Using Shifts in Amino Acid Frequency and Substitution Rate to Identify Latent Structural Characters in Base-Excision Repair Enzymes

Protein evolution includes the birth and death of structural motifs. For example, a zinc finger or a salt bridge may be present in some, but not all, members of a protein family. We propose that such transitions are manifest in sequence phylogenies as concerted shifts in substitution rates of amino acids that are neighbors in a representative structure. First, we identified rate shifts in a quartet from the Fpg/Nei family of base excision repair enzymes using a method developed by Xun Gu and coworkers. We found the shifts to be spatially correlated, more precisely, associated with a flexible loop involved in bacterial Fpg substrate specificity. Consistent with our result, sequences and structures provide convincing evidence that this loop plays a very different role in other family members. Second, then, we developed a method for identifying latent protein structural characters (LSC) given a set of homologous sequences based on Gu's method and proximity in a high-resolution structure. Third, we identified LSC and assigned states of LSC to clades within the Fpg/Nei family of base excision repair enzymes. We describe seven LSC; an accompanying Proteopedia page (http://proteopedia.org/wiki/index.php/Fpg_Nei_Protein_Family) describes these in greater detail and facilitates 3D viewing. The LSC we found provided a surprisingly complete picture of the interaction of the protein with the DNA capturing familiar examples, such as a Zn finger, as well as more subtle interactions. Their preponderance is consistent with an important role as phylogenetic characters. Phylogenetic inference based on LSC provided convincing evidence of independent losses of Zn fingers. Structural motifs may serve as important phylogenetic characters and modeling transitions involving structural motifs may provide a much deeper understanding of protein evolution

Elevated Thyroid Autoantibodies and Intracranial Stenosis in Stroke at an Early Age

BACKGROUND: Previous studies have shown that hyperthyroidism was related to Moyamoya disease and intracranial artery stenosis. However, it is not clear whether thyroid hormone or thyroid autoantibodies was associated with them. AIMS AND/OR HYPOTHESIS: Thyroid autoimmunity was previously shown to be associated with Moyamoya disease. Our study aimed to investigate the association between thyroid autoantibodies and intracranial large artery stenosis in young ischemic stroke patients with apparent euthyroid states. METHODS: We retrospectively reviewed first-onset ischemic stroke patients (age ≤55 years old) consecutively admitted to a single academic center. Intracranial large artery stenosis was defined as ≥50% luminal diameter narrowing. We compared demographic profiles, risk factors (age, hypertension, diabetes, current smoker, atrial fibrillation, hyperlipidemia), thyroid function test, and thyroid autoantibodies including antithyroperoxidase antibody and antithyroglobulin antibody between patients with and without intracranial large artery stenosis. We also performed multivariate logistic regression analysis to evaluate the association between thyroid autoantibodies and intracranial large artery stenosis. RESULTS: A total of 351 patients were analyzed. The mean age of the patients was 47.0 ± 7.7 (range, 10–55 years), and 252 (71.8%) patients were male. We identified intracranial large artery stenosis in 121 (34.5%) patients. Patients with intracranial large artery stenosis showed a higher frequency of elevated antithyroperpxidase antibody levels in comparison with nonintracranial large artery stenosis group (16.5% vs. 3.9%, P < 0.001). After adjusting for covariates, the presence of elevated antithyroperpxidase antibody levels (odds ratio: 5.318; 95% confidence interval: 2.157–13.110, P < 0.001), age (odds ratio: 1.037; 95% confidence interval: 1.002–1.073, P = 0.039), and atrial fibrillation (odds ratio: 0.091; 95% confidence interval: 0.011–0.756, P = 0.027) was independently associated with intracranial large artery stenosis. CONCLUSIONS: Thyroid autoantibodies may be associated with the presence of intracranial large artery stenosis in young stroke patients, potentially providing insight on immune pathogenesis of intracranial large artery stenosis

Factors affecting responsiveness to hepatitis B immunization in dialysis patients

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are widespread health problems all over the world and have high morbidity and mortality. Hemodialysis patients are more frequently exposed to these viruses as they have poor immune system and frequently undergo parenteral interventions. The vaccination against HBV prevents infection and it has been recommended for the prevention of HBV infection in all susceptible dialysis patients. This study aimed to determine the seroprevalence of HBV and HCV infections and analyzed the factors affecting inadequate response to HBV vaccine in dialysis patients