Fetal programming effects of testosterone on the reward system and behavioral approach tendencies in humans

BACKGROUND: Sex differences are present in many neuropsychiatric conditions that affect emotion and approach-avoidance behavior. One potential mechanism underlying such observations is testosterone in early development. Although much is known about the effects of testosterone in adolescence and adulthood, little is known in humans about how testosterone in fetal development influences later neural sensitivity to valenced facial cues and approach-avoidance behavioral tendencies. METHODS: With functional magnetic resonance imaging we scanned 25 8-11-year-old children while viewing happy, fear, neutral, or scrambled faces. Fetal testosterone (FT) was measured via amniotic fluid sampled between 13 and 20 weeks gestation. Behavioral approach-avoidance tendencies were measured via parental report on the Sensitivity to Punishment and Sensitivity to Rewards questionnaire. RESULTS: Increasing FT predicted enhanced selectivity for positive compared with negatively valenced facial cues in reward-related regions such as caudate, putamen, and nucleus accumbens but not the amygdala. Statistical mediation analyses showed that increasing FT predicts increased behavioral approach tendencies by biasing caudate, putamen, and nucleus accumbens but not amygdala to be more responsive to positive compared with negatively valenced cues. In contrast, FT was not predictive of behavioral avoidance tendencies, either through direct or neurally mediated paths. CONCLUSIONS: This work suggests that testosterone in humans acts as a fetal programming mechanism on the reward system and influences behavioral approach tendencies later in life. As a mechanism influencing atypical development, FT might be important across a range of neuropsychiatric conditions that asymmetrically affect the sexes, the reward system, emotion processing, and approach behavior.

Trafficking and signaling of G protein-coupled receptors in the nervous system: implications for disease and therapy

G protein-coupled receptors (GPCRs) are expressed throughout the nervous system where they regulate multiple physiological processes, participate in neurological diseases, and are major targets for therapy. Given that many GPCRs respond to neurotransmitters and hormones that are present in the extracellular fluid and which do not readily cross the plasma membrane, receptor trafficking to and from the plasma membrane is a critically important determinant of cellular responsiveness. Moreover, trafficking of GPCRs throughout the endosomal system can initiate signaling events that are mechanistically and functionally distinct from those operating at the plasma membrane. This review discusses recent advances in the relationship between signaling and trafficking of GPCRs in the nervous system. It summarizes how receptor modifications influence trafficking, discusses mechanisms that regulate GPCR trafficking to and from the plasma membrane, reviews the relationship between trafficking and signaling, and considers the implications of GPCR trafficking to drug development.

Assessment of surface winds over the Atlantic, Indian and Pacific Ocean sectors of the Southern Ocean in CMIP5 models: historical bias, forcing response, and state dependence

An assessment of the fifth Coupled Models Intercomparison Project (CMIP5) models’ simulation of the near-surface westerly wind jet position and strength over the Atlantic, Indian and Pacific sectors of the Southern Ocean is presented. Compared with reanalysis climatologies there is an equatorward bias of 3.7° (inter-model standard deviation of ± 2.2°) in the ensemble mean position of the zonal mean jet. The ensemble mean strength is biased slightly too weak, with the largest biases over the Pacific sector (-1.6±1.1 m/s, 27 -22%). An analysis of atmosphere-only (AMIP) experiments indicates that 41% of the zonal mean position bias comes from coupling of the ocean/ice models to the atmosphere. The response to future emissions scenarios (RCP4.5 and RCP8.5) is characterized by two phases: (i) the period of most rapid ozone recovery (2000-2049) during which there is insignificant change in summer; and (ii) the period 2050-2098 during which RCP4.5 simulations show no significant change but RCP8.5 simulations show poleward shifts (0.30, 0.19 and 0.28°/decade over the Atlantic, Indian and Pacific sectors respectively), and increases in strength (0.06, 0.08 and 0.15 m/s/decade respectively). The models with larger equatorward position biases generally show larger poleward shifts (i.e. state dependence). This inter-model relationship is strongest over the Pacific sector (r=-0.89) and insignificant over the Atlantic sector (r=-0.50). However, an assessment of jet structure shows that over the Atlantic sector jet shift is significantly correlated with jet width whereas over the Pacific sector the distance between the sub-polar and sub-tropical westerly jets appears to be more important.

Market power and its effects on equilibrium in the food system

When food processors have conjectures about rival firms' responses, their profit functions can be used to estimate the degree of market power in the food system. The effects of this power are investigated analytically and through applying the results to the U.S. pork sector

On the connection between the 1984 Atlantic warm event and the 1982-1983 ENSO

The warm event which spread in the tropical Atlantic during Spring-Summer 1984 is assumed to be partially initiated by atmospheric disturbances, themselves related to the major 1982–1983 El-Niño which occurred 1 year earlier in the Pacific. This paper tests such an hypothesis. For that purpose, an atmospheric general circulation model (AGCM) is forced by different conditions of climatic and observed sea surface temperature and an Atlantic ocean general circulation model (OGCM) is subsequently forced by the outputs of the AGCM. It is firstly shown that both the AGCM and the OGCM correctly behave when globally observed SST are used: the strengthening of the trades over the tropical Atlantic during 1983 and their subsequent weakening at the beginning of 1984 are well captured by the AGCM, and so is the Spring 1984 deepening of the thermocline in the eastern equatorial Atlantic, simulated by the OGCM. As assumed, the SST anomalies located in the El-Niño Pacific area are partly responsible for wind signal anomaly in the tropical Atlantic. Though this remotely forced atmospheric signal has a small amplitude, it can generate, in the OGCM run, an anomalous sub-surface signal leading to a flattening of the thermocline in the equatorial Atlantic. This forced oceanic experiment cannot explain the amplitude and phase of the observed sub-surface oceanic anomaly: part of the Atlantic ocean response, due to local interaction between ocean and atmosphere, requires a coupled approach. Nevertheless this experiment showed that anomalous conditions in the Pacific during 82–83 created favorable conditions for anomaly development in the Atlantic.

The European Flood Alert System and the communication, perception, and use of ensemble predictions for operational flood risk management

Although ensemble prediction systems (EPS) are increasingly promoted as the scientific state-of-the-art for operational flood forecasting, the communication, perception, and use of the resulting alerts have received much less attention. Using a variety of qualitative research methods, including direct user feedback at training workshops, participant observation during site visits to 25 forecasting centres across Europe, and in-depth interviews with 69 forecasters, civil protection officials, and policy makers involved in operational flood risk management in 17 European countries, this article discusses the perception, communication, and use of European Flood Alert System (EFAS) alerts in operational flood management. In particular, this article describes how the design of EFAS alerts has evolved in response to user feedback and desires for a hydrographic-like way of visualizing EFAS outputs. It also documents a variety of forecaster perceptions about the value and skill of EFAS forecasts and the best way of using them to inform operational decision making. EFAS flood alerts were generally welcomed by flood forecasters as a sort of ‘pre-alert’ to spur greater internal vigilance. In most cases, however, they did not lead, by themselves, to further preparatory action or to earlier warnings to the public or emergency services. Their hesitancy to act in response to medium-term, probabilistic alerts highlights some wider institutional obstacles to the hopes in the research community that EPS will be readily embraced by operational forecasters and lead to immediate improvements in flood incident management. The EFAS experience offers lessons for other hydrological services seeking to implement EPS operationally for flood forecasting and warning. Copyright © 2012 John Wiley & Sons, Ltd.

Mathematics applied to the climate system: outstanding challenges and recent progress

The societal need for reliable climate predictions and a proper assessment of their uncertainties is pressing. Uncertainties arise not only from initial conditions and forcing scenarios, but also from model formulation. Here, we identify and document three broad classes of problems, each representing what we regard to be an outstanding challenge in the area of mathematics applied to the climate system. First, there is the problem of the development and evaluation of simple physically based models of the global climate. Second, there is the problem of the development and evaluation of the components of complex models such as general circulation models. Third, there is the problem of the development and evaluation of appropriate statistical frameworks. We discuss these problems in turn, emphasizing the recent progress made by the papers presented in this Theme Issue. Many pressing challenges in climate science require closer collaboration between climate scientists, mathematicians and statisticians. We hope the papers contained in this Theme Issue will act as inspiration for such collaborations and for setting future research directions.

Mid-Holocene land-surface conditions in northern Africa and the Arabian peninsula: a data set for the analysis of biogeophysical feedbacks in the climate system

Large changes in the extent of northern subtropical arid regions during the Holocene are attributed to orbitally forced variations in monsoon strength and have been implicated in the regulation of atmospheric trace gas concentrations on millenial timescales. Models that omit biogeophysical feedback, however, are unable to account for the full magnitude of African monsoon amplification and extension during the early to middle Holocene (˜9500–5000 years B.P.). A data set describing land-surface conditions 6000 years B.P. on a 1° × 1° grid across northern Africa and the Arabian Peninsula has been prepared from published maps and other sources of palaeoenvironmental data, with the primary aim of providing a realistic lower boundary condition for atmospheric general circulation model experiments similar to those performed in the Palaeoclimate Modelling Intercomparison Project. The data set includes information on the percentage of each grid cell occupied by specific vegetation types (steppe, savanna, xerophytic woods/scrub, tropical deciduous forest, and tropical montane evergreen forest), open water (lakes), and wetlands, plus information on the flow direction of major drainage channels for use in large-scale palaeohydrological modeling.