A Tale of Two Checkpoints: ATR Inhibition and PD-(L)1 Blockade

2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Natalie Y.L. Ngoi ◽  
Guang Peng ◽  
Timothy A. Yap
Keyword(s):  
Ataxia Telangiectasia ◽  
Innate Immune ◽  
Annual Review ◽  
Publication Date ◽  
Checkpoint Activation ◽  
Cycle Arrest ◽  
Specific Effects ◽  
Damage Response ◽  
Shed Light

Innate immunity and the DNA damage response (DDR) pathway are inextricably linked. Within the DDR, ataxia telangiectasia and Rad3-related (ATR) is a key kinase responsible for sensing replication stress and facilitating DNA repair through checkpoint activation, cell cycle arrest, and promotion of fork recovery. Recent studies have shed light on the immunomodulatory role of the ATR-CHK1 pathway in the tumor microenvironment and the specific effects of ATR inhibition in stimulating an innate immune response. With several potent and selective ATR inhibitors in developmental pipelines, the combination of dual ATR and PD-(L)1 blockade has attracted increasing interest in cancer therapy. In this review, we summarize the clinical and preclinical data supporting the combined inhibition of ATR and PD-(L)1, discuss the potential challenges surrounding this approach, and highlight biomarkers relevant for selected patients who are most likely to benefit from the blockade of these two checkpoints. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals On Broken Ne(c)ks and Broken DNA: The Role of Human NEKs in the DNA Damage Response

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 507
Author(s):  
Isadora Carolina Betim Pavan ◽  
Andressa Peres de Oliveira ◽  
Pedro Rafael Firmino Dias ◽  
Fernanda Luisa Basei ◽  
Luidy Kazuo Issayama ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Dna Damage Response ◽  
Ataxia Telangiectasia ◽  
General Role ◽  
Cycle Arrest ◽  
Damage Response ◽  
Repair Pathways

NIMA-related kinases, or NEKs, are a family of Ser/Thr protein kinases involved in cell cycle and mitosis, centrosome disjunction, primary cilia functions, and DNA damage responses among other biological functional contexts in vertebrate cells. In human cells, there are 11 members, termed NEK1 to 11, and the research has mainly focused on exploring the more predominant roles of NEKs in mitosis regulation and cell cycle. A possible important role of NEKs in DNA damage response (DDR) first emerged for NEK1, but recent studies for most NEKs showed participation in DDR. A detailed analysis of the protein interactions, phosphorylation events, and studies of functional aspects of NEKs from the literature led us to propose a more general role of NEKs in DDR. In this review, we express that NEK1 is an activator of ataxia telangiectasia and Rad3-related (ATR), and its activation results in cell cycle arrest, guaranteeing DNA repair while activating specific repair pathways such as homology repair (HR) and DNA double-strand break (DSB) repair. For NEK2, 6, 8, 9, and 11, we found a role downstream of ATR and ataxia telangiectasia mutated (ATM) that results in cell cycle arrest, but details of possible activated repair pathways are still being investigated. NEK4 shows a connection to the regulation of the nonhomologous end-joining (NHEJ) repair of DNA DSBs, through recruitment of DNA-PK to DNA damage foci. NEK5 interacts with topoisomerase IIβ, and its knockdown results in the accumulation of damaged DNA. NEK7 has a regulatory role in the detection of oxidative damage to telomeric DNA. Finally, NEK10 has recently been shown to phosphorylate p53 at Y327, promoting cell cycle arrest after exposure to DNA damaging agents. In summary, this review highlights important discoveries of the ever-growing involvement of NEK kinases in the DDR pathways. A better understanding of these roles may open new diagnostic possibilities or pharmaceutical interventions regarding the chemo-sensitizing inhibition of NEKs in various forms of cancer and other diseases.

New Directions in the Study of Institutional Logics: From Tools to Phenomena

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Michael Lounsbury ◽  
Christopher W.J. Steele ◽  
Milo Shaoqing Wang ◽  
Madeline Toubiana
Keyword(s):  
Recent Work ◽  
Online Publication ◽  
Institutional Logics ◽  
Annual Review ◽  
Publication Date ◽  
Complex Dynamic ◽  
New Directions ◽  
Analytical Tools ◽  
Dynamic Phenomena

In this article, we take stock of the institutional logics perspective and highlight opportunities for new scholarship. While we celebrate the growth and generativity of the literature on institutional logics, we also note that there has been a troubling tendency in recent work to use logics as analytical tools, feeding disquiet about reification and reductionism. Seeding a broader scholarly agenda that addresses such weaknesses in the literature, we highlight nascent efforts that aim to more systematically understand institutional logics as complex, dynamic phenomena in their own right. In doing so, we argue for more research that probes how logics cohere and endure by unpacking the role of values, the centrality of practice, and the governance dynamics of institutional logics and their orders. Furthermore, we encourage bridging the study of institutional logics with various literatures, including ethnomethodology, phenomenology, professions, elites, world society, and the old institutionalism, to enhance progress in these directions. Expected final online publication date for the Annual Review of Sociology, Volume 47 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The Role of Citizen Science in Promoting Health Equity

2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Lisa G. Rosas ◽  
Patricia Rodriguez Espinosa ◽  
Felipe Montes Jimenez ◽  
Abby C. King
Keyword(s):  
Public Health ◽  
Citizen Science ◽  
Health Equity ◽  
Healthy Eating ◽  
Mobile Applications ◽  
Health Inequities ◽  
Annual Review ◽  
Publication Date ◽  
Scientific Process

While there are many definitions of citizen science, the term usually refers to the participation of the general public in the scientific process in collaboration with professional scientists. Citizen scientists have been engaged to promote health equity, especially in the areas of environmental contaminant exposures, physical activity, and healthy eating. Citizen scientists commonly come from communities experiencing health inequities and have collected data using a range of strategies and technologies, such as air sensors, water quality kits, and mobile applications. On the basis of our review, and to advance the field of citizen science to address health equity, we recommend ( a) expanding the focus on topics important for health equity, ( b) increasing the diversity of people serving as citizen scientists, ( c) increasing the integration of citizen scientists in additional research phases, ( d) continuing to leverage emerging technologies that enable citizen scientists to collect data relevant for health equity, and ( e) strengthening the rigor of methods to evaluate impacts on health equity. Expected final online publication date for the Annual Review of Public Health, Volume 43 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Recent Research on the Archaeology of War and Violence

2021 ◽  
Vol 50 (1) ◽  
Author(s):  
Andrew K. Scherer
Keyword(s):  
State Formation ◽  
Online Publication ◽  
General Trend ◽  
Annual Review ◽  
Publication Date ◽  
Modern Times ◽  
The Past ◽  
Definition Of ◽  
Consequences Of Violence

The mid-1990s through the first decade of the new millennium marked an increase in publications pertaining to war and violence in the ancient past. This review considers how scholars of the past decade have responded to that work. The emerging consensus is that war and violence were endemic to all societies studied by archaeologists, and yet the frequency, intensity, causes, and consequences of violence were highly variable for reasons that defy simplistic explanation. The general trend has been toward archaeologies of war and violence that focus on understanding the nuances of particular places and historical moments. Nevertheless, archaeologists continue to grapple with grand narratives of war, such as the proposition that violence has decreased from ancient to modern times and the role of war and violence in state formation and collapse. Recent research also draws attention to a more expansive definition of violence. Expected final online publication date for the Annual Review of Anthropology, Volume 50 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

The Role of the Medial Prefrontal Cortex in Moderating Neural Representations of Self and Other in Primates

2021 ◽  
Vol 44 (1) ◽  
Author(s):  
Masaki Isoda
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Critical Role ◽  
Autism Spectrum ◽  
Annual Review ◽  
Publication Date ◽  
Self And Other ◽  
Neural Representations ◽  
The Social

As a frontal node in the primate social brain, the medial prefrontal cortex (MPFC) plays a critical role in coordinating one's own behavior with respect to that of others. Current literature demonstrates that single neurons in the MPFC encode behavior-related variables such as intentions, actions, and rewards, specifically for self and other, and that the MPFC comes into play when reflecting upon oneself and others. The social moderator account of MPFC function can explain maladaptive social cognition in people with autism spectrum disorder, which tips the balance in favor of self-centered perspectives rather than taking into consideration the perspective of others. Several strands of evidence suggest a hypothesis that the MPFC represents different other mental models, depending on the context at hand, to better predict others’ emotions and behaviors. This hypothesis also accounts for aberrant MPFC activity in autistic individuals while they are mentalizing others. Expected final online publication date for the Annual Review of Neuroscience, Volume 44 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Constructed Languages

2021 ◽  
Vol 50 (1) ◽  
Author(s):  
Christine Schreyer
Keyword(s):  
Community Of Practice ◽  
Real World ◽  
Annual Review ◽  
Endangered Languages ◽  
Publication Date ◽  
Speech Community ◽  
New Directions ◽  
University Classrooms ◽  
The Relationship

Constructed languages, also known as conlangs, are languages that have been purposefully created for either real-world or fictional speakers. Within this article, I provide a summary of the language creation process and how the community of conlangers, people who make languages, come to know each other's work, as well as how language creation assignments are being adopted within university classrooms. I also explore the role of the language creator in bringing a community of speakers into existence through the invention of a language. I discuss whether speakers of a constructed language are part of a community of practice or a speech community and the implications for this distinction within anthropology. I also describe conscripts, or constructed orthographies, as well as the relationship between endangered languages and constructed languages, how invented worlds can create real-world shifts in worldview, and suggestions for new directions in research linking anthropology and constructed languages. Expected final online publication date for the Annual Review of Anthropology, Volume 50 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

A Comparative Overview of the Intracellular Guardians of Plants and Animals: NLRs in Innate Immunity and Beyond

2021 ◽  
Vol 72 (1) ◽  
Author(s):  
Zane Duxbury ◽  
Chih-hang Wu ◽  
Pingtao Ding
Keyword(s):  
Immune Responses ◽  
Genetic Architecture ◽  
Pathogen Detection ◽  
Current Knowledge ◽  
Plant Immunity ◽  
Innate Immune ◽  
Plant Biology ◽  
Annual Review ◽  
Publication Date ◽  
Nucleotide Binding Domain

Nucleotide-binding domain leucine-rich repeat receptors (NLRs) play important roles in the innate immune systems of both plants and animals. Recent breakthroughs in NLR biochemistry and biophysics have revolutionized our understanding of how NLR proteins function in plant immunity. In this review, we summarize the latest findings in plant NLR biology and draw direct comparisons to NLRs of animals. We discuss different mechanisms by which NLRs recognize their ligands in plants and animals. The discovery of plant NLR resistosomes that assemble in a comparable way to animal inflammasomes reinforces the striking similarities between the formation of plant and animal NLR complexes. Furthermore, we discuss the mechanisms by which plant NLRs mediate immune responses and draw comparisons to similar mechanisms identified in animals. Finally, we summarize the current knowledge of the complex genetic architecture formed by NLRs in plants and animals and the roles of NLRs beyond pathogen detection. Expected final online publication date for the Annual Review of Plant Biology, Volume 72 is May 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Role of the Inflammasome in Liver Disease

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Marcelle de Carvalho Ribeiro ◽  
Gyongyi Szabo
Keyword(s):  
Liver Disease ◽  
Liver Diseases ◽  
Annual Review ◽  
Publication Date ◽  
Inflammasome Activation ◽  
Proinflammatory Response ◽  
Nonalcoholic Fatty Liver ◽  
Pyrin Domain ◽  
Different Types

The involvement of inflammasomes in the proinflammatory response observed in chronic liver diseases, such as alcohol-associated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD), is widely recognized. Although there are different types of inflammasomes, most studies to date have given attention to NLRP3 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3) in the pathogenesis of ALD, NAFLD/nonalcoholic steatohepatitis, and fibrosis. Canonical inflammasomes are intracellular multiprotein complexes that are assembled after the sensing of danger signals and activate caspase-1, which matures interleukin (IL)-1β, IL-18, and IL-37 and also induces a form of cell death called pyroptosis. Noncanonical inflammasomes activate caspase-11 to induce pyroptosis. We discuss the different types of inflammasomes involved in liver diseases with a focus on ( a) signals and mechanisms of inflammasome activation, ( b) the role of different types of inflammasomes and their products in the pathogenesis of liver diseases, and ( c) potential therapeutic strategies targeting components of the inflammasomes or cytokines produced upon inflammasome activation. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Information and Communications Technology (ICT) and Agricultural Extension in Developing Countries

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
David Spielman ◽  
Els Lecoutere ◽  
Simrin Makhija ◽  
Bjorn Van Campenhout
Keyword(s):  
Developing Countries ◽  
Agricultural Extension ◽  
Information And Communications Technology ◽  
Annual Review ◽  
Publication Date ◽  
Communications Technology ◽  
Impact Pathways ◽  
Methodological Rigor ◽  
Multiple Impact

With new possibilities offered by information and communications technology (ICT), an abundance of products, services, and projects has emerged with the promise of revitalizing agricultural extension in developing countries. However, a growing body of evidence suggests that not all ICT-enabled extension approaches are equally effective in improving adoption, productivity, income, or welfare outcomes. In this review, we explore various conceptual and methodological threads in the literature on ICT-enabled extension in developing countries. We examine the role of multiple impact pathways, highlighting how ICTs influence behaviors and preferences, gender and intrahousehold dynamics, spillovers, and public worker incentives. We also explore the opportunities presented by ICT-enabled extension for increasing the methodological rigor with which extension outcomes are identified. These conceptual and methodological insights—coupled with empirical evidence from prior studies—offer direction for several lines of policy-relevant research on ICT-enabled extension. Expected final online publication date for the Annual Review of Resource Economics, Volume 13 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

53BP1: function and mechanisms of focal recruitment

2009 ◽  
Vol 37 (4) ◽  
pp. 897-904 ◽  
Author(s):  
Jennifer E. FitzGerald ◽  
Muriel Grenon ◽  
Noel F. Lowndes
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Dna Damage Response ◽  
Dna Damage Checkpoint ◽  
Checkpoint Activation ◽  
Damage Response ◽  
Nuclear Structures ◽  
Genotoxic Insult ◽  
Covalent Histone Modifications

53BP1 (p53-binding protein 1) is classified as a mediator/adaptor of the DNA-damage response, and is recruited to nuclear structures termed foci following genotoxic insult. In the present paper, we review the functions of 53BP1 in DNA-damage checkpoint activation and DNA repair, and the mechanisms of its recruitment and activation following DNA damage. We focus in particular on the role of covalent histone modifications in this process.

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