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Reduction in activity and abundance of mitochondrial electron transport chain supercomplexes in pulmonary hypertension-induced right ventricular dysfunction bioRxiv. Pathol. Pub Date : 2024-03-13 Wenzhuo Ma, Peng Zhang, Alexander Vang, Alexsandra Zimmer, Scarlett Huck, Preston Nicely, Eric Wang, Thomas J Mancini, Joseph Owusu-Sarfo, Clarissa F Cavarsan, Andriy E Belyvech, Kenneth S Campbell, Dmitry Terentyev, Gaurav Choudhary, Richard T Clements
Pulmonary hypertension (PH) results in RV hypertrophy, fibrosis and dysfunction resulting in RV failure which is associated with impaired RV metabolism and mitochondrial respiration. Mitochondrial supercomplexes (mSC) are assemblies of multiple electron transport chain (ETC) complexes that consist of physically associated complex I, III and IV that may enhance respiration and lower ROS generation.
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Two new qPCR assays for detecting and quantifying the Aspergillus flavus and Aspergillus parasiticus clades in maize kernels bioRxiv. Pathol. Pub Date : 2024-03-11 Alexandre Leharanger, Delphine Paumier, Beatrice Orlando, Sylviane Bailly, Romain VALADE
The fungi of Aspergillus section Flavi mostly produce carcinogenic mycotoxins, aflatoxins (AFs), of two types: types B and G (AFBs and AFGs). AF are highly hazardous for human and animal health. Their levels in food and feed are therefore highly regulated, with a low acceptable limit for AF content. In France, global warming has led to the detection of AFs in maize harvests since 2015. Mycoflora analyses
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A unique subset of pericystic endothelium associates with aberrant microvascular remodelling and impaired blood perfusion early in polycystic kidney disease bioRxiv. Pathol. Pub Date : 2024-03-06 Daniyal J Jafree, Charith Perera, Mary Ball, Daniele Tolomeo, Gideon Pomeranz, Laura Wilson, Benjamin Davis, William J Mason, Eva Maria Funk, Maria Kolatsi-Joannou, Radu Polschi, Saif Malik, Benjamin J Stewart, Karen L Price, Hannah Mitchell, Reza Motallebzadeh, Yoshiharu Muto, Robert Lees, Sarah R Needham, Dale Moulding, Jennifer C Chandler, Claire L Walsh, Adrian S Woolf, Paul JD Winyard, Peter J
Hallmarks of autosomal dominant polycystic kidney disease (ADPKD), the most common hereditary kidney anomaly, include expanding fluid-filled epithelial cysts, inflammation, and fibrosis. Despite previous work showing the potential of vascular-based therapies, renal microvascular alterations in ADPKD, and their timing, are poorly understood. Using single-cell transcriptomics of human kidney microvasculature
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Graph perceiver network for lung tumor and bronchial premalignant lesion stratification from histopathology bioRxiv. Pathol. Pub Date : 2024-03-04 Rushin H Gindra, Yi Zheng, Emily J Green, Mary E Reid, Sarah A Mazzilli, Daniel T Merrick, Eric J Burks, Vijaya B Kolachalama, Jennifer E Beane
Bronchial premalignant lesions (PMLs) precede the development of invasive lung squamous carcinoma (LUSC), posing a significant challenge in distinguishing those likely to advance to LUSC from those that might regress without intervention. In this context, we present a novel computational approach, the Graph Perceiver Network (GRAPE-Net), leveraging hematoxylin and eosin (H&E) stained whole slide images
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ADP-dependent platelet activation is required for thrombus formation during a long-distance flight bioRxiv. Pathol. Pub Date : 2024-03-04 Julie Tour,, Estelle Carminita, Laurie Bruzzese, Lydie Crescence, Nabil Adjiriou, Regis Guieu, Christophe Dubois, Laurence Panicot-Dubois
The association between venous thromboembolism (VTE) and air travel is well documented.Prolonged exposure to reduced atmospheric pressure and low oxygen levels during flights triggers coagulation disorders, representing the primary risk factor for Deep Vein Thrombosis (DVT), surpassing immobility. In our study, we investigated how long-distance flight conditions affect VTE development in mice exposed
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Enhanced intracranial aneurysm development in a rat model of polycystic kidney disease. bioRxiv. Pathol. Pub Date : 2024-03-03 Anne F. Cayron, Sandrine Morel, Maral Azam, Julien Haemmerli, Tomohiro Aoki, Philippe Bijlenga, Eric Allemann, Brenda R. Kwak
Background: Polycystic kidney disease (PKD) patients have a high intracranial aneurysms (IAs) incidence and risk of rupture. The mechanisms that make PKD patients more vulnerable to IA disease are still not completely understood. The PCK rat is a well-known PKD model and has been extensively used to study cyst development and kidney damage. Here, we used this rat model to study IA induction and vulnerability
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Expression of fibroblast activation protein-α in human deep venous thrombus bioRxiv. Pathol. Pub Date : 2024-03-02 Nobuyuki Oguri, Toshihiro Gi, Eriko Nakamura, Eiji Furukoji, Hiroki Goto, Kazunari Maekawa, Atsushi B Tsuji, Ryuichi Nishii, Murasaki Aman, Sayaka Moriguchi-Goto, Tatefumi Sakae, Minako Azuma, Atsushi Yamashita
Background: Fibroblast activation protein-α (FAP), a type-II transmembrane serine protease, is expressed during wound healing, in cancer-associated fibroblasts, and in chronic fibrosing diseases. However, its expression in deep vein thrombus (DVT) remains unclear. Therefore, in this study, we investigated FAP expression and localization in DVT. Methods: First, we pathologically accessed aspirated thrombi
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Single-nucleus Multiomic Analyses Identifies Gene Regulatory Dynamics of Phenotypic Modulation in Human Aneurysmal Aortic Root bioRxiv. Pathol. Pub Date : 2024-03-02 Xuanyu Liu, Qingyi Zeng, Hang Yang, Wenke Li, Qianlong Chen, Kunlun Yin, Zihang Pan, Kai Wang, Mingyao Luo, Chang Shu, Zhou Zhou
Aortic root aneurysm is a potentially life-threatening condition that may lead to aortic rupture and is often associated with genetic syndromes, such as Marfan syndrome (MFS). Although studies with MFS animal models have provided valuable insights into the pathogenesis of aortic root aneurysms, our understanding of the transcriptomic and epigenomic landscape in human aortic root tissue remains incomplete
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Experimental evidence and meta-analysis indicate the negative effect of nosemosis on the survivorship of honeybees bioRxiv. Pathol. Pub Date : 2024-02-29 Monika Ostap-Chec, Jessica Cait, Wilder R Scott, Aneta Arct, Dawid Moron, Marcin Rapacz, Krzysztof Miler
Nosemosis, caused by microsporidian parasites of the genus Nosema, is considered a significant health concern for insect pollinators, including the most economically significant, the honeybee (Apis mellifera L.). Despite its acknowledged importance, the impact of this disease on honeybee survivorship remains unclear. In this study, we used a standard laboratory cage trial to compare mortality rates
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Single Testicular Biopsy: Changes in the vascular architecture of the tunica albuginea bioRxiv. Pathol. Pub Date : 2024-02-29 Antonio Barbosa de Oliveira Filho, Rita Peruquetti, Lucas Trevizani Rasmussen, Marcos Teixeira Cesar, Crescencio Alberto Pereira Centola, Agnaldo Pereira Cedenho
Open testicular biopsy is a commonly indicated procedure for diagnosis of testicular histopathology prior to referral to testicular sperm extraction (TESE) or microsurgical testicular sperm extraction (M TESE) in men with non-obstructive azoospermia (NOA). There are known hematological changes resulting from the rupture of the blood testis barrier in the TESE and M TESE procedures, but changes to the
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Stiffness Measurement of Retinal Capillaries and Subendothelial Matrix using Atomic Force Microscopy bioRxiv. Pathol. Pub Date : 2024-02-29 Irene Santiago Tierno, Mahesh Agarwal, Nikolaos Matisioudis, Sathishkumar Chandrakumar, Kaustabh Ghosh
Retinal capillary degeneration is a clinical hallmark of the early stages of diabetic retinopathy (DR). Our recent studies have revealed that diabetes-induced increase in retinal capillary stiffness plays a crucial and previously unrecognized causal role in inflammation-mediated degeneration of retinal capillaries. Retinal capillary stiffening results from overexpression of lysyl oxidase, an enzyme
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Distinctive retinal peri-arteriolar versus peri-venular amyloid plaque distribution correlates with the cognitive performance bioRxiv. Pathol. Pub Date : 2024-02-29 Oana M. Dumitrascu, Jonah Doustar, Dieu-Trang Fuchs, Yosef Koronyo, Dale S. Sherman, Michelle Shizu Miller, Kenneth O. Johnson, Roxana O. Carare, Steven R. Verdooner, Patrick D. Lyden, Julie A. Schneider, Keith L. Black, Maya Koronyo-Hamaoui
Introduction: The vascular contribution to Alzheimer's disease (AD) is tightly connected to cognitive performance across the AD continuum. We topographically describe retinal perivascular amyloid plaque (AP) burden in subjects with normal or impaired cognition. Methods: Using scanning laser ophthalmoscopy, we quantified retinal peri-arteriolar and peri-venular curcumin-positive APs in the first, secondary
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ADAMTS7 Promotes Smooth Muscle Cell Foam Cell Expansion in Atherosclerosis bioRxiv. Pathol. Pub Date : 2024-02-29 Allen Chung, Hyun K. Chang, Huize Pan, Alexander C Bashore, Karissa Shuck, Caio V. Matias, Juliana Gomez, Hanying Yan, Mingyao Li, Robert C Bauer
Human genetic studies have repeatedly associated SNPs near the gene ADAMTS7 with atherosclerotic cardiovascular disease. Subsequent investigations in mice demonstrated that ADAMTS7 is proatherogenic, induced in response to vascular injury, and alters smooth muscle cell function. However, the mechanisms governing this function and its relationship to atherosclerosis remain unclear. Here, we report the
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Enhanced microbiota profiling in patients with quiescent Crohn's disease through comparison with paired healthy first-degree relatives using fecal metagenomics and metabolomics bioRxiv. Pathol. Pub Date : 2024-02-28 Wanning Chen, Yichen Li, Wenxia Wang, Sheng Gao, Dingfeng Wu, Na Jiao, Tao Xu, Min Zhi, Lixin Zhu, Ruixin Zhu
Prior studies indicate no correlation between gut microbiota of healthy first-degree relatives (HFDRs) of Crohn's disease (CD) patients and development of CD. Here, we utilized HFDRs as controls to examine the microbiota and metabolome in individuals with active (CD-A) and quiescent (CD-R) CD, thereby minimizing the influence of genetic and environmental factors. Compared to non-relative controls,
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The Ubiquitin Ligase RBX2/SAG Regulates Mitochondrial Ubiquitination and Mitophagy bioRxiv. Pathol. Pub Date : 2024-02-28 Wenjuan Wang, Ermin Li, Jianqiu Zou, Chen Qu, Juan Ayala, Yuan Wen, Md Sadikul Islam, Neal L Weintraub, David J Fulton, Qiangrong Liang, Jiliang Zhou, Jinbao Liu, Jie Li, Yi Sun, Huabo Su
Clearance of damaged mitochondria via mitophagy is crucial for cellular homeostasis. While the role of ubiquitin (Ub) ligase PARKIN in mitophagy has been extensively studied, increasing evidence suggests the existence of PARKIN-independent mitophagy in highly metabolically active organs such as the heart. Here, we identify a crucial role for Cullin-RING Ub ligase 5 (CRL5) in basal mitochondrial turnover
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Multimodal histopathologic models stratify hormone receptor-positive early breast cancer bioRxiv. Pathol. Pub Date : 2024-02-28 Kevin Michael Boehm, Omar S. M. El Nahhas, Antonio Marra, Pier Selenica, Hannah Y Wen, Britta Weigelt, Evan D Paul, Pavol Cekan, Ramona Erber, Chiara M. L. Loeffler, Elena Guerini-Rocco, Nicola Fusco, Chiara Frascarelli, Eltjona Mane, Elisabetta Munzone, Silvia Dellapasqua, Paola Zagami, Giuseppe Curigliano, Pedram Razavi, Jorge S. Reis-Filho, Fresia Pareja, Sarat Chandarlapaty, Sohrab P Shah, Jakob
For patients with hormone receptor-positive, early breast cancer without HER2 amplification, multigene expression assays including Oncotype DX (R) recurrence score (RS) have been clinically validated to identify patients who stand to derive added benefit from adjuvant cytotoxic chemotherapy. However, cost and turnaround time have limited its global adoption despite recommendation by practice guidelines
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Transcriptomic signature and pro-osteoclastic secreted factors of abnormal bone marrow stromal cells in fibrous dysplasia bioRxiv. Pathol. Pub Date : 2024-02-28 Zachary Michel, Layne N Raborn, Tiahna Spencer, Kristen S Pan, Daniel Martin, Kelly L Roszko, Yan Wang, Pamela Robey, Alison Boyce, Michae T Collins, Luis Fernandez de Castro
Fibrous dysplasia (FD) is a mosaic skeletal disorder caused by somatic activating variants in GNAS, encoding for Gαs, which leads to excessive cAMP signaling in bone marrow stromal cells (BMSCs). Despite advancements in our understanding of FD pathophysiology, the effect of Gαs activation in the BMSC transcriptome remains unclear, as well as how this translates into their local influence in the lesional
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In-Vivo and In-Vitro Toxicity Evaluation of 2,3-Dimethylquinoxaline: an Antimicrobial Found in a Traditional Herbal Medicine bioRxiv. Pathol. Pub Date : 2024-02-28 Abdelbagi Alfadil, Hamoud Alsamhan, Ahmed Ali, Huda Alkreathy, Mohammad Alrabia, Asif fatani, Karem A Ibrahem
2,3-dimethylquinoxaline (DMQ) is a broad-spectrum antimicrobial phytochemical. This study aims to assess its toxicological profile. In vitro studies conducted in appropriate cell cultures, included assessment of cardiotoxicity, nephrotoxicity, and hepatotoxicity. An in vivo study was conducted in mice to determine acute oral toxicity (AOT), and subacute oral toxicity (SAOT). Acute dermal toxicity (ADT)
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Unraveling the Complexity of Abdominal Aortic Aneurysm: Multiplexed Imaging Insights into C-Reactive Protein-Related Variations bioRxiv. Pathol. Pub Date : 2024-02-26 Eun Na Kim, Hee Young Seok, Jiwon Koh, Wookyeom Yang, Gyu Ho Lee, Woo Hee Choi, Joon Seo Lim, You Jung Ok, Jae-Sung Choi, Chong Jai Kim, Lizhe Zhuang, Young Hwan Chang, Se Jin Oh
Background: Abdominal aortic aneurysm (AAA) is a potentially lethal condition that often remains asymptomatic until it ruptures. Recent research suggests that immune-inflammatory processes are associated with AAA development, yet the exact mechanisms remain unclear. Serum C-reactive protein (CRP) serves as a prognostic marker for AAA and various cardiovascular diseases. When CRP accumulates in damaged
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Neutrophil extracellular traps drive acute lupus flares with skin and kidney inflammation triggered by ultraviolet irradiation bioRxiv. Pathol. Pub Date : 2024-02-23 Xing Lyu, Minghui Li, Ping L. Zhang, Wei Wei, Victoria P. Werth, Ming-Lin Liu
Sunlight overexposure triggers acute lupus flares, causing local skin and systemic inflammation and tissue injury, including the kidneys, through poorly understood mechanisms. To address this knowledge gap, we exposed asymptomatic, young female lupus-prone mice to UVB, inducing skin and kidney inflammation with proteinuria, accompanied by neutrophil infiltration in both organs and formation of neutrophil
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Targeted NAD+ Delivery for Intimal Hyperplasia and Re-endothelialization: A Novel Anti-restenotic Therapy Approach bioRxiv. Pathol. Pub Date : 2024-02-23 Li Yin, Yao Tong, Zain Husain Islam, Kaijie Zhang, Ruosen Xie, Jacobus Burger, Nicholas Hoyt, Eric William Kent, William Aaron Marcum, Campbell Johnston, Rohan Kanchetty, Zoe Tetz, Sophia Stanisic, Yitao Huang, Lian-Wang Guo, Shaoqin Gong, Bowen Wang
Endovascular interventions often fail due to restenosis, primarily caused by smooth muscle cell (SMC) proliferation, leading to intimal hyperplasia (IH). Current strategies to prevent restenosis are far from perfect and impose significant collateral damage on the fragile endothelial cell (EC), causing profound thrombotic risks. Nicotinamide adenine dinucleotide (NAD+) is a co-enzyme and signaling substrate
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Enhanced cardiac mitochondrial biogenesis by nitro-oleic acid remedies diastolic dysfunction in a mouse model of heart failure with preserved ejection fraction bioRxiv. Pathol. Pub Date : 2024-02-22 Marion Mueller, Torben Schubert, Cornelius Welke, Tina Johanna Schulz, Thomas Patschkowski, Tibor Maske, Luisa Andrea Lengenfelder, Lucia Landwehrjohann, Elfi Donhauser, Elisa Theres Vogt, Bernd Stratmann, Jurek Hense, Simon Luedtke, Martina Duefer, Elen Tolstik, Johann Dierks, Felix-Levin Hormann, Sven Heiles, Kristina Lorenz, Jan-Christian Reil, Francisco Jose Schopfer, Bruce A Freeman, Volker Rudolph
Prevalence of heart failure with preserved ejection fraction (HFpEF) is increasing, while treatment options are inadequate. Hypertension and obesity-related metabolic dysfunctions contribute to HFpEF progression. Nitro-oleic acid (NO2-OA) impacts metabolic processes by improving glucose tolerance and adipocyte function. In this study, 4 week treatment with NO2-OA ameliorated diastolic dysfunction in
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The Rift Valley fever (RVF) vaccine candidate 40Fp8 shows an extreme attenuation in IFNARKO mice following intranasal inoculation bioRxiv. Pathol. Pub Date : 2024-02-22 Belen Borrego, Celia Alonso, Sandra Moreno, Nuria de la Losa, Pedro Jose Sanchez-Cordon, Alejandro Brun
Rift Valley fever (RVF) is an important zoonotic viral disease affecting several species of domestic and wild ruminants, causing major economic losses and dozens of human deaths in various geographical areas of Africa, where it is endemic. Although it is not present in Europe, there is a risk of its introduction and spread linked to globalisation and climate change. At present, the only measure that
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PathEX: Make Good Choice for Whole Slide Image Extraction bioRxiv. Pathol. Pub Date : 2024-02-22 Xinda Yang, Ranze Zhang, Yuan Yang, Yu Zhang, Kai Chen
Background: The tile-based approach has been widely used for slide-level predictions in whole slide image (WSI) analysis. However, the irregular shapes and variable dimensions of tumor regions pose challenges for the process. To address this issue, we proposed PathEX, a framework that integrates intersection over tile (IoT) and background over tile (BoT) algorithms to extract tile images around boundaries
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Risk and loss aversion and attitude to COVID and vaccines in anxious individuals bioRxiv. Pathol. Pub Date : 2024-02-22 Filippo Ferrari, Jesse Alexander, Peggy Seriès
Anxious individuals are known to show impaired decision-making in economic gambling task and in everyday life decisions. This impairment can be due to aversion to uncertainty about outcomes (risk aversion) and/or aversion to negative outcomes (loss aversion). We investigate how non-clinical individuals with high levels of Generalised Anxiety Disorder (GAD) (N = 54) behave compared to less anxious subjects
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Lineage-tracing of Acta2+ cells in aged mice during lung fibrosis formation and resolution supports the lipofibroblasts to myofibroblast reversible switch bioRxiv. Pathol. Pub Date : 2024-02-22 Arun Lingampally, Marin Truchi, Olivier Mauduit, Vanessa Delcroix, Stefan Hadzic, Janine Koepke, Ana-Ivonne Vazquez-Armendariz, Susanne Herold, Christos Samakovlis, Helena Makarenkova, Elie El Agha, Chengshui Chen, Bernard Mari, Saverio Bellusci
Idiopathic pulmonary fibrosis (IPF) develops mostly in old man and is characterized by the irreversible accumulation of excessive extracellular matrix components by activated myofibroblasts (aMYFs) leading to lung failure. Following bleomycin administration in young mice, fibrosis formation associated with efficient resolution takes place, the later limiting the clinical relevance of this model for
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Comparative analyses of adsorbed circulating proteins in the PMMA and PES hemodiafilters in patients on predilution online hemodiafiltration bioRxiv. Pathol. Pub Date : 2024-02-22 Md. Shoriful Islam, Shingo Ema, Md. Mahamodun Nabi, Md. Muedur Rahman, A.S.M. Waliullah, Jing Yan, Rafia Ferdous, Takumi Sakamoto, Yutaka Takahashi, Akihiko Kato, Tomoaki Kahyo, Tomohito Sato, Mitsutoshi Setou
Acute and chronic inflammation are common in patients with end-stage kidney disease (ESKD). So, the adsorption of pro-inflammatory cytokines by the hollow fiber has been expected to modify the inflammatory dysregulation in ESKD patients. However, it remains to be determined in detail what molecules of fiber materials can preferably adsorb proteins from the circulating circuit. We aimed this study to
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Host 5-HT affects Plasmodium transmission in mosquitoes via modulating mosquito mitochondrial homeostasis bioRxiv. Pathol. Pub Date : 2024-02-21 Li Gao, Benguang Zhang, Yuebiao Feng, Wenxu Yang, Shibo Zhang, Jingwen Wang
Malaria parasites hijack the metabolism of their mammalian host during the blood-stage cycle. Anopheles mosquitoes depend on mammalian blood to survive and to transmit malaria parasites. However, it remains understudied whether changes in host metabolism affect parasite transmission in mosquitoes. In this study, we discovered that Plasmodium infection significantly decreased the levels of the tryptophan
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Genetic diversity in vector populations influences the transmission efficiency of an important plant virus bioRxiv. Pathol. Pub Date : 2024-02-21 Daniel Joseph Leybourne, Mark Andrew Whitehead, Torsten Will
The transmission efficiency of aphid-vectored plant viruses can differ between aphid populations. Intra-species diversity (genetic variation, endosymbionts) is a key determinant of aphid phenotype; however, the extent of which intra-species diversity contributes towards variation in virus transmission efficiency is unclear. Here, we use multiple populations of two key aphid species that vector barley
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Interlimb coordination in Parkinson's disease is minimally affected by a visuospatial dual task bioRxiv. Pathol. Pub Date : 2024-02-21 Allen Hill, Julie Nantel
Parkinson's disease (PD) leads to reduced spatial and temporal interlimb coordination during gait as well as reduced coordination in the upper or lower limbs. Multi-tasking when walking is common during real-world activities, and affects some gait characteristics, like gait speed and variability. However, the impact of a dual task (DT) on intra and interlimb coordination of both lower and upper limbs
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Membrane Bound O-Acyltransferase 7 (MBOAT7) Shapes Lysosomal Lipid Homeostasis and Function to Control Alcohol-Associated Liver Injury bioRxiv. Pathol. Pub Date : 2024-02-21 Venkateshwari Varadharajan, Iyappan Ramachandiran, William J Massey, Raghav Jain, Rakhee Banerjee, Anthony J Horak, Megan R McMullen, Emily Huang, Annette Bellar, Shuhui W Lorkowski, Kailash Gulshan, Robert N Helsley, Isabella James, Vai Pathak, Jaividhya Dasarathy, Nicole Welch, Srinivasan Dasarathy, David Streem, Ofer Reizes, Daniela S Allende, Jonathan D Smith, Judith Simcox, Laura E Nagy, J. Mark
Several recent genome-wide association studies (GWAS) have identified single nucleotide polymorphism (SNPs) near the gene encoding membrane-bound O-acyltransferase 7 (MBOAT7) that is associated with advanced liver diseases. In fact, a common MBOAT7 variant (rs641738), which is associated with reduced MBOAT7 expression, confers increased susceptibility to non-alcoholic fatty liver disease (NAFLD), alcohol-associated
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MicroRNA-26b protects against MASH development and can be efficiently targeted with lipid nanoparticles. bioRxiv. Pathol. Pub Date : 2024-02-21 Linsey Peters, Leonida Rakateli, Rosanna Huchzermeier, Andreas Bonnin-Marquez, Sanne L. Maas, Cheng Lin, Alexander Jans, Yana Geng, Alan Gorter, Marion Gijbels, Sander Rensen, Peter Olinga, Tim Hendrikx, Marcin Krawczyk, Malvina Brisbois, Joachim Jankowski, Kiril Bidzhekov, Christian Weber, Erik A.L. Biessen, Ronit Shiri-Sverdlov, Tom Houben, Yvonne Doering, Mathias Bartneck, Emiel P.C. van der Vorst
Background & Aims. The prevalence of metabolic dysfunction-associated steatohepatitis (MASH) is increasing, urging more research into the underlying mechanisms. MicroRNA-26b (miR-26b) might play a role in several MASH-related pathways. Therefore, we aimed to determine the role of miR-26b in MASH and its therapeutic potential using miR-26b mimic-loaded lipid nanoparticles (LNPs). Methods. Apoe-/-Mir26b-/-
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PKR activation-induced mitochondrial dysfunction in HIV-transgenic mice with nephropathy bioRxiv. Pathol. Pub Date : 2024-02-19 Teruhiko Yoshida, Khun Zaw Latt, Avi Z. Rosenberg, Briana A Santo, Komuraiah Myakala, Yu Ishimoto, Yongmei Zhao, Shashi Shrivastav, Bryce A. Jones, Xiaoping Yang, Xiaoxin Wang, Vincent M. Tutino, Pinaki Sarder, Moshe Levi, Koji Okamoto, Cheryl A. Winkler, Jeffrey B. Kopp
HIV disease remains prevalent in the USA and chronic kidney disease remains a major cause of morbidity in HIV-1-positive patients. Host double-stranded RNA (dsRNA)-activated protein kinase (PKR) is a sensor for viral dsRNA, including HIV-1. We show that PKR inhibition by compound C16 ameliorates the HIV-associated nephropathy (HIVAN) kidney phenotype in the Tg26 transgenic mouse model, with reversal
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COVID-19 during pregnancy alters circulating extracellular vesicle cargo and their effects on trophoblast bioRxiv. Pathol. Pub Date : 2024-02-19 Thea N Golden, Sneha Mani, Lauren Anton, Colin C Conine, Rebecca L Linn, Rita Leite, Brett A Kaufman, Monica Mainigi, Natalie A Trigg, Annette Wilson, Jerome F Strauss, Samuel Parry, Rebecca A Simmons
SARS-CoV-2 infection and the resulting coronavirus disease (COVID-19) complicate pregnancies as the result of placental dysfunction which increases the risk of adverse pregnancy outcomes. While abnormal placental pathology resulting from COVID-19 is common, direct infection of the placenta is rare. This suggests maternal response to infection is responsible for placental dysfunction. We hypothesized
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Monoclonal antibody chP3R99 reduces subendothelial retention of atherogenic lipoproteins in Insulin-Resistant rats: Acute treatment versus long-term protection as an idiotypic vaccine for atherosclerosis bioRxiv. Pathol. Pub Date : 2024-02-17 Yosdel Soto, Arletty Hernández, Roger Sarduy, Victor Brito, Sylvie Marleau, Donna Vine, Ana Maria Vázquez, Spencer D Proctor
BACKGROUND: Atherosclerosis is triggered by the retention of apolipoprotein B containing lipoproteins by proteoglycans. In addition to LDL, remnant lipoproteins have emerged as pivotal contributors to this pathology, particularly in the context of insulin resistance and diabetes. We have previously reported anti-atherogenic properties of a monoclonal antibody (chP3R99) that recognizes sulfated glycosaminoglycans
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Human iPSC-derived Committed Cardiac Progenitors Generate Cardiac Tissue Grafts in a Swine Ischemic Cardiomyopathy Model without Triggering Ventricular Arrhythmias bioRxiv. Pathol. Pub Date : 2024-02-17 Amish N. Raval, Eric G. Schmuck, Sushmita Roy, Yukihiro Saito, Tianhua Zhou, James Conklin, Timothy A. Hacker, Chad Koonce, Meghan Boyer, Kristin Stack, Ellen Hebron, Scott K. Nagle, Patrick C.H. Hsieh, Timothy J Kamp
Background: The adult human heart following a large myocardial infarction is unable to regenerate heart muscle and instead forms scar with the risk of progressive heart failure. Large animal studies have shown that intramyocardial injection of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) following a myocardial infarction result in cell grafts but also ventricular arrhythmias. We hypothesized
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Meiotic recombination in Leptosphaeria maculans favours the rise of transgressive isolates adapted to a nonhost species, Brassica carinata bioRxiv. Pathol. Pub Date : 2024-02-16 Julie M Noah, Mathilde Gorse, Carole-Anne Romain, Elise J Gay, Thierry Rouxel, Marie-Helene Balesdent, Jessica L Soyer
Leptosphaeria maculans is one of the major fungal pathogens on oilseed rape (Brassica napus), causing stem canker disease. The closely related Brassica species Brassica nigra, Brassica juncea, and Brassica carinata display extreme resistance toward stem canker. In this study, we demonstrate the nonhost status of B. carinata toward L. maculans in France through field experiments and inoculations performed
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Identification of retinal tau oligomers, citrullinated tau, and other tau isoforms in early and advanced AD and relations to disease status bioRxiv. Pathol. Pub Date : 2024-02-16 Haoshen Shi, Nazanin Mirzaei, Yosef Koronyo, Miyah R. Davis, Edward Robinson, Gila M. Braun, Ousman Jallow, Altan Rentsendorj, V Krishnan Ramanujan, Justyna Fert-Bober, Andrei A. Kramerov, Alexander V. Ljubimov, Lon S. Schneider, Warren G. Tourtellotte, Debra Hawes, Julie A. Schneider, Keith L. Black, Rakez Kayed, Maj-Linda B. Selenica, Daniel C. Lee, Dieu-Trang Fuchs, Maya Koronyo-Hamaoui
Importance: This study identifies and quantifies diverse pathological tau isoforms in the retina of both early and advanced-stage Alzheimer's disease (AD) and determines their relationship with disease status. Objective: A case-control study was conducted to investigate the accumulation of retinal neurofibrillary tangles (NFTs), paired helical filament (PHF)-tau, oligomeric tau (oligo-tau), hyperphosphorylated
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Enhancing Bone Regeneration and Osseointegration using rhPTH(1-34) and Dimeric R25CPTH(1-34) in an Osteoporotic Beagle Model bioRxiv. Pathol. Pub Date : 2024-02-12 Jeong-Oh Shin, Jong-bin Lee, Sihoon Lee, Jinwoo Kim
Introduction: Despite continuous parathyroid hormone (PTH) exposure potentially accelerating bone resorption, intermittent PTH administration has shown anabolic effects on bone microarchitecture. This study investigates the therapeutic impacts of two PTH analogs, rhPTH(1-34) and dimeric R25CPTH(1-34) on bone regeneration and osseointegration in a postmenopausal osteoporosis animal model. Methods: Twelve
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NRP1-expressing myeloid cells promote arteriogenesis in the ischemic limb bioRxiv. Pathol. Pub Date : 2024-02-12 Jun Seok Cho, Ashish S Patel, Alessandro Fantin, Francesca E Ludwinski, Celine Pichette, Martina Rudnicki, Laura Denti, Angeles Mondragon, Prakash Saha, Alberto Smith, Christiana Ruhrberg, Bijan Moderai
Peripheral arterial disease can cause limb threatening blood flow restriction, requiring amputation in up to a third of patients despite contemporary treatments. Stimulating new blood vessel growth in ischemic limbs using growth factors such as VEGF-A or supplying mixed cell populations via autologous transplantation has been investigated as a therapy for surgically intractable cases, but to date has
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Therapeutic potential of glabridin and gymnemic acid alleviates eye choroidal thickness and neovascularization in diabetic model rats bioRxiv. Pathol. Pub Date : 2024-02-12 Wipapan Khimmaktong, Manaras Komolkriengkrai, Udomlak Matsathit
Small blood vessels in the eyes are more susceptible to injury, which can lead to complications. However, since diabetic retinopathy is often a serious clinical condition, most of this study focuses on the vascular system of the choroid. As part of this study, we looked at how gymnemic acid (from Gymnema sylvestre) and glabridin (from Glycyrrhiza glabra, or licorice) might help diabetic rats' choroid
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Impaired islet function with normal exocrine enzyme secretion is consistent across the head, body, and tail pancreas regions in type 1 diabetes bioRxiv. Pathol. Pub Date : 2024-02-12 Denise Drotar, Ana Karen Mojica-Avila, Drew T Bloss, Christian M Cohrs, Cameron T Manson, Amanda L Posgai, MacKenzie D Williams, Maigan A Brusko, Edward A Phelps, Clive H Wasserfall, Stephan Speier, Mark A Atkinson
Histopathological heterogeneity in human pancreas has been well documented; however, functional evidence at the tissue level is scarce. Herein we investigated in situ glucose-stimulated islet and carbachol-stimulated acinar cell secretion across the pancreas head (PH), body (PB), and tail (PT) regions in no diabetes (ND, n=15), single islet autoantibody-positive (1AAb+, n=7), and type 1 diabetes donors
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Loss of endogenous estrogen alters mitochondrial metabolism and muscle clock-related protein Rbm20 in female mdx mice bioRxiv. Pathol. Pub Date : 2024-02-12 Cara A Timpani, Didier Debrincat, Stephanie Kourakis, Rebecca Boyer, Luke E Formosa, Joel R Steele, Haijian Zhang, Ralf B Schittenhelm, Aaron P Russell, Emma Rybalka, Angus Lindsay
Female carriers of a Duchenne muscular dystrophy (DMD) gene mutation manifest exercise intolerance and metabolic anomalies that may be exacerbated following menopause due to the loss of estrogen, a known regulator of skeletal muscle function and metabolism. Here, we studied the impact of estrogen depletion (via ovariectomy) on exercise tolerance and muscle mitochondrial metabolism in female mdx mice
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The Xanthomonas fragariae effector XopK suppresses stomatal immunity by perturbing abscisic acid signaling in strawberry bioRxiv. Pathol. Pub Date : 2024-02-09 Jiayue Feng, Xiaolin Cai, WenYao Zhang, Haiyan Yu, Ying-Qiang Wen
Xanthomonas fragariae (Xaf) usually causes angular leaf spot (ALS) in strawberry all over the world. Recently, we isolated a new strain of Xaf called Xaf YL19. This strain causes not only typical ALS symptoms, but also dry cavity rot in the crown tissues of strawberries. This was the first time a Xaf strain had both of these effects in strawberries. Pathogen effectors play a crucial role in plant colonization
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An image segmentation pipeline optimized for human microglia uncovers sources of morphological diversity in Alzheimer's disease bioRxiv. Pathol. Pub Date : 2024-02-07 Robert M De Jager, Annie J Lee, Alina Sigalov, Mariko Taga
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and the accumulation of beta-amyloid plaques and neurofibrillary tangles. Microglia, the resident immune cells in the brain, play a crucial role in AD pathology, particularly in relation to amyloid plaques. However, the exact role of plaque-associated microglia and their morphological changes in AD progression
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Disconnection Between Microvascular Damage and Neurodegeneration in Early Diabetic Retinopathy bioRxiv. Pathol. Pub Date : 2024-02-02 Qian Yang, Marina Yasvoina, Abraham Olvera-Barrios, Joel Mendes, Meidong Zhu, Cathy Egan, Adnan Tufail, Marcus Fruttiger
Aim: Diabetic retinopathy (DR) is a common complication of diabetes mellitus and can result in vision loss. Early clinically diagnosed signs of DR are linked to vascular damage, impacting on the neural retina typically at later stages. However, vascular changes and potential effects on neural cells before clinical diagnosis of DR are less understood. Methods: To learn more about the earliest stages
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The Effect of Adrenalectomy on Bleomycin-Induced Pulmonary Fibrosis in Mice bioRxiv. Pathol. Pub Date : 2024-02-02 John McGovern, Carrighan Perry, Alexander Ghincea, Shuai Shao, Erica L Herzog, Huanxing Sun
Progressive lung fibrosis is often fatal and has limited treatment options. Though the mechanisms are poorly understood, fibrosis is increasingly linked with catecholamines such as adrenaline (AD) and noradrenaline (NA), and hormones such as aldosterone (ALD). The essential functions of adrenal glands include the production of catecholamines and numerous hormones, but the contribution of adrenal glands
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Loss of TIM4-Dependent Efferocytosis in Kupffer Cells Promotes Liver Fibrosis in Nonalcoholic Steatohepatitis bioRxiv. Pathol. Pub Date : 2024-02-02 Hongxue Shi, Xiaobo Wang, Brennan Gerlach, Arif Yurdagul, Mary Moore, Faridoddin Mirshahi, Luisa Ronzoni, Arun Sanyal, Luca Valenti, Chyuan-Sheng Lin, Ira Tabas
Background and aims: Hepatocyte apoptosis is a key feature of non-alcoholic steatohepatitis (NASH), but the fate of apoptotic hepatocytes in NASH is poorly understood. Herein we explore the hypothesis that impaired TIM4-mediated clearance of dead hepatocytes by liver macrophages (efferocytosis) is impaired in NASH and drives the progression to liver fibrosis. Methods: Kupffer cell (KC)-TIM4 expression
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The Intricate Relationship of G-Quadruplexes and Bacterial Pathogenicity Islands bioRxiv. Pathol. Pub Date : 2024-02-01 Bo Lyu, Qisheng Song
The dynamic interplay between guanine-quadruplex (G4) structures and pathogenicity islands (PAIs) represents a captivating area of research with implications for understanding the molecular mechanisms underlying pathogenicity. This study conducted a comprehensive analysis of a large-scale dataset from reported 89 pathogenic strains of bacteria to investigate the potential interactions between G4 structures
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A drug cocktail of rapamycin, acarbose, and phenylbutyrate enhances resilience to features of early-stage Alzheimer's disease in aging mice bioRxiv. Pathol. Pub Date : 2024-01-30 Jackson Wezeman, Martin Darvas, Nadia Postupna, Jenna Klug, Ruby Sue Mangalindan, Addison Keely, Kathryn Nguyen, Chloe Johnson, Manuela Rosenfeld, Warren Ladiges
The process of aging is defined by the breakdown of critical maintenance pathways leading to an accumulation of damage and its associated phenotypes. Aging affects many systems and is considered the greatest risk factor for a number of diseases. Therefore, interventions aimed at establishing resilience to aging should delay or prevent the onset of age-related diseases. Recent studies have shown a three-drug
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Nephrectomy and high-salt diet inducing pulmonary hypertension and kidney damage by increasing Ang II concentration in rats bioRxiv. Pathol. Pub Date : 2024-01-30 Yuqin Chen, Qian Jiang, qifeng yang, Chenting Zhang, Chi Hou, wei hong, min du, Xiaoqian Shan, xuanyi li, Dansha Zhou, dongmei wen, yuanhui xiong, Kai Yang, Ziying Lin, jingjing song, zhanjie mo, Huazhuo Feng, Yue Xing, Xin Fu, Chunli Liu, fang peng, Bing Li, wenju lu, Jason Yuan, Jian Wang
Background: Pulmonary hypertension (PH) is a common complication in patients with chronic kidney disease (CKD), affecting prognosis. However, the pathogenesis is not clear, and the lack of a stable animal model is a significant factor. Methods: In this study, a rat model of chronic kidney disease with pulmonary hypertension (CKD-PH) was developed through 5/6 nephrectomy combined with a high-salt diet
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Comparative transcriptome analysis provides insights into the resistance regulation mechanism and inhibitory effect of fungicide phenamacril in Fusarium asiaticum bioRxiv. Pathol. Pub Date : 2024-01-29 Zhitian Zheng, Huaqi Liu, Xiao Luo, Runze Liu, Alexxander Joe, Haolin Li, Haiyan Sun, Lin Yanling, Yanzhong Li, Yunpeng Wang
Fusarium asiaticum is a destructive phytopathogenic fungus that causes Fusarium head blight of wheat (FHB), leading to serious yield and economic losses to cereal crops worldwide. Our previous studies indicated that target-site mutations (K216R/E, S217P/L, or E420K/G/D) of Type I myosin FaMyo5 conferred high resistance to phenamacril. Here, we first constructed a sensitive strain H1S and point mutation
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XKidneyOnco: An Explainable Framework to Classify Renal Oncocytoma and Chromophobe Renal Cell Carcinoma with a Small Sample Size bioRxiv. Pathol. Pub Date : 2024-01-26 Tahereh Javaheri, Samar Heidari, Xu Yang, Sandeep Yerra, Khaled Seidi, Tahereh Setayesh, Guanglan Zhang, Lou Chitkushev, Sayeeduddin Shahida Salar, Zahida Sayeeduddin, Neda Zarrin-Khameh, Mohammad Hadi Gharib, Patricia Castro, Mohammad Haeri, Reza Rawassizadeh
Renal oncocytoma and chromophobe renal cell carcinoma are two kidney cancer types that present a diagnostic challenge to pathologists and other clinicians due to their microscopic similarities. While RO is a benign renal neoplasm, ChRCC is considered malignant. Therefore, the differentiation between the two is crucial. In this study, we introduce an explainable framework to accurately differentiate
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Functional studies of deafness-associated pendrin and prestin variants bioRxiv. Pathol. Pub Date : 2024-01-26 Satoe Takahashi, Takashi Kojima, Koichiro Wasano, Kazuaki Homma
Pendrin and prestin are evolutionary conserved membrane proteins that are essential for normal hearing. Pendrin is an anion transporter required for normal development and maintenance of ion homeostasis in the inner ear, while prestin is a voltage-dependent motor responsible for cochlear amplification essential for high sensitivity and frequency selectivity of mammalian hearing. Dysfunction of these
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LRG1 promotes atherosclerosis by activating macrophages bioRxiv. Pathol. Pub Date : 2024-01-25 Juan Wang, Sitao Zhang, Jing Wang, Jiuchang Zhong, Hongbin Liu, Weiming Li, Mulei Chen, Li Xu, Wenbin Zhang, Ze Zhang, Zhizhong Wei, Jia Guo, Xinyu Wang, Jianhua Sui, Xingpeng Liu, Xiaodong Wang
Background Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by the accumulation of cholesterol-rich lipoproteins in macrophages. Leucine-rich alpha-2 glycoprotein 1 (LRG1) is a circulating protein associated with inflammation, however, its role in atherosclerosis remains unclear. This study identified its role in macrophage pro-inflammatory differentiation and revealed
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Activation of HIF2 leads to vascular remodeling and inflammation, coronary thrombosis and arterial dilation, recapitulating cardiac involvement of Kawasaki disease. bioRxiv. Pathol. Pub Date : 2024-01-25 Beatriz Escobar, Ivan Menendez-Montes, Teresa Albendea-Gomez, Susana Mendoza-Tamajon, Rosana Castro-Mecinas, Covadonga Diaz-Diaz, Beatriz Palacios, Jesus Ruiz-Cabello, Luis Jesus Jimenez-Borreguero, Maria C Cid, Kei Takahashi, Silvia Martin-Puig
Background: global deletion of Vhl leads to vascular defects and early lethality, precluding the study of VHL/HIF signaling during coronary formation and homeostasis. Hypoxia pathway has been associated with cardiovascular diseases involving inflammation and vascular remodeling like atherosclerosis, but its role in Kawasaki Disease (KD) remains unknown. Coronary dilatation and vessel rupture are the
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The SUbventral-Gland master Regulator (SUGR) of nematode virulence bioRxiv. Pathol. Pub Date : 2024-01-24 Clement Pellegrin, Anika Damm, Alexis L. Sperling, Beth Molloy, Dio S. Shin, Jonathan Long, Paul Brett, Andrea Diaz-Tendero Bravo, Sarah Jane Lynch, Beatrice Senatori, Paulo Vieira, Joffrey Mejias, Anil Kumar, Rick E. Masonbrink, Tom R. Maier, Thomas J. Baum, Sebastian Eves-van den Akker
All pathogens must tailor their gene expression to their environment. Therefore, targeting host:parasite biology that regulates these changes in gene expression could open up routes to pathogen control. Here, we show that in the plant-parasitic nematode Heterodera schachtii, host signals (termed effectostimulins) within plant roots activate the master regulator sugr1. SUGR1, then, directly binds effector
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Feline tooth resorption in a case-control study based on a subpopulation of 944 dentally examined cats from a Finnish questionnaire survey of over 8000 cats bioRxiv. Pathol. Pub Date : 2024-01-24 Katariina Vapalahti, Henriikka Neittaanmäki, Hannes Lohi, Anna-Maija Virtala
Tooth resorption (TR) is one of cats' most common dental diseases. It is a painful condition characterized by progressive dental destruction, which eventually results in loss of teeth. The aetiology of the TR remains unclear, but associations with old age, breed, other oral and dental diseases, and certain environmental factors have been suspected. In our study, we used part of the data from the extensive
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Impact of Mesotherapy with Sodium Deoxycholate on Liver: Metabolic- and Sex-Specific Insights in Swiss mice bioRxiv. Pathol. Pub Date : 2024-01-23 Leidyanne Ferreira Goncalves, Beatriz Rodrigues Rosa, Isabela Terra Tavares Ramos, Julia Bueno Feder, Julia Rajczuk Martins Messina, Raissa Moreira Barreira, Vanessa Morales Torres, Vitor Lima Simoes, Elan Cardozo Paes-de-Almeida, Caroline Fernandes-Santos
Background: Sodium deoxycholate (DC) is often used in mesotherapy for the aesthetic improvement of body contouring. Although it is a minimally invasive procedure, DC use is off-label since, to date, it is approved solely for submental fat reduction, lacking evidence to support its safety to other body regions. Objective: To investigate the systemic and hepatic effects of the prolonged use of DC in
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Cross-institutional HER2 assessment via a computer-aided system using federated learning and stain composition augmentation bioRxiv. Pathol. Pub Date : 2024-01-22 Chia-Hung Yang, Yung-An Chen, Shao-Yu Chang, Yu-Han Hsieh, Yu-Ling Hung, Yi-Wen Lin, Yi-Hsuan Lee, Ching-Hung Lin, Yu-Chieh Lin, Yen-Shen Lu, Yen-Yin Lin
The rapid advancement of precision medicine and personalized healthcare has heightened the demand for accurate diagnostic tests. These tests are crucial for administering novel treatments like targeted therapy. To ensure the widespread availability of accurate diagnostics with consistent standards, the integration of computer-aided systems has become essential. Specifically, computer-aided systems