NAF-1 and mitoNEET are central to human breast cancer proliferation by maintaining mitochondrial homeostasis and promoting tumor growth

Mitochondria are emerging as important players in the transformation process of cells, maintaining the biosynthetic and energetic capacities of cancer cells and serving as one of the primary sites of apoptosis and autophagy regulation. Although several avenues of cancer therapy have focused on mitochondria, progress in developing mitochondria-targeting anticancer drugs nonetheless has been slow, owing to the limited number of known mitochondrial target proteins that link metabolism with autophagy or cell death. Recent studies have demonstrated that two members of the newly discovered family of NEET proteins, NAF-1 (CISD2) and mitoNEET (mNT; CISD1), could play such a role in cancer cells. NAF-1 was shown to be a key player in regulating autophagy, and mNT was proposed to mediate iron and reactive oxygen homeostasis in mitochondria. Here we show that the protein levels of NAF-1 and mNT are elevated in human epithelial breast cancer cells, and that suppressing the level of these proteins using shRNA results in significantly reduced cell proliferation and tumor growth, decreased mitochondrial performance, uncontrolled accumulation of iron and reactive oxygen in mitochondria, and activation of autophagy. Our findings highlight NEET proteins as promising mitochondrial targets for cancer therapy

SNP Array Karyotyping Allows for the Detection of Uniparental Disomy and Cryptic Chromosomal Abnormalities in MDS/MPD-U and MPD

We applied single nucleotide polymorphism arrays (SNP-A) to study karyotypic abnormalities in patients with atypical myeloproliferative syndromes (MPD), including myeloproliferative/myelodysplastic syndrome overlap both positive and negative for the JAK2 V617F mutation and secondary acute myeloid leukemia (AML). In typical MPD cases (N = 8), which served as a control group, those with a homozygous V617F mutation showed clear uniparental disomy (UPD) of 9p using SNP-A. Consistent with possible genomic instability, in 19/30 MDS/MPD-U patients, we found additional lesions not identified by metaphase cytogenetics. In addition to UPD9p, we also have detected UPD affecting other chromosomes, including 1 (2/30), 11 (4/30), 12 (1/30) and 22 (1/30). Transformation to AML was observed in 8/30 patients. In 5 V617F+ patients who progressed to AML, we show that SNP-A can allow for the detection of two modes of transformation: leukemic blasts evolving from either a wild-type jak2 precursor carrying other acquired chromosomal defects, or from a V617F+ mutant progenitor characterized by UPD9p. SNP-A-based detection of cryptic lesions in MDS/MPD-U may help explain the clinical heterogeneity of this disorder

Dissolved organic matter in sea spray: a transfer study from marine surface water to aerosols

Atmospheric aerosols impose direct and indirect effects on the climate system, for example, by absorption of radiation in relation to cloud droplets size, on chemical and organic composition and cloud dynamics. The first step in the formation of Organic primary aerosols, i.e. the transfer of dissolved organic matter from the marine surface into the atmosphere, was studied. We present a molecular level description of this phenomenon using the high resolution analytical tools of Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and nuclear magnetic resonance spectroscopy (NMR). Our experiments confirm the chemoselective transfer of natural organic molecules, especially of aliphatic compounds from the surface water into the atmosphere via bubble bursting processes. Transfer from marine surface water to the atmosphere involves a chemical gradient governed by the physicochemical properties of the involved molecules when comparing elemental compositions and differentiating CHO, CHNO, CHOS and CHNOS bearing compounds. Typical chemical fingerprints of compounds enriched in the aerosol phase were CHO and CHOS molecular series, smaller molecules of higher aliphaticity and lower oxygen content, and typical surfactants. A non-targeted metabolomics analysis demonstrated that many of these molecules corresponded to homologous series of oxo-, hydroxy-, methoxy-, branched fatty acids and mono-, di- and tricarboxylic acids as well as monoterpenes and sugars. These surface active biomolecules were preferentially transferred from surface water into the atmosphere via bubble bursting processes to form a significant fraction of primary organic aerosols. This way of sea spray production leaves a selective biological signature of the surface water in the corresponding aerosol that may be transported into higher altitudes up to the lower atmosphere, thus contributing to the formation of secondary organic aerosol on a global scale or transported laterally with possible deposition in the context of global biogeocycling

Nontarget analysis of Murchison soluble organic matter by high-field NMR spectroscopy and FTICR mass spectrometry.

High-field NMR spectra of Murchison meteorite methanolic extracts revealed primarily aliphatic extraterrestrial organic matter (EOM) with near statistical branching of commonly C3-5 units separated by heteroatoms and aromatic units. The ratios of CCH, OCH and Csp2 H units were 89 : 8 : 3, whereas carbon-based aliphatic chain termination was in the order methyl > COOH > CH(CH3 )COOH. Aliphatic methine carbon was abundant, but its weak NMR signatures were primarily deduced from JRES (J-resolved) NMR spectra. Carbon NMR spectra were dominated by methylene and methyl carbon; strong apodization revealed methine carbon, of which about 20% was aromatic. Extrapolation provided 5-7% aromatic carbon present in Murchison soluble EOM. Compositional heterogeneity in Murchison methanolic extracts was visible in NMR and Fourier transform ion cyclotron (FTICR) mass spectra obtained from a few cubic millimeters of solid Murchison meteorite; increasing sample size enhanced uniformity of NMR spectra. Intrinsic chemical diversity and pH-dependent chemical shift variance contributed to the disparity of NMR spectra. FTICR mass spectra provided distinct clustering of CHO/CHOS and CHNO/CHNOS molecular series and confirmed the prevalence of aliphatic/alicyclic (73%) over single aromatic (21%) and polyaromatic (6%) molecular compositions, suggesting extensive aliphatic substitution of aromatic units as proposed by NMR. Murchison soluble EOM molecules feature a center with enhanced aromatic and heteroatom content, which provides rather diffuse and weak NMR signatures resulting from a huge overall chemical diversity. The periphery of Murchison EOM molecules comprises flexible branched aliphatic chains and aliphatic carboxylic acids. These project on narrow ranges of chemical shift, facilitating observation in one-dimensional and two-dimensional NMR spectra. The conformational entropy provided by these flexible surface moieties facilitates the solubility of EOM