bluuebunny/crossref_metadata_2025 huggingface dataset:
Visualisation of chicken macrophages using transgenic reporter genes: insights into the development of the avian macrophage lineage
Authors: Balic Adam , Garcia-Morales Carla , Vervelde Lonneke , Gilhooley Hazel , Sherman Adrian , Garceau Valerie , Gutowska Maria W. , Burt David W. , Kaiser Pete , Hume David A. , Sang Helen M.
Published: July 2014

We have generated the first transgenic chickens in which reporter genes are expressed in a specific immune cell lineage, based upon control elements of the colony stimulating factor 1 receptor (CSF1R) locus. The Fms intronic regulatory element (FIRE) within CSF1R is shown to be highly conserved in amniotes and absolutely required for myeloid-restricted expression of fluorescent reporter genes. As in mammals, CSF1R-reporter genes were specifically expressed at high levels in cells of the macrophage lineage and at a much lower level in granulocytes. The cell lineage specificity of reporter gene expression was confirmed by demonstration of coincident expression with the endogenous CSF1R protein. In transgenic birds, expression of the reporter gene provided a defined marker for macrophage-lineage cells, identifying the earliest stages in the yolk sac, throughout embryonic development and in all adult tissues. The reporter genes permit detailed and dynamic visualisation of embryonic chicken macrophages. Chicken embryonic macrophages are not recruited to incisional wounds, but are able to recognise and phagocytose microbial antigens.
ECM stiffness regulates glial migration in Drosophila and mammalian glioma models
Authors: Kim Su Na , Jeibmann Astrid , Halama Kathrin , Witte Hanna Teresa , Wälte Mike , Matzat Till , Schillers Hermann , Faber Cornelius , Senner Volker , Paulus Werner , Klämbt Christian
Published: July 2014

Cell migration is an important feature of glial cells. Here, we used the Drosophila eye disc to decipher the molecular network controlling glial migration. We stimulated glial motility by pan-glial PDGF receptor (PVR) activation and identified several genes acting downstream of PVR. Drosophila lox is a non-essential gene encoding a secreted protein that stiffens the extracellular matrix (ECM). Glial-specific knockdown of Integrin results in ECM softening. Moreover, we show that lox expression is regulated by Integrin signaling and vice versa, suggesting that a positive-feedback loop ensures a rigid ECM in the vicinity of migrating cells. The general implication of this model was tested in a mammalian glioma model, where a Lox-specific inhibitor unraveled a clear impact of ECM rigidity in glioma cell migration.
Kinesin-II recruits Armadillo and Dishevelled for Wingless signaling in Drosophila
Authors: Vuong Linh Thuong , Mukhopadhyay Bibhash , Choi Kwang-Wook
Published: July 2014

Wingless (Wg)/Wnt signaling is fundamental in metazoan development. Armadillo (Arm)/β-catenin and Dishevelled (Dsh) are key components of Wnt signal transduction. Recent studies suggest that intracellular trafficking of Wnt signaling components is important, but underlying mechanisms are not well known. Here, we show that Klp64D, the Drosophila homolog of Kif3A kinesin II subunit, is required for Wg signaling by regulating Arm during wing development. Mutations in klp64D or RNAi cause wing notching and loss of Wg target gene expression. The wing notching phenotype by Klp64D knockdown is suppressed by activated Arm but not by Dsh, suggesting that Klp64D is required for Arm function. Furthermore, klp64D and arm mutants show synergistic genetic interaction. Consistent with this genetic interaction, Klp64D directly binds to the Arm repeat domain of Arm and can recruit Dsh in the presence of Arm. Overexpression of Klp64D mutated in the motor domain causes dominant wing notching, indicating the importance of the motor activity. Klp64D shows subcellular localization to intracellular vesicles overlapping with Arm and Dsh. In klp64D mutants, Arm is abnormally accumulated in vesicular structures including Golgi, suggesting that intracellular trafficking of Arm is affected. Human KIF3A can also bind β-catenin and rescue klp64D RNAi phenotypes. Taken together, we propose that Klp64D is essential for Wg signaling by trafficking of Arm via the formation of a conserved complex with Arm.
Leading and trailing cells cooperate in collective migration of the zebrafish posterior lateral line primordium
Authors: Dalle Nogare Damian , Somers Katherine , Rao Swetha , Matsuda Miho , Reichman-Fried Michal , Raz Erez , Chitnis Ajay B.
Published: July 2014

Collective migration of cells in the zebrafish posterior lateral line primordium (PLLp) along a path defined by Cxcl12a expression depends on Cxcr4b receptors in leading cells and on Cxcr7b in trailing cells. Cxcr7b-mediated degradation of Cxcl12a by trailing cells generates a local gradient of Cxcl12a that guides PLLp migration. Agent-based computer models were built to explore how a polarized response to Cxcl12a, mediated by Cxcr4b in leading cells and prevented by Cxcr7b in trailing cells, determines unidirectional migration of the PLLp. These chemokine signaling-based models effectively recapitulate many behaviors of the PLLp and provide potential explanations for the characteristic behaviors that emerge when the PLLp is severed by laser to generate leading and trailing fragments. As predicted by our models, the bilateral stretching of the leading fragment is lost when chemokine signaling is blocked in the PLLp. However, movement of the trailing fragment toward the leading cells, which was also thought to be chemokine dependent, persists. This suggested that a chemokine-independent mechanism, not accounted for in our models, is responsible for this behavior. Further investigation of trailing cell behavior shows that their movement toward leading cells depends on FGF signaling and it can be re-oriented by exogenous FGF sources. Together, our observations reveal the simple yet elegant manner in which leading and trailing cells coordinate migration; while leading cells steer PLLp migration by following chemokine cues, cells further back play follow-the-leader as they migrate toward FGFs produced by leading cells.
Auxin represses stomatal development in dark-grown seedlings via Aux/IAA proteins
Authors: Balcerowicz Martin , Ranjan Aashish , Rupprecht Laura , Fiene Gabriele , Hoecker Ute
Published: July 2014

Stomatal development is tightly regulated through internal and external factors that are integrated by a complex signalling network. Light represents an external factor that strongly promotes stomata formation. Here, we show that auxin-resistant aux/iaa mutants, e.g. axr3-1, exhibit a de-repression of stomata differentiation in dark-grown seedlings. The higher stomatal index in dark-grown axr3-1 mutants when compared with the wild type is due to increased cell division in the stomatal lineage. Excessive stomata in dark-grown seedlings were also observed in mutants defective in auxin biosynthesis or auxin perception and in seedlings treated with the polar auxin transport inhibitor NPA. Consistent with these findings, exogenous auxin repressed stomata formation in light-grown seedlings. Taken together, these results indicate that auxin is a negative regulator of stomatal development in dark-grown seedlings. Epistasis analysis revealed that axr3-1 acts genetically upstream of the bHLH transcription factors SPCH, MUTE and FAMA, as well as the YDA MAP kinase cascade, but in parallel with the repressor of photomorphogenesis COP1 and the receptor-like protein TMM. The effect of exogenous auxin required the ER family of leucine-rich repeat receptor-like kinases, suggesting that auxin acts at least in part through the ER family. Expression of axr3-1 in the stomatal lineage was insufficient to alter the stomatal index, implying that cell-cell communication is necessary to mediate the effect of auxin. In summary, our results show that auxin signalling contributes to the suppression of stomatal differentiation observed in dark-grown seedlings.
Visualization of the Drosophila dKeap1-CncC interaction on chromatin illumines cooperative, xenobiotic-specific gene activation
Authors: Deng Huai , Kerppola Tom K.
Published: July 2014

Interactions among transcription factors control their physiological functions by regulating their binding specificities and transcriptional activities. We implement a strategy to visualize directly the genomic loci that are bound by multi-protein complexes in single cells in Drosophila. This method is based on bimolecular fluorescence complementation (BiFC) analysis of protein interactions on polytene chromosomes. Drosophila Keap1 (dKeap1)-CncC complexes localized to the nucleus and bound chromatin loci that were not bound preferentially by dKeap1 or CncC when they were expressed separately. dKeap1 and CncC binding at these loci was enhanced by phenobarbital, but not by tert-butylhydroquinone (tBHQ) or paraquat. Endogenous dKeap1 and CncC activated transcription of the Jheh (Jheh1, Jheh2, Jheh3) and dKeap1 genes at these loci, whereas CncC alone activated other xenobiotic response genes. Ectopic dKeap1 expression increased CncC binding at the Jheh and dKeap1 gene loci and activated their transcription, whereas dKeap1 inhibited CncC binding at other xenobiotic response gene loci and suppressed their transcription. The combinatorial chromatin-binding specificities and transcriptional activities of dKeap1-CncC complexes mediated the selective activation of different sets of genes by different xenobiotic compounds, in part through feed-forward activation of dKeap1 transcription.
Major transcriptome re-organisation and abrupt changes in signalling, cell cycle and chromatin regulation at neural differentiationin vivo
Authors: Olivera-Martinez Isabel , Schurch Nick , Li Roman A. , Song Junfang , Halley Pamela A. , Das Raman M. , Burt Dave W. , Barton Geoffrey J. , Storey Kate G.
Published: July 2014

Here, we exploit the spatial separation of temporal events of neural differentiation in the elongating chick body axis to provide the first analysis of transcriptome change in progressively more differentiated neural cell populations in vivo. Microarray data, validated against direct RNA sequencing, identified: (1) a gene cohort characteristic of the multi-potent stem zone epiblast, which contains neuro-mesodermal progenitors that progressively generate the spinal cord; (2) a major transcriptome re-organisation as cells then adopt a neural fate; and (3) increasing diversity as neural patterning and neuron production begin. Focussing on the transition from multi-potent to neural state cells, we capture changes in major signalling pathways, uncover novel Wnt and Notch signalling dynamics, and implicate new pathways (mevalonate pathway/steroid biogenesis and TGFβ). This analysis further predicts changes in cellular processes, cell cycle, RNA-processing and protein turnover as cells acquire neural fate. We show that these changes are conserved across species and provide biological evidence for reduced proteasome efficiency and a novel lengthening of S phase. This latter step may provide time for epigenetic events to mediate large-scale transcriptome re-organisation; consistent with this, we uncover simultaneous downregulation of major chromatin modifiers as the neural programme is established. We further demonstrate that transcription of one such gene, HDAC1, is dependent on FGF signalling, making a novel link between signals that control neural differentiation and transcription of a core regulator of chromatin organisation. Our work implicates new signalling pathways and dynamics, cellular processes and epigenetic modifiers in neural differentiation in vivo, identifying multiple new potential cellular and molecular mechanisms that direct differentiation.
Age-dependent pattern of cerebellar susceptibility to bilirubin neurotoxicityin vivo
Authors: Bortolussi Giulia , Baj Gabriele , Vodret Simone , Viviani Giulia , Bittolo Tamara , Muro Andrés F.
Published: July 2014

Neonatal jaundice is caused by high levels of unconjugated bilirubin. It is usually a temporary condition due to delayed induction of Ugt1a1, which conjugates bilirubin in the liver. To reduce bilirubin levels, affected babies are exposed to phototherapy (PT), which converts toxic bilirubin into water-soluble photoisomers, readily excreted out. However, in some cases uncontrolled hyperbilirubinemia leads to neurotoxicity. To study the mechanisms of bilirubin-induced neurological damage (BIND) in vivo we generated a mouse model lacking the Ugt1a1 protein and, consequently, mutant mice developed jaundice as early as 36 h after birth. The mutation was transferred into two genetic backgrounds (C57Bl/6 and FVB/NJ). We exposed mutant mice to PT for different periods and analyzed the resulting phenotypes from the molecular, histological and behavioral points of view. Severity of BIND was associated with the genetic background, with 50% survival of C57Bl/6-Ugt1-/- mutant mice at postnatal day 5 (P5) and at P11 for FVB/NJ-Ugt1-/- mice. Life-long exposure to PT prevented cerebellar architecture alterations and rescued neuronal damage in FVB/NJ-Ugt1-/- mice, but not in C57Bl/6 ones. Survival of FVB/NJ-Ugt1-/- mice was directly related to the extent of PT treatment. PT treatment of FVB/NJ-Ugt1-/- mice from P0 to P8 did not prevent bilirubin-induced reduction in dendritic arborization and spine density of Purkinje cells. Moreover, PT treatment from P8 to P20 did not rescue bilirubin-induced neurological damage accumulated up to P8. However, PT treatment administered in the time-window P0-P15 was sufficient to obtain full rescue of cerebellar damage and motor impairment in FVB/NJ-Ugt1-/- mice. The possibility to modulate the severity of the phenotype by PT makes the FVB/NJ-Ugt1-/- mice an excellent and versatile model to study bilirubin neurotoxicity, the role of modifier genes, alternative therapies and cerebellar development during high-bilirubin conditions.
A hierarchy of factors influence discontinuous gas exchange in the grasshopper Paracinema tricolor (Orthoptera: Acrididae)
Authors: Groenewald Berlizé , Chown Steven L. , Terblanche John S.
Published: July 2014

The evolutionary origin and maintenance of discontinuous gas exchange (DGE) in tracheate arthropods are poorly understood and highly controversial. We investigated prioritisation of abiotic factors in the gas exchange control cascade by examining oxygen, water and haemolymph pH regulation in the grasshopper Paracinema tricolor. Using a full-factorial design, grasshoppers were acclimated to hypoxic or hyperoxic (5%O2, 40%O2) gas conditions, or dehydrated or hydrated, whereafter their CO2 release was measured under a range of O2 and relative humidity (RH) conditions (5%, 21%, 40%O2 and 5%, 60%, 90%RH). DGE was significantly less common in grasshoppers acclimated to dehydrating conditions compared to the other acclimations (hypoxia=98%; hyperoxia=100%; hydrated=100%; dehydrated=67%). The dehydrated acclimation resulted in a significant decrease in haemolymph pH from 7.0 ± 0.3 to 6.6 ± 0.1 (mean ± standard deviation, p=0.018) and also significantly increased the O-phase duration under 5%O2 treatment conditions (5%O2=44.1 ± 29.3 min; 40%O2=15.8 ± 8.0 min; 5%RH=17.8 ± 1.3 min; 60%RH=24.0 ± 9.7 min; 90%RH=20.6 ± 8.9 min (mean ± standard deviation)). The observed acidosis could potentially explain the extension of the O-phase under low RH conditions, when it would perhaps seem more useful to reduce the O-phase to lower respiratory water loss. The results confirm that DGE occurrence and modulation is affected by multiple abiotic factors. A hierarchical framework for abiotic factors influencing DGE is proposed in which the following stressors are prioritised in decreasing order of importance: oxygen supply; CO2 excretion and pH modulation; oxidative damage protection and water savings.
Paracellular nutrient absorption is higher in bats than rodents: integrating from intact animals to the molecular level
Authors: Price Edwin R. , Rott Katherine H. , Caviedes-Vidal Enrique , Karasov William H.
Published: July 2014

Flying vertebrates have been hypothesized to rely heavily on paracellular absorption of nutrients to compensate for having smaller intestines than non-flyers. We tested this hypothesis in an insectivorous bat (Myotis lucifugus) and two insect-eating rodents (Onychomys leucogaster and Peromyscus leucopus). In intact animals, the fractional absorption of orally dosed L-arabinose (Mr 150) was 82% in M. lucifugus, which was more than twice that of the rodents. Absorption of creatinine (Mr 113) was greater than 50% for all species and did not differ between M. lucifugus and the rodents. We also conducted intestinal luminal perfusions on anesthetized animals. Absorption of L-arabinose per nominal surface area in M. lucifugus was nearly double that of the rodents, while absorption of creatinine was not different among species. Using an everted sleeve preparation, we demonstrated that high concentrations of L-arabinose and creatinine did not inhibit their own uptake, validating their use as passive, paracellular probes. Histological measurements indicated that M. lucifugus has more cells, and presumably more tight junctions, per nominal surface area than P. leucopus. This seems unlikely to explain entirely the higher absorption of L-arabinose in M. lucifugus during perfusions, because L-arabinose absorption normalized to the number of enterocytes was still double that of P. leucopus. As an alternative, we investigated tight junction gene expression. M. lucifugus had higher expression of claudin-1 and -15, and lower expression of claudin-2 relative to P. leucopus. Expression of claudin-7 and occludin did not differ among species. Taken together, our results support the hypothesis that bats have evolved higher paracellular nutrient absorption than non-flying animals, and that this phenomenon might be driven by both histological characteristics and differences in tight-junction gene expression.
Effects of field-realistic doses of glyphosate on honeybee appetitive behaviour
Authors: Herbert Lucila H. , Vazquez Diego E. , Arenas Andres , Farina Walter M.
Published: July 2014

Glyphosate (GLY) is a broad spectrum herbicide used for weed control. Presently, sub-lethal impact of GLY on non-target organisms such as insect pollinators has not been evaluated yet. Apis mellifera is the main pollinator in agricultural environments and a well-known model for behavioural research. Moreover, honeybees are accurate biosensors of environmental pollutants and their appetitive behavioural response is a suitable tool to test sub-lethal effects of agrochemicals. We studied the effects of field-realistic doses of GLY on honeybees exposed chronically or acutely to it. We focused on sucrose sensitivity, elemental and non-elemental associative olfactory conditioning of the proboscis extension response (PER) and on foraging related behaviour. We found a reduced sensitivity to sucrose and learning performance for the groups chronically exposed to GLY concentrations within the range of recommended doses. When olfactory PER conditioning was performed with sucrose reward with the same GLY concentrations (acute exposure), elemental learning and short-term memory retention decreased significantly compared to controls. Non-elemental associative learning was also impaired by an acute exposure to GLY traces. Altogether, these results imply that GLY at concentrations found in agro-ecosystems due to standard spraying can reduce sensitivity to nectar reward and impair associative learning in honeybees. However, no effect on foraging related behaviour was found. Therefore, we speculate that successful forager bees could become a source of constant inflow of nectar with GLY traces that could then be distributed among nest mates, stored in the hive and have long-term negative consequences on colony performance.
New Brazilian species of Archisotoma Linnaniemi, 1912 (Collembola: Isotomidae)
Authors: Neves Ana Carolina Da Rocha , Mendonça Maria Cleide
Published: July 2014

A new species of Archisotoma Linnaniemi, 1912 is described and illustrated based on material from littoral sand of Praia do Sossego beach, Niterói municipality, Rio de Janeiro State, Brazil. The new species Archisotoma arariboia sp.nov., the second of the genus described from Brazil, can be distinguished from its congeners by a set of characters: 6+6 eyes, maxillary capitulum unidentate and subequal to internal lamellae, 10 posterior chaetae on manubrium, 4–5 chaetae between the anterior trichobothria and lastly by 1 thick and curved chaetae on trochanter and femur of leg III and 1–2 on femur and 1–2 on tibiotarsus of leg I.
Listen to Nodes of Empire: Speech and Whiteness in Victorian Hawker’s License Courts
Authors: Rhook Nadia
Published: July 2014

The late nineteenth century saw a wave of Indian, Syrian and Afghan immigrants arrive in Victoria, Australia, many of whom took up the highly mobile and audible occupation of hawking. New transnational and Imperial histories have illuminated the racially circumscribed mobility of colonial and Imperial subjects in traveling in and across Empire(s). In this article I conceive the Hawker’s License Courts of colonial Victoria as linguistic “nodes” where met subjects from locales in and beyond the British Empire. I argue that further than studying the mobility of colonial subjects, and of Indian hawkers in Victoria in particular, focusing on the speech uttered by hawkers demonstrates the importance of studying the linguistic colonial past. Doing so brings into focus the spatially located processes by which Whiteness and English language ability were gaining affinity in the late nineteenth century.
Following the “Hippie Sahibs”: Colonial cultures of travel and the Hippie Trail
Authors: Sobocinska Agnieszka
Published: July 2014

Imperial attitudes and colonial cultures persisted long beyond the period of formal colonisation. This article investigates how colonial attitudes were translated into the postcolonial context within the “alternative” subculture of travel and tourism in South and Southeast Asia. It argues that colonial-era attitudes were translated into the culture of “alternative” tourism through the dual conduits of the Oxford-Cambridge Far Eastern Expedition and the Hippie Trail. The genealogy suggested in this article, from imperial exploration, through the translated mid-points of the Expedition and the Hippie Trail to contemporary “alternative” travel, points to the enduring connections between tourism and imperialism.
“On the Side of Law and Order”: Indigenous aides to the mounted police on the settler frontiers of Australia and Canada
Authors: Nettelbeck Amanda
Published: July 2014

The history of colonial policing has received considerable scholarly attention in terms of its function to extend and consolidate the legal jurisdiction of British rule over colonised territories and populations. This paper compares some of the complex roles played by Indigenous people who were employed primarily as “trackers” and “scouts” within mounted police forces on Australia’s and Canada’s settler frontiers. A comparative picture of indigenous participation in policing reveals parallels in colonial decision-making that went beyond local conditions, but also illuminates the different pressures of local conditions which affected the value of Indigenous auxiliaries to mounted police. These not only provide insight into the motivations of colonial authorities in enlisting indigenous people into policing networks, but also into how Indigenous people influenced the rule of law into which they were co-opted.
“A Danger Which More or Less Threatens Us All”: Yellow fever and the politics of disease control in Senegal 1890–1914
Authors: Strother Christian
Published: July 2014

Prior to 1900, the colony of Senegal had suffered from periodic epidemics of yellow fever. In an attempt to combat the disease, the government of Senegal began to enact new legislation to prevent the spread of epidemics. The government hoped that these new laws would allow them to control yellow fever epidemics without hurting the economic viability of the colony, but they found that the new laws created new challenges. Within the first decade of the passage of the new legislation a series of formal complaints and court cases would challenge sanitation laws and test the limits of government authority.
Void and Space in Stoic Ontology
Authors: Powers Nathan M.
Published: July 2014

The Stoics claim that the cosmos is a finite plenum containing all substance within itself, but also that it is surrounded by something: namely, an infinite expanse of void. The standard scholarly view has been that the latter claim is forced upon the Stoics by their own physical theory (in particular, their view that the cosmos will eventually expand in size.) I argue the claim is rather the consequence of a Stoic commitment to absolute space, the unoccupied “part” of which is void. I then consider how this commitment fits in with (or at least fails to undermine) the Stoics’ corporealist ontology.
Hobbes’s and Zabarella’s Methods: A Missing Link
Authors: Hattab Helen
Published: July 2014

A common point of departure for interpreting Hobbes’ philosophical/scientific method is Jacopo Zabarella’s regressus which lies squarely in the Aristotelian Posterior Analytics tradition developed at the University of Padua, in the sixteenth century. Whereas parallels between Hobbes’ philosophical method and the geometrical methods of analysis and synthesis also receive attention, the differences in Hobbes’ presentation of each are significant: hence the Paduan reading that ties Hobbes’ philosophical method to Zabarella’s regressus retains its currency. In this paper, I argue that the Paduan reading of Hobbes relies on an overly narrow understanding of Zabarella’s method, and tends to identify his scientific method with one small component, the regressus . Zabarella’s writings on method, broadly speaking, influence subsequent philosophers, most notably Protestant logicians relevant to Hobbes’ context, who take up and develop Zabarella’s discussion of method as order. I show that interpreting Hobbes’ method within this fuller context has three distinct advantages over the Paduan reading. Firstly, it saves Hobbes from the charge of being inconsistent to his stated method in his particular explanations of natural and political phenomena. Secondly, it advances our understanding of the sense in which his method would have been regarded as ‘mathematical’ although it remains non-quantitative. Thirdly, my approach illuminates Hobbes’ odd combination of Aristotelian and geometrical elements within his philosophical system.
Descartes’s Argument for the Existence of the Idea of an Infinite Being
Authors: Schechtman Anat
Published: July 2014

Descartes’ Third Meditation presents an alleged proof for the existence of God that proceeds from the existence of an idea of an infinite being, God—an idea with infinite objective reality—to the existence of God himself. There is a tendency to understand the meditator as simply assuming the premise that he has an idea with infinite objective reality, or alternatively, as drawing it from the reach of introspection and the transparency of thought. Either way, readers of the Meditations often find the premise unmotivated, and do not take Descartes to provide any argument for it. This paper aims to show that Descartes does provide an argument for the premise. My interpretation focuses on the meditator’s evolving conception of his idea of an infinite being in the Third Meditation. In so doing, the interpretation highlights a way in which epistemic progress is achieved in the Meditations , namely, through a process of correcting misconceptions.
Ibn Sīnā and the Early History of Thought Experiments
Authors: Kukkonen Taneli
Published: July 2014

The early history of philosophical thought experiments remains largely unwritten. In this article I argue for the importance of Ibn Sina (the Latin Avicenna, 980-1037) for understanding the gradual systematization of Aristotelian thought experiments and their methodology. Through a close examination of Avicenna's novel take on Aristotle’s refutation of self-motion, I develop a case for Ibn Sina being possibly the first Peripatetic to have a reflected view of what thought experiments are and how they function. Important here is Ibn Sina’s theory of the inner senses, especially his distinction between the faculties of imagination and estimation, which allows Ibn Sina to set apart idealized abstractions from imaginative feats. Ibn Sina’s case demonstrates how in the Aristotelian tradition, a naturalized basis can be postulated that will underwrite the dependability of (properly conducted) philosophical thought experiments, something to which more modern thinkers no longer have access.
Spinoza’s Language
Authors: Lærke Mogens
Published: July 2014

In this article, I analyze Spinoza’s philosophical language use. Arguing against David Savan, according to whom Spinoza’s own conception of language sits so uncomfortably with his epistemology that he bars himself from putting his philosophy into words, I study the basic conditions under which Spinoza thinks that there can be any such thing as a successful philosophical language, what conceptual resources Spinoza’s philosophy make available to him for constructing such a language, and the systematic role the geometrical method has to play in this regard.
Does Kant Demand Explanations for All Synthetic A Priori Claims?
Authors: Marshall Colin
Published: July 2014

Kant’s philosophy promises to explain various synthetic a priori claims. Yet, as several of his commentators have noted, it is hard to see how these explanations could work unless they themselves rested on unexplained synthetic a priori claims. Since Kant appears to demand explanations for all synthetic a priori claims, it would seem that his project fails on its own terms. I argue, however, that Kant holds that explanations are required only for synthetic a priori claims about (purportedly) experience-independent entities, and that his project rests on a rationalist method of reflection that justifies certain basic synthetic a priori claims.
Collingwood’s “Reformed Metaphysics” and the Radical Conversion Hypothesis
Authors: Vanheeswijck Guido
Published: July 2014

Collingwood scholars have always been divided concerning his so-called radical conversion regarding the role of metaphysics. In particular, the radical conversion hypothesis refers to two alleged changes in Collingwood’s thought after 1936. First, Collingwood did no longer make a distinction between philosophy and history and, second, he did no longer believe in metaphysics as a study of “the One, the True, and the Good.” In this article, I try to expose the untenability of the radical conversion hypothesis by showing the incorrect character of three objections, raised against his so-called later concept of metaphysics. In order to do that, two things are necessary. First, the relevant passages from his work after 1936 must be situated in the context of his complete work, including his unpublished manuscripts. Second, a reconstruction is necessary of the philosophical climate in which Collingwood was working during the second half of the 1930s.
Lyrical Legacies: Milton’s Tributary Sonnets X and XXI
Authors: Blanchard Jane
Published: July 2014

Continuing the heroic lyrical tradition of Horace and Tasso, John Milton writes "Sonnet X" and "Sonnet XXI" about actual persons living in mid-seventeenth-century England, the Lady Margaret Ley and Cyriack Skinner, respectively. In these short poems, he combines praise or admonition for the living with adulation for a deceased forbear.
Not a Fox but a Lion: A Machiavellian Reading of Chile’s First President, José Miguel Carrera
Authors: Vilches Patricia
Published: July 2014

The first president of Chile is, and has been, beloved by some Chileans and vilified by others. An icon of Chilean independence, Carrera is also a symbol of the country’s perpetual internal divisions.
"League with you I seek": Inspiration and Narrative Control in Paradise Lost
Authors: Conley Lacey
Published: July 2014

The purpose of this article is to suggest that the Epic Voice of Paradise Lost has, perhaps unknowingly, from the first moments of the poem, entered into "league" with Satan. This occurs when the inspiration the Voice calls for is provided not through divine, but rather satanic, involvement.
The Cambridge Introduction to William Faulkner by Theresa M. Towner (review)
Authors: Smith-Riel Alisa M.
Published: July 2014

Towner demonstrates her Faulkner expertise throughout the text; furthermore, she references numerous sources by prominent Faulkner scholars in support of her claims and analysis. Consequently, literature professors, at all levels, could use this text to guide their high school and undergraduate students through Faulkner’s works.
Voices and Songs in Safi Faye’s Mossane
Authors: Dima Vlad
Published: July 2014

The work of Faye can certainly be taken as feminist, but I would argue that ultimately her films function primarily as ethnographic texts that are capable of raising certain awareness. Faye’s characters, and Mossane may be the best example, do defy the strict traditions of the Senegalese village and do manage to circumvent temporarily the classic Hollywood cinema restrictions imposed on the female body and voice.
Displaced Memories: The Poetics of Trauma in Argentine Women’s Writing by M. Edurne Portela (review)
Authors: Fugate Marissa
Published: July 2014

While Portela’s argument reads as an overly optimistic view of the work the narrative can accomplish, it is nonetheless an important piece of the intricate puzzle of justice.
Petrarch’s Epistolary Ego and the Authorizing Maternal
Authors: Grimes Kristen Ina
Published: July 2014

In 1345 the poet and humanist Petrarch uncovered a manuscript that had lain forgotten for half a century: a codex containing the epistolary collections of Marcus Tullius Cicero. Petrarch spent weeks copying the text; five years later, he began to arrange his own letters, assembling by the end of his life four collections containing more than five hundred epistles. Taken as a whole, the extensive epistolary presents an idealized intellectual autobiography.
A Guide Through Finnegans Wake by Edmund Lloyd Epstein (review)
Authors: Brick Martin
Published: July 2014

Perhaps the ultimate question for any book that puts “guide” in its title ought to be, would you lend it out? Essentially, is it actually a valuable guide? A Guide Through Finnegans Wake passes this test.
The Power of Vision in Charles Dickens’s Dombey and Son
Authors: Kikendall Stacey
Published: July 2014

The use of vision in literary works in the nineteenth century, including those of Dickens, has been the topic of study for numerous critics and theorists. Yet no one has fully examined or explained the complex ways in which vision and the gaze are used in Charles Dickens’s Dombey and Son
The Sympathetic Medium: Feminine Channeling, the Occult, and Communication Technologies by Jill Galvan (review)
Authors: Putnam LuElla
Published: July 2014

Overall, Galvan’s interdisciplinary research offers equally entertaining and valuable insights to scholars in the fields of history, literature, and gender studies alike. She provides readers an energetic, historical account that will certainly stimulate future debates about women’s intertwined relationships to spirituality, technology, and communication.
The Use of Illocutionary Force Indicating Devices in the Performance of the Speech Act of Apology by Learners of English as a Foreign Language
Authors: Mulamba Kashama
Published: July 2014

Only by conducting research and by introducing linguistic rules of use as a regular part of EFL curricula can we help learners to communicate appropriately in the target language. The inability of EFL learners to use the expressions of politeness appropriately may result in communication breakdowns, conflicts, or misinterpretations. Hence, besides other functions of language, the teaching and designing of EFL curricula should include explicit emphasis on using expressions of politeness in the target language.
Teaching the Graphic Novel ed. by Stephen E. Tabachnick (review)
Authors: Breckenridge Janis
Published: July 2014

In short, Teaching the Graphic Novel is the kind of work that one consults again and again. And if my personal experience is any indication, Stephen Tabachnick’s volume will instruct and inspire a new generation of comic enthusiasts and critics alike.
Sexuality and Subjectivity in Dorothy Richardson’s Pilgrimage
Authors: Nyman Micki
Published: July 2014

Physical spaces in Pilgrimage , according to Elizabeth Bronfen, facilitate the transaction between body, memory, and environment in three ways. Spaces can be fairly neutral, allowing for mobility in thought and action. Spaces can serve more specifically as zones of liminality, accommodating the transition of one mode of being to the next. And spaces can be particularly privileged, in Richardson’s imagining, as places where memories can be evoked and recounted.
Cystic Fibrosis Transmembrane Conductance Regulator Protein (CFTR) Expression in the Developing Human Brain
Authors: Marcorelles Pascale , Friocourt Gaëlle , Uguen Arnaud , Ledé Françoise , Férec Claude , Laquerrière Annie
Published: July 2014

Cystic Fibrosis Transmembrane conductance Regulator (CFTR) protein has recently been shown to be expressed in the human adult central nervous system (CNS). As CFTR expression has also been documented during embryonic development in several organs, such as the respiratory tract, the intestine and the male reproductive system, suggesting a possible role during development we decided to investigate the expression of CFTR in the human developing CNS. In addition, as some, although rare, neurological symptoms have been reported in patients with CF, we compared the expression of normal and mutated CFTR at several fetal stages. Immunohistochemistry was performed on brain and spinal cord samples of foetuses between 13 and 40 weeks of gestation and compared with five patients with cystic fibrosis (CF) of similar ages. We showed in this study that CFTR is only expressed in neurons and has an early and widespread distribution during development. Although we did not observe any cerebral abnormality in patients with CF, we observed a slight delay in the maturation of several brain structures. We also observed different expression and localization of CFTR depending on the brain structure or the cell maturation stage. Our findings, along with a literature review on the neurological phenotypes of patients with CF, suggest that this gene may play previously unsuspected roles in neuronal maturation or function.
Comparative Analysis of H&E and Prussian Blue Staining in a Mouse Model of Cerebral Microbleeds
Authors: Liu Shuo , Grigoryan Mher Mahoney , Vasilevko Vitaly , Sumbria Rachita K. , Paganini-Hill Annlia , Cribbs David H. , Fisher Mark J.
Published: July 2014

Cerebral microbleeds are microscopic hemorrhages with deposits of blood products in the brain, which can be visualized with MRI and are implicated in cerebrovascular diseases. Hematoxylin and eosin (H&E) and Perl’s Prussian blue are popular staining methods used to localize cerebral microbleeds in pathology. This paper compared these two staining techniques in a mouse model of cerebral microbleeds. We used lipopolysaccharide (LPS) to induce cerebral microhemorrhages. C57B6 mice were treated with LPS (5 mg/kg, i.p.) or vehicle at baseline and at 24 hr. The brains were extracted 48 hr after the first injection and adjacent coronal sections were stained with H&E and Prussian blue to compare the effectiveness of the two staining techniques. H&E-positive stains were increased with LPS treatment and were correlated with grossly visible microhemorrhages on the brain surface; Prussian blue-positive stains, by comparison, showed no significant increase with LPS treatment and did not correlate with either H&E-positive stains or surface microhemorrhages. H&E staining is thus a more reliable indicator of acute bleeding events induced by LPS in this model within a short time span.
Cardiac Troponin I Associated with the Development of Unrecognized Myocardial Infarctions Detected with MRI
Authors: Barbier Charlotte Ebeling , Themudo Raquel , Bjerner Tomas , Johansson Lars , Lindahl Bertil , Venge Per , Lind Lars , Ahlström Håkan
Published: July 2014

BACKGROUND

Late enhancement MRI (LE-MRI) and cardiac troponin I (cTnI) are sensitive methods to detect subclinical myocardial injury. We sought to investigate the relation between plasma concentrations of cTnI measured with a high-sensitivity assay (hs-cTnI) and the development of unrecognized myocardial infarctions (UMIs) detected with LE-MRI.

METHODS

After approval from the ethics committee and written informed consent were obtained, LE-MRI was performed on 248 randomly selected community-living 70-year-old volunteers and hs-cTnI was determined with a highly sensitive premarket assay. Five years later these individuals were invited to a second LE-MRI, and 176 of them (82 women, 94 men), who did not have a hospital diagnosis of MI, constitute the present study population. LE-MR images were analyzed by 2 radiologists independently and in a consensus reading, blinded to any information on previous disease or assessments.

RESULTS

New or larger UMIs were detected in 37 participants during follow-up. Plasma concentrations of hs-cTnI at 70 years of age, which were mainly within what is considered to be the reference interval, were related to new or larger UMIs at 75 years of age with an odds ratio of 1.98 per 1 unit increase in ln-transformed cTnI (95% CI, 1.17–3.35; P = 0.010). Plasma concentrations of hs-cTnI at 70 years of age were associated with the volumes of the UMIs detected at 75 years of age (P = 0.028).

CONCLUSIONS

hs-cTnI in 70-year-old community-living women and men was associated with the development of MRI-detected UMIs within 5 years.
Reduced pachytene piRNAs and translation underlie spermiogenic arrest in Maelstrom mutant mice
Authors: Castañeda Julio , Genzor Pavol , van der Heijden Godfried W , Sarkeshik Ali , Yates John R , Ingolia Nicholas T , Bortvin Alex
Published: July 2014

Pachytene piRNAs are a class of Piwi‐interacting small RNAs abundant in spermatids of the adult mouse testis. They are processed from piRNA primary transcripts by a poorly understood mechanism and, unlike fetal transposon‐derived piRNAs, lack complementary targets in the spermatid transcriptome. We report that immunopurified complexes of a conserved piRNA pathway protein Maelstrom (MAEL) are enriched in MIWI (Piwi partner of pachytene piRNAs), Tudor‐domain proteins and processing intermediates of pachytene piRNA primary transcripts. We provide evidence of functional significance of these complexes in Mael129 knockout mice that exhibit spermiogenic arrest with acrosome and flagellum malformation. Mael129‐null mutant testes possess low levels of piRNAs derived from MAEL‐associated piRNA precursors and exhibit reduced translation of numerous spermiogenic mRNAs including those encoding acrosome and flagellum proteins. These translation defects in haploid round spermatids are likely indirect, as neither MAEL nor piRNA precursors associate with polyribosomes, and they may arise from an imbalance between pachytene piRNAs and MIWI.
TLR sorting by Rab11 endosomes maintains intestinal epithelial‐microbial homeostasis
Authors: Yu Shiyan , Nie Yingchao , Knowles Byron , Sakamori Ryotaro , Stypulkowski Ewa , Patel Chirag , Das Soumyashree , Douard Veronique , Ferraris Ronaldo P , Bonder Edward M , Goldenring James R , Ip Yicktung Tony , Gao Nan
Published: July 2014

Compartmentalization of Toll‐like receptors (TLRs) in intestinal epithelial cells (IECs) regulates distinct immune responses to microbes; however, the specific cellular machinery that controls this mechanism has not been fully identified. Here we provide genetic evidences that the recycling endosomal compartment in enterocytes maintains a homeostatic TLR9 intracellular distribution, supporting mucosal tolerance to normal microbiota. Genetic ablation of a recycling endosome resident small GTPase, Rab11a, a gene adjacent to a Crohn's disease risk locus, in mouse IECs and in Drosophila midgut caused epithelial cell‐intrinsic cytokine production, inflammatory bowel phenotype, and early mortality. Unlike wild‐type controls, germ‐free Rab11a‐deficient mouse intestines failed to tolerate the intraluminal stimulation of microbial agonists. Thus, Rab11a endosome controls intestinal host‐microbial homeostasis at least partially via sorting TLRs.
A positive signal prevents secretory membrane cargo from recycling between the Golgi and the ER
Authors: Fossati Matteo , Colombo Sara F , Borgese Nica
Published: July 2014

The Golgi complex and ER are dynamically connected by anterograde and retrograde trafficking pathways. To what extent and by what mechanism outward‐bound cargo proteins escape retrograde trafficking has been poorly investigated. Here, we analysed the behaviour of several membrane proteins at the ER/Golgi interface in live cells. When Golgi‐to‐plasma membrane transport was blocked, vesicular stomatitis virus glycoprotein (VSVG), which bears an ER export signal, accumulated in the Golgi, whereas an export signal‐deleted version of VSVG attained a steady state determined by the balance of retrograde and anterograde traffic. A similar behaviour was displayed by EGF receptor and by a model tail‐anchored protein, whose retrograde traffic was slowed by addition of VSVG's export signal. Retrograde trafficking was energy‐ and Rab6‐dependent, and Rab6 inhibition accelerated signal‐deleted VSVG's transport to the cell surface. Our results extend the dynamic bi‐directional relationship between the Golgi and ER to include surface‐directed proteins, uncover an unanticipated role for export signals at the Golgi complex, and identify recycling as a novel factor that regulates cargo transport out of the early secretory pathway.
Aberrant methylation of tRNAs links cellular stress to neuro‐developmental disorders
Authors: Blanco Sandra , Dietmann Sabine , Flores Joana V , Hussain Shobbir , Kutter Claudia , Humphreys Peter , Lukk Margus , Lombard Patrick , Treps Lucas , Popis Martyna , Kellner Stefanie , Hölter Sabine M , Garrett Lillian , Wurst Wolfgang , Becker Lore , Klopstock Thomas , Fuchs Helmut , Gailus‐Durner Valerie , Hrabĕ de Angelis Martin , Káradóttir Ragnhildur T , Helm Mark , Ule Jernej , Gleeson Joseph G , Odom Duncan T , Frye Michaela
Published: July 2014

Mutations in the cytosine‐5 RNA methyltransferase NSun2 cause microcephaly and other neurological abnormalities in mice and human. How post‐transcriptional methylation contributes to the human disease is currently unknown. By comparing gene expression data with global cytosine‐5 RNA methylomes in patient fibroblasts and NSun2‐deficient mice, we find that loss of cytosine‐5 RNA methylation increases the angiogenin‐mediated endonucleolytic cleavage of transfer RNAs (tRNA) leading to an accumulation of 5′ tRNA‐derived small RNA fragments. Accumulation of 5′ tRNA fragments in the absence of NSun2 reduces protein translation rates and activates stress pathways leading to reduced cell size and increased apoptosis of cortical, hippocampal and striatal neurons. Mechanistically, we demonstrate that angiogenin binds with higher affinity to tRNAs lacking site‐specific NSun2‐mediated methylation and that the presence of 5′ tRNA fragments is sufficient and required to trigger cellular stress responses. Furthermore, the enhanced sensitivity of NSun2‐deficient brains to oxidative stress can be rescued through inhibition of angiogenin during embryogenesis. In conclusion, failure in NSun2‐mediated tRNA methylation contributes to human diseases via stress‐induced RNA cleavage.
Stop competing, start talking!
Authors: Fava Luca L , Villunger Andreas
Published: July 2014

According to current belief, the molecular networks orchestrating cell death or exit from mitosis upon extended mitotic arrest do not interact, stubbornly executing two parallel biological programs and competing to define a stochastic decision between death and a chance for survival with uncertain destiny. However, recent findings by Diaz‐Martinez et al () in this issue of The EMBO Journal now call for a reassessment of the “competing network” hypothesis.