Riberrindom1161
A C164S_C545S double mutant had considerably decreased redox sensitivity as compared to wild type AtSS1 (30% vs 77%). Michaelis-Menten kinetics and molecular modeling suggest that both cysteines play important roles in enzyme catalysis, namely, Cys545 is involved in ADP-glucose binding and Cys164 is involved in acceptor binding. All the other single mutants had essentially complete redox sensitivity (98-99%). In addition of being part of a redox directed activity "light switch", reactivation tests and low heterologous expression levels indicate that specific cysteine residues might play additional roles. Specifically, Cys265 in combination with Cys164 can be involved in proper protein folding or/and stabilization of translated protein prior to its transport into the plastid. Cys442 can play an important role in enzyme stability upon oxidation. The physiological and phylogenetic relevance of these findings is discussed.Hepatoma-derived growth factor (HDGF) related protein 2 (HRP2) and lens epithelium-derived growth factor (LEDGF)/p75 are closely related members of the HRP2 protein family. LEDGF/p75 has been implicated in numerous human pathologies including cancer, autoimmunity, and infectious disease. Knockout of the Psip1 gene, which encodes for LEDGF/p75 and the shorter LEDGF/p52 isoform, was previously shown to cause perinatal lethality in mice. The function of HRP2 was by contrast largely unknown. To learn about the role of HRP2 in development, we knocked out the Hdgfrp2 gene, which encodes for HRP2, in both normal and Psip1 knockout mice. Hdgfrp2 knockout mice developed normally and were fertile. By contrast, the double deficient mice died at approximate embryonic day (E) 13.5. Histological examination revealed ventricular septal defect (VSD) associated with E14.5 double knockout embryos. To investigate the underlying molecular mechanism(s), RNA recovered from ventricular tissue was subjected to RNA-sequencing on the Illumina platform. Bioinformatic analysis revealed several genes and biological pathways that were significantly deregulated by the Psip1 knockout and/or Psip1/Hdgfrp2 double knockout. Among the dozen genes known to encode for LEDGF/p75 binding factors, only the expression of Nova1, which encodes an RNA splicing factor, was significantly deregulated by the knockouts. However the expression of other RNA splicing factors, including the LEDGF/p52-interacting protein ASF/SF2, was not significantly altered, indicating that deregulation of global RNA splicing was not a driving factor in the pathology of the VSD. Tumor growth factor (Tgf) β-signaling, which plays a key role in cardiac morphogenesis during development, was the only pathway significantly deregulated by the double knockout as compared to control and Psip1 knockout samples. We accordingly speculate that deregulated Tgf-β signaling was a contributing factor to the VSD and prenatal lethality of Psip1/Hdgfrp2 double-deficient mice.Anthropogenic nitrogen (N) enrichment can alter N dynamics associated with decomposing plant litter. However, it is unclear to what extent these alterations occur via microbial effects (e.g., changes in gene regulation, physiology, or community composition) versus plant litter effects (e.g., changes in composition of N and C compounds). To isolate microbial effects from plant litter effects, we collected plant litter from long-term N fertilized and control plots, reciprocally inoculated it with microbes from the two treatments, and incubated it in a common field setting for three months. We used quantum dots (QDs) to track fungal uptake of glycine and chitosan. Glycine is a relatively simple organic N compound; chitosan is more complex. We found that microbial and litter origins each contributed to a shift in fungal uptake capacities under N fertilization. Specifically, N fungi preferred glycine over chitosan, but control fungi did not. In comparison, litter effects were more subtle, and manifested as a three-way interaction between litter origin, microbial origin, and type of organic N (glycine versus chitosan). In particular, control fungi tended to target chitosan only when incubated with control litter, while N fungi targeted glycine regardless of litter type. Overall, microbial effects may mediate how N dynamics respond to anthropogenic N enrichment in ecosystems.Patients with ST segment elevation myocardial infarction and multivessel disease represent a high percentage of ischemic patient with a worse outcome than patient with single coronary artery disease. Therefore, initial management of these patients is of high importance, but unfortunately this is not clarified yet. We analyze the available literature trying to afford current doubts to determine which way of revascularization is to be preferred. © 2015 Wiley Periodicals, Inc.
To evaluate the predicting value of MUC1 expression in lymph node and distant metastasis of colorectal cancer (CRC).
Pubmed/ MEDLINE and EMBASE were searched to identify eligible studies that evaluated the correlation between MUC1 and CRC. A meta-analysis was conducted to evaluate the impact of MUC1 expression on CRC metastasis.
A total of 18 studies (n = 3271) met inclusion criteria and the mean Newcastle-Ottawa Scale (NOS) score was 6.3 with a range from 4 to 8. The pooled OR in the meta-analysis of 15 studies indicated that positive MUC1 expression correlated with more CRC node metastasis (OR = 2.32, 95% CI = 1.63-3.29). The data synthesis of 6 studies suggested that MUC1 expression predicted more possibility of CRC distant metastasis (OR = 2.22, 95% CI = 1.23-4.00). In addition, the combined OR of 7 studies showed that MUC1 expression indicated higher Duke's stage (OR = 3.02, 95% CI = 2.11-4.33). No publication bias was found in the mate-analysis by Begg's test or Egger's test with the exception of the meta-analysis of MUC1 with CRC node metastasis (Begg's test p = 0.729, Egger's test p = 0.000).
Despite of some modest bias, the pooled evidence suggested that MUC1 expression was significantly correlated with CRC metastasis.
Despite of some modest bias, the pooled evidence suggested that MUC1 expression was significantly correlated with CRC metastasis.
Medication overuse headache (MOH) is a condition bordering between a chronic pain condition and a substance dependence disorder. Activation of immunocompetent glial cells in the central nervous system has been linked to both pathological pain and drug addiction/reward. Preclinically, ibudilast attenuates glial activation and is able to reduce neuropathic pain and markers of substance dependence. We therefore hypothesized ibudilast would reduce headache burden and opioid analgesic requirements in patients with opioid overuse headache.
To determine if treatment with ibudilast provides a greater reduction in headache index than placebo in MOH patients consuming opioids.
Participants with MOH who were using opioids were randomized via computer-generated code to ibudilast 40 mg or placebo twice daily for 8 weeks in a double-blind, parallel groups study. Before randomization participants completed a 4-week baseline headache diary. During treatment, headache diary data collection continued and participants attregimen, ibudilast does not improve headache or reduce opioid use in patients with MOH without mandated opioid withdrawal. However, it would be of interest to determine in future trials if ibudilast is able to improve ease of withdrawal during a forced opioid down-titration when incorporated into an MOH detoxification program.
Using the current dosing regimen, ibudilast does not improve headache or reduce opioid use in patients with MOH without mandated opioid withdrawal. However, it would be of interest to determine in future trials if ibudilast is able to improve ease of withdrawal during a forced opioid down-titration when incorporated into an MOH detoxification program.DNA damage response (DDR) leads to DNA repair, and depending on the extent of the damage, to further events, including cell death. learn more Evidence suggests that cell differentiation may also be a consequence of the DDR. During the formation of the infective hypha in the phytopathogenic fungus Ustilago maydis, two DDR kinases, Atr1 and Chk1, are required to induce a G2 cell cycle arrest, which in turn is essential to display the virulence program. However, the triggering factor of DDR in this process has remained elusive. In this report we provide data suggesting that no DNA damage is associated with the activation of the DDR during the formation of the infective filament in U. maydis. We have analyzed bulk DNA replication during the formation of the infective filament, and we found no signs of impaired DNA replication. Furthermore, using RPA-GFP fusion as a surrogate marker of the presence of DNA damage, we were unable to detect any sign of DNA damage at the cellular level. In addition, neither MRN nor 9-1-1 complexes, both instrumental to transmit the DNA damage signal, are required for the induction of the above mentioned cell cycle arrest, as well as for virulence. In contrast, we have found that the claspin-like protein Mrc1, which in other systems serves as scaffold for Atr1 and Chk1, was required for both processes. We discuss possible alternative ways to trigger the DDR, independent of DNA damage, in U. maydis during virulence program activation.We derive statistical properties of standard methods for monitoring of habitat cover worldwide, and criticize them in the context of mandated seagrass monitoring programs, as exemplified by Posidonia oceanica in the Mediterranean Sea. We report the novel result that cartographic methods with non-trivial classification errors are generally incapable of reliably detecting habitat cover losses less than about 30 to 50%, and the field labor required to increase their precision can be orders of magnitude higher than that required to estimate habitat loss directly in a field campaign. We derive a universal utility threshold of classification error in habitat maps that represents the minimum habitat map accuracy above which direct methods are superior. Widespread government reliance on blind-sentinel methods for monitoring seafloor can obscure the gradual and currently ongoing losses of benthic resources until the time has long passed for meaningful management intervention. We find two classes of methods with very high statistical power for detecting small habitat cover losses 1) fixed-plot direct methods, which are over 100 times as efficient as direct random-plot methods in a variable habitat mosaic; and 2) remote methods with very low classification error such as geospatial underwater videography, which is an emerging, low-cost, non-destructive method for documenting small changes at millimeter visual resolution. General adoption of these methods and their further development will require a fundamental cultural change in conservation and management bodies towards the recognition and promotion of requirements of minimal statistical power and precision in the development of international goals for monitoring these valuable resources and the ecological services they provide.
People with knee osteoarthritis may benefit from exercise prescriptions that minimize knee loads in the frontal plane. The primary objective of this study was to determine whether a novel 12-week strengthening program designed to minimize exposure to the knee adduction moment (KAM) could improve symptoms and knee strength in women with symptomatic knee osteoarthritis. A secondary objective was to determine whether the program could improve mobility and fitness, and decrease peak KAM during gait. The tertiary objective was to evaluate the biomechanical characteristics of this yoga program. In particular, we compared the peak KAM during gait with that during yoga postures at baseline. We also compared lower limb normalized mean electromyography (EMG) amplitudes during yoga postures between baseline and follow-up. Primary measures included self-reported pain and physical function (Knee injury and Osteoarthritis Outcome Score) and knee strength (extensor and flexor torques). Secondary measures included mobility (six-minute walk, 30-second chair stand, stair climbing), fitness (submaximal cycle ergometer test), and clinical gait analysis using motion capture synchronized with electromyography and force measurement.
