Imaging of prolonged BOLD response in the somatosensory cortex of the rat.

Blood oxygenation level-dependent (BOLD) functional MRI is a widely employed methodology in experimental and clinical neuroscience, although its nature is not fully understood. To gain insights into BOLD mechanisms and take advantage of the new functional methods, it is of interest to investigate prolonged paradigms of activation suitable for long experimental protocols and to observe any long-term modifications induced by these functional challenges. While different types of sustained stimulation paradigm have been explored in human studies, the BOLD response is typically limited to a few minutes in animal models, due to fatigue, anesthesia effects and physiological instability. In the present study, the rat forepaw was electrically stimulated for 2 h, which resulted in a prolonged and localized cortical BOLD response over that period. The stimulation paradigm, including an inter-stimulus interval (ISI) of 10 s, that is 25% of the total time, was applied at constant or variable frequency over 2 h. The steady-state level of the BOLD response was reached after 15-20 min of stimulation and was maintained until the end of the stimulation. On average, no substantial loss in activated volume was observed at the end of the stimulation, but less variability in the fraction of remaining activated volume and higher steady-state BOLD amplitude were observed when stimulation frequency was varied between 2 and 3 Hz every 5 min. We conclude that the combination of ISI and variable stimulus frequency reproducibly results in robust, prolonged and localized BOLD activation. Copyright © 2015 John Wiley & Sons, Ltd.

Growth variability of Scots pine (Pinus sylvestris) along a West-East gradient across northern Fennoscandia: a dendroclimatic approach

We performed a spatiotemporal analysis of a network of 21 Scots pine (Pinus sylvestris) ring-width chronologies in northern Fennoscandia by means of chronology statistics and multivariate analyses. Chronologies are located on both sides (western and eastern) of the Scandes Mountains (67°N-70°N, 15°E-29°E). Growth relationships with temperature, precipitation, and North Atlantic Oscillation (NAO) indices were calculated for the period 1880-1991. We also assessed their temporal stability. Current July temperature and, to a lesser degree, May precipitation are the main growth limiting factors in the whole area of study. However, Principal Component Analysis (PCA) and mean interseries correlation revealed differences in radial growth between both sides of the Scandes Mountains, attributed to the Oceanic-Continental climatic gradient in the area. The gradient signal is temporally variable and has strengthened during the second half of the 20th century. Northern Fennoscandia Scots pine growth is positively related to early winter NAO indices previous to the growth season and to late spring NAO. NAO/growth relationships are unstable and have dropped in the second half of the 20th century. Moreover, they are noncontinuous through the range of NAO values: for early winter, only positive NAO indices enhance tree growth in the next growing season, while negative NAO does not. For spring, only negative NAO is correlated with radial growth.

Natural Products from Antarctic Colonial Ascidians of the Genera Aplidium and Synoicum: Variability and Defensive Role

Ascidians have developed multiple defensive strategies mostly related to physical, nutritional or chemical properties of the tunic. One of such is chemical defense based on secondary metabolites. We analyzed a series of colonial Antarctic ascidians from deep-water collections belonging to the genera Aplidium and Synoicum to evaluate the incidence of organic deterrents and their variability. The ether fractions from 15 samples including specimens of the species A. falklandicum, A. fuegiense, A. meridianum, A. millari and S. adareanum were subjected to feeding assays towards two relevant sympatric predators: the starfish Odontaster validus, and the amphipod Cheirimedon femoratus. All samples revealed repellency. Nonetheless, some colonies concentrated defensive chemicals in internal body-regions rather than in the tunic. Four ascidian-derived meroterpenoids, rossinones B and the three derivatives 2,3-epoxy-rossinone B, 3-epi-rossinone B, 5,6-epoxy-rossinone B, and the indole alkaloids meridianins A-G, along with other minoritary meridianin compounds were isolated from several samples. Some purified metabolites were tested in feeding assays exhibiting potent unpalatabilities, thus revealing their role in predation avoidance. Ascidian extracts and purified compound-fractions were further assessed in antibacterial tests against a marine Antarctic bacterium. Only the meridianins showed inhibition activity, demonstrating a multifunctional defensive role. According to their occurrence in nature and within our colonial specimens, the possible origin of both types of metabolites is discussed.

Spatiotemporal variability in radial growth of trees in the Central Pyrenees: climatic and site influences.

To understand how tree growth has responded to recent climate warming, an understanding of the tree-climate-site complex is necessary. To achieve this, radial growth variability among 204 trees established before 1850 was studied in relation to both climatic and site factors. Seventeen forest stands were sampled in the Spanish Central Pyrenees. Three species were studied: Pinus uncinata, Abies alba, and Pinus sylvestris. For each tree, a ring-width residual chronology was built. All trees cross-dated well, indicating a common influence of the regional climate. For the 1952-1993 period, the radial growth of all species, especially P. uncinata, was positively correlated with warm Novembers during the year before ring formation and warm Mays of the year the annual ring formed. Differences in species-stand elevation modulated the growth-climate associations. Radial growth in P. uncinata at high elevation sites was reduced when May temperatures were colder and May precipitation more abundant. In the 20th century, two contrasting periods in radial growth were observed: one (1900-1949) with low frequency of narrow and wide rings, low mean annual sensitivity, and low common growth variation; and another (1950-1994) with the reverse characteristics. The increased variability in radial growth since the 1950s was observed for all species and sites, which suggests a climatic cause. The low shared variance among tree chronologies during the first half of the 20th century may result from a"relaxation" of the elevation gradient, allowing local site conditions to dominate macroclimatic influence. These temporal trends may be related to the recently reported increase of climatic variability and warmer conditions. This study emphasizes the need to carefully assess the relationships between radial growth and site conditions along ecological gradients to improve dendroclimatic reconstructions.

Extra Forces induced by wide-pulse, high-frequency electrical stimulation: Occurrence, magnitude, variability and underlying mechanisms.

OBJECTIVE: In contrast to conventional (CONV) neuromuscular electrical stimulation (NMES), the use of "wide-pulse, high-frequencies" (WPHF) can generate higher forces than expected by the direct activation of motor axons alone. We aimed at investigating the occurrence, magnitude, variability and underlying neuromuscular mechanisms of these "Extra Forces" (EF). METHODS: Electrically-evoked isometric plantar flexion force was recorded in 42 healthy subjects. Additionally, twitch potentiation, H-reflex and M-wave responses were assessed in 13 participants. CONV (25Hz, 0.05ms) and WPHF (100Hz, 1ms) NMES consisted of five stimulation trains (20s on-90s off). RESULTS: K-means clustering analysis disclosed a responder rate of almost 60%. Within this group of responders, force significantly increased from 4% to 16% of the maximal voluntary contraction force and H-reflexes were depressed after WPHF NMES. In contrast, non-responders showed neither EF nor H-reflex depression. Twitch potentiation and resting EMG data were similar between groups. Interestingly, a large inter- and intrasubject variability of EF was observed. CONCLUSION: The responder percentage was overestimated in previous studies. SIGNIFICANCE: This study proposes a novel methodological framework for unraveling the neurophysiological mechanisms involved in EF and provides further evidence for a central contribution to EF in responders.

Apple biological and physiological disorders in the orchard and in postharvest according to production system

The study aimed to evaluate the incidence of biological and physiological disorders in the field and postharvested apples cvs. Gala, Fuji and Catarina grown in four production systems: conventional, organic transition, integrated and organic. Apples were evaluated for damages related to biological and physiological disorders in the orchard and after harvest. The greatest damages were attributed to pests, especially Anastrepha fraterculus in the organic system and Grapholita molesta in the organic transition. Apples produced in organic orchards had higher damage levels caused by postharvest physiological disorders than those grown in other production systems. For apples becoming from organic orchards most of the damage was due to lenticels breakdown and degeneration ('Gala'), and bitter pit ('Fuji' and 'Catarina'). The incidence of postharvest rot was not influenced by apple production system.

Long-term X-ray variability of the microquasar system LS5039/RX J1826.2-1450

We report on the results of the spectral and timing analysis of a BeppoSAX observation of the microquasar system LS 5039/RX J1826.2-1450. The source was found in a low-flux state with Fx(1-10 keV)= 4.7 x 10^{-12} erg cm^{-2} s^{-1}, which represents almost one order of magnitude lower than a previous RXTE observation 2.5 years before. The 0.1--10 keV spectrum is described by an absorbed power-law continuum with photon-number spectral index Gamma=1.8+-0.2 and hydrogen column density of NH=1.0^{+0.4}_{-0.3} x 10^{22} cm^{-2}. According to the orbital parameters of the system the BeppoSAX observation covers the time of an X-ray eclipse should one occur. However, the 1.6-10 keV light curve does not show evidence for such an event, which allows us to give an upper limit to the inclination of the system. The low X-ray flux detected during this observation is interpreted as a decrease in the mass accretion rate onto the compact object due to a decrease in the mass-loss rate from the primary.

The down-regulation of disgust by implementation intentions: experiential and physiological concomitants

Emotion regulation plays a key role in mental health and psychopathology. Therefore, it seems important to develop effective forms of emotion regulation. Implementation intentions are if-then plans that help people attain their self-regulatory goals. Perspective-taking and response-focused implementation intentions have been shown to reduce feelings of unpleasantness and arousal, respectively, in response to briefly presented disgusting pictures. The present study addressed the open research questions whether forming these types of implementation intentions is effective in regulating affect during prolonged presentation of disgusting pictures, and whether it is associated with changes in physiological arousal. Eighty-one participants viewed disgusting, neutral, and pleasant pictures of 6 s duration under four instructions: the goal intention to not get disgusted, this goal intention furnished with a perspective-taking or a response-focused implementation intention, and no emotion regulation instructions. The dependent variables were ratings of disgust, valence, arousal, and electrodermal activity. Only perspective-taking implementation intention participants significantly reduced their disgust and unpleasantness as compared to goal-intention and control participants. Arousal and skin conductance did not significantly differ between conditions. The effectiveness of response-focused but not perspective-taking implementation intentions seems to be substantially reduced during sustained exposure duration.

Physiological noise in human cerebellar fMRI.

OBJECTIVES: To compare physiological noise contributions in cerebellar and cerebral regions of interest in high-resolution functional magnetic resonance imaging (fMRI) data acquired at 7T, to estimate the need for physiological noise removal in cerebellar fMRI. MATERIALS AND METHODS: Signal fluctuations in high resolution (1 mm isotropic) 7T fMRI data were attributed to one of the following categories: task-induced BOLD changes, slow drift, signal changes correlated with the cardiac and respiratory cycles, signal changes related to the cardiac rate and respiratory volume per unit of time or other. [Formula: see text] values for all categories were compared across regions of interest. RESULTS: In this high-resolution data, signal fluctuations related to the phase of the cardiac cycle and cardiac rate were shown to be significant, but comparable between cerebellar and cerebral regions of interest. However, respiratory related signal fluctuations were increased in the cerebellar regions, with explained variances that were up to 80 % higher than for the primary motor cortex region. CONCLUSION: Even at a millimetre spatial resolution, significant correlations with both cardiac and respiratory RETROICOR components were found in all healthy volunteer data. Therefore, physiological noise correction is highly likely to improve the temporal signal-to-noise ratio (SNR) for cerebellar fMRI at 7T, even at high spatial resolution.

Practice variability and efficacy of clonazepam, lorazepam, and midazolam in status epilepticus: A multicenter comparison.

OBJECTIVE: Benzodiazepines (BZD) are recommended as first-line treatment for status epilepticus (SE), with lorazepam (LZP) and midazolam (MDZ) being the most widely used drugs and part of current treatment guidelines. Clonazepam (CLZ) is also utilized in many countries; however, there is no systematic comparison of these agents for treatment of SE to date. METHODS: We identified all patients treated with CLZ, LZP, or MDZ as a first-line agent from a prospectively collected observational cohort of adult patients treated for SE in four tertiary care centers. Relative efficacies of CLZ, LZP, and MDZ were compared by assessing the risk of developing refractory SE and the number of antiseizure drugs (ASDs) required to control SE. RESULTS: Among 177 patients, 72 patients (40.62%) received CLZ, 82 patients (46.33%) LZP, and 23 (12.99%) MDZ; groups were similar in demographics and SE characteristics. Loading dose was considered insufficient in the majority of cases for LZP, with a similar rate (84%, 95%, and 87.5%) in the centers involved, and CLZ was used as recommended in 52% of patients. After adjustment for relevant variables, LZP was associated with an increased risk of refractoriness as compared to CLZ (odds ratio [OR] 6.4, 95% confidence interval [CI] 2.66-15.5) and with an increased number of ASDs needed for SE control (OR 4.35, 95% CI 1.8-10.49). SIGNIFICANCE: CLZ seems to be an effective alternative to LZP and MDZ. LZP is frequently underdosed in this setting. These findings are highly relevant, since they may impact daily practice.

Influence of M. tuberculosis lineage variability within a clinical trial for pulmonary tuberculosis.

Recent studies suggest that M. tuberculosis lineage and host genetics interact to impact how active tuberculosis presents clinically. We determined the phylogenetic lineages of M. tuberculosis isolates from participants enrolled in the Tuberculosis Trials Consortium Study 28, conducted in Brazil, Canada, South Africa, Spain, Uganda and the United States, and secondarily explored the relationship between lineage, clinical presentation and response to treatment. Large sequence polymorphisms and single nucleotide polymorphisms were analyzed to determine lineage and sublineage of isolates. Of 306 isolates genotyped, 246 (80.4%) belonged to the Euro-American lineage, with sublineage 724 predominating at African sites (99/192, 51.5%), and the Euro-American strains other than 724 predominating at non-African sites (89/114, 78.1%). Uneven distribution of lineages across regions limited our ability to discern significant associations, nonetheless, in univariate analyses, Euro-American sublineage 724 was associated with more severe disease at baseline, and along with the East Asian lineage was associated with lower bacteriologic conversion after 8 weeks of treatment. Disease presentation and response to drug treatment varied by lineage, but these associations were no longer statistically significant after adjustment for other variables associated with week-8 culture status.