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Background The redox‐sensitive chaperone DJ ‐1 and uncoupling protein 2 are protective against mitochondrial oxidative stress. We previously reported that renal‐selective depletion and germline deletion of DJ ‐1 increases blood pressure in mice. This study aimed to determine the mechanisms involved in the oxidative stress–mediated hypertension in DJ ‐1 −/− mice. Methods and Results There were no differences in sodium excretion, renal renin expression, renal NADPH oxidase activity, and serum creatinine levels between DJ ‐1 −/− and wild‐type mice. Renal expression of nitro‐tyrosine, malondialdehyde, and urinary kidney injury marker‐1 were increased in DJ ‐1 −/− mice relative to wild‐type littermates. mRNA expression of mitochondrial heat shock protein 60 was also elevated in kidneys from DJ ‐1 −/− mice, indicating the presence of oxidative stress. Tempol‐treated DJ ‐1 −/− mice presented higher serum nitrite/nitrate levels than vehicle‐treated DJ ‐1 −/− mice, suggesting a role of the NO system in the high blood pressure of this model. Tempol treatment normalized renal kidney injury marker‐1 and malondialdehyde expression as well as blood pressure in DJ ‐1 −/− mice, but had no effect in wild‐type mice. The renal Ucp2 mRNA expression was increased in DJ ‐1 −/− mice versus wild‐type and was also normalized by tempol. The renal‐selective silencing of Ucp2 led to normalization of blood pressure and serum nitrite/nitrate ratio in DJ ‐1 −/− mice. Conclusions The deletion of DJ ‐1 leads to oxidative stress–induced hypertension associated with downregulation of NO function, and overexpression of Ucp2 in the kidney increases blood pressure in DJ ‐1 −/− mice. To our knowledge, this is the first report providing evidence of the role of uncoupling protein 2 in blood pressure regulation.

DJ-1 and uncoupling protein 2 (UCP2) exert protective roles against mitochondrial (MT) oxidative stress. DJ-1 -/- mice have increased systolic blood pressure (BP) (+30±3% vs WT, n=6). This study determined the mechanisms involved in the oxidative stress-mediated hypertension due to DJ-1 germline deletion. There were no differences in sodium excretion, renal renin expression, NADPH oxidase activity and serum creatinine between DJ-1 -/- and WT mice (n=5). However, renal expression of nitro-tyrosine was increased in DJ-1 -/- mice (+176.8±31% vs WT mice, n=5). Tempol, a radical scavenger, normalized the BP (tempol: 118±2% vs 100±1% vs WT, n=4) and renal malondialdehyde (tempol: 160±23% vs 109±15% vs WT, n=4) in DJ-1 -/- mice. Tempol-treated DJ-1 -/- mice had higher serum nitrite/nitrate levels than placebo-treated (172±30% vs WT, n=4). Heat shock protein mtHSP60 was increased in DJ-1 -/- mice (2.9±0.1-fold increase vs WT, n=4), indicating MT stress. However, there were no changes in the renal mRNA expression of mitophagy, MT fusion and MT biosynthesis markers indicating that MT function was not altered. Renal expression of UCP2 was increased in DJ-1 -/- mice (4.1±1.1-fold change vs WT, n=4), and was partially normalized by tempol (1.8±0.2-fold change vs WT, n=4), UCP2 may have a protective role on MT function in this model. UCP2 was selectively silenced via sub-capsular infusion of UCP2 siRNA in the kidney (WT: 63%±7 vs control: DJ-1 -/- :60%±6 vs control; n=4). mRNA expression of mitophagy markers BNIP3 (-0.65±6-fold) and PINK1 (1.55±0.3-fold), MT fusion markers FIS1 (-0.29±0.03-fold) and NFN2 (1.42±0.06-fold), and MT biosynthesis marker PPRC1 (1.71±0.07-fold) were altered by UCP2 silencing in DJ-1 -/- mice (n=4). Renal-selective silencing of UCP2 normalized BP in DJ-1 -/- mice ( DJ-1 -/- mice: 122±5 vs 98±7 mmHg, n=4), and the serum nitrite and nitrate concentrations (-40±9% vs WT, n=4). In conclusion, deletion of DJ-1 leads to oxidative stress-induced hypertension associated with down-regulation of NO synthesis. UCP2 has protective properties against the development of MT dysfunction in MT oxidative stress conditions . However, excessive and chronic over expression of UCP2 could have deleterious consequences on BP regulation.

Endothelin-1 (ET-1) promotes renal damage during cardiovascular disease; yet, the molecular mechanisms involved remain unknown. Endoplasmic reticulum (ER) stress, triggered by unfolded protein accumulation in the ER, contributes to apoptosis and organ injury. These studies aimed to determine whether the ET-1 system promotes renal ER stress development in response to tunicamycin. ETB deficient (ETB def) or transgenic control (TG-con) rats were used in the presence or absence of ETA receptor antagonism. Tunicamycin treatment similarly increased cortical ER stress markers in both rat genotypes; however, only ETB def rats showed a 14–24 fold increase from baseline for medullary GRP78, sXBP-1, and CHOP. Pre-treatment of TG-con rats with the ETA blocker ABT-627 for 1 week prior to tunicamycin injection significantly reduced the ER stress response in cortex and medulla, and also inhibited renal apoptosis. Pre-treatment with ABT-627 failed to decrease renal ER stress and apoptosis in ETB def rats. In conclusion, the ET-1 system is important for the development of tunicamycin-induced renal ER stress and apoptosis. ETA receptor activation induces renal ER stress genes and apoptosis, while functional activation of the ETB receptor has protective effects. These results highlight targeting the ETA receptor as a therapeutic approach against ER stress-induced kidney injury.

DJ-1 -/- mice, relative to wild-type (WT) littermates, have increased blood pressure (BP) ( DJ-1 -/- :130±4 vs WT:100±3 mmHg, n=6/8). and renal expressions of nitro-tyrosine (+76±31% of WT mice, n=5) and malondialdenyde (+63±23% of WT mice, n=4). Tempol, a superoxide dismutase mimetic, decreased the BP of DJ-1 -/- mice ( DJ-1 -/- : before tempol:119±3; after tempol:100±1 mmHg vs WT, n=4) and renal malondialdehyde production ( DJ-1 -/- : before tempol:+40±5%; after tempol:-24±5% vs WT, n=4) but increased serum nitrate/nitrite levels (+72±30%, n=4), indicating the presence of both oxidative and nitrosative stress. Lack of DJ-1 makes some cells vulnerable to endoplasmic reticulum (ER) stress. However, renal mRNA expression of ER stress markers, GRP94, ATF-4, ATF-6, sXBP-1, CHOP, caspase-12, and caspase-3 was not different between DJ-1 -/- and WT (n=7) mice. Markers of inflammation, IL-6, TNF α, MCP-1, NFκB, and T-cell and macrophage infiltration, were also not increased in the kidney of DJ-1 -/- mice. By contrast, renal mitochondrial (mt) HSP60, but not mtHSP40, was increased in DJ-1 -/- mice (2.9±0.1 fold, n=4) but there were no changes in the renal mRNA expressions of Nix/BNIP3L, BNIP3, PINK, FIS1, MFN1, MFN2, PPRC1, NRF-1, and PGC1, indicating that mt oxidative stress did not affect mt function. The renal expression of UCP2, which is involved in the control of mt-reactive oxygen species production, was elevated in DJ-1 -/- mice (4.1±1.1 fold of WT, n=4). Silencing UCP2 in mouse renal proximal tubule cells (-0.46.5±0.01 fold) increased the expression of ER stress and apoptosis markers CHOP (2±0.4 fold), ATF4 (2.6±0.6 fold), caspase-3 (2.3±0.4 fold), and caspase-12 (1.7±0.2 fold)(n=3). There were no differences in renal renin expression, sodium excretion, and serum creatinine between DJ-1 -/- and WT mice (n=5). There were no abnormalities in renal morphology, including fibrosis, in the kidneys of DJ-1 -/- mice. However, urinary KIM-1 was increased in DJ-1 -/- mice (148±22% of WT mice, n=4) and decreased by tempol (-58±3%, n=4); renal UCP2 expression was also partially normalized by tempol (1.8±0.2 fold of WT, n=4). UCP2 may protect from the development of renal ER stress and damage in the mt oxidative/nitrosative stress associated with DJ-1 depletion.

(2001). An Interview with the Editor. Journal of the British Society for Phenomenology: Vol. 32, No. 1, pp. 24-35.

Etude dela relation entre l'imagination et l'empathie. Face a l'incapacite de la science cognitive a rendre compte de la dimension morale de l'empathie, l'A. privilegie son acces par l'imagination litteraire, telle qu'elle est concue par P. Ricoeur et M. Nussbaum.

L'A. vise a montrer que Merleau-Ponty, quoiqu'il n'ait jamais reellement ecrit une philosophie de la creativite, a traite tout au long de son oeuvre de ce theme et de ses consequences philosophiques. Pour ce, il explore ses theories de la perception, du sens et du langage, en montrant qu'elles supposent une creation active du sujet

L'A. montre comment la phenomenologie de la perception et de la corporeite, comprise comme phenomenologie de l'incarnation, peut eclairer le phenomene de bonte, qui consiste en un certain pouvoir d'humanisation de nos relations a autrui

This paper will analyze certain claims and arguments in Tony O’Connor’s “O Friend, Where Art Thou?: Derridean Deconstruction and Friendship.” The essay will then attempt to show that its author’s recent work, Kindness and the Good Society: Connections of the Heart, can provide some of the desired empirical evidence to supplement Derrida’s deconstructive critique of traditional concepts of friendship. In doing so, the paper will extend and deepen a key notion from the kindness book, that of aesthetic humanism. Drawing on the work of Maurice Merleau-Ponty, on whom Tony O’Connor has also written well, the essay will conclude by outlining the tasks of an ontology of friendship as a means of countering certain of Derrida’s deconstructive criticisms.

Adult male Wistar rats were trained in a simple odor detection task, with peppermint odor serving as either an S+, S− or as a randomly presented odor. Twenty-four hours after the last training session, rats were injected with [ 14 C]2-deoxyglucose and exposed to the odor. Mean relative 2-deoxyglucose uptake to the odor was enhanced in the pars dorsalis of the anterior olfactory nucleus of S+ and S− trained rats compared to controls. In contrast, no differences in uptake were detected in either odor-specific focal regions of the olfactory bulb glomerular layer, the pyriform cortex, or the hippocampus.

Maurice Merleau-Ponty was born in Rochefort-sur-Mer on March 14,1908. On his own admission, he spent an idyllic childhood, the recovery of which, according to Jean-Paul Sartre, constituted a key motive of his philosophy. In 1913, upon the death of his father, the family moved to Paris, and Merleau-Ponty entered the lycee system. He graduated from the Lycee Louis-le-Grand and in 1926 was admitted to the Ecole Normale Superieure. It was during his years there that he met Sartre and Simone de Beauvoir. Since Bergson had already retired, Merleau-Ponty studied with the German idealist Leon Brunschvicg. Sartre graduated in 1929 and Merleau-Ponty in 1930.

Study area boundaries often are delineated by subjective methods without considering animal movements and behavior and may result in inaccurate density estimates and incorrect research conclusions. Consequently, we delineated study area boundaries for use with capture-recapture models to calculate density estimates of wild turkey gobblers (Meleagris gallopavo). From january to March, 1984-89, 189 gobblers were captured by cannon-net or drug at 38 permanent bait sites in central Mississippi. Fifty-six marked gobblers were harvested from 17-19 March to 1 May 1984-89. As distance from bait sites increased, proportion of unmarked gobblers to marked gobblers increased