Recurrent Motifs Research Articles

Identifying novel sequence variants of RNA 3D motifs.

Predicting RNA 3D structure from sequence is a major challenge in biophysics. An important sub-goal is accurately identifying recurrent 3D motifs from RNA internal and hairpin loop sequences extracted from secondary structure (2D) diagrams. We have developed and validated new probabilistic models for 3D motif sequences based on hybrid Stochastic Context-Free Grammars and Markov Random Fields (SCFG/MRF). The SCFG/MRF models are constructed using atomic-resolution RNA 3D structures. To parameterize each model, we use all instances of each motif found in the RNA 3D Motif Atlas and annotations of pairwise nucleotide interactions generated by the FR3D software. Isostericity relations between non-Watson–Crick basepairs are used in scoring sequence variants. SCFG techniques model nested pairs and insertions, while MRF ideas handle crossing interactions and base triples. We use test sets of randomly-generated sequences to set acceptance and rejection thresholds for each motif group and thus control the false positive rate. Validation was carried out by comparing results for four motif groups to RMDetect. The software developed for sequence scoring (JAR3D) is structured to automatically incorporate new motifs as they accumulate in the RNA 3D Motif Atlas when new structures are solved and is available free for download.

Fat in Contemporary Autobiographical Writing and Publishing

Fat in Contemporary Autobiographical Writing and Publishing

The Punch Historical Archive, 1841–1992 : A Sustainable Brand for the Digital Age

The Punch Historical Archive, 1841–1992:A Sustainable Brand for the Digital Age Seth Cayley (bio) and Clare Horrocks (bio) Punch is one of the most enduring symbols of the Victorian age. It surpassed other Victorian weekly satirical magazines in popularity due in part to its awareness of the importance of branding. This extended beyond the weekly magazine to include almanacks, seasonal supplements, pocket books, and volume editions of popular serials. These additional publications provided supplemental income that ensured the magazine’s continued survival. Punch’s sustainability as a brand continues today with the release of the beta site for the Punch Historical Archive, 1841–1992; an enhanced edition, complete with author attributions and improved metadata, is scheduled for release in April 2015. This site, produced by Cengage Learning, is the most complete online collection of Punch available, in part due to the fact that it incorporates both regular issues and seasonal supplements.1 First published in 1841, Punch entered into a vibrant and competitive market for popular periodicals. Outliving many of its contemporaries, it endured until the end of the twentieth century. Punch is a particularly rich source for studying mid-Victorian life and urban change, with its full-page main cuts providing striking visual representations of current news and events. Its enduring importance is confirmed by the fact that for decades scholars have used full-page cartoons from Punch in a wide variety of scholarly publications. However, the main cuts are only a small percentage of the total contents of the magazine. By taking these images out of context, scholars have overlooked important recurrent motifs and tropes in the magazine as a whole. Drawing on a wide variety of popular interests, Punch developed a form and style that was accessible to a broad spectrum [End Page 238] of readers. Imitating its predecessors, Punch married its textual content to visual representations by emphasizing shared motifs and emblems. Textual and visual metaphors produced a common language through which readers could begin to imagine and debate social and cultural change. Knowing how this textual/visual relationship evolved is crucial for understanding Punch’s enduring popularity. The launch of the Punch Historical Archive provides a unique opportunity to examine the satirical narratives that remain comparatively unstudied but were central to Punch’s success. By investigating this archive using keyword searches, students and scholars will be able to study the text and language of Punch in depth rather than just focusing on its fabulous cartoons. Punch was initially started as a private venture between Henry Mayhew, Mark Lemon, Joseph Stirling Coyne, Ebenezer Landells, and Joseph Last. However, as with many of its predecessors, it soon found itself in financial difficulties. Competition drove a wedge between the five men as they disputed who would have controlling power of the magazine. As a result, Punch was initially a rather fractured organisation. Although Mark Lemon wrote short plays to finance the magazine, after a few months it was clear that it needed other sources of revenue. Consequently, at the close of 1841, the Punch Almanack for 1842 was introduced as a supplementary number. The sale of the additional number boosted the magazine’s circulation figures significantly and became a permanent offering every Christmas. All of these almanacks are available for the first time in searchable form as part of the Punch Historical Archive. The availability of these materials will no doubt inspire exciting new research on the popularity and appeal of supplementary publications. The astrologer’s almanack was one of the most popular types of advertising in the eighteenth century, a genre that would have been familiar to readers of Punch. In the 1842 Punch almanacks, the traditional dated format was replaced by a more dominant visual iconography associated with the weekly magazine, thus drawing on cultural reference points the reader would have immediately recognised. Such intertextual references added to the rich complexity of the magazine, and the repetition of form and symbol enhanced the reader’s experience of the text. This was especially true for regular readers; it is more difficult to chart the experience of the occasional reader. As a supplement to the magazine, the Punch almanacks are vital resources for investigating the traditions...

Architecture of Signature miRNA Regulatory Networks in Cancer Chemoprevention

With new high-throughput technologies and superior computational power available for application to current pharmacology research, biomarker discovery has probably entered its most exciting phase to date, especially with the concurrent advent of systems network biology for “big data.” Study of recurrent network motifs in network architecture can inform us better about regulatory pathways in the cellular milieu, more so in complex disease states like cancer. In this review, we focus on the architecture of miRNA networks with emphasis on chemoresistance networks in response to chemotherapeutic drugs, chemoprevention networks modulated by dietary phytochemicals, and novel bifunctional networks comprised of bifunctional miRNAs that operate in both chemoresistance and chemoprevention. Since miRNA cancer networks are very complex, the regulatory architecture in chemoresistance and/or chemoprevention may likely include added dimensions of modulation by epigenetic miRNAs and lncRNAs, which may explain, at least in part, the bifunctionality associated with signature miRNA nodes in these networks in addition to temporal dynamics, spatial localization, and stress conditions in the dynamic networks representing the complex cellular milieu. Collectively, by a perusal of our chemoresistance, chemoprevention, and bifunctional networks, we can gain deeper insights into the architecture of signature miRNA regulatory networks in cancer that will serve as the basis for future dynamic network studies and facilitate the discovery of novel miRNA/target biomarkers for preventive and/or therapeutic intervention in cancer.

The cultural uses of the A-Z London street atlas: navigational performance and the imagining of urban form

For a decade from the late 1990s, the A-Z London street atlas became a recurrent motif within art works and popular media texts. This essay collates and explores these cultural responses to the atlas, to consider what this might reveal about the affective dimensions of ordinary urban way-finding. There were three persistent motifs that ran through these diverse works: a basic fascination with the destruction of the atlas, the foregrounding of a stoic or heroic pedestrian figure, and the attachment of the atlas to a projected network of mobile individuals that connected on the streets at random times and places. An interrogation of these tropes reveals how the A-Z became a means to explore the terms of an expanded pedestrian experience, as well as a possible configuration of metropolitan movement and contact. Furthermore, the popularity of these texts points to an excess of affect that might have become embedded within acts of A-Z way-finding. Using, owning or being seen with the atlas briefly became a potential mechanism for imagining one’s contribution to a mobile metropolitan community. Hence, this essay is both a focussed exploration of street-atlas poetics and an attempt to think more deeply about the cultural dynamics of everyday urban navigation.

Brickworx builds recurrent RNA and DNA structural motifs into medium- and low-resolution electron-density maps.

Brickworx is a computer program that builds crystal structure models of nucleic acid molecules using recurrent motifs including double-stranded helices. In a first step, the program searches for electron-density peaks that may correspond to phosphate groups; it may also take into account phosphate-group positions provided by the user. Subsequently, comparing the three-dimensional patterns of the P atoms with a database of nucleic acid fragments, it finds the matching positions of the double-stranded helical motifs (A-RNA or B-DNA) in the unit cell. If the target structure is RNA, the helical fragments are further extended with recurrent RNA motifs from a fragment library that contains single-stranded segments. Finally, the matched motifs are merged and refined in real space to find the most likely conformations, including a fit of the sequence to the electron-density map. The Brickworx program is available for download and as a web server at http://iimcb.genesilico.pl/brickworx.

Speaking of Climate Change

Representations of climate change have been a recurrent motif in media and political domains spanning over 20 years. However, relatively scant scholarly work has addressed how laypeople make sense of this phenomenon in talk. The current study, employing a discursive approach, demonstrates how the salience of climate change, as a social issue, is accounted for and made contingent on social, financial, and political factors. Moreover, the issue of climate change was accounted for as an intergenerational issue, and moral considerations were mobilized in arguing for why the issue should be provided increased attention. We argue that science communication research could fruitfully examine the discursive building blocks underpinning taken-for-granted ways of talking about climate change, informing the design of alternative discourses.

Voracious Vampires and other Monsters: Masculinity and the Terror genre in Spanish Cinema of the Transición

VAMPIRES, werewolves, and other monstrous beings abound in Spanish cinema of late 1960s and 1970s. Though they appear almost exclusively in what has been marginalized as a fringe sexploitation genre, horror films constitute a significant contribution to Spanish cinematic tradition. They represent a face and a voice that have often been neglected in discussions of Spanish cinema of highly politically and socially volatile years of late Francoist dictatorship and transition to democracy. Rife with images of sexism and violence--and often made quickly on very small budgets--horror genre films have been lauded for their ability to speak that which cannot otherwise be spoken and in turn to set about blasting open continuum of history (Lowenstein 16). These genre films were relatively unregulated and, according to Andrew Willis, they offered a space for directors to find a way of articulating challenges to dominant ideas and beliefs of Francoist cinema and its celebration of family values (167). Along these lines, Robin Wood states that the true subject of horror genre is struggle for recognition of all that our civilization or its reemergence dramatized, as in our nightmares (4). Like dreams, they contain images unsettling to behold yet fruitful to contemplate for their insistent and problematic focus on gender relations, consumption, and identity. By placing three representative films of this genre, La noche de Walpurgis/Werewolf versus Vampire Woman (Leon Klimovsky, 1971), El retorno de Walpurgis/Ourse of Devil (Carlos Aured, 1974), and La semana del asesino/Cannibal Man (Eloy de la Iglesia, 1972), within their larger cultural context, this study demonstrates how recurrent themes, motifs, and symbols link them despite their disparate styles, and indicates a profound ambivalence over phenomenon of consumption--an ambivalence from which monsters emerge. Through representation of most prevalent monsters that appear during this period, werewolf, vampire, and cannibal, these films blur line between human and beast, and this ambiguity can be seen to represent anxieties produced as body was caught within a web of both consuming and being consumed during period of Spain's rapid modernization. The 1960s and 1970s witnessed dramatic economic and social changes in Spain causing a radical change in attitudes and behavior: migration to cities, encounter with foreign tourists, and rise of television advertising estimulaba a los espanoles al consumo y al bienestar, identificado con automoviles, vacaciones al sol, viajes, electrodomesticos, aperitivos internacionales y perfumeria de lujo (Jover Zamora et al 755). This period saw the most accelerated, deep seated social, economic, and cultural transformation in Spanish history (Graham and Labanyi 259). From 1961 to 1973, Spain's economy grew by 7 percent a year, outpaced in developed world only by Japan (Tremlett 53). Suddenly driven to encounter with that which had been forbidden during much of dictatorship for economic or cultural reasons such as products, sexuality on display, and omnipresent advertising, individual finds her/himself subject to order in which one's consumer is required and exploited by system, and one's body, male or female, is presented as object for visual consumption. It is within this changing order that anxieties, or that which Spanish civilization represses or oppresses, surfaced as viewer confronted her/his role in new context. Jean Baudrillard defines consummativity as an indefinite calculus of growth rooted in abstraction of needs (83), and describes how individual, who considers himself as autonomous exercising his power of choice, becomes caught up in a system which compels him to consume: there is a compulsion to need and a compulsion to consume (82). …

Computer-based prediction of mitochondria-targeting peptides.

Computational methods are invaluable when protein sequences, directly derived from genomic data, need functional and structural annotation. Subcellular localization is a feature necessary for understanding the protein role and the compartment where the mature protein is active and very difficult to characterize experimentally. Mitochondrial proteins encoded on the cytosolic ribosomes carry specific patterns in the precursor sequence from where it is possible to recognize a peptide targeting the protein to its final destination. Here we discuss to which extent it is feasible to develop computational methods for detecting mitochondrial targeting peptides in the precursor sequences and benchmark our and other methods on the human mitochondrial proteins endowed with experimentally characterized targeting peptides. Furthermore, we illustrate our newly implemented web server and its usage on the whole human proteome in order to infer mitochondrial targeting peptides, their cleavage sites, and whether the targeting peptide regions contain or not arginine-rich recurrent motifs. By this, we add some other 2,800 human proteins to the 124 ones already experimentally annotated with a mitochondrial targeting peptide.

Structure-affinity properties of a high-affinity ligand of FKBP12 studied by molecular simulations of a binding intermediate.

With a view to explaining the structure-affinity properties of the ligands of the protein FKBP12, we characterized a binding intermediate state between this protein and a high-affinity ligand. Indeed, the nature and extent of the intermolecular contacts developed in such a species may play a role on its stability and, hence, on the overall association rate. To find the binding intermediate, a molecular simulation protocol was used to unbind the ligand by gradually decreasing the biasing forces introduced. The intermediate was subsequently refined with 17 independent stochastic boundary molecular dynamics simulations that provide a consistent picture of the intermediate state. In this state, the core region of the ligand remains stable, notably because of the two anchoring oxygen atoms that correspond to recurrent motifs found in all FKBP12 ligand core structures. Besides, the non-core regions participate in numerous transient intermolecular and intramolecular contacts. The dynamic aspect of most of the contacts seems important both for the ligand to retain at least a part of its configurational entropy and for avoiding a trapped state along the binding pathway. Since the transient and anchoring contacts contribute to increasing the stability of the intermediate, as a corollary, the dissociation rate constant of this intermediate should be decreased, resulting in an increase of the affinity constant . The present results support our previous conclusions and provide a coherent rationale for explaining the prevalence in high-affinity ligands of (i) the two oxygen atoms found in carbonyl or sulfonyl groups of dissimilar core structures and of (ii) symmetric or pseudo-symmetric mobile groups of atoms found as non-core moieties. Another interesting aspect of the intermediate is the distortion of the flexible 80 s loop of the protein, mainly in its tip region, that promotes the accessibility to the bound state.

The splenic autoimmune response to ADAMTS13 in thrombotic thrombocytopenic purpura contains recurrent antigen-binding CDR3 motifs

AbstractAcquired thrombotic thrombocytopenic purpura (TTP) is the consequence of a severe ADAMTS13 deficiency resulting from autoantibodies inhibiting ADAMTS13 or accelerating its clearance. Despite the success of plasma exchange the risk of relapse is high. From 2 patients (A and B), splenectomized for recurrent episodes of acquired TTP, the splenic B-cell response against ADAMTS13 was characterized through generation of human monoclonal anti-ADAMTS13 autoantibodies (mAbs) by cloning an immunoglobulin G (IgG)4κ- and IgG4λ-Fab library using phage display technology and by Epstein-Barr virus transformation of switched memory B cells (CD19+/CD27+/IgG+). Sequence analysis of the anti-ADAMTS13 IgGs of both patients revealed that the VH gene use was limited in our patients to VH1-3 (55%), VH1-69 (17%), VH3-30 (7%), and VH4-28 (21%) and contained 8 unique and thus far not reported heavy-chain complementarity determining region 3 motifs, of which 4 were shared by the 2 patients. The discovery of several highly similar anti-ADAMTS13 autoantibodies in 2 unrelated TTP patients suggests that the autoimmune response is antigen driven, because the probability that such similar immunoglobulin rearrangements happen by chance is very low (<10−9).

Una iconografía del ojo en &lt;em&gt;Un chien andalou&lt;/em&gt;

This article sets out to analyse the eye motif in Un chien andalou. The eye—cut open in the film with a razor blade—has a symbolic function that is present in Bunuel’s entire filmography, where eyes are a recurrent motif: from the eyes of people who were born blind, a key character in Bunuel’s films, to the allusions to the spectator’s eyes. This article lists the eyes appearing in Bunuel’s films, and using reception theory, seeks to explain the significance of this visual symbol in the filmmaker’s work. The conclusion is that when the eye appears in a film it means that the images of the film come from the artist’s inner sources. Therefore, the eye in Luis Bunuel’s work refers to a reflection by the filmmaker about his own creative process.

The Vision of New China Suggested by the Politics of Language: Liu Shipei’s Interpretation of the “Rectification of Names” and Its Utopian Moment

This paper focuses on the “rectification of names” (zhengming 正 名), an important and recurrent motif in the writings produced by Liu Shipei 劉師培 (1884–1919) before he betrayed the anti-Qing revolution. On the one hand, Liu has argued that the Chinese signifying system should be modified in response to the challenges posed by the West. On the other hand, he also understood that, within the prevailing imperialist world order, China’s acceptance of this universal law entailed the acceptance of an inferior position vis-a-vis the dominant world powers. Liu’s interpretation of the “rectification of names” was aimed at overcoming the boundaries between the West and China, and ultimately led him to support a radical anarchist revolution. Therefore, Liu Shipei’s approach to the “rectification of names” is representative of the way in which late Qing intellectuals responded to the great clashes between the traditional and the modern, the West and the East. One might argue that the discourse surrounding the “rectification of names” brought about a moment of “origin,”—that is to say, a moment of reconstructing the relationship between names and things—the scope of which was not limited to China. In this context, the political utopia conceptualized by Liu Shipei can be regarded as one explicit form of the “rectification of names.” Thus, the different ways in which Liu Shipei, Zhang Taiyan 章太炎 (1868–1936; also known as Zhang Binglin 章炳麟), and Lu Xun approach the problem of language suggest their different visions of the future of China.

Synchronization among neuronal pools without common inputs: in vivo study.

Periodic synchronization of activity among neuronal pools has been related to substantial neural processes and information throughput in the neocortical network. However, the mechanisms of generating such periodic synchronization among distributed pools of neurons remain unclear. We hypothesize that to a large extent there is interplay between the topology of the neocortical networks and their reverberating modes of activity. The firing synchronization is governed by a nonlocal mechanism, the network delay loops, such that distant neuronal pools without common drives can be synchronized. This theoretical interplay between network topology and the synchronized mode is verified using an iterative procedure of a single intracellularly recorded neuron in vivo, imitating the dynamics of the entire network. The input is injected to the neuron via the recording electrode as current and computed from the filtered, evoked spikes of its pre-synaptic sources, previously emulated by the same neuron. In this manner we approximate subthreshold synaptic inputs from afferent neuronal pools to the neuron. Embedding the activity of these recurrent motifs in the intact brain allows us to measure the effects of connection probability, synaptic strength, and ongoing activity on the neuronal synchrony. Our in vivo experiments indicate that an initial stimulus given to a single pool is dynamically evolving into the formations of zero-lag and cluster synchronization. By applying results from theoretical models and in vitro experiments to in vivo activity in the intact brain, we support the notion that this mechanism may account for the binding activity across distributed brain areas.

Investigating the functional implications of reinforcing feedback loops in transcriptional regulatory networks.

Transcription factors (TFs) and microRNAs (miRNAs) can jointly regulate transcriptional networks in the form of recurrent circuits or motifs. A motif can be divided into a feedforward loop (FFL) and a feedback loop (FBL). Incoherent FFLs have been the recent focus due to their potential to dampen gene expression noise in maintaining physiological norms. However, a cell is not only able to manage noise but also able to exploit it during development or tumorigenesis to initiate radical transformation such as cell differentiation or metastasis. A plausible mechanism may involve reinforcing FBLs (rFBLs), which amplify changes to a sufficient level in order to complete the state transition. To study the behaviour of rFBLs, we developed a novel theoretical framework based on biochemical kinetics. The proposed rFBL follows a parsimonious design, involving two TFs and two miRNAs. A simulation study based on our model suggested that a system with rFBLs is robust to only a certain level of fluctuation but prone to a complete paradigm shift when the change exceeds a threshold level. To investigate the natural occurrence of rFBLs, we performed a rigorous network motif analysis using a recently available TF/miRNA regulatory network from the Encyclopedia of DNA Elements (ENCODE). Our analysis suggested that the rFBL is significantly depleted in the observed network. Nonetheless, we identified 9 rFBL instances. Among them, we found a double-rFBL involving three TFs SUZ12/BCLAF1/ZBTB33 and three miRNAs miR-9/19a/129-5p, which together serve as an intriguing toggle switch between nerve development and telomere maintenance. Additionally, we investigated the interactions implicated in the rFBLs using expression profiles of cancer patients from The Cancer Genome Atlas (TCGA). Together, we provided a novel and comprehensive view of the profound impacts of rFBLs and highlighted several TFs and miRNAs as the leverage points for potential therapeutic targets in cancers due to their eminent roles in the identified rFBLs.

Fedorova, Milla. Yankees in Petrograd, Bolsheviks in New York: America and Americans in Russian Literary Perception (review)

SEER, 92, 3, JULY 2014 518 literature does not reduce itself to the principle that ‘we are all the same’, a temptation that Tolstoi’s own polemical pronouncements might tend to affirm. Rather — and this is where the transnational becomes very handy indeed — Foster permits interpretation of Tolstoi as one whose notion of world literature affirms variety and difference rather than confining them to the strenuously concealed margins of a hegemonic view. In the end Foster’s engaging study makes a crucial point: that, far from being a monologist or solipsist or hegemonic universalist, Tolstoi developed an ever more nuanced recognition of the incredibly complex interplay of different influences on which any cultural product must depend. In this sense, Foster captures the slippery Tolstoi of War and Peace who argued so eloquently against viewing an event from one perspective, who claimed that events are created by reciprocal interaction in regard to which no one interaction can pretend to describe the event as a whole. To have returned this magnificently plural Tolstoi to us, as Foster has in lucid and mercifully jargon-free prose, is a substantial achievement. Clemson University Jeff Love Fedorova, Milla. Yankees in Petrograd, Bolsheviks in New York: America and Americans in Russian Literary Perception. Northern Illinois University Press, DeKalb, IL, 2013. xi + 229 pp. Appendices. Notes. Bibliography. Index. $49.00. With brief glimpses backward and forward, this book offers the first indepth study of Russian literary travelogues to America in the crucial years between the twilight of the Romanov empire and the triumph of Stalinism. That description is too narrow, however, to encompass what Fedorova actually addresses. She considers a wide swathe of materials, including fictional, poetic, essayistic and cinematic texts that depict, through Russian eyes, journeys to America and Russian-authored ‘reverse travelogues’ about American characters encountering the Soviet Union. Fedorova’s larger ambition, then, is to analyse what she describes as the Russian ‘American narrative’ in all its genres and with all its invariants and modifications in the context of Russian and Soviet cultural and technological rivalry with the United States. Fedorova’s analysis pursues two modes of approach. First, there is a synchronic account of three stages of development from pre-Revolutionary to early Soviet and Stalin-era travelogues to America. Briefly stated, there is a shift from idealistic populist encounters with an American utopia or dystopia to ideologically-driven depictions of a false paradise and capitalist hell followed later by more nuanced accounts of the United States as an imperfect REVIEWS 519 model society. Each period is epitomised by several prominent writers. The harsh disillusionment of Korolenko and Gor´kii yields to the hyperbolic denunciations of Esenin and Maiakovskii succeeded by the anecdotal and factual cross-country accounts by Pil´niak and Il´f and Petrov. Second, Fedorova launches a diachronic argument that links all three periods within a larger pattern of recurrent motifs and fixed archetypes that is said to constitute Russia’s ‘American narrative’. In this regard, an initial focus on a select set of influential literary travelogues and their dialogic relationship to one another gradually is subsumed within a more mythopoeic construct — namely, a stable Russian ‘chronotype’ of America. The scholarship that informs this study is comprehensive with regard to both primary and secondary sources. With rare exceptions, the primary texts under close scrutiny are not readily available for classroom use nor are they ‘major’ enough to figure in most academic curricula. Fedorova’s discussion lends depth to underappreciated works by Korolenko, Esenin, Pil´niak and Marietta Shaginian; she also draws attention to valuable recent Russian publications on the topic by Etkind (2001) and Arustamova (2009). Along the way, there are some surprising insights such as the differential treatment of blacks and native Americans and the recurrent theme of the ‘arrested voice’ of the monolingual Russian observer who goes unheard and ‘tongueless’ in America. Chapter five provides an interesting addendum with its enriching discussion of cinematic (Kuleshov’s Mr. West) and poetic (Marshak’s Mister Tvister) ‘reverse travelogues’ depicting fictional American travellers in the USSR. The conclusion sketches all too briefly a post-Soviet epilogue in which the Russians’ ‘otherworldly’ image of America persists; a sequel volume would be most...

Network-dosage compensation topologies as recurrent network motifs in natural gene networks.

BackgroundGlobal noise in gene expression and chromosome duplication during cell-cycle progression cause inevitable fluctuations in the effective number of copies of gene networks in cells. These indirect and direct alterations of network copy numbers have the potential to change the output or activity of a gene network. For networks whose specific activity levels are crucial for optimally maintaining cellular functions, cells need to implement mechanisms to robustly compensate the effects of network dosage fluctuations.ResultsHere, we determine the necessary conditions for generalized N-component gene networks to be network-dosage compensated and show that the compensation mechanism can robustly operate over large ranges of gene expression levels. Furthermore, we show that the conditions that are necessary for network-dosage compensation are also sufficient. Finally, using genome-wide protein-DNA and protein-protein interaction data, we search the yeast genome for the abundance of specific dosage-compensation motifs and show that a substantial percentage of the natural networks identified contain at least one dosage-compensation motif.ConclusionsOur results strengthen the hypothesis that the special network topologies that are necessary for network-dosage compensation may be recurrent network motifs in eukaryotic genomes and therefore may be an important design principle in gene network assembly in cells.

The Feminist Orientation in Edith Nesbit's Gothic Short Fiction

For a long time critically neglected or disparaged, Edith Nesbit's Gothic fiction is beginning to receive the scholarly attention it deserves. This essay extends analysis beyond the much anthologized “Man-Size in Marble” (1893) to argue that a feminist orientation is in evidence more widely in her works of supernatural short fiction. A preoccupation with gender is discernible in several stories that offer distinct gender critiques, and in further tales through imagery of the dead female body and the female revenant, as well as through the recurrent character motifs of the female Cassandra and the male Frankenstein. The essay also argues that the anti-vivisectionism of several stories is an aspect of this feminist orientation. The article recognizes Nesbit as being a problematic figure for scholarly attempts to reclaim feminist authors, since she herself evinced ambivalence about the women's movement and the New Woman, but argues that the unleashing of Nesbit's most counter-hegemonic impulses in her Gothic writings points to the political significance of this generic form, making Nesbit a figure of substantial interest for scholars working on women's supernatural fiction.

Editor’s Introduction: Jorge Luis Borges and the Jewish Question

Editor’s Introduction:Jorge Luis Borges and the Jewish Question David N. Myers Keywords Jorge Luis Borges, Judaism, Holocaust One of the greatest writers of the twentieth century—and indeed one of the greatest never to receive a Nobel Prize in Literature—was the Argentine Jorge Luis Borges (1899–1986). Borges was a master innovator in style, a compelling and ceaselessly inventive storyteller, and an unusually probing philosophical writer. He was also a deeply committed citizen of his country and the world, whose fiction engaged with major political and ethical concerns of the day. Despite a brief and atypical period in the 1970s in which he expressed sympathy for the dictatorial regimes of Jorge Rafael Videla in Argentina and Augusto Pinochet in Chile, Borges tended to find himself on the right side of history, using his extraordinary writerly talent to strip away the façade of toxic political ideologies. Among his chief targets were the intersecting currents of fascism and anti-Semitism, which he observed with growing trepidation in the 1920s and 1930s. Part of what animated Borges’s critique of anti-Semitism was a deep and almost obsessive sense of connection to Jews and Judaism. This connection was first nurtured in Geneva, where he moved with his family in 1914 and where he gained his first formative insights into Jewish literature and culture, in part through a close friendship with two Jewish boys. From that point forward, Borges felt a powerful bond to the Jewish tradition—to the point that fascist sympathizers back in his native Argentine accused him of being Jewish. Rather than curb or conceal his feelings, he responded to his fascist critics in Argentina in 1934 with courageous directness in an essay, “Yo, Judio” (I, a Jew). He was not in fact Jewish, but he declared that he wished he were, given his heartfelt admiration for Jews and Judaism. Borges’s sense of identification was based on not only his adolescent friendships but also an engagement with Jewish history and thought that was neither superficial nor fleeting. Concomitant with his sharp condemnation [End Page 335] of anti-Semitism, Borges developed a deep interest in the Jewish mystical tradition of the Kabbalah. His 1932 essay “A Defense of the Kabbalah” launched a lifetime of investigation into the subject, nurtured by his voracious reading of modern scholars, including and especially his friend in Jerusalem, Gershom Scholem. In “A Defense of Kabbalah,” Borges admitted to his “almost complete ignorance of the Hebrew language” but further elaborated that he was motivated to delve into the esoteric Jewish tradition by “my desire to defend not the doctrine but rather the hermeneutical or cryptographic procedures that lead to it.” Perhaps his most renowned fictional engagement with those procedures came in his story “El Aleph” (The Aleph), from 1945. Attuned to the great symbolic importance that kabbalists place on the Hebrew letters in their cosmological universe, especially the first (aleph), Borges depicts a mysterious phenomenon, an “aleph” described as a lens that opens up perspectives on the entire universe, from all possible angles at once. Through it one peers into infinity—a recurrent motif in Borges’s writing, as well as a central concept in the Kabbalah, denoting the boundless power of God. Gazing into infinity, or grasping the ultimate meaning of letters of the Hebrew alphabet, were not simple matters. They were tasks burdened by the inherent limitations of the human mind. But those limitations inspired, in turn, manifold waves of interpretive ingenuity in hopes of gaining a proximate understanding of the infinite. Borges seized on that relentless quest to grasp that which could not be fully grasped to reflect not only on the Kabbalah but on the nature of the world more broadly. His fiction was animated by the desire for the ever elusive goal of epistemological certainty, resulting in the creation of a dream-like fantastical world in which one’s sense of reality was altogether shaken. Both the Kabbalah and, to a great extent, the Jewish condition at large gave Borges a language to represent this world. It is in this regard that Borges has become a figure of interest in and to the field of Jewish studies...

RNA self-assembly and RNA nanotechnology.

CONSPECTUS: Nanotechnology's central goal involves the direct control of matter at the molecular nanometer scale to build nanofactories, nanomachines, and other devices for potential applications including electronics, alternative fuels, and medicine. In this regard, the nascent use of nucleic acids as a material to coordinate the precise arrangements of specific molecules marked an important milestone in the relatively recent history of nanotechnology. While DNA served as the pioneer building material in nucleic acid nanotechnology, RNA continues to emerge as viable alternative material with its own distinct advantages for nanoconstruction. Several complementary assembly strategies have been used to build a diverse set of RNA nanostructures having unique structural attributes and the ability to self-assemble in a highly programmable and controlled manner. Of the different strategies, the architectonics approach uniquely endeavors to understand integrated structural RNA architectures through the arrangement of their characteristic structural building blocks. Viewed through this lens, it becomes apparent that nature routinely uses thermodynamically stable, recurrent modular motifs from natural RNA molecules to generate unique and more complex programmable structures. With the design principles found in natural structures, a number of synthetic RNAs have been constructed. The synthetic nanostructures constructed to date have provided, in addition to affording essential insights into RNA design, important platforms to characterize and validate the structural self-folding and assembly properties of RNA modules or building blocks. Furthermore, RNA nanoparticles have shown great promise for applications in nanomedicine and RNA-based therapeutics. Nevertheless, the synthetic RNA architectures achieved thus far consist largely of static, rigid particles that are still far from matching the structural and functional complexity of natural responsive structural elements such as the ribosome, large ribozymes, and riboswitches. Thus, the next step in synthetic RNA design will involve new ways to implement these same types of dynamic and responsive architectures into nanostructures functioning as real nanomachines in and outside the cell. RNA nanotechnology will likely garner broader utility and influence with a greater focus on the interplay between thermodynamic and kinetic influences on RNA self-assembly and using natural RNAs as guiding principles.