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1.  Salivary Gland Branching Morphogenesis – Recent Progress and Future Opportunities 
Salivary glands provide saliva to maintain oral health, and a loss of salivary gland function substantially decreases quality-of-life. Understanding the biological mechanisms that generate salivary glands during embryonic development may identify novel ways to regenerate function or design artificial salivary glands. This review article summarizes current research on the process of branching morphogenesis of salivary glands, which creates gland structure during development. We highlight exciting new advances and opportunities in studies of cell-cell interactions, mechanical forces, growth factors, and gene expression patterns to improve our understanding of this important process.
PMCID: PMC3168569  PMID: 21125789
salivary gland; epithelium; branching morphogenesis; fibronectin; E-cadherin; growth factor
2.  Oral Microbiology: Past, Present and Future 
Since the initial observations of oral bacteria within dental plaque by van Leeuwenhoek using his primitive microscopes in 1680, an event that is generally recognized as the advent of oral microbiological investigation, oral microbiology has gone through phases of “reductionism” and “holism”. From the small beginnings of the Miller and Black period, in which microbiologists followed Koch’s postulates, took the reductionist approach to try to study the complex oral microbial community by analyzing individual species; to the modern era when oral researchers embrace “holism” or “system thinking”, adopt new concepts such as interspecies interaction, microbial community, biofilms, poly-microbial diseases, oral microbiological knowledge has burgeoned and our ability to identify the resident organisms in dental plaque and decipher the interactions between key components has rapidly increased, such knowledge has greatly changed our view of the oral microbial flora, provided invaluable insight into the etiology of dental and periodontal diseases, opened the door to new approaches and techniques for developing new therapeutic and preventive tools for combating oral poly-microbial diseases.
PMCID: PMC2949409  PMID: 20687296
3.  Salivary Gland Branching Morphogenesis — Recent Progress and Future Opportunities 
Salivary glands provide saliva to maintain oral health, and a loss of salivary gland function substantially decreases quality-of-life. Understanding the biological mechanisms that generate salivary glands during embryonic development may identify novel ways to regenerate function or design artificial salivary glands. This review article summarizes current research on the process of branching morphogenesis of salivary glands, which creates gland structure during development. We highlight exciting new advances and opportunities in studies of cell-cell interactions, mechanical forces, growth factors, and gene expression patterns to improve our understanding of this important process.
doi:10.4248/IJOS10042
PMCID: PMC3168569  PMID: 21125789
salivary gland; epithelium; branching morphogenesis; fibronectin; E-cadherin; growth factor
4.  Porphyromonas gingivalis Resistance to Polymyxin B Is Determined by the Lipid A 4′-Phosphatase, PGN_0524 
Aim
To elucidate the genetic basis for the pronounced resistance that the oral pathogen, Porphyromonas gingivalis (P. gingivalis), exhibits towards the cationic antimicrobial peptide, polymyxin B.
Methodology
A genetic screen of P. gingivalis clones generated by a Tn4400′-based random insertion mutagenesis strategy was performed to identify bacteria harboring novel genetic mutations that render P. gingivalis susceptible to killing by the cationic antimicrobial peptide, polymyxin B (PMB, 50 μg·mL−1).
Results
P. gingivalis (ATCC 33277) is unusually resistant to the cationic antimicrobial peptide, PMB at relatively high concentrations (200 μg·mL−1). Approximately 2,700 independent Tn4400′-derived mutants of P. gingivalis were examined for increased sensitivity to PMB killing at a relatively low dose (50 μg·mL−1). A single PMB-sensitive mutant was obtained in this phenotypic screen. We determined that the Tn4400′ transposon was integrated into the gene encoding the lipid A 4′-phosphatase, PGN_0524, demonstrating that this insertion event was responsible for its increased susceptibility of this clone to PMB-dependent killing. The resulting mutant strain, designated 0524-Tn4400′, was highly sensitive to PMB killing relative to wild-type P. gingivalis, and exhibited the same sensitivity as the previously characterized strain, 0524KO, which bears a genetically engineered deletion in the PGN_0524 locus. Positive ion mass spectrometric structural (MALDI-TOF MS) analyses revealed that lipid A isolates from 0524-Tn4400′ and 0524KO strains displayed strikingly similar MALDI-TOF MS spectra that were substantially different from the wild-type P. gingivalis lipid A spectrum. Finally, intact 0524-Tn4400′ and 0524KO mutant bacteria, as well as their corresponding LPS isolates, were significantly more potent in stimulating Toll-like receptor 4 (TLR4)-dependent E-selectin expression in human endothelial cells relative to intact wild-type P. gingivalis or its corresponding LPS isolate.
Conclusion
The combined molecular evidence provided in this report suggests that PGN_0524, a lipid A 4′-phosphatase, is the sole genetic element conferring the ability of the periodontopathogen, P. gingivalis, to evade the killing activity of cationic antimicrobial peptides, such as PMB. These data strongly implicate PGN_0524 as a critical virulence factor for the ability of P. gingivalis to evade front-line host innate defenses that are dependent upon cationic antimicrobial peptide activity and TLR4 sensing.
doi:10.4248/IJOS.09062
PMCID: PMC2909122  PMID: 20657724
P. gingivalis; antimicrobial peptide; lipid A phosphatase; polymyxin B; transposon; lipopolysaccharide
5.  Porphyromonas gingivalis Resistance to Polymyxin B Is Determined by the Lipid A 4′-Phosphatase, PGN_0524 
Aim
To elucidate the genetic basis for the pronounced resistance that the oral pathogen, Porphyromonas gingivalis (P. gingivalis), exhibits towards the cationic antimicrobial peptide, polymyxin B.
Methodology
A genetic screen of P. gingivalis clones generated by a Tn4400′-based random insertion mutagenesis strategy was performed to identify bacteria harboring novel genetic mutations that render P. gingivalis susceptible to killing by the cationic antimicrobial peptide, polymyxin B (PMB, 50 μg·mL−1).
Results
P. gingivalis (ATCC 33277) is unusually resistant to the cationic antimicrobial peptide, PMB at relatively high concentrations (200 μg·mL−1). Approximately 2,700 independent Tn4400′-derived mutants of P. gingivalis were examined for increased sensitivity to PMB killing at a relatively low dose (50 μg·mL−1). A single PMB-sensitive mutant was obtained in this phenotypic screen. We determined that the Tn4400′ transposon was integrated into the gene encoding the lipid A 4′-phosphatase, PGN_0524, demonstrating that this insertion event was responsible for its increased susceptibility of this clone to PMB-dependent killing. The resulting mutant strain, designated 0524-Tn4400′, was highly sensitive to PMB killing relative to wild-type P. gingivalis, and exhibited the same sensitivity as the previously characterized strain, 0524KO, which bears a genetically engineered deletion in the PGN_0524 locus. Positive ion mass spectrometric structural (MALDI-TOF MS) analyses revealed that lipid A isolates from 0524-Tn4400′ and 0524KO strains displayed strikingly similar MALDI-TOF MS spectra that were substantially different from the wild-type P. gingivalis lipid A spectrum. Finally, intact 0524-Tn4400′ and 0524KO mutant bacteria, as well as their corresponding LPS isolates, were significantly more potent in stimulating Toll-like receptor 4 (TLR4)-dependent E-selectin expression in human endothelial cells relative to intact wild-type P. gingivalis or its corresponding LPS isolate.
Conclusion
The combined molecular evidence provided in this report suggests that PGN_0524, a lipid A 4′-phosphatase, is the sole genetic element conferring the ability of the periodontopathogen, P. gingivalis, to evade the killing activity of cationic antimicrobial peptides, such as PMB. These data strongly implicate PGN_0524 as a critical virulence factor for the ability of P. gingivalis to evade front-line host innate defenses that are dependent upon cationic antimicrobial peptide activity and TLR4 sensing.
doi:10.4248/IJOS.09062
PMCID: PMC2909122  PMID: 20657724
P. gingivalis; antimicrobial peptide; lipid A phosphatase; polymyxin B; transposon; lipopolysaccharide
6.  Oral Microbiology: Past, Present and Future 
Since the initial observations of oral bacteria within dental plaque by van Leeuwenhoek using his primitive microscopes in 1680, an event that is generally recognized as the advent of oral microbiological investigation, oral microbiology has gone through phases of “reductionism” and “holism”. From the small beginnings of the Miller and Black period, in which microbiologists followed Koch's postulates, took the reductionist approach to try to study the complex oral microbial community by analyzing individual species; to the modern era when oral researchers embrace “holism” or “system thinking”, adopt new concepts such as interspecies interaction, microbial community, biofilms, poly-microbial diseases, oral microbiological knowledge has burgeoned and our ability to identify the resident organisms in dental plaque and decipher the interactions between key components has rapidly increased, such knowledge has greatly changed our view of the oral microbial flora, provided invaluable insight into the etiology of dental and periodontal diseases, opened the door to new approaches and techniques for developing new therapeutic and preventive tools for combating oral poly-microbial diseases.
doi:10.4248/ijos.09029
PMCID: PMC2949409  PMID: 20687296
oral microbiology; biofilms; dental caries; oral pathogenesis

Results 1-6 (6)