845 research outputs found

    Circuit dissection of the role of somatostatin in itch and pain

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    Stimuli that elicit itch are detected by sensory neurons that innervate the skin. This information is processed by the spinal cord; however, the way in which this occurs is still poorly understood. Here we investigated the neuronal pathways for itch neurotransmission, particularly the contribution of the neuropeptide somatostatin. We find that in the periphery, somatostatin is exclusively expressed in Nppb+ neurons, and we demonstrate that Nppb+somatostatin+ cells function as pruriceptors. Employing chemogenetics, pharmacology and cell-specific ablation methods, we demonstrate that somatostatin potentiates itch by inhibiting inhibitory dynorphin neurons, which results in disinhibition of GRPR+ neurons. Furthermore, elimination of somatostatin from primary afferents and/or from spinal interneurons demonstrates differential involvement of the peptide released from these sources in itch and pain. Our results define the neural circuit underlying somatostatin-induced itch and characterize a contrasting antinociceptive role for the peptide

    Nurse managers' experience with ethical issues in six government hospitals in Malaysia: A cross-sectional study

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    <p>Abstract</p> <p>Background</p> <p>Nurse managers have the burden of experiencing frequent ethical issues related to both their managerial and nursing care duties, according to previous international studies. However, no such study was published in Malaysia. The purpose of this study was to explore nurse managers' experience with ethical issues in six government hospitals in Malaysia including learning about the way they dealt with the issues.</p> <p>Methods</p> <p>A cross-sectional study was conducted in August-September, 2010 involving 417 (69.2%) of total 603 nurse managers in the six Malaysian government hospitals. Data were collected using three-part self-administered questionnaire. Part I was regarding participants' demographics. Part II was about the frequency and areas of management where ethical issues were experienced, and scoring of the importance of 11 pre-identified ethical issues. Part III asked how they dealt with ethical issues in general; ways to deal with the 11 pre-identified ethical issues, and perceived stress level. Data were analyzed using descriptive statistics, cross-tabulations and Pearson's Chi-square.</p> <p>Results</p> <p>A total of 397 (95.2%) participants experienced ethical issues and 47.2% experienced them on weekly to daily basis. Experiencing ethical issues were not associated with areas of practice. Top area of management where ethical issues were encountered was "staff management", but "patient care" related ethical issues were rated as most important. Majority would "discuss with other nurses" in dealing generally with the issues. For pre-identified ethical issues regarding "patient care", "discuss with doctors" was preferred. Only 18.1% referred issues to "ethics committees" and 53.0% to the code of ethics.</p> <p>Conclusions</p> <p>Nurse managers, regardless of their areas of practice, frequently experienced ethical issues. For dealing with these, team-approach needs to be emphasized. Proper understanding of the code of ethics is needed to provide basis for reasoning.</p

    Designing sequential transcription logic: a simple genetic circuit for conditional memory

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    The ability to learn and respond to recurrent events depends on the capacity to remember transient biological signals received in the past. Moreover, it may be desirable to remember or ignore these transient signals conditioned upon other signals that are active at specific points in time or in unique environments. Here, we propose a simple genetic circuit in bacteria that is capable of conditionally memorizing a signal in the form of a transcription factor concentration. The circuit behaves similarly to a "data latch" in an electronic circuit, i.e. it reads and stores an input signal only when conditioned to do so by a "read command". Our circuit is of the same size as the well-known genetic toggle switch (an unconditional latch) which consists of two mutually repressing genes, but is complemented with a "regulatory front end" involving protein heterodimerization as a simple way to implement conditional control. Deterministic and stochastic analysis of the circuit dynamics indicate that an experimental implementation is feasible based on well-characterized genes and proteins. It is not known, to which extent molecular networks are able to conditionally store information in natural contexts for bacteria. However, our results suggest that such sequential logic elements may be readily implemented by cells through the combination of existing protein-protein interactions and simple transcriptional regulation.Comment: 20 pages, 5 figures; supplementary material available upon request from the author

    Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

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    The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO

    Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy

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    A search for new physics is performed in events with two same-sign isolated leptons, hadronic jets, and missing transverse energy in the final state. The analysis is based on a data sample corresponding to an integrated luminosity of 4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of 7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of 140 increase in integrated luminosity over previously published results. The observed yields agree with the standard model predictions and thus no evidence for new physics is found. The observations are used to set upper limits on possible new physics contributions and to constrain supersymmetric models. To facilitate the interpretation of the data in a broader range of new physics scenarios, information on the event selection, detector response, and efficiencies is provided.Comment: Published in Physical Review Letter
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