6,225 research outputs found

    A geometric model of defensive peripersonal space

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    Potentially harmful stimuli occurring within the defensive peripersonal space (DPPS), a protective area surrounding the body, elicit stronger defensive reactions. The spatial features of the DPPS are poorly defined and limited to descriptive estimates of its extent along a single dimension. Here we postulated a family of geometric models of the DPPS, to address two important questions with respect to its spatial features: What is its fine-grained topography? How does the nervous system represent the body area to be defended? As a measure of the DPPS, we used the strength of the defensive blink reflex elicited by electrical stimulation of the hand (hand-blink reflex, HBR), which is reliably modulated by the position of the stimulated hand in egocentric coordinates. We tested the goodness of fit of the postulated models to HBR data from six experiments in which we systematically explored the HBR modulation by hand position in both head-centered and body-centered coordinates. The best-fitting model indicated that 1) the nervous system's representation of the body area defended by the HBR can be approximated by a half-ellipsoid centered on the face and 2) the DPPS extending from this area has the shape of a bubble elongated along the vertical axis. Finally, the empirical observation that the HBR is modulated by hand position in head-centered coordinates indicates that the DPPS is anchored to the face. The modeling approach described in this article can be generalized to describe the spatial modulation of any defensive response

    Acupuncture in Treating Hepatic Fibrosis: A Review with Recommendation for Future Studies

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    Hepatic fibrosis, as a major medical problem, is characterized with significant morbidity and mortality. Acupuncture has potential advantages in treating hepatic fibrosis as acupuncture functions well to reduce Qi and Blood stagnation, resolve stasis and enhance body immunity, which are important factors in treating hepatic fibrosis. The aim of this review was to appraise the current limited evidence of acupuncture in treating hepatic fibrosis from both animal experiments and clinical trials by using both Chinese and western databases and to provide recommendations for future studies

    Second trimester inflammatory and metabolic markers in women delivering preterm with and without preeclampsia.

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    ObjectiveInflammatory and metabolic pathways are implicated in preterm birth and preeclampsia. However, studies rarely compare second trimester inflammatory and metabolic markers between women who deliver preterm with and without preeclampsia.Study designA sample of 129 women (43 with preeclampsia) with preterm delivery was obtained from an existing population-based birth cohort. Banked second trimester serum samples were assayed for 267 inflammatory and metabolic markers. Backwards-stepwise logistic regression models were used to calculate odds ratios.ResultsHigher 5-α-pregnan-3β,20α-diol disulfate, and lower 1-linoleoylglycerophosphoethanolamine and octadecanedioate, predicted increased odds of preeclampsia.ConclusionsAmong women with preterm births, those who developed preeclampsia differed with respect metabolic markers. These findings point to potential etiologic underpinnings for preeclampsia as a precursor to preterm birth

    Signal Transduction Pathways in the Pentameric Ligand-Gated Ion Channels

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    The mechanisms of allosteric action within pentameric ligand-gated ion channels (pLGICs) remain to be determined. Using crystallography, site-directed mutagenesis, and two-electrode voltage clamp measurements, we identified two functionally relevant sites in the extracellular (EC) domain of the bacterial pLGIC from Gloeobacter violaceus (GLIC). One site is at the C-loop region, where the NQN mutation (D91N, E177Q, and D178N) eliminated inter-subunit salt bridges in the open-channel GLIC structure and thereby shifted the channel activation to a higher agonist concentration. The other site is below the C-loop, where binding of the anesthetic ketamine inhibited GLIC currents in a concentration dependent manner. To understand how a perturbation signal in the EC domain, either resulting from the NQN mutation or ketamine binding, is transduced to the channel gate, we have used the Perturbation-based Markovian Transmission (PMT) model to determine dynamic responses of the GLIC channel and signaling pathways upon initial perturbations in the EC domain of GLIC. Despite the existence of many possible routes for the initial perturbation signal to reach the channel gate, the PMT model in combination with Yen's algorithm revealed that perturbation signals with the highest probability flow travel either via the β1-β2 loop or through pre-TM1. The β1-β2 loop occurs in either intra- or inter-subunit pathways, while pre-TM1 occurs exclusively in inter-subunit pathways. Residues involved in both types of pathways are well supported by previous experimental data on nAChR. The direct coupling between pre-TM1 and TM2 of the adjacent subunit adds new insight into the allosteric signaling mechanism in pLGICs. © 2013 Mowrey et al

    Facile Synthesis of High Quality Graphene Nanoribbons

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    Graphene nanoribbons have attracted attention for their novel electronic and spin transport properties1-6, and because nanoribbons less than 10 nm wide have a band gap that can be used to make field effect transistors. However, producing nanoribbons of very high quality, or in high volumes, remains a challenge. Here, we show that pristine few-layer nanoribbons can be produced by unzipping mildly gas-phase oxidized multiwalled carbon nanotube using mechanical sonication in an organic solvent. The nanoribbons exhibit very high quality, with smooth edges (as seen by high-resolution transmission electron microscopy), low ratios of disorder to graphitic Raman bands, and the highest electrical conductance and mobility reported to date (up to 5e2/h and 1500 cm2/Vs for ribbons 10-20 nm in width). Further, at low temperature, the nanoribbons exhibit phase coherent transport and Fabry-Perot interference, suggesting minimal defects and edge roughness. The yield of nanoribbons was ~2% of the starting raw nanotube soot material, which was significantly higher than previous methods capable of producing high quality narrow nanoribbons1. The relatively high yield synthesis of pristine graphene nanoribbons will make these materials easily accessible for a wide range of fundamental and practical applications.Comment: Nature Nanotechnology in pres

    The optical counterpart to gamma-ray burst GRB970228 observed using the Hubble Space Telescope

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    Although more than 2,000 astronomical gamma-ray bursts (GRBs) have been detected, and numerous models proposed to explain their occurrence, they have remained enigmatic owing to the lack of an obvious counterpart at other wavelengths. The recent ground-based detection of a transient source in the vicinity of GRB 970228 may therefore have provided a breakthrough. The optical counterpart appears to be embedded in an extended source which, if a galaxy as has been suggested, would lend weight to those models that place GRBs at cosmological distances. Here we report the observations using the Hubble Space Telescope of the transient counterpart and extended source 26 and 39 days after the initial gamma-ray outburst. We find that the counterpart has faded since the initial detection (and continues to fade), but the extended source exhibits no significant change in brightness between the two dates of observations reported here. The size and apparent constancy between the two epochs of HST observations imply that it is extragalactic, but its faintness makes a definitive statement about its nature difficult. Nevertheless, the decay profile of the transient source is consistent with a popular impulsive-fireball model, which assumes a merger between two neutron stars in a distant galaxy.Comment: 11 pages + 2 figures. To appear in Nature (29 May 1997 issue

    CDK-dependent nuclear localization of B-Cyclin Clb1 promotes FEAR activation during meiosis I in budding yeast

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    Cyclin-dependent kinases (CDK) are master regulators of the cell cycle in eukaryotes. CDK activity is regulated by the presence, post-translational modification and spatial localization of its regulatory subunit cyclin. In budding yeast, the B-cyclin Clb1 is phosphorylated and localizes to the nucleus during meiosis I. However the functional significance of Clb1's phosphorylation and nuclear localization and their mutual dependency is unknown. In this paper, we demonstrate that meiosis-specific phosphorylation of Clb1 requires its import to the nucleus but not vice versa. While Clb1 phosphorylation is dependent on activity of both CDK and polo-like kinase Cdc5, its nuclear localization requires CDK but not Cdc5 activity. Furthermore we show that increased nuclear localization of Clb1 during meiosis enhances activation of FEAR (Cdc Fourteen Early Anaphase Release) pathway. We discuss the significance of our results in relation to regulation of exit from meiosis I

    Using biomarkers to predict TB treatment duration (Predict TB): a prospective, randomized, noninferiority, treatment shortening clinical trial

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    Background : By the early 1980s, tuberculosis treatment was shortened from 24 to 6 months, maintaining relapse rates of 1-2%. Subsequent trials attempting shorter durations have failed, with 4-month arms consistently having relapse rates of 15-20%. One trial shortened treatment only among those without baseline cavity on chest x-ray and whose month 2 sputum culture converted to negative. The 4-month arm relapse rate decreased to 7% but was still significantly worse than the 6-month arm (1.6%, P<0.01).  We hypothesize that PET/CT characteristics at baseline, PET/CT changes at one month, and markers of residual bacterial load will identify patients with tuberculosis who can be cured with 4 months (16 weeks) of standard treatment.Methods: This is a prospective, multicenter, randomized, phase 2b, noninferiority clinical trial of pulmonary tuberculosis participants. Those eligible start standard of care treatment. PET/CT scans are done at weeks 0, 4, and 16 or 24. Participants who do not meet early treatment completion criteria (baseline radiologic severity, radiologic response at one month, and GeneXpert-detectable bacilli at four months) are placed in Arm A (24 weeks of standard therapy). Those who meet the early treatment completion criteria are randomized at week 16 to continue treatment to week 24 (Arm B) or complete treatment at week 16 (Arm C). The primary endpoint compares the treatment success rate at 18 months between Arms B and C.Discussion: Multiple biomarkers have been assessed to predict TB treatment outcomes. This study uses PET/CT scans and GeneXpert (Xpert) cycle threshold to risk stratify participants. PET/CT scans are not applicable to global public health but could be used in clinical trials to stratify participants and possibly become a surrogate endpoint. If the Predict TB trial is successful, other immunological biomarkers or transcriptional signatures that correlate with treatment outcome may be identified. TRIAL REGISTRATION: NCT02821832

    Anti-epileptic effect of Ganoderma lucidum polysaccharides by inhibition of intracellular calcium accumulation and stimulation of expression of CaMKII a in epileptic hippocampal neurons

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    Purpose: To investigate the mechanism of the anti-epileptic effect of Ganoderma lucidum polysaccharides (GLP), the changes of intracellular calcium and CaMK II a expression in a model of epileptic neurons were investigated. Method: Primary hippocampal neurons were divided into: 1) Control group, neurons were cultured with Neurobasal medium, for 3 hours; 2) Model group I: neurons were incubated with Mg2+ free medium for 3 hours; 3) Model group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with the normal medium for a further 3 hours; 4) GLP group I: neurons were incubated with Mg2+ free medium containing GLP (0.375 mg/ml) for 3 hours; 5) GLP group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with a normal culture medium containing GLP for a further 3 hours. The CaMK II a protein expression was assessed by Western-blot. Ca2+ turnover in neurons was assessed using Fluo-3/AM which was added into the replacement medium and Ca2+ turnover was observed under a laser scanning confocal microscope. Results: The CaMK II a expression in the model groups was less than in the control groups, however, in the GLP groups, it was higher than that observed in the model group. Ca2+ fluorescence intensity in GLP group I was significantly lower than that in model group I after 30 seconds, while in GLP group II, it was reduced significantly compared to model group II after 5 minutes. Conclusion: GLP may inhibit calcium overload and promote CaMK II a expression to protect epileptic neuron
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