689 research outputs found

    Chemo- and Thermosensory Responsiveness of Grueneberg Ganglion Neurons Relies on Cyclic Guanosine Monophosphate Signaling Elements

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    Neurons of the Grueneberg ganglion (GG) in the anterior nasal region of mouse pups respond to cool temperatures and to a small set of odorants. While the thermosensory reactivity appears to be mediated by elements of a cyclic guanosine monophosphate (cGMP) cascade, the molecular mechanisms underlying the odor-induced responses are unclear. Since odor-responsive GG cells are endowed with elements of a cGMP pathway, specifically the transmembrane guanylyl cyclase subtype GC-G and the cyclic nucleotide-gated ion channel CNGA3, the possibility was explored whether these cGMP signaling elements may also be involved in chemosensory GG responses. Experiments with transgenic mice deficient for GC-G or CNGA3 revealed that GG responsiveness to given odorants was significantly diminished in these knockout animals. These findings suggest that a cGMP cascade may be important for both olfactory and thermosensory signaling in the GG. However, in contrast to the thermosensory reactivity, which did not decline over time, the chemosensory response underwent adaptation upon extended stimulation, suggesting that the two transduction processes only partially overlap. Copyright (C) 2011 S. Karger AG, Base

    The Canine Papillomavirus and Gamma HPV E7 Proteins Use an Alternative Domain to Bind and Destabilize the Retinoblastoma Protein

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    The high-risk HPV E6 and E7 proteins cooperate to immortalize primary human cervical cells and the E7 protein can independently transform fibroblasts in vitro, primarily due to its ability to associate with and degrade the retinoblastoma tumor suppressor protein, pRb. The binding of E7 to pRb is mediated by a conserved Leu-X-Cys-X-Glu (LXCXE) motif in the conserved region 2 (CR2) of E7 and this domain is both necessary and sufficient for E7/pRb association. In the current study, we report that the E7 protein of the malignancy-associated canine papillomavirus type 2 encodes an E7 protein that has serine substituted for cysteine in the LXCXE motif. In HPV, this substitution in E7 abrogates pRb binding and degradation. However, despite variation at this critical site, the canine papillomavirus E7 protein still bound and degraded pRb. Even complete deletion of the LXSXE domain of canine E7 failed to interfere with binding to pRb in vitro and in vivo. Rather, the dominant binding site for pRb mapped to the C-terminal domain of canine E7. Finally, while the CR1 and CR2 domains of HPV E7 are sufficient for degradation of pRb, the C-terminal region of canine E7 was also required for pRb degradation. Screening of HPV genome sequences revealed that the LXSXE motif of the canine E7 protein was also present in the gamma HPVs and we demonstrate that the gamma HPV-4 E7 protein also binds pRb in a similar way. It appears, therefore, that the type 2 canine PV and gamma-type HPVs not only share similar properties with respect to tissue specificity and association with immunosuppression, but also the mechanism by which their E7 proteins interact with pRb

    Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

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    Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface

    Pharmacist intervention program to enhance hypertension control: a randomised controlled trial

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    Objective Studies have demonstrated that hypertension remains inadequately managed throughout the world, with lack of adherence to BP-lowering medication being a major factor. The aim of the present study was to evaluate if a pharmaceutical care program could improve antihypertensive medication adherence and blood pressure control. Setting This study was conducted in a secondary care hypertension/dyslipidemia outpatient clinic in the university teaching hospital of Cova da Beira Hospital Centre, Covilhã, located in the Eastern Central Region of Portugal. Method This report evaluates the pharmacist’s interventions during a prospective randomised controlled trial, from July 2009 to June 2010. Patients with diagnosis of essential hypertension attending the clinic for routine follow-up were randomly allocated either to a control group (no pharmaceutical care) or to an intervention group (quarterly follow-up by a hospital pharmacist during a 9-month period). The pharmacist interventions, aimed to increase medication adherence and blood pressure control, involved educational interventions and counselling tips directed to the patient. Main outcome measure Systolic blood pressure, diastolic blood pressure and blood pressure control (according to JNC 7 guidelines) assessed at the baseline visit and at the end of pharmaceutical care were the main outcome measures. Blood pressure measurements were performed by blinded nurses. Medication adherence was also evaluated, using a validated questionnaire at baseline and at the end of investigation. Results A total of 197 hypertensive patients were randomly assigned to the study (99 in the control group and 98 in the intervention group). Although there were no significant differences (P > 0.05) in both groups concerning mean age, gender, body mass index, and antihypertensive pharmacotherapy, blood pressure control was higher in the intervention group (P = 0.005) at the end of the study. Significant lower systolic blood pressure (−6.8 mmHg, P = 0.006) and diastolic blood pressure (−2.9 mmHg, P = 0.020) levels were observed in the intervention group. Medication adherence was also significantly higher in the intervention group at the end of the study (74.5% vs. 57.6%, P = 0.012).Conclusion Pharmacist intervention can significantly improve medication adherence and blood pressure control in patients treated with antihypertensive agents

    Do experts see it in slow motion? Altered timing of action simulation uncovers domain-specific perceptual processing in expert athletes

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    Accurate encoding of the spatio-temporal properties of others' actions is essential for the successful implementation of daily activities and, even more, for successful sportive performance, given its role in movement coordination and action anticipation. Here we investigated whether athletes are provided with special perceptual processing of spatio-temporal properties of familiar sportive actions. Basketball and volleyball players and novices were presented with short video-clips of free basketball throws that were partially occluded ahead of realization and were asked to judge whether a subsequently presented pose was either taken from the same throw depicted in the occluded video (action identification task) or temporally congruent with the expected course of the action during the occlusion period (explicit timing task). Results showed that basketball players outperformed the other groups in detecting action compatibility when the pose depicted earlier or synchronous, but not later phases of the movement as compared to the natural course of the action during occlusion. No difference was obtained for explicit estimations of timing compatibility. This leads us to argue that the timing of simulated actions in the experts might be slower than that of perceived actions ("slow-motion" bias), allowing for more detailed representation of ongoing actions and refined prediction abilities

    High prevalence of vitamin D deficiency among children aged 1 month to 16 years in Hangzhou, China

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    <p>Abstract</p> <p>Background</p> <p>Recent studies have suggested that vitamin D deficiency in children is widespread. But the vitamin D status of Chinese children is seldom investigated. The objective of the present study was to survey the serum levels of 25-hydroxyvitamin D [25(OH)D] in more than 6,000 children aged 1 month to 16 years in Hangzhou (latitude: 30°N), the capital of Zhejiang Province, southeast China.</p> <p>Methods</p> <p>The children aged 1 month to 16 years who came to the child health care department of our hospital, the children's hospital affiliated to Zhejiang university school of medicine, for health examination were taken blood for 25(OH) D measurement. Serum 25(OH) D levels were determined by direct enzyme-linked immunosorbent assay and categorized as < 25, < 50, and < 75 nmol/L.</p> <p>Results</p> <p>A total of 6,008 children aged 1 month to 16 years participated in this cross-sectional study. All the subjects were divided into subgroups according to their age: 0-1y, 2-5y, 6-11y and 12-16y representing infancy, preschool, school age and adolescence stages respectively. The highest mean level of serum 25(OH)D was found in the 0-1y stage (99 nmol/L) and the lowest one was found in 12-16y stage (52 nmol/L). Accordingly, the prevalence of serum 25(OH)D levels of < 75 nmol/L and < 50 nmol/L were at the lowest among infants (33.6% and 5.4% respectively) and rose to the highest among adolescents (89.6% and 46.4% respectively). The mean levels of serum 25(OH)D and the prevalence of vitamin D deficiency changed according to seasons. In winter and spring, more than 50% of school age children and adolescents had a 25(OH)D level at < 50 nmol/L. If the threshold is changed to < 75 nmol/L, all of the adolescents (100%) had low 25(OH)D levels in winter and 93.7% school age children as well.</p> <p>Conclusions</p> <p>The prevalence of vitamin D deficiency and insufficiency among children in Hangzhou Zhejiang province is high, especially among children aged 6-16 years. We suggest that the recommendation for vitamin D supplementation in Chinese children should be extended to adolescence.</p

    How nanotechnology-enabled concepts could contribute to the prevention, diagnosis and therapy of bacterial infections

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    This viewpoint summarizes a selection of nanotechnology-based key concepts relevant to critical care medicine. It focuses on novel approaches for a trigger-dependent release of antimicrobial substances from degradable nano-sized carriers, the ultra-sensitive detection of analytes in body fluid samples by plasmonic and fluorescent nanoparticles, and the rapid removal of pathogens from whole blood using magnetic nanoparticles. The concepts presented here could significantly contribute to the prevention, diagnosis and therapy of bacterial infections in future and it is now our turn to bring them from the bench to the bedside
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