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2018: PloS One
Ryszard Rzepecki, Yosef Gruenbaum
Lamins are evolutionarily conserved nuclear intermediate filament proteins. They provide structural support for the nucleus and help regulate many other nuclear activities. Mutations in human lamin genes, and especially in the LMNA gene, cause numerous diseases, termed laminopathies, including muscle, cardiac, metabolic, neuronal and early aging diseases. Most laminopathies arise from autosomal dominant missense mutations. Many of the mutant residues are conserved in the lamin genes of the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster...
March 20, 2018: Nucleus
Jean-Christophe Billeter, Mariana F Wolfner
Chemicals released into the environment by food, predators and conspecifics play critical roles in Drosophila reproduction. Females and males live in an environment full of smells, whose molecules communicate to them the availability of food, potential mates, competitors or predators. Volatile chemicals derived from fruit, yeast growing on the fruit, and flies already present on the fruit attract Drosophila, concentrating flies at food sites, where they will also mate. Species-specific cuticular hydrocarbons displayed on female Drosophila as they mature are sensed by males and act as pheromones to stimulate mating by conspecific males and inhibit heterospecific mating...
March 19, 2018: Journal of Chemical Ecology
Xiaoping Su, Kuiqing Cui, Shanshan Du, Hongli Li, Fenghua Lu, Deshun Shi, Qingyou Liu
Myostatin (MSTN), a protein encoded by growth differentiation factor 8 (GDF8), is primarily expressed in skeletal muscle and negatively regulates the development and regeneration of muscle. Accordingly, myostatin-deficient animals exhibit a double-muscling phenotype. The CRISPR/Cas9 system has proven to be an efficient genome-editing tool and has been applied to gene modification in cells from many model organisms such as Drosophila melanogaster, zebrafish, mouse, rat, sheep, and human. Here, we edited the GDF8 gene in fibroblasts and embryos of Debao pig and swamp buffalo using the CRISPR/Cas9 system...
March 19, 2018: In Vitro Cellular & Developmental Biology. Animal
Amy Reilein, David Melamed, Simon Tavaré, Daniel Kalderon
Cancer-initiating gatekeeper mutations that arise in stem cells would be especially potent if they stabilize and expand an affected stem cell lineage. It is therefore important to understand how different stem cell organization strategies promote or prevent variant stem cell amplification in response to different types of mutation, including those that activate proliferation. Stem cell numbers can be maintained constant while producing differentiated products through individually asymmetrical division outcomes or by population asymmetry strategies in which individual stem cell lineages necessarily compete for niche space...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jian Guo, Hong-Wen Tang, Jing Li, Norbert Perrimon, Dong Yan
N 6 -methyladenosine (m6 A), the most abundant chemical modification in eukaryotic mRNA, has been implicated in Drosophila sex determination by modifying Sex-lethal ( Sxl ) pre-mRNA and facilitating its alternative splicing. Here, we identify a sex determination gene, CG7358 , and rename it xio according to its loss-of-function female-to-male transformation phenotype. xio encodes a conserved ubiquitous nuclear protein of unknown function. We show that Xio colocalizes and interacts with all previously known m6 A writer complex subunits (METTL3, METTL14, Fl(2)d/WTAP, Vir/KIAA1429, and Nito/Rbm15) and that loss of xio is associated with phenotypes that resemble other m6 A factors, such as sexual transformations, Sxl splicing defect, held-out wings, flightless flies, and reduction of m6 A levels...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Olga Y Rybina, Yakov M Rozovsky, Ekaterina R Veselkina, Elena G Pasyukova
Molecular mechanisms governing gene expression and defining complex phenotypes are central to understanding the basics of development and aging. Here, we demonstrate that naturally occurring polymorphisms of the Lim3 regulatory region that are associated with variation in gene expression and Drosophila lifespan control are located exclusively in the Polycomb response element (PRE). We find that the Polycomb group (PcG) protein Polycomb (PC) is bound to the PRE only in embryos where Lim3 is present in both repressed and active states...
March 16, 2018: Biochimica et Biophysica Acta
Chantal Beatrice Magne Nde, Gloria Casas Gimeno, Maria Docanto, Kevin C Knower, Morag J Young, Jakob Buehn, Edris Sayed, Colin D Clyne
Activation of oestrogen receptor α (ERα) stimulates cell division and tumour growth by modulating the expression of ERα target genes. This activation involves the recruitment of specific proteins with activities that are still not fully understood. Timeless, the human homologue of the Drosophila gene involved in circadian rhythm, was previously shown to be a strong predictor of tamoxifen relapse, and is involved in genomic stability and cell cycle control. In this study, we investigated the interplay between Timeless and ERα, and showed that human Timeless is an ERα coactivator...
March 16, 2018: Journal of Molecular Biology
Xiaodong Li, Hiroshi Ishimoto, Azusa Kamikouchi
In birds and higher mammals, auditory experience during development is critical to discriminate sound patterns in adulthood. However, the neural and molecular nature of this acquired ability remains elusive. In fruit flies, acoustic perception has been thought to be innate. Here we report, surprisingly, that auditory experience of a species-specific courtship song in developing Drosophila shapes adult song perception and resultant sexual behavior. Preferences in the song-response behaviors of both males and females were tuned by social acoustic exposure during development...
March 20, 2018: ELife
Xiaonan Zhang, Quentin Gaudry
Here, a new technique termed Tetrotoxin (TTX) Engineered Resistance for Probing Synapses (TERPS) is applied to test for monosynaptic connections between target neurons. The method relies on co-expression of a transgenic activator with the tetrodotoxin-resistant sodium channel, NaChBac, in a specific presynaptic neuron. Connections with putative post-synaptic partners are determined by whole-cell recordings in the presence of TTX, which blocks electrical activity in neurons that do not express NaChBac. This approach can be modified to work with any activator or calcium imaging as a reporter of connections...
February 14, 2018: Journal of Visualized Experiments: JoVE
Karen Sophia Park, Dorothea Godt, Daniel Kalderon
Unlike adult Drosophila ovaries, pupal ovaries are relatively difficult to access and examine due to their small size, translucence, and encasing within a pupal case. The challenge of dissecting pupal ovaries also lies in their physical location within the pupa: the ovaries are surrounded by fat body cells inside the pupal abdomen, and these fat cells must be removed to allow for proper antibody staining. To overcome these challenges, this protocol utilizes customized Pasteur pipets to extract fat body cells from the pupal abdomen...
March 2, 2018: Journal of Visualized Experiments: JoVE
Ju-Chun Chang, Se Jin Lee, Jae Su Kim, Chung-Hsiung Wang, Yu-Shin Nai
The transient gene expression system is one of the most important technologies for performing protein functional analysis in the baculovirus in vitro cell culture system. This system was developed to express foreign genes under the control of the baculoviral promoter in transient expression plasmids. Furthermore, this system can be applied to a functional assay of either the baculovirus itself or foreign proteins. The most widely and commercially available transient gene expression system is developed based on the immediate-early gene (IE) promoter of Orgyia pseudotsugata multicapsid nucleopolyhedrovirus (OpMNPV)...
February 22, 2018: Journal of Visualized Experiments: JoVE
Laura C D Pomatto, Sarah Wong, John Tower, Kelvin J A Davies
Adaptive homeostasis enables rapid cellular signaling, leading to transcriptional and translational modifications (Davies, 2016) [1]. The Proteasome is one of the main cellular proteolytic enzymes that plays an essential role in the rapid clearance of oxidatively damaged cellular proteins, and is highly responsive to oxidative stress. Upon exposure to even very low, signaling levels of oxidants, the predominant form of the Proteasome becomes the ATP-independent 20S proteasome that enables rapid clearance of damaged proteins...
April 2018: Data in Brief
Guomin Li, Qian Shen, Li Sun, Haimei Liu, Yu An, Hong Xu
Branchio-oto-renal (BOR) syndrome is a rare autosomal dominant disorder characterized by branchial cleft fistulae or cysts, preauricular pits, ear malformations, hearing loss, and renal anomalies. Mutations in the human homologue of the Drosophila eyes absent gene ( EYA1 ) are the most common cause of BOR syndrome. PCR and direct sequencing were used to investigate all of the exons and exon-intron boundaries in the EYA1 gene in a patient with BOR syndrome from China. The patient was a child who displayed clinical features of BOR syndrome...
February 2018: Intractable & Rare Diseases Research
Emily Tubman, Yungui He, Thomas S Hays, David J Odde
Introduction: The microtubule motor protein kinesin-5 is well known to establish the bipolar spindle by outward sliding of antiparallel interpolar microtubules. In yeast, kinesin-5 also facilitates chromosome alignment "congression" at the spindle equator by preferentially depolymerizing long kinetochore microtubules (kMTs). The motor protein kinesin-8 has also been linked to chromosome congression. Therefore, we sought to determine whether kinesin-5 or kinesin-8 facilitates chromosome congression in insect spindles...
February 2018: Cellular and Molecular Bioengineering
Marta Zamarbide, Adam W Oaks, Heather L Pond, Julia S Adelman, M Chiara Manzini
Hundreds of genes are mutated in non-syndromic intellectual disability (ID) and autism spectrum disorder (ASD), with each gene often involved in only a handful of cases. Such heterogeneity can be daunting, but rare recessive loss of function (LOF) mutations can be a good starting point to provide insight into the mechanisms of neurodevelopmental disease. Biallelic LOF mutations in the signaling scaffold CC2D1A cause a rare form of autosomal recessive ID, sometimes associated with ASD and seizures. In parallel, we recently reported that Cc2d1a -deficient mice present with cognitive and social deficits, hyperactivity and anxiety...
2018: Frontiers in Genetics
Natsuki Hemmi, Yasuko Akiyama-Oda, Koichi Fujimoto, Hiroki Oda
One of the conserved traits of arthropod embryonic development is striped expression of homologs of Drosophila segment polarity genes, including hedgehog (hh). Although a diversity of stripe-forming processes is recognized among arthropod embryos, such varied stripe-forming processes have not been well characterized from cellular and quantitative perspectives. The spider Parasteatoda tepidariorum embryo, which has a hh-dependent mechanism of axis formation, offers a cell-based field where the stripes of Pt-hh (a hh homolog) expression dynamically develop in accordance with axis formation and growth, with the patterning processes varying among the regions of the field...
March 15, 2018: Developmental Biology
Alexandra Moraru, Janica Wiederstein, Daniel Pfaff, Thomas Fleming, Aubry K Miller, Peter Nawroth, Aurelio A Teleman
The molecular causes of type 2 diabetes (T2D) are not well understood. Both type 1 diabetes (T1D) and T2D are characterized by impaired insulin signaling and hyperglycemia. From analogy to T1D, insulin resistance and hyperglycemia are thought to also play causal roles in T2D. Recent clinical studies, however, found that T2D patients treated to maintain glycemia below the diabetes definition threshold (HbA1c  < 6.5%) still develop diabetic complications. This suggests additional insulin- and glucose-independent mechanisms could be involved in T2D progression and/or initiation...
February 28, 2018: Cell Metabolism
Damiano Zanini, Diego Giraldo, Ben Warren, Radoslaw Katana, Marta Andrés, Suneel Reddy, Stephanie Pauls, Nicola Schwedhelm-Domeyer, Bart R H Geurten, Martin C Göpfert
Animals rely on mechanosensory feedback from proprioceptors to control locomotory body movements. Unexpectedly, we found that this movement control requires visual opsins. Disrupting the Drosophila opsins NINAE or Rh6 impaired larval locomotion and body contractions, independently of light and vision. Opsins were detected in chordotonal proprioceptors along the larval body, localizing to their ciliated dendrites. Loss of opsins impaired mechanically evoked proprioceptor spiking and cilium ultrastructure. Without NINAE or Rh6, NOMPC mechanotransduction channels leaked from proprioceptor cilia and ciliary Inactive (Iav) channels partly disappeared...
March 8, 2018: Neuron
Xuchen Zhang, Qian Li, Lianzhang Wang, Zhong-Jian Liu, Yi Zhong
Active forgetting explains the intrinsic instability of a labile memory lasting for hours. However, how such memory maintains stability against unwanted disruption is not completely understood. Here, we report a learning-activated active protection mechanism that enables labile memory to resist disruptive sensory experiences in Drosophila. Aversive olfactory conditioning activates mitogen-activated protein kinase (MAPK) transiently in the mushroom-body γ lobe, where labile-aversive memory is stored. This increased MAPK activity significantly prolongs labile memory retention and enhances its resistance to disruption induced by heat shock, electric shock, or odor reactivation...
March 7, 2018: Neuron
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