Dietary vitamin E decreases doxorubicin-induced oxidative stress without preventing mitochondrial dysfunction

Abstract Doxorubicin (DOX) is a widely prescribed antineoplastic and although the precise mechanism(s) have yet to be identified, DOX-induced oxidative stress to mitochondrial membranes is implicated in the pathogenic process. Previous attempts to protect against DOX-induced cardiotoxicity with a-tocopherol (vitamin E) have met with limited success possibly as a result of inadequate delivery to relevant subcellular targets such as mitochondrial membranes. The present investigation was designed to assess whether enrichment of cardiac membranes with a-ocopherol is sufficient to protect against DOX-induced mitochondrial cardiotoxicity. Adult male Sprague-Dawley rats received seven weekly subcutaneous injections of 2 mg/kg DOX and fed either standard diet or diet supplemented with a-tocopherol succinate. Treatment with a cumulative dose of 14 mg/kg DOX caused mitochondrial cardiomyopathy as evidenced by histology, accumulation of oxidized cardiac proteins, and a significant decrease in mitochondrial calcium loading capacity. Maintaining rats on the a-tocopherol supplemented diet resulted in a significant (two-to fourfold) enrichment of cardiac mitochondrial membranes with a-tocopherol and diminished the content of oxidized cardiac proteins associated with DOX treatment. However, dietary a-tocopherol succinate failed to protect against mitochondrial dysfunction and cardiac histopathology. From this we conclude that although dietary vitamin E supplementation enriches cardiac mitochondrial membranes with a-tocopherol, either (1) this tocopherol enrichment is not sufficient to protect cardiac mitochondrial membranes from DOX toxicity or (2) oxidative stress alone is not responsible for the persistent mitochondrial cardiomyopathy caused by long-term DOX therapy

Introducing iPods in the Second Language Classroom

In conversational English classes designed for high intermediate level learners, teachers must motivate students to learn the second language by meeting the student\u27s goals and interests. Providing access to new learning resources helps round out a student\u27s education and promotes their marketability upon graduation, motivating them to continue onto the next class activity. For this purpose the teacher is compelled to bring meaning, relevance, and a feeling of engagement to their lessons

Quantum Reed-Solomon Codes

After a brief introduction to both quantum computation and quantum error correction, we show how to construct quantum error-correcting codes based on classical BCH codes. With these codes, decoding can exploit additional information about the position of errors. This error model - the quantum erasure channel - is discussed. Finally, parameters of quantum BCH codes are provided.Comment: Summary only (2 pages), for the full version see: Proceedings Applied Algebra, Algebraic Algorithms and Error-Correcting Codes (AAECC-13), Lecture Notes in Computer Science 1719, Springer, 199

Matched case-control studies: a review of reported statistical methodology

Background: Case-control studies are a common and efficient means of studying rare diseases or illnesses with long latency periods. Matching of cases and controls is frequently employed to control the effects of known potential confounding variables. The analysis of matched data requires specific statistical methods. Methods: The objective of this study was to determine the proportion of published, peer-reviewed matched case-control studies that used statistical methods appropriate for matched data. Using a comprehensive set of search criteria we identified 37 matched case-control studies for detailed analysis. Results: Among these 37 articles, only 16 studies were analyzed with proper statistical techniques (43%). Studies that were properly analyzed were more likely to have included case patients with cancer and cardiovascular disease compared to those that did not use proper statistics (10/16 or 63%, versus 5/21 or 24%, P = 0.02). They were also more likely to have matched multiple controls for each case (14/16 or 88%, versus 13/21 or 62%, P = 0.08). In addition, studies with properly analyzed data were more likely to have been published in a journal with an impact factor listed in the top 100 according to the Journal Citation Reports index (12/16 or 69%, versus 1/21 or 5%, P Conclusion: The findings of this study raise concern that the majority of matched case-control studies report results that are derived from improper statistical analyses. This may lead to errors in estimating the relationship between a disease and exposure, as well as the incorrect adaptation of emerging medical literature.</p

Experimental Demonstration of Squeezed State Quantum Averaging

We propose and experimentally demonstrate a universal quantum averaging process implementing the harmonic mean of quadrature variances. The harmonic mean protocol can be used to efficiently stabilize a set of fragile squeezed light sources with statistically fluctuating noise levels. The averaged variances are prepared probabilistically by means of linear optical interference and measurement induced conditioning. We verify that the implemented harmonic mean outperforms the standard arithmetic mean strategy. The effect of quantum averaging is experimentally tested both for uncorrelated and partially correlated noise sources with sub-Poissonian shot noise or super-Poissonian shot noise characteristics.Comment: 4 pages, 5 figure

Highly Upregulated Lhx2 in the Foxn1−/−^{−/−} Nude Mouse Phenotype Reflects a Dysregulated and Expanded Epidermal Stem Cell Niche

Hair cycling is a prime example of stem cell dependent tissue regeneration and replenishment, and its regulatory mechanisms remain poorly understood. In the present study, we evaluated the effect of a blockage in terminal keratinocytic lineage differentiation in the Foxn1$^{−/−}$ nude phenotype on the epithelial progeny. Most notably we found a constitutive upregulation of LIM homeobox protein 2 (Lhx2), a marker gene of epithelial stem cellness indispensible for hair cycle progression. However, histological evidence along with an erratic, acyclic rise of otherwise suppressed CyclinD1 levels along with several key markers of keratinocyte lineage differentiation indicate a frustrated expansion of epithelial stem cell niches in skin. In addition, CD49f/CD34/CD200–based profiling demonstrated highly significant shifts in subpopulations of epithelial progeny. Intriguingly this appeared to include the expansion of Oct4+ stem cells in dermal fractions of skin isolates in the Foxn1 knock-out opposed to wild type. Overall our findings indicate that the Foxn1$^{−/−}$ phenotype has a strong impact on epithelial progeny and thus offers a promising model to study maintenance and regulation of stem cell niches within skin not feasible in other in vitro or in vivo models

An isotope dilution model for partitioning of phenylalanine and tyrosine uptake by the liver of lactating dairy cows

An isotope dilution model to describe the partitioning of phenylalanine (PHE) and tyrosine (TYR) in the bovine liver was developed. The model comprises four intracellular and six extracellular pools and various flows connecting these pools and external blood. Conservation of mass principles were applied to generate the fundamental equations describing the behaviour of the system in the steady state. The model was applied to datasets from multi-catheterised dairy cattle during a constant infusion of [1-13C] phenylalanine and [2,3,5,6-2H] tyrosine tracers. Model solutions described the extraction of PHE and TYR from the liver via the portal vein and hepatic artery. In addition, the exchange of free PHE and TYR between extracellular and intracellular pools was explained and the hydroxylation of PHE to TYR was estimated. The model was effective in providing information about the fates of PHE and TYR in the liver and could be used as part of a more complex system describing amino acid metabolism in the whole animal

Prolonged refractory status epilepticus following acute traumatic brain injury: a case report of excellent neurological recovery

INTRODUCTION: Refractory status epilepticus (RSE) secondary to traumatic brain injury (TBI) may be under-recognized and is associated with significant morbidity and mortality. METHODS: This case report describes a 20 year old previously healthy woman who suffered a severe TBI as a result of a motor vehicle collision and subsequently developed RSE. Pharmacological coma, physiological support and continuous electroencephalography (cEEG) were undertaken. RESULTS: Following 25 days of pharmacological coma, electrographic and clinical seizures subsided and the patient has made an excellent cognitive recovery. CONCLUSION: With early identification, aggressive physiological support, appropriate monitoring, including cEEG, and an adequate length of treatment, young trauma patients with no previous seizure history and limited structural damage to the brain can have excellent neurological recovery from prolonged RSE

Fe limitation decreases transcriptional regulation over the diel cycle in the model diatom Thalassiosira pseudonana.

Iron (Fe) is an important growth factor for diatoms and its availability is further restricted by changes in the carbonate chemistry of seawater. We investigated the physiological attributes and transcriptional profiles of the diatom Thalassiosira pseudonana grown on a day: night cycle under different CO2/pH and iron concentrations, that in combination generated available iron (Fe\u27) concentrations of 1160, 233, 58 and 12 pM. We found the light-dark conditions to be the main driver of transcriptional patterns, followed by Fe\u27 concentration and CO2 availability, respectively. At the highest Fe\u27 (1160 pM), 55% of the transcribed genes were differentially expressed between day and night, whereas at the lowest Fe\u27 (12 pM), only 28% of the transcribed genes displayed comparable patterns. While Fe limitation disrupts the diel expression patterns for genes in most central metabolism pathways, the diel expression of light- signaling molecules and glycolytic genes was relatively robust in response to reduced Fe\u27. Moreover, we identified a non-canonical splicing of transcripts encoding triose-phosphate isomerase, a key-enzyme of glycolysis, generating transcript isoforms that would encode proteins with and without an active site. Transcripts that encoded an active enzyme maintained a diel expression at low Fe\u27, while transcripts that encoded the non-active enzyme lost the diel expression. This work illustrates the interplay between nutrient limitation and transcriptional regulation over the diel cycle. Considering that future ocean conditions will reduce the availability of Fe in many parts of the oceans, our work identifies some of the regulatory mechanisms that may shape future ecological communities