scholarly journals Extrachromosomal DNA: An Emerging Hallmark in Human Cancer

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Sihan Wu ◽  
Vineet Bafna ◽  
Howard Y. Chang ◽  
Paul S. Mischel
Keyword(s):  
Human Cancer ◽  
Regulatory Elements ◽  
Annual Review ◽  
Publication Date ◽  
Cancer Evolution ◽  
Form And Function ◽  
Current State ◽  
Human Genes ◽  
Cancer Tumor ◽  
And Function

Human genes are arranged on 23 pairs of chromosomes, but in cancer, tumor-promoting genes and regulatory elements can free themselves from chromosomes and relocate to circular, extrachromosomal pieces of DNA (ecDNA). ecDNA, because of its nonchromosomal inheritance, drives high-copy-number oncogene amplification and enables tumors to evolve their genomes rapidly. Furthermore, the circular ecDNA architecture fundamentally alters gene regulation and transcription, and the higher-order organization of ecDNA contributes to tumor pathogenesis. Consequently, patients whose cancers harbor ecDNA have significantly shorter survival. Although ecDNA was first observed more than 50 years ago, its critical importance has only recently come to light. In this review, we discuss the current state of understanding of how ecDNAs form and function as well as how they contribute to drug resistance and accelerated cancer evolution. 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.

scholarly journals Mutant Allele Imbalance in Cancer

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Craig M. Bielski ◽  
Barry S. Taylor
Keyword(s):  
Cancer Biology ◽  
Mutant Allele ◽  
Tumor Biology ◽  
Cellular Level ◽  
Driver Mutations ◽  
Annual Review ◽  
Publication Date ◽  
Cancer Evolution ◽  
Allele Imbalance ◽  
And Function

The search for somatic mutations that drive the initiation and progression of human tumors has dominated recent cancer research. While much emphasis has been placed on characterizing the prevalence and function of driver mutations, comparatively less is known about their serial genetic evolution. Indeed, study of this phenomenon has largely focused on tumor-suppressor genes recessive at the cellular level or mechanisms of resistance in tumors with mutant oncogenes targeted by therapy. There is, however, a growing appreciation that despite a decades-old presumption of heterozygosity, changes in mutant oncogene zygosity are common and drive dosage and stoichiometry changes that lead to selective growth advantages. Here, we review the recent progress in understanding mutant allele imbalance and its implications for tumor biology, cancer evolution, and response to anticancer therapy. Expected final online publication date for the Annual Review of Cancer Biology, Volume 5 is March 4, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Biological Phase Separation and Biomolecular Condensates in Plants

2021 ◽  
Vol 72 (1) ◽  
Author(s):  
Ryan J. Emenecker ◽  
Alex S. Holehouse ◽  
Lucia C. Strader
Keyword(s):  
Phase Separation ◽  
Cell Biology ◽  
Condensed Matter ◽  
Annual Review ◽  
Publication Date ◽  
Nuclear Speckles ◽  
The Past ◽  
Shared Property ◽  
And Function ◽  
Physical Principles

A surge in research focused on understanding the physical principles governing the formation, properties, and function of membraneless compartments has occurred over the past decade. Compartments such as the nucleolus, stress granules, and nuclear speckles have been designated as biomolecular condensates to describe their shared property of spatially concentrating biomolecules. Although this research has historically been carried out in animal and fungal systems, recent work has begun to explore whether these same principles are relevant in plants. Effectively understanding and studying biomolecular condensates require interdisciplinary expertise that spans cell biology, biochemistry, and condensed matter physics and biophysics. As such, some involved concepts may be unfamiliar to any given individual. This review focuses on introducing concepts essential to the study of biomolecular condensates and phase separation for biologists seeking to carry out research in this area and further examines aspects of biomolecular condensates that are relevant to plant systems. 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.

The Psychology of Pandemics

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Steven Taylor
Keyword(s):  
Psychological Factors ◽  
Disease Outbreaks ◽  
Annual Review ◽  
Publication Date ◽  
Prolonged Grief ◽  
Psychological Phenomena ◽  
Current State ◽  
Health Authorities ◽  
Important Field ◽  
Mitigation Methods

This article reviews the current state of knowledge and promising new directions concerning the psychology of pandemics. Pandemics are disease outbreaks that spread globally. Historically, psychological factors have been neglected by researchers and health authorities despite evidence that pandemics are, to a large extent, psychological phenomena whereby beliefs and behaviors influence the spreading versus containment of infection. Psychological factors are important in determining ( a) adherence to pandemic mitigation methods (e.g., adherence to social distancing), ( b) pandemic-related social disruption (e.g., panic buying, racism, antilockdown protests), and ( c) pandemic-related distress and related problems (e.g., anxiety, depression, posttraumatic stress disorder, prolonged grief disorder). The psychology of pandemics has emerged as an important field of research and practice during the coronavirus 2019 (COVID-19) pandemic. As a scholarly discipline, the psychology of pandemics is fragmented and diverse, encompassing various psychological subspecialties and allied disciplines, but is vital for shaping clinical practice and public health guidelines for COVID-19 and future pandemics. Expected final online publication date for the Annual Review of Clinical Psychology, Volume 18 is May 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals A-Kinase Anchoring Protein 1: Emerging Roles in Regulating Mitochondrial Form and Function in Health and Disease

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 298 ◽  
Author(s):  
Yujia Liu ◽  
Ronald A. Merrill ◽  
Stefan Strack
Keyword(s):  
Cell Survival ◽  
Intracellular Signaling ◽  
Neuronal Cell ◽  
Supporting Cell ◽  
In Vivo Studies ◽  
Form And Function ◽  
Anchoring Protein ◽  
Cancer Tumor ◽  
And Function

Best known as the powerhouse of the cell, mitochondria have many other important functions such as buffering intracellular calcium and reactive oxygen species levels, initiating apoptosis and supporting cell proliferation and survival. Mitochondria are also dynamic organelles that are constantly undergoing fission and fusion to meet specific functional needs. These processes and functions are regulated by intracellular signaling at the mitochondria. A-kinase anchoring protein 1 (AKAP1) is a scaffold protein that recruits protein kinase A (PKA), other signaling proteins, as well as RNA to the outer mitochondrial membrane. Hence, AKAP1 can be considered a mitochondrial signaling hub. In this review, we discuss what is currently known about AKAP1′s function in health and diseases. We focus on the recent literature on AKAP1′s roles in metabolic homeostasis, cancer and cardiovascular and neurodegenerative diseases. In healthy tissues, AKAP1 has been shown to be important for driving mitochondrial respiration during exercise and for mitochondrial DNA replication and quality control. Several recent in vivo studies using AKAP1 knockout mice have elucidated the role of AKAP1 in supporting cardiovascular, lung and neuronal cell survival in the stressful post-ischemic environment. In addition, we discuss the unique involvement of AKAP1 in cancer tumor growth, metastasis and resistance to chemotherapy. Collectively, the data indicate that AKAP1 promotes cell survival throug regulating mitochondrial form and function. Lastly, we discuss the potential of targeting of AKAP1 for therapy of various disorders.

scholarly journals Critical Phenomena in Plasma Membrane Organization and Function

2020 ◽  
Vol 72 (1) ◽  
Author(s):  
Thomas R. Shaw ◽  
Subhadip Ghosh ◽  
Sarah L. Veatch
Keyword(s):  
Plasma Membrane ◽  
Critical Phenomena ◽  
Model Systems ◽  
Annual Review ◽  
Publication Date ◽  
Membrane Composition ◽  
Lipid Organization ◽  
And Function ◽  
Lateral Organization ◽  
Liquid Liquid Phase Separation

Lateral organization in the plane of the plasma membrane is an important driver of biological processes. The past dozen years have seen increasing experimental support for the notion that lipid organization plays an important role in modulating this heterogeneity. Various biophysical mechanisms rooted in the concept of liquid–liquid phase separation have been proposed to explain diverse experimental observations of heterogeneity in model and cell membranes with distinct but overlapping applicability. In this review, we focus on the evidence for and the consequences of the hypothesis that the plasma membrane is poised near an equilibrium miscibility critical point. Critical phenomena explain certain features of the heterogeneity observed in cells and model systems but also go beyond heterogeneity to predict other interesting phenomena, including responses to perturbations in membrane composition. Expected final online publication date for the Annual Review of Physical Chemistry, Volume 72 is April 20, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

A Balancing Act: p53 Activity from Tumor Suppression to Pathology and Therapeutic Implications

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Mengxiong Wang ◽  
Laura D. Attardi
Keyword(s):  
Tumor Suppression ◽  
Human Cancer ◽  
Suppressor Gene ◽  
Premature Aging ◽  
Annual Review ◽  
Publication Date ◽  
Cancer Therapies ◽  
Therapeutic Implications ◽  
Cycle Arrest ◽  
Stress Signals

TP53, encoding the p53 transcription factor, is the most frequently mutated tumor suppressor gene across all human cancer types. While p53 has long been appreciated to induce antiproliferative cell cycle arrest, apoptosis, and senescence programs in response to diverse stress signals, various studies in recent years have revealed additional important functions for p53 that likely also contribute to tumor suppression, including roles in regulating tumor metabolism, ferroptosis, signaling in the tumor microenvironment, and stem cell self-renewal/differentiation. Not only does p53 loss or mutation cause cancer, but hyperactive p53 also drives various pathologies, including developmental phenotypes, premature aging, neurodegeneration, and side effects of cancer therapies. These findings underscore the importance of balanced p53 activity and influence our thinking of how to best develop cancer therapies based on modulating the p53 pathway. 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.

Single-Cell Epigenomics Reveals Mechanisms of Cancer Progression

2022 ◽  
Vol 6 (1) ◽  
Author(s):  
Lindsay M. LaFave ◽  
Rachel Savage ◽  
Jason D. Buenrostro
Keyword(s):  
Single Cell ◽  
Cancer Progression ◽  
Cancer Biology ◽  
Annual Review ◽  
Publication Date ◽  
Cancer Evolution ◽  
Regulatory State ◽  
Cellular Functions ◽  
Cancer Initiation ◽  
Gene Regulatory

Cancer initiation is driven by the cooperation between genetic and epigenetic aberrations that disrupt gene regulatory programs critical to maintain specialized cellular functions. After initiation, cells acquire additional genetic and epigenetic alterations influenced by tumor-intrinsic and -extrinsic mechanisms, which increase intratumoral heterogeneity, reshape the cell's underlying gene regulatory network, and promote cancer evolution. Furthermore, environmental or therapeutic insults drive the selection of heterogeneous cell states, with implications for cancer initiation, maintenance, and drug resistance. The advancement of single-cell genomics has begun to uncover the full repertoire of chromatin and gene expression states (cell states) that exist within individual tumors. These single-cell analyses suggest that cells diversify in their regulatory states upon transformation by co-opting damage-induced and nonlineage regulatory programs that can lead to epigenomic plasticity. Here, we review these recent studies related to regulatory state changes in cancer progression and highlight the growing single-cell epigenomics toolkit poised to address unresolved questions in the field. Expected final online publication date for the Annual Review of Cancer Biology, Volume 6 is April 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

New Advances and Applications in Field-Flow Fractionation

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Christine L. Plavchak ◽  
William C. Smith ◽  
Carmen R.M. Bria ◽  
S. Kim Ratanathanawongs Williams
Keyword(s):  
Food Systems ◽  
Coming Of Age ◽  
Size Composition ◽  
Annual Review ◽  
Publication Date ◽  
Field Flow Fractionation ◽  
Multiple Components ◽  
Flow Fractionation ◽  
And Function ◽  
Size Scales

Field-flow fractionation (FFF) is a family of techniques that was created especially for separating and characterizing macromolecules, nanoparticles, and micrometer-sized analytes. It is coming of age as new nanomaterials, polymers, composites, and biohybrids with remarkable properties are introduced and new analytical challenges arise due to synthesis heterogeneities and the motivation to correlate analyte properties with observed performance. Appreciation of the complexity of biological, pharmaceutical, and food systems and the need to monitor multiple components across many size scales have also contributed to FFF's growth. This review highlights recent advances in FFF capabilities, instrumentation, and applications that feature the unique characteristics of different FFF techniques in determining a variety of information, such as averages and distributions in size, composition, shape, architecture, and microstructure and in investigating transformations and function. Expected final online publication date for the Annual Review of Analytical Chemistry, Volume 14 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Native Mass Spectrometry: Recent Progress and Remaining Challenges

2022 ◽  
Vol 51 (1) ◽  
Author(s):  
Kelly R. Karch ◽  
Dalton T. Snyder ◽  
Sophie R. Harvey ◽  
Vicki H. Wysocki
Keyword(s):  
Mass Spectrometry ◽  
Gas Phase ◽  
Structural Biology ◽  
Recent Progress ◽  
Native Mass Spectrometry ◽  
Structure And Function ◽  
Annual Review ◽  
Publication Date ◽  
Analysis Software ◽  
And Function

Native mass spectrometry (nMS) has emerged as an important tool in studying the structure and function of macromolecules and their complexes in the gas phase. In this review, we cover recent advances in nMS and related techniques including sample preparation, instrumentation, activation methods, and data analysis software. These advances have enabled nMS-based techniques to address a variety of challenging questions in structural biology. The second half of this review highlights recent applications of these technologies and surveys the classes of complexes that can be studied with nMS. Complementarity of nMS to existing structural biology techniques and current challenges in nMS are also addressed. Expected final online publication date for the Annual Review of Biophysics, Volume 51 is May 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Dendritic Cell Regulation of T Helper Cells

2021 ◽  
Vol 39 (1) ◽  
Author(s):  
Xiangyun Yin ◽  
Shuting Chen ◽  
Stephanie C. Eisenbarth
Keyword(s):  
Cell Differentiation ◽  
T Regulatory Cells ◽  
Adaptive Immune Response ◽  
Annual Review ◽  
Publication Date ◽  
T Helper ◽  
Follicular Helper ◽  
Th Cell ◽  
And Function ◽  
Antigen Presenting

As the professional antigen-presenting cells of the immune system, dendritic cells (DCs) sense the microenvironment and shape the ensuing adaptive immune response. DCs can induce both immune activation and immune tolerance according to the peripheral cues. Recent work has established that DCs comprise of several phenotypically and functionally heterogeneous subsets that differentially regulate T lymphocyte differentiation. This review summarizes both mouse and human DC subset phenotypes, development, diversification, and function. We focus on advances in our understanding of how different DC subsets regulate distinct CD4+ T helper (Th) cell differentiation, including Th1, Th2, Th17, T follicular helper, and T regulatory cells. We review DC subset intrinsic properties, local tissue microenvironments, and other immune cells that together determine Th cell differentiation during homeostasis and inflammation. Expected final online publication date for the Annual Review of Immunology, Volume 39 is April 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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