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  1. Article ; Online: The nuclear bodies conference: Hubs of genomic activity, June 24-28, Western Shore, Nova Scotia, Canada.

    Kaufman, Paul D / Huang, Sui / Pederson, Thoru

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology

    2022  Volume 36, Issue 11, Page(s) e22588

    Abstract: This conference brought together leaders in the investigation of various bodies that populate the nucleus, a field that complements research on chromosome biology. These nuclear bodies had been receiving increasing attention as hubs of genome activity ... ...

    Abstract This conference brought together leaders in the investigation of various bodies that populate the nucleus, a field that complements research on chromosome biology. These nuclear bodies had been receiving increasing attention as hubs of genome activity and the new findings reported at the conference strongly confirmed and significantly expanded this principle.
    MeSH term(s) Nova Scotia ; Nuclear Bodies ; Genome ; Chromosomes/genetics ; Genomics
    Language English
    Publishing date 2022-10-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 639186-2
    ISSN 1530-6860 ; 0892-6638
    ISSN (online) 1530-6860
    ISSN 0892-6638
    DOI 10.1096/fj.202201455R
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Close to the edge: Heterochromatin at the nucleolar and nuclear peripheries.

    Bizhanova, Aizhan / Kaufman, Paul D

    Biochimica et biophysica acta. Gene regulatory mechanisms

    2020  Volume 1864, Issue 1, Page(s) 194666

    Abstract: Chromatin is a dynamic structure composed of DNA, RNA, and proteins, regulating storage and expression of the genetic material in the nucleus. Heterochromatin plays a crucial role in driving the three-dimensional arrangement of the interphase genome, and ...

    Abstract Chromatin is a dynamic structure composed of DNA, RNA, and proteins, regulating storage and expression of the genetic material in the nucleus. Heterochromatin plays a crucial role in driving the three-dimensional arrangement of the interphase genome, and in preserving genome stability by maintaining a subset of the genome in a silent state. Spatial genome organization contributes to normal patterns of gene function and expression, and is therefore of broad interest. Mammalian heterochromatin, the focus of this review, mainly localizes at the nuclear periphery, forming Lamina-associated domains (LADs), and at the nucleolar periphery, forming Nucleolus-associated domains (NADs). Together, these regions comprise approximately one-half of mammalian genomes, and most but not all loci within these domains are stochastically placed at either of these two locations after exit from mitosis at each cell cycle. Excitement about the role of these heterochromatic domains in early development has recently been heightened by the discovery that LADs appear at some loci in the preimplantation mouse embryo prior to other chromosomal features like compartmental identity and topologically-associated domains (TADs). While LADs have been extensively studied and mapped during cellular differentiation and early embryonic development, NADs have been less thoroughly studied. Here, we summarize pioneering studies of NADs and LADs, more recent advances in our understanding of cis/trans-acting factors that mediate these localizations, and discuss the functional significance of these associations.
    MeSH term(s) Animals ; Cell Nucleolus/genetics ; Cell Nucleolus/metabolism ; Genome, Human ; Genomic Instability ; Heterochromatin/genetics ; Heterochromatin/metabolism ; Humans
    Chemical Substances Heterochromatin
    Language English
    Publishing date 2020-12-08
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2918786-2
    ISSN 1876-4320 ; 1874-9399
    ISSN (online) 1876-4320
    ISSN 1874-9399
    DOI 10.1016/j.bbagrm.2020.194666
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Want reprogramming? Cut back on the chromatin assembly!

    Kaufman, Paul D

    Nature structural & molecular biology

    2015  Volume 22, Issue 9, Page(s) 648–650

    MeSH term(s) Animals ; Cell Differentiation ; Chromatin Assembly and Disassembly ; Proteins/antagonists & inhibitors ; Totipotent Stem Cells/physiology
    Chemical Substances Cnot7 protein, mouse ; Proteins
    Language English
    Publishing date 2015-09
    Publishing country United States
    Document type Comment ; News
    ZDB-ID 2126708-X
    ISSN 1545-9985 ; 1545-9993
    ISSN (online) 1545-9985
    ISSN 1545-9993
    DOI 10.1038/nsmb.3081
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Correction to: Novel genetic tools for probing individual H3 molecules in each nucleosome.

    Ichikawa, Yuichi / Kaufman, Paul D

    Current genetics

    2018  Volume 65, Issue 2, Page(s) 379–380

    Abstract: In the original publication, Fig. 1 was incorrectly published. The amino acid sequence was shifted to the left relative to the rest of the diagram in the published version and the corrected figure is given here. ...

    Abstract In the original publication, Fig. 1 was incorrectly published. The amino acid sequence was shifted to the left relative to the rest of the diagram in the published version and the corrected figure is given here.
    Language English
    Publishing date 2018-12-12
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ZDB-ID 282876-5
    ISSN 1432-0983 ; 0172-8083
    ISSN (online) 1432-0983
    ISSN 0172-8083
    DOI 10.1007/s00294-018-0919-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Biochemical Analysis of Dimethyl Suberimidate-crosslinked Yeast Nucleosomes.

    Ichiakwa, Yuichi / Kaufman, Paul D

    Bio-protocol

    2018  Volume 8, Issue 6

    Abstract: Nucleosomes are the fundamental unit of eukaryotic chromosome packaging, comprised of 147 bp of DNA wrapped around two molecules of each of the core histone proteins H2A, H2B, H3, and H4. Nucleosomes are symmetrical, with one axis of symmetry centered on ...

    Abstract Nucleosomes are the fundamental unit of eukaryotic chromosome packaging, comprised of 147 bp of DNA wrapped around two molecules of each of the core histone proteins H2A, H2B, H3, and H4. Nucleosomes are symmetrical, with one axis of symmetry centered on the homodimeric interaction between the C-termini of the H3 molecules. To explore the functional consequences of nucleosome symmetry, we designed an obligate pair of H3 heterodimers, termed H3X and H3Y, allowing us to compare cells with single or double H3 alterations. Our biochemical validation of the heterodimeric X-Y interaction included intra-nucleosomal H3 crosslinking using dimethyl suberimidate (DMS). Here, we provide a detailed protocol for the use of DMS to analyze yeast nucleosomes.
    Language English
    Publishing date 2018-03-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2833269-6
    ISSN 2331-8325
    ISSN 2331-8325
    DOI 10.21769/BioProtoc.2770
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Structural and genetic diversity in the secreted mucins,

    Plender, Elizabeth G / Prodanov, Timofey / Hsieh, PingHsun / Nizamis, Evangelos / Harvey, William T / Sulovari, Arvis / Munson, Katherine M / Kaufman, Eli J / O'Neal, Wanda K / Valdmanis, Paul N / Marschall, Tobias / Bloom, Jesse D / Eichler, Evan E

    bioRxiv : the preprint server for biology

    2024  

    Abstract: The secreted mucins MUC5AC and MUC5B play critical defensive roles in airway pathogen entrapment and mucociliary clearance by encoding large glycoproteins with variable number tandem repeats (VNTRs). These polymorphic and degenerate protein coding VNTRs ... ...

    Abstract The secreted mucins MUC5AC and MUC5B play critical defensive roles in airway pathogen entrapment and mucociliary clearance by encoding large glycoproteins with variable number tandem repeats (VNTRs). These polymorphic and degenerate protein coding VNTRs make the loci difficult to investigate with short reads. We characterize the structural diversity of
    Language English
    Publishing date 2024-03-20
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.03.18.585560
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Novel genetic tools for probing individual H3 molecules in each nucleosome.

    Ichikawa, Yuichi / Kaufman, Paul D

    Current genetics

    2018  Volume 65, Issue 2, Page(s) 371–377

    Abstract: In eukaryotes, genomic DNA is packaged into the nucleus together with histone proteins, forming chromatin. The fundamental repeating unit of chromatin is the nucleosome, a naturally symmetric structure that wraps DNA and is the substrate for numerous ... ...

    Abstract In eukaryotes, genomic DNA is packaged into the nucleus together with histone proteins, forming chromatin. The fundamental repeating unit of chromatin is the nucleosome, a naturally symmetric structure that wraps DNA and is the substrate for numerous regulatory post-translational modifications. However, the biological significance of nucleosomal symmetry until recently had been unexplored. To investigate this issue, we developed an obligate pair of histone H3 heterodimers, a novel genetic tool that allowed us to modulate modification sites on individual H3 molecules within nucleosomes in vivo. We used these constructs for molecular genetic studies, for example demonstrating that H3K36 methylation on a single H3 molecule per nucleosome in vivo is sufficient to restrain cryptic transcription. We also used asymmetric nucleosomes for mass spectrometric analysis of dependency relationships among histone modifications. Furthermore, we extended this system to the centromeric H3 isoform (Cse4/CENP-A), gaining insights into centromeric nucleosomal symmetry and structure. In this review, we summarize our findings and discuss the utility of this novel approach.
    MeSH term(s) Centromere/genetics ; Centromere/metabolism ; Gene Expression Regulation ; Genomics/methods ; Histones/chemistry ; Histones/genetics ; Histones/metabolism ; Mutation ; Nucleosomes/chemistry ; Nucleosomes/genetics ; Nucleosomes/metabolism ; Protein Multimerization ; Structure-Activity Relationship ; Transcription, Genetic
    Chemical Substances Histones ; Nucleosomes
    Language English
    Publishing date 2018-11-26
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 282876-5
    ISSN 1432-0983 ; 0172-8083
    ISSN (online) 1432-0983
    ISSN 0172-8083
    DOI 10.1007/s00294-018-0910-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Ki-67: more than a proliferation marker.

    Sun, Xiaoming / Kaufman, Paul D

    Chromosoma

    2018  Volume 127, Issue 2, Page(s) 175–186

    Abstract: Ki-67 protein has been widely used as a proliferation marker for human tumor cells for decades. In recent studies, multiple molecular functions of this large protein have become better understood. Ki-67 has roles in both interphase and mitotic cells, and ...

    Abstract Ki-67 protein has been widely used as a proliferation marker for human tumor cells for decades. In recent studies, multiple molecular functions of this large protein have become better understood. Ki-67 has roles in both interphase and mitotic cells, and its cellular distribution dramatically changes during cell cycle progression. These localizations correlate with distinct functions. For example, during interphase, Ki-67 is required for normal cellular distribution of heterochromatin antigens and for the nucleolar association of heterochromatin. During mitosis, Ki-67 is essential for formation of the perichromosomal layer (PCL), a ribonucleoprotein sheath coating the condensed chromosomes. In this structure, Ki-67 acts to prevent aggregation of mitotic chromosomes. Here, we present an overview of functional roles of Ki-67 across the cell cycle and also describe recent experiments that clarify its role in regulating cell cycle progression in human cells.
    MeSH term(s) Amino Acid Sequence ; Cell Line, Tumor ; Cell Nucleolus/metabolism ; Cell Nucleolus/ultrastructure ; Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor p21/genetics ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Gene Expression Regulation ; Heterochromatin/metabolism ; Heterochromatin/ultrastructure ; Humans ; Interphase ; Ki-67 Antigen/genetics ; Ki-67 Antigen/metabolism ; Mitosis ; Protein Domains ; Protein Isoforms/genetics ; Protein Isoforms/metabolism ; Retinoblastoma Protein/genetics ; Retinoblastoma Protein/metabolism ; Ribonucleoproteins/chemistry ; Ribonucleoproteins/genetics ; Ribonucleoproteins/metabolism ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism
    Chemical Substances Cyclin-Dependent Kinase Inhibitor p21 ; Heterochromatin ; Ki-67 Antigen ; Protein Isoforms ; Retinoblastoma Protein ; Ribonucleoproteins ; Tumor Suppressor Protein p53
    Language English
    Publishing date 2018-01-10
    Publishing country Austria
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 203083-4
    ISSN 1432-0886 ; 0009-5915
    ISSN (online) 1432-0886
    ISSN 0009-5915
    DOI 10.1007/s00412-018-0659-8
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  9. Article ; Online: Traffic-related air pollution and dementia incidence in the Adult Changes in Thought Study.

    Blanco, Magali N / Shaffer, Rachel M / Li, Ge / Adar, Sara D / Carone, Marco / Szpiro, Adam A / Kaufman, Joel D / Larson, Timothy V / Hajat, Anjum / Larson, Eric B / Crane, Paul K / Sheppard, Lianne

    Environment international

    2024  Volume 183, Page(s) 108418

    Abstract: Background: While epidemiologic evidence links higher levels of exposure to fine particulate matter (PM: Objective: To evaluate associations between TRAP exposures (UFP, black carbon [BC], and nitrogen dioxide [NO: Methods: We ascertained dementia ...

    Abstract Background: While epidemiologic evidence links higher levels of exposure to fine particulate matter (PM
    Objective: To evaluate associations between TRAP exposures (UFP, black carbon [BC], and nitrogen dioxide [NO
    Methods: We ascertained dementia incidence in the Seattle-based Adult Changes in Thought (ACT) prospective cohort study (beginning in 1994) and assessed ten-year average TRAP exposures for each participant based on prediction models derived from an extensive mobile monitoring campaign. We applied Cox proportional hazards models to investigate TRAP exposure and dementia incidence using age as the time axis and further adjusting for sex, self-reported race, calendar year, education, socioeconomic status, PM
    Results: We identified 1,041 incident all-cause dementia cases in 4,283 participants over 37,102 person-years of follow-up. We did not find evidence of a greater hazard of late-life dementia incidence with elevated levels of long-term TRAP exposures. The estimated hazard ratio of all-cause dementia was 0.98 (95 % CI: 0.92-1.05) for every 2000 pt/cm
    Discussion: We did not find evidence of a greater hazard of late-life dementia risk with elevated long-term TRAP exposures in this population-based prospective cohort study.
    MeSH term(s) Adult ; Humans ; Air Pollutants/analysis ; Air Pollution/analysis ; Environmental Exposure/analysis ; Prospective Studies ; Nitrogen Dioxide/analysis ; Incidence ; Particulate Matter/analysis ; Dementia/epidemiology
    Chemical Substances Air Pollutants ; Nitrogen Dioxide (S7G510RUBH) ; Particulate Matter
    Language English
    Publishing date 2024-01-03
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 554791-x
    ISSN 1873-6750 ; 0160-4120
    ISSN (online) 1873-6750
    ISSN 0160-4120
    DOI 10.1016/j.envint.2024.108418
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  10. Article ; Online: A purified reconstituted bilayer matrix shows improved outcomes in treatment of non-healing diabetic foot ulcers when compared to the standard of care: Final results and analysis of a prospective, randomized, controlled, multi-centre clinical trial.

    Armstrong, David G / Orgill, Dennis P / Galiano, Robert D / Glat, Paul M / Kaufman, Jarrod P / Carter, Marissa J / DiDomenico, Lawrence A / Zelen, Charles M

    International wound journal

    2024  Volume 21, Issue 4, Page(s) e14882

    Abstract: As the incidence of diabetic foot ulcers (DFU) increases, better treatments that improve healing should reduce complications of these ulcers including infections and amputations. We conducted a randomized controlled trial comparing outcomes between a ... ...

    Abstract As the incidence of diabetic foot ulcers (DFU) increases, better treatments that improve healing should reduce complications of these ulcers including infections and amputations. We conducted a randomized controlled trial comparing outcomes between a novel purified reconstituted bilayer membrane (PRBM) to the standard of care (SOC) in the treatment of non-healing DFUs. This study included 105 patients who were randomized to either of two treatment groups (n = 54 PRBM; n = 51 SOC) in the intent to treat (ITT) group and 80 who completed the study per protocol (PP) (n = 47 PRBM; n = 33 SOC). The primary endpoint was the percentage of wounds closed after 12 weeks. Secondary outcomes included percent area reduction, time to healing, quality of life, and cost to closure. The DFUs that had been treated with PRBM healed at a higher rate than those treated with SOC (ITT: 83% vs. 45%, p = 0.00004, PP: 92% vs. 67%, p = 0.005). Wounds treated with PRBM also healed significantly faster than those treated with SOC with a mean of 42 versus 62 days for SOC (p = 0.00074) and achieved a mean wound area reduction within 12 weeks of 94% versus 51% for SOC (p = 0.0023). There were no adverse events or serious adverse events that were related to either the PRBM or the SOC. In comparison to the SOC, DFUs healed faster when treated with PRBM. Thus, the use of this PRBM is an effective option for the treatment of chronic DFUs.
    MeSH term(s) Humans ; Diabetic Foot/surgery ; Standard of Care ; Prospective Studies ; Quality of Life ; Wound Healing ; Treatment Outcome ; Diabetes Mellitus
    Language English
    Publishing date 2024-04-12
    Publishing country England
    Document type Randomized Controlled Trial ; Multicenter Study ; Journal Article
    ZDB-ID 2170920-8
    ISSN 1742-481X ; 1742-4801
    ISSN (online) 1742-481X
    ISSN 1742-4801
    DOI 10.1111/iwj.14882
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