‘Big’ and ‘little’ Quo Vadis? in the United States, 1913–1916: Using GIS to map rival modes of feature cinema during the transitional era

This article emanates from a geospatial database of over 600 premieres of the Cines company’s Quo Vadis? (1913), an eight-reel film distributed by George Kleine, and nearly 250 premieres of the Quo Vadis Film Company’s Quo Vadis? (1913), a three-reel film of ambiguous origins distributed by Paul De Outo. By mapping local premieres of both films across the United States from 1913 through 1916, the data show with spatiotemporal precision the spread of Quo Vadis? as one of cinema’s early blockbuster titles. Yet within this national phenomenon, the two films’ footprints reveal differing cultural geographies served by competing efforts to feature Quo Vadis? using alternative practices of distribution and exhibition. The study finds that Quo Vadis? played a more complex role mediating the rise of features than is yet known, serving rival modes of cinema where longer, more expensive films were celebrated but also contested

‘Big’ and ‘Little’ Quo Vadis? in the United States, 1913–1916: Using GIS to Map Rival Modes of Feature Cinema During the Transitional Era

This article emanates from a geospatial database of over 600 premieres of the Cines company’s Quo Vadis? (1913), an eight-reel film distributed by George Kleine, and nearly 250 premieres of the Quo Vadis Film Company’s Quo Vadis? (1913), a three-reel film of ambiguous origins distributed by Paul De Outo. By mapping local premieres of both films across the United States from 1913 through 1916, the data show with spatiotemporal precision the spread of Quo Vadis? as one of cinema’s early blockbuster titles. Yet within this national phenomenon, the two films’ footprints reveal differing cultural geographies served by competing efforts to feature Quo Vadis? using alternative practices of distribution and exhibition. The study finds that Quo Vadis? played a more complex role mediating the rise of features than is yet known, serving rival modes of cinema where longer, more expensive films were celebrated but also contested

Mapping Flat, Deep, and Slow: On the \u27Spirit of Place\u27 in New Cinema History

This essay engages in a creative, heuristic, and reflexive consideration of the ‘localities’ of cinema audiences by exploring New Cinema History as a place. New Cinema History is conceptualised as a place continually produced in and through its interactions with the heterogeneous multiplicities of situated audiences and experiences of cinema that form the topoi of its landscape of inquiry. In reflecting on how this placialised landscape has been and might be represented, I argue that New Cinema History’s ‘spirit of place’ is most productive when rendered within a ‘splatial’ framework that draws upon practices of flat, deep, and slow mapping to offer new possibilities for bridging space and place, narrative and cartography, and history and geography. These practices motivate myriad forms of collaboration and data exchange among diverse projects and stakeholders that perforate and continually redraw boundaries of knowledge using dynamic, multiple, open tactics for representing and recombining research

C-mannosylation supports folding and enhances stability of thrombospondin repeats.

Previous studies demonstrated importance of C-mannosylation for efficient protein secretion. To study its impact on protein folding and stability, we analyzed both C-mannosylated and non-C-mannosylated thrombospondin type 1 repeats (TSRs) of netrin receptor UNC-5. In absence of C-mannosylation, UNC-5 TSRs could only be obtained at low temperature and a significant proportion displayed incorrect intermolecular disulfide bridging, which was hardly observed when C-mannosylated. Glycosylated TSRs exhibited higher resistance to thermal and reductive denaturation processes, and the presence of C-mannoses promoted the oxidative folding of a reduced and denatured TSR in vitro. Molecular dynamics simulations supported the experimental studies and showed that C-mannoses can be involved in intramolecular hydrogen bonding and limit the flexibility of the TSR tryptophan-arginine ladder. We propose that in the endoplasmic reticulum folding process, C-mannoses orient the underlying tryptophan residues and facilitate the formation of the tryptophan-arginine ladder, thereby influencing the positioning of cysteines and disulfide bridging

Shear stress-induced angiogenesis in mouse muscle is independent of the vasodilator mechanism and quickly reversible.

Aim: Is modulation of skeletal muscle capillary supply by altering blood flow due to a presumptive shear stress response per se, or dependent on the vasodilator mechanism? Methods: The response to four different vasodilators, and cotreatment with blockers of NO and prostaglandin synthesis, was compared. Femoral artery blood flow was correlated with capillary-to-fibre ratio (C:F) and protein levels of putative angiogenic compounds. Results: All vasodilators induced a similar increase in blood flow after 14 days, with a similar effect on C:F (1.62 ± 0.05, 1.60 ± 0.01, 1.57 ± 0.06, 1.57 ± 0.07, respectively, all P < 0.05 vs. control 1.20 ± 0.01). Concomitant inhibitors revealed differential effects on blood flow and angiogenesis, demonstrating that a similar response may have different signalling origins. The time course of this response with the most commonly used vasodilator, prazosin, showed that blood flow increased from 0.40 mL min−1 to 0.61 mL min−1 by 28 days (P < 0.05), dropped within 1 week after the cessation of treatment (0.54 mL min−1; P < 0.05) and returned to control levels by 6 weeks. In parallel with FBF, capillary rarefaction began within 1 week (P < 0.05), giving C:F values similar to control by 2 weeks. Of the dominant signalling pathways, prazosin decreased muscle VEGF, but increased its cognate receptor Flk-1 (both P < 0.01); levels of eNOS varied with blood flow (P < 0.05), and Ang-1 initially increased, while its receptor Tie-2 was unchanged, with only modest changes in the antiangiogenic factor TSP-1. Conclusion: Hyperaemia-induced angiogenesis, likely in response to elevated shear stress, is independent of the vasodilator involved, with a rapid induction and quick regression following the stimulus withdrawal

Overexpression of HTRA1 Leads to Ultrastructural Changes in the Elastic Layer of Bruch's Membrane via Cleavage of Extracellular Matrix Components

Variants in the chromosomal region 10q26 are strongly associated with an increased risk for age-related macular degeneration (AMD). Two potential AMD genes are located in this region: ARMS2 and HTRA1 (high-temperature requirement A1). Previous studies have suggested that polymorphisms in the promotor region of HTRA1 result in overexpression of HTRA1 protein. This study investigated the role of HTRA1 overexpression in the pathogenesis of AMD. Transgenic Htra1 mice overexpressing the murine protein in the retinal pigment epithelium (RPE) layer of the retina were generated and characterized by transmission electron microscopy, immunofluorescence staining and Western Blot analysis. The elastic layer of Bruch's membrane (BM) in the Htra1 transgenic mice was fragmented and less continuous than in wild type (WT) controls. Recombinant HTRA1 lacking the N-terminal domain cleaved various extracellular matrix (ECM) proteins. Subsequent Western Blot analysis revealed an overexpression of fibronectin fragments and a reduction of fibulin 5 and tropoelastin in the RPE/choroid layer in transgenic mice compared to WT. Fibulin 5 is essential for elastogenesis by promoting elastic fiber assembly and maturation. Taken together, our data implicate that HTRA1 overexpression leads to an altered elastogenesis in BM through fibulin 5 cleavage. It highlights the importance of ECM related proteins in the development of AMD and links HTRA1 to other AMD risk genes such as fibulin 5, fibulin 6, ARMS2 and TIMP3

Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease

Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the 'preclinical' stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome.CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n = 24) and cognitively normal controls (CDR 0) (n = 24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and Aβ42 ELISAs) to a larger independent cohort (n = 292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85-0.94 95% confidence interval [CI]) and 0.88 (0.81-0.94 CI), respectively.Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of Aβ42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding subject enrollment and monitoring disease progression. Further studies will be required to validate this panel and evaluate its potential for distinguishing AD from other dementing conditions

Mapping Flat, Deep, and Slow: On the ‘Spirit of Place’ in New Cinema History

This essay engages in a creative, heuristic, and reflexive consideration of the ‘localities’ of cinema audiences by exploring New Cinema History as a place. New Cinema History is conceptualised as a place continually produced in and through its interactions with the heterogeneous multiplicities of situated audiences and experiences of cinema that form the topoi of its landscape of inquiry. In reflecting on how this placialised landscape has been and might be represented, I argue that New Cinema History’s ‘spirit of place’ is most productive when rendered within a ‘splatial’ framework that draws upon practices of flat, deep, and slow mapping to offer new possibilities for bridging space and place, narrative and cartography, and history and geography. These practices motivate myriad forms of collaboration and data exchange among diverse projects and stakeholders that perforate and continually redraw boundaries of knowledge using dynamic, multiple, open tactics for representing and recombining research