Why would a brain tumor oncologist be stopped from trying a drug that is known to be efficacious against the genomically similar liver tumor?
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At the location corresponding to the I/M site of GABRA3 in frog and pufferfish there is a genomically encoded methionine. In all other species, there is an isoleucine at the position.
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An investigation of the amber initiator tRNA showed that it was orthogonal to the regular AUG start codon showing no detectable off-target translation initiation events in a genomically recoded E. coli strain.
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Cécile Vogt-Mugnier and her husband Oskar Vogt came up with the idea of pathoclisis through their research on insects and the human cerebral cortex. They defined it as the "genomically-determined excessive variability, reaching in intensity the degree of pathological change".
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Typically identification is done by growing the organism in a wide range of cultures which can take up to 48 hours. The growth is then visually or genomically identified. The cultured organism is then subjected to various assays to observe reactions to help further identify species and strain.
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The gene for factor V is located on the first chromosome (1q24). It is genomically related to the family of multicopper oxidases, and is homologous to coagulation factor VIII. The gene spans 70 kb, consists of 25 exons, and the resulting protein has a relative molecular mass of approximately 330kDa.
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Why editing exists at this site instead of a genomically encoded arginine is unknown since nearly 100% of transcripts are edited. Cancer Decreased editing at the Q/R site is also found in some human brain tumors. Reduction of ADAR2 expression is thought to be associated with epileptic seizures in malignant glioma.
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Genomically, ADAMTS13 shares many properties with the 19 member ADAMTS family, all of which are characterised by a protease domain (the part that performs the protein hydrolysis), an adjacent disintegrin domain and one or more thrombospondin domains. ADAMTS13 in fact has eight thrombospondin domains. It has no hydrophobic transmembrane domain, and hence it is not anchored in the cell membrane.
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Editing results in a codon change from a glutamine codon (CAG) to an arginine codon (CIG). Editing at R/G results in a codon change. The region of the editing site is known to be the region that controls divalent cation permeability. The other ionotropic AMPA glutamate receptors have a genomically encoded have a glutamine residue, while GluR2 has an arginine.
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Altering the genetic machinery of the cell leads to semantic containment. In analogy to information processing in IT, this safety concept is termed a “genetic firewall”. The concept of the genetic firewall seems to overcome a number of limitations of previous safety systems. A first experimental evidence of the theoretical concept of the genetic firewall was achieved in 2013 with the construction of a genomically recoded organism (GRO).
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Molecular diagnostics are used in combination with traditional clinicopathologic factors to decide on a treatment plan. MammaPrint provides a binary result, either high risk or low risk. Patients with a low risk result are unlikely to develop distant metastases and are therefore unlikely to benefit from chemotherapy. Since many breast cancers are considered genomically low-risk independent from clinicopathology, a significant number of patients can be saved from overtreatment with chemotherapy.
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The candidate editing sites were determined experimentally by comparison of cDNA sequences and genomically encoded DNA from the same individual to avoid single nucleotide polymorphisms (SNPs). Two of the three editing sites found in mouse gene were found in the human transcript. However, only the Q/R site was detected in all RNA, with the T/A site detected just once. Both sites are found within exon 1.
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The predicted double stranded region is 30 base pairs in length. The adenosine residue is mismatched in genomically encoded transcript, however this is not the case following editing. Despite similar sequences to the Q/R site of GluR-B, editing at this site does not occur in GluR-3 pre-mRNA. Editing results in the targeted adenosine, which is mismatched prior to editing in the double-stranded RNA structure to become matched after editing.
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The adenosine residue is mismatched in genomically encoded transcript, however this is not the case following editing. Despite similar sequences to the Q/R site of GluR-B, editing this site does not occur in GluR-3 pre-mRNA. Editing results in the targeted adenosine, which is mismatched prior to editing in the double-stranded RNA structure to become matched after editing. The intronic sequence involved contains a 5' donor splice site.
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"The maternal ancestry of the Brazilian white was one-third African, one third Amerindian, and one third European. An individual who considers himself white may be genomically more African than an individual who considers himself to be brown or black." In April 2008, Ronaldo was involved in a scandal involving three travesti prostitutes whom he met in a nightclub in Rio de Janeiro. Ronaldo claimed that upon discovering that they were legally male, he offered them $600 to leave.
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It was discovered that retrotransposons can influence mammalian transcription and transcriptional regulation of both coding and non-coding RNAs in various tissues. Further efforts found a genomically and evolutionary widespread new class of RNAs, called transcription initiation RNAs (tiRNA). This species of RNA are relatively tiny (~18 nucleotides long) and are typically found downstream of TSSs of CpG rich promoters. tiRNAs are low in abundance and are associated with highly expressed genes, as well as RNA polymerase II binding and TSSs.
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The recombinant vector that is genomically modified will express the antigen. The antigen (one or more subunits of protein) is extracted from the vector. Just like the highly successful subunit vaccines, the recombinant-vector-produced antigen will be of little to no risk to the patient. This is the type of vaccine currently in use for hepatitis B, and it is experimentally popular, being used to try to develop new vaccines for difficult-to-vaccinate-against viruses such as ebolavirus and HIV.
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The purpose of the patrocladogram in biological classification is to form a hypothesis about which evolutionary processes are actually involved before making a taxonomic decision. Patrocladograms are based on biostatistics that include but are not limited to: parsimony, distance matrix, likelihood methods, and Bayesian probability. Some examples of genomically related data that can be used as inputs for these methods are: molecular sequences, whole genome sequences, gene frequencies, restriction sites, distance matrices, unique characters, mutations such as SNPs, and mitochondrial genome data.
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A common strategy for avoiding genomic insertion has been to use a different vector for input. Plasmids, adenoviruses, and transposon vectors have all been explored, but these often come with the tradeoff of lower throughput. # Tumorigenicity: Depending on the methods used, reprogramming of adult cells to obtain iPSCs may pose significant risks that could limit their use in humans. For example, if viruses are used to genomically alter the cells, the expression of oncogenes (cancer-causing genes) may potentially be triggered.
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In medicine, it offers prospects of using designer biological parts as a starting point for new classes of therapies and diagnostic tools. A living "artificial cell" has been defined as a completely synthetic cell that can capture energy, maintain ion gradients, contain macromolecules as well as store information and have the ability to mutate. Nobody has been able to create such a cell. A completely synthetic bacterial chromosome was produced in 2010 by Craig Venter, and his team introduced it to genomically emptied bacterial host cells.
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These studies have, for example, provided a basis for a clinical trial of the efficacy of phenytoin, a sodium channel blocker in patients with optic neuritis. Waxman's studies have combined molecular genetics, molecular biology, and biophysics to show how specific ion channels relate to human pain. He has been a member of an international coalition that showed that sodium channel mutations can cause of peripheral neuropathy. He has used atomic-level modeling to study pharmacogenomics, at first in laboratory studies, and then in early studies on genomically guided approaches to the treatment of pain.
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The European zoo population clearly shows a lower allelic diversity than the Israeli population, and both these populations are less genomically diverse than the wild Iranian stock, which interestingly has about the same genetic diversity as the nominate Dama dama from Europe. Genetic variation is a concern in small populations because of an effect known as inbreeding depression, where deleterious genetic diseases build up and the fecundity of the population drops. In Israel the population does not appear to suffer from any of these small population size effects.
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That same day, it was reported that the Mount Roskill Evangelical Fellowship church had risen to eight cases, with three being genomically to the Auckland cluster. On 28 August, 12 new confirmed cases (five from the community and seven imported) were reported, bringing the total number of cases to 1,714 (1,363 confirmed and 351 probable), and seven new recoveries were reported, bringing the total to 1,561 and the number of active cases to 130. Eleven people are in hospital, an increase of one from the previous day. 11,010 tests were conducted the previous day.
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Their basic genomic organization appears maintained for a period exceeding 100 million years, and these sequence comparisons have laid the foundation for a PV taxonomy, which is now officially recognized by the International Committee on Taxonomy of Viruses. All PVs form the family Papillomaviridae, which is distinct from the Polyomaviridae thus eliminating the term Papovaviridae. Major branches of the phylogenetic tree of PVs are considered genera, which are identified by Greek letters. Minor branches are considered species and unite PV types that are genomically distinct without exhibiting known biological differences.
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Xenobiology might challenge the regulatory framework, as currently laws and directives deal with genetically modified organisms and do not directly mention chemically or genomically modified organisms. Taking into account that real xenobiology organisms are not expected in the next few years, policy makers do have some time at hand to prepare themselves for an upcoming governance challenge. Since 2012, the following groups have picked up the topic as a developing governance issue: policy advisers in the US,ISGP. 2013. 21st Century Borders/Synthetic Biology: Focus on Responsibility and Governance pp.
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J Insect Physiol 41, 41-46 This nutritional provisioning has been examined genomically (metabolic complementary, discussed below) and experimentally. Isolated bacteriocytes containing Buchnera have been shown to actively take up 14C labeled glutamine (a nonessential amino acid) where it is then converted into glutamic acid. This glutamic acid is then taken up by the individual Buchnera cells and used to synthesize the essential amino acids isoleucine, leucine, phenylalanine, and valine as well as nonessential amino acids that can be returned to A. pisum. Mutual nutrient provisioning is likely the main reason for the persistence of this symbiosis.
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A discrepancy between the genomic data and reactor performance data was the lack of a functional respiratory nitrate reductase gene. Previous work had shown CAP could use nitrate as the terminal electron acceptor, but the genomic data indicate the periplasmic nitrate reductase gene could not function in the electron transport chain, as it lacked the necessary quinol reductase subunit. To resolve these issues, lab-scale EBPR reactors enriched with CAP IA and CAP IIA were tested for their nitrate-reduction capabilities. CAP IA was able to couple nitrate reduction to phosphate uptake, while the genomically characterised CAP IIA could not.
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In the area of synthetic biology, a "living" artificial cell has been defined as a completely synthetically made cell that can capture energy, maintain ion gradients, contain macromolecules as well as store information and have the ability to mutate. Such a cell is not technically feasible yet, but a variation of an artificial cell has been created in which a completely synthetic genome was introduced to genomically emptied host cells. Although not completely artificial because the cytoplasmic components as well as the membrane from the host cell are kept, the engineered cell is under control of a synthetic genome and is able to replicate.
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Members from the J. Craig Venter Institute have used a top-down computational approach to knock out genes in a living organism to a minimum set of genes. In 2010, the team succeeded in creating a replicating strain of Mycoplasma mycoides (Mycoplasma laboratorium) using synthetically created DNA deemed to be the minimum requirement for life which was inserted into a genomically empty bacterium. It is hoped that the process of top-down biosynthesis will enable the insertion of new genes that would perform profitable functions such as generation of hydrogen for fuel or capturing excess carbon dioxide in the atmosphere. the myriad regulatory, metabolic, and signaling networks are not completely characterized.
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Without much doubt, Ser integrases are the current tools of choice for integrating transgenes into a restricted number of well-understood genomic acceptor sites that mostly (but not always) mimic the phage attP site in that they attract an attB-containing donor vector. At this time the most prominent member is PhiC31-INT with proven potential in the context of human and mouse genomes. Contrary to the above Tyr recombinases, PhiC31-INT as such acts in a unidirectional manner, firmly locking in the donor vector at a genomically anchored target. An obvious advantage of this system is that it can rely on unmodified, native attP (acceptor) and attB donor sites.
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As part of the 2018 Everest/Lhotse summit expedition, Moniz and Benegas announced that in cooperation with Dr. Christopher Mason, an associate professor at Weill Cornell Medicine in New York City and leader of the NASA gene expression study, they will be the lead subjects in the Everest Twin Study. Modeled after the Mason Lab’s recent ground-breaking NASA Twin Study, Moniz and Benegas will be collecting blood samples to compare with their respective twin siblings to research how they genomically adapt to their near- space mission. The goal of the study was to sequence DNA and RNA from the climbers' white blood cells to discover possible changes in gene expression.
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A number of studies have defined C. concisus to be composed of two phenotypically identical, yet genomically distinct genomospecies by analysis of amplified fragment length polymorphisms (AFLP), housekeeping genes and a PCR method targeting the polymorphisms of C. concisus 23S rRNA gene. The two genomospecies appear to harbor different levels of enteric pathogenic potential, with oral C. concisus strains that were invasive to human epithelial cell line (Caco2) found only in Genomospecies-2 (GS2). Recently, a C. concisus molecular marker csep1, particularly the csep1 gene with a six- nucleotide insertion (csep1-6bpi) was found to be associated with active Crohn's disease. The csep1 gene can be located in either the pICON plasmid or the chromosome.
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Unlike most lncRNAs which are assembled from introns by the spliceosome, hTR is directly transcribed from a dedicated promoter site located at genomic locus 3q26.2 by RNA polymerase II. Mature hTR is 451nt in length, but approximately 1/3 of cellular hTR transcripts at steady state have ~10nt genomically encoded 3’ tails. The majority of those extended hTR species have additional oligo-A 3’ extension. Processing of immature 3’-tailed hTR to mature 451nt hTR can be accomplished by direct 3’-5’ exoribonucleolytic degradation or by an indirect pathway of oligoadenylation by PAPD5, removal of 3’ oligo-A tail by the 3’-5’ RNA exonuclease PARN, and subsequent 3’-5’ exoribonucleolytic degradation. Extended hTR transcripts are also degraded by the RNA exosome. The 5’ ends of hTR transcripts are also additionally processed.
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Under the hypothesis, as organisms increase in complexity population-wide genetic diversity is regulated by the need to maintain a harmonious balance between those two broad categories: fast-mutating alleles that adapt quickly to the pressure of a given environment, and slow-mutating ones that preserve the most fundamental and basal instructions for the organism. Maintaining this balance means that simpler organisms will have a higher percentage of their genome able to tolerate mutational change, since simple means less-complex biological and epigenetic processes that are more tolerable to change than those of more and genomically delicate complex organisms according to the hypothesis. As organismal complexity increases, the margin for genomic error narrows and toleration for new mutations shrinks since within the framework higher-order life means more complex cellular mechanisms and more fragile biological processes. The hypothesis suggests that maximum population-wide genetic diversity can increase up to a point that is set by the physiological and epigenetic complexity of the organism and its environmental interactions, but past that maximal fitness is decreased because the level of mutation becomes maladaptive by deleteriously altering an organism's fundamental instructions.
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