44 resultados para Marilyn Lutz
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Cardiac surgery modulates pro- and anti-inflammatory cytokine balance involving plasma tumour necrosis factor alpha (TNFa) and interleukin-10 (IL-10) together with urinary transforming growth factor beta-1 (TGFß1), interleukin-1 receptor antagonist (IL1ra) and tumour necrosis factor soluble receptor-2 (TNFsr2). Effects on post-operative renal function are unclear. We investigated if following cardiac surgery there is a relationship between cytokine (a) phenotype and renal outcome; (b) genotype and phenotype and (c) genotype and renal outcome. Since angiotensin-2 (AG2), modulates TGFß1 production, we determined whether angiotensin converting enzyme insertion/deletion (ACE I/D) genotype affects urinary TGFß1 phenotype as well as renal outcome.
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To evaluate the mortality and long-term morbidity rates of extremely low birth weight (ELBW) infants admitted to neonatal intensive care units (NICUs).
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Procedural pain in the neonatal intensive care unit triggers a cascade of physiological, behavioral and hormonal disruptions which may contribute to altered neurodevelopment in infants born very preterm, who undergo prolonged hospitalization at a time of physiological immaturity and rapid brain development. The aim of this study was to examine relationships between cumulative procedural pain (number of skin-breaking procedures from birth to term, adjusted for early illness severity and overall intravenous morphine exposure), and later cognitive, motor abilities and behavior in very preterm infants at 8 and 18 months corrected chronological age (CCA), and further, to evaluate the extent to which parenting factors modulate these relationships over time. Participants were N=211 infants (n=137 born preterm 32 weeks gestational age [GA] and n=74 full-term controls) followed prospectively since birth. Infants with significant neonatal brain injury (periventricular leucomalacia, grade 3 or 4 intraventricular hemorrhage) and/or major sensori-neural impairments, were excluded. Poorer cognition and motor function were associated with higher number of skin-breaking procedures, independent of early illness severity, overall intravenous morphine, and exposure to postnatal steroids. The number of skin-breaking procedures as a marker of neonatal pain was closely related to days on mechanical ventilation. In general, greater overall exposure to intravenous morphine was associated with poorer motor development at 8 months, but not at 18 months CCA, however, specific protocols for morphine administration were not evaluated. Lower parenting stress modulated effects of neonatal pain, only on cognitive outcome at 18 months.
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To compare aerobic capacity, strength, flexibility, and activity level in extremely low birth weight (ELBW) adolescents at 17 years of age with term-born control subjects.
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Large regions of recurrent genomic loss are common in cancers; however, with a few well-characterized exceptions, how they contribute to tumor pathogenesis remains largely obscure. Here we identified primate-restricted imprinting of a gene cluster on chromosome 20 in the region commonly deleted in chronic myeloid malignancies. We showed that a single heterozygous 20q deletion consistently resulted in the complete loss of expression of the imprinted genes L3MBTL1 and SGK2, indicative of a pathogenetic role for loss of the active paternally inherited locus. Concomitant loss of both L3MBTL1 and SGK2 dysregulated erythropoiesis and megakaryopoiesis, 2 lineages commonly affected in chronic myeloid malignancies, with distinct consequences in each lineage. We demonstrated that L3MBTL1 and SGK2 collaborated in the transcriptional regulation of MYC by influencing different aspects of chromatin structure. L3MBTL1 is known to regulate nucleosomal compaction, and we here showed that SGK2 inactivated BRG1, a key ATP-dependent helicase within the SWI/SNF complex that regulates nucleosomal positioning. These results demonstrate a link between an imprinted gene cluster and malignancy, reveal a new pathogenetic mechanism associated with acquired regions of genomic loss, and underline the complex molecular and cellular consequences of "simple" cancer-associated chromosome deletions.
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Berlin high (BEH) and Berlin low (BEL) strains selected for divergent growth differ 3-fold in body weight. We aimed at examining muscle mass, which is a major contributor to body weight, by exploring anatomical characteristics of the soleus muscle, its fiber numbers and their cross sectional area (CSA), by analysing transcriptome of the gastrocnemius and by initiating quantitative trait locus (QTL) mapping. BEH muscles were 4-to-8 times larger compared to BEL strain. In sub-strain BEH+/+, mutant myostatin was replaced with a wild type allele, however, BEH+/+muscles still were 2-to-4 times larger compared to the BEL strain. BEH soleus contained 2-times more (P<0.0001) and 2-times larger in CSA (P<0.0001) fibers compared to BEL strain. In addition, soleus femoral attachment anomaly (SFAA) was observed in all BEL mice. One significant (chromosome 1) and four suggestive (chromosomes 3, 4, 6 and 9) muscle weight QTLs were mapped in 21-day old F2 intercross (n=296) between BEH and BEL strains. The frequency of SFAA incidence in the F2 and in the backcross to BEL strain (BCL) suggested the presence of more than one causative gene. Two suggestive SFAA QTLs were mapped in BCL, however, their peak markers were not associated with the phenotype in F2. RNA-Seq analysis revealed 2,148 differentially expressed (P<0.1) genes and 45,673 SNPs and >2,000 indels between BEH+/+ and BEL males. In conclusion, contrasting muscle traits, genomic and gene expression differences between BEH and BEL strains provide a promising model for the search of genes involved in muscle growth and musculoskeletal morphogenesis.
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Reports of substantial evidence for genetic linkage of schizophrenia to chromosome 1q were evaluated by genotyping 16 DNA markers across 107 centimorgans of this chromosome in a multicenter sample of 779 informative schizophrenia pedigrees. No significant evidence was observed for such linkage, nor for heterogeneity in allele sharing among the eight individual samples. Separate analyses of European-origin families, recessive models of inheritance, and families with larger numbers of affected cases also failed to produce significant evidence for linkage. If schizophrenia susceptibility genes are present on chromosome 1q, their population-wide genetic effects are likely to be small.
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Summary
-Predatory functional responses play integral roles in predator–prey dynamics, and their assessment promises greater understanding and prediction of the predatory impacts of invasive species.
-Other interspecific interactions, however, such as parasitism and higher-order predation, have the potential to modify predator–prey interactions and thus the predictive capability of the comparative functional response approach.
-We used a four-species community module (higher-order predator; focal native or invasive predators; parasites of focal predators; native prey) to compare the predatory functional responses of native Gammarus duebeni celticus and invasive Gammarus pulex amphipods towards three invertebrate prey species (Asellus aquaticus, Simulium spp., Baetis rhodani), thus, quantifying the context dependencies of parasitism and a higher-order fish predator on these functional responses.
-Our functional response experiments demonstrated that the invasive amphipod had a higher predatory impact (lower handling time) on two of three prey species, which reflects patterns of impact observed in the field. The community module also revealed that parasitism had context-dependent influences, for one prey species, with the potential to further reduce the predatory impact of the invasive amphipod or increase the predatory impact of the native amphipod in the presence of a higher-order fish predator.
-Partial consumption of prey was similar for both predators and occurred increasingly in the order A. aquaticus, Simulium spp. and B. rhodani. This was associated with increasing prey densities, but showed no context dependencies with parasitism or higher-order fish predator.
-This study supports the applicability of comparative functional responses as a tool to predict and assess invasive species impacts incorporating multiple context dependencies.
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Pseudomonas aeruginosa is a major opportunistic pathogen in cystic fibrosis (CF) patients and causes a wide range of infections among other susceptible populations. Its inherent resistance to many antimicrobials also makes it difficult to treat infections with this pathogen. Recent evidence has highlighted the diversity of this species, yet despite this, the majority of studies on virulence and pathogenesis focus on a small number of strains. There is a pressing need for a P. aeruginosa reference panel to harmonize and coordinate the collective efforts of the P. aeruginosa research community. We have collated a panel of 43 P. aeruginosa strains that reflects the organism's diversity. In addition to the commonly studied clones, this panel includes transmissible strains, sequential CF isolates, strains with specific virulence characteristics, and strains that represent serotype, genotype or geographic diversity. This focussed panel of P. aeruginosa isolates will help accelerate and consolidate the discovery of virulence determinants, improve our understanding of the pathogenesis of infections caused by this pathogen, and provide the community with a valuable resource for the testing of novel therapeutic agents.
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The collection of the data for this volume formed part of the work of the European Science Foundation project on Writing National Histories. I was a member of the Research Team (1) which produced the volume. I also wrote two contributions for the Atlas. I collected the data and wrote the section on academic historians in Ireland. I also wrote a synthesis of the data on academic women historians in Europe, 1815-2005.
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Irreversibility is one of the most intriguing concepts in physics. While microscopic physical laws are perfectly reversible, macroscopic average behavior has a preferred direction of time. According to the second law of thermodynamics, this arrow of time is associated with a positive mean entropy production. Using a nuclear magnetic resonance setup, we measure the nonequilibrium entropy produced in an isolated spin-1/2 system following fast quenches of an external magnetic field and experimentally demonstrate that it is equal to the entropic distance, expressed by the Kullback-Leibler divergence, between a microscopic process and its time-reverse. Our result addresses the concept of irreversibility from a microscopic quantum standpoint.