The tumor suppressor MIR139 is silenced by POLR2M to promote AML oncogenesis

MIR139 is a tumor suppressor and is commonly silenced in acute myeloid leukemia (AML). However, the tumor-suppressing activities of miR-139 and molecular mechanisms of MIR139-silencing remain largely unknown. Here, we studied the poorly prognostic MLL-AF9 fusion protein-expressing AML. We show that MLL-AF9 expression in hematopoietic precursors caused epigenetic silencing of MIR139, whereas overexpression of MIR139 inhibited in vitro and in vivo AML outgrowth. We identified novel miR-139 targets that mediate the tumor-suppressing activities of miR-139 in MLL-AF9 AML. We revealed that two enhancer regions control MIR139 expression and found that the polycomb repressive complex 2 (PRC2) downstream of MLL-AF9 epigenetically silenced MIR139 in AML. Finally, a genome-wide CRISPR-Cas9 knockout screen revealed RNA Polymerase 2 Subunit M (POLR2M) as a novel MIR139-regulatory factor. Our findings elucidate the molecular control of tumor suppressor MIR139 and reveal a role for POLR2M in the MIR139-silencing mechanism, downstream of MLL-AF9 and PRC2 in AML. In addition, we confirmed these findings in human AML cell lines with different oncogenic aberrations, suggesting that this is a more common oncogenic mechanism in AML. Our results may pave the way for new targeted therapy in AML.Proteomic

Towards colloidal spintronics through Rashba spin-orbit interaction in lead sulphide nanosheets

Employing the spin degree of freedom of charge carriers offers the possibility to extend the functionality of conventional electronic devices, while colloidal chemistry can be used to synthesize inexpensive and tuneable nanomaterials. In order to benefit from both concepts, Rashba spin-orbit interaction has been investigated in colloidal lead sulphide nanosheets by electrical measurements on the circular photo-galvanic effect. Lead sulphide nanosheets possess rock salt crystal structure, which is centrosymmetric. The symmetry can be broken by quantum confinement, asymmetric vertical interfaces and a gate electric field leading to Rashba-type band splitting in momentum space at the M points, which results in an unconventional selection mechanism for the excitation of the carriers. The effect, which is supported by simulations of the band structure using density functional theory, can be tuned by the gate electric field and by the thickness of the sheets. Spin-related electrical transport phenomena in colloidal materials open a promising pathway towards future inexpensive spintronic devices.Comment: 25 pages, 4 figure

Динамика насаждений сосны крымской (Pinus pallasiana L. ) в горном Крыму

За период 1938 – 2000 гг. произошло "смещение" мест произрастания сосновых древостоев в более богатые и влажные условия. Увеличилась площадь насаждений сосны крымской. Площадь сосновых культур больше чем в 3 раза превысила площадь естественных лесов. Средний запас сосновых лесов составляет 136 м³/га. Древостои ІІ и высших классов бонитета занимают лишь 12 % сосновых лесов.За період 1938 – 2000 рр. відбувся "зсув" місць виростання соснових деревостанів у багатші й вологіші умови. Збільшилася площа насаджень сосни кримської. Площа соснових культур у понад 3 рази перевершила площу природних лісів. Середній запас соснових лісів становить 136 м³/га. Деревостани ІІ і вищих класів бонітету займають лише 12 % соснових лісів.For 1938 – 2000 "displacement" of pine stands to more rich and moist sites has occurred. Area of P. pallasiana has increased. Pine plantation area has exceeded area of natural pine forests more than 3 times. Mean stock of pine forests is 136 m³/ha. Stands of the ІІ and higher growth classes take only 12 % of pine forests

The inbreeding strategy of a solitary primate, Microcebus murinus

International audienceInbreeding depression may be common in nature, reflecting either the failure of inbreeding avoidance strategies or inbreeding tolerance when avoidance is costly. The combined assessment of inbreeding risk, avoidance and depression is therefore fundamental to evaluate the inbreeding strategy of a population, that is how individuals respond to the risk of inbreeding. Here, we use the demographic and genetic monitoring of 10 generations of wild grey mouse lemurs (Microcebus murinus), small primates from Madagascar with overlapping generations, to examine their inbreeding strategy. Grey mouse lemurs have retained ancestral mammalian traits, including solitary lifestyle, polygynandry and male-biased dispersal, and may therefore offer a representative example of the inbreeding strategy of solitary mammals. The occurrence of close kin among candidate mates was frequent in young females (~37%, most often the father) and uncommon in young males (~6%) due to male-biased dispersal. However, close kin consistently represented a tiny fraction of candidate mates (< 1%) across age and sex categories. Mating biases favouring partners with intermediate relatedness were detectable in yearling females and adult males, possibly partly caused by avoidance of daughter-father matings. Finally, inbreeding depression, assessed as the effect of heterozygosity on survival, was undetectable using a capture-mark-recapture study. Overall, these results indicate that sex-biased dispersal is a primary inbreeding avoidance mechanism at the population level, and mating biases represent an additional strategy that may mitigate residual inbreeding costs at the individual level. Combined, these mechanisms explain the rarity of inbreeding and the lack of detectable inbreeding depression in this large, genetically diverse population

Iron Nitride and Carbide: from Crystalline Nanoparticles to Stable Aqueous Dispersions

Iron nitride and carbide nanoparticles were synthesized using iron oxide particles as template. They were furthermore dispersed in aqueous solution via stabilization with a poly(ionic liquid). They provide a great potential combining a high saturation magnetization with low toxicity compared to the iron based compounds that are currently used in several applications such as cell-sorting and hyperthermia or as contrast enhancers for magnetic resonance imaging. We here present a sustainable and green procedure to synthesize iron nitride and carbide by resorting to the variety of iron oxide template nanoparticles. In this way the shape and the size can be precisely controlled and tuned within the nanometer range. During calcination, urea enables to control the composition of the product material, whereas a biopolymer agar protects the particles from agglomeration. We dispersed the particles in water by using poly(1-ethyl-3-vinylimidazolium bromide) as stabilizing agent. Magnetic measurements of the converted particles show that particles with a diameter of 18 nm are located at the border of superparamagnetic and ferromagnetic behavior. As expected after conversion the saturation magnetization of the particles was notably increased. The herein presented synthetic approach can be applied to other metals and has thus the potential to be important for the synthesis of nitrides and carbides in general