Extra-matrix Mg\u3csup\u3e2+\u3c/sup\u3e Limits Ca\u3csup\u3e2+\u3c/sup\u3e Uptake and Modulates Ca\u3csup\u3e2+\u3c/sup\u3e Uptake-independent Respiration and Redox State in Cardiac Isolated Mitochondria

Cardiac mitochondrial matrix (m) free Ca2+ ([Ca2+]m) increases primarily by Ca2+ uptake through the Ca2+ uniporter (CU). Ca2+ uptake via the CU is attenuated by extra-matrix (e) Mg2+ ([Mg2+]e). How [Ca2+]m is dynamically modulated by interacting physiological levels of [Ca2+]e and [Mg2+]e and how this interaction alters bioenergetics are not well understood. We postulated that as [Mg2+]e modulates Ca2+ uptake via the CU, it also alters bioenergetics in a matrix Ca2+–induced and matrix Ca2+–independent manner. To test this, we measured changes in [Ca2+]e, [Ca2+]m, [Mg2+]e and [Mg2+]m spectrofluorometrically in guinea pig cardiac mitochondria in response to added CaCl2 (0–0.6 mM; 1 mM EGTA buffer) with/without added MgCl2 (0–2 mM). In parallel, we assessed effects of added CaCl2 and MgCl2 on NADH, membrane potential (ΔΨm), and respiration. We found that \u3e0.125 mM MgCl2 significantly attenuated CU-mediated Ca2+ uptake and [Ca2+]m. Incremental [Mg2+]e did not reduce initial Ca2+uptake but attenuated the subsequent slower Ca2+ uptake, so that [Ca2+]m remained unaltered over time. Adding CaCl2 without MgCl2 to attain a [Ca2+]m from 46 to 221 nM enhanced state 3 NADH oxidation and increased respiration by 15 %; up to 868 nM [Ca2+]m did not additionally enhance NADH oxidation or respiration. Adding MgCl2 did not increase [Mg2+]m but it altered bioenergetics by its direct effect to decrease Ca2+ uptake. However, at a given [Ca2+]m, state 3 respiration was incrementally attenuated, and state 4 respiration enhanced, by higher [Mg2+]e. Thus, [Mg2+]e without a change in [Mg2+]m can modulate bioenergetics independently of CU-mediated Ca2+ transport

The role of parental investments for cognitive and noncognitive skill formation : evidence for the first 11 years of life

This paper examines the impact of parental investments on the development of cognitive, mental and emotional skills during childhood using data from a longitudinal study, the Mannheim Study of Children at Risk, starting at birth. Our work offers three important innovations. First, we use reliable measures of the child’s cognitive, mental and emotional skills as well as accurate measures of parental investment. Second, we estimate latent factor models to account for unobserved characteristics of children. Third, we examine the skill development for girls and boys separately, as well as for children who were born with either organic or psychosocial risk. We find a decreasing impact of parental investments on cognitive and mental skills, while emotional skills seem to be unaffected by parental investment throughout childhood. Thus, initial inequality persists during childhood. Since families are the main sources of education during the first years of life, our results have important implications for the quality of the parent-child relationship

Entwicklung und Ungleichheit von Fähigkeiten : Anmerkungen aus ökonomischer Sicht

Nirgends sonst im ökonomischen Handeln fallen Kosten und Nutzen im Zeitablauf und aufgeteilt nach Investoren und Nutznießern so eklatant auseinander wie bei Bildungsinvestitionen. In dem vorliegenden Beitrag wird argumentiert, dass in der sozialen Realität die Bildungsungleichheit im Vorschulalter eine der wichtigsten Ursachen für die Ungleichheit von Fähigkeiten und Kompetenzen auch im Schulalter und im Erwerbsleben ist. Für benachteiligte Kinder scheint somit die Bildungsungleichheit vor dem Schulalter bei uns, ebenso wie in anderen Ländern mit hohen Bildungsausgaben und hoher Wirtschaftskraft ihren schicksalhaften Charakter noch keineswegs verloren zu haben. Um dies zu ändern, bleibt es eine vordringliche Aufgabe auch der Bildungspolitik, den Zugang zu einer angemessenen emotionalen Fürsorge von Anfang an weiter zu verbessern. Darüber hinaus ist es notwendig, den betroffenen Kindern bis ins Jugendalter altersgemäß und individuell zur Seite zu stehen

The development of study-specific self-efficacy during grammar school.(Zur Entwicklung der studienspezifischen Selbstwirksamkeit in der Oberstufe)

Article is in German. Even if more and more German adolescents acquire a university entrance qualification, not all of them finally enrol at a university. In particular, the transition from school to university strongly depends on parent’s education. Even with the same marks in school, adolescents from non-academic households are less likely to enrol in universities than adolescents from academic housholds. One important reason is their lower belief to master a university study. This study analyses a specific intervention in grammar school to improve study-specific self- efficacy, the belief in one’s capabilities to master a university study, using a longitudinal design. We apply a difference-in-difference framework and show that programme participation significantly improves the study-specific self-efficacy for puplis from non- academic families but not for those from academic families. Hence, such a programme could reduce social disparities between both groups

Slow Ca2+ Efflux by Ca2+/H+ Exchange in Cardiac Mitochondria Is Modulated by Ca2+ Re-uptake via MCU, Extra-Mitochondrial pH, and H+ Pumping by FOF1-ATPase

Mitochondrial (m) Ca2+ influx is largely dependent on membrane potential (ΔΨm), whereas mCa2+ efflux occurs primarily via Ca2+ ion exchangers. We probed the kinetics of Ca2+/H+ exchange (CHEm) in guinea pig cardiac muscle mitochondria. We tested if net mCa2+ flux is altered during a matrix inward H+ leak that is dependent on matrix H+ pumping by ATPm hydrolysis at complex V (FOF1-ATPase). We measured [Ca2+]m, extra-mitochondrial (e) [Ca2+]e, ΔΨm, pHm, pHe, NADH, respiration, ADP/ATP ratios, and total [ATP]m in the presence or absence of protonophore dinitrophenol (DNP), mitochondrial uniporter (MCU) blocker Ru360, and complex V blocker oligomycin (OMN). We proposed that net slow influx/efflux of Ca2+ after adding DNP and CaCl2 is dependent on whether the ΔpHm gradient is/is not maintained by reciprocal outward H+ pumping by complex V. We found that adding CaCl2 enhanced DNP-induced increases in respiration and decreases in ΔΨm while [ATP]m decreased, ΔpHm gradient was maintained, and [Ca2+]m continued to increase slowly, indicating net mCa2+ influx via MCU. In contrast, with complex V blocked by OMN, adding DNP and CaCl2 caused larger declines in ΔΨm as well as a slow fall in pHm to near pHe while [Ca2+]m continued to decrease slowly, indicating net mCa2+ efflux in exchange for H+ influx (CHEm) until the ΔpHm gradient was abolished. The kinetics of slow mCa2+ efflux with slow H+ influx via CHEm was also observed at pHe 6.9 vs. 7.6 by the slow fall in pHm until ΔpHm was abolished; if Ca2+ reuptake via the MCU was also blocked, mCa2+ efflux via CHEm became more evident. Of the two components of the proton electrochemical gradient, our results indicate that CHEm activity is driven largely by the ΔpHm chemical gradient with H+ leak, while mCa2+ entry via MCU depends largely on the charge gradient ΔΨm. A fall in ΔΨm with excess mCa2+ loading can occur during cardiac cell stress. Cardiac cell injury due to mCa2+ overload may be reduced by temporarily inhibiting FOF1-ATPase from pumping H+ due to ΔΨm depolarization. This action would prevent additional slow mCa2+ loading via MCU and permit activation of CHEm to mediate efflux of mCa2+.HIGHLIGHTS-We examined how slow mitochondrial (m) Ca2+ efflux via Ca2+/H+ exchange (CHEm) is triggered by matrix acidity after a rapid increase in [Ca2+]m by adding CaCl2 in the presence of dinitrophenol (DNP) to permit H+ influx, and oligomycin (OMN) to block H+ pumping via FOF1-ATP synthase/ase (complex V).-Declines in ΔΨm and pHm after DNP and added CaCl2 were larger when complex V was blocked.-[Ca2+]m slowly increased despite a fall in ΔΨm but maintained pHm when H+ pumping by complex V was permitted.-[Ca2+]m slowly decreased and external [Ca2+]e increased with declines in both ΔΨm and pHm when complex V was blocked.-ATPm hydrolysis supports a falling pHm and redox state and promotes a slow increase in [Ca2+]m.-After rapid Ca2+ influx due to a bolus of CaCl2, slow mCa2+ efflux by CHEm occurs directly if pHe is low

Adolescent Binge Drinking Leads to Changes in Alcohol Drinking, Anxiety, and Amygdalar Corticotropin Releasing Factor Cells in Adulthood in Male Rats

Heavy episodic drinking early in adolescence is associated with increased risk of addiction and other stress-related disorders later in life. This suggests that adolescent alcohol abuse is an early marker of innate vulnerability and/or binge exposure impacts the developing brain to increase vulnerability to these disorders in adulthood. Animal models are ideal for clarifying the relationship between adolescent and adult alcohol abuse, but we show that methods of involuntary alcohol exposure are not effective. We describe an operant model that uses multiple bouts of intermittent access to sweetened alcohol to elicit voluntary binge alcohol drinking early in adolescence (∼postnatal days 28–42) in genetically heterogeneous male Wistar rats. We next examined the effects of adolescent binge drinking on alcohol drinking and anxiety-like behavior in dependent and non-dependent adult rats, and counted corticotropin-releasing factor (CRF) cell in the lateral portion of the central amygdala (CeA), a region that contributes to regulation of anxiety- and alcohol-related behaviors. Adolescent binge drinking did not alter alcohol drinking under baseline drinking conditions in adulthood. However, alcohol-dependent and non-dependent adult rats with a history of adolescent alcohol binge drinking did exhibit increased alcohol drinking when access to alcohol was intermittent. Adult rats that binged alcohol during adolescence exhibited increased exploration on the open arms of the elevated plus maze (possibly indicating either decreased anxiety or increased impulsivity), an effect that was reversed by a history of alcohol dependence during adulthood. Finally, CRF cell counts were reduced in the lateral CeA of rats with adolescent alcohol binge history, suggesting semi-permanent changes in the limbic stress peptide system with this treatment. These data suggest that voluntary binge drinking during early adolescence produces long-lasting neural and behavioral effects with implications for anxiety and alcohol use disorders

Genetic association of human Corticotropin-Releasing Hormone Receptor 1 (CRHR1) with Internet gaming addiction in Korean male adolescents

Background The number of people with Internet gaming addiction (IGA) is increasing around the world. IGA is known to be associated with personal characteristics, psychosocial factors, and physiological factors. However, few studies have examined the genetic factors related to IGA. This study aimed to investigate the association between IGA and stress-related genetic variants. Methods This cross-sectional study was conducted with 230 male high school students in a South Korean city. We selected five stress-related candidate genes: DAT1, DRD4, NET8, CHRNA4, and CRHR1. The DAT1 and DRD4 genes were genotyped by polymerase chain reaction, and the NET8, CHRNA4, and CRHR1 genes were genotyped by pyrosequencing analysis. We performed a Chi-square test to examine the relationship of these five candidate genes to IGA. Results Having the AA genotype and the A allele of the CRHR1 gene (rs28364027) was associated with higher odds of belonging to the IGA participant group (p = .016 and p = .021, respectively) than to the non-IGA group. By contrast, the DAT1, DRD4, NET8, and CHRNA4 gene polymorphisms showed no significant difference between the IGA group and control group. Conclusions These results indicate that polymorphism of the CRHR1 gene may play an important role in IGA susceptibility in the Korean adolescent male population. These findings provide a justification and foundation for further investigation of genetic factors related to IGA