Electrochemical detection of parts-per-billion lead via an electrode-bound DNAzyme assembly.
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Biosensing Techniques↗
Biomedical subjects
Yi Xiao
Publications and source records attributed to Yi Xiao.
All-atom contact potential approach to protein thermostability analysis.
In this paper we use all-atom potential energy to define and analyze the inter-residue contacts in mesophilic and thermophilic proteins. Fifteen families of proteins are selected and each family has two representative proteins with greatly different preferred environmental temperatures. We find that both the number and energy of the contacts defined in this way show stronger correlations with the preferred temperatures of proteins than other factors used before. We also find that the charged-polar and charged-nonpolar residue contacts not only have larger contact numbers but also have lower single contact energies. Furthermore, the most important is that most of the thermophilic proteins have more charged-polar and charged-nonpolar residue contacts than their mesophilic counterparts. This suggests that they may play an important role in the thermostability of proteins, except usual charged-charged and nonpolar-nonpolar residue contacts. Charged residues may exert their profound influence by forming contacts not only with other charged residues but also with polar or nonpolar residues, thus further increasing the strength of contact network and then the thermostability of proteins.
Models, Chemical↗
Single-step electronic detection of femtomolar DNA by target-induced strand displacement in an electrode-bound duplex.
We report a signal-on, electronic DNA (E-DNA) sensor that is label-free and achieves a subpicomolar detection limit. The sensor, which is based on a target-induced strand displacement mechanism, is composed of a "capture probe" attached by its 5' terminus to a gold electrode and a 5' methylene blue-modified "signaling probe" that is complementary at both its 3' and 5' termini to the capture probe. In the absence of target, hybridization between the capture and signaling probes minimizes contact between the methylene blue and electrode surface, limiting the observed redox current. Target hybridization displaces the 5' end of the signaling probe, generating a short, flexible single-stranded DNA element and producing up to a 7-fold increase in redox current. The observed signal gain is sufficient to achieve a demonstrated (not extrapolated) detection limit of 400 fM, which is among the best reported for single-step electronic DNA detection. Moreover, because sensor fabrication is straightforward, the approach appears to provide a ready alternative to the more cumbersome femtomolar electrochemical assays described to date.
Base Sequence↗
Molecular dynamics simulations of folding processes of a beta-hairpin in an implicit solvent.
Computer simulations of beta-hairpin folding are relatively difficult, especially those based on the explicit water model. This greatly limits the complete analysis and understanding of their folding mechanisms. In this paper, we use the generalized Born/solvent accessible implicit solvent model to simulate the folding processes of a nine-residue beta-hairpin. We find that the beta-hairpin can fold into its native structure very easily, even using the traditional molecular dynamics method. This allows us to extract 21 complete folding events and investigate the folding process sufficiently. Our results show that there exist four most stable states on the free energy landscape of the short peptide, one native state and three intermediates. We find that two of the non-native stable states have almost the same potential energy as the native state but with lower entropy. This suggests that the native state can be stabilized entropically. Furthermore, we find that the folding processes of this peptide have common features: to fold into its native state, the peptide undergoes a continuous collapsing-extending-recollapsing process to adjust the positions of the side chains in order to form the native middle inter-strand hydrogen bonds. The formations of these bonds are the key step of the folding process. Once these bonds are formed, the peptide can fold into the native state quickly.
Computer Simulation↗
Quasiperiodic property in Alu repeats.
We investigate the possible quasiperiodic property in the sequences of Alu repeats, one of typical noncoding DNA sequences. We calculated the quasiperiods of the right and left monomers of Alu repeats of different families with quasiperiodic matrix algorithm. It is interesting that the right monomers of all families show significant quasiperiod 8 in their sequences while the left monomers show quasiperiods 8 or 5. Our results indicate that there exist common quasiperiods in most Alu repeats. This may be helpful to further explore possible functions of Alu repeats.
Algorithms↗
Identification and fine mapping of AvrPi15, a novel avirulence gene of Magnaporthe grisea.
Avirulence of Magnaporthe grisea isolate CHL346 on rice cultivar GA25 was studied with 242 ascospore progenies derived from the cross CHL346 x CHL42. Segregation analysis of the avirulence in the progeny population was in agreement with the existence of a single avirulence (Avr) gene, designated as AvrPi15. For mapping the Avr gene, we developed a total of 121 microsatellite DNA markers [simple sequence repeat (SSR)], which evenly distributed in the whole-genome of M. grisea through bioinformatics analysis (BIA) using the publicly available sequence. Linkage analysis of the AvrPi15 gene with these SSR markers showed that six markers on chromosome 6, MS6-1, MS6-2, MS6-3, MS6-7, MS6-8 and MS6-10, were linked to the AvrPi15 locus. To further define the chromosomal location of the AvrPi15 locus, two additional markers, MS6-17 and STS6-6, which were developed based on the sequences of telomeric region 11 (TEL11), were subjected to linkage analysis. The results showed that MS6-17 and STS6-6 were associated with the locus by 3.3 and 0.8 cM, respectively. To finely map the Avr gene, two additional candidate avirulence gene (CAG) markers, CAG6-1 and CAG6-2, were developed based on the gene annotation of the sequence of TEL 11. Linkage analysis of the Avr gene with these two markers revealed that both of them completely cosegregated with the AvrPi15 locus. Finally, this locus was physically mapped into approximately 7.2-kb interval of the TEL11 by BIA using these sequence-ready markers. This is the key step toward positional cloning of the AvrPi15 gene.
Chromosome Segregation↗
Characterization of genes involved in the initial reactions of 4-chloronitrobenzene degradation in Pseudomonas putida ZWL73.
The genes encoding enzymes involved in the initial reactions during degradation of 4-chloronitrobenzene (4CNB) were characterized from the 4CNB utilizer Pseudomonas putida ZWL73, in which a partial reductive pathway was adopted. A DNA fragment containing genes coding for chloronitrobenzene nitroreductase (CnbA) and hydroxylaminobenzene mutase (CnbB) were PCR-amplified and subsequently sequenced. These two genes were actively expressed in Escherichia coli, and recombinant E. coli cells catalyzed the conversion of 4CNB to 2-amino-5-chlorophenol, which is the ring-cleavage substrate in the degradation of 4CNB. Phylogenetic analyses on sequences of chloronitrobenzene nitroreductase and hydroxylaminobenzene mutase revealed that these two enzymes are closely related to the functionally identified nitrobenzene nitroreductase and hydroxylaminobenzene mutase from Pseudomonas strains JS45 and HS12. The nitroreductase from strain ZWL73 showed a higher specific activity toward 4CNB than nitrobenzene (approximately at a ratio of 1.6:1 for the recombinant or 2:1 for the wild type), which is in contrast to the case where the nitroreductase from nitrobenzene utilizers Pseudomonas pseudoalcaligenes JS45 with an apparently lower specific activity against 4CNB than nitrobenzene (0.16:1) [Kadiyala et al. Appl Environ Microbiol 69:6520-6526, 2003]. This suggests that the nitroreductase from 4-chloronitrobenzene utilizer P. putida ZWL73 may have evolved to prefer chloronitrobenzene to nitrobenzene as its substrate.
Bacterial Proteins↗
Identification of key residues in proteins by using their physical characters.
Key residues in proteins are important to their stability, folding, and functions. They usually are highly conserved and can be identified by sequence or structure alignments. However, these methods can only determine the locations of key residues in sequences and structures and give less information about their physical characters. In this paper, we try to identify key residues by analyzing their inter-residue interactions. The model we study is the protein domain from transducin. We show that the usual Gaussian network analysis and distance-based contact analysis have difficulty identifying the key residues in this protein, but the contact energies can do it well. We find that most key residues can be located by the lowest contact energies. This enables us to predict and analyze the key residues in other proteins. Our results suggest that contact energy analysis may provide an alternative approach to investigating the folding and stability of proteins.
Amino Acid Sequence↗
Signal therapy of human pancreatic cancer and NF1-deficient breast cancer xenograft in mice by a combination of PP1 and GL-2003, anti-PAK1 drugs (Tyr-kinase inhibitors).
The majority of cancers are caused by mutations of a few signal transducers such as the GTPase RAS, the kinase Src and the tumor suppressor p53. Thus, a group of specific chemical compounds called 'signal therapeutics', that block or reverse selectively these abnormally activated signaling pathways would be very useful for the treatment of these signally disordered cancers. More than 90% of human pancreatic cancers are associated with oncogenic mutations of RAS, in particular K-RAS at codon 12. We have previously shown that, PAK1, the Rac/CDC42-dependent Ser/Thr kinase, is essential for RAS/estrogen-induced transformation and neurofibromatosis (NF). Furthermore, we and others have demonstrated that the growth of mouse RAS-induced sarcomas allografts in mice is almost completely suppressed by either FK228 or a combination of two complimentary Tyr-kinase inhibitors, PP1 and AG 879, all of which block the RAS-induced activation of PAK1. Since, so far no effective therapeutic is available for the treatment of pancreatic cancer patients, we have examined the therapeutic potential of either FK228, the combination of these two Tyr-kinase inhibitors or GL-2003, a water-soluble derivative of AG 879, on human pancreatic cancer (Capan-1) xenograft in mice. Among these PAK1-blocking approaches, the PP1/GL-2003 combination is the most effective in the therapy of this cancer xenograft model. Its therapeutic potential is equivalent to those of gemcitabine and kigamicin D which suppress by 70-80% the growth of a similar human pancreatic cancer xenograft model. Also, this PP1/GL-2003 combination therapy has been proven to be very effective to suppress the estrogen-independent growth of an NF1-deficient multidrug/FK228-resistant human breast cancer (MDA-MB-231) xenograft in mice.
Animals↗
Design, synthesis, and antitumor evaluation of novel acenaphtho[1,2-b]pyrrole-carboxylic acid esters with amino chain substitution.
8-Oxo-8H-acenaphtho[1,2-b]pyrrole-9-carboxylic acid esters and derivatives were prepared and evaluated for cytotoxicity against A549 and P388 cell lines. Based on a novel chromophore precursor 8-oxo-8H-acenaphtho[1,2-b]pyrrol-9-carbonitrile 1, the very insoluble 1 was converted to more soluble esters 5 and a series of 3-amino derivatives from 5 were obtained by mild S(N)Ar(H) reaction between 5 and various amines. The biological evaluation indicated that methyl esters 5a are the most cytotoxic with IC(50) values of 0.45 and 0.80 microM (against A549 and P388, respectively) among the parent esters 5a-5f, but 3-amino derivatives 4b and 4c of 5f with bromine showed the highest activity (with IC(50) values of 0.019-0.60 microM) among the 3-amino derivatives.
Acenaphthenes↗
Synthesis and evaluation of novel 8-oxo-8H-cyclopenta[a]acenaphthylene-7-carbonitriles as long-wavelength fluorescent markers for hypoxic cells in solid tumor.
Novel bioreductive and long-wavelength fluorescent markers for hypoxic cells in solid tumor, 9-isocyano-8H-acenaphtho[l,2-b]pyrrol-8-one with the side chain of 2-nitroimidazole, were designed, synthesized, and evaluated in V79 379A Chinese hamster cells in vitro. Compounds A(2) and A(4) showed good hypoxic-oxic fluorescence differential in vitro (V79 cells) by using fluorescence scan ascent.
Acenaphthenes↗
[Transsphincteric surgery of rectal lesions: a report of 120 cases].
OBJECTIVE: To generalize the clinical use of transsphincteric operation (Mason operation) for rectal lesions. METHODS: Clinical data of 120 patients with middle and lower rectal lesions who underwent Mason operation from Aug. 1990 to Aug. 2005 were analyzed retrospectively. RESULTS: There were 61 cases with villous adenoma including 26 with cancerization, 25 cases with rectal cancer including 16 cases with early rectal cancer, and 17 with submucosal tumor. Of the 103 patients with rectal tumor, 98 underwent partial rectectomy, 5 segmental rectectomy. The postoperative complications included incision infection in two cases (1.6%), fistula in 4 cases (3.3%). Three patients (3.0%) had postoperative local recurrence. 90.2% of the rectal cancer patients (46/51) survived more than five years after Mason operation. CONCLUSION: Mason operation is satisfactory because of good exposure and simple access to the rectum, which is suitable for those lesions that could be locally resected on the mid and low rectum.
Adult↗
[Sleep breathing disorders: a view of conceptions and syndrome definition].
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Diagnosis, Differential↗
[Transbronchial needle aspiration in the diagnosis of bronchogenic carcinoma with enlarged mediastinal and /or hilar lymph nodes].
OBJECTIVE: To evaluate the role of transbronchial needle aspiraion (TBNA) in the diagnosis of bronchogenic carcinoma with enlarged mediastinal and/or hilar lymph node. METHODS: Patients with mediastinal and/or hilar lymphoadenopathy proven by CT scan were eligible for TBNA as reported by WANG. All specimen was directly and instantly smeared for cytological examination. RESULTS: From June 2004 to May 2006, 77 such patients were examined: including 38 lung cancers, 35 lung benign diseases and 4 without definite diagnosis. All TBNA procedures were successfully carried out in 222/225 ( 98.7%). Positive TBNA rate was 81.6% (31/38) in patients who had been proven to suffer from bronchogenic carcinoma. The diagnosis of lung cancer was confirmed via TBNA only in 9 patients. A total of 63 lymph nodes in the 38 lung cancer patients were aspirated by TBNA with a positive rate of 65.1% (41/63). The sensitivity of TBNA was significantly correlated with pathology type, lymph node size and experience of the cytologist. Severe complications were rare except small amount of bleeding at the TBNA site (52/77, 67.5%). CONCLUSION: TBNA is quite safe and helpful in diagnosis and staging of bronchogenic carcinoma, yet it is not helpful in diagnosis of benign lung diseases.
Adolescent↗
A reagentless signal-on architecture for electronic, aptamer-based sensors via target-induced strand displacement.
Thrombin binding stabilizes the alternative G-quadruplex conformation of the aptamer, liberating the methylene blue (MB)-tagged oligonucleotide to produce a flexible, single-stranded DNA element. This allows the MB tag to collide with the gold electrode surface, producing a readily detectable Faradaic current at thrombin concentrations as low as approximately 3 nM.
Aptamers, Nucleotide↗
Improvement on a simplified model for protein folding simulation.
Improvements were made on a simplified protein model--the Ramachandran model-to achieve better computer simulation of protein folding. To check the validity of such improvements, we chose the ultrafast folding protein Engrailed Homeodomain as an example and explored several aspects of its folding. The engrailed homeodomain is a mainly alpha-helical protein of 61 residues from Drosophila melanogaster. We found that the simplified model of Engrailed Homeodomain can fold into a global minimum state with a tertiary structure in good agreement with its native structure.
Amino Acid Sequence↗
Label-free electronic detection of thrombin in blood serum by using an aptamer-based sensor.
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Aptamers, Nucleotide↗
Condensation properties of vesicles formed from an amphiphilic N-phosphorylamino acid.
Stable unilamellar vesicles were formed in water under appropriate pH from dispersions of N-(O,O-di-n-hexadecyl)phosphorylalanine, an amphiphilic N-phosphorylamino acid. We found that condensation occurred in the vesicle solution after incubated at 40 degrees C, which may contribute to the stability of the vesicular system. Dipeptide derivative in the vesicle solution was identified by electrospray ionization mass spectrometry (ESI-MS), which suggests the peptide formation without any coupling reagents. Hydrogen bond and electrostatic interactions play important roles in the process of vesicle formation, while the suitable orientation and packing of the amphiphilic molecules at the vesicle/water interface together with certain conformational freedom in the vesicular bilayer are considered to be most favorable for the condensation in ordered systems as vesicles.
Alanine↗