Human NR5A1/SF-1 mutations show decreased activity on BDNF (brain-derived neurotrophic factor), an important regulator of energy balance: testing impact of novel SF-1 mutations beyond steroidogenesis

CONTEXT Human NR5A1/SF-1 mutations cause 46,XY disorder of sex development (DSD) with broad phenotypic variability, and rarely cause adrenal insufficiency although SF-1 is an important transcription factor for many genes involved in steroidogenesis. In addition, the Sf-1 knockout mouse develops obesity with age. Obesity might be mediated through Sf-1 regulating activity of brain-derived neurotrophic factor (BDNF), an important regulator of energy balance in the ventromedial hypothalamus. OBJECTIVE To characterize novel SF-1 gene variants in 4 families, clinical, genetic and functional studies were performed with respect to steroidogenesis and energy balance. PATIENTS 5 patients with 46,XY DSD were found to harbor NR5A1/SF-1 mutations including 2 novel variations. One patient harboring a novel mutation also suffered from adrenal insufficiency. METHODS SF-1 mutations were studied in cell systems (HEK293, JEG3) for impact on transcription of genes involved in steroidogenesis (CYP11A1, CYP17A1, HSD3B2) and in energy balance (BDNF). BDNF regulation by SF-1 was studied by promoter assays (JEG3). RESULTS Two novel NR5A1/SF-1 mutations (Glu7Stop, His408Profs*159) were confirmed. Glu7Stop is the 4th reported SF-1 mutation causing DSD and adrenal insufficiency. In vitro studies revealed that transcription of the BDNF gene is regulated by SF-1, and that mutant SF-1 decreased BDNF promoter activation (similar to steroid enzyme promoters). However, clinical data from 16 subjects carrying SF-1 mutations showed normal birth weight and BMI. CONCLUSIONS Glu7Stop and His408Profs*159 are novel SF-1 mutations identified in patients with 46,XY DSD and adrenal insufficiency (Glu7Stop). In vitro, SF-1 mutations affect not only steroidogenesis but also transcription of BDNF which is involved in energy balance. However, in contrast to mice, consequences on weight were not found in humans with SF-1 mutations.

Application and comparison of UTCI and PET in temperature climate conditions

The assessment of the thermal bioclimate is based on the human energy balance and derived indices such as Physiologically equivalent temperature (Pet) or Universal thermal Climate index (UtCi). These two indices were compared over a period often year based on hourly data in a middle european city with a temperate climate. The analysis performed shows that the differences obtained result from the different thermo-physiological settings of clothing insulation. For conditions with extremely high vapour pressure values, UtCi yields higher values than Pet, which could describe the thermo-physiological stress more appropriately.

Joy, Schadenfreude, Sorrow, and Resentment as Responses Restoring Balance in Cognitive Units

Based on Heider’s (1958) balance theory we hypothesize that emotional responses to other persons’ outcomes depend on attitudes towards these persons. Positive attitudes towards others lead to empathic responses to their outcomes– joy after a success and sorrow after a failure. Negative attitudes result in paradoxical responses – negative to a success (resentment) and positive to a failure (schadenfreude). These emotions function as responses restoring balance within cognitive units consisting of the perceiver, other persons and their outcomes. Three studies supported these hypotheses and showed that deservingness considerations play a weaker role in shaping emotional responses of joy and sorrow to others’ outcomes when strong interpersonal attitudes are involved. However, deservingness plays an independent role in shaping the emotional response of resentment.

Response of the cholesterol metabolism to a negative energy balance in dairy cows depends on the lactational stage.

The response of cholesterol metabolism to a negative energy balance (NEB) induced by feed restriction for 3 weeks starting at 100 days in milk (DIM) compared to the physiologically occurring NEB in week 1 postpartum (p.p.) was investigated in 50 dairy cows (25 control (CON) and 25 feed-restricted (RES)). Blood samples, liver biopsies and milk samples were taken in week 1 p.p., and in weeks 0 and 3 of feed restriction. Plasma concentrations of total cholesterol (C), phospholipids (PL), triglycerides (TAG), very low density lipoprotein-cholesterol (VLDL-C) and low density lipoprotein-cholesterol (LDL-C) increased in RES cows from week 0 to 3 during feed restriction and were higher in week 3 compared to CON cows. In contrast, during the physiologically occurring NEB in week 1 p.p., C, PL, TAG and lipoprotein concentrations were at a minimum. Plasma phospholipid transfer protein (PLTP) and lecithin:cholesterol acyltransferase (LCAT) activities did not differ between week 0 and 3 for both groups, whereas during NEB in week 1 p.p. PLTP activity was increased and LCAT activity was decreased. Milk C concentration was not affected by feed restriction in both groups, whereas milk C mass was decreased in week 3 for RES cows. In comparison, C concentration and mass in milk were elevated in week 1 p.p. Hepatic mRNA abundance of sterol regulatory element-binding factor-2 (SREBF-2), 3-hydroxy-3-methylglutaryl-coenzyme A synthase 1 (HMGCS1), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), and ATP-binding cassette transporter (ABCA1) were similar in CON and RES cows during feed restriction, but were upregulated during NEB in week 1 p.p. compared to the non-lactating stage without a NEB. In conclusion, cholesterol metabolism in dairy cows is affected by nutrient and energy deficiency depending on the stage of lactation.

Large-scale land acquisition and its effects on the water balance in investor and host countries

This study examines the validity of the assumption that international large-scale land acquisition (LSLA) is motivated by the desire to secure control over water resources, which is commonly referred to as ‘water grabbing’. This assumption was repeatedly expressed in recent years, ascribing the said motivation to the Gulf States in particular. However, it must be considered of hypothetical nature, as the few global studies conducted so far focused primarily on the effects of LSLA on host countries or on trade in virtual water. In this study, we analyse the effects of 475 intended or concluded land deals recorded in the Land Matrix database on the water balance in both host and investor countries. We also examine how these effects relate to water stress and how they contribute to global trade in virtual water. The analysis shows that implementation of the LSLAs in our sample would result in global water savings based on virtual water trade. At the level of individual LSLA host countries, however, water use intensity would increase, particularly in 15 sub-Saharan states. From an investor country perspective, the analysis reveals that countries often suspected of using LSLA to relieve pressure on their domestic water resources—such as China, India, and all Gulf States except Saudi Arabia—invest in agricultural activities abroad that are less water-intensive compared to their average domestic crop production. Conversely, large investor countries such as the United States, Saudi Arabia, Singapore, and Japan are disproportionately externalizing crop water consumption through their international land investments. Statistical analyses also show that host countries with abundant water resources are not per se favoured targets of LSLA. Indeed, further analysis reveals that land investments originating in water-stressed countries have only a weak tendency to target areas with a smaller water risk.

Prediction of Benthic Impact for Salmon Net-Pens Based on the Balance of Benthic Oxygen Supply and Demand

The ratio between oxygen supply and oxygen demand was examined as a predictor of benthic response to organic enrichment caused by salmon net-pen aquaculture. Oxygen supply to the benthos was calculated based on Fickian diffusion and near-bottom flow velocities. A strong linear correlation was found between measured carbon sedimentation rates and rates of benthic metabolism. This relationship allowed an estimation of oxygen demand based on sedimentation rates. Comparison of several production sites in Maine (USA) coastal waters showed that for sites where oxygen demand exceeded supply benthic impacts were high and for sites where oxygen supply exceeded demand benthic impacts were low. These findings were summarized in the form of a predictive model that should be useful in siting salmon production facilities.

Testing for Balance Sheet Effects in Emerging Market Countries

This paper tests the presence of balance sheets effects and analyzes the implications for exchange rate policies in emerging markets. The results reveal that the emerging market bond index (EMBI) is negatively related to the banks' foreign currency leverage, and that these banks' foreign currency exposures are relatively unhedged. Panel SVAR methods using EMBI instead of advanced country lending rates find, contrary to the literature, that the amplitude of output responses to foreign interest rate shocks are smaller under relatively fixed regimes. The findings are robust to the local projections method of obtaining impulse responses, using country specific and GARCH-SVAR models.

Monetary Policy in a Portfolio Balance Model with Endogenous Physical Capital

We develop a portfolio balance model with real capital accumulation. The introduction of real capital as an asset as well as a good produced and demanded by firms enriches extant portfolio balance models of exchange rate determination. We show that expansionary monetary policy causes exchange rate overshooting, not once, but twice; the secondary repercussion comes through the reaction of firms to changed asset prices and the firms' decisions to invest in real capital. The model sheds further light on the volatility of real and nominal exchange rates, and it suggests that changes in corporate sector profitability may affect exchange rates through portfolio diversification in corporate securities.

Targeting AKT/mTOR Signaling Pathways During Murine Skin Tumor Promotion and the Impact of Dietary Energy Balance Manipulation

The prevalence of obesity has continued to rise over the last several decades in the United States lending to overall increases in risk for chronic diseases including many types of cancer. In contrast, reduction in energy consumption via calorie restriction (CR) has been shown to be a potent inhibitor of carcinogenesis across a broad range of species and tumor types. Previous data has demonstrated differential signaling through Akt and mTOR via the IGF-1R and other growth factor receptors across the diet-induced obesity (DIO)/CR spectrum. Furthermore, mTORC1 is known to be regulated directly via nutrient availability, supporting its role in the link between epithelial carcinogenesis and diet-induced obesity. In an effort to better understand the importance of mTORC1 in the context of both positive and negative energy balance during epithelial carcinogenesis, we have employed the use of specific pharmacological inhibitors, rapamycin (mTORC1 inhibitor) and metformin (AMPK activator) to target mTORC1 or various components of this pathway during skin tumor promotion. Two-stage skin carcinogenesis studies demonstrated that mTORC1 inhibition via rapamycin, metformin or combination treatments greatly inhibited skin tumor development in normal, overweight and obese mice. Furthermore, mechanisms by which these chemopreventive agents may be exerting their anti-tumor effects were explored. In addition, the effect of these compounds on the epidermal proliferative response was analyzed and drastic decreases in epidermal hyperproliferation and hyperplasia were found. Rapamycin also inhibited dermal inflammatory cell infiltration in a dose-dependent manner. Both compounds also blocked or attenuated TPA-induced signaling through epidermal mTORC1 as well as several downstream targets. In addition, inhibition of this pathway by metformin appeared to be, at least in part, dependent on AMPK activation in the skin. Overall, the data indicate that pharmacological strategies targeting this pathway offset the tumor-enhancing effects of DIO and may serve as possible CR mimetics. They suggest that mTORC1 contributes significantly to the process of skin tumor promotion, specifically during dietary energy balance effects. Exploiting the mechanistic information underlying dietary energy balance responsive pathways will help translate decades of research into effective strategies for prevention of epithelial carcinogenesis.

Behavioral decision making and the levels of change: An application of the transtheoretical model to prenatal smoking in low -income women

Despite continued research and public health efforts to reduce smoking during pregnancy, prenatal cessation rates in the United States have decreased and the incidence of low birth weight has increased from 1985 to 1991. Lower socioeconomic status women who are at increased risk for poor pregnancy outcomes may be resistant to current intervention efforts during pregnancy. The purpose of this dissertation was to investigate the determinants of continued smoking and quitting among low-income pregnant women.^ Using data from cross-sectional surveys of 323 low-income pregnant smokers, the first study developed and tested measures of the pros and cons of smoking during pregnancy. The original decisional balance measure for smoking was compared with a new measure that added items thought to be more salient to the target population. Confirmatory factor analysis using structural equation modeling showed neither the original nor new measure fit the data adequately. Using behavioral science theory, content from interviews with the population, and statistical evidence, two 7-item scales representing the pros and cons were developed from a portion (n = 215) of the sample and successfully cross-validated on the remainder of the sample (n = 108). Logistic regression found only pros were significantly associated with continued smoking. In a discriminant function analysis, stage of change was significantly associated with pros and cons of smoking.^ The second study examined the structural relationships between psychosocial constructs representing some of the levels of and the pros and cons of smoking. The cross-sectional design mandates that statements made regarding prediction do not prove causation or directionality from the data or methods analysis. Structural equation modeling found the following: more stressors and family criticism were significantly more predictive of negative affect than social support; a bi-directional relationship was found between negative affect and current nicotine addiction; and negative affect, addiction, stressors, and family criticism were significant predictors of pros of smoking.^ The findings imply reversing the trend of decreasing smoking cessation during pregnancy may require supplementing current interventions for this population of pregnant smokers with programs addressing nicotine addiction, negative affect, and other psychosocial factors such as family functioning and stressors. ^

Para un balance crítico de la filosofía iberoamericana en la llamada etapa de los fundadores

Fil: Fornet-Betancourt, Raúl.

Balance energético en unidades de tierra de una cuenca rural basado en un sistema de información geográfica.

El objetivo de este trabajo fue desarrollar una metodología de procesamiento de información espacial basada en un Sistema de Información Geográfica (SIG), para la determinación del balance de energía en unidades de tierra (UT) definidas en una cuenca hidrográfica rural. Se determinaron las UT a partir de mapas de unidades de paisaje y de mapas de estratos de superficie operada por productor. Se caracterizaron los ingresos (IE) y egresos energéticos (EE) en los sistemas de producción agrícolas. Se calculó la energía neta (EN) y la relación EE/IE (Re). Los datos se analizaron mediante un ANVA (p < 0,05). Los parámetros IE, EE, EN y Re no fueron significativamente diferentes entre UT, por lo que se infiere que el modelo productivo actualmente desarrollado, desde el punto de vista energético, resulta similar. Se hallaron relaciones de interés entre las variables de estudio y su ubicación geográfica, lo que permite recomendar para los sistemas agrícolas de una cuenca rural la planificación general del uso de la energía considerando las capacidades de los SIG.

En búsqueda de las huellas del posneoliberalismo venezolano y latinoamericano. Mario Ayala, Pablo Quintero (comps). Diez años de revolución en Venezuela. Historia, balance y perspectivas (1999-2009). Editorial MAIPUE, Buenos Aires, 2009. 384 páginas.

Fil: Astorga, Sergio. Universidad Nacional de Cuyo. Facultad de Ciencias Políticas y Sociales

Aplicación de la herramienta EX -ACT para el cálculo del balance de carbono en un proyecto de incremento de la superficie forestal en la provincia de Mendoza mediante el uso de cortinas forestales en los cultivos de vid

El presente trabajo tiene como objetivo principal la aplicación de la herramienta de balance de Carbono (EX –ACT, FAO 2012), cuyo fin es proporcionar estimaciones ex-ante sobre el impacto de la mitigación de proyectos de desarrollo agrícolas o forestales, estimando el balance de Carbono (C) neto proveniente de las emisiones de gases de efecto invernadero (GEI) y de la secuestración de C. Para esto se utilizó como área de estudio la superficie cultivada con vid dentro de los oasis de regadío de la provincia de Mendoza y una propuesta de proyecto que consiste en aumentar la superficie de cultivo forestal de álamos como cortinas cortavientos acompañando los cultivos de vid. La herramienta muestra que en las condiciones actuales, con el tipo de manejo que se realiza sobre el cultivo de vid, este en su conjunto es una fuente de gases de efecto invernadero, a pesar de ser vegetación. Dicho resultado es producto del número y la cantidad de insumos utilizados en el manejo convencional de la vid. Cuando se integra a esta situación la propuesta del cultivo de álamos, el resultado final cambia, pasando a ser el sistema en su conjunto, un sumidero de gases de efecto invernadero. La razón principal del cambio es que el aumento de superficie forestal tiene un bajo consumo de insumos generadores de emisiones, lo cual hace que disminuya la cantidad de insumos por hectárea de cultivo. En vistas de los resultados se considera que la viabilidad del proyecto se dará siempre y cuando existan cambios a nivel provincial que permitan, por ejemplo hacer más eficiente la distribución de agua para poder hacer uso de la misma en mayor superficie de cultivos.