Molecular Insights into Reprogramming-Initiation Events Mediated by the OSKM Gene Regulatory Network

Somatic cells can be reprogrammed to induced pluripotent stem cells by over-expression of OCT4, SOX2, KLF4 and c-MYC (OSKM). With the aim of unveiling the early mechanisms underlying the induction of pluripotency, we have analyzed transcriptional profiles at 24, 48 and 72 hours post-transduction of OSKM into human foreskin fibroblasts. Experiments confirmed that upon viral transduction, the immediate response is innate immunity, which induces free radical generation, oxidative DNA damage, p53 activation, senescence, and apoptosis, ultimately leading to a reduction in the reprogramming efficiency. Conversely, nucleofection of OSKM plasmids does not elicit the same cellular stress, suggesting viral response as an early reprogramming roadblock. Additional initiation events include the activation of surface markers associated with pluripotency and the suppression of epithelial-to-mesenchymal transition. Furthermore, reconstruction of an OSKM interaction network highlights intermediate path nodes as candidates for improvement intervention. Overall, the results suggest three strategies to improve reprogramming efficiency employing: 1) anti-inflammatory modulation of innate immune response, 2) pre-selection of cells expressing pluripotency-associated surface antigens, 3) activation of specific interaction paths that amplify the pluripotency signal

NUCLEAR FACTOR Y, Subunit C (NF-YC) Transcription Factors Are Positive Regulators of Photomorphogenesis in Arabidopsis thaliana

We thank Dr. Ben Smith (University of Oklahoma) for assistance with FLIM-FRET measurements and Dr. Min Ni (University of Minnesota) for critical reading of the manuscript. The cop1-4 mutant allele and cop1-4 co-9 cross were kindly provided by George Coupland (Max Planck Institute).Author Summary Light perception is critically important for the fitness of plants in both natural and agricultural settings. Plants not only use light for photosynthesis, but also as a cue for proper development. As a seedling emerges from soil it must determine the light environment and adopt an appropriate growth habit. When blue and red wavelengths are the dominant sources of light, plants will undergo photomorphogenesis. Photomorphogenesis describes a number of developmental responses initiated by light in a seedling, and includes shortened stems and establishing the ability to photosynthesize. The genes regulating photomorphogenesis have been studied extensively, but a complete picture remains elusive. Here we describe the finding that NUCLEAR FACTOR-Y (NF-Y) genes are positive regulators of photomorphogenesis—i.e., in plants where NF-Y genes are mutated, they display some characteristics of dark grown plants, even though they are in the light. Our data suggests that the roles of NF-Y genes in light perception do not fit in easily with those of other described pathways. Thus, studying these genes promises to help develop a more complete picture of how light drives plant development.Yeshttp://www.plosgenetics.org/static/editorial#pee

Biogeochemical cycling of sulphur in karst and transfer into speleothem archives at Grotta di Ernesto, Italy

Trace amounts of sulphur in speleothems suggest that stalagmites may act as archives of sulphur deposition, thereby recording aspects of atmospheric variability in sulphur content. Accurate interpretation of this novel sulphur archive depends upon understanding how biogeochemical cycling in the soil and epikarst above the cave may modify the precursor atmospheric values of sulphur concentration and isotopic composition prior to incorporation into the speleothem record. Dual isotope analysis of δ34S-SO4 and δ18O-SO4 is used to trace biogeochemical transformations of atmospheric sulphur through the cave system at Grotta di Ernesto in the Italian Alps and builds towards a framework for interpretation of speleothem sulphur archives which depends on overlying ecosystem dynamics and karst hydrological properties. A three component model of atmospheric signal modification is proposed to be driven by 1. vegetation and soil cycling, 2. the degree of groundwater mixing in the karst aquifer; and 3. redox status. The relative influence of each process is specific to individual drip flow sites and associated stalagmites, rendering each suphur archive a unique signal of environmental conditions. Under conditions found in the soil and epikarst above Grotta di Ernesto, the dual isotope signatures of sulphate sulphur and oxygen incorporated into speleothem carbonate, closely reflect past conditions of industrial sulphur loading to the atmosphere and the extent of signal modification through biogeochemical cycling and aquifer mixing

PCO2 variations of cave air and cave water in a subtropical cave, SW China

Cave CO2 is an important part of the carbon cycle in a karst system. From 2008 to 2009 the partial pressure of CO2 (PCO2) of the cave air and cave water (cave stream and dripwater) in Xueyu Cave was studied. The PCO2 for cave air and cave water over two years showed that CO2 concentrations vary seasonally in all field sites, with higher CO2 concentrations in the wet season and lower concentrations in the dry season. These seasonal CO2 variations of cave air and cave water are attributed to seasonally variable soil CO2 production that is controlled by outside temperature fluctuations. Cave ventilation controls synchronous sharp variations of PCO2 from wet season to dry season or dry season to wet season in cave water and cave air. In the wet season, there were no obvious spatial differences of mean PCO2 in cave stream and cave air from upstream to downstream cave. Conversely, there were significant spatial differences of mean PCO2 in cave stream and cave air from upstream to downstream cave in the dry season because of cave ventilation. Mean dripwater PCO2 in D1 site where near cave entrance is much higher than that of the D2 and D3 sites where located in inner cave because D1 has a shorter flowpath from cave ceiling to soda-straw tip and lesser CO2 degassing along the flowpath. Further work in Xueyu Cave needs to clarify the quantitative relationship of CO2 cycle between cave air CO2 and cave water and focus on the influence of CO2 cycle on speleothem form

Changes in serum cytokine and cortisol levels in normothermic and hypothermic term neonates after perinatal asphyxia

OBJECTIVE: Perinatal asphyxia is characterized by an inflammatory response that contributes to cerebral injury. Therapeutic hypothermia improves neurological outcome in asphyxiated term neonates, but its clear effect on the inflammatory response is unknown. SUBJECTS AND METHODS: A range of cytokines and cortisol levels were measured at the 6th, 12th and 24th postnatal hours in neonates with hypoxic-ischemic encephalopathy treated with standard intensive care on hypothermia (n = 10) or normothermia (n = 8). The influence of postnatal age and hypothermia on serum cytokine and cortisol levels was evaluated. RESULTS: Interleukin (IL)-6 levels (at 6 h of age) and IL-4 levels (at all time points) were significantly lower in asphyxiated neonates treated with hypothermia compared to normothermic neonates. Vascular endothelial growth factor levels were higher in the hypothermia than in the normothermia group at the 6th and 12th postnatal hours. IL-10 levels decreased significantly between 6 and 24 h of age in both groups. However, no difference of IL-10 levels was observed between the study groups. The duration of hypothermia before 6 hours of age correlated with lower levels of IL-6, interferon-gamma and tumor necrosis factor-alpha measured at 6 h of age and IL-10 levels at 12 h of age. Cortisol levels did not differ between the study groups, but did gradually decrease in both groups during the study period. At 6 and 24 h of age, a positive correlation was observed between cortisol and IL-10 levels. CONCLUSIONS: Therapeutic hypothermia may rapidly suppress and modify the immediate cytokine response to asphyxia. The correlation between cytokine levels and duration of hypothermia suggests that the earlier hypothermia is introduced, the more pronounced its beneficial immunomodulatory effect