The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver

Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement.     

Pectic Galactan Polysaccharide-Based Gene Delivery System for Targeting Neuroinflammation

Treating neuroinflammation-related injuries and disorders through manipulation of neuroinflammation functions is being heralded as a new therapeutic strategy. In this study, a novel pectic galactan (PG) polysaccharide based gene therapy approach is developed for targeting reactive gliosis in neuroinflammation. Galectin-3 (Gal-3) is a cell protein with a high affinity to β-galactoside sugars and is highly expressed in reactive gliosis. Since PG carries galactans, it can target reactive gliosis via specific carbohydrate interaction between galactan and Gal-3 on the cell membrane, and therefore can be utilized as a carrier for delivering genes to these cells. The carrier is synthesized by modifying quaternary ammonium groups on the PG. The resulting quaternized PG (QPG) is found to form complexes with plasmid DNA with a mean diameter of 100 nm and have the characteristics required for targeted gene therapy. The complexes efficiently condense large amounts of plasmid per particle and successfully bind to Gal-3. The in vivo study shows that the complexes are biocompatible and safe for administration and can selectively transfect reactive glial cells of an induced cortical lesion. The results confirm that this PG-based delivery system is a promising platform for targeting Gal-3 overexpressing neuroinflammation cells for treating neuroinflammation-related injuries and neurodegenerative diseases.     

Milk from cows fed a diet with a high forage:concentrate ratio improves inflammatory state,oxidative stress,and mitochondrial function in rats

Excessive energy intake may evoke complex biochemical processes characterized by inflammation, oxidative stress, and impairment of mitochondrial function that represent the main factors underlying noncommunicable diseases. Because cow milk is widely used for human nutrition and in food industry processing, the nutritional quality of milk is of special interest with respect to human health. In our study, we analyzed milk produced by dairy cows fed a diet characterized by a high forage:concentrate ratio (high forage milk, HFM). In view of the low n-6:n-3 ratio and high content of conjugated linoleic acid of HFM, we studied the effects of this milk on lipid metabolism, inflammation, mitochondrial function, and oxidative stress in a rat model. To this end, we supplemented for 4 wk the diet of male Wistar rats with HFM and with an isocaloric amount (82 kJ, 22 mL/d) of milk obtained from cows fed a diet with low forage:concentrate ratio, and analyzed the metabolic parameters of the animals. Our results indicate that HFM may positively affect lipid metabolism, leptin:adiponectin ratio, inflammation, mitochondrial function, and oxidative stress, providing the first evidence of the beneficial effects of HFM on rat metabolism.     

Editorial

Journal of Computer Virology and Hacking Techniques -     

Single chamber Solid Oxide Fuel Cells selective electrodes: A real chance with brownmillerite-based nanocomposites

In this contribution brownmillerite-based nanocomposite cathode for Single-Chamber Solid Oxide Fuel Cells is developed. These cells can be very attractive especially for small and cheap devices because of the absence of seals. The efficiency of SC-SOFCs is strictly connected to the selectivity of anode and cathode, the bottleneck for this technology. The development of a cathode inert in fuel oxidation is particularly challenging. Our strategy is to start from a catalytically un-active support (CFA = Ca₂FeAl_0.95Mg_0.05O₅) and induce the formation of iron oxide based nanoparticles, expected to activate oxygen. Symmetric (CFA + FeO_x/CGO/CFA + FeO_x) and complete cells (CFA + FeO_x/CGO/Ni-CGO) are studied in air and methane/oxygen 2:1 mixture. The Area Specific Resistance of CFA + FeO_x is less than 1/3 that of CFA. The high selectivity allows to reach an efficiency of 25%; power still needs to be increased but we demonstrated the possibility to develop selective low cost electrodes. The effect of air, methane/oxygen exposure and the heat treatments were carefully investigated.     

Adrenocorticotropin and cortisol hyperresponsiveness to hexarelin in patients with Cushing's disease bearing a pituitary microadenoma, but not in those with macroadenoma

We previously reported that in Cushing's disease (CD) the ACTH- and cortisol (F)-releasing activity of Hexarelin (HEX), a GH secretagogue, is exaggerated with respect to that in normal subjects and is higher than that of human CRH (hCRH), but it is absent in Cushing's syndrome. Our aim was to extend the study about the effects of HEX (2.0 microg/kg, iv) on ACTH and F secretion in 21 patients with CD (3 men and 18 women, 16-68 yr old). Based on magnetic resonance imaging, 15 CD patients had pituitary microadenoma, and 6 had macroadenoma. The results in CD patients were compared with those in 27 normal age-matched controls (NS; 10 men and 17 women, 24-69 yr old). Basal ACTH and F levels in CD were similar in patients with microadenom (mean+/-SEM, 78.3+/-7.2 pg/mL and 237.1+/-23.6 microg/L, respectively) and macroadenoma (57.4+/-9.0 pg/mL and 196.9+/-20.1 microg/L, respectively) and were higher (P < 0.001) than those in NS (17.7+/-2.0 pg/mL and 115.3+/-6.7 microg/L, respectively). In microadenoma CD patients, HEX induced marked ACTH and F increases (delta peak, mean+/-SEM: 261.2+/-77.6 pg/mL and 226.1+/-87.2 microg/L, respectively), which were higher (P < 0.04) than those induced by hCRH (45.6+/-16.9 pg/mL and 84.6+/-25.7 microg/L, respectively). Moreover, in microadenoma CD patients, the ACTH and F responses to HEX were higher (P < 0.001) than those in NS (18.5+/-4.0 pg/mL and 36.1+/-6.8 microg/L, respectively). In macroadenoma CD patients, HEX induced a slight, but significant increase (P < 0.02) in ACTH and F levels (33.9+/-18.0 pg/mL and 89.6+/-34.3 microg/L, respectively), which was not significantly different from that elicited by hCRH (20.0+/-7.0 pg/mL and 54.8+/-21.3 microg/L, respectively). In macroadenoma CD patients, the ACTH and F responses to HEX and hCRH were, in turn, similar to those in NS. In conclusion, our findings demonstrate that the ACTH and F hyperresponsiveness to HEX is present in Cushing's disease with micro-, but not macro- ACTH-secreting pituitary adenoma. This finding agrees with other evidence pointing toward differences in the hormonal behavior between micro- and ACTH-secreting pituitary macroadenomas.     

Modeling Crosstalk Effects in CNT Bus Architectures

Carbon nanotubes (CNTs) have been widely proposed as interconnect fabric for nano and very deep submicron (silicon-based) technologies due to their robustness to electromigration. In this paper, issues associated with crosstalk among bus lines implemented by CNTs are investigated in detail. CNT-based interconnects are modeled and the effects of crosstalk on performance and correct operation are evaluated by simulation. Existing models are modified to account for geometries in bus architectures made of parallel single-walled nanotubes and a single multiwalled nanotube. New RLC equivalent circuits are proposed for these bus architectures. A novel bus architecture with low crosstalk features is also proposed. This bus architecture is made of dual-walled nanotubes arranged in parallel. In this architecture, the crosstalk-induced delay and corresponding uncertainty (as well as crosstalk-induced peak voltage) are significantly reduced; a modest area penalty is incurred. Reductions up to 59% for the crosstalk-induced delay and up to 81% for the crosstalk-induced peak voltage are reported. These results confirm that the proposed bus arrangement noticeably improves performance and provides reliable operation     

An evolutionary approach to visual sensing for vehicle navigation

This paper presents an evolutionary approach able to process a digital image and detect tracks left by preceding vehicles on ice and snow in Antarctica. Biologically inspired by a colony of ants able to interact and cooperate to determine the shortest path to the food, this approach is based on autonomous agents moving along the image pixels and iteratively improving an initial coarse solution. The unfriendly Antarctic environment makes this image analysis problem extremely challenging, since light reflections, abruptly varying brightness conditions, and different terrain slopes must be considered as well. The ant-based approach is compared to a more traditional Hough-based solution and the results are discussed.     

Estimation of the angle between ultrasound beam and blood velocitythrough correlation functions

Correlation functions, calculated on the ultrasonic echoes scattered by blood, provide a rich harvest of information concerning the local speed, which has often been underestimated; in particular, blood flow measurement usually yields only the longitudinal component of the velocity, even if significant information about the speed direction can be extracted. In this paper it is shown how correlation functions, calculated on the dependency of both time and space displacements, allow us to evaluate the angle Θ between ultrasound beam and blood flow; when straight vessels are considered, this single parameter, combined with the longitudinal velocity profile, permits the complete hemodynamic characterization. The underlying theory is developed and preliminary experimental results are presented