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Article ; Online: Advanced microscopy and imaging techniques in immunology and cell biology.

Hawkins, Edwin D

2017 Volume 95, Issue 6, Page(s) 499–500

MeSH term(s)	Allergy and Immunology ; Animals ; Cell Biology ; Diagnostic Imaging/methods ; Humans ; Microscopy/instrumentation ; Microscopy/methods ; Phantoms, Imaging
Language	English
Publishing date	2017-08-03
Publishing country	United States
Document type	Editorial ; Introductory Journal Article
ZDB-ID	284057-1
ISSN	1440-1711 ; 0818-9641
ISSN (online)	1440-1711
ISSN	0818-9641
DOI	10.1038/icb.2017.34
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Article ; Online: An arrayed CRISPR screen of primary B cells reveals the essential elements of the antibody secretion pathway.

Trezise, Stephanie / Kong, Isabella Y / Hawkins, Edwin D / Herold, Marco J / Willis, Simon N / Nutt, Stephen L

Frontiers in immunology

2023 Volume 14, Page(s) 1089243

Abstract: Background: Humoral immunity depends on the differentiation of B cells into antibody secreting cells (ASCs). Excess or inappropriate ASC differentiation can lead to antibody-mediated autoimmune diseases, while impaired differentiation results in ... ...

Abstract	Background: Humoral immunity depends on the differentiation of B cells into antibody secreting cells (ASCs). Excess or inappropriate ASC differentiation can lead to antibody-mediated autoimmune diseases, while impaired differentiation results in immunodeficiency. Methods: We have used CRISPR/Cas9 technology in primary B cells to screen for regulators of terminal differentiation and antibody production. Results: We identified several new positive ( Discussion: The genes identified in this study represent weak links in the antibody-secretion pathway that are potential drug targets for antibody-mediated diseases, as well as candidates for genes whose mutation results in primary immune deficiency.
MeSH term(s)	Endoplasmic Reticulum-Associated Degradation ; Secretory Pathway ; Antibodies ; B-Lymphocytes ; Immunity, Humoral
Chemical Substances	Antibodies
Language	English
Publishing date	2023-02-13
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.2023.1089243
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Article: Science Communication Training Imparts Confidence and Influences Public Engagement Activity.

Swords, Christina M / Porter, Jerlym S / Hawkins, Amy J / Li, Edwin / Rowland-Goldsmith, Melissa / Koci, Matthew D / Tansey, John T / Woitowich, Nicole C

Journal of microbiology & biology education

2023 Volume 24, Issue 2

Abstract: The impacts of science are felt across all socio-ecological levels, ranging from the individual to societal. In order to adapt or respond to scientific discoveries, novel technologies, or biomedical or environmental challenges, a fundamental ... ...

Abstract	The impacts of science are felt across all socio-ecological levels, ranging from the individual to societal. In order to adapt or respond to scientific discoveries, novel technologies, or biomedical or environmental challenges, a fundamental understanding of science is necessary. However, antiscientific rhetoric, mistrust in science, and the dissemination of misinformation hinder the promotion of science as a necessary and beneficial component of our world. Scientists can promote scientific literacy by establishing dialogues with nonexperts, but they may find a lack of formal training as a barrier to public engagement. To address this, the American Society for Biochemistry and Molecular Biology (ASBMB) launched the Art of Science Communication course in 2015 in order to provide scientists at all career stages with introductory science communication training. In 2020, we conducted a retrospective survey of former participants to evaluate how the course had impacted participants' science communication behaviors and their confidence engaging with nonexperts, as well as other benefits to their professional development. We found that scientists were significantly more likely to communicate with nonexpert audiences following the course compared to before (77% versus 51%;
Language	English
Publishing date	2023-07-17
Publishing country	United States
Document type	Journal Article
ISSN	1935-7877
ISSN	1935-7877
DOI	10.1128/jmbe.00037-23
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Article ; Online: Speculations on the evolution of humoral adaptive immunity.

Horton, Miles B / Hawkins, Edwin D / Heinzel, Susanne / Hodgkin, Philip D

Immunology and cell biology

2020 Volume 98, Issue 6, Page(s) 439–448

Abstract: The protection of a multicellular organism from infection, at both cell and humoral levels, has been a tremendous driver of gene selection and cellular response strategies. Here we focus on a critical event in the development of humoral immunity: The ... ...

Abstract	The protection of a multicellular organism from infection, at both cell and humoral levels, has been a tremendous driver of gene selection and cellular response strategies. Here we focus on a critical event in the development of humoral immunity: The transition from principally innate responses to a system of adaptive cell selection, with all the attendant mechanical problems that must be solved in order for it to work effectively. Here we review recent advances, but our major goal is to highlight that the development of adaptive immunity resulted from the adoption, reuse and repurposing of an ancient, autonomous cellular program that combines and exploits three titratable cellular fate timers. We illustrate how this common cell machinery recurs and appears throughout biology, and has been essential for the evolution of complex organisms, at many levels of scale.
MeSH term(s)	Adaptive Immunity ; Biological Evolution ; Cell Differentiation ; Humans ; Immunity, Humoral
Language	English
Publishing date	2020-03-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	284057-1
ISSN	1440-1711 ; 0818-9641
ISSN (online)	1440-1711
ISSN	0818-9641
DOI	10.1111/imcb.12323
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Article ; Online: The interplay of leukemia cells and the bone marrow microenvironment.

Duarte, Delfim / Hawkins, Edwin D / Lo Celso, Cristina

Blood

2018 Volume 131, Issue 14, Page(s) 1507–1511

Abstract: The interplay of cancer cells and surrounding stroma is critical in disease progression. This is particularly evident in hematological malignancies that infiltrate the bone marrow and peripheral lymphoid organs. Despite clear evidence for the existence ... ...

Abstract	The interplay of cancer cells and surrounding stroma is critical in disease progression. This is particularly evident in hematological malignancies that infiltrate the bone marrow and peripheral lymphoid organs. Despite clear evidence for the existence of these interactions, the precise repercussions on the growth of leukemic cells are poorly understood. Recent development of novel imaging technology and preclinical disease models has advanced our comprehension of leukemia-microenvironment crosstalk and has potential implications for development of novel treatment options.
MeSH term(s)	Animals ; Bone Marrow/metabolism ; Bone Marrow/pathology ; Hematologic Neoplasms/metabolism ; Hematologic Neoplasms/pathology ; Hematologic Neoplasms/therapy ; Humans ; Leukemia/metabolism ; Leukemia/pathology ; Leukemia/therapy ; Neoplasms, Experimental/metabolism ; Neoplasms, Experimental/pathology ; Neoplasms, Experimental/therapy ; Tumor Microenvironment
Language	English
Publishing date	2018-02-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2017-12-784132
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Article ; Online: The Immuno-Modulatory Effects of Inhibitor of Apoptosis Protein Antagonists in Cancer Immunotherapy.

Michie, Jessica / Kearney, Conor J / Hawkins, Edwin D / Silke, John / Oliaro, Jane

Cells

2020 Volume 9, Issue 1

Abstract: One of the hallmarks of cancer cells is their ability to evade cell death via apoptosis. The inhibitor of apoptosis proteins (IAPs) are a family of proteins that act to promote cell survival. For this reason, upregulation of IAPs is associated with a ... ...

Abstract	One of the hallmarks of cancer cells is their ability to evade cell death via apoptosis. The inhibitor of apoptosis proteins (IAPs) are a family of proteins that act to promote cell survival. For this reason, upregulation of IAPs is associated with a number of cancer types as a mechanism of resistance to cell death and chemotherapy. As such, IAPs are considered a promising therapeutic target for cancer treatment, based on the role of IAPs in resistance to apoptosis, tumour progression and poor patient prognosis. The mitochondrial protein smac (second mitochondrial activator of caspases), is an endogenous inhibitor of IAPs, and several small molecule mimetics of smac (smac-mimetics) have been developed in order to antagonise IAPs in cancer cells and restore sensitivity to apoptotic stimuli. However, recent studies have revealed that smac-mimetics have broader effects than was first attributed. It is now understood that they are key regulators of innate immune signalling and have wide reaching immuno-modulatory properties. As such, they are ideal candidates for immunotherapy combinations. Pre-clinically, successful combination therapies incorporating smac-mimetics and oncolytic viruses, as with chimeric antigen receptor (CAR) T cell therapy, have been reported, and clinical trials incorporating smac-mimetics and immune checkpoint blockade are ongoing. Here, the potential of IAP antagonism to enhance immunotherapy strategies for the treatment of cancer will be discussed.
MeSH term(s)	Apoptosis/drug effects ; Apoptosis/immunology ; Humans ; Immunologic Factors/immunology ; Immunologic Factors/pharmacology ; Immunotherapy ; Inhibitor of Apoptosis Proteins/antagonists & inhibitors ; Inhibitor of Apoptosis Proteins/immunology ; Neoplasms/immunology ; Neoplasms/pathology ; Neoplasms/therapy
Chemical Substances	Immunologic Factors ; Inhibitor of Apoptosis Proteins
Language	English
Publishing date	2020-01-14
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells9010207
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Article ; Online: The Immuno-Modulatory Effects of Inhibitor of Apoptosis Protein Antagonists in Cancer Immunotherapy

Jessica Michie / Conor J. Kearney / Edwin D. Hawkins / John Silke / Jane Oliaro

Cells, Vol 9, Iss 1, p

2020 Volume 207

Abstract	One of the hallmarks of cancer cells is their ability to evade cell death via apoptosis. The inhibitor of apoptosis proteins (IAPs) are a family of proteins that act to promote cell survival. For this reason, upregulation of IAPs is associated with a number of cancer types as a mechanism of resistance to cell death and chemotherapy. As such, IAPs are considered a promising therapeutic target for cancer treatment, based on the role of IAPs in resistance to apoptosis, tumour progression and poor patient prognosis. The mitochondrial protein smac (second mitochondrial activator of caspases), is an endogenous inhibitor of IAPs, and several small molecule mimetics of smac (smac-mimetics) have been developed in order to antagonise IAPs in cancer cells and restore sensitivity to apoptotic stimuli. However, recent studies have revealed that smac-mimetics have broader effects than was first attributed. It is now understood that they are key regulators of innate immune signalling and have wide reaching immuno-modulatory properties. As such, they are ideal candidates for immunotherapy combinations. Pre-clinically, successful combination therapies incorporating smac-mimetics and oncolytic viruses, as with chimeric antigen receptor (CAR) T cell therapy, have been reported, and clinical trials incorporating smac-mimetics and immune checkpoint blockade are ongoing. Here, the potential of IAP antagonism to enhance immunotherapy strategies for the treatment of cancer will be discussed.
Keywords	smac-mimetics ; tnf ; cancer immunotherapy ; checkpoint blockade ; car t cells ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Regulatory T Cells Suppress Effector T Cell Proliferation by Limiting Division Destiny.

Dowling, Mark R / Kan, Andrey / Heinzel, Susanne / Marchingo, Julia M / Hodgkin, Philip D / Hawkins, Edwin D

Frontiers in immunology

2018 Volume 9, Page(s) 2461

Abstract: Understanding how the strength of an effector T cell response is regulated is a fundamental problem in immunology with implications for immunity to pathogens, autoimmunity, and immunotherapy. The initial magnitude of the T cell response is determined by ... ...

Abstract	Understanding how the strength of an effector T cell response is regulated is a fundamental problem in immunology with implications for immunity to pathogens, autoimmunity, and immunotherapy. The initial magnitude of the T cell response is determined by the sum of independent signals from antigen, co-stimulation and cytokines. By applying quantitative methods, the contribution of each signal to the number of divisions T cells undergo (division destiny) can be measured, and the resultant exponential increase in response magnitude accurately calculated. CD4
MeSH term(s)	Animals ; Cell Division/immunology ; Cells, Cultured ; Cytokines/immunology ; Homeostasis/immunology ; Lymphocyte Activation/immunology ; Mice ; Mice, Inbred C57BL ; Signal Transduction/immunology ; T-Lymphocytes, Regulatory/immunology
Chemical Substances	Cytokines
Language	English
Publishing date	2018-10-30
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.2018.02461
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Article ; Online: Cyton2: A Model of Immune Cell Population Dynamics That Includes Familial Instructional Inheritance.

Cheon, HoChan / Kan, Andrey / Prevedello, Giulio / Oostindie, Simone C / Dovedi, Simon J / Hawkins, Edwin D / Marchingo, Julia M / Heinzel, Susanne / Duffy, Ken R / Hodgkin, Philip D

Frontiers in bioinformatics

2021 Volume 1, Page(s) 723337

Abstract: Lymphocytes are the central actors in adaptive immune responses. When challenged with antigen, a small number of B and T cells have a cognate receptor capable of recognising and responding to the insult. These cells proliferate, building an exponentially ...

Abstract	Lymphocytes are the central actors in adaptive immune responses. When challenged with antigen, a small number of B and T cells have a cognate receptor capable of recognising and responding to the insult. These cells proliferate, building an exponentially growing, differentiating clone army to fight off the threat, before ceasing to divide and dying over a period of weeks, leaving in their wake memory cells that are primed to rapidly respond to any repeated infection. Due to the non-linearity of lymphocyte population dynamics, mathematical models are needed to interrogate data from experimental studies. Due to lack of evidence to the contrary and appealing to arguments based on Occam's Razor, in these models newly born progeny are typically assumed to behave independently of their predecessors. Recent experimental studies, however, challenge that assumption, making clear that there is substantial inheritance of timed fate changes from each cell by its offspring, calling for a revision to the existing mathematical modelling paradigms used for information extraction. By assessing long-term live-cell imaging of stimulated murine B and T cells
Language	English
Publishing date	2021-10-26
Publishing country	Switzerland
Document type	Journal Article
ISSN	2673-7647
ISSN (online)	2673-7647
DOI	10.3389/fbinf.2021.723337
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Article ; Online: Development and survival of MYC-driven lymphomas require the MYC antagonist MNT to curb MYC-induced apoptosis.

Nguyen, Hai Vu / Vandenberg, Cassandra J / Ng, Ashley P / Robati, Mikara R / Anstee, Natasha S / Rimes, Joel / Hawkins, Edwin D / Cory, Suzanne

Blood

2020 Volume 135, Issue 13, Page(s) 1019–1031

Abstract: Deregulated overexpression of MYC is implicated in the development and malignant progression of most (∼70%) human tumors. MYC drives cell growth and proliferation, but also, at high levels, promotes apoptosis. Here, we report that the proliferative ... ...

Abstract	Deregulated overexpression of MYC is implicated in the development and malignant progression of most (∼70%) human tumors. MYC drives cell growth and proliferation, but also, at high levels, promotes apoptosis. Here, we report that the proliferative capacity of MYC-driven normal and neoplastic B lymphoid cells depends on MNT, a MYC-related transcriptional repressor. Our genetic data establish that MNT synergizes with MYC by suppressing MYC-driven apoptosis, and that it does so primarily by reducing the level of pro-apoptotic BIM. In Eμ-Myc mice, which model the MYC/IGH chromosome translocation in Burkitt's lymphoma, homozygous Mnt deletion greatly reduced lymphoma incidence by enhancing apoptosis and markedly decreasing premalignant B lymphoid cell populations. Strikingly, by inducing Mnt deletion within transplanted fully malignant Eμ-Myc lymphoma cells, we significantly extended transplant recipient survival. The dependency of lymphomas on MNT for survival suggests that drugs inhibiting MNT could significantly boost therapy of MYC-driven tumors by enhancing intrinsic MYC-driven apoptosis.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Apoptosis/drug effects ; Apoptosis/genetics ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics ; Bone Marrow/metabolism ; Bone Marrow/pathology ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics ; Disease Models, Animal ; Gene Deletion ; Gene Expression Regulation, Neoplastic ; Humans ; Kaplan-Meier Estimate ; Lymphoma/drug therapy ; Lymphoma/genetics ; Lymphoma/mortality ; Lymphoma/pathology ; Lymphoma, B-Cell/genetics ; Mice ; Mice, Transgenic ; Proto-Oncogene Proteins c-myc/antagonists & inhibitors ; Proto-Oncogene Proteins c-myc/genetics ; Repressor Proteins/genetics ; Xenograft Model Antitumor Assays
Chemical Substances	Antineoplastic Agents ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Mnt protein, mouse ; Proto-Oncogene Proteins c-myc ; Repressor Proteins
Language	English
Publishing date	2020-01-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2019003014
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