bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of Apoptosis-Related Genes and Proteins in Experimental Chronic Renal Scarring
Authors: YANG BIN , JOHNSON TIMOTHY S. , THOMAS GRAHAM L. , WATSON PHILIP F. , WAGNER BART , SKILL NICHOLAS J. , HAYLOR JOHN L. , NAHAS A. MEGUID EL
Published: April 2021

Apoptosis has been proposed to play an important role in the progression of renal scarring. The mechanisms that determine whether a cell enters the apoptotic program are complex. Bax and Bcl-2 are recognized modulators of this event; their relative levels determine the fate of cells. A role for apoptosis in the progression of renal scarring in the remnant kidneys of rats submitted to subtotal nephrectomy (SNx) has been described. This study investigated the expression (protein and mRNA) of Bax and Bcl-2 in remnant kidneys between day 7 and day 120 post-SNx. Northern blot analysis showed that bax mRNA was increased in remnant kidneys from day 7 (150% of control; P < 0.05), whereas bcl-2 mRNA was decreased from day 15 (23% of control; P < 0.05) resulting in a 14-fold increase in the ratio of bax to bcl-2 mRNA by day 120. Western blot analysis showed similar changes in Bax and Bcl-2 protein in remnant kidneys, resulting in a 147-fold increase in the ratio of Bax to Bcl-2 on day 120. Immunohistochemistry showed increases in Bax to be located predominantly in tubules in SNx kidneys. Interstingly, Bcl-2 immunostaining increased in some epithelial cells within atrophic tubules despite the overall decrease in Bcl-2 protein and mRNA. The overall renal apoptotic cells correlated closely with the ratio of bax to bcl-2 at both the mRNA and protein levels (r = 0.594 and 0.308, respectively; P < 0.05). Furthermore, tubular apoptosis correlated positively with the mRNA level of bax (r = 0.471; P < 0.01) and negatively with the mRNA and protein levels of bcl-2 (r = -0.443 and -0.607, respectively; P < 0.01). The increase in the ratio of the death inducer (Bax) to the death repressor (Bcl-2) at the mRNA and protein levels may control the apoptosis associated with the progression of tubular atrophy and chronic renal fibrosis within remnant rat kidneys. These observations may have prognostic and therapeutic implications in chronic renal failure.
Trends of Analgesic Nephropathy in Two High-Endemic Regions with Different Legislation
Authors: MICHIELSEN PAUL , SCHEPPER PAUL DE
Published: April 2021

Analgesic abuse is related to a specific form of interstitial nephritis, but the exact nature of the causal agent remains controversial and this has resulted in differences in regulation. In Flanders, the free sale of phenacetin was banned, but the consumption of other combined analgesics remained free. In New South Wales, phenacetin was also banned, but 2 yr later the sales of all combined analgesics were also prohibited. This study compared the evolution of end-stage renal disease as a result of analgesic nephropathy (AN) in these two high-endemic regions with different legislation. In both regions, the time trend of the age-specific incidence of end-stage renal disease as a result of AN is similar in the age group 45 to 54 yr. In all age groups combined, the time trend of the percentage of AN among the patients admitted for renal replacement therapy is also similar. This finding does not support the hypothesis that non-phenacetin mixed analgesics play a significant role in the occurrence of AN.
Angiotensinogen in Essential Hypertension
Authors: LALOUEL JEAN-MARC , ROHRWASSER ANDREAS , TERREROS DANIEL , MORGAN TERRY , WARD KENNETH
Published: April 2021

There is general consensus that genetic variation accounts in part for individual susceptibilities to essential hypertension. In marked contrast to classic mendelian disorders, in which genetic alterations produce a gain or loss of function, genetic determinants of essential hypertension, high blood pressure of unknown cause, are expected to be small, achieving significance through the cumulative effects of environmental exposure over the course of a lifetime. Whether and how genetic factors that contribute to common diseases can be identified remain unclear. Research on a link between angiotensinogen and essential hypertension illustrates a path that began in genetics and is now leading toward nephrology. Various challenges encountered along the way may prove to be characteristic features of genetic investigations of the pathogenesis of common diseases. The implication of a gene by statistical analysis is only the beginning of a protracted process of functional analysis at increasing levels of biologic integration. The ultimate goal is to develop an understanding of the manner in which genetic variation at a locus can affect a physiologic parameter and to extract from this inference new knowledge of significance for the prevention or treatment of disease.
Transcytosis of Retinol-Binding Protein across Renal Proximal Tubule Cells after Megalin (gp 330)-Mediated Endocytosis
Authors: MARINÓ MICHELE , ANDREWS DAVID , BROWN DENNIS , McCLUSKEY ROBERT T.
Published: April 2021

Plasma retinol-binding protein (RBP) combined with vitamin A (retinol) is partially filtered through the glomerulus and then absorbed by proximal tubule cells, leading to recycling of retinol to the circulation. Recently, it was shown that reabsorption of RBP-retinol complexes by proximal tubule cells is mediated by megalin (gp 330), an apical endocytic receptor. It was proposed that RBP is transported by megalin to lysosomes, where it is degraded, thus liberating retinol, which then combines with newly synthesized RBP to be secreted into the bloodstream. This study shows that passage of RBP through immortalized rat renal proximal tubule (IRPT) cells occurs by transcytosis after megalin-mediated endocytosis, which provides an alternative pathway for recycling of retinol. IRPT cells cultured as polarized monolayers with tight junctions were used on permeable filters in the upper chamber of dual-chambered devices, with megalin expression exclusively on the upper surface. After addition of RBP to the upper chamber and incubation at 37°C, intact RBP was found in fluids that were collected from the lower chamber. In contrast, control substances (mannitol, lysozyme, albumin, and glutathione-S-transferase) were not appreciably transported across IRPT cells, indicating that passage of RBP was by transcytosis and not by paracellular leakage. Confocal microscopy analysis of IRPT cells after addition of RBP to the upper chamber revealed RBP-containing granules at the apical membrane, subapically, and also at basolateral membranes. When RBP was added to IRPT cells together with megalin competitors, the amount of transcytosed RBP was markedly reduced. We also found that some RBP was internalized and degraded by IRPT cells, but this process was not appreciably affected by megalin competitors, indicating that RBP endocytosed by megalin was not transported to lysosomes and degraded but rather transcytosed across IRPT cells.
Upregulation of Ciliary Neurotrophic Factor (CNTF) and CNTF Receptor α in Rat Kidney with Ischemia-Reperfusion Injury
Authors: YANG CHUL WOO , LIM SUN WOO , HAN KI WHAN , AHN HEE JONG , PARK JUNG HEE , KIM YOUNG HEE , KIRSH MATTHIAS , CHA JUNG HO , PARK JOO HYUN , KIM YONG SOO , KIM JIN , BANG BYUNG KEE
Published: April 2021

Ciliary neurotrophic factor (CNTF) is presumed to play a role as a survival factor in neuronal cells, but little is known about its role in the kidney. To investigate this, the expression of CNTF and CNTF receptor α (CNTFR α) was analyzed in the ischemic rat kidney. An ischemia/reperfusion (I/R) injury was induced by clamping both renal arteries for 45 min. Animals were killed at 1, 2, 3, 5, 7, 14, and 28 d after ischemia. The expression of CNTF and CNTFR α was monitored by reverse transcription-PCR, in situ hybridization, immunoblotting, immunohistochemistry, and electron microscopy. In sham-operated rat kidneys, CNTF expression was weak and limited to the descending thin limb of the loop of Henle. With I/R injury, CNTF mRNA and protein expressions were strikingly increased as compared with the sham-operated rat kidney, and the immunoreactivity of CNTF was mainly observed in the regenerating proximal tubules. The expression of CNTFR α mRNA was also increased after I/R injury, and its location and expression patterns were similar to the expression of CNTF. These findings suggest a possible role of CNTF as a growth factor during renal tubular repair processes after I/R injury and an autocrine or paracrine function of CNTF acting against CNTFR α.
Puromycin Aminonucleoside Suppresses Integrin Expression in Cultured Glomerular Epithelial Cells
Authors: KRISHNAMURTI UMA , ZHOU BING , FAN WEI-WEI , TSILIBARY EFFIE , WAYNER ELIZABETH , KIM YOUNGKI , KASHTAN CLIFFORD E. , MICHAEL ALFRED
Published: April 2021

Puromycin aminonucleoside (PAN)-induced nephrosis is a well-described model of human idiopathic nephrotic syndrome, but the mechanism of PAN's effect is not completely understood. Because PAN injection into rats results in retraction of glomerular epithelial cell foot processes and glomerular epithelial cell detachment, it was hypothesized that PAN might alter the contacts between these cells and the glomerular basement membrane. The major integrin expressed by glomerular epithelial cells is α3β1, which mediates attachment of these cells to extracellular matrix proteins including type IV collagen. T-SV 40 immortalized human glomerular epithelial cells were used to study PAN's effects on α3β1 expression, as well as that of podocalyxin and the slit diaphragm component ZO-1. Glomerular epithelial cells were seeded into plastic flasks and allowed to attach and proliferate for 48 h. The cells were then incubated for another 48 h in media containing 0, 0.5, or 5.0 μg/ml PAN. PAN exposure resulted in dose-dependent decreases in α3 and β1 expression, both at the protein level and at the mRNA level. This was accompanied by a significant decrease in the adhesion of glomerular epithelial cells to type IV collagen. PAN did not affect ZO-1 protein expression. Treatment with PAN increased the expression of podocalyxin at the protein and mRNA levels. Reduced glomerular epithelial cell expression of α3β1 integrins and impaired adhesion to type IV collagen may contribute to the glomerular epithelial cell detachment from glomerular basement membrane seen in the PAN nephrosis model.
Approaching the Therapeutic Window for Cyclosporine in Kidney Transplantation
Authors: MAHALATI KAMRAN , BELITSKY PHILIP , WEST KENNETH , KIBERD BRYCE , FRASER ALBERT , SKETRIS INGRID , MACDONALD ALAN S. , MCALISTER VIVIAN , LAWEN JOSEPH
Published: April 2021

Neoral dosing is traditionally based on cyclosporine (CyA) trough levels (C0). Four-h area under the curve (AUC0-4) for Neoral in the early posttransplantation period was shown previously to have a better correlation to acute rejection (AR) and CyA nephrotoxicity (CyANT), compared with C0. An AUC0-4 range of 4400 to 5500 μg/h per L during the first week was associated with the lowest AR and CyANT. This article describes a prospective study to assess the feasibility, safety, and efficacy of dosing Neoral solely by AUC0-4 monitoring, regardless of C0, in the first 3 mo after kidney transplantation. Fifty-nine kidney transplant recipients received Neoral-based triple immunosuppression. AUC0-4 was measured on days 3, 5, 7, 10, and 14 and weeks 3, 4, 6, and 8, then monthly. Target AUC0-4 was 4400 to 5500 μg/h per L. Dose was adjusted by percentage difference from target AUC0-4. Ninety-four percent of AUC were performed on the scheduled day or close to it. No patients had CyANT while AUC0-4 was in target range. Four patients had reversible CyANT with AUC0-4 > 5500. Only 1 of 33 patients (3%) who achieved and maintained AUC0-4 > 4400 by day 3 posttransplantation had AR, whereas 10 of 22 (45%) of those with day 3 to 5 AUC0-4 < 4400 had AR (P = 0.0002). In logistic regression analysis, higher early AUC0-4 was the only significant variable associated with lower serum creatinine at 3 mo. Neoral dose monitoring by AUC0-4 is a potentially valuable tool for optimizing Neoral immunosuppression. Attainment of a target range of 4400 to 5500 μg/h per L for AUC0-4 early after transplantation has been demonstrated to reduce significantly the risk of AR and CyANT.
Polycystin
Authors: WILSON PATRICIA D.
Published: April 2021

Polycystin-1 is a modular membrane protein with a long extracellular N-terminal portion that bears several ligand-binding domains, 11 transmembrane domains, and a ≥200 amino acid intracellular C-terminal portion with several phosphorylation signaling sites. Polycystin-1 is highly expressed in the basal membranes of ureteric bud epithelia during early development of the metanephric kidney, and disruption of the PKD1 gene in mice leads to cystic kidneys and embryonic or perinatal death. It is proposed that polycystin-1 functions as a matrix receptor to link the extracellular matrix to the actin cytoskeleton via focal adhesion proteins. Co-localization, co-sedimentation, and co-immunoprecipitation studies show that polycystin-1 forms multiprotein complexes with α2β1-integrin, talin, vinculin, paxillin, p130cas, focal adhesion kinase, and c-src in normal human fetal collecting tubules and sub-confluent epithelial cultures. In normal adult kidneys and confluent epithelial cultures, polycystin-1 is downregulated and forms complexes with the cell-cell adherens junction proteins E-cadherin and β-, γ-, and α-catenin. Polycystin-1 activation at the cell membrane leads to intracellular signaling via phosphorylation through the c-Jun terminal kinase and wnt pathways leading to activation of AP-1 and TCF/LEF-dependent genes, respectively. The C-terminal of polcystin-1 has been shown to be phosphorylated by c-src at Y4237, by protein kinase A at S4252, and by focal adhesion kinase and protein kinase X at yet-to-be identified residues. Inhibition of tyrosine phosphorylation or increased cellular calcium increases polycystin-1 focal adhesion complexes versus polycystin-1 adherens junction complexes, whereas disruption of the actin cytoskeleton dissociates all polycystin-1 complexes. Genetic evidence suggests that PKD1, PKD2, NPHP1, and tensin are in the same pathway.
Peritoneal Glucose Exposure and Changes in Membrane Solute Transport with Time on Peritoneal Dialysis
Authors: DAVIES SIMON J. , PHILLIPS LOUISE , NAISH PATRICK F. , RUSSELL GAVIN I.
Published: April 2021

Peritoneal solute transport increases with time on treatment in a proportion of peritoneal dialysis (PD) patients, contributing to ultrafiltration failure. Continuous exposure of the peritoneum to hypertonic glucose solutions results in morphologic damage that may have a causative role in changes in peritoneal function. The purpose of this analysis was to establish whether increased exposure to glucose preceded changes in solute transport in a selected group of long-term PD patients. Peritoneal solute transport, residual renal function, peritonitis rate, and peritoneal exposure to glucose were recorded prospectively in a cohort of 303 patients at a single dialysis center. A subgroup of individuals, treated continuously for 5 yr, were identified and defined retrospectively as having either stable or increasing transport status. Of the 22 patients who were treated continuously for 5 yr, 13 had stable solute transport (solute transport at start, 0.67 [±0.1]; at 5 yr, 0.67 [±0.1]), whereas 9 had a sustained increase (solute transport at start, 0.56 [±0.08]; at 5 yr, 0.77 [±0.09]). Compared with the stable patients, those with increasing transport had earlier loss in residual renal function and were exposed to significantly more hypertonic glucose during the first 2 yr of treatment that preceded the increase in solute transport. This was associated with greater achieved ultrafiltration compensating for the reduced urinary volumes in these patients. Further increases in glucose exposure were observed as solute transport continued to rise. Peritonitis, including severity of infection and causative organism, was similar in both groups. In this selected group of long-term survivors on PD, an increase in solute transport with time was preceded by increased peritoneal exposure to hypertonic glucose. This is supportive evidence that hypertonic glucose may play a causative role in alterations in peritoneal membrane function.
Role of Renocortical Cyclooxygenase-2 for Renal Vascular Resistance and Macula Densa Control of Renin Secretion
Authors: CASTROP HAYO , SCHWEDA FRANK , SCHUMACHER KARL , WOLF KONRAD , KURTZ ARMIN
Published: April 2021

This study aimed to assess the role of cyclooxygenase-2 (COX-2)-derived prostanoids for the macula densa control of renal afferent arteriolar resistance and for renin secretion. For this purpose, studied were the effects of blocking macula densa salt transport by the loop diuretic bumetanide (100 μM) on renal perfusate flow and on renin secretion in isolated perfused rats, in which renocortical COX-2 expression was prestimulated in vivo by treatment with the angiotensin-converting enzyme inhibitor ramipril, with low-salt diet, or with a combination of both. These maneuvers stimulated COX-2 expression in an order of ramipril + low salt ≫ low salt > ramipril > controls. Flow rates through isolated kidneys at a constant pressure of 100 mmHg were dependent on the pretreatment regimen, in the way that they went in parallel with COX-2 expression. The COX-2 inhibitor NS-398 (10 μM) lowered flow rates depending on the COX-2 expression level and was most pronounced therefore after pretreatment with low salt + ramipril. NS-398 did not change the increase of flow in response to bumetanide but attenuated the stimulation of renin secretion in response to bumetanide in a manner depending on the expression level of COX-2. These findings suggest that in states of increased renocortical expression of COX-2, overall renal vascular resistance and the macula densa control of renin secretion become dependent on COX-2—derived prostanoids.
Cisplatin Decreases the Abundance of Aquaporin Water Channels in Rat Kidney
Authors: KIM SOO-WAN , LEE JONG-UN , NAH MYONG-YUN , KANG DAE-GILL , AHN KYU-YOUN , LEE HO-SUB , CHOI KI-CHUL
Published: April 2021

The present study examined whether the cisplatininduced urinary concentration defect can be related to an altered regulation of aquaporin (AQP) water channels in the kidney. Cisplatin (8 mg/kg) was injected intraperitoneally into male Sprague-Dawley rats. The control group was without cisplatin treatment. Four d later, the expression of AQP1, AQP2, and AQP3 proteins was determined in the kidney. To specify further the primary point of derangement in the pathway that activates the arginine vasopressin—mediated AQP channels, different components of adenylyl cyclase complex were examined separately. The cisplatin treatment caused a polyuric renal failure in association with decreases of free water reabsorption. The expression of AQP1 and AQP2 was decreased in the cortex, the outer medulla, and the inner medulla, whereas that of AQP3 was decreased in the outer medulla and the inner medulla. The expression of AQP2 proteins in the apical membrane-enriched fraction decreased in parallel with that in the subapical vesicle-enriched fraction, indicating a preserved targeting. Immunohistochemistry of the outer medulla also revealed that cisplatin decreased immunoreactivity for AQP1, AQP2, and AQP3. The arginine vasopressin—evoked generation of cyclic adenosine monophosphate was attenuated by cisplatin, being most prominent in the outer medulla. However, the cyclic adenosine monophosphate generation in response to forskolin was not affected, whereas that to sodium fluoride was diminished significantly. Cisplatin also decreased the expression of Gsα proteins in the outer medulla and the inner medulla. These results suggest that a reduced expression of AQP water channels accounts at least in part for the cisplatin-induced urinary concentration defect.
Proteinase 3 Enhances Endothelial Monocyte Chemoattractant Protein-1 Production and Induces Increased Adhesion of Neutrophils to Endothelial Cells by Upregulating Intercellular Cell Adhesion Molecule-1
Authors: TAEKEMA-ROELVINK MIRIAM E. J. , VAN KOOTEN CEES , VAN DER KOOIJ SANDRA , HEEMSKERK EVERT , DAHA MOHAMED R.
Published: April 2021

Wegener's granulomatosis is an autoimmune disease that is characterized by systemic vasculitis and granuloma formation. Early influx of polymorphonuclear neutrophils (PMN), followed at a later stage by mononuclear cells, contributes to the granulomatous inflammation. Previous studies have shown that proteinase 3 (PR3), the major autoantigen in Wegener's granulomatosis, specifically binds to endothelial cells and plays a possible role in activation of these cells by enhancing interleukin-8 production, thus providing a chemotactic and activating stimulus for PMN. The present study demonstrated that PR3 enhances the production of monocyte chemoattractant protein-1 (MCP-1) by human umbilical vein endothelial cells (HUVEC) in a dose- and time-dependent manner. The PR3-induced increase in MCP-1 production was demonstrated at both the protein and the mRNA levels and was chemotactic for monocytes. In addition, it was demonstrated that PR3 induces a dose- and time-dependent increase in the expression of intercellular adhesion molecule-1 (ICAM-1) as determined by fluorescence-activated cell sorter analysis. The PR3-induced increase in expression of ICAM-1 was also demonstrated at the mRNA level. PR3 induced a slight increase in vascular cell adhesion molecule-1 expression and had no effect on the expression of both P- and E-selectin. Incubation of HUVEC for 24 h in the presence of PR3 resulted in a significant increase in adhesion of PMN, which was reduced to baseline levels in the presence of blocking monoclonal antibody anti—ICAM-1 or anti-CD18 or a combination of both. Monocytes showed a slight but statistically not significant increase in adhesion. Incubation of HUVEC with PR3 for 4 h did not result in enhanced adhesion of either PMN or monocytes. It was hypothesized that PR3, which may be released locally at inflammatory sites after activation of cytokineprimed PMN, plays a role in endothelial cell activation by enhancing both interleukin-8 and MCP-1 production, thus providing a chemotactic and activating stimulus for both PMN and monocytes. In addition, PR3 may contribute to the ongoing inflammation by enhancing the adhesion of PMN to endothelial cells by upregulating ICAM-1 expression.
Antibodies against Vascular Endothelial Growth Factor Improve Early Renal Dysfunction in Experimental Diabetes
Authors: DE VRIESE AN S. , TILTON RONALD G. , ELGER MARLIES , STEPHAN CLIFFORD C. , KRIZ WILHELM , LAMEIRE NORBERT H.
Published: April 2021

Vascular endothelial growth factor (VEGF) is a cytokine that potently stimulates angiogenesis, microvascular hyperpermeability, and endothelium-dependent vasodilation, effects that are largely mediated by endothelial nitric oxide synthase (eNOS). The expression of VEGF is pronounced in glomerular visceral epithelial cells, but its function in renal physiology and pathophysiology is unknown. VEGF expression is upregulated by high ambient glucose concentrations in several cell types in vitro and in glomeruli of diabetic rats. To assess the role of VEGF in the pathophysiology of early renal dysfunction in diabetes, monoclonal anti-VEGF antibodies (Ab) were administered to control and streptozotocin-induced diabetic rats for 6 wk after induction of diabetes. Based on in vitro binding studies, an adequate serum VEGF inhibitory activity was achieved during the entire course of anti-VEGF Ab administration. Anti-VEGF Ab treatment but not administration of isotype-matched control Ab decreased hyperfiltration, albuminuria, and glomerular hypertrophy in diabetic rats. VEGF blockade also prevented the upregulation of eNOS expression in glomerular capillary endothelial cells of diabetic rats. Antagonism of VEGF had no effect on GFR and glomerular volume in control rats. These results identify VEGF as a pathogenetic link between hyperglycemia and early renal dysfunction in diabetes. Targeting VEGF may prove useful as a therapeutic strategy for the treatment of early diabetic nephropathy.
Altered Signaling and Regulatory Mechanisms of Apoptosis in Focal and Segmental Glomerulosclerosis
Authors: WANG WANSHENG , TZANIDIS ALEX , DIVJAK MAJA , THOMSON NAPIER MAURICE , STEIN-OAKLEY ALICIA NOEMI
Published: April 2021

The purpose of this study was to investigate signaling and regulatory mechanisms of apoptosis in a model of focal and segmental glomerulosclerosis. Sprague-Dawley rats received two doses of puromycin aminonucleoside (PAN) (day 0 and week 3) and a uninephrectomy (PAN model). Apoptosis was detected with the use of the terminal deoxynucleotidyl transferase mediated dUTP nick end labeling technique. Bax, Bcl-2, Fas, and Fas ligand expression was analyzed by competitive reverse transcription-PCR. Bax, Bcl-2, and Fas mRNA were localized by in situ hybridization. Renal function was transiently impaired after the first PAN dose. After the second PAN dose, further progressive renal impairment, tubular atrophy, interstitial fibrosis, and glomerulosclerosis were evident. Eighteen percent of PAN samples demonstrated up to 4 apoptotic cells/50 glomeruli, compared with 7% of sham controls (not significant). No consistent significant change in glomerular Bax, Bcl-2, Fas, and Fas ligand mRNA was evident by reverse transcription-PCR, although focal increases in glomerular Bcl-2 mRNA were demonstrated by in situ hybridization. In the tubulointerstitium, apoptosis was increased from weeks 1 to 12 (P < 0.01 PAN versus sham), correlated to renal function and tubulointerstitial injury (P < 0.01). Total renal Bax, Fas, and Fas ligand mRNA were upregulated in the PAN model, peaking at week 17 (P < 0.01 versus sham), whereas Bcl-2 mRNA was not significantly different in PAN versus sham controls. In situ hybridization in the PAN model demonstrated prominent Bax mRNA in dilated tubules and infiltrating leukocytes. Fas mRNA signal was localized to tubular epithelial cells and leukocytes. The results suggest that altered apoptotic signaling and regulatory mechanisms contribute to the tubulointerstitial injury in this model.
Relative Potencies of 1,25-(OH)2D3 and 19-Nor-1,25-(OH)2D2 on Inducing Differentiation and Markers of Bone Formation in MG-63 Cells
Authors: FINCH JANE L. , DUSSO ADRIANA S. , PAVLOPOULOS TRICIA , SLATOPOLSKY EDUARDO A.
Published: April 2021

19-Nor-1,25-(OH)2D2, an analog of 1,25-(OH)2D3, is used to treat secondary hyperparathyroidism because it suppresses parathyroid hormone synthesis and secretion with lower calcemic and phosphatemic activities. 19-Nor-1,25-(OH)2D2 is approximately 10 times less active than 1,25-(OH)2D3 in promoting bone resorption, which accounts in part for the low potency of this analog in increasing serum calcium and phosphorus. Concern that 19-nor-1,25-(OH)2D2 also could be less potent than 1,25-(OH)2D3 on bone formation led to a comparison of the potency of both compounds on osteoblasts. In the human osteoblast-like cell line MG-63, 1,25-(OH)2D3 and 19-nor-1,25-(OH)2D2 had a similar potency in upregulating vitamin D receptor content and suppressing proliferation. Both sterols caused a similar reduction in DNA content and proliferating cell nuclear antigen protein expression. Time-course and dose-response studies on 1,25-(OH)2D3 and 19-nor-1,25-(OH)2D2 induction of the marker of bone formation, osteocalcin, showed overlapping curves. The effects on alkaline phosphatase (ALP) activity also were studied in MG-63 cells that had been co-treated with either sterol and transforming growth factor-β, an enhancer of 1,25-(OH)2D3—induced ALP activity in this cell line. Transforming growth factor-β alone had no effect, whereas 1,25-(OH)2D3 and 19-nor-1,25-(OH)2D2 increased ALP activity similarly. These studies demonstrate that 19-nor-1,25-(OH)2D2 has the same potency as 1,25-(OH)2D3 not only in inducing vitamin D receptor content, osteocalcin levels, and ALP activity but also in controlling osteoblastic growth. Therefore, it is unlikely that 19-nor-1,25-(OH)2D2 would have deleterious effects on bone remodeling.
Angiotensin III Activates Nuclear Transcription Factor-κB in Cultured Mesangial Cells Mainly via AT2 Receptors
Authors: Lorenzo Óscar , Ruiz-Ortega Marta , Suzuki Yusuke , Rupérez Mónica , Esteban Vanesa , Sugaya Takeshi , Egido Jesús
Published: April 2021

Nuclear factor-κB (NF-κB) regulates many genes involved in renal pathophysiologic processes. It was previously demonstrated that angiotensin II (AngII) and its amino-terminal degradation product AngIII activate NF-κB in mesangial cells. However, which are the Ang receptor subtypes involved in the NF-κB pathway and whether these Ang peptides act through the same or different receptors in mesangial cells have not been evaluated. Under the culture conditions used, quiescent rat mesangial cells expressed both AT1 and AT2 receptors. To investigate the receptors involved in the NF-κB pathway, two different approaches were used, i.e., pharmacologic studies, using specific AT1 and AT2 receptor antagonists and agonists, and studies in AT1 receptor-knockout mice. In cultured rat mesangial cells, both AT1 and AT2 receptor antagonists inhibited AngII-induced NF-κB DNA binding activity, whereas NF-κB activation elicited by AngIII was mainly blocked by the AT2 receptor antagonist. Similar results were observed for cytosolic IκBα degradation. An AT2 receptor agonist also activated NF-κB. In AT1 receptor-knockout murine mesangial cells, AngIII and AngII increased NF-κB activity and degraded cytosolic IκBα; both processes were blocked by the AT2 receptor antagonist. These data demonstrate that, in mesangial cells, NF-κB activation is mediated by AT1 and AT2 receptors, suggesting a novel intracellular signaling mechanism for AT2 receptors in the kidney. Some differences in Ang peptide receptor-mediated responses were also observed. AngII activates NF-κB via AT1 and AT2 receptors, whereas AngIII acts mainly via AT2 receptors. These results suggest the potential involvement of the AngIII/AT2 receptor/NF-κB pathway in pathophysiologic processes in the kidney and provide a better understanding of the renin-angiotensin system.
Osteopontin Synthesis and Localization along the Human Nephron
Authors: Verhulst Anja , Persy Veerle P. , Van Rompay An R. , Verstrepen Walter A. , Helbert Mark F. , De Broe Marc E.
Published: April 2021

In normal human and rat kidneys, osteopontin (OPN) is present at the apical surface of cells in the distal nephron. After ischemic or toxic renal damage in rats, OPN is upregulated in distal tubular cells (DTC) and expressed de novo in perinuclear vesicles in proximal tubular cells (PTC). In the first phase of this study, OPN localization in ischemic human biopsies was compared with that in ischemic rat kidneys. In the second phase, cultures of PTC and DTC were used to investigate human renal OPN synthesis, secretion, and localization. OPN localization in human biopsies after renal ischemia was comparable to that in ischemic rat kidneys. Microscopic and flow cytometric detection of immunofluorescent OPN staining in tubular cell cultures demonstrated strong plasma membrane localization in DTC, whereas mainly perinuclear intracellular expression was observed in PTC. Northern blotting and reverse transcription-PCR demonstrated production of a single OPN mRNA in PTC and DTC. Detection of OPN by Western blotting and enzyme-linked immunosorbent assay demonstrated that PTC and DTC synthesized and secreted the same three molecular mass OPN forms, in comparable amounts. Finally, confocal microscopy demonstrated different staining patterns for endocytotic/lysosomal vesicles and perinuclear OPN; however, perinuclear OPN exhibited colocalization with the Golgi apparatus. In conclusion, human renal OPN localization in cell cultures demonstrated differences between PTC and DTC comparable to those observed after renal ischemia in vivo. Therefore, these cell cultures represented an excellent model for the study of human OPN synthesis, secretion, and localization in PTC versus DTC. It is reported for the first time that intracellular OPN is located in the Golgi apparatus of both PTC and DTC and that PTC and DTC are able to produce and secrete the same OPN isoforms, in comparable amounts.
Ömer Seyfettin’in And Adlı Eserinde Yer Alan Şiddet Olgusuna İlişkin Öğrenci Görüşleri
Authors: KAYMAN Faruk , AYDIN Erkan
Published: April 2021

Bu araştırmanın amacı, ortaokul 6. sınıf öğrencilerinin Ömer Seyfettin’in And adlı öyküsünde yer alan şiddet olgusu hakkındaki görüşlerini tespit etmektir. Araştırma, Tuşba Kaymakamlık makamından araştırma izni alındıktan sonra 2021 yılı Ocak ayında gerçekleştirilmiştir. Araştırmanın örneklemini, Van ili Tuşba ilçesine bağlı İsmail Hakkı Tonguç Ortaokulu 6-A sınıfında öğrenim gören 22 öğrenci oluşturmaktadır. Araştırmada nitel araştırma desenlerinden fenomenoloji (olgubilim) kullanılmıştır. Verilerin toplanmasında uzman görüşü alınarak geliştirilen ve açık uçlu sorulardan oluşan yarı yapılandırılmış görüşme formu kullanılmış, verilerin çözümlenmesinde ise içerik analizi yöntemine başvurulmuştur. Araştırma sonucunda öğrencilerin eserde yer alan şiddet sahnelerini beğenmedikleri, şiddet içeren bölümlerden etkilendikleri, bu bölümleri eserden çıkarmak istedikleri tespit edilmiştir.
Strateji Öğretiminde Kullanılan Farklı Yaklaşımların Öğrencilerin Okuma Stratejileri Üstbilişsel Farkındalık Becerilerine Etkisi
Authors: AMANVERMEZ İNCİRKUŞ Funda , BEYRELİ Latif
Published: April 2021

Çalışmanın amacı, strateji öğretiminde kullanılan farklı yaklaşımlarla öğrencilerin okuma stratejileri bilişsel farkındalık becerileri arasında nasıl bir ilişki olduğunu belirlemektir. Araştırmada 6. sınıf düzeyinde 2 deney ve 1 kontrol grubuyla çalışılmıştır. 1. grupta öğretmenin “rehber”; 2. grupta öğretmenin stratejileri açıklayarak “model” olduğu açık strateji öğretim yaklaşımları benimsenmiştir. Deney gruplarında strateji öğretiminde, bütüncül okuma stratejileri kullanılmıştır. Kontrol grubunda stratejiler öğretmen rehberliğinde örtük bir yaklaşımla ve birbirinden bağımsız olarak öğretilmiştir. Araştırmanın modeli kısmen karma sıralı baskın statülü tasarımdır. Örneklem ölçüt örneklemeyle belirlenmiştir. Deneysel süreçte 95 öğrenci, nitel süreçte 32 öğrenciyle çalışılmıştır. Uygulama 10 hafta sürmüştür. Veriler, “Okuma Stratejileri Üstbilişsel Farkındalık Envanteri (MARSI)” ve yarı yapılandırılmış görüşme formuyla toplanmıştır. Analizler SPSS 22 ve MAXQDA 12 programıyla yapılmıştır. Açık strateji öğretimi yaklaşımının ve bütüncül okuma stratejilerinin kullanıldığı, öğretmenin stratejileri açıklayarak “model” ve “rehber” olduğu deney gruplarında öğrencilerin okuma stratejileri bilişsel farkındalık becerilerinde farklılaşma olurken; stratejilerin örtük yaklaşımla öğretmen rehberliğinde ve bağımsız olarak öğretildiği kontrol grubunda farklılaşma gerçekleşmemiştir. Nitel veriler de nicel verileri desteklemektedir.
Covid-19 Temporalities: Ruptures of Everyday Life in Urban Burkina Faso
Authors: Samuelsen Helle , Toé Lea Paré
Published: April 2021

Globalisation intensifies global interconnectedness; reorders time and space; and stretches social, political, and economic practices across boundaries. However, globalisation is not a linear process; it takes place in discrete phases of short and concentrated bursts. The COVID-19 pandemic is one such time-space burst, or ‘eruption’. In this paper, we focus on COVID-19 as an ‘emerging epidemic’ from the perspective of citizens in Bobo-Dioulasso, the second-largest city in Burkina Faso. We explore how these citizens experience ruptures of their everyday life due to COVID-19 and how their understandings and responses to the pandemic were shaped in a context of instability and political turbulence. We are inspired by Giddens’s notion of ‘time-space distanciation’, which refers to ‘the condition under which time and space are organized so as to connect presence and absence’. We focus on the temporality of the pandemic by looking at a specific period during the pandemic, during which the government of Burkina Faso introduced a number of restrictions as preventive measures at a time when COVID-19 as a disease was still an absent phenomenon for most people. The pandemic had not (yet) infected large numbers of people in the country and most people did not yet have any experiences of the disease. We argue that the local responses to the pandemic and the various control measures during this period must be understood in the wider context of Burkina Faso’s specific socio-economic, political, and security situations, which are distinctly fragile.
‘Spirit Children’: Care, Uncertainty and ‘Infanticide’
Authors: Van der Geest Sjaak
Published: April 2021

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Global health Initiatives as a ‘Drunken Boat’: The Meningitis Vaccines Project Case Study
Authors: Thiongane Oumy Baala
Published: April 2021

Based on an analysis of the Meningitis Vaccine Project (MVP), a public-private partnership (PPP) set up to introduce the MenAfriVac® vaccine in African countries, this article examines the failures of an accelerated disease control programme that targeted a highly infectious disease. I argue that the integration of MenAfriVac® into the World Health Organization’s (WHO) Expanded Programme on Immunisation had the effect of reinforcing inequalities in access, in particular during epidemic emergencies. I will also show how vaccine shortages during an outbreak in Niger led to political tensions and to the emergence of a parallel and unregulated ‘black market’ of vaccines.
Detonation nanodiamonds: from synthesis theory to application practice
Authors: Dolmatov Valerii Yu. , Shames Alexander I. , Ōsawa Eiji , Vehanen Asko , Myllymäki Vesa , Dorokhov Alexander O. , Marchukov Valerii A. , Kozlov Anatoly S. , Naryzhny Sergey Yu. , Smirnova Anastasia Z.
Published: April 2021

The review is devoted to the current state of research and advances in the production and study of the properties of detonation nanodiamonds (DND), their application in technology and medicine. New data on the theory and practice of DND synthesis for the last 1–5 years are considered and systematized. It is shown that the zone of chemical reactions (ZCR) during the blust of explosive materials (EM) is decisive for the fractal pre-diamond structure formation, the final region of the nanodiamonds (1/3–3/4 of the diameter of the explosive charge) formation is determined. The possibility of predicting the DND yield and the influence of parameters on the synthesis process of nanodiamonds from individual EMs of binary and ternary compositions is shown, their optimal formulations are determined. The optimal ZCR width and the existence time of chemical reactions have been identified. The dependence of the DND yield on the nitrogen content in the EM was shown. The most effective method of DND purification and the possibility of obtaining graphite-diamond compositions of a given formulation are presented. The most informative indicators of nanodiamonds characterization are given. The magnetic properties of nanodiamonds are considered and the identity of the properties of DNDs from different EMs is shown. The characteristics of new compositions based on DND are indicated: electrochemical coatings (gold and chromium-diamond), thermal pastes, diamond-containing polymer filaments for a 3D printer, fuel compositions, enterosorbents, compatible with biosystems of the nanodiamond-drug composition.
Editorial Board Contents Аrchive Publication Ethics Subscription Review policy For Authors Call for Papers FAQ Address: Armyanskii ln., 4-2, Moscow, 101000, Russia Е-mail: psychology.hse@gmail.com Search text Отправить the website and texts of articles by authors by title (or part of title) by keyword Galina Ozhiganova 1 1 nstitute of Psychology, Russian Academy of Sciences, 13 build. 1, Yaroslavskaya Str., Moscow, 129366, Russian Federation Spiritual Capacities of Personality and Productive Life Activity
Authors: Ozhiganova Galina
Published: April 2021

The article deals with the psychological aspects of spirituality. The concepts of spiritual intelligence, spiritual capacities, and spiritual personality are analyzed. The study was based on the idea of a psychological model of spiritual capacities proposed by the author. This model includes three components: moral, mental, and transcendent. The moral component was selected to be explored in detail and was empirically studied. The principal constituent of the moral component of spiritual capacities is a spiritual altruistic tendency; its connection with productive life is analyzed in the article. The objective of the study was the investigation of the relationships between spiritual personality, spiritual capacities and productive life activity. The participants were 662 adults (206 males, 456 females): students and full-time employees aged 18–45 years (M = 26.08) from two cities of the Russian Federation (Kostroma and Taganrog). Correlational and comparative analysis was used for data processing. It was found that respondents with higher levels of “spiritual personality” significantly differed, according to the Mann–Whitney U test by a higher productivity of life activity (U = 43028; p < .001) and had higher levels of spiritual capacities — the spiritual altruistic tendency (U = 46328,5; p < .022). The correlational analysis showed that the higher was the level of manifestation of spiritual capacities — the spiritual altruistic tendency, the higher was the productivity of life activity. The results obtained make it possible to note the importance of the construct “spiritual capacities” and the need for its further scientific psychological research, as well as to emphasize the practical significance of spiritual capacities for the prosperous and productive functioning of society.
Разработка и адаптация методики «Интегративный опросник межкультурной компетентности»
Authors: Хухлаев О.Е. , Гриценко В.В. , Макарчук А.В. , Павлова О.С. , Ткаченко Т.В. , Усубян Ш.А. , Шорохова В.А.
Published: April 2021

В статье приводятся описание разработки и результаты апробации новой методики «Интегративный опросник межкультурной компетентности», направленной на изучение способности эффективно функционировать при общении с представителями различных культур и в разных культурных средах. Опросник создан на основе интеграции 52 конструктов из 14 методов измерения межкультурной компетентности. Исследование (N = 1024) показало, что методика содержит четыре субшкалы: «Межкультурная стабильность» (индивидуальные особенности личности, которые позволяют человеку быть устойчивым к стрессовым ситуациям межкультурного общения), «Межкультурный интерес» (желание общаться с людьми из других культур, интерес к культуре и культурным различиям), «Отсутствие этноцентризма» (установка на уважение и принятие культурного разнообразия) и «Управление межкультурным взаимодействием» (владение широким спектром коммуникативных навыков, важных при межкультурном общении). Субшкалы обладают хорошей внутренней согласованностью, а также инвариантностью с некоторыми ограничениями в части сравнения людей разных возрастов. Исследование также продемонстрировало внешнюю валидность методики. Шкалы «Интегративного опросника межкультурной компетентности» положительно связаны с «Расширенной шкалой культурного интеллекта». Люди, демонстрирующие более высокие показатели по отдельным шкалам опросника, отличаются большим количеством конкретных межкультурных достижений. Наблюдаются предсказуемые взаимосвязи опросника с показателями адаптации иностранных студентов, выраженностью эмоционального выгорания и самоэффективности у педагогов, работающих в мультикультурной среде.
CRIAÇÃO DE DISPOSITIVOS METODOLÓGICOS E DE AMBIÊNCIAS TRANSFORMATIVAS NA PESQUISA-FORMAÇÃO
Authors: Ribeiro Mayra Rodrigues Fernandes , Oliveira Bruna Rafaela Evangelista , Alves Cledna Kalyne Medeiros Dantas
Published: April 2021

Neste artigo objetivamos apresentar dispositivos metodológicos autorais e a bricolagem epistemológica da/na pesquisa-formação de duas dissertações de mestrado defendidas no ano de 2019 no Programa de Pós-Graduação em Educação - POSEDUC, da Universidade do Estado do Rio Grande do Norte - UERN. Inspiramo-nos nas abordagens epistemológicas multirreferencial (ARDOINO, 1998) e nos cotidianos (CERTEAU, 2014; ALVES, 2015), que nos possibilita assumir uma postura outra de pesquisadoras ativas e implicadas com o processo de fazer pesquisa em uma relação formativa que é devir. Aprendemos e tecemos ambiências formativas com os sujeitos da/na pesquisa com um rigor outro (MACEDO, 2009), afastando-se do reducionismo positivista de enquadramento e dirigindo-se para a produção do conhecimento em diálogo com os saberes produzidos no cotidiano. Os resultados evidenciam a possibilidade do inesperado, do caminhar na pesquisa incluindo-se no processo de suceder, sendo, portanto, potência formativa em um devir autorizante.
POSSIBILIDADES DA AÇÃO COMUNICATIVA PARA A PEDAGOGIA: PRÁTICAS DE GESTÃO EM UMA ESCOLA PÚBLICA DO RN
Authors: Paiva Amanda Santos de Queiroz Oliveira , Carneiro Rosalvo Nobre
Published: April 2021

O estudo aborda, a partir da teoria da Ação Comunicativa de Jürgen Habermas, as possibilidades para uma pedagogia intersubjetiva no espaço escolar. Utilizou-se da pesquisa etnográfica educacional, tendo como objetivo analisar as práticas pedagógicas desenvolvidas pela equipe gestora, pedagógica e docente, em uma escola pública de nível médio no Estado do Rio Grande do Norte, de modo a refletir acerca dos alcances do agir comunicativo orientado ao entendimento frente aos limites impostos pelo agir técnico. Empregou-se a pesquisa exploratória e bibliográfica, além de observações participantes com registros em diário de bordo. Constatou-se consideráveis limites ao agir comunicativo. Entretanto, verificou-se a presença de ações intersubjetivas da equipe pedagógica e docente. Nesse contexto, a pedagogia se desvela como ciência; por sua abrangência, se torna potencial para o campo educativo de maneira holística e concomitante a realização de ações intersubjetivas que possam considerar o mundo da vida dos sujeitos.
EDUCAÇÃO INFANTIL EM TEMPOS DE PANDEMIA: CONTRIBUIÇÕES DAS PEDAGOGIAS DA AUTONOMIA E DA INFÂNCIA PARA A FORMAÇÃO HUMANA
Authors: Alves Kallyne Kafuri , Vieira Maria Nilceia de Andrade
Published: April 2021

Em tempos de distanciamento social, consequência da pandemia causada pela Covid-19, em que a vida em sociedade se altera drasticamente, este artigo problematiza alguns desafios que envolvem a educação infantil. Ele abarca quatro apontamentos para análise: possiblidades de manutenção de vínculos dos educadores com as crianças e suas famílias; condições de trabalho e formação dos docentes; proteção à saúde e à vida de adultos e crianças; e atenção às diferenças culturais e necessidades especiais das crianças. Discute acerca das contribuições advindas do campo educacional para análises desse contexto com foco em pressupostos de uma Pedagogia da Autonomia (FREIRE, 2006) e de uma Pedagogia da Infância (ROCHA, 1999). Em uma abordagem qualitativa, na perspectiva de discussão teórica, o estudo organiza as reflexões em diálogo com normativas educacionais e com registros do cenário atual produzidos e veiculados por entidades de pesquisa e pesquisadores. As observações desenvolvidas indicam as práticas de humanização como elementos primordiais nas relações educacionais, impulsionadoras de transformações sociais e mobilizadoras de esperança para a formação humana por meio da dialogia. Apontam ainda que as contribuições da Pedagogia, na análise desse contexto, se situam como possibilidades de fomentar o fortalecimento da docência, além de ressaltar e vivificar singularidades do trabalho desenvolvido com as crianças na primeira etapa da educação básica.