Human malarial disease: a consequence of inflammatory cytokine release

Malaria causes an acute systemic human disease that bears many similarities, both clinically and mechanistically, to those caused by bacteria, rickettsia, and viruses. Over the past few decades, a literature has emerged that argues for most of the pathology seen in all of these infectious diseases being explained by activation of the inflammatory system, with the balance between the pro and anti-inflammatory cytokines being tipped towards the onset of systemic inflammation. Although not often expressed in energy terms, there is, when reduced to biochemical essentials, wide agreement that infection with falciparum malaria is often fatal because mitochondria are unable to generate enough ATP to maintain normal cellular function. Most, however, would contend that this largely occurs because sequestered parasitized red cells prevent sufficient oxygen getting to where it is needed. This review considers the evidence that an equally or more important way ATP deficency arises in malaria, as well as these other infectious diseases, is an inability of mitochondria, through the effects of inflammatory cytokines on their function, to utilise available oxygen. This activity of these cytokines, plus their capacity to control the pathways through which oxygen supply to mitochondria are restricted (particularly through directing sequestration and driving anaemia), combine to make falciparum malaria primarily an inflammatory cytokine-driven disease

Background Risk and the Performance of Insurance Markets under Adverse Selection

Background risk can influence the performance of insurance markets that must deal with adverse selection when applicants are risk vulnerable, since they are more averse to bearing the insurable risk as a result of their exposures to background risk. We show that background risk always results in a lower deductible for the incentive constrained contract, and that a broader range of markets attains the stable sequential equilibrium cross-subsidized pair of separating contracts. We conclude that background risk always improves the performance of markets for coverage against (insurable) foreground risks that must deal with adverse selection. We also find, however, that these improvements are never sufficient to offset the cost to insureds of bearing the background risk. The Geneva Risk and Insurance Review (2008) 33, 137–160. doi:10.1057/grir.2008.12

Teaching a Broad Discipline: The Critical Role of Text Based Learning to Building Disciplinary Literacy in Architectural Education

Architecture is a demanding discipline with multiple, complex concerns and identities shaping the profession. The discipline requires analysis of complex and multifaceted issues and synthesizing broad knowledge through a focused creative process. While twenty-first-century education may leverage many sources to educate students of architecture, texts remain the primary repository par excellence of the rich and diverse body of knowledge and ideas that continue to inspire and ground architects, theorists, historians, planners, and policy makers tied to the discipline. Perusing and engaging with the diverse body of architectural literature is a strong approach to support one’s learning to think, speak, and write in the discipline with a high level of fluency and expertise. Yet reading, the foundational skill that provides access to the literature is often overlooked in the development of curriculum and the pedagogy of architectural education. This chapter explores in detail the challenges that inhibit student reading and reading effectiveness followed by strategies for building student reading skills in architectural education to support increased disciplinary literacy. Central to the strategies discussed is increased integration of text-based learning and explicit foregrounding of reading and study tools to support students’ learning through text. Key learning principles that serve a foundational role in text-based learning are analyzed to underpin the strategies discussed. Finally, two case studies are provided that exemplify the integration of these strategies that support increased disciplinary literacy in architectural education

A novel vasopressin-induced transcript promotes MAP kinase activation and ENaC downregulation

In the principal cell of the renal collecting duct, vasopressin regulates the expression of a gene network responsible for sodium and water reabsorption through the regulation of the water channel and the epithelial sodium channel (ENaC). We have recently identified a novel vasopressin-induced transcript (VIT32) that encodes for a 142 amino acid vasopressin-induced protein (VIP32), which has no homology with any protein of known function. The Xenopus oocyte expression system revealed two functions: (i) when injected alone, VIT32 cRNA rapidly induces oocyte meiotic maturation through the activation of the maturation promoting factor, the amphibian homolog of the universal M phase trigger Cdc2/cyclin; and (ii) when co-injected with the ENaC, VIT32 cRNA selectively downregulates channel activity, but not channel cell surface expression. In the kidney principal cell, VIP32 may be involved in the downregulation of transepithelial sodium transport observed within a few hours after vasopressin treatment. VIP32 belongs to a novel gene family ubiquitously expressed in oocyte and somatic cells that may be involved in G to M transition and cell cycling