PubMed Health⌕ Search

Biomedical subjects

Feng Lin

Publications and source records attributed to Feng Lin.

At least 19 recordsLinked to original sources
PubMed2026

Functional divergence of two soybean cytosolic serine hydroxymethyltransferases in development and defense against soybean cyst nematode.

Serine hydroxymethyltransferase (SHMT) is an enzyme essential for one-carbon metabolism. In higher plants, multiple SHMT genes code for isoforms that function in the cytosol, nucleus, mitochondria, and chloroplasts. The soybean genome contains two cytosolic SHMTs, GmSHMT05 and GmSHMT08, sharing high sequence identity and similar expression throughout soybean development. In certain soybean genotypes, two amino acid substitutions negatively impact GmSHMT08's ability to bind to tetrahydrofolate (THF), leading to a gain-of-function in resistance to the soybean cyst nematode (SCN). Whether this perturbation to the enzyme has other functional consequences for soybean growth and development remains unknown. Here, we investigated the roles of cytosolic GmSHMTs in soybean growth and development. We determined that the 3D structure and folate-binding affinity of GmSHMT05 are highly similar to the version of GmSHMT08 found in susceptible soybeans. We further measured phenotypic traits of two ethyl methanesulfonate-derived Gmshmt08 mutant plants in an SCN-resistant soybean background. Aboveground soybean growth and development were similar, except the Gmshmt08 mutant plants showed a significant increase in pods/plant in field phenotyping trials. Belowground analyses revealed a significant increase in lateral root and total root length in mutant plants, and CRISPR-Cas9 editing demonstrated an essential role of cytosolic SHMTs in root growth. Taken together, our results indicate that GmSHMT05 sustains overall soybean growth and development in the absence of GmSHMT08; however, GmSHMT08's gain-of-function in SCN resistance negatively influences pod and root growth, highlighting a potential trade-off between soybean defense and development that may impact yield when breeding with GmSHMT08 to develop SCN-resistant varieties.

1-C folate metabolism↗
PubMed2024

Assessing the causal link between liver function and acute pancreatitis: A Mendelian randomisation study.

A correlation has been reported to exist between exposure factors (e.g. liver function) and acute pancreatitis. However, the specific causal relationship remains unclear. This study aimed to infer the causal relationship between liver function and acute pancreatitis using the Mendelian randomisation method. We employed summary data from a genome-wide association study involving individuals of European ancestry from the UK Biobank and FinnGen. Single-nucleotide polymorphisms (SCNPs), closely associated with liver function, served as instrumental variables. We used five regression models for causality assessment: MR-Egger regression, the random-effect inverse variance weighting method (IVW), the weighted median method (WME), the weighted model, and the simple model. We assessed the heterogeneity of the SNPs using Cochran's Q test. Multi-effect analysis was performed using the intercept term of the MR-Egger method and leave-one-out detection. Odds ratios (ORs) were used to evaluate the causal relationship between liver function and acute pancreatitis risk. A total of 641 SNPs were incorporated as instrumental variables. The MR-IVW method indicated a causal effect of gamma-glutamyltransferase (GGT) on acute pancreatitis (OR = 1.180, 95%CI [confidence interval]: 1.021-1.365, P = 0.025), suggesting that GGT may influence the incidence of acute pancreatitis. Conversely, the results for alkaline phosphatase (ALP) (OR = 0.997, 95%CI: 0.992-1.002, P = 0.197) and aspartate aminotransferase (AST) (OR = 0.939, 95%CI: 0.794-1.111, P = 0.464) did not show a causal effect on acute pancreatitis. Additionally, neither the intercept term nor the zero difference in the MR-Egger regression attained statistical significance (P = 0.257), and there were no observable gene effects. This study suggests that GGT levels are a potential risk factor for acute pancreatitis and may increase the associated risk. In contrast, ALP and AST levels did not affect the risk of acute pancreatitis.

Humans↗
PubMed2006

A structural core within apolipoprotein C-II amyloid fibrils identified using hydrogen exchange and proteolysis.

Plasma apolipoproteins show alpha-helical structure in the lipid-bound state and limited conformational stability in the absence of lipid. This structural instability of lipid-free apolipoproteins may account for the high propensity of apolipoproteins to aggregate and accumulate in disease-related amyloid deposits. Here, we explore the properties of amyloid fibrils formed by apolipoproteins using human apolipoprotein (apo) C-II as a model system. Hydrogen-deuterium exchange and NMR spectroscopy of apoC-II fibrils revealed core regions between residues 19-37 and 57-74 with reduced amide proton exchange rates compared to monomeric apoC-II. The C-terminal core region was also identified by partial proteolysis of apoC-II amyloid fibrils using endoproteinase GluC and proteinase K. Complete tryptic hydrolysis of apoC-II fibrils followed by centrifugation yielded a single peptide in the pellet fraction identified using mass spectrometry as apoC-II(56-76). Synthetic apoC-II(56-76) readily formed fibrils, albeit with a different morphology and thioflavinT fluorescence yield compared to full-length apoC-II. Studies with smaller peptides narrowed this fibril-forming core to a region within residues 60-70. We postulate that the ability of apoC-II(60-70) to independently form amyloid fibrils drives fibril formation by apoC-II. These specific amyloid-forming regions within apolipoproteins may underlie the propensity of apolipoproteins and their peptide derivatives to accumulate in amyloid deposits in vivo.

Amino Acid Motifs↗
PubMed2006

In silico modelling of hormone response elements.

BACKGROUND: An important step in understanding the conditions that specify gene expression is the recognition of gene regulatory elements. Due to high diversity of different types of transcription factors and their DNA binding preferences, it is a challenging problem to establish an accurate model for recognition of functional regulatory elements in promoters of eukaryotic genes. RESULTS: We present a method for precise prediction of a large group of transcription factor binding sites - steroid hormone response elements. We use a large training set of experimentally confirmed steroid hormone response elements, and adapt a sequence-based statistic method of position weight matrix, for identification of the binding sites in the query sequences. To estimate the accuracy level, a table of correspondence of sensitivity vs. specificity values is constructed from a number of independent tests. Furthermore, feed-forward neural network is used for cross-verification of the predicted response elements on genomic sequences. CONCLUSION: The proposed method demonstrates high accuracy level, and therefore can be used for prediction of hormone response elements de novo. Experimental results support our analysis by showing significant improvement of the proposed method over previous HRE recognition methods.

Binding Sites↗
PubMed2006

Essential helix interactions in the anion transporter domain of prestin revealed by evolutionary trace analysis.

Prestin, a member of the SLC26A family of anion transporters, is a polytopic membrane protein found in outer hair cells (OHCs) of the mammalian cochlea. Prestin is an essential component of the membrane-based motor that enhances electromotility of OHCs and contributes to frequency sensitivity and selectivity in mammalian hearing. Mammalian cells expressing prestin display a nonlinear capacitance (NLC), widely accepted as the electrical signature of electromotility. The associated charge movement requires intracellular anions reflecting the membership of prestin in the SLC26A family. We used the computational approach of evolutionary trace analysis to identify candidate functional (trace) residues in prestin for mutational studies. We created a panel of mutations at each trace residue and determined membrane expression and nonlinear capacitance associated with each mutant. We observe that several residue substitutions near the conserved sulfate transporter domain of prestin either greatly reduce or eliminate NLC, and the effect is dependent on the size of the substituted residue. These data suggest that packing of helices and interactions between residues surrounding the "sulfate transporter motif" is essential for normal prestin activity.

Amino Acid Sequence↗
PubMed2006

Molecular genetic analysis of five spike-related traits in wheat using RIL and immortalized F2 populations.

Kernel number per spike is one of the most important yield components of wheat. To map QTLs related to kernel number including spike length (SPL), spikelet number per spike (SPN), fertile spikelet number (FSPN), sterile spikelet number (SSPN) and compactness, and to characterize the inheritance modes of the QTLs and two-locus interactions, 136 recombinant inbred lines (RILs) derived from 'Nanda2419' x 'Wangshuibai' and an immortalized F(2 )population (IF(2)) generated by randomly permutated intermating of these RILs were investigated. QTL mapping made use of the previously constructed over 3300 cM linkage map of the RIL population. Three, five, two, two and six chromosome regions were identified, respectively, for their association with SPL, SPN, FSPN, SSPN, and compactness in at least two of the three environments examined. All compactness QTLs but one shared the respective intervals of QSpn.nau-5A and the SPL QTLs. Xcfd46-Xwmc702 interval on chromosome 7D was related to all traits but SSPN and had consistently the largest effects. The fact that not all the compactness QTL intervals were related to both SPL and SPN indicates that compactness is regulated by different mechanisms. Interval coincidence between QTLs of SPL and SPN and between QTLs of FSPN and SSPN was minimal. For all the traits, favorable alleles exist in both parents. Inheritance modes from additiveness to overdominance of the QTLs were revealed and two-locus interactions were detected, implying that the traits studied are under complex genetic control. The results could contribute to wheat yield improvement and better use of Wangshuibai and Nanda2419 the two special germplasms in wheat breeding program.

Chromosome Mapping↗
PubMed2006

Establishing a statistic model for recognition of steroid hormone response elements.

Identification of hormone response elements (HREs) is essential for understanding the mechanism of hormone-regulated gene expression. To date, there has been a lack of effective bioinformatics tools for recognition of specific HRE such as Progesterone Response Elements (PRE). In this paper, a comprehensive survey and comparison of in silico methods is conducted for establishing a more accurate statistic model. Homogeneity of steroid HRE is analyzed and a reliable training dataset is constructed through extensive searching for experimentally validated response elements from more than 150 literature sources. Based on the observation that the verified HREs carry di-nucleotide preservation in comparison with uniform nucleotide distributions, both mono and di-nucleotide Position Weight Matrices are computed to extract the statistic pattern of the positions. It is followed by the sequence transition pattern recognition using a specifically designed profile Hidden Markov Model. Reciprocal combination of the statistic and transition patterns significantly improves the performance of the model in terms of higher sensitivity and specificity. Upon acquisition of the putative response elements in the promoter areas of vertebrate genes, a qualitative scheme is applied to assess the probability for each gene to be a hormone primary target. Using >650 records of experimentally validated steroid hormone response elements, a high sensitivity level of 73% and high specificity level of one prediction per 8.24 kb is reached, allowing this model to be used for further prediction of primary target genes through the analysis of their upstream promoters, for human or other vertebrate genomes of interest. Additional documents, supplementary data and the web-based program developed for response elements prediction are freely available for academic research at . Submission of putative gene promoter regions for recognition of potential regulatory PREs can be as long as 5 kb.

Animals↗
PubMed2006

Solution structure and characterization of the LGR8 receptor binding surface of insulin-like peptide 3.

Insulin-like peptide 3 (INSL3), a member of the relaxin peptide family, is produced in testicular Leydig cells and ovarian thecal cells. Gene knock-out experiments have identified a key biological role in initiating testes descent during fetal development. Additionally, INSL3 has an important function in mediating male and female germ cell function. These actions are elicited via its recently identified receptor, LGR8, a member of the leucine-rich repeat-containing G-protein-coupled receptor family. To identify the structural features that are responsible for the interaction of INSL3 with its receptor, its solution structure was determined by NMR spectroscopy together with in vitro assays of a series of B-chain alanine-substituted analogs. Synthetic human INSL3 was found to adopt a characteristic relaxin/insulin-like fold in solution but is a highly dynamic molecule. The four termini of this two-chain peptide are disordered, and additional conformational exchange is evident in the molecular core. Alanine-substituted analogs were used to identify the key residues of INSL3 that are responsible for the interaction with the ectodomain of LGR8. These include Arg(B16) and Val(B19), with His(B12) and Arg(B20) playing a secondary role, as evident from the synergistic effect on the activity in double and triple mutants involving these residues. Together, these amino acids combine with the previously identified critical residue, Trp(B27), to form the receptor binding surface. The current results provide clear direction for the design of novel specific agonists and antagonists of this receptor.

Amino Acid Sequence↗
PubMed2006

Deficiency of decay accelerating factor and CD59 leads to crisis in experimental myasthenia.

In myasthenia gravis (MG), neuromuscular transmission is disrupted due to the production of autoantibodies against acetylcholine receptors (AChR). In previous work, we showed that decay accelerating factor (DAF or CD55), an intrinsic cell surface complement regulator that disables C3/C5 amplification convertases, protects against receptor loss and muscle weakness. In this study, we examined whether, and if so, to what extent CD59, a downstream intrinsic cell surface regulator that prevents assembly of membrane attack complexes (MACs), contributes to this protection. Twenty-four hours after anti-AChR injection, we found that CD59a-/- mice did not significantly differ from WTs, all Daf1-/- CD59a-/- mice either died or required euthanasia. At 48h, Daf1-/- were significantly weaker than CD59a-/- and WT mice, and for these mice immunohistochemistry revealed marked C9 deposition at postsynaptic junctions, radioimmunoassays showed reductions in AChR levels, and electron microscopy demonstrated massive junctional damage. These data indicate that DAF serves as the initial shield that protects the neuromuscular junction whereas CD59 is a further barrier. They argue that complement inhibitor, particularly if targeted to the receptor, could then have therapeutic value in human MG.

Analysis of Variance↗
PubMed2006

Detection and identification of intestinal pathogens in clinical specimens using DNA microarrays.

The detection and identification of intestinal pathogens is critical for clinical patient diagnosis and antimicrobial therapy. No currently available assays with DNA microarrays can simultaneously detect and identify multiple intestinal pathogens, because there is no appropriate method for choosing target probes. To solve the problem we have experimented for facilitating screening of specific probes and developed a rapid (<3h) and reliable assay for simultaneous detection of intestinal pathogens using two universal PCR primers to amplify two variable regions of bacterial 16S and 23S ribosomal DNA (rDNA) genes, and then applied to DNA microarrays, hybridization between probes and amplicons occurred. Through this idea for screening of probes the assay was successful in discriminating 15 genera or species of intestinal pathogens. The limit of detection was approximately 10(3)CFU/mL for one species of pathogen and 10(5)CFU/mL for six species pathogens existing simultaneously in stool. When this assay was applied directly to identify 99 clinical specimens, 80(80.8%) were correctly analyzed, including four with mixed pathogens; 8(8.08%) received negative results due to no corresponding probes in this array and 11(11.11%) belonging to our targets were misidentified due to low-level pathogens and other factors. This approach is also convenient to obtain specific and proper probes while establishing assays for the applications in other aspects using DNA microarrays. In addition, the more species may be added to this system easily and endlessly by screening of candidate target probes in order to increase the power of simultaneous detection.

Bacterial Infections↗
PubMed2006

The sensitivity and specificity of a simple test to distinguish between urge and stress urinary incontinence.

BACKGROUND: Urinary incontinence is common in women. Because treatments differ, urge incontinence should be distinguished from stress incontinence. To make this distinction, current guidelines recommend an extensive evaluation that is too time-consuming for primary care practice. OBJECTIVE: To test the accuracy of a simple questionnaire to categorize type of urinary incontinence in women. DESIGN: Multicenter, prospective study of the accuracy of the 3 Incontinence Questions (3IQ) compared with an extended evaluation to distinguish between urge incontinence and stress incontinence. SETTING: 5 academic medical centers in the United States. PARTICIPANTS: 301 women enrolled from April to December 2004 who were older than 40 years of age (mean age, 56 years [SD, 11]) with untreated incontinence for an average of 7 years (SD, 7) and a broad range of incontinence severity. MEASUREMENTS: All participants included in the analyses answered the 3IQ questionnaire, and a urologist or urogynecologist who was blinded to the responses performed the extended evaluation. Sensitivity, specificity, and likelihood ratios were determined for the 3IQ. RESULTS: For classification of urge incontinence and with the extended evaluation as the gold standard, the 3IQ had a sensitivity of 0.75 (95% CI, 0.68 to 0.81), a specificity of 0.77 (CI, 0.69 to 0.84), and a positive likelihood ratio of 3.29 (CI, 2.39 to 4.51). For classification of stress incontinence, the sensitivity was 0.86 (CI, 0.79 to 0.90), the specificity was 0.60 (CI, 0.51 to 0.68), and the positive likelihood ratio was 2.13 (CI, 1.71 to 2.66). LIMITATIONS: Participants were enrolled by urologists and urogynecologists at academic medical centers. CONCLUSIONS: The 3IQ questionnaire is a simple, quick, and noninvasive test with acceptable accuracy for classifying urge and stress incontinence and may be appropriate for use in primary care settings. Similar studies are needed in other populations. We also need a clinical trial comparing the outcomes of treatments based on the 3IQ and the extended evaluation.

Adult↗
PubMed2006

The carboxyl-terminal nucleoplasmic region of MAN1 exhibits a DNA binding winged helix domain.

MAN1 is an integral protein of the inner nuclear membrane that interacts with nuclear lamins and emerin, thus playing a role in nuclear organization. It also binds to chromatin-associated proteins and transcriptional regulators, including the R-Smads, Smad1, Smad2, and Smad3. Mutations in the human gene encoding MAN1 cause sclerosing bone dysplasias, which sometimes have associated skin abnormalities. At the molecular level, these mutations lead to loss of the MAN1-R-Smads interaction, thus perturbing transforming growth factor beta superfamily signaling pathway. As a first step to understanding the physical basis of MAN1 interaction with R-Smads, we here report the structural characterization of the carboxyl-terminal nucleoplasmic region of MAN1, which is responsible for Smad binding. This region exhibits an amino-terminal globular domain adopting a winged helix fold, as found in several Smad-associated sequence-specific DNA binding factors. Consistently, it binds to DNA through the positively charged recognition helix H3 of its winged helix motif. However, it does not show the predicted carboxyl-terminal U2AF homology domain in solution, suggesting that the folding and stability of such a domain in MAN1 depend upon binding to an unidentified partner. Modeling the complex between DNA and the winged helix domain shows that the regions involved in DNA binding are essentially distinct from those reported to be involved in Smad binding. This suggests that MAN1 binds simultaneously to R-Smads and their targeted DNA sequences.

Amino Acid Sequence↗
PubMed2006

Analogs of insulin-like peptide 3 (INSL3) B-chain are LGR8 antagonists in vitro and in vivo.

Insulin-like peptide 3 (INSL3) is a member of the insulin superfamily that plays an important role in mediating testes descent during fetal development. More recently, it has also been demonstrated to initiate oocyte maturation and suppress male germ cell apoptosis. These actions are mediated via a specific G-protein-coupled receptor, LGR8. Little is known regarding the structure and function relationship of INSL3, although it is believed that the principal receptor binding site resides within its B-chain. We subsequently observed that the linear B-chain alone (INSL3B-(1-31)) bound to LGR8 and was able to antagonise INSL3 stimulated cAMP accumulation in HEK-293T cells expressing LGR8. Sequentially N- and C-terminally shortened linear analogs were prepared by solid phase synthesis and subsequent assay showed that the minimum length required for binding was residues 11-27. It was also observed that increased binding affinity correlated with a corresponding increase in alpha-helical content as measured by circular dichroism spectroscopy. Molecular modeling studies suggested that judicious placement of a conformational constraint within this peptide would increase its alpha-helix content and result in increased structural similarity to the B-chain within native INSL3. Consequently, intramolecularly disulfide-linked analogs of the B-chain showed a potentiation of INSL3 antagonistic activity, as well as exhibiting increased proteolytic stability, as assessed in rat serum in vitro. Administration of one of these peptides into the testes of rats resulted in a substantial decrease in testis weight probably due to the inhibition of germ cell survival, suggesting that INSL3 antagonists may have potential as novel contraceptive agents.

Amino Acid Sequence↗
PubMed2006

The role of decay-accelerating factor as a receptor for Helicobacter pylori and a mediator of gastric inflammation.

Persistent gastritis induced by Helicobacter pylori is the strongest known risk factor for peptic ulcer disease and distal gastric adenocarcinoma, a process for which adherence of H. pylori to gastric epithelial cells is critical. Decay-accelerating factor (DAF), a protein that protects epithelial cells from complement-mediated lysis, also functions as a receptor for several microbial pathogens. In this study, we investigated whether H. pylori utilizes DAF as a receptor and the role of DAF within H. pylori-infected gastric mucosa. In vitro studies showed that H. pylori adhered avidly to Chinese hamster ovary cells expressing human DAF but not to vector controls. In H. pylori, disruption of the virulence factors vacA, cagA, and cagE did not alter adherence, but deletion of DAF complement control protein (CCP) domains 1-4 or the heavily O-glycosylated serine-threonine-rich COOH-terminal domain reduced binding. In cultured gastric epithelial cells, H. pylori induced transcriptional up-regulation of DAF, and genetic deficiency of DAF attenuated the development of inflammation among H. pylori-infected mice. These results indicate that DAF may regulate H. pylori-epithelial cell interactions relevant to pathogenesis.

Animals↗
PubMed2006

[Early outcome of orthotopic heart transplantation: a report of 21 cases].

OBJECTIVE: To report the preliminary experience of 21 orthotopic heart transplantations without early death. METHODS: Between April 2002 and June 2005, 21 patients underwent orthotopic heart transplantation. Recipients' pulmonary vascular resistance ranged from 3.0 to 5.9 wood units [mean (4.3 +/- 1.4) wood units]; Stanford myocardial protective solution or HTK solution was perfused for donor heart myocardial preservation, donor heart cold ischemic period ranged from 52 to 310 min [mean (81 +/- 23) min]; Three patients had previous cardiac operations under cardiopulmonary bypass, conventional Stanford orthotopic cardiac transplantation in 20 cases and total heart technique in 1 case; Recipients received simulect preoperatively and cyclosporine A, cellcept and prednisone postoperatively for prevention of acute allograft rejection; Patients received appropriate medical control of hypertension, hyperglycemia, hypercholesterolemia and uricacidemia. RESULTS: Acute right heart failure in 3 cases and pericardial effusion in 4 cases were observed at the early postoperative stage, but no any infection and acute rejection were found. All patients survived with good life quality. CONCLUSIONS: Heart transplantation may produce satisfying early results. Suitable selection of recipients with low pulmonary vascular resistance, excellent donor heart conservation, practised anastomotic technique, proper immunosuppression treatment and efficient postoperative management are key measures of orthotopic heart transplantation with excellent early outcome.

Adolescent↗
PubMed2006

Phenotypic predictors of response to simvastatin therapy among African-Americans and Caucasians: the Cholesterol and Pharmacogenetics (CAP) Study.

Although statins are effective lipid-lowering agents, the phenotypic and demographic predictors of such lowering have been less well examined. We enrolled 944 African-American and white men and women who completed an open-label, 6-week pharmacogenetics trial of 40 mg of simvastatin. The phenotypic and demographic variables were examined as predictors of the change in lipids and lipoproteins using linear regression analysis. On average, treatment with simvastatin lowered low-density lipoprotein (LDL) cholesterol by 54 mg/dl and increased high-density lipoprotein (HDL) cholesterol by 2 mg/dl. Compared with African-Americans, whites had a 3-mg/dl greater LDL reduction and a 1-mg/dl higher HDL elevation, independent of other variables, including baseline lipoprotein levels (p <0.01). Multivariate analyses revealed moderate subgroup differences, with older participants having a larger decrease in LDL cholesterol and apolipoprotein B levels compared with younger participants (p <0.001), women having larger increases in HDL than men (p <0.01), nonsmokers having larger decreases in LDL and triglyceride levels compared with smokers (p <0.05), those with hypertension having smaller decreases in apolipoprotein B than those without hypertension (p <0.05), and those with a larger waist circumference having a diminished lowering of triglycerides in response to treatment with simvastatin (p <0.01). In conclusion, treatment with simvastatin produced favorable lipid and lipoprotein changes among all participants. The magnitude of the lipid and lipoprotein responses, however, differed among participants according to a number of phenotypic and demographic characteristics.

Adult↗