Risk of Subsequent Primary Cancer in Thyroid Cancer Survivors: A Nationwide Population-Based Study.

Despite obtaining a good prognosis and long life expectancy, survivors of thyroid cancer can nevertheless develop subsequent primary cancer (SPC). We investigated the risk and types of SPC in patients with thyroid cancer and compared them with subjects without thyroid cancer history (controls). We conducted a nationwide, population-based, retrospective cohort study based on the Korean National Health Insurance Database.

Associations of Earphone Use with Tinnitus and Anxiety/Depression.

Objective: This study aimed to investigate the association of earphone use with audiologic and psychologic factors.

Materials And Methods: Korea National Health and Nutrition Examination Survey 2010-2012 data were collected for participants aged ≥12 years old with earphone use ≥1 hour/day. They were matched to a control group for age, sex, income, and education level.

The interplay between effector binding and allostery in an engineered protein switch.

The protein design rules for engineering allosteric regulation are not well understood. A fundamental understanding of the determinants of ligand binding in an allosteric context could facilitate the design and construction of versatile protein switches and biosensors. Here, we conducted extensive in vitro and in vivo characterization of the effects of 285 unique point mutations at 15 residues in the maltose-binding pocket of the maltose-activated β-lactamase MBP317-347.

Electrochemical activation of engineered protein switches.

Engineered protein switches have a large dynamic range, high specificity for the activating ligand, and a modular architecture, and have been explored for a wide range of applications including biosensors and therapeutics. The ability to externally control switch function is important in extending applications for protein switches. We recently demonstrated that the on/off state could be controlled by the redox state of disulfide bonds introduced into the switches at select locations.

Design of protein switches based on an ensemble model of allostery.

Switchable proteins that can be regulated through exogenous or endogenous inputs have a broad range of biotechnological and biomedical applications. Here we describe the design of switchable enzymes based on an ensemble allosteric model. First, we insert an enzyme domain into an effector-binding domain such that both domains remain functionally intact.

Rational design of a fusion protein to exhibit disulfide-mediated logic gate behavior.

Synthetic cellular logic gates are primarily built from gene circuits owing to their inherent modularity. Single proteins can also possess logic gate functions and offer the potential to be simpler, quicker, and less dependent on cellular resources than gene circuits. However, the design of protein logic gates that are modular and integrate with other cellular components is a considerable challenge.

Non-allosteric enzyme switches possess larger effector-induced changes in thermodynamic stability than their non-switch analogs.

The ability to regulate cellular protein activity offers a broad range of biotechnological and biomedical applications. Such protein regulation can be achieved by modulating the specific protein activity or through processes that regulate the amount of protein in the cell. We have previously demonstrated that the nonhomologous recombination of the genes encoding maltose binding protein (MBP) and TEM1 β-lactamase (BLA) can result in genes that confer maltose-dependent resistance to β-lactam antibiotics even though the encoded proteins are not allosteric enzymes.

In vitro recombination of non-homologous genes can result in gene fusions that confer a switching phenotype to cells.

Regulation of protein activity is central to the complexity of life. The ability to regulate protein activity through exogenously added molecules has biotechnological/biomedical applications and offers tools for basic science. Such regulation can be achieved by establishing a means to modulate the specific activity of the protein (i.

Molecular modeling of the misfolded insulin subunit and amyloid fibril.

Insulin, a small hormone protein comprising 51 residues in two disulfide-linked polypeptide chains, adopts a predominantly alpha-helical conformation in its native state. It readily undergoes protein misfolding and aggregates into amyloid fibrils under a variety of conditions. Insulin is a unique model system in which to study protein fibrillization, since its three disulfide bridges are retained in the fibrillar state and thus limit the conformational space available to the polypeptide chains during misfolding and fibrillization.

Site-directed mutagenesis demonstrates the plasticity of the beta helix: implications for the structure of the misfolded prion protein.

The left-handed parallel beta helix (LbetaH) fold has recently received attention as a possible structure for the prion protein (PrP) in its misfolded state. In light of this interest, we have developed an experimental system to examine the structural requirements of the LbetaH fold, using a known LbetaH protein, UDP-N-acetylglucosamine acyltransferase (LpxA), from E. coli.

Analysis of the sequence and structural features of the left-handed beta-helical fold.

The left-handed parallel beta-helix (LbetaH) is a structurally repetitive, highly regular, and symmetrical fold formed by coiling of elongated beta-sheets into helical "rungs." This canonical fold has recently received interest as a possible solution to the fibril structure of amyloid and as a building block of self-assembled nanotubular structures. In light of this interest, we aimed to understand the structural requirements of the LbetaH fold.