Role of Cerebellar Interpositus Nucleus in the Genesis and Control of Reflex and Conditioned Eyelid Responses

The role of cerebellar circuits in the acquisition of new motor abilities is still a matter of intensive debate. To establish the contribution of posterior interpositus nucleus (PIN) to the performance and/or acquisition of reflex and classically conditioned responses (CRs) of the eyelid, the effects of microstimulation and/or pharmacological inhibition by muscimol of the nucleus were investigated in conscious cats. Microstimulation of the PIN in naive animals evoked ramp-like eyelid responses with a wavy appearance, without producing any noticeable plastic functional change in the cerebellar and brainstem circuits involved. Muscimol microinjections decreased the amplitude of reflex eyeblinks evoked by air puffs, both when presented alone or when paired with a tone as conditioned stimulus (CS). In half-conditioned animals, muscimol injections also decreased the amplitude and damped the typical wavy profile of CRs, whereas microstimulation of the same sites increased both parameters. However, neither muscimol injections nor microstimulation modified the expected percentage of CRs, suggesting a major role of the PIN in the performance of eyelid responses rather than in the learning process. Moreover, the simultaneous presentation of CS and microstimulation in well trained animals evoked CRs similar in amplitude to the added value of those evoked by the two stimuli presented separately. In contrast, muscimol-injected animals developed CRs to paired CS and microstimulation presentations, larger than those evoked by the two stimuli when presented alone. It is concluded that the PIN contributes to the enhancement of both reflex and conditioned eyelid responses and to the damping of resonant properties of neuromuscular elements controlling eyelid kinematics

Fine particle pH and the partitioning of nitric acid during winter in the northeastern United States

Particle pH is a critical but poorly constrained quantity that affects many aerosol processes and properties, including aerosol composition, concentrations, and toxicity. We assess PM1 pH as a function of geographical location and altitude, focusing on the northeastern U.S., based on aircraft measurements from the Wintertime Investigation of Transport, Emissions, and Reactivity campaign (1 February to 15 March 2015). Particle pH and water were predicted with the ISORROPIA-II thermodynamic model and validated by comparing predicted to observed partitioning of inorganic nitrate between the gas and particle phases. Good agreement was found for relative humidity (RH) above 40%; at lower RH observed particle nitrate was higher than predicted, possibly due to organic-inorganic phase separations or nitrate measurement uncertainties associated with low concentrations (nitrate \u3c 1 µg m−3). Including refractory ions in the pH calculations did not improve model predictions, suggesting they were externally mixed with PM1 sulfate, nitrate, and ammonium. Sample line volatilization artifacts were found to be minimal. Overall, particle pH for altitudes up to 5000 m ranged between −0.51 and 1.9 (10th and 90th percentiles) with a study mean of 0.77 ± 0.96, similar to those reported for the southeastern U.S. and eastern Mediterranean. This expansive aircraft data set is used to investigate causes in variability in pH and pH-dependent aerosol components, such as PM1 nitrate, over a wide range of temperatures (−21 to 19°C), RH (20 to 95%), inorganic gas, and particle concentrations and also provides further evidence that particles with low pH are ubiquitous

Cardiac Rehabilitation Models around the Globe.

Alternative models of cardiac rehabilitation (CR) delivery, such as home or community-based programs, have been developed to overcome underutilization. However, their availability and characteristics have never been assessed globally. In this cross-sectional study, a piloted survey was administered online to CR programs globally. CR was available in 111/203 (54.7%) countries globally; data were collected in 93 (83.8% country response rate). 1082 surveys (32.1% program response rate) were initiated. Globally, 85 (76.6%) countries with CR offered supervised programs, and 51 (45.9%; or 25.1% of all countries) offered some alternative model. Thirty-eight (34.2%) countries with CR offered home-based programs, with 106 (63.9%) programs offering some form of electronic CR (eCR). Twenty-five (22.5%) countries with CR offered community-based programs. Where available, programs served a mean of 21.4% ± 22.8% of their patients in home-based programs. The median dose for home-based CR was 3 sessions (Q25-Q75 = 1.0⁻4.0) and for community-based programs was 20 (Q25⁻Q75 = 9.6⁻36.0). Seventy-eight (47.0%) respondents did not perceive they had sufficient capacity to meet demand in their home-based program, for reasons including funding and insufficient staff. Where alternative CR models are offered, capacity is insufficient half the time. Home-based CR dose is insufficient to achieve health benefits. Allocation to program model should be evidence-based

Phase IV open-label study of the efficacy and safety of deferasirox after allogeneic stem cell transplantation

This is the first prospective study of deferasirox in adult allogeneic hematopoietic stem cell transplant recipients with transfusional iron overload in hematologic malignancies. Patients at least six months post transplant were treated with deferasirox at a starting dose of 10 mg/kg/day for 52 weeks or until serum ferritin was less than 400 ng/mL on two consecutive occasions. Thirty patients were enrolled and 22 completed the study. A significant reduction from baseline in median serum ferritin and in liver iron concentration at 52 weeks was observed in the overall population: from 1440 to 755.5 ng/mL (P=0.002) and from 14.5 to 4.6 mg Fe/g dw (P=0.0007), respectively. Reduction in serum ferritin in patients who did not discontinue deferasirox therapy was significantly greater than that found in those who prematurely discontinued the treatment (from 1541 to 581 ng/mL vs. from 1416 to 1486 ng/mL; P=0.008). Drug-related adverse events, reported in 17 patients (56.7%), were mostly mild to moderate in severity. There were no drug-related serious adverse events. Twelve patients (40.0%) showed an increase of over 33% in serum creatinine compared to baseline and greater than the upper limit of normal on two consecutive visits. Two patients (6.7%) with active graft-versus-host disease showed an increase in alanine aminotransferase exceeding 10 times upper limit of normal; both resolved. In this prospective study, deferasirox provided a significant reduction in serum ferritin and liver iron concentration over one year of treatment in allogeneic hematopoietic stem cell transplant recipients with iron overload. In addition, the majority of adverse events related to deferasirox were mild or moderate in severity. (clinicaltrials.gov identifier:01335035)

Spectroscopic Observations of Convective Patterns in the Atmospheres of Metal-Poor Stars

Convective line asymmetries in the optical spectrum of two metal-poor stars, Gmb1830 and HD140283, are compared to those observed for solar metallicity stars. The line bisectors of the most metal-poor star, the subgiant HD140283, show a significantly larger velocity span that the expectations for a solar-metallicity star of the same spectral type and luminosity class. The enhanced line asymmetries are interpreted as the signature of the lower metal content, and therefore opacity, in the convective photospheric patterns. These findings point out the importance of three-dimensional convective velocity fields in the interpretation of the observed line asymmetries in metal-poor stars, and in particular, urge for caution when deriving isotopic ratios from observed line shapes and shifts using one-dimensional model atmospheres. The mean line bisector of the photospheric atomic lines is compared with those measured for the strong Mg I b1 and b2 features. The upper part of the bisectors are similar, and assuming they overlap, the bottom end of the stronger lines, which are formed higher in the atmosphere, goes much further to the red. This is in agreement with the expected decreasing of the convective blue-shifts in upper atmospheric layers, and compatible with the high velocity redshifts observed in the chromosphere, transition region, and corona of late-type stars.Comment: 27 pages, LaTeX; 10 Figures (14 PostScript files); to be published in The Astrophysical Journa

Potential benefits of melatonin in organ transplantation: a review

Organ transplantation is a useful therapeutic tool for patients with end-stage organ failure; however, graft rejection is a major obstacle in terms of a successful treatment. Rejection is usually a consequence of a complex immunological and nonimmunological antigen-independent cascade of events, including free radical-mediated ischemia-reperfusion injury (IRI). To reduce the frequency of this outcome, continuing improvements in the efficacy of antirejection drugs are a top priority to enhance the long-term survival of transplant recipients. Melatonin (N-acetyl-5-methoxytryptamine) is a powerful antioxidant and ant-inflammatory agent synthesized from the essential amino acid L-tryptophan; it is produced by the pineal gland as well as by many other organs including ovary, testes, bone marrow, gut, placenta, and liver. Melatonin has proven to be a potentially useful therapeutic tool in the reduction of graft rejection. Its benefits are based on its direct actions as a free radical scavenger as well as its indirect antioxidative actions in the stimulation of the cellular antioxidant defense system. Moreover, it has significant anti-inflammatory activity. Melatonin has been found to improve the beneficial effects of preservation fluids when they are enriched with the indoleamine. This article reviews the experimental evidence that melatonin is useful in reducing graft failure, especially in cardiac, bone, otolaryngology, ovarian, testicular, lung, pancreas, kidney, and liver transplantation

The LSM1-7 Complex Differentially Regulates Arabidopsis Tolerance to Abiotic Stress Conditions by Promoting Selective mRNA Decapping

This work was supported by Grants BIO2010-17545 and BIO2013-47788-R from MINECO to J.S., GA14-34792S from CSFtoO.N., andMCB-1022435 fromtheNationalScience Foundation to L.S. R.C. is supported by a JAE-DOCcontract fromtheCSIC, andC.C.-L. is a recipient of a FPI fellowship from MINECO.International audienceIn eukaryotes, the decapping machinery is highly conserved and plays an essential role in controlling mRNA stability, a key step in the regulation of gene expression. Yet, the role of mRNA decapping in shaping gene expression profiles in response to environmental cues and the operating molecular mechanisms are poorly understood. Here, we provide genetic and molecular evidence that a component of the decapping machinery, the LSM1-7 complex, plays a critical role in plant tolerance to abiotic stresses. Our results demonstrate that, depending on the stress, the complex from Arabidopsis thaliana interacts with different selected stress-inducible transcripts targeting them for decapping and subsequent degradation. This interaction ensures the correct turnover of the target transcripts and, consequently, the appropriate patterns of downstream stress-responsive gene expression that are required for plant adaptation. Remarkably, among the selected target transcripts of the LSM1-7 complex are those encoding NCED3 and NCED5, two key enzymes in abscisic acid (ABA) biosynthesis. We demonstrate that the complex modulates ABA levels in Arabidopsis exposed to cold and high salt by differentially controlling NCED3 and NCED5 mRNA turnover, which represents a new layer of regulation in ABA biosynthesis in response to abiotic stress. Our findings uncover an unanticipated functional plasticity of the mRNA decapping machinery to modulate the relationship between plants and their environment

Paleohydrological dynamics in the Western Mediterranean during the last glacial cycle

The transitional regions between the low and high latitudes of the Northern Hemisphere are highly vulnerable to future climate change yet most of the current climate models usually diverge in their projections. To better understand the dynamics in these regions, the reconstruction of past hydrological fluctuations and precipitation patterns is of paramount importance to accurately constrain present and future climate scenarios. In this study, we investigated paleohydrological dynamics in the western Mediterranean region, a transitional zone between low-mid latitudes and Atlantic - Mediterranean realms. We reconstruct precipitation and moisture source changes during the last -35 ka in order to propose the potential mechanisms driving these oscillations. To do so, we use hydrogen isotopes from sedimentary leaf waxes, more specifically the C31 n-alkane homologue, and a precipitation proxy based on previously published pollen data from a sedimentary core (Padul-15-05) in southern Iberia (Padul wetland -37-N). With this combination we disentangle the coupled effect of precipitation amount and source on the hydrogen isotopic signature of the studied C31 n-alkane record. Our results show three main periods characterized by different precipitation patterns. Low precipitation, mainly linked to a significant contribution from an isotopically-enriched Mediterranean precipitation source, occurred from -30 to -15.5 ka BP and during the last -5 ka, whereas enhanced precipitation with a predominant isotopically-depleted Atlantic precipitation source prevailed from -15.5 to -5 ka BP. This latter stage is here defined as the Western Mediterranean Humid Period (WMHP). In addition, some occasional millennial-scale opposite precipitation patterns can be observed during these climatically distinct periods. These changes in the source of precipitation were likely coupled to a shift in the main rainy season from winter, when Atlantic precipitation prevailed, to late winter-early spring, when the contribution of Mediterranean moisture is higher. Comparison between the studied mid-latitude terrestrial Padul-15-05 core and a low-latitude marine record offshore of northwestern Africa shows clear long-term synchronous responses of both western Mediterranean precipitation and western African monsoon systems to northern Hemisphere atmospheric dynamics, ultimately controlled by orbital forcing and ice-sheets fluctuations.Peer reviewe

Serum melatonin levels during the first seven days of severe sepsis diagnosis are associated with sepsis severity and mortality

Objective: Higher serum melatonin levels have previously been found in patients with severe sepsis who died within 30 days of diagnosis than in survivors. The objective of our study were to determine whether serum melatonin levels during the first seven days of severe sepsis diagnosis could be associated with sepsis severity and mortality. Methods: Multicentre study in eight Spanish Intensive Care Units which enrolled 308 patients with severe sepsis. We determined serum levels of melatonin, malondialdehyde (as biomarker of lipid peroxidation) and tumor necrosis factor-alpha at days 1, 4 and 8 of severe sepsis diagnosis. The study's primary endpoint was 30-day mortality. Results: A total of 103 patients had died and 205 survived at 30 days of severe sepsis diagnosis, with the non-survivors presenting higher serum melatonin levels at days 1 (p<0.001), 4 (p<0.001) and 8 (p<0.001) of severe sepsis diagnosis than the survivor patient group. The multiple logistic regression analysis found that serum melatonin levels at days 1, 4 and 8 of severe sepsis diagnosis (p<0.001, p = 0.01 and p = 0.001, respectively) were associated with mortality adjusted for age, serum lactic acid, SOFA score and diabetes mellitus. Conclusions: The novel and more interesting findings of our study were that serum melatonin levels during the first seven days of severe sepsis diagnosis are associated with sepsis severity and mortality. (C) 2017 Elsevier Espana, S.L.U. and Sociedad Espanola de Enfermedades lnfecciosas y Microbiologia Clinica