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https://www.readbyqxmd.com/read/28813421/stromal-r-spondin-orchestrates-gastric-epithelial-stem-cells-and-gland-homeostasis
#1
Michael Sigal, Catriona Y Logan, Marta Kapalczynska, Hans-Joachim Mollenkopf, Hilmar Berger, Bertram Wiedenmann, Roeland Nusse, Manuel R Amieva, Thomas F Meyer
The constant regeneration of stomach epithelium is driven by long-lived stem cells, but the mechanism that regulates their turnover is not well understood. We have recently found that the gastric pathogen Helicobacter pylori can activate gastric stem cells and increase epithelial turnover, while Wnt signalling is known to be important for stem cell identity and epithelial regeneration in several tissues. Here we find that antral Wnt signalling, marked by the classic Wnt target gene Axin2, is limited to the base and lower isthmus of gastric glands, where the stem cells reside...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813420/biogeochemistry-food-for-early-animal-evolution
#2
Andrew H Knoll
No abstract text is available yet for this article.
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813419/vaccine-driven-pharmacodynamic-dissection-and-mitigation-of-fenethylline-psychoactivity
#3
Cody J Wenthur, Bin Zhou, Kim D Janda
Fenethylline, also known by the trade name Captagon, is a synthetic psychoactive stimulant that has recently been linked to a substance-use disorder and 'pharmacoterrorism' in the Middle East. Although fenethylline shares a common phenethylamine core with other amphetamine-type stimulants, it also incorporates a covalently linked xanthine moiety into its parent structure. These independently active pharmacophores are liberated during metabolism, resulting in the release of a structurally diverse chemical mixture into the central nervous system...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813418/mechanism-of-intracellular-allosteric-%C3%AE-2ar-antagonist-revealed-by-x-ray-crystal-structure
#4
Xiangyu Liu, Seungkirl Ahn, Alem W Kahsai, Kai-Cheng Meng, Naomi R Latorraca, Biswaranjan Pani, A J Venkatakrishnan, Ali Masoudi, William I Weis, Ron O Dror, Xin Chen, Robert J Lefkowitz, Brian K Kobilka
G-protein-coupled receptors (GPCRs) pose challenges for drug discovery efforts because of the high degree of structural homology in the orthosteric pocket, particularly for GPCRs within a single subfamily, such as the nine adrenergic receptors. Allosteric ligands may bind to less-conserved regions of these receptors and therefore are more likely to be selective. Unlike orthosteric ligands, which tonically activate or inhibit signalling, allosteric ligands modulate physiologic responses to hormones and neurotransmitters, and may therefore have fewer adverse effects...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813417/cmtm6-maintains-the-expression-of-pd-l1-and-regulates-anti-tumour-immunity
#5
Marian L Burr, Christina E Sparbier, Yih-Chih Chan, James C Williamson, Katherine Woods, Paul A Beavis, Enid Y N Lam, Melissa A Henderson, Charles C Bell, Sabine Stolzenburg, Omer Gilan, Stuart Bloor, Tahereh Noori, David W Morgens, Michael C Bassik, Paul J Neeson, Andreas Behren, Phillip K Darcy, Sarah-Jane Dawson, Ilia Voskoboinik, Joseph A Trapani, Jonathan Cebon, Paul J Lehner, Mark A Dawson
Cancer cells exploit the expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) to subvert T-cell-mediated immunosurveillance. The success of therapies that disrupt PD-L1-mediated tumour tolerance has highlighted the need to understand the molecular regulation of PD-L1 expression. Here we identify the uncharacterized protein CMTM6 as a critical regulator of PD-L1 in a broad range of cancer cells, by using a genome-wide CRISPR-Cas9 screen. CMTM6 is a ubiquitously expressed protein that binds PD-L1 and maintains its cell surface expression...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813415/cdk4-6-inhibition-triggers-anti-tumour-immunity
#6
Shom Goel, Molly J DeCristo, April C Watt, Haley BrinJones, Jaclyn Sceneay, Ben B Li, Naveed Khan, Jessalyn M Ubellacker, Shaozhen Xie, Otto Metzger-Filho, Jeremy Hoog, Matthew J Ellis, Cynthia X Ma, Susanne Ramm, Ian E Krop, Eric P Winer, Thomas M Roberts, Hye-Jung Kim, Sandra S McAllister, Jean J Zhao
Cyclin-dependent kinases 4 and 6 (CDK4/6) are fundamental drivers of the cell cycle and are required for the initiation and progression of various malignancies. Pharmacological inhibitors of CDK4/6 have shown significant activity against several solid tumours. Their primary mechanism of action is thought to be the inhibition of phosphorylation of the retinoblastoma tumour suppressor, inducing G1 cell cycle arrest in tumour cells. Here we use mouse models of breast carcinoma and other solid tumours to show that selective CDK4/6 inhibitors not only induce tumour cell cycle arrest, but also promote anti-tumour immunity...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813414/a-randomized-synbiotic-trial-to-prevent-sepsis-among-infants-in-rural-india
#7
Pinaki Panigrahi, Sailajanandan Parida, Nimai C Nanda, Radhanath Satpathy, Lingaraj Pradhan, Dinesh S Chandel, Lorena Baccaglini, Arjit Mohapatra, Subhranshu S Mohapatra, Pravas R Misra, Rama Chaudhry, Hegang H Chen, Judith A Johnson, J Glenn Morris, Nigel Paneth, Ira H Gewolb
Sepsis in early infancy results in one million annual deaths worldwide, most of them in developing countries. No efficient means of prevention is currently available. Here we report on a randomized, double-blind, placebo-controlled trial of an oral synbiotic preparation (Lactobacillus plantarum plus fructooligosaccharide) in rural Indian newborns. We enrolled 4,556 infants that were at least 2,000 g at birth, at least 35 weeks of gestation, and with no signs of sepsis or other morbidity, and monitored them for 60 days...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813413/polylox-barcoding-reveals-haematopoietic-stem-cell-fates-realized-in-vivo
#8
Weike Pei, Thorsten B Feyerabend, Jens Rössler, Xi Wang, Daniel Postrach, Katrin Busch, Immanuel Rode, Kay Klapproth, Nikolaus Dietlein, Claudia Quedenau, Wei Chen, Sascha Sauer, Stephan Wolf, Thomas Höfer, Hans-Reimer Rodewald
Developmental deconvolution of complex organs and tissues at the level of individual cells remains challenging. Non-invasive genetic fate mapping has been widely used, but the low number of distinct fluorescent marker proteins limits its resolution. Much higher numbers of cell markers have been generated using viral integration sites, viral barcodes, and strategies based on transposons and CRISPR-Cas9 genome editing; however, temporal and tissue-specific induction of barcodes in situ has not been achieved. Here we report the development of an artificial DNA recombination locus (termed Polylox) that enables broadly applicable endogenous barcoding based on the Cre-loxP recombination system...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813412/the-primed-snare-complexin-synaptotagmin-complex-for-neuronal-exocytosis
#9
Qiangjun Zhou, Peng Zhou, Austin L Wang, Dick Wu, Minglei Zhao, Thomas C Südhof, Axel T Brunger
Synaptotagmin, complexin, and neuronal SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) proteins mediate evoked synchronous neurotransmitter release, but the molecular mechanisms mediating the cooperation between these molecules remain unclear. Here we determine crystal structures of the primed pre-fusion SNARE-complexin-synaptotagmin-1 complex. These structures reveal an unexpected tripartite interface between synaptotagmin-1 and both the SNARE complex and complexin. Simultaneously, a second synaptotagmin-1 molecule interacts with the other side of the SNARE complex via the previously identified primary interface...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813411/mammals-divert-endogenous-genotoxic-formaldehyde-into-one-carbon-metabolism
#10
Guillermo Burgos-Barragan, Niek Wit, Johannes Meiser, Felix A Dingler, Matthias Pietzke, Lee Mulderrig, Lucas B Pontel, Ivan V Rosado, Thomas F Brewer, Rebecca L Cordell, Paul S Monks, Christopher J Chang, Alexei Vazquez, Ketan J Patel
The folate-driven one-carbon (1C) cycle is a fundamental metabolic hub in cells that enables the synthesis of nucleotides and amino acids and epigenetic modifications. This cycle might also release formaldehyde, a potent protein and DNA crosslinking agent that organisms produce in substantial quantities. Here we show that supplementation with tetrahydrofolate, the essential cofactor of this cycle, and other oxidation-prone folate derivatives kills human, mouse and chicken cells that cannot detoxify formaldehyde or that lack DNA crosslink repair...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813410/identification-of-cmtm6-and-cmtm4-as-pd-l1-protein-regulators
#11
Riccardo Mezzadra, Chong Sun, Lucas T Jae, Raquel Gomez-Eerland, Evert de Vries, Wei Wu, Meike E W Logtenberg, Maarten Slagter, Elisa A Rozeman, Ingrid Hofland, Annegien Broeks, Hugo M Horlings, Lodewyk F A Wessels, Christian U Blank, Yanling Xiao, Albert J R Heck, Jannie Borst, Thijn R Brummelkamp, Ton N M Schumacher
The clinical benefit for patients with diverse types of metastatic cancers that has been observed upon blockade of the interaction between PD-1 and PD-L1 has highlighted the importance of this inhibitory axis in the suppression of tumour-specific T-cell responses. Notwithstanding the key role of PD-L1 expression by cells within the tumour micro-environment, our understanding of the regulation of the PD-L1 protein is limited. Here we identify, using a haploid genetic screen, CMTM6, a type-3 transmembrane protein of previously unknown function, as a regulator of the PD-L1 protein...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813409/the-rise-of-algae-in-cryogenian-oceans-and-the-emergence-of-animals
#12
Jochen J Brocks, Amber J M Jarrett, Eva Sirantoine, Christian Hallmann, Yosuke Hoshino, Tharika Liyanage
The transition from dominant bacterial to eukaryotic marine primary productivity was one of the most profound ecological revolutions in the Earth's history, reorganizing the distribution of carbon and nutrients in the water column and increasing energy flow to higher trophic levels. But the causes and geological timing of this transition, as well as possible links with rising atmospheric oxygen levels and the evolution of animals, remain obscure. Here we present a molecular fossil record of eukaryotic steroids demonstrating that bacteria were the only notable primary producers in the oceans before the Cryogenian period (720-635 million years ago)...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813408/biochemistry-a-toxin-that-fuels-metabolism
#13
Xiaojing Liu, Jason W Locasale
No abstract text is available yet for this article.
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813407/global-health-probiotic-prevents-infections-in-newborns
#14
Daniel J Tancredi
No abstract text is available yet for this article.
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28813416/large-turbulent-reservoirs-of-cold-molecular-gas-around-high-redshift-starburst-galaxies
#15
E Falgarone, M A Zwaan, B Godard, E Bergin, R J Ivison, P M Andreani, F Bournaud, R S Bussmann, D Elbaz, A Omont, I Oteo, F Walter
Starburst galaxies at the peak of cosmic star formation are among the most extreme star-forming engines in the Universe, producing stars over about 100 million years (ref. 2). The star-formation rates of these galaxies, which exceed 100 solar masses per year, require large reservoirs of cold molecular gas to be delivered to their cores, despite strong feedback from stars or active galactic nuclei. Consequently, starburst galaxies are ideal for studying the interplay between this feedback and the growth of a galaxy...
August 14, 2017: Nature
https://www.readbyqxmd.com/read/28792927/genome-scale-activation-screen-identifies-a-lncrna-locus-regulating-a-gene-neighbourhood
#16
Julia Joung, Jesse M Engreitz, Silvana Konermann, Omar O Abudayyeh, Vanessa K Verdine, Francois Aguet, Jonathan S Gootenberg, Neville E Sanjana, Jason B Wright, Charles P Fulco, Yuen-Yi Tseng, Charles H Yoon, Jesse S Boehm, Eric S Lander, Feng Zhang
Mammalian genomes contain thousands of loci that transcribe long noncoding RNAs (lncRNAs), some of which are known to carry out critical roles in diverse cellular processes through a variety of mechanisms. Although some lncRNA loci encode RNAs that act non-locally (in trans), there is emerging evidence that many lncRNA loci act locally (in cis) to regulate the expression of nearby genes-for example, through functions of the lncRNA promoter, transcription, or transcript itself. Despite their potentially important roles, it remains challenging to identify functional lncRNA loci and distinguish among these and other mechanisms...
August 11, 2017: Nature
https://www.readbyqxmd.com/read/28792939/mrna-3-uridylation-and-poly-a-tail-length-sculpt-the-mammalian-maternal-transcriptome
#17
Marcos Morgan, Christian Much, Monica DiGiacomo, Chiara Azzi, Ivayla Ivanova, Dimitrios M Vitsios, Jelena Pistolic, Paul Collier, Pedro N Moreira, Vladimir Benes, Anton J Enright, Dónal O'Carroll
A fundamental principle in biology is that the program for early development is established during oogenesis in the form of the maternal transcriptome. How the maternal transcriptome acquires the appropriate content and dosage of transcripts is not fully understood. Here we show that 3' terminal uridylation of mRNA mediated by TUT4 and TUT7 sculpts the mouse maternal transcriptome by eliminating transcripts during oocyte growth. Uridylation mediated by TUT4 and TUT7 is essential for both oocyte maturation and fertility...
August 9, 2017: Nature
https://www.readbyqxmd.com/read/28792938/m-6-a-mrna-methylation-controls-t-cell-homeostasis-by-targeting-the-il-7-stat5-socs-pathways
#18
Hua-Bing Li, Jiyu Tong, Shu Zhu, Pedro J Batista, Erin E Duffy, Jun Zhao, Will Bailis, Guangchao Cao, Lina Kroehling, Yuanyuan Chen, Geng Wang, James P Broughton, Y Grace Chen, Yuval Kluger, Matthew D Simon, Howard Y Chang, Zhinan Yin, Richard A Flavell
N(6)-methyladenosine (m(6)A) is the most common and abundant messenger RNA modification, modulated by 'writers', 'erasers' and 'readers' of this mark. In vitro data have shown that m(6)A influences all fundamental aspects of mRNA metabolism, mainly mRNA stability, to determine stem cell fates. However, its in vivo physiological function in mammals and adult mammalian cells is still unknown. Here we show that the deletion of m(6)A 'writer' protein METTL3 in mouse T cells disrupts T cell homeostasis and differentiation...
August 9, 2017: Nature
https://www.readbyqxmd.com/read/28792937/rewiring-the-taste-system
#19
Hojoon Lee, Lindsey J Macpherson, Camilo A Parada, Charles S Zuker, Nicholas J P Ryba
In mammals, taste buds typically contain 50-100 tightly packed taste-receptor cells (TRCs), representing all five basic qualities: sweet, sour, bitter, salty and umami. Notably, mature taste cells have life spans of only 5-20 days and, consequently, are constantly replenished by differentiation of taste stem cells. Given the importance of establishing and maintaining appropriate connectivity between TRCs and their partner ganglion neurons (that is, ensuring that a labelled line from sweet TRCs connects to sweet neurons, bitter TRCs to bitter neurons, sour to sour, and so on), we examined how new connections are specified to retain fidelity of signal transmission...
August 9, 2017: Nature
https://www.readbyqxmd.com/read/28792936/genetics-role-of-mutation-in-fly-wing-evolution
#20
James Cheverud
No abstract text is available yet for this article.
August 9, 2017: Nature
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