Herein we summarize important discoveries made over many years about Leydig cell function and regulation. Fetal Leydig cells produce the high levels of androgen (testosterone or androstenedione, ...depending upon the species) required for differentiation of male genitalia and brain masculinization. Androgen production declines with loss of these cells, reaching a nadir at postpartum. Testosterone then gradually increases to high levels with adult Leydig cell development from stem cells. In the adult, luteinizing hormone (LH) binding to Leydig cell LH receptors stimulates cAMP production, increasing the rate of cholesterol translocation into the mitochondria. Cholesterol is metabolized to pregnenolone by the CYP11A1 enzyme at the inner mitochondrial membrane, and pregnenolone to testosterone by mitochondria and smooth endoplasmic reticulum enzymes. Cholesterol translocation to the inner mitochondrial membrane is mediated by a protein complex formed at mitochondrial contact sites that consists of the cholesterol binding translocator protein, voltage dependent anion channel, and other mitochondrial and cytosolic proteins. Steroidogenic acute regulatory protein acts at this complex to enhance cholesterol movement across the membranes and thus increase testosterone formation. The 14-3-3γ and ϵ adaptor proteins serve as negative regulators of steroidogenesis, controlling the maximal amount of steroid formed. Decline in testosterone production occurs in many aging and young men, resulting inmetabolic and quality-of-life changes. Testosterone replacement therapy is widely used to elevate serum testosterone levels in hypogonadal men. With knowledge gained of the mechanisms involved in testosterone formation, it is also conceivable to use pharmacological means to increase serum testosterone by Leydig cell stimulation. Summary Sentence A summary of important discoveriesmade over the course of many years about Leydig cell function and regulation, and discussion of important issues that remain to be understood.
This essay contributes to second generation fiscal federalism (SGFF), which traces the implications of incentives created by political and fiscal institutions. The approach explores how various forms ...of fiscal federalism work in the presence of political officials who, rather than being benevolent social planners, face various forms of political incentives. The paper focuses on three sets of positive models: First, it explores self-enforcing federalism; that is, how federal systems are held together given various tendencies for federal systems to become centralized or fall apart. Second, it considers how specific political institutions, such as democracy, interact with decentralization. Finally, it studies various political impediments to economic growth, again highlighting the interaction with decentralization.
Manganese is a non‐toxic, inexpensive and earth abundant metal, so is a perfect candidate for catalysis whether as a replacement for precious metals or in the search for novel reactivity. Despite ...this, manganese catalysis has not undergone the same development of other earth‐abundant metals (particularly iron and cobalt). This review details recent synthetic methodologies using manganese catalysts, including C–H activation, late stage fluorination, hydrosilylation and cross‐coupling.
The manganese‐catalysed functionalisation of organic molecules is reviewed with regard to synthetic applications. Manganese‐catalysed C–H oxidations, halogenations, cross‐couplings and C–H activations are discussed with mechanisms details.
All societies must deal with the possibility of violence, and they do so in different ways. This book integrates the problem of violence into a larger social science and historical framework, showing ...how economic and political behavior are closely linked. Most societies, which we call natural states, limit violence by political manipulation of the economy to create privileged interests. These privileges limit the use of violence by powerful individuals, but doing so hinders both economic and political development. In contrast, modern societies create open access to economic and political organizations, fostering political and economic competition. The book provides a framework for understanding the two types of social orders, why open access societies are both politically and economically more developed, and how some 25 countries have made the transition between the two types.
Great progress has been made over the past half-century, but TB remains a formidable global health problem, particularly in low- and middle-income countries. Understanding the mechanisms of ...pathogenesis and necessary and sufficient conditions for protection are critical. The need for inexpensive and sensitive point-of-care diagnostic tests for earlier detection of infection and disease, shorter and less-toxic drug regimens for drug-sensitive and -resistant TB, and a more effective vaccine than BCG is immense. New and better tools, greater support for international research, collaborations, and training will be required to dramatically reduce the burden of this devastating disease which still kills 1.6 million people annually.
The measure of the quality of a systems biology model is how well it can reproduce and predict the behaviors of a biological system such as a microbial cell. In recent years, these models have been ...built up in layers, and each layer has been growing in sophistication and accuracy in parallel with a global data set to challenge and validate the models in predicting the content or activities of genes (genomics), proteins (proteomics), metabolites (metabolomics), and ultimately cell phenotypes (phenomics). This review focuses on the latter, the phenotypes of microbial cells. The development of Phenotype MicroArrays, which attempt to give a global view of cellular phenotypes, is described. In addition to their use in fleshing out and validating systems biology models, there are many other uses of this global phenotyping technology in basic and applied microbiology research, which are also described.
Abstract Background Tract-tracing studies in cats and rats demonstrated that the auricular branch of the vagus nerve (ABVN) projects to the nucleus tractus solitarii (NTS); it has remained unclear as ...to whether or not the ABVN projects to the NTS in humans. Objective To ascertain whether non-invasive electrical stimulation of the cymba conchae, a region of the external ear exclusively innervated by the ABVN, activates the NTS and the “classical” central vagal projections in humans. Methods Twelve healthy adults underwent two fMRI scans in the same session. Electrical stimulation (continuous 0.25ms pulses, 25Hz) was applied to the earlobe (control, scan #1) and left cymba conchae (scan #2). Statistical analyses were performed with FSL. Two region-of-interest analyses were performed to test the effects of cymba conchae stimulation (compared to baseline and control, earlobe, stimulation) on the central vagal projections (corrected; brainstem P < 0.01, forebrain P < 0.05), followed by a whole-brain analysis (corrected, P < 0.05). Results Cymba conchae stimulation, compared to earlobe (control) stimulation, produced significant activation of the “classical” central vagal projections, e.g., widespread activity in the ipsilateral NTS, bilateral spinal trigeminal nucleus, dorsal raphe, locus coeruleus, and contralateral parabrachial area, amygdala, and nucleus accumbens. Bilateral activation of the paracentral lobule was also observed. Deactivations were observed bilaterally in the hippocampus and hypothalamus. Conclusion These findings provide evidence in humans that the central projections of the ABVN are consistent with the “classical” central vagal projections and can be accessed non-invasively via the external ear.
In this letter, we present indoor multipath dispersion characteristics for visible light communications (VLC). Since the VLC uses a wide spectrum between 380 nm and 780 nm, the conventional ...narrowband model for infrared may not apply. We generalize the Barry's model by including wavelength-dependent white LED characteristics and spectral reflectance of indoor reflectors. We perform a computer simulation to compare the power delay profile of the VLC with that of infrared communications. From our studies, we show that the VLC provides a larger transmission bandwidth than infrared communications.
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