457 research outputs found

    Distinct patterns of thought mediate the link between brain functional connectomes and well-being

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    Ongoing thought patterns constitute important aspects of both healthy and abnormal human cognition. However, the neural mechanisms behind these daily experiences and their contribution to well-being remain a matter of debate. Here, using resting-state fMRI and retrospective thought sampling in a large neurotypical cohort (n = 211), we identified two distinct patterns of thought, broadly describing the participants’ current concerns and future plans, that significantly explained variability in the individual functional connectomes. Consistent with the view that ongoing thoughts are an emergent property of multiple neural systems, network-based analysis highlighted the central importance of both unimodal and transmodal cortices in the generation of these experiences. Importantly, while state-dependent current concerns predicted better psychological health, mediating the effect of functional connectomes, trait-level future plans were related to better social health, yet with no mediatory influence. Collectively, we show that ongoing thoughts can influence the link between brain physiology and well-being

    Three-Dimensional Holographic Refractive-Index Measurement of Continuously Flowing Cells in a Microfluidic Channel

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    The refractive index of biological specimens is a source of intrinsic contrast that can be explored without any concerns of photobleaching or harmful effects caused by extra contrast agents. In addition, the refractive index contains rich information related to the metabolism of cells at the cellular and subcellular levels. Here, we report a no-moving-parts approach that provides three-dimensional refractive-index maps of biological samples continuously flowing in a microfluidic channel. Specifically, we use line illumination and off-axis digital holography to record the angular spectra of light scattered from flowing samples at high speed. Applying the scalar diffraction theory, we obtain accurate refractive-index maps of the samples from the measured spectra. Using this method, we demonstrate label-free three-dimensional imaging of live RKO human colon cancer cells and RPMI8226 multiple myeloma cells, and obtain the volume, dry mass, and density of these cells from the measured three-dimensional refractive-index maps. Our results show that the reported method, alone or in combination with the existing flow cytometry techniques, shows promise as a quantitative tool for stain-free characterization of a large number of cells.National Institutes of Health (U.S.) (9P41EB015871-26A1)National Institutes of Health (U.S.) (P41 EB002503)Hamamatsu Corporatio

    Metabolic adaptations in skeletal muscle after 84 days of bed rest with and without concurrent flywheel resistance exercise

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    As metabolic changes in human skeletal muscle after long-term (simulated) spaceflight are not well understood, this study examined the effects of long-term microgravity, with and without concurrent resistance exercise, on skeletal muscle oxidative and glycolytic capacity. Twenty-one men were subjected to 84 days head-down tilt bed rest with (BRE; n 9) or without (BR; n 12) concurrent flywheel resistance exercise. Activity and gene expression of glycogen synthase, glycogen phosphorylase (GPh), hexokinase, phosphofructokinase-1 (PFK-1), and citrate synthase (CS), as well as gene expression of succinate dehydrogenase (SDH), vascular endothelial growth factor (VEFG), peroxisome proliferator-activated receptor gamma coactivator- 1 (PGC-1 ), and myostatin, were analyzed in samples from m.vastus lateralis collected before and after bed rest. Activity and gene expression of enzymes controlling oxidative metabolism (CS, SDH) decreased in BR but were partially maintained in BRE. Activity of enzymes regulating anaerobic glycolysis (GPh, PFK-1) was unchanged in BR. Resistance exercise increased the activity of GPh. PGC-1 and VEGF expression decreased in both BR and BRE. Myostatin increased in BR but decreased in BRE after bed rest. The analyses of these unique samples indicate that long-term microgravity induces marked alterations in the oxidative, but not the glycolytic, energy system. The proposed flywheel resistance exercise was effective in counteracting some of the metabolic alterations triggered by 84-day bed rest. Given the disparity between gene expression vs. enzyme activity in several key metabolic markers, posttranscriptional mechanisms should be explored to fully evaluate metabolic adaptations to long-term microgravity with/without exercise countermeasures in human skeletal muscle

    Neutrophils self-limit swarming to contain bacterial growth in vivo

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    Neutrophils communicate with each other to form swarms in infected organs. Coordination of this population response is critical for the elimination of bacteria and fungi. Using transgenic mice, we found that neutrophils have evolved an intrinsic mechanism to self-limit swarming and avoid uncontrolled aggregation during inflammation. G protein–coupled receptor (GPCR) desensitization acts as a negative feedback control to stop migration of neutrophils when they sense high concentrations of self-secreted attractants that initially amplify swarming. Interference with this process allows neutrophils to scan larger tissue areas for microbes. Unexpectedly, this does not benefit bacterial clearance as containment of proliferating bacteria by neutrophil clusters becomes impeded. Our data reveal how autosignaling stops self-organized swarming behavior and how the finely tuned balance of neutrophil chemotaxis and arrest counteracts bacterial escape

    Influenţa condiţiilor de păstrare asupra unor compuşi bioactivi din fructele de pădure şi contribuţia acestora asupra sănătăţii umane

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    The main criteria underlying this research consist in assessing the influence of the principal storage technologies on the content of some bioactive compounds contained by berry fruits. To balance fluctuations in product supply and market demand, fresh berry fruits often require short-or long-term storage in order to extend the supply of the berry fruits beyond the end ofthe harvest season. Understanding the interaction between the fruits and the environment is crucial for obtaining the most suitable conditions for extending shelf life. Portions of 250 g of strawberries, cranberries, gooseberries, blackberries or raspberries contain considerably more than the minimum daily requirement of vitamin C, while most of the other fruit can provide more than half the daily requirement. In order to freeze the berries fruits, generally no pretreatments are applied and therefore no changes in nutritive values occur during storage if proper packaging is used. During thawing, however, losses may occur. The fruits were monitorized in three fixed time points of refrigerated storage conditions at 20C, and also after different freezing condition (-180C in laboratory freezing condition and from supermarket freezing condition). The biological material studied was represented by 4 types of berries, as follows: Vaccinum myrtillius, Ribes rubrum, Rubus fructicocus and Rubus idaeus which were asseassed in terms of quality in fresh condition (T0 –moment), and after 3, respectively 7 days of refrigerate storage condition as well as after 6 month of freezing (in bulk and packaged in polyethylene bags). The soluble dry matter substances content was noticed to decrease in refrigerated storage condition between T1 and T2 time points (p<0.001). As concerning the differences in vitamin C content between fruits storage in bulk and packaged with polyethylene film were highlight significantly higher values (p<0.001) for all analyzed species that were packaged also in freezing storage conditions. When compared to the other fruits tested, the red gooseberries (43.5 mg/ 100 g), followed by raspberries (35.6 mg/ 100 g) were evidenced by their high vitamin C content. By keeping the fruits refrigerated for 7 days, although the sensory characteristics have undergone major changes, a significant decrease in vitamin C content is noted, however its final values at Tf moment are still remarkable: 27.8 mg/ 100 g for currants and 24.3 mg/ 100 g for raspberries

    Synthetic spatially graded Rac activation drives directed cell polarization and locomotion

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    Migrating cells possess intracellular gradients of Rho GTPases, but it is unknown whether these shallow gradients themselves can induce motility. Here we describe a new method to present cells with induced linear gradients of active, endogenous Rac without receptor activation. Gradients as low as 15% were sufficient to not only trigger cell migration up the synthetic gradient, but also to induce both cell polarization and repolarization. Response kinetics were inversely proportional to Rac gradient values, in agreement with a new mathematical model, suggesting a role for natural input gradient amplification upstream of Rac. Increases in Rac levels beyond a well-defined threshold dramatically augmented polarization and decreased sensitivity to the gradient value. The threshold was governed by initial cell polarity and PI3K activity, supporting a role for both in defining responsiveness to natural or synthetic Rac activation. Our methodology suggests a general way to investigate processes regulated by intracellular signaling gradients

    A Highly Conserved Program of Neuronal Microexons Is Misregulated in Autistic Brains

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    SummaryAlternative splicing (AS) generates vast transcriptomic and proteomic complexity. However, which of the myriad of detected AS events provide important biological functions is not well understood. Here, we define the largest program of functionally coordinated, neural-regulated AS described to date in mammals. Relative to all other types of AS within this program, 3-15 nucleotide “microexons” display the most striking evolutionary conservation and switch-like regulation. These microexons modulate the function of interaction domains of proteins involved in neurogenesis. Most neural microexons are regulated by the neuronal-specific splicing factor nSR100/SRRM4, through its binding to adjacent intronic enhancer motifs. Neural microexons are frequently misregulated in the brains of individuals with autism spectrum disorder, and this misregulation is associated with reduced levels of nSR100. The results thus reveal a highly conserved program of dynamic microexon regulation associated with the remodeling of protein-interaction networks during neurogenesis, the misregulation of which is linked to autism

    Plasmon oscillations in ellipsoid nanoparticles: beyond dipole approximation

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    The plasmon oscillations of a metallic triaxial ellipsoid nanoparticle have been studied within the framework of the quasistatic approximation. A general method has been proposed for finding the analytical expressions describing the potential and frequencies of the plasmon oscillations of an arbitrary multipolarity order. The analytical expressions have been derived for an electric potential and plasmon oscillation frequencies of the first 24 modes. Other higher orders plasmon modes are investigated numerically.Comment: 33 pages, 12 figure

    Evolutionary Convergence on Highly-Conserved 3′ Intron Structures in Intron-Poor Eukaryotes and Insights into the Ancestral Eukaryotic Genome

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    The presence of spliceosomal introns in eukaryotes raises a range of questions about genomic evolution. Along with the fundamental mysteries of introns' initial proliferation and persistence, the evolutionary forces acting on intron sequences remain largely mysterious. Intron number varies across species from a few introns per genome to several introns per gene, and the elements of intron sequences directly implicated in splicing vary from degenerate to strict consensus motifs. We report a 50-species comparative genomic study of intron sequences across most eukaryotic groups. We find two broad and striking patterns. First, we find that some highly intron-poor lineages have undergone evolutionary convergence to strong 3′ consensus intron structures. This finding holds for both branch point sequence and distance between the branch point and the 3′ splice site. Interestingly, this difference appears to exist within the genomes of green alga of the genus Ostreococcus, which exhibit highly constrained intron sequences through most of the intron-poor genome, but not in one much more intron-dense genomic region. Second, we find evidence that ancestral genomes contained highly variable branch point sequences, similar to more complex modern intron-rich eukaryotic lineages. In addition, ancestral structures are likely to have included polyT tails similar to those in metazoans and plants, which we found in a variety of protist lineages. Intriguingly, intron structure evolution appears to be quite different across lineages experiencing different types of genome reduction: whereas lineages with very few introns tend towards highly regular intronic sequences, lineages with very short introns tend towards highly degenerate sequences. Together, these results attest to the complex nature of ancestral eukaryotic splicing, the qualitatively different evolutionary forces acting on intron structures across modern lineages, and the impressive evolutionary malleability of eukaryotic gene structures
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