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  • Stoichiometry of Rtt109 complexes with Vps75 and histones H3-H4.
    Life Sci. Alliance (IF 2.622) Pub Date : 2020-09-10
    Noushin Akhavantabib; Daniel D Krzizike; Victoria Neumann; Sheena D'Arcy

    Histone acetylation is one of many posttranslational modifications that affect nucleosome accessibility. Vps75 is a histone chaperone that stimulates Rtt109 acetyltransferase activity toward histones H3-H4 in yeast. In this study, we use sedimentation velocity and light scattering to characterize various Vps75-Rtt109 complexes, both with and without H3-H4. These complexes were previously ill-defined

    更新日期:2020-09-13
  • multicrispr: gRNA design for prime editing and parallel targeting of thousands of targets.
    Life Sci. Alliance (IF 2.622) Pub Date : 2020-09-09
    Aditya M Bhagwat; Johannes Graumann; Rene Wiegandt; Mette Bentsen; Jordan Welker; Carsten Kuenne; Jens Preussner; Thomas Braun; Mario Looso

    Targeting the coding genome to introduce nucleotide deletions/insertions via the CRISPR/Cas9 technology has become a standard procedure. It has quickly spawned a multitude of methods such as prime editing, APEX proximity labeling, or homology directed repair, for which supporting bioinformatics tools are, however, lagging behind. New CRISPR/Cas9 applications often require specific gRNA design functionality

    更新日期:2020-09-13
  • MicroRNA regulation of murine trophoblast stem cell self-renewal and differentiation.
    Life Sci. Alliance (IF 2.622) Pub Date : 2020-09-09
    Sarbani Saha; Rupasri Ain

    Proper placentation is fundamental to successful pregnancy. Placenta arises from differentiation of trophoblast stem (TS) cells during development. Despite being recognized as the counterpart of ES cells in placental development, the role of regulatory miRNAs in TS cell differentiation remains inadequately explored. Here, we have identified complete repertoire of microRNAs present in mouse trophoblast

    更新日期:2020-09-13
  • Multiplexed chemogenetics in astrocytes and motoneurons restore blood-spinal cord barrier in ALS.
    Life Sci. Alliance (IF 2.622) Pub Date : 2020-09-08
    Najwa Ouali Alami; Linyun Tang; Diana Wiesner; Barbara Commisso; David Bayer; Jochen Weishaupt; Luc Dupuis; Phillip Wong; Bernd Baumann; Thomas Wirth; Tobias M Boeckers; Deniz Yilmazer-Hanke; Albert Ludolph; Francesco Roselli

    Blood-spinal cord barrier (BSCB) disruption is thought to contribute to motoneuron (MN) loss in amyotrophic lateral sclerosis (ALS). It is currently unclear whether impairment of the BSCB is the cause or consequence of MN dysfunction and whether its restoration may be directly beneficial. We revealed that SOD1 G93A , FUSΔNLS , TDP43 G298S , and Tbk1 +/- ALS mouse models commonly shared alterations

    更新日期:2020-09-11
  • An atlas of human proximal epididymis reveals cell-specific functions and distinct roles for CFTR.
    Life Sci. Alliance (IF 2.622) Pub Date : 2020-08-27
    Shih-Hsing Leir,Shiyi Yin,Jenny L Kerschner,Wilmel Cosme,Ann Harris

    Spermatozoa released from the testis are unable to fertilize an egg without a coordinated process of maturation in the lumen of the epididymis. Relatively little is known about the molecular events that integrate this critical progression along the male genital ducts in man. Here, we use single cell RNA-sequencing to construct an atlas of the human proximal epididymis. We find that the CFTR, which

    更新日期:2020-08-30
  • A dichotomy of gene regulatory associations during the activated B-cell to plasmablast transition.
    Life Sci. Alliance (IF 2.622) Pub Date : 2020-08-25
    Mario Cocco,Matthew A Care,Amel Saadi,Muna Al-Maskari,Gina Doody,Reuben Tooze

    The activated B-cell (ABC) to plasmablast transition encompasses the cusp of antibody-secreting cell (ASC) differentiation. We explore this transition with integrated analysis in human cells, focusing on changes that follow removal from CD40-mediated signals. Within hours of input signal loss, cell growth programs shift toward enhanced proliferation, accompanied by ER-stress response, and up-regulation

    更新日期:2020-08-29
  • Biochemical and functional characterization of a meiosis-specific Pch2/ORC AAA+ assembly.
    Life Sci. Alliance (IF 2.622) Pub Date : 2020-08-21
    María Ascensión Villar-Fernández,Richard Cardoso da Silva,Magdalena Firlej,Dongqing Pan,Elisabeth Weir,Annika Sarembe,Vivek B Raina,Tanja Bange,John R Weir,Gerben Vader

    Pch2 is a meiosis-specific AAA+ protein that controls several important chromosomal processes. We previously demonstrated that Orc1, a subunit of the ORC, functionally interacts with budding yeast Pch2. The ORC (Orc1-6) AAA+ complex loads the AAA+ MCM helicase to origins of replication, but whether and how ORC collaborates with Pch2 remains unclear. Here, we show that a Pch2 hexamer directly associates

    更新日期:2020-08-24
  • Plasma membrane phosphatidylinositol (4,5)-bisphosphate promotes Weibel-Palade body exocytosis.
    Life Sci. Alliance (IF 2.622) Pub Date : 2020-08-21
    Tu Thi Ngoc Nguyen,Sophia N Koerdt,Volker Gerke

    Weibel-Palade bodies (WPB) are specialized secretory organelles of endothelial cells that control vascular hemostasis by regulated, Ca2+-dependent exocytosis of the coagulation-promoting von-Willebrand factor. Some proteins of the WPB docking and fusion machinery have been identified but a role of membrane lipids in regulated WPB exocytosis has so far remained elusive. We show here that the plasma

    更新日期:2020-08-24
  • PGE2 accounts for bidirectional changes in alveolar macrophage self-renewal with aging and smoking.
    Life Sci. Alliance (IF 2.622) Pub Date : 2020-08-20
    Loka R Penke,Jennifer M Speth,Christina Draijer,Zbigniew Zaslona,Judy Chen,Peter Mancuso,Christine M Freeman,Jeffrey L Curtis,Daniel R Goldstein,Marc Peters-Golden

    Alveolar macrophages (AMs) are resident immune cells of the lung that are critical for host defense. AMs are capable of proliferative renewal, yet their numbers are known to decrease with aging and increase with cigarette smoking. The mechanism by which AM proliferation is physiologically restrained, and whether dysregulation of this brake contributes to altered AM numbers in pathologic circumstances

    更新日期:2020-08-24
  • The RECQL helicase prevents replication fork collapse during replication stress.
    Life Sci. Alliance (IF 2.622) Pub Date : 2020-08-20
    Bente Benedict,Marit Ae van Bueren,Frank Pa van Gemert,Cor Lieftink,Sergi Guerrero Llobet,Marcel Atm van Vugt,Roderick L Beijersbergen,Hein Te Riele

    Most tumors lack the G1/S phase checkpoint and are insensitive to antigrowth signals. Loss of G1/S control can severely perturb DNA replication as revealed by slow replication fork progression and frequent replication fork stalling. Cancer cells may thus rely on specific pathways that mitigate the deleterious consequences of replication stress. To identify vulnerabilities of cells suffering from replication

    更新日期:2020-08-24
  • DDX5 promotes oncogene C3 and FABP1 expressions and drives intestinal inflammation and tumorigenesis.
    Life Sci. Alliance (IF 2.622) Pub Date : 2020-08-18
    Nazia Abbasi,Tianyun Long,Yuxin Li,Brian A Yee,Benjamin S Cho,Juan E Hernandez,Evelyn Ma,Parth R Patel,Debashis Sahoo,Ibrahim M Sayed,Nissi Varki,Soumita Das,Pradipta Ghosh,Gene W Yeo,Wendy Jia Men Huang

    Tumorigenesis in different segments of the intestinal tract involves tissue-specific oncogenic drivers. In the colon, complement component 3 (C3) activation is a major contributor to inflammation and malignancies. By contrast, tumorigenesis in the small intestine involves fatty acid-binding protein 1 (FABP1). However, little is known of the upstream mechanisms driving their expressions in different

    更新日期:2020-08-24
  • Thymosin α1 protects from CTLA-4 intestinal immunopathology.
    Life Sci. Alliance (IF 2.622) Pub Date : 2020-08-14
    Giorgia Renga,Marina M Bellet,Marilena Pariano,Marco Gargaro,Claudia Stincardini,Fiorella D'Onofrio,Paolo Mosci,Stefano Brancorsini,Andrea Bartoli,Allan L Goldstein,Enrico Garaci,Luigina Romani,Claudio Costantini

    The advent of immune checkpoint inhibitors has represented a major boost in cancer therapy, but safety concerns are increasingly being recognized. Indeed, although beneficial at the tumor site, unlocking a safeguard mechanism of the immune response may trigger autoimmune-like effects at the periphery, thus making the safety of immune checkpoint inhibitors a research priority. Herein, we demonstrate

    更新日期:2020-08-24
  • Robust repression of tRNA gene transcription during stress requires protein arginine methylation.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-06-03
    Richoo B Davis,Neah Likhite,Christopher A Jackson,Tao Liu,Michael C Yu

    Protein arginine methylation is an important means by which protein function can be regulated. In the budding yeast, this modification is catalyzed by the major protein arginine methyltransferase Hmt1. Here, we provide evidence that the Hmt1-mediated methylation of Rpc31, a subunit of RNA polymerase III, plays context-dependent roles in tRNA gene transcription: under conditions optimal for growth,

    更新日期:2020-08-21
  • Molecular characterization of Chlamydomonas reinhardtii telomeres and telomerase mutants.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-06-03
    Stephan Eberhard,Sona Valuchova,Julie Ravat,Jaroslav Fulneček,Pascale Jolivet,Sandrine Bujaldon,Stéphane D Lemaire,Francis-André Wollman,Maria Teresa Teixeira,Karel Riha,Zhou Xu

    Telomeres are repeated sequences found at the end of the linear chromosomes of most eukaryotes and are required for chromosome integrity. Expression of the reverse-transcriptase telomerase allows for extension of telomeric repeats to counteract natural telomere shortening. Although Chlamydomonas reinhardtii, a photosynthetic unicellular green alga, is widely used as a model organism in photosynthesis

    更新日期:2020-08-21
  • The m6A pathway protects the transcriptome integrity by restricting RNA chimera formation in plants.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-05-29
    Dominique Pontier,Claire Picart,Moaine El Baidouri,François Roudier,Tao Xu,Sylvie Lahmy,Christel Llauro,Jacinthe Azevedo,Michèle Laudié,Aurore Attina,Christophe Hirtz,Marie-Christine Carpentier,Lisha Shen,Thierry Lagrange

    Global, segmental, and gene duplication-related processes are driving genome size and complexity in plants. Despite their evolutionary potentials, those processes can also have adverse effects on genome regulation, thus implying the existence of specialized corrective mechanisms. Here, we report that an N6-methyladenosine (m6A)-assisted polyadenylation (m-ASP) pathway ensures transcriptome integrity

    更新日期:2020-08-21
  • PKAc is not required for the preerythrocytic stages of Plasmodium berghei.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-05-29
    Hadi Hasan Choudhary,Roshni Gupta,Satish Mishra

    Plasmodium sporozoites invade hepatocytes to initiate infection in the mammalian host. In the infected hepatocytes, sporozoites undergo rapid expansion and differentiation, resulting in the formation and release of thousands of invasive merozoites into the bloodstream. Both sporozoites and merozoites invade their host cells by activation of a signaling cascade followed by discharge of micronemal content

    更新日期:2020-08-21
  • The S. Typhi effector StoD is an E3/E4 ubiquitin ligase which binds K48- and K63-linked diubiquitin.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-05-29
    Melanie A McDowell,Alexander Mp Byrne,Elli Mylona,Rebecca Johnson,Agnes Sagfors,Valerie F Crepin,Susan Lea,Gad Frankel

    Salmonella enterica (e.g., serovars Typhi and Typhimurium) relies on translocation of effectors via type III secretion systems (T3SS). Specialization of typhoidal serovars is thought to be mediated via pseudogenesis. Here, we show that the Salmonella Typhi STY1076/t1865 protein, named StoD, a homologue of the enteropathogenic Escherichia coli/enterohemorrhagic E. coli/Citrobacter rodentium NleG, is

    更新日期:2020-08-21
  • Tumor-intrinsic response to IFNγ shapes the tumor microenvironment and anti-PD-1 response in NSCLC.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-05-27
    Bonnie L Bullock,Abigail K Kimball,Joanna M Poczobutt,Alexander J Neuwelt,Howard Y Li,Amber M Johnson,Jeff W Kwak,Emily K Kleczko,Rachael E Kaspar,Emily K Wagner,Katharina Hopp,Erin L Schenk,Mary Cm Weiser-Evans,Eric T Clambey,Raphael A Nemenoff

    Targeting PD-1/PD-L1 is only effective in ∼20% of lung cancer patients, but determinants of this response are poorly defined. We previously observed differential responses of two murine K-Ras-mutant lung cancer cell lines to anti-PD-1 therapy: CMT167 tumors were eliminated, whereas Lewis Lung Carcinoma (LLC) tumors were resistant. The goal of this study was to define mechanism(s) mediating this difference

    更新日期:2020-08-21
  • Molecular characterization of CHAD domains as inorganic polyphosphate-binding modules.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-05-27
    Laura Lorenzo-Orts,Ulrich Hohmann,Jinsheng Zhu,Michael Hothorn

    Inorganic polyphosphates (polyPs) are linear polymers of orthophosphate units linked by phosphoanhydride bonds. Here, we report that bacterial, archaeal, and eukaryotic conserved histidine α-helical (CHAD) domains are specific polyP-binding modules. Crystal structures reveal that CHAD domains are formed by two four-helix bundles, giving rise to a central pore surrounded by conserved basic surface patches

    更新日期:2020-08-21
  • Rate of brain aging and APOE ε4 are synergistic risk factors for Alzheimer's disease.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-05-27
    Christin A Glorioso,Andreas R Pfenning,Sam S Lee,David A Bennett,Etienne L Sibille,Manolis Kellis,Leonard P Guarente

    Advanced age and the APOE ε4 allele are the two biggest risk factors for Alzheimer's disease (AD) and declining cognitive function. We describe a universal gauge to measure molecular brain age using transcriptome analysis of four human postmortem cohorts (n = 673, ages 25-97) free of neurological disease. In a fifth cohort of older subjects with or without neurological disease (n = 438, ages 67-108)

    更新日期:2020-08-21
  • The hypoxia-response pathway modulates RAS/MAPK-mediated cell fate decisions in Caenorhabditis elegans.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-05-24
    Sabrina Maxeiner,Judith Grolleman,Tobias Schmid,Jan Kammenga,Alex Hajnal

    Animals need to adjust many cellular functions to oxygen availability to adapt to changing environmental conditions. We have used the nematode Caenorhabditis elegans as a model to investigate how variations in oxygen concentrations affect cell fate specification during development. Here, we show that several processes controlled by the conserved RTK/RAS/MAPK pathway are sensitive to changes in the

    更新日期:2020-08-21
  • Loss of PGC-1α in RPE induces mesenchymal transition and promotes retinal degeneration.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-05-17
    Mariana Aparecida Brunini Rosales,Daisy Y Shu,Jared Iacovelli,Magali Saint-Geniez

    The retinal pigment epithelium (RPE) supports visual processing and photoreceptor homeostasis via energetically demanding cellular functions. Here, we describe the consequences of repressing peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α), a master regulator of mitochondrial function and biogenesis, on RPE epithelial integrity. The sustained silencing of PGC-1α in differentiating

    更新日期:2020-08-21
  • An N-terminal-truncated isoform of FAM134B (FAM134B-2) regulates starvation-induced hepatic selective ER-phagy.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-05-17
    Shohei Kohno,Yuji Shiozaki,Audrey L Keenan,Shinobu Miyazaki-Anzai,Makoto Miyazaki

    Autophagy is a conserved system that adapts to nutrient starvation, after which proteins and organelles are degraded to recycle amino acids in response to starvation. Recently, the ER was added to the list of targets of autophagic degradation. Autophagic degradation pathways of bulk ER and the specific proteins sorted through the ER are considered key mechanisms in maintaining ER homeostasis. Four

    更新日期:2020-08-21
  • MicroRNA-155 is essential for the optimal proliferation and survival of plasmablast B cells.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-05-16
    Giuseppina Arbore,Tom Henley,Laura Biggins,Simon Andrews,Elena Vigorito,Martin Turner,Rebecca Leyland

    A fast antibody response can be critical to contain rapidly dividing pathogens. This can be achieved by the expansion of antigen-specific B cells in response to T-cell help followed by differentiation into plasmablasts. MicroRNA-155 (miR-155) is required for optimal T-cell-dependent extrafollicular responses via regulation of PU.1, although the cellular processes underlying this defect are largely

    更新日期:2020-08-21
  • Chitinase 1 regulates pulmonary fibrosis by modulating TGF-β/SMAD7 pathway via TGFBRAP1 and FOXO3.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-05-13
    Chang-Min Lee,Chuan-Hua He,Jin Wook Park,Jae Hyun Lee,Suchita Kamle,Bing Ma,Bedia Akosman,Roberto Cotez,Emily Chen,Yang Zhou,Erica L Herzog,Changwan Ryu,Xueyan Peng,Ivan O Rosas,Sergio Poli,Carol Feghali Bostwick,Augustine M Choi,Jack A Elias,Chun Geun Lee

    TGF-β1 is a critical mediator of tissue fibrosis in health and disease whose effects are augmented by chitinase 1 (CHIT1). However, the mechanisms that CHIT1 uses to regulate TGF-β1-mediated fibrotic responses have not been defined. Here, we demonstrate that CHIT1 enhances TGF-β1-stimulated fibrotic cellular and tissue responses and TGF-β1 signaling. Importantly, we also demonstrate that these effects

    更新日期:2020-08-21
  • Cellular response upon proliferation in the presence of an active mitotic checkpoint.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-05-08
    Andrea Corno,Elena Chiroli,Fridolin Gross,Claudio Vernieri,Vittoria Matafora,Stefano Maffini,Marco Cosentino Lagomarsino,Angela Bachi,Andrea Ciliberto

    Eukaryotic cells treated with microtubule-targeting agents activate the spindle assembly checkpoint to arrest in mitosis and prevent chromosome mis-segregation. A fraction of mitotically arrested cells overcomes the block and proliferates even under persistent checkpoint-activating conditions. Here, we asked what allows proliferation in such unfavourable conditions. We report that yeast cells are delayed

    更新日期:2020-08-21
  • Development of a new monoclonal antibody specific to mouse Vγ6 chain.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-05-07
    Shinya Hatano,Xin Tun,Naoto Noguchi,Dan Yue,Hisakata Yamada,Xun Sun,Mitsuru Matsumoto,Yasunobu Yoshikai

    There are seven Vγ gene segments in the TCR γ chain loci of mice. We developed monoclonal antibodies (mAbs) specific to the Vγ6 chain (Heilig & Tonegawa nomenclature). By immunizing Vγ4/6 KO mice with complementarity-determining region peptides in Vγ6 chains, we generated three hybridomas. These hybridomas produced mAbs capable of cell surface staining of Vγ6/Vδ1 gene-transfected T-cell line lacking

    更新日期:2020-08-21
  • The early-acting glycosome biogenic protein Pex3 is essential for trypanosome viability.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-07-24
    Hiren Banerjee,Barbara Knoblach,Richard A Rachubinski

    Trypanosomatid parasites are infectious agents for diseases such as African sleeping sickness, Chagas disease, and leishmaniasis that threaten millions of people, mostly in the emerging world. Trypanosomes compartmentalize glycolytic enzymes to an organelle called the glycosome, a specialized peroxisome. Functionally intact glycosomes are essential for trypanosomatid viability, making glycosomal proteins

    更新日期:2020-08-21
  • Stromal fibroblasts induce metastatic tumor cell clusters via epithelial-mesenchymal plasticity.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-07-22
    Yuko Matsumura,Yasuhiko Ito,Yoshihiro Mezawa,Kaidiliayi Sulidan,Yataro Daigo,Toru Hiraga,Kaoru Mogushi,Nadila Wali,Hiromu Suzuki,Takumi Itoh,Yohei Miyagi,Tomoyuki Yokose,Satoru Shimizu,Atsushi Takano,Yasuhisa Terao,Harumi Saeki,Masayuki Ozawa,Masaaki Abe,Satoru Takeda,Ko Okumura,Sonoko Habu,Okio Hino,Kazuyoshi Takeda,Michiaki Hamada,Akira Orimo

    Emerging evidence supports the hypothesis that multicellular tumor clusters invade and seed metastasis. However, whether tumor-associated stroma induces epithelial-mesenchymal plasticity in tumor cell clusters, to promote invasion and metastasis, remains unknown. We demonstrate herein that carcinoma-associated fibroblasts (CAFs) frequently present in tumor stroma drive the formation of tumor cell clusters

    更新日期:2020-08-21
  • TAF-ChIP: an ultra-low input approach for genome-wide chromatin immunoprecipitation assay.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-07-22
    Junaid Akhtar,Piyush More,Steffen Albrecht,Federico Marini,Waldemar Kaiser,Apurva Kulkarni,Leszek Wojnowski,Jean-Fred Fontaine,Miguel A Andrade-Navarro,Marion Silies,Christian Berger

    Chromatin immunoprecipitation (ChIP) followed by next generation sequencing (ChIP-Seq) is a powerful technique to study transcriptional regulation. However, the requirement of millions of cells to generate results with high signal-to-noise ratio precludes it in the study of small cell populations. Here, we present a tagmentation-assisted fragmentation ChIP (TAF-ChIP) and sequencing method to generate

    更新日期:2020-08-21
  • The miRNA bantam regulates growth and tumorigenesis by repressing the cell cycle regulator tribbles.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-07-22
    Stephan U Gerlach,Moritz Sander,Shilin Song,Héctor Herranz

    One of the fundamental issues in biology is understanding how organ size is controlled. Tissue growth has to be carefully regulated to generate well-functioning organs, and defects in growth control can result in tumor formation. The Hippo signaling pathway is a universal growth regulator and has been implicated in cancer. In Drosophila, the Hippo pathway acts through the miRNA bantam to regulate cell

    更新日期:2020-08-21
  • PRDM9 forms a trimer by interactions within the zinc finger array.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-07-15
    Theresa Schwarz,Yasmin Striedner,Andreas Horner,Karin Haase,Jasmin Kemptner,Nicole Zeppezauer,Philipp Hermann,Irene Tiemann-Boege

    PRDM9 is a trans-acting factor directing meiotic recombination to specific DNA-binding sites by its zinc finger (ZnF) array. It was suggested that PRDM9 is a multimer; however, we do not know the stoichiometry or the components inducing PRDM9 multimerization. In this work, we used in vitro binding studies and characterized with electrophoretic mobility shift assays, mass spectrometry, and fluorescence

    更新日期:2020-08-21
  • Membrane curvature sensing of the lipid-anchored K-Ras small GTPase.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-07-11
    Hong Liang,Huanwen Mu,Frantz Jean-Francois,Bindu Lakshman,Suparna Sarkar-Banerjee,Yinyin Zhuang,Yongpeng Zeng,Weibo Gao,Ana Maria Zaske,Dwight V Nissley,Alemayehu A Gorfe,Wenting Zhao,Yong Zhou

    Plasma membrane (PM) curvature defines cell shape and intracellular organelle morphologies and is a fundamental cell property. Growth/proliferation is more stimulated in flatter cells than the same cells in elongated shapes. PM-anchored K-Ras small GTPase regulates cell growth/proliferation and plays key roles in cancer. The lipid-anchored K-Ras form nanoclusters selectively enriched with specific

    更新日期:2020-08-21
  • Human DNA polymerase delta requires an iron-sulfur cluster for high-fidelity DNA synthesis.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-07-05
    Stanislaw K Jozwiakowski,Sandra Kummer,Kerstin Gari

    Replication of eukaryotic genomes relies on the family B DNA polymerases Pol α, Pol δ, and Pol ε. All of these enzymes coordinate an iron-sulfur (FeS) cluster, but the function of this cofactor has remained largely unclear. Here, we show that the FeS cluster in the catalytic subunit of human Pol δ is coordinated by four invariant cysteines of the C-terminal CysB motif. FeS cluster loss causes a partial

    更新日期:2020-08-21
  • Systematic identification of recognition motifs for the hub protein LC8.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-07-02
    Nathan Jespersen,Aidan Estelle,Nathan Waugh,Norman E Davey,Cecilia Blikstad,York-Christoph Ammon,Anna Akhmanova,Ylva Ivarsson,David A Hendrix,Elisar Barbar

    Hub proteins participate in cellular regulation by dynamic binding of multiple proteins within interaction networks. The hub protein LC8 reversibly interacts with more than 100 partners through a flexible pocket at its dimer interface. To explore the diversity of the LC8 partner pool, we screened for LC8 binding partners using a proteomic phage display library composed of peptides from the human proteome

    更新日期:2020-08-21
  • De novo prediction of cell-type complexity in single-cell RNA-seq and tumor microenvironments.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-07-02
    Jun Woo,Boris J Winterhoff,Timothy K Starr,Constantin Aliferis,Jinhua Wang

    Recent single-cell transcriptomic studies revealed new insights into cell-type heterogeneities in cellular microenvironments unavailable from bulk studies. A significant drawback of currently available algorithms is the need to use empirical parameters or rely on indirect quality measures to estimate the degree of complexity, i.e., the number of subgroups present in the sample. We fill this gap with

    更新日期:2020-08-21
  • Fibril-induced glutamine-/asparagine-rich prions recruit stress granule proteins in mammalian cells.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-07-02
    Katrin Riemschoss,Verena Arndt,Benedetta Bolognesi,Philipp von Eisenhart-Rothe,Shu Liu,Oleksandra Buravlova,Yvonne Duernberger,Lydia Paulsen,Annika Hornberger,André Hossinger,Nieves Lorenzo-Gotor,Sebastian Hogl,Stephan A Müller,Gian Tartaglia,Stefan F Lichtenthaler,Ina M Vorberg

    Prions of lower eukaryotes are self-templating protein aggregates that replicate by converting homotypic proteins into stable, tightly packed beta-sheet-rich protein assemblies. Propagation is mediated by prion domains, low-complexity regions enriched in polar and devoid of charged amino acid residues. In mammals, compositionally similar domains modulate the assembly of dynamic stress granules (SGs)

    更新日期:2020-08-21
  • The cancer cell proteome and transcriptome predicts sensitivity to targeted and cytotoxic drugs.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-06-28
    Mattias Rydenfelt,Matthew Wongchenko,Bertram Klinger,Yibing Yan,Nils Blüthgen

    Tumors of different molecular subtypes can show strongly deviating responses to drug treatment, making stratification of patients based on molecular markers an important part of cancer therapy. Pharmacogenomic studies have led to the discovery of selected genomic markers (e.g., BRAFV600E), whereas transcriptomic and proteomic markers so far have been largely absent in clinical use, thus constituting

    更新日期:2020-08-21
  • Dietary restriction induces posttranscriptional regulation of longevity genes.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-06-28
    Jarod A Rollins,Dan Shaffer,Santina S Snow,Pankaj Kapahi,Aric N Rogers

    Dietary restriction (DR) increases life span through adaptive changes in gene expression. To understand more about these changes, we analyzed the transcriptome and translatome of Caenorhabditis elegans subjected to DR. Transcription of muscle regulatory and structural genes increased, whereas increased expression of amino acid metabolism and neuropeptide signaling genes was controlled at the level

    更新日期:2020-08-21
  • Human organotypic brain slice culture: a novel framework for environmental research in neuro-oncology.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-06-27
    Vidhya M Ravi,Kevin Joseph,Julian Wurm,Simon Behringer,Nicklas Garrelfs,Paolo d'Errico,Yashar Naseri,Pamela Franco,Melanie Meyer-Luehmann,Roman Sankowski,Mukesch Johannes Shah,Irina Mader,Daniel Delev,Marie Follo,Jürgen Beck,Oliver Schnell,Ulrich G Hofmann,Dieter Henrik Heiland

    When it comes to the human brain, models that closely mimic in vivo conditions are lacking. Living neuronal tissue is the closest representation of the in vivo human brain outside of a living person. Here, we present a method that can be used to maintain therapeutically resected healthy neuronal tissue for prolonged periods without any discernible changes in tissue vitality, evidenced by immunohistochemistry

    更新日期:2020-08-21
  • Inhibition of host NOX1 blocks tumor growth and enhances checkpoint inhibitor-based immunotherapy.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-06-27
    Jimmy Stalin,Sarah Garrido-Urbani,Freddy Heitz,Cédric Szyndralewiez,Stephane Jemelin,Oriana Coquoz,Curzio Ruegg,Beat A Imhof

    NADPH oxidases catalyze the production of reactive oxygen species and are involved in physio/pathological processes. NOX1 is highly expressed in colon cancer and promotes tumor growth. To investigate the efficacy of NOX1 inhibition as an anticancer strategy, tumors were grown in immunocompetent, immunodeficient, or NOX1-deficient mice and treated with the novel NOX1-selective inhibitor GKT771. GKT771

    更新日期:2020-08-21
  • Assembly mechanisms of the bacterial cytoskeletal protein FilP.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-06-26
    Ala Javadi,Niklas Söderholm,Annelie Olofsson,Klas Flärdh,Linda Sandblad

    Despite low-sequence homology, the intermediate filament (IF)-like protein FilP from Streptomyces coelicolor displays structural and biochemical similarities to the metazoan nuclear IF lamin. FilP, like IF proteins, is composed of central coiled-coil domains interrupted by short linkers and flanked by head and tail domains. FilP polymerizes into repetitive filament bundles with paracrystalline properties

    更新日期:2020-08-21
  • Tamoxifen blocks retrograde trafficking of Shiga toxin 1 and 2 and protects against lethal toxicosis.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-06-26
    Andrey S Selyunin,Steven Hutchens,Stanton F McHardy,Somshuvra Mukhopadhyay

    Shiga toxin 1 (STx1) and 2 (STx2), produced by Shiga toxin-producing Escherichia coli, cause lethal untreatable disease. The toxins invade cells via retrograde trafficking. Direct early endosome-to-Golgi transport allows the toxins to evade degradative late endosomes. Blocking toxin trafficking, particularly at the early endosome-to-Golgi step, is appealing, but transport mechanisms of the more disease-relevant

    更新日期:2020-08-21
  • Fibro-adipogenic progenitors of dystrophic mice are insensitive to NOTCH regulation of adipogenesis.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-06-25
    Milica Marinkovic,Claudia Fuoco,Francesca Sacco,Andrea Cerquone Perpetuini,Giulio Giuliani,Elisa Micarelli,Theodora Pavlidou,Lucia Lisa Petrilli,Alessio Reggio,Federica Riccio,Filomena Spada,Simone Vumbaca,Alessandro Zuccotti,Luisa Castagnoli,Matthias Mann,Cesare Gargioli,Gianni Cesareni

    Fibro-adipogenic progenitors (FAPs) promote satellite cell differentiation in adult skeletal muscle regeneration. However, in pathological conditions, FAPs are responsible for fibrosis and fatty infiltrations. Here we show that the NOTCH pathway negatively modulates FAP differentiation both in vitro and in vivo. However, FAPs isolated from young dystrophin-deficient mdx mice are insensitive to this

    更新日期:2020-08-21
  • An unusual and vital protein with guanylate cyclase and P4-ATPase domains in a pathogenic protist.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-06-24
    Özlem Günay-Esiyok,Ulrike Scheib,Matthias Noll,Nishith Gupta

    cGMP signaling is one of the master regulators of diverse functions in eukaryotes; however, its architecture and functioning in protozoans remain poorly understood. Herein, we report an exclusive guanylate cyclase coupled with N-terminal P4-ATPase in a common parasitic protist, Toxoplasma gondii This bulky protein (477-kD), termed TgATPaseP-GC to fairly reflect its envisaged multifunctionality, localizes

    更新日期:2020-08-21
  • Expression of a constitutively active human STING mutant in hematopoietic cells produces an Ifnar1-dependent vasculopathy in mice.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-06-20
    Gary R Martin,Kimiora Henare,Carolina Salazar,Teresa Scheidl-Yee,Laura J Eggen,Pankaj P Tailor,Jung Hwan Kim,John Podstawka,Marvin J Fritzler,Margaret M Kelly,Bryan G Yipp,Frank R Jirik

    STING-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disorder characterized by blood vessel occlusions, acral necrosis, myositis, rashes, and pulmonary inflammation that are the result of activating mutations in the STimulator of Interferon Genes (STING). We generated a transgenic line that recapitulates many of the phenotypic aspects of SAVI by targeting the expression

    更新日期:2020-08-21
  • Evidence for vesicle-mediated antigen export by the human pathogen Babesia microti.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-06-13
    Jose Thekkiniath,Nicole Kilian,Lauren Lawres,Meital A Gewirtz,Morven M Graham,Xinran Liu,Michel Ledizet,Choukri Ben Mamoun

    The apicomplexan parasite Babesia microti is the primary agent of human babesiosis, a malaria-like illness and potentially fatal tick-borne disease. Unlike its close relatives, the agents of human malaria, B. microti develops within human and mouse red blood cells in the absence of a parasitophorous vacuole, and its secreted antigens lack trafficking motifs found in malarial secreted antigens. Here

    更新日期:2020-08-21
  • CRISPR-induced double-strand breaks trigger recombination between homologous chromosome arms.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-06-13
    Erich Brunner,Ryohei Yagi,Marc Debrunner,Dezirae Beck-Schneider,Alexa Burger,Eliane Escher,Christian Mosimann,George Hausmann,Konrad Basler

    CRISPR-Cas9-based genome editing has transformed the life sciences, enabling virtually unlimited genetic manipulation of genomes: The RNA-guided Cas9 endonuclease cuts DNA at a specific target sequence and the resulting double-strand breaks are mended by one of the intrinsic cellular repair pathways. Imprecise double-strand repair will introduce random mutations such as indels or point mutations, whereas

    更新日期:2020-08-21
  • The WT1-BASP1 complex is required to maintain the differentiated state of taste receptor cells.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-06-05
    Yankun Gao,Debarghya Dutta Banik,Mutia M Muna,Stefan Ge Roberts,Kathryn F Medler

    WT1 is a transcriptional activator that controls the boundary between multipotency and differentiation. The transcriptional cofactor BASP1 binds to WT1, forming a transcriptional repressor complex that drives differentiation in cultured cells; however, this proposed mechanism has not been demonstrated in vivo. We used the peripheral taste system as a model to determine how BASP1 regulates the function

    更新日期:2020-08-21
  • ATP hydrolysis by KaiC promotes its KaiA binding in the cyanobacterial circadian clock system.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-06-03
    Yasuhiro Yunoki,Kentaro Ishii,Maho Yagi-Utsumi,Reiko Murakami,Susumu Uchiyama,Hirokazu Yagi,Koichi Kato

    The cyanobacterial clock is controlled via the interplay among KaiA, KaiB, and KaiC, which generate a periodic oscillation of KaiC phosphorylation in the presence of ATP. KaiC forms a homohexamer harboring 12 ATP-binding sites and exerts ATPase activities associated with its autophosphorylation and dephosphorylation. The KaiC nucleotide state is a determining factor of the KaiB-KaiC interaction; however

    更新日期:2020-08-21
  • Mesenchymal stromal cell activation by breast cancer secretomes in bioengineered 3D microenvironments.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-06-03
    Ulrich Blache,Edward R Horton,Tian Xia,Erwin M Schoof,Lene H Blicher,Angelina Schönenberger,Jess G Snedeker,Ivan Martin,Janine T Erler,Martin Ehrbar

    Mesenchymal stromal cells (MSCs) are key contributors of the tumour microenvironment and are known to promote cancer progression through reciprocal communication with cancer cells, but how they become activated is not fully understood. Here, we investigate how breast cancer cells from different stages of the metastatic cascade convert MSCs into tumour-associated MSCs (TA-MSCs) using unbiased, global

    更新日期:2020-08-21
  • Opposing functions of F-BAR proteins in neuronal membrane protrusion, tubule formation, and neurite outgrowth.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-06-03
    Kendra L Taylor,Russell J Taylor,Karl E Richters,Brandon Huynh,Justin Carrington,Maeve E McDermott,Rebecca L Wilson,Erik W Dent

    The F-BAR family of proteins play important roles in many cellular processes by regulating both membrane and actin dynamics. The CIP4 family of F-BAR proteins is widely recognized to function in endocytosis by elongating endocytosing vesicles. However, in primary cortical neurons, CIP4 concentrates at the tips of extending lamellipodia and filopodia and inhibits neurite outgrowth. Here, we report that

    更新日期:2020-08-21
  • HELZ directly interacts with CCR4-NOT and causes decay of bound mRNAs.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-09-30
    Aoife Hanet,Felix Räsch,Ramona Weber,Vincenzo Ruscica,Maria Fauser,Tobias Raisch,Duygu Kuzuoğlu-Öztürk,Chung-Te Chang,Dipankar Bhandari,Cátia Igreja,Lara Wohlbold

    Eukaryotic superfamily (SF) 1 helicases have been implicated in various aspects of RNA metabolism, including transcription, processing, translation, and degradation. Nevertheless, until now, most human SF1 helicases remain poorly understood. Here, we have functionally and biochemically characterized the role of a putative SF1 helicase termed "helicase with zinc-finger," or HELZ. We discovered that

    更新日期:2020-08-21
  • Detecting sequence signals in targeting peptides using deep learning.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-09-30
    Jose Juan Almagro Armenteros,Marco Salvatore,Olof Emanuelsson,Ole Winther,Gunnar von Heijne,Arne Elofsson,Henrik Nielsen

    In bioinformatics, machine learning methods have been used to predict features embedded in the sequences. In contrast to what is generally assumed, machine learning approaches can also provide new insights into the underlying biology. Here, we demonstrate this by presenting TargetP 2.0, a novel state-of-the-art method to identify N-terminal sorting signals, which direct proteins to the secretory pathway

    更新日期:2020-08-21
  • Glycine cleavage system determines the fate of pluripotent stem cells via the regulation of senescence and epigenetic modifications.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-09-27
    Shengya Tian,Junru Feng,Yang Cao,Shengqi Shen,Yongping Cai,Dongdong Yang,Ronghui Yan,Lihua Wang,Huafeng Zhang,Xiuying Zhong,Ping Gao

    Metabolic remodelling has emerged as critical for stem cell pluripotency; however, the underlying mechanisms have yet to be fully elucidated. Here, we found that the glycine cleavage system (GCS) is highly activated to promote stem cell pluripotency and during somatic cell reprogramming. Mechanistically, we revealed that the expression of Gldc, a rate-limiting GCS enzyme regulated by Sox2 and Lin28A

    更新日期:2020-08-21
  • Engineering Photorhabdus luminescens toxin complex (PTC) into a recombinant injection nanomachine.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-09-20
    Peter Njenga Ng Ang A,Julia K Ebner,Matthias Plessner,Klaus Aktories,Gudula Schmidt

    Engineering delivery systems for proteins and peptides into mammalian cells is an ongoing challenge for cell biological studies as well as for therapeutic approaches. Photorhabdus luminescens toxin complex (PTC) is a heterotrimeric protein complex able to deliver diverse protein toxins into mammalian cells. We engineered the syringe-like nanomachine for delivery of protein toxins from different species

    更新日期:2020-08-21
  • Mechanistic insights into the protective roles of polyphosphate against amyloid cytotoxicity.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-09-18
    Justine Lempart,Eric Tse,James A Lauer,Magdalena I Ivanova,Alexandra Sutter,Nicholas Yoo,Philipp Huettemann,Daniel Southworth,Ursula Jakob

    The universally abundant polyphosphate (polyP) accelerates fibril formation of disease-related amyloids and protects against amyloid cytotoxicity. To gain insights into the mechanism(s) by which polyP exerts these effects, we focused on α-synuclein, a well-studied amyloid protein, which constitutes the major component of Lewy bodies found in Parkinson's disease. Here, we demonstrate that polyP is unable

    更新日期:2020-08-21
  • The huntingtin inclusion is a dynamic phase-separated compartment.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-09-16
    Fahmida Aktar,Chakkapong Burudpakdee,Mercedes Polanco,Sen Pei,Theresa C Swayne,Peter N Lipke,Lesley Emtage

    Inclusions of disordered protein are a characteristic feature of most neurodegenerative diseases, including Huntington's disease. Huntington's disease is caused by expansion of a polyglutamine tract in the huntingtin protein; mutant huntingtin protein (mHtt) is unstable and accumulates in large intracellular inclusions both in affected individuals and when expressed in eukaryotic cells. Using mHtt-GFP

    更新日期:2020-08-21
  • Pleiotropic requirements for human TDP-43 in the regulation of cell and organelle homeostasis.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-09-16
    Agnes Roczniak-Ferguson,Shawn M Ferguson

    TDP-43 is an RNA-binding protein that forms cytoplasmic aggregates in multiple neurodegenerative diseases. Although the loss of normal TDP-43 functions likely contributes to disease pathogenesis, the cell biological consequences of human TDP-43 depletion are not well understood. We, therefore, generated human TDP-43 knockout (KO) cells and subjected them to parallel cell biological and transcriptomic

    更新日期:2020-08-21
  • Structural and functional characterization of the mitochondrial complex IV assembly factor Coa6.
    Life Sci. Alliance (IF 2.622) Pub Date : 2019-09-12
    Shadi Maghool,N Dinesha G Cooray,David A Stroud,David Aragão,Michael T Ryan,Megan J Maher

    Assembly factors play key roles in the biogenesis of many multi-subunit protein complexes regulating their stability, activity, and the incorporation of essential cofactors. The human assembly factor Coa6 participates in the biogenesis of the CuA site in complex IV (cytochrome c oxidase, COX). Patients with mutations in Coa6 suffer from mitochondrial disease due to complex IV deficiency. Here, we present

    更新日期:2020-08-21
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