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1.
Cell Genom ; 3(11): 100435, 2023 Nov 08.
Article in English | MEDLINE | ID: mdl-38020970

ABSTRACT

Chromosome-level design-build-test-learn cycles (chrDBTLs) allow systematic combinatorial reconfiguration of chromosomes with ease. Here, we established chrDBTL with a redesigned synthetic Saccharomyces cerevisiae chromosome XV, synXV. We designed and built synXV to harbor strategically inserted features, modified elements, and synonymously recoded genes throughout the chromosome. Based on the recoded chromosome, we developed a method to enable chrDBTL: CRISPR-Cas9-mediated mitotic recombination with endoreduplication (CRIMiRE). CRIMiRE allowed the creation of customized wild-type/synthetic combinations, accelerating genotype-phenotype mapping and synthetic chromosome redesign. We also leveraged synXV as a "build-to-learn" model organism for translation studies by ribosome profiling. We conducted a locus-to-locus comparison of ribosome occupancy between synXV and the wild-type chromosome, providing insight into the effects of codon changes and redesigned features on translation dynamics in vivo. Overall, we established synXV as a versatile reconfigurable system that advances chrDBTL for understanding biological mechanisms and engineering strains.

2.
Langmuir ; 39(19): 6846-6854, 2023 May 16.
Article in English | MEDLINE | ID: mdl-37130319

ABSTRACT

To investigate the microscopic electrochemical dynamics of a stable trioxotriangulene (TOT) organic neutral π-radical on a graphite electrode surface, voltammetric and in situ infrared (IR) spectroelectrochemical studies were conducted using electrolyte solutions containing TOT monoanions. Upright columnar crystals (face-on alignment) of the TOT neutral radical were preferentially formed and dissolved in a rather reversible manner in the electrolyte with a low concentration of TOT monoanion under electrochemical conditions; however, more flat-lying columnar crystals (edge-on alignment) were formed in a higher concentration electrolyte. The flat-lying crystals remained on the graphite surface even at a fully reduced potential, owing to the lack of direct π-π interactions between the molecules and the graphite electrode. In situ IR attenuated total reflectance spectroscopy analyses successfully characterized the alignment of the columnar crystals of the TOT neutral radicals and their electrochemical behaviors, including the possible origins of the irreversible redox reaction of TOT on the graphite electrode.

3.
PLoS Biol ; 21(4): e3002116, 2023 04.
Article in English | MEDLINE | ID: mdl-37099620

ABSTRACT

Since its inception, synthetic biology has overcome many technical barriers but is at a crossroads for high-precision biological design. Devising ways to fully utilize big biological data may be the key to achieving greater heights in synthetic biology.


Subject(s)
Big Data , Synthetic Biology
4.
Chem Rev ; 123(1): 31-72, 2023 01 11.
Article in English | MEDLINE | ID: mdl-36317983

ABSTRACT

The human microbiome is composed of a collection of dynamic microbial communities that inhabit various anatomical locations in the body. Accordingly, the coevolution of the microbiome with the host has resulted in these communities playing a profound role in promoting human health. Consequently, perturbations in the human microbiome can cause or exacerbate several diseases. In this Review, we present our current understanding of the relationship between human health and disease development, focusing on the microbiomes found across the digestive, respiratory, urinary, and reproductive systems as well as the skin. We further discuss various strategies by which the composition and function of the human microbiome can be modulated to exert a therapeutic effect on the host. Finally, we examine technologies such as multiomics approaches and cellular reprogramming of microbes that can enable significant advancements in microbiome research and engineering.


Subject(s)
Microbiota , Humans , Technology
5.
Genes Cells ; 23(4): 274-284, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29446201

ABSTRACT

Transposons are major drivers of mammalian genome evolution. To obtain new insights into the contribution of transposons to the regulation of protein translation, we here examined how transposons affected the genesis and function of upstream open reading frames (uORFs), which serve as cis-acting elements to regulate translation from annotated ORFs (anORFs) located downstream of the uORFs in eukaryotic mRNAs. Among 39,786 human uORFs, 3,992 had ATG trinucleotides of a transposon origin, termed "transposon-derived upstream ATGs" or TuATGs. Luciferase reporter assays suggested that many TuATGs modulate translation from anORFs. Comparisons with transposon consensus sequences revealed that most TuATGs were generated by nucleotide substitutions in non-ATG trinucleotides of integrated transposons. Among these non-ATG trinucleotides, GTG and ACG were converted into TuATGs more frequently, indicating a CpG methylation-mediated process of TuATG formation. Interestingly, it is likely that this process accelerated human-specific upstream ATG formation within transposon sequences in 5' untranslated regions after divergence between human and nonhuman primates. Methylation-mediated TuATG formation seems to be ongoing in the modern human population and could alter the expression of disease-related proteins. This study shows that transposons have potentially been shaping the human proteome landscape via cis-acting uORF creation.


Subject(s)
DNA Methylation , DNA Transposable Elements , Open Reading Frames , Proteome/genetics , 5' Untranslated Regions , Computational Biology , Evolution, Molecular , Genome, Human , Humans , Polymorphism, Single Nucleotide , Regulatory Sequences, Nucleic Acid
6.
Opt Lett ; 38(20): 4224-7, 2013 Oct 15.
Article in English | MEDLINE | ID: mdl-24321965

ABSTRACT

Bi-doped siliconoxynitride (SiON:Bi) thin films were prepared by a sputtering method and the photoluminescence (PL) properties were studied. Without any thermal treatments, broad Bi-related luminescence was observed in the near-infrared (NIR) range. The luminescence efficiency depended strongly on the film composition. It was found that N atoms play a crucial role for the formation of Bi NIR luminescence centers. The effect of annealing on the luminescence efficiency was also studied. The optimum annealing temperature to have the largest number of Bi NIR luminescence centers depended strongly on the film composition and it was lower for films with lower N concentration. The PL excitation spectra revealed that two different Bi NIR luminescence centers exist in the films.

7.
J Neurosurg ; 96(4): 654-9, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11990803

ABSTRACT

OBJECT: The authors describe their experience in remodeling the shape of the cranium in children with craniosynostosis by using gradual distraction. In half of the cases, a new distraction device developed by the authors was used. METHODS: Twenty children with craniosynostosis underwent frontoorbital advancement and cranial remodeling assisted by gradual distraction. There were five children with brachycephaly, two with oxycephaly, five with scaphocephaly, two with plagiocephaly, one with combined scaphocephaly and plagiocephaly, and five with trigonocephaly. Four cases were syndromic and 16 were nonsyndromic. The patients ranged in age from 3 to 50 months (mean 14.5 months) at the first surgery. Simulated surgery was first performed on a three-dimensional solid model made of polyurethane, which accurately represented cranial flexibility, to determine the most favorable osteotomy line. Distraction was initiated 1 week postoperatively. The speed and extent of advancement (maximum extension 45 mm) were predetermined on the basis of previously reported criteria and the results of simulated surgery. Postoperatively, the cranial configuration was favorable in all cases. Spontaneous remodeling of irregularities and/or gaps apparent after distraction was found to occur 2 to 5 months after removal of the distraction devices, especially in patients with trigonocephaly or scaphocephaly. No major perioperative complication was observed in any patient. There were minor complications in six of the first 10 cases, including exposure of the device, shaft slippage, and fluid discharge. A new device was developed and used on the last 10 patients treated; it successfully eliminated device exposure and shaft slippage. A 3-year follow-up review confirmed that there was no relapse of advanced bones. CONCLUSIONS: Highly satisfactory results were achieved in cases of both syndromic and nonsyndromic craniosynostosis when gradual distraction was performed.


Subject(s)
Bone Remodeling/physiology , Craniosynostoses/physiopathology , Craniosynostoses/surgery , Osteogenesis, Distraction/instrumentation , Osteogenesis, Distraction/methods , Skull/physiopathology , Skull/surgery , Child, Preschool , Equipment Design , External Fixators , Female , Follow-Up Studies , Humans , Infant , Male , Osteotomy/instrumentation , Osteotomy/methods , Treatment Outcome
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