scholarly journals Intron Sliding and Length Variability of Genes Enriched of Phase 1 Long Introns

2017 ◽  
Vol 12 (2) ◽  
pp. 302-316 ◽  
Author(s):  
И.В. Поверенная ◽  
I.V. Poverennaya
Keyword(s):  
Average Length ◽  
Phase 1 ◽  
Intron Position ◽  
Intron Length ◽  
Intron Phase ◽  
Orthologous Genes ◽  
Reading Frame ◽  
Initial Hypothesis ◽  
Evolutionary Event ◽  
Taxonomic Groups

Due to high mutagenesis of intron sequences, intron evolution is usually considered in terms of evolution of exon-intron structures (EIS). The shifting of intron over short distances (rare evolutionary event called intron sliding) could lead to the change of intron phase, i.e. the intron position relative to the open reading frame. Here we analyze the EIS from four datasets of eukaryotic orthologues in order to find out the preferable choice of intron phase during sliding and to study the correlation between orthologous intron lengths. To identify the orthologous introns we have constructed the alignments of EIS of orthologous genes. Several sliding events with intron phase change were revealed from the analysis; however, our initial hypothesis that in the process of sliding introns prefer to change its phase to 0 more frequently, was not been confirmed. Nevertheless, it is necessary to expand the analysis on a larger dataset for making a proper conclusions. Despite high variability of intron length, some taxonomic groups share the similar length values. Moreover, some length conservation could be observed if instead of intron length L we consider a normalized length N = (L-A)/A, where A is an average length within an orthologous intron group. E.g. for ptprd genes of birds (28 species) the normalized value is in the interval (-0.15, 0.15) for 85.2 % of introns what is significantly higher than the values for random lengths set in accordance with the intron lengths distribution. That length “conservation” leads us to the question what intron length was in the ancient introns.

scholarly journals Sequence and structure of mtr, an amino acid transport gene of Neurospora crassa

Genome ◽  
1991 ◽  
Vol 34 (4) ◽  
pp. 644-651 ◽  
Author(s):  
Kenneth Koo ◽  
W. Dorsey Stuart
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Neurospora Crassa ◽  
Rna Binding ◽  
Signal Sequence ◽  
Average Length ◽  
Open Reading Frame ◽  
Mrna Transcript ◽  
S1 Nuclease ◽  
Reading Frame

The gene product of the mtr locus of Neurospora crassa is required for the transport of neutral aliphatic and aromatic amino acids via the N system. We have previously cloned three cosmids containing Neurospora DNA that complement the mtr-6(r) mutant allele. The cloned DNAs were tightly linked to restriction fragment length polymorphisms that flank the mtr locus. A 2.9-kbp fragment from one cosmid was subcloned and found to complement the mtr-6(r) allele. Here we report the sequence of the fragment that hybridized to a poly(A)+ mRNA transcript of about 2300 nucleotides. We have identified an 845-bp open reading frame (ORF) having a 59-bp intron as the potential mtr ORF. S1 nuclease analysis of the transcript confirmed the transcript size and the presence of the intron. A second open reading frame was found upstream in the same reading frame as the mtr ORF and appears to be present in the mRNA transcript. The mtr ORF is predicted to encode a 261 amino acid polypeptide with a molecular mass of 28 613 Da. The proposed polypeptide exhibits six potential α-helical transmembrane domains with an average length of 23 amino acids, does not have a signal sequence, and contains amino acid sequence homologous to an RNA binding motif.Key words: sequence, membranes, ribonucleoprotein.

scholarly journals The Complete Nucleotide Sequence and Biotype Variability of Papaya leaf distortion mosaic virus

2005 ◽  
Vol 95 (2) ◽  
pp. 128-135 ◽  
Author(s):  
Tetsuo Maoka ◽  
Tatsuji Hataya
Keyword(s):  
Amino Acids ◽  
Nucleotide Sequence ◽  
Mosaic Virus ◽  
Complete Nucleotide Sequence ◽  
Distinct Species ◽  
Cleavage Sites ◽  
Reading Frame ◽  
The Family ◽  
Evolutionary Event ◽  
Leaf Distortion

The complete nucleotide sequence of the genome of Papaya leaf distortion mosaic virus (PLDMV) was determined. The viral RNA genome of strain LDM (leaf distortion mosaic) comprised 10,153 nucleotides, excluding the poly(A) tail, and contained one long open reading frame encoding a polyprotein of 3,269 amino acids (molecular weight 373,347). The polyprotein contained nine putative proteolytic cleavage sites and some motifs conserved in other potyviral polyproteins with 44 to 50% identities, indicating that PLDMV is a distinct species in the genus Potyvirus. Like the W biotype of Papaya ringspot virus (PRSV), the non-papaya-infecting biotype of PLDMV (PLDMV-C) was found in plants of the family Cucurbitaceae. The coat protein (CP) sequence of PLDMV-C in naturally infected-Trichosanthes bracteata was compared with those of three strains of the P biotype (PLDMV-P), LDM and two additional strains M (mosaic) and YM (yellow mosaic), which are biologically different from each other. The CP sequences of three strains of PLDMV-P share high identities of 95 to 97%, while they share lower identities of 88 to 89% with that of PLDMV-C. Significant changes in hydrophobicity and a deletion of two amino acids at the N-terminal region of the CP of PLDMV-C were observed. The finding of two biotypes of PLDMV implies the possibility that the papaya-infecting biotype evolved from the cucurbitaceae-infecting potyvirus, as has been previously suggested for PRSV. In addition, a similar evolutionary event acquiring infectivity to papaya may arise frequently in viruses in the family Cucurbitaceae.

Gene structure dynamics and divergence of the polygalacturonase gene family of plants and fungus

Genome ◽  
2008 ◽  
Vol 51 (1) ◽  
pp. 30-40 ◽  
Author(s):  
K.-C. Park ◽  
S.-J. Kwon ◽  
P.-H. Kim ◽  
T. Bureau ◽  
N.-S. Kim
Keyword(s):  
Gene Structure ◽  
Tandem Duplication ◽  
Phase Distribution ◽  
Gene Diversity ◽  
Phase 1 ◽  
Phase 2 ◽  
Intron Phase ◽  
The Third ◽  
Phase 0 ◽  
Per Gene

Whole copies of the polygalacturonase (PG) genes from rice ( Oryza sativa subsp. japonica) and a filamentous fungus ( Aspergillus oryzae ) were isolated. The orthologs of the rice PGs were also retrieved from other plant species. The 106 plant PGs analyzed were divided into 5 clades, A, B, C, D, and E. The fungus PGs were classified into 3 clades, of which one formed a loose cluster with clade E of the plant PGs. Four domain motifs (I, II, III, IV) were identified in all PGs. Motifs II and III were split by introns such as G/DDC and CGPGHGIS/IGSLG, respectively. In plant PGs there were 446 introns in total and 3.98 introns per gene. Intron phase distribution was 65.5% for phase 0, 19.7% for phase 1, and 14.8% for phase 2 in plant PGs. In the PGs of A. oryzae there were 37 introns of phase 0 (59.5%), phase 1 (24.3%), and phase 2 (16.2%), with 2.47 introns per gene. The 5 clades of plant PGs were divided into 3 basic gene structure lineages. Intron positions and phases were conserved among the PGs in the first 2 lineages. The third lineage consisted of PGs of clade E, which also carried highly conserved introns at different positions from other PGs. Intron positions were not as highly conserved in fungus PGs as in plant PGs. The introns in the current PGs have been present since before the divergence of monocots from dicots. The results obtained show that differential losses of introns created gene diversity, which was followed by segmental and tandem duplication in plant PGs.

Molecular characterization of a gene encoding N-myristoyl transferase (NMT) from Triticum aestivum (bread wheat)

Genome ◽  
2004 ◽  
Vol 47 (6) ◽  
pp. 1036-1042 ◽  
Author(s):  
Tim Dumonceaux ◽  
Raju V.S Rajala ◽  
Rajendra Sharma ◽  
Gopalan Selvaraj ◽  
Raju Datla
Keyword(s):  
Triticum Aestivum ◽  
Protein Modification ◽  
Wheat Plant ◽  
Single Copy ◽  
Gene Encoding ◽  
Growth And Survival ◽  
Reading Frame ◽  
Eukaryotic Proteins ◽  
Taxonomic Groups

Myristoyl-CoA:protein N-myristoyl transferase (NMT; EC 2.3.1.97) acylates the Gly residue abutting the N-terminal Met with a myristic acid following the removal of the Met residue in certain eukaryotic proteins, and in some cases myristoylation is essential to cell growth and survival. We report the cloning of a full-length cDNA encoding NMT from Triticum aestivum (TaNMT). The cDNA included a predicted open reading frame of 1317 nucleotides, which encoded a predicted protein of 438 amino acids containing all of the residues that are important for NMT activity. The TaNMT amino acid and nucleotide sequences were compared with NMTs from 14 other species encompassing a wide array of taxonomic groups. Among the experimentally validated NMTs, TaNMT was most similar to that of Arabidopsis thaliana. Southern blot analysis of wheat genomic DNA showed that TaNMT is encoded by a single copy gene, with one copy per haploid genome. We expressed TaNMT in Escherichia coli cells and determined that the recombinant protein possessed NMT activity, catalyzing the N-myristoylation of peptides from known or putatively myristoylated proteins from plants and animals without a strong preference for the plant peptides. TaNMT is the second experimentally validated plant NMT sequence and the first from a monocotyledonous species.Key words: N-myristoyl transferase, myristoylation, protein modification, wheat, plant development.

scholarly journals Convergent inactivation of the skin-specific C-C motif chemokine ligand 27 in mammalian evolution

2019 ◽  
Author(s):  
Monica Lopes-Marques ◽  
Luis Q. Alves ◽  
Miguel Fonseca ◽  
Giulia Secci-Petretto ◽  
Andre M. Machado ◽  
...  
Keyword(s):  
T Cells ◽  
Stop Codon ◽  
Mammalian Species ◽  
Mammalian Evolution ◽  
Reading Frame ◽  
Life Styles ◽  
Skin Physiology ◽  
Adequate Hydration ◽  
Chemokine Ligand ◽  
Evolutionary Event

The appearance of mammalian-specific skin features was a key evolutionary event contributing for the elaboration of physiological processes such as thermoregulation, adequate hydration, locomotion and inflammation. Skin inflammatory and autoimmune processes engage a population of skin-infiltrating T cells expressing a specific C-C chemokine receptor (CCR10), which interacts with an epidermal CC chemokine, the skin-specific C-C motif chemokine ligand 27 (CCL27). CCL27 is selectively produced in the skin by keratinocytes, particularly upon inflammation, mediating the adhesion and homing of skin-infiltrating T cells. Here, we examined the evolution and coding condition of Ccl27 in 112 placental mammalian species. Our findings reveal that a number of open reading frame inactivation events such as insertions, deletions, start and stop codon mutations, independently occurred in Cetacea, Pholidota, Sirenia, Chiroptera, and Rodentia, totalizing 18 species. The diverse habitat settings and life-styles of Ccl27-eroded lineages probably implied distinct evolutionary triggers rendering this gene unessential. For example, in Cetacea the rapid renewal of skin layers minimizes the need for an elaborate inflammatory mechanism, mirrored by the absence of epidermal scabs. Our findings suggest that the convergent and independent loss of Ccl27 in mammalian evolution concurred with unique adaptive roads for skin physiology.

The Token Economy Package: Social v. Token Reinforcement

1976 ◽  
Vol 4 (4) ◽  
pp. 68-69 ◽  
Author(s):  
P. A. Elliott ◽  
F. Barwell ◽  
A. Hooper ◽  
P. E. Kingerlee
Keyword(s):  
Rating Scales ◽  
Average Length ◽  
Baseline Period ◽  
Token Economy ◽  
Social Reinforcement ◽  
Experimental Phase ◽  
Psychotic Reaction ◽  
Initial Hypothesis ◽  
Psychiatric Rating ◽  
Group 2

AbstractThe paper reports a Token Economy project involving 18 long stay male patients (diagnosis chronic schozophrenia), average length of hospitalisation twenty-five years. The project comprised a one month baseline period, a six month Token Economy phase, a two month experimental phase and a second three months Token Economy. Conditions were the same for all patients except during the experimental phase where they were randomly assigned to one of three experimental groups to investigate the relative importance of social reinforcement and other variables involved in token systems. The groups were (1) a social reinforcement only group; (2) a social reinforcement and non-contingent tokens; (3) a social reinforcement and contingent, non-spendable tokens. Each groups' performance was compared both with the other groups and with their own performance over all phases of the study. Assessment measures comprised standardised psychiatric rating scales - the Nurses Observation Scale for In-patient Evaluation (Honigfeld and Klett, 1965; Honigfeld et al 1966), and the Psychotic Reaction Profile (Lorr et al, 1960); other rating checklists, and time-sampling data. Analysis of Variance was carried out on all data over the four phases of the programme. The total token economy package as represented by the first token economy period was shown to be effective in promoting improvements in most areas of patients' functioning as compared to baseline. Results during the experimental phase suggest that contrary to our initial hypothesis social factors involved in exchanging tokens are not demonstrably important sources of reinforcement in Token Economies. There were no inter-group differences during the experimental phase, suggesting that none of the variables studied were critical factors. After the experimental phase the return to the complete token package produced an unclear picture where there were significant improvements on some scales, but significant declines on others.

scholarly journals Myxospermy Evolution in Brassicaceae: A Highly Complex and Diverse Trait with Arabidopsis as an Uncommon Model

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2470
Author(s):  
Sébastien Viudes ◽  
Christophe Dunand ◽  
Vincent Burlat
Keyword(s):  
Secretory Cell ◽  
Secretory Cells ◽  
Orthologous Genes ◽  
Brassicaceae Species ◽  
The One ◽  
Species Specific ◽  
Taxonomic Groups ◽  
Evo Devo ◽  
Brassicaceae Family ◽  
Seed Mucilage

The ability to extrude mucilage upon seed imbibition (myxospermy) occurs in several Angiosperm taxonomic groups, but its ancestral nature or evolutionary convergence origin remains misunderstood. We investigated seed mucilage evolution in the Brassicaceae family with comparison to the knowledge accumulated in Arabidopsis thaliana. The myxospermy occurrence was evaluated in 27 Brassicaceae species. Phenotyping included mucilage secretory cell morphology and topochemistry to highlight subtle myxospermy traits. In parallel, computational biology was driven on the one hundred genes constituting the so-called A. thaliana mucilage secretory cell toolbox to confront their sequence conservation to the observed phenotypes. Mucilage secretory cells show high morphology diversity; the three studied Arabidopsis species had a specific extrusion modality compared to the other studied Brassicaceae species. Orthologous genes from the A. thaliana mucilage secretory cell toolbox were mostly found in all studied species without correlation with the occurrence of myxospermy or even more sub-cellular traits. Seed mucilage may be an ancestral feature of the Brassicaceae family. It consists of highly diverse subtle traits, probably underlined by several genes not yet characterized in A. thaliana or by species-specific genes. Therefore, A. thaliana is probably not a sufficient reference for future myxospermy evo–devo studies.

Open-label extension study of the RNAi therapeutic ALN-VSP02 in cancer patients responding to therapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3062-3062 ◽  
Author(s):  
Maria Alsina ◽  
Josep Tabernero ◽  
Geoffrey Shapiro ◽  
Howard Burris ◽  
Jeffrey R. Infante ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Adverse Events ◽  
Phase I ◽  
Cell Carcinoma ◽  
Phase I Trial ◽  
Tumor Regression ◽  
Average Length ◽  
Phase 1 ◽  
Extension Study ◽  
Phase Ii Trials

3062 Background: ALN-VSP02 is an RNA interference (RNAi) therapeutic comprised of lipid nanoparticle-formulated small interfering RNAs targeting vascular endothelial growth factor (VEGF)-A and kinesin spindle protein (KSP). In a phase 1 trial, ALN-VSP02 administered as an iv infusion q2 wks was well-tolerated and showed evidence of anti-VEGF pharmacology and antitumor activity. Methods: Patients treated on the phase I trial with stable disease (SD) or better after 4 months (8 doses) were eligible to continue on an extension study until disease progression. Main objectives included continued evaluation of safety/tolerability and assessment of disease response. Results: Seven of 37 patients (18.9%) evaluable for response went onto the extension study, including 1 of 7 (14.2%) at 0.4 mg/kg, 2 of 5 (40%) at 0.7 mg/kg, and 4 of 11 (36.3%) at 1.0 mg/kg. All had progressed after one or more prior therapies. Tumor types included head and neck squamous cell carcinoma, angiosarcoma, endometrial cancer, renal cell carcinoma (RCC, N=2), and pancreatic neuroendocrine tumor (PNET, N=2). At the time of enrollment, 6 had SD and one (endometrial cancer with multiple liver metastases) had an unconfirmed partial response (PR). The average length of time on treatment (including phase I and extension studies) was 9.5 months (range 5-19). As of January 2012, 3 patients remain on study, including the endometrial cancer patient with an ongoing PR who has had >80% tumor regression after 19 months of treatment at 0.7 mg/kg and two patients with RCC and PNET with continued SD after nearly 1 year of treatment at 1.0 mg/kg. The other patients with RCC and PNET at 1.0 mg/kg with SD came off after 8.5 and 5.5 months, respectively, for adverse events that included fatigue or elevated alkaline phosphatase. A decrease in spleen volume, likely an on-target effect and not associated with any adverse events, occurred to a greater degree on the extension study than on the phase I trial and was most pronounced in patients receiving ≥ 12 doses. Conclusions: ALN-VSP02 has preliminary activity against endometrial cancer, RCC and PNET and a favorable safety profile that permits chronic dosing. Phase II trials are warranted in these and other VEGF-overexpressing tumors.

Patterns of oestrus, time of LH release and ovulation and effects of time of artificial insemination in Mediterranean buffalo cows

1998 ◽  
Vol 66 (1) ◽  
pp. 87-91 ◽  
Author(s):  
B. M. Moioli ◽  
F. Napolitano ◽  
S. Puppo ◽  
V. L. Barile ◽  
G. M. Terzano ◽  
...  
Keyword(s):  
Phase Ii ◽  
Artificial Insemination ◽  
Average Length ◽  
Post Partum ◽  
Phase 1 ◽  
Phase Iii ◽  
Housing System ◽  
Mucous Discharge ◽  
Lh Release ◽  
Three Phases

AbstractThirty-two post-partum Mediterranean river buffalo cows were continuously observed for signs of oestrus from September to December with the aid of two vasectomized bulls. Symptoms of oestrus among female Mediterranean buffaloes are weak, therefore oestrus was assessed based on bull behaviour (following and licking a cow and trying to mount her). Oestrus was divided into three phases based on the bull behaviour assessment. Status of the uterus and ovarian follicles were checked rectally every day for each cow which was detected by a teaser bull to be in oestrus. All cows in oestrus were bred twice by artificial insemination (AI), the first at ovulation and the second (using a different bull) 22 h later.The average duration of interest shown by the bull towards a cow (from the very first to the last sign of interest) was 68 h and the average length of the three phases was: phase 1 = 21 (s.d. 29) h, phase II = 32 (s.d. 24) h and phase III = 15 (s.d. 15) h. Fifteen buffaloes were bled during oestrus, and LH profiles were determined. No differences were evident among oestruses followed by pregnancy (no. = 18) and the others (no. = 26) for the variables describing behavioural events. Neither intensity of the bull courtship, presence or clarity of mucous discharge, or housing system affected the success of AI. The only differences between pregnant and non-pregnant cows were in the timing between the LH peak and the end of phase II (2·4 v. 14·7 h, P < 0·001), end of phase III (22 v. 40 h, P > 0·05) and ovulation (25 v. 46 h, P < 0·05). Successful pregnancies occurred 34 (s.d. 14) h after the end of phase II. The endocrinology and behavioural patterns of buffalo reproduction need further research to clarify the reasons for non-optimal pregnancy rates after AI.

Systemic administration of the antisense oligonucleotide NS-065/NCNP-01 for skipping of exon 53 in patients with Duchenne muscular dystrophy

2018 ◽  
Vol 10 (437) ◽  
pp. eaan0713 ◽  
Author(s):  
Hirofumi Komaki ◽  
Tetsuya Nagata ◽  
Takashi Saito ◽  
Satoru Masuda ◽  
Eri Takeshita ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Protein ◽  
Phase 1 ◽  
Exon Skipping ◽  
Muscle Disease ◽  
Dependent Manner ◽  
Reading Frame ◽  
Dystrophin Expression

Duchenne muscular dystrophy (DMD) is a lethal hereditary muscle disease caused by mutations in the gene encoding the muscle protein dystrophin. These mutations result in a shift in the open reading frame leading to loss of the dystrophin protein. Antisense oligonucleotides (ASOs) that induce exon skipping correct this frame shift during pre-mRNA splicing and partially restore dystrophin expression in mouse and dog models. We conducted a phase 1, open-label, dose-escalation clinical trial to determine the safety, pharmacokinetics, and activity of NS-065/NCNP-01, a morpholino ASO that enables skipping of exon 53. Ten patients with DMD (6 to 16 years old), carrying mutations in the dystrophin gene whose reading frame would be restored by exon 53 skipping, were administered NS-065/NCNP-01 at doses of 1.25, 5, or 20 mg/kg weekly for 12 weeks. The primary endpoint was safety; the secondary endpoints were pharmacokinetics and successful exon skipping. No severe adverse drug reactions were observed, and no treatment discontinuation occurred. Muscle biopsy samples were taken before and after treatment and compared by reverse transcription polymerase chain reaction (RT-PCR), immunofluorescence, and Western blotting to assess the amount of exon 53 skipping and dystrophin expression. NS-065/NCNP-01 induced exon 53 skipping in dystrophin-encoding mRNA in a dose-dependent manner and increased the dystrophin/spectrin ratio in 7 of 10 patients. Furthermore, the amount of exon skipping correlated with the maximum drug concentration in plasma (Cmax) and the area under the concentration-time curve in plasma (AUC0-t). These results indicate that NS-065/NCNP-01 has a favorable safety profile and promising pharmacokinetics warranting further study in a phase 2 clinical trial.

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