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21.
Seegmiller A; Williams KR; Hammersmith RL; Doak TG; Witherspoon D; Messick T; Storjohann LL; Herrick G 《Molecular biology and evolution》1996,13(10):1351-1362
Internal eliminated sequences (IESs) often interrupt ciliate genes in the
silent germline nucleus but are exactly excised and eliminated from the
developing somatic nucleus from which genes are then expressed. Some long
IESs are transposons, supporting the hypothesis that short IESs are ancient
transposon relics. In light of that hypothesis and to explore the
evolutionary history of a collection of IESs, we have compared various
alleles of a particular locus (the 81 locus) of the ciliated protozoa
Oxytricha trifallax and O. fallax. Three short IESs that interrupt two
genes of the locus are found in alleles from both species, and thus must be
relatively ancient, consistent with the hypothesis that short IESs are
transposon relics. In contrast, TBE1 transposon interruptions of the locus
are allele-specific and probably the results of recent transpositions.
These IESs (and the TBE1s) are precisely excised from the DNA of the
developing somatic macronucleus. Each IES interrupts a highly conserved
sequence. A few nucleotides at the ends of each IES are also conserved,
suggesting that they interact critically with IES excision machinery.
However, most IES nucleotide positions have evolved at high rates, showing
little or no selective constraint for function. Nonetheless, the length of
each IES has been maintained (+/- 3 bp). While one IES is approximately 33
bp long, three other IESs have very similar sizes, approximately 70 bp
long. Two IESs are surrounded by direct repeats of the sequence TTCTT. No
other sequence similarities were found between any of the four IESs.
However, the ends of one IES do match the inverted terminal repeat
consensus sequence of the "TA" IESs of Paramecium. Three O. trifallax
alleles appear to have been recipients in recent conversion events that
could have been provoked by double-strand breaks associated with IES ends
subsequent to IES transposition. Our findings support the hypothesis that
short IESs evolved from ancient transposons that have lost most of their
sequences, except those necessary for precise excision during macronuclear
development.
相似文献
22.
Vikalp Raj Kaustubh G. Naik Bairav S. Vishnugopi Ajeet Kumar Rana Andrew Scott Manning Smruti Rekha Mahapatra KR Varun Vipin Singh Abhineet Nigam Josefine D. McBrayer Partha P. Mukherjee Naga Phani B. Aetukuri David Mitlin 《Liver Transplantation》2024,14(15):2303062
This study illustrates how the microstructure of garnet solid-state electrolytes (SSE) affects the stress-state and dendrite growth. Tantalum-doped lithium lanthanum zirconium oxide (LLZTO, Li6.4La3Zr1.4Ta0.6O12) is synthesized by powder processing and sintering (AS), or with the incorporation of intermediate-stage high-energy milling (M). The M compact displays higher density (91.5% vs 82.5% of theoretical), and per quantitative stereology, lower average grain size (5.4 ± 2.6 vs 21.3 ± 11.1 µm) and lower AFM-derived RMS surface roughness contacting the Li metal (45 vs 161 nm). These differences enable symmetric M cells to electrochemically cycle at constant capacity (0.1 mAh cm−2) with enhanced critical current density (CCD) of 1.4 versus 0.3 mA cm−2. It is demonstrated that LLZTO grain size distribution and internal porosity critically affect electrical short-circuit failure, indicating the importance of electronic properties. Lithium dendrites propagate intergranularly through regions where LLZTO grains are smaller than the bulk average (7.4 ± 3.8 µm for AS in a symmetric cell, 3.1 ± 1.4 µm for M in a half-cell). Metal also accumulates in the otherwise empty pores of the sintered compact present along the dendrite path. Mechanistic modeling indicates that reaction and stress heterogeneities are interrelated, leading to current focusing and preferential plating at grain boundaries. 相似文献
23.
Shashank M Patil KR Maruthi Shrisha Naik Bajpe VM Vyshali S Sushmitha Chagalamari Akhila Ramith Ramu 《Bioinformation》2021,17(11):932
Treatment of SARS-CoV-2 targeting its RNA dependent RNA polymerase (RdRp) is of current interest. Remdesivir has been approved for the treatment of COVID-19 around the world. However, the drug has been linked with pharmacological limitations like adverse effects and reduced efficiency. Nevertheless, recent advancements have depicted molnupiravir as an effective therapeutic agent to target the SARS-CoV-2 RdRp. The drug has cleared both in vitro and in vivo screening. It is in phase-III clinical trial. Nonetheless, there are no data on themolecular binding interaction of molnupiravir with RdRp. Therefore, it is of interest to report the binding interaction of molnupiravir using molecular docking. It is also of interest to show its stability during interaction using molecular dynamics and binding free energy calculations along with drug likeliness and pharmacokinetic properties in comparison with remdesivir. 相似文献
24.
25.
Freya KR Swinnen Paul J Coucke Anne M De Paepe Sofie Symoens Fransiska Malfait Filomena V Gentile Luca Sangiorgi Patrizia D’Eufemia Mauro Celli Ton JTM Garretsen Cor WRJ Cremers Ingeborg JM Dhooge Els MR De Leenheer 《Orphanet journal of rare diseases》2011,6(1):1-8
Background
Neurofibromatosis 1 (NF1), a common autosomal dominant disorder, was shown in one study to be associated with a 15-year decrease in life expectancy. However, data on mortality in NF1 are limited. Our aim was to evaluate mortality in a large retrospective cohort of NF1 patients seen in France between 1980 and 2006.Methods
Consecutive NF1 patients referred to the National French Referral Center for Neurofibromatoses were included. The standardized mortality ratio (SMR) with its 95% confidence interval (CI) was calculated as the ratio of observed over expected numbers of deaths. We studied factors associated with death and causes of death.Results
Between 1980 and 2006, 1895 NF1 patients were seen. Median follow-up was 6.8 years (range, 0.4-20.6). Vital status was available for 1226 (65%) patients, of whom 1159 (94.5%) survived and 67 (5.5%) died. Overall mortality was significantly increased in the NF1 cohort (SMR, 2.02; CI, 1.6-2.6; P < 10-4). The excess mortality occurred among patients aged 10 to 20 years (SMR, 5.2; CI, 2.6-9.3; P < 10-4) and 20 to 40 years (SMR, 4.1; 2.8-5.8; P < 10-4). Significant excess mortality was found in both males and females. In the 10-20 year age group, females had a significant increase in mortality compared to males (SMR, 12.6; CI, 5.7-23.9; and SMR, 1.8; CI, 0.2-6.4; respectively). The cause of death was available for 58 (86.6%) patients; malignant nerve sheath tumor was the main cause of death (60%).Conclusions
We found significantly increased SMRs indicating excess mortality in NF1 patients compared to the general population. The definitive diagnosis of NF1 in all patients is a strength of our study, and the high rate of death related to malignant transformation is consistent with previous work. The retrospective design and hospital-based recruitment are limitations of our study. Mortality was significantly increased in NF1 patients aged 10 to 40 years and tended to be higher in females than in males. 相似文献26.
Nidhi Jatana Sarvesh Jangid Garima Khare Anil K. Tyagi Narayanan Latha 《Journal of molecular modeling》2011,17(2):301-313
Tuberculosis (TB) is a global health problem and the situation has become more precarious due to the advent of HIV infections
and continuous rise in the number of multi-drug resistant strains of Mycobacterium tuberculosis (M. tb). Biochemical studies on Fatty Acyl-CoA Synthetases (FadD13), one of the gene products of mymA operon, have provided insights
into the involvement of this protein in the activation of fatty acids. Due to non-availability of the crystal structure of
FadD13, we have employed in silico approaches to resolve and characterize the structure of this important protein of M. tb. A three dimensional model of M. tb FadD13 was predicted by a de novo structure prediction server that integrates fragment assembly with SimFold energy function.
With the aid of molecular mechanics and dynamics methods, the final model was obtained and assessed subsequently for global
and local accuracy by various assessment programs. With this model, a flexible docking study with the substrates was performed.
Results of ligand interactions with key amino acids in the binding site are also summarized. The molecular model for the M. tb FadD13 obtained sheds light on the topographical features of the binding pocket of the protein and provides atomic insight
into the possible modes of substrate recognition. The three-dimensional model of FadD13 presented here would be helpful in
guiding both enzymatic studies as well as design of specific inhibitors. 相似文献
27.
Structure and dynamics of DRD4 bound to an agonist and an antagonist using in silico approaches 下载免费PDF全文
Human dopamine receptor D4 (DRD4), a member of G‐protein coupled receptor (GPCR) family, plays a central role in cell signaling and trafficking. Dysfunctional activity of DRD4 can lead to several psychiatric conditions and, therefore, represents target for many neurological disorders. However, lack of atomic structure impairs our understanding of the mechanism regulating its activity. Here, we report the modeled structure of DRD4 alone and in complex with dopamine and spiperone, its natural agonist and antagonist, respectively. To assess the conformational dynamics induced upon ligand binding, all‐atom explicit solvent molecular dynamics simulations in membrane environment were performed. Comprehensive analyses of simulations reveal that agonist binding triggers a series of conformational changes in the transmembrane region, including rearrangement of residues, characteristic of transmission and tyrosine toggle molecular switches. Further, the trajectories indicate that a loop region in the intracellular region––ICL3, is significantly dynamic in nature, mainly due to the side‐chain movements of conserved proline residues involved in SH3 binding domains. Interestingly, in dopamine‐bound receptor simulation, ICL3 represents an open conformation ideal for G protein binding. The structural and dynamical information presented here suggest a mode of activation of DRD4, upon ligand binding. Our study will help in further understanding of receptor activation, as acquiring structural information is crucial for the design of highly selective DRD4 ligands. Proteins 2014; 83:867–880. © 2014 Wiley Periodicals, Inc. 相似文献
28.
Facile labeling of oligosaccharides (acidic and neutral) in a nonselective
manner was achieved with highly fluorescent anthranilic acid (AA,
2-aminobenzoic acid) (more than twice the intensity of 2- aminobenzamide,
AB) for specific detection at very high sensitivity. Quantitative labeling
in acetate-borate buffered methanol (approximately pH 5.0) at 80 degreesC
for 60 min resulted in negligible or no desialylation of the
oligosaccharides. A high resolution high performance liquid chromatographic
method was developed for quantitative oligosaccharide mapping on a
polymeric-NH2bonded (Astec) column operating under normal phase and anion
exchange (NP-HPAEC) conditions. For isolation of oligosaccharides from the
map by simple evaporation, the chromatographic conditions developed use
volatile acetic acid-triethylamine buffer (approximately pH 4.0) systems.
The mapping and characterization technology was developed using well
characterized standard glycoproteins. The fluorescent oligosaccharide maps
were similar to the maps obtained by the high pH anion-exchange
chromatography with pulsed amperometric detection (HPAEC-PAD), except that
the fluorescent maps contained more defined peaks. In the map, the
oligosaccharides separated into groups based on charge, size, linkage, and
overall structure in a manner similar to HPAEC-PAD with contribution of
-COOH function from the label, anthranilic acid. However, selectivity of
the column for sialic acid linkages was different. A second dimension
normal phase HPLC (NP-HPLC) method was developed on an amide column (TSK
Gel amide-80) for separation of the AA labeled neutral complex type and
isomeric structures of high mannose type oligosaccharides. The
oligosaccharides labeled with AA are compatible with biochemical and
biophysical techniques, and use of matrix assisted laser desorption mass
spectrometry for rapid determination of oligosaccharide mass map of
glycoproteins is demonstrated. High resolution of NP-HPAEC and NP-HPLC
methods combined with mass spectrometry (MALDI-TOF) can provide an
effective technology for analyzing a wide repertoire of oligosaccharide
structures and for determining the action of both transferases and
glycosidases.
相似文献
29.
MOTIVATION: Molecular biology databases hold a large number of empirical
facts about many different aspects of biological entities. That data is
static in the sense that one cannot ask a database 'What effect has protein
A on gene B?' or 'Do gene A and gene B interact, and if so, how?'. Those
questions require an explicit model of the target organism. Traditionally,
biochemical systems are modelled using kinetics and differential equations
in a quantitative simulator. For many biological processes however,
detailed quantitative information is not available, only qualitative or
fuzzy statements about the nature of interactions. RESULTS: We designed and
implemented a qualitative simulation model of lambda phage growth control
in Escherichia coli based on the existing simulation environment QSim.
Qualitative reasoning can serve as the basis for automatic transformation
of contents of genomic databases into interactive modelling systems that
can reason about the relations and interactions of biological entities.
相似文献
30.
The inhibitory effect of 23N-alkyl-4-piperidylesters (alkyl = ethyl-butyl) (APEA) and 8N-ethyl-2-pyrrolidinylmethylesters (EPMEA) of 2- and 3-substituted alkoxyphenylcarbamic acids (alkoxy = butoxy-heptyloxy-) on photosynthetic Hill reaction activity of spinach chloroplasts and on chlorophyll (Chl) synthesis in green algaeChlorella vulgaris was investigated. Inhibitory activities of these compounds were strongly connected with the lipophilicity of the whole molecule. A lower inhibitory activity of 2-alkoxy-substituted derivatives in relation to the corresponding 3-substituted ones was confirmed. Electron spin resonance (ESR) spectra of spinach chloroplasts demonstrated that the studied compounds affected the structure of photosystem (PS) 2 with the release of Mn2+ ions into interior of thylakoid membranes. 相似文献