Biomedical subjects

Gang Fang

Publications and source records attributed to Gang Fang.

14 recordsLinked to original sources

PubMed2026

Barcoded oligonucleotide system (BOLT) for targeted organ delivery.

The therapeutic potential of oligonucleotides (oligos) is limited by insufficient delivery to extrahepatic tissues. In vitro assays often fail to accurately predict in vivo behavior, while testing each oligo candidate in animals remains inherently low throughput. Here, we conceive a barcoded oligonucleotide system (BOLT), a platform that enables high-throughput in vivo evaluations of small-molecule ligands and identifies tissue-specific oligo delivery. BOLT integrates rational design of oligo barcodes, modular conjugation chemistry, and next-generation sequencing (NGS)-based quantification, allowing simultaneous evaluation of many chemically diverse ligand-oligo conjugates within a single animal. Notably, this platform is applicable in both mice and nonhuman primates (NHPs). Using BOLT, we discovered ligands with tropism for tissues such as the brain, lung, and muscle. Collectively, these results indicate that the BOLT platform can accelerate the discovery of tissue-targeting ligands for broad oligo therapeutics.

Journal Article↗

PubMed2026

A single DNA methylation site regulates cell fate during Clostridioides difficile sporulation.

DNA methylation is a widespread phenomenon in bacteria that can regulate gene expression, although the mechanisms underlying this epigenetic regulation are often poorly understood. In Clostridioides difficile, the orphan DNA methyltransferase CamA promotes sporulation, a process critical for the persistence and transmission of this nosocomial pathogen. However, the specific CamA target genes that drive this increased sporulation phenotype were unknown. Here, we show that methylation of a single CamA motif in the promoter region of spoIIE, which encodes a factor critical for activating the early-acting sporulation sigma factor, σF, is sufficient to promote spoIIE transcription, σF activation, and spore formation. Surprisingly, the CamA-dependent increase in spoIIE expression also increases the frequency with which cells prematurely activate σF prior to asymmetric division, resulting in miscompartmentalized σF activity. While this premature activation event triggers cell lysis in the well-studied spore-former Bacillus subtilis, we show that C. difficile cells retain developmental plasticity: predivisional cells that have prematurely activated σF can abort sporulation and resume vegetative growth, whereas cells that activate σF in the forespore after asymmetric division remain committed to sporulation. Thus, DNA methylation controls a critical cell fate decision in C. difficile without compromising its capacity to adapt to fluctuating environmental conditions. Finally, we show that CamA confers a significant fitness advantage during murine infection through mechanisms largely independent of its ability to promote sporulation. Since CamA is specific to C. difficile and epigenetically regulates multiple pathways critical for pathogen persistence, these analyses imply that CamA could be a promising antimicrobial target.

DNA Methylation↗

PubMed2006

[Use of PAR index to evaluate the treatment outcome for Class II division 1 malocclusion with different tooth extraction patterns].

PURPOSE: To assess the outcome of orthodontic treatment for Class II division 1 malocclusion with different tooth extraction patterns using PAR index. METHODS: PAR index was applied on pre- and post-orthodontic treatment cast for 64 Class II division 1 malocclusion patients with two different tooth extraction patterns: extraction of maxillary teeth only (Group 1), and extraction of maxillary and mandibular teeth(Group 2). SPSS 10.0 software package was used for Student's t test. RESULTS: The PAR index of group 1 and group 2 pre-orthodontic treatment was 36.21+/-6.82 and 38.34+/-7.51. There were no significant difference (P>0.05) between the two groups. The PAR index of group 1 and group 2 post-orthodontic treatment was 6.13+/-1.64 and 5.89+/-1.75. There were no significant difference (P>0.05) between the two groups. The decrement and the rate of reduction of group 1 was 30.05+/-7.43 and 85.33%+/-5.68%. The decrement and the rate of reduction of group 2 was 32.38+/-8.12 and 87.47%+/-5.21%. The occlusal relationship improved significantly in the two groups after treatment. CONCLUSIONS: Treatment for Class II division 1 malocclusion with different extraction patterns can both acquire satisfactory results.

Humans↗

PubMed2005

The two authentic methionine aminopeptidase genes are differentially expressed in Bacillus subtilis.

BACKGROUND: Two putative methionine aminopeptidase genes, map (essential) and yflG (non-essential), were identified in the genome sequence of Bacillus subtilis. We investigated whether they can function as methionine aminopeptidases and further explored possible reasons for their essentiality or dispensability in B. subtilis. RESULTS: In silico analysis of MAP evolution uncovered a coordinated pattern of MAP and deformylase that did not correlate with the pattern of 16S RNA evolution. Biochemical assays showed that both MAP (MAP_Bs) and YflG (YflG_Bs) from B. subtilis overproduced in Escherichia coli and obtained as pure proteins exhibited a methionine aminopeptidase activity in vitro. Compared with MAP_Bs, YflG_Bs was approximately two orders of magnitude more efficient when assayed on synthetic peptide substrates. Both map and yflG genes expressed in multi-copy plasmids could complement the function of a defective map gene in the chromosomes of both E. coli and B. subtilis. In contrast, lacZ gene transcriptional fusions showed that the promoter activity of map was 50 to 100-fold higher than that of yflG. Primer extension analysis detected the transcription start site of the yflG promoter. Further work identified that YvoA acted as a possible weak repressor of yflG expression in B. subtilis in vivo. CONCLUSION: Both MAP_Bs and YflG_Bs are functional methionine aminopeptidases in vitro and in vivo. The high expression level of map and low expression level of yflG may account for their essentiality and dispensality in B. subtilis, respectively, when cells are grown under laboratory conditions. Their difference in activity on synthetic substrates suggests that they have different protein targets in vivo.

Aminopeptidases↗

PubMed2005

Coping with cold: the genome of the versatile marine Antarctica bacterium Pseudoalteromonas haloplanktis TAC125.

A considerable fraction of life develops in the sea at temperatures lower than 15 degrees C. Little is known about the adaptive features selected under those conditions. We present the analysis of the genome sequence of the fast growing Antarctica bacterium Pseudoalteromonas haloplanktis TAC125. We find that it copes with the increased solubility of oxygen at low temperature by multiplying dioxygen scavenging while deleting whole pathways producing reactive oxygen species. Dioxygen-consuming lipid desaturases achieve both protection against oxygen and synthesis of lipids making the membrane fluid. A remarkable strategy for avoidance of reactive oxygen species generation is developed by P. haloplanktis, with elimination of the ubiquitous molybdopterin-dependent metabolism. The P. haloplanktis proteome reveals a concerted amino acid usage bias specific to psychrophiles, consistently appearing apt to accommodate asparagine, a residue prone to make proteins age. Adding to its originality, P. haloplanktis further differs from its marine counterparts with recruitment of a plasmid origin of replication for its second chromosome.

Adaptation, Physiological↗

PubMed2005

How essential are nonessential genes?

Gene essentiality in bacteria has been identified in silico, focusing on gene persistence, or experimentally, focusing on the growth of knockouts in rich media. Comparing 55 genomes of Firmicutes and Gamma-proteobacteria to identify the genes which, while persistent among genomes, do not lead to a lethal phenotype when inactivated, we show that the characteristics of persistence, conservation, expression, and location are shared between persistent nonessential (PNE) genes and experimentally essential genes. PNE genes show an overrepresentation of genes related to maintenance and stress response. This outlines the limits of current experimental techniques to define gene essentiality and highlights the essential role of genes implicated in maintenance which, although dispensable for growth, are not dispensable from an evolutionary point of view. Firmicutes and Gamma-proteobacteria are mostly differing in the construction of the cell envelope, DNA replication and proofreading, and RNA degradation. In addition to suggesting functions for persistent genes that had until now resisted identification, we show that these genes have many characters in common with experimentally identified essential genes. They should then be regarded as truly essential genes.

Codon↗

PubMed2005

Specialized microbial databases for inductive exploration of microbial genome sequences.

BACKGROUND: The enormous amount of genome sequence data asks for user-oriented databases to manage sequences and annotations. Queries must include search tools permitting function identification through exploration of related objects. METHODS: The GenoList package for collecting and mining microbial genome databases has been rewritten using MySQL as the database management system. Functions that were not available in MySQL, such as nested subquery, have been implemented. RESULTS: Inductive reasoning in the study of genomes starts from "islands of knowledge", centered around genes with some known background. With this concept of "neighborhood" in mind, a modified version of the GenoList structure has been used for organizing sequence data from prokaryotic genomes of particular interest in China. GenoChore http://bioinfo.hku.hk/genochore.html, a set of 17 specialized end-user-oriented microbial databases (including one instance of Microsporidia, Encephalitozoon cuniculi, a member of Eukarya) has been made publicly available. These databases allow the user to browse genome sequence and annotation data using standard queries. In addition they provide a weekly update of searches against the world-wide protein sequences data libraries, allowing one to monitor annotation updates on genes of interest. Finally, they allow users to search for patterns in DNA or protein sequences, taking into account a clustering of genes into formal operons, as well as providing extra facilities to query sequences using predefined sequence patterns. CONCLUSION: This growing set of specialized microbial databases organize data created by the first Chinese bacterial genome programs (ThermaList, Thermoanaerobacter tencongensis, LeptoList, with two different genomes of Leptospira interrogans and SepiList, Staphylococcus epidermidis) associated to related organisms for comparison.

Algorithms↗

PubMed2005

Total synthesis of scutellarin-7-O-glucuronide.

Scutellarin-7-O-glucuronide (1) has been synthesized from 2-hydroxyl-4,5,6-trimethoxyacetophenone through eight steps, including Michael addition, cyclization, hydrogenation, hydroxyl protection, deprotection, etc. The overall yield of 13% is much higher than that reported (0.6%) by L. Farkas, G. Mezey-Vàndor et al. in 1974.

Acetophenones↗

PubMed2005

[Effect of Twin-block appliance in the treatment of Class II and division I malocclusion: a cephalometric study in 12 patients].

PURPOSE: To quantitatively evaluate the skeletal and dentoalveolar changes induced by Twin-block appliance for treatment of Class II,division I malocclusions in growing children. METHODS: Twelve patients with Class II, division I malocclusions aged 10 to 12 years were investigated. The records were evaluated and compared with an age-matched sample of untreated Class II control subjects. The follow-up period was 12 months. Group t test was used for comparison. RESULTS: In the treatment group, the upper incisors retroclination of the upper incisors and the mandibular forward movement contributed more to the overjet reduction. The skeletal and dental effects changes molar correction were almost similar. The mandibular growth in the treatment group was 2.29 mm, greater than that in the control group. The posterior facial height and the anterior lower facial height increased by 2.28 mm and 2.58 mm respectively. On the other hand, unfavorable vertical changes were not observed. CONCLUSIONS: The treatment of Class II division I malocclusion with Twin-block appliance was effective in reducing overjet, correcting molar relationship and improving soft tissue profile. It can also enhance mandibular growth.

Case-Control Studies↗

PubMed2004

Population-based medication reviews: a descriptive analysis of the medication issues identified in a medicare not-for-profit prescription discount program.

BACKGROUND: Medication reviews may be an important strategy to improve medication use, especially for individuals receiving many drugs. OBJECTIVE: To describe the types of medication issues and recommendations identified in the Iowa Priority Brown Bag Medication Reviews, compare individuals with medication issues with those without medication issues, and describe Iowa Priority enrollees' experiences with and satisfaction of the review. METHODS: A retrospective review of enrollment forms and medication review records and a survey of Iowa Priority members were conducted in 2002. Subjects were Medicare-eligible individuals who joined the Iowa Priority Prescription Savings Program. Frequency distributions and descriptive statistics were calculated. Analysis using t-test and chi(2) test determined differences between individuals with and without issues regarding use of drug therapy. RESULTS: Almost 13% of Iowa Priority enrollees received a review. There were 1167 individuals with 2123 medication issues identified. Nonprescription medications accounted for one-third of drug interactions and >40% of duplications. People with issues had poorer health, more chronic conditions, and took more drugs than people without medication issues. One-third of survey respondents discussed the review with their physicians, and 17.7% reported medication changes. Satisfaction with the review was good; however, only 24% were likely to have received an annual review. CONCLUSIONS: Iowa Priority Brown Bag Medication Reviews showed that individuals with fair/poor health, higher numbers of medications, and more chronic conditions were likely to have medication issues. Reviews generated discussions between physicians and patients, produced some medication changes, and helped individuals save money.

Aged↗

PubMed2003

PepPat, a pattern-based oligopeptide homology search method and the identification of a novel tachykinin-like peptide.

UNLABELLED: PepPat, a hybrid method that combines pattern matching with similarity scoring, is described. We also report PepPat's application in the identification of a novel tachykinin-like peptide. PepPat takes as input a query peptide and a user-specified regular expression pattern within the peptide. It first performs a database pattern match and then ranks candidates on the basis of their similarity to the query peptide. PepPat calculates similarity over the pattern spanning region, enhancing PepPat's sensitivity for short query peptides. PepPat can also search for a user-specified number of occurrences of a repeated pattern within the target sequence. We illustrate PepPat's application in short peptide ligand mining. As a validation example, we report the identification of a novel tachykinin-like peptide, C14TKL-1, and show it is an NK1 (neuokinin receptor 1) agonist whose message is widely expressed in human periphery. AVAILABILITY: PepPat is offered online at: http://peppat.cbi.pku.edu.cn.

Algorithms↗

PubMed2003

[Introduction to genome databases].

A brief introduction to the genome databases GDB, GenoList and Ensembl is given. These databases, mirrored and maintained at the Centre of Bioinformatics, Peking University, provide useful information for genome research.

English Abstract↗

PubMed2002

Parallel cloning, expression, purification and crystallization of human proteins for structural genomics.

54 human genes were selected as test targets for parallel cloning, expression, purification and crystallization. Proteins from these genes were selected to have a molecular weight of between 14 and 50 kDa, not to have a high percentage of hydrophobic residues (i.e. more likely to be soluble) and to have no known crystal structures and were not known to be subunits of heterocomplexes. Four proteins containing transmembrane regions were selected for comparative tests. To date, 44 expression clones have been constructed with the Gateway cloning system (Invitrogen, The Netherlands). Of these, 35 clones were expressed as recombinant proteins in Escherichia coli strain BL21 (DE3)-pLysS, of which 12 were soluble and four have been purified to homogeneity. Crystallization conditions were screened for the purified proteins in 96-well plates under oil. After further refinement with the same device or by the hanging-drop method, crystals were grown, with needle, plate and prism shapes. A 2.12 A data set was collected for protein NCC27. The results provide insights into the high-throughput target selection, cloning, expression and crystallization of human genomic proteins.

Base Sequence↗

PubMedDate not supplied

Outcomes-based pharmacist reimbursement: reimbursing pharmacists for cognitive services part 1.

OBJECTIVES: (1) Describe the structure of an outcomes-based method of pharmacist reimbursement for cognitive services, (2) outline the structure of an intervention program, (3) explain a mechanism to increase the provision of pharmacists. cognitive services, and (4) summarize findings from the first year of operations of this outcomes-based pharmacist reimbursement program (OBPR). METHODS: A cross-sectional descriptive study was completed using the claims submitted by pharmacists to summarize findings from the first year of operations of this OBPR. The program involves collaboration between pharmacy benefit managers (PBMs) and community pharmacists to improve medication use. Pharmacists were reimbursed for (1) converting therapeutic regimens to generic drugs or preferred formulary medications when a prescriber contact is required; (2) conducting patient education and follow-up after initiation of new medications, changes in drug therapy, or following an over-the-counter (OTC) consultation; and (3) resolving drug-therapy problems. An efficient, no-cost billing system was created. Pharmacies participating in this program are located in cities throughout Iowa, ranging in population from a few hundred to more than 100,000. The main outcome measures were descriptive statistics of prescriptions, intervention claims, and pharmacist participation in the program. Frequency distributions and descriptive statistics were used to summarize the first year of claims. Comparisons of averages were completed with t tests. Chi-square tests were used to compare frequency distributions. RESULTS: Data analysis for the first year of operation, July 1, 2000, through June 30, 2001, showed that 11,326 enrollees obtained 124,768 prescriptions. The majority of individuals (n=8335, 74%) received some intervention service. The majority (90%) of intervention services were patient education and follow-up on new prescriptions or changes in prescriptions. More than 200 individuals had drug-related problems. There was variability in the level of service per pharmacy as the median number of intervention services was 30, while the mean was 113?188, among those providing any interventions. CONCLUSION: This unique system of outcomes-based pharmacist reimbursement permits community pharmacists to document and bill for cognitive services. It has demonstrated that PBMs and community pharmacists can work together to improve drug therapy, and it may reduce health care costs.

Journal Article↗