• Journal of Microbiology and Biotechnology
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• 제29권9호
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• pp.1375-1382
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• 2019

Phenylalanine hydroxylase from Chromobacterium violaceum (CvPAH) is a monomeric enzyme that converts phenylalanine to tyrosine. It shares high amino acid identity and similar structure with a subunit of human phenylalanine hydroxylase that is a tetramer, resulting in the latent application in medications. In this study, semirational design was applied to CvPAH to improve the catalytic ability based on molecular dynamics simulation analyses. Four N-terminal truncated variants and one single point variant were constructed and characterized. The D267P variant showed a 2.1-fold increased thermal stability compared to the wild type, but lower specific activity was noted compared with the wild type. The specific activity of all truncated variants was a greater than 25% increase compared to the wild type, and these variants showed similar or slightly decreased thermostability with the exception of the $N-{\Delta}9$ variant. Notably, the $N-{\Delta}9$ variant exhibited a 1.2-fold increased specific activity, a 1.3-fold increased thermostability and considerably increased catalytic activity under the neutral environment compared with the wild type. These properties of the $N-{\Delta}9$ variant could advance medical and pharmaceutical applications of CvPAH. Our findings indicate that the N-terminus might modulate substrate binding, and are directives for further modification and functional research of PAH and other enzymes.

• Journal of Genetic Medicine
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• 제18권2호
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• pp.132-136
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• 2021

Maturity-onset diabetes of the young (MODY) is caused by autosomal dominant pathogenic variants in one of 14 currently known monogenic genes. Characteristics of patients with MODY include early-onset clinical disease with a family history of diabetes and negative autoantibodies and may present with heterogeneous phenotypes according to the different subtypes. Here, we report a patient with early-onset diabetes who presented asymptomatic mild fasting hyperglycemia with the absence of autoantibodies. She was diagnosed with glucokinase (GCK)-MODY caused by a GCK variant, c.1289T>C (p.L430P), identified by targeted gene-panel testing, and the affected father had the same variant. We interpreted this rare missense variant as a likely pathogenic variant and then she stopped taking oral medication. This case highlights the usefulness of gene-panel testing for accurate diagnosis and appropriate management of MODY. We also note the importance of familial genetic testing and genetic counseling for the proper interpretation of MODY variants.

• Computers and Concrete
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• 제17권4호
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• pp.499-521
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• 2016

In this paper, a probabilistic- and finite element-based approach to evaluate and predict the lifetime performance of reinforced concrete (RC) bridges undergoing various maintenance actions is proposed with the time-variant system reliability being utilized as a performance indicator. Depending on their structural state during the degradation process, the classical maintenance actions for RC bridges are firstly categorized into four types: Preventive type I, Preventive type II, Strengthening and Replacement. Preventive type I is used to delay the onset of steel corrosion, Preventive type II can suppress the corrosion process of reinforcing steel, Strengthening is the application of various maintenance materials to improve the structural performance and Replacement is performed to restore the individual components or overall structure to their original conditions. The quantitative influence of these maintenance types on structural performance is investigated and the respective analysis modules are written and inputted into the computer program. Accordingly, the time-variant system reliability can be calculated by the use of Monte Carlo simulations and the updated the program. Finally, an existing RC continuous bridge located in Shanghai, China, is used as an illustrative example and the lifetime structural performance with and without each of the maintenance types are discussed. It is felt that the proposed approach can be applied to various RC bridges with different structural configurations, construction methods and environmental conditions.

• Journal of Microbiology and Biotechnology
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• 제26권3호
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• pp.452-460
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• 2016

Acid stress can affect the viability of probiotics, especially Bifidobacterium. This study aimed to improve the acid tolerance of Bifidobacterium longum BBMN68 using adaptive evolution. The stress response, and genomic differences of the parental strain and the variant strain were compared by acid stress. The highest acid-resistant mutant strain (BBMN68m) was isolated from more than 100 asexual lines, which were adaptive to the acid stress for 10^th, 20^th, 30^th, 40^th, and 50^th repeats, respectively. The variant strain showed a significant increase in acid tolerance under conditions of pH 2.5 for 2 h (from 7.92 to 4.44 log CFU/ml) compared with the wild-type strain (WT, from 7.87 to 0 log CFU/ml). The surface of the variant strain was also smoother. Comparative whole-genome analysis showed that the galactosyl transferase D gene (cpsD, bbmn68_1012), a key gene involved in exopolysaccharide (EPS) synthesis, was altered by two nucleotides in the mutant, causing alteration in amino acids, pI (from 8.94 to 9.19), and predicted protein structure. Meanwhile, cpsD expression and EPS production were also reduced in the variant strain (p < 0.05) compared with WT, and the exogenous WT-EPS in the variant strain reduced its acid-resistant ability. These results suggested EPS was related to acid responses of BBMN68.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제41권3호
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• pp.165-167
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• 2015

It has recently been reported that long-standing post-traumatic open bite can be successfully corrected with botulinum toxin type A (BTX-A) injection into the anterior belly of the digastric muscle (ABDM). The report documented an individual with bilaterally symmetrical and otherwise unremarkable anterior digastric musculature. However, the existence of variant anterior digastric musculature is common and may complicate the management of anterior open bite with BTX-A injection. Screening for variant ABDM can be accomplished via ultrasound, computed tomography, and magnetic resonance imaging. Screening for variant ABDM should be performed prior to BTX-A injection in order to account for musculature that may exert undesired forces, such as inferolateral deviation, on the anterior mandible in patients with anterior open bite.

• Clinics in Shoulder and Elbow
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• 제2권1호
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• pp.41-46
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• 1999

견관절의 병변에 대해 관절경적 검사 및 치료를 시행한 50례의 환자중 상부 관절순이 관절와를 비정상적으로 넓게 덮고 있는 meniscoid variant 변형을 4례에서 볼 수 있었으며 이는 SLAPⅡ 병변과는 다르게 관절와부위에 견고히 부착되어 있었다. Meniscoid type의 상부관절순은 .기본적으로 정상적인 변형이지만 반복된 기상운동을 통해 상부 관절순이 과운동성을 갖게 되면 이차적인 변형 및 증상을 유발할 수 있으므로, 저자들은 이에 대해 변연절제 및 재조절을 다른 병변의 치료와 함께 시행하였다. 향후 meniscoid variant변형에 대한 생역학적인 연구와 임상적 의의 그리고 동반된 관절내 병변과의 관계에 대한 연구가 필요할 것으로 생각되었다

• Biomolecules & Therapeutics
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• 제27권6호
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• pp.577-583
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• 2019

Human cytochrome P450 2C9 is a highly polymorphic enzyme that is required for drug and xenobiotic metabolism. Here, we studied eleven P450 2C9 genetic variants-including three novel variants F69S, L310V, and Q324X-that were clinically identified in Korean patients. P450 2C9 variant enzymes were expressed in Escherichia coli and their bicistronic membrane fractions were prepared The CO-binding spectra were obtained for nine enzyme variants, indicating P450 holoenzymes, but not for the M02 (L90P) variant. The M11 (Q324X) variant could not be expressed due to an early nonsense mutation. LC-MS/MS analysis was performed to measure the catalytic activities of the P450 2C9 variants, using diclofenac as a substrate. Steady-state kinetic analysis revealed that the catalytic efficiency of all nine P450 2C9 variants was lower than that of the wild type P450 2C9 enzyme. The M05 (R150L) and M06 (P279T) variants showed high $k_{cat}$ values; however, their $K_m$ values were also high. As the M01 (F69S), M03 (R124Q), M04 (R125H), M08 (I359L), M09 (I359T), and M10 (A477T) variants exhibited higher $K_m$ and lower $k_{cat}$ values than that of the wild type enzyme, their catalytic efficiency decreased by approximately 50-fold compared to the wild type enzyme. Furthermore, the novel variant M07 (L310V) showed lower $k_{cat}$ and $K_m$ values than the wild type enzyme, which resulted in its decreased (80%) catalytic efficiency. The X-ray crystal structure of P450 2C9 revealed the presence of mutations in the residues surrounding the substrate-binding cavity. Functional characterization of these genetic variants can help understand the pharmacogenetic outcomes.

• 대한수의학회지
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• 제38권4호
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• pp.777-783
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• 1998

Antigenic types of 114 Salmonella pullorum and 152 Salmonella gallinarum field isolates were evaluated. All 3 antigenic types were identified among field isolates of S pullorum by factor-serum analysis but the majority of them were standard type(90.4%). Of the 114 S pullorum isolates, only eight(7.0%) were intermediate type and 3(2.6%) were variant type. Using the ammonium sulfate precipitation(ASP) test, one-hundred and three(90.4%) S pullorum isolates were standard type, while intermediate and variant types were 8.4% and 1.4%, respectively. One-hundred and fifty-two S gallinarum isolates were identified as standard type by ASP test and serological analysis. According to the random amplified polymorphisms of DNA(RAPD) patterns, most of S pullorum isolates were differentiated with 3 types in their fragment-patterns. No correlations were found between SDS-PAGE profiles and antigenic types of S pullorum isolates.

• Journal of Medicine and Life Science
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• 제15권1호
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• pp.19-22
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• 2018

Castleman's disease is a benign lympho-proliferative disorder that commonly occurs in mediastinum. It is known that the disease rarely occurs in mesentery. Most localized abdominal Castleman's diseases are histologically hyaline vascular type. The contrast-enhanced CT in patient with hyaline vascular type Castleman's disease shows a well-defined mass with homogenously intense enhancement. On the other hand, the patient with plasma cell variant has systemic symptoms, but not specific imaging features. We report a unicentric plasma cell variant Castleman's disease in mesentery nearby superior mesenteric artery as presenting a single mass, not accompanied by systemic symptoms with similar characteristics to hyaline vascular type.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1355-1360
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• 2012

Background: The cell cycle checkpoint kinase 2 (CHEK2) gene I157T variant may be associated with an increased risk of breast cancer, but it is unclear whether the evidence is sufficient to recommend testing for the mutation in clinical practice. Materials and Methods: We systematically searched PubMed, Embase, Elsevier and Springer for relevant articles published before Nov 2011. Summary odds ratio (OR) and 95% confidence interval (95% CI) incidence rates were calculated using a random-effects model with STATA (version 10.0) software. Results: A total of fifteen case-control studies, including 19,621 cases and 27,001 controls based on the search criteria, were included for analysis. A significant association was found between carrying the CHEK2 I157T variant and increased risk of unselected breast cancer (OR = 1.48, 95% CI = 1.31-1.66, P < 0.0001), familial breast cancer (OR = 1.48, 95% CI = 1.16-1.89, P < 0.0001), and early-onset breast cancer (OR = 1.47, 95% CI = 1.29-1.66, P < 0.0001). We found an even stronger significant association between the CHEK2 I157T C variant and increased risk of lobular type breast tumors (OR = 4.17, 95% CI = 2.89-6.03, P < 0.0001). Conclusion: Our research indicates that the CHEK2 I157T variant may be another important genetic mutation which increases risk of breast cancer, especially the lobular type.