Author information: Elhesha R1, Kahveci T2.
1CISE Department, University of Florida, 432 Newell Dr, Gainesville, Florida, 32611, USA. firstname.lastname@example.org.
2CISE Department, University of Florida, 432 Newell Dr, Gainesville, Florida, 32611, USA.
Journal: BMC Bioinformatics
Date of e-pub: October 2016
Abstract: Biological networks provide great potential to understand how cells function. Network motifs, frequent topological patterns, are key structures through which biological networks operate. Finding motifs in biological networks remains to be computationally challenging task as the size of the motif and the underlying network grow. Often, different copies of a given motif topology in a network share nodes or edges. Counting such overlapping copies introduces significant problems in motif identification.
In this paper, we develop a scalable algorithm for finding network motifs. Unlike most of the existing studies, our algorithm counts independent copies of each motif topology. We introduce a set of small patterns and prove that we can construct any larger pattern by joining those patterns iteratively. By iteratively joining already identified motifs with those patterns, our algorithm avoids (i) constructing topologies which do not exist in the target network (ii) repeatedly counting the frequency of the motifs generated in subsequent iterations. Our experiments on real and synthetic networks demonstrate that our method is significantly faster and more accurate than the existing methods including SUBDUE and FSG.
We conclude that our method for finding network motifs is scalable and computationally feasible for large motif sizes and a broad range of networks with different sizes and densities. We proved that any motif with four or more edges can be constructed as a join of the small patterns.
Author information: Gao M1, Nguyen HT2, Salas Gonzalez I3, Teplitski M4.
1University of Florida, Soil and Water Sciences , 2169 McCarty Hall A , Gainsville, Florida, United States , 110290 ; email@example.com.
2Gainesville, United States ; firstname.lastname@example.org.
3Gainesville, United States ; email@example.com.
4University of Florida, Soil and Water Science , 1376 Mowry Rd , Rm 330E, CGRC , Gainesivlle, United States , 32610 ; firstname.lastname@example.org.
Journal: Molecular Plant-Microbiome Interactions
Date of e-pub: October 2016
Abstract: The RNA-binding chaperone Hfq plays a critical role in the establishment and functionality of the symbiosis between Sinorhizobium meliloti and its legume hosts. A mutation in hfq reduces symbiotic efficiency resulting in a Fix- phenotype, characterized by the inability of the bacterium to fix nitrogen. At least in part, this is due to the ability of Hfq to regulate the fixLJ operon, which encodes a sensor kinase-response regulator pair that controls expression of the nitrogenase genes. The ability of Hfq to bind fixLJ in vitro and in planta was demonstrated with gel shift and co-immunoprecipitation experiments. Two (ARN)2 motifs in the fixLJ message were the likely sites through which Hfq exerted its post-transcriptional control. Consistent with the regulatory effects of Hfq, downstream genes controlled by FixLJ (such as nifK, noeB) were also subject to Hfq regulation in planta.
The sensitivity of exome sequencing in identifying pathogenic mutations for LGMD in the United States.
Author information: Reddy HM1, Cho KA1, Lek M2,3, Estrella E4, Valkanas E2,3, Jones MD1, Mitsuhashi S5, Darras BT5, Amato AA6, Lidov HG7, Brownstein CA4,8, Margulies DM4,8, Yu TW4, Salih MA9, Kunkel LM4, MacArthur DG2,3, Kang PB1,5,10,11.
1Division of Pediatric Neurology, Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA.
2Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
3Program in Medical and Population Genetics, Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
4Division of Genetics and Genomics, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA.
5Department of Neurology, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA.
6Department of Neurology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA.
7Department of Pathology, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA.
8Research Connection and Manton Center for Orphan Disease Research, Division of Genetics and Genomics, Boston Children’s Hospital and Harvard Medical School, Boston, MA, USA.
9Department of Pediatrics, Division of Neurology, College of Medicine and King Khalid University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia.
10Department of Neurology and Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL, USA.
11Genetics Institute, University of Florida, Gainesville, FL, USA.
Journal: Journal of Human Genetics
Date of e-pub: October 2016
Abstract: The current study characterizes a cohort of limb-girdle muscular dystrophy (LGMD) in the United States using whole-exome sequencing. Fifty-five families affected by LGMD were recruited using an institutionally approved protocol. Exome sequencing was performed on probands and selected parental samples. Pathogenic mutations and cosegregation patterns were confirmed by Sanger sequencing. Twenty-two families (40%) had novel and previously reported pathogenic mutations, primarily in LGMD genes, and also in genes for Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, congenital myopathy, myofibrillar myopathy, inclusion body myopathy and Pompe disease. One family was diagnosed via clinical testing. Dominant mutations were identified in COL6A1, COL6A3, FLNC, LMNA, RYR1, SMCHD1 and VCP, recessive mutations in ANO5, CAPN3, GAA, LAMA2, SGCA and SGCG, and X-linked mutations in DMD. A previously reported variant in DMD was confirmed to be benign. Exome sequencing is a powerful diagnostic tool for LGMD. Despite careful phenotypic screening, pathogenic mutations were found in other muscle disease genes, largely accounting for the increased sensitivity of exome sequencing. Our experience suggests that broad sequencing panels are useful for these analyses because of the phenotypic overlap of many neuromuscular conditions. The confirmation of a benign DMD variant illustrates the potential of exome sequencing to help determine pathogenicity.Journal of Human Genetics advance online publication, 6 October 2016; doi:10.1038/jhg.2016.116.
Transcriptional Profiling Reveals a Common Metabolic Program in High-Risk Human Neuroblastoma and Mouse Neuroblastoma Sphere-Forming Cells.
Author information: Liu M1, Xia Y1, Ding J2, Ye B2, Zhao E3, Choi JH4, Alptekin A5, Yan C5, Dong Z6, Huang S7, Yang L3, Cui H3, Zha Y8, Ding HF9.
1Department of Neurology, Institute of Neural Regeneration and Repair, The First Hospital of Yichang, Three Gorges University College of Medicine, Yichang, 443000, China.
2The Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA.
3State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and System Biology, Southwest University, Chongqing 400715, China.
4The Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA; Department of Biostatistics and Epidemiology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
5The Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
6The Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA; Department of Cell Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
7Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL 32611, USA.
8Department of Neurology, Institute of Neural Regeneration and Repair, The First Hospital of Yichang, Three Gorges University College of Medicine, Yichang, 443000, China. Electronic address: email@example.com.
9The Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA; Department of Pathology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA. Electronic address: firstname.lastname@example.org.
Journal: Cell Reports
Date of e-pub: October 2016
Abstract: High-risk neuroblastoma remains one of the deadliest childhood cancers. Identification of metabolic pathways that drive or maintain high-risk neuroblastoma may open new avenues of therapeutic interventions. Here, we report the isolation and propagation of neuroblastoma sphere-forming cells with self-renewal and differentiation potential from tumors of the TH-MYCN mouse, an animal model of high-risk neuroblastoma with MYCN amplification. Transcriptional profiling reveals that mouse neuroblastoma sphere-forming cells acquire a metabolic program characterized by transcriptional activation of the cholesterol and serine-glycine synthesis pathways, primarily as a result of increased expression of sterol regulatory element binding factors and Atf4, respectively. This metabolic reprogramming is recapitulated in high-risk human neuroblastomas and is prognostic for poor clinical outcome. Genetic and pharmacological inhibition of the metabolic program markedly decreases the growth and tumorigenicity of both mouse neuroblastoma sphere-forming cells and human neuroblastoma cell lines. These findings suggest a therapeutic strategy for targeting the metabolic program of high-risk neuroblastoma.
Author information: Torbati M1, Lele TP2, Agrawal A3.
1Department of Mechanical Engineering, University of Houston, Houston, TX 77204.
2Department of Chemical Engineering, University of Florida, Gainesville, FL 32611.
3Department of Mechanical Engineering, University of Houston, Houston, TX 77204; email@example.com.
Journal: Proceedings of the National Academy of Sciences
Date of e-pub: October 2016
Abstract: The nuclear envelope is a unique topological structure formed by lipid membranes in eukaryotic cells. Unlike other membrane structures, the nuclear envelope comprises two concentric membrane shells fused at numerous sites with toroid-shaped pores that impart a “geometric” genus on the order of thousands. Despite the intriguing architecture and vital biological functions of the nuclear membranes, how they achieve and maintain such a unique arrangement remains unknown. Here, we used the theory of elasticity and differential geometry to analyze the equilibrium shape and stability of this structure. Our results show that modest in- and out-of-plane stresses present in the membranes not only can define the pore geometry, but also provide a mechanism for destabilizing membranes beyond a critical size and set the stage for the formation of new pores. Our results suggest a mechanism wherein nanoscale buckling instabilities can define the global topology of a nuclear envelope-like structure.
Role of Host-Driven Mutagenesis in Determining Genome Evolution of Sigma Virus (DMelSV; Rhabdoviridae) in Drosophila melanogaster.
Author information: Piontkivska H1, Matos LF2, Paul S3, Scharfenberg B4, Farmerie WG5, Miyamoto MM6, Wayne ML7.
1Department of Biological Sciences and School of Biomedical Sciences, Kent State University, Kent, OH firstname.lastname@example.org.
2Department of Entomology & Nematology, University of Florida, Gainesville, FL Department of Biology, Eastern Washington University, Cheney, WA.
3Department of Biological Sciences and School of Biomedical Sciences, Kent State University, Kent, OH Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA.
4Department of Biological Sciences and School of Biomedical Sciences, Kent State University, Kent, OH Ohio University Heritage College of Osteopathic Medicine, Athens, OH.
5Interdisciplinary Center for Biotechnology Research University of Florida, Gainesville, FL.
6Department of Biology, University of Florida, Gainesville, FL.
7Department of Biology, University of Florida, Gainesville, FL Emerging Pathogens Institute University of Florida, Gainesville, FL.
Journal: Genome Biology and Evolution
Date of e-pub: October 2016
Abstract: Sigma virus (DMelSV) is ubiquitous in natural populations of Drosophila melanogaster. Host-mediated, selective RNA editing of adenosines to inosines (ADAR) may contribute to control of viral infection by preventing transcripts from being transported into the cytoplasm or being translated accurately; or by increasing the viral genomic mutation rate. Previous PCR-based studies showed that ADAR mutations occur in DMelSV at low frequency. Here we use SOLiDTM deep sequencing of flies from a single host population from Athens, GA, USA to comprehensively evaluate patterns of sequence variation in DMelSV with respect to ADAR. GA dinucleotides, which are weak targets of ADAR, are strongly overrepresented in the positive strand of the virus, consistent with selection to generate ADAR resistance on this complement of the transient, double-stranded RNA intermediate in replication and transcription. Potential ADAR sites in a worldwide sample of viruses are more likely to be “resistant” if the sites do not vary among samples. Either variable sites are less constrained and hence are subject to weaker selection than conserved sites, or the variation is driven by ADAR. We also find evidence of mutations segregating within hosts, hereafter referred to as hypervariable sites. Some of these sites were variable only in one or two flies (i.e., rare); others were shared by four or even all five of the flies (i.e., common). Rare and common hypervariable sites were indistinguishable with respect to susceptibility to ADAR; however, polymorphism in rare sites were more likely to be consistent with the action of ADAR than in common ones, again suggesting that ADAR is deleterious to the virus. Thus, in DMelSV, host mutagenesis is constraining viral evolution both within and between hosts.
Author information: Geng S1,2, Misra BB2, de Armas E3, Huhman DV4, Alborn HT5, Sumner LW4, Chen S6,7,8.
1Plant Molecular and Cellular Biology Program, University of Florida, Gainesville, FL, 32610, USA.
2Department of Biology, Genetics Institute, University of Florida, Gainesville, FL, 32610, USA.
3Thermo Fisher Scientific, 1400 Northpoint Parkway, West Palm Beach, FL, 33407, USA.
4Samuel Roberts Noble Foundation, Ardmore, OK, 73401, USA.
5Chemistry Research Unit, Agricultural Research Service, United States Department of Agriculture, Gainesville, FL, 32608, USA.
6Plant Molecular and Cellular Biology Program, University of Florida, Gainesville, FL, 32610, USA. email@example.com.
7Department of Biology, Genetics Institute, University of Florida, Gainesville, FL, 32610, USA. firstname.lastname@example.org.
8Proteomics and Mass Spectrometry, Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, FL, 32610, USA. email@example.com.
Journal: Plant Journal
Date of e-pub: October 2016
Abstract: Foliar stomatal movements are critical for regulating plant water loss and gas exchange. Elevated carbon dioxide (CO2 ) levels are known to induce stomatal closure. However, the current knowledge on CO2 signal transduction in stomatal guard cells is limited. Here we report metabolomic responses of Brassica napus guard cells to elevated CO2 using three hyphenated metabolomics platforms: gas chromatography-mass spectrometry (MS); liquid chromatography (LC)-multiple reaction monitoring-MS; and ultra-high-performance LC-quadrupole time-of-flight-MS. A total of 358 metabolites from guard cells were quantified in a time-course response to elevated CO2 level. Most metabolites increased under elevated CO2 , showing the most significant differences at 10 min. In addition, reactive oxygen species production increased and stomatal aperture decreased with time. Major alterations in flavonoid, organic acid, sugar, fatty acid, phenylpropanoid and amino acid metabolic pathways indicated changes in both primary and specialized metabolic pathways in guard cells. Most interestingly, the jasmonic acid (JA) biosynthesis pathway was significantly altered in the course of elevated CO2 treatment. Together with results obtained from JA biosynthesis and signaling mutants as well as CO2 signaling mutants, we discovered that CO2 -induced stomatal closure is mediated by JA signaling.
NOTE: These abstracts were retrieved from the U.S. National Library of Medicine website managed in collaboration with the U.S. National Library of Medicine