SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "L773:0092 8674 OR L773:1097 4172 ;lar1:(umu)"

Sökning: L773:0092 8674 OR L773:1097 4172 > Umeå universitet

  • Resultat 1-10 av 24
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Billker, Oliver, et al. (författare)
  • Calcium and a calcium-dependent protein kinase regulate gamete formation and mosquito transmission in a malaria parasite
  • 2004
  • Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 117:4, s. 503-514
  • Tidskriftsartikel (refereegranskat)abstract
    • Transmission of malaria parasites to mosquitoes is initiated by the obligatory sexual reproduction of the parasite within the mosquito bloodmeal. Differentiation of specialized transmission stages, the gametocytes, into male and female gametes is induced by a small mosquito molecule, xanthurenic acid (XA). Using a Plasmodium berghei strain expressing a bioluminescent calcium sensor, we show that XA triggers a rapid rise in cytosolic calcium specifically in gametocytes that is essential for their differentiation into gametes. A member of a family of plant-like calcium dependent protein kinases, CDPK4, is identified as the molecular switch that translates the XA-induced calcium signal into a cellular response by regulating cell cycle progression in the male gametocyte. CDPK4 is shown to be essential for the sexual reproduction and mosquito transmission of P. berghei. This study reveals an unexpected function for a plant-like signaling pathway in cell cycle regulation and life cycle progression of a malaria parasite.
  •  
2.
  • Åström, Stefan U, et al. (författare)
  • Rit1, a tRNA backbone-modifying enzyme that mediates initiator and elongator tRNA discrimination
  • 1994
  • Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 79:3, s. 535-546
  • Tidskriftsartikel (refereegranskat)abstract
    • Using a genetic screen in yeast aimed at identifying cellular factors involved in initiator and elongator methionine tRNA discrimination in the translational process, we have identified a mutation that abolish the requirement for elongator methionine tRNA. The gene affected, which we call the ribosylation of the initiator tRNA gene or RIT1, encodes a 2'-O-ribosyl phosphate transferase. This enzyme modifies exclusively the initiator tRNA in position 64 using 5'-phosphoribosyl-1'-pyrophosphate as the modification donor. As the initiator tRNA participates both in the initiation and elongation of translation in a rit1 strain, we conclude that the 2'-O-ribosyl phosphate modification discriminates the initiator tRNAs from the elongator tRNAs during protein synthesis. The modification enzyme was shown to recognize the stem-loop IV region that is unique in eukaryotic cytoplasmic initiator tRNAs.
  •  
3.
  • Boj, Sylvia F, et al. (författare)
  • Organoid models of human and mouse ductal pancreatic cancer
  • 2015
  • Ingår i: Cell. - : Cell press. - 0092-8674 .- 1097-4172. ; 160:1-2, s. 324-338
  • Tidskriftsartikel (refereegranskat)abstract
    • Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation, and exhibit ductal- and disease-stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy.
  •  
4.
  • Bushell, Ellen, et al. (författare)
  • Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes
  • 2017
  • Ingår i: Cell. - : Cell Press. - 0092-8674 .- 1097-4172. ; 170:2, s. 260-272.e1-e4
  • Tidskriftsartikel (refereegranskat)abstract
    • The genomes of malaria parasites contain many genes of unknown function. To assist drug development through the identification of essential genes and pathways, we have measured competitive growth rates in mice of 2,578 barcoded Plasmodium berghei knockout mutants, representing >50% of the genome, and created a phenotype database. At a single stage of its complex life cycle, P. berghei requires two-thirds of genes for optimal growth, the highest proportion reported from any organism and a probable consequence of functional optimization necessitated by genomic reductions during the evolution of parasitism. In contrast, extreme functional redundancy has evolved among expanded gene families operating at the parasite-host interface. The level of genetic redundancy in a single-celled organism may thus reflect the degree of environmental variation it experiences. In the case of Plasmodium parasites, this helps rationalize both the relative successes of drugs and the greater difficulty of making an effective vaccine.
  •  
5.
  • Chabes, Andrei, et al. (författare)
  • Survival of DNA damage in yeast directly depends on increased dNTP levels allowed by relaxed feedback inhibition of ribonucleotide reductase.
  • 2003
  • Ingår i: Cell. - 0092-8674 .- 1097-4172. ; 112:3, s. 391-401
  • Tidskriftsartikel (refereegranskat)abstract
    • In eukaryotes, DNA damage elicits a multifaceted response that includes cell cycle arrest, transcriptional activation of DNA repair genes, and, in multicellular organisms, apoptosis. We demonstrate that in Saccharomyces cerevisiae, DNA damage leads to a 6- to 8-fold increase in dNTP levels. This increase is conferred by an unusual, relaxed dATP feedback inhibition of ribonucleotide reductase (RNR). Complete elimination of dATP feedback inhibition by mutation of the allosteric activity site in RNR results in 1.6-2 times higher dNTP pools under normal growth conditions, and the pools increase an additional 11- to 17-fold during DNA damage. The increase in dNTP pools dramatically improves survival following DNA damage, but at the same time leads to higher mutation rates. We propose that increased survival and mutation rates result from more efficient translesion DNA synthesis at elevated dNTP concentrations.
  •  
6.
  • Chio, Iok In Christine, et al. (författare)
  • NRF2 Promotes Tumor Maintenance by Modulating mRNA Translation in Pancreatic Cancer
  • 2016
  • Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 166:4, s. 936-976
  • Tidskriftsartikel (refereegranskat)abstract
    • Pancreatic cancer is a deadly malignancy that lacks effective therapeutics. We previously reported that oncogenic Kras induced the redox master regulator Nfe2l2/Nrf2 to stimulate pancreatic and lung cancer initiation. Here, we show that NRF2 is necessary to maintain pancreatic cancer proliferation by regulating mRNA translation. Specifically, loss of NRF2 led to defects in autocrine epidermal growth factor receptor (EGFR) signaling and oxidation of specific translational regulatory proteins, resulting in impaired cap-dependent and cap-independent mRNA translation in pancreatic cancer cells. Combined targeting of the EGFR effector AKT and the glutathione antioxidant pathway mimicked Nrf2 ablation to potently inhibit pancreatic cancer ex vivo and in vivo, representing a promising synthetic lethal strategy for treating the disease.
  •  
7.
  • Cruz-Ramírez, Alfredo, et al. (författare)
  • A Bistable Circuit Involving SCARECROW-RETINOBLASTOMA Integrates Cues to Inform Asymmetric Stem Cell Division
  • 2012
  • Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 150:5, s. 1002-1015
  • Tidskriftsartikel (refereegranskat)abstract
    • In plants, where cells cannot migrate, asymmetric cell divisions (ACDs) must be confined to the appropriate spatial context. We investigate tissue-generating asymmetric divisions in a stem cell daughter within the Arabidopsis root. Spatial restriction of these divisions requires physical binding of the stem cell regulator SCARECROW (SCR) by the RETINOBLASTOM-RELATED (RBR) protein. In the stem cell niche, SCR activity is counteracted by phosphorylation of RBR through a cyclinD6;1-CDK complex. This cyclin is itself under transcriptional control of SCR and its partner SHORT ROOT (SHR), creating a robust bistable circuit with either high or low SHR-SCR complex activity. Auxin biases this circuit by promoting CYCD6;1 transcription. Mathematical modeling shows that ACDs are only switched on after integration of radial and longitudinal information, determined by SHR and auxin distribution, respectively. Coupling of cell-cycle progression to protein degradation resets the circuit, resulting in a "flip flop" that constrains asymmetric cell division to the stem cell region.
  •  
8.
  • Gardai, Shyra J, et al. (författare)
  • Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte
  • 2005
  • Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 123:2, s. 321-334
  • Tidskriftsartikel (refereegranskat)abstract
    • Apoptotic-cell removal is critical for development, tissue homeostasis, and resolution of inflammation. Although many candidate systems exist, only phosphatidylserine has been identified as a general recognition ligand on apoptotic cells. We demonstrate here that calreticulin acts as a second general recognition ligand by binding and activating LDL-receptor-related protein (LRP) on the engulfing cell. Since surface calreticulin is also found on viable cells, a mechanism preventing inadvertent uptake was sought. Disruption of interactions between CD47 (integrin-associated protein) on the target cell and SIRPalpha (SHPS-1), a heavily glycosylated transmembrane protein on the engulfing cell, permitted uptake of viable cells in a calreticulin/LRP-dependent manner. On apoptotic cells, CD47 was altered and/or lost and no longer activated SIRPalpha. These changes on the apoptotic cell create an environment where "don't eat me" signals are rendered inactive and "eat me" signals, including calreticulin and phosphatidylserine, congregate together and signal for removal.
  •  
9.
  • Gardino, Alexandra K, et al. (författare)
  • Transient Non-native Hydrogen Bonds Promote Activation of a Signaling Protein
  • 2009
  • Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 139:6, s. 1109-18
  • Tidskriftsartikel (refereegranskat)abstract
    • SummaryPhosphorylation is a common mechanism for activating proteins within signaling pathways. Yet, the molecular transitions between the inactive and active conformational states are poorly understood. Here we quantitatively characterize the free-energy landscape of activation of a signaling protein, nitrogen regulatory protein C (NtrC), by connecting functional protein dynamics of phosphorylation-dependent activation to protein folding and show that only a rarely populated, pre-existing active conformation is energetically stabilized by phosphorylation. Using nuclear magnetic resonance (NMR) dynamics, we test an atomic scale pathway for the complex conformational transition, inferred from molecular dynamics simulations (Lei et al., 2009). The data show that the loss of native stabilizing contacts during activation is compensated by non-native transient atomic interactions during the transition. The results unravel atomistic details of native-state protein energy landscapes by expanding the knowledge about ground states to transition landscapes.
  •  
10.
  • Hille, Frank, et al. (författare)
  • The Biology of CRISPR-Cas : Backward and Forward
  • 2018
  • Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 172:6, s. 1239-1259
  • Forskningsöversikt (refereegranskat)abstract
    • In bacteria and archaea, clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins constitute an adaptive immune system against phages and other foreign genetic elements. Here, we review the biology of the diverse CRISPR-Cas systems and the major progress achieved in recent years in understanding the underlying mechanisms of the three stages of CRISPR-Cas immunity: adaptation, crRNA biogenesis, and interference. The ecology and regulation of CRISPR-Cas in the context of phage infection, the roles of these systems beyond immunity, and the open questions that propel the field forward are also discussed.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 24
Typ av publikation
tidskriftsartikel (23)
forskningsöversikt (1)
Typ av innehåll
refereegranskat (23)
övrigt vetenskapligt/konstnärligt (1)
Författare/redaktör
Billker, Oliver (3)
Metcalf, Tom (2)
Thelander, Lars (2)
Li, Y. (1)
Kim, Y. J. (1)
Uhlin, Bernt Eric (1)
visa fler...
Olsen, Anja (1)
Overvad, Kim (1)
Boutron-Ruault, Mari ... (1)
Boeing, Heiner (1)
Trichopoulou, Antoni ... (1)
Masala, Giovanna (1)
Tumino, Rosario (1)
Khaw, Kay-Tee (1)
Häggström, Christel (1)
Wilson, John (1)
Miskolczi, Pal (1)
Bako, Laszlo (1)
Pojer, Florence (1)
Jass, Jana (1)
Melander, Olle (1)
Weiderpass, Elisabet ... (1)
Sandblad, Linda (1)
Anar, Burcu (1)
Ljung, Karin (1)
Harlid, Sophia, 1978 ... (1)
Tsilidis, Konstantin ... (1)
Severi, Gianluca (1)
Katzke, Verena (1)
Dahm, Christina C. (1)
Agudo, Antonio (1)
Karakatsani, Anna (1)
Martimianaki, Georgi ... (1)
Panico, Salvatore (1)
Bueno-de-Mesquita, B ... (1)
Freisling, Heinz (1)
Sieri, Sabina (1)
Ricceri, Fulvio (1)
van Gils, Carla H. (1)
Trichopoulos, Dimitr ... (1)
Johansson, Mattias (1)
Tjonneland, Anne (1)
Wareham, Nicholas J. (1)
Björklund, Stefan (1)
Sandberg, Göran (1)
Oscarsson, Jan (1)
Öst, Anita (1)
Wai, Sun Nyunt (1)
Lee, Eun Jung (1)
Holmberg, Dan (1)
visa färre...
Lärosäte
Linköpings universitet (2)
Uppsala universitet (1)
Karolinska Institutet (1)
Sveriges Lantbruksuniversitet (1)
Språk
Engelska (24)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (8)
Naturvetenskap (6)
Lantbruksvetenskap (1)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy