Starving leukemia to induce differentiation

A new study shows that fasting induces the differentiation and elimination of some types of leukemia in mice, which implicates fasting or its mimetics as a novel strategy for the treatment of this disease

Cell size is a determinant of stem cell potential during aging

Stem cells are remarkably small. Whether small size is important for stem cell function is unknown. We find that hematopoietic stem cells (HSCs) enlarge under conditions known to decrease stem cell function. This decreased fitness of large HSCs is due to reduced proliferation and was accompanied by altered metabolism. Preventing HSC enlargement or reducing large HSCs in size averts the loss of stem cell potential under conditions causing stem cell exhaustion. Last, we show that murine and human HSCs enlarge during aging. Preventing this age-dependent enlargement improves HSC function. We conclude that small cell size is important for stem cell function in vivo and propose that stem cell enlargement contributes to their functional decline during aging.Peer reviewe

mTORC1 in the Paneth cell niche couples intestinal stem cell function to calorie intake

How adult tissue stem and niche cells respond to the nutritional state of an organism is not well understood. Here we find that Paneth cells, a key constituent of the mammalian intestinal stem-cell (ISC) niche, augment stem-cell function in response to calorie restriction. Calorie restriction acts by reducing mechanistic target of rapamycin complex 1 (mTORC1) signalling in Paneth cells, and the ISC-enhancing effects of calorie restriction can be mimicked by rapamycin. Calorie intake regulates mTORC1 in Paneth cells, but not ISCs, and forced activation of mTORC1 in Paneth cells during calorie restriction abolishes the ISC-augmenting effects of the niche. Finally, increased expression of bone stromal antigen 1 (Bst1) in Paneth cells—an ectoenzyme that produces the paracrine factor cyclic ADP ribose—mediates the effects of calorie restriction and rapamycin on ISC function. Our findings establish that mTORC1 non-cell-autonomously regulates stem-cell self-renewal, and highlight a significant role of the mammalian intestinal niche in coupling stem-cell function to organismal physiology.National Institutes of Health (U.S.) (CA103866)National Institutes of Health (U.S.) (CA129105)David H. Koch Institute for Integrative Cancer Research at MIT (Initiator Award)Ellison Medical FoundationNational Cancer Institute (U.S.) (NCI (T32CA09216) fellowship support)Academy of FinlandFoundations’ Postdoc PoolNational Institutes of Health (U.S.) (NIH (1F32AG032833-01A1))Jane Coffin Childs Memorial Fund for Medical Researc

Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells

Recent advances have highlighted extensive phenotypic and functional similarities between normal stem cells and cancer stem cells. This raises the question of whether disease therapies can be developed that eliminate cancer stem cells without eliminating normal stem cells. Here we address this issue by conditionally deleting the Pten tumour suppressor gene in adult haematopoietic cells. This led to myeloproliferative disease within days and transplantable leukaemias within weeks. Pten deletion also promoted haematopoietic stem cell (HSC) proliferation. However, this led to HSC depletion via a cell-autonomous mechanism, preventing these cells from stably reconstituting irradiated mice. In contrast to leukaemia-initiating cells, HSCs were therefore unable to maintain themselves without Pten. These effects were mostly mediated by mTOR as they were inhibited by rapamycin. Rapamycin not only depleted leukaemia-initiating cells but also restored normal HSC function. Mechanistic differences between normal stem cells and cancer stem cells can thus be targeted to deplete cancer stem cells without damaging normal stem cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62514/1/nature04703.pd

Додатковий том «Словника української мови»

У статті подано історію роботи над Додатковим томом «Словника української мови» в 11-ти томах, описано джерела наповнення реєстру, структуру словникових статей, наведено приклади розробки статей різного типу – як нововведених слів, так і таких, що були в «Словнику української мови» і зазнали доповнення. Завдання лексикографів, які працювали над Додатковим томом, – відобразити динаміку лексичного шару української мови 1980-их рр. ХХ ст. – початку ХХІ ст. з акцентуванням її інноваційних й актуалізованих аспектів

High fat diet enhances stemness and tumorigenicity of intestinal progenitors

Little is known about how pro-obesity diets regulate tissue stem and progenitor cell function. Here we find that high fat diet (HFD)-induced obesity augments the numbers and function of Lgr5+ intestinal stem-cells (ISCs) of the mammalian intestine. Mechanistically, HFD induces a robust peroxisome proliferator-activated receptor delta (PPAR-d) signature in intestinal stem and (non-ISC) progenitor cells, and pharmacologic activation of PPAR-d recapitulates the effects of a HFD on these cells. Like a HFD, ex vivo treatment of intestinal organoid cultures with fatty acid constituents of the HFD enhances the self-renewal potential of these organoid bodies in a PPAR-d dependent manner. Interestingly, HFD- and agonist-activated PPAR-d signaling endow organoid-initiating capacity to progenitors, and enforced PPAR-d signaling permits these progenitors to form in vivo tumors upon loss of the tumor suppressor Apc. These findings highlight how diet-modulated PPAR-d activation alters not only the function of intestinal stem and progenitor cells, but also their capacity to initiate tumors

Alteration Mineralogy and Geochemistry of the rocks from Tekirova (Antalya) Ophiolite Nappe

The Tekirova Ophiolite Nappe, part of the Antalya Unit in the southwest Anatolia, consists of a dismembered oceanic crust sequence with tectonic slices in different sizes. Three types of subsequent mineralizations are present in the ophiolitic rocks during the oceanic crust formation, emplacement and post-emplacement, respectively. First stage, pyrometamorphism (pyrometasomatization) caused to occurrence of metamorphic minerals such as scapolite, diopside, garnet, epidote and tremolite. Second stage, hydrothermal metamorphism(alteration) is represented byserpentinization of ultramafic rocks. Third stage is followed by listwaenite formation, and age neoformation and/or alteration products contain carbonates (calcite, dolomite, aragonite, magnesite, hydromagnesite, hydrotalcite), oxides and hydroxides (brucite, goethite, hematite), phyllosilicates (smectite, illite, chlorite, talc, C-V, C-S, I-S) and quartz. The serpentine minerals can be distinguished from each other by morphology: ribbon-like shapes for antigorite, platy for lizardite and fibrous for chrysotile. Serpentines are represented by three polytypes as structural groups of A- (clinochrysotile-2M(1)), C- (lizardite-1T) and D- (lizardite-2H(1)). Chondrite-normalized trace and rare earth element patterns of 1T and 2H(1) Fe-lizardites, Fe-tremolite and Ca-hydromagnesite minerals show similar trends indicating similar ophioliticparent rocks and differentiated form each others. The delta O-18 and delta D values of serpentines indicate two different serpantinization under hypogene conditions as oceanic (lizardite-1T) and supergene as Alpin types (clinochrysotile-2M(1) and lizardite-2H(1)) at temperatures of about 200 degrees C and 100 degrees C, respectively

Mineralogical characteristics of metamorphic massif units outcropping in Göksun, Afşin and Ekinözü (Kahramanmaraş) region

This study aims to investigate and correlate the mineralogical-petrographic characteristics of Metamorphites in Göksun, Afşin and Ekinözü in the Southeast Anatolian Metamorphic Massifs. In this context, the optical microscopy and XRD investigations were performed on several samples. Göksun Metamorphites are constituted by phyllite, calcphyllite, marble and they contain mainly calcite, dolomite, quartz, feldspar, phyllosilicate. KI and b-cell dimension data reflect high anchizone-epizone and medium pressure conditions. Afşin Metamorphites are represented by phyllite, calcphyllite, calcschist, micaschist, amphiboleschist, marble. Phyllosilicates have consisted of illite/mica, IIb chlorite, mixed-layers, smectite. KI and b-cell dimension data correspond to the subgreenschist-greenschist facies conditions. Ekinözü Metamorphites are made of chloriteschist, amphiboleschist, micaschist, micagneiss in lower parts, while calcitic and/or dolomitic marbles are present in the upper parts. Mica is dioctahedral and trioctahedral, whereas chlorite tends to be trioctahedral. Based on mineral associations, Ekinözü Metamorphites belong to amphibolite facies in the lower parts, but the greenschist facies conditions at the upper parts. The coarse-grained biotite, muscovite and chlorite are accompanied by mixed-layers. According to mineral composition and degrees of metamorphism, Göksun and Afşin Metamorphites are similar to the Keban and Malatya Metamorphites; however, Ekinözü Metamorphites to Pütürge Metamorphites. The data show that metamorphics in the western extension of the Southeast Anatolian Metamorphic Massifs have different origin and/or lithologies according to the regions, increasing temperature-pressure conditions from Göksun to Ekinözü and have groups of rock with different geological evolutions. © 2020 General Directorate of Mineral Research and Exploration (MTA). All rights reserved