TAp73 depletion accelerates aging through metabolic dysregulation

Aging is associated with impaired scavenging of reactive oxygen species (ROS). Here, we show that TAp73, a p53 family member, protects against aging by regulating mitochondrial activity and preventing ROS accumulation. TAp73-null mice show more pronounced aging with increased oxidative damage and senescence. TAp73 deletion reduces cellular ATP levels, oxygen consumption, and mitochondrial complex IV activity, with increased ROS production and oxidative stress sensitivity. We show that the mitochondrial complex IV subunit cytochrome C oxidase subunit 4 (Cox4i1) is a direct TAp73 target and that Cox4i1 knockdown phenocopies the cellular senescence of TAp73-null cells. Results indicate that TAp73 affects mitochondrial respiration and ROS homeostasis, thus regulating aging.     

Anti-Diabetic Activities of the Methanol Leaf Extracts of Hymenocardia Acida (Tul.) in Alloxan-Induced Diabetic Rats

The effect of methanolic extract of Hymenocardia acida leaves on diabetes and associated lipidemia were investigated on experimentally-induced diabetic rats. The extract did not demonstrate any acutely toxic effect in rats within the dose range (250 mg/kg – 2000 mg/kg) employed in the study; hence it was well tolerated by the rats. In all experiments, the anti-diabetic effects were dose-dependent and comparable to that of glibenclamide (2 mg/kg) standard. At a dose of 500 mg/kg, lipid profile markers such as the serum total cholesterol (TC) levels, LDL-C, triglycerides and HDL-C were significantly lower (p <0.05) than those of both the treated and untreated controls.     

Perceptual separation of transparent motion components: the interaction of motion, luminance and shape cues

Transparency is perceived when two or more objects or surfaces can be separated by the visual system whilst they are presented in the same region of the visual field at the same time. This segmentation of distinct entities on the basis of overlapping local visual cues poses an interesting challenge for the understanding of cortical information processing. In psychophysical experiments, we studied stimuli that contained randomly positioned disc elements, moving at two different speeds in the same direction, to analyse the interaction of cues during the perception of motion transparency. The current work extends findings from previous experiments with sine wave luminance gratings which only vary in one spatial dimension. The reported experiments manipulate low-level cues, like differences in speed or luminance, and what are likely to be higher level cues such as the relative size of the elements or the superposition rules that govern overlapping regions. The mechanism responsible for separation appears to be mediated by combination of the relevant and available cues. Where perceived transparency is stronger, the neural representations of components are inferred to be more distinguishable from each other across what appear to be multiple cue dimensions. The disproportionally large effect on transparency strength of the type of superposition of disc suggests that with this manipulation, there may be enhanced separation above what might be expected from the linear combination of low-level cues in a process we term labelling. A mechanism for transparency perception consistent with the current results would require a minimum of three stages; in addition to the local motion detection and global pooling and separation of motion signals, findings suggest a powerful additional role of higher level separation cues.     

A systematic review of resource habitat taboos and human health outcomes in the context of global environmental change

The dependence of humans on the ecosystem services that natural resources provide is absolute. The need for social taboos as frameworks for governing natural resource abstraction is gaining widespread recognition especially within the context of climate change. However, the complex relationship between resource and habitat taboos (RHTs) and human health is not entirely understood. We conducted a systematic review of existing studies of the association between RHTs and human health outcomes, focusing on the best evidence available. We searched JSTOR, SocINDEX, Greenfile and Academic Search Complete databases from 1970 to July 2015; and also searched the reference lists of reviews and relevant articles. About 779 studies and data from 26 studies were eligible for the analysis. Only 9 out of 26 studies clearly linked RHTs to human health. Overall, nine taboos, spatial, temporal, gear, method, effort, catch, species-specific, life history and segment, were covered by the empirical studies. This systematic review provides new evidence of relationships between RHTs and human health outcomes. Several methodological limitations were identified in the empirical material. The findings suggest the need for context-specific conservation policies to reduce erosion of RHTs in order to sustain human health in the face of climate change.     

Multimodal molecular 3D imaging for the tumoral volumetric distribution assessment of folate-based biosensors

The aim of this study was to characterize the in vivo volumetric distribution of three folate-based biosensors by different imaging modalities (X-ray, fluorescence, Cerenkov luminescence, and radioisotopic imaging) through the development of a tridimensional image reconstruction algorithm. The preclinical and multimodal Xtreme imaging system, with a Multimodal Animal Rotation System (MARS), was used to acquire bidimensional images, which were processed to obtain the tridimensional reconstruction. Images of mice at different times (biosensor distribution) were simultaneously obtained from the four imaging modalities. The filtered back projection and inverse Radon transformation were used as main image-processing techniques. The algorithm developed in Matlab was able to calculate the volumetric profiles of ^99mTc-Folate-Bombesin (radioisotopic image), ¹⁷⁷Lu-Folate-Bombesin (Cerenkov image), and FolateRSense? 680 (fluorescence image) in tumors and kidneys of mice, and no significant differences were detected in the volumetric quantifications among measurement techniques. The imaging tridimensional reconstruction algorithm can be easily extrapolated to different 2D acquisition-type images. This characteristic flexibility of the algorithm developed in this study is a remarkable advantage in comparison to similar reconstruction methods.     

Reproducibility of angiotensin converting enzyme inhibitor induced cough: A double-blind randomised study

1 The reproducibility of angiotensin converting enzyme inhibitor induced cough was examined in a double-blind cross over study in patients previously shown to have exhibited this side effect.

2 Ninety-seven patients who had experienced angiotensin converting enzyme inhibitor cough within the last 2 years were challenged with enalapril 20 mg daily for 4 weeks to establish eligibility. Eighty-eight of 97 (91%) patients experienced a repeat of their cough symptoms. Sixty-four patients entered the double-blind part of the study where they were treated with enalapril 20 mg and a renin inhibitor for up to 4 weeks in random order. These periods were separated by a minimum 4 week placebo wash out.

3 Of 59 evaluable patients who received enalapril a second time, 37 (62.7%) experienced cough again. Of 62 patients on the renin inhibitor 16 (25.8%) experienced cough, however as it was not equi-efficacious to enalapril no valid comparison could be made.

4 Angiotensin converting enzyme inhibitor cough is not reproducible within patients, as other factors are involved in the aetiology. Objective testing with blinded assessment together with symptom reporting, would give a more accurate measure of the incidence, and mechanism of this side effect.

     

Eyelash enhancement properties of topical dechloro ethylcloprostenolamide

Objective: To assess subjective reports by users of MD Lash Factor^TM that it improved the appearance of their eyelashes, especially in length. Methods: A randomized, double‐blind, clinical trial was performed on 34 healthy volunteers who were randomly assigned to one of three different treatment groups of varying concentrations of the key ingredient (dechloro ethylcloprostenolamide, a novel synthetic topical prostaglandin analogue) and a placebo group. Results: All treatment groups demonstrated a statistically significant increase in eyelash length after 4 weeks of daily use. Group A: 1.69?mm, Group B: 1.94?mm, Group D: 1.44?mm, and Group C (placebo): 0.63?mm. There were no complications. Fifteen patients reported minimal initial transient irritation. Conclusion: Subjective reports by users of improved appearance in their eyelashes were confirmed. Use of dechloro ethylcloprostenolamide had minimal side effects.     

Heptanoate as a neural fuel: energetic and neurotransmitter precursors in normal and glucose transporter I-deficient (G1D) brain

It has been postulated that triheptanoin can ameliorate seizures by supplying the tricarboxylic acid cycle with both acetyl-CoA for energy production and propionyl-CoA to replenish cycle intermediates. These potential effects may also be important in other disorders associated with impaired glucose metabolism because glucose supplies, in addition to acetyl-CoA, pyruvate, which fulfills biosynthetic demands via carboxylation. In patients with glucose transporter type I deficiency (G1D), ketogenic diet fat (a source only of acetyl-CoA) reduces seizures, but other symptoms persist, providing the motivation for studying heptanoate metabolism. In this work, metabolism of infused [5,6,7-¹³C₃]heptanoate was examined in the normal mouse brain and in G1D by ¹³C-nuclear magnetic resonance spectroscopy, gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS). In both groups, plasma glucose was enriched in ¹³C, confirming gluconeogenesis from heptanoate. Acetyl-CoA and glutamine levels became significantly higher in the brain of G1D mice relative to normal mice. In addition, brain glutamine concentration and ¹³C enrichment were also greater when compared with glutamate in both animal groups, suggesting that heptanoate and/or C5 ketones are primarily metabolized by glia. These results enlighten the mechanism of heptanoate metabolism in the normal and glucose-deficient brain and encourage further studies to elucidate its potential antiepileptic effects in disorders of energy metabolism.