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A brief history of comic book movies
A Brief History of Comic Book Movies traces the meteoric rise of the hybrid art form of the comic book film. These films trace their origins back to the early 1940s, when the first Batman and Superman serials were made. The serials, and later television shows in the 1950s and 60s, were for the most part designed for children. But today, with the continuing rise of Comic-Con, they seem to be more a part of the mainstream than ever, appealing to adults as well as younger fans. This book examines comic book movies from the past and present, exploring how these films shaped American culture from the post-World War II era to the present day, and how they adapted to the changing tastes and mores of succeeding generations.
Book
A resource for improved predictions of Trypanosoma and Leishmania protein three-dimensional structure
AlphaFold2 and RoseTTAfold represent a transformative advance for predicting protein structure. They are able to make very high-quality predictions given a high-quality alignment of the protein sequence with related proteins. These predictions are now readily available via the AlphaFold database of predicted structures and AlphaFold or RoseTTAfold Colaboratory notebooks for custom predictions. However, predictions for some species tend to be lower confidence than model organisms. Problematic species include Trypanosoma cruzi and Leishmania infantum : important unicellular eukaryotic human parasites in an early-branching eukaryotic lineage. The cause appears to be due to poor sampling of this branch of life (Discoba) in the protein sequences databases used for the AlphaFold database and ColabFold. Here, by comprehensively gathering openly available protein sequence data for Discoba species, significant improvements to AlphaFold2 protein structure prediction over the AlphaFold database and ColabFold are demonstrated. This is made available as an easy-to-use tool for the parasitology community in the form of Colaboratory notebooks for generating multiple sequence alignments and AlphaFold2 predictions of protein structure for Trypanosoma , Leishmania and related species.
Journal Article
Special responsibilities : global problems and American power
\"The language of special responsibilities is ubiquitous in world politics, with policymakers and commentators alike speaking and acting as though particular states have, or ought to have, unique obligations in managing global problems. Surprisingly, scholars are yet to provide any in-depth analysis of this fascinating aspect of world politics. This path-breaking study examines the nature of special responsibilities, the complex politics that surround them and how they condition international social power. The argument is illustrated with detailed case-studies of nuclear proliferation, climate change and global finance. All three problems have been addressed by an allocation of special responsibilities, but while this has structured politics in these areas, it has also been the subject of ongoing contestation. With a focus on the United States, this book argues that power must be understood as a social phenomenon and that American power varies significantly across security, economic and environmental domains\"-- Provided by publisher.
Book
Controlling compartmentalization by non-membrane-bound organelles
Compartmentalization is a characterizing feature of complexity in cells, used to organize their biochemistry. Membrane-bound organelles are most widely known, but non-membrane-bound liquid organelles also exist. These have recently been shown to form by phase separation of specific types of proteins known as scaffolds. This forms two phases: a condensate that is enriched in scaffold protein separated by a phase boundary from the cytoplasm or nucleoplasm with a low concentration of the scaffold protein. Phase separation is well known for synthetic polymers, but also appears important in cells. Here, we review the properties of proteins important for forming these non-membrane-bound organelles, focusing on the energetically favourable interactions that drive condensation. On this basis we make qualitative predictions about how cells may control compartmentalization by condensates; the partition of specific molecules to a condensate; the control of condensation and dissolution of condensates; and the regulation of condensate nucleation. There are emerging data supporting many of these predictions, although future results may prove incorrect. It appears that many molecules may have the ability to modulate condensate formation, making condensates a potential target for future therapeutics. The emerging properties of condensates are fundamentally unlike the properties of membrane-bound organelles. They have the capacity to rapidly integrate cellular events and act as a new class of sensors for internal and external environments.
This article is part of the theme issue ‘Self-organization in cell biology’.
Journal Article
نظم المعلومات المحاسبية : أسس إدارة مخاطر المؤسسة
يتناول كتاب (نظم المعلومات المحاسبية : أسس إدارة مخاطر المؤسسة ) والذي قامه بتأليفه (Richard B. Dull, Ulric J. Gelinas, Jr., Patrick R. Wheeler) في حوالي (860) صفحة من القطع المتوسط مستعرضا المحتويات التالية الفصل الأول : مقدمة في نظم المعلومات المحاسبية، الفصل الثاني : أنظمة المؤسسة، الفصل الثالث : نظم العمل الإلكتروني، الفصل الرابع : توثيق نظم المعلومات، الفصل الخامس : نظم إدارة قواعد البيانات، الفصل السادس : قواعد البيانات المترابطة ولغة الاستعلامات البنائية، الفصل السابع : رقابة نظم المعلومات : مقدمة في إدارة مخاطر المؤسسة والرقابة الداخلية، الفصل الثامن : الرقابة على نظم المعلومات : مقدمة لعناصر الرقابة الرئيسية، الفصل التاسع : الرقابة على نظم المعلومات : العمليات التجارية وتطبيق الرقابة، الفصل العاشر : عملية إدخال الطلب-المبيعات الفصل الحادي عشر : عملية-الذمم المدينة-المقوضات النقدية الفصل الثاني عشر : عمليات الشراء الفصل الثالث عشر : الذمم الدائنة-عملية سداد النقدية، الفصل الرابع عشر : إدارة الموارد البشرية وإدارة عملية الرواتب، الفصل الخامس عشر : عمليات الإنتاج المتكامل، الفصل السادس عشر : عمليات تقارير العمل ودفتر الأستاذ العام، الفصل السابع عشر : الحصول على نظم المعلومات المحاسبية واستخدامها.
BOOK
Use of chiral cell shape to ensure highly directional swimming in trypanosomes
Swimming cells typically move along a helical path or undergo longitudinal rotation as they swim, arising from chiral asymmetry in hydrodynamic drag or propulsion bending the swimming path into a helix. Helical paths are beneficial for some forms of chemotaxis, but why asymmetric shape is so prevalent when a symmetric shape would also allow highly directional swimming is unclear. Here, I analyse the swimming of the insect life cycle stages of two human parasites; Trypanosoma brucei and Leishmania mexicana. This showed quantitatively how chirality in T. brucei cell shape confers highly directional swimming. High speed videomicrographs showed that T. brucei, L. mexicana and a T. brucei RNAi morphology mutant have a range of shape asymmetries, from wild-type T. brucei (highly chiral) to L. mexicana (near-axial symmetry). The chiral cells underwent longitudinal rotation while swimming, with more rapid longitudinal rotation correlating with swimming path directionality. Simulation indicated hydrodynamic drag on the chiral cell shape caused rotation, and the predicted geometry of the resulting swimming path matched the directionality of the observed swimming paths. This simulation of swimming path geometry showed that highly chiral cell shape is a robust mechanism through which microscale swimmers can achieve highly directional swimming at low Reynolds number. It is insensitive to random variation in shape or propulsion (biological noise). Highly symmetric cell shape can give highly directional swimming but is at risk of giving futile circular swimming paths in the presence of biological noise. This suggests the chiral T. brucei cell shape (associated with the lateral attachment of the flagellum) may be an adaptation associated with the bloodstream-inhabiting lifestyle of this parasite for robust highly directional swimming. It also provides a plausible general explanation for why swimming cells tend to have strong asymmetries in cell shape or propulsion.
Journal Article
Proteins with proximal-distal asymmetries in axoneme localisation control flagellum beat frequency
The 9 + 2 microtubule-based axoneme within motile flagella is well known for its symmetry. However, examples of asymmetric structures and proteins asymmetrically positioned within the 9 + 2 axoneme architecture have been identified. These occur in multiple different organisms, particularly involving the inner or outer dynein arms. Here, we comprehensively analyse conserved proximal-distal asymmetries in the uniflagellate trypanosomatid eukaryotic parasites. Building on the genome-wide localisation screen in
Trypanosoma brucei
we identify conserved proteins with an analogous asymmetric localisation in the related parasite
Leishmania mexicana
. Using deletion mutants, we find which are necessary for normal cell swimming, flagellum beat parameters and axoneme ultrastructure. Using combinatorial endogenous fluorescent tagging and deletion, we map co-dependencies for assembly into their normal asymmetric localisation. This revealed 15 proteins, 9 known and 6 novel, with a conserved proximal or distal axoneme-specific localisation. Most are outer dynein arm associated and show that there are multiple classes of proximal-distal asymmetry – one which is dependent on the docking complex. Many of these proteins are necessary for retaining the normal frequency of the tip-to-base symmetric flagellar waveform. Our comprehensive mapping reveals unexpected contributions of proximal-specific axoneme components to the frequency of waveforms initiated distally.
This study investigates conserved proximal-distal asymmetries in the axoneme of trypanosomatid parasite flagella, identifying 15 proteins predominantly in the outer dynein arms. This reveals proximal proteins can regulate distally initiated beats.
Journal Article
Genetic dissection of a Leishmania flagellar proteome demonstrates requirement for directional motility in sand fly infections
The protozoan parasite Leishmania possesses a single flagellum, which is remodelled during the parasite's life cycle from a long motile flagellum in promastigote forms in the sand fly to a short immotile flagellum in amastigotes residing in mammalian phagocytes. This study examined the protein composition and in vivo function of the promastigote flagellum. Protein mass spectrometry and label free protein enrichment testing of isolated flagella and deflagellated cell bodies defined a flagellar proteome for L. mexicana promastigote forms (available via ProteomeXchange with identifier PXD011057). This information was used to generate a CRISPR-Cas9 knockout library of 100 mutants to screen for flagellar defects. This first large-scale knockout screen in a Leishmania sp. identified 56 mutants with altered swimming speed (52 reduced and 4 increased) and defined distinct mutant categories (faster swimmers, slower swimmers, slow uncoordinated swimmers and paralysed cells, including aflagellate promastigotes and cells with curled flagella and disruptions of the paraflagellar rod). Each mutant was tagged with a unique 17-nt barcode, providing a simple barcode sequencing (bar-seq) method for measuring the relative fitness of L. mexicana mutants in vivo. In mixed infections of the permissive sand fly vector Lutzomyia longipalpis, paralysed promastigotes and uncoordinated swimmers were severely diminished in the fly after defecation of the bloodmeal. Subsequent examination of flies infected with a single paralysed mutant lacking the central pair protein PF16 or an uncoordinated swimmer lacking the axonemal protein MBO2 showed that these promastigotes did not reach anterior regions of the fly alimentary tract. These data show that L. mexicana need directional motility for successful colonisation of sand flies.
Journal Article
The Limits on Trypanosomatid Morphological Diversity
Cell shape is one, often overlooked, way in which protozoan parasites have adapted to a variety of host and vector environments and directional transmissions between these environments. Consequently, different parasite life cycle stages have characteristic morphologies. Trypanosomatid parasites are an excellent example of this in which large morphological variations between species and life cycle stage occur, despite sharing well-conserved cytoskeletal and membranous structures. Here, using previously published reports in the literature of the morphology of 248 isolates of trypanosomatid species from different hosts, we perform a meta-analysis of the occurrence and limits on morphological diversity of different classes of trypanosomatid morphology (trypomastigote, promastigote, etc.) in the vertebrate bloodstream and invertebrate gut environments. We identified several limits on cell body length, cell body width and flagellum length diversity which can be interpreted as biomechanical limits on the capacity of the cell to attain particular dimensions. These limits differed for morphologies with and without a laterally attached flagellum which we suggest represent two morphological superclasses, the 'juxtaform' and 'liberform' superclasses. Further limits were identified consistent with a selective pressure from the mechanical properties of the vertebrate bloodstream environment; trypanosomatid size showed limits relative to host erythrocyte dimensions. This is the first comprehensive analysis of the limits of morphological diversity in any protozoan parasite, revealing the morphogenetic constraints and extrinsic selection pressures associated with the full diversity of trypanosomatid morphology.
Journal Article
TransLeish: Identification of membrane transporters essential for survival of intracellular Leishmania parasites in a systematic gene deletion screen
For the protozoan parasite
Leishmania
, completion of its life cycle requires sequential adaptation of cellular physiology and nutrient scavenging mechanisms to the different environments of a sand fly alimentary tract and the acidic mammalian host cell phagolysosome. Transmembrane transporters are the gatekeepers of intracellular environments, controlling the flux of solutes and ions across membranes. To discover which transporters are vital for survival as intracellular amastigote forms, we carried out a systematic loss-of-function screen of the
L. mexicana
transportome. A total of 312 protein components of small molecule carriers, ion channels and pumps were identified and targeted in a CRISPR-Cas9 gene deletion screen in the promastigote form, yielding 188 viable null mutants. Forty transporter deletions caused significant loss of fitness in macrophage and mouse infections. A striking example is the Vacuolar H
+
ATPase (V-ATPase), which, unexpectedly, was dispensable for promastigote growth in vitro but essential for survival of the disease-causing amastigotes.
A systematic gene deletion screen targeting all predicted transmembrane transporters of the protozoan parasite
Leishmania
identified forty mutants that had a significant loss of fitness in macrophage and mouse infections. Loss of the V-type H
+
ATPase was particularly deleterious in vivo.
Journal Article