Biology subjects

Seto, J.

Publications and source records attributed to Seto, J..

4 recordsLinked to original sources

bioRxiv2018

Accurate informatic modeling of tooth enamel pellicle interactions by training substitution matrices with Mat4Pep

MotivationProtein-hydroxyapatite interactions govern the development and homeostasis of teeth and bone. Characterization would enable design of peptides to regenerate mineralized tissues and control attachments such as ligaments and dental plaque. Progress has been limited because no available methods produce robust data for assessing phase interfaces.\n\nResultsWe show that tooth enamel pellicle peptides contain subtle sequence similarities that encode hydroxyapatite binding mechanisms, by segregating pellicle peptides from control sequences using our previously developed substitution matrix-based peptide comparison protocol (Oren et al., 2007), with improvements. Sampling diverse matrices, adding biological control sequences, and optimizing matrix refinement algorithms improves discrimination from 0.81 to 0.99 AUC in leave-one-out experiments. Other contemporary methods fail on this problem. We find hydroxyapatite interaction sequence patterns by applying the resulting selected refined matrix (\"pellitrix\") to cluster the peptides and build subgroup alignments. We identify putative hydroxyapatite maturation domains by application to enamel biomineralization proteins and prioritize putative novel pellicle peptides identified by In stageTip (iST) mass spectrometry. The sequence comparison protocol outperforms other contemporary options for this small and heterogeneous group, and is generalized for application to any group of peptides.\n\nAvailabilitySoftware to apply this protocol is freely available at github.com/JeremyHorst/Mat4Pep and compbio.org/protinfo/ Mat4Pep.\n\nContactjahorst@gmail.com, ram@compbio.org.\n\nSupplementary informationAvailable at Bioinformatics online.

bioinformatics↗

bioRxiv2018

On a Robust, Sensitive Cell-Free Method for Pseudomonas Sensing and Quantification

Cell - free lysates have found a utility in performing cellular functions and providing biologically-relevant metabolic products without the optimal biological conditions for growth and proliferation. By teasing out the biological components and constructing artificial conditions that enable for biological transcription and translation processes to occur, specific cell - like functions can be reconstituted in vitro without requiring the entire cell and milieu of cellular organelles. This enables for optimization of biological circuits, either by concentration or on/off switches, simply through the addition or removal of genetic components (plasmids, inducers, or repressors) of regulatory elements. Here, we demonstrate an application of cell - free process that is robust and portable, independent of a substrate, to apply for sensing and reporting functions of a quorum sensing molecule N-3-oxododecanoyl homoserine lactone (3OC12HSL) found crucial for pathological Pseudomonas infections. Using droplet microfluidics to integrate cell - free related functions into hydrogel scaffolds, we show that these cell - free circuits can be encapsulated, delivered, and activated in most environments--even in conditions with very little hydration.

synthetic biology↗

bioRxiv2017

Silver fluoride as a treatment for the disease dental caries

The current paradigm of treatment for dental caries (tooth decay) in primary teeth is dangerous, fails to reach many children, and suffers high recurrence. Acceptance of the paradigm arises from a misperception that untreated caries in primary teeth is a threat to life. We show a linear relationship between age and deaths in the United States from 1999 through 2015 caused by dental caries, pulpal / periapical abscess, or facial cellulitis. The intercept of 6 years coincides with emergence of the first permanent tooth: it appears that caries in primary teeth is not a threat to life. Thus, treatment goals should be to avoid pain, which is not possible with operative dentistry, as it causes pain. Medical management of caries is a distinct treatment philosophy which employs topical minimally invasive therapies that treat the disease, and is not merely prevention. Silver diamine fluoride (SDF) is a central agent to enable effective non-invasive treatment. The announcement of FDA Breakthrough Therapy designation suggests that SDF will become the first FDA approved drug for treating the disease dental caries. Since our last review, 4 clinical trials have been completed, which inform an update to the application protocol and frequency regimen. Suggestions from these studies are to skip the rinsing step due to demonstration of safety and concern of diminished effectiveness by dilution, and to start patients with an intensive regimen of multiple applications over the first few weeks. Breakthroughs in elucidating the impact of SDF on tooth structure and the plaque microbiome inform potential opportunities for bioengineering and understanding caries arrest, respectively. Dentists have been surprised by preference of this treatment over traditional invasive approaches. Renewed interest in this old material has delivered progress to optimize the judicious use of SDF, and enable a revolution in caries management - particularly for primary teeth.\n\nONE SENTENCE SUMMARYAnesthesia is inappropriate for first-line treatment of early childhood caries now that safe topical treatments such as silver diamine fluoride are available.

pharmacology and toxicology↗

bioRxiv2017

Silver microwires from treating tooth decay with silver diamine fluoride

Silver diamine fluoride (SDF) is a brush-on treatment for tooth decay that stops 81% of cavitated caries lesions (dental cavities). Before this innovation, caries was treatable only with operative approaches (dental fillings). SDF-treated lesions harden and become resistant to further decay. We hypothesized that the hardening is due to reaction with silver, rather than classic fluoride-mediated remineralization, because infected dentin is not amenable to remineralization. Using synchrotron microCT with 1.3 m resolution, we observe filamentous densities up to 500 m in length and 0.25-7.0 m in diameter, formed in situ by applying SDF to caries lesions. We show that these \"microwires\" fill voids in the lesion caused by disease, and permeate through surrounding dentinal tubules. Using spectroscopy, we confirm that the chemical composition of the observed microwires is predominantly silver. To our knowledge, this represents the first structural microscale observations resulting from clinical SDF treatment. These novel observations hint at mechanistic explanations for the first clinical method to harden carious dentin besides remineralization. We hypothesize that SDF may not only achieve its antimicrobial functions by biochemical interactions, but also through its inherent ability to integrate into dentin.

pharmacology and toxicology↗