Chemical PARP Inhibition Enhances Growth of Arabidopsis and Reduces Anthocyanin Accumulation and the Activation of Stress Protective Mechanisms

Poly-ADP-ribose polymerase (PARP) post-translationally modifies proteins through the addition of ADP-ribose polymers, yet its role in modulating plant development and stress responses is only poorly understood. The experiments presented here address some of the gaps in our understanding of its role in stress tolerance and thereby provide new insights into tolerance mechanisms and growth. Using a combination of chemical and genetic approaches, this study characterized phenotypes associated with PARP inhibition at the physiological level. Molecular analyses including gene expression analysis, measurement of primary metabolites and redox metabolites were used to understand the underlying processes. The analysis revealed that PARP inhibition represses anthocyanin and ascorbate accumulation under stress conditions. The reduction in defense is correlated with enhanced biomass production. Even in unstressed conditions protective genes and molecules are repressed by PARP inhibition. The reduced anthocyanin production was shown to be based on the repression of transcription of key regulatory and biosynthesis genes. PARP is a key factor for understanding growth and stress responses of plants. PARP inhibition allows plants to reduce protection such as anthocyanin, ascorbate or Non-Photochemical-Quenching whilst maintaining high energy levels likely enabling the observed enhancement of biomass production under stress, opening interesting perspectives for increasing crop productivity

A Fully Digital Background Calibration Technique for M-Channel Time-Interleaved ADCs

In this paper, we propose a pure digital blind calibration method to estimate and calibrate offset, gain and timing mismatches. Gain errors are calibrated based on first channel correction using an overall reference, whereas for the rest of the (M−1) channels, the corrected first channel becomes the reference channel. Time skew calibration is performed using a derivative filter followed by a fractional delay filter and a scaling factor. The proposed technique significantly reduces the required hardware resources, specifically for the derivative and fractional delay filters for which no look-up table is required. In addition, the proposed method requires only two finite impulse response filters with fixed coefficients, thus reducing complexity and hardware resources, as compared to adaptive filter techniques. For a sampling frequency of 3.072 GHz, the maximum achievable signal-to-noise and distortion ratio is 67 dB, resulting in effective number of bits of 10.83 for a 12-bit resolution analog-to-digital converter

Antiretroviral neurotoxicity

Combination antiretroviral therapy (CART) has proven to effectively suppress systemic HIV burden, however, poor penetration into the central nervous system (CNS) provides incomplete protection. Although the severity of HIV-associated neurocognitive disorders (HAND) has been reduced, neurological disease is expected to exert an increasing burden as HIV-infected patients live longer. Strategies to enhance penetration of antiretroviral compounds into the CNS could help to control HIV replication in this reservoir but also carries an increased risk of neurotoxicity. Efforts to target antiretroviral compounds to the CNS will have to balance these risks against the potential gain. Unfortunately, little information is available on the actions of antiretroviral compounds in the CNS, particularly at concentrations that provide effective virus suppression. The current studies evaluated the direct effects of 15 anti-retroviral compounds on neurons to begin to provide basic neurotoxicity data that will serve as a foundation for the development of dosing and drug selection guidelines. Using sensitive indices of neural damage, we found a wide range of toxicities, with median toxic concentrations ranging from 2 to 10,000 ng/ml. Some toxic concentrations overlapped concentrations currently seen in the CSF but the level of toxicity was generally modest at clinically relevant concentrations. Highest neurotoxicities were associated with abacavir, efavarenz, etravirine, nevaripine, and atazanavir, while the lowest were with darunavir, emtracitabine, tenofovir, and maraviroc. No additive effects were seen with combinations used clinically. These data provide initial evidence useful for the development of treatment strategies that might reduce the risk of antiretroviral neurotoxicity

The neglect of racism as an ethical issue in health care

Race and racism has been increasingly implicated in known disparities in the health and health care of racial, ethnic and cultural minorities groups. Despite the obvious ethical implications of this observation, racism as an ethical issue per se has been relatively neglected in health care ethics discourse. In this paper consideration is given to addressing the following questions: What is it about racism and racial disparities in health and health care that these command our special moral scrutiny? Why has racism per se tended to be poorly addressed as an ethical issue in health care ethics discourse? And why, if at all, must racism be addressed as an ethical issue in addition to its positioning as a social, political, cultural and legal issue? It is suggested that unless racism is reframed and redressed as a pre-eminent ethical issue by health service providers, its otherwise preventable harmful consequences will remain difficult to identify, anticipate, prevent, manage, and remedy. <br /