bluuebunny/crossref_metadata_2025 huggingface dataset:
L-type calcium channels in the auditory system
Authors: Nothwang H.G. , Engel J. , Knipper M. , Friauf E.
Published: April 2017

The voltage-activated L-type calcium chan­nels Cav1.2 and Cav1.3 mediate Ca2+ influx into neurons at the soma or at dendrites, whereas they are not observed at the pre­synapse. Surprisingly, in the inner ear, Cav1.3 is indispensable for signal transmission from the presynaptic cochlear inner hair cells to the postsynaptic auditory nerve fibers. Due to Cav1.3 channel clustering at ribbons, i.e., specific presynaptic structures of the hair cells, they promote Ca2+ influx, which triggers calcium-dependent fusion of synaptic vesi­cles with the plasma membrane. Mutations in Cacna1d, a gene that encodes Cav1.3, re­sult in deafness because release of the neu­rotransmitter glutamate at the synapses is abolished. Moreover, studies of the auditory pathway have revealed that Cav1.3 plays an important part in the central auditory system as well. Absence of the channel results in se­vere changes in auditory pathway cytoarchi­tecture and in abnormal electrophysiological performance of auditory neurons. Further­more, developmental refinement of tonotop­ic inhibitory projections in sound localization circuits is disrupted. These aberrations are as­sociated with abnormal sound processing in the auditory pathway. This goes to show that the Cav1.3 channel is essential for in­ner ear functioning as well as auditory path­way development and performance. Cac­na1d therefore represents a prototypal deaf­ness-associated gene, in which mutations re­sult in both peripheral and central audito­ry deficiencies. This, in turn, has implications for auditory rehabilitation using cochlear im­plants that address only peripheral dysfunc­tions. Exploratory research into the closely re­lated Cav1.2 isoform points to an important role of this channel in acoustic trauma. Cav1.2 is mainly expressed in the auditory nerve, but apparently not essential for normal audito­ry function. Loss of function of the channel, however, does influence the effects of trau­matic noise exposure. Loss of this channel in­duced by noise trauma results in reduced au­ditory threshold increase-as compared with the control group. This phenomenon points to the fact that Cav1.2-mediated Ca2+ influx is involved in noise trauma-induced damage. Deeper insight into this function might result in new therapeutic approaches.
Giant synapses in the central auditory system
Authors: Felmy F. , Künzel T.
Published: April 2017

Giant synapses occur in four nuclei of the au­ditory brainstem. They are characterized by numerous active zones concentrated on the soma of the postsynaptic neuron and by rap­id postsynaptic currents. At these sites, in the ventral cochlear nucleus, the medial and lat­eral nucleus of the trapezoid body and the ventral nucleus of the lateral lemniscus, faith­ful preservation of the temporal relation of action potentials to the sound-intercellu­lar precision-is of the utmost importance for neuronal function. The precision of action potential transfer is supported by the large­ly unimodal integration and homogeneity of the single postsynaptic compartment. Due to the much more rapid time constant of the synaptic currents compared with the mem­brane time constant, membrane capacitance dominates postsynaptic integration, enhanc­ing precision of action potential generation. Taken together, the properties of these gi­ant synapses reduce the temporal jitter of the transmission of information in these audito­ry circuits.
Hereditary hearing loss in humans: the importance of genetic approaches for clinical medicine and basic science
Authors: Kubisch C.
Published: April 2017

Hereditary hearing loss is one of the most common monogenic diseases in humans and, depending on the severity of symptoms and age of onset, dysfunction of one of the main sensory systems can cause significant problems for the affected individual and his/her social environment. The diagnostic work­up of hearing impairment is complicated by a pronounced phenotypic variability and ex­tensive genetic heterogeneity. Nevertheless, many forms of monogenic hearing impair­ment have been elucidated in recent years by genetic approaches. In addition to improved counselling and medical management of pa­tients and families, these research findings have contributed significantly to the identi­fication of functionally relevant molecules of the inner ear and have thus helped us to bet­ter understand the molecular physiology of hearing and the pathophysiology of hearing impairment.
Optogenetic analyses of neuronal network function and synaptic transmission in Caenorhabditis elegans
Authors: Gottschalk A.
Published: April 2017

The transparent nematode Caenorhabditis elegans, with its anatomically well-defined nervous system comprising 302 neurons that regulate quantifiable behaviors, is an ideal model system for the development and ap­plication of optogenetic methods. Optoge­netically modified neurons can be acutely ex­cited or inhibited by light and the effects on a distinct behavior observed. Special light­ing systems allow the manipulation of several nerve cells that act as “nodes” of small neural circuits, with different colors of light, so as to control different optogenetic tools indepen­dently and simultaneously. In addition, ge­netically encoded optical sensors for neuro­nal activity make it possible to draw conclu­sions even when the optogenetic interven­tion causes no obvious behavioral change. The stimulation of quantifiable behaviors permits the analysis of the function of genes necessary in the corresponding neuron for the encoding or amplification of the primary signal. Finally, following optogenetic stimu­lation, the function of chemical synapses and their proteins can also be analyzed by elec­trophysiology or electron microscopy.
Sound localization with microsecond precision in mammals: what is it we do not understand?
Authors: Leibold C. , Grothe B.
Published: April 2017

The Jeffress model for the computation and encoding of interaural time differences (ITDs) is one of the most widely known theoretical models of a neuronal microcircuit. In archosaurs (birds and reptiles), several features envisioned by Jeffress in 1948 seem to be implemented, like a topographic map of space and axonal delay lines. In mammals, however, most of the model predictions could not be verified or have been disproved. This led to an ongoing competition of alternative models and hypothesis, which is not settled by far. Particularly the role of the feed-forward inhibitory inputs to the binaural coincidence detector neurons in the medial superior olive (MSO) remains a matter of debate. In this paper, we review the present state of the field and indicate what in our opinion are the most important gaps in understanding of the mammalian circuitry. Approaching these issues requires integrating all levels of neuroscience from cellular biophysics to behavior and even evolution.
Evoking plasticity through sensory stimulation: Implications for learning and rehabilitation
Authors: Dinse Hubert R. , Tegenthoff Martin
Published: April 2017

The gold standard for improving sensory, motor and or cognitive abilities is longterm training and practicing. Recent work, however, suggests that intensive training may not be necessary. Improved performance can be effectively acquired by a complementary approach in which the learning occurs in response to mere exposure to repetitive sensory stimulation. Such training-independent sensory learning (TISL), which has been intensively studied in the somatosensory system, induces in humans lasting changes in perception and neural processing, without any explicit task training. It has been suggested that the effectiveness of this form of learning stems from the fact that the stimulation protocols used are optimized to alter synaptic transmission and efficacy. TISL provides novel ways to investigate in humans the relation between learning processes and underlying cellular and molecular mechanisms, and to explore alternative strategies for intervention and therapy.
TASK, TREK & Co.: a mutable potassium channel family for diverse tasks in the brain
Authors: Ehling P. , Bittner Stefan , Meuth Sven G. , Budde Thomas
Published: April 2017

Discovered during the 1990s and in the beginning regarded as passive membrane pores, the family of two-pore domain potassium (K2P)-channels initially received only little attention. Today the view on this channel family comprising 15 ubiquitously expressed members in mammals has greatly changed. K2P-channels carry potassium outward current that counterbalances membrane depolarization and stabilizes the resting membrane potential. Thereby they are important regulators for the excitability and the firing behaviour especially in neurons. The long list of modulating mechanisms underlines the channels’ relevance. K2P-channels in the thalamus contribute to the regulation of the sleep-wake cycle. They also mediate the effect of volatile anaesthetics by supporting the thalamic activity mode that is also typical for sleep. This review summarizes our knowledge about K2P-channel physiology in the brain, provides an idea of the role of these channels in neurological diseases and lists open questions as well as technical challenges in K2P-channel research.
Neuron–glia synapses in the brain: properties, diversity and functions of NG2 glia
Authors: Steinhäuser Christian , Dietrich Dirk
Published: April 2017

Although NG2 glial cells represent a frequent glial cell type in the brain, characterized by expression of the NG2 proteoglycan, the functional impact of these cells is still enigmatic. A large proportion of NG2 glia are proliferatively active throughout life. These cells express a plethora of ion channels and transmitter receptors, which enable them to detect neuronal activity. Intriguingly, NG2 glial cells receive synaptic input from glutamatergic and GABAergic neurons. Since these postsynaptic glial currents are very small, their spatial and temporal integration might play an important role. In white matter, most NG2 glial cells differentiate into oligodendrocytes and this process might be influenced through the activity of the aforementioned neuron-glia synapses. Increasing evidence suggests that the properties of NG2 glia vary across brain regions; however, the impact of this variability is not understood yet.
Oligodendroglial heterogeneity in time and space (NG2 glia in the CNS)
Authors: Dimou Leda , Wegner Michael
Published: April 2017

NG2 glia represent a neural cell population that expresses the proteoglycan NG2 and is distinct from other cell types of the central nervous system. While they generate oligodendrocytes and a subset of astrocytes during development, their progeny in the adult brain solely consists of oligodendrocytes and further NG2 glia. In the last years, it has become clear that NG2 glia represent a heterogeneous population of cells with different properties and potential. In this review we will first discuss the similarities and differences between NG2 glia of the developing and adult CNS, before we will describe the regulatory mechanisms in these cells to finally concentrate on the heterogeneity of NG2 glia under physiological and pathological conditions.
GABAA receptor subtypes: structural variety raises hope for new therapy concepts
Authors: Ernst Margot , Sieghart Werner
Published: April 2017

GABAA receptors are ligand-gated chloride ion channels composed of five subunits that can be opened by GABA, and modulated by multiple drugs, some of utmost clinical importance. GABAA receptors occur in the nervous system as well as in peripheral tissues where their function is largely unknown. The existence of multiple GABAA receptor subtypes with distinct subunit composition leads to multiple homologous binding sites with different degrees of similarity. Crystal structures of proteins homologous to GABAA receptors and of a GABAA receptor subtype, combined with homology modeling studies, have provided insights into the possible location of drug interaction sites. Some of these sites have been confirmed by experimental studies. For many receptor ligands, however, binding sites are not yet known. Here we will briefly review the function of distinct types of GABAA receptors and provide structural insights and experimental evidence on binding sites for ligands that could be of considerable clinical interest.
Neurobiology of food choices-between energy homeostasis, reward system, and neuroeconomics
Authors: Enax Laura , Weber Bernd
Published: April 2017

The rate of patients with obesity has been rapidly increasing, and this imposes a heavy economic burden on health-care systems. Food decisions, under the influence of different internal and external factors, lie at the core of this increasing health problem. Due to the biological necessity to consume sufficient amounts of food and to correctly regulate energy expenditure, there are different systems that control food intake. This article first focuses on neurobiological and hormonal foundations and explains various metabolic short- and long-term signals, such as leptin, insulin, and ghrelin. We then also present genetic factors, which directly or indirectly (via other genes or environmental influences) may affect nutritional status. Since the consumption of high-caloric foods is accompanied by dopamine release and the activation of the brain’s reward system, we will then present the interdependence of metabolic and reward systems. Last, we will present a neuroeconomic perspective that complements research on metabolic and hedonic feeding regulation.
Neuronal pathways of embarrassment
Authors: Krach Sören , Müller-Pinzler Laura , Rademacher Lena , Stolz David Sören , Paulus Frieder Michel
Published: April 2017

Embarrassment is a genuine human emotion that we experience while being publicly exposed in unfavorable situations. The embarrassment we feel informs us how we perform according to prevalent norms and moral values and helps to regulate the impression we make on others. One cornerstone of embarrassment is the capacity to take another’s perspective and reflect on the thoughts, feelings, and intentions of others. On the neural systems level, these processes of perspective taking are linked to neural activation in the medial prefrontal cortex and precuneus. In addition, the mishap and the expected negative evaluation induce affective arousal and activity in the anterior insula and anterior cingulate cortex. Both networks contribute to the experience of embarrassment and it is their orchestrated activity in the (para-) limbic system that accounts for this complex emotional phenomenon. From a conceptual point of view embarrassment thus presupposes the presence of others. This witnessing audience however also reacts to the mishaps of others and embarrassment may also be experienced vicariously. Here, processes of perspective taking also play an important role, while bystanders embody threats to another’s social integrity. Such interpersonal emotional phenomena gain particular relevance in the context of psychiatric disorders. Specifically, autism spectrum disorders and social anxiety disorders have core symptoms in the social domain that manifest in social interactions causing disturbances in social behavior and reduced well-being of affected individuals.
The dynamic connectome
Authors: Rumpel Simon , Triesch Jochen
Published: April 2017

When trying to gain intuitions about the computations implemented in neural circuits, we often use comparisons with electronic circuits. However, one fundamental difference to hard-wired electronic circuits is that the structure of neural circuits undergoes constant remodeling. Here, we discuss recent findings highlighting the dynamic nature of neural circuits and the underlying mechanisms. The dynamics of neural circuits follows rules that explain steady state statistics of synaptic properties observed at a single time point. Interestingly, these rules allow the prediction of future network states and extend the insights gained from serial sectioning electron microscopy of brain samples, which inherently provides information from only a single time point. We argue how the connectome’s dynamic nature can be reconciled with stable functioning and long-termmemory storage and how it may even benefit learning.
Linking connectomics and dynamics in the human brain
Authors: Stefanovski Leon , Ghani Amna , McIntosh Anthony Randal , Ritter Petra
Published: April 2017

To understand human cognition, it is essential to study the brain on multiple levels, from microscopic to macroscopic scales. Computational connectomics is a new area of neuroscience where scientists seek to combine empirical observations within a computational theory of the brain. The whole-brain network modeling and simulation platform, The Virtual Brain (TVB), is a remarkable innovation in the field of computational connectomics. By combining the connectivity of individual persons with local biologically realistic populationmodels, TVB allows simulation and prediction of the local activity of neuronal populations and the global activity unfolding along the gray matter, both of which can be linked to empiricalmeasures of electrical, hemodynamic, and structural aspects of the brain. TVB is currently used to study the structural, functional, and computational alterations in the diseased brain with reported successes in stroke and epilepsy. Subjectspecific brain models provided by TVB will result in robust and efficient personalized diagnostics, prognostics, and treatment.
Connectivity and cortical architecture
Authors: Hilgetag Claus C. , Amunts Katrin
Published: April 2017

Brain regions of the cerebral cortex differ in their cytoarchitecture as well as in the intrinsic connectivity within an area and the organization of macroscopic connections between different cortical areas. Nonetheless, it is not clear which rules underlie the relationship of cellular and fiber architecture, and how the characteristic cortical microand macro-connectivity are related to each other. In order to identify principles of cortical connectivity, we systematically investigate various parameters of cortical architecture and their relation to the organization of anatomical connections among cortical areas. Characteristic parameters of cortical architecture include the differential density and distribution of neurons and neuron types across the layers of cortical areas, as well as the regional distribution of different receptors of neurotransmitter systems. The cytoarchitectonic characterization of the brain is a classic approach of neuroanatomy, which recently has been supplemented by new techniques for labeling specific neural components as well as novel optical and analytical approaches. However, the systematic quantitative acquisition of architectonic and morphological parameters of the human brain has only just begun. It is a fundamental challenge to gather and quantify the extremely extensive and detailed histological data (“big data”) by novel image processing techniques. This challenge is taken up in the BigBrain project. Extensive anatomical data already exist for a number of animal models, for example, the brains of nonhuman primates, the cat or the mouse. However, for each single parameter it has to be demonstrated how far these data can be generalized across species. Previous analyses support the notion that the regionally specific cytoarchitecture of the cerebral cortex is closely linked to the existence and the laminar projection patterns of corticocortical connections. These results imply systematic relationships between the patterns of macroscopic connections among cortical areas and the regionally specific intrinsic circuitry within cortical areas. Such relations are the basis of generic models of multiscale cortical connectivity, which reflect essential anatomical and functional properties of mammalian cortical organization.
Democratisation and New Social Movements
Authors: Vodovnik Žiga
Published: April 2017

The article offers a reflection on the processes of democratisation in Slovenia, arguing that the new social movements were a key player in initiating and directing democratic transformation, but later came to be gradually marginalised with the consolidation of the “new” or “bourgeois” civil society. Furthermore, a new chronotope of analysis shows that the role of social movements was a necessary but not a sufficient condition for political, economic and social changes, since during the second phase of the democratisation a political detachment is already underway. The key point of contestation and discordance can be identified in their completely opposite understanding of democracy and the process of democratisation itself.
Harvest time: crop-reaping technologies and the Neolithisation of the Central Mediterranean
Authors: Mazzucco Niccolò , Guilbeau Denis , Petrinelli-Pannocchia Cristiana , Gassin Bernard , Ibáñez Juan José , Gibaja Juan Francisco
Published: April 2017

Neolithic societies were defined by the development of agricultural economies not only because part of their diet was obtained from cultivated plants, but also because crop-husbandry practices strongly affected people's lifestyles in a variety of ways. It is therefore unsurprising that the development and diffusion of agriculture can be studied from diverse perspectives and with different approaches, by analysing, for example, the macro- and micro-botanical remains of fruits and grains for morphometric and taxonomic variation (Colledge & Conolly 2007) and genetic history (Mascher et al.2016). Conversely, agriculture can be indirectly assessed through its impact on the environment and subsequent landscape modifications (Zanchetta et al.2013; Mercuri 2014). Yet another approach explores crop-husbandry practices as reflected in changing technology. New agricultural tasks required the adaptation of existing technologies and the adoption of new tools and practices, including querns, millstones and other grain-grinding equipment, as well as artefacts and structures for grain storage, cooking and processing.
Social science and archaeological enquiry
Authors: Smith Michael E.
Published: April 2017

Is archaeology a social science? Most archaeologists would probably agree that the goal of our discipline is to learn about the people, societies and cultures of the past. Thus there should be little objection to labelling archaeology a ‘social’ field of study. We study both people and society, but what about the ‘science’ part? This label is more controversial. Many archaeologists reject the notion that archaeology is, can be or should be a science. Others assume that archaeology is indeed a science and get on with their work, not worrying much about epistemology or definitions of science. Still others pursue decidedly non-scientific goals yet borrow scientific techniques from other disciplines and call it ‘archaeological science’.
Archaeometric analysis of ceramic production and exchange from the Neolithic to the Gallo-Roman period in Brittany, France
Authors: Gehres Benjamin
Published: April 2017

This short article reports research on the development of ceramic production and exchange between the mainland and islands of Brittany from the Neolithic to the Gallo-Roman period. Archaeometric analysis of ceramics is used to explore the development of communication networks: the movement of people and of products between the islands and the mainland. Did these islands produce their own pottery or were they dependent on mainland production? By determining whether pottery was locally produced or imported, it is possible to identify the changing degrees of connection with, or isolation from, wider networks.
Color-Change Detection Activity in the Primate Superior Colliculus
Authors: Herman James P. , Krauzlis Richard J.
Published: April 2017

The primate superior colliculus (SC) is a midbrain structure that participates in the control of spatial attention. Previous studies examining the role of the SC in attention have mostly used luminance-based visual features (e.g., motion, contrast) as the stimuli and saccadic eye movements as the behavioral response, both of which are known to modulate the activity of SC neurons. To explore the limits of the SC’s involvement in the control of spatial attention, we recorded SC neuronal activity during a task using color, a visual feature dimension not traditionally associated with the SC, and required monkeys to detect threshold-level changes in the saturation of a cued stimulus by releasing a joystick during maintained fixation. Using this color-based spatial attention task, we found substantial cue-related modulation in all categories of visually responsive neurons in the intermediate layers of the SC. Notably, near-threshold changes in color saturation, both increases and decreases, evoked phasic bursts of activity with magnitudes as large as those evoked by stimulus onset. This change-detection activity had two distinctive features: activity for hits was larger than for misses, and the timing of change-detection activity accounted for 67% of joystick release latency, even though it preceded the release by at least 200 ms. We conclude that during attention tasks, SC activity denotes the behavioral relevance of the stimulus regardless of feature dimension and that phasic event-related SC activity is suitable to guide the selection of manual responses as well as saccadic eye movements.
Active Dentate Granule Cells Encode Experience to Promote the Addition of Adult-Born Hippocampal Neurons
Authors: Kirschen Gregory W. , Shen Jia , Tian Mu , Schroeder Bryce , Wang Jia , Man Guoming , Wu Song , Ge Shaoyu
Published: April 2017

The continuous addition of new dentate granule cells (DGCs), which is regulated exquisitely by brain activity, renders the hippocampus plastic. However, how neural circuits encode experiences to affect the addition of adult-born neurons remains unknown. Here, we used endoscopic Ca2+imaging to track the real-time activity of individual DGCs in freely behaving mice. For the first time, we found that active DGCs responded to a novel experience by increasing their Ca2+event frequency preferentially. This elevated activity, which we found to be associated with object exploration, returned to baseline by 1 h in the same environment, but could be dishabituated via introduction to a novel environment. To transition seamlessly between environments, we next established a freely controllable virtual reality system for unrestrained mice. We again observed increased firing of active neurons in a virtual enriched environment. Interestingly, multiple novel virtual experiences increased the number of newborn neurons accumulatively compared with a single experience. Finally, optogenetic silencing of existing DGCs during novel environmental exploration perturbed experience-induced neuronal addition. Our study shows that the adult brain conveys novel, enriched experiences to increase the addition of adult-born hippocampal neurons by increasing the firing of active DGCs.

SIGNIFICANCE STATEMENTAdult brains are constantly reshaping themselves from synapses to circuits as we encounter novel experiences from moment to moment. Importantly, this reshaping includes the addition of newborn hippocampal neurons. However, it remains largely unknown how our circuits encode experience-induced brain activity to govern the addition of new hippocampal neurons. By couplingin vivoCa2+imaging of dentate granule neurons with a novel, unrestrained virtual reality system for rodents, we discovered that a new experience increased firing of active dentate granule neurons rapidly and robustly. Exploration in multiple novel virtual environments, compared with a single environment, promoted dentate activation and enhanced the addition of new hippocampal neurons accumulatively. Finally, silencing this activation optogenetically during novel experiences perturbed experience-induced neuronal addition.
On Singing and Listening in Vaughan Williams's Early Songs
Authors: Owen Ceri
Published: April 2017

Vaughan Williams's celebrated set of Robert Louis Stevenson settings, Songs of Travel, has lately garnered liberal scholarly attention, not least on account of the vicissitudes of its publication history. Following the cycle's premiere in 1904 it was issued in two separate books, each gathering stylistically different songs. Though a credible case for narrative coherence has been advanced in numerous accounts, the cycle's peculiar amalgamation of materials might rather be read as a signal to its projection of multiple voices, which unsettle the longstanding critical tendency to map a single protagonist through its progress. The division marked by the cycle's publication history may productively be understood to reflect a tension inherent in its aesthetic propositions, one constitutive of much of Vaughan Williams's work, which frequently mediates between the individualistic and the collective, the “artistic” and the “accessible,” and, as I suggest, the subjective voice of the individual artist in its invitation to the participation of a singing and listening community.

I propose that Vaughan Williams's early songs frequently frame the idea or demand the engagement of a listener's contribution, as particular modes of singing and listening—and singing-as-listening—are figured and invited within the music's constitution. Composed as he was searching for an individual creative voice that simultaneously sustained a nascent commitment to the social utility and intelligibility of national art music, these songs explore the possibility of achieving a self-consciously collective authorial subjectivity, often reaching toward a musical intersubjectivity wherein boundaries between self and other—and between composer, performer, and listener—are collapsed. In the recognition of such processes lies a means of examining the tendency of Vaughan Williams's work toward projecting a powerfully subjective voice that simultaneously claims identification with no single agency.
Hepatic stellate cells limit hepatocellular carcinoma progression through the orphan receptor endosialin
Authors: Mogler Carolin , König Courtney , Wieland Matthias , Runge Anja , Besemfelder Eva , Komljenovic Dorde , Longerich Thomas , Schirmacher Peter , Augustin Hellmut G
Published: April 2017

Hepatocellular carcinoma (HCC) is among the most common and deadliest cancers worldwide. A major contributor to HCC progression is the cross talk between tumor cells and the surrounding stroma including activated hepatic stellate cells (HSC). Activation of HSC during liver damage leads to upregulation of the orphan receptor endosialin (CD248), which contributes to regulating the balance of liver regeneration and fibrosis. Based on the established role of endosialin in regulating HSC/hepatocyte cross talk, we hypothesized that HSC‐expressed endosialin might similarly affect cell proliferation during hepatocarcinogenesis. Indeed, the histological analysis of human HCC samples revealed an inverse correlation between tumor cell proliferation and stromal endosialin expression. Correspondingly, global genetic inactivation of endosialin resulted in accelerated tumor growth in an inducible mouse HCC model. A candidate‐based screen of tumor lysates and differential protein arrays of cultured HSC identified several established hepatotropic cytokines, including IGF2, RBP4, DKK1, and CCL5 as being negatively regulated by endosialin. Taken together, the experiments identify endosialin‐expressing HSC as a negative regulator of HCC progression.
Longitudinal analyses of the steroid metabolome in obese PCOS girls with weight loss
Authors: Reinehr Thomas , Kulle Alexandra , Rothermel Juliane , Knop-Schmenn Caroline , Lass Nina , Bosse Christina , Holterhus Paul-Martin
Published: April 2017

Objective

The underlying mechanisms of polycystic ovarian syndrome (PCOS) are not fully understood yet. The aim of the study was to get functional insights into the regulation of steroid hormones in PCOS by steroid metabolomics.

Design

This is a longitudinal study of changes of steroid hormones in 40 obese girls aged 13–16 years (50% with PCOS) participating in a 1-year lifestyle intervention. Girls with and without PCOS were matched to age, BMI and change of weight status.

Methods

We measured progesterone, 17-hydroxyprogesterone, 17-hydroxyprogenolon, 11-deoxycorticosterone, 21-deoxycorticosterone, deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol, cortisone, androstenedione, testosterone, dehydroepiandrostendione-sulfate (DHEA-S), estrone and estradiol by LC–MS/MS steroid profiling at baseline and one year later.

Results

At baseline, obese PCOS girls demonstrated significantly higher androstenedione and testosterone concentrations compared to obese girls without PCOS, whereas the other steroid hormones including glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ significantly. Weight loss in obese PCOS girls was associated with a significant decrease of testosterone, androstenedione, DHEA-S, cortisol and corticosterone concentrations. Weight loss in obese non-PCOS girls was associated with a significant decrease of DHEA-S, cortisol and corticosterone concentrations, whereas no significant changes of testosterone and androstenedione concentrations could be observed. Without weight loss, no significant changes of steroid hormones were measured except an increase of estradiol in obese PCOS girls without weight loss.

Conclusions

The key steroid hormones in obese adolescents with PCOS are androstenedione and testosterone, whereas glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ between obese girls with and without PCOS.
Corrupción política, transparencia y movimientos ciudadanos: una aproximación comparativa entre China y Japón
Authors: Ruiz Morillas Nuria
Published: April 2017

La corrupción política es uno de los temas que más preocupan al gobierno de Xi Jinping y a la sociedad china en general. En este artículo se analizan los efectos perjudiciales de la corrupción sobre determinadas variables sociales, económicas e institucionales. En primer lugar, se presenta el estado actual de la corrupción política en China y se exploran algunos movimientos sociales surgidos como respuesta a este fenómeno. Como indicadores de corrupción se han utilizado el índice de percepción de la corrupción (elaborado por Transparencia Internacional) y el índice de control de la corrupción (uno de los seis indicadores de gobernabilidad desarrollados por el Banco Mundial). A continuación, se ha extendido el estudio a Japón por tratarse de un país de contexto político y económico distinto al de China. A partir de los datos obtenidos, se ha realizado una aproximación comparativa del estado de la corrupción entre los dos países y se han estudiado las correlaciones de los indicadores anteriores con el grado de libertad (publicado por la Casa de la Libertad) y con el producto interior bruto per cápita (publicado por el Banco Mundial) en los últimos años. Political corruption is one of the most important issues for the Xi Jinping´s government and Chinese society in general. This article analyses the harmful effects of corruption on certain social, economic and institutional variables. First, it presents the current state of political corruption in China and it explores some social movements that have emerged in response to this phenomenon. The corruption perceptions index (prepared by Transparency International) and the control of corruption index (one of the six governance indicators developed by the World Bank) have been used as indicators of corruption. The study was then extended to Japan as a country with a different political and economic context than China. Based on the data obtained, a comparative analysis of the state of corruption between the two countries was carried out. We have studied the correlations of the previous indicators with the degree of freedom (published by Freedom House) and with the Gross Domestic Product per capita (published by the World Bank) in recent years.
Los mitos de gran alcance social: el caso boliviano en la visión de sus intelectuales progresistas
Authors: Mansilla H.C.F.
Published: April 2017

Desde una perspectiva racionalista, que hoy aparece como anacrónica ante la popularidad de posiciones relativistas y postmodernistas, se intenta analizar las grandes leyendas sociales bolivianas acerca de los recursos naturales y la Revolución Nacional de 1952. En la visión colectiva en torno a los recursos naturales, Bolivia aparece como un país potencialmente riquísimo, cuya pobreza actual sería la obra de pérfidos agentes externos y élites antipatrióticas. Algo similar ocurre con la exagerada importancia atribuida a la Revolución Nacional. La fortaleza de los mitos sociales reside en que estos comparten los prejuicios colectivos mejor. A rationalist perspective appears today as anachronistic because of the popularity of relativist and postmodernist approaches. Nevertheless such a perspective is important in order to analize Bolivia’s largely spread social legends about natural resources and the so-called National Revolution of 1952. According to the collective legend on natural resources, Bolivia is perceived as a potentially very rich country, whose actual poverty is due to the perverse work of foreign factors and unpatriotic elites. Something similar occurs with the exaggerated relevance granted to the National Revolution. The strength of social myths lies in the fact that the myths share the well-rooted social prejudices of the Bolivian population.
Racionalización, reforma y modernización administrativa: estado del proceso en Galicia
Authors: Alonso Suárez Lorena
Published: April 2017

La crisis económica en España reveló una crisis multinivel en el sector público. El agotado sistema de financiamiento autonómico, caracterizado por una excesiva dependencia de las transferencias del Estado central y una gestión muy limitada de las comunidades autónomas en la gestión de los tributos propios y los cedidos; el excesivo e insostenible gasto público, en una Administración Pública sobre dimensionada y una estructura organizativa y procedimental desfasada fueron algunos de los condicionantes que alertaron a los poderes públicos.En consecuencia, desde el año 2009, el gobierno central y los gobiernos autonómicos llevaron a cabo numerosas reformas legislativas en torno a la racionalización del gasto público, la simplificación de estructuras y procedimientos administrativos, la transparencia y el acceso a la información pública, el buen gobierno y la modernización administrativa, con la consolidación de la Administración electrónica. Este nuevo marco normativo ha ido acompañado de medidas y acciones en todos esos ámbitos, con especial atención a la comunidad gallega. En el caso de Galicia es necesario destacar el Plan de racionalización de la Administración paralela, como proceso pionero de reestructuración de la administración instrumental en España.
La corrupción política en la República Dominicana y la entronización del partido cartel
Authors: Jiménez Polanco Jacqueline
Published: April 2017

Este artículo analiza la crisis institucional que padece la República Dominicana producto de los altos niveles de corrupción administrativa del gobernante Partido de la Liberación Dominicana (PLD), que la autora identifica como un partido cartel siguiendo el modelo de Katz y Mair (1995, 1996, 2002, 2004, 2009). Se examinan la relación entre corrupción, crecimiento macroeconómico y pobreza, el modelo de partido cartel, la práctica electoral y gubernativa del PLD como un partido cartel y casos factuales de corrupción que involucran a funcionarios del PLD de las administraciones de Leonel Fernández y Danilo Medina, incluyendo el propio expresidente Fernández. Se destaca la impunidad imperante en el país ante los casos de corrupción sostenido por el carácter neo-corporativo del sistema político mediante la entronización del PLD como una organización partido/Estado que controla todos los estratos de la función pública. La autora plantea que ello permite la impunidad de los actos de corrupción y el trasvase a otras funciones administrativas de los funcionarios implicados en actividades de corrupción, frente a un sistema judicial disfuncional, un prevalente sistema de prevaricación y prebendas, y un electorado cautivo sostenido mediante nóminas supernumerarias y subvenciones estatales de carácter populista y clientelar.  This article analyzes the institutional crisis prevailing in the Dominican Republic as a result of the high levels of administrative corruption of the official Dominican Liberation Party (PLD) that the author identifies as a cartel party following Katz and Mair’s model (1995, 1996, 2002, 2004, 2009). It is examined the relation between corruption, macroeconomic growth and poverty, the cartel party model, the electoral and governmental practice of the PLD as a cartel party and factual cases of corruption involving PLD officials from Leonel Fernández and Danilo Medina’s administrations, including ex-president Fernández. It emphasizes the country’s prevailing impunity of corruption cases sustained by the neo-corporatist character of the political system through the enthronement of PLD as a party/State organization that controls all the strata of public function. The author points out that this allows the impunity of corruption acts and the transference to other administrative functions of officials implicated in corruption activities versus a dysfunctional judicial system, a prevalent breach of trust and prebends, and a captive electorate sustained through supernumerary appointments and state subventions of popular and patronizing character.
Maestros argentinos: patriotas y nacionalistas. La pedagogía de la patria en las escuelas primarias (1930-1940)
Authors: Casas Matías Emiliano
Published: April 2017

El sistema escolar argentino estuvo caracterizado, desde sus inicios, por la “imperiosa necesidad” de inculcar sentimientos de patriotismo en sus estudiantes. Un conjunto de ceremonias y efemérides fueron constituyendo los “rituales patrióticos” que se ocupaban, y se ocupan, de exaltar a personajes de la historia y a emblemas de la nación. Este trabajo se concentra en las prescripciones esbozadas para el personal de educación argentino en el contexto del fervor nacionalista que caracterizó la década del treinta. En ese período, la impronta nacionalista –con diversas facetas y manifestaciones- se visualizaba en expresiones políticas, culturales, religiosas y sociales. Para ese estudio, nos concentramos en las publicaciones de las revistas educativas que reprodujeron las normativas e intervinieron en los debates desde sus editoriales. Las recetas patrióticas recuperadas en ese período consolidaron prácticas educativas que se cristalizaron en el sistema escolar argentino.
Maintenance of Certification and the Challenge of Professionalism
Authors: Nichols David G.
Published: April 2017

Board certification has been part of the social contract in which physicians commit to maintaining up-to-date scientific knowledge and improving the quality of patient care. However, the maintenance of certification program has been controversial. This review summarizes the philosophical underpinnings, published literature, recent improvements, and future directions of the American Board of Pediatrics maintenance of certification program.
Antiplatelet Therapy in Acute Coronary Syndrome
Authors: Layne Kerry ,   Department of Clinical Pharmacology, Cardiovascular Division, King’s College London, London, UK, Ferro Albert ,   Department of Clinical Pharmacology, Cardiovascular Division, King’s College London, London, UK
Published: April 2017

Antiplatelet agents have for decades been used to improve outcomes in patients with acute coronary syndromes and have become increasingly valued, not only for their antithrombotic properties but also for their anti-inflammatory effects. The drug class continues to evolve as novel agents with increasingly efficacious antiplatelet actions are identified. This review will discuss antiplatelet agents, including aspirin, the P2Y12 receptor antagonists and the glycoprotein IIb/IIIa inhibitors, that are currently used to treat patients with unstable angina and myocardial infarction, focusing on their pharmacological properties and the clinical evidence supporting their use.
¿MÁS CONSULTAS, MEJORES RESULTADOS?: CONSULTAS PARTIDISTAS PARA LA SELECCIÓN DE CANDIDATOS EN LAS ELECCIONES SUBNACIONALES DE 2015
Authors: Acuña Villarraga Fabián Alejandro
Published: April 2017

Este artículo repasa los principales postulados de la literatura sobre mecanismos de selección de candidatos, como un instrumento que promueve un proceso de democratización al interior de las organizaciones políticas. Con estos postulados se realiza una caracterización de las consultas partidistas del 25 de abril de 2015 en Colombia. Esto permite otra mirada al análisis de los resultados de las consultas y su relación con las elecciones subnacionales que tuvieron lugar en octubre de 2015 en Colombia.
SELECCIÓN DE CANDIDATOS Y RELACIONES DE PODER EN LA ESTRUCTURA DE PARTIDO: ELECCIONES PARA CONCEJO DE MEDELLÍN Y ASAMBLEA DE ANTIOQUIA, 2015
Authors: Escobar E. Juan Carlos , Bedoya John Fredy , Sánchez Parra Aura
Published: April 2017

Este texto se encarga de analizar los diferentes mecanismos de selección de candidatos usados por los partidos políticos para enfrentar las contiendas subnacionales, destacando de allí los diversos métodos usados, la calidad del selectorado y los requisitos de los postulantes, situaciones cambiantes de acuerdo con dónde se sitúan los centros de poder (quién realmente toma la decisión), así como la forma en que se tramitan las luchas internas por ostentar este privilegio (las tensiones que nacen entre los líderes locales y nacionales). Para cumplir con este objetivo se usan las experiencias de selección de candidatos de los partidos que participaron en las elecciones de autoridades locales de 2015 en Colombia, específicamente en las de Concejo de Medellín y de Asamblea de Antioquia.
SELECCIÓN DE CANDIDATOS EN ESCENARIOS DE ATOMIZACIÓN DIRIGENCIAL. ANÁLISIS DE LOS CASOS DE CALI Y EL VALLE DEL CAUCA, ELECCIONES LOCALES Y REGIONALES 2015
Authors: Milanese Juan Pablo , Barrero Escobar Fredy A.
Published: April 2017

El presente artículo analiza el proceso de selección de candidatos para las elecciones locales y regionales de 2015 en el departamento del Valle del Cauca y en el municipio de Santiago de Cali (Colombia). Más precisamente, hace referencia al impacto que tuvieron sobre dicho proceso variables institucionales, en especial aquellas pertenecientes al sistema electoral en un escenario de atomización dirigencial y de identidades partidarias débiles. De este modo, se evalúa cómo arreglos institucionales como la magnitud del distrito electoral y el tipo de lista impactan en la designación de los candidatos de los distintos partidos a la gobernación, asamblea departamental (Valle) y la alcaldía y el concejo municipal (Cali, capital del departamento).
La tormenta perfecta: crisis e impeachment en el segundo mandato de Dilma Rousseff
Authors: Goldstein Ariel
Published: April 2017

Este artículo se propone analizar la emergencia de las distintas crisis –económica, política y social– y el modo en que las mismas se fueron amalgamando, conduciendo al impeachment durante el segundo mandato de la presidenta Dilma Rousseff (2014-2016). Con la confluencia de estas crisis en una "tormenta perfecta", se terminaría desarmando el pacto social lulista que había garantizado la gobernabilidad de la coalición liderada por el Partido de los Trabajadores (PT) en estos años. Para ello, se realiza una breve reconstrucción del itinerario de los cuatro gobiernos del PT en Brasil. En tanto el éxito del impeachment concluye con un ciclo de trece años de gobiernos petistas en el poder, consideramos apropiado elaborar un balance provisorio acerca de los límites y las posibilidades que habilitaron este proceso político. El trabajo, si bien no cuenta con perspectiva histórica ni análisis sistemático, puede brindar unas primeras explicaciones para los acontecimientos de relevancia que se produjeron en el país de mayor gravitación geopolítica de Sudamérica.