‘To mask, by slight differences in the manner, a virtual identity in the substance’: Berlioz's Symphonie fantastique and De Quincey's ‘Confessions of an English Opium-Eater’

De Quincey's ‘Confessions of an English Opium-Eater’ (1821) and Berlioz's Symphonie Fantastique (1830) both take an unusual form in which seemingly digressive wanderings coalesce around an obsessively repeated motif: in both cases, an idealized young woman whose evasive near-presence is continually suggested through minimally varied repetitions of formal elements the artist associates with her. Although others have noted similarities between the two works – chiefly that both foreground a young artist-protagonist's opium visions – the works' structural parallels have been little discussed. This essay argues that an analysis of the commonalities between these strikingly similar formal innovations supplements previous arguments in significant ways, illuminating the oeuvres of both Berlioz and De Quincey as well as aspects of Romantic formal experimentation in general.

BRCA2 binding through a cryptic repeated motif to HSF2BP oligomers does not impact meiotic recombination

BRCA2 and its interactors are required for meiotic homologous recombination (HR) and fertility. Loss of HSF2BP, a BRCA2 interactor, disrupts HR during spermatogenesis. We test the model postulating that HSF2BP localizes BRCA2 to meiotic HR sites, by solving the crystal structure of the BRCA2 fragment in complex with dimeric armadillo domain (ARM) of HSF2BP and disrupting this interaction in a mouse model. This reveals a repeated 23 amino acid motif in BRCA2, each binding the same conserved surface of one ARM domain. In the complex, two BRCA2 fragments hold together two ARM dimers, through a large interface responsible for the nanomolar affinity — the strongest interaction involving BRCA2 measured so far. Deleting exon 12, encoding the first repeat, from mBrca2 disrupts BRCA2 binding to HSF2BP, but does not phenocopy HSF2BP loss. Thus, results herein suggest that the high-affinity oligomerization-inducing BRCA2-HSF2BP interaction is not required for RAD51 and DMC1 recombinase localization in meiotic HR.

Agglutination Activity of Fasciola gigantica DM9-1, a Mannose-Binding Lectin

The DM9 domain is a protein unit of 60-75 amino acids that has been first detected in the fruit fly <i>Drosophila</i> as a repeated motif of unknown function. Recent research on proteins carrying DM9 domains in the mosquito <i>Anopheles gambiae</i> and the oyster <i>Crassostrea gigas</i> indicated an association with the uptake of microbial organisms. Likewise, in the trematode <i>Fasciola gigantica</i> DM9-1 showed intracellular relocalization following microbial, heat and drug stress. In the present research, we show that FgDM9-1 is a lectin with a novel mannose-binding site that has been recently described for the protein CGL1 of <i>Crassostrea gigas</i>. This property allowed FgDM9-1 to agglutinate gram-positive and -negative bacteria with appropriate cell surface glycosylation patterns. Furthermore, FgDM9-1 caused hemagglutination across all ABO blood group phenotypes. It is speculated that the parenchymal located FgDM9-1 has a role in cellular processes that involve the transport of mannose-carrying molecules in the parenchymal cells of the parasite.

A cryptic BRCA2 repeated motif binds to HSF2BP oligomers with no impact on meiotic recombination

BRCA2 plays a prominent role in meiotic homologous recombination (HR). Loss of BRCA2 or several of its meiotic partners causes fertility defects. One of these partners, HSF2BP, was recently discovered as expressed physiologically in germline and ectopically produced in cancer cells. It has an N-terminal coiled coil motif involved in direct binding to the protein BRME1, and both HSF2BP and BRME1 are essential for meiotic HR during spermatogenesis. It also interacts through its C-terminal Armadillo (ARM) domain with a conserved region of BRCA2 of unknown function. We analyzed the structural properties and functional consequences of the BRCA2-HSF2BP interaction and tested the emerging model of its involvement in meiosis. We solved the crystal structure of the complex between the BRCA2 fragment that is disordered in solution and the HSF2BP dimeric ARM domain. This revealed two previously unrecognized BRCA2 repeats that each interact with one ARM monomer from two different dimers. BRCA2 binding triggers ARM tetramerization, resulting in a complex containing two BRCA2 fragments connecting two ARM dimers. The 3D structures of the BRCA2 repeats are superimposable, revealing conserved contacts between the BRCA2 residues defining the repeats and the HSF2BP residues lining the groove of the ARM. This large interface is responsible for the nanomolar affinity of the interaction, significantly stronger than any other measured interaction involving BRCA2. Deleting exon 12 from Brca2, encoding the first repeat, disrupted BRCA2 binding to HSF2BP in vitro and in cells. However, Brca2Δ12/Δ12 mice with the same deletion were fertile and did not show any meiotic defects, contrary to the prediction from the model positing that HSF2BP acts as a meiotic localizer of BRCA2. We conclude that the high-affinity interaction between BRCA2 and HSF2BP and the resulting HSF2BP oligomerization are not required for RAD51 and DMC1 recombinase localization to meiotic double strand breaks and for productive meiotic HR.

Finding and extending ancient simple sequence repeat-derived regions in the human genome

BackgroundPreviously, 3% of the human genome has been annotated as simple sequence repeats (SSRs), similar to the proportion annotated as protein coding. The origin of much of the genome is not well annotated, however, and some of the unidentified regions are likely to be ancient SSR-derived regions not identified by current methods. The identification of these regions is complicated because SSRs appear to evolve through complex cycles of expansion and contraction, often interrupted by mutations that alter both the repeated motif and mutation rate. We applied an empirical, kmer-based, approach to identify genome regions that are likely derived from SSRs.ResultsThe sequences flanking annotated SSRs are enriched for similar sequences and for SSRs with similar motifs, suggesting that the evolutionary remains of SSR activity abound in regions near obvious SSRs. Using our previously described P-clouds approach, we identified ‘SSR-clouds’, groups of similar kmers (or ‘oligos’) that are enriched near a training set of unbroken SSR loci, and then used the SSR-clouds to detect likely SSR-derived regions throughout the genome.ConclusionsOur analysis indicates that the amount of likely SSR-derived sequence in the human genome is 6.77%, over twice as much as previous estimates, including millions of newly identified ancient SSR-derived loci. SSR-clouds identified poly-A sequences adjacent to transposable element termini in over 74% of the oldest class ofAlu(roughly,AluJ), validating the sensitivity of the approach. Poly-A’s annotated by SSR-clouds also had a length distribution that was more consistent with their poly-A origins, with mean about 35 bp even in olderAlus. This work demonstrate that the high sensitivity provided by SSR-Clouds improves the detection of SSR-derived regions and will enable deeper analysis of how decaying repeats contribute to genome structure.

“And God Remembered:” Barrenness and Hope in Genesis

For a book of beginnings,[1] Genesis is ironically replete with beginnings that almost were not. Indeed, the motif of the barren woman, the woman unable to produce a new beginning in the form of a child, is so common it becomes almost redundant in the narrative. What is most characteristic of God in Genesis—to be a fertile source of life[2]—is painfully denied the matriarchs. This pain is heightened by the steadily increasing tension in the text regarding the fulfillment of God’s covenant with Abraham. God’s promise to Abraham that he will be “a great nation”[3] with many descendants requires Abraham to have offspring in order for it to be fulfilled, yet nature repeatedly opposes the fulfillment of the promise. Through the repeated motif of the barrenness of the matriarchs, the reader is inducted into the struggle of the primary characters to have faith in a God “whose promise tarries too long.”[4] This paper examines the motif of barrenness in Genesis in order to argue that the barrenness of the matriarchs functions literarily as a “type-scene” that is meant to signify a complex series of messages in a few simple plot details. The motif also functions theologically. Through negative contrast, the barren wombs recall the goodness of creation as well as God’s nature as the fertile giver of life. Furthermore, the repetition of the motif in Genesis, far from indicating a lack of creativity on the part of the redactors, instead serves to inculcate through repetition an expectation in the reader that God will do what God always does in this situation—namely, bring life from death. The motif’s power is in its predictability. In this way, the motif of barrenness in Genesis is a tutor in the school of hope. [1] Jon D. Levenson. “Genesis: Introduction,” Jewish Study Bible, 8. [2] As Phyllis Trible notes in God and the Rhetoric of Sexuality (Philadelphia: Fortress Press, 1978), “making is a familiar activity for God,” 90. [3] Genesis 12:2, Jewish Study Bible, 30. [4] Victor Hamilton, The Book of Genesis: Chapter 1-17 (Grand Rapids, MI: W.B. Eerdmans, 1990), 151.

ON COUNTING THE FREQUENCY DISTRIBUTION OF STRING MOTIFS IN MOLECULAR SEQUENCES

This work investigates frequency distributions of strings within a text. The mathematical derivation accounts for variable alphabet size, character probabilities, and string/text lengths, under both the Bernoullian and the Markovian model for string generation. The analysis is limited to the set of non-clumpable strings, that cannot overlap with themselves. Two formulae (exact and approximated) are derived, calculating the frequency distribution of a string of length m found inside a text of length n (with m < n). The approximated formula has a constant complexity (in contrast to an exponential complexity of the exact) and makes it applicable to very long texts. The proposed formulae were applied to analyze string frequencies in a portion of the human genome, and to recalculate frequencies of known repeated motif within genes, associated to genetic diseases. A comparison with state-of-the-art methods was provided. The formulae presented here can be of use in the statistical evaluation of specific motif frequencies within very long texts (e.g. genes or genomes) and help in characterizing motifs in pathologic conditions.

The ‘Blind Space’ that Lies Beyond the Frame: and

‘Blind space’ is a filmic term more widely referred to as ‘off-screen space’ in cinematography. It refers to the unseen area outside the frame of the screen and beyond the margins of the visible. The effects of blind space on the film viewer are similar to those of mise en abîme on the reader of narrative fiction. The term mise en abîme is here used in its most literal sense to refer to the determination of meaning outside of a normative frame of reference. This article explores the visual implications of the ‘out-of-frame’ in two young adult novels, Anne Provoost's Falling (1997) and John Boyne's The Boy in the Striped Pyjamas (2006). Blind space in these texts, in which the Holocaust is theme or sub-theme, is the space in which the cultural minorities reside. A foregrounding of the blind space thus calls for increased social awareness. In both novels a repeated motif of impenetrable walls, barriers and borders highlights the need for the apolitical protagonists to turn their gazes towards the blind spaces and to restore the marginalised occupants with visibility and voice. Blind space here becomes the interpretative key with which to unlock the texts' call for multiracial acceptance.