DNA damage and repair system in spinal cord ischemia

AbstractBackground and Purpose: Spinal cord ischemia-reperfusion injury may be initiated by a number of mediators, including reactive oxygen species. Recent studies have shown that human MutY homologue (hMYH), human 8-oxo-7,8-dihydrodeoxyguanine (8-oxoG) glycosylase (hOGG1), and human MutS homologue 2 (hMSH2) are important DNA mismatch repair genes. We hypothesized that ischemia-reperfusion injury in spinal cord causes DNA damage manifested by 8-oxoG production and activates the DNA repair system involving hMYH, hOGG1, and hMSH2. Methods: Spinal cords of rabbits were removed at 1, 3, 6, 24, and 48 hours after 30 minutes of infrarenal aortic occlusion. DNA damage was determined with 8-oxoG staining. The expression and localization of DNA repair enzymes, such as hMYH, hOGG1, and hMSH2, were studied with Western blot analysis and immunohistochemical staining. The level of apoptosis was determined with TUNEL study. Activation of caspase-3, an enzyme induced by cellular injury that leads to apoptosis by degrading cellular structural proteins, was also studied. Results: DNA damage monitored with 8-oxoG level was significantly present from 1 hour to 6 hours after reperfusion in gray matter neurons of ischemic spinal cord. The levels of hMYH, hOGG1, and hMSH2 were markedly increased in gray matter neurons at 6 hours after reperfusion. Caspase-3 was also induced at 6 hours to 24 hours after reperfusion in ischemic spinal cord. However, the peak level of TUNEL reactivity was found at 48 hours after reperfusion in spinal cord neurons. Conclusion: This study has shown, for the first time, the rapid expression of DNA damage-repair processes associated with spinal cord ischemia and subsequent reperfusion. (J Vasc Surg 2003;37:847-58.

Direct imaging of a zero-field target skyrmion and its polarity switch in a chiral magnetic nanodisk

A target skyrmion is a flux-closed spin texture that has two-fold degeneracy and is promising as a binary state in next generation universal memories. Although its formation in nanopatterned chiral magnets has been predicted, its observation has remained challenging. Here, we use off-axis electron holography to record images of target skyrmions in a 160-nm-diameter nanodisk of the chiral magnet FeGe. We compare experimental measurements with numerical simulations, demonstrate switching between two stable degenerate target skyrmion ground states that have opposite polarities and rotation senses and discuss the observed switching mechanism.Comment: 18 pages, 4 figure

Edge-Mediated Skyrmion Chain and Its Collective Dynamics in a Confined Geometry

The emergence of a topologically nontrivial vortex-like magnetic structure, the magnetic skyrmion, has launched new concepts for memory devices. There, extensive studies have theoretically demonstrated the ability to encode information bits by using a chain of skyrmions in one-dimensional nanostripes. Here, we report the first experimental observation of the skyrmion chain in FeGe nanostripes by using high resolution Lorentz transmission electron microscopy. Under an applied field normal to the nanostripes plane, we observe that the helical ground states with distorted edge spins would evolves into individual skyrmions, which assemble in the form of chain at low field and move collectively into the center of nanostripes at elevated field. Such skyrmion chain survives even as the width of nanostripe is much larger than the single skyrmion size. These discovery demonstrates new way of skyrmion formation through the edge effect, and might, in the long term, shed light on the applications.Comment: 7 pages, 3 figure

Electrical Probing of Field-Driven Cascading Quantized Transitions of Skyrmion Cluster States in MnSi Nanowires

Magnetic skyrmions are topologically stable whirlpool-like spin textures that offer great promise as information carriers for future ultra-dense memory and logic devices1-4. To enable such applications, particular attention has been focused on the skyrmions properties in highly confined geometry such as one dimensional nanowires5-8. Hitherto it is still experimentally unclear what happens when the width of the nanowire is comparable to that of a single skyrmion. Here we report the experimental demonstration of such scheme, where magnetic field-driven skyrmion cluster (SC) states with small numbers of skyrmions were demonstrated to exist on the cross-sections of ultra-narrow single-crystal MnSi nanowires (NWs) with diameters, comparable to the skyrmion lattice constant (18 nm). In contrast to the skyrmion lattice in bulk MnSi samples, the skyrmion clusters lead to anomalous magnetoresistance (MR) behavior measured under magnetic field parallel to the NW long axis, where quantized jumps in MR are observed and directly associated with the change of the skyrmion number in the cluster, which is supported by Monte Carlo simulations. These jumps show the key difference between the clustering and crystalline states of skyrmions, and lay a solid foundation to realize skyrmion-based memory devices that the number of skyrmions can be counted via conventional electrical measurements

Porous Pyrene Organic Cage with Unusual Absorption Bathochromic-Shift Enables Visible Light Photocatalysis

We have constructed a novel porous pyrene-based organic cage, PyTC1, through the condensation reaction of cyclohexanediamine with 5,5&prime;-(pyrene-1,6-diyl)diisophthalaldehyde. Single-crystal X-ray diffraction analysis reveals the effective intercage C&ndash;H...&pi; interaction between cyclohexanediimine and pyrene segments. Such a soft intercage C&ndash;H...&pi; interaction, rather than a classic J-aggregate with slipped &pi;&ndash;&pi;-stacking configuration, induced an unusual bathochromic shift of pyrene-based chromophore absorption from an ultraviolet region of PyTC1 in solution to the visible light region of PyTC1 in solid-state. This enabled heterogeneous visible light photocatalysis of aerobic hydroxylation of benzeneboronic acid derivatives. To the best of our knowledge, this is the first report that represents an absorption bathochromic shift caused by C&ndash;H...&pi; interaction. Such phenomenon could endow visible-light-driven photocatalysis that originally could only be achieved using UV light with the same chromophore. &nbsp;</p

The role of angiotensin II and TGF-beta on the progression of chronic allograft nephropathy

Chronic allograft nephropathy is the most prevalent cause of graft dysfunction and failure. Its pathogenesis and treatment remains poorly defined. The calcineurin inhibitors, cyclosporine and tacrolimus, may play a role in the progressive loss of renal function in patients with chronic allograft nephropathy. This effect may be either related to the direct stimulation of profibrogenic cytokines such as transforming growth factor (TGF-β) or indirect mechanisms, through increases in blood pressure or alterations in either carbohydrate or lipid metabolism. Experimental studies have demonstrated that angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARBs) can attenuate cyclosporine-mediated increases in TGF-β production in renal tissue. Clinical studies have demonstrated that either cyclosporine or tacrolimus dose reduction may help reduce the rate of loss of renal function in patients with chronic allograft nephropathy. Moreover, other studies have demonstrated that a chronic reduction in the dose of cyclosporine in transplant patients can reduce serum TGF-β levels. Treatment with an ARB can normalise the plasma levels of TGF-β in renal transplant patients receiving cyclosporine. All these observations suggest that there may be a role of cyclosporine, and possibly tacrolimus, in worsening chronic allograft nephropathy through their effects on the renin-angiotensin-aldosterone system (RAAS) and TGF-β production

Interaction between drinking and dietary inflammatory index affects prostate specific antigen: a cross-sectional study

Abstract Background Numerous studies have shown that the dietary inflammatory index (DII) is associated with adverse health effects. However, the relationship between DII and prostate cancer (PCa) remains controversial. Although alcohol is included in DII as a dietary factor, the various adverse health effects of alcohol consumption are not only related to inflammation. On the other hand, it has been a long-standing debate whether alcohol consumption is linked to the risk of PCa. Therefore, to clarify whether drinking affects the relationship between DII and PCa, we evaluated the correlation between DII and prostate-specific antigen (PSA) based on the National Health and Nutrition Examination Survey (NHANES) database. Methods We used data from the NHANES spanning from 2005 to 2010 to analyze the relationship between PCa and DII. Out of the 31,034 NHANES participants, we enrolled 4,120 individuals in our study, utilizing dietary intake data from a twenty-four-hour period to determine DII scores. Demographic data, physical and laboratory test results were collected to compare between low PSA and high PSA groups, and to calculate the odds ratio between both groups, we employed a logistic regression analysis. Results In this cross-sectional investigation of PCa, drinkers and non-drinkers had different relationships between DII and PSA levels (OR: 1.2, 95% Cl: 1-1.44 vs. OR: 0.98, 95% Cl: 0.9–1.07), and DII and abstaining from alcohol were effective in reducing the incidence of PSA (p-value for significant interaction = 0.037). Conclusion The results of our study suggest that drinking may influence the relationship between DII and PSA levels. DII is likely to be a reliable indicator for estimating PSA levels among non-drinkers, who may limit their intake of pro-inflammatory ingredients to lower the incidence and death of PCa