Working Papers, Open Access and Cyber-Infrastructure in Classical Studies

Princeton–Stanford Working Papers in Classics is a web-based series of work-in-progress scripts by members of two leading departments of classics. It introduces the humanities to a new form of scholarly communication and represents a major advance in the free availability of classical-studies scholarship in cyberspace. This article both reviews the initial performance of this open-access experiment and the benefits and challenges of working papers more generally for classical studies. After two years of operation Princeton–Stanford Working Papers in Classics has proven to be a clear success. This series has built up a large international readership and a sizeable body of preprints and performs important scholarly and community-outreach functions. As this performance is largely due to its congruency with the working arrangements of ancient historians and classicists and the global demand for open-access scholarship, the series confirms the viability of this means of scholarly communication and the likelihood of its expansion in our discipline. But modifications are required to increase the benefits this series brings and the amount of scholarship it makes freely available online. Finally departments wishing to replicate its success will have to consider other important developments, such as the increasing availability of postprints, the linking of research funding to open access, and the emergence of new cyber-infrastructure

Survival of red blood cells after transfusion: processes and consequences

Contains fulltext : 140543.pdf (publisher's version ) (Open Access)THE CURRENTLY AVAILABLE DATA SUGGEST THAT EFFORTS TOWARD IMPROVING THE QUALITY OF RED BLOOD CELL (RBC) BLOOD BANK PRODUCTS SHOULD CONCENTRATE ON: (1) preventing the removal of a considerable fraction of the transfused RBCs that takes place within the first hours after transfusion; (2) minimizing the interaction of the transfused RBCs with the patient's immune system. These issues are important in reducing the number and extent of the damaging side effects of transfusions, such as generation of alloantibodies and autoantibodies and iron accumulation, especially in transfusion-dependent patients. Thus, it becomes important for blood bank research not only to assess the classical RBC parameters for quality control during storage, but even more so to identify the parameters that predict RBC survival, function and behavior in the patient after transfusion. These parameters are likely to result from elucidation of the mechanisms that underly physiological RBC aging in vivo, and that lead to the generation of senescent cell antigens and the accumulation of damaged molecules in vesicles. Also, study of RBC pathology-related mechanisms, such as encountered in various hemoglobinopathies and membranopathies, may help to elucidate the mechanisms underlying a storage-associated increase in susceptibility to physiological stress conditions. Recent data indicate that a combination of new approaches in vitro to mimick RBC behavior in vivo, the growing knowledge of the signaling networks that regulate RBC structure and function, and the rapidly expanding set of proteomic and metabolomic data, will be instrumental to identify the storage-associated processes that control RBC survival after transfusion

Apoptosis and Alzheimer's disease

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The involvement of erythrocyte metabolism in organismal homeostasis in health and disease

Historically, study of erythrocyte homeostasis has focussed on the survival of erythrocytes in the blood bank and, especially in pathological circumstances, on the mechanisms leading to accelerated aging and removal from the circulation. Recent proteomic and metabolomic data suggest that erythrocyte metabolism involves more than ATP production and transport of oxygen and carbondioxide; is subject to regulation; and is likely to reflect organismal metabolism. Also, it has become clear that systemic diseases affect erythrocyte homeostasis. The perspectives emerging from these data include new possibilities to manipulate erythrocyte function and survival in vivo, and thereby organismal homeostasis

Erythrocyte aging in sickle cell disease.

Physiological removal of old erythrocytes from the circulation by macrophages is initiated by binding of autologous IgG to senescent cell antigen (SCA). SCA is generated from the anion exchanger band 3. This process is accompanied by a number of alterations in the function and structure of band 3. We measured these aging-related parameters in erythrocytes from individuals with sickle cell anemia. Most sickle erythrocytes have characteristics that are also found in senescent normal erythrocytes, such as an increased density and considerable concentrations of cell-bound IgG. Together with the concomitant changes in structure and function of band 3, these data suggest that most sickle erythrocytes have undergone a process of accelerated aging. Preliminary results indicate that this process is reversed upon vitamin E supplementation. These data show that the erythrocyte aging paradigm may provide a useful conceptual framework for the study of the pathophysiology and the evalution of therapeutic intervention in sickle cell disease, and support the view that oxidation can generate neoantigens that are recognized by autoantibodies

Disturbed Red Blood Cell Structure and Function: An Exploration of the Role of Red Blood Cells in Neurodegeneration

Contains fulltext : 196101.pdf (publisher's version ) (Open Access)The structure of red blood cells is affected by many inborn and acquired factors, but in most cases this does not seem to affect their function or survival in physiological conditions. Often, functional deficits become apparent only when they are subjected to biochemical or mechanical stress in vitro, or to pathological conditions in vivo. Our data on the misshapen red blood cells of patients with neuroacanthocytosis illustrate this general mechanism: an abnormal morphology is associated with an increase in the susceptibility of red blood cells to osmotic and mechanical stress, and alters their rheological properties. The underlying mutations may not only affect red cell function, but also render neurons in specific brain areas more susceptible to a concomitant reduction in oxygen supply. Through this mechanism, an increased susceptibility of already compromised red blood cells to physiological stress conditions may constitute an additional risk factor in vulnerable individuals. Also, susceptibility may be induced or enhanced by systemic pathological conditions such as inflammation. An exploration of the literature suggests that disturbed red blood cell function may play a role in the pathophysiology of various neurodegenerative diseases. Therefore, interventions that reduce the susceptibility of red blood cells to physiological and pathological stress may reduce the extent or progress of neurodegeneration

Neuroacanthocytosis: Observations, Theories and Perspectives on the Origin and Significance of Acanthocytes

Contains fulltext : 153491.pdf (publisher's version ) (Open Access)The presence of acanthocytes in the blood is characteristic of patients suffering from neuroacanthocytosis (NA). Recent studies have described abnormal phosphorylation of the proteins involved in connecting the membrane and cytoskeleton in patient-derived erythrocytes. The involvement of lipids in the underlying signaling pathways and recent reports on in vitro disease-associated lipid alterations support renewed research into lipid composition, signal transduction, and metabolism in patient erythrocytes. In addition to morphology, changes in membrane organization affect erythrocyte function and survival. Patient erythrocytes may have a decreased ability to deform, and this may contribute to accelerated erythrocyte removal and a decreased oxygen supply, especially in vulnerable brain regions. The presently available data indicate that acanthocytes are likely to originate in the bone marrow, making erythropoiesis an obvious new focus in NA research. Moreover, new, detailed morphological observations indicate that acanthocytes may be the tip of the iceberg with regard to misshapen erythrocytes in the circulation of patients with NA. A systematic assessment of patient erythrocyte morphology, deformability, oxygen delivery, and metabolism will be instrumental in determining the putative contribution of erythrocyte function to NA clinical symptoms

Acanthocytosis-related changes in erythrocyte band 3: Clues for a mechanism and inspiration for future research.

Contains fulltext : 48753.pdf (publisher's version ) (Closed access