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Lei Liu

Publications and source records attributed to Lei Liu.

At least 145 records · Page 8Linked to original sources
PubMed2003

Contribution of Drosophila DEG/ENaC genes to salt taste.

The ability to detect salt is critical for the survival of terrestrial animals. Based on amiloride-dependent inhibition, the receptors that detect salt have been postulated to be DEG/ENaC channels. We found the Drosophila DEG/ENaC genes Pickpocket11 (ppk11) and Pickpocket19 (ppk19) expressed in the larval taste-sensing terminal organ and in adults on the taste bristles of the labelum, the legs, and the wing margins. When we disrupted PPK11 or PPK19 function, larvae lost their ability to discriminate low concentrations of Na(+) or K(+) from water, and the electrophysiologic responses to low salt concentrations were attenuated. In both larvae and adults, disrupting PPK11 or PPK19 affected the behavioral response to high salt concentrations. In contrast, the response of larvae to sucrose, pH 3, and several odors remained intact. These results indicate that the DEG/ENaC channels PPK11 and PPK19 play a key role in detecting Na(+) and K(+) salts.

Amiloride↗
PubMed2003

Synthesis and partial biological evaluation of a small library of differentially-linked beta-C-disaccharides.

The synthesis of a small library of differentially-linked beta-C-disaccharides has been carried out through the use of a radical allylation-RCM strategy. Acids 6 were prepared by Keck allylation of a suitable carbohydrate-based radical precursor, followed by oxidative cleavage of the formed alkene. Dehydrative coupling of these acids with the known olefin alcohol 5 then gave the precursor esters 7 in excellent yield. Methylenation of the esters 7 was followed by RCM and in situ hydroboration-oxidation of the formed glycals to furnish the protected beta-C-disaccharides 10 in good overall yield. Five examples were then deprotected and screened for their efficacy as enzyme inhibitors of beta-glycosidase and against several solid-tumor cell lines for in vitro differential cytotoxicity.

Combinatorial Chemistry Techniques↗
PubMed2003

Remote substituent effects on homolytic bond dissociation energies.

In the study we tried to answer two questions. First, does X-Z homolytic bond dissociation energy (BDE) of Y-C6H4-X-Z obey the Hammett relationship? Second, if it does what factors determine the magnitude and sign of the slope (rho+) of Hammett regression against substituent sigma(p)(+) constants? We collected a large number of X-Z BDEs for over one-thousand Y-C6H4-X-Z systems using the RMP2/6-311++G**//UB3LYP/6-31G* method. We found that remote substituent effects on X-Z BDEs are determined by both the ground effect (i.e. stabilization/destabilization of X-Z by the substituents) and the radical effect (i.e. stabilization/destabilization of X. by the substituents). The ground or radical effect is determined by the electron demand of X-Z or X. in the same way as the deprotonation enthalpy of HOOC-C6H4-X-Z or HOOC-C6H4-X. is affected by X-Z or X. . As a result, rho+ (BDE) for X-Z bond homolysis can be quantitatively predicted by using the change in deprotonation enthalpy from HOOC-C6H4-X-Z to HOOC-C6H4-X. .

Journal Article↗
PubMed2003

Effects of alpha-ammonium, alpha-phosphonium, and alpha-sulfonium groups on C-H bond dissociation energies.

C-H bond dissociation energies of alpha-ammonium-, alpha-phosphonium-, or alpha-sulfonium-substituted methanes and toluenes were calculated to a precision of 1-2 kcal/mol. It was found that alpha-ammonium, alpha-phosphonium, and alpha-sulfonium groups all destabilize a methyl radical. alpha-Ammonium also destabilizes a benzyl radical, whereas alpha-phosphonium and alpha-sulfonium either slightly stabilize or destabilize a benzyl radical depending on their alkylation state.

Journal Article↗
PubMed2003

EWI2/PGRL associates with the metastasis suppressor KAI1/CD82 and inhibits the migration of prostate cancer cells.

Cancer metastasis suppressor KAI1/CD82 belongs to the tetraspanin superfamily and inversely correlates with the metastatic potential of a variety of cancers. The mechanism of KAI1/CD82-mediated metastasis suppression remains unclear. In this study, we found a M(r) 68,00 cell-surface protein physically associated with KAI1/CD82 and named it KASP: a KAI1/CD82-associated surface protein. Distinctive from known KAI1/CD82 associations that usually occur in the context of "tetraspanin web," the KAI1/CD82-KASP association is likely to be direct because it is: (a) highly stoichiometric; (b) stabilized by chemical cross-linking; and (c) independent of cholesterol-enriched lipid rafts. Therefore, KASP is one of the major transmembrane proteins that associates with KAI1/CD82. Consistent with the wide distribution of KAI1/CD82, KASP is expressed ubiquitously in human tissues. Through peptide sequencing, KASP was identified as an immunoglobulin superfamily member called EWI2 or PGRL. Although EWI2/PGRL has been found to associate with tetraspanins CD9 and CD81, it forms distinct complexes with different tetraspanins, and its association with KAI1/CD82 could be independent of CD81 and CD9. Overexpression of EWI2/PGRL in Du145 metastatic prostate cancer cells inhibits cell migration on both fibronectin- and laminin-coated substratum, indicating that EWI2/PGRL directly regulates cell migration. Furthermore, EWI2/PGRL synergizes KAI1/CD82 in inhibiting cell migration, indicating that EWI2/PGRL is likely required for the function of KAI1/CD82. In summary, we identified a major KAI1/CD82-associated protein, EWI2/PGRL, that is important for KAI1/CD82-mediated suppression of cancer cell migration.

Amino Acid Sequence↗
PubMed2003

[Detection of HIV DNA in Chinese AIDS kidney by in situ PCR].

OBJECTIVE: To investigate the relationship between HIV and AIDS kidney. METHODS: Nine Chinese AIDS kidney autopsies were detected by PCR in situ. RESULTS: The results were all positive: brown in karyon and cytoplasm of renal tubular cells. CONCLUSION: Kidneys can be directly infected by HIV.

Acquired Immunodeficiency Syndrome↗
PubMed2003

RNA cargoes associating with FMRP reveal deficits in cellular functioning in Fmr1 null mice.

The Fragile X mental retardation-1 (Fmr1) gene encodes a multifunctional protein, FMRP, with intrinsic RNA binding activity. We have developed an approach, antibody-positioned RNA amplification (APRA), to identify the RNA cargoes associated with the in vivo configured FMRP messenger ribonucleoprotein (mRNP) complex. Using APRA as a primary screen, putative FMRP RNA cargoes were assayed for their ability to bind directly to FMRP using traditional methods of assessing RNA-protein interactions, including UV-crosslinking and filter binding assays. Approximately 60% of the APRA-defined mRNAs directly associate with FMRP. By examining a subset of these mRNAs and their encoded proteins in brain tissue from Fmr1 knockout mice, we have observed that some of these cargoes as well as the proteins they encode show discrete changes in abundance and/or differential subcellular distribution. These data are consistent with spatially selective regulation of multiple biological pathways by FMRP.

Animals↗
PubMed2003

Drosophila DEG/ENaC pickpocket genes are expressed in the tracheal system, where they may be involved in liquid clearance.

The Drosophila tracheal system and mammalian airways are branching networks of tubular epithelia that deliver oxygen to the organism. In mammals, the epithelial Na(+) channel (ENaC) helps clear liquid from airways at the time of birth and removes liquid from the airspaces in adults. We tested the hypothesis that related Drosophila degenerin (DEG)/ENaC family members might play a similar role in the fly. Among 16 Drosophila DEG/ENaC genes, called pickpocket (PPK) genes, we found 9 expressed in the tracheal system. By in situ hybridization, expression appeared in late-stage embryos after tracheal tube formation, with individual PPK genes showing distinct temporal and spatial expression patterns as development progressed. Promoters for several PPK genes drove reporter gene expression in the larval and adult tracheal systems. Adding the DEG/ENaC channel blocker amiloride to the medium inhibited liquid clearance from the trachea of first instar larvae. Moreover, when RNA interference was used to silence PPK4 and PPK11, larvae failed to clear tracheal liquid. These data suggest substantial molecular diversity of DEG/ENaC channel expression in the Drosophila tracheal system where the PPK proteins likely play a role in Na(+) absorption. Extensive similarities between Drosophila and mammalian airways offer opportunities for genetic studies that may decipher further the structure and function of DEG/ENaC proteins and development of the airways.

Amiloride↗
PubMed2003

Remote substituent effects on N-X (X = H, F, Cl, CH3, Li) bond dissociation energies in para-substituted anilines.

UB3LYP/6-311++g**//UB3LYP/6-31+g* and ROMP2/6-311++g**//UB3LYP/6-31+g* methods were used to calculate (i) N-X bond dissociation energies (BDE) in 4-YC6H4NH-X and (ii) N-H BDEs in 4-YC6H4NU-H, where Y = H, Me, OCH3, SMe, NH2, NMe2, SiMe3, F, Cl, CN, COOH, CF3, and NO2, X = H, CH3, F, Cl, and Li, and U = H, F, and CH(3). It was found that N-H BDEs of 4-YC6H4NH2 have a positive correlation with the substituent sigma(p+) constants. The slope (rho+) is about 3.0-4.3 kcal/mol, which is in good agreement with the experimental results. It was also found that the substituent effects on N-X BDEs of 4-YC6H4NH-X change considerably when X changes. rho(+)values for N-CH3, N-F, N-Cl, and N-Li BDEs were calculated to be 3.1-4.6, 1.3-1.9, 1.8-2.6, and 4.9-6.8 kcal/mol, respectively. The reason for the variation of substituent effects was proposed to be the ground-state effect, i.e., the interaction between the intact NH-X moiety and the parasubstituents. Finally, alpha-substitution was found to be able to significantly change the substituent effects. rho(+)values for N-H BDEs of 4-C6H4NCH3(-)H and 4-C6H4NF-H are 2.5-4.0 and 1.7-1.9 kcal/mol, respectively.

Journal Article↗
PubMed2003

Alternate forms of MHC class II-associated invariant chain are not produced by alternative splicing in rainbow trout (Oncorhynchus mykiss) but are encoded by separate genes.

A major limiting factor in understanding teleost major histocompatibility receptor function is the lack of knowledge about antigen presentation accessory molecules. We report here two cDNA clones encoding teleost versions of invariant chain and one encoding a related protein that may play a protease inhibition role in antigen presentation. The two invariant chain equivalents are similar to each other where they overlap, but differ in the presence or absence of a thyroglobulin domain. This domain is added to tetrapod invariant chain protein by alternative splicing but there was no evidence of alternative splicing of the two trout genes. Southern blotting confirmed that all three trout cDNAs are derived from single copy genes and Northern blotting indicated that they are expressed in antigen tissues. Thus the encoded proteins are probably involved in antigen presentation, but their expression is probably regulated in a manner different from tetrapods.

Alternative Splicing↗
PubMed2003

Impact of a critical pathway on inpatient management of diabetic ketoacidosis.

To assess the management of diabetic ketoacidosis (DKA) and evaluate if introduction of a critical pathway improves management, we studied adults admitted with DKA to the Medicine and Critical Care Services in a US teaching hospital. Patients admitted with DKA in 1997 before implementation of the critical pathway were the control group (n=72). In 1998, housestaff and nurses in the emergency department (ED) and on the General Medicine and Critical Care Services were instructed in the use of the critical pathway. Patients admitted with DKA during 1998 (n=77) were the intervention group. Length of stay (LOS), hospital cost, adherence to guidelines, and medical outcomes to be avoided were compared, and regression analyses were performed to correlate processes and outcomes of care. Mean LOS and variability in LOS decreased during the intervention period, especially in patients treated without endocrinology consultation (EC) (5.2 +/- 10.6 vs. 2.4 +/- 2.1 days, P=0.01), and hospital cost and variability in cost tended to decrease ($6441 +/- 15,204 vs. $3625 +/- 3478, P=0.24). More intervention subjects received the recommended intravenous fluid volume (88 vs. 71%, P=0.013), education in sick-day management (77 vs. 54%, P=0.006), and EC (38 vs. 21%, P=0.03). Insulin management was not changed. We conclude that implementation of a DKA critical pathway reduced practice variation and was associated with shorter LOS and a trend toward decreased cost. Some processes of care were improved but many require additional interventions.

APACHE↗
PubMed2003

Identification and function of thermosensory neurons in Drosophila larvae.

Although the ability to sense temperature is critical for many organisms, the underlying mechanisms are poorly understood. Using the calcium reporter yellow cameleon 2.1 and electrophysiological recordings, we identified thermosensitive neurons and examined their physiologic response in Drosophila melanogaster larvae. In the head, terminal sensory organ neurons showed increased activity in response to cooling by < or =1 degrees C, heating reduced their basal activity, and different units showed distinct response patterns. Neither cooling nor heating affected dorsal organ neurons. Body wall neurons showed a variety of distinct response patterns to both heating and cooling; the diverse thermal responses were strikingly similar to those described in mammals. These data establish a functional map of thermoresponsive neurons in Drosophila larvae and provide a foundation for understanding mechanisms of thermoreception in both insects and mammals.

Animals↗
PubMed2003

A cattle-human comparative map built with cattle BAC-ends and human genome sequence.

As a step toward the goal of adding the cattle genome to those available for multispecies comparative genome analysis, 40,224 cattle BAC clones were end-sequenced, yielding 60,547 sequences (BAC end sequences, BESs) after trimming with an average read length of 515 bp. Cattle BACs were anchored to the human and mouse genome sequences by BLASTN search, revealing 29.4% and 10.1% significant hits (E < e-5), respectively. More than 60% of all cattle BES hits in both the human and mouse genomes are located within known genes. In order to confirm in silico predictions of orthologyand their relative position on cattle chromosomes, 84 cattle BESs with similarity to sequences on HSA11 were mapped using a cattle-hamster radiation hybrid (RH) panel. Resulting RH maps of BTA15 and BTA29 cover approximately 85% of HSA11 sequence, revealing a complex patchwork shuffling of segments not explained by a simple translocation followed by internal rearrangements. Overlay of the mouse conserved syntenies onto HSA11 revealed that segmental boundaries appear to be conserved in all three species. The BAC clone-based comparative map provides a foundation for the evolutionary analysis of mammalian karyotypes and for sequencing of the cattle genome.

Animals↗
PubMed2003

Microbial transformation of naproxen by Cunninghamella species.

AIM: The metabolites of naproxen produced by Cunninghamella species were isolated and identified, and further to compare the similarities between microbial transformation and mammalian metabolism. METHODS: Naproxen was transformed by three strains of Cunninghammella species (Cunninghamella blakeslesna AS 3.153, Cunninghamella echinulata AS 3.2004, and Cunninghamella elegans AS 3.156). The metabolites of naproxen were separated and assayed by liquid chromatography-mass spectrometry method. Semi-preparative HPLC was used to isolate the major metabolite, and the structure was identified by nuclear magnetic resonance (NMR) and mass spectrometry. RESULTS: Naproxen was transformed into 2 metabolites, desmethylnaproxen and desmethylnaproxen-6-O-sulfate, both were the known mammalian metabolites. The conjugated metabolite was newly detected in microbial transformation samples. CONCLUSION: The microbial transformation of naproxen has some similarities with the metabolism of naproxen in mammals. The fungi belonging to Cunninghamella species could be used as complementary in vitro models for drug metabolism to predict and produce the metabolites of drugs in mammals.

Biotransformation↗
PubMed2003

[Influence of super high molecular weight poly D,L-lactic acid on viability and new bone formation of osteoblasts].

OBJECTIVE: To investigate the influence of the viability and new bone formation of osteoblasts by the super high molecular weight poly D,L-lactic acid (SHMW-PDLLA). METHODS: 1. The osteoblasts derived from neonatal rat were grown and maintained at steep of SHMW-PDLLA and normal culture medium. The viability and function of the osteoblasts were measured with MTT array. 2. The plate and screws made of SHMW-PDLLA were implanted and fixed at the artificial fractured mandible of dogs. Specimens were gained at 3 and 6 months and examined with macroscopy and SEM. RESULTS: 1. There is no significant difference of OD values between the experimental group and the control group (P > 0.05). The SHMW-PDLLA isn't toxic to osteoblast at 1 week and 2 weeks, and the toxicity is 3% at 3 days. 2. There were a lot of new bone formed between the implanted SHMW-PDLLA plate and bone tissues under SEM. CONCLUSION: SHMW-PDLLA hasn't pathological influence on the viability and new bone formation of osteoblasts and it is feasible in tissue engineering of bone.

Animals↗
PubMed2003

Experimental study on the adhesion, migration and three-dimensional growth of Schwann cells on absorbable biological materials.

OBJECTIVE: To study the adhesion, migration and three-dimentional growth of Schwann cells on PLA (polylactic acid) nonspinning fibre cloth and polyglycolic/polylactic acid (PLGA) fibres. METHODS: Schwann cells/ECM gel solution and PLA nonspinning fibre cloth and PLGA fibres pretreated by collagen, polylysine and ECM were co-cultured. Then the migration and three-dimensional growth of Schwann cells on the fibres were observed under phase contrast microscope and laser scanning confocal microscope. RESULTS: Schwann cell/ECM solution was compounded with PLA nonspinning fibre cloth. With formation of gel, most Schwann cells resided in the fibre net holes, and adhered to the fibres to form a multiplayer-arranged Schwann cell column like Büngner band. Schwann cells could adhere to PLGA fibres and grew and migrated along the fibres. ECM gel could significantly increase the adhering and migrating cell number. CONCLUSIONS: ECM gel can facilitate the adhesion, growth and migration of Schwann cells on the seteroframe. It is a good integrating material for tissue engineering bioartificial nerve.

Cell Adhesion↗