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Article ; Online: Surviving without BRCA2: MLH1 gets R-looped in to curtail genomic instability.

Johnson, Neil

2024 Volume 134, Issue 7

Abstract: While breast cancer 2 (BRCA2) loss of heterozygosity (LOH) promotes cancer initiation, it can also induce death in nontransformed cells. In contrast, mismatch repair gene mutL homolog 1 (MLH1) is a tumor-suppressor gene that protects cells from cancer ... ...

Abstract	While breast cancer 2 (BRCA2) loss of heterozygosity (LOH) promotes cancer initiation, it can also induce death in nontransformed cells. In contrast, mismatch repair gene mutL homolog 1 (MLH1) is a tumor-suppressor gene that protects cells from cancer development through repairing mismatched base pairs during DNA mismatch repair (MMR). Sengodan et al., in this issue of the JCI, reveal an interplay between the 2 genes: MLH1 promoted the survival of BRCA2-deficient cells independently of its MMR function. MLH1 protected replication forks from degradation, while also resolving R-loops, thereby reducing genomic instability. Moreover, MLH1 expression was regulated directly by estrogen, shedding light into the hormone-responsive nature of many BRCA2 mutant breast cancers. These results provide important insight into the genetics that drive the initiation of BRCA2-mutated breast cancers.
MeSH term(s)	Humans ; Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; BRCA2 Protein/genetics ; BRCA2 Protein/metabolism ; Genomic Instability ; MutL Protein Homolog 1/genetics ; MutL Protein Homolog 1/metabolism ; MutS Homolog 2 Protein/genetics ; MutS Homolog 2 Protein/metabolism ; Neoplasms/genetics ; Neoplasms/metabolism ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism
Chemical Substances	Adaptor Proteins, Signal Transducing ; BRCA2 Protein ; BRCA2 protein, human ; MLH1 protein, human ; MutL Protein Homolog 1 (EC 3.6.1.3) ; MutS Homolog 2 Protein (EC 3.6.1.3) ; Nuclear Proteins
Language	English
Publishing date	2024-04-01
Publishing country	United States
Document type	Journal Article ; News
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI179325
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Article ; Online: Researching online communities of inquiry through digital ethnography

Johnson Neil

SHS Web of Conferences, Vol 102, p

2021 Volume 01006

Abstract: Research into providing effective online education has suggested an important goal for instructors is the creation of an online community of inquiry (CoI) where social, cognitive, and teacher presence are all important aspects of successful online ... ...

Abstract	Research into providing effective online education has suggested an important goal for instructors is the creation of an online community of inquiry (CoI) where social, cognitive, and teacher presence are all important aspects of successful online learning. With reference to a recent reflective practice case study, this paper describes ways that the research on online communities of inquiry may be enriched through the use of digital ethnography. In the target reflective case study, data analysis tasks were designed and presented in an online VoiceThread site, promoting dialogic and multimodal engagement with data from actual research studies that are central to the module theme in teacher education. Interaction around these tasks is coded using the CoI framework. Ethnographic data from the participants was collected and coded using qualitative research protocols to contextualise the interaction data and provide a clearer understanding of how participants had come together throughout the module. The ethnographic data revealed some interesting concerns with online learning, including the use of technology as a barrier to participation.
Keywords	Social Sciences ; H
Subject code	028
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	EDP Sciences
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Nonlinear spreading behavior across multi-platform social media universe.

Xia, Chenkai / Johnson, Neil F

Chaos (Woodbury, N.Y.)

2024 Volume 34, Issue 4

Abstract: Understanding how harmful content (mis/disinformation, hate, etc.) manages to spread among online communities within and across social media platforms represents an urgent societal challenge. We develop a non-linear dynamical model for such viral ... ...

Abstract	Understanding how harmful content (mis/disinformation, hate, etc.) manages to spread among online communities within and across social media platforms represents an urgent societal challenge. We develop a non-linear dynamical model for such viral spreading, which accounts for the fact that online communities dynamically interconnect across multiple social media platforms. Our mean-field theory (Effective Medium Theory) compares well to detailed numerical simulations and provides a specific analytic condition for the onset of outbreaks (i.e., system-wide spreading). Even if the infection rate is significantly lower than the recovery rate, it predicts system-wide spreading if online communities create links between them at high rates and the loss of such links (e.g., due to moderator pressure) is low. Policymakers should, therefore, account for these multi-community dynamics when shaping policies against system-wide spreading.
Language	English
Publishing date	2024-04-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	1472677-4
ISSN	1089-7682 ; 1054-1500
ISSN (online)	1089-7682
ISSN	1054-1500
DOI	10.1063/5.0199655
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Controlling bad-actor-artificial intelligence activity at scale across online battlefields.

Johnson, Neil F / Sear, Richard / Illari, Lucia

PNAS nexus

2024 Volume 3, Issue 1, Page(s) pgae004

Abstract: We consider the looming threat of bad actors using artificial intelligence (AI)/Generative Pretrained Transformer to generate harms across social media globally. Guided by our detailed mapping of the online multiplatform battlefield, we offer answers to ... ...

Abstract	We consider the looming threat of bad actors using artificial intelligence (AI)/Generative Pretrained Transformer to generate harms across social media globally. Guided by our detailed mapping of the online multiplatform battlefield, we offer answers to the key questions of what bad-actor-AI activity will likely dominate, where, when-and what might be done to control it at scale. Applying a dynamical Red Queen analysis from prior studies of cyber and automated algorithm attacks, predicts an escalation to daily bad-actor-AI activity by mid-2024-just ahead of United States and other global elections. We then use an exactly solvable mathematical model of the observed bad-actor community clustering dynamics, to build a Policy Matrix which quantifies the outcomes and trade-offs between two potentially desirable outcomes: containment of future bad-actor-AI activity vs. its complete removal. We also give explicit plug-and-play formulae for associated risk measures.
Language	English
Publishing date	2024-01-23
Publishing country	England
Document type	Journal Article
ISSN	2752-6542
ISSN (online)	2752-6542
DOI	10.1093/pnasnexus/pgae004
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Article ; Online: Inhalation Toxicity of Talc.

Johnson, Neil F

Journal of aerosol medicine and pulmonary drug delivery

2020 Volume 34, Issue 2, Page(s) 79–107

Abstract: Respirable talc powder (RTP) is a complex mineral mixture of talc along with accessory minerals, including tremolite, anthophyllite, quartz, magnesite, dolomite, antigorite, lizardite, and chlorite. The industrial mining, milling, and processing of talc ... ...

Abstract	Respirable talc powder (RTP) is a complex mineral mixture of talc along with accessory minerals, including tremolite, anthophyllite, quartz, magnesite, dolomite, antigorite, lizardite, and chlorite. The industrial mining, milling, and processing of talc ore is associated with elevated incidences of fibrotic and neoplastic diseases, which are also seen among workers exposed to RTP in secondary industries and individuals using processed cosmetic talc for personal use. There is controversial evidence of a link between the talc-induced lung diseases and a potential contamination with asbestos fibers. This controversy is fueled by inadequate exposure data and the complex mineralogy and terminology of the accessory minerals. Talc aerosols exhibit a wide range of mineral habits, including particulates and fibrous structures that have dimensional and compositional characteristics related to the development of asbestos-related lung disease. The inhalation toxicology of RTP is based on the analysis of occupational hygiene and animal inhalation studies conducted between the 1940s and the 1990s and more recent mechanistic studies conducted both
MeSH term(s)	Administration, Inhalation ; Animals ; Carcinogens ; Humans ; Lung ; Lung Neoplasms ; Talc/toxicity
Chemical Substances	Carcinogens ; Talc (14807-96-6)
Language	English
Publishing date	2020-08-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2417924-3
ISSN	1941-2703 ; 1941-2711
ISSN (online)	1941-2703
ISSN	1941-2711
DOI	10.1089/jamp.2020.1609
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Article ; Online: Explaining conflict violence in terms of conflict actor dynamics.

Tkacova, Katerina / Idler, Annette / Johnson, Neil / López, Eduardo

Scientific reports

2023 Volume 13, Issue 1, Page(s) 21187

Abstract: We study the severity of conflict-related violence in Colombia at an unprecedented granular scale in space and across time. Splitting the data into different geographical regions and different historically-relevant periods, we uncover variations in the ... ...

Abstract	We study the severity of conflict-related violence in Colombia at an unprecedented granular scale in space and across time. Splitting the data into different geographical regions and different historically-relevant periods, we uncover variations in the patterns of conflict severity which we then explain in terms of local conflict actors' different collective behaviors and/or conditions using a simple mathematical model of conflict actors' grouping dynamics (coalescence and fragmentation). Specifically, variations in the approximate scaling values of the distributions of event lethalities can be explained by the changing strength ratio of the local conflict actors for distinct conflict eras and organizational regions. In this way, our findings open the door to a new granular spectroscopy of human conflicts in terms of local conflict actor strength ratios for any armed conflict.
MeSH term(s)	Humans ; Violence ; Colombia ; Group Dynamics
Language	English
Publishing date	2023-12-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-48218-x
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Article ; Online: Rise of post-pandemic resilience across the distrust ecosystem.

Illari, Lucia / Restrepo, Nicholas J / Johnson, Neil F

Scientific reports

2023 Volume 13, Issue 1, Page(s) 15640

Abstract: Why does online distrust (e.g., of medical expertise) continue to grow despite numerous mitigation efforts? We analyzed changing discourse within a Facebook ecosystem of approximately 100 million users who were focused pre-pandemic on vaccine (dis)trust. ...

Abstract	Why does online distrust (e.g., of medical expertise) continue to grow despite numerous mitigation efforts? We analyzed changing discourse within a Facebook ecosystem of approximately 100 million users who were focused pre-pandemic on vaccine (dis)trust. Post-pandemic, their discourse interconnected multiple non-vaccine topics and geographic scales within and across communities. This interconnection confers a unique, system-level (i.e., at the scale of the full network) resistance to mitigations targeting isolated topics or geographic scales-an approach many schemes take due to constrained funding. For example, focusing on local health issues but not national elections. Backed by numerical simulations, we propose counterintuitive solutions for more effective, scalable mitigation: utilize "glocal" messaging by blending (1) strategic topic combinations (e.g., messaging about specific diseases with climate change) and (2) geographic scales (e.g., combining local and national focuses).
MeSH term(s)	Humans ; Ecosystem ; Pandemics ; Climate Change ; Trust
Language	English
Publishing date	2023-09-20
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-42893-6
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Article ; Online: Inductive detection of influence operations via graph learning.

Gabriel, Nicholas A / Broniatowski, David A / Johnson, Neil F

Scientific reports

2023 Volume 13, Issue 1, Page(s) 22571

Abstract: Influence operations are large-scale efforts to manipulate public opinion. The rapid detection and disruption of these operations is critical for healthy public discourse. Emergent AI technologies may enable novel operations that evade detection and ... ...

Abstract	Influence operations are large-scale efforts to manipulate public opinion. The rapid detection and disruption of these operations is critical for healthy public discourse. Emergent AI technologies may enable novel operations that evade detection and influence public discourse on social media with greater scale, reach, and specificity. New methods of detection with inductive learning capacity will be needed to identify novel operations before they indelibly alter public opinion and events. To this end, we develop an inductive learning framework that: (1) determines content- and graph-based indicators that are not specific to any operation; (2) uses graph learning to encode abstract signatures of coordinated manipulation; and (3) evaluates generalization capacity by training and testing models across operations originating from Russia, China, and Iran. We find that this framework enables strong cross-operation generalization while also revealing salient indicators-illustrating a generic approach which directly complements transductive methodologies, thereby enhancing detection coverage.
Language	English
Publishing date	2023-12-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-49676-z
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Article ; Online: Brca1 Mouse Models: Functional Insights and Therapeutic Opportunities.

Yueh, Wei-Ting / Glass, David J / Johnson, Neil

Journal of molecular biology

2023 Volume 436, Issue 1, Page(s) 168372

Abstract: Brca1 mouse models were first reported in the mid-1990's shortly after cloning the human gene. Since then, many mouse models with a range of mutations have been generated, some mimic patient mutations, others are designed to probe specific protein ... ...

Abstract	Brca1 mouse models were first reported in the mid-1990's shortly after cloning the human gene. Since then, many mouse models with a range of mutations have been generated, some mimic patient mutations, others are designed to probe specific protein domains and functions. In this review, we discuss early and recent studies using engineered Brca1 mouse alleles, and their implications for understanding Brca1 protein function in the context of DNA repair, tumorigenesis, and anti-cancer therapeutics.
MeSH term(s)	Animals ; Humans ; Mice ; BRCA1 Protein/genetics ; BRCA1 Protein/metabolism ; DNA Repair ; Mutation ; Neoplasms, Experimental/drug therapy ; Neoplasms, Experimental/genetics
Chemical Substances	BRCA1 Protein
Language	English
Publishing date	2023-11-17
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	80229-3
ISSN	1089-8638 ; 0022-2836
ISSN (online)	1089-8638
ISSN	0022-2836
DOI	10.1016/j.jmb.2023.168372
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Zs.A 867: Show issues

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Book ; Online: Unprecedented reach and rich online journeys drive hate and extremism globally

Sear, Richard / Johnson, Neil F.

2023

Abstract: Hate and extremism cannot be controlled globally without understanding how they operate at scale. Both have escalated dramatically during the Israel-Hamas and Ukraine-Russia wars. Here we show how the online hate-extremism system is now operating at ... ...

Abstract	Hate and extremism cannot be controlled globally without understanding how they operate at scale. Both have escalated dramatically during the Israel-Hamas and Ukraine-Russia wars. Here we show how the online hate-extremism system is now operating at unprecedented scale across 26 social media platforms of all sizes, audience demographics, and geographic locations; and we analyze individuals' journeys through it. This new picture contradicts notions of rabbit-hole activity at the fringe of the Internet. Instead, it shows that hate-extremism support now enjoys a direct link to more than a billion of the general global population, and that newcomers now enjoy a rich variety of online journey experiences during which they get to mingle with experienced violent actors, discuss topics from diverse news sources, and learn to collectively adapt in order to bypass platform shutdowns. Our results mean that law enforcement must expect future mass shooters to have increasingly hard-to-understand online journeys; that new E.U. laws will fall short because the combined impact of many smaller, lesser-known platforms outstrips larger ones like Twitter; and that the current global hate-extremism infrastructure will become increasingly robust in 2024 and beyond. Fortunately, it also reveals a new opportunity for system-wide control akin to adaptive vs. extinction treatments for cancer.
Keywords	Computer Science - Social and Information Networks ; Computer Science - Human-Computer Interaction ; Nonlinear Sciences - Adaptation and Self-Organizing Systems ; Physics - Physics and Society
Subject code	303
Publishing date	2023-11-14
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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