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Annual Review of Pathology

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https://www.readbyqxmd.com/read/30379619/systems-wide-approaches-in-induced-pluripotent-stem-cell-models
#1
Edward Lau, David T Paik, Joseph C Wu
Human induced pluripotent stem cells (iPSCs) provide a renewable supply of patient-specific and tissue-specific cells for cellular and molecular studies of disease mechanisms. Combined with advances in various omics technologies, iPSC models can be used to profile the expression of genes, transcripts, proteins, and metabolites in relevant tissues. In the past 2 years, large panels of iPSC lines have been derived from hundreds of genetically heterogeneous individuals, further enabling genome-wide mapping to identify coexpression networks and elucidate gene regulatory networks...
October 31, 2018: Annual Review of Pathology
https://www.readbyqxmd.com/read/30355155/molecular-pathogenesis-of-the-tauopathies
#2
Jürgen Götz, Glenda Halliday, Rebecca M Nisbet
The tauopathies constitute a group of diseases that have Tau inclusions in neurons or glia as their common denominator. In this review, we describe the biochemical and histological differences in Tau pathology that are characteristic of the spectrum of frontotemporal lobar degeneration as primary tauopathies and of Alzheimer's disease as a secondary tauopathy, as well as the commonalities and differences between the familial and sporadic forms. Furthermore, we discuss selected advances in transgenic animal models in delineating the pathomechanisms of Tau in the different subtypes...
October 24, 2018: Annual Review of Pathology
https://www.readbyqxmd.com/read/30355154/clinical-metagenomic-next-generation-sequencing-for-pathogen-detection
#3
Wei Gu, Steve Miller, Charles Y Chiu
Nearly all infectious agents contain DNA or RNA genomes, making sequencing an attractive approach for pathogen detection. The cost of high-throughput or next-generation sequencing has been reduced by several orders of magnitude since its advent in 2004, and it has emerged as an enabling technological platform for the detection and taxonomic characterization of microorganisms in clinical samples from patients. This review focuses on the application of untargeted metagenomic next-generation sequencing to the clinical diagnosis of infectious diseases, particularly in areas in which conventional diagnostic approaches have limitations...
October 24, 2018: Annual Review of Pathology
https://www.readbyqxmd.com/read/30355153/modeling-disease-with-inducible-pluripotent-stem-cells
#4
Rodrigo Grandy, Rute Tomaz, Ludovic Vallier
Understanding the physiopathology of disease remains an essential step in developing novel therapeutics. Although animal models have certainly contributed to advancing this enterprise, their limitation in modeling all the aspects of complex human disorders is one of the major challenges faced by the biomedical research field. Human induced pluripotent stem cells (hiPSCs) derived from patients represent a great opportunity to overcome this deficiency because these cells cover the genetic diversity needed to fully model human diseases...
October 24, 2018: Annual Review of Pathology
https://www.readbyqxmd.com/read/30355152/pathology-and-pathogenesis-of-chagas-heart-disease
#5
Kevin M Bonney, Daniel J Luthringer, Stacey A Kim, Nisha J Garg, David M Engman
Chagas heart disease is an inflammatory cardiomyopathy that develops in approximately one-third of people infected with the protozoan parasite Trypanosoma cruzi. One way T. cruzi is transmitted to people is through contact with infected kissing bugs, which are found in much of the Western Hemisphere, including in vast areas of the United States. The epidemiology of T. cruzi and Chagas heart disease and the varied mechanisms leading to myocyte destruction, mononuclear cell infiltration, fibrosis, and edema in the heart have been extensively studied by hundreds of scientists for more than 100 years...
October 24, 2018: Annual Review of Pathology
https://www.readbyqxmd.com/read/30355151/rna-binding-proteins-and-the-pathogenesis-of-frontotemporal-lobar-degeneration
#6
Jeffrey W Hofmann, William W Seeley, Eric J Huang
Frontotemporal dementia is a group of early onset dementia syndromes linked to underlying frontotemporal lobar degeneration (FTLD) pathology that can be classified based on the formation of abnormal protein aggregates involving tau and two RNA binding proteins, TDP-43 and FUS. Although elucidation of the mechanisms leading to FTLD pathology is in progress, recent advances in genetics and neuropathology indicate that a majority of FTLD cases with proteinopathy involving RNA binding proteins show highly congruent genotype-phenotype correlations...
October 24, 2018: Annual Review of Pathology
https://www.readbyqxmd.com/read/30355150/cellular-and-molecular-mechanisms-of-prion-disease
#7
Christina J Sigurdson, Jason C Bartz, Markus Glatzel
Prion diseases are rapidly progressive, incurable neurodegenerative disorders caused by misfolded, aggregated proteins known as prions, which are uniquely infectious. Remarkably, these infectious proteins have been responsible for widespread disease epidemics, including kuru in humans, bovine spongiform encephalopathy in cattle, and chronic wasting disease in cervids, the latter of which has spread across North America and recently appeared in Norway and Finland. The hallmark histopathological features include widespread spongiform encephalopathy, neuronal loss, gliosis, and deposits of variably sized aggregated prion protein, ranging from small, soluble oligomers to long, thin, unbranched fibrils, depending on the disease...
October 24, 2018: Annual Review of Pathology
https://www.readbyqxmd.com/read/30332563/molecular-genetics-of-endometrial-carcinoma
#8
Daphne W Bell, Lora Hedrick Ellenson
Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States. Endometrioid endometrial carcinomas constitute approximately 85% of newly diagnosed cases; serous carcinomas represent approximately 3-10% of diagnoses; clear cell carcinoma accounts for <5% of diagnoses; and uterine carcinosarcomas are rare, biphasic tumors. Longstanding molecular observations implicate PTEN inactivation as a major driver of endometrioid carcinomas; TP53 inactivation as a major driver of most serous carcinomas, some high-grade endometrioid carcinomas, and many uterine carcinosarcomas; and inactivation of either gene as drivers of some clear cell carcinomas...
October 17, 2018: Annual Review of Pathology
https://www.readbyqxmd.com/read/30332562/pathophysiology-of-sickle-cell-disease
#9
Prithu Sundd, Mark T Gladwin, Enrico M Novelli
Since the discovery of sickle cell disease (SCD) in 1910, enormous strides have been made in the elucidation of the pathogenesis of its protean complications, which has inspired recent advances in targeted molecular therapies. In SCD, a single amino acid substitution in the β-globin chain leads to polymerization of mutant hemoglobin S, impairing erythrocyte rheology and survival. Clinically, erythrocyte abnormalities in SCD, manifest in hemolytic anemia and cycles of microvascular vaso-occlusion leading to endorgan ischemia-reperfusion injury and infarction...
October 17, 2018: Annual Review of Pathology
https://www.readbyqxmd.com/read/30332561/opportunities-for-micrornas-in-the-crowded-field-of-cardiovascular-biomarkers
#10
Perry V Halushka, Andrew J Goodwin, Marc K Halushka
Cardiovascular diseases exist across all developed countries societies. Biomarkers that can predict or diagnose diseases early in their pathogeneses can reduce their morbidity and mortality in afflicted individuals. microRNAs are small regulatory RNAs that modulate translation and have been identified as potential fluid-based biomarkers across numerous maladies. We describe the current state of cardiovascular disease biomarkers across a range of diseases, including myocardial infarction, acute coronary syndrome, myocarditis, hypertension, heart failure, heart transplantation, aortic stenosis, diabetic cardiomyopathy, atrial fibrillation, and sepsis...
October 17, 2018: Annual Review of Pathology
https://www.readbyqxmd.com/read/30332560/type-i-interferons-in-autoimmune-disease
#11
Mary K Crow, Mikhail Olferiev, Kyriakos A Kirou
Type I interferons, which make up the first cytokine family to be described and are the essential mediators of antivirus host defense, have emerged as central elements in the immunopathology of systemic autoimmune diseases, with systemic lupus erythematosus as the prototype. Lessons from investigation of interferon regulation following virus infection can be applied to lupus, with the conclusion that sustained production of type I interferon shifts nearly all components of the immune system toward pathologic functions that result in tissue damage and disease...
October 17, 2018: Annual Review of Pathology
https://www.readbyqxmd.com/read/30230967/innate-immune-signaling-in-nonalcoholic-fatty-liver-disease-and-cardiovascular-diseases
#12
Jingjing Cai, Meng Xu, Xiaojing Zhang, Hongliang Li
The physiological significance of innate immune signaling lies primarily in its role in host defense against invading pathogens. It is becoming increasingly clear that innate immune signaling also modulates the development of metabolic diseases, especially nonalcoholic fatty liver disease and cardiovascular diseases, which are characterized by chronic, low-grade inflammation due to a disarrangement of innate immune signaling. Notably, recent studies indicate that in addition to regulating canonical innate immune-mediated inflammatory responses (or immune-dependent signaling-induced responses), molecules of the innate immune system regulate pathophysiological responses in multiple organs during metabolic disturbances (termed immune-independent signaling-induced responses), including the disruption of metabolic homeostasis, tissue repair, and cell survival...
September 19, 2018: Annual Review of Pathology
https://www.readbyqxmd.com/read/30183507/immunological-basis-for-recurrent-fetal-loss-and-pregnancy-complications
#13
Hitesh Deshmukh, Sing Sing Way
Pregnancy stimulates an elaborate assortment of dynamic changes, allowing intimate approximation of genetically discordant maternal and fetal tissues. Although the cellular and molecular details about how this works remain largely undefined, important clues arise from evaluating how a prior pregnancy influences the outcome of a future pregnancy. The risk of complications is consistently increased when complications occurred in a prior pregnancy. Reciprocally, a prior successful pregnancy protects against complications in a future pregnancy...
September 5, 2018: Annual Review of Pathology
https://www.readbyqxmd.com/read/30148688/pathogenesis-of-rickettsial-diseases-pathogenic-and-immune-mechanisms-of-an-endotheliotropic-infection
#14
Abha Sahni, Rong Fang, Sanjeev K Sahni, David H Walker
Obligately intracytosolic rickettsiae that cycle between arthropod and vertebrate hosts cause human diseases with a spectrum of severity, primarily by targeting microvascular endothelial cells, resulting in endothelial dysfunction. Endothelial cells and mononuclear phagocytes have important roles in the intracellular killing of rickettsiae upon activation by the effector molecules of innate and adaptive immunity. In overwhelming infection, immuno-suppressive effects contribute to the severity of illness. Rickettsia-host cell interactions involve host cell receptors for rickettsial ligands that mediate cell adhesion and, in some instances, trigger induced phagocytosis...
August 27, 2018: Annual Review of Pathology
https://www.readbyqxmd.com/read/30148687/pathological-issues-in-dystrophinopathy-in-the-age-of-genetic-therapies
#15
Nazima Shahnoor, Emily M Siebers, Kristy J Brown, Michael W Lawlor
Dystrophinopathy is a class of genetic skeletal muscle disease characterized by myofiber degeneration and regeneration due to insufficient levels or functioning of dystrophin. Pathological evaluation for dystrophinopathy includes the identification of dystrophic skeletal muscle pathology and the immuno-histochemical evaluation of dystrophin epitopes, but biopsies have become rare in recent years. However, the evaluation of dystrophin expression in the research setting has become critically important due to recent advances in genetic therapies, including exon skipping and gene therapy...
August 27, 2018: Annual Review of Pathology
https://www.readbyqxmd.com/read/30125150/insights-into-pathogenic-interactions-among-environment-host-and-tumor-at-the-crossroads-of-molecular-pathology-and-epidemiology
#16
Shuji Ogino, Jonathan A Nowak, Tsuyoshi Hamada, Danny A Milner, Reiko Nishihara
Evidence indicates that diet, nutrition, lifestyle, the environment, the microbiome, and other exogenous factors have pathogenic roles and also influence the genome, epigenome, transcriptome, proteome, and metabolome of tumor and nonneoplastic cells, including immune cells. With the need for big-data research, pathology must transform to integrate data science fields, including epidemiology, biostatistics, and bioinformatics. The research framework of molecular pathological epidemiology (MPE) demonstrates the strengths of such an interdisciplinary integration, having been used to study breast, lung, prostate, and colorectal cancers...
August 20, 2018: Annual Review of Pathology
https://www.readbyqxmd.com/read/30125149/epstein-barr-virus-and-cancer
#17
Paul J Farrell
Epstein-Barr virus (EBV) contributes to about 1.5% of all cases of human cancer worldwide, and viral genes are expressed in the malignant cells. EBV also very efficiently causes the proliferation of infected human B lymphocytes. The functions of the viral proteins and small RNAs that may contribute to EBV-associated cancers are becoming increasingly clear, and a broader understanding of the sequence variation of the virus genome has helped to interpret their roles. The improved understanding of the mechanisms of these cancers means that there are great opportunities for the early diagnosis of treatable stages of EBV-associated cancers and the use of immunotherapy to target EBV-infected cells or overcome immune evasion...
August 20, 2018: Annual Review of Pathology
https://www.readbyqxmd.com/read/30125148/exposure-to-ultraviolet-radiation-in-the-modulation-of-human-diseases
#18
Prue H Hart, Mary Norval, Scott N Byrne, Lesley E Rhodes
This review focuses primarily on the beneficial effects for human health of exposure to ultraviolet radiation (UVR). UVR stimulates anti-inflammatory and immunosuppressive pathways in skin that modulate psoriasis, atopic dermatitis, and vitiligo; suppresses cutaneous lesions of graft-versus-host disease; and regulates some infection and vaccination outcomes. While polymorphic light eruption and the cutaneous photosensitivity of systemic lupus erythematosus are triggered by UVR, polymorphic light eruption also frequently benefits from UVR-induced immunomodulation...
August 20, 2018: Annual Review of Pathology
https://www.readbyqxmd.com/read/30089230/polyglutamine-repeats-in-neurodegenerative-diseases
#19
Andrew P Lieberman, Vikram G Shakkottai, Roger L Albin
Among the age-dependent protein aggregation disorders, nine neurodegenerative diseases are caused by expansions of CAG repeats encoding polyglutamine (polyQ) tracts. We review the clinical, pathological, and biological features of these inherited disorders. We discuss insights into pathogenesis gleaned from studies of model systems and patients, highlighting work that informs efforts to develop effective therapies. An important conclusion from these analyses is that expanded CAG/polyQ domains are the primary drivers of neurodegeneration, with the biology of carrier proteins influencing disease-specific manifestations...
August 8, 2018: Annual Review of Pathology
https://www.readbyqxmd.com/read/29414251/pathogenesis-of-peripheral-t-cell-lymphoma
#20
Marco Pizzi, Elizabeth Margolskee, Giorgio Inghirami
Peripheral T cell lymphomas (PTCLs) are highly heterogeneous tumors, displaying distinct clinical and biological features. The pathogenesis and normal counterpart of such entities have been elusive for decades. Recent studies have, however, disclosed key mechanisms of peripheral T cell transformation, including (a) the deregulation of signaling pathways controlling T cell development, differentiation, and maturation; (b) the remodeling of the peritumor microenvironment; and (c) the virus-mediated rewiring of T cell biology...
January 24, 2018: Annual Review of Pathology
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