Development of an accurate classification system of proteins into structured and unstructured regions that uncovers novel structural domains: its application to human transcription factors

<p>Abstract</p> <p>Background</p> <p>In addition to structural domains, most eukaryotic proteins possess intrinsically disordered (ID) regions. Although ID regions often play important functional roles, their accurate identification is difficult. As human transcription factors (TFs) constitute a typical group of proteins with long ID regions, we regarded them as a model of all proteins and attempted to accurately classify TFs into structural domains and ID regions. Although an extremely high fraction of ID regions besides DNA binding and/or other domains was detected in human TFs in our previous investigation, 20% of the residues were left unassigned. In this report, we exploit the generally higher sequence divergence in ID regions than in structural regions to completely divide proteins into structural domains and ID regions.</p> <p>Results</p> <p>The new dichotomic system first identifies domains of known structures, followed by assignment of structural domains and ID regions with a combination of pre-existing tools and a newly developed program based on sequence divergence, taking un-aligned regions into consideration. The system was found to be highly accurate: its application to a set of proteins with experimentally verified ID regions had an error rate as low as 2%. Application of this system to human TFs (401 proteins) showed that 38% of the residues were in structural domains, while 62% were in ID regions. The preponderance of ID regions makes a sharp contrast to TFs of <it>Escherichia coli </it>(229 proteins), in which only 5% fell in ID regions. The method also revealed that 4.0% and 11.8% of the total length in human and <it>E. coli </it>TFs, respectively, are comprised of structural domains whose structures have not been determined.</p> <p>Conclusion</p> <p>The present system verifies that sequence divergence including information of unaligned regions is a good indicator of ID regions. The system for the first time estimates the complete fractioning of structured/un-structured regions in human TFs, also revealing structural domains without homology to known structures. These predicted novel structural domains are good targets of structural genomics. When applied to other proteins, the system is expected to uncover more novel structural domains.</p

Effects of Birth Month on Talent Identification Participation and the Identification Process in Sports

Topics in Exercise Science and Kinesiology Volume 2: Issue 1, Article 7, 2021. The purpose of this study was to clarify the effect of the birth month on Talent Identification (TI) participation and the identification process in sports. The subjects were 4th grade elementary school children (mean age, 9±5.8 years) who participated in the Talent Identification Project. The method of identification was two-stage. In the first stage, the 30 m sprint, standing broad jump, and medicine ball front throw (1 kg) were performed, and 99 boys and 97 girls with high overall scores were selected to participate in the second stage. In the second stage, in addition to the results of the first stage, the T-test, 20 m shuttle run, standing triple jump, rebound jump (RJ-index), medicine ball back throw (1 kg), and repeated horizontal jump were performed. In the T-test, subjects run straight to a point 10 m ahead, then, ran 5 m to the right, 10 m to the left, 5 m to the right, and returned 10 m back to the start. A total of 15 boys and 15 girls with high overall scores were selected from the second stage. As in a previous study, the birth month was divided into yearly quarters (1, April to June; 2, July to September; 3, October to December; and 4, January to March). Point of application ＃1: There was a bias in participation rates and final members in the TI project for 4th graders by birth month for both boys and girls. Point of application ＃2: In the case of 4th grade boys of the TI project, the medicine ball front throw, as an index of whole body power, was influenced by the birth month. Point of application ＃3: It was speculated that boys born between January and March had a smaller morphology (height and weight), and were disadvantaged in measurement tests related to morphology, such as the medicine ball front throw

Effect of Obstructive Jaundice and Nitric Oxide on the Profiles of Intestinal Bacterial Flora in Wild and iNOS−/− Mice

We previously reported that the plasma level of endotoxin and colonic expression of IgA in the mouse increased with obstructive jaundice induced by bile duct ligation (BDL). To elucidate the mechanism of the BDL-induced increase, we analyzed the effect of BDL on intestinal flora in wild type and inducible nitric oxide synthase (iNOS)-deficient mice (iNOS−/−) using the terminal restriction fragment length polymorphism analysis (T-RFLP) and 16S rDNA clone libraries. The amounts of bacterial DNA detected in fecal samples from both animal groups pretreated with antibiotics were extremely low as compared with untreated groups. We found that the profiles of enteric bacteria changed markedly after BDL. The bacterial composition is significantly different between not only wild type and iNOS−/− mice but also those before and after BDL, respectively. Among enteric bacteria examined, Lactobacillus murinus was found to increase markedly after BDL in rectum of both animal groups. However, Escherichia coli markedly increased after BDL in the iNOS−/− mice. These findings suggest that profiles of enteric flora change markedly in animals during obstructive jaundice by some mechanism that is affected by bile constituents and iNOS-derived NO

Lung inflammation by fungus, Bjerkandera adusta isolated from Asian sand dust (ASD) aerosol and enhancement of ovalbumin-induced lung eosinophilia by ASD and the fungus in mice.

BackgroundBjerkandera adusta (B. adusta) is one of the most important etiological fungi associated with chronic cough. However, precise details of the inflammatory response to exposure are not well understood yet. B. adusta was recently identified in Asian sand dust (ASD) aerosol. Therefore, in the present study the exacerbating effects of ASD on B. adusta-induced lung inflammation and B. adusta + ASD on ovalbumin (OVA)-induced murine lung eosinophilia were investigated using experimental mice.MethodsIn order to prepare testing samples, B. adusta obtained from ASD aerosol was inactivated by formalin and ASD collected from the atmosphere was heated to remove toxic organic substances (H-ASD). CD-1 mice were instilled intratracheally with 12 different samples prepared with various combinations of B. adusta, H-ASD, and OVA in a normal saline solution. The lung pathology, cytological profiles in bronchoalveolar lavage fluid (BALF), and the levels of inflammatory cytokines/chemokines in BALF were investigated.ResultsH-ASD aggravated the lung eosinophilia induced by B. adusta alone, which also aggravated the lung eosinophilia induced by OVA. The mixture of OVA, H-ASD, and B. adusta caused serious fibrous thickening of the subepithelial layer, eosinophil infiltration, and proliferation of goblet cells in the airways along with remarkable increases of IL-13, eotaxin, IL-5, and MCP-3 in BALF.ConclusionsThe results of the present study demonstrated that B. adusta isolated from ASD aerosol induces allergic lung diseases. H-ASD enhanced allergic reactions caused by OVA or B. adusta. A mixture of B. adusta, H-ASD, and OVA caused the most remarkable exacerbation to the allergic airway inflammation via remarkable increases of pro-inflammatory mediators

Clinical Relevance of Parafoveal Intercapillary Spaces and Foveal Avascular Zone in Diabetic Retinopathy Without Macular Edema

Purpose: To investigate the clinical significance of intercapillary spaces on swept source optical coherence tomography angiography images in diabetic retinopathy. Methods: We retrospectively reviewed 110 eyes of 110 patients suffering from diabetic retinopathy without macular edema for whom 3 × 3 mm swept source optical coherence tomography angiography images centered on the fovea were obtained. Automatic image processing of the superficial slab images allowed us to define the areas encircled by retinal vessels as intercapillary spaces within the central 2-mm circle. We evaluated how the quantitative parameters of intercapillary spaces are associated with logMAR and feasible to diagnose diabetic macular ischemia. Results: Total counts (ρ = −0.419; P < 0.001) rather than morphologic parameters of the intercapillary spaces showed a significant correlation with logMAR. There were individual levels of correlations between logMAR and counts of intercapillary spaces in individual sectors. In particular, the summed numbers of the spaces in three highly significant sectors were more significantly associated with logMAR (ρ = −0.515; P < 0.001). Multivariate analyses confirmed that the number of the intercapillary spaces (β = −0.266; P = 0.016) and foveal avascular zone area (β = 0.227; P = 0.042) were related to logMAR. The clustering using the foveal avascular zone area and the number of intercapillary spaces revealed two major clusters; one had fewer intercapillary spaces (P < 0.001) and poorer logMAR (P < 0.001) than the other, with a wide range of the foveal avascular zone area. Conclusions: Decreased intercapillary spaces contribute to visual impairment in diabetic retinopathy and suggest one possible criterion of objective diagnosis of diabetic macular ischemia

Some Observations on EEG Response to Photic Flicker Stimulation

By applying a combined method of crosscorrelation and frequency analysis to EEG tracings, the average response patterns to photic flicker stimulation with a frequency in the alpha wave range were sorted out, even when the application of the frequency analysis only could not separate the response from the irrelevant oscillations to the stimulation. During the stimulation, low volage fast pattern (alpha blocking state), in which the response was hard to recognize by visual inspection of the tracing, occurred in the EEG tracings from time to time. In the frequency spectra of them, however, not only a peak at the stimulating frequency, but the other ones at slightly higher frequency and sometimes with subharmonic frequency were appeared to suggest they are the response to the stimulation, though they are far lower than the peak of the dominant alpha wave before the initiation of the stimulation, rised up at the stimulating frequency in the power spectra of the crosscorrelogram between the stimulation and the tracing to indicate the other peaks were not related response, at least directly, to the stimulation, but by others