78 research outputs found

    Vasopressin excites interneurons to suppress hippocampal network activity across a broad span of brain maturity at birth

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    During birth in mammals, a pronounced surge of fetal peripheral stress hormones takes place to promote survival in the transition to the extrauterine environment. However, it is not known whether the hormonal signaling involves central pathways with direct protective effects on the perinatal brain. Here, we show that arginine vasopressin specifically activates interneurons to suppress spontaneous network events in the perinatal hippocampus. Experiments done on the altricial rat and precocial guinea pig neonate demonstrated that the effect of vasopressin is not dependent on the level of maturation (depolarizing vs. hyperpolarizing) of postsynaptic GABA(A) receptor actions. Thus, the fetal mammalian brain is equipped with an evolutionarily conserved mechanism well-suited to suppress energetically expensive correlated network events under conditions of reduced oxygen supply at birth.Peer reviewe

    Longitudinal assessment of Allergic Outcomes and Atopic Dermatitis Phenotypes in The Children\u27s Respiratory and Environmental Workgroup (CREW) Birth Cohort Consortium

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    Rationale: Atopic dermatitis (AD) is a heterogenous inflammatory skin disease often associated with other allergic diseases. We characterized AD phenotypes and associated allergic outcomes longitudinally across a multi-site consortium. Methods: AD expression in 11 U.S. birth cohorts from the CREW (Children’s Respiratory and Environmental Workgroup) consortium was assessed in each year of life from age 0-7 years (N=7,900). Longitudinal Latent Class Analysis was performed to identify AD phenotypes. Five classes of AD were identified: Persistent AD (15.4%), Early AD with Potential Reoccurrence (2.7%), Late-Onset AD (7.0%), Transient Early AD (3.0%), and Minimal/No AD (72.0%). Serum allergen sensitization patterns and allergic clinical disease were associated with AD phenotype using multinomial logistic regression with a 3-step procedure to account for uncertainty in class membership. Results: Children with Persistent AD, Early AD with Potential Reoccurrence, and Transient Early AD were more likely to have food allergy compared to those with Minimal/No AD (OR[95% CI]=2.73[2.15, 3.45], 2.69[1.63, 4.45], 2.54[1.55, 4.16], respectively). These groups had similarly higher odds of food sensitization. Persistent AD (OR[95% CI]=1.81[1.48, 2.21]) and Early AD with Potential Reoccurrence (OR[95% CI]=3.66[1.90, 7.05]) had significantly higher odds of ever asthma relative to Minimal/No AD. At both 2-4 years and 5-7 years, persistent AD (OR[95% CI]=1.35[1.04, 1.74], 1.25[1.01, 1.53]) and Late-Onset AD (OR[95% CI]=1.68[1.13, 2.50], 2.22[1.33, 3.70]) relative to Minimal/No AD had higher odds of allergic rhinitis. Conclusions: Longitudinal AD phenotypes had varying associations with allergic sensitization, food allergy, asthma and allergic rhinitis, demonstrating the heterogeneity of allergic comorbidity risk associated with AD

    Longitudinal Characterization of Atopic Dermatitis Phenotypes in The Children\u27s Respiratory and Environmental Workgroup (CREW) Birth Cohort Consortium

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    Rationale: Previously identified longitudinal patterns of atopic dermatitis (AD) may lack generalizability and precision due to small sample size and limited time points. We identify and describe longitudinal AD phenotypes in a large consortium study. Methods: Data from 11 birth cohorts across the United States from the CREW (Children’s Respiratory and Environmental Workgroup) consortium were harmonized to determine physician diagnosis of AD in each year of life from 0-7 years of age (N=7,900). AD phenotypes were identified using Longitudinal Latent Class Analysis, and relationships with demographic variables were determined using multinomial logistic regression with a 3-step procedure to account for uncertainty in class membership. Results: We identified 5 classes of AD expression, selected based on model fit, interpretability, and clinical utility: Persistent AD (15.4%), Early AD with Potential Reoccurrence (2.7%), Late-Onset AD (7.0%), Transient Early AD (3.0%), and Minimal/No AD (72.0%). Males had significantly higher odds of Persistent AD (OR [95% CI]=1.47 [1.22, 1.75]) and Early AD with Potential Reoccurrence (OR [95% CI]=1.89 [1.19, 2.94]). Relative to White children, Black children had higher odds of Persistent AD (OR [95% CI]=2.50 [2.05, 3.05]), Early AD with Potential Reoccurrence (OR [95% CI]=3.07 [1.94, 4.85]), and Transient Early AD (OR [95% CI]=4.12 [2.62, 6.48]). Conclusions: Five AD phenotypes exist in a diverse national sample of children. Black children and males are at increased risk of early and persistent AD. These findings illustrate potential risk factors to target AD prevention

    Carbonic anhydrase seven bundles filamentous actin and regulates dendritic spine morphology and density

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    Intracellular pH is a potent modulator of neuronal functions. By catalyzing (de)hydration of CO2, intracellular carbonic anhydrase (CA(i)) isoforms CA2 and CA7 contribute to neuronal pH buffering and dynamics. The presence of two highly active isoforms in neurons suggests that they may serve isozyme-specific functions unrelated to CO2-(de)hydration. Here, we show that CA7, unlike CA2, binds to filamentous actin, and its overexpression induces formation of thick actin bundles and membrane protrusions in fibroblasts. In CA7-overexpressing neurons, CA7 is enriched in dendritic spines, which leads to aberrant spine morphology. We identified amino acids unique to CA7 that are required for direct actin interactions, promoting actin filament bundling and spine targeting. Disruption of CA7 expression in neocortical neurons leads to higher spine density due to increased proportion of small spines. Thus, our work demonstrates highly distinct subcellular expression patterns of CA7 and CA2, and a novel, structural role of CA7.Peer reviewe

    Habitat-Specific Morphological Variation among Threespine Sticklebacks (Gasterosteus aculeatus) within a Drainage Basin

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    Habitat-specific morphological variation, often corresponding to resource specialization, is well documented in freshwater fishes. In this study we used landmark based morphometric analyses to investigate morphological variation among threespine sticklebacks (Gasterosteus aculeatus L.) from four interconnected habitat types within a single lowland drainage basin in eastern England. These included the upper and lower reaches of the river, the estuary, a connected ditch network and a coastal salt marsh. We found significant habitat-specific differences in morphology, with three axes of variation describing differences in orbit diameter, body depth, caudal peduncle shape and pectoral fin positioning as well as variation in relative dorsal and pelvic spine size. Interestingly, the ditch system, an artificial and heavily managed habitat, is populated by sticklebacks with a characteristic morphology, suggesting that human management of habitats can in some circumstances lead to morphological variation among the animals that inhabit them. We discuss the mechanisms that conceivably underlie the observed morphological variation and the further work necessary to identify them. Finally, we consider the implications of habitat-specific body shape variation for the behavioural ecology of this ecologically generalist species

    Polystyrene cellulose fiber composites: effect of the processing conditions on mechanical and dynamic mechanical properties

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    ABSTRACT The usage of natural fibers on the composites development has grown rapidly in the recent years due to the fibers plentiful availability, renewable source, low density and biodegradability. However, there are some drawbacks, for instance, the fiber dispersion on a polyolefin matrix. In this work, the influence of processing speed on the mechanical and dynamic mechanical properties of polystyrene (PS) filled with cellulose fiber composites was investigated. The composites were processed on a twin-screw co-rotating extruder, using screw speeds of 200 rpm, 400 rpm and 600 rpm. The dynamic mechanical properties and the mechanical properties were investigated as a function of fiber content. The composites processed on a screw speed of 400 rpm had presented an increase on flexural and impact strength, compared to the composites processed at 200 rpm. The flexural and storage modulus had increased when increasing the fiber content, as well as increasing the processing speed. The greater fiber dispersion obtained at a screw speed of 400 rpm hinders the agglomeration arrangement and distributes the fibers more equally on the matrix. The increase on processing speed probably generates a fiber size reduction, increasing the fiber superficial area and generating a greater contact with the matrix as well. Therefore, the efforts transference of matrix to fibers is improved, originating an increase on the evaluated properties

    Polypropylene-microcrystalline cellulose composites with enhanced compatibility and properties

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    Polypropylene (PP)-microcrystalline cellulose (MCC) composites were prepared containing Poly(propylene-graft-maleic anhydride) (PP-g-MA) and MCC treated with silicone oil, stearic acid or alkyltitanate coupling agent to promote matrix-filler dispersion and compatability. Infrared spectroscopy confirmed surface treatment. MCC content and PP-g-MA increased PP thermal stability and crystallisation temperature (Tc), though reduced crystallinity due to cellulose II crystals. Tensile stress¿strain analysis revealed increased modulus with MCC content, PP-g-MA, alkyltitanate and stearic acid. MCC and PP-g-MA reduced creep deformation and increased permanent strain. Storage modulus, loss modulus and glass transition temperature increased with MCC concentration due to effective interaction between PP and MCC

    Crystalline polymorphism in polypropylene-copolymer nanocomposites

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