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Essential genome

Pooja Gopal, Michelle Yee, Jickky Sarathy, Jian Liang Low, Jansy P Sarathy, Firat Kaya, Véronique Dartois, Martin Gengenbacher, Thomas Dick
Pyrazinamide (PZA) is a critical component of first- and second-line treatments of tuberculosis (TB), yet its mechanism of action largely remains an enigma. We carried out a genetic screen to isolate Mycobacterium bovis BCG mutants resistant to pyrazinoic acid (POA), the bioactive derivative of PZA, followed by whole genome sequencing of 26 POA resistant strains. Rather than finding mutations in the proposed candidate targets fatty acid synthase I and ribosomal protein S1, we found resistance conferring mutations in two pathways: missense mutations in aspartate decarboxylase panD, involved in the synthesis of the essential acyl carrier coenzyme A (CoA), and frameshift mutations in the vitro nonessential polyketide synthase genes mas and ppsA-E, involved in the synthesis of the virulence factor phthiocerol dimycocerosate (PDIM)...
September 9, 2016: ACS Infectious Diseases
Zhong-Guo Shan, Ke-Xin Zhu, Fang-Yi Chen, Jie Liu, Bei Chen, Kun Qiao, Hui Peng, Ke-Jian Wang
A new gene homologous to the reported antimicrobial peptide (AMP) hyastatin from Hyas araneus was screened in the SSH library constructed from the hemocytes of Scylla paramamosain, and named SpHyastatin. In vivo study showed that SpHyastatin was predominantly expressed in hemocytes of S. paramamosain. With the challenge of either Vibrio parahaemolyticus or lipopolysaccharide (LPS), SpHyastatin showed a positive response, meaning that it was probably involved in the immune reaction against bacterial infection in vivo...
October 14, 2016: Fish & Shellfish Immunology
Bingjie Shi, Juan Li, Xuanling Shi, Wenxu Jia, Yi Wen, Xiongbing Hu, Fengfeng Zhuang, Jianzhong Xi, Linqi Zhang
Transcription activator-like effector nuclease (TALEN) represents a valuable tool for genomic engineering due to its single-nucleotide precision, high nuclease activity and low cytotoxicity. We report here systematic design and characterization of twenty eight novel TALENs targeting multiple regions of CCR5 gene (CCR5-TALEN) which encodes the co-receptor critical for entry of human immunodeficiency virus type I (HIV-1). By systemic characterization of these CCR5-TALENs, we have identified one (CCR5-TALEN-515) with higher nuclease activity, specificity and lower cytotoxicity compared to zinc-finger nuclease (CCR5-ZFN) currently undergoing clinical trials...
October 3, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Anna Maria Pinto, Valentina Imperatore, Laura Bianciardi, Margherita Baldassarri, Paolo Galluzzi, Simone Furini, Giovanni Centini, Alessandra Renieri, Francesca Mari
Orofacial clefts are the most common congenital craniofacial anomalies and can occur as an isolated defect or be associated with other anomalies such as posterior fossa anomalies as a part of several genetic syndromes. We report two consecutive voluntary pregnancy interruptions in a nonconsanguineous couple following the fetal ultrasound finding of cleft lip and palate and posterior fossa anomalies confirmed by means of post-termination examination on the second fetus. The quantitative fluorescent PCR, the karyotype, and the comparative genomic hybridization-array analysis after amniocentesis were normal...
October 4, 2016: Clinical Dysmorphology
D-L Qi, D Cobrinik
Retinoblastomas can arise from cone photoreceptor precursors in response to the loss of pRB function. Cone precursor-specific circuitry cooperates with pRB loss to initiate this process and subsequently contributes to the malignancy. Intrinsic high-level MDM2 expression is a key component of the cone precursor circuitry and is thought to inactivate p53-mediated tumor surveillance, which could otherwise be induced in response to pRB loss. However, the MDM2-related MDM4 has also been proposed to abrogate p53-mediated tumor surveillance in the absence of detectable MDM2 in retinoblastoma cells, bringing into question the importance of high-level MDM2 versus MDM4 expression...
October 17, 2016: Oncogene
Prosenjit Paul, Himangshu Deka, Arup K Malakar, Binata Halder, Supriyo Chakraborty
Among all cancers, the incidence of nasopharyngeal carcinoma (NPC) is quite high in the endemic regions. NPC is a head and neck cancer with poor survival rate, and is rare throughout most of the world but common in certain geographic areas, like southern Asia and some regions of North East India (Nagaland, Manipur, and Mizoram). A clear understanding of its etiology is still lacking, but NPC is widely suspected to be the result of both genetic susceptibility and exposure to environmental factors or Epstein-Barr virus infection...
September 29, 2016: European Journal of Cancer Prevention
Madeleine Berger, Alin Mirel Puinean, Emma Randall, Christoph T Zimmer, Wellington M Silva, Pablo Bielza, Linda M Field, David Hughes, Ian Mellor, Keywan Hassani-Pak, Herbert A A Siqueira, Martin S Williamson, Chris Bass
Many genes increase coding capacity by alternate exon usage. The gene encoding the insect nicotinic acetylcholine receptor (nAChR) α6 subunit, target of the bio-insecticide spinosad, is one example of this and expands protein diversity via alternative splicing of mutually exclusive exons. Here we show that spinosad resistance in the tomato leafminer, Tuta absoluta is associated with aberrant regulation of splicing of Taα6 resulting in a novel form of insecticide resistance mediated by exon skipping. Sequencing of the α6 subunit cDNA from spinosad selected and unselected strains of T...
October 17, 2016: Molecular Ecology
Abdullah Alzaid, Samuel A M Martin, Daniel J Macqueen
The insulin-like growth factor (IGF) receptor (IGF-IR) is necessary for IGF signalling and has essential roles in cellular growth. In teleost fish, two distinct IGF-IR duplicates are conserved called IGF-IRa and IGF-IRb. However, while a salmonid-specific whole genome duplication (ssWGD) is known to have expanded several key genes within the IGF axis, its impact on the IGF-IR repertoire remains unresolved. Using bioinformatic and phylogenetic approaches, we establish that salmonids retain two IGF-IRa paralogues from ssWGD and a single IGF-IRb copy...
October 17, 2016: Scientific Reports
Bastian Minkenberg, Kabin Xie, Yinong Yang
The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 nuclease (Cas9) system depends on a guide RNA (gRNA) to specify its target. By efficiently co-expressing multiple gRNAs that target different genomic sites, the polycistronic tRNA-gRNA gene (PTG) strategy enables multiplex gene editing in the family of closely related rice mitogen-activated protein kinase (MPK) genes. In this study, we identified MPK1 and MPK6 (Arabidopsis AtMPK6 and AtMPK4 orthologues, respectively) as essential genes for rice development by finding the preservation of MPK functional alleles and normal phenotypes in CRISPR-edited mutants...
October 16, 2016: Plant Journal: for Cell and Molecular Biology
Utsav Pandey, Andrew S Bell, Daniel W Renner, David A Kennedy, Jacob T Shreve, Chris L Cairns, Matthew J Jones, Patricia A Dunn, Andrew F Read, Moriah L Szpara
The intensification of the poultry industry over the last 60 years facilitated the evolution of increased virulence and vaccine breaks in Marek's disease virus (MDV-1). Full-genome sequences are essential for understanding why and how this evolution occurred, but what is known about genome-wide variation in MDV comes from laboratory culture. To rectify this, we developed methods for obtaining high-quality genome sequences directly from field samples without the need for sequence-based enrichment strategies prior to sequencing...
September 2016: MSphere
Sumera Rizvi, Mitesh J Borad
Cholangiocarcinomas (CCAs) are heterogeneous tumors arising from the biliary tract with features of cholangiocyte differentiation. CCAs are aggressive tumors with limited treatment options and poor overall survival. Only a subset of CCA patients with early stage disease can avail potentially curative treatment options. For advanced biliary tract tumors, currently there are limited effective treatment modalities. Recent advances have provided greater insight into the genomic landscape of CCAs. The fibroblast growth factor receptor (FGFR) pathway is involved in key cellular processes essential to survival and differentiation...
October 2016: Journal of Gastrointestinal Oncology
Julia Bally, Glen J McIntyre, Rachel L Doran, Karen Lee, Alicia Perez, Hyungtaek Jung, Fatima Naim, Ignacio M Larrinua, Kenneth E Narva, Peter M Waterhouse
Expressing double-stranded RNA (dsRNA) in transgenic plants to silence essential genes within herbivorous pests is referred to as trans-kingdom RNA interference (TK-RNAi) and has emerged as a promising strategy for crop protection. However, the dicing of dsRNA into siRNAs by the plant's intrinsic RNAi machinery may reduce this pesticidal activity. Therefore, genetic constructs, encoding ∼200 nt duplex-stemmed-hairpin (hp) RNAs, targeting the acetylcholinesterase gene of the cotton bollworm, Helicoverpa armigera, were integrated into either the nuclear or the chloroplast genome of Nicotiana benthamiana...
2016: Frontiers in Plant Science
Abdullah M Alhadheq, Jilani Purusottapatnam Shaik, Abdullah Alamri, Abdulrahman M Aljebreen, Othman Alharbi, Majid A Almadi, Faten Alhadeq, Nahla A Azzam, Abdelhabib Semlali, Mohammad Alanazi, Mohammad D Bazzi, Narasimha Reddy Parine
Background. DNA repair systems are essential for each cell to repair and maintain the genome integrity. Base excision repair pathway is one of the crucial pathways to maintain genome integrity and PARP-1 plays a key role in BER pathway. The purpose of this study is to evaluate the association between polymorphisms in PARP-1 3'untranslated region (3'UTR) SNP rs8679 and its expression in colorectal cancer. Methods. Genotyping and gene expression were performed using TaqMan assays. The effects of age, gender, and tumor location were evaluated in cases and controls regarding the genotyping results...
2016: Disease Markers
Roshan J Thapa, Justin P Ingram, Katherine B Ragan, Shoko Nogusa, David F Boyd, Asiel A Benitez, Haripriya Sridharan, Rachelle Kosoff, Maria Shubina, Vanessa J Landsteiner, Mark Andrake, Peter Vogel, Luis J Sigal, Benjamin R tenOever, Paul G Thomas, Jason W Upton, Siddharth Balachandran
Influenza A virus (IAV) is an RNA virus that is cytotoxic to most cell types in which it replicates. IAV activates the host kinase RIPK3, which induces cell death via parallel pathways of necroptosis, driven by the pseudokinase MLKL, and apoptosis, dependent on the adaptor proteins RIPK1 and FADD. How IAV activates RIPK3 remains unknown. We report that DAI (ZBP1/DLM-1), previously implicated as a cytoplasmic DNA sensor, is essential for RIPK3 activation by IAV. Upon infection, DAI recognizes IAV genomic RNA, associates with RIPK3, and is required for recruitment of MLKL and RIPK1 to RIPK3...
October 8, 2016: Cell Host & Microbe
Joo Hwa Lee, Nam Jin Yoo, Min Sung Kim, Sug Hyung Lee
Alterations of genes involved in histone modification are common in cancers. A histone demethylase-encoding gene PHF2 is considered a putative tumor suppressor gene (TSG). PHF2 is essential for p53-mediated TSG functions such as chemotherapy-mediated cancer cell killing. However, inactivating mutations of PHF2 that could inactivate its functions are not reported in cancers. In a genome database, we observed that the PHF2 gene possessed mononucleotide repeats, which could be mutated in cancers with high microsatellite instability (MSI-H)...
October 15, 2016: Pathology Oncology Research: POR
Teija Ojala, Pia K S Laine, Terhi Ahlroos, Jarna Tanskanen, Saara Pitkänen, Tuomas Salusjärvi, Matti Kankainen, Soile Tynkkynen, Lars Paulin, Petri Auvinen
Propionibacterium freudenreichii is a commercially important bacterium that is essential for the development of the characteristic eyes and flavor of Swiss-type cheeses. These bacteria grow actively and produce large quantities of flavor compounds during cheese ripening at warm temperatures but also appear to contribute to the aroma development during the subsequent cold storage of cheese. Here, we advance our understanding of the role of P. freudenreichii in cheese ripening by presenting the 2.68-Mbp annotated genome sequence of P...
September 26, 2016: International Journal of Food Microbiology
Marlene Teubner, Janina Fuß, Kristina Kühn, Kirsten Krause, Christian Schmitz-Linneweber
Chloroplast RNA metabolism depends on a multitude of nuclear-encoded RNA binding proteins (RBPs). Most known chloroplast RBPs address specific RNA targets and RNA-processing functions. However, members of the small chloroplast ribonucleoprotein family (cpRNPs) play a global role in processing and stabilizing chloroplast RNAs. Here, we show that the cpRNP, CP33A, localizes to a distinct sub-chloroplastic domain and is essential for chloroplast development. The loss of CP33A yields albino seedlings that exhibit aberrant leaf development and can only survive in the presence of an external carbon source...
October 15, 2016: Plant Journal: for Cell and Molecular Biology
Magali De Koninck, Ana Losada
Cohesin is a large ring-shaped protein complex, conserved from yeast to human, which participates in most DNA transactions that take place in the nucleus. It mediates sister chromatid cohesion, which is essential for chromosome segregation and homologous recombination (HR)-mediated DNA repair. Together with architectural proteins and transcriptional regulators, such as CTCF and Mediator, respectively, it contributes to genome organization at different scales and thereby affects transcription, DNA replication, and locus rearrangement...
October 14, 2016: Cold Spring Harbor Perspectives in Medicine
James M Brown, Neil R Horner, Thomas N Lawson, Tanja Fiegel, Simon Greenaway, Hugh Morgan, Natalie Ring, Luis Santos, Duncan Sneddon, Lydia Teboul, Jennifer Vibert, Gagarine Yaikhom, Henrik Westerberg, Ann-Marie Mallon
High-throughput phenotyping is a cornerstone of numerous functional genomics projects. In recent years, imaging screens have become increasingly important in understanding gene-phenotype relationships in studies of cells, tissues and whole organisms. Three-dimensional (3D) imaging has risen to prominence in the field of developmental biology for its ability to capture whole embryo morphology and gene expression, as exemplified by the International Mouse Phenotyping Consortium (IMPC). Large volumes of image data are being acquired by multiple institutions around the world that encompass a range of modalities, proprietary software and metadata...
October 14, 2016: Briefings in Bioinformatics
Otília Menyhárt, Hajnalka Harami-Papp, Saraswati Sukumar, Reinhold Schäfer, Luca Magnani, Oriol de Barrios, Balázs Győrffy
The hallmarks of cancer capture the most essential phenotypic characteristics of malignant transformation and progression. Although numerous factors involved in this multi-step process are still unknown to date, an ever-increasing number of mutated/altered candidate genes are being identified within large-scale cancer genomic projects. Therefore, investigators need to be aware of available and appropriate techniques capable of determining characteristic features of each hallmark. We review the methods tailored to experimental cancer researchers to evaluate cell proliferation, programmed cell death, replicative immortality, induction of angiogenesis, invasion and metastasis, genome instability, and reprogramming of energy metabolism...
October 11, 2016: Biochimica et Biophysica Acta
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