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  1. Article ; Online: Coronavirus: global solutions to prevent a pandemic.

    Watts, Charlotte H / Vallance, Patrick / Whitty, Christopher J M

    Nature

    2020  Volume 578, Issue 7795, Page(s) 363

    MeSH term(s) Age Distribution ; Biomedical Research ; COVID-19 ; COVID-19 Testing ; COVID-19 Vaccines ; Clinical Laboratory Techniques ; Coronavirus Infections/diagnosis ; Coronavirus Infections/epidemiology ; Coronavirus Infections/prevention & control ; Coronavirus Infections/transmission ; Disease Susceptibility ; Epidemiological Monitoring ; Health Education ; Humans ; International Cooperation ; Pandemics/prevention & control ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/prevention & control ; Pneumonia, Viral/transmission ; Seasons ; Survival Rate ; Viral Vaccines/supply & distribution ; World Health Organization/organization & administration
    Chemical Substances COVID-19 Vaccines ; Viral Vaccines
    Keywords covid19
    Language English
    Publishing date 2020-02-18
    Publishing country England
    Document type Letter
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/d41586-020-00457-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Staphylococcal Complement Evasion Protein Sbi Stabilises C3d Dimers by Inducing an N-Terminal Helix Swap.

    Dunphy, Rhys W / Wahid, Ayla A / Back, Catherine R / Martin, Rebecca L / Watts, Andrew G / Dodson, Charlotte A / Crennell, Susan J / van den Elsen, Jean M H

    Frontiers in immunology

    2022  Volume 13, Page(s) 892234

    Abstract: Staphylococcus ... ...

    Abstract Staphylococcus aureus
    MeSH term(s) Animals ; Bacterial Proteins ; Carrier Proteins/metabolism ; Disulfides/metabolism ; Rats ; Staphylococcus/metabolism ; Staphylococcus aureus
    Chemical Substances Bacterial Proteins ; Carrier Proteins ; Disulfides
    Language English
    Publishing date 2022-05-25
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.892234
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Detection of glioblastoma intratumor heterogeneity in radiosensitivity using patient-derived neurosphere cultures.

    McAbee, Joseph H / Degorre-Kerbaul, Charlotte / Valdez, Kristin / Wendler, Astrid / Shankavaram, Uma T / Watts, Colin / Camphausen, Kevin / Tofilon, Philip J

    Journal of neuro-oncology

    2020  Volume 149, Issue 3, Page(s) 383–390

    Abstract: Purpose: Glioblastoma (GBM) is characterized by extensive clonal diversity suggesting the presence of tumor cells with varying degrees of treatment sensitivity. Radiotherapy is an integral part of glioblastoma treatment. Whether GBMs are comprised of ... ...

    Abstract Purpose: Glioblastoma (GBM) is characterized by extensive clonal diversity suggesting the presence of tumor cells with varying degrees of treatment sensitivity. Radiotherapy is an integral part of glioblastoma treatment. Whether GBMs are comprised of spatially distinct cellular populations with uniform or varying degrees of radiosensitivity has not been established.
    Methods: Spatially distinct regions of three GBMs (J3, J7 and J14) were resected and unique cell lines were derived from each region. DNA from cell lines, corresponding tumor fragments, and patient blood was extracted for whole exome sequencing. Variants, clonal composition, and functional implications were compared and analyzed with superFreq and IPA. Limiting dilution assays were performed on cell lines to measure intrinsic radiosensitivity.
    Results: Based on WES, cell lines generated from different regions of the same tumor were more closely correlated with their tumor of origin than the other GBMs. Variant and clonal composition comparisons showed that cell lines from distinct tumors displayed increasing levels of ITH with J3 and J14 having the lowest and highest, respectively. The radiosensitivities of the cell lines generated from the J3 tumor were similar as were those generated from the J7 tumor. However, the radiosensitivities of the 2 cell lines generated from the J14 tumor (J14T3 and J14T6) were significantly different with J14T6 being more sensitive than J14T3.
    Conclusion: Data suggest a tumor dependent ITH in radiosensitivity. The existence of ITH in radiosensitivity may impact not only the initial therapeutic response but also the effectiveness of retreatment protocols.
    MeSH term(s) Biomarkers, Tumor/genetics ; Gene Expression Regulation, Neoplastic/radiation effects ; Glioblastoma/genetics ; Glioblastoma/pathology ; Glioblastoma/radiotherapy ; Humans ; Mutation ; Prognosis ; Radiation Tolerance ; Tumor Cells, Cultured ; Whole Exome Sequencing/methods
    Chemical Substances Biomarkers, Tumor
    Language English
    Publishing date 2020-10-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604875-4
    ISSN 1573-7373 ; 0167-594X
    ISSN (online) 1573-7373
    ISSN 0167-594X
    DOI 10.1007/s11060-020-03643-0
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  6. Article ; Online: Staphylococcal Complement Evasion Protein Sbi Stabilises C3d Dimers by Inducing an N-Terminal Helix Swap

    Rhys W. Dunphy / Ayla A. Wahid / Catherine R. Back / Rebecca L. Martin / Andrew G. Watts / Charlotte A. Dodson / Susan J. Crennell / Jean M. H. van den Elsen

    Frontiers in Immunology, Vol

    2022  Volume 13

    Abstract: Staphylococcus aureus is an opportunistic pathogen that is able to thwart an effective host immune response by producing a range of immune evasion molecules, including S. aureus binder of IgG (Sbi) which interacts directly with the central complement ... ...

    Abstract Staphylococcus aureus is an opportunistic pathogen that is able to thwart an effective host immune response by producing a range of immune evasion molecules, including S. aureus binder of IgG (Sbi) which interacts directly with the central complement component C3, its fragments and associated regulators. Recently we reported the first structure of a disulfide-linked human C3d17C dimer and highlighted its potential role in modulating B-cell activation. Here we present an X-ray crystal structure of a disulfide-linked human C3d17C dimer, which undergoes a structurally stabilising N-terminal 3D domain swap when in complex with Sbi. These structural studies, in combination with circular dichroism and fluorescence spectroscopic analyses, reveal the mechanism underpinning this unique helix swap event and could explain the origins of a previously discovered N-terminally truncated C3dg dimer isolated from rat serum. Overall, our study unveils a novel staphylococcal complement evasion mechanism which enables the pathogen to harness the ability of dimeric C3d to modulate B-cell activation.
    Keywords complement ; structural biology ; Staphylococcus aureus ; C3d ; 3D domain swapping ; Immunologic diseases. Allergy ; RC581-607
    Subject code 572
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Using data from 'visible' populations to estimate the size and importance of 'hidden' populations in an epidemic: A modelling technique.

    Foss, Anna M / Prudden, Holly J / Mitchell, Kate M / Pickles, Michael / Washington, Reynold / Phillips, Anna E / Alary, Michel / Boily, Marie-Claude / Moses, Stephen / Watts, Charlotte H / Vickerman, Peter T

    Infectious Disease Modelling

    2020  Volume 5, Page(s) 798–813

    Abstract: We used reported behavioural data from cisgender men who have sex with men and transgender women (MSM/TGW) in Bangalore, mainly collected from 'hot-spot' locations that attract MSM/TGW, to illustrate a technique to deal with potential issues with the ... ...

    Abstract We used reported behavioural data from cisgender men who have sex with men and transgender women (MSM/TGW) in Bangalore, mainly collected from 'hot-spot' locations that attract MSM/TGW, to illustrate a technique to deal with potential issues with the representativeness of this sample. A deterministic dynamic model of HIV transmission was developed, incorporating three subgroups of MSM/TGW, grouped according to their reported predominant sexual role (insertive, receptive or versatile). Using mathematical modelling and data triangulation for 'balancing' numbers of partners and role preferences, we compared three different approaches to determine if our technique could be useful for inferring characteristics of a more 'hidden' insertive MSM subpopulation, and explored their potential importance for the HIV epidemic. Projections for 2009 across all three approaches suggest that HIV prevalence among insertive MSM was likely to be less than half that recorded in the surveys (4.5-6.5% versus 13.1%), but that the relative size of this subgroup was over four times larger (61-69% of all MSM/TGW versus 15%). We infer that the insertive MSM accounted for 10-20% of all prevalent HIV infections among urban males aged 15-49. Mathematical modelling can be used with data on 'visible' MSM/TGW to provide insights into the characteristics of 'hidden' MSM. A greater understanding of the sexual behaviour of all MSM/TGW is important for effective HIV programming. More broadly, a hidden subgroup with a lower infectious disease prevalence than more visible subgroups, has the potential to contain more infections, if the hidden subgroup is considerably larger in size.
    Language English
    Publishing date 2020-09-30
    Publishing country China
    Document type Journal Article
    ZDB-ID 3015225-2
    ISSN 2468-0427 ; 2468-2152
    ISSN (online) 2468-0427
    ISSN 2468-2152
    DOI 10.1016/j.idm.2020.09.007
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  8. Article ; Online: Discovery of ASTX029, A Clinical Candidate Which Modulates the Phosphorylation and Catalytic Activity of ERK1/2.

    Heightman, Tom D / Berdini, Valerio / Bevan, Luke / Buck, Ildiko M / Carr, Maria G / Courtin, Aurélie / Coyle, Joseph E / Day, James E H / East, Charlotte / Fazal, Lynsey / Griffiths-Jones, Charlotte M / Howard, Steven / Kucia-Tran, Justyna / Martins, Vanessa / Muench, Sandra / Munck, Joanne M / Norton, David / O'Reilly, Marc / Palmer, Nicholas /
    Pathuri, Puja / Peakman, Torren M / Reader, Michael / Rees, David C / Rich, Sharna J / Shah, Alpesh / Wallis, Nicola G / Walton, Hugh / Wilsher, Nicola E / Woolford, Alison J-A / Cooke, Michael / Cousin, David / Onions, Stuart / Shannon, Jonathan / Watts, John / Murray, Christopher W

    Journal of medicinal chemistry

    2021  Volume 64, Issue 16, Page(s) 12286–12303

    Abstract: Aberrant activation of the mitogen-activated protein kinase pathway frequently drives tumor growth, and the ERK1/2 kinases are positioned at a key node in this pathway, making them important targets for therapeutic intervention. Recently, a number of ... ...

    Abstract Aberrant activation of the mitogen-activated protein kinase pathway frequently drives tumor growth, and the ERK1/2 kinases are positioned at a key node in this pathway, making them important targets for therapeutic intervention. Recently, a number of ERK1/2 inhibitors have been advanced to investigational clinical trials in patients with activating mutations in B-Raf proto-oncogene or Ras. Here, we describe the discovery of the clinical candidate ASTX029 (
    MeSH term(s) Animals ; Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/metabolism ; Antineoplastic Agents/pharmacokinetics ; Antineoplastic Agents/therapeutic use ; Crystallography, X-Ray ; Dogs ; Humans ; Indoles/chemical synthesis ; Indoles/metabolism ; Indoles/pharmacokinetics ; Indoles/therapeutic use ; Male ; Mice, Inbred BALB C ; Mitogen-Activated Protein Kinase 1/antagonists & inhibitors ; Mitogen-Activated Protein Kinase 1/chemistry ; Mitogen-Activated Protein Kinase 1/metabolism ; Molecular Structure ; Neoplasms/drug therapy ; Phosphorylation/drug effects ; Protein Binding ; Protein Kinase Inhibitors/chemical synthesis ; Protein Kinase Inhibitors/metabolism ; Protein Kinase Inhibitors/pharmacokinetics ; Protein Kinase Inhibitors/therapeutic use ; Proto-Oncogene Mas ; Pyrimidines/chemical synthesis ; Pyrimidines/metabolism ; Pyrimidines/pharmacokinetics ; Pyrimidines/therapeutic use ; Rats, Sprague-Dawley ; Rats, Wistar ; Structure-Activity Relationship ; Xenograft Model Antitumor Assays ; Mice ; Rats
    Chemical Substances Antineoplastic Agents ; Indoles ; MAS1 protein, human ; Protein Kinase Inhibitors ; Proto-Oncogene Mas ; Pyrimidines ; Mitogen-Activated Protein Kinase 1 (EC 2.7.11.24)
    Language English
    Publishing date 2021-08-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.1c00905
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  9. Article ; Online: Is modelling complexity always needed? Insights from modelling PrEP introduction in South Africa.

    Grant, Hannah / Foss, Anna M / Watts, Charlotte / Medley, Graham F / Mukandavire, Zindoga

    Journal of public health (Oxford, England)

    2020  Volume 42, Issue 4, Page(s) e551–e560

    Abstract: Background: Mathematical models can be powerful policymaking tools. Simple, static models are user-friendly for policymakers. More complex, dynamic models account for time-dependent changes but are complicated to understand and produce. Under which ... ...

    Abstract Background: Mathematical models can be powerful policymaking tools. Simple, static models are user-friendly for policymakers. More complex, dynamic models account for time-dependent changes but are complicated to understand and produce. Under which conditions are static models adequate? We compare static and dynamic model predictions of whether behavioural disinhibition could undermine the impact of HIV pre-exposure prophylaxis (PrEP) provision to female sex workers in South Africa.
    Methods: A static model of HIV risk was developed and adapted into a dynamic model. Both models were used to estimate the possible reduction in condom use, following PrEP introduction, without increasing HIV risk. The results were compared over a 20-year time horizon, in two contexts: at epidemic equilibrium and during an increasing epidemic.
    Results: Over time horizons of up to 5 years, the models are consistent. Over longer timeframes, the static model overstates the tolerated reduction in condom use where initial condom use is reasonably high ($\ge$50%) and/or PrEP effectiveness is low ($\le$45%), especially during an increasing epidemic.
    Conclusions: Static models can provide useful deductions to guide policymaking around the introduction of a new HIV intervention over short-medium time horizons of up to 5 years. Over longer timeframes, static models may not sufficiently emphasise situations of programmatic importance, especially where underlying epidemics are still increasing.
    MeSH term(s) Anti-HIV Agents/therapeutic use ; Cost-Benefit Analysis ; Female ; HIV Infections/drug therapy ; HIV Infections/epidemiology ; HIV Infections/prevention & control ; Humans ; Pre-Exposure Prophylaxis ; Sex Workers ; South Africa/epidemiology
    Chemical Substances Anti-HIV Agents
    Language English
    Publishing date 2020-02-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 2142082-8
    ISSN 1741-3850 ; 1741-3842
    ISSN (online) 1741-3850
    ISSN 1741-3842
    DOI 10.1093/pubmed/fdz178
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  10. Article ; Online: Gaining a foothold: tackling poverty, gender inequality, and HIV in Africa.

    Kim, Julia C / Watts, Charlotte H

    BMJ (Clinical research ed.)

    2005  Volume 331, Issue 7519, Page(s) 769–772

    MeSH term(s) Adolescent ; Adult ; Africa ; Domestic Violence ; Female ; Financing, Organized ; HIV Infections/prevention & control ; Health Policy ; Health Services Accessibility/economics ; Health Services Accessibility/organization & administration ; Humans ; Male ; Poverty/prevention & control ; Prejudice
    Language English
    Publishing date 2005-09-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 1362901-3
    ISSN 1756-1833 ; 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
    ISSN (online) 1756-1833
    ISSN 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
    DOI 10.1136/bmj.331.7519.769
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