Positive effect of the induction of p21WAF1/CIP1 on the course of ischemic acute renal failure

Positive effect of the induction of p21WAF1/CIP1 on the course of ischemic acute renal failure.BackgroundThe p21 protein is found in the nucleus of most cells where it modulates cell cycle activity. At low levels, p21 stabilizes interactions between D cyclins and their cyclin-dependent kinases (cdks), but at high levels after induction by several different stress pathways, it causes cell cycle arrest. The p21 mRNA is induced in murine kidney after several types of acute renal failure, including cisplatin administration, ischemia-reperfusion, and ureteral obstruction. We reported that after cisplatin injection, mice with a p21 gene deletion developed much more severe renal damage than wild-type mice. To dissociate the effects of cisplatin-induced DNA damage and subsequent initiation of DNA damage-dependent cell death pathways from effects of acute renal failure, we have now examined mice after ischemia-reperfusion, a model of renal failure not associated with genotoxin-induced DNA damage early after the injury.MethodsWild-type and p21(-/-) mice were made ischemic by clamping both renal hila for 30 or 50 minutes. At various times after reflow, mortality and parameters of renal function and morphology were quantified. Also, the nuclear proteins p21 and proliferating cell nuclear antigen (PCNA) were localized in kidney sections by immunohistochemistry.ResultsKidney function was more impaired and mortality increased significantly in p21(-/-) mice as compared with p21(+/+) mice. We found more cell cycle activity, indicated by increased number of mitotic cells and nuclear PCNA-positive cells, in kidney of p21(-/-) mice.ConclusionsIn this study, p21(-/-) mice were more susceptible to ischemia-induced acute renal failure, with similarly elevated levels of parameters of cell cycle activity. We propose that the increased and inappropriate cell cycle activity in kidney cells is responsible for the increased kidney impairment and mortality

Pathfinder cells provide a novel therapeutic intervention for acute kidney injury

Pathfinder cells (PCs) are a novel class of adult-derived cells that facilitate functional repair of host tissue. We used rat PCs to demonstrate that they enable the functional mitigation of ischemia reperfusion (I/R) injury in a mouse model of renal damage. Female C57BL/6 mice were subjected to 30 min of renal ischemia and treated with intravenous (i.v.) injection of saline (control) or male rat pancreas-derived PCs in blinded experimentation. Kidney function was assessed 14 days after treatment by measuring serum creatinine (SC) levels. Kidney tissue was assessed by immunohistochemistry (IHC) for markers of cellular damage, proliferation, and senescence (TUNEL, Ki67, p16ink4a, p21). Fluorescence in situ hybridization (FISH) was performed to determine the presence of any rat (i.e., pathfinder) cells in the mouse tissue. PC-treated animals demonstrated superior renal function at day 14 post-I/R, in comparison to saline-treated controls, as measured by SC levels (0.13 mg/dL vs. 0.23 mg/dL, p<0.001). PC-treated kidney tissue expressed significantly lower levels of p16ink4a in comparison to the control group (p=0.009). FISH analysis demonstrated that the overwhelming majority of repaired kidney tissue was mouse in origin. Rat PCs were only detected at a frequency of 0.02%. These data confirm that PCs have the ability to mitigate functional damage to kidney tissue following I/R injury. Kidneys of PC-treated animals showed evidence of improved function and reduced expression of damage markers. The PCs appear to act in a paracrine fashion, stimulating the host tissue to recover functionally, rather than by differentiating into renal cells. This study demonstrates that pancreatic-derived PCs from the adult rat can enable functional repair of renal damage in mice. It validates the use of PCs to regenerate damaged tissues and also offers a novel therapeutic intervention for repair of solid organ damage in situ

Teaching indicators to unravel the kinetic features of host-guest inclusion complexes

Both thermodynamic and kinetic insights are needed for a proper analysis of association and dissociation processes of host–guest interactions. However, kinetic descriptions of supramolecular systems are scarce in the literature because suitable experimental protocols are lacking. We introduce here three time-resolved methods that allow for convenient determination of kinetic rate constants of spectroscopically silent or even insoluble guests with the macrocyclic cucurbit[n]uril family and human serum albumin (HSA) protein as representative hosts

On Hilberg's Law and Its Links with Guiraud's Law

Hilberg (1990) supposed that finite-order excess entropy of a random human text is proportional to the square root of the text length. Assuming that Hilberg's hypothesis is true, we derive Guiraud's law, which states that the number of word types in a text is greater than proportional to the square root of the text length. Our derivation is based on some mathematical conjecture in coding theory and on several experiments suggesting that words can be defined approximately as the nonterminals of the shortest context-free grammar for the text. Such operational definition of words can be applied even to texts deprived of spaces, which do not allow for Mandelbrot's ``intermittent silence'' explanation of Zipf's and Guiraud's laws. In contrast to Mandelbrot's, our model assumes some probabilistic long-memory effects in human narration and might be capable of explaining Menzerath's law.Comment: To appear in Journal of Quantitative Linguistic

Educational Evaluation, Assessment, & Effectiveness Glossary: A Claremont Graduate University EDUC 445 Fall 2021 Course Publication

This glossary is intended to support professionals who are seeking to understand evaluation, assessment, and effectiveness in the context of K-12 and higher education. The definitions in this e-book represent the shared meanings that were co-created by education professionals in EDUC 445 at the Claremont Graduate University during Fall 2021 under the guidance of Dr. Gwen Garrison, PhD

The history of degenerate (bipartite) extremal graph problems

This paper is a survey on Extremal Graph Theory, primarily focusing on the case when one of the excluded graphs is bipartite. On one hand we give an introduction to this field and also describe many important results, methods, problems, and constructions.Comment: 97 pages, 11 figures, many problems. This is the preliminary version of our survey presented in Erdos 100. In this version 2 only a citation was complete

Alteration of renal respiratory Complex-III during experimental type-1 diabetes

<p>Abstract</p> <p>Background</p> <p>Diabetes has become the single most common cause for end-stage renal disease in the United States. It has been established that mitochondrial damage occurs during diabetes; however, little is known about what initiates mitochondrial injury and oxidant production during the early stages of diabetes. Inactivation of mitochondrial respiratory complexes or alteration of their critical subunits can lead to generation of mitochondrial oxidants, mitochondrial damage, and organ injury. Thus, one goal of this study was to determine the status of mitochondrial respiratory complexes in the rat kidney during the early stages of diabetes (5-weeks post streptozotocin injection).</p> <p>Methods</p> <p>Mitochondrial complex activity assays, blue native gel electrophoresis (BN-PAGE), Complex III immunoprecipitation, and an ATP assay were performed to examine the effects of diabetes on the status of respiratory complexes and energy levels in renal mitochondria. Creatinine clearance and urine albumin excretion were measured to assess the status of renal function in our model.</p> <p>Results</p> <p>Interestingly, of all four respiratory complexes only cytochrome c reductase (Complex-III) activity was significantly decreased, whereas two Complex III subunits, Core 2 protein and Rieske protein, were up regulated in the diabetic renal mitochondria. The BN-PAGE data suggested that Complex III failed to assemble correctly, which could also explain the compensatory upregulation of specific Complex III subunits. In addition, the renal F₀F₁-ATPase activity and ATP levels were increased during diabetes.</p> <p>Conclusion</p> <p>In summary, these findings show for the first time that early (and selective) inactivation of Complex-III may contribute to the mitochondrial oxidant production which occurs in the early stages of diabetes.</p

Transformation tools enabling the implementation of nature-based solutions for creating a resourceful circular city

The linear pattern of production-consumption-disposal of cities around the world will continue to increase the emission of pollutants and stocks of waste, as well as to impact on the irreversible deterioration of non-renewable stocks of raw materials. A transition towards a circular pattern proposed by the concept of ‘Circular Cities’ is gaining momentum. As part of this urban transition, the emergent use of Nature-based Solutions (NBS) intends to shift public opinion and utilize technology to mitigate the urban environmental impact. In this paper, an analysis of the current research and practical investments for implementing NBS under the umbrella of Circular Cities is conducted. A combined appraisal of the latest literature and a survey of ongoing and completed National-European research and development projects provides an overview of the current enabling tools, methodologies, and initiatives for public engagement. It also identifies and describes the links between facilitators and barriers with respect to existing policies and regulations, public awareness and engagement, and scientific and technological instruments. The paper concludes introducing the most promising methods, physical and digital technologies that may lead the way to Sustainable Circular Cities. The results of this research provide useful insight for citizens, scientists, practitioners, investors, policy makers, and strategists to channel efforts on switching from a linear to a circular thinking for the future of cities

Reversible Nanoparticle–Micelle Transformation of Ionic Liquid–Sulfonatocalix[6]arene Aggregates

The effect of temperature and NaCl concentration variations on the self-assembly of 1-methyl-3- tetradecylimidazolium (C14mim+) and 4-sulfonatocalix[6]- arene (SCX6) was studied by dynamic light scattering and isothermal calorimetric methods at pH 7. Inclusion complex formation promoted the self-assembly to spherical nanoparticles (NP), which transformed to supramolecular micelles (SM) in the presence of NaCl. Highly reversible, temperature-responsive behavior was observed, and the conditions of the NP−SM transition could be tuned by the alteration of C14mim+:SCX6 mixing ratio and NaCl concentration. The association to SM was always exothermic with enthalpy independent of the amount of NaCl. In contrast, NPs were produced in endothermic process at low temperature, and the enthalpy change became less favorable upon increase in NaCl concentration. The NP formation was accompanied by negative molar heat capacity change, which further diminished when NaCl concentration was raised