710 research outputs found

    Chandrasekhar-Kendall functions in astrophysical dynamos

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    Some of the contributions of Chandrasekhar to the field of magnetohydrodynamics are highlighted. Particular emphasis is placed on the Chandrasekhar-Kendall functions that allow a decomposition of a vector field into right- and left-handed contributions. Magnetic energy spectra of both contributions are shown for a new set of helically forced simulations at resolutions higher than what has been available so far. For a forcing function with positive helicity, these simulations show a forward cascade of the right-handed contributions to the magnetic field and nonlocal inverse transfer for the left-handed contributions. The speed of inverse transfer is shown to decrease with increasing value of the magnetic Reynolds number.Comment: 10 pages, 5 figures, proceedings of the Chandrasekhar Centenary Conference, to be published in PRAMANA - Journal of Physic

    Family-led rehabilitation in India (ATTEND)—Findings from the process evaluation of a randomized controlled trial

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    Background Training family carers to provide evidence-based rehabilitation to stroke patients could address the recognized deficiency of access to stroke rehabilitation in low-resource settings. However, our randomized controlled trial in India (ATTEND) found that this model of care was not superior to usual care alone. Aims This process evaluation aimed to better understand trial outcomes through assessing trial implementation and exploring patients’, carers’, and providers’ perspectives. Methods Our mixed methods study included process, healthcare use data and patient demographics from all sites; observations and semi-structured interviews with participants (22 patients, 22 carers, and 28 health providers) from six sampled sites. Results Intervention fidelity and adherence to the trial protocol was high across the 14 sites; however, early supported discharge (an intervention component) was not implemented. Within both randomized groups, some form of rehabilitation was widely accessed. ATTEND stroke coordinators provided counseling and perceived that sustaining patients’ motivation to continue with rehabilitation in the face of significant emotional and financial stress as a key challenge. The intervention was perceived as an acceptable community-based package with education as an important component in raising the poor awareness of stroke. Many participants viewed family-led rehabilitation as a necessary model of care for poor and rural populations who could not access rehabilitation. Conclusion Difficulty in sustaining patient and carer motivation for rehabilitation without ongoing support, and greater than anticipated access to routine rehabilitation may explain the lack of benefit in the trial. Nonetheless, family-led rehabilitation was seen as a concept worthy of further development

    Diagnostic accuracy of cyst fluid amphiregulin in pancreatic cysts

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    <p>Abstract</p> <p>Background</p> <p>Accurate tests to diagnose adenocarcinoma and high-grade dysplasia among mucinous pancreatic cysts are clinically needed. This study evaluated the diagnostic utility of amphiregulin (AREG) as a pancreatic cyst fluid biomarker to differentiate non-mucinous, benign mucinous, and malignant mucinous cysts.</p> <p>Methods</p> <p>A single-center retrospective study to evaluate AREG levels in pancreatic cyst fluid by ELISA from 33 patients with a histological gold standard was performed.</p> <p>Results</p> <p>Among the cyst fluid samples, the median (IQR) AREG levels for non-mucinous (n = 6), benign mucinous (n = 15), and cancerous cysts (n = 15) were 85 pg/ml (47-168), 63 pg/ml (30-847), and 986 pg/ml (417-3160), respectively. A significant difference between benign mucinous and malignant mucinous cysts was observed (<it>p </it>= 0.025). AREG levels greater than 300 pg/ml possessed a diagnostic accuracy for cancer or high-grade dysplasia of 78% (sensitivity 83%, specificity 73%).</p> <p>Conclusion</p> <p>Cyst fluid AREG levels are significantly higher in cancerous and high-grade dysplastic cysts compared to benign mucinous cysts. Thus AREG exhibits potential clinical utility in the evaluation of pancreatic cysts.</p

    Suppression of Adenosine-Activated Chloride Transport by Ethanol in Airway Epithelia

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    Alcohol abuse is associated with increased lung infections. Molecular understanding of the underlying mechanisms is not complete. Airway epithelial ion transport regulates the homeostasis of airway surface liquid, essential for airway mucosal immunity and lung host defense. Here, air-liquid interface cultures of Calu-3 epithelial cells were basolaterally exposed to physiologically relevant concentrations of ethanol (0, 25, 50 and 100 mM) for 24 hours and adenosine-stimulated ion transport was measured by Ussing chamber. The ethanol exposure reduced the epithelial short-circuit currents (ISC) in a dose-dependent manner. The ion currents activated by adenosine were chloride conductance mediated by cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel. Alloxazine, a specific inhibitor for A2B adenosine receptor (A2BAR), largely abolished the adenosine-stimulated chloride transport, suggesting that A2BAR is a major receptor responsible for regulating the chloride transport of the cells. Ethanol significantly reduced intracellular cAMP production upon adenosine stimulation. Moreover, ethanol-suppression of the chloride secretion was able to be restored by cAMP analogs or by inhibitors to block cAMP degradation. These results imply that ethanol exposure dysregulates CFTR-mediated chloride transport in airways by suppression of adenosine-A2BAR-cAMP signaling pathway, which might contribute to alcohol-associated lung infections

    Kaposi's Sarcoma-Associated Herpesvirus-Encoded LANA Down-Regulates IL-22R1 Expression through a Cis-Acting Element within the Promoter Region

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    Kaposi's sarcoma-associated herpesvirus (KSHV) is considered to be a necessary, but not sufficient, causal agent of Kaposi's sarcoma (KS). All forms of KS are characterized by the proliferation of spindle-shaped cells, and most (>90%) spindle cells from KS lesions are latently infected with KSHV. During KSHV latency, only a few viral genes are expressed. Among those latent genes, the ORF 73 gene encodes the latency-associated nuclear antigen (LANA), which is critical for the establishment and maintenance of the latent KSHV infection. Much evidence suggests that many cytokines can increase the frequency and aggressiveness of KS. In this study, a microarray analysis of KS and normal tissues revealed that multiple cytokines and cytokine receptors are regulated by KSHV latent infection. Of special interest, IL-22R1 transcript level was found to be down-regulated in the KS tissue. To study the possible regulation of IL-22R1 by LANA, the IL-22R1 promoter was constructed and found to contain a LANA-binding site (LBS). LANA was demonstrated to down-regulate IL-22R1 expression via direct binding to the LBS located within the IL-22R1 promoter region. Furthermore, KSHV latently infected cells showed an impaired response to IL-22 stimulation. These results suggest that LANA can regulate host factor expression by directly binding to a cis-acting element within the factor's promoter to benefit latent viral infection and suppression of the antiviral immune response

    Sebacinales Everywhere: Previously Overlooked Ubiquitous Fungal Endophytes

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    Inconspicuous basidiomycetes from the order Sebacinales are known to be involved in a puzzling variety of mutualistic plant-fungal symbioses (mycorrhizae), which presumably involve transport of mineral nutrients. Recently a few members of this fungal order not fitting this definition and commonly referred to as ‘endophytes’ have raised considerable interest by their ability to enhance plant growth and to increase resistance of their host plants against abiotic stress factors and fungal pathogens. Using DNA-based detection and electron microscopy, we show that Sebacinales are not only extremely versatile in their mycorrhizal associations, but are also almost universally present as symptomless endophytes. They occurred in field specimens of bryophytes, pteridophytes and all families of herbaceous angiosperms we investigated, including liverworts, wheat, maize, and the non-mycorrhizal model plant Arabidopsis thaliana. They were present in all habitats we studied on four continents. We even detected these fungi in herbarium specimens originating from pioneering field trips to North Africa in the 1830s/40s. No geographical or host patterns were detected. Our data suggest that the multitude of mycorrhizal interactions in Sebacinales may have arisen from an ancestral endophytic habit by specialization. Considering their proven beneficial influence on plant growth and their ubiquity, endophytic Sebacinales may be a previously unrecognized universal hidden force in plant ecosystems

    Tolerance to drug-induced cell death favours the acquisition of multidrug resistance in Leishmania

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    The control of the protozoan parasite Leishmania relies on few drugs with unknown cellular targets and unclear mode of action. Several antileishmanials, however, were shown to induce apoptosis in Leishmania and this death mechanism was further studied in drug-sensitive and drug-resistant Leishmania infantum. In sensitive parasites, antimonials (SbIII), miltefosine (MF) and amphotericin B (AMB), but not paromomycin (PARO), triggered apoptotic cell death associated with reactive oxygen species (ROS). In contrast, Leishmania mutants resistant to SbIII, MF or AMB not only failed to undergo apoptosis following exposure to their respective drugs, but also were more tolerant towards apoptosis induced by other antileishmanials, provided that these killed Leishmania via ROS production. Such tolerance favored the rapid acquisition of multidrug resistance. PARO killed Leishmania in a non-apoptotic manner and failed to produce ROS. PARO resistance neither protected against drug-induced apoptosis nor provided an increased rate of acquisition of resistance to other antileishmanials. However, the PARO-resistant mutant, but not SbIII-, MF- or AMB-resistant mutants, became rapidly cross-resistant to methotrexate, a model drug also not producing ROS. Our results therefore link the mode of killing of drugs to tolerance to cell death and to a facilitated emergence of multidrug resistance. These findings may have fundamental implications in the field of chemotherapeutic interventions
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