Biomedical subjects

Min Wei

Publications and source records attributed to Min Wei.

At least 19 recordsLinked to original sources

PubMed2026

Analyzing salinity tolerance in grass carp (Ctenopharyngodon idella): Insights from genome-wide association study and genomic selection.

Grass carp (Ctenopharyngodon idella) is one of the most widely cultured freshwater fish species globally. However, the expansion of its farming scale faces severe limitation owing to freshwater scarcity; therefore, the development of strains with greater salinity tolerance is key for expanding production using brackish water resources. To investigate the genetic basis of salinity tolerance in grass carp, a genome-wide association study (GWAS) was conducted using 200 individuals representing extreme phenotypes, namely salinity-tolerant and salinity-sensitive groups. In total, 17 single nucleotide polymorphisms (SNPs) related to salinity tolerance were detected, which were distributed across 11 chromosomes. Through gene annotation, 38 candidate genes were obtained from these loci. Enrichment analysis revealed these candidate genes are primarily implicated in key biological processes, including osmotic regulation, energy metabolism, and stress responses. Analyses of different SNP densities revealed that the 5 K SNP density panel can balance prediction accuracy and computational efficiency. The BayesA model achieved the highest prediction accuracy under the GWAS_Evenly selection strategy, with substantial reductions in mean absolute error and mean square error. This study reveals the genetic mechanisms of salinity tolerance in grass carp, which might be optimized through genomic selection, and provides insights for selectively breeding new varieties with greater salinity tolerance.

Animals↗

PubMed2023

H4S47 O-GlcNAcylation regulates the activation of mammalian replication origins.

The transmission and maintenance of genetic information in eukaryotic cells relies on the faithful duplication of the entire genome. In each round of division, excessive replication origins are licensed, with only a fraction activated to give rise to bi-directional replication forks in the context of chromatin. However, it remains elusive how eukaryotic replication origins are selectively activated. Here we demonstrate that O-GlcNAc transferase (OGT) enhances replication initiation by catalyzing H4S47 O-GlcNAcylation. Mutation of H4S47 impairs DBF4-dependent protein kinase (DDK) recruitment on chromatin, causing reduced phosphorylation of the replicative helicase mini-chromosome maintenance (MCM) complex and compromised DNA unwinding. Our short nascent-strand sequencing results further confirm the importance of H4S47 O-GlcNAcylation in origin activation. We propose that H4S47 O-GlcNAcylation directs origin activation through facilitating MCM phosphorylation, and this may shed light on the control of replication efficiency by chromatin environment.

Animals↗

PubMed2006

Benzothiazole benzimidazole (S)-isothiazolidinone derivatives as protein tyrosine phosphatase-1B inhibitors.

Benzothiazole benzimidazole (S)-isothiazolidinone ((S)-IZD) derivatives 5 were discovered through a peptidomimetic modification of the tripeptide (S)-IZD protein tyrosine phosphatase 1B (PTP1B) inhibitor 1. These derivatives are potent, competitive, and reversible inhibitors of PTP1B with improved caco-2 permeability. An X-ray co-crystal structure of inhibitor 5/PTP1B at 2.2A resolution demonstrated that the benzothiazole benzimidazole forms bi-dentate H-bonds to Asp48, and the benzothiazole interacts with the surface of the protein in a solvent exposed region towards the C-site. The design, synthesis, and SAR of this novel series of benzothiazole benzimidazole containing (S)-IZD inhibitors of PTP1B are presented herein.

Benzimidazoles↗

PubMed2006

Micelle density regulated by a reversible switch of protein secondary structure.

Protein secondary structures may exhibit reversible transitions that occur in an abrupt and controllable manner. In this report, we demonstrate that such transitions may be utilized in the design of a "smart" protein micellar system, in which a stimulus-induced change in protein structure triggers a rapid change in micelle compacticity and size. Specifically, recombinant DNA methods were used to prepare a protein triblock copolymer containing a central hydrophilic block and two hydrophobic end blocks derived from elastin-mimetic peptide sequences. Below the copolymer inverse transition temperature (T(t)), dilute solutions of this amphiphilic protein formed monodispersed micelles in a narrow range of R(H) of approximately 100 nm. When the the temperature was raised above T(t), an abrupt increase in micelle internal density was observed with a concomitant reduction in micelle size. This reversible change in micelle compacticity was triggered by helix-to-sheet protein folding transition. Significantly, these protein polymer-based micelles, which are rapidly responsive to environmental stimuli, establish a new mechanism for the design of controlled drug delivery vehicles.

Amino Acid Sequence↗

PubMed2006

Isothiazolidinone heterocycles as inhibitors of protein tyrosine phosphatases: synthesis and structure-activity relationships of a peptide scaffold.

The structure-based design and discovery of the isothiazolidinone (IZD) heterocycle as a mimic of phosphotyrosine (pTyr) has led to the identification of novel IZD-containing inhibitors of protein tyrosine phosphatase 1B (PTP1B). The structure-activity relationships (SARs) of peptidic IZD-containing inhibitors of PTP1B are described along with a novel synthesis of the aryl-IZD fragments via a Suzuki coupling. The SAR revealed the saturated IZD heterocycle (42) is the most potent heterocyclic pTyr mimetic compared to the unsaturated IZD (25), the thiadiazolidinone (TDZ) (38), and the regioisomeric unsaturated IZD (31). The X-ray crystal structures of 11c and 25 complexed with PTP1B were solved and revealed nearly identical binding interactions in the active site. Ab initio calculations effectively explain the strong binding of the (S)-IZD due to the preorganized binding of the IZD in its low energy conformation.

Escherichia coli↗

PubMed2006

Structural basis for inhibition of protein-tyrosine phosphatase 1B by isothiazolidinone heterocyclic phosphonate mimetics.

Crystal structures of protein-tyrosine phosphatase 1B in complex with compounds bearing a novel isothiazolidinone (IZD) heterocyclic phosphonate mimetic reveal that the heterocycle is highly complementary to the catalytic pocket of the protein. The heterocycle participates in an extensive network of hydrogen bonds with the backbone of the phosphate-binding loop, Phe(182) of the flap, and the side chain of Arg(221). When substituted with a phenol, the small inhibitor induces the closed conformation of the protein and displaces all waters in the catalytic pocket. Saturated IZD-containing peptides are more potent inhibitors than unsaturated analogs because the IZD heterocycle and phenyl ring directly attached to it bind in a nearly orthogonal orientation with respect to each other, a conformation that is close to the energy minimum of the saturated IZD-phenyl moiety. These results explain why the heterocycle is a potent phosphonate mimetic and an ideal starting point for designing small nonpeptidic inhibitors.

Binding Sites↗

PubMed2006

Potent benzimidazole sulfonamide protein tyrosine phosphatase 1B inhibitors containing the heterocyclic (S)-isothiazolidinone phosphotyrosine mimetic.

Potent nonpeptidic benzimidazole sulfonamide inhibitors of protein tyrosine phosphatase 1B (PTP1B) were derived from the optimization of a tripeptide containing the novel (S)-isothiazolidinone ((S)-IZD) phosphotyrosine (pTyr) mimetic. An X-ray cocrystal structure of inhibitor 46/PTP1B at 1.8 A resolution demonstrated that the benzimidazole sulfonamides form a bidentate H bond to Asp48 as designed, although the aryl group of the sulfonamide unexpectedly interacts intramolecularly in a pi-stacking manner with the benzimidazole. The ortho substitution to the (S)-IZD on the aryl ring afforded low nanomolar enzyme inhibitors of PTP1B that also displayed low caco-2 permeability and cellular activity in an insulin receptor (IR) phosphorylation assay and an Akt phosphorylation assay. The design, synthesis, and SAR of this novel series of benzimidazole sulfonamide containing (S)-IZD inhibitors of PTP1B are presented herein.

Benzimidazoles↗

PubMed2006

Deficits and recovery in visuospatial memory during head motion after bilateral labyrinthine lesion.

To keep a stable internal representation of the environment as we move, extraretinal sensory or motor cues are critical for updating neural maps of visual space. Using a memory-saccade task, we studied whether visuospatial updating uses vestibular information. Specifically, we tested whether trained rhesus monkeys maintain the ability to update the conjugate and vergence components of memory-guided eye movements in response to passive translational or rotational head and body movements after bilateral labyrinthine lesion. We found that lesioned animals were acutely compromised in generating the appropriate horizontal versional responses necessary to update the directional goal of memory-guided eye movements after leftward or rightward rotation/translation. This compromised function recovered in the long term, likely using extravestibular (e.g., somatosensory) signals, such that nearly normal performance was observed 4 mo after the lesion. Animals also lost their ability to adjust memory vergence to account for relative distance changes after motion in depth. Not only were these depth deficits larger than the respective effects on version, but they also showed little recovery. We conclude that intact labyrinthine signals are functionally useful for proper visuospatial memory updating during passive head and body movements.

Animals↗

PubMed2006

Scaling of the fore-aft vestibulo-ocular reflex by eye position during smooth pursuit.

An eye position signal scales the amplitude of compensatory eye velocity in the translational vestibulo-ocular reflex (TVOR). To investigate the origin of such a modulatory signal, we studied the kinematics of the fore-aft TVOR as rhesus monkeys pursued a horizontally moving target at velocities between 0.5 and 30 degrees /s. We found that the "V-shaped" curve of the fore-aft TVOR amplitude as a function of eye position was shifted opposite to the direction of pursuit eye movement. As a result, the tip of the V-shaped curve that occurred close to zero eye position during steady-state fixation was shifted to the right during leftward pursuit and to the left during rightward pursuit eye movements. The faster the pursuit velocity the larger the observed shift. These results suggest that the scaling of the TVOR can precede actual eye position changes by several tens of milliseconds, which averaged 169 +/- 87 ms in three rhesus monkeys. Thus, central motor commands, rather than low-level efference copy or proprioceptive information, may be the signals scaling TVOR amplitude.

Algorithms↗

PubMed2006

Uptake of chloride ion from aqueous solution by calcined layered double hydroxides: equilibrium and kinetic studies.

Layered double hydroxides (LDH) calcined within a certain temperature range (denoted as CLDH) have been shown to recover their original layered structure in the presence of appropriate anions. In the light of this so-called "memory effect", uptake of chloride ion from aqueous solution by calcined MgAl-CO3 LDH was investigated in batch mode. The equilibrium isotherm showed that the uptake of chloride ion by CLDH was consistent with the Langmuir and Freundlich equations and that the Langmuir model gave a better fit to the experimental data than the Freundlich model. The maximum uptake capacity of CLDH for chloride ion was 149.5 mg/g, close to the stoichiometric uptake (168 mg/g). The influence of varying pH of solution, initial chloride concentration, adsorbent quantity, and temperature on the kinetics of chloride removal has also been explored. Four kinetic models were used to fit the experimental data, and it was found that the pseudo-second-order kinetics model could be used to describe the uptake process satisfactorily. The calculated value of Ea was found to be 56.8 kJ/mol, which suggests that the process of uptake of chloride ion is controlled by the rate of reaction of chloride ion with the CLDH rather than diffusion. A mechanism for removal of chloride ion has been confirmed by X-ray diffraction, FT-IR spectroscopy and TG-MS measurements.

Adsorption↗

PubMed2006

Existence of no-observed effect levels for 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline on hepatic preneoplastic lesion development in BN rats.

There is increasing evidence that dose-response curve of genotoxic carcinogen is nonlinear and a practical threshold dose exists. However, little is known about differences in the dose-response relationship of genotoxic carcinogen among different strain rats. Herein, we showed that low doses of genotoxic carcinogen 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx) had no effects on induction of liver glutathione S-transferase placental form (GST-P)-positive foci in both BN and F344 rats, and therefore demonstrated the existence of no-observed effect level for hepatocarcinogenicity of this genotoxic carcinogen irrespective of strains. These findings further support our notion that a practical threshold dose for MeIQx hepatocarcinogenicity exists in rats.

Animals↗

PubMed2006

Foveal visual strategy during self-motion is independent of spatial attention.

Translational self-motion disturbs the stability of retinal images by inducing a pattern of retinal optic flow that cannot be compensated globally by a single eye movement. The eyes must rotate by different amounts, depending on which spatial location needs to be stabilized on the retina. However, compensatory eye movements during steady fixation are always such as to maintain visual acuity on the fovea at the expense of significant image slip on the peripheral retina. We investigated whether such a foveal visual strategy during translation is hard-wired or whether it embeds enough flexibility to also allow for behaviorally relevant objects outside the foveae to be stabilized preferentially on the retinas. Monkeys were moved forward or backward and leftward or rightward passively in darkness while planning a saccade or bar release to peripheral dimmed targets. By comparing the eye movements made during these tasks with those under conditions of steady fixation, we found that the motion-induced eye movements depended only on current fixation. This was true even during the last milliseconds just before a saccade to the peripheral target. We conclude that the foveal stabilization strategy is invariant and solely dependent on current eye position, a strategy that is optimal for both processing speed and efficiency in the extraction of heading information from retinal flow during self-motion.

Adaptation, Physiological↗

PubMed2006

Pro- and antiinflammatory cytokine signaling: reciprocal antagonism regulates interferon-gamma production by human natural killer cells.

Activated monocytes produce proinflammatory cytokines (monokines) such as interleukin (IL)-12, IL-15, and IL-18 for induction of interferon-gamma (IFN-gamma) by natural killer (NK) cells. NK cells provide the antiinflammatory cytokine transforming growth factor (TGF)-beta, an autocrine/negative regulator of IFN-gamma. The ability of one signaling pathway to prevail over the other is likely important in controlling IFN-gamma for the purposes of infection and autoimmunity, but the molecular mechanism(s) of how this counterregulation occurs is unknown. Here we show that in isolated human NK cells, proinflammatory monokines antagonize antiinflammatory TGF-beta signaling by downregulating the expression of the TGF-beta type II receptor, and its signaling intermediates SMAD2 and SMAD3. In contrast, TGF-beta utilizes SMAD2, SMAD3, and SMAD4 to suppress IFN-gamma and T-BET, a positive regulator of IFN-gamma. Indeed, activated NK cells from Smad3(-/-) mice produce more IFN-gamma in vivo than NK cells from wild-type mice. Collectively, our data suggest that pro- and antiinflammatory cytokine signaling reciprocally antagonize each other in an effort to prevail in the regulation of NK cell IFN-gamma production.

Animals↗

PubMed2006

Involvement of ubiquitination and sumoylation in bladder lesions induced by persistent long-term low dose ionizing radiation in humans.

PURPOSE: We determined whether ubiquitination and sumoylation processes are up-regulated in bladder urothelium by chronic, long-term, persistent low doses of ionizing radiation in male patients with benign prostate hyperplasia and females with chronic cystitis living more than 19 years in 137Cs contaminated areas after the Chernobyl accident in Ukraine. MATERIALS AND METHODS: Bladder urothelial biopsies from 45 patients were subjected to histopathological and immunohistochemical study of Ub, SUMO1, SUMO E2 conjugating enzyme Ubc9, and the cell cycle inhibitors p53 and p27(Kip1). RESULTS: Of 25 group 1 patients from radio contaminated areas chronic proliferative atypical cystitis (Chernobyl cystitis), featuring multiple foci of dysplasia, and carcinoma in situ were observed in 23 (92%) and 19 (76%), respectively, in addition to 1 small pTa grade 1 urothelial carcinoma. Chronic cystitis with areas of dysplasia and urothelial hyperplasia were detected in 2 (10%) and 3 (15%), respectively of the 20 patients in control group 2 from clean (without radio contamination) areas of Ukraine. Greatly increased levels of Ub, SUMO1, Ubc9 and p53 as well as decreased levels of p27(Kip1) were evident in patients in group 1 compared to those in group 2 (all p <0.001). CONCLUSIONS: These findings support the hypothesis that up-regulated ubiquitination and sumoylation processes might be an adaptive response to unscheduled proteolysis of aberrant p53 and p27(Kip1) cell cycle regulators occurring with long-term low dose rate ionizing radiation exposure with a possible contribution to urothelial carcinogenesis.

Aged↗

PubMed2006

Absence of beta-catenin alteration in hepatic tumors induced by p-nitroanisole in Crj:BDF1 mice.

In the present study, beta-catenin localization in hepatocellular neoplasms and hepatoblastomas, induced by oral administration of p-Nitroanisole (pNA) in Crj:BDF1 for 2 years, was evaluated by immunohistochemistry along with genetic alterations in exon 2 of beta-catenin by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) approach. Genomic DNA was isolated from paraffin sections of a total of 53 liver tumors. Immunohistochemical analysis revealed no abnormal accumulation of the beta-catenin protein in any of the cases. No mutations (0/13), 20% silent mutations (3/15) and 8% silent plus 12% functional mutations (2 + 3/25), not in the multiple phosphorylation sites of beta-catenin, were observed in hepatocellular adenomas, carcinomas and hepatoblastomas, respectively. The results indicate that beta-catenin does not play an important role in development of hepatic tumors induced by pNA in Crj:BDF1 mice.

Animals↗

PubMed2006

Existence of no hepatocarcinogenic effect levels of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline with or without coadministration with ethanol.

There is increasing evidence of the existence of no effect levels for genotoxic carcinogens. However, only limited information is available regarding dose-response curves for combination effects of multiple carcinogens at low dose. In the present study, 280 male F344 rats were divided into 14 groups to determine the effects of co-administration of various doses of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 10% ethanol on the development of glutathione S-transferase placental form (GST-P)-positive foci in the liver. The results provided concrete evidence for the existence of no effect levels for hepatocarcinogenicity of MeIQx either in presence or absence of ethanol and, therefore, for a practical threshold for this genotoxic carcinogen.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2006

Diagnosis and classification of congenital craniofacial cleft deformities.

Classification and diagnosis of congenital craniofacial cleft deformities are helpful in discerning the severity of the deformity and providing guidance for surgical repair. Eighty-one cases of congenital craniofacial cleft deformity were analyzed using the Tessier classification. Depending on the location, status of the deformity, and results of examinations such as computed tomography, according to the range affected, the location and status of the deformity were designated by the STO classification, with S for skin, T for soft tissue, and O for os (craniofacial bone). The severity of the deformity is delineated by Arabic numerals. The analysis of 81 cases by the STO classification method showed that suborbital deformities mainly were Tessier 3 and 4 clefts (24.70%) and supraorbital deformities mainly were Tessier 9 and 10 clefts (38.27%). There was no definite regular pattern for the affected extent of tissues. STO classification can be a supplement to Tessier classification and can provide references for the surgical repair of craniofacial cleft deformity.

Adolescent↗

PubMed2006

[Screening differentially expressed genes in denucleated K562 cells with restriction display technique].

OBJECTIVE: To screen differentially expressed genes in cytochalasin B (CB)-induced denucleated K562 cells by restriction display (RD) technique. METHODS: The total RNA was isolated and purified from K562 cells before and after CB (10 mug/ml) treatment. The mRNA from both treated and untreated K562 cells were reversely transcribed into cDNA, and the differentially expressed genes were separated using RD technique combined with polyacrylamide gel electrophoresis and sliver staining, followed by cloning, sequencing and homology analysis against GenBank database of these genes. RESULTS: Seven differentially expressed genes were identified in CB-treated cells including aquaporin 1 (AQP1) gene, which was verified to be up-regulated after CB treatment by RT-PCR. CONCLUSION: AQP1 gene might be in close association with the regulation of denucleation processes and CB-induced proliferation inhibition of K562 cells.

Aquaporin 1↗