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Drosophila human disease

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https://www.readbyqxmd.com/read/28737703/autophagy-and-human-neurodegenerative-diseases-a-fly-s-perspective
#1
REVIEW
Myungjin Kim, Allison Ho, Jun Hee Lee
Neurodegenerative diseases in humans are frequently associated with prominent accumulation of toxic protein inclusions and defective organelles. Autophagy is a process of bulk lysosomal degradation that eliminates these harmful substances and maintains the subcellular environmental quality. In support of autophagy's importance in neuronal homeostasis, several genetic mutations that interfere with autophagic processes were found to be associated with familial neurodegenerative disorders. In addition, genetic mutations in autophagy-regulating genes provoked neurodegenerative phenotypes in animal models...
July 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28728902/role-of-mirnas-in-development-and-disease-lessons-learnt-from-small-organisms
#2
REVIEW
Swati Chandra, Divya Vimal, Divya Sharma, Vipin Rai, Subash Chandra Gupta, D Kar Chowdhuri
MicroRNAs (miRNAs) constitute a class of small (21-24 nucleotides) non-coding RNAs that regulate gene expression at the post-transcriptional level. Caenorhabditis elegans, Drosophila melanogaster, and many other small organisms have been instrumental in deciphering the biological functions of miRNAs. While some miRNAs from small organisms are highly conserved across the taxa, others are organism specific. The miRNAs are known to play a crucial role during development and in various cellular functions such as cell survival, cell proliferation, and differentiation...
July 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/28719866/cell-competition-in-mammals-novel-homeostatic-machinery-for-embryonic-development-and-cancer-prevention
#3
REVIEW
Takeshi Maruyama, Yasuyuki Fujita
In the multi-cellular community, cells with different properties often compete with each other for survival and space. This process is named cell competition and was originally discovered in Drosophila. Recent studies have revealed that comparable phenomena also occur in mammals under various physiological and pathological conditions. Within the epithelium, normal cells often recognize the presence of the neighboring transformed cells and actively eliminate them from the epithelium; a process termed EDAC (Epithelial Defense Against Cancer)...
July 15, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28712876/drosophila-sce-dring-e3-ligase-inhibits-apoptosis-in-a-dp53-dependent-manner
#4
Rocío Simón, Carolina J Simoes da Silva, Sol Fereres, Ana Busturia
The Polycomb group (PcG) of proteins control developmental gene silencing and are highly conserved between flies and mammals. PcG proteins function by controlling post-translational modification of histones, such as ubiquitylation, which impacts chromatin compaction and thus gene transcription. Changes in PcG cellular levels have drastic effects on organismal development and are involved in the generation of human pathologies such as cancer. However, the mechanisms controlling their levels of expression and their physiological effects are only partially understood...
July 13, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28711868/human-ttbk1-ttbk2-and-mark1-kinase-toxicity-in-drosophila-melanogaster-is-exacerbated-by-co-expression-of-human-tau
#5
Josefin Fernius, Annika Starkenberg, Malgorzata Pokrzywa, Stefan Thor
Tau protein is involved in numerous human neurodegenerative diseases, and Tau hyper-phosphorylation has been linked to Tau aggregation and toxicity. Previous studies have addressed toxicity and phospho-biology of human Tau (hTau) in Drosophila melanogaster However, hTau transgenes have most often been randomly inserted in the genome, thus making it difficult to compare between different hTau isoforms and phospho-mutants. In addition, many studies have expressed hTau also in mitotic cells, causing non-physiological toxic effects...
July 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28701701/systematic-discovery-of-genetic-modulation-by-jumonji-histone-demethylases-in-drosophila
#6
Nevine A Shalaby, Raheel Sayed, Qiao Zhang, Shane Scoggin, Susan Eliazer, Adrian Rothenfluh, Michael Buszczak
Jumonji (JmjC) domain proteins influence gene expression and chromatin organization by way of histone demethylation, which provides a means to regulate the activity of genes across the genome. JmjC proteins have been associated with many human diseases including various cancers, developmental and neurological disorders, however, the shared biology and possible common contribution to organismal development and tissue homeostasis of all JmjC proteins remains unclear. Here, we systematically tested the function of all 13 Drosophila JmjC genes...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698598/classification-and-function-of-small-open-reading-frames
#7
REVIEW
Juan-Pablo Couso, Pedro Patraquim
Small open reading frames (smORFs) of 100 codons or fewer are usually - if arbitrarily - excluded from proteome annotations. Despite this, the genomes of many metazoans, including humans, contain millions of smORFs, some of which fulfil key physiological functions. Recently, the transcriptome of Drosophila melanogaster was shown to contain thousands of smORFs of different classes that actively undergo translation, which produces peptides of mostly unknown function. Here, we present a comprehensive analysis of smORFs in flies, mice and humans...
July 12, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28697314/grainyhead-like-transcription-factors-in-craniofacial-development
#8
M R Carpinelli, M E de Vries, S M Jane, S Dworkin
Craniofacial development in vertebrates involves the coordinated growth, migration, and fusion of several facial prominences during embryogenesis, processes governed by strict genetic and molecular controls. A failure in any of the precise spatiotemporal sequences of events leading to prominence fusion often leads to anomalous facial, skull, and jaw formation-conditions termed craniofacial defects (CFDs). Affecting approximately 0.1% to 0.3% of live births, CFDs are a highly heterogeneous class of developmental anomalies, which are often underpinned by genetic mutations...
July 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28693471/spatial-pattern-analysis-of-nuclear-migration-in-remodelled-muscles-during-drosophila-metamorphosis
#9
Kuleesha, Lin Feng, Martin Wasser
BACKGROUND: Many human muscle wasting diseases are associated with abnormal nuclear localization. During metamorphosis in Drosophila melanogaster, multi-nucleated larval dorsal abdominal muscles either undergo cell death or are remodeled to temporary adult muscles. Muscle remodeling is associated with anti-polar nuclear migration and atrophy during early pupation followed by polar migration and muscle growth during late pupation. Muscle remodeling is a useful model to study genes involved in myonuclear migration...
July 10, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28686708/drosophila-lines-with-mutant-and-wild-type-human-tdp-43-replacing-the-endogenous-gene-reveals-phosphorylation-and-ubiquitination-in-mutant-lines-in-the-absence-of-viability-or-lifespan-defects
#10
Jer-Cherng Chang, David B Morton
Mutations in TDP-43 are associated with proteinaceous inclusions in neurons and are believed to be causative in neurodegenerative diseases such as frontotemporal dementia or amyotrophic lateral sclerosis. Here we describe a Drosophila system where we have engineered the genome to replace the endogenous TDP-43 orthologue with wild type or mutant human TDP-43(hTDP-43). In contrast to other models, these flies express both mutant and wild type hTDP-43 at similar levels to those of the endogenous gene and importantly, no age-related TDP-43 accumulation observed among all the transgenic fly lines...
2017: PloS One
https://www.readbyqxmd.com/read/28684721/drosophila-melanogaster-models-of-metal-related-human-diseases-and-metal-toxicity
#11
REVIEW
Pablo Calap-Quintana, Javier González-Fernández, Noelia Sebastiá-Ortega, José Vicente Llorens, María Dolores Moltó
Iron, copper and zinc are transition metals essential for life because they are required in a multitude of biological processes. Organisms have evolved to acquire metals from nutrition and to maintain adequate levels of each metal to avoid damaging effects associated with its deficiency, excess or misplacement. Interestingly, the main components of metal homeostatic pathways are conserved, with many orthologues of the human metal-related genes having been identified and characterized in Drosophila melanogaster...
July 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28676676/identifying-pathways-modulating-sleep-duration-from-genomics-to-transcriptomics
#12
Karla V Allebrandt, Maris Teder-Laving, Paola Cusumano, Goar Frishman, Rosa Levandovski, Andreas Ruepp, Maria P L Hidalgo, Rodolfo Costa, Andres Metspalu, Till Roenneberg, Cristiano De Pittà
Recognizing that insights into the modulation of sleep duration can emerge by exploring the functional relationships among genes, we used this strategy to explore the genome-wide association results for this trait. We detected two major signalling pathways (ion channels and the ERBB signalling family of tyrosine kinases) that could be replicated across independent GWA studies meta-analyses. To investigate the significance of these pathways for sleep modulation, we performed transcriptome analyses of short sleeping flies' heads (knockdown for the ABCC9 gene homolog; dSur)...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28673935/functions-of-long-non-coding-rnas-in-human-disease-and-their-conservation-in-drosophila-development
#13
REVIEW
Oliver M Rogoyski, Jose Ignacio Pueyo, Juan Pablo Couso, Sarah F Newbury
Genomic analysis has found that the transcriptome in both humans and Drosophila melanogaster features large numbers of long non-coding RNA transcripts (lncRNAs). This recently discovered class of RNAs regulates gene expression in diverse ways and has been involved in a large variety of important biological functions. Importantly, an increasing number of lncRNAs have also been associated with a range of human diseases, including cancer. Comparative analyses of their functions among these organisms suggest that some of their modes of action appear to be conserved...
July 3, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28660197/a-mighty-protein-extractor-of-the-cell-structure-and-function-of-the-p97-cdc48-atpase
#14
REVIEW
Yihong Ye, Wai Kwan Tang, Ting Zhang, Di Xia
p97/VCP (known as Cdc48 in S. cerevisiae or TER94 in Drosophila) is one of the most abundant cytosolic ATPases. It is highly conserved from archaebacteria to eukaryotes. In conjunction with a large number of cofactors and adaptors, it couples ATP hydrolysis to segregation of polypeptides from immobile cellular structures such as protein assemblies, membranes, ribosome, and chromatin. This often results in proteasomal degradation of extracted polypeptides. Given the diversity of p97 substrates, this "segregase" activity has profound influence on cellular physiology ranging from protein homeostasis to DNA lesion sensing, and mutations in p97 have been linked to several human diseases...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28649423/ubiquitous-overexpression-of-the-dna-repair-factor-dprp19-reduces-dna-damage-and-extends-drosophila-life-span
#15
Kathrin Garschall, Hanna Dellago, Martina Gáliková, Markus Schosserer, Thomas Flatt, Johannes Grillari
Mechanisms that ensure and maintain the stability of genetic information are fundamentally important for organismal function and can have a large impact on disease, aging, and life span. While a multi-layered cellular apparatus exists to detect and respond to DNA damage, various insults from environmental and endogenous sources continuously affect DNA integrity. Over time this can lead to the accumulation of somatic mutations, which is thought to be one of the major causes of aging. We have previously found that overexpression of the essential human DNA repair and splicing factor SNEV, also called PRP19 or hPso4, extends replicative life span of cultured human endothelial cells and impedes accumulation of DNA damage...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/28640802/peroxisomal-biogenesis-is-genetically-and-biochemically-linked-to-carbohydrate-metabolism-in-drosophila-and-mouse
#16
Michael F Wangler, Yu-Hsin Chao, Vafa Bayat, Nikolaos Giagtzoglou, Abhijit Babaji Shinde, Nagireddy Putluri, Cristian Coarfa, Taraka Donti, Brett H Graham, Joseph E Faust, James A McNew, Ann Moser, Marco Sardiello, Myriam Baes, Hugo J Bellen
Peroxisome biogenesis disorders (PBD) are a group of multi-system human diseases due to mutations in the PEX genes that are responsible for peroxisome assembly and function. These disorders lead to global defects in peroxisomal function and result in severe brain, liver, bone and kidney disease. In order to study their pathogenesis we undertook a systematic genetic and biochemical study of Drosophila pex16 and pex2 mutants. These mutants are short-lived with defects in locomotion and activity. Moreover these mutants exhibit severe morphologic and functional peroxisomal defects...
June 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28636161/infinity-sperm-storage-the-gift-that-keeps-on-giving
#17
Gauthier Schang, Beatriz Fernandez-Fuertes, Samantha C Lean, Alexandra L Nguyen, Osvaldo Bogado Pascottini
Female Drosophila retain sperm for up to two weeks post-copulation in a network of storage organs includng the bursa, the seminal receptacle, and the spermathecae. This image shows the seminal receptacle of a Drosophila melanogaster female, 2-hrs post-copulation between a LHM (wild-type) female with a Protamine B (green), β-Tubulin (blue) fluorescently tagged male, whose sperm can be visualized within the female. This 'infinity' structure of the seminal receptacle resembles the tubular coil that allows for the storage of very long sperm relative to female body size -up to 20 times the length of the female in some Drosophila species...
June 21, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28625786/drug-induces-depression-like-phenotypes-and-alters-gene-expression-profiles-in-drosophila
#18
Ming-Di Jiang, Ya Zheng, Jia-Lin Wang, Yu-Feng Wang
BACKGROUND: Major depressive disorder (MDD) is a severe mental illness that affects more than 350 million people worldwide. However, the molecular mechanisms of depression are currently unclear. Studies suggest that Drosophila and humans have similar depression-like symptoms under pressure. In this research, we choose Drosophila melanogaster as the animal model to explore the molecular mechanisms that trigger depression. RESULTS: We found that feeding D. melanogaster with the medium containing Levodopa or Chlorpromazine could induce depression-like phenotypes in both behavioral and biochemical biomarkers, including significantly decreased food intake, mating frequency, serotonin (5-HT) concentration, and increased malondialdehyde (MDA) concentration as well as reduced activity of superoxide dismutase (SOD)...
June 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28623239/-ccug-n-rna-toxicity-in-a-drosophila-model-for-myotonic-dystrophy-type-2-dm2-activates-apoptosis
#19
Vildan Betul Yenigun, Mario Sirito, Alla Amcheslavky, Tomek Czernuszewicz, Jordi Colonques-Bellmunt, Irma García-Alcover, Marzena Wojciechowska, Clare Bolduc, Zhihong Chen, Arturo López Castel, Ralf Krahe, Andreas Bergmann
The myotonic dystrophies are prototypic toxic RNA gain-of-function diseases. Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are caused by different unstable, noncoding microsatellite repeat expansions -- (CTG)DM1 in DMPK and (CCTG)DM2 in CNBP Although transcription of mutant repeats into (CUG)DM1 or (CCUG)DM2 appears to be necessary and sufficient to cause disease, their pathomechanisms remain incompletely understood. To study the mechanisms of (CCUG)DM2 toxicity and develop a convenient model for drug screening, we generated a transgenic DM2 model in the fruit fly Drosophila melanogaster with (CCUG)n repeats of variable length (n=16 and 106)...
June 16, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28621416/all-in-one-integrating-cell-polarity-meiosis-mitosis-and-mechanical-forces-in-early-oocyte-differentiation-in-vertebrates
#20
Yaniv M Elkouby
While the differentiation of oocytes is key for embryonic development, and its investigation is crucial for advancing our understanding of human reproduction and fertility, many fundamental questions in oogenesis have been long standing. However, recent technical advances have led to several breakthroughs mainly in mice and zebrafish. Here I review these recent findings, including regulation and organization of the germline cyst, the mechanistics of chromosomal pairing, establishment of cell polarity, and formation of a universal mRNA-protein (mRNP) granule called the Balbiani body...
2017: International Journal of Developmental Biology
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