Different mouse models of nemaline myopathy harboring Acta1 mutations display differing abnormalities related to mitochondrial biology
ACTA1 encodes skeletal muscle-specific α-actin, which polymerizes to form the thin filament of the sarcomere. Mutations in ACTA1 are responsible for roughly 30% of nemaline myopathy (NM) cases. Previous studies of weakness in NM have focused on muscle structure and contractility, but genetic issues alone do not explain the phenotypic he terogeneity observed in NM patients or mouse models. To identify additional biological processes related to NM phenotypic severity, proteomic analysis was performed using muscle protein isolates from wild type (WT) mice in comparison to moderately affected KI. (Source: American Journal of Pathology)
Source: American Journal of Pathology - July 5, 2023 Category: Pathology Authors: Jennifer A. Tinklenberg, Rebecca A. Slick, Jessica Sutton, Liwen Zhang, Hui Meng, Margaret J. Beatka, Mark Vanden Avond, Mariah J. Prom, Emily Ott, Federica Montanaro, James Heisner, Rafael Toro, Edna C. Hardeman, Aron M. Geurts, David Stowe, R. Blake Hil Tags: Regular Article Source Type: research
Deep Learning –Based Stratification of Gastric Cancer Patients from Hematoxylin and Eosin–Stained Whole Slide Images by Predicting Molecular Features for Immunotherapy Response
Determining the molecular characteristics of cancer patients is crucial for optimal immunotherapy decisions. The aim of this study was to screen immunotherapy beneficiaries by predicting key molecular features from hematoxylin and eosin –stained images based on deep learning models. An independent data set from Asian gastric cancer patients was included for external validation. In addition, a segmentation model (HoVer-Net) was used to quantify the cellular composition of tumor stroma. The model performance was evaluated by measur ing the area under the curve (AUC). (Source: American Journal of Pathology)
Source: American Journal of Pathology - June 23, 2023 Category: Pathology Authors: Zheng Wei, Xu Zhao, Jing Chen, Qiuyan Sun, Zeyang Wang, Yanli Wang, Zhiyi Ye, Yuan Yuan, Liping Sun, Jingjing Jing Tags: Regular article Source Type: research
Progression of arterial vasa vasorum from regulator of arterial homeostasis to promoter of atherogenesis
The vasa vasorum (vessels of vessels) are a dynamic microvascular system uniquely distributed to maintain physiological homeostasis of the artery wall by supplying nutrients and oxygen to the outer layers of the artery wall, adventitia, and perivascular adipose tissue (PVAT), and in large arteries, to the outer portion of the medial layer. Vasa vasorum endothelium and contractile mural cells regulate direct access of bioactive cells and factors present both in the systemic circulation and in the arterial PVAT and adventitia to the artery wall. (Source: American Journal of Pathology)
Source: American Journal of Pathology - June 23, 2023 Category: Pathology Authors: Jonah Burke-Kleinman, Avrum I. Gotlieb Tags: Review Source Type: research
Prolonged early exposure to a high-fat diet augments the adverse effects on neurobehavior and hippocampal neuroplasticity: Involvement of microglial insulin signaling
High-fat diet (HFD) consumption may contribute to the high prevalence of cognitive-emotional issues in modern society. Our group previously demonstrated that mice fed a HFD for a prolonged period developed more severe neurobehavioral disturbances when first exposed to a HFD in the juvenile period than in adulthood, suggesting an initial age-related difference in the detrimental effects of long-term HFD feeding; however, the mechanism underlying this difference remains unclear. Here, male C57BL/6J mice initially aged 4 (IA4W) or 8 (IA8W) weeks were fed a control diet (CD) or HFD for 6 months and then subjected to metabolic,...
Source: American Journal of Pathology - June 23, 2023 Category: Pathology Authors: Xiuting Yao, Jingyi Zhao, Yang Yuan, Conghui Wang, Zhehao Yu, Zhihui Huang, Chen Chen, Chenxi Yang, Jiayi Ren, Yu Ma, Yi Rong, Yi Huang, Yue Ming, Lijie Liu Tags: Regular Article Source Type: research
Deep learning-based stratification of gastric cancer patients from hematoxylin and eosin-stained whole slide images by predicting molecular features for immunotherapy response
Determining the molecular characteristics of cancer patients is crucial for optimal immunotherapy decisions. The aim of this study was to screen immunotherapy beneficiaries by predicting key molecular features from hematoxylin and eosin-stained images based on deep learning (DL) models. An independent data-set from Asian GC patients was included for external validation. Besides, a segmentation model (HoVer-Net) was used to quantify the cellular composition of tumor stroma. The model performance was evaluated by measuring the area under the curve (AUC). (Source: American Journal of Pathology)
Source: American Journal of Pathology - June 23, 2023 Category: Pathology Authors: Zheng Wei, Xu Zhao, Jing Chen, Qiuyan Sun, Zeyang Wang, Yanli Wang, Zhiyi Ye, Yuan Yuan, Liping Sun, Jingjing Jing Tags: Regular Article Source Type: research
Oxidative Stress –Induced Liver Damage and Remodeling of the Liver Vasculature
As an organ critically important for targeting and clearing viruses, bacteria, and other foreign material, the liver operates via immune-tolerant, anti-inflammatory mechanisms indispensable to the immune response. Stress and stress-induced factors disrupt the homeostatic balance in the liver, inflicting tissue damage, injury, and remodeling. These factors include oxidative stress (OS) induced by viral infections, environmental toxins, drugs, alcohol, and diet. A recurrent theme seen among stressors common to multiple liver diseases is the induction of mitochondrial dysfunction, increased reactive oxygen species expression,...
Source: American Journal of Pathology - June 22, 2023 Category: Pathology Authors: Priyanka Banerjee, Niyanshi Gaddam, Vanessa Chandler, Sanjukta Chakraborty Tags: Review Source Type: research
Computer Vision Identifies Recurrent and Nonrecurrent Ductal Carcinoma in Situ Lesions with Special Emphasis on African-American Women
Although the existence of nonrecurrent and recurrent forms of ductal carcinoma in situ (DCIS) of the breast are observed, no evidence-based test can make this distinction. This retrospective case-control study used archival DCIS samples stained with anti –phospho-Ser226-glucose transporter type 1 and anti–phosphofructokinase type L antibodies. Immunofluorescence micrographs were used to create machine learning models of recurrent and nonrecurrent biomarker patterns, which were evaluated in cross-validation studies. (Source: American Journal of Pathology)
Source: American Journal of Pathology - June 22, 2023 Category: Pathology Authors: Yunus Saatchi, Parker Schanen, Richard A. Cheung, Howard R. Petty Tags: Regular article Source Type: research
Oxidative Stress-induced liver damage and remodeling of the liver vasculature
As an organ critically important for targeting and clearing viruses, bacteria, and other foreign material, the liver operates via immune-tolerant, anti-inflammatory mechanisms indispensable to the immune response. Stress and stress-induced factors disrupt the homeostatic balance in the liver, inflicting tissue damage, injury, and remodeling. These factors include oxidative stress induced by viral infections, environmental toxins, drugs, alcohol, and diet. A recurrent theme seen amongst stressors common to multiple liver disease is the induction of mitochondrial dysfunction, increased ROS expression and depletion of ATP. (S...
Source: American Journal of Pathology - June 22, 2023 Category: Pathology Authors: Priyanka Banerjee, Niyanshi Gaddam, Vanessa Chandler, Sanjukta Chakraborty Tags: Review Source Type: research
Computer Vision Identifies Recurrent and Non-Recurrent Ductal Carcinoma in situ Lesions with Special Emphasis on African American Women
Although the existence of non-recurrent and recurrent forms of ductal carcinoma in situ (DCIS) of the breast are observed, no evidence-based test can make this distinction. This retrospective case-control study used archival DCIS samples stained with anti-phospho-Ser226-GLUT1 (glucose transporter type 1) and anti-phosphofructokinase type L (PFKL) antibodies. Immunofluorescence micrographs were used to create machine learning (ML) models of recurrent and non-recurrent biomarker patterns, which were evaluated in cross-validation studies. (Source: American Journal of Pathology)
Source: American Journal of Pathology - June 22, 2023 Category: Pathology Authors: Yunus Saatchi, Parker Schanen, Richard A. Cheung, Howard R. Petty Tags: Regular Article Source Type: research
Role of HIF1 α and HIF2α in Cre Recombinase–Induced Retinal Pigment Epithelium Pathology and Its Secondary Effect on Choroidal Neovascularization
This article characterizes Cre-mediated pathology in the CreTrp1 line to elucidate the impact of RPE degeneration on both developmental and pathologic choroidal neovascularization. (Source: American Journal of Pathology)
Source: American Journal of Pathology - June 15, 2023 Category: Pathology Authors: Enrico Cristante, Sidath E. Liyanage, Alexander J. Smith, Robin R. Ali, James W.B. Bainbridge Tags: Short communication Source Type: research
Role of Hif1a and Hif2a in Cre recombinase-induced retinal pigment epithelium pathology and its secondary effect on choroidal neovascularisation
CreTrp1 mice are widely used for conditional retinal pigment epithelium (RPE) gene function studies. Like other Cre/LoxP models, phenotypes in CreTrp1 mice can be affected by Cre-mediated cellular toxicity, leading to RPE dysfunction, altered morphology and atrophy, activation of innate immunity and consequent impairment of photoreceptor function. These effects are common to the age-related alterations of RPE that feature in early/intermediate forms of age-related macular degeneration. This manuscript characterises Cre-mediated pathology in the CreTrp1 line to elucidate the impact of RPE degeneration on both developmental ...
Source: American Journal of Pathology - June 15, 2023 Category: Pathology Authors: Enrico Cristante, Sidath E. Liyanage, Alexander J. Smith, Robin R. Ali, James W.B. Bainbridge Tags: Short Communication Source Type: research
Editorial Board
(Source: American Journal of Pathology)
Source: American Journal of Pathology - June 14, 2023 Category: Pathology Source Type: research
Table of Contents
(Source: American Journal of Pathology)
Source: American Journal of Pathology - June 14, 2023 Category: Pathology Source Type: research
Inhibition of Erb-B2 Receptor Tyrosine Kinase 3 and Associated Regulatory Pathways Potently Impairs Malignant Peripheral Nerve Sheath Tumor Proliferation and Survival
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive, currently untreatable Schwann cell –derived neoplasms with hyperactive mitogen-activated protein kinase and mammalian target of rapamycin signaling pathways. To identify potential therapeutic targets, previous studies used genome-scale shRNA screens that implicated the neuregulin-1 receptor erb-B2 receptor tyrosine kinase 3 (erbB3) in MPNST proliferation and/or survival. The current study shows that erbB3 is commonly expressed in MPNSTs and MPNST cell lines and that erbB3 knockdown inhibits MPNST proliferation and survival. (Source: American Journal of Pathology)
Source: American Journal of Pathology - June 14, 2023 Category: Pathology Authors: Laurel E. Black, Jody F. Longo, Joshua C. Anderson, Steven L. Carroll Tags: Regular article Source Type: research
Increased Matrix Metalloproteinase-1 Activation Enhances Disruption and Regression of k-RasV12 –Expressing Arteriovenous Malformation-Like Vessels
This study sought to identify potential mechanisms by which k-RasV12 –expressing endothelial cell (EC) tubes demonstrate an increased propensity to regress compared with controls. Activated k-Ras mutations play a role in a variety of pathological conditions, including arteriovenous malformations, which are prone to bleed, causing serious hemorrhagic complications. Previously, the authors reported that ECs expressing active k-RasV12 demonstrate markedly excessive lumen formation with widened and shortened tubes accompanied by reduced pericyte recruitment and basement membrane deposition, leading to deficient capillary net...
Source: American Journal of Pathology - June 14, 2023 Category: Pathology Authors: Zheying Sun, Prisca K. Lin, Ksenia Yrigoin, Scott S. Kemp, George E. Davis Tags: Regular article Source Type: research
