Switching between forest and trees: Opposite relationship of progesterone and testosterone to global–local processing

AbstractSex differences in attentional selection of global and local components of stimuli have been hypothesized to underlie sex differences in cognitive strategy choice. A Navon figure paradigm was employed in 32 men, 41 naturally cycling women (22 follicular, 19 luteal) and 19 users of oral contraceptives (OCs) containing first to third generation progestins in their active pill phase. Participants were first asked to detect targets at any level (divided attention) and then at either the global or the local level only (focused attention). In the focused attention condition, luteal women showed reduced global advantage (i.e. faster responses to global vs. local targets) compared to men, follicular women and OC users. Accordingly, global advantage during the focused attention condition related significantly positively to testosterone levels and significantly negatively to progesterone, but not estradiol levels in a multiple regression model including all naturally cycling women and men. Interference (i.e. delayed rejection of stimuli displaying targets at the non-attended level) was significantly enhanced in OC users as compared to naturally cycling women and related positively to testosterone levels in all naturally cycling women and men. Remarkably, when analyzed separately for each group, the relationship of testosterone to global advantage and interference was reversed in women during their luteal phase as opposed to men and women during their follicular phase. As global processing is lateralized to the right and local processing to the left hemisphere, we speculate that these effects stem from a testosterone-mediated enhancement of right-hemisphere functioning as well as progesterone-mediated inter-hemispheric decoupling

Stimulation of the noradrenergic system enhances and blockade reduces memory for emotional material in man

Background. It is clearly established that emotional events tend to be remembered particularly vividly. The neurobiological substrates of this phenomenon are poorly understood. Recently, the noradrenergic system has been implicated in that beta blockade has been shown to reduce significantly the delayed recall of emotional material with matched neutral material being unaffected. Methods. In the present study, 36 healthy young adults were randomly allocated to receive either yohimbine, which stimulates central noradrenergic activity, metoprolol which blocks noradrenergic activity, or matched placebo. The three groups were well matched. All capsules were taken orally, prior to viewing a narrated 11 slide show described a boy being involved in an accident. Results. Yohimbine significantly elevated, and metoprolol reduced mean heart rate during the slide show relative to placebo, thus confirming the efficacy of the pharmacological manipulation. One week later, in a ‘surprise’ test, memory for the slide show was tested. As predicted, yohimbine-treated subjects recalled significantly more and metoprolol subjects fewer slides relative to placebo. This result was confirmed via analysis of multiple-choice recognition memory scores. Conclusions. We conclude that stimulation of the noradrenergic system results in the enhancement and blockade in a reduction of recall and recognition of emotional material in man

Variations in the Abundances of Potassium and Thorium on the Surface of Mercury: Results from the MESSENGER Gamma-Ray Spectrometer

A technique for converting gamma-ray count rates measured by the Gamma-Ray Spectrometer on the MESSENGER spacecraft to spatially resolved maps of the gamma-ray emission from the surface of Mercury is utilized to map the surface distributions of the elements Si, O, and K over the planet's northern hemisphere. Conversion of the K gamma-ray count rates to elemental abundances on the surface reveals variations from 300 to 2400 ppm. A comparison of these abundances with models for the maximum surface temperature suggests the possibility that a temperature-related process is controlling the K abundances on the surface as well as providing K to the exosphere. The abundances of K and Th have been determined for several geologically distinct regions, including Mercury's northern smooth plains and the plains interior to the Caloris basin. The lack of a significant variation in the measured Th abundances suggests that there may be considerable variability in the K/Th abundance ratio over the mapped regions

The brain decade in debate: I. Neurobiology of learning and memory

This article is a transcription of an electronic symposium in which some active researchers were invited by the Brazilian Society for Neuroscience and Behavior (SBNeC) to discuss the last decade's advances in neurobiology of learning and memory. The way different parts of the brain are recruited during the storage of different kinds of memory (e.g., short-term vs long-term memory, declarative vs procedural memory) and even the property of these divisions were discussed. It was pointed out that the brain does not really store memories, but stores traces of information that are later used to create memories, not always expressing a completely veridical picture of the past experienced reality. To perform this process different parts of the brain act as important nodes of the neural network that encode, store and retrieve the information that will be used to create memories. Some of the brain regions are recognizably active during the activation of short-term working memory (e.g., prefrontal cortex), or the storage of information retrieved as long-term explicit memories (e.g., hippocampus and related cortical areas) or the modulation of the storage of memories related to emotional events (e.g., amygdala). This does not mean that there is a separate neural structure completely supporting the storage of each kind of memory but means that these memories critically depend on the functioning of these neural structures. The current view is that there is no sense in talking about hippocampus-based or amygdala-based memory since this implies that there is a one-to-one correspondence. The present question to be solved is how systems interact in memory. The pertinence of attributing a critical role to cellular processes like synaptic tagging and protein kinase A activation to explain the memory storage processes at the cellular level was also discussed.University of Bristol Department of PsychologyUniversidade Federal de São Paulo (UNIFESP) Departamento de PsicobiologiaUniversity of California Center for Neurobiology of Learning and Memory Department of Neurobiology and BehaviorUniversity of California Neuropsychiatric InstituteUniversidade Federal do Rio Grande do Sul Instituto de Biociências Departamento de BioquímicaUniversity of Edinburgh Department of NeuroscienceUniversity of Arizona Department of PsychologyNorthwestern UniversityUniversidade de São Paulo Instituto de Biociências Departamento de FisiologiaUniversidade Federal do Paraná Departamento de Farmacologia Laboratório de Fisiologia e Farmacologia do Sistema Nervoso CentralUNIFESP, Depto. de PsicobiologiaSciEL

Major-Element Abundances on the Surface of Mercury: Results from the MESSENGER Gamma-Ray Spectrometer

Orbital gamma-ray measurements obtained by the MESSENGER spacecraft have been analyzed to determine the abundances of the major elements Al, Ca, S, Fe, and Na on the surface of Mercury. The Si abundance was determined and used to normalize those of the other reported elements. The Na analysis provides the first abundance estimate of 2.9 plus or minus 0.1 wt% for this element on Mercury's surface. The other elemental results (S/Si = 0.092 plus or minus 0.015, Ca/Si = 0.24 plus or minus 0.05, and Fe/Si = 0.077 plus or minus 0.013) are consistent with those previously obtained by the MESSENGER X-Ray Spectrometer, including the high sulfur and low iron abundances. Because of different sampling depths for the two techniques, this agreement indicates that Mercury's regolith is, on average, homogenous to a depth of tens of centimeters. The elemental results from gamma-ray and X-ray spectrometry are most consistent with petrologic models suggesting that Mercury's surface is dominated by Mg-rich silicates. We also compare the results with those obtained during the MESSENGER flybys and with ground-based observations of Mercury's surface and exosphere

Chemical Heterogeneity on Mercury's Surface Revealed by the MESSENGER X-Ray Spectrometer

We present the analysis of 205 spatially resolved measurements of the surface composition of Mercury from MESSENGER's X-Ray Spectrometer. The surface footprints of these measurements are categorized according to geological terrain. Northern smooth plains deposits and the plains interior to the Caloris basin differ compositionally from older terrain on Mercury. The older terrain generally has higher Mg/Si, S/Si, and Ca/Si ratios, and a lower Al/Si ratio than the smooth plains. Mercury's surface mineralogy is likely dominated by high-Mg mafic minerals (e.g., enstatite), plagioclase feldspar, and lesser amounts of Ca, Mg, and/or Fe sulfides (e.g., oldhamite). The compositional difference between the volcanic smooth plains and the older terrain reflects different abundances of these minerals and points to the crystallization of the smooth plains from a more chemically evolved magma source. High-degree partial melts of enstatite chondrite material provide a generally good compositional and mineralogical match for much of the surface of Mercury. An exception is Fe, for which the low surface abundance on Mercury is still higher than that of melts from enstatite chondrites and may indicate an exogenous contribution from meteoroid impacts

Reducing the duration of untreated psychosis and its impact in the U.S.: the STEP-ED study

Background: Early intervention services for psychotic disorders optimally interlock strategies to deliver: (i) Early Detection (ED) to shorten the time between onset of psychotic symptoms and effective treatment (i.e. Duration of Untreated Psychosis, DUP); and (ii) comprehensive intervention during the subsequent 2 to 5 years. In the latter category, are teams (‘First-episode Services’ or FES) that integrate several empirically supported treatments and adapt their delivery to younger patients and caregivers. There is an urgent need to hasten access to established FES in the U.S. Despite improved outcomes for those in treatment, these FES routinely engage patients a year or more after psychosis onset. The Scandinavian TIPS study was able to effectively reduce DUP in a defined geographic catchment. The guiding questions for this study are: can a U.S. adaptation of the TIPS approach to ED substantially reduce DUP and improve outcomes beyond existing FES? Methods/Design The primary aim is to determine whether ED can reduce DUP in the US, as compared to usual detection. ED will be implemented by one FES (STEP) based in southern Connecticut, and usual detection efforts will continue at a comparable FES (PREPR) serving the greater Boston metropolitan area. The secondary aim is to determine whether DUP reduction can improve presentation, engagement and early outcomes in FES care. A quasi-experimental design will compare the impact of ED on DUP at STEP compared to PREPR over 3 successive campaign years. The campaign will deploy 3 components that seek to transform pathways to care in 8 towns surrounding STEP. Social marketing approaches will inform a public education campaign to enable rapid and effective help-seeking behavior. Professional outreach and detailing to a wide variety of care providers, including those in the healthcare, educational and judicial sectors, will facilitate rapid redirection of appropriate patients to STEP. Finally, performance improvement measures within STEP will hasten engagement upon referral. Discussion STEP-ED will test an ED campaign adapted to heterogeneous U.S. pathways to care while also improving our understanding of these pathways and their impact on early outcomes. Trial registration ClinicalTrials.gov: NCT02069925. Registered 20 February 2014

Synthesis and anticancer activity of novel bisindolylhydroxymaleimide derivatives with potent GSK-3 kinase inhibition

Synthesis and biological evaluation of a series of novel indole derivatives as anticancer agents is described. A bisindolylmaleimide template has been derived as a versatile pharmacophore with which to pursue chemical diversification. Starting from maleimide, the introduction of an oxygen to the headgroup (hydroxymaleimide) was initially investigated and the bioactivity assessed by screening of kinase inhibitory activity, identifying substituent derived selectivity. Extension of the hydroxymaleimide template to incorporate substitution of the indole nitrogens was next completed and assessed again by kinase inhibition identifying unique selectivity patterns with respect to GSK-3 and CDK kinases. Subsequently, the anticancer activity of bisindolylmaleimides were assessed using the NCI-60 cell screen, disclosing the discovery of growth inhibitory profiles towards a number of cell lines, such as SNB-75 CNS cancer, A498 and UO-31 renal, MDA MB435 melanoma and a panel of leukemia cell lines. The potential for selective kinase inhibition by modulation of this template is evident and will inform future selective clinical candidates

Emissions pathways, climate change, and impacts on California

The magnitude of future climate change depends substantially on the greenhouse gas emission pathways we choose. Here we explore the implications of the highest and lowest Intergovernmental Panel on Climate Change emissions pathways for climate change and associated impacts in California. Based on climate projections from two state-of-the-art climate models with low and medium sensitivity (Parallel Climate Model and Hadley Centre Climate Model, version 3, respectively), we find that annual temperature increases nearly double from the lower B1 to the higher A1fi emissions scenario before 2100. Three of four simulations also show greater increases in summer temperatures as compared with winter. Extreme heat and the associated impacts on a range of temperature-sensitive sectors are substantially greater under the higher emissions scenario, with some interscenario differences apparent before midcentury. By the end of the century under the B1 scenario, heatwaves and extreme heat in Los Angeles quadruple in frequency while heat-related mortality increases two to three times; alpine subalpine forests are reduced by 50–75%; and Sierra snowpack is reduced 30–70%. Under A1fi, heatwaves in Los Angeles are six to eight times more frequent, with heat-related excess mortality increasing five to seven times; alpine subalpine forests are reduced by 75–90%; and snowpack declines 73–90%, with cascading impacts on runoff and streamflow that, combined with projected modest declines in winter precipitation, could fundamentally disrupt California’s water rights system. Although interscenario differences in climate impacts and costs of adaptation emerge mainly in the second half of the century, they are strongly dependent on emissions from preceding decades

Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases