Kooperativer Bibliotheksverbund

Berlin Brandenburg


Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

  • 1
    Language: English
    In: Science (New York, N.Y.), 07 December 2018, Vol.362(6419), pp.1156-1160
    Description: Many bacterial infections are hard to treat and tend to relapse, possibly due to the presence of antibiotic-tolerant persisters. In vitro, persister cells appear to be dormant. After uptake of species by macrophages, nongrowing persisters also occur, but their physiological state is poorly understood. In this work, we show that persisters arising during macrophage infection maintain a metabolically active state. Persisters reprogram macrophages by means of effectors secreted by the pathogenicity island 2 type 3 secretion system. These effectors dampened proinflammatory innate immune responses and induced anti-inflammatory macrophage polarization. Such reprogramming allowed nongrowing cells to survive for extended periods in their host. Persisters undermining host immune defenses might confer an advantage to the pathogen during relapse once antibiotic pressure is relieved.
    Keywords: Drug Resistance, Bacterial ; Host-Pathogen Interactions -- Immunology ; Macrophages -- Immunology ; Salmonella Infections -- Drug Therapy ; Salmonella Typhimurium -- Metabolism ; Type III Secretion Systems -- Metabolism
    ISSN: 00368075
    E-ISSN: 1095-9203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: Nature, 2018
    Description: Gametes are highly specialized cells that can give rise to the next generation through their ability to generate a totipotent zygote. In mice, germ cells are first specified in the developing embryo around embryonic day (E) 6.25 as primordial germ cells (PGCs)1. Following subsequent migration into the developing gonad, PGCs undergo a wave of extensive epigenetic reprogramming around E10.5–E11.52,3,4,5,6,7,8,9,10,11, including genome-wide loss of 5-methylcytosine2,3,4,5,7,8,9,10,11. The underlying molecular mechanisms of this process have remained unclear, leading to our inability to recapitulate this step of germline development in vitro12,13,14. Here we show, using an integrative approach, that this complex reprogramming process involves coordinated interplay among promoter sequence characteristics, DNA (de)methylation, the polycomb (PRC1) complex and both DNA demethylation-dependent and -independent functions of TET1 to enable the activation of a critical set of germline reprogramming-responsive genes involved in gamete generation and meiosis. Our results also reveal an unexpected role for TET1 in maintaining but not driving DNA demethylation in gonadal PGCs. Collectively, our work uncovers a fundamental biological role for gonadal germline reprogramming and identifies the epigenetic principles of the PGC-to-gonocyte transition that will help to guide attempts to recapitulate complete gametogenesis in vitro.
    Keywords: Science & Technology ; Multidisciplinary Sciences ; Science & Technology - Other Topics ; Embryonic Stem-Cells ; Promoter DNA Methylation ; Genome-Wide ; Tet Proteins ; In-Vitro ; 5-Hydroxymethylcytosine ; Dynamics ; Differentiation ; Demethylation ; Chromatin ; MD Multidisciplinary ; General Science & Technology;
    ISSN: 0028-0836
    E-ISSN: 1476-4687
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    Language: English
    In: Genomics, November 2014, Vol.104(5), pp.324-33
    Description: Epigenetic reprogramming involves processes that lead to the erasure of epigenetic information, reverting the chromatin template to a less differentiated state. Extensive epigenetic reprogramming occurs both naturally during mammalian development in the early embryo and the developing germ line, and artificially in various in vitro reprogramming systems. Global DNA demethylation appears to be a shared attribute of reprogramming events, and understanding DNA methylation dynamics is thus of considerable interest. Recently, the Tet enzymes, which catalyse the iterative oxidation of 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine, have emerged as potential drivers of epigenetic reprogramming. Although some of the recent studies point towards the direct role of Tet proteins in the removal of DNA methylation, the accumulating evidence suggests that the processes underlying DNA methylation dynamics might be more complex. Here, we review the current evidence, highlighting the agreements and the discrepancies between the suggested models and the experimental evidence.
    Keywords: 5-Hydroxymethylcytosine ; Demethylation ; Germ Cells ; Methylation ; Reprogramming ; Tet ; Ips ; Cellular Reprogramming ; 5-Methylcytosine -- Metabolism ; Cytosine -- Analogs & Derivatives ; DNA-Binding Proteins -- Metabolism
    ISSN: 08887543
    E-ISSN: 1089-8646
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Language: English
    In: The Journal of cell biology, 09 August 2017
    Description: In mammals, histone H1 consists of a family of related proteins, including five replication-dependent (H1.1-H1.5) and two replication-independent (H1.10 and H1.0) subtypes, all expressed in somatic cells. To systematically study the expression and function of H1 subtypes, we generated knockin mouse lines in which endogenous H1 subtypes are tagged. We focused on key developmental periods when epigenetic reprogramming occurs: early mouse embryos and primordial germ cell development. We found that dynamic changes in H1 subtype expression and localization are tightly linked with chromatin remodeling and might be crucial for transitions in chromatin structure during reprogramming. Although all somatic H1 subtypes are present in the blastocyst, each stage of preimplantation development is characterized by a different combination of H1 subtypes. Similarly, the relative abundance of somatic H1 subtypes can distinguish male and female chromatin upon sex differentiation in developing germ cells. Overall, our data provide new insights into the chromatin changes underlying epigenetic reprogramming. We suggest that distinct H1 subtypes may mediate the extensive chromatin remodeling occurring during epigenetic reprogramming and that they may be key players in the acquisition of cellular totipotency and the establishment of specific cellular states.
    Keywords: Research Articles ; 24 ; 13 ; 38;
    ISSN: 00219525
    E-ISSN: 1540-8140
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    Language: English
    In: Nature Cell Biology, 2/2016, Vol.18(2), pp.225-233
    Description: Zygotic epigenetic reprogramming entails genome-wide DNA demethylation that is accompanied by Tet methylcytosine dioxygenase 3 (Tet3)-driven oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC; refs 1-4). Here we demonstrate using detailed immunofluorescence analysis and ultrasensitive LC-MS-based quantitative measurements that the initial loss of paternal 5mC does not require 5hmC formation. Small-molecule inhibition of Tet3 activity, as well as genetic ablation, impedes 5hmC accumulation in zygotes without affecting the early loss of paternal 5mC. Instead, 5hmC accumulation is dependent on the activity of zygotic Dnmt3a and Dnmt1, documenting a role for Tet3-driven hydroxylation in targeting de novo methylation activities present in the early embryo. Our data thus provide further insights into the dynamics of zygotic reprogramming, revealing an intricate interplay between DNA demethylation, de novo methylation and Tet3-driven hydroxylation.
    Keywords: Cellular Reprogramming ; DNA Methylation ; Epigenesis, Genetic ; 5-Methylcytosine -- Metabolism ; Cytosine -- Analogs & Derivatives ; Zygote -- Metabolism;
    ISSN: 1465-7392
    E-ISSN: 1476-4679
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    Language: English
    In: Molecular cell, 19 November 2015, Vol.60(4), pp.611-25
    Description: The integrity of chromatin, which provides a dynamic template for all DNA-related processes in eukaryotes, is maintained through replication-dependent and -independent assembly pathways. To address the role of histone deposition in the absence of DNA replication, we deleted the H3.3 chaperone Hira in developing mouse oocytes. We show that chromatin of non-replicative developing oocytes is dynamic and that lack of continuous H3.3/H4 deposition alters chromatin structure, resulting in increased DNase I sensitivity, the accumulation of DNA damage, and a severe fertility phenotype. On the molecular level, abnormal chromatin structure leads to a dramatic decrease in the dynamic range of gene expression, the appearance of spurious transcripts, and inefficient de novo DNA methylation. Our study thus unequivocally shows the importance of continuous histone replacement and chromatin homeostasis for transcriptional regulation and normal developmental progression in a non-replicative system in vivo.
    Keywords: Oogenesis ; Cell Cycle Proteins -- Genetics ; Chromatin -- Metabolism ; Histone Chaperones -- Genetics ; Histones -- Metabolism ; Transcription Factors -- Genetics
    ISSN: 10972765
    E-ISSN: 1097-4164
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    Language: English
    In: Annals of Thoracic Surgery, June, 2011, Vol.91(6), p.1852(7)
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.athoracsur.2011.03.022 Byline: Xiumei Sun, Steven W. Boyce, Peter C. Hill, Ammar S. Bafi, Zhengyi Xue, Joseph Lindsay, Paul J. Corso Abstract: Postoperative atrial fibrillation (AF) frequently complicates coronary artery bypass grafting (CABG) operations. As the frequency of obesity has increased in the United States, the number of obese patients undergoing CABG has kept pace. This study sought to define the association between body mass index (BMI) and postoperative AF. Author Affiliation: Department of Surgery, Section of Cardiac Surgery, Washington Hospital Center, Washington, DC Article History: Accepted 9 March 2011
    Keywords: Atrial Fibrillation ; Surgery ; Coronary Artery Bypass ; Body Mass Index
    ISSN: 0003-4975
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Language: English
    In: PLoS ONE, 2012, Vol.7(2), p.e31640
    Description: Human ether-à-go-go -related gene (hERG) K + channels have unusual gating kinetics. Characterised by slow activation/deactivation but rapid inactivation/recovery from inactivation, the unique gating kinetics underlie the central role hERG channels play in cardiac repolarisation. The slow activation and deactivation kinetics are regulated in part by the S4–S5 linker, which couples movement of the voltage sensor domain to opening of the activation gate at the distal end of the inner helix of the pore domain. It has also been suggested that cytosolic domains may interact with the S4–S5 linker to regulate activation and deactivation kinetics. Here, we show that the solution structure of a peptide corresponding to the S4–S5 linker of hERG contains an amphipathic helix. The effects of mutations at the majority of residues in the S4–S5 linker of hERG were consistent with the previously identified role in coupling voltage sensor movement to the activation gate. However, mutations to Ser543, Tyr545, Gly546 and Ala548 had more complex phenotypes indicating that these residues are involved in additional interactions. We propose a model in which the S4–S5 linker, in addition to coupling VSD movement to the activation gate, also contributes to interactions that stabilise the closed state and a separate set of interactions that stabilise the open state. The S4–S5 linker therefore acts as a signal integrator and plays a crucial role in the slow deactivation kinetics of the channel.
    Keywords: Research Article ; Biology ; Chemistry ; Medicine ; Chemistry ; Computational Biology ; Neuroscience ; Biochemistry
    E-ISSN: 1932-6203
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    In: Medicine and Science in Sports and Exercise, 2001, Vol.33(1), pp.148-151
    Description: HILL. R. J., and P. S. W. DAVIES. Energy expenditure during 2 wk of an ultra-endurance run around Australia. Med. Sci. Sports Exerc., Vol. 33, No. 1, 2001, pp. 148–151. PURPOSE:: For ultra-endurance athletes, whose energy expenditure is likely to be at the extremes of human tolerance for sustained periods of time, there is increased concern regarding meeting energy needs. Due to the lack of data outlining the energy requirements of such athletes, it is possible that those participating in ultra-endurance exercise are compromising performance, as well as health, as a result of inadequate nutrition and energy intake. To provide insight into this dilemma, we have presented a case study of a 37-yr-old ultra-marathon runner as he runs around the coast of Australia. METHODS:: Total energy expenditure was measured over a 2-wk period using the doubly labeled water technique. RESULTS:: The average total energy expenditure of the case subject was 6321 kcal·d. Based on the expected accuracy and precision of the doubly labeled water technique the subject’s total energy expenditure might range between 6095 and 6550 kcal·d. The subject’s average daily water turnover was 6.083 L over the 14-d period and might range between 5.9 L and 6.3 L·d. CONCLUSIONS:: This information will provide a guide to the energy requirements of ultra-endurance running and enable athletes, nutritionists, and coaches to optimize performance without compromising the health of the participant.
    Keywords: Adult–Physiology ; Australia–Physiology ; Body Water–Physiology ; Energy Metabolism–Physiology ; Humans–Physiology ; Male–Physiology ; Physical Endurance–Physiology ; Running–Physiology ; Space Life Sciences;
    ISSN: 0195-9131
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    In: Stroke, 2011, Vol.42(10), pp.2801-2805
    Description: BACKGROUND AND PURPOSE—: Stroke development is a major concern in patients undergoing coronary artery bypass grafting (CABG). Whether asymptomatic severe carotid artery stenosis (CAS) contributes to the development of stroke and mortality in such patients remains uncertain. METHODS—: A retrospective analysis of 878 consecutive patients with documented carotid duplex ultrasound who underwent isolated CABG in our institution from January 2003 to December 2009 was performed. Patients with severe CAS (n=117) were compared with those without severe CAS (n=761) to assess the rates of stroke and mortality during hospitalization for CABG. The 30-day mortality rate was also assessed. RESULTS—: Patients with severe CAS were older and had a higher prevalence of peripheral arterial disease and heart failure. Patients with severe CAS had similar rates of in-hospital stroke (3.4% versus 3.6%; P=1.0) and mortality (3.4% versus 4.2%; P=1.0) compared with patients without severe CAS. The 30-day rate of mortality was also similar between the 2 cohorts (3.4% versus 2.9%; P=0.51). CONCLUSIONS—: Severe CAS alone is not a risk factor for stroke or mortality in patients undergoing CABG. The decision to perform carotid imaging and subsequent revascularization in association with CABG must be individualized and based on clinical judgment.
    Keywords: Medicine;
    ISSN: 0039-2499
    E-ISSN: 15244628
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages