Disease Models & Mechanisms
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#1Kyoko Yamashita (UTokyo: University of Tokyo)H-Index: 3
#2Ayano Oi (UTokyo: University of Tokyo)H-Index: 1
Last. Fumiaki Obata (UTokyo: University of Tokyo)H-Index: 12
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Early-life inflammatory response is associated with risks of age-related pathologies. How transient immune signalling activity during animal development influences life-long fitness is not well understood. Using Drosophila as a model, we find that activation of innate immune pathway IMD signalling in the developing larvae increases adult starvation resistance, decreases food intake, and shortens organismal lifespan. Interestingly, lifespan is shortened by the IMD activation in the larval gut and...
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Cell competition is a process by which suboptimal cells are eliminated to the benefit of cells with higher fitness. It is a surveillance mechanism that senses differences in the fitness status by several modes, such as expression of fitness fingerprints, survival factor uptake rate and resistance to mechanical stress. Fitness fingerprints-mediated cell competition recognizes isoforms of the transmembrane protein Flower, and translates the relative fitness of cells into distinct fates through the...
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#1Anne E. Turco (UW: University of Wisconsin-Madison)H-Index: 4
#2Steven R. Oakes (UW: University of Wisconsin-Madison)H-Index: 3
Last. Celeste M Sheftel (UW: University of Wisconsin-Madison)
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Benign Prostatic Hyperplasia / Lower Urinary Tract Dysfunction (BPH/LUTD) is a classic disease of aging which affects nearly all men. Symptoms typically present in the fifth or sixth decade and progressively worsen over the remainder of life. Here, we identify a surprising origin of this disease that traces back to the intrauterine environment of the developing male, challenging existing paradigms about when this disease process begins. We delivered a single bolus dose of a widespread environmen...
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#1Kim Wong (Wellcome Trust Sanger Institute)H-Index: 25
#2Latasha Ludwig (U of G: University of Guelph)H-Index: 2
Last. Louise van der Weyden (Wellcome Trust Sanger Institute)H-Index: 38
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Angiosarcoma (AS) is a highly aggressive tumor of blood and lymphatic vessels in humans that carries a poor prognosis. The rarity of AS, together with its heterogeneous nature, and locations (skin, breast, visceral organs and deep soft tissues), makes understanding the pathogenesis of AS challenging. Dogs and cats spontaneously develop hemangiosarcoma (HSA), an aggressive tumor that shares many histopathological and clinical similarities to AS. To investigate the genetic suitability of spontaneo...
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#1Peu Santra (State University of New York Upstate Medical University)H-Index: 2
#2Jeffrey D. Amack (State University of New York Upstate Medical University)
The vacuolar type H+-ATPase (V-ATPase) is a ubiquitous membrane-bound, multi-subunit proton pump that regulates pH of cellular compartments. V-ATPase activity is known to modulate several cellular processes, but cell type-specific V-ATPase functions remain poorly understood. Patients with mutations in specific V-ATPase subunits can develop sensorineural deafness, but underlying mechanisms are unclear. Here, we show that V-ATPase mutations disrupt formation of zebrafish neuromasts, which serve as...
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#1Anna F Fusco (Duke University)H-Index: 1
#2Logan A. Pucci (Duke University)H-Index: 1
Last. Mai K. ElMallah (Duke University)H-Index: 14
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Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in the coding region of the ataxin-7 gene. Infantile-onset SCA7 patients display extremely large repeat expansions (>200 CAGs) and exhibit progressive ataxia, dysarthria, dysphagia and retinal degeneration. Severe hypotonia, aspiration pneumonia and respiratory failure often contribute to death in affected infants. To better understand the features of respiratory and upper ai...
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#1Jordan M Wall (LSU: Louisiana State University)
#2Ankita Basu (LSU: Louisiana State University)
Last. Alyssa E Johnson (LSU: Louisiana State University)
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Valosin containing protein (VCP) is a hexameric type II AAA ATPase required for several cellular processes including ER-associated degradation, organelle biogenesis, autophagy and membrane fusion. VCP contains three domains: a regulatory N-terminal domain and two ATPase domains (D1 and D2). Mutations in the N-terminal and D1 domains are associated with several degenerative diseases, including Multisystem Proteinopathy (MSP-1) and ALS. However, patients with VCP mutations vary widely in their pat...
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#1Lindsay B Murphy (Centre for Life)
#2Adrián Santos-Ledo (Centre for Life)H-Index: 2
Last. Bill Chaudhry (Centre for Life)H-Index: 21
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As the human heart ages, the myocardium undergoes fibrotic remodelling, there is declining cardiovascular performance and eventual heart failure. It is suggested that exercise is an important intervention to ameliorate these changes. In this study we establish zebrafish as a laboratory model to understand how aging and exercise affect cardiomyocyte turnover. We show the zebrafish heart does not exhibit indeterminate growth but follows the pattern seen in human aging. In zebrafish, cardiomyocyte ...
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#1Jharna R. Das (GW: George Washington University)H-Index: 7
#2Marina Jerebtsova (HU: Howard University)H-Index: 16
Last. Patricio E. Ray (UVA: University of Virginia)H-Index: 2
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Over 80% of all children living with HIV reside in Africa and are at risk of developing HIV-associated nephropathy (HIVAN). Once HIVAN is established in children, it is difficult to revert its progression to chronic kidney failure even using antiretroviral drugs. Therefore, new therapeutic strategies are needed. Previous studies showed that the risk of developing HIVAN increases in children with high circulating levels of FGF-2, but it is unclear whether FGF-2 per se precipitates HIVAN. To unrav...
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#1Elin Schoultz (University of Gothenburg)
#2Ellen Johansson (University of Gothenburg)H-Index: 2
Last. Mikael Nilsson (University of Gothenburg)H-Index: 28
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Cancer cells hijack developmental growth mechanisms but whether tissue morphogenesis and architecture modify tumorigenesis is unknown. Here, we characterized a new mouse model of sporadic thyroid carcinogenesis based on inducible expression of BRAFV600E from the thyroglobulin promoter (TgCreERT2). Spontaneous activation of this Braf-mutant allele due to leaky CRE activity revealed that intrinsic properties of thyroid follicles determined BRAF-mutant cell fate. Papillary thyroid carcinomas develo...
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