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BMC Biology

Parvathy Krishnan, Lukas Meile, Clémence Plissonneau, Xin Ma, Fanny E Hartmann, Daniel Croll, Bruce A McDonald, Andrea Sánchez-Vallet
BACKGROUND: Fungal plant pathogens pose major threats to crop yield and sustainable food production if they are highly adapted to their host and the local environment. Variation in gene expression contributes to phenotypic diversity within fungal species and affects adaptation. However, very few cases of adaptive regulatory changes have been reported in fungi and the underlying mechanisms remain largely unexplored. Fungal pathogen genomes are highly plastic and harbor numerous insertions of transposable elements, which can potentially contribute to gene expression regulation...
July 16, 2018: BMC Biology
Santosh Kumar Maharana, Gerhard Schlosser
BACKGROUND: The neural plate border ectoderm gives rise to key developmental structures during embryogenesis, including the neural crest and the preplacodal ectoderm. Many sensory organs and ganglia of vertebrates develop from cranial placodes, which themselves arise from preplacodal ectoderm, defined by expression of transcription factor Six1 and its coactivator Eya1. Here we elucidate the gene regulatory network underlying the specification of the preplacodal ectoderm in Xenopus, and the functional interactions among transcription factors that give rise to this structure...
July 16, 2018: BMC Biology
Santiago Martínez-Lumbreras, Ewelina M Krysztofinska, Arjun Thapaliya, Alessandro Spilotros, Dijana Matak-Vinkovic, Enrico Salvadori, Peristera Roboti, Yvonne Nyathi, Janina H Muench, Maxie M Roessler, Dmitri I Svergun, Stephen High, Rivka L Isaacson
BACKGROUND: Protein quality control mechanisms are essential for cell health and involve delivery of proteins to specific cellular compartments for recycling or degradation. In particular, stray hydrophobic proteins are captured in the aqueous cytosol by a co-chaperone, the small glutamine-rich, tetratricopeptide repeat-containing protein alpha (SGTA), which facilitates the correct targeting of tail-anchored membrane proteins, as well as the sorting of membrane and secretory proteins that mislocalize to the cytosol and endoplasmic reticulum-associated degradation...
July 11, 2018: BMC Biology
Pavitra Roychoudhury, Harshana De Silva Feelixge, Daniel Reeves, Bryan T Mayer, Daniel Stone, Joshua T Schiffer, Keith R Jerome
BACKGROUND: RNA-guided CRISPR/Cas9 systems can be designed to mutate or excise the integrated HIV genome from latently infected cells and have therefore been proposed as a curative approach for HIV. However, most studies to date have focused on molecular clones with ideal target site recognition and do not account for target site variability observed within and between patients. For clinical success and broad applicability, guide RNA (gRNA) selection must account for circulating strain diversity and incorporate the within-host diversity of HIV...
July 11, 2018: BMC Biology
Aaron McKenna, Jay Shendure
BACKGROUND: Genome-wide knockout studies, noncoding deletion scans, and other large-scale studies require a simple and lightweight framework that can quickly discover and score thousands of candidate CRISPR guides targeting an arbitrary DNA sequence. While several CRISPR web applications exist, there is a need for a high-throughput tool to rapidly discover and process hundreds of thousands of CRISPR targets. RESULTS: Here, we introduce FlashFry, a fast and flexible command-line tool for characterizing large numbers of CRISPR target sequences...
July 5, 2018: BMC Biology
Hao Yan, Jiawei Zhang, Jia Wen, Yibo Wang, Wanbao Niu, Zhen Teng, Tongtong Zhao, Yanli Dai, Yan Zhang, Chao Wang, Yingying Qin, Guoliang Xia, Hua Zhang
BACKGROUND: In mammalian females, progressive activation of dormant primordial follicles in adulthood is crucial for the maintenance of the reproductive lifespan. Misregulated activation of primordial follicles leads to various ovarian diseases, such as premature ovarian insufficiency (POI). Although recent studies have revealed that several functional genes and pathways, such as phosphoinositide 3-kinase (PI3K) signaling, play roles in controlling the activation of primordial follicles, our understanding of the molecular networks regulating the activation progress is still incomplete...
July 5, 2018: BMC Biology
Richard Borowsky, Alissa Luk, Xinjian He, Rebecca S Kim
BACKGROUND: The phenotypes of sperm are generally believed to be under the control of the diploid genotype of the male producing them rather than their own haploid genotypes, because developing spermatids share cytoplasm through intercellular bridges. This sharing is believed to homogenize their content of gene products. However, not all developing spermatids have identical gene products and estimates are that alleles at numerous gene loci are unequally expressed in sperm. This provides scope for the hypothesis that sperm phenotypes might be influenced by their unique haplotypes...
July 5, 2018: BMC Biology
Amanda L Pendleton, Feichen Shen, Angela M Taravella, Sarah Emery, Krishna R Veeramah, Adam R Boyko, Jeffrey M Kidd
BACKGROUND: Domesticated from gray wolves between 10 and 40 kya in Eurasia, dogs display a vast array of phenotypes that differ from their ancestors, yet mirror other domesticated animal species, a phenomenon known as the domestication syndrome. Here, we use signatures persisting in dog genomes to identify genes and pathways possibly altered by the selective pressures of domestication. RESULTS: Whole-genome SNP analyses of 43 globally distributed village dogs and 10 wolves differentiated signatures resulting from domestication rather than breed formation...
June 28, 2018: BMC Biology
Anthony J Hannan
Huntington's disease (HD) is one of the most common tandem repeat disorders and presents as a unique trilogy of cognitive, psychiatric and motor symptoms. One of the major mysteries of HD is why it selectively affects specific neuronal populations. A new article in BMC Biology provides a piece in the puzzle of pathogenesis. By demonstrating the delicate relationship between cortical and striatal neurons, it provokes broader questions of how we might understand HD as a disorder of synapses, neural circuits and systems biology...
June 27, 2018: BMC Biology
Mandi E Schmidt, Caodu Buren, James P Mackay, Daphne Cheung, Louisa Dal Cengio, Lynn A Raymond, Michael R Hayden
BACKGROUND: Huntington disease (HD) is a fatal neurodegenerative disorder caused by a CAG expansion in the huntingtin (HTT) gene, leading to selective and progressive neuronal death predominantly in the striatum. Mutant HTT expression causes dysfunctional cortico-striatal (CS) transmission, loss of CS synapses, and striatal medium spiny neuron (MSN) dendritic spine instability prior to neuronal death. Co-culturing cortical and striatal neurons in vitro promotes the formation of functional CS synapses and is a widely used approach to elucidate pathogenic mechanisms of HD and to validate potential synapto-protective therapies...
June 27, 2018: BMC Biology
Lukasz Kowalski, Piotr Bragoszewski, Anton Khmelinskii, Edyta Glow, Michael Knop, Agnieszka Chacinska
BACKGROUND: The proteome of mitochondria comprises mostly proteins that originate as precursors in the cytosol. Before import into the organelle, such proteins are exposed to cytosolic quality control mechanisms. Multiple lines of evidence indicate a significant contribution of the major cytosolic protein degradation machinery, the ubiquitin-proteasome system, to the quality control of mitochondrial proteins. Proteins that are directed to the mitochondrial intermembrane space (IMS) exemplify an entire class of mitochondrial proteins regulated by proteasomal degradation...
June 22, 2018: BMC Biology
Eva Zöller, R Todd Alexander, Johannes M Herrmann
Tandem fluorescent protein timers are elegant tools to determine proteolytic stabilities of cytosolic proteins with high spatial and temporal resolution. In a new study published in BMC Biology, Kowalski et al. fused timers to precursors of proteins of the mitochondrial intermembrane space and found that they are under surveillance of the ubiquitin-proteasome system. Ubiquitination at lysine residues of these precursors directly inhibits their translocation into the intermembrane space and targets them for proteasomal degradation...
June 22, 2018: BMC Biology
Gemma F Codner, Joffrey Mianné, Adam Caulder, Jorik Loeffler, Rachel Fell, Ruairidh King, Alasdair J Allan, Matthew Mackenzie, Fran J Pike, Christopher V McCabe, Skevoulla Christou, Sam Joynson, Marie Hutchison, Michelle E Stewart, Saumya Kumar, Michelle M Simon, Loranne Agius, Quentin M Anstee, Kirill E Volynski, Dimitri M Kullmann, Sara Wells, Lydia Teboul
BACKGROUND: Recent advances in clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome editing have led to the use of long single-stranded DNA (lssDNA) molecules for generating conditional mutations. However, there is still limited available data on the efficiency and reliability of this method. RESULTS: We generated conditional mouse alleles using lssDNA donor templates and performed extensive characterization of the resulting mutations...
June 21, 2018: BMC Biology
Denise G Lanza, Angelina Gaspero, Isabel Lorenzo, Lan Liao, Ping Zheng, Ying Wang, Yu Deng, Chonghui Cheng, Chuansheng Zhang, John R Seavitt, Francesco J DeMayo, Jianming Xu, Mary E Dickinson, Arthur L Beaudet, Jason D Heaney
BACKGROUND: The International Mouse Phenotyping Consortium is generating null allele mice for every protein-coding gene in the genome and characterizing these mice to identify gene-phenotype associations. While CRISPR/Cas9-mediated null allele production in mice is highly efficient, generation of conditional alleles has proven to be more difficult. To test the feasibility of using CRISPR/Cas9 gene editing to generate conditional knockout mice for this large-scale resource, we employed Cas9-initiated homology-driven repair (HDR) with short and long single stranded oligodeoxynucleotides (ssODNs and lssDNAs)...
June 21, 2018: BMC Biology
Anton Strunov, Lidiya V Boldyreva, Evgeniya N Andreyeva, Gera A Pavlova, Julia V Popova, Alena V Razuvaeva, Alina F Anders, Fioranna Renda, Alexey V Pindyurin, Maurizio Gatti, Elena Kiseleva
BACKGROUND: S2 cells are one of the most widely used Drosophila melanogaster cell lines. A series of studies has shown that they are particularly suitable for RNAi-based screens aimed at the dissection of cellular pathways, including those controlling cell shape and motility, cell metabolism, and host-pathogen interactions. In addition, RNAi in S2 cells has been successfully used to identify many new mitotic genes that are conserved in the higher eukaryotes, and for the analysis of several aspects of the mitotic process...
June 15, 2018: BMC Biology
Claire Maynard, Ian Cummins, Jacalyn Green, David Weinkove
BACKGROUND: To prevent folate deficiencies, many countries supplement various foodstuffs with folic acid. This compound is a synthetic oxidised folate that differs from naturally occurring reduced folates in its metabolism and uptake. Notably, safety reviews of folic acid supplementation have not considered interactions with gut bacteria. Here, we use the Caenorhabditis elegans - Escherichia coli animal- microbe model to examine a possible bacterial route for folic acid uptake. It has been assumed that supplements are taken up directly by the worm, especially because E...
June 15, 2018: BMC Biology
Florian A Britto, Fabienne Cortade, Yassine Belloum, Marine Blaquière, Yann S Gallot, Aurélie Docquier, Allan F Pagano, Elodie Jublanc, Nadia Bendridi, Christelle Koechlin-Ramonatxo, Béatrice Chabi, Marc Francaux, François Casas, Damien Freyssenet, Jennifer Rieusset, Sophie Giorgetti-Peraldi, Gilles Carnac, Vincent Ollendorff, François B Favier
BACKGROUND: Skeletal muscle atrophy is a common feature of numerous chronic pathologies and is correlated with patient mortality. The REDD1 protein is currently recognized as a negative regulator of muscle mass through inhibition of the Akt/mTORC1 signaling pathway. REDD1 expression is notably induced following glucocorticoid secretion, which is a component of energy stress responses. RESULTS: Unexpectedly, we show here that REDD1 instead limits muscle loss during energetic stresses such as hypoxia and fasting by reducing glycogen depletion and AMPK activation...
June 12, 2018: BMC Biology
Benjamin E Mead, Jose Ordovas-Montanes, Alexandra P Braun, Lauren E Levy, Prerna Bhargava, Matthew J Szucs, Dustin A Ammendolia, Melanie A MacMullan, Xiaolei Yin, Travis K Hughes, Marc H Wadsworth, Rushdy Ahmad, Seth Rakoff-Nahoum, Steven A Carr, Robert Langer, James J Collins, Alex K Shalek, Jeffrey M Karp
BACKGROUND: Single-cell genomic methods now provide unprecedented resolution for characterizing the component cell types and states of tissues such as the epithelial subsets of the gastrointestinal tract. Nevertheless, functional studies of these subsets at scale require faithful in vitro models of identified in vivo biology. While intestinal organoids have been invaluable in providing mechanistic insights in vitro, the extent to which organoid-derived cell types recapitulate their in vivo counterparts remains formally untested, with no systematic approach for improving model fidelity...
June 5, 2018: BMC Biology
Alba Domènech, José Ayté, Fernando Antunes, Elena Hidalgo
BACKGROUND: Hydrogen peroxide (H2 O2 ) is generated as a by-product of metabolic reactions during oxygen use by aerobic organisms, and can be toxic or participate in signaling processes. Cells, therefore, need to be able to sense and respond to H2 O2 in an appropriate manner. This is often accomplished through thiol switches: Cysteine residues in proteins that can act as sensors, and which are both scarce and finely tuned. Bacteria and eukaryotes use different types of such sensors-either a one-component (OxyR) or two-component (Pap1-Tpx1) redox relay, respectively...
June 1, 2018: BMC Biology
Wenjing Zheng, Florentina Rus, Ana Hernandez, Ping Kang, William Goldman, Neal Silverman, Marc Tatar
BACKGROUND: Drosophila is a powerful model for the study of factors modulating innate immunity. This study examines the effect of water-loss dehydration on innate immune responsiveness in the Drosophila renal system (Malpighian tubules; MTs), and how this leads to elevated host defense and contributes to immunosenescence. RESULTS: A short period of desiccation-elevated peptidoglycan recognition protein-LC (PGRP-LC) expression in MTs, increased antimicrobial peptide (AMP) gene induction, and protected animals from bacterial infection...
May 31, 2018: BMC Biology
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