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Centroacinar cells (CACs) are ductal Notch-responsive progenitors that in the larval zebrafish pancreas differentiate to form new islets and ultimately contribute to the majority of the adult endocrine mass. Uncovering the mechanisms regulating CAC differentiation will facilitate understanding how insulin-producing β cells are formed. Previously we reported retinoic acid (RA) signaling and Notch signaling both regulate larval CAC differentiation, suggesting a shared downstream intermediate. Sox9b is a transcription factor important for islet formation whose expression is upregulated by Notch signaling in larval CACs. Here we report that sox9b expression in larval CACs is also regulated by RA signaling. Therefore, we hypothesized that Sox9b is an intermediate between both RA- and Notch-signaling pathways. In order to study the role of Sox9b in larval CACs, we generated two cre/lox based transgenic tools, which allowed us to express full-length or truncated Sox9b in larval CACs. In this way we were able to perform spatiotemporal-controlled Sox9b gain- and loss-of-function studies and observe the subsequent effect on progenitor differentiation. Our results are consistent with Sox9b regulating CAC differentiation by being a downstream intermediate of both RA- and Notch-signaling pathways. We also demonstrate that adult zebrafish with only one functional allele of sox9b undergo accelerated β-cell regeneration, an observation consistent with sox9b regulating CAC differentiation in adults. [ABSTRACT FROM AUTHOR]

The suprachiasmatic nucleus (SCN) defines 24 h of time via a transcriptional/posttranslational feedback loop in which transactivation of Per (period) and Cry (cryptochrome) genes by BMAL1-CLOCK complexes is suppressed by PER-CRY complexes. The molecular/structural basis of how circadian protein complexes function is poorly understood. We describe a novel N-ethyl-N-nitrosourea (ENU)-induced mutation, early doors (Edo), in the PER-ARNTSIM (PAS) domain dimerization region of period 2 (PER2) (I324N) that accelerates the circadian clock of Per2Edo/Edo mice by 1.5 h. Structural and biophysical analyses revealed that Edo alters the packing of the highly conserved interdomain linker of the PER2 PAS core such that, although PER2Edo complexeswith clock proteins, its vulnerability to degradation mediated by casein kinase 1e (CSNK1E) is increased. The functional relevance of this mutation is revealed by the ultrashort (<19 h) but robust circadian rhythms in Per2Edo/Edo; Csnk1eTau/Tau mice and the SCN. These periods are unprecedented inmice. Thus, Per2Edo reveals a direct causal link between the molecular structure of the PER2 PAS core and the pace of SCN circadian timekeeping. [ABSTRACT FROM AUTHOR]

Diabetes is associated with a paucity of insulin-producing β-cells. With the goal of finding therapeutic routes to treat diabetes, we aim to find molecular and cellular mechanisms involved in β-cell neogenesis and regeneration. To facilitate discovery of such mechanisms, we use a vertebrate organism where pancreatic cells readily regenerate. The larval zebrafish pancreas contains Notch-responsive progenitors that during development give rise to adult ductal, endocrine, and centroacinar cells (CACs). Adult CACs are also Notch responsive and are morphologically similar to their larval predecessors. To test our hypothesis that adult CACs are also progenitors, we took two complementary approaches: 1) We established the transcriptome for adult CACs. Using gene ontology, transgenic lines, and in situ hybridization, we found that the CAC transcriptome is enriched for progenitor markers. 2) Using lineage tracing, we demonstrated that CACs do form new endocrine cells after β-cell ablation or partial pancreatectomy. We concluded that CACs and their larval predecessors are the same cell type and represent an opportune model to study both β-cell neogenesis and β-cell regeneration. Furthermore, we show that in cftr loss-of-function mutants, there is a deficiency of larval CACs, providing a possible explanation for pancreatic complications associated with cystic fibrosis. [ABSTRACT FROM AUTHOR]

Sleep paralysis is a relatively common but under-researched phenomenon. In this paper we examine prevalence in a UK sample and associations with candidate risk factors. This is the first study to investigate the heritability of sleep paralysis in a twin sample and to explore genetic associations between sleep paralysis and a number of circadian expressed single nucleotide polymorphisms. Analyses are based on data from the Genesis1219 twin/sibling study, a community sample of twins/siblings from England and Wales. In total, data from 862 participants aged 22-32 years (34% male) were used in the study. This sample consisted of monozygotic and dizygotic twins and siblings. It was found that self-reports of general sleep quality, anxiety symptoms and exposure to threatening events were all associated independently with sleep paralysis. There was moderate genetic influence on sleep paralysis (53%). Polymorphisms in the PER2 gene were associated with sleep paralysis in additive and dominant models of inheritance-although significance was not reached once a Bonferroni correction was applied. It is concluded that factors associated with disrupted sleep cycles appear to be associated with sleep paralysis. In this sample of young adults, sleep paralysis was moderately heritable. Future work should examine specific polymorphisms associated with differences in circadian rhythms and sleep homeostasis further in association with sleep paralysis. [ABSTRACT FROM AUTHOR]

As the developing zebrafish pancreas matures, hormone-producing endocrine cells differentiate from pancreatic Notch-responsive cells (PNCs) that reside within the ducts. These new endocrine cells form small clusters known as secondary (2°) islets. We use the formation of 2° islets in the pancreatic tail of the larval zebrafish as a model of β-cell neogenesis. Pharmacological inhibition of Notch signaling leads to precocious endocrine differentiation and the early appearance of 2° islets in the tail of the pancreas. Following a chemical screen, we discovered that blocking the retinoic acid (RA)-signaling pathway also leads to the induction of 2° islets. Conversely, the addition of exogenous RA blocks the differentiation caused by Notch inhibition. In this report we characterize the interaction of these two pathways. We first verified that signaling via both RA and Notch ligands act together to regulate pancreatic progenitor differentiation. We produced a transgenic RA reporter, which demonstrated that PNCs directly respond to RA signaling through the canonical transcriptional pathway. Next, using a genetic lineage tracing approach, we demonstrated these progenitors produce endocrine cells following inhibition of RA signaling. Lastly, inhibition of RA signaling using a cell-type specific inducible cre/lox system revealed that RA signaling acts cell-autonomously in PNCs to regulate their differentiation. Importantly, the action of RA inhibition on endocrine formation is evolutionarily conserved, as shown by the differentiation of human embryonic stem cells in a model of human pancreas development. Together, these results revealed a biphasic function for RA in pancreatogenesis. As previously shown by others, RA initially plays an essential role during embryogenesis as it patterns the endoderm and specifies the pancreatic field. We reveal here that later in development RA is involved in negatively regulating the further differentiation of pancreatic progenitors and expands upon the developmental mechanisms by which this occurs. [ABSTRACT FROM AUTHOR]

Highlights: [•] Q transcriptional regulatory system of Neurospora crassa functions in zebrafish. [•] Tissue-specific QF driver lines activate a QUAS:GFP transgenic reporter. [•] Silencing of QUAS-regulated transgenes not observed in F4 generation. [•] Q reagents cloned into Tol2 Gateway vectors for ease of use and distribution. [Copyright &y& Elsevier]

The term Nobrow refers to the expression "highbrow" (a designation of arts and literature, which characterizes them as "intellectuals, high-quality"), and the term "lowbrow" (an expression that characterizes the literature and art as with no connection or interest in serious cultural / intellectual ideas), so that it represents the concept of art without a qualification of "lowbrow" or "highbrow", the concept of relativist art, without specific direction to a particular type of audience, or to particular areas of knowledge, an art that is neither popular nor scholarly. The century began with a strong tendency towards this art Nobrow aesthetic, so this research tries to analyze this new aesthetic and its actual application in the fine arts, also with a brief analysis of literature and cinema by investigating the artistic movements of the 21st Century, and relating them to the cultural history of the first ten years of this century, to outline the goals and aesthetic bases of these movements, comparing the writings of poetics and aesthetics from different times in their applications in due course and now, establishing this way, parameters for contemporary aesthetics. [ABSTRACT FROM AUTHOR]

Abstract: Recent zebrafish studies have shown that the late appearing pancreatic endocrine cells are derived from pancreatic ducts but the regulatory factors involved are still largely unknown. Here, we show that the zebrafish sox9b gene is expressed in pancreatic ducts where it labels the pancreatic Notch-responsive cells previously shown to be progenitors. Inactivation of sox9b disturbs duct formation and impairs regeneration of beta cells from these ducts in larvae. sox9b expression in the midtrunk endoderm appears at the junction of the hepatic and ventral pancreatic buds and, by the end of embryogenesis, labels the hepatopancreatic ductal system as well as the intrapancreatic and intrahepatic ducts. Ductal morphogenesis and differentiation are specifically disrupted in sox9b mutants, with the dysmorphic hepatopancreatic ducts containing misdifferentiated hepatocyte-like and pancreatic-like cells. We also show that maintenance of sox9b expression in the extrapancreatic and intrapancreatic ducts requires FGF and Notch activity, respectively, both pathways known to prevent excessive endocrine differentiation in these ducts. Furthermore, beta cell recovery after specific ablation is severely compromised in sox9b mutant larvae. Our data position sox9b as a key player in the generation of secondary endocrine cells deriving from pancreatic ducts in zebrafish. [Copyright &y& Elsevier]

Pancreatic β-cells are an essential source of insulin and their destruction because of autoimmunity causes type I diabetes. We conducted a chemical screen to identify compounds that would induce the differentiation of insulin-producing β-cells in vivo. To do this screen, we brought together the use of transgenic zebrafish as a model of β-cell differentiation, a unique multiwell plate that allows easy visualization of lateral views of swimming larval fish and a library of clinical drugs. We identified six hits that can induce precocious differentiation of secondary islets in larval zebrafish. Three of these six hits were known drugs with a considerable background of published data on mechanism of action. Using pharmacological approaches, we have identified and characterized two unique pathways in β-cell differentiation in the zebrafish, including down-regulation of GTP production and retinoic acid biosynthesis. [ABSTRACT FROM AUTHOR]

Research on cultural consumption and its social conditions mainly focuses on tastes and on products consumed rather than on modes of consumption. This article takes up this desideratum and studies the modes of listening to classical music in opera audiences based on a visitor survey. In contrast to the prevailing image of the silent and intellectual audience in high-brow institutions, the study shows there is a broad array of modes people use to listen to classical music. With respect to Bourdieu's theory of arts perception, in particular his notion of cultural capital, one can show empirically that the modes of cultural consumption in this case are determined by listeners' cultural capital. [ABSTRACT FROM AUTHOR]

Abstract: In mammals, cerebellar neurons are categorized as glutamatergic or GABAergic, and are derived from progenitors that express the proneural genes atoh1 or ptf1a, respectively. In zebrafish, three atoh1 genes, atoh1a, atoh1b, and atoh1c, are expressed in overlapping but distinct expression domains in the upper rhombic lip (URL): ptf1a is expressed exclusively in the ventricular zone (VZ). Using transgenic lines expressing fluorescent proteins under the control of the regulatory elements of atoh1a and ptf1a, we traced the lineages of the cerebellar neurons. The atoh1 + progenitors gave rise not only to granule cells but also to neurons of the anteroventral rhombencephalon. The ptf1a + progenitors generated Purkinje cells. The olig2 + eurydendroid cells, which are glutamatergic, were derived mostly from ptf1a + progenitors in the VZ but some originated from the atoh1 + progenitors in the URL. In the adult cerebellum, atoh1a, atoh1b, and atoh1c are expressed in the molecular layer of the valvula cerebelli and of the medial corpus cerebelli, and ptf1a was detected in the VZ. The proneural gene expression patterns coincided with the sites of proliferating neuronal progenitors in the adult cerebellum. Our data indicate that proneural gene-linked neurogenesis is evolutionarily conserved in the cerebellum among vertebrates, and that the continuously generated neurons help remodel neural circuits in the adult zebrafish cerebellum. [Copyright &y& Elsevier]

Prior analyses of congressional action on the issue of black civil rights have typically examined either of the two major Reconstructions. Our paper attempts to fill the large five-decade black box between the end of the First Reconstruction and the beginning of the Second, routinely skipped over in scholarship on Congress, parties, and racial politics. Using a variety of sources—bill-introduction data, statements by members in the Congressional Record, roll-call votes, and newspaper reports, among others—we challenge the common assumption that civil rights largely disappeared from the congressional agenda between 1891 and 1940, documenting instead the continued contestation over racial issues in Congress. By examining several failed anti-lynching initiatives, this article uncovers a largely untold story about how and when the Republican and Democratic Parties reorganized around race, finding that the realignment began earlier than is commonly understood. [ABSTRACT FROM AUTHOR]

Child spectators and adult theatre critics often hold opposite views on what makes the “best” theatre for young people. To explain why this enormous gap exists, we discuss children's aesthetic criteria as cross-cultural spectators and examine the theoretical and methodological differences between aesthetic appreciation and artistic criticism. To explain aesthetic transactions between child spectators and adult actors, we discuss our different philosophical interpretations of aesthetic distance and propose two models to stimulate further discussions. Future reception studies need to integrate theories of aesthetic philosophy and developmental psychology to raise the artistic quality of TYA around the world. [ABSTRACT FROM AUTHOR]

Abstract: Prior studies with transgenic zebrafish confirmed the functionality of the transcription factor Gal4 to drive expression of other genes under the regulation of upstream activator sequences (UAS). However, widespread application of this powerful binary system has been limited, in part, by relatively inefficient techniques for establishing transgenic zebrafish and by the inadequacy of Gal4 to effect high levels of expression from UAS-regulated genes. We have used the Tol2 transposition system to distribute a self-reporting gene/enhancer trap vector efficiently throughout the zebrafish genome. The vector uses the potent, hybrid transcription factor Gal4-VP16 to activate expression from a UAS:eGFP reporter cassette. In a pilot screen, stable transgenic lines were established that express eGFP in reproducible patterns encompassing a wide variety of tissues, including the brain, spinal cord, retina, notochord, cranial skeleton and muscle, and can transactivate other UAS-regulated genes. We demonstrate the utility of this approach to track Gal4-VP16 expressing migratory cells in UAS:Kaede transgenic fish, and to induce tissue-specific cell death using a bacterial nitroreductase gene under UAS control. The Tol2-mediated gene/enhancer trapping system together with UAS transgenic lines provides valuable tools for regulated gene expression and for targeted labeling and ablation of specific cell types and tissues during early zebrafish development. [Copyright &y& Elsevier]

Abstract: In order to generate a zebrafish model of β cell regeneration, we have expressed an Escherichia coli gene called nfsB in the β cells of embryonic zebrafish. This bacterial gene encodes a nitroreductase (NTR) enzyme, which can convert prodrugs such as metronidazole (Met) to cytotoxins. By fusing nfsB to mCherry, we can simultaneously render β cells susceptible to prodrug and visualize Met dependent cell ablation. We show that the neighboring α and δ cells are unaffected by prodrug treatment and that ablation is β cell specific. Following drug removal and 36h of recovery, β cells regenerate. Using ptf1a morphants, it is clear that this β cell recovery occurs independently of the presence of the exocrine pancreas. Also, by using photoconvertible Kaede to cell lineage trace and BrdU incorporation to label proliferation, we investigate mechanisms for β regeneration. Therefore, we have developed a unique resource for the study of β cell regeneration in a living vertebrate organism, which will provide the opportunity to conduct large-scale screens for pharmacological and genetic modifiers of β cell regeneration. [Copyright &y& Elsevier]

The author reflects on the government's policy of conserving endangered species particularly the Mexican wolf in the U.S. He said that despite this policy, there are still problems which are needed to be resolved specifically the imperiled Mexican wolf. The author believes that U.S. efforts must fully coordinated with Mexican efforts to recover Mexican wolf. He suggested an effective manipulative management without economic or ideological interest to be attain the goal of wildlife recovery.

The election of 1896 is regarded as a critical one in which a significant and enduring shift in party electoral fortunes occurred. This evidence is so important because it supports the more general argument that critical realignments are the way that significant electoral changes occur. Change is seen as abrupt, with new alignments persisting for decades. Voters are seen as detached, briefly attentive, and then relatively stable in a new alignment. In this view, the political process is not seen as one in which there is continuous political debate, electoral attention, and secular electoral change. This analysis reexamines the evidence for the occurrence of a critical realignment in 1896, using results for presidential and House elections. The data do not indicate that an abrupt change occurred in 1896. The changes that occurred were gradual, with most occurring after 1896. The evidence suggests that secular change and gradual electoral shifts should receive much more attention. [ABSTRACT FROM AUTHOR]

Discusses the political practice of genetic epistemology. Key aspects of the genetic epistemological perspective which differentiate it from other structural perspectives; Common objections to genetic epistemology and its extension to political development; Political practice consonant with genetic epistemology.

The article presents a response by Michael J. Parsons to the reviews of his book "How We Understand Art: A Cognitive Developmental Account of Aesthetic Experience." Parsons claimed that his book advances a new account of aesthetic development. He said that he wanted the reader to understand what the necessary assumptions were but not to be diverted from the main point into a debate about them. According to him, there are three assumptions at issue in the book. The first is what one might call a hermeneutic assumption, and the second has to do with the social and public character of interpretation. A third assumption at issue is that art has a particular function in the economy of mind, an essense or nature that defines it.

Buddhist aesthetics, as a profound intrinsic value of pleasure, has continually attracted scholars to shed light on its influential effects. Its aesthetic nature, however, has drawn on the laws of profound Buddhist thoughts, which is challenging for empiricists to generate evidence for. Though some individual components or factors deriving from Buddhist aesthetics have been developed and exploited in previous studies, a holistic construct of Buddhist aesthetics remains ambiguous and lacks a pragmatically useable measure. This study fills this gap by creating a Buddhist aesthetics scale. A total of fifteen items have been found valid and reliable to measure three determinants, namely, value, acumen, and response. This scale can be used in further empirical studies in designing objects aiming to elicit the unique Buddhist aesthetic experience. Moreover, it can be utilized in measuring Buddhist aesthetics as a determinant in relevant practices, such as religious psychotherapy, cognitive engineering, and business. [ABSTRACT FROM AUTHOR]

The article lists books received by the journal including: "Philosophy and the Spontaneous Philosophy of the Scientists and Other Essays," by Louis Althusser; "The Ideology of the Aesthetic," by Terry Eagleton; and "Sound Sentiment: An Essay on the Musical Emotions Including the Complete Text of The Corded Shell," by Peter Kivy.

The article provides a list of books received including "Living Powers: The Arts in Education," edited by Peter Abbs, "Creativity and the Philosophy of C. S. Peirce," by Douglas R. Anderson, and "The Art of Liberation: Alexander A. Ivanov," by Vahan D. Barooshian.