The fast advancing RNA‐seq technology has unveiled an unexpected diversity and expression specificity of 3′ untranslated regions (3′UTRs) of mRNAs. In particular, neural mRNAs seem to express significantly longer 3′UTRs, some of which are over 10 kb in length. The extensive elongation of 3′UTRs in neural tissues provides intriguing possibilities for cell type‐specific regulations that are governed by miRNAs, RNA‐binding proteins and ribonucleoprotein aggregates. In this article, we review recent progress in the characterization of mRNA 3′UTRs and discuss their implications (...) in the understanding of 3′UTR‐mediated gene regulation. (shrink)

Alternative cleavage and polyadenylation (APA) can diversify coding and non‐coding regions, but has particular impact on increasing 3′ UTR diversity. Through the gain or loss of regulatory elements such as RNA binding protein and microRNA sites, APA can influence transcript stability, localization, and translational efficiency. Strikingly, the central nervous systems of invertebrate and vertebrate species express a broad range of transcript isoforms bearing extended 3′ UTRs. The molecular mechanism that permits proximal 3′ end bypass in neurons is mysterious, and only (...) beginning to be elucidated. This landscape of neural 3′ UTR extensions, many reaching unprecedented lengths, may help service the unique post‐transcriptional regulatory needs of neurons. A combination of approaches, including transcriptome‐wide profiling, genetic screening to identify APA factors, biochemical dissection of alternative 3′ end formation, and manipulation of individual neural APA targets, will be necessary to gain fuller perspectives on the mechanism and biology of neural‐specific 3′ UTR lengthening. (shrink)

The poly(A)‐dependent translational regulation of maternal mRNAs is an important mechanism to execute stage‐specific programs of protein synthesis during early development. This control underlies many crucial developmental events including the meiotic maturation of oocytes and activation of the mitotic cell cycle at fertilization. A recent report(1) demonstrates that the 3′ untranslated region of the cyclin A1, B1, B2 and c‐mos mRNAs determines the timing and extent of their cytoplasmic polyadenylation and translational activation during Xenopus oocyte maturation. These studies further establish (...) that protein synthesis can be temporally and quantitatively controlled by developmentally regulated changes in the polyadenylation of maternal mRNAs. (shrink)

Although introns in 5′‐ and 3′‐untranslated regions (UTRs) are found in many protein coding genes, rarely are they considered distinctive entities with specific functions. Indeed, mammalian transcripts with 3′‐UTR introns are often assumed nonfunctional because they are subject to elimination by nonsense‐mediated decay (NMD). Nonetheless, recent findings indicate that 5′‐ and 3′‐UTR intron status is of significant functional consequence for the regulation of mammalian genes. Therefore these features should be ignored no longer.

Abstract3′ untranslated regions (3′ UTRs) of mRNAs have many functions, including mRNA processing and transport, translational regulation, and mRNA degradation and stability. These different functions require cis‐elements in 3′ UTRs that can be either sequence motifs or RNA structures. Here we review the role of secondary structures in the functioning of 3′ UTRs and discuss some of the trans‐acting factors that interact with these secondary structures in eukaryotic organisms. We propose potential participation of 3′‐UTR secondary structures in cytoplasmic polyadenylation in (...) the model organism Drosophila melanogaster. Because the secondary structures of 3′ UTRs are essential for post‐transcriptional regulation of gene expression, their disruption leads to a wide range of disorders, including cancer and cardiovascular diseases. Trans‐acting factors, such as STAU1 and nucleolin, which interact with 3′‐UTR secondary structures of target transcripts, influence the pathogenesis of neurodegenerative diseases and tumor metastasis, suggesting that they are possible therapeutic targets. (shrink)

It is well established that microRNAs (miRNAs) induce mRNA degradation by binding to 3′ untranslated regions (UTRs). The functionality of sites in the coding domain sequence (CDS), on the other hand, remains under discussion. Such sites have limited impact on target mRNA abundance and recent work suggests that miRNAs bind in the CDS to inhibit translation. What then could be the regulatory benefits of translation inhibition through CDS targeting compared to mRNA degradation following 3′ UTR binding? We propose that these (...) domain‐dependent effects serve to diversify the functional repertoire of post‐transcriptional gene expression control. Possible regulatory benefits may include tuning the time‐scale and magnitude of post‐transcriptional regulation, regulating protein abundance depending on or independently of the cellular state, and regulation of the protein abundance of alternative splice variants. Finally, we review emerging evidence that these ideas may generalize to RNA‐binding proteins beyond miRNAs and Argonaute proteins. (shrink)

hiCLIP (RNA hybrid and individual‐nucleotide resolution ultraviolet cross‐linking and immunoprecipitation), is a novel technique developed by Sugimoto et al. (2015). Here, the use of different adaptors permits a controlled ligation of the two strands of a RNA duplex allowing the identification of each arm in the duplex upon sequencing. The authors chose a notoriously difficult to study double‐stranded RNA‐binding protein (dsRBP) termed Staufen1, a mammalian homolog of Drosophila Staufen involved in mRNA localization and translational control. Using hiCLIP, they discovered a (...) dominance of intramolecular RNA duplexes compared to the total RNA duplexes identified. Importantly, the authors discovered two different types of intramolecular duplexes in the cell: highly translated mRNAs with long‐range duplexes in their 3′‐UTRs and poorly translated mRNAs with duplexes in their coding region. In conclusion, the authors establish hiCLIP as an important novel technique for the identification of RNA secondary structures that serve as in vivo binding sites for dsRBPs. (shrink)

Phenotypic divergence among animal species may be due in part to species‐specific (SS) regulation of gene expression by small, non‐coding regulatory RNAs termed “microRNAs”. This phenomenon can be modulated by several variables. First, microRNA genes vary by their level of conservation, many of them being SS, or unique to a particular evolutionary lineage. Second, microRNA expression levels vary spatially and temporally in different species. Lastly, while microRNAs bind the 3′UTR of target genes in order to silence their expression, the binding (...) sites themselves are often non‐conserved. The variability of the miRNA‐target paradigm between different species is thus multifactorial, and this paradigm has only just started to gain attention from researchers in various fields. Here we present and discuss recent findings regarding the characteristics and implications of SS microRNA regulation. (shrink)

The mechanisms used to establish embryonic polarity are still largely unknown. A recent paper(1) describes the expression pattern of the gene glp‐1, which is required for induction events during development of the nematode Caenorhabditis elegans. Although glp‐1 RNA is found throughout the early embryo, Glp‐1 protein is only expressed in anterior cells. This negative translational regulation in posterior cells is shown to be mediated through sequences in the glp‐1 3′ untranslated region (3′UTR). Thus in nematodes, as in Drosophila, translational repression (...) is one mechanism used to establish the embryonic anterior‐posterior axis. (shrink)

Incomplete penetrance and variable expressivity are non‐Mendelian phenomena resulting in the lack of correlation between genotype and phenotype. Not withstanding the diversity in mechanisms, differential expression of homologous alleles within cells manifests as variations in penetrance and expressivity of mutations between individuals of the same genotype. These phenomena are seen most often in dominantly inherited diseases, implying that they are sensitive to concentration of the gene product. In this framework and the advances in understanding the role of microRNA (miRNA) in (...) fine‐tuning gene expression at translational level, we propose miRNA‐mediated regulation as a mechanism for incomplete penetrance and variable expressivity. The presence of miRNA binding sites at 3′ UTR, co‐expression of target gene–miRNA pairs for genes showing incomplete penetrance and variable expressivity derived from available data lend support to our hypothesis. Single nucleotide polymorphisms in the miRNA target site facilitate the implied differential targeting of the transcripts from homologous alleles. (shrink)

AbstractmRNA stability is increasingly recognized as being essential for controlling the expression of a wide variety of transcripts during neuronal development and synaptic plasticity. In this context, the role of AU‐rich elements (ARE) contained within the 3′ untranslated region (UTR) of transcripts has now emerged as key because of their high incidence in a large number of cellular mRNAs. This important regulatory element is known to significantly modulate the longevity of mRNAs by interacting with available stabilizing or destabilizing RNA‐binding proteins (...) (RBP). Thus, in parallel with the emergence of ARE, RBP are also gaining recognition for their pivotal role in regulating expression of a variety of mRNAs. In the nervous system, the member of the Hu family of ARE‐binding proteins known as HuD, has recently been implicated in multiple aspects of neuronal function including the commitment and differentiation of neuronal precursors as well as synaptic remodeling in mature neurons. Through its ability to interact with ARE and stabilize multiple transcripts, HuD has now emerged as an important regulator of mRNA expression in neurons. The present review is designed to provide a comprehensive and updated view of HuD as an RBP in the nervous system. Additionally, we highlight the role of HuD in multiple aspects of a neuron's life from early differentiation to changes in mature neurons during learning paradigms and in response to injury and regeneration. Finally, we describe the current state of knowledge concerning the molecular and cellular events regulating the expression and activity of HuD in neurons. BioEssays 28: 822–833, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Even after multiple cycles of ABET accreditation, many engineering programs are unsure of how much curriculum content is needed to meet the requirements of ABET’s Criterion 3.f (an understanding of professional and ethical responsibility). This study represents the first scholarly attempt to assess the impact of curriculum reform following the introduction of ABET Criterion 3.f. This study sought to determine how much professional and ethical responsibility curriculum content was used between 1995 and 2005, as well as how, when, why, and (...) to what effect changes in the amount of content occurred. Subsequently, the study sought to evaluate if different amounts of curriculum content generated differing student outcomes. The amount of curriculum content used by each of the participating programs was identified during semi-structured interviews with program administrators and a review of ABET Self-Study documents. Quantitative methods were applied to determine if a relationship existed between the curriculum content and performance on a nationally administered, engineering-specific standardized examination. The findings indicate a statistical relationship, but a lack of structure between the amount of required content in the curriculum and performance on the examination. Additional findings were also generated regarding the way that programs interpret the Criterion 3.f feedback generated during accreditation visits. The primary impact of this study is that it dispels the myth that more courses or course time on professionalism and ethics will necessarily lead to positive engineering education outcomes. Much of the impetus to add more curriculum content results from a lack of conclusive feedback during ABET accreditation visits. (shrink)

Este artigo discute a influência da segunda parte do Parmênides de Platão, e mais especificamente a sua 3ª hipótese, na obra de Plotino e Jâmblico. Ou seja, a inter- elação entre a apropriação do conceito central da 3ª hipótese, o instante (exaiphnes), (1) em Plotino através da apropriação original do conceito de presença (parousia) e (2) em Jâmblico quando da modificação da estrutura das hipóteses parmenidianas, ao introduzir antes da primeira hipótese, o Inefável, e deslocar a alma para a 4ª (...) hipótese, alocando na 3ª hipótese, os daemons, os anjos e os heróis. A posição da alma na estrutura das hipóteses irá determinar a ascese proposta por cada um deles: se para Plotino a ascese é intelectual, para Jâmblico a mesma se realiza, depois de esgotados os recursos filosóficos, através da teurgia, entendida como um complemento e não em oposição à filosofia, sendo esta a sua novidade. (shrink)

I’ve been looking back on what’s happened with the JSE since we parted ways with our former publisher, Allen Press, and switched to a more cost-effective and flexible online publishing system that allowed us to offer both print and electronic versions of the Journal. We were quite sure, when this happened, that the transition would reduce our production costs, and we figured that the savings could partially be passed along to readers by allowing us to increase the size of our (...) journal issues—provided (of course) that we had enough acceptable submissions to sustain the increase. I predicted at the time that we’d probably be able to add about 100 pages annually to the JSE. And I’m pleased to report that the prediction has so far panned out, by a comfortable margin. So I submit the following for your consideration. (shrink)

In ‘Many-valued Logics’, a lecture broadcast over New Zealand's public radio in 1957, Arthur N. Prior (1914–1969) complained that conjunctions are put ‘to something like forced labour’ in Łukasiewicz's three-valued semantics, Ł3. In this paper, we discuss what Prior might have meant by this.

Hyperlinked chapter headings will open in a second window, showing the full text (usually the Latin text with English translation parallel). Resize the browser windows so that windows cascade, or use the taskbar to switch from one window to the other.

Hauptbeschreibung Der Begriff der Gleichheit gehört spätestens seit der Französischen Revolution zum europäischen Grundvokabular. Formen des Gleichheitsgedankens finden sich bereits in der stoischen Philosophie oder dem christlichen Denken. Die Erklärung der Menschenrechte im 20. Jahrhundert unterstreicht die Bedeutung dieses Begriffs, der in der jüngeren Geistesgeschichte untrennbar mit dem Begriff der ""Menschenwürde"" verbunden ist. Aber ist ""Gleichheit"" ein spezifisch europäischer Wert? Wie steht es um das Verständnis von Gleichheit in amerikanischen oder asiatischen Kul.