536 research outputs found

    Inflammation: Cause or Consequence of Epilepsy?

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    Epilepsy is the third most common neurological disorder, affecting about 70 million people worldwide. It is defined as a central nervous system disorder which affects the neuronal activity in the brain, causing unprovoked seizures and other behavioral changes. Unfortunately, one-third of epilepsy patients are unresponsive to available therapies and patients who respond to antiepileptic drugs often complain of debilitating side effects. In the effort of devising a suitable therapy for epilepsy treatment, researchers delved into the origin of seizures and the epileptogenic process and found an association between epilepsy and inflammation. Here, we discuss the involvement of inflammatory mediators in the development and progression of seizures and epileptogenesis, supported by clinical shreds of evidence. Subsequently, we discuss the role of inflammation in the generation of seizures, as it is debatable whether inflammation is the cause or consequence of epilepsy, along with experimental models in inflammation and epilepsy research

    Erythrocyte enrichment in hematopoietic progenitor cell cultures based on magnetic susceptibility of the hemoglobin

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    Using novel media formulations, it has been demonstrated that human placenta and umbilical cord blood-derived CD34+ cells can be expanded and differentiated into erythroid cells with high efficiency. However, obtaining mature and functional erythrocytes from the immature cell cultures with high purity and in an efficient manner remains a significant challenge. A distinguishing feature of a reticulocyte and maturing erythrocyte is the increasing concentration of hemoglobin and decreasing cell volume that results in increased cell magnetophoretic mobility (MM) when exposed to high magnetic fields and gradients, under anoxic conditions. Taking advantage of these initial observations, we studied a noninvasive (label-free) magnetic separation and analysis process to enrich and identify cultured functional erythrocytes. In addition to the magnetic cell separation and cell motion analysis in the magnetic field, the cell cultures were characterized for cell sedimentation rate, cell volume distributions using differential interference microscopy, immunophenotyping (glycophorin A), hemoglobin concentration and shear-induced deformability (elongation index, EI, by ektacytometry) to test for mature erythrocyte attributes. A commercial, packed column high-gradient magnetic separator (HGMS) was used for magnetic separation. The magnetically enriched fraction comprised 80% of the maturing cells (predominantly reticulocytes) that showed near 70% overlap of EI with the reference cord blood-derived RBC and over 50% overlap with the adult donor RBCs. The results demonstrate feasibility of label-free magnetic enrichment of erythrocyte fraction of CD34+ progenitor-derived cultures based on the presence of paramagnetic hemoglobin in the maturing erythrocytes. © 2012 Jin et al

    Channa striatus in inflammatory conditions: A systematic review

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    Channa striatus (CS), or snakehead murrel, is an obligate air-breathing freshwater fish. Besides its wound healing properties, CS has also been reported to exhibit anti-inflammatory effects in multiple studies. While there are anti-inflammatory medications such as nonsteroidal anti-inflammatory drugs (NSAIDs), their long-term use is associated with an increased risk of peptic ulcers, acute renal failure, stroke, and myocardial infarction. Thus, it is essential to look at natural methods such as CS extract. While there is an abundant number of investigative studies on the inflammatory properties of CS, the quality of these studies has not been evaluated effectively. Thus, this review aims to summarise, evaluate, and critically appraise currently available literature regarding the anti-inflammatory properties of CS extract. This is done by performing a search using four databases, namely Google Scholar, Embase via Elsevier, Scopus, and Web of Science, with the following terms: Channa striatus AND inflammation. From our review, CS has been experimentally shown to positively affect inflammatory conditions such as gastric ulcers, dermatitis, osteoarthritis, and allergic rhinitis. Beneficial effects were also found on inflammation in the presence of tuberculosis and in situations that involve inflammation, such as wound healing. While CS clearly has potential for treating inflammatory conditions, much work needs to be done on identifying and isolating the active constituents before exact mechanisms of action can be worked out to develop future anti-inflammatory medications

    Anti-Inflammatory Activity of Chitooligosaccharides in Vivo

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    All the reports to date on the anti-inflammatory activity of chitooligosaccharides (COS) are mostly based on in vitro methods. In this work, the anti-inflammatory activity of two COS mixtures is characterized in vivo (using balb/c mice), following the carrageenan-induced paw edema method. This is a widely accepted animal model of acute inflammation to evaluate the anti-inflammatory effect of drugs. Our data suggest that COS possess anti-inflammatory activity, which is dependent on dose and, at higher doses, also on the molecular weight. A single dose of 500 mg/kg b.w. weight may be suitable to treat acute inflammation cases; however, further studies are needed to ascertain the effect upon longer inflammation periods as well as studies upon the bioavailability of these compounds

    The Gemini Planet Imager Exoplanet Survey: Giant Planet and Brown Dwarf Demographics From 10-100 AU

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    We present a statistical analysis of the first 300 stars observed by the Gemini Planet Imager Exoplanet Survey (GPIES). This subsample includes six detected planets and three brown dwarfs; from these detections and our contrast curves we infer the underlying distributions of substellar companions with respect to their mass, semi-major axis, and host stellar mass. We uncover a strong correlation between planet occurrence rate and host star mass, with stars M >> 1.5 MM_\odot more likely to host planets with masses between 2-13 MJup_{\rm Jup} and semi-major axes of 3-100 au at 99.92% confidence. We fit a double power-law model in planet mass (m) and semi-major axis (a) for planet populations around high-mass stars (M >> 1.5M_\odot) of the form d2Ndmdamαaβ\frac{d^2 N}{dm da} \propto m^\alpha a^\beta, finding α\alpha = -2.4 ±\pm 0.8 and β\beta = -2.0 ±\pm 0.5, and an integrated occurrence rate of 94+59^{+5}_{-4}% between 5-13 MJup_{\rm Jup} and 10-100 au. A significantly lower occurrence rate is obtained for brown dwarfs around all stars, with 0.80.5+0.8^{+0.8}_{-0.5}% of stars hosting a brown dwarf companion between 13-80 MJup_{\rm Jup} and 10-100 au. Brown dwarfs also appear to be distributed differently in mass and semi-major axis compared to giant planets; whereas giant planets follow a bottom-heavy mass distribution and favor smaller semi-major axes, brown dwarfs exhibit just the opposite behaviors. Comparing to studies of short-period giant planets from the RV method, our results are consistent with a peak in occurrence of giant planets between ~1-10 au. We discuss how these trends, including the preference of giant planets for high-mass host stars, point to formation of giant planets by core/pebble accretion, and formation of brown dwarfs by gravitational instability.Comment: 52 pages, 18 figures. AJ in pres

    relating conversational expressiveness to social presence and accpetance of an assistive social robot

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    Exploring the relationship between social presence, conversational expressiveness, and robot acceptance, we set up an experiment with a robot in an eldercare institution, comparing a more and less social condition. Participants showed more expressiveness with a more social agent and a higher score on expressiveness correlated with higher scores on social presence. Furthermore, scores on social presence correlated with the scores on the intention to use the system in the near future. However, we found no correlation between conversational expressiveness and robot acceptance

    The response of the maize nitrate transport system to nitrogen demand and supply across the lifecycle

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    The definitive version is available at www.newphytologist.comAn understanding of nitrate (NO3-) uptake throughout the lifecycle of plants, and how this process responds to nitrogen (N) availability, is an important step towards the development of plants with improved nitrogen use efficiency (NUE). NO3- uptake capacity and transcript levels of putative high- and low-affinity NO3- transporters (NRTs) were profiled across the lifecycle of dwarf maize (Zea mays) plants grown at reduced and adequate NO3-. Plants showed major changes in high-affinity NO3- uptake capacity across the lifecycle, which varied with changing relative growth rates of roots and shoots. Transcript abundances of putative high-affinity NRTs (predominantly ZmNRT2.1 and ZmNRT2.2) were correlated with two distinct peaks in high-affinity root NO3- uptake capacity and also N availability. The reduction in NO3- supply during the lifecycle led to a dramatic increase in NO3- uptake capacity, which preceded changes in transcript levels of NRTs, suggesting a model with short-term post-translational regulation and longer term transcriptional regulation of NO3- uptake capacity. These observations offer new insight into the control of NO3- uptake by both plant developmental processes and N availability, and identify key control points that may be targeted by future plant improvement programmes to enhance N uptake relative to availability and/or demand.Trevor Garnett, Vanessa Conn, Darren Plett, Simon Conn, Juergen Zanghellini, Nenah Mackenzie, Akiko Enju, Karen Francis, Luke Holtham, Ute Roessner, Berin Boughton, Antony Bacic, Neil Shirley, Antoni Rafalski, Kanwarpal Dhugga, Mark Tester, and Brent N. Kaise

    Lasp-1 Regulates Podosome Function

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    Eukaryotic cells form a variety of adhesive structures to connect with their environment and to regulate cell motility. In contrast to classical focal adhesions, podosomes, highly dynamic structures of different cell types, are actively engaged in matrix remodelling and degradation. Podosomes are composed of an actin-rich core region surrounded by a ring-like structure containing signalling molecules, motor proteins as well as cytoskeleton-associated proteins

    A novel approach to investigate tissue-specific trinucleotide repeat instability

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    Abstract Background In Huntington's disease (HD), an expanded CAG repeat produces characteristic striatal neurodegeneration. Interestingly, the HD CAG repeat, whose length determines age at onset, undergoes tissue-specific somatic instability, predominant in the striatum, suggesting that tissue-specific CAG length changes could modify the disease process. Therefore, understanding the mechanisms underlying the tissue specificity of somatic instability may provide novel routes to therapies. However progress in this area has been hampered by the lack of sensitive high-throughput instability quantification methods and global approaches to identify the underlying factors. Results Here we describe a novel approach to gain insight into the factors responsible for the tissue specificity of somatic instability. Using accurate genetic knock-in mouse models of HD, we developed a reliable, high-throughput method to quantify tissue HD CAG repeat instability and integrated this with genome-wide bioinformatic approaches. Using tissue instability quantified in 16 tissues as a phenotype and tissue microarray gene expression as a predictor, we built a mathematical model and identified a gene expression signature that accurately predicted tissue instability. Using the predictive ability of this signature we found that somatic instability was not a consequence of pathogenesis. In support of this, genetic crosses with models of accelerated neuropathology failed to induce somatic instability. In addition, we searched for genes and pathways that correlated with tissue instability. We found that expression levels of DNA repair genes did not explain the tissue specificity of somatic instability. Instead, our data implicate other pathways, particularly cell cycle, metabolism and neurotransmitter pathways, acting in combination to generate tissue-specific patterns of instability. Conclusion Our study clearly demonstrates that multiple tissue factors reflect the level of somatic instability in different tissues. In addition, our quantitative, genome-wide approach is readily applicable to high-throughput assays and opens the door to widespread applications with the potential to accelerate the discovery of drugs that alter tissue instability

    Pediatric melioidosis in Sarawak, Malaysia: Epidemiological, clinical and microbiological characteristics

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    Background Melioidosis is a serious, and potentially fatal community-acquired infection endemic to northern Australia and Southeast Asia, including Sarawak, Malaysia. The disease, caused by the usually intrinsically aminoglycoside-resistant Burkholderia pseudomallei, most commonly affects adults with predisposing risk factors. There are limited data on pediatric melioidosis in Sarawak. Methods A part prospective, part retrospective study of children aged <15 years with culture-confirmed melioidosis was conducted in the 3 major public hospitals in Central Sarawak between 2009 and 2014. We examined epidemiological, clinical and microbiological characteristics. Findings Forty-two patients were recruited during the 6-year study period. The overall annual incidence was estimated to be 4.1 per 100,000 children <15 years, with marked variation between districts. No children had pre-existing medical conditions. Twenty-three (55%) had disseminated disease, 10 (43%) of whom died. The commonest site of infection was the lungs, which occurred in 21 (50%) children. Other important sites of infection included lymph nodes, spleen, joints and lacrimal glands. Seven (17%) children had bacteremia with no overt focus of infection. Delays in diagnosis and in melioidosis-appropriate antibiotic treatment were observed in nearly 90% of children. Of the clinical isolates tested, 35/36 (97%) were susceptible to gentamicin. Of these, all 11 isolates that were genotyped were of a single multi-locus sequence type, ST881, and possessed the putative B. pseudomallei virulence determinants bimABp, fhaB3, and the YLF gene cluster. Conclusions Central Sarawak has a very high incidence of pediatric melioidosis, caused predominantly by gentamicin-susceptible B. pseudomallei strains. Children frequently presented with disseminated disease and had an alarmingly high death rate, despite the absence of any apparent predisposing risk factor
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