrato, invece, in grado di migliorare la stabilità abitativa e ha un rapporto costo/beneficio migliore per i pazienti affetti da doppia diagnosi.
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Schäper, Simon; Steinchen, Wieland; Krol, Elizaveta; Altegoer, Florian; Skotnicka, Dorota; Bange, Gert; Becker, Anke
2017-01-01
Cyclic dimeric GMP (c-di-GMP) has emerged as a key regulatory player in the transition between planktonic and sedentary biofilm-associated bacterial lifestyles. It controls a multitude of processes including production of extracellular polysaccharides (EPSs). The PilZ domain, consisting of an N-terminal “RxxxR” motif and a β-barrel domain, represents a prototype c-di-GMP receptor. We identified a class of c-di-GMP–responsive proteins, represented by the AraC-like transcription factor CuxR in plant symbiotic α-proteobacteria. In Sinorhizobium meliloti, CuxR stimulates transcription of an EPS biosynthesis gene cluster at elevated c-di-GMP levels. CuxR consists of a Cupin domain, a helical hairpin, and bipartite helix-turn-helix motif. Although unrelated in sequence, the mode of c-di-GMP binding to CuxR is highly reminiscent to that of PilZ domains. c-di-GMP interacts with a conserved N-terminal RxxxR motif and the Cupin domain, thereby promoting CuxR dimerization and DNA binding. We unravel structure and mechanism of a previously unrecognized c-di-GMP–responsive transcription factor and provide insights into the molecular evolution of c-di-GMP binding to proteins. PMID:28559336
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Nakamura, Takashi; Miyabe, Hiroko; Hyodo, Mamoru; Sato, Yusuke; Hayakawa, Yoshihiro; Harashima, Hideyoshi
2015-10-28
Malignant melanomas escape immunosurveillance via the loss/down-regulation of MHC-I expression. Natural killer (NK) cells have the potential to function as essential effector cells for eliminating melanomas. Cyclic di-GMP (c-di-GMP), a ligand of the stimulator of interferon genes (STING) signal pathway, can be thought of as a new class of adjuvant against cancer. However, it is yet to be tested, because technologies for delivering c-di-GMP to the cytosol are required. Herein, we report that c-di-GMP efficiently activates NK cells and induces antitumor effects against malignant melanomas when loaded in YSK05 lipid containing liposomes, by assisting in the efficient delivery of c-di-GMP to the cytosol. The intravenous administration of c-di-GMP encapsulated within YSK05-liposomes (c-di-GMP/YSK05-Lip) into mice efficiently induced the production of type I interferon (IFN) as well as the activation of NK cells, resulting in a significant antitumor effect in a lung metastasis mouse model using B16-F10. This antitumor effect was dominated by NK cells. The infiltration of NK cells was observed in the lungs with B16-F10 melanomas. These findings indicate that the c-di-GMP/YSK05-Lip induces MHC-I non-restricted antitumor immunity mediated by NK cells. Consequently, c-di-GMP/YSK05-Lip represents a potentially new adjuvant system for use in immunotherapy against malignant melanomas. Copyright © 2015 Elsevier B.V. All rights reserved.
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Khan, Mike; Harms, Jerome S; Marim, Fernanda M; Armon, Leah; Hall, Cherisse L; Liu, Yi-Ping; Banai, Menachem; Oliveira, Sergio C; Splitter, Gary A; Smith, Judith A
2016-12-01
Brucella species are facultative intracellular bacteria that cause brucellosis, a chronic debilitating disease significantly impacting global health and prosperity. Much remains to be learned about how Brucella spp. succeed in sabotaging immune host cells and how Brucella spp. respond to environmental challenges. Multiple types of bacteria employ the prokaryotic second messenger cyclic di-GMP (c-di-GMP) to coordinate responses to shifting environments. To determine the role of c-di-GMP in Brucella physiology and in shaping host-Brucella interactions, we utilized c-di-GMP regulatory enzyme deletion mutants. Our results show that a ΔbpdA phosphodiesterase mutant producing excess c-di-GMP displays marked attenuation in vitro and in vivo during later infections. Although c-di-GMP is known to stimulate the innate sensor STING, surprisingly, the ΔbpdA mutant induced a weaker host immune response than did wild-type Brucella or the low-c-di-GMP guanylate cyclase ΔcgsB mutant. Proteomics analysis revealed that c-di-GMP regulates several processes critical for virulence, including cell wall and biofilm formation, nutrient acquisition, and the type IV secretion system. Finally, ΔbpdA mutants exhibited altered morphology and were hypersensitive to nutrient-limiting conditions. In summary, our results indicate a vital role for c-di-GMP in allowing Brucella to successfully navigate stressful and shifting environments to establish intracellular infection. Copyright © 2016, American Society for Microbiology. All Rights Reserved.
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Ginossar, Tamar; Heckman, Carolyn J; Cragun, Deborah; Quintiliani, Lisa M; Proctor, Enola K; Chambers, David A; Skolarus, Ted; Brownson, Ross C
2018-01-01
Physicians are charged with implementing evidence-based medicine, yet few are trained in the science of Dissemination and Implementation (D&I). In view of the potential of evidence-based training in D&I to help close the gap between research and practice, the goal of this review is to examine the importance of D&I training in medical education, describe challenges to implementing such training, and provide strategies and resources for building D&I capacity. We conducted (1) a systematic review to identify US-based D&I training efforts and (2) a critical review of additional literature to inform our evaluation of the challenges and opportunities of integrating D&I training in medical education. Out of 269 unique articles reviewed, 11 described US-based D&I training. Although vibrant and diverse training opportunities exist, their capacity is limited, and they are not designed to meet physicians' needs. Synthesis of relevant literature using a critical review approach identified challenges inherent to changing medical education, as well as challenges related to D&I science. Finally, selected strategies and resources are available for facilitating incorporation of D&I training into medical education and overcoming existing challenges. Integrating D&I training in the medical education curriculum, and particularly in residency and fellowship training, holds promise for bridging the chasm between scientific discoveries and improved patient care and outcomes. However, unique challenges should be addressed, including the need for greater evidence.
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Zhang, Y; Bunting, L D; Kappel, L C; Hafley, J L
1995-08-01
Two experiments were conducted to determine the seasonal effects of N fertilizer (NF) and defoliation interval (DI) on specific N fractions within annual ryegrass (AR) and overall usage of AR N by growing lambs. In Exp. 1, NF (0, 112, 224, and 336 kg of N/ha) and DI of 2, 4, or 6 wk were factorially applied to AR plots. Both decreasing DI and increasing NF increased N levels in AR in a manner that depended on harvest date (NF or DI x harvest date interaction, P < .05). The proportions of .2% NaOH soluble N or soluble protein N were not affected (P > .05) by NF or DI. Although NF had no effect (P > .05) on in situ disappearance of DM, decreasing the DI seemed to reduce the severity of the season-induced reduction in DM disappearance (DI x harvest date interaction, P = .04). In Exp. 2, NF (0 or 224 kg of N/ha) and a DI of 2 or 6 wk were factorially applied to AR plots. Fresh, frozen AR was fed in semipurified diets (48% of DM as AR) to four wether lambs (23 +/- 1.3 kg) using a 4 x 4 Latin square. Diets including AR had greater ruminal DM and plant N digestibilities when AR had a 2-wk vs a 6-wk DI with NF but had reduced digestibilities when AR had a 2-wk vs a 6-wk DI without NF.(ABSTRACT TRUNCATED AT 250 WORDS)
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NASA Astrophysics Data System (ADS)
Wasowski, J.; Chiaradia, M.; Bovenga, F.; Nutricato, R.; Nitti, D. O.; Milillo, G.; Guerriero, L.
2014-12-01
The improving temporal and spatial resolutions of new generation space-borne X-Band SAR sensors such as COSMO-SkyMed (CSK) constellation, and therefore their better monitoring capabilities, will guarantee increasing and more efficient use of multi-temporal interferometry (MTI) in landslide investigations. Thanks to their finer spatial resolution with respect to C-band data, X-band InSAR applications are very promising also for monitoring smaller landslides and single engineering structures sited on potentially unstable slopes. This work is focused on the detection of precursory signals of an impending slope failure from MTI time series of ground deformations obtained by exploiting 3 m resolution CSK data. We show the case of retrospectively captured pre-failure strains related to the landslide which occurred on January 2014 close to the town of Marina di Andora. The landslide caused the derailment of a train and the interruption of the railway line connecting north-western Italy to France. A dataset of 56 images acquired in STRIPMAP HIMAGE mode by CSK constellation from October 2008 to May 2014 was processed through SPINUA algorithm to derive the ground surface deformation map and the time series of displacement rates for each coherent radar target. We show that a cluster of moving targets coincides with the structures (buildings and terraces) affected by the 2014 landslide. The analysis of the MTI time series further shows that the targets had been moving since 2009, and thus could have provided a forewarning signal about ongoing slope or engineering structure instability. Although temporal landslide prediction remains difficult even via in situ monitoring, the presented case study indicates that MTI relying on high resolution radars such as CSK can provide very useful information for slope hazard mapping and possibly for early warning. Acknowledgments DIF provided contribution to data analysis within the framework of CAR-SLIDE project funded by MIUR (PON01_00536).
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Pratheesh, Ravindran; Swallow, Diane Margaret A; Rajaratnam, Simon; Jacob, K S; Chacko, Geeta; Joseph, Mathew; Chacko, Ari G
2013-06-01
This study aims to determine the incidence, predictors, early post-operative course of diabetes insipidus (DI) in paediatric craniopharyngiomas(CP) and compare the findings with adults. Retrospective analysis of clinical, biochemical, radiological and operative data for 102 consecutive CP surgeries (45 paediatric and 57 adult cases) was done. Bivariate and multivariate analyses were done to determine the predictors of DI. The incidence of the triphasic response and electrolyte abnormalities in the first post-operative week was compared between children and adults. Children had larger tumours and higher incidence of cystic tumours and hydrocephalus. Preoperative DI was close to 15 % in both the age groups. Radical/subtotal excision was achieved in 58 % of children and 53 % of adults. The incidence of post-operative DI was 80 % and 63 % in children and adults, respectively. Children had significantly higher incidence of permanent DI (55.6 %). Radical excision in children (p = 0.000); previous tumour surgery (p = 0.014) and new onset hypopituitarism (p = 0.019) in adults were associated with permanent DI. The triphasic response (23 %), wide intra-day serum sodium fluctuations and hyponatraemia were more common in children. Post-operative DI is a frequent and significant cause of morbidity in children undergoing surgery for CP. Children have a higher incidence of permanent DI. Radical excision is a predictor of permanent DI in children, whereas previous tumour excision and new onset hypopituitarism were predictors of permanent DI among adults. The management of post-operative DI is more difficult in children and the treating physician needs to be alert to detect the triphasic response.
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Cooper, Peter D; Petrovsky, Nikolai
2011-05-01
We report a novel isoform of β-D-[2 → 1] poly(fructo-furanosyl) α-D-glucose termed delta inulin (DI), comparing it with previously described alpha (AI), beta (BI) and gamma (GI) isoforms. In vitro, DI is the most immunologically active weight/weight in human complement activation and in binding to monocytes and regulating their chemokine production and cell surface protein expression. In vivo, this translates into potent immune adjuvant activity, enhancing humoral and cellular responses against co-administered antigens. As a biocompatible polysaccharide particle, DI is safe and well tolerated by subcutaneous or intramuscular injection. Physico-chemically, DI forms as an insoluble precipitate from an aqueous solution of suitable AI, BI or GI held at 37-48°C, whereas the precipitate from the same solution at lower temperatures has the properties of AI or GI. DI can also be produced by heat conversion of GI suspensions at 56°C, whereas GI is converted from AI at 45°C. DI is distinguished from GI by its higher temperature of solution in dilute aqueous suspension and by its lower solubility in dimethyl sulfoxide, both consistent with greater hydrogen bonding in DI's polymer packing structure. DI suspensions can be dissolved by heat, re-precipitated by cooling as AI and finally re-converted back to DI by repeated heat treatment. Thus, DI, like the previously described inulin isoforms, reflects the formation of a distinct polymer aggregate packing structure via reversible noncovalent bonding. DI forms the basis for a potent new human vaccine adjuvant and further swells the growing family of carbohydrate structures with immunological activity.
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Postoperative Copeptin Concentration Predicts Diabetes Insipidus After Pituitary Surgery.
Winzeler, Bettina; Zweifel, Christian; Nigro, Nicole; Arici, Birsen; Bally, Martina; Schuetz, Philipp; Blum, Claudine Angela; Kelly, Christopher; Berkmann, Sven; Huber, Andreas; Gentili, Fred; Zadeh, Gelareh; Landolt, Hans; Mariani, Luigi; Müller, Beat; Christ-Crain, Mirjam
2015-06-01
Copeptin is a stable surrogate marker of vasopressin release; the peptides are stoichiometrically secreted from the neurohypophysis due to elevated plasma osmolality or nonosmotic stress. We hypothesized that following stress from pituitary surgery, patients with neurohypophyseal damage and eventual diabetes insipidus (DI) would not exhibit the expected pronounced copeptin elevation. The objective was to evaluate copeptin's accuracy to predict DI following pituitary surgery. This was a prospective multicenter observational cohort study. Three Swiss or Canadian referral centers were used. Consecutive pituitary surgery patients were included. Copeptin was measured postoperatively daily until discharge. Logistic regression models and diagnostic performance measures were calculated to assess relationships of postoperative copeptin levels and DI. Of 205 patients, 50 (24.4%) developed postoperative DI. Post-surgically, median [25th-75th percentile] copeptin levels were significantly lower in patients developing DI vs those not showing this complication: 2.9 [1.9-7.9] pmol/L vs 10.8 [5.2-30.4] pmol/L; P < .001. Logistic regression analysis revealed strong association between postoperative copeptin concentrations and DI even after considering known predisposing factors for DI: adjusted odds ratio (95% confidence interval) 1.41 (1.16-1.73). DI was seen in 22/27 patients with copeptin <2.5 pmol/L (positive predictive value, 81%; specificity, 97%), but only 1/40 with copeptin >30 pmol/L (negative predictive value, 95%; sensitivity, 94%) on postoperative day 1. Lack of standardized DI diagnostic criteria; postoperative blood samples for copeptin obtained during everyday care vs at fixed time points. In patients undergoing pituitary procedures, low copeptin levels despite surgical stress reflect postoperative DI, whereas high levels virtually exclude it. Copeptin therefore may become a novel tool for early goal-directed management of postoperative DI.
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Coordinated Cyclic-Di-GMP Repression of Salmonella Motility through YcgR and Cellulose
Zorraquino, Violeta; García, Begoña; Latasa, Cristina; Echeverz, Maite; Toledo-Arana, Alejandro; Valle, Jaione
2013-01-01
Cyclic di-GMP (c-di-GMP) is a secondary messenger that controls a variety of cellular processes, including the switch between a biofilm and a planktonic bacterial lifestyle. This nucleotide binds to cellular effectors in order to exert its regulatory functions. In Salmonella, two proteins, BcsA and YcgR, both of them containing a c-di-GMP binding PilZ domain, are the only known c-di-GMP receptors. BcsA, upon c-di-GMP binding, synthesizes cellulose, the main exopolysaccharide of the biofilm matrix. YcgR is dedicated to c-di-GMP-dependent inhibition of motility through its interaction with flagellar motor proteins. However, previous evidences indicate that in the absence of YcgR, there is still an additional element that mediates motility impairment under high c-di-GMP levels. Here we have uncovered that cellulose per se is the factor that further promotes inhibition of bacterial motility once high c-di-GMP contents drive the activation of a sessile lifestyle. Inactivation of different genes of the bcsABZC operon, mutation of the conserved residues in the RxxxR motif of the BcsA PilZ domain, or degradation of the cellulose produced by BcsA rescued the motility defect of ΔycgR strains in which high c-di-GMP levels were reached through the overexpression of diguanylate cyclases. High c-di-GMP levels provoked cellulose accumulation around cells that impeded flagellar rotation, probably by means of steric hindrance, without affecting flagellum gene expression, exportation, or assembly. Our results highlight the relevance of cellulose in Salmonella lifestyle switching as an architectural element that is both essential for biofilm development and required, in collaboration with YcgR, for complete motility inhibition. PMID:23161026
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Remote Sensing Global Surface Air Pressure Using Differential Absorption BArometric Radar (DiBAR)
NASA Technical Reports Server (NTRS)
Lin, Bing; Harrah, Steven; Lawrence, Wes; Hu, Yongxiang; Min, Qilong
2016-01-01
Tropical storms and severe weathers are listed as one of core events that need improved observations and predictions in World Meteorological Organization and NASA Decadal Survey (DS) documents and have major impacts on public safety and national security. This effort tries to observe surface air pressure, especially over open seas, from space using a Differential-absorption BArometric Radar (DiBAR) operating at the 50-55 gigahertz O2 absorption band. Air pressure is among the most important variables that affect atmospheric dynamics, and currently can only be measured by limited in-situ observations over oceans. Analyses show that with the proposed space radar the errors in instantaneous (averaged) pressure estimates can be as low as approximately 4 millibars (approximately 1 millibar under all weather conditions). With these sea level pressure measurements, the forecasts of severe weathers such as hurricanes will be significantly improved. Since the development of the DiBAR concept about a decade ago, NASA Langley DiBAR research team has made substantial progress in advancing the concept. The feasibility assessment clearly shows the potential of sea surface barometry using existing radar technologies. The team has developed a DiBAR system design, fabricated a Prototype-DiBAR (P-DiBAR) for proof-of-concept, conducted lab, ground and airborne P-DiBAR tests. The flight test results are consistent with the instrumentation goals. Observational system simulation experiments for space DiBAR performance based on the existing DiBAR technology and capability show substantial improvements in tropical storm predictions, not only for the hurricane track and position but also for the hurricane intensity. DiBAR measurements will lead us to an unprecedented level of the prediction and knowledge on global extreme weather and climate conditions.
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Use of ferrous iron by metallo-β-lactamases.
Cahill, Samuel T; Tarhonskaya, Hanna; Rydzik, Anna M; Flashman, Emily; McDonough, Michael A; Schofield, Christopher J; Brem, Jürgen
2016-10-01
Metallo-β-lactamases (MBLs) catalyse the hydrolysis of almost all β-lactam antibacterials including the latest generation carbapenems and are a growing worldwide clinical problem. It is proposed that MBLs employ one or two zinc ion cofactors in vivo. Isolated MBLs are reported to use transition metal ions other than zinc, including copper, cadmium and manganese, with iron ions being a notable exception. We report kinetic and biophysical studies with the di-iron(II)-substituted metallo-β-lactamase II from Bacillus cereus (di-Fe(II) BcII) and the clinically relevant B1 subclass Verona integron-encoded metallo-β-lactamase 2 (di-Fe(II) VIM-2). The results reveal that MBLs can employ ferrous iron in catalysis, but with altered kinetic and inhibition profiles compared to the zinc enzymes. A crystal structure of di-Fe(II) BcII reveals only small overall changes in the active site compared to the di-Zn(II) enzyme including retention of the di-metal bridging water; however, the positions of the metal ions are altered in the di-Fe(II) compared to the di-Zn(II) structure. Stopped-flow analyses reveal that the mechanism of nitrocefin hydrolysis by both di-Fe(II) BcII and di-Fe(II) VIM-2 is altered compared to the di-Zn(II) enzymes. Notably, given that the MBLs are the subject of current medicinal chemistry efforts, the results raise the possibility the Fe(II)-substituted MBLs may be of clinical relevance under conditions of low zinc availability, and reveal potential variation in inhibitor activity against the differently metallated MBLs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
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Cyclic di-GMP: the First 25 Years of a Universal Bacterial Second Messenger
Galperin, Michael Y.; Gomelsky, Mark
2013-01-01
SUMMARY Twenty-five years have passed since the discovery of cyclic dimeric (3′→5′) GMP (cyclic di-GMP or c-di-GMP). From the relative obscurity of an allosteric activator of a bacterial cellulose synthase, c-di-GMP has emerged as one of the most common and important bacterial second messengers. Cyclic di-GMP has been shown to regulate biofilm formation, motility, virulence, the cell cycle, differentiation, and other processes. Most c-di-GMP-dependent signaling pathways control the ability of bacteria to interact with abiotic surfaces or with other bacterial and eukaryotic cells. Cyclic di-GMP plays key roles in lifestyle changes of many bacteria, including transition from the motile to the sessile state, which aids in the establishment of multicellular biofilm communities, and from the virulent state in acute infections to the less virulent but more resilient state characteristic of chronic infectious diseases. From a practical standpoint, modulating c-di-GMP signaling pathways in bacteria could represent a new way of controlling formation and dispersal of biofilms in medical and industrial settings. Cyclic di-GMP participates in interkingdom signaling. It is recognized by mammalian immune systems as a uniquely bacterial molecule and therefore is considered a promising vaccine adjuvant. The purpose of this review is not to overview the whole body of data in the burgeoning field of c-di-GMP-dependent signaling. Instead, we provide a historic perspective on the development of the field, emphasize common trends, and illustrate them with the best available examples. We also identify unresolved questions and highlight new directions in c-di-GMP research that will give us a deeper understanding of this truly universal bacterial second messenger. PMID:23471616
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Teymouri, Manouchehr; Barati, Nastaran; Pirro, Matteo; Sahebkar, Amirhosein
2018-01-01
Dimethoxycurcumin (DiMC) is a synthetic analog of curcumin with superior inter-related pro-oxidant and anti-cancer activity, and metabolic stability. Numerous studies have shown that DiMC reserves the biologically beneficial features, including anti-inflammatory, anti-carcinogenic, and cytoprotective properties, almost to the same extent as curcumin exhibits. DiMC lacks the phenolic-OH groups as opposed to curcumin, dimethoxycurcumin, and bis-demethoxycurcumin that all vary in the number of methoxy groups per molecule, and has drawn the attentions of researchers who attempted to discover the structure-activity relationship (SAR) of curcumin. In this regard, tetrahydrocurcumin (THC), the reduced and biologically inert metabolite of curcumin, denotes the significance of the conjugated α,β diketone moiety for the curcumin activity. DiMC exerts unique molecular activities compared to curcumin, including induction of androgen receptor (AR) degradation and suppression of the transcription factor activator protein-1 (AP-1). The enhanced AR degradation on DiMC treatment suggests it as a novel anticancer agent against resistant tumors with androgenic etiology. Further, DiMC might be a potential treatment for acne vulgaris. DiMC induces epigenetic alteration more effectively than curcumin, although both showed no direct DNA hypomethylating activity. Given the metabolic stability, nanoparticulation of DiMC is more promising for in vivo effectiveness. However, studies in this regard are still in its infancy. In the current review, we portray the various molecular and biological functions of DiMC reported so far. Whenever possible, the efficiency is compared with curcumin and the reasons for DiMC being more metabolically stable are elaborated. We also provide future perspective investigations with respect to varying DiMC-nanoparticles. © 2016 Wiley Periodicals, Inc.
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Post-operative diabetes insipidus after endoscopic transsphenoidal surgery.
Schreckinger, Matthew; Walker, Blake; Knepper, Jordan; Hornyak, Mark; Hong, David; Kim, Jung-Min; Folbe, Adam; Guthikonda, Murali; Mittal, Sandeep; Szerlip, Nicholas J
2013-12-01
Diabetes insipidus (DI) after endoscopic transsphenoidal surgery (ETSS) can lead to increased morbidity, longer hospital stays, and increased medication requirements. Predicting which patients are at high risk for developing DI can help direct services to ensure adequate care and follow-up. The objective of this study was to review our institution's experience with ETSS and determine which clinical/laboratory variables are associated with DI in this patient population. The authors wanted to see if there was an easily determined single value that would help predict which patients develop DI. This represents the largest North American series of this type. We retrospectively reviewed the charts of patients who had undergone ETSS for resection of sellar and parasellar pathology between 2006 and 2011. We examined patient and tumor characteristics and their relationship to postoperative DI. Out of 172 endoscopic transsphenoidal surgeries, there were 15 cases of transient DI (8.7%) and 14 cases of permanent DI (8.1%). Statistically significant predictors of postoperative DI (p < 0.05) included tumor volume and histopathology (Rathke's cleft cyst and craniopharyngioma). Significant indicators of development of DI were postoperative serum sodium, preoperative to postoperative change in sodium level, and urine output prior to administration of 1-deamino-8-D-arginine vasopressin. An increase in serum sodium of ≥2.5 mmol/L is a positive marker of development of DI with 80% specificity, and a postoperative serum sodium of ≥145 mmol/L is a positive indicator with 98% specificity. Identifying perioperative risk factors and objective indicators of DI after ETSS will help physicians care for patients postoperatively. In this large series, we demonstrated that there were multiple perioperative risk factors for the development of DI. These findings, which are consistent with other reports from microscopic surgical series, will help identify patients at risk for diabetes insipidus, aid in planning treatment algorithms, and increase vigilance in high risk patients.
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Shakuntala, K; Naveen, S; Lokanath, N K; Suchetan, P A
2017-05-01
The crystal structures of three isomeric compounds of formula C 14 H 13 Cl 2 NO 2 S, namely 3,5-di-chloro- N -(2,3-di-methyl-phen-yl)-benzene-sulfonamide (I), 3,5-di-chloro- N -(2,6-di-methyl-phen-yl)benzene-sulfonamide (II) and 3,5-di-chloro- N -(3,5-di-methyl-phen-yl)benzene-sulfonamide (III) are described. The mol-ecules of all the three compounds are U-shaped with the two aromatic rings inclined at 41.3 (6)° in (I), 42.1 (2)° in (II) and 54.4 (3)° in (III). The mol-ecular conformation of (II) is stabilized by intra-molecular C-H⋯O hydrogen bonds and C-H⋯π inter-actions. The crystal structure of (I) features N-H⋯O hydrogen-bonded R 2 2 (8) loops inter-connected via C (7) chains of C-H⋯O inter-actions, forming a three-dimensional architecture. The structure also features π-π inter-actions [ Cg ⋯ Cg = 3.6970 (14) Å]. In (II), N-H⋯O hydrogen-bonded R 2 2 (8) loops are inter-connected via π-π inter-actions [inter-centroid distance = 3.606 (3) Å] to form a one-dimensional architecture running parallel to the a axis. In (III), adjacent C (4) chains of N-H⋯O hydrogen-bonded mol-ecules running parallel to [010] are connected via C-H⋯π inter-actions, forming sheets parallel to the ab plane. Neighbouring sheets are linked via offset π-π inter-actions [inter-centroid distance = 3.8303 (16) Å] to form a three-dimensional architecture.
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Stonis, Jonas R; Diškus, Arūnas; Remeikis, Andrius; Gerulaitis, Virginijus; Karsholt, Ole
2016-11-01
The monograph treats 29 species of leaf-mining pygmy moths (Insecta, Lepidoptera, Nepticulidae) discovered in the northern Andean bush and grass páramo and the central Andean puna at altitudes above 3700 m. They represent the world's highest-altitudinal Nepticulidae fauna known. The height record belongs to Stigmella nivea sp. nov. from Peru collected at an elevation of 4700 m. Except for one species, all belong to Stigmella Schrank. Twenty-two of the species recorded are new and are named and described in the current paper: Stigmella paramica Diškus & Stonis, sp. nov.; S. lachemillae Diškus & Stonis, sp. nov.; S. gynoxyphaga Diškus & Stonis, sp. nov.; S. calceolariae Diškus & Stonis, sp. nov.; S. rigida Diškus & Stonis, sp. nov.; S. altiplanica Diškus & Stonis, sp. nov.; S. robusta Remeikis & Stonis, sp. nov.; S. pseudorobusta Remeikis & Stonis, sp. nov.; S. auriargentata Remeikis & Stonis, sp. nov.; S. altimontana Remeikis & Stonis, sp. nov.; S. pandora Remeikis & Stonis, sp. nov.; S. ampla Diškus & Stonis, sp. nov.; S. evanida Diškus & Stonis, sp. nov.; S. mustelina Remeikis & Stonis, sp. nov.; S. angusta Diškus & Stonis, sp. nov.; S. alticosma Remeikis & Stonis, sp. nov.; S. nivea Remeikis & Stonis, sp. nov.; S. kristenseni Diškus & Stonis, sp. nov.; S. lobata Remeikis & Stonis, sp. nov.; S. ageratinae Diškus & Stonis, sp. nov.; S. clinopodiella Diškus & Stonis, sp. nov.; and S. calceolarifoliae Diškus & Stonis, sp. nov. Some of these species are leaf-miners on Asteraceae (Pentacalia, Baccharis, Gynoxys, and Ageratina plants), Calceolariaceae (Calceolaria), Lamiaceae (Clinopodium), and Rosaceae (Lachemilla). Twenty species are known only from adults with no data on their biology and host-plants. In addition, we present data and discuss recently discovered nepticulid taxa associated with Polylepis forests that is the natural vegetation in much of the High Andes. All High-Andean Stigmella species treated are illustrated with photographs of the adults and genitalia, distribution maps, including some with photographs of the leaf-mines and habitats.
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A new adjuvant delivery system 'cyclic di-GMP/YSK05 liposome' for cancer immunotherapy.
Miyabe, Hiroko; Hyodo, Mamoru; Nakamura, Takashi; Sato, Yusuke; Hayakawa, Yoshihiro; Harashima, Hideyoshi
2014-06-28
Cyclic dinucleotides are of importance in the field of microbiology and immunology. They function as second messengers and are thought to participate in the signal transduction of cytosolic DNA immune responses. One such dinucleotide, cyclic di-GMP (c-di-GMP), stimulates the immune system. It is thought that c-di-GMP is recognized by ATP dependent RNA helicase (DDX41) in the cytosol, forms a complex with the Stimulator of interferon genes protein (STING), triggers a signal via the tank binding kinase 1-interferon regulatory factor 3 (TBK1-IRF3) pathway and induces the production of type I interferons. Therefore c-di-GMP can be thought of as a new class of adjuvant. However, because c-di-GMP contains two phosphate groups, this prevents its use as an adjuvant because it cannot pass through the cell membrane, even though the target molecule of c-di-GMP is located in the cytoplasm. Our group has been developing a series of liposomal drug delivery systems and recently investigated YSK05 which is a synthetic, pH sensitive lipid that has a high fusogenicity. We utilized this lipid as a carrier to transport c-di-GMP into the cytosol to then use c-di-GMP as an adjuvant. Based on screening experiments, YSK05/POPE/cholesterol=40/25/35 was found to induce IFN-β in Raw264.7 cells. The induction of IFN-β from c-di-GMP liposomes was inhibited by adding BX795, a TBK1 inhibitor, indicating that the production of IFN-β caused the activation of the STING-TBK1 pathway. C-di-GMP liposomes also showed significantly higher levels of expression of CD80, CD86 and MHC class I. The c-di-GMP/YSK05 liposome facilitated antigen specific cytotoxic T cell activity and the inhibition of tumor growth in a mouse model. These findings indicate that c-di-GMP/YSK05 liposomes could be used, not only to transfer c-di-GMP to the cytosol and induce an innate immune system but also as a platform for investigating the mechanism of immune sensing with cyclic dinucleotides in vitro and in vivo. Copyright © 2014 Elsevier B.V. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Liu, Nanjun; Tengstrand, Elizabeth A.; Chourb, Lisa
The inability to routinely monitor drug-induced phospholipidosis (DIPL) presents a challenge in pharmaceutical drug development and in the clinic. Several nonclinical studies have shown di-docosahexaenoyl (22:6) bis(monoacylglycerol) phosphate (di-22:6-BMP) to be a reliable biomarker of tissue DIPL that can be monitored in the plasma/serum and urine. The aim of this study was to show the relevance of di-22:6-BMP as a DIPL biomarker for drug development and safety assessment in humans. DIPL shares many similarities with the inherited lysosomal storage disorder Niemann–Pick type C (NPC) disease. DIPL and NPC result in similar changes in lysosomal function and cholesterol status that leadmore » to the accumulation of multi-lamellar bodies (myeloid bodies) in cells and tissues. To validate di-22:6-BMP as a biomarker of DIPL for clinical studies, NPC patients and healthy donors were classified by receiver operator curve analysis based on urinary di-22:6-BMP concentrations. By showing 96.7-specificity and 100-sensitivity to identify NPC disease, di-22:6-BMP can be used to assess DIPL in human studies. The mean concentration of di-22:6-BMP in the urine of NPC patients was 51.4-fold (p ≤ 0.05) above the healthy baseline range. Additionally, baseline levels of di-22:6-BMP were assessed in healthy non-medicated laboratory animals (rats, mice, dogs, and monkeys) and human subjects to define normal reference ranges for nonclinical/clinical studies. The baseline ranges of di-22:6-BMP in the plasma, serum, and urine of humans and laboratory animals were species dependent. The results of this study support the role of di-22:6-BMP as a biomarker of DIPL for pharmaceutical drug development and health care settings. - Highlights: • A reliable biomarker of drug-induced phospholipidosis (DIPL) is needed for humans. • Di-22:6-BMP is specific/sensitive for DIPL in animals as published in literatures. • The di-22:6-BMP biomarker can be validated for humans via NPC patients. • DIPL shares morphologic/mechanistic similarities with Niemann–Pick type C disease. • Di-22:6-BMP is an effective DIPL biomarker in humans via NPC patient validation.« less
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Yoshida, Asuka; Kawabata, Ryoko; Honda, Tomoyuki; Sakai, Kouji; Ami, Yasushi; Sakaguchi, Takemasa; Irie, Takashi
2018-03-01
One of the first defenses against infecting pathogens is the innate immune system activated by cellular recognition of pathogen-associated molecular patterns (PAMPs). Although virus-derived RNA species, especially copyback (cb)-type defective interfering (DI) genomes, have been shown to serve as real PAMPs, which strongly induce interferon-beta (IFN-β) during mononegavirus infection, the mechanisms underlying DI generation remain unclear. Here, for the first time, we identified a single amino acid substitution causing production of cbDI genomes by successful isolation of two distinct types of viral clones with cbDI-producing and cbDI-nonproducing phenotypes from the stock Sendai virus (SeV) strain Cantell, which has been widely used in a number of studies on antiviral innate immunity as a representative IFN-β-inducing virus. IFN-β induction was totally dependent on the presence of a significant amount of cbDI genome-containing viral particles (DI particles) in the viral stock, but not on deficiency of the IFN-antagonistic viral accessory proteins C and V. Comparison of the isolates indicated that a single amino acid substitution found within the N protein of the cbDI-producing clone was enough to cause the emergence of DI genomes. The mutated N protein of the cbDI-producing clone resulted in a lower density of nucleocapsids than that of the DI-nonproducing clone, probably causing both production of the DI genomes and their formation of a stem-loop structure, which serves as an ideal ligand for RIG-I. These results suggested that the integrity of mononegaviral nucleocapsids might be a critical factor in avoiding the undesirable recognition of infection by host cells. IMPORTANCE The type I interferon (IFN) system is a pivotal defense against infecting RNA viruses that is activated by sensing viral RNA species. RIG-I is a major sensor for infection with most mononegaviruses, and copyback (cb)-type defective interfering (DI) genomes have been shown to serve as strong RIG-I ligands in real infections. However, the mechanism underlying production of cbDI genomes remains unclear, although DI genomes emerge as the result of an error during viral replication with high doses of viruses. Sendai virus has been extensively studied and is unique in that its interaction with innate immunity reveals opposing characteristics, such as high-level IFN-β induction and strong inhibition of type I IFN pathways. Our findings provide novel insights into the mechanism of production of mononegaviral cbDI genomes, as well as virus-host interactions during innate immunity. Copyright © 2018 American Society for Microbiology.
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Code of Federal Regulations, 2013 CFR
2013-07-01
... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Siloxanes and Silicones, di-Me, Me... Substances § 721.10483 Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with...) The chemical substance identified as Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated...
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Code of Federal Regulations, 2014 CFR
2014-07-01
... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Siloxanes and Silicones, di-Me, Me... Substances § 721.10483 Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated, reaction products with...) The chemical substance identified as Siloxanes and Silicones, di-Me, Me vinyl, hydroxy-terminated...
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Two studies were designed to examine amniotic fluid and maternal urine concentrations of the di(2-ethylhexyl) phthalate (DEHP) metabolite mono(2-ethylhexyl) phthalate (MEHP) and the di-n-butyl phthalate (DBP) metabolite monobutyl phthalate (MBP) after administration of DEHP and D...
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Characteristics of sheltered homeless families.
Bassuk, E L; Rubin, L; Lauriat, A S
1986-01-01
To describe the characteristics of homeless families, we interviewed 80 homeless mothers and 151 children living in 14 family shelters in Massachusetts (two-thirds of the shelters in the state). Ninety-four per cent of the families were headed by women, 91 per cent were on AFDC (aid to families with dependent children), with twice as many as the state average having been on AFDC for at least two years; most had long histories of residential instability. Although 60 per cent had completed high school, only a third had worked for longer than one month. One-third of the mothers reported having been abused during their childhood, and two-thirds had experienced a major family disruption. At the time of the interview, almost two-thirds either lacked or had minimal supportive relationships and one-fourth of these named their child as the major support. Eighteen mothers were involved with the Department of Social Services because of probable child abuse or neglect. Seventy-one per cent of the mothers had personality disorders. In contrast to many adult homeless individuals, however, deinstitutionalized persons or those suffering from psychoses were not overrepresented. About 50 percent of the homeless children were found to have developmental lags, anxiety, depression, and learning difficulties, and about half required further psychiatric evaluation. Two-thirds described housing and social welfare agencies as not helpful. Given the many serious problems of the mothers and the difficulties already manifested by their children, comprehensive psychosocial and economic interventions must be made to interrupt a cycle of extreme instability and family breakdown. PMID:3740332
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Belnap, Starlie C; Lickliter, Robert
2017-06-01
Sensory-motor development begins early during embryogenesis and is influenced by sensory experience. Little is known about the prenatal factors that influence the development of motor coordination. Here we investigated whether and to what extent prenatal light experience can influence the development of motor coordination in bobwhite quail hatchlings. Quail embryos were incubated under four light conditions: no light (dark), 2h of total light (2HR), 6h of total light (6HR), and diffused sunlight (controls). Hatchlings were video recording walking down a runway at three developmental ages (12, 24, and 48h). Videos were assessed for forward locomotion, a measurement of motor coordination, falls, a measurement of motor instability, and motivation to complete the task. We anticipated a linear decline of coordination with a reduction in prenatal light experience and improved coordination with age. Furthermore, as motor coordination becomes more laborious we anticipated motivation to complete the task would decline. However, our findings revealed hatchlings did not uniformly improve with age as expected, nor did the reduction of light result in a linear reduction in motor coordination. Instead, we found a more complex relationship with 6HR and 2HR hatchlings showing distinct patterns of stability and instability. Similarly, we found a reduction in motivation within the 6HR light condition. It appears that prenatal light exposure influences the development of postnatal motor coordination and we discuss these finding in light of neurodevelopmental processes influenced by light experience. Copyright © 2017 Elsevier B.V. All rights reserved.
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Disparity between Clinical and Ultrasound Examinations in Neonatal Hip Screening.
Kyung, Bong Soo; Lee, Soon Hyuck; Jeong, Woong Kyo; Park, Si Young
2016-06-01
For early detection of developmental dysplasia of the hip (DDH), neonatal hip screening using clinical examination and/or ultrasound has been recommended. Although there have been many studies on the reliability of both screening techniques, there is still controversy in the screening strategies; clinical vs. selective or universal ultrasound screening. To determine the screening strategy, we assessed the agreement among the methods; clinical examination by an experienced pediatric orthopedic surgeon, sonographic morphology, and sonographic stability. From January 2004 to June 2009, a single experienced pediatric orthopedic surgeon performed clinical hip screenings for 2,686 infants in the neonatal unit and 43 infants who were referred due to impressions of hip dysplasia before 3 months of age. Among them, 156 clinically unstable or high-risk babies selectively received bilateral hip ultrasound examinations performed by the same surgeon using the modified Graf method. The results were analyzed statistically to detect any correlations between the clinical and sonographic findings. Although a single experienced orthopedic surgeon conducted all examinations, we detected only a limited relationship between the results of clinical and ultrasound examinations. Ninety-three percent of the clinically subluxatable hips were normal or immature based on static ultrasound examination, and 74% of dislocating hips and 67% of limited abduction hips presented with the morphology below Graf IIa. A total of 80% of clinically subluxatable, 42% of dislocating and 67% of limited abduction hips appeared stable or exhibited minor instability on dynamic ultrasound examination. About 7% of clinically normal hips were abnormal upon ultrasound examination; 5% showed major instability and 3% showed dysplasia above Graf IIc. Clinical stability had small coefficients between ultrasound examinations; 0.39 for sonographic stability and 0.37 for sonographic morphology. Between sonographic stability and morphology, although 71% of hips with major instability showed normal or immature morphology according to static ultrasound examination, the coefficient was as high as 0.64. Discrepancies between clinical and ultrasound examinations were present even if almost all of the exams were performed by a single experienced pediatric orthopedic surgeon. In relation to screening for DDH, it is recommended that both sonographic morphology and stability be checked in addition to clinical examination.
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Lin, Xinrong; Chapman Varela, Jennifer; Grinstaff, Mark W
2016-12-20
The chemical instability of the traditional electrolyte remains a safety issue in widely used energy storage devices such as Li-ion batteries. Li-ion batteries for use in devices operating at elevated temperatures require thermally stable and non-flammable electrolytes. Ionic liquids (ILs), which are non-flammable, non-volatile, thermally stable molten salts, are an ideal replacement for flammable and low boiling point organic solvent electrolytes currently used today. We herein describe the procedures to: 1) synthesize mono- and di-phosphonium ionic liquids paired with chloride or bis(trifluoromethane)sulfonimide (TFSI) anions; 2) measure the thermal properties and stability of these ionic liquids by differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA); 3) measure the electrochemical properties of the ionic liquids by cyclic voltammetry (CV); 4) prepare electrolytes containing lithium bis(trifluoromethane)sulfonamide; 5) measure the conductivity of the electrolytes as a function of temperature; 6) assemble a coin cell battery with two of the electrolytes along with a Li metal anode and LiCoO2 cathode; and 7) evaluate battery performance at 100 °C. We additionally describe the challenges in execution as well as the insights gained from performing these experiments.
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Proton behaviour, structure and elasticity of serpentine at high-pressure
NASA Astrophysics Data System (ADS)
Mookherjee, Mainak; Stixrude, Lars
2007-03-01
Serpentine occurs in oceanic crust as the alteration product of ultramafic rocks and is a possible candidate for carrying water to the deep earth. The presence of sub-surface serpentine may be manifested by mud volcanoes, high electrical conductivities, and seismic anomalies. Using density functional theory, we predict a phase transition in serpentine near 22 GPa. The phase transition is caused by a re-orientation of the hydroxyl vector coupled with changes in the di-trigonal rings of SiO4 tetrahedra. The symmetry of the crystal-structure remains unaffected. Evidence of pressure-induced hydrogen bonding is absent in serpentine, as evident from the reduction of O-H bond length upon compression. Results of compression for the low-pressure phase is well represented by a fourth order Birch-Murnaghan finite strain expression with KO= 63 GPa, K'O= 10.2 and KOK''O = -120, where K is the bulk modulus, prime indicates pressure derivatives, and O refers to zero pressure. At low pressures, the elastic constant tensor is highly anisotropic with C11^o ˜2.4xC33^o , and becomes more isotropic with compression. We find an elastic instability near 36 GPa that may be related to experimentally observed amorphization.
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Geo-database use to promote dengue infection prevention and control.
Wongbutdee, Jaruwan; Chaikoolvatana, Anun; Saengnill, Wacharapong; Krasuaythong, Nantaya; Phuphak, Surajit
2010-07-01
Dengue infection (DI) is a major health problem in Thailand and is especially prevalent in Ubon Ratchathani Province. The objectives of the project were: (1) to develop a geo-database system for DI prevention and control, (2) to perform an Aedes aegypti larval vector survey for DI prevention and control in Ubon Ratchathani Province, (3) to study the behavior and perceptions regarding DI prevention among the target population in Ubon Ratchathani Province. Ten villages with high incidences of DI over a 3 year period from 2005 to 2007 were selected. The survey was divided into 2 periods, pre-outbreak period (February-April 2008) and outbreak period (June-August 2008). The data were collected in April and June 2008. The households in each village were purposively sampled. Water containers inside and outside of the houses were surveyed using the World Health Organization's house index (HI), container index (CI), and Breteau index (BI). The location of each household was recorded using the global positioning system (GPS). Data regarding people's perceptions and behaviors concerning DI prevention were collected during interviews of 383 families in Mach 2008. A database for DI was developed using ArcView version 9.2. The results showed during the pre-outbreak period, Non Jig, Non Sawang, and Huai Teeneu villages had the highest risk level (BI > or =50). During the outbreak period, Non Jig and Huai Teeneu village had the highest risk level (BI > or =50). Results regarding DI perceptions showed the target population had high levels of DI perceptions. DI preventive behavior was found in 50.9%.
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Integration of the Second Messenger c-di-GMP into the Chemotactic Signaling Pathway
Russell, Matthew H.; Bible, Amber N.; Fang, Xin; Gooding, Jessica R.; Campagna, Shawn R.; Gomelsky, Mark; Alexandre, Gladys
2013-01-01
ABSTRACT Elevated intracellular levels of the bacterial second messenger c-di-GMP are known to suppress motility and promote sessility. Bacterial chemotaxis guides motile cells in gradients of attractants and repellents over broad concentration ranges, thus allowing bacteria to quickly adapt to changes in their surroundings. Here, we describe a chemotaxis receptor that enhances, as opposed to suppresses, motility in response to temporary increases in intracellular c-di-GMP. Azospirillum brasilense’s preferred metabolism is adapted to microaerophily, and these motile cells quickly navigate to zones of low oxygen concentration by aerotaxis. We observed that changes in oxygen concentration result in rapid changes in intracellular c-di-GMP levels. The aerotaxis and chemotaxis receptor, Tlp1, binds c-di-GMP via its C-terminal PilZ domain and promotes persistent motility by increasing swimming velocity and decreasing swimming reversal frequency, which helps A. brasilense reach low-oxygen zones. If c-di-GMP levels remain high for extended periods, A. brasilense forms nonmotile clumps or biofilms on abiotic surfaces. These results suggest that association of increased c-di-GMP levels with sessility is correct on a long-term scale, while in the short-term c-di-GMP may actually promote, as opposed to suppress, motility. Our data suggest that sensing c-di-GMP by Tlp1 functions similar to methylation-based adaptation. Numerous chemotaxis receptors contain C-terminal PilZ domains or other sensory domains, suggesting that intracellular c-di-GMP as well as additional stimuli can be used to modulate adaptation of bacterial chemotaxis receptors. PMID:23512960
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Noh, O Kyu; Park, Se Jin; Park, Hyeon Jin; Ju, HeeYoung; Han, Seung Hyon; Jung, Hyun Joo; Park, Jun Eun
2017-09-01
We aimed to investigate the prognostic value of DNA index (DI) in children with precursor B cell acute lymphoblastic lymphoma (pre-B ALL). From January 2003 to December 2014, 72 children diagnosed with pre-B ALL were analyzed. We analyzed the prognostic value of DI and its relations with other prognostic factors. The DI cut-point of 1.16 did not discriminate significantly the groups between high and low survivals (DI≥1.16 versus <1.16; 5-year OS, 90.5% vs. 82.8%, p =0.665). We explored the survivals according to the level of DI (<1.00, 1.00, 1.01-1.30, 1.31-1.60, 1.61-1.90, and >1.90), and the survival of children with a DI between 1.00-1.90 were significantly higher than that of children with DI of <1.00 or >1.90 (5-year OS, 90.6% vs. 50.0%, p <0.001). The DI of 1.16 was not a significant cut-point discriminating the risk group in children with pre-B ALL. However, the DI divided by specific ranges of values remained an independent prognostic factor. Further studies are warranted to re-evaluate the prognostic value and cut-point of DI in children treated with recent treatment protocols. © 2017 by the Association of Clinical Scientists, Inc.
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The cyclic-di-GMP signaling pathway in the Lyme disease spirochete, Borrelia burgdorferi
Novak, Elizabeth A.; Sultan, Syed Z.; Motaleb, Md. A.
2014-01-01
In nature, the Lyme disease spirochete Borrelia burgdorferi cycles between the unrelated environments of the Ixodes tick vector and mammalian host. In order to survive transmission between hosts, B. burgdorferi must be able to not only detect changes in its environment, but also rapidly and appropriately respond to these changes. One manner in which this obligate parasite regulates and adapts to its changing environment is through cyclic-di-GMP (c-di-GMP) signaling. c-di-GMP has been shown to be instrumental in orchestrating the adaptation of B. burgdorferi to the tick environment. B. burgdorferi possesses only one set of c-di-GMP-metabolizing genes (one diguanylate cyclase and two distinct phosphodiesterases) and one c-di-GMP-binding PilZ-domain protein designated as PlzA. While studies in the realm of c-di-GMP signaling in B. burgdorferi have exploded in the last few years, there are still many more questions than answers. Elucidation of the importance of c-di-GMP signaling to B. burgdorferi may lead to the identification of mechanisms that are critical for the survival of B. burgdorferi in the tick phase of the enzootic cycle as well as potentially delineate a role (if any) c-di-GMP may play in the transmission and virulence of B. burgdorferi during the enzootic cycle, thereby enabling the development of effective drugs for the prevention and/or treatment of Lyme disease. PMID:24822172
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Evaluation of skeletal maturation using mandibular third molar development in Indian adolescents.
Mehta, Nishit; Patel, Dolly; Mehta, Falguni; Gupta, Bhaskar; Zaveri, Grishma; Shah, Unnati
2016-01-01
This study was done with the following objectives: to estimate dental maturity using the Demirjian Index (DI) for the mandibular third molar; to investigate the relationship between dental maturity and skeletal maturity among growing patients; to evaluate the use of the mandibular third molar as an adjunctive tool for adolescent growth assessment in combination with the cervical vertebrae; to evaluate the clinical value of the third molar as a growth evaluation index. Samples were derived from panoramic radiographs and lateral cephalograms of 615 subjects (300 males and 315 females) of ages ranging 9-18 years, and estimates of dental maturity (DI) and skeletal maturity [cervical vertebrae maturation indicators (CVMI)] were made. A highly significant association (r = 0.81 for males and r = 0.72 for females) was found between DI and CVMI. DI Stage B corresponded to Stage 2 of CVMI (prepeak of pubertal growth spurt) in both sexes. In males, DI stages C and D represent the peak of the pubertal growth spurt. In females, stages B and C show that the peak of the pubertal growth spurt has not been passed. DI stage E in females and DI Stage F in males correlate that the peak of the pubertal growth spurt has been passed. A highly significant association exists between DI and CVMI. Mandibular third molar DI stages are reliable adjunctive indicators of skeletal maturity.
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Lista dei caratteri macroscopici per l’identificazione dei legni
Flavio Ruffinatto; Alan Crivellaro; Alex C. Wiedenhoeft
2016-01-01
Lâidentificazione dei legni costituisce il primo passo per ottenere conoscenze indispensabili in molti ambiti di studio. Ad esempio, prima di eseguire il restauro di un manufatto di interesse culturale è indispensabile conoscere il nome dei legni che lo compongono. Oppure, nel caso in cui si sospetti che un legno protetto da convenzioni internazionali sia stato...
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European Conference on Visual Perception (6th).
1983-11-30
Institut fuer Verhaltenswissenschaft, ETH- Zentrum, 8092 Zuerich - Switzerland W. GERBINO: Istituto di Psicologia , Universitk di Padova, Piazza Capitaniato...fuer medizinische Psychologie, Schillerstrasse 42 - 8000 Muenchen 2, West Germany L. JANEZ ESCALADA: Psicologia Matem&tica, Facultad de Psicologla...Norway P. MANCINI: Istituto di Fisiologia clinica del C.N.R., Via Bonanno Pisano - 56100 Pisa, Italy C.A. MARZI: Istituto di Psicologia . Universit
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An individual (male, 36 years, 87 kg) ingested two separate doses of di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP) at a rate of ~60 µg/kg. Key monoester and oxidized metabolites were identified and quantified in urine continuously collected until 48 hours post dos...
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Diabetes insipidus following resection of pituitary tumors.
Schreckinger, Matthew; Szerlip, Nicholas; Mittal, Sandeep
2013-02-01
Diabetes insipidus (DI) is a common complication following pituitary surgery and can be transient or permanent. Neurogenic DI occurs following injury to the magnocellular neurons in the hypothalamus that produce and transport arginine vasopressin (AVP) and form the hypothalamo-hypophyseal tract. DI is defined by a constellation of signs and symptoms resulting in dilute high-volume urine output and increasing serum osmolality. The body's inability to concentrate urine leaves the patient dehydrated and leads to metabolic abnormalities that can be life threatening if not recognized and treated in a timely manner with an exogenous AVP analog. The reported incidence of postsurgical central DI varies from 1 to 67%. This wide range likely reflects inconsistencies in the working definition of DI across the literature. Factors affecting the rate of DI include pituitary tumor size, adherence to surrounding structures, surgical approach, and histopathology of pituitary lesion. The likelihood of postoperative DI can be reduced by careful preservation of the neurovascular structures of the hypothalamus, infundibulum, and neurohypophysis. Vigilance and meticulous surgical technique are essential to minimize injury to these critical regions that can lead to postsurgical DI. Copyright © 2012 Elsevier B.V. All rights reserved.
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The Effect of a Shear Flow on the Uptake of LDL and Ac-LDL by Cultured Vascular Endothelial Cells
NASA Astrophysics Data System (ADS)
Niwa, Koichi; Karino, Takeshi
The effects of a shear flow on the uptake of fluorescence-labeled low-density lipoprotein (DiI-LDL), acetylated LDL (DiI-Ac-LDL), and lucifer yellow (LY; a tracer of fluid-phase endocytosis) by cultured bovine aortic ECs were studied using a rotating-disk shearing apparatus. It was found that 2hours’ exposure of ECs to a laminar shear flow that imposed ECs an area-mean shear stress of 10dynes/cm2 caused an increase in the uptake of DiI-LDL and LY. By contrast, the uptake of DiI-Ac-LDL was decreased by exposure of the ECs to a shear flow. Addition of dextran sulfate (DS), a competitive inhibitor of scavenger receptors, reversed the effect of a shear flow on the uptake of DiI-Ac-LDL, resulting in an increase by the imposition of a shear flow, while the uptake of DiI-LDL and LY remained unaffected. It was concluded that a shear flow promotes the endocytosis of DiI-LDL and LY by ECs, but suppresses the uptake of DiI-Ac-LDL by ECs by inhibiting scavenger receptor-mediated endocytosis.
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NASA Astrophysics Data System (ADS)
De Vido, M.; Ertel, K.; Mason, P. D.; Banerjee, S.; Phillips, P. J.; Smith, J. M.; Butcher, T. J.; Chekhlov, O.; Divoky, M.; Pilar, J.; Hooker, C.; Shaikh, W.; Lucianetti, A.; Hernandez-Gomez, C.; Mocek, T.; Edwards, C.; Collier, J. L.
2017-02-01
In this paper, we review the development, at the STFC's Central Laser Facility (CLF), of high energy, high repetition rate diode-pumped solid-state laser (DPSSL) systems based on cryogenically-cooled multi-slab ceramic Yb:YAG. Up to date, two systems have been completed, namely the DiPOLE prototype and the DiPOLE100 system. The DiPOLE prototype has demonstrated amplification of nanosecond pulses in excess of 10 J at 10 Hz repetition rate with an opticalto- optical efficiency of 22%. The larger scale DiPOLE100 system, designed to deliver 100J temporally-shaped nanosecond pulses at 10 Hz repetition rate, has been developed at the CLF for the HiLASE project in the Czech Republic. Recent experiments conducted on the DiPOLE100 system demonstrated the energy scalability of the DiPOLE concept to the 100 J pulse energy level. Furthermore, second harmonic generation experiments carried out on the DiPOLE prototype confirmed the suitability of DiPOLE-based systems for pumping high repetition rate PW-class laser systems based on Ti:sapphire or optical parametric chirped pulse amplification (OPCPA) technology.
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Li, Weihui; He, Zheng-Guo
2012-01-01
In a bis-(3′-5′)-cyclic dimeric guanosine monophosphate (c-di-GMP)/transcription factor binding screen, we identified Mycobacterium smegmatis Ms6479 as the first c-di-GMP-responsive transcriptional factor in mycobacteria. Ms6479 could specifically bind with c-di-GMP and recognize the promoters of 37 lipid transport and metabolism genes. c-di-GMP could enhance the ability of Ms6479 to bind to its target DNA. Furthermore, our results establish Ms6479 as a global activator that positively regulates the expression of diverse target genes. Overexpression of Ms6479 in M. smegmatis significantly reduced the permeability of the cell wall to crystal violet and increased mycobacterial resistance to anti-tuberculosis antibiotics. Interestingly, Ms6479 lacks the previously reported c-di-GMP binding motifs. Our findings introduce Ms6479 (here designated LtmA for lipid transport and metabolism activator) as a new c-di-GMP-responsive regulator. PMID:23047950
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DI: An interactive debugging interpreter for applicative languages
DOE Office of Scientific and Technical Information (OSTI.GOV)
Skedzielewski, S.K.; Yates, R.K.; Oldehoeft, R.R.
1987-03-12
The DI interpreter is both a debugger and interpreter of SISLAL programs. Its use as a program interpreter is only a small part of its role; it is designed to be a tool for studying compilation techniques for applicative languages. DI interprets dataflow graphs expressed in the IF1 and IF2 languages, and is heavily instrumented to report the activity of dynamic storage activity, reference counting, copying and updating of structured data values. It also aids the SISAL language evaluation by providing an interim execution vehicle for SISAL programs. DI provides determinate, sequential interpretation of graph nodes for sequential and parallelmore » operations in a canonical order. As a debugging aid, DI allows tracing, breakpointing, and interactive display of program data values. DI handles creation of SISAL and IF1 error values for each data type and propagates them according to a well-defined algebra. We have begun to implement IF1 optimizers and have measured the improvements with DI.« less
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Peterman, Dean R [Idaho Falls, ID; Meikrantz, David H [Idaho Falls, ID; Law, Jack D [Pocatello, ID; Riddle, Catherine L [Idaho Falls, ID; Todd, Terry A [Firth, ID; Greenhalgh, Mitchell R [Iona, ID; Tillotson, Richard D [Moore, ID; Bartsch, Richard A [Lubbock, TX; Moyer, Bruce A [Oak Ridge, TN; Delmau, Laetitia H [Oak Ridge, TN; Bonnesen, Peter V [Knoxville, TN
2012-04-17
A mixed extractant solvent that includes at least one dialkyloxycalix[4]arenebenzocrown-6 compound, 4',4',(5')-di-(t-butyldicyclohexano)-18-crown-6, at least one modifier, and, optionally, a diluent. The dialkyloxycalix[4]arenebenzocrown-6 compound is 1,3-alternate-25,27-di(octyloxy)calix[4]arenebenzocrown-6, 1,3-alternate-25,27-di(decyloxy)calix[4]arenebenzocrown-6, 1,3-alternate-25,27-di(dodecyloxy)calix[4]arenebenzocrown-6, 1,3-alternate-25,27-di(2-ethylhexyl-1-oxy)calix[4]arenebenzocrown-6, 1,3-alternate-25,27-di(3,7-dimethyloctyl-1-oxy)calix[4]arenebenzocrown-6, 1,3-alternate-25,27-di(4-butyloctyl-1-oxy)calix[4]arenebenzocrown-6, or combinations thereof. The modifier is a primary alcohol. A method of separating cesium and strontium from an aqueous feed is also disclosed, as are dialkyloxycalix[4]arenebenzocrown-6 compounds and an alcohol modifier.
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Disability Benefit Generosity and Labor Force Withdrawal*
Mullen, Kathleen J.; Staubli, Stefan
2016-01-01
A key component for estimating the optimal size and structure of disability insurance (DI) programs is the elasticity of DI claiming with respect to benefit generosity. Yet, in many countries, including the United States, all workers face identical benefit schedules, which are a function of one’s labor market history, making it difficult to separate the effect of the benefit level from the effect of unobserved preferences for work on individuals’ claiming decisions. To circumvent this problem, we exploit exogenous variation in DI benefits in Austria arising from several reforms to its DI and old age pension system in the 1990s and 2000s. We use comprehensive administrative social security records data on the universe of Austrian workers to compute benefit levels under six different regimes, allowing us to identify and precisely estimate the elasticity of DI claiming with respect to benefit generosity. We find that, over this time period, a one percent increase in potential DI benefits was associated with a 1.2 percent increase in DI claiming. PMID:28216797
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Skeletal maturation evaluation using mandibular second molar calcification stages.
Kumar, Sushil; Singla, Anu; Sharma, Rekha; Virdi, Mandeep S; Anupam, Anant; Mittal, Bindia
2012-05-01
To investigate (1) the relationships between the stages of mandibular second molar calcification and skeletal maturity; and (2) whether second molar calcification stages can be used as a reliable diagnostic tool to determine skeletal maturity. Samples were derived from panoramic radiographs and lateral cephalograms of 300 subjects (137 males and 163 females) with ages ranging from 9 to 18 years, and estimates of dental maturity (Demirjian Index [DI]) and skeletal maturity (cervical vertebrae maturation indicators [CVMI]) were made. A highly significant association (C* = 0.854 for males and 0.866 for females) was found between DI and CVMI. DI stage E corresponded to stage 2 of CVMI (pre-peak of pubertal growth spurt) and DI stages F and G corresponded to stages 3 and 4 of CVMI (peak of pubertal growth spurt). DI stage H was associated with stages 5 and 6 of CVMI (end of pubertal growth spurt). A highly significant association exists between DI and CVMI. Mandibular second molar DI stages are reliable indicators of skeletal maturity.
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Delusional infestation with unusual pathogens: a report of three cases.
Dewan, P; Miller, J; Musters, C; Taylor, R E; Bewley, A P
2011-10-01
Delusional infestation (DI) is a psychiatric disorder characterized by a fixed, false belief that the patient is infested with extracorporeal agents. It is known by several names, including the more commonly used term 'delusional parasitosis'. The psychiatric disease is responsible for the cutaneous pathology. About 90% of patients with DI seek help from dermatologists, and most reject psychiatric referral. Thus, effective management requires incorporation of psychiatric principles. We report three cases of DI with inanimate materials, and examine 'Morgellons' disease. We believe that patients with unusual presentations of DI are likely to be seen more commonly in the future. These patients appear to be a subgroup of DI, and may be even more difficult to treat than other patients with DI. © The Author(s). CED © 2011 British Association of Dermatologists.
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Off-equatorial current-driven instabilities ahead of approaching dipolarization fronts
NASA Astrophysics Data System (ADS)
Zhang, Xu; Angelopoulos, V.; Pritchett, P. L.; Liu, Jiang
2017-05-01
Recent kinetic simulations have revealed that electromagnetic instabilities near the ion gyrofrequency and slightly away from the equatorial plane can be driven by a current parallel to the magnetic field prior to the arrival of dipolarization fronts. Such instabilities are important because of their potential contribution to global electromagnetic energy conversion near dipolarization fronts. Of the several instabilities that may be consistent with such waves, the most notable are the current-driven electromagnetic ion cyclotron instability and the current-driven kink-like instability. To confirm the existence and characteristics of these instabilities, we used observations by two Time History of Events and Macroscale Interactions during Substorms satellites, one near the neutral sheet observing dipolarization fronts and the other at the boundary layer observing precursor waves and currents. We found that such instabilities with monochromatic signatures are rare, but one of the few cases was selected for further study. Two different instabilities, one at about 0.3 Hz and the other at a much lower frequency, 0.02 Hz, were seen in the data from the off-equatorial spacecraft. A parallel current attributed to an electron beam coexisted with the waves. Our instability analysis attributes the higher-frequency instability to a current-driven ion cyclotron instability and the lower frequency instability to a kink-like instability. The current-driven kink-like instability we observed is consistent with the instabilities observed in the simulation. We suggest that the currents needed to excite these low-frequency instabilities are so intense that the associated electron beams are easily thermalized and hence difficult to observe.
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Nayak, D P; Tobita, K; Janda, J M; Davis, A R; De, B K
1978-01-01
A temperature-sensitive group II mutant of influenza virus, ts-52, with a presumed defect in viral RNA synthesis, readily produced von Magnus-type defective interfering virus (DI virus) when passed serially (four times) at high multiplicity in MDBK cells. The defective virus (ts-52 DI virus) had a high hemagglutinin and a low infectivity titer, and strongly interfered with the replication of standard infectious viruses (both ts-52 and wild-type ts+) in co-infected cells. Progeny virus particles produced by co-infection of DI virus and infectious virus were also defective and also had low infectivity, high hemagglutinating activity, and a strong interfering property. Infectious viruses ts+ and ts-52 were indistinguishable from ts-52 DI viruses by sucrose velocity or density gradient analysis. Additionally, these viruses all possessed similar morphology. However, when the RNA of DI viruses was analyzed by use of polyacrylamide gels containing 6 M urea, there was a reduction in the amount of large RNA species (V1 to V4), and a number of new smaller RNA species (D1 to D6) with molecular weights ranging from 2.9 X 10(5) to 1.05 X 10(5) appeared. Since these smaller RNA species (D1 to D6) were absent in some clones of infectious viruses, but were consistently associated with DI viruses and increased during undiluted passages and during co-infection of ts-52 with DI virus, they appeared to be a characteristic of DI viruses. Additionally, the UV target size of interfering activity and infectivity of DI virus indicated that interfering activity was 40 times more resistant to UV irradiation than was infectivity, further implicating small RNA molecules in interference. Our data suggest that the loss of infectivity observed among DI viruses may be due to nonspecific loss of a viral RNA segment(s), and the interfering property of DI viruses may be due to interfering RNA segments (DIRNA, D1 to D6). ts-52 DI virus interfered with the replication of standard virus (ts+) at both permissive (34 degrees C) and nonpermissive temperatures. The infectivity of the progeny virus was reduced to 0.2% for ts+ and 0.05% for ts-52 virus without a reduction in hemagglutinin titer. Interference was dependent on the concentration of DI virus. A particle ratio of 1 between DI virus (0.001 PFU/cell) and infectious virus (1.0 PFU/cell) produced a maximal amount of interference. Infectious virus yield was reduced 99.9% without any reduction of the yield of DI viruses Interference was also dependent on the time of addition of DI virus. Interference was most effective within the first 3 h of infection by infectious virus, indicating interference with an early function during viral replication. Images PMID:702654
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Kellenberger, Colleen A; Sales-Lee, Jade; Pan, Yuchen; Gassaway, Madalee M; Herr, Amy E; Hammond, Ming C
2015-01-01
Cyclic di-GMP (c-di-GMP) is a second messenger that is important in regulating bacterial physiology and behavior, including motility and virulence. Many questions remain about the role and regulation of this signaling molecule, but current methods of detection are limited by either modest sensitivity or requirements for extensive sample purification. We have taken advantage of a natural, high affinity receptor of c-di-GMP, the Vc2 riboswitch aptamer, to develop a sensitive and rapid electrophoretic mobility shift assay (EMSA) for c-di-GMP quantitation that required minimal engineering of the RNA.
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How Financial Incentives Induce Disability Insurance Recipients to Return to Work.
Kostol, Andreas Ravndal; Mogstad, Magne
2014-02-01
Using a local randomized experiment that arises from a sharp discontinuity in Disability Insurance (DI) policy in Norway, we provide transparent and credible identification of how financial incentives induce DI recipients to return to work. We find that many DI recipients have considerable capacity to work that can be effectively induced by providing financial work incentives. We further show that providing work incentives to DI recipients may both increase their disposable income and reduce program costs. Our findings also suggest that targeted policies may be the most effective in encouraging DI recipients to return to work.
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NASA Astrophysics Data System (ADS)
Lapenta, Giovanni; Oieroset, Marit; Phan, Tai; Eastwood, Jonathan; Goldman, Martin; Newman, David L.; Russel, Christopher; Strangeway, Robert; Paterson, William; Giles, Barbara; Lavraud, Benoit; Khotyaintsev, Yuri; Ergun, Robert; Torbert, Roy; Burch, James
2017-04-01
Recently Øieroset et al. [2016] reported evidence for reconnection between colliding reconnection jets in a compressed current sheet at the center of a magnetic flux rope at Earth's magnetopause. Here, we set up a simulation with parameters similar to those observed: in particular we used the same guide field ratio to the in plane field. The initial state is a Harris sheet with mass ratio 256 and temperature ratio 10. The domain is 3D with box size 20x15x10 di. Reconnection is initiated at the two edges of the box by seeding an initial localized x-line. Reconnection starts at the two x-lines by design due to the strong perturbation. The subsequent evolution shows reconnection taking root in the initially seeded x-lines. Later an instability develops within the flux rope, likely similar to those reported in Lapenta et al. [2015], and secondary reconnection starts in a ring near the center of the flux rope. The analogy with the kink mode of laboratory and solar wind flux ropes[Lapenta et al., 2006] is striking and future work will be needed to investigate if the instability satisfies the Kruskal-Shafranov limit [Shafranov, 1957, Kruskal and Tuck, 1958]. At late times, the primary reconnection site becomes inactive and the secondary reconnection site becomes dominant. In this later stage, agyrotropy and J · E' are stronger in the center. But more strikingly, the ions are outflowing predominantly away from the secondary reconnection site in the central region of the flux rope and the ring near the center where reconnection signatures (agyrotropy and J · E') are strongest. The electron pressure presents several intense loci, identifying where strong electron energization by secondary reconnection takes place. The results of the simulation are studied producing synthetic virtual satellite diagnostics obtained from the simulation results but with a format similar to in situ spacecraft observations. With these data formats the results can be more readily be compared with the MMS data reported in Øieroset et al. [2016]. References M. Kruskal and J. Tuck. The instability of a pinched fluid with a longitudinal magnetic field. Proceedings of the Royal Society of London. Series A. Mathematical and Physical Sciences, 245(1241):222-237, 1958. G. Lapenta, I. Furno, and T. Intrator. Kink instability of flux ropes anchored at one end and free at the other. J. Geophys. Res., 111:A12S06, 2006. G. Lapenta, S. Markidis, M. V. Goldman, and D. L. Newman. Secondary reconnection sites in reconnection-generated flux ropes and reconnection fronts. Nature Physics, 11(8):690-695, 2015. M. Øieroset, T. Phan, C. Haggerty, M. Shay, J. Eastwood, et al. Mms observations of large guide field symmetric reconnection between colliding reconnection jets at the center of a magnetic flux rope at the magnetopause. Geophysical Research Letters, 2016.
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Biedermann, Sandra; Zurfluh, Michael; Grob, Koni; Vedani, Angelo; Brüschweiler, Beat J
2013-08-01
Cyclo-diBA, the cyclic product formed from bisphenol A and bisphenol A diglycidyl ether during production of epoxy resins, was measured in canned food using reversed phase HPLC with fluorescence detection. Half (9 of 17) of the samples of canned fish in oil collected in April 2010 contained cyclo-diBA with an average concentration of 1025 μg/kg and a maximum of 1980 μg/kg. In September 2012, cyclo-diBA was detectable (>25 μg/kg) in merely 13 from 44 such products; the average concentration in these was 807 μg/kg and the maximum now reached 2640 μg/kg. Fish in brine contained far less cyclo-diBA. The majority of the canned meat products contained cyclo-diBA at a mean concentration of 477 μg/kg and a maximum of 1050 μg/kg. All prepared meals, such as ravioli or soups, contained cyclo-diBA, with a mean at 287 μg/kg. In canned tomatoes, peas and other vegetables in water or fruits in syrup, no cyclo-diBA was detected (<25 μg/kg). Since no experimental toxicity data are available except for its cytotoxicity, an in silico hazard profiling was performed. Cyclo-diBA seems to be stable and of low reactivity. There is indication for considerable oral bioavailability and for the potential to accumulate in the human body. Cyclo-diBA can be metabolized into cyclic and acyclic compounds. Based on SAR assessment for cyclo-diBA and read-across from BADGE to linear cyclo-diBA metabolites, genotoxic effects are improbable. Specific binding of cyclo-diBA to nuclear receptors, such as ERβ, can be predicted, indicating a potential endocrine-disrupting potency. The limit by the EFSA guidelines of 50 μg/person/d for compounds shown not to be genotoxic as well as the TTC-based Cramer structural class III value of 90 μg/person/d could be exceeded several fold by high consumers of canned fish in oil with high brand loyalty. As a consequence, risk reduction measures were taken. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Wang, Yiming; Zhang, Hongming; Chai, Fangxian; Liu, Xingde; Berk, Michael
2014-12-04
Major depressive disorder (MDD) is an independent risk factor for coronary heart disease (CHD), and influences the occurrence and prognosis of cardiovascular events. Although there is evidence that antidepressants may be cardioprotective after acute myocardial infarction (AMI) comorbid with MDD, the operative pathophysiological mechanisms remain unclear. Our aim was therefore to explore the molecular mechanisms of escitalopram on myocardial apoptosis and the expression of Bax and Bcl-2 in a rat model of depression during myocardial ischemia/reperfusion (I/R). Rats were divided randomly into 3 groups (n = 8): D group (depression), DI/R group (depression with myocardial I/R) and escitalopram + DI/R group. The rats in all three groups underwent the same chronic mild stress and separation for 21 days, at the same time, in the escitalopram + DI/R group, rats were administered escitalopram by gavage (10 mg/kg/day). Ligation of the rat's left anterior descending branch was done in the myocardial I/R model. Following which behavioral tests were done. The size of the myocardial infarction was detected using 1.5% TTC dye. The Tunel method was used to detect apoptotic myocardial cells, and both the Rt-PCR method and immunohistochemical techniques were used to detect the expression of Bcl-2 and Bax. Compared with the D and DI/R groups, rats in Escitalopram + DI/R group showed significantly increased movements and sucrose consumption (P < .01). Compared with the DI/R group, the myocardial infarct size in the escitalopram + DI/R group was significantly decreased (P < .01). Compared with the D group, there were significantly increased apoptotic myocardial cells in the DI/R and escitalopram + DI/R groups (P < .01); however compared with the DI/R group, apoptotic myocardial cell numbers in the escitalopram + DI/R group were significantly decreased (P < .01). Compared with the DI/R group, there was a down-regulated Bax:Bcl-2 ratio in the escitalopram + DI/R group (P < .01). These results suggest that in patients with AMI comorbid with MDD, there is an increase in pro-apoptotic pathways that is reversed by escitalopram. This suggests that clinically escitalopram may have a direct cardioprotective after acute myocardial infarction.
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Pirolli, Davide; Sciandra, Francesca; Bozzi, Manuela; Giardina, Bruno; Brancaccio, Andrea; De Rosa, Maria Cristina
2014-01-01
A missense amino acid mutation of valine to aspartic acid in 567 position of alpha-dystroglycan (DG), identified in dag1-mutated zebrafish, results in a reduced transcription and a complete absence of the protein. Lacking experimental structural data for zebrafish DG domains, the detailed mechanism for the observed mutation-induced destabilization of the DG complex and membrane damage, remained unclear. With the aim to contribute to a better clarification of the structure-function relationships featuring the DG complex, three-dimensional structural models of wild-type and mutant (V567D) C-terminal domain of alpha-DG from zebrafish were constructed by a template-based modelling approach. We then ran extensive molecular dynamics (MD) simulations to reveal the structural and dynamic properties of the C-terminal domain and to evaluate the effect of the single mutation on alpha-DG stability. A comparative study has been also carried out on our previously generated model of murine alpha-DG C-terminal domain including the I591D mutation, which is topologically equivalent to the V567D mutation found in zebrafish. Trajectories from MD simulations were analyzed in detail, revealing extensive structural disorder involving multiple beta-strands in the mutated variant of the zebrafish protein whereas local effects have been detected in the murine protein. A biochemical analysis of the murine alpha-DG mutant I591D confirmed a pronounced instability of the protein. Taken together, the computational and biochemical analysis suggest that the V567D/I591D mutation, belonging to the G beta-strand, plays a key role in inducing a destabilization of the alpha-DG C-terminal Ig-like domain that could possibly affect and propagate to the entire DG complex. The structural features herein identified may be of crucial help to understand the molecular basis of primary dystroglycanopathies. PMID:25078606
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Pirolli, Davide; Sciandra, Francesca; Bozzi, Manuela; Giardina, Bruno; Brancaccio, Andrea; De Rosa, Maria Cristina
2014-01-01
A missense amino acid mutation of valine to aspartic acid in 567 position of alpha-dystroglycan (DG), identified in dag1-mutated zebrafish, results in a reduced transcription and a complete absence of the protein. Lacking experimental structural data for zebrafish DG domains, the detailed mechanism for the observed mutation-induced destabilization of the DG complex and membrane damage, remained unclear. With the aim to contribute to a better clarification of the structure-function relationships featuring the DG complex, three-dimensional structural models of wild-type and mutant (V567D) C-terminal domain of alpha-DG from zebrafish were constructed by a template-based modelling approach. We then ran extensive molecular dynamics (MD) simulations to reveal the structural and dynamic properties of the C-terminal domain and to evaluate the effect of the single mutation on alpha-DG stability. A comparative study has been also carried out on our previously generated model of murine alpha-DG C-terminal domain including the I591D mutation, which is topologically equivalent to the V567D mutation found in zebrafish. Trajectories from MD simulations were analyzed in detail, revealing extensive structural disorder involving multiple beta-strands in the mutated variant of the zebrafish protein whereas local effects have been detected in the murine protein. A biochemical analysis of the murine alpha-DG mutant I591D confirmed a pronounced instability of the protein. Taken together, the computational and biochemical analysis suggest that the V567D/I591D mutation, belonging to the G beta-strand, plays a key role in inducing a destabilization of the alpha-DG C-terminal Ig-like domain that could possibly affect and propagate to the entire DG complex. The structural features herein identified may be of crucial help to understand the molecular basis of primary dystroglycanopathies.
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Padek, Margaret; Colditz, Graham; Dobbins, Maureen; Koscielniak, Nikolas; Proctor, Enola K; Sales, Anne E; Brownson, Ross C
2015-08-12
With demand increasing for dissemination and implementation (D&I) training programs in the USA and other countries, more structured, competency-based, and tested curricula are needed to guide training programs. There are many benefits to the use of competencies in practice-based education such as the establishment of rigorous standards as well as providing an additional metrics for development and growth. As the first aim of a D&I training grant, an exploratory study was conducted to establish a new set of D&I competencies to guide training in D&I research. Based upon existing D&I training literature, the leadership team compiled an initial list of competencies. The research team then engaged 16 additional colleagues in the area of D&I science to provide suggestions to the initial list. The competency list was then additionally narrowed to 43 unique competencies following feedback elicited from these D&I researchers. Three hundred additional D&I researchers were then invited via email to complete a card sort in which the list of competencies were sorted into three categories of experience levels. Participants had previous first-hand experience with D&I or knowledge translation training programs in the past. Participants reported their self-identified D&I expertise level as well as the country in which their home institution is located. A mean score was calculated for each competency based on their experience level categorization. From these mean scores, beginner-, intermediate-, and advanced-level tertiles were created for the competencies. The card sort request achieved a 41 % response rate (n = 124). The list of 43 competencies was organized into four broad domains and sorted based on their experience level score. Eleven competencies were classified into the "Beginner" category, 27 into "Intermediate," and 5 into "Advanced." Education and training developers can use this competency list to formalize future trainings in D&I research, create more evidence-informed curricula, and enable overall capacity building and accompanying metrics in the field of D&I training and research.
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2012-01-01
Background Dietary habits in Morocco are changing and the causes are not well understood. This study aimed to analyse socio-demographic factors associated with adherence to the Mediterranean diet (MeDi) in a national random sample of the adult Moroccan population. Methods The data collected in this cross-sectional survey included socio-demographic factors and a food frequency questionnaire. MeDi adherence was assessed in 2214 individuals with complete dietary data. MeDi adherence was measured according to a simplified MeDi score based on the weekly frequency of intake of eight food groups (vegetables, legumes, fruits, cereal or potatoes, fish, red meat, dairy products and olive oil) with the use of the sex specific medians of the sample as cut-offs. A value of 0 or 1 was assigned to consumption of each component according to its presumed detrimental or beneficial effect on health. Logistic regression was used to estimate the association between MeDi adherence (low score 1-4 vs. high 5-8) and other factors. Results Mean age of the sample was 41.4 (standard deviation 15.3) years, 45.4% were men and 29.9% had a low MeDi adherence. Married subjects (adjusted odds ratio ORa=0.68, 95% CI 0.55-0.84) were less likely to have a low MeDi adherence compared to single, divorced or widowed persons. Persons from rural areas (ORa=1.46, 95% CI: 1.02-2.08), were more often low MeDi adherents compared to those from urban areas. Obese persons (ORa=1.56, 95% CI: 1.16-2.11) were more prone to low MeDi adherence than normal weight individuals. Conclusion MeDi is far from being a universal pattern in the Moroccan population. Intervention strategies should be implemented in target groups to maintain the traditional MeDi pattern considered as the original diet in Morocco. PMID:22578133
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Miner, Kyle D; Kurtz, Donald M
2016-02-16
HD-GYPs make up a subclass of the metal-dependent HD phosphohydrolase superfamily and catalyze conversion of cyclic di(3',5')-guanosine monophosphate (c-di-GMP) to 5'-phosphoguanylyl-(3'→5')-guanosine (pGpG) and GMP. Until now, the only reported crystal structure of an HD-GYP that also exhibits c-di-GMP phosphodiesterase activity contains a His/carboxylate ligated triiron active site. However, other structural and phylogenetic correlations indicate that some HD-GYPs contain dimetal active sites. Here we provide evidence that an HD-GYP c-di-GMP phosphodiesterase, TM0186, from Thermotoga maritima can accommodate both di- and trimetal active sites. We show that an as-isolated iron-containing TM0186 has an oxo/carboxylato-bridged diferric site, and that the reduced (diferrous) form is necessary and sufficient to catalyze conversion of c-di-GMP to pGpG, but that conversion of pGpG to GMP requires more than two metals per active site. Similar c-di-GMP phosphodiesterase activities were obtained with divalent iron or manganese. On the basis of activity correlations with several putative metal ligand residue variants and molecular dynamics simulations, we propose that TM0186 can accommodate both di- and trimetal active sites. Our results also suggest that a Glu residue conserved in a subset of HD-GYPs is required for formation of the trimetal site and can also serve as a labile ligand to the dimetal site. Given the anaerobic growth requirement of T. maritima, we suggest that this HD-GYP can function in vivo with either divalent iron or manganese occupying di- and trimetal sites.
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Wilmoth, Janet M; London, Andrew S; Heflin, Colleen M
2015-07-01
Although there is substantial disability among veterans, relatively little is known about working-aged veterans' uptake of Department of Veterans Affairs (VA) Disability Compensation and Social Security Disability Insurance (DI). This study identifies levels of veteran participation in VA disability and/or DI benefit programs, examines transitions into and out of VA and DI programs among veterans, and estimates the size and composition of the veteran population receiving VA and/or DI benefits over time. Data from the 1992, 1993, 1996, 2001, 2004, and 2008 Survey of Income and Program Participation (SIPP) are used to describe VA and DI program participation among veterans under the age of 65. The majority of working-aged veterans do not receive VA or DI benefits and joint participation is low, but use of these programs has increased over time. A higher percentage of veterans receive VA compensation, which ranges from 4.9% in 1992 to 13.2% in 2008, than DI compensation, which ranges from 2.9% in 1992 to 6.7% in 2008. The rate of joint participation ranges from less than 1% in 1992 to 3.6% in 2008. Veterans experience few transitions between VA and DI programs during the 36-48 months they are observed. The number of veterans receiving benefits from VA and/or DI nearly doubled between 1992 and 2008. There have been substantial shifts in the composition of veterans using these programs, as cohorts who served prior to 1964 are replaced by those who served after 1964. The findings suggest potential gaps in veterans' access to disability programs that might be addressed through improved coordination of VA and DI benefits. Copyright © 2015 Elsevier Inc. All rights reserved.
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Chu, Chia-Ching; Hoffmann, Mark; Braswell, W Evan; Pelz-Stelinski, Kirsten S
2017-12-29
Wolbachia can profoundly influence the survival, reproduction, and defenses of insect hosts. These interactions could potentially be harnessed for managing pests or insect-transmitted diseases. Diaphorina citri Kuwayama is a phloem-feeding pest capable of transmitting the putative causal agent of citrus greening, Candidatus Liberibacter asiaticus (CLas). Like many insects, D. citri is also infected with Wolbachia (wDi). Recent studies indicate that the relative abundance of wDi could be associated with the abundance of CLas, and that wDi may contribute to regulating expression of phage lytic cycle genes in CLas, suggesting the need for better understanding of wDi biology in general. This study investigated the genetic diversity of wDi among D. citri in populations spanning eleven countries and two U.S. territories. Six Wolbachia genes, wsp, coxA, fbpA, ftsZ, gatB, and hcpA, were sequenced and compared across samples. Two prevalent wDi strains were identified across the samples, and screening of clone libraries revealed possible coinfection of wDi strains in specific populations. D. citri mitochondrial cytochrome oxidase subunit I gene (mtCOI) were more divergent between D. citri populations that were infected with different wDi strains or had different infection statuses (single infection vs. coinfection). While we could not eliminate the possibility that maternal transmission may contribute to such patterns, it is also possible that wDi may induce cytoplasmic incompatibility in their host. These findings should contribute to the understanding of wDi population ecology, which may facilitate manipulation of this endosymbiont for management of citrus greening disease worldwide. © 2017 The Authors. Insect Science published by John Wiley & Sons Australia, Ltd on behalf of Institute of Zoology, Chinese Academy of Sciences.
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Yuen, Kevin C J; Kołtowska-Häggström, Maria; Cook, David M; Fox, Janet L; Jönsson, Peter J; Geffner, Mitchell E; Abs, Roger
2014-04-01
Craniopharyngiomas are often associated with significant morbidity due to their location and treatment effects. Little is known of the effects of primary treatment regimen and diabetes insipidus (DI), a clinical surrogate of hypothalamic obesity, on health outcomes in adults with childhood-onset craniopharyngioma (COCP). The objective of the study was to examine health outcomes of adults with COCP based on primary treatment regimens and the presence of DI. This study included a retrospective KIMS (Pfizer International Metabolic Database) data analysis of 180 adults with COCP according to the primary treatment regimen [one surgery (1Surg) vs complex treatment regimen (CTrR) of more than 1Surg and/or radiotherapy] and the presence of DI. The majority of COCP patients underwent transcranial surgery (77%) without receiving radiotherapy (84%). Compared with the 1Surg group, more CTrR patients developed visual field defects and ophthalmoplegia (all P < .01). Compared with patients without DI, those with DI had higher rates of anterior pituitary hormone deficits, body mass index, and fat mass (all P < .01). By contrast, fasting glucose, hemoglobin A1c, lipid panel, and quality of life were comparable among 1Surg vs CTrR patients, and patients with vs without DI. Regardless of primary treatment received, the presence of DI in either group was associated with higher rates of anterior pituitary hormone deficits and obesity. CTrR and DI predicted health outcomes differently. CTrR predisposed to the development of visual dysfunction, whereas DI was associated with higher rates of anterior pituitary dysfunction and weight gain. Higher body mass index and fat mass in patients with DI further implicate the role of hypothalamic damage as an important causal factor of obesity in these patients.
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Murphy, Michelle C.; Fox, Edward A.
2007-01-01
The mouse is an extremely valuable model for studying vagal development in relation to strain differences, genetic variation, gene manipulations, or pharmacological manipulations. Therefore, a method using 1, 1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI) was developed for labeling vagal innervation of the gastrointestinal (GI) tract in embryonic and postnatal mice. DiI labeling was adapted and optimized for this purpose by varying several facets of the method. For example, insertion and crushing of DiI crystals into the nerve led to faster DiI diffusion along vagal axons and diffusion over longer distances as compared with piercing the nerve with a micropipette tip coated with dried DiI oil. Moreover, inclusion of EDTA in the fixative reduced leakage of DiI out of nerve fibers that occurred with long incubations. Also, mounting labeled tissue in PBS was superior to glycerol with n-propyl gallate, which resulted in reduced clarity of DiI labeling that may have been due to DiI leaking out of fibers. Optical sectioning of flattened wholemounts permitted examination of individual tissue layers of the GI tract wall. This procedure aided identification of nerve ending types because in most instances each type innervates a different tissue layer. Between embryonic day 12.5 and postnatal day 8, growth of axons into the GI tract, formation and patterning of fiber bundles in the myenteric plexus and early formation of putative afferent and efferent nerve terminals were observed. Thus, the DiI tracing method developed here has opened up a window for investigation during an important phase of vagal development. PMID:17418900
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Yuuki, Arata; Muneta, Takeshi; Ohara, Toshiyuki; Sekiya, Ichiro; Koga, Hideyuki
2017-03-01
Associations of lateral/medial knee instability with anterior cruciate ligament (ACL) injury have not been thoroughly investigated. The purposes of this study were to investigate whether lateral/medial knee instability is associated with ACL injury, and to clarify relevant factors for lateral/medial knee instability in ACL-injured knees. One hundred and nineteen patients with unilateral ACL-injured knees were included. Lateral/medial knee instability was assessed with varus/valgus stress X-ray examination for both injured and uninjured knees by measuring varus/valgus angle, lateral/medial joint opening, and lateral/medial joint opening index. Manual knee instability tests for ACL were evaluated to investigate associations between lateral/medial knee instability and anterior and/or rotational instabilities. Patients' backgrounds were evaluated to identify relevant factors for lateral/medial knee instability. Damage on the lateral collateral ligament (LCL) on MRI was also evaluated. All parameters regarding lateral knee instability in injured knees were significantly greater than in uninjured knees. There were significant correlations between lateral knee instability and the Lachman test as well as the pivot shift test. Patients with LCL damage had significantly greater lateral joint opening than those without LCL damage on MRI. Sensitivity of LCL damage on MRI to lateral joint opening was 100%, while its specificity was 36%. No other relevant factors were identified. In medial knee instability, there were also correlations between medial knee instability and the Lachman test/pivot shift test. However, the correlations were weak and other parameters were not significant. Lateral knee instability was greater in ACL-deficient knees than in uninjured knees. Lateral knee instability was associated with ACL-related instabilities as well as LCL damage on MRI, whereas MRI had low specificity to lateral knee instability. On the other hand, the association of medial knee instability on ACL-related instability was less than that of lateral knee instability. Level IV, case series with no comparison group. Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.
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Riboswitches in eubacteria sense the second messenger c-di-AMP
Nelson, James W.; Sudarsan, Narasimhan; Furukawa, Kazuhiro; Weinberg, Zasha; Wang, Joy X.; Breaker, Ronald R.
2013-01-01
Cyclic di-adenosine monophosphate (c-di-AMP) is a recently discovered bacterial second messenger implicated in the control of cell wall metabolism, osmotic stress responses, and sporulation. However, the mechanisms by which c-di-AMP triggers these physiological responses have remained largely unknown. Intriguingly, a candidate riboswitch class called ydaO associates with numerous genes involved in these same processes. Although a representative ydaO motif RNA recently was reported to weakly bind ATP, we report that numerous members of this noncoding RNA class selectively respond to c-di-AMP with sub-nanomolar affinity. Our findings resolve the mystery regarding the primary ligand for this extremely common riboswitch class and expose a major portion of the super-regulon of genes that are controlled by the widespread bacterial second messenger c-di-AMP. PMID:24141192
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Opposed Effects of Dityrosine Formation in Soluble and Aggregated α-Synuclein on Fibril Growth.
Wördehoff, Michael M; Shaykhalishahi, Hamed; Groß, Luca; Gremer, Lothar; Stoldt, Matthias; Buell, Alexander K; Willbold, Dieter; Hoyer, Wolfgang
2017-10-13
Parkinson's disease is the second most common neurodegenerative disease. It is characterized by aggregation of the protein α-synuclein (α-syn) in Lewy bodies, mitochondrial dysfunction, and increased oxidative stress in the substantia nigra. Oxidative stress leads to several modifications of biomolecules including dityrosine (DiY) crosslinking in proteins, which has recently been detected in α-syn in Lewy bodies from Parkinson's disease patients. Here we report that α-syn is highly susceptible to ultraviolet-induced DiY formation. We investigated DiY formation of α-syn and nine tyrosine-to-alanine mutants and monitored its effect on α-syn fibril formation in vitro. Ultraviolet irradiation of intrinsically disordered α-syn generates DiY-modified monomers and dimers, which inhibit fibril formation of unmodified α-syn by interfering with fibril elongation. The inhibition depends on both the DiY group and its integration into α-syn. When preformed α-syn fibrils are crosslinked by DiY formation, they gain increased resistance to denaturation. DiY-stabilized α-syn fibrils retain their high seeding efficiency even after being exposed to denaturant concentrations that completely depolymerize non-crosslinked seeds. Oxidative stress-associated DiY crosslinking of α-syn therefore entails two opposing effects: (i) inhibition of aggregation by DiY-modified monomers and dimers, and (ii) stabilization of fibrillar aggregates against potential degradation mechanisms, which can lead to promotion of aggregation, especially in the presence of secondary nucleation. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
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Transposable Elements in Human Cancer: Causes and Consequences of Deregulation.
Anwar, Sumadi Lukman; Wulaningsih, Wahyu; Lehmann, Ulrich
2017-05-04
Transposable elements (TEs) comprise nearly half of the human genome and play an essential role in the maintenance of genomic stability, chromosomal architecture, and transcriptional regulation. TEs are repetitive sequences consisting of RNA transposons, DNA transposons, and endogenous retroviruses that can invade the human genome with a substantial contribution in human evolution and genomic diversity. TEs are therefore firmly regulated from early embryonic development and during the entire course of human life by epigenetic mechanisms, in particular DNA methylation and histone modifications. The deregulation of TEs has been reported in some developmental diseases, as well as for different types of human cancers. To date, the role of TEs, the mechanisms underlying TE reactivation, and the interplay with DNA methylation in human cancers remain largely unexplained. We reviewed the loss of epigenetic regulation and subsequent genomic instability, chromosomal aberrations, transcriptional deregulation, oncogenic activation, and aberrations of non-coding RNAs as the potential mechanisms underlying TE deregulation in human cancers.
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Transposable Elements in Human Cancer: Causes and Consequences of Deregulation
Anwar, Sumadi Lukman; Wulaningsih, Wahyu; Lehmann, Ulrich
2017-01-01
Transposable elements (TEs) comprise nearly half of the human genome and play an essential role in the maintenance of genomic stability, chromosomal architecture, and transcriptional regulation. TEs are repetitive sequences consisting of RNA transposons, DNA transposons, and endogenous retroviruses that can invade the human genome with a substantial contribution in human evolution and genomic diversity. TEs are therefore firmly regulated from early embryonic development and during the entire course of human life by epigenetic mechanisms, in particular DNA methylation and histone modifications. The deregulation of TEs has been reported in some developmental diseases, as well as for different types of human cancers. To date, the role of TEs, the mechanisms underlying TE reactivation, and the interplay with DNA methylation in human cancers remain largely unexplained. We reviewed the loss of epigenetic regulation and subsequent genomic instability, chromosomal aberrations, transcriptional deregulation, oncogenic activation, and aberrations of non-coding RNAs as the potential mechanisms underlying TE deregulation in human cancers. PMID:28471386
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Suzuki, Naoya M; Niwa, Akira; Yabe, Miharu; Hira, Asuka; Okada, Chihiro; Amano, Naoki; Watanabe, Akira; Watanabe, Ken-Ichiro; Heike, Toshio; Takata, Minoru; Nakahata, Tatsutoshi; Saito, Megumu K
2015-04-01
Fanconi anemia (FA) is a disorder of genomic instability characterized by progressive bone marrow failure (BMF), developmental abnormalities, and an increased susceptibility to cancer. Although various consequences in hematopoietic stem/progenitor cells have been attributed to FA-BMF, the quest to identify the initial pathological event is still ongoing. To address this issue, we established induced pluripotent stem cells (iPSCs) from fibroblasts of six patients with FA and FANCA mutations. An improved reprogramming method yielded iPSC-like colonies from all patients, and iPSC clones were propagated from two patients. Quantitative evaluation of the differentiation ability demonstrated that the differentiation propensity toward the hematopoietic and endothelial lineages is already defective in early hemoangiogenic progenitors. The expression levels of critical transcription factors were significantly downregulated in these progenitors. These data indicate that the hematopoietic consequences in FA patients originate from the early hematopoietic stage and highlight the potential usefulness of iPSC technology for elucidating the pathogenesis of FA-BMF. ©AlphaMed Press.
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Trajectories of Social Withdrawal from Middle Childhood to Early Adolescence
Oh, Wonjung; Bowker, Julie C.; Booth-LaForce, Cathryn; Rose-Krasnor, Linda; Laursen, Brett
2013-01-01
Heterogeneity and individual differences in the developmental course of social withdrawal were examined longitudinally in a community sample (N=392). General Growth Mixture Modeling (GGMM) was used to identify distinct pathways of social withdrawal, differentiate valid subgroup trajectories, and examine factors that predicted change in trajectories within subgroups. Assessments of individual (social withdrawal), interactive (prosocial behavior), relationship (friendship involvement, stability and quality, best friend’s withdrawal and exclusion/victimization) and group- (exclusion/victimization) level characteristics were used to define growth trajectories from the final year of elementary school, across the transition to middle school, and then to the final year of middle school (fifth-to-eighth grades). Three distinct trajectory classes were identified: low stable, increasing, and decreasing. Peer exclusion, prosocial behavior, and mutual friendship involvement differentiated class membership. Friendlessness, friendship instability, and exclusion were significant predictors of social withdrawal for the increasing class, whereas lower levels of peer exclusion predicted a decrease in social withdrawal for the decreasing class. PMID:18193479
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A critical review of recent biological research on human sexual orientation.
Mustanski, Brian S; Chivers, Meredith L; Bailey, J Michael
2002-01-01
This article provides a comprehensive review and critique of biological research on sexual orientation published over the last decade. We cover research investigating (a) the neurohormonal theory of sexual orientation (psychoneuroendocrinology, prenatal stress, cerebral asymmetry, neuroanatomy, otoacoustic emissions, anthropometrics), (b) genetic influences, (c) fraternal birth-order effects, and (d) a putative role for developmental instability. Despite inconsistent results across both studies and traits, some support for the neurohormonal theory is garnered, but mostly in men. Genetic research using family and twin methodologies has produced consistent evidence that genes influence sexual orientation, but molecular research has not yet produced compelling evidence for specific genes. Although it has been well established that older brothers increase the odds of homosexuality in men, the route by which this occurs has not been resolved. We conclude with an examination of the limitations of biological research on sexual orientation, including measurement issues (paper and pencil, cognitive, and psychophysiological), and lack of research on women.
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Leppert, Katherine A; Kushner, Marissa; Smith, Victoria C; Lemay, Edward P; Dougherty, Lea R
2016-12-01
This study examined the stability of children's cortisol responses to a social evaluative laboratory stressor from early to middle childhood. Ninety-six children (51 males) completed stress-inducing laboratory tasks and provided five salivary cortisol samples in early (W1) and middle (W2) childhood. Although W1 cortisol responses did not predict W2 cortisol responses, children's cortisol responses demonstrated change: compared to their W1 cortisol responses, children's W2 cortisol responses demonstrated an increased slope and more negative quadratic curvature. Furthermore, child psychiatric symptoms at W1 moderated the stability of children's cortisol responses. Children with fewer preschool psychiatric symptoms demonstrated greater inter-individual and intra-individual stability, whereas children with higher preschool psychiatric symptoms and comorbidity demonstrated systematic inter-individual and intra-individual instability in cortisol responses over time. Findings suggest a developmental shift toward increasing cortisol stress responses from early to middle childhood and highlight preschool psychopathology as a moderator of stability in children's cortisol responses over time. © 2016 Wiley Periodicals, Inc.
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Relations between Housing Characteristics and the Well-Being of Low-Income Children and Adolescents
Coley, Rebekah Levine; Leventhal, Tama; Lynch, Alicia Doyle; Kull, Melissa
2013-01-01
Extant research has highlighted the importance of multiple characteristics of housing, but has not comprehensively assessed a broad range of housing characteristics and their relative contributions to children's well-being. Using a representative, longitudinal sample of low-income children and adolescents from low-income urban neighborhoods (N = 2,437, ages 2 through 21 years) from the Three-City Study, this study assessed housing quality, stability, type (i.e., ownership status and subsidy status), and cost simultaneously to delineate their unique associations with children's development. Hierarchical linear models found that poor housing quality was most consistently associated with children's and adolescents’ development, including worse emotional and behavioral functioning and lower cognitive skills. These associations operated in part through mothers’ psychological functioning. Residential instability showed mixed links with functioning, whereas housing cost and type were not consistently predictive. Results suggest that housing contexts are associated with functioning across the developmental span from early childhood through late adolescence, with some differences in patterns by child age. PMID:23244408
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Mercury exposure may influence fluctuating asymmetry in waterbirds
Herring, Garth; Eagles-Smith, Collin A.; Ackerman, Joshua T.
2017-01-01
Variation in avian bilateral symmetry can be an indicator of developmental instability in response to a variety of stressors, including environmental contaminants. The authors used composite measures of fluctuating asymmetry to examine the influence of mercury concentrations in 2 tissues on fluctuating asymmetry within 4 waterbird species. Fluctuating asymmetry increased with mercury concentrations in whole blood and breast feathers of Forster's terns (Sterna forsteri), a species with elevated mercury concentrations. Specifically, fluctuating asymmetry in rectrix feather 1 was the most strongly correlated structural variable of those tested (wing chord, tarsus, primary feather 10, rectrix feather 6) with mercury concentrations in Forster's terns. However, for American avocets (Recurvirostra americana), black-necked stilts (Himantopus mexicanus), and Caspian terns (Hydroprogne caspia), the authors found no relationship between fluctuating asymmetry and either whole-blood or breast feather mercury concentrations, even though these species had moderate to elevated mercury exposure. The results indicate that mercury contamination may act as an environmental stressor during development and feather growth and contribute to fluctuating asymmetry of some species of highly contaminated waterbirds.
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Foster home integration as a temporal indicator of relational well-being.
Waid, Jeffrey; Kothari, Brianne H; McBeath, Bowen M; Bank, Lew
2017-12-01
This study sought to identify factors that contribute to the relational well-being of youth in substitute care. Using data from the [BLIND] study, youth responded to a 9-item measure of positive home integration, a scale designed to assess the relational experiences of youth to their caregivers and their integration into the foster home. Data were collected from youth in six month intervals, for an 18-month period of time. Latent growth curve modeling procedures were employed to determine if child, family, and case characteristics influenced youth's home integration trajectories. Results suggest stability in youth reports of home integration over time; however, children who were older at the time of study enrollment and youth who experienced placement changes during the period of observation experienced decreased home integration during the 18-month period. Results suggest youth's perspectives of home integration may in part be a function of the child's developmental stage and their experiences with foster care placement instability. Implications for practice and future research are discussed.
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Left-right asymmetries and shape analysis on Ceroglossus chilensis (Coleoptera: Carabidae)
NASA Astrophysics Data System (ADS)
Bravi, Raffaella; Benítez, Hugo A.
2013-10-01
Bilateral symmetry is widespread in animal kingdom, however most animal can deviate from expected symmetry and manifest some kind of asymmetries. Fluctuating asymmetry is considered as a tool for valuating developmental instability, whereas directional asymmetry is inherited and could be used for evaluating evolutionary development. We use the method of geometric morphometrics to analyze left/right asymmetries in the whole body, in two sites and totally six populations of Ceroglossus chilensis with the aim to infer and explain morphological disparities between populations and sexes in this species. In all individuals analyzed we found both fluctuating asymmetry and directional asymmetry for size and shape variation components, and a high sexual dimorphism. Moreover a high morphological variability between the two sites emerged as well. Differences in diet could influence the expression of morphological variation and simultaneously affect body sides, and therefore contribute to the symmetric component of variation. Moreover differences emerged between two sites could be a consequence of isolation and fragmentation, rather than a response to local environmental differences between sampling sites.
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Segmentation in cohesive systems constrained by elastic environments
NASA Astrophysics Data System (ADS)
Novak, I.; Truskinovsky, L.
2017-04-01
The complexity of fracture-induced segmentation in elastically constrained cohesive (fragile) systems originates from the presence of competing interactions. The role of discreteness in such phenomena is of interest in a variety of fields, from hierarchical self-assembly to developmental morphogenesis. In this paper, we study the analytically solvable example of segmentation in a breakable mass-spring chain elastically linked to a deformable lattice structure. We explicitly construct the complete set of local minima of the energy in this prototypical problem and identify among them the states corresponding to the global energy minima. We show that, even in the continuum limit, the dependence of the segmentation topology on the stretching/pre-stress parameter in this problem takes the form of a devil's type staircase. The peculiar nature of this staircase, characterized by locking in rational microstructures, is of particular importance for biological applications, where its structure may serve as an explanation of the robustness of stress-driven segmentation. This article is part of the themed issue 'Patterning through instabilities in complex media: theory and applications.'
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Alados, Concepcion L.; Escos, Juan; Emlen, John M.
1995-01-01
The effects of inbreeding on the developmental instability of skulls of dorcas (Gazella dorcas) and dama (G. dama) gazelles were investigated. In total, 132 dorcas gazelle skulls and 74 dama gazelle skulls from the Estación Experimental de Zonas Aridas in Almera, Spain, were measured. The fluctuating asymmetry of 9 meristic characters, consisting of the numbers of foramina on the two sides of the skull and mandible, was calculated. Although only the foramen infraorbitalis showed a significant increase in asymmetry with inbreeding in dorcas gazelles, the sum of the foramina in 5 of the skull regions clearly indicates an increase in asymmetry with inbreeding in both dorcas and dama gazelles. The fractal dimension of the sagittal suture was calculated by means of the coastline method. A greater effect of inbreeding on the sagittal suture in dama than in dorcas gazelle was observed, in concordance with the more evident deleterious effects of inbreeding depression in dama than in dorcas gazelles.
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Musculo-Skeletal Abnormalities in Patients with Marfan Syndrome
Al Kaissi, Ali; Zwettler, Elisabeth; Ganger, Rudolf; Schreiner, Simone; Klaushofer, Klaus; Grill, Franz
2013-01-01
Background A leptosomic body type is tall and thin with long hands. Marfanoid features may be familial in nature or pathological, as occurs in congenital contractual arachnodactyly (Beal’s syndrome) and Shprintzen-Goldberg syndrome mimicking some of the changes of Marfan syndrome, although not accompanied by luxation of lens and dissecting aneurysm of aorta. Methods In this article we collected eight patients who were consistent with the diagnosis of Marfan syndrome via phenotypic and genotypic characterization. Results Our patients manifested a constellation of variable presentations of musculo-skeletal abnormalities ranging from developmental dysplasia of the hip, protrusio acetabuli, leg length inequality, patellar instability, scoliosis, to early onset osteoarthritis. Each abnormality has been treated accordingly. Conclusion This is the first paper which includes the diagnosis and the management of the associated musculo-skeletal abnormalities in patients with Marfan syndrome, stressing that patients with Marfan syndrome are exhibiting great variability in the natural history and the severity of musculo-skeletal abnormalities. PMID:23399831
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Trajectories of social withdrawal from middle childhood to early adolescence.
Oh, Wonjung; Rubin, Kenneth H; Bowker, Julie C; Booth-LaForce, Cathryn; Rose-Krasnor, Linda; Laursen, Brett
2008-05-01
Heterogeneity and individual differences in the developmental course of social withdrawal were examined longitudinally in a community sample (N = 392). General Growth Mixture Modeling (GGMM) was used to identify distinct pathways of social withdrawal, differentiate valid subgroup trajectories, and examine factors that predicted change in trajectories within subgroups. Assessments of individual (social withdrawal), interactive (prosocial behavior), relationship (friendship involvement, stability and quality, best friend's withdrawal and exclusion/victimization) and group- (exclusion/victimization) level characteristics were used to define growth trajectories from the final year of elementary school, across the transition to middle school, and then to the final year of middle school (fifth-to-eighth grades). Three distinct trajectory classes were identified: low stable, increasing, and decreasing. Peer exclusion, prosocial behavior, and mutual friendship involvement differentiated class membership. Friendlessness, friendship instability, and exclusion were significant predictors of social withdrawal for the increasing class, whereas lower levels of peer exclusion predicted a decrease in social withdrawal for the decreasing class.
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Numerical MHD study for plasmoid instability in uniform resistivity
NASA Astrophysics Data System (ADS)
Shimizu, Tohru; Kondoh, Koji; Zenitani, Seiji
2017-11-01
The plasmoid instability (PI) caused in uniform resistivity is numerically studied with a MHD numerical code of HLLD scheme. It is shown that the PI observed in numerical studies may often include numerical (non-physical) tearing instability caused by the numerical dissipations. By increasing the numerical resolutions, the numerical tearing instability gradually disappears and the physical tearing instability remains. Hence, the convergence of the numerical results is observed. Note that the reconnection rate observed in the numerical tearing instability can be higher than that of the physical tearing instability. On the other hand, regardless of the numerical and physical tearing instabilities, the tearing instability can be classified into symmetric and asymmetric tearing instability. The symmetric tearing instability tends to occur when the thinning of current sheet is stopped by the physical or numerical dissipations, often resulting in the drastic changes in plasmoid chain's structure and its activity. In this paper, by eliminating the numerical tearing instability, we could not specify the critical Lundquist number Sc beyond which PI is fully developed. It suggests that Sc does not exist, at least around S = 105.
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European Upper Atmosphere Server DIAS - Final Conference/ Abstract
2007-01-10
PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) INGV - Istituto Nazionale di Geofisica e Vulcanologia (Nat Instit Geophysics, Volcanology) Via di Vigna...organised by the Istituto Nazionale di Geofisica e Vulcanologia (INGV), Rome, Italy. D6.8 Report on the Final Conference - 3 - In general, the DIAS...the Istituto Nazionale di Geofisica e Vulcanologia in Rome focused on the general overview of scientific and technical tools adopted by the DIAS
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Pallavicini, Marco
1995-01-01
Oggetto di questa tesi è la misura di alcune caratteristiche fisiche ( massa, larghezza, e larghezza parziale in p - p) degli stati 3 Pi e 3 A del charmonio, - overo del sistema legato di un quark "charm" e del suo antiquark-, nell'ambito dell'esperimento E-760, installato nell'accumulatore di antiprotoni del Fermilab (U.S.A).
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Rubio, Teresa; Borja, Marisé; Scholthof, Herman B.; Feldstein, Paul A.; Morris, T. Jack; Jackson, Andrew O.
1999-01-01
We have designed a DNA cassette to transcribe defective interfering (DI) RNAs of tomato bushy stunt virus (TBSV) and have investigated their potential to protect transgenic Nicotiana benthamiana plants from tombusvirus infections. To produce RNAs with authentic 5′ and 3′ termini identical to those of the native B10 DI RNA, the DI RNA sequences were flanked by ribozymes (RzDI). When RzDI RNAs transcribed in vitro were mixed with parental TBSV transcripts and inoculated into protoplasts or plants, they became amplified, reduced the accumulation of the parental RNA, and mediated attenuation of the lethal syndrome characteristic of TBSV infections. Analysis of F1 and F2 RzDI transformants indicated that uninfected plants expressed the DI RNAs in low abundance, but these RNAs were amplified to very high levels during TBSV infection. By two weeks postinoculation with TBSV, all untransformed N. benthamiana plants and transformed negative controls died. Although infection of transgenic RzDI plants initially induced moderate to severe symptoms, these plants subsequently recovered, flowered, and set seed. Plants from the same transgenic lines also exhibited broad-spectrum protection against related tombusviruses but remained susceptible to a distantly related tombus-like virus and to unrelated viruses. PMID:10233970
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Eison, A S; Eison, M S; Iversen, S D
1982-04-22
The behavioural response following infusion of a novel, stable substance P (SP) analogue, DiMe-C7, into the ventral tegmental area (VTA) of rats was characterized and contrasted with the response to an equal dose of the parent compound SP. DiMe-C7 produced a longer-lasting behavioural stimulation than SP as evidenced in several behaviours, including locomotor activity, wet dog shakes, rearing and grooming. DiMe-C7-induced locomotor activity and rearing were potentiated by concurrent peripheral administration of D-amphetamine and blocked by pretreatment with haloperidol. Such responses to DiMe-C7 may thus be dependent upon dopaminergic activity. When given immediately following VTA infusion of DiMe-C7, morphine decreased, while naloxone had no effect upon most behavioural measures. The effect of methysergide on DiMe-C7 or SP into the substantia nigra reticulata produced a pattern of responses similar to nature to those produced by VTA infusion but different with respect to time course. These findings suggest that DiMe-C7 is a metabolically stable analogue of substance P which manifests prolonged actions on behaviour when centrally administered. Further, a role for central dopaminergic mechanisms is implicated in DiMe-C7-induced behavioural action.
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Correlation between Maxillary Canine Calcification and Skeletal Maturation.
Kumar, Sushil; Roy, Abhishek Singha; Garg, Ankit; Hamid, Saeed Bin; Tyagi, Sumit; Kumar, Atish
2017-05-01
Skeletal maturation assessment has a great role in many health professions especially in Orthodontics & Dentofacial Orthopedics. Functional appliances have proved to be more effective when used at the peak of mandibular growth, rather than before. The aim of this study was to evaluate whether the calcification stages of permanent maxillary canine are useful to assess skeletal maturity. In this cross-sectional study, samples were derived from panoramic radiographs and lateral cephalograms of 300 subjects (137 males and 163 females) with their age ranging from 9 to 18 years. Dental maturity {Demirjian Index (DI)} and skeletal maturity {Cervical Stages (CS)} were assessed from radiographs. The Pearson chi-square test (χ 2 ) and Sakoda adjusted Pearson contingency coefficient (C*) were calculated to determine the correlation between DI and CS. A highly significant association (C* = 0.851, p <.001for males and 0.879, p <.001 for females) was found between DI and CS. DI stage E coincided with CS2 (pre-peak of pubertal growth spurt) & DI stage F coincided with CS3 (peak of pubertal growth spurt) for all the subjects. DI stage H corresponded to CS5 and CS6 (end of peak of pubertal growth spurt). A highly significant association was found between DI and CS. Maxillary canine DI stages could be useful to assess skeletal maturity.
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Synergistic Effect of Carbon Nanotubes and Graphene on Diopside Scaffolds.
Liu, Tingting; Wu, Ping; Gao, Chengde; Feng, Pei; Xiao, Tao; Deng, Youwen; Shuai, Cijun; Peng, Shuping
2016-01-01
A synergetic effect between carbon nanotubes (CNTs) and graphene on diopside (Di) scaffolds was demonstrated. 3D network architecture in the matrix was formed through the 1D CNTs inlaid among the 2D graphene platelets (GNPs). The mechanical properties of the CNTs/GNPs/Di scaffolds were significantly improved compared with the CNTs/Di scaffolds and GNPs/Di scaffolds. In addition, the scaffolds exhibited excellent apatite-forming ability, a modest degradation rate, and stable mechanical properties in simulated body fluid (SBF). Moreover, cell culturing tests indicated that the scaffolds supported the cells attachment and proliferation. Taken together, the CNTs/GNPs/Di scaffolds offered great potential for bone tissue engineering.
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The oxidation of 2,6-di-tert-butyl-4-methylphenol
Yohe, G.R.; Dunbar, J.E.; Pedrotti, R.L.; Scheidt, F.M.; Lee, F.G.H.; Smith, E.C.
1956-01-01
The products formed in the oxidation of 2,6-di-tert-butyl-4-methylphenol with oxygen and sodium hydroxide at about 100?? are 3,5-di-tert-butyl-4-hydroxybenzaldehyde, trimethylacetic acid, an acidic compound C14H22O3, and probably 2,6-di-tert-butylbenzoquinone (which was actually isolated in the similar oxidation of the above-named benzaldehyde), in addition to compounds previously reported. Some of the properties of C14H22O3 are given, and the oxidation of it to 2,3-di-tert-butylsuccinic anhydride is described, but assignment of structure is reserved pending the completion of more experimental work.
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IRIS (Integrity and Reliability in Integrated Circuits) Test Article Generation (ITAG)
2015-03-31
67 M12 edram_di_19 O 111 B9 edram_addr_9 O 24 L1 edram_do_12 I 68 N14 edram_di_18 O 112 A9 edram_addr_8 O 25 K2 edram_do_11 I 69 M13 edram_di_17 O 113... M13 edram_di_17 O 113 A8 padVDD 2.5V 26 M1 edram_do_10 I 70 L12 edram_di_16 O 114 B8 padVSS GND 27 L2 edram_do_9 I 71 M14 padVDD 2.5V 115 C8
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Dissemination and Implementation Research for Occupational Safety and Health.
Dugan, Alicia G; Punnett, Laura
2017-12-01
The translation of evidence-based health innovations into real-world practice is both incomplete and exceedingly slow. This represents a poor return on research investment dollars for the general public. U.S. funders of health sciences research (e.g., NIH, CDC, NIOSH) are increasingly calling for dissemination plans, and to a lesser extent for dissemination and implementation (D&I) research, which are studies that examine the effectiveness of D&I efforts and strategies and the predictors of D&I success. For example, rather than merely broadcasting information about a preventable hazard, D&I research in occupational safety and health (OSH) might examine how employers or practitioners are most likely to receive and act upon that information. We propose here that D&I research should be seen as a dedicated and necessary area of study within OSH, as a way to generate new knowledge that can bridge the research-to-practice gap. We present D&I concepts, frameworks, and examples that can increase the capacity of OSH professionals to conduct D&I research and accelerate the translation of research findings into meaningful everyday practice to improve worker safety and health.
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[La diagnosi del disturbo da uso di alcol dal punto di vista psicologico].
Coriale, Giovanna; Fiorentino, Daniela; Porrari, Raffaella; Battagliese, Gemma; Capriglione, Ida; Cereatti, Federica; Iannuzzi, Silvia; Mauri, Benilde; Galli, Domenica; Fiore, Marco; Attilia, Maria Luisa; Ceccanti, Mauro
2018-01-01
RIASSUNTO. Il disturbo da uso di alcol (DUA) è uno dei disturbi psichiatrici più comuni nella popolazione generale. Il DUA è caratterizzato da un pattern di bere eccessivo, che si mantiene nonostante gli effetti negativi che l'alcol ha sul funzionamento lavorativo, sulla salute, sulle problematiche legali, sull'educazione e sulla vita sociale. Attualmente, il modello bio-psico-sociale è quello che spiega meglio il DUA. Infatti, molte ricerche hanno fornito evidenze su come il DUA sia una patologia multidimensionale. Variabili biologiche, psicologiche e socio-culturali entrano in gioco nell'eziologia, nella natura, nel mantenimento e nel cambiamento nel tempo del disturbo. La fase diagnostica è un momento importante del processo di cura, perché il successo del trattamento dipende in larga misura dall'esattezza e dall'adeguatezza della diagnosi. La diagnosi clinica si basa su una valutazione globale del funzionamento del paziente e utilizza il colloquio e gli strumenti psicometrici come mezzo di raccolta di informazioni. Questo articolo fornirà una panoramica delle dimensioni psicologiche più importanti da valutare e sui migliori strumenti psicometrici da usare per una diagnosi adeguata.
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PREFACE: Fourth Meeting on Constrained Dynamics and Quantum Gravity
NASA Astrophysics Data System (ADS)
Cadoni, Mariano; Cavaglia, Marco; Nelson, Jeanette E.
2006-04-01
The formulation of a quantum theory of gravity seems to be the unavoidable endpoint of modern theoretical physics. Yet the quantum description of the gravitational field remains elusive. The year 2005 marks the tenth anniversary of the First Meeting on Constrained Dynamics and Quantum Gravity, held in Dubna (Russia) due to the efforts of Alexandre T. Filippov (JINR, Dubna) and Vittorio de Alfaro (University of Torino, Italy). At the heart of this initiative was the desire for an international forum where the status and perspectives of research in quantum gravity could be discussed from the broader viewpoint of modern gauge field theories. Since the Dubna meeting, an increasing number of scientists has joined this quest. Progress was reported in two other conferences in this series: in Santa Margherita Ligure (Italy) in 1996 and in Villasimius (Sardinia, Italy) in 1999. After a few years of ``working silence'' the time was now mature for a new gathering. The Fourth Meeting on Constrained Dynamics and Quantum Gravity (QG05) was held in Cala Gonone (Sardinia, Italy) from Monday 12th to Friday 16th September 2005. Surrounded by beautiful scenery, 100 scientists from 23 countries working in field theory, general relativity and related areas discussed the latest developments in the quantum treatment of gravitational systems. The QG05 edition covered many of the issues that had been addressed in the previous meetings and new interesting developments in the field, such as brane world models, large extra dimensions, analogue models of gravity, non-commutative techniques etc. The format of the meeting was similar to the previous ones. The programme consisted of invited plenary talks and parallel sessions on cosmology, quantum gravity, strings and phenomenology, gauge theories and quantisation and black holes. A major goal was to bring together senior scientists and younger people at the beginning of their scientific career. We were able to give financial support to both groups. In particular, help was provided to students and scientists from non-EU countries. It is our great pleasure to thank those people and institutions whose help and support was crucial to the success of the meeting. We appreciate the enthusiastic support of our colleagues of the academic community, especially those from the Istituto Nazionale di Fisica Nucleare and the Universities of Cagliari, Pisa, Torino and Mississippi. Financial support was provided by the Istituto Nazionale di Fisica Nucleare, the Universities of Cagliari, Torino, Pisa and Mississippi. This was used largely to support participants, especially younger people. Special thanks go to Pietro Menotti (University of Pisa) and Stefano Sciuto (University of Torino) for their friendship and their universities' financial contributions. It is also a pleasure to acknowledge financial support from the Regione Autonoma della Sardegna and from Tiscali, the communications and Internet company, for providing free telephone cards. Technical support and local organisation was provided by the Sezione di Cagliari of the Istituto Nazionale di Fisica Nucleare. Warmest thanks go to our administrative and technical staff - Maria Assunta Lecca and Simona Renieri, for their untiring assistance, and to Palmasera Village and Hotel Smeraldo for their splendid hospitality. And finally, our gratitude goes to all the participants and especially the many experienced scientists. Their contributions highlighted the meeting and were largely without support. The success of the meeting is due to them and to the enthusiasm of the younger participants. The Editors January 2006 COMMITTEES Organising Committee Mariano Cadoni (Università and INFN Cagliari) Marco Cavaglià (University of Mississippi) Jeanette E. Nelson (Università and INFN Torino) Advisory Committee Orfeu Bertolami (IST Lisboa, Portugal) Luca Bombelli (Univ. Mississippi) Steve Carlip (UC Davis, USA) Alessandro D'Adda (INFN Torino, Italy) Stanley Deser (Brandeis, USA) Georgi Dvali (NYU, USA) Sergio Ferrara (CERN) Gian Francesco Giudice (CERN) Roman Jackiw (MIT, USA) Edward W. Kolb (Fermilab, USA) Luca Lusanna (INFN Firenze, Italy) Roy Maartens (Univ. Portsmouth, UK) Hermann Nicolai (AEI, Potsdam, Germany) Tullio Regge (Politecnico di Torino, Italy) Augusto Sagnotti (Univ. Roma Tor Vergata, Italy) Kellogg S. Stelle (Imperial College London, UK) Ruth Williams (DAMTP, Cambridge, UK) SPONSORS Istituto Nazionale di Fisica Nucleare Università di Cagliari Università di Torino University of Mississippi Università di Pisa Regione autonoma della Sardegna Tiscali LIST OF PARTICIPANTS Eun-Joo Ahn (University of Chicago, USA) David Alba (Università di Firenze, Italy) Stanislav Alexeyev (Lomonosov Moscow State U., Russia) Damiano Anselmi (Università di Pisa, Italy) Ignatios Antoniadis (CERN, Geneva, Switzerland) Maria Da Conceicao Bento (Instituto Superior Técnico, Lisboa, Portugal) Orfeu Bertolami (Instituto Superior Técnico, Lisboa, Portugal) Massimo Bianchi (Università di Roma Tor Vergata, Italy) Mariam Bouhmadi-Lopez (University of Portsmouth, UK) Raphael Bousso (University of California at Berkeley, USA) Mariano Cadoni (Università di Cagliari, Italy) Steven Carlip (University of California at Davis, USA) Roberto Casadio (Università di Bologna, Italy) Marco Cavaglià (University of Mississippi, USA) Demian Cho (Raman Research Institute, Bangalore, India) Theodosios Christodoulakis (University of Athens, Greece) Chryssomalis Chryssomalakos (Inst. de Ciencias Nucleares - UNAM, Mexico) Diego Julio Cirilo-Lombardo (JINR, Dubna, Russia) Denis Comelli INFN, Sezione di Ferrara, Italy ) Ruben Cordero-Elizalde (Instituto Politecnico Nacional, Mexico) Lorenzo Cornalba (Università di Roma Tor Vergata, Italy) Branislav Cvetkovic (Institute of Physics, Belgrade, Serbia ) Maro Cvitan (University of Zagreb, Croatia) Alessandro D'Adda (Università di Torino, Italy) Claudio Dappiaggi (Università di Pavia, Italy) Roberto De Leo (Università di Cagliari, Italy) Roberto De Pietri (Università di Parma, Italy) Giuseppe De Risi (Università di Bari, Italy) Hans-Thomas Elze (Univ. Federal do Rio de Janeiro, Brasil) Alessandro Fabbri (Università di Bologna, Italy) Sergey Fadeev (VNIIMS, Moscow, Russia) Serena Fagnocchi (Università di Bologna, Italy) Sara Farese (Universidad de Valencia, Spain) Alessandra Feo (Università di Parma, Italy) Dario Francia (Università di Roma Tor Vergata, Italy) Francesco Fucito (Università di Roma Tor Vergata, Italy) Dmitri Fursaev (JINR, Dubna, Russia) Daniel Galehouse (University of Akron, Ohio, USA) Remo Garattini (Università di Bergamo, Italy) Florian Girelli (Perimeter Institute, Waterloo, Canada) Luca Griguolo (Università di Parma, Italy) Daniel Grumiller (Universität Leipzig, Germany) Shinichi Horata (Hayama Center of Advanced Research, Japan) Giorgio Immirzi (Università di Perugia, Italy) Roman Jackiw (MIT, Cambridge, USA) Matyas Karadi (DAMTP, University of Cambridge, UK) Mikhail Katanaev (Steklov Mathematical Institute, Moscow, Russia) Claus Kiefer (Universität Koln, Germany) John Klauder (University of Florida, Gainesville, USA) Pavel Klepac (Masaryk University, Brno, Czech Republic) Jen-Chi Lee (National Chiao-Tung University, Taiwan) Carlos Leiva (Universidad de Tarapacá, Arica, Chile) Stefano Liberati (SISSA/ISAS, Trieste, Italy) Jorma Louko (University of Nottingham, UK) Luca Lusanna (INFN, Sezione di Firenze, Italy) Roy Maartens (University of Portsmouth, UK) Fotini Markopoulou (Perimeter Institute, Waterloo, Canada) Annalisa Marzuoli (Università di Pavia, Italy) Evangelos Melas (QMW, University of London, UK) Maurizio Melis (Università di Cagliary, Italy) Vitaly Melnikov (VNIIMS, Moscow, Russia) Guillermo A. Mena Marugan (CSIC, Madrid, Spain) Pietro Menotti (Università di Pisa, Italy) Salvatore Mignemi (Università di Cagliari, Italy) Aleksandar Mikovic (Universidade Lusófona, Lisboa, Portugal) Leonardo Modesto (Université de la Mediterranée, Marseille, France) Michael Mueller (Sardinien.com, Cagliari, Italy) Mario Nadalini (Università di Trento, Italy) José Navarro-Salas (Universidad de Valencia, Spain) Jeanette E. Nelson (Università di Torino, Italy) Alexander Nesterov (Universidad de Guadalajara, Mexico) Hermann Nicolai (Albert-Einstein-Institut, Golm, Germany) Daniele Oriti (DAMTP, University of Cambridge, UK) Marcello Ortaggio (Charles University, Prague, Czech Republic) Silvio Pallua (University of Zagreb, Croatia) Matej Pavsic (Jozef Stefan Institute, Ljubljana, Slovenia) Wlodzimierz Piechocki (Soltan Inst. for Nuclear Studies, Warsaw, Poland) Nicola Pinamonti (Università di Trento, Italy) J. Brian Pitts (University of Notre Dame, Indiana, USA) Vojtech Pravda (Academy of Sciences, Praha, Czech Rep.) Gianpaolo Procopio (DAMTP, University of Cambridge, UK) Alice Rogers (King's College London, UK) Efrain Rojas (Universidad Veracruzana, Mexico) James Ryan (DAMTP, University of Cambridge, UK) Augusto Sagnotti (Università di Roma Tor Vergata, Italy) Wenceslao Santiago-German (University of California at Davis, USA) Stefano Sciuto (Università di Torino, Italy) Domenico Seminara (Università di Firenze, Italy) Lorenzo Sindoni (Università di Udine, Italy) Kellogg S. Stelle (Imperial College, London, UK) Cosimo Stornaiolo (INFN, Sezione di Napoli, Italy) Ward Struyve (Perimeter Institute, Waterloo, Canada) Makoto Tanabe (Waseda University, Tokyo, Japan) Daniel Terno (Perimeter Institute, Waterloo, Canada) Charles Wang (Lancaster University, UK) Silke Weinfurtner (Victoria University, Wellington, New Zealand) Hans Westman (Perimeter Institute, Waterloo, Canada) Ruth Williams (DAMTP, University of Cambridge, UK) Tetsuyuki Yukawa (Graduate U. for Adv. Studies, Kanagawa, Japan) Jorge Zanelli (CECS, Santiago, Chile)
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Harr, Jennifer C; Luperchio, Teresa Romeo; Wong, Xianrong; Cohen, Erez; Wheelan, Sarah J; Reddy, Karen L
2015-01-05
Nuclear organization has been implicated in regulating gene activity. Recently, large developmentally regulated regions of the genome dynamically associated with the nuclear lamina have been identified. However, little is known about how these lamina-associated domains (LADs) are directed to the nuclear lamina. We use our tagged chromosomal insertion site system to identify small sequences from borders of fibroblast-specific variable LADs that are sufficient to target these ectopic sites to the nuclear periphery. We identify YY1 (Ying-Yang1) binding sites as enriched in relocating sequences. Knockdown of YY1 or lamin A/C, but not lamin A, led to a loss of lamina association. In addition, targeted recruitment of YY1 proteins facilitated ectopic LAD formation dependent on histone H3 lysine 27 trimethylation and histone H3 lysine di- and trimethylation. Our results also reveal that endogenous loci appear to be dependent on lamin A/C, YY1, H3K27me3, and H3K9me2/3 for maintenance of lamina-proximal positioning. © 2015 Harr et al.
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Non-surgical root canal treatment of Dens invaginatus: reports of three cases.
Cengiz, Sevi Burcak; Korasli, Deniz; Ziraman, Fatmagul; Orhan, Kaan
2006-02-01
Dens invaginatus is a rare developmental malformation of teeth showing a deep infolding of enamel and dentine which may extend deep into the root. To date, conventional root canal therapy, endodontic surgery and extraction have been reported as treatment modalities, when the pulpo-dentinal complex of such teeth is affected. In the present report, non-surgical endodontic treatment of three maxillary lateral incisors with invaginatus (DI) is discussed. The Tri Auto ZX rotary system was used for shaping the root canals of two affected teeth and the Profile system was used in the third. Teeth with periradicular lesions received calcium hydroxide as an interim therapy. Two teeth were obturated with gutta percha points and AH Plus sealer using cold lateral compaction. In the third case, obturation was accomplished using a coated carrier system (Thermafil) due to the specific shape of the root canal system. Twelve months postoperatively all teeth were asymptomatic with resolution of the periapical radiolucency on two affected teeth, as confirmed radiographically. Healing was achieved without any need for further surgical intervention.
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Repeated deflation-inflation events at Kilauea Volcano, Hawai'i: What's up (and down) with that?
NASA Astrophysics Data System (ADS)
Poland, M. P.; Miklius, A.; Lundgren, P.; Sutton, A. J.
2011-12-01
Cyclic deflation-inflation ("DI") events are a common occurrence at Kilauea Volcano. Most DI events begin with deflation at the summit that generally lasts 12-72 hours and accumulate ~1-5 microradians of tilt as measured on the rim of Kilauea caldera, followed by inflation that is initially rapid but wanes as the net deformation approaches pre-event levels over the course of 12-48 hours. In rare cases, the initial deflation is followed by large-magnitude (~20 microradians) inflation over a few hours followed by hours to days of deflation to pre-event levels. Such DID events have only been recorded during 2000-2004. DI events are also manifested at the Pu'u 'O'o eruptive vent on Kilauea's east rift zone, about 15 km from the summit, and lag summit deformation by about 1-2 hours. For DI events with relatively large-magnitudes (i.e., several microradians) and long-durations (i.e., several days), deformation is manifested along the east rift zone between Pu'u 'O'o and the summit, and eruptive activity at Pu'u 'O'o is impacted with long periods of deflation and inflation associated with eruptive pauses and surges, respectively. During a period of increased magma transport between the summit and Pu'u 'O'o in 2005-2007, DI events recorded at the summit were not detected at Pu'u 'O'o. Since the March 2008 start of Kilauea's ongoing summit eruption, the number of DI events per year has increased from about 5-10 to about 50-60. The level of the summit lava column (continuously visible since early 2010), has generally tracked DI deformation. Surface deformation associated with DI events is measured by tilt, GPS, and InSAR. At the summit, preliminary source models suggest a depth of 1-2 km and a sill-like geometry beneath the center of the caldera, with volume loss and subsequent recovery on the order of tens of thousands of cubic meters with each DI cycle. The localized nature of the DI signal at Pu'u 'O'o argues for a shallow source that is probably less than 1 km deep. At least two mechanisms are consistent with the occurrence of DI events at Kilauea. First, blockage and subsequent clearing of the transport pathway that feeds the shallow summit magma system and conduit to Pu'u 'O'o could cause the observed deformation. A second possibility is that DI events represent convective overturns caused by replacement of degassed magma with gas-rich magma. Such a model is consistent with the increased number of DI events following the onset of Kilauea's summit eruption, when summit gas emissions increased by a factor of about 5, but there have been no changes in degassing rates during periods of frequent (i.e., daily) or rare (i.e., monthly) DI events during 2008-2011. The source of DI events therefore remains a target of continued study.
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Electrothermal instability growth in magnetically driven pulsed power liners
NASA Astrophysics Data System (ADS)
Peterson, Kyle J.; Sinars, Daniel B.; Yu, Edmund P.; Herrmann, Mark C.; Cuneo, Michael E.; Slutz, Stephen A.; Smith, Ian C.; Atherton, Briggs W.; Knudson, Marcus D.; Nakhleh, Charles
2012-09-01
This paper explores the role of electro-thermal instabilities on the dynamics of magnetically accelerated implosion systems. Electro-thermal instabilities result from non-uniform heating due to temperature dependence in the conductivity of a material. Comparatively little is known about these types of instabilities compared to the well known Magneto-Rayleigh-Taylor (MRT) instability. We present simulations that show electrothermal instabilities form immediately after the surface material of a conductor melts and can act as a significant seed to subsequent MRT instability growth. We also present the results of several experiments performed on Sandia National Laboratories Z accelerator to investigate signatures of electrothermal instability growth on well characterized initially solid aluminum and copper rods driven with a 20 MA, 100 ns risetime current pulse. These experiments show excellent agreement with electrothermal instability simulations and exhibit larger instability growth than can be explained by MRT theory alone.
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Mathematical Models of Smart Obstacles
2006-10-01
Matematica “G. Castelnuovo” Università di Roma “La Sapienza”, Piazzale Aldo Moro 2 00185 Roma Italy Ph. N. +39-06-49913282, FAX N. +39-06...Dipartimento di Matematica G. Castelnuovo Università di Roma La Sapienza, Piazzale Aldo Moro 2 00185 Roma Italy 8. PERFORMING ORGANIZATION REPORT NUMBER 9... Matematica G. Castelnuovo Università di Roma “La Sapienza” 00185 Roma, Italy 2 Smart (or active) obstacles are obstacles that when illuminated by an
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Nakayama, Shizuka; Kelsey, Ilana; Wang, Jingxin; Sintim, Herman O
2011-04-28
The ubiquitous bacterial biofilm regulator, c-di-GMP can form G-quadruplexes at physiological conditions in the presence of some aromatic compounds, such as acriflavine and proflavine. The fluorescence of these compounds is quenched upon c-di-GMP binding and some of the formed c-di-GMP G-quadruplexes are stable even at 75 °C. © The Royal Society of Chemistry 2011
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Nakayama, Shizuka; Roelofs, Kevin; Lee, Vincent T; Sintim, Herman O
2012-03-01
Herein, we demonstrate that the bacterial signaling molecule, c-di-GMP, can enhance the peroxidation of hemin when proflavine is present. The c-di-GMP-proflavine-hemin nucleotidezyme can oxidize the colorless compound 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), ABTS, to the colored radical cation ABTS˙(+) and hence provides simple colorimetric detection of c-di-GMP at low micromolar concentrations.
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Hadfield holds bubble detectors for the RaDI-N Experiment in the Columbus Module
2013-01-25
ISS034-E-034506 (25 Jan. 2013) --- Canadian Space Agency astronaut Chris Hadfield, Expedition 34 flight engineer, holds bubble detectors for the RaDI-N experiment in the International Space Station?s Kibo laboratory. RaDI-N measures neutron radiation levels onboard the space station. RaDI-N uses bubble detectors as neutron monitors which have been designed to only detect neutrons and ignore all other radiation.
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Data Economics in Army Information Systems
1989-03-01
CONTACTED: LtCol Robert DiBona Chief, Policy Plans and Integration Division (703) 664-3986 DATE: 17 January 1989 DISCUSSION: 1. The MITRE study group called...LtCol Robert DiBona on the recommendation of Mr. James Glymph of Data Management Directorate (DMD), Information Systems Engineering Command (ISEC...LtCol DiBona is in charge of the ISEC Standard Army Management Information System (STAMIS) Modernization (STAMOD) program. 2. LtCol DiBona did not know
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Vasopressin Receptor Signaling and Cycling of Water Channels in Renal Epithelia (HBC)
1993-08-27
in the cellular ultrastructure that results in mucosal membrane reorganization to numerous microvilli from the normal phase of microridges ( DiBona ...a restructuring of the apical membrane microridges into numerous microvilli with an increase in membrane surface area ( DiBona , 1981; DiBona et aL...markers in freeze-fracture studies of toad urinary bladder. J. Histochem. Cytochem., 35, 1405-1414. DiBona , D.R. 1981. Vasopressin action on the
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Lin, Chun-Han; Su, Chia-Ying; Chen, Chung-Hui
Further reduction of the efficiency droop effect and further enhancements of internal quantum efficiency (IQE) and output intensity of a surface plasmon coupled, blue-emitting light-emitting diode (LED) by inserting a dielectric interlayer (DI) of a lower refractive index between p-GaN and surface Ag nanoparticles are demonstrated. The insertion of a DI leads to a blue shift of the localized surface plasmon (LSP) resonance spectrum and increases the LSP coupling strength at the quantum well emitting wavelength in the blue range. With SiO{sub 2} as the DI, a thinner DI leads to a stronger LSP coupling effect, when compared with themore » case of a thicker DI. By using GaZnO, which is a dielectric in the optical range and a good conductor under direct-current operation, as the DI, the LSP coupling results in the highest IQE, highest LED output intensity, and weakest droop effect.« less
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Workplace injuries and the take-up of Social Security disability benefits.
O'Leary, Paul; Boden, Leslie I; Seabury, Seth A; Ozonoff, Al; Scherer, Ethan
2012-01-01
Workplace injuries and illnesses are an important cause of disability. State workers' compensation programs provide almost $60 billion per year in cash and medical-care benefits for those injuries and illnesses. Social Security Disability Insurance (DI) is the largest disability insurance program in the United States, with annual cash payments to disabled workers of $95 billion in 2008. Because injured workers may also receive DI benefits, it is important to understand how those two systems interact to provide benefits. This article uses matched state workers' compensation and Social Security data to study the relationship between workplace injuries and illnesses and DI benefit receipt. We find that having a lost-time injury substantially increases the probability of DI receipt, and, for people who become DI beneficiaries, those with injuries receive DI benefits at younger ages. This relationship remains robust even after we account for important personal and work characteristics.
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Martínez-Montero, Saúl; Deleavey, Glen F; Kulkarni, Anupriya; Martín-Pintado, Nerea; Lindovska, Petra; Thomson, Michael; González, Carlos; Götte, Matthias; Damha, Masad J
2014-06-20
We report on the synthesis and conformational properties of 2'-deoxy-2',4'-difluorouridine (2',4'-diF-rU) and cytidine (2',4'-diF-rC) nucleosides. NMR analysis and quantum mechanical calculations show that the strong stereoelectronic effects induced by the two fluorines essentially "lock" the conformation of the sugar in the North region of the pseudorotational cycle. Our studies also demonstrate that NS5B HCV RNA polymerase was able to accommodate 2',4'-diF-rU 5'-triphosphate (2',4'-diF-rUTP) and to link the monophosphate to the RNA primer strand. 2',4'-diF-rUTP inhibited RNA synthesis in dinucleotide-primed reactions, although with relatively high half-maximal inhibitory concentrations (IC50 > 50 μM). 2',4'-diF-rU/C represents rare examples of "locked" ribonucleoside mimics that lack a bicyclic ring structure.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Claus, Claudia; Tzeng, W.-P.; Liebert, Uwe Gerd
During serial passaging of rubella virus (RUB) in cell culture, the dominant species of defective-interfering RNA (DI) generated contains an in-frame deletion between the capsid protein (C) gene and E1 glycoprotein gene resulting in production of a C-E1 fusion protein that is necessary for the maintenance of the DI [Tzeng, W.P., Frey, T.K. (2006). C-E1 fusion protein synthesized by rubella virus DI RNAs maintained during serial passage. Virology 356 198-207.]. A BHK cell line stably expressing the RUB structural proteins was established which was used to package DIs into virus particles following transfection with in vitro transcripts from DI infectiousmore » cDNA constructs. Packaging of a DI encoding an in-frame C-GFP-E1 reporter fusion protein corresponding to the C-E1 fusion protein expressed in a native DI was only marginally more efficient than packaging of a DI encoding GFP, indicating that the C-E1 fusion protein did not function by enhancing packaging. However, infection with the DI encoding the C-GFP-E1 fusion protein (in the absence of wt RUB helper virus) resulted in formation of clusters of GFP-positive cells and the percentage of GFP-positive cells in the culture following infection remained relatively constant. In contrast, a DI encoding GFP did not form GFP-positive clusters and the percentage of GFP-positive cells declined by roughly half from 2 to 4 days post-infection. Cluster formation and sustaining the percentage of infected (GFP-positive) cells required the C part of the fusion protein, including the downstream but not the upstream of two arginine clusters (both of which are associated with RNA binding and association with mitochondrial p32 protein) and the E1 part through the transmembrane sequence, but not the C-terminal cytoplasmic tail. Among a collection of mutant DI constructs, cluster formation and sustaining infected cell percentage correlated with maintenance during serial passage with wt RUB. We hypothesize that cluster formation and sustaining infected cell percentage increase the likelihood of co-infection by a DI and wt RUB during serial passage thus enhancing maintenance of the DI. Cluster formation and sustaining infected cell percentage were found to be due to a combination of attenuated cytopathogenicity of DIs that express the C-E1 fusion protein and cell-to-cell movement of the DI. In infected cells, the C-GFP-E1 fusion protein was localized to potentially novel vesicular structures that appear to originate from ER-Golgi transport vacuoles. This species of DI expressing a C-E1 fusion protein that exhibits attenuated cytopathogenicity and the ability to increase the number of infected cells through cell-to-cell movement could be the basis for development of an attractive vaccine vector.« less
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Clofibrate and gemfibrozil induce an embryonic malabsorption syndrome in zebrafish
DOE Office of Scientific and Technical Information (OSTI.GOV)
Raldua, Demetrio; Andre, Michele; Babin, Patrick J.
2008-05-01
Nutrient availability is one of the major non-genetic factors determining embryonic growth and larval or fetal size. Due to the high human consumption of blood lipid regulators, fibrates have recently been reported as pollutants in rivers. Our study investigated the developmental toxicity of fibrates in zebrafish. Treatment with micromolar concentrations of clofibrate or gemfibrozil induced an embryonic malabsorption syndrome (EMS) with very little yolk consumption, resulting in small-sized larvae. This effect was reversible on removing the drug from the water. Clofibrate delayed hatching time and decreased the amount of oil red O lipid staining in the vasculature. It also inducedmore » higher density, round-shaped neuromuscular junctions associated with disorganization and less striation of muscular fibers, and pericardial edema, as well as impairing thyroid gland morphogenesis. acox1, apoa1 and mtp hybridization transcript signals were not affected in the yolk syncytial layer (YSL) after clofibrate exposure. Di-(2-ethylhexyl)-phthalate did not slow down yolk resorption, whereas brefeldin A induced EMS. These findings suggest that the inhibition of yolk sac resorption on exposure to fibrate is not at a pre-translational level or peroxisome proliferator-activated receptor alpha dependent and may be due to an inhibition of the YSL constitutive cell secretion. The effects of fibrates and the potential bioconcentration in eggs as well as the additive action of structurally related toxicants warrant an evaluation of the developmental impact of these compounds after long-term exposure at environmentally relevant concentrations. Fibrate-induced EMS in zebrafish seems useful for studying the morphogenetic consequences of impaired nutrient availability during the early stages of vertebrate development.« less
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Utz, Sandra; Schachtner, Joachim
2005-04-01
The antennal lobe (AL) of the sphinx moth Manduca sexta is a well-established model system for studying mechanisms of neuronal development. To understand whether neuropeptides are suited to playing a role during AL development, we have studied the cellular localization and temporal expression pattern of neuropeptides of the A-type allatostatin family. Based on morphology and developmental appearance, we distinguished four types of AST-A-immunoreactive cell types. The majority of the cells were local interneurons of the AL (type Ia) which acquired AST-A immunostaining in a complex pattern consisting of three rising (RI-RIII) and two declining phases (DI, DII). Type Ib neurons consisted of two local neurons with large cell bodies not appearing before 7/8 days after pupal ecdysis (P7/P8). Types II and III neurons accounted for single centrifugal neurons, with type II neurons present in the larva and disappearing in the early pupa. The type III neuron did not appear before P7/P8. RI and RII coincided with the rises of the ecdysteroid hemolymph titer. Artificially shifting the pupal 20-hydroxyecdysone (20E) peak to an earlier developmental time point resulted in the precocious appearance of AST-A immunostaining in types Ia, Ib, and III neurons. This result supports the hypothesis that the pupal rise in 20E plays a role in AST-A expression during AL development. Because of their early appearance in newly forming glomeruli, AST-A-immunoreactive fibers could be involved in glomerulus formation. Diffuse AST-A labeling during early AL development is discussed as a possible signal providing information for ingrowing olfactory receptor neurons.
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Stadler, Florian; Kolb, Gabriele; Rubusch, Lothar; Baker, Stephen P; Jones, Edward G; Akbarian, Schahram
2005-07-01
Glutamatergic signaling is regulated, in part, through differential expression of NMDA and AMPA/KA channel subunits and G protein-coupled metabotropic receptors. In human brain, region-specific expression patterns of glutamate receptor genes are maintained over the course of decades, suggesting a role for molecular mechanisms involved in long-term regulation of transcription, including methylation of lysine residues at histone N-terminal tails. Using a native chromatin immunoprecipitation assay, we studied histone methylation marks at proximal promoters of 16 ionotropic and metabotropic glutamate receptor genes (GRIN1,2A-D; GRIA1,3,4; GRIK2,4,5; GRM1,3,4,6,7 ) in cerebellar cortex collected across a wide age range from midgestation to 90 years old. Levels of di- and trimethylated histone H3-lysine 4, which are associated with open chromatin and transcription, showed significant differences between promoters and a robust correlation with corresponding mRNA levels in immature and mature cerebellar cortex. In contrast, levels of trimethylated H3-lysine 27 and H4-lysine 20, two histone modifications defining silenced or condensed chromatin, did not correlate with transcription but were up-regulated overall in adult cerebellum. Furthermore, differential gene expression patterns in prefrontal and cerebellar cortex were reflected by similar differences in H3-lysine 4 methylation at promoters. Together, these findings suggest that histone lysine methylation at gene promoters is involved in developmental regulation and maintenance of region-specific expression patterns of ionotropic and metabotropic glutamate receptors. The association of a specific epigenetic mark, H3-(methyl)-lysine 4, with the molecular architecture of glutamatergic signaling in human brain has potential implications for schizophrenia and other disorders with altered glutamate receptor function.