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Pathogenic Mechanisms Underlying Idiopathic Pulmonary Fibrosis Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Benjamin J. Moss, Stefan W. Ryter, Ivan O. Rosas
The pathogenesis of idiopathic pulmonary fibrosis (IPF) involves a complex interplay of cell types and signaling pathways. Recurrent alveolar epithelial cell (AEC) injury may occur in the context of predisposing factors (e.g., genetic, environmental, epigenetic, immunologic, and gerontologic), leading to metabolic dysfunction, senescence, aberrant epithelial cell activation, and dysregulated epithelial
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Engineering β Cell Replacement Therapies for Type 1 Diabetes: Biomaterial Advances and Considerations for Macroscale Constructs Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Michelle J. Quizon, Andrés J. García
While significant progress has been made in treatments for type 1 diabetes (T1D) based on exogenous insulin, transplantation of insulin-producing cells (islets or stem cell–derived β cells) remains a promising curative strategy. The current paradigm for T1D cell therapy is clinical islet transplantation (CIT)—the infusion of islets into the liver—although this therapeutic modality comes with its own
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Lysophospholipid Mediators in Health and Disease Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Kuniyuki Kano, Junken Aoki, Timothy Hla
Lysophospholipids, exemplified by lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), are produced by the metabolism and perturbation of biological membranes. Both molecules are established extracellular lipid mediators that signal via specific G protein–coupled receptors in vertebrates. This widespread signaling axis regulates the development, physiological functions, and pathological processes
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Innate Immunity and Cancer Pathophysiology Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Laura Maiorino, Juliane Daßler-Plenker, Lijuan Sun, Mikala Egeblad
Chronic inflammation increases the risk of several cancers, including gastric, colon, and hepatic cancers. Conversely, tumors, similar to tissue injury, trigger an inflammatory response coordinated by the innate immune system. Cellular and molecular mediators of inflammation modulate tumor growth directly and by influencing the adaptive immune response. Depending on the balance of immune cell types
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Multiplexed Ion Beam Imaging: Insights into Pathobiology Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Candace C. Liu, Erin F. McCaffrey, Noah F. Greenwald, Erin Soon, Tyler Risom, Kausalia Vijayaragavan, John-Paul Oliveria, Dunja Mrdjen, Marc Bosse, Dmitry Tebaykin, Sean C. Bendall, Michael Angelo
Next-generation tools for multiplexed imaging have driven a new wave of innovation in understanding how single-cell function and tissue structure are interrelated. In previous work, we developed multiplexed ion beam imaging by time of flight, a highly multiplexed platform that uses secondary ion mass spectrometry to image dozens of antibodies tagged with metal reporters. As instrument throughput has
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Extrachromosomal DNA: An Emerging Hallmark in Human Cancer Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Sihan Wu, Vineet Bafna, Howard Y. Chang, Paul S. Mischel
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
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Role of the Inflammasome in Liver Disease Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Marcelle de Carvalho Ribeiro, Gyongyi Szabo
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
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Molecular Pathogenesis of Gastrointestinal Stromal Tumor: A Paradigm for Personalized Medicine Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Josephine K. Dermawan, Brian P. Rubin
Over the past three to four decades, the molecular pathogenesis of gastrointestinal stromal tumors (GISTs) has been elucidated in great detail. In this review, we discuss the biological genesis of GISTs, identification of the various primary activating driver mutations (focusing on KIT and PDGFRA), oncogene addiction and targeted therapies with imatinib and other tyrosine kinase inhibitors, and the
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DNA Methylation Profiling: An Emerging Paradigm for Cancer Diagnosis Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Antonios Papanicolau-Sengos, Kenneth Aldape
Histomorphology has been a mainstay of cancer diagnosis in anatomic pathology for many years. DNA methylation profiling is an additional emerging tool that will serve as an adjunct to increase accuracy of pathological diagnosis. Genome-wide interrogation of DNA methylation signatures, in conjunction with machine learning methods, has allowed for the creation of clinical-grade classifiers, most prominently
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In Vivo Dynamics of the Latent Reservoir for HIV-1: New Insights and Implications for Cure Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Janet D. Siliciano, Robert F. Siliciano
Although antiretroviral therapy (ART) can reduce viremia to below the limit of detection and allow persons living with HIV-1 (PLWH) to lead relatively normal lives, viremia rebounds when treatment is interrupted. Rebound reflects viral persistence in a stable latent reservoir in resting CD4+ T cells. This reservoir is now recognized as the major barrier to cure and is the focus of intense international
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Polycystic Liver Disease: Advances in Understanding and Treatment Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Tatyana V. Masyuk, Anatoliy I. Masyuk, Nicholas F. LaRusso
Polycystic liver disease (PLD) is a group of genetic disorders characterized by progressive development of cholangiocyte-derived fluid-filled hepatic cysts. PLD is the most common manifestation of autosomal dominant and autosomal recessive polycystic kidney diseases and rarely occurs as autosomal dominant PLD. The mechanisms of PLD are a sequence of the primary (mutations in PLD-causative genes), secondary
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Inherited Autoinflammatory Syndromes Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Julia E. Rood, Edward M. Behrens
Autoinflammation describes a collection of diverse diseases caused by indiscriminate activation of the immune system in an antigen-independent manner. The rapid advancement of genetic diagnostics has allowed for the identification of a wide array of monogenic causes of autoinflammation. While the clinical picture of these syndromes is diverse, it is possible to thematically group many of these diseases
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A Balancing Act: p53 Activity from Tumor Suppression to Pathology and Therapeutic Implications Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Mengxiong Wang, Laura D. Attardi
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
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Molecular Pathology of Laminopathies Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Ji-Yeon Shin, Howard J. Worman
The nuclear envelope is composed of the nuclear membranes, nuclear lamina, and nuclear pore complexes. Laminopathies are diseases caused by mutations in genes encoding protein components of the lamina and these other nuclear envelope substructures. Mutations in the single gene encoding lamin A and C, which are expressed in most differentiated somatic cells, cause diseases affecting striated muscle
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Infection-Related Myelopathies Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 E. Ann Yeh, Carmen Yea, Ari Bitnun
Recent years have seen growing attention to inflammatory and infectious disorders of the spinal cord, not only due to the discovery of autoantibody-mediated disorders of the spinal cord [e.g., aquaporin-4 immunoglobulin G (IgG) antibodies and myelin oligodendrocyte glycoprotein IgG antibodies], but also due to the emergence of clusters of infection-related myelopathy, now known as acute flaccid myelitis
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The Immune Response in Multiple Sclerosis Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Sofía Rodríguez Murúa, Mauricio F. Farez, Francisco J. Quintana
Multiple sclerosis (MS) is a chronic autoimmune, inflammatory, and neurodegenerative disease that affects the central nervous system (CNS). MS is characterized by immune dysregulation, which results in the infiltration of the CNS by immune cells, triggering demyelination, axonal damage, and neurodegeneration. Although the exact causes of MS are not fully understood, genetic and environmental factors
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Apolipoprotein E and Alzheimer's Disease: Findings, Hypotheses, and Potential Mechanisms Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Nicole Koutsodendris, Maxine R. Nelson, Antara Rao, Yadong Huang
Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that involves dysregulation of many cellular and molecular processes. It is notoriously difficult to develop therapeutics for AD due to its complex nature. Nevertheless, recent advancements in imaging technology and the development of innovative experimental techniques have allowed researchers to perform in-depth analyses to uncover
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Desmosomal Cadherins in Health and Disease Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Marihan Hegazy, Abbey L. Perl, Sophia A. Svoboda, Kathleen J. Green
Desmosomal cadherins are a recent evolutionary innovation that make up the adhesive core of highly specialized intercellular junctions called desmosomes. Desmosomal cadherins, which are grouped into desmogleins and desmocollins, are related to the classical cadherins, but their cytoplasmic domains are tailored for anchoring intermediate filaments instead of actin to sites of cell–cell adhesion. The
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Cystic Fibrosis and the Cells of the Airway Epithelium: What Are Ionocytes and What Do They Do? Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Viral S. Shah, Raghu R. Chivukula, Brian Lin, Avinash Waghray, Jayaraj Rajagopal
Cystic fibrosis (CF) is caused by defects in an anion channel, the cystic fibrosis transmembrane conductance regulator (CFTR). Recently, a new airway epithelial cell type has been discovered and dubbed the pulmonary ionocyte. Unexpectedly, these ionocytes express higher levels of CFTR than any other airway epithelial cell type. However, ionocytes are not the sole CFTR-expressing airway epithelial cells
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Long Noncoding RNAs and Human Liver Disease Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Johanna K. DiStefano, Glenn S. Gerhard
Long noncoding RNAs (lncRNAs) are pervasively transcribed in the genome, exhibit a diverse range of biological functions, and exert effects through a variety of mechanisms. The sheer number of lncRNAs in the human genome has raised important questions about their potential biological significance and roles in human health and disease. Technological and computational advances have enabled functional
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Precision Medicine in Low- and Middle-Income Countries Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Jerald P. Radich, Edward Briercheck, Daniel T. Chiu, Manoj P. Menon, Olga Sala Torra, Cecilia C.S. Yeung, Edus H. Warren
Most cancer cases occur in low- and middle-income countries (LMICs). The sophisticated technical and human infrastructure needed for optimal diagnosis, treatment, and monitoring of cancers is difficult enough in affluent countries; it is especially challenging in LMICs. In Western, educated, industrial, rich, democratic countries, there is a growing emphasis on and success with precision medicine,
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Pathogenesis of Triple-Negative Breast Cancer Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Fatemeh Derakhshan, Jorge S. Reis-Filho
Triple-negative breast cancer (TNBC) encompasses a heterogeneous group of fundamentally different diseases with different histologic, genomic, and immunologic profiles, which are aggregated under this term because of their lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. Massively parallel sequencing and other omics technologies have demonstrated
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Cutaneous Squamous Cell Carcinoma: The Frontier of Cancer Immunoprevention Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2022-01-24 Michael S. Chang, Marjan Azin, Shadmehr Demehri
Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer, with its incidence rising steeply. Immunosuppression is a well-established risk factor for cSCC, and this risk factor highlights the critical role of the immune system in regulating cSCC development and progression. Further highlighting the nature of cSCC as an immunological disorder, substantial evidence demonstrates a tight
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The Complex Clinical and Genetic Landscape of Hereditary Peripheral Neuropathy Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-26 Soumitra Ghosh, Warren G. Tourtellotte
Hereditary peripheral neuropathy (HPN) is a complex group of neurological disorders caused by mutations in genes expressed by neurons and Schwann cells. The inheritance of a single mutation or multiple mutations in several genes leads to disease phenotype. Patients exhibit symptoms during development, at an early age or later in adulthood. Most of the mechanistic understanding about these neuropathies
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The Membrane Interactions of Synuclein: Physiology and Pathology Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-26 Gautam Runwal, Robert H. Edwards
Specific proteins accumulate in neurodegenerative disease, and human genetics has indicated a causative role for many. In most cases, however, the mechanisms remain poorly understood. Degeneration is thought to involve a gain of abnormal function, although we do not know the normal function of many proteins implicated. The protein α-synuclein accumulates in the Lewy pathology of Parkinson's disease
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Pathogenesis of Cholangiocarcinoma Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-26 Pedro M. Rodrigues, Paula Olaizola, Nuno A. Paiva, Irene Olaizola, Alona Agirre-Lizaso, Ana Landa, Luis Bujanda, Maria J. Perugorria, Jesus M. Banales
Cholangiocarcinoma (CCA) encompasses a group of malignancies that can arise at any point in the biliary tree. Although considered a rare cancer, the incidence of CCA is increasing globally. The silent and asymptomatic nature of these tumors, particularly in their early stages, in combination with their high aggressiveness, intra- and intertumor heterogeneity, and chemoresistance, significantly compromises
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When a House Is Not a Home: A Survey of Antimetastatic Niches and Potential Mechanisms of Disseminated Tumor Cell Suppression Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-26 Sarah B. Crist, Cyrus M. Ghajar
Over the last four decades, the cancer biology field has concentrated on cellular and microenvironmental drivers of metastasis. Despite this focus, mortality rates upon diagnosis of metastatic disease remain essentially unchanged. Would a small change in perspective help? Knowing what constitutes an inhospitable, rather than hospitable, microenvironment could provide the inspiration necessary to develop
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Perspectives and Advances in the Understanding of Tuberculosis Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-26 Rachel L. Kinsella, Dennis X. Zhu, Gregory A. Harrison, Anne E. Mayer Bridwell, Jerome Prusa, Sthefany M. Chavez, Christina L. Stallings
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains a leading cause of death due to infection in humans. To more effectively combat this pandemic, many aspects of TB control must be developed, including better point of care diagnostics, shorter and safer drug regimens, and a protective vaccine. To address all these areas of need, better understanding of the pathogen
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Genetic Insights into Alzheimer's Disease Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-26 Caitlin S. Latimer, Katherine L. Lucot, C. Dirk Keene, Brenna Cholerton, Thomas J. Montine
Alzheimer's disease (AD) is a pervasive, relentlessly progressive neurodegenerative disorder that includes both hereditary and sporadic forms linked by common underlying neuropathologic changes and neuropsychological manifestations. While a clinical diagnosis is often made on the basis of initial memory dysfunction that progresses to involve multiple cognitive domains, definitive diagnosis requires
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Metabolic Gatekeepers of Pathological B Cell Activation Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-26 Teresa Sadras, Lai N. Chan, Gang Xiao, Markus Müschen
Unlike other cell types, B cells undergo multiple rounds of V(D)J recombination and hypermutation to evolve high-affinity antibodies. Reflecting high frequencies of DNA double-strand breaks, adaptive immune protection by B cells comes with an increased risk of malignant transformation. In addition, the vast majority of newly generated B cells express an autoreactive B cell receptor (BCR). Thus, B cells
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The Hippo Pathway in Liver Homeostasis and Pathophysiology Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-26 Jordan H. Driskill, Duojia Pan
Studies of the regenerative capacity of the liver have converged on the Hippo pathway, a serine/threonine kinase cascade discovered in Drosophila and conserved from unicellular organisms to mammals. Genetic studies of mouse and rat livers have revealed that the Hippo pathway is a key regulator of liver size, regeneration, development, metabolism, and homeostasis and that perturbations in the Hippo
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Complement in Neurologic Disease Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-26 Nicholas E. Propson, Manasee Gedam, Hui Zheng
Classic innate immune signaling pathways provide most of the immune response in the brain. This response activates many of the canonical signaling mechanisms identified in peripheral immune cells, despite their relative absence in this immune-privileged tissue. Studies over the past decade have strongly linked complement protein production and activation to age-related functional changes and neurodegeneration
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Gut Microbiota in Intestinal and Liver Disease Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-26 Rheinallt M. Jones, Andrew S. Neish
It is known that the gut microbiota, the numerically vast and taxonomically diverse microbial communities that thrive in a symbiotic fashion within our alimentary tract, can affect the normal physiology of the gastrointestinal tract and liver. Further, disturbances of the microbiota community structure from both endogenous and exogenous influences as well as the failure of host responsive mechanisms
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Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-26 Sreya Bagchi, Robert Yuan, Edgar G. Engleman
Immune checkpoint inhibitors (ICIs) have made an indelible mark in the field of cancer immunotherapy. Starting with the approval of anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4) for advanced-stage melanoma in 2011, ICIs—which now also include antibodies against programmed cell death 1 (PD-1) and its ligand (PD-L1)—quickly gained US Food and Drug Administration approval for the treatment
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Detection and Diagnostic Utilization of Cellular and Cell-Free Tumor DNA Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-26 Jonathan C. Dudley, Maximilian Diehn
Because cancer is caused by an accumulation of genetic mutations, mutant DNA released by tumors can be used as a highly specific biomarker for cancer. Although this principle was described decades ago, the advent and falling costs of next-generation sequencing have made the use of tumor DNA as a biomarker increasingly practical. This review surveys the use of cellular and cell-free DNA for the detection
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Opposing Roles of Type I Interferons in Cancer Immunity Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-26 Giselle M. Boukhaled, Shane Harding, David G. Brooks
The immune system is tasked with identifying malignant cells to eliminate or prevent cancer spread. This involves a complex orchestration of many immune cell types that together recognize different aspects of tumor transformation and growth. In response, tumors have developed mechanisms to circumvent immune attack. Type I interferons (IFN-Is) are a class of proinflammatory cytokines produced in response
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Genetic Disease and Therapy Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-26 Theodore L. Roth, Alexander Marson
Genetic diseases cause numerous complex and intractable pathologies. DNA sequences encoding each human's complexity and many disease risks are contained in the mitochondrial genome, nuclear genome, and microbial metagenome. Diagnosis of these diseases has unified around applications of next-generation DNA sequencing. However, translating specific genetic diagnoses into targeted genetic therapies remains
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The Spectrum of Helicobacter-Mediated Diseases Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-26 Karen Robinson, John C. Atherton
Helicobacter pylori is the leading cause of peptic ulcer disease. The infection has been implicated in more than 75% of duodenal ulcer cases and 17% of gastric ulcer cases. H. pylori has been classified as a human carcinogen, since it is the main cause of distal gastric adenocarcinoma and B cell mucosa-associated lymphoid tissue lymphoma. Evidence also links H. pylori with extragastric conditions including
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Monocytes in the Tumor Microenvironment Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-26 Stefano Ugel, Stefania Canè, Francesco De Sanctis, Vincenzo Bronte
Immunotherapy has revolutionized cancer treatment over the past decade. Nonetheless, prolonged survival is limited to relatively few patients. Cancers enforce a multifaceted immune-suppressive network whose nature is progressively shaped by systemic and local cues during tumor development. Monocytes bridge innate and adaptive immune responses and can affect the tumor microenvironment through various
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Lethal Infectious Diseases as Inborn Errors of Immunity: Toward a Synthesis of the Germ and Genetic Theories Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-26 Jean-Laurent Casanova, Laurent Abel
It was first demonstrated in the late nineteenth century that human deaths from fever were typically due to infections. As the germ theory gained ground, it replaced the old, unproven theory that deaths from fever reflected a weak personal or even familial constitution. A new enigma emerged at the turn of the twentieth century, when it became apparent that only a small proportion of infected individuals
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The Accidental Pathologist: A Curiosity-Driven Journey from Plant Evolution to Innate Immunity Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-26 Vinay Kumar
I have had the singular opportunity to perform research and to participate in medical education. Not unexpectedly, people have asked me which of the two was more important to me. My answer has always been and remains that I am equally passionate about research and teaching. My research has been curiosity driven and not purposeful; hence, I was willing to take risks. That my research led to the discovery
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Molecular Pathogenesis of Merkel Cell Carcinoma Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-26 James A. DeCaprio
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin with two distinct etiologies. Clonal integration of Merkel cell polyomavirus DNA into the tumor genome with persistent expression of viral T antigens causes at least 60% of all MCC. UV damage leading to highly mutated genomes causes a nonviral form of MCC. Despite these distinct etiologies, both forms of MCC are similar
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Animal Models and Their Role in Understanding the Pathophysiology of Cystic Fibrosis-Associated Gastrointestinal Lesions. Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-24 Katherine N Gibson-Corley,John F Engelhardt
The life expectancy of cystic fibrosis (CF) patients has greatly increased over the past decade, and researchers and clinicians must now navigate complex disease manifestations that were not a concern prior to the development of modern therapies. Explosive growth in the number of CF animal models has also occurred over this time span, clarifying CF disease pathophysiology and creating opportunities
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Animal Models and Their Role in Understanding the Pathophysiology of Cystic Fibrosis-Associated Gastrointestinal Lesions. Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-24 Katherine N Gibson-Corley,John F Engelhardt
The life expectancy of cystic fibrosis (CF) patients has greatly increased over the past decade, and researchers and clinicians must now navigate complex disease manifestations that were not a concern prior to the development of modern therapies. Explosive growth in the number of CF animal models has also occurred over this time span, clarifying CF disease pathophysiology and creating opportunities
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Genetic Insights into Alzheimer's Disease. Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-24 Caitlin S Latimer,Katherine L Lucot,C Dirk Keene,Brenna Cholerton,Thomas J Montine
Alzheimer's disease (AD) is a pervasive, relentlessly progressive neurodegenerative disorder that includes both hereditary and sporadic forms linked by common underlying neuropathologic changes and neuropsychological manifestations. While a clinical diagnosis is often made on the basis of initial memory dysfunction that progresses to involve multiple cognitive domains, definitive diagnosis requires
-
Genetic Insights into Alzheimer's Disease. Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-24 Caitlin S Latimer,Katherine L Lucot,C Dirk Keene,Brenna Cholerton,Thomas J Montine
Alzheimer's disease (AD) is a pervasive, relentlessly progressive neurodegenerative disorder that includes both hereditary and sporadic forms linked by common underlying neuropathologic changes and neuropsychological manifestations. While a clinical diagnosis is often made on the basis of initial memory dysfunction that progresses to involve multiple cognitive domains, definitive diagnosis requires
-
Monocytes in the Tumor Microenvironment. Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-24 Stefano Ugel,Stefania Canè,Francesco De Sanctis,Vincenzo Bronte
Immunotherapy has revolutionized cancer treatment over the past decade. Nonetheless, prolonged survival is limited to relatively few patients. Cancers enforce a multifaceted immune-suppressive network whose nature is progressively shaped by systemic and local cues during tumor development. Monocytes bridge innate and adaptive immune responses and can affect the tumor microenvironment through various
-
Monocytes in the Tumor Microenvironment. Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-24 Stefano Ugel,Stefania Canè,Francesco De Sanctis,Vincenzo Bronte
Immunotherapy has revolutionized cancer treatment over the past decade. Nonetheless, prolonged survival is limited to relatively few patients. Cancers enforce a multifaceted immune-suppressive network whose nature is progressively shaped by systemic and local cues during tumor development. Monocytes bridge innate and adaptive immune responses and can affect the tumor microenvironment through various
-
The Accidental Pathologist: A Curiosity-Driven Journey from Plant Evolution to Innate Immunity. Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-24 Vinay Kumar
I have had the singular opportunity to perform research and to participate in medical education. Not unexpectedly, people have asked me which of the two was more important to me. My answer has always been and remains that I am equally passionate about research and teaching. My research has been curiosity driven and not purposeful; hence, I was willing to take risks. That my research led to the discovery
-
The Accidental Pathologist: A Curiosity-Driven Journey from Plant Evolution to Innate Immunity. Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-24 Vinay Kumar
I have had the singular opportunity to perform research and to participate in medical education. Not unexpectedly, people have asked me which of the two was more important to me. My answer has always been and remains that I am equally passionate about research and teaching. My research has been curiosity driven and not purposeful; hence, I was willing to take risks. That my research led to the discovery
-
Genetic Disease and Therapy. Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-24 Theodore L Roth,Alexander Marson
Genetic diseases cause numerous complex and intractable pathologies. DNA sequences encoding each human's complexity and many disease risks are contained in the mitochondrial genome, nuclear genome, and microbial metagenome. Diagnosis of these diseases has unified around applications of next-generation DNA sequencing. However, translating specific genetic diagnoses into targeted genetic therapies remains
-
Genetic Disease and Therapy. Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-24 Theodore L Roth,Alexander Marson
Genetic diseases cause numerous complex and intractable pathologies. DNA sequences encoding each human's complexity and many disease risks are contained in the mitochondrial genome, nuclear genome, and microbial metagenome. Diagnosis of these diseases has unified around applications of next-generation DNA sequencing. However, translating specific genetic diagnoses into targeted genetic therapies remains
-
The Membrane Interactions of Synuclein: Physiology and Pathology. Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-24 Gautam Runwal,Robert H Edwards
Specific proteins accumulate in neurodegenerative disease, and human genetics has indicated a causative role for many. In most cases, however, the mechanisms remain poorly understood. Degeneration is thought to involve a gain of abnormal function, although we do not know the normal function of many proteins implicated. The protein α-synuclein accumulates in the Lewy pathology of Parkinson's disease
-
The Membrane Interactions of Synuclein: Physiology and Pathology. Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-24 Gautam Runwal,Robert H Edwards
Specific proteins accumulate in neurodegenerative disease, and human genetics has indicated a causative role for many. In most cases, however, the mechanisms remain poorly understood. Degeneration is thought to involve a gain of abnormal function, although we do not know the normal function of many proteins implicated. The protein α-synuclein accumulates in the Lewy pathology of Parkinson's disease
-
Perspectives and Advances in the Understanding of Tuberculosis. Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-24 Rachel L Kinsella,Dennis X Zhu,Gregory A Harrison,Anne E Mayer Bridwell,Jerome Prusa,Sthefany M Chavez,Christina L Stallings
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains a leading cause of death due to infection in humans. To more effectively combat this pandemic, many aspects of TB control must be developed, including better point of care diagnostics, shorter and safer drug regimens, and a protective vaccine. To address all these areas of need, better understanding of the pathogen
-
Perspectives and Advances in the Understanding of Tuberculosis. Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-24 Rachel L Kinsella,Dennis X Zhu,Gregory A Harrison,Anne E Mayer Bridwell,Jerome Prusa,Sthefany M Chavez,Christina L Stallings
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), remains a leading cause of death due to infection in humans. To more effectively combat this pandemic, many aspects of TB control must be developed, including better point of care diagnostics, shorter and safer drug regimens, and a protective vaccine. To address all these areas of need, better understanding of the pathogen
-
The Complex Clinical and Genetic Landscape of Hereditary Peripheral Neuropathy. Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-24 Soumitra Ghosh,Warren G Tourtellotte
Hereditary peripheral neuropathy (HPN) is a complex group of neurological disorders caused by mutations in genes expressed by neurons and Schwann cells. The inheritance of a single mutation or multiple mutations in several genes leads to disease phenotype. Patients exhibit symptoms during development, at an early age or later in adulthood. Most of the mechanistic understanding about these neuropathies
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The Complex Clinical and Genetic Landscape of Hereditary Peripheral Neuropathy. Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2021-01-24 Soumitra Ghosh,Warren G Tourtellotte
Hereditary peripheral neuropathy (HPN) is a complex group of neurological disorders caused by mutations in genes expressed by neurons and Schwann cells. The inheritance of a single mutation or multiple mutations in several genes leads to disease phenotype. Patients exhibit symptoms during development, at an early age or later in adulthood. Most of the mechanistic understanding about these neuropathies
-
Animal Models and Their Role in Understanding the Pathophysiology of Cystic Fibrosis–Associated Gastrointestinal Lesions Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2020-11-16 Katherine N. Gibson-Corley, John F. Engelhardt
The life expectancy of cystic fibrosis (CF) patients has greatly increased over the past decade, and researchers and clinicians must now navigate complex disease manifestations that were not a concern prior to the development of modern therapies. Explosive growth in the number of CF animal models has also occurred over this time span, clarifying CF disease pathophysiology and creating opportunities
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DAMPs, PAMPs, and LAMPs in Immunity and Sterile Inflammation Ann. Review Paleopathol. Mech. Disease (IF 32.35) Pub Date : 2020-01-24 Joel Zindel, Paul Kubes
Recognizing the importance of leukocyte trafficking in inflammation led to some therapeutic breakthroughs. However, many inflammatory pathologies remain without specific therapy. This review discusses leukocytes in the context of sterile inflammation, a process caused by sterile (non-microbial) molecules, comprising damage-associated molecular patterns (DAMPs). DAMPs bind specific receptors to activate