Age Related Changes in NAD+ Metabolism Oxidative Stress and Sirt1 Activity in Wistar Rats

The cofactor nicotinamide adenine dinucleotide (NAD+) has emerged as a key regulator of metabolism, stress resistance and longevity. Apart from its role as an important redox carrier, NAD+ also serves as the sole substrate for NAD-dependent enzymes, including poly(ADP-ribose) polymerase (PARP), an important DNA nick sensor, and NAD-dependent histone deacetylases, Sirtuins which play an important role in a wide variety of processes, including senescence, apoptosis, differentiation, and aging. We examined the effect of aging on intracellular NAD+ metabolism in the whole heart, lung, liver and kidney of female wistar rats. Our results are the first to show a significant decline in intracellular NAD+ levels and NAD∶NADH ratio in all organs by middle age (i.e.12 months) compared to young (i.e. 3 month old) rats. These changes in [NAD(H)] occurred in parallel with an increase in lipid peroxidation and protein carbonyls (o- and m- tyrosine) formation and decline in total antioxidant capacity in these organs. An age dependent increase in DNA damage (phosphorylated H2AX) was also observed in these same organs. Decreased Sirt1 activity and increased acetylated p53 were observed in organ tissues in parallel with the drop in NAD+ and moderate over-expression of Sirt1 protein. Reduced mitochondrial activity of complex I–IV was also observed in aging animals, impacting both redox status and ATP production. The strong positive correlation observed between DNA damage associated NAD+ depletion and Sirt1 activity suggests that adequate NAD+ concentrations may be an important longevity assurance factor

Advances in tenascin-C biology

Tenascin-C is an extracellular matrix glycoprotein that is specifically and transiently expressed upon tissue injury. Upon tissue damage, tenascin-C plays a multitude of different roles that mediate both inflammatory and fibrotic processes to enable effective tissue repair. In the last decade, emerging evidence has demonstrated a vital role for tenascin-C in cardiac and arterial injury, tumor angiogenesis and metastasis, as well as in modulating stem cell behavior. Here we highlight the molecular mechanisms by which tenascin-C mediates these effects and discuss the implications of mis-regulated tenascin-C expression in driving disease pathology

The role of tenascin-C in tissue injury and tumorigenesis

The extracellular matrix molecule tenascin-C is highly expressed during embryonic development, tissue repair and in pathological situations such as chronic inflammation and cancer. Tenascin-C interacts with several other extracellular matrix molecules and cell-surface receptors, thus affecting tissue architecture, tissue resilience and cell responses. Tenascin-C modulates cell migration, proliferation and cellular signaling through induction of pro-inflammatory cytokines and oncogenic signaling molecules amongst other mechanisms. Given the causal role of inflammation in cancer progression, common mechanisms might be controlled by tenascin-C during both events. Drugs targeting the expression or function of tenascin-C or the tenascin-C protein itself are currently being developed and some drugs have already reached advanced clinical trials. This generates hope that increased knowledge about tenascin-C will further improve management of diseases with high tenascin-C expression such as chronic inflammation, heart failure, artheriosclerosis and cancer

Design, additive manufacturing, processing, and characterization of metal mirror made of aluminum silicon alloy for space applications

Metal mirrors are used for spaceborne optical systems, such as telescopes and spectrometers. In addition to the optical performance, the mechanical needs and the mass restrictions are important aspects during the design and manufacturing process. Using the additive manufacturing process, optimized internal lightweight structures are realized to reduce the weight of the system while keeping the mechanical stability. A mass reduction of ≈60.5  %   is achieved. Using the aluminum silicon alloy AlSi40, the thermal mismatch of the mirror base body to a necessary electroless nickel-polishing layer is minimized. Based on an exemplary mirror design, the optimization of the interior lightweight structure is described, followed by the manufacturing process from additive manufacturing to diamond turning, plating, and polishing. Finally, the results of surface metrology and light scattering measurements are presented. A final form deviation below 80 nm p  .    −  v  .   and a roughness of ∼1  nm rms could be demonstrated

Additive manufacturing of metal mirrors for TMA telescope

Additive manufacturing enables enhanced designs for metal mirrors and housings of optical systems like telescopes. Internal lightweight structures are used for the mirror modules to reduce the weight of the system while keeping the mechanical stability. Internal structures can be produced by selective laser melting, which cannot be realized by conventional machining. Using an aluminum silicon alloy, the thermal mismatch of the mirror base body to the necessary polishing layer is minimized. Resulting thermal induced deformations are greatly reduced. The additive manufacturing of a mirror module with two optical surfaces is described in detail. Using a adapted process chain for the application in the visible range, first results of the additive manufacturing as well as subsequent machining steps like diamond turning of the optical surfaces are presented

BNP as a marker dysfunction in the general population: Importance of left ventricular hypertrophy.

BNP is a marker of systolic left ventricular dysfunction (LVSD) and heart failure. To assess BNP for the detection of diastolic dysfunction in the general population, we examined 1678 subjects within an age- and sex-stratified survey (MONICA Augsburg). BNP was measured using a commercially available RIA (Shionogi).BNP increased in subjects with diastolic dysfunction (mean 20.3±4.7 pg/ml vs. control 9.6±0.5 pg/ml, p<0.001), but to a lesser extent than in subjects with LV hypertrophy (LVH, mean 37.3±49.1 pg/ml, p<0.001 vs. control) or LVSD (mean 76.2±23.2 pg/ml, p<0.001 vs. control). Individuals with sole diastolic abnormality displayed BNP concentrations at the control level (mean 9.7±1.7 pg/ml). In univariate analysis, age, BMI, systolic blood pressure, left atrial size, LV mass index, diastolic dysfunction and EF displayed a significant correlation with BNP (p<0.001). However, LV mass index displaced diastolic dysfunction as a significant predictor of BNP in multivariate analysis. Upon ROC analysis, sensitivity and specificity for the detection of diastolic dysfunction by BNP were only 61% and 55%, respectively. Nevertheless, a normal BNP test virtually excluded the presence of diastolic dysfunction and concomitant LVH (NPV 99.9%).Increased BNP concentrations in subjects with diastolic dysfunction are strongly related to LVH. Population-wide screening for diastolic dysfunction with BNP cannot be recommended although a normal BNP test usually excludes diastolic dysfunction and LV hypertrophy. &nbsp

Intensive Fischhaltung Moeglichkeiten und Probleme der modernen Aquakultur

TIB: RN 7920 (65) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman