Mitotic cell cycle proteins increase in podocytes despite lack of proliferation

Mitotic cell cycle proteins increase in podocytes despite lack of proliferation.BackgroundPodocyte proliferation is an uncommon response to glomerular injury and its lack may underlie the development of glomerulosclerosis. However, whether podocytes have the capacity to enter and finish mitosis and cytokinesis is not known.MethodsThe expression of mitotic cell cycle proteins (phosphorylated Histone 3, Cdc2, cyclin B1 and B2) was examined by immunohistochemistry in kidneys of embryonal mice, transgenic HIV-mice, and rats with experimental membranous nephropathy (passive Heymann nephritis, PHN). Mitotic proteins also were measured by Western blot in glomerular protein from PHN-rats and the activity of mitotic cyclins was quantified by histone kinase assay.ResultsMitotic proteins were increased in embryonal mouse glomeruli during the S- and comma-shaped stages and were absent at the capillary loop stage and in mature rodent glomeruli. There was an increase in podocyte expression of Cdc2, cyclin B1 and B2 and phosphorylated histone 3 in PHN rats, and in HIV transgenic mice.ConclusionsPodocytes have the ability to increase cell cycle proteins required for mitosis. Without obvious differences in the expression of the major mitotic proteins in PHN- and HIV-nephropathy, a regulatory disturbance in cytokinesis might be responsible for the development of polynucleated cells and a lack of podocyte proliferation in experimental glomerular disease

Considerations Surrounding the Effects of Race, Age, and Gender on GED Success among Jail Inmates

When viewed in a historical context, researchers have found consistent linkage between criminal offending and lowered educational levels among the general population of incarcerated offenders. Evidence of this is demonstrated by a disproportionate representation of illiterate persons among jail and prison inmates. After reviewing the literature, ample evidence revealed the utility in examining the isolated relationships concerning age, race, and gender on GED success for under-educated jail inmates. The purpose of this study was to explore the many considerations concerning the isolation of those factors, and to assist jail educators with achieving GED certification among subjects. No statistically significant differences were found among the independent variables race, age, and gender; however the effort gave rise to several implications that will assist in establishing guidelines for future research

p35, the non-cyclin activator of Cdk5, protects podocytes against apoptosis in vitro and in vivo

Cyclin-dependent kinase-5 is widely expressed and predominantly regulated by the non-cyclin activator p35. Since we recently showed that expression of p35 in the kidney is restricted to podocytes, we examined here its function in mice in which p35 was genetically deleted. The mice did not exhibit kidney abnormalities during glomerular development or during adult life. Conditionally immortalized cultured podocytes, derived from these null mice, did not have any change in their morphology, differentiation, or proliferation. However, when these cultured podocytes were exposed to UV-C irradiation, serum depletion, puromycin aminonucleoside, or transforming growth factor-β-1, they showed increased apoptosis compared to those from wild-type mice. Levels of Bcl-2 were decreased in these null podocytes but increased after transduction with human p35. Restoration of p35 or the ectopic expression of Bcl-2 reduced the susceptibility of p35-null podocytes to apoptosis. Experimental glomerulonephritis, characterized by podocyte apoptosis and subsequent crescent formation, was utilized to test these findings in vivo. Podocyte apoptosis was significantly increased in diseased p35-null compared with wild-type mice, accompanied by increased glomerulosclerosis and decreased renal function. Our study shows that p35 does not affect glomerulogenesis but controls podocyte survival following injury, in part, by regulating Bcl-2 expression

The Art of Hegel's Aesthetics. Hegelian Philosophy and the Perspectives of Art History

This volume explores one of modernity’s most profound and far-reaching philosophies of art: the Vorlesungen über die Ästhetik, delivered by Georg Friedrich Wilhelm Hegel in the 1820s. The book has two overriding objectives: first, to ask how Hegel’s work illuminates specific periods and artworks in light of contemporary art-historical discussions; second, to explore how art history helps us make better sense and use of Hegelian aesthetics. In bringing together a range of internationally acclaimed critical voices, the volume establishes an important disciplinary bridge between aesthetics and art history. Given the recent resurgence of interest in ‘global’ art history, and calls for more comparative approaches to ‘visual culture’, contributors ask what role Hegel has played within the field – and what role he could play in the future. What can a historical treatment of art accomplish? How should we explain the ‘need’ for certain artistic forms at different historical junctures? Has art history been ‘Hegelian’ without fully acknowledging it? Indeed, have art historians shirked some of the fundamental questions that Hegel raised

Demonstration of an off-axis parabolic receiver for near-range retrieval of lidar ozone profiles

During the 2017 Ozone Water Land Environmental Transition Study (OWLETS), the Langley mobile ozone lidar system utilized a new small diameter receiver to improve the retrieval of near-surface signals from 0.1 to 1&thinsp;km in altitude. This new receiver utilizes a single 90&thinsp;∘ fiber-coupled, off-axis parabolic mirror resulting in a compact form that is easy to align. The single reflective surface offers the opportunity to easily expand its use to multiple wavelengths for additional measurement channels such as visible wavelength aerosol measurements. Detailed results compare the performance of the receiver to both ozonesonde and in situ measurements from a UAV platform, validating the performance of the near-surface ozone retrievals. Absolute O3 differences averaged 7&thinsp;% between lidar and ozonesonde data from 0.1 to 1.0&thinsp;km and yielded a 2.3&thinsp;% high bias in the lidar data, well within the uncertainty of the sonde measurements. Conversely, lidar O3 measurements from 0.1 to 0.2&thinsp;km averaged 10.5&thinsp;% lower than coincident UAV O3. A more detailed study under more stable atmospheric conditions would be necessary to resolve the residual instrument differences reported in this work. Nevertheless, this unique added capability is a significant improvement allowing for near-surface observation of ozone.</p

Inhibiting ERK Activation with CI-1040 Leads to Compensatory Upregulation of Alternate MAPKs and Plasminogen Activator Inhibitor-1 following Subtotal Nephrectomy with No Impact on Kidney Fibrosis

Extracellular-signal regulated kinase (ERK) activation by MEK plays a key role in many of the cellular processes that underlie progressive kidney fibrosis including cell proliferation, apoptosis and transforming growth factor β1-mediated epithelial to mesenchymal transition. We therefore assessed the therapeutic impact of ERK1/2 inhibition using a MEK inhibitor in the rat 5/6 subtotal nephrectomy (SNx) model of kidney fibrosis. There was a twentyfold upregulation in phospho-ERK1/2 expression in the kidney after SNx in Male Wistar rats. Rats undergoing SNx became hypertensive, proteinuric and developed progressive kidney failure with reduced creatinine clearance. Treatment with the MEK inhibitor, CI-1040 abolished phospho- ERK1/2 expression in kidney tissue and prevented phospho-ERK1/2 expression in peripheral lymphocytes during the entire course of therapy. CI-1040 had no impact on creatinine clearance, proteinuria, glomerular and tubular fibrosis, and α-smooth muscle actin expression. However, inhibition of ERK1/2 activation led to significant compensatory upregulation of the MAP kinases, p38 and JNK in kidney tissue. CI-1040 also increased the expression of plasminogen activator inhibitor-1 (PAI-1), a key inhibitor of plasmin-dependent matrix metalloproteinases. Thus inhibition of ERK1/2 activation has no therapeutic effect on kidney fibrosis in SNx possibly due to increased compensatory activation of the p38 and JNK signalling pathways with subsequent upregulation of PAI-1

Education, knowledge, and symbolic form

This article aims to introduce Ernst Cassirer, and his philosophy of symbolic form, to education studies, and, in doing so, to challenge the widespread but deeply flawed views of knowledge and so-called knowledge-based education that have shaped recent education policy in England. After sketching the current educational landscape, and then some of the main lines of flight in Cassirer’s work, time is given to a comparison with Heidegger—a more familiar figure by far in Anglophone philosophy than Cassirer, and who contributed to the displacement of Cassirer—in order to illustrate more clearly Cassirer’s original contribution, in particular to the relationship between knowledge and time. Cassirer’s view of knowledge stands in marked and critical contrast to that which has shaped recent educational reform in England, as he sees knowledge as a productive and expressive matter, and repudiates what I call the ‘building-blocks’ picture of knowledge and the hierarchisation of subject areas

New Clathrin-Based Nanoplatforms for Magnetic Resonance Imaging

Background: Magnetic Resonance Imaging (MRI) has high spatial resolution, but low sensitivity for visualization of molecular targets in the central nervous system (CNS). Our goal was to develop a new MRI method with the potential for non-invasive molecular brain imaging. We herein introduce new bio-nanotechnology approaches for designing CNS contrast media based on the ubiquitous clathrin cell protein. Methodology/Principal Findings: The first approach utilizes three-legged clathrin triskelia modified to carry 81 gadolinium chelates. The second approach uses clathrin cages self-assembled from triskelia and designed to carry 432 gadolinium chelates. Clathrin triskelia and cages were characterized by size, structure, protein concentration, and chelate and gadolinium contents. Relaxivity was evaluated at 0.47 T. A series of studies were conducted to ascertain whether fluorescent-tagged clathrin nanoplatforms could cross the blood brain barriers (BBB) unaided following intranasal, intravenous, and intraperitoneal routes of administration. Clathrin nanoparticles can be constituted as triskelia (18.5 nm in size), and as cages assembled from them (55 nm). The mean chelate: clathrin heavy chain molar ratio was 27.0464.8: 1 fo