225 research outputs found
Polaron effects in electron channels on a helium film
Using the Feynman path-integral formalism we study the polaron effects in
quantum wires above a liquid helium film. The electron interacts with
two-dimensional (2D) surface phonons, i.e. ripplons, and is confined in one
dimension (1D) by an harmonic potential. The obtained results are valid for
arbitrary temperature (), electron-phonon coupling strength (), and
lateral confinement (). Analytical and numerical results are
obtained for limiting cases of , , and . We found the
surprising result that reducing the electron motion from 2D to quasi-1D makes
the self-trapping transition more continuous.Comment: 6 pages, 7 figures, submitted to Phys. Rev.
Accuracy of Five Serologic Tests for the Follow up of Strongyloides stercoralis Infection
BACKGROUND: Traditional faecal-based methods have poor
sensitivity for the detection of S. stercoralis, therefore are
inadequate for post-treatment evaluation of infected patients
who should be carefully monitored to exclude the persistence of
the infection. In a previous study, we demonstrated high
accuracy of five serology tests for the screening and diagnosis
of strongyloidiasis. Aim of this study is to evaluate the
performance of the same five tests for the follow up of patients
infected with S. stercoralis. METHODS: Retrospective study on
anonymized, cryo-preserved samples available at the Centre for
Tropical Diseases (Negrar, Verona, Italy). Samples were
collected before and from 3 to 12 months after treatment. The
samples were tested with two commercially-available ELISA tests
(IVD, Bordier), two techniques based on a recombinant antigen
(NIE-ELISA and NIE-LIPS) and one in-house IFAT. The results of
each test were evaluated both in relation to the results of
fecal examination and to those of a composite reference standard
(classifying as positive a sample with positive stools and/or at
least three positive serology tests). The associations between
the independent variables age and time and the dependent
variable value of serological test (for all five tests), were
analyzed by linear mixed-effects regression model. RESULTS: A
high proportion of samples demonstrated for each test a
seroreversion or a relevant decline (optical density/relative
light units halved or decrease of at least two titers for IFAT)
at follow up, results confirmed by the linear mixed effects
model that showed a trend to seroreversion over time for all
tests. In particular, IVD-ELISA (almost 90% samples demonstrated
relevant decline) and IFAT (almost 87%) had the best
performance. Considering only samples with a complete
negativization, NIE-ELISA showed the best performance (72.5%
seroreversion). CONCLUSIONS: Serology is useful for the follow
up of patients infected with S. stercoralis and determining test
of cure
Breast imaging technology: Application of magnetic resonance imaging to angiogenesis in breast cancer
Magnetic resonance imaging (MRI) techniques enable vascular function to be mapped with high spatial resolution. Current methods for imaging in breast cancer are described, and a review of recent studies that compared dynamic contrast-enhanced MRI with histopathological indicators of tumour vascular status is provided. These studies show correlation between in vivo dynamic contrast measurements and in vitro histopathology. Dynamic contrast enhanced MRI is also being applied to assessment of the response of breast tumours to treatment
Checklists in the operating room: Help or hurdle? A qualitative study on health workers' experiences
<p>Abstract</p> <p>Background</p> <p>Checklists have been used extensively as a cognitive aid in aviation; now, they are being introduced in many areas of medicine. Although few would dispute the positive effects of checklists, little is known about the process of introducing this tool into the health care environment. In 2008, a pre-induction checklist was implemented in our anaesthetic department; in this study, we explored the nurses' and physicians' acceptance and experiences with this checklist.</p> <p>Method</p> <p>Focus group interviews were conducted with a purposeful sample of checklist users (nurses and physicians) from the Department of Anaesthesia and Intensive Care in a tertiary teaching hospital. The interviews were analysed qualitatively using systematic text condensation.</p> <p>Results</p> <p>Users reported that checklist use could divert attention away from the patient and that it influenced workflow and doctor-nurse cooperation. They described senior consultants as both sceptical and supportive; a head physician with a positive attitude was considered crucial for successful implementation. The checklist improved confidence in unfamiliar contexts and was used in some situations for which it was not intended. It also revealed insufficient equipment standardisation.</p> <p>Conclusion</p> <p>Our findings suggest several issues and actions that may be important to consider during checklist use and implementation.</p
A Tale of Switched Functions: From Cyclooxygenase Inhibition to M-Channel Modulation in New Diphenylamine Derivatives
Cyclooxygenase (COX) enzymes are molecular targets of nonsteroidal anti-inflammatory drugs (NSAIDs), the most used medication worldwide. However, the COX enzymes are not the sole molecular targets of NSAIDs. Recently, we showed that two NSAIDs, diclofenac and meclofenamate, also act as openers of Kv7.2/3 K+ channels underlying the neuronal M-current. Here we designed new derivatives of diphenylamine carboxylate to dissociate the M-channel opener property from COX inhibition. The carboxylate moiety was derivatized into amides or esters and linked to various alkyl and ether chains. Powerful M-channel openers were generated, provided that the diphenylamine moiety and a terminal hydroxyl group are preserved. In transfected CHO cells, they activated recombinant Kv7.2/3 K+ channels, causing a hyperpolarizing shift of current activation as measured by whole-cell patch-clamp recording. In sensory dorsal root ganglion and hippocampal neurons, the openers hyperpolarized the membrane potential and robustly depressed evoked spike discharges. They also decreased hippocampal glutamate and GABA release by reducing the frequency of spontaneous excitatory and inhibitory post-synaptic currents. In vivo, the openers exhibited anti-convulsant activity, as measured in mice by the maximal electroshock seizure model. Conversion of the carboxylate function into amide abolished COX inhibition but preserved M-channel modulation. Remarkably, the very same template let us generating potent M-channel blockers. Our results reveal a new and crucial determinant of NSAID-mediated COX inhibition. They also provide a structural framework for designing novel M-channel modulators, including openers and blockers
Selective Interaction of Syntaxin 1A with KCNQ2: Possible Implications for Specific Modulation of Presynaptic Activity
KCNQ2/KCNQ3 channels are the molecular correlates of the neuronal M-channels, which play a major role in the control of neuronal excitability. Notably, they differ from homomeric KCNQ2 channels in their distribution pattern within neurons, with unique expression of KCNQ2 in axons and nerve terminals. Here, combined reciprocal coimmunoprecipitation and two-electrode voltage clamp analyses in Xenopus oocytes revealed a strong association of syntaxin 1A, a major component of the exocytotic SNARE complex, with KCNQ2 homomeric channels resulting in a ∼2-fold reduction in macroscopic conductance and ∼2-fold slower activation kinetics. Remarkably, the interaction of KCNQ2/Q3 heteromeric channels with syntaxin 1A was significantly weaker and KCNQ3 homomeric channels were practically resistant to syntaxin 1A. Analysis of different KCNQ2 and KCNQ3 chimeras and deletion mutants combined with in-vitro binding analysis pinpointed a crucial C-terminal syntaxin 1A-association domain in KCNQ2. Pull-down and coimmunoprecipitation analyses in hippocampal and cortical synaptosomes demonstrated a physical interaction of brain KCNQ2 with syntaxin 1A, and confocal immunofluorescence microscopy showed high colocalization of KCNQ2 and syntaxin 1A at presynaptic varicosities. The selective interaction of syntaxin 1A with KCNQ2, combined with a numerical simulation of syntaxin 1A's impact in a firing-neuron model, suggest that syntaxin 1A's interaction is targeted at regulating KCNQ2 channels to fine-tune presynaptic transmitter release, without interfering with the function of KCNQ2/3 channels in neuronal firing frequency adaptation
Defining Global Gene Expression Changes of the Hypothalamic-Pituitary-Gonadal Axis in Female sGnRH-Antisense Transgenic Common Carp (Cyprinus carpio)
BACKGROUND: The hypothalamic-pituitary-gonadal (HPG) axis is critical in the development and regulation of reproduction in fish. The inhibition of neuropeptide gonadotropin-releasing hormone (GnRH) expression may diminish or severely hamper gonadal development due to it being the key regulator of the axis, and then provide a model for the comprehensive study of the expression patterns of genes with respect to the fish reproductive system. METHODOLOGY/PRINCIPAL FINDINGS: In a previous study we injected 342 fertilized eggs from the common carp (Cyprinus carpio) with a gene construct that expressed antisense sGnRH. Four years later, we found a total of 38 transgenic fish with abnormal or missing gonads. From this group we selected the 12 sterile females with abnormal ovaries in which we combined suppression subtractive hybridization (SSH) and cDNA microarray analysis to define changes in gene expression of the HPG axis in the present study. As a result, nine, 28, and 212 genes were separately identified as being differentially expressed in hypothalamus, pituitary, and ovary, of which 87 genes were novel. The number of down- and up-regulated genes was five and four (hypothalamus), 16 and 12 (pituitary), 119 and 93 (ovary), respectively. Functional analyses showed that these genes involved in several biological processes, such as biosynthesis, organogenesis, metabolism pathways, immune systems, transport links, and apoptosis. Within these categories, significant genes for neuropeptides, gonadotropins, metabolic, oogenesis and inflammatory factors were identified. CONCLUSIONS/SIGNIFICANCE: This study indicated the progressive scaling-up effect of hypothalamic sGnRH antisense on the pituitary and ovary receptors of female carp and provided comprehensive data with respect to global changes in gene expression throughout the HPG signaling pathway, contributing towards improving our understanding of the molecular mechanisms and regulative pathways in the reproductive system of teleost fish
KRIT1 Regulates the Homeostasis of Intracellular Reactive Oxygen Species
KRIT1 is a gene responsible for Cerebral Cavernous Malformations (CCM), a major cerebrovascular disease characterized by abnormally enlarged and leaky capillaries that predispose to seizures, focal neurological deficits, and fatal intracerebral hemorrhage. Comprehensive analysis of the KRIT1 gene in CCM patients has suggested that KRIT1 functions need to be severely impaired for pathogenesis. However, the molecular and cellular functions of KRIT1 as well as CCM pathogenesis mechanisms are still research challenges. We found that KRIT1 plays an important role in molecular mechanisms involved in the maintenance of the intracellular Reactive Oxygen Species (ROS) homeostasis to prevent oxidative cellular damage. In particular, we demonstrate that KRIT1 loss/down-regulation is associated with a significant increase in intracellular ROS levels. Conversely, ROS levels in KRIT1−/− cells are significantly and dose-dependently reduced after restoration of KRIT1 expression. Moreover, we show that the modulation of intracellular ROS levels by KRIT1 loss/restoration is strictly correlated with the modulation of the expression of the antioxidant protein SOD2 as well as of the transcriptional factor FoxO1, a master regulator of cell responses to oxidative stress and a modulator of SOD2 levels. Furthermore, we show that the KRIT1-dependent maintenance of low ROS levels facilitates the downregulation of cyclin D1 expression required for cell transition from proliferative growth to quiescence. Finally, we demonstrate that the enhanced ROS levels in KRIT1−/− cells are associated with an increased cell susceptibility to oxidative DNA damage and a marked induction of the DNA damage sensor and repair gene Gadd45α, as well as with a decline of mitochondrial energy metabolism. Taken together, our results point to a new model where KRIT1 limits the accumulation of intracellular oxidants and prevents oxidative stress-mediated cellular dysfunction and DNA damage by enhancing the cell capacity to scavenge intracellular ROS through an antioxidant pathway involving FoxO1 and SOD2, thus providing novel and useful insights into the understanding of KRIT1 molecular and cellular functions
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