374 research outputs found

    Identification of putative domain linkers by a neural network – application to a large sequence database

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    BACKGROUND: The reliable dissection of large proteins into structural domains represents an important issue for structural genomics/proteomics projects. To provide a practical approach to this issue, we tested the ability of neural network to identify domain linkers from the SWISSPROT database (101602 sequences). RESULTS: Our search detected 3009 putative domain linkers adjacent to or overlapping with domains, as defined by sequence similarity to either Protein Data Bank (PDB) or Conserved Domain Database (CDD) sequences. Among these putative linkers, 75% were "correctly" located within 20 residues of a domain terminus, and the remaining 25% were found in the middle of a domain, and probably represented failed predictions. Moreover, our neural network predicted 5124 putative domain linkers in structurally un-annotated regions without sequence similarity to PDB or CDD sequences, which suggest to the possible existence of novel structural domains. As a comparison, we performed the same analysis by identifying low-complexity regions (LCR), which are known to encode unstructured polypeptide segments, and observed that the fraction of LCRs that correlate with domain termini is similar to that of domain linkers. However, domain linkers and LCRs appeared to identify different types of domain boundary regions, as only 32% of the putative domain linkers overlapped with LCRs. CONCLUSION: Overall, our study indicates that the two methods detect independent and complementary regions, and that the combination of these methods can substantially improve the sensitivity of the domain boundary prediction. This finding should enable the identification of novel structural domains, yielding new targets for large scale protein analyses

    Kokumi Substances, Enhancers of Basic Tastes, Induce Responses in Calcium-Sensing Receptor Expressing Taste Cells

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    Recently, we reported that calcium-sensing receptor (CaSR) is a receptor for kokumi substances, which enhance the intensities of salty, sweet and umami tastes. Furthermore, we found that several γ-glutamyl peptides, which are CaSR agonists, are kokumi substances. In this study, we elucidated the receptor cells for kokumi substances, and their physiological properties. For this purpose, we used Calcium Green-1 loaded mouse taste cells in lingual tissue slices and confocal microscopy. Kokumi substances, applied focally around taste pores, induced an increase in the intracellular Ca2+ concentration ([Ca2+]i) in a subset of taste cells. These responses were inhibited by pretreatment with the CaSR inhibitor, NPS2143. However, the kokumi substance-induced responses did not require extracellular Ca2+. CaSR-expressing taste cells are a different subset of cells from the T1R3-expressing umami or sweet taste receptor cells. These observations indicate that CaSR-expressing taste cells are the primary detectors of kokumi substances, and that they are an independent population from the influenced basic taste receptor cells, at least in the case of sweet and umami

    Discrepancy in the Responsiveness to Hip Range of Motion Between Harris and Oxford Hip Scores

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    Background: The primary objectives of total hip arthroplasty (THA) include mobility improvement and pain relief; however, the correlation between hip range of motion (ROM) and function remains unclear. We aimed to explore how ROM affects hip functions after THA and compare the responsiveness of each component of the modified Harris Hip Score (mHHS) and Oxford Hip Score (OHS) to preoperative and postoperative ROM. Methods: This prospective observational study involved 120 patients who underwent unilateral THA. Univariate regression analyses were performed using the University of California Los Angeles activity score and mHHS and OHS to determine the effects of preoperative and postoperative flex ROM on clinical scores at 12 months. Multivariate regressions were performed to adjust for the confounding effects of patient factors: age, sex, body mass index, and diagnosis. Results: A larger preoperative flexion ROM was associated with a higher score in the mHHS socks component (standardized coefficient [SC] = 0.26, P = .0041) at 12 months; the effect on the OHS socks component was not significant (P = .34). A larger flexion ROM at 12 months was associated with higher scores in the mHHS support (SC = 0.21, P = .026), stairs (SC = 0.35, P = .0002), and socks (SC = 0.32, P = .0007) components but had no significant effect on any OHS component. The effects of ROM on University of California Los Angeles activity score were limited. Conclusions: A discrepancy was noted in the responsiveness to ROM between the two major measurement tools; this difference might be because mHHS and OHS are surgeon- and patient-administered questionnaires, respectively. This discrepancy also suggests that the patients have higher satisfaction than that assumed by the surgeons

    High Subsidence Rate After Primary Total Hip Arthroplasty Using a Zweymüller-type Noncemented Implant With a Matte Surface

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    INTRODUCTION: The surface topography is one key factor that affects the initial fixation of prosthesis in total hip arthroplasty (THA). We aimed to evaluate the mid-term results of a Zweymüller-type noncemented femoral implant (Elance stem) that had a matte surface with a target average roughness of 1.0 to 2.5 μm. The prosthesis was subjected to alkali and heat treatments to enhance its bone-bonding property. METHODS: In this retrospective study, 30 THAs (27 patients) done using an Elance stem from September 2012 to October 2014 were evaluated clinically and radiographically for a mean follow-up of 6.3 ± 1.7 years after the index THA. RESULTS: Stem revision was indicated for six hips (20%). The survival rate with stem revision for any reason was 86.4% (95% confidence interval, 68.9%-94.8%) at 5 years. Stem subsidence >5 mm was noted in 17 hips (56.7%). The survival rate with stem subsidence >5 mm as the end point was 46.6% (95% confidence interval, 29.9%-64.2%) at 5 years. CONCLUSION: The Zweymüller-type noncemented stem with a low-roughness matte surface demonstrated a high subsidence rate, although the bone-bonding property was potentially enhanced by the alkali and heat treatments. Surgeons should be aware that an insufficient surface roughness could lead to poor mechanical fixation of the noncemented stem, even with an appropriate stem geometry and surface chemistry

    Difference in Therapeutic Strategies for Joint‐Preserving Surgery for Non‐Traumatic Osteonecrosis of the Femoral Head between the United States and Japan: A Review of the Literature

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    For patients with non-traumatic osteonecrosis of the femoral head (ONFH), core decompression (CD) and bone grafts (BG) are mainly performed in the West, while osteotomy is found to be predominant in Japan. It is not well recognized how the surgical procedures for joint preservation in patients with ONFH are completely different between the United States and Japan. This paper identifies the contexts and the differences in treatment strategies for ONFH between the two countries. We compared the surgical trends of the two countries over three periods, 1997-2001, 2002-2006, and 2007-2011 (the US data for the third period was 2007-2008), based on a 2014 US paper and a 2013 national publication in Japan. We compared the details of surgery for non-traumatic ONFH under the same conditions in the two reports. For the period 1997-2001, the rates of surgeries for ONFH in the US were as follows: total hip arthroplasty (THA), 86%; CD, 10%; and osteotomy, 0.4%. In Japan, THA was 61%, osteotomy 38%, and CD 0%. For the recent period, 2007-2011 (US 2007-2008), the rate of THA was 91%, CD 6%, and osteotomy 0.1%, in the US, compared to a THA rate of 73%, CD 0%, and osteotomy 26% in Japan. The results for the interim period (2002-2006) were between the old and new data. The use of joint-preserving surgery for ONFH differs greatly between the US and Japan. The first-line joint-preserving surgery was CD in the US and osteotomy in Japan. Each procedure was rarely done in the other country. From about 2000 to 2010, the percentage of THA increased in both countries. The proportion of joint-preserving surgery (CD in the US and osteotomy in Japan) declined. The decrease in joint-preserving procedures may be largely attributed to improved long-term outcomes of THA due to technological advances. There is also a reluctance for young ONFH patients to undergo joint-preserving procedures, such as osteotomy, that require long-term hospitalization

    Strategies for increasing gait speed in patients with hip osteoarthritis: their clinical significance and effects on hip loading

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    BACKGROUND: Changes in gait speed are required in various situations and can be achieved by changing stride length, cadence, or both. Differences in strategies for increasing gait speed may have different effects on hip joint and physical function. The purpose of this study was to determine the effects of strategies for increasing gait speed on hip pain, physical function, and changes in hip loading during gait in patients with hip osteoarthritis (OA). We hypothesized that patients who increase gait speed mainly by increasing cadence would have lesser hip pain, a higher physical function, and a lower rate of increase in hip moments with increasing gait speed. METHODS: Forty-seven patients with secondary hip OA (age, 48.3 ± 11.0 years) were included. Gait speed, stride length, cadence, and peak and impulse of the hip moments were measured during gait at self-selected normal and fast gait speeds. The patients were classified as types S (with mainly increasing stride length, n = 11 [23.4%]), C (with mainly increasing cadence, n = 23 [48.9%]), and SC (with increasing stride length and cadence, n = 13 [27.7%]) according to whether they used changes in stride length and/or cadence to transition from normal to fast gait. Hip pain, physical function, and hip moment changes during gait were compared between types. RESULTS: The physical function was higher in types C (38.0 ± 8.8, P = 0.018) and SC (40.6 ± 8.5, P = 0.015) than in type S (28.2 ± 7.8), even after adjustment for age and minimum joint space width. Hip pain was not significantly different between types. The robustness of these results was confirmed with sensitivity analysis. The rates of increases in peak external hip adduction (P = 0.003) and internal rotation moments (P = 0.009) were lower in type C than in type SC. CONCLUSIONS: Type C tended to suppress the increase in hip moments during fast gait. Types C and SC, which included increased cadence, maintained higher physical function levels than type S. Encouraging the use of cadence-increasing strategy may be useful for reducing hip loading and maintaining physical function in patients with hip OA