226 research outputs found

    Patterns of Coupled Theta Activity in Amygdala-Hippocampal-Prefrontal Cortical Circuits during Fear Extinction

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    Signals related to fear memory and extinction are processed within brain pathways involving the lateral amygdala (LA) for formation of aversive stimulus associations, the CA1 area of the hippocampus for context-dependent modulation of these associations, and the infralimbic region of the medial prefrontal cortex (mPFC) for extinction processes. While many studies have addressed the contribution of each of these modules individually, little is known about their interactions and how they function as an integrated system. Here we show, by combining multiple site local field potential (LFP) and unit recordings in freely behaving mice in a fear conditioning paradigm, that theta oscillations may provide a means for temporally and functionally connecting these modules. Theta oscillations occurred with high specificity in the CA1-LA-mPFC network. Theta coupling increased between all areas during retrieval of conditioned fear, and declined during extinction learning. During extinction recall, theta coupling partly rebounded in LA-mPFC and CA1-mPFC, and remained at a low level in CA1-LA. Interfering with theta coupling through local electrical microstimulation in CA1-LA affected conditioned fear and extinction recall depending on theta phase. These results support the hypothesis that theta coupling provides a means for inter-areal coordination in conditioned behavioral responsiveness. More specifically, theta oscillations seem to contribute to a population code indicating conditioned stimuli during recall of fear memory before and after extinction

    Neuropeptide S-Mediated Facilitation of Synaptic Transmission Enforces Subthreshold Theta Oscillations within the Lateral Amygdala

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    The neuropeptide S (NPS) receptor system modulates neuronal circuit activity in the amygdala in conjunction with fear, anxiety and the expression and extinction of previously acquired fear memories. Using in vitro brain slice preparations of transgenic GAD67-GFP (Ξ”neo) mice, we investigated the effects of NPS on neural activity in the lateral amygdala as a key region for the formation and extinction of fear memories. We are able to demonstrate that NPS augments excitatory glutamatergic synaptic input onto both projection neurons and interneurons of the lateral amygdala, resulting in enhanced spike activity of both types of cells. These effects were at least in part mediated by presynaptic mechanisms. In turn, inhibition of projection neurons by local interneurons was augmented by NPS, and subthreshold oscillations were strengthened, leading to their shift into the theta frequency range. These data suggest that the multifaceted effects of NPS on amygdaloid circuitry may shape behavior-related network activity patterns in the amygdala and reflect the peptide's potent activity in various forms of affective behavior and emotional memory

    Overexpression of Hydroxynitrile Lyase in Cassava Roots Elevates Protein and Free Amino Acids while Reducing Residual Cyanogen Levels

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    Cassava is the major source of calories for more than 250 million Sub-Saharan Africans, however, it has the lowest protein-to-energy ratio of any major staple food crop in the world. A cassava-based diet provides less than 30% of the minimum daily requirement for protein. Moreover, both leaves and roots contain potentially toxic levels of cyanogenic glucosides. The major cyanogen in cassava is linamarin which is stored in the vacuole. Upon tissue disruption linamarin is deglycosylated by the apolplastic enzyme, linamarase, producing acetone cyanohydrin. Acetone cyanohydrin can spontaneously decompose at pHs >5.0 or temperatures >35Β°C, or is enzymatically broken down by hydroxynitrile lyase (HNL) to produce acetone and free cyanide which is then volatilized. Unlike leaves, cassava roots have little HNL activity. The lack of HNL activity in roots is associated with the accumulation of potentially toxic levels of acetone cyanohydrin in poorly processed roots. We hypothesized that the over-expression of HNL in cassava roots under the control of a root-specific, patatin promoter would not only accelerate cyanogenesis during food processing, resulting in a safer food product, but lead to increased root protein levels since HNL is sequestered in the cell wall. Transgenic lines expressing a patatin-driven HNL gene construct exhibited a 2–20 fold increase in relative HNL mRNA levels in roots when compared with wild type resulting in a threefold increase in total root protein in 7 month old plants. After food processing, HNL overexpressing lines had substantially reduced acetone cyanohydrin and cyanide levels in roots relative to wild-type roots. Furthermore, steady state linamarin levels in intact tissues were reduced by 80% in transgenic cassava roots. These results suggest that enhanced linamarin metabolism contributed to the elevated root protein levels

    A reconstruction of the initial conditions of the Universe by optimal mass transportation

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    Reconstructing the density fluctuations in the early Universe that evolved into the distribution of galaxies we see today is a challenge of modern cosmology [ref.]. An accurate reconstruction would allow us to test cosmological models by simulating the evolution starting from the reconstructed state and comparing it to the observations. Several reconstruction techniques have been proposed [8 refs.], but they all suffer from lack of uniqueness because the velocities of galaxies are usually not known. Here we show that reconstruction can be reduced to a well-determined problem of optimisation, and present a specific algorithm that provides excellent agreement when tested against data from N-body simulations. By applying our algorithm to the new redshift surveys now under way [ref.], we will be able to recover reliably the properties of the primeval fluctuation field of the local Universe and to determine accurately the peculiar velocities (deviations from the Hubble expansion) and the true positions of many more galaxies than is feasible by any other method. A version of the paper with higher-quality figures is available at http://www.obs-nice.fr/etc7/nature.pdfComment: Latex, 4 pages, 3 figure

    Collagen based magnetic nanocomposites for oil removal applications

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    A stable magnetic nanocomposite of collagen and superparamagnetic iron oxide nanoparticles (SPIONs) is prepared by a simple process utilizing protein wastes from leather industry. Molecular interaction between helical collagen fibers and spherical SPIONs is proven through calorimetric, microscopic and spectroscopic techniques. This nanocomposite exhibited selective oil absorption and magnetic tracking ability, allowing it to be used in oil removal applications. The environmental sustainability of the oil adsorbed nanobiocomposite is also demonstrated here through its conversion into a bi-functional graphitic nanocarbon material via heat treatment. The approach highlights new avenues for converting bio-wastes into useful nanomaterials in scalable and inexpensive ways

    Unequal household carbon footprints in China

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    Households’ carbon footprints are unequally distributed among the rich and poor due to differences in the scale and patterns of consumption. We present distributional focused carbon footprints for Chinese households and use a carbon-footprint-Gini coefficient to quantify inequalities. We find that in 2012 the urban very rich, comprising 5% of population, induced 19% of the total carbon footprint from household consumption in China, with 6.4 tCO2/cap. The average Chinese household footprint remains comparatively low (1.7 tCO2/cap), while those of the rural population and urban poor, comprising 58% of population, are 0.5–1.6 tCO2/cap. Between 2007 and 2012 the total footprint from households increased by 19%, with 75% of the increase due to growing consumption of the urban middle class and the rich. This suggests that a transformation of Chinese lifestyles away from the current trajectory of carbon-intensive consumption patterns requires policy interventions to improve living standards and encourage sustainable consumption

    Global gene expression analyses of bystander and alpha particle irradiated normal human lung fibroblasts: Synchronous and differential responses

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    <p>Abstract</p> <p>Background</p> <p>The existence of a radiation bystander effect, in which non-irradiated cells respond to signals from irradiated cells, is now well established. It raises concerns for the interpretation of risks arising from exposure to low doses of ionizing radiation. However, the regulatory mechanisms involved in the bystander response have not been well elucidated. To provide insight into the signaling pathways responding in bystanders, we have measured global gene expression four hours after bystander and direct alpha particle exposure of primary human lung fibroblasts.</p> <p>Results</p> <p>Although common p53-regulated radiation response genes like <it>CDKN1A </it>were expressed at elevated levels in the directly exposed cultures, they showed little or no change in the bystanders. In contrast, genes regulated by NFΞΊB, such as <it>PTGS2 </it>(cyclooxygenase-2), <it>IL8 </it>and <it>BCL2A1</it>, responded nearly identically in bystander and irradiated cells. This trend was substantiated by gene ontology and pathway analyses of the microarray data, which suggest that bystander cells mount a full NFΞΊB response, but a muted or partial p53 response. In time-course analyses, quantitative real-time PCR measurements of <it>CDKN1A </it>showed the expected 4-hour peak of expression in irradiated but not bystander cells. In contrast, <it>PTGS2, IL8 </it>and <it>BCL2A1 </it>responded with two waves of expression in both bystander and directly irradiated cells, one peaking at half an hour and the other between four and six hours after irradiation.</p> <p>Conclusion</p> <p>Two major transcriptional hubs that regulate the direct response to ionizing radiation are also implicated in regulation of the bystander response, but to dramatically different degrees. While activation of the p53 response pathway is minimal in bystander cells, the NFΞΊB response is virtually identical in irradiated and bystander cells. This alteration in the balance of signaling is likely to lead to different outcomes in irradiated cells and their bystanders, perhaps leading to greater survival of bystanders and increased risk from any long-term damage they have sustained.</p

    Factors that could explain the increasing prevalence of type 2 diabetes among adults in a Canadian province: a critical review and analysis

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    Abstract: Background: The prevalence of diabetes has increased since the last decade in New Brunswick. Identifying factors contributing to the increase in diabetes prevalence will help inform an action plan to manage the condition. The objective was to describe factors that could explain the increasing prevalence of type 2 diabetes in New Brunswick since 2001. Methods: A critical literature review was conducted to identify factors potentially responsible for an increase in prevalence of diabetes. Data from various sources were obtained to draw a repeated cross-sectional (2001–2014) description of these factors concurrently with changes in the prevalence of type 2 diabetes in New Brunswick. Linear regressions, Poisson regressions and Cochran Armitage analysis were used to describe relationships between these factors and time. Results: Factors identified in the review were summarized in five categories: individual-level risk factors, environmental risk factors, evolution of the disease, detection effect and global changes. The prevalence of type 2 diabetes has increased by 120% between 2001 and 2014. The prevalence of obesity, hypertension, prediabetes, alcohol consumption, immigration and urbanization increased during the study period and the consumption of fruits and vegetables decreased which could represent potential factors of the increasing prevalence of type 2 diabetes. Physical activity, smoking, socioeconomic status and education did not present trends that could explain the increasing prevalence of type 2 diabetes. During the study period, the mortality rate and the conversion rate from prediabetes to diabetes decreased and the incidence rate increased. Suggestion of a detection effect was also present as the number of people tested increased while the HbA1c and the age at detection decreased. Period and birth cohort effect were also noted through a rise in the prevalence of type 2 diabetes across all age groups, but greater increases were observed among the younger cohorts. Conclusions: This study presents a comprehensive overview of factors potentially responsible for population level changes in prevalence of type 2 diabetes. Recent increases in type 2 diabetes in New Brunswick may be attributable to a combination of some individual-level and environmental risk factors, the detection effect, the evolution of the disease and global changes

    Stabilization of Dicentric Translocations through Secondary Rearrangements Mediated by Multiple Mechanisms in S. cerevisiae

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    The gross chromosomal rearrangements (GCRs) observed in S. cerevisiae mutants with increased rates of accumulating GCRs include predicted dicentric GCRs such as translocations, chromosome fusions and isoduplications. These GCRs resemble the genome rearrangements found as mutations underlying inherited diseases as well as in the karyotypes of many cancers exhibiting ongoing genome instabilityThe structures of predicted dicentric GCRs were analyzed using multiple strategies including array-comparative genomic hybridization, pulse field gel electrophoresis, PCR amplification of predicted breakpoints and sequencing. The dicentric GCRs were found to be unstable and to have undergone secondary rearrangements to produce stable monocentric GCRs. The types of secondary rearrangements observed included: non-homologous end joining (NHEJ)-dependent intramolecular deletion of centromeres; chromosome breakage followed by NHEJ-mediated circularization or broken-end fusion to another chromosome telomere; and homologous recombination (HR)-dependent non-reciprocal translocations apparently mediated by break-induced replication. A number of these GCRs appeared to have undergone multiple bridge-fusion-breakage cycles. We also observed examples of chromosomes with extensive ongoing end decay in mec1 tlc1 mutants, suggesting that Mec1 protects chromosome ends from degradation and contributes to telomere maintenance by HR.HR between repeated sequences resulting in secondary rearrangements was the most prevalent pathway for resolution of dicentric GCRs regardless of the structure of the initial dicentric GCR, although at least three other resolution mechanisms were observed. The resolution of dicentric GCRs to stable rearranged chromosomes could in part account for the complex karyotypes seen in some cancers
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