Muscimol acts in dorsomedial but not paraventricular hypothalamic nucleus to suppress cardiovascular effects of stress

Both the dorsomedial hypothalamic nucleus (DMH) and the paraventricular hypothalamic nucleus (PVN) have been implicated in the neural control of the cardiovascular response to stress. We used the GABAA agonist muscimol to inhibit neuronal activation and attempted to identify hypothalamic nuclei required for the cardiovascular response to air stress. Chronically instrumented rats received bilateral injections of either 80 pmol of muscimol or 100 nl of saline vehicle into the DMH, the PVN, or an intermediate area (including the rostral edge of the DMH and the region between the two nuclei) and were placed immediately in a restraining tube and subjected to 20 min of air stress. In all rats, air stress after vehicle injections caused marked increases in heart rate (137 +/- 6 beats/min) and blood pressure (26 +/- 2 mmHg). Microinjection of muscimol into the DMH suppressed the heart rate and blood pressure response by 85 and 68%, respectively. Identical microinjection of muscimol into the intermediate area between the DMH and the PVN attenuated the increases in heart rate by only 46% and in blood pressure by 52%. In contrast, similar injections into the vicinity of the PVN failed to alter the cardiovascular response to air stress. These findings demonstrate that muscimol-induced inhibition of neuronal activity in the region of the DMH blocks air stress-induced increases in heart rate and arterial pressure, whereas similar treatment in the area of the PVN has no effect

Mesoscopic spin confinement during acoustically induced transport

Long coherence lifetimes of electron spins transported using moving potential dots are shown to result from the mesoscopic confinement of the spin vector. The confinement dimensions required for spin control are governed by the characteristic spin-orbit length of the electron spins, which must be larger than the dimensions of the dot potential. We show that the coherence lifetime of the electron spins is independent of the local carrier densities within each potential dot and that the precession frequency, which is determined by the Dresselhaus contribution to the spin-orbit coupling, can be modified by varying the sample dimensions resulting in predictable changes in the spin-orbit length and, consequently, in the spin coherence lifetime.Comment: 10 pages, 2 figure

Fulminant neuroleptic malignant syndrome after perioperative withdrawal of antiParkinsonian medication

Neuroleptic malignant syndrome is a rare complication when using neuroleptic drugs. We report the case of a patient with severe Parkinson's disease who developed neuroleptic malignant syndrome after withdrawal of his antiParkinsonian medication for elective coronary artery bypass grafting. Sodium dantrolene may be a therapeutic option in severe case

A peptide mimic of the chemotaxis inhibitory protein of Staphylococcus aureus: towards the development of novel anti-inflammatory compounds

Complement factor C5a is one of the most powerful pro-inflammatory agents involved in recruitment of leukocytes, activation of phagocytes and other inflammatory responses. C5a triggers inflammatory responses by binding to its G-protein-coupled C5a-receptor (C5aR). Excessive or erroneous activation of the C5aR has been implicated in numerous inflammatory diseases. The C5aR is therefore a key target in the development of specific anti-inflammatory compounds. A very potent natural inhibitor of the C5aR is the 121-residue chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS). Although CHIPS effectively blocks C5aR activation by binding tightly to its extra-cellular N terminus, it is not suitable as a potential anti-inflammatory drug due to its immunogenic properties. As a first step in the development of an improved CHIPS mimic, we designed and synthesized a substantially shorter 50-residue adapted peptide, designated CHOPS. This peptide included all residues important for receptor binding as based on the recent structure of CHIPS in complex with the C5aR N terminus. Using isothermal titration calorimetry we demonstrate that CHOPS has micromolar affinity for a model peptide comprising residues 7–28 of the C5aR N terminus including two O-sulfated tyrosine residues at positions 11 and 14. CD and NMR spectroscopy showed that CHOPS is unstructured free in solution. Upon addition of the doubly sulfated model peptide, however, the NMR and CD spectra reveal the formation of structural elements in CHOPS reminiscent of native CHIPS

Observation of second-harmonic generation induced by pure spin currents

Extensive efforts are currently being devoted to developing a new electronic technology, called spintronics, where the spin of electrons is explored to carry information. [1,2] Several techniques have been developed to generate pure spin currents in many materials and structures. [3-10] However, there is still no method available that can be used to directly detect pure spin currents, which carry no net charge current and no net magnetization. Currently, studies of pure spin currents rely on measuring the induced spin accumulation with optical techniques [5, 11-13] or spin-valve configurations. [14-17] However, the spin accumulation does not directly reflect the spatial distribution or temporal dynamics of the pure spin current, and therefore cannot monitor the pure spin current in a real-time and real-space fashion. This imposes severe constraints on research in this field. Here we demonstrate a second-order nonlinear optical effect of the pure spin current. We show that such a nonlinear optical effect, which has never been explored before, can be used for the non-invasive, non-destructive, and real-time imaging of pure spin currents. Since this detection scheme does not rely on optical resonances, it can be generally applied in a wide range of materials with different electronic bandstructures. Furthermore, the control of nonlinear optical properties of materials with pure spin currents may have potential applications in photonics integrated with spintronics.Comment: 19 pages, 3 figures, supplementary discussion adde

Validation of the prognostic relevance of plasma C-reactive protein levels in soft-tissue sarcoma patients

Background: The concept of the involvement of systemic inflammation in cancer progression and metastases has gained attraction within the past decade. C-reactive protein (CRP), a non-specific blood-based marker of the systemic inflammatory response, has been associated with decreased survival in several cancer types. The aim of the present study was to validate the prognostic value of pre-operative plasma CRP levels on clinical outcome in a large cohort of soft-tissue sarcoma (STS) patients. Methods: Three hundred and four STS patients, operated between 1998 and 2010, were retrospectively evaluated. CRP levels and the impact on cancer-specific survival (CSS), disease-free survival (DFS) and overall survival (OS) were assessed using Kaplan–Meier curves and univariate as well as multivariate Cox proportional models. Additionally, we developed a nomogram by supplementing the plasma CRP level to the well-established Kattan nomogram and evaluated the improvement of predictive accuracy of this novel nomogram by applying calibration and Harrell’s concordance index (c-index). Results: An elevated plasma CRP level was significantly associated with established prognostic factors, including age, tumour grade, size and depth (P<0.05). In multivariate analysis, increased CRP levels were significantly associated with a poor outcome for CSS (HR=2.05; 95% CI=1.13–3.74; P=0.019) and DFS (HR=1.88; 95% CI=1.07–3.34; P=0.029). The estimated c-index was 0.74 using the original Kattan nomogram and 0.77 when the plasma CRP level was added. Conclusion: An elevated pre-operative CRP level represents an independent prognostic factor that predicts poor prognosis and improves the predictive ability of the Kattan nomogram in STS patients. Our data suggest to further prospectively validate its potential utility for individual risk stratification and clinical management of STS patients

Increased neutrophil-lymphocyte ratio is a poor prognostic factor in patients with primary operable and inoperable pancreatic cancer

Background: The neutrophil-lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response. Previous findings from small-scale studies revealed conflicting results about its independent prognostic significance with regard to different clinical end points in pancreatic cancer (PC) patients. Therefore, the aim of our study was the external validation of the prognostic significance of NLR in a large cohort of PC patients. Methods: Data from 371 consecutive PC patients, treated between 2004 and 2010 at a single centre, were evaluated retrospectively. The whole cohort was stratified into two groups according to the treatment modality. Group 1 comprised 261 patients with inoperable PC at diagnosis and group 2 comprised 110 patients with surgically resected PC. Cancer-specific survival (CSS) was assessed using the Kaplan–Meier method. To evaluate the independent prognostic significance of the NLR, the modified Glasgow prognostic score (mGPS) and the platelet-lymphocyte ratio univariate and multivariate Cox regression models were applied. Results: Multivariate analysis identified increased NLR as an independent prognostic factor for inoperable PC patients (hazard ratio (HR)=2.53, confidence interval (CI)=1.64–3.91, P<0.001) and surgically resected PC patients (HR=1.61, CI=1.02–2.53, P=0.039). In inoperable PC patients, the mGPS was associated with poor CSS only in univariate analysis (HR=1.44, CI=1.04–1.98). Conclusion: Risk prediction for cancer-related end points using NLR does add independent prognostic information to other well-established prognostic factors in patients with PC, regardless of the undergoing therapeutic modality. Thus, the NLR should be considered for future individual risk assessment in patients with PC

Genetic mapping of quantitative trait loci for agronomical and morpho-physiological traits under drought environments in spring barley (Hordeum vulgare L.)

Drought is one of the major abiotic stresses that severely limit barley production which is well adapted to drought conditions in the Mediterranean basin where the unpredictable climatic conditions, particularly rainfall, rainfall distribution and both high and low temperatures, may lead to dramatic decreases in yield. Landraces and wild species, represent an important source of variation for adaptive traits that may contribute to increased yield and yield stability under drought conditions. The study includes mapping of Quantitative QTLs for agronomical and morpho-physiological traits associated with drought tolerance. A total of 76 QTLs identified to 11 traits that describe grain yield, biological yield, harvest index, kernel weight, seed per head, days to heading, kernel filling duration, growth vigor, growth habit, lodging and plant height were mapped using RIL population Arta x Harmal-2//Esp/1808-4L which was evaluated at six dry and semi-dry areas over three years. The linkage map contained 254 markers (80 SSR, 174 AFLP) spanning 691cM. Eighty-Four markers’ loci (38 SSR and 46 AFLP) were used for QTLs mapping using the Simple Interval Mapping (SIM) and Simplified Composite Interval Mapping (sCIM). The QTLs which explained the largest part of the phenotypic variation in the dry areas (rainfall &lt;250 mm) were found on the following chromosomes: 2H for biological yield, 1H for harvest index, 2H, 4H and 5H for kernel weight, 2H for days to heading, 1H for the duration of kernel filling period and plant height. While in the semi-dry areas (rainfall between 250- 400mm) QTLs were identified on chromosomes 6H for grain yield, 2H and 5H for kernel weight, 1H and 6H for seed per head, 2H for days to heading. Some of the QTLs were common to those in other published work and some QTLs seemed specific to this study. Chromosomes 1H, 2H, 4H and 5H harbor more than 60% of mapped QTLs for dry areas. For the first time, QTLs explained the variation for grain yield, biological yield, harvest index, kernel weight and days to heading in very dry areas with rainfall less than 150 mm. An understanding of coincidental locations of QTL for correlated phenotypes allows a genetic dissection of different traits and better prediction of the loci most amendable for selection in a breeding program. The identification of marker-trait associations provides suitable opportunities for marker-assisted selection of genomic regions to improve adaptation to low rainfall environments provided interactions with other loci and with the target environments are reasonably well understood