Neurosteroid Dehydroepiandrosterone Interacts with Nerve Growth Factor (NGF) Receptors, Preventing Neuronal Apoptosis

The neurosteroid dehydroepiandrosterone (DHEA), produced by neurons and glia, affects multiple processes in the brain, including neuronal survival and neurogenesis during development and in aging. We provide evidence that DHEA interacts with pro-survival TrkA and pro-death p75NTR membrane receptors of neurotrophin nerve growth factor (NGF), acting as a neurotrophic factor: (1) the anti-apoptotic effects of DHEA were reversed by siRNA against TrkA or by a specific TrkA inhibitor; (2) [3H]-DHEA binding assays showed that it bound to membranes isolated from HEK293 cells transfected with the cDNAs of TrkA and p75NTR receptors (KD: 7.4±1.75 nM and 5.6±0.55 nM, respectively); (3) immobilized DHEA pulled down recombinant and naturally expressed TrkA and p75NTR receptors; (4) DHEA induced TrkA phosphorylation and NGF receptor-mediated signaling; Shc, Akt, and ERK1/2 kinases down-stream to TrkA receptors and TRAF6, RIP2, and RhoGDI interactors of p75NTR receptors; and (5) DHEA rescued from apoptosis TrkA receptor positive sensory neurons of dorsal root ganglia in NGF null embryos and compensated NGF in rescuing from apoptosis NGF receptor positive sympathetic neurons of embryonic superior cervical ganglia. Phylogenetic findings on the evolution of neurotrophins, their receptors, and CYP17, the enzyme responsible for DHEA biosynthesis, combined with our data support the hypothesis that DHEA served as a phylogenetically ancient neurotrophic factor

A luteinizing hormone receptor intronic variant is significantly associated with decreased risk of Alzheimer's disease in males carrying an apolipoprotein E ε4 allele

Genetic and biochemical studies support the apolipoprotein E (APOE) ε4 allele as a major risk factor for late-onset Alzheimer's disease (AD), though ~50% of AD patients do not carry the allele. APOE transports cholesterol for luteinizing hormone (LH)-regulated steroidogenesis, and both LH and neurosteroids have been implicated in the etiology of AD. Since polymorphisms of LH beta-subunit (LHB) and its receptor (LHCGR) have not been tested for their association with AD, we scored AD and age-matched control samples for APOE genotype and 14 polymorphisms of LHB and LHCGR. Thirteen gene-gene interactions between the loci of LHB, LHCGR, and APOE were associated with AD. The most strongly supported of these interactions was between an LHCGR intronic polymorphism (rs4073366; lhcgr2) and APOE in males, which was detected using all three interaction analyses: linkage disequilibrium, multi-dimensionality reduction, and logistic regression. While the APOE ε4 allele carried significant risk of AD in males [p = 0.007, odds ratio (OR) = 3.08(95%confidence interval: 1.37, 6.91)], ε4-positive males carrying 1 or 2 C-alleles at lhcgr2 exhibited significantly decreased risk of AD [OR = 0.06(0.01, 0.38); p = 0.003]. This suggests that the lhcgr2 C-allele or a closely linked locus greatly reduces the risk of AD in males carrying an APOE ε4 allele. The reversal of risk embodied in this interaction powerfully supports the importance of considering the role gene-gene interactions play in the etiology of complex biological diseases and demonstrates the importance of using multiple analytic methods to detect well-supported gene-gene interactions

Promoting behind-the-meter battery storage: options for more effective government support and regulation

We examine the use of subsidies to promote behind-the-meter battery installation, the limitations and perverse outcomes created by these subsidies, particularly as a result of suboptimal spatial concentration. We suggest the use of consumer subsidies to promote behind-the-meter batteries is unlikely to lead to optimal outcomes in aiding the integration of distributed generation sources (solar PV). It is also possible batteries could reduce the reliability of the grid. The problems identified relate to the undirected installations of batteries within the grid due to the reliance on consumers to take part in a subsidy scheme. Recommendations for policy makers and regulators are to encourage optimal installations through directing subsidies, and in lieu of that, to orchestrate and/or coordinate individual installed battery capacity

Privatisierung und Bankperformance

Anknüpfend an die kontrovers geführte Diskussion über die Performance der Kreditwirtschaft in Deutschland geht dieser Beitrag auf Basis einer empirischen Analyse der Frage nach den Haupteinflussfaktoren der Rentabilität von Banken und Bankensystemen in Europa nach: Lassen sich Performanceunterschiede im Wesentlichen auf institutionelle oder strukturelle länderspezifische Systemmerkmale zurückführen, die insbesondere an divergierenden Eigentumsstrukturen bzw. Konsolidierungs- und Konzentrationsprozessen ansetzen? Oder prägen vielmehr bankindividuelle geschäftspolitische Merkmale die Rentabilität? Mittels rekursiver Partitionierung wird das Untersuchungssample bestehend aus 3000 europäischen Banken im Hinblick auf die ausgewählte Performance-Zielgröße “Eigenkapitalrendite“ schrittweise anhand des jeweils trennschärfsten Inputfaktors in möglichst homogene Subsegmente unterteilt. Das vom Algorithmus als trennschärfstes Kriterium ausgewiesene institutionelle Merkmal “Eigentum an Sparkassen“ separiert Banken aus Ländern mit Privatisierungserfolgen von Banken aus Ländern mit einem durch öffentliches Eigentum dominierten Sparkassensektor. Demnach weisen Banken aus Ländern mit ersten Privatisierungserfolgen signifikant höhere Renditen auf. Abstract Following the controversial discussion on banking industry's performance, this study analyses the main driving forces of banks and banking systems profitability: Are performance differences primarily due to country specific institutional attributes (here related to ownership structures in the European banking industries) or structural characteristics of the banking system (aligned to consolidation and concentration processes in banking markets), or can they mainly be attributed to bank specific, strategic features expressed by financial ratios? Using recursive partitioning, the sample of around 3,000 European banks is successively divided by the most discriminatory predictor with regard to the dependent variable return on equity in as homogenous sub-segments as possible. The algorithm chooses the institutional characteristic ownership of savings banks as the most selective input factor. Banks located in countries with at least first privatization success indicate a significant higher profitability than banks resident in countries with public dominated savings banks sectors

Air quality and climate impacts due to CNG conversion of motor vehicles in Dhaka, Bangladesh.

Dhaka had recently experienced rapid conversion of its motor vehicle fleet to run on compressed natural gas (CNG). This paper quantifies ex-post the air quality and climate benefits of the CNG conversion policy, including monetary valuations, through an impact pathway approach. Around 2045 (1665) avoided premature deaths in greater Dhaka (City Corporation) can be attributed to air quality improvements from the CNG conversion policy in 2010, resulting in a saving of around USD 400 million. Majority of these health benefits resulted from the conversion of high-emitting diesel vehicles. CNG conversion was clearly detrimental from climate change perspective using the changes in CO2 and CH4 only (CH4 emissions increased); however, after considering other global pollutants (especially black carbon), the climate impact was ambiguous. Uncertainty assessment using input distributions and Monte Carlo simulation along with a sensitivity analysis show that large uncertainties remain for climate impacts. For our most likely estimate, there were some climate costs, valued at USD 17.7 million, which is an order of magnitude smaller than the air quality benefits. This indicates that such policies can and should be undertaken on the grounds of improving local air pollution alone and that precautions should be taken to reduce the potentially unintended increases in GHG emissions or other unintended effects