52 research outputs found
A multi-iron system capable of rapid N\u3csub\u3e2\u3c/sub\u3e formation and N \u3csub\u3e2\u3c/sub\u3e cleavage
The six-electron oxidation of two nitrides to N2 is a key step of ammonia synthesis and decomposition reactions on surfaces. In molecular complexes, nitride coupling has been observed with terminal nitrides, but not with bridging nitride complexes that more closely resemble catalytically important surface species. Further, nitride coupling has not been reported in systems where the nitrides are derived from N2. Here, we show that a molecular diiron(II) diiron(III) bis(nitride) complex reacts with Lewis bases, leading to the rapid six-electron oxidation of two bridging nitrides to form N2. Surprisingly, these mild reagents generate high yields of iron(I) products from the iron(II/III) starting material. This is the first molecular system that both breaks and forms the triple bond of N2 at room temperature. These results highlight the ability of multi-iron species to decrease the energy barriers associated with the activation of strong bonds. © 2014 American Chemical Society
Role of Saw1 in Rad1/Rad10 complex assembly at recombination intermediates in budding yeast
Phagocytosis of Staphylococcus aureus by Macrophages Exerts Cytoprotective Effects Manifested by the Upregulation of Antiapoptotic Factors
It is becoming increasingly apparent that Staphylococcus aureus are able to survive engulfment by macrophages, and that the intracellular environment of these host cells, which is essential to innate host defenses against invading microorganisms, may in fact provide a refuge for staphylococcal survival and dissemination. Based on this, we postulated that S. aureus might induce cytoprotective mechanisms by changing gene expression profiles inside macrophages similar to obligate intracellular pathogens, such as Mycobacterium tuberculosis. To validate our hypothesis we first ascertained whether S. aureus infection could affect programmed cell death in human (hMDMs) and mouse (RAW 264.7) macrophages and, specifically, protect these cells against apoptosis. Our findings indicate that S. aureus-infected macrophages are more resistant to staurosporine-induced cell death than control cells, an effect partly mediated via the inhibition of cytochrome c release from mitochondria. Furthermore, transcriptome analysis of human monocyte-derived macrophages during S. aureus infection revealed a significant increase in the expression of antiapoptotic genes. This was confirmed by quantitative RT-PCR analysis of selected genes involved in mitochondria-dependent cell death, clearly showing overexpression of BCL2 and MCL1. Cumulatively, the results of our experiments argue that S. aureus is able to induce a cytoprotective effect in macrophages derived from different mammal species, which can prevent host cell elimination, and thus allow intracellular bacterial survival. Ultimately, it is our contention that this process may contribute to the systemic dissemination of S. aureus infection
Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation
Publisher Copyright: © 2022 The AuthorsBackground: Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits. Methods: We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. We also examined associations of child sex with DNA methylation in older children ages 5.5–10 years from 8 cohorts (n = 4268). Results: In newborn blood, sex was associated at Bonferroni level significance with differences in DNA methylation at 46,979 autosomal CpG sites (p < 1.3 × 10−7) after adjusting for white blood cell proportions and batch. Most of those sites had lower methylation levels in males than in females. Of the differentially methylated CpG sites identified in newborn blood, 68% (31,727) met look-up level significance (p < 1.1 × 10−6) in older children and had methylation differences in the same direction. Conclusions: This is a large-scale meta-analysis examining sex differences in DNA methylation in newborns and older children. Expanding upon previous studies, we replicated previous findings and identified additional autosomal sites with sex-specific differences in DNA methylation. Differentially methylated sites were enriched in genes involved in cancer, psychiatric disorders, and cardiovascular phenotypes.Peer reviewe
Correction to “Density Functional Calculations for Prediction of 57Fe Mossbauer Isomer Shifts and Quadrupole Splittings in β‑Diketiminate Complexes”
A Multi-iron System Capable of Rapid N<sub>2</sub> Formation and N<sub>2</sub> Cleavage
The six-electron oxidation of two
nitrides to N<sub>2</sub> is
a key step of ammonia synthesis and decomposition reactions on surfaces.
In molecular complexes, nitride coupling has been observed with terminal
nitrides, but not with bridging nitride complexes that more closely
resemble catalytically important surface species. Further, nitride
coupling has not been reported in systems where the nitrides are derived
from N<sub>2</sub>. Here, we show that a molecular diiron(II) diiron(III)
bis(nitride) complex reacts with Lewis bases, leading to the rapid
six-electron oxidation of two bridging nitrides to form N<sub>2</sub>. Surprisingly, these mild reagents generate high yields of iron(I)
products from the iron(II/III) starting material. This is the first
molecular system that both breaks and forms the triple bond of N<sub>2</sub> at room temperature. These results highlight the ability
of multi-iron species to decrease the energy barriers associated with
the activation of strong bonds
microRNA-2110 functions as an onco-suppressor in neuroblastoma by directly targeting Tsukushi.
microRNA-2110 (miR-2110) was previously identified as inducing neurite outgrowth in a neuroblastoma cell lines BE(2)-C, suggesting its differentiation-inducing and oncosuppressive function in neuroblastoma. In this study, we demonstrated that synthetic miR-2110 mimic had a generic effect on reducing cell survival in neuroblastoma cell lines with distinct genetic backgrounds, although the induction of cell differentiation traits varied between cell lines. In investigating the mechanisms underlying such functions of miR-2110, we identified that among its predicted target genes down-regulated by miR-2110, knockdown of Tsukushi (TSKU) expression showed the most potent effect in inducing cell differentiation and reducing cell survival, suggesting that TSKU protein plays a key role in mediating the functions of miR-2110. In investigating the clinical relevance of miR-2110 and TSKU expression in neuroblastoma patients, we found that low tumor miR-2110 levels were significantly correlated with high tumor TSKU mRNA levels, and that both low miR-2110 and high TSKU mRNA levels were significantly correlated with poor patient survival. These findings altogether support the oncosuppressive function of miR-2110 and suggest an important role for miR-2110 and its target TSKU in neuroblastoma tumorigenesis and in determining patient prognosis
Density Functional Calculations for Prediction of <sup>57</sup>Fe Mössbauer Isomer Shifts and Quadrupole Splittings in β‑Diketiminate Complexes
The
relative ease of Mössbauer spectroscopy and of density
functional theory (DFT) calculations encourages the use of Mössbauer
parameters as a validation method for calculations, and the use of
calculations as a double check on crystallographic structures. A number
of studies have proposed correlations between the computationally
determined electron density at the iron nucleus and the observed isomer
shift, but deviations from these correlations in low-valent iron β-diketiminate
complexes encouraged us to determine a new correlation for these compounds.
The use of B3LYP/def2-TZVP in the ORCA platform provides an excellent
balance of accuracy and speed. We provide here not only this new correlation
and a clear guide to its use but also a systematic analysis of the
limitations of this approach. We also highlight the impact of crystallographic
inaccuracies, DFT model truncation, and spin states, with intent to
assist experimentalists to use Mössbauer spectroscopy and calculations
together
Geometric and redox flexibility of pyridine as a redox-active ligand that can reversibly accept one or two electrons
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