~disease-models-mech | Bookmarks (24)

Abca4, mutated in Stargardt disease, is required for structural integrity of cone outer segments

biologists.com

ABSTRACTStargardt disease (STGD), the leading cause of inherited childhood blindness, is primarily caused by mutations in...
ABSTRACTStargardt disease (STGD), the leading cause of inherited childhood blindness, is primarily caused by mutations in the ABCA4 gene; yet, the underlying mechanisms of photoreceptor degeneration remain elusive, partly due to limitations in existing animal disease models. To expand our understanding, we mutated the human ABCA4 paralogues abca4a and abca4b in zebrafish, which has a cone-rich retina. Our study unveiled striking dysmorphology and elongation...
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The Company of Biologists: celebrating 100 years

biologists.com

Summary: As we begin celebrating our 100-year anniversary, we reflect on our extraordinary story so far,...
Summary: As we begin celebrating our 100-year anniversary, we reflect on our extraordinary story so far, consider the Company's current support for our communities and prepare for some inspiring activities.
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Dose-dependent effects of Nrf2 on the epidermis in chronic skin inflammation

biologists.com

ABSTRACTAtopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by an impaired epidermal barrier and...
ABSTRACTAtopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by an impaired epidermal barrier and immunological alterations. The activity of the cytoprotective NRF2 transcription factor is reduced in the epidermis of AD patients. To determine the functional relevance of this deficiency, we used mice lacking fibroblast growth factor receptors 1 and 2 in keratinocytes (K5-R1/R2 mice), which exhibit several AD-like symptoms. Proteomics analysis...
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First person – Michael Koch

biologists.com

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers...
ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping researchers promote themselves alongside their papers. Michael Koch is first author on ‘ Dose-dependent effects of Nrf2 on the epidermis in chronic skin inflammation’, published in DMM. Michael conducted the research described in this article while a PhD candidate and research...
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Loss of function of VCP/TER94 causes neurodegeneration

biologists.com

ABSTRACTVariants in several genes are linked to human frontotemporal lobar degeneration (FTLD) associated with TDP43- and/or...
ABSTRACTVariants in several genes are linked to human frontotemporal lobar degeneration (FTLD) associated with TDP43- and/or ubiquitin-positive inclusions. However, it is not yet clear whether the underlying mechanism is a gain-of-function or a loss-of-function one. To answer this question, we used Drosophila expressing double-stranded RNA against the FTLD-associated gene TER94 (an ortholog of VCP/p97) and found that the knockdown (KD) of this gene caused...
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From mechanisms of carcinogenesis to early intervention: an interview with Ashok Venkitaraman

biologists.com
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Making sense of missense: challenges and opportunities in variant pathogenicity prediction

biologists.com

ABSTRACTComputational tools for predicting variant pathogenicity are widely used to support clinical variant interpretation. Recently, several...
ABSTRACTComputational tools for predicting variant pathogenicity are widely used to support clinical variant interpretation. Recently, several models, which do not rely on known variant classifications during training, have been developed. These approaches can potentially overcome biases of current clinical databases, such as misclassifications, and can potentially better generalize to novel, unclassified variants. AlphaMissense is one such model, built on the highly successful protein structure...
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First person – Mireia Sueca-Comes

biologists.com

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers...
ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping researchers promote themselves alongside their papers. Mireia Sueca-Comes is first author on ‘ The role of mesenchymal cells in cholangiocarcinoma’, published in DMM. Mireia conducted the research described in this article while a PhD student in Anna M. Grabowska's lab at...
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The role of mesenchymal cells in cholangiocarcinoma

biologists.com

ABSTRACTThe tumour microenvironment (TME) significantly influences tumour formation and progression through dynamic interactions. Cholangiocarcinoma (CCA), a...
ABSTRACTThe tumour microenvironment (TME) significantly influences tumour formation and progression through dynamic interactions. Cholangiocarcinoma (CCA), a highly desmoplastic tumour, lacks early diagnostic biomarkers and has limited effective treatments owing to incomplete understanding of its molecular pathogenesis. Investigating the role of the TME in CCA progression could lead to better therapies. RNA sequencing was performed on seven CCA patient-derived xenografts (PDXs) and their corresponding patient...
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Slc26a2 -mediated sulfate metabolism is important in tooth development

biologists.com

ABSTRACTThe sulfate transporter gene SLC26A2 is crucial for skeletal formation, as evidenced by its role in...
ABSTRACTThe sulfate transporter gene SLC26A2 is crucial for skeletal formation, as evidenced by its role in diastrophic dysplasia, a type of skeletal dysplasia in humans. Although SLC26A2-related chondrodysplasia also affects craniofacial and tooth development, its specific role in these processes remains unclear. In this study, we explored the pivotal roles of SLC26A2-mediated sulfate metabolism during tooth development. We found that Slc26a2 was predominantly expressed...
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Stat3 mediates Fyn kinase-driven dopaminergic neurodegeneration and microglia activation

biologists.com

ABSTRACTThe Alzheimer's disease and Parkinson's disease risk locus FYN kinase is implicated in neurodegeneration and inflammatory...
ABSTRACTThe Alzheimer's disease and Parkinson's disease risk locus FYN kinase is implicated in neurodegeneration and inflammatory signaling. To investigate in vivo mechanisms of Fyn-driven neurodegeneration, we built a zebrafish neural-specific Gal4:UAS model of constitutively active FynY531F signaling. Using in vivo live imaging, we demonstrated that neural FynY531F expression leads to dopaminergic neuron loss and mitochondrial aggregation in 5 day larval brain. Dopaminergic loss coincided with...
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Generation of a zebrafish neurofibromatosis model via inducible knockout of nf2a/b

biologists.com

ABSTRACTNeurofibromatosis type 2 (NF-2) is a dominantly inherited genetic disorder that results from variants in the...
ABSTRACTNeurofibromatosis type 2 (NF-2) is a dominantly inherited genetic disorder that results from variants in the tumor suppressor gene, neurofibromin 2 (NF2). Here, we report the generation of a conditional zebrafish model of neurofibromatosis established by inducible genetic knockout of nf2a/b, the zebrafish homologs of human NF2. Analysis of nf2a and nf2b expression revealed ubiquitous expression of nf2b in the early embryo, with overlapping...
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Timing is everything: an inducible model for neurofibromatosis type 2 in zebrafish

biologists.com
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First person – Ayyappa Raja Desingu Rajan

biologists.com

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers...
ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping researchers promote themselves alongside their papers. Ayyappa Raja Desingu Rajan is first author on ‘ Generation of a zebrafish neurofibromatosis model via inducible knockout of nf2a/b’, published in DMM. Ayyappa Raja is a postdoctoral researcher in the lab of Marianne Bronner...
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Modelling quiescence exit of neural stem cells reveals a FOXG1-FOXO6 axis

biologists.com

ABSTRACTThe molecular mechanisms controlling the balance of quiescence and proliferation in adult neural stem cells (NSCs)...
ABSTRACTThe molecular mechanisms controlling the balance of quiescence and proliferation in adult neural stem cells (NSCs) are often deregulated in brain cancers such as glioblastoma multiforme (GBM). Previously, we reported that FOXG1, a forebrain-restricted neurodevelopmental transcription factor, is frequently upregulated in glioblastoma stem cells (GSCs) and limits the effects of cytostatic pathways, in part by repression of the tumour suppressor Foxo3. Here, we show...
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A high-fat plus high-sucrose diet induces age-related macular degeneration in an experimental rabbit model

biologists.com

ABSTRACTAge-related macular degeneration (AMD) is a leading cause of blindness. Metabolic disorders and diets are risk...
ABSTRACTAge-related macular degeneration (AMD) is a leading cause of blindness. Metabolic disorders and diets are risk factors. We compared lipid profiles and retinal phenotypes with long-term feeding of four diets in male Chinchilla rabbits. Animals were fed a normal diet (ND), high-fat diet (HFD), high-sucrose diet (HSD) or a high-fat plus high-sucrose diet (HFSD) for 6 months. Eyes were examined using multimodal imaging modalities and...
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First person – Yujiao Wang

biologists.com

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers...
ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping researchers promote themselves alongside their papers. Yujiao Wang is first author on ‘ A high-fat plus high-sucrose diet induces age-related macular degeneration in an experimental rabbit model’, published in DMM. Yujiao is a Lecturer and Ophthalmologist in the lab of Danian...
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It's about time: the heterochronic background for the 2024 Nobel Prize in Physiology or Medicine

biologists.com

ABSTRACTThe 2024 Nobel Prize in Physiology or Medicine has been awarded to Victor Ambros and Gary...
ABSTRACTThe 2024 Nobel Prize in Physiology or Medicine has been awarded to Victor Ambros and Gary Ruvkun “for the discovery of microRNA and its role in post-transcriptional gene regulation”. The award celebrates the discovery of small regulatory miRNAs and their mRNA targets, published over three decades ago. The groundwork for this discovery was laid during the early 1980s, when Ambros began studying mutations that...
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Early-life cisplatin exposure induces neuroinflammation and chemotherapy-induced neuropathic pain

biologists.com

ABSTRACTChemotherapy-induced neuropathic pain (CINP) is a common adverse health-related comorbidity that manifests later in life in...
ABSTRACTChemotherapy-induced neuropathic pain (CINP) is a common adverse health-related comorbidity that manifests later in life in patients with paediatric cancer. Current analgesia is ineffective, aligning closely with our lack of understanding of CINP. The aim of this study was to investigate how cisplatin induces nerve growth factor (NGF)-mediated neuroinflammation and nociceptor sensitisation. In a rat model of cisplatin-induced survivorship pain, cisplatin induced a neuroinflammatory...
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First person – Nouf Khan and Talhah Mohd Salmi

biologists.com

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers...
ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping researchers promote themselves alongside their papers. Nouf Khan and Talhah Mohd Salmi are co-first authors on ‘ Optimized methods to image hepatic lipid droplets in zebrafish larvae’, published in DMM. Nouf is a research assistant in the lab of Kirsten C....
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Optimized methods to image hepatic lipid droplets in zebrafish larvae

biologists.com

ABSTRACTThe optical transparency of zebrafish larvae enables visualization of subcellular structures in intact organs, and these...
ABSTRACTThe optical transparency of zebrafish larvae enables visualization of subcellular structures in intact organs, and these vertebrates are widely used to study lipid biology and liver disease. Lipid droplet (LD) presence is a prevalent feature of healthy cells, but, under conditions such as nutrient excess, toxicant exposure or metabolic imbalance, LD accumulation in hepatocytes can be a harbinger of more severe forms of liver...
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Zebrafish streamline the way to understanding steatotic liver disease

biologists.com
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Beyond genomic studies of congenital heart defects through systematic modelling and phenotyping

biologists.com

ABSTRACTCongenital heart defects (CHDs), the most common congenital anomalies, are considered to have a significant genetic...
ABSTRACTCongenital heart defects (CHDs), the most common congenital anomalies, are considered to have a significant genetic component. However, despite considerable efforts to identify pathogenic genes in patients with CHDs, few gene variants have been proven as causal. The complexity of the genetic architecture underlying human CHDs likely contributes to this poor genetic discovery rate. However, several other factors are likely to contribute. For example,...
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Modulation of SNARE-dependent exocytosis in astrocytes improves neuropathology in Huntington's disease

biologists.com

ABSTRACTHuntington's disease (HD) is a fatal, progressive neurodegenerative disorder. Prior studies revealed an increase in extracellular...
ABSTRACTHuntington's disease (HD) is a fatal, progressive neurodegenerative disorder. Prior studies revealed an increase in extracellular glutamate levels after evoking astrocytic SNARE-dependent exocytosis from cultured primary astrocytes from mutant huntingtin (mHTT)-expressing BACHD mice compared to control astrocytes, suggesting alterations in astrocytic SNARE-dependent exocytosis in HD. We used BACHD and dominant-negative (dn)SNARE mice to decrease SNARE-dependent exocytosis from astrocytes to determine whether reducing SNARE-dependent exocytosis...
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~disease-models-mech | Bookmarks (24)

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