Identification of protein functions using a machine-learning approach based on sequence-derived properties

<p>Abstract</p> <p>Background</p> <p>Predicting the function of an unknown protein is an essential goal in bioinformatics. Sequence similarity-based approaches are widely used for function prediction; however, they are often inadequate in the absence of similar sequences or when the sequence similarity among known protein sequences is statistically weak. This study aimed to develop an accurate prediction method for identifying protein function, irrespective of sequence and structural similarities.</p> <p>Results</p> <p>A highly accurate prediction method capable of identifying protein function, based solely on protein sequence properties, is described. This method analyses and identifies specific features of the protein sequence that are highly correlated with certain protein functions and determines the combination of protein sequence features that best characterises protein function. Thirty-three features that represent subtle differences in local regions and full regions of the protein sequences were introduced. On the basis of 484 features extracted solely from the protein sequence, models were built to predict the functions of 11 different proteins from a broad range of cellular components, molecular functions, and biological processes. The accuracy of protein function prediction using random forests with feature selection ranged from 94.23% to 100%. The local sequence information was found to have a broad range of applicability in predicting protein function.</p> <p>Conclusion</p> <p>We present an accurate prediction method using a machine-learning approach based solely on protein sequence properties. The primary contribution of this paper is to propose new <it>PNPRD </it>features representing global and/or local differences in sequences, based on positively and/or negatively charged residues, to assist in predicting protein function. In addition, we identified a compact and useful feature subset for predicting the function of various proteins. Our results indicate that sequence-based classifiers can provide good results among a broad range of proteins, that the proposed features are useful in predicting several functions, and that the combination of our and traditional features may support the creation of a discriminative feature set for specific protein functions.</p

Analysis of abnormal muscle activities in patients with loss of cervical lordosis: a cross-sectional study

Background This study aimed to detect the differences in cervical muscle activation patterns in people with versus without cervical lordosis and explore the possible mechanism of cervical pain originating therein. Methods This cross-sectional design included 39 participants without and 18 with normal cervical lordosis. Muscular activation was measured for 5 s in both groups using surface electromyography. Subsequently, the root mean square (RMS) of muscle amplitude was obtained at the bilateral splenius capitis, upper and lower parts of the splenius cervicis, upper and lower parts of the semispinalis cervicis, sternocleidomastoid, upper trapezius, and rhomboid muscles in five cervical positions: 0° (resting), 30° of flexion, 30° of extension, 60° of extension, and upon a 1-kg load on the head in a resting posture. Results The RMS values of the upper trapezius muscle at all postures and the rhomboid muscles at 60° of extension were significantly lower in the loss of lordosis than control group. Comparing the RMS ratio of each posture to the resting position, the ratio of the upper trapezius at flexion was significantly higher and that of the rhomboids at 60° of extension and upon loading was significantly lower in the loss of lordosis than control group. Moreover, the pattern changes in the RMS values according to posture showed a similar shape in these two muscles, and lower in the loss of lordosis than the normal group. Conclusions The loss of normal cervical alignment may correlate with predisposed conditions such as reduced muscle activation of the trapezius and rhomboid muscle, and may also provoke over-firing of the upper trapezius muscle, possibly increasing neck musculoskeletal pain. Trial registration. Clinicaltrials.gov, registration number: NCT03710785.This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI18C1169

Severe protein C deficiency in a newborn caused by a homozygous pathogenic variant in the PROC gene: a case report

Background Severe protein C deficiency is a rare and inherited cause of thrombophilia in neonates. Protein C acts as an anticoagulant, and its deficiency results in vascular thrombosis. Herein, we report a case of protein C deficiency with a homozygous pathogenic variant in a term neonate, with good outcomes after proper treatment. Case presentation A four-day-old male newborn was transferred to the Seoul National University Hospital on account of dark red to black skin lesions. He was born full-term with an average birth weight without perinatal problems. There were no abnormal findings in the prenatal tests, including intrauterine sonography. The first skin lesion was observed on his right toes and rapidly progressed to proximal areas, such as the lower legs, left arm, and buttock. Under the impression of thromboembolism or vasculitis, we performed a coagulopathy workup, which revealed a high D-dimer level of 23.05 μg/ml. A skin biopsy showed fibrin clots in most capillaries, and his protein C activity level was below 10%, from which we diagnosed protein C deficiency. On postnatal day 6, he experienced an apnea event with desaturation and an abnormal right pupillary light reflex. Brain computed tomography showed multifocal patchy intracranial hemorrhage and intraventricular hemorrhage with an old ischemic lesion. Ophthalmic examination revealed bilateral retinal traction detachments with retinal folds. Protein C concentrate replacement therapy was added to previous treatments including steroids, prostaglandin E1, and anticoagulation. After replacement therapy, there were no new skin lesions, and the previous lesions recovered with scarring. Although there were no new brain hemorrhagic infarctions, there was ongoing ischemic tissue loss, which required further rehabilitation. Ophthalmic surgical interventions were performed to treat the bilateral retinal traction detachments with retinal folds. Molecular analysis revealed a homozygous pathogenic variant in the PROC gene. Conclusion Severe protein C deficiency can manifest as a fatal coagulopathy in any organ. Early diagnosis and proper treatment, including protein C concentrate replacement, may improve outcomes without serious sequelae

Polymeric tandem organic light-emitting diodes using a self-organized interfacial layer

The authors have demonstrated efficient polymeric tandem organic light-emitting diodes (OLEDs) with a self-organized interfacial layer, which was formed by differences in chemical surface energy. Hydrophilic poly(styrene sulfonate)-doped poly(3,4-ethylene dioxythiophene) (PEDOT:PSS) was spin coated onto the hydrophobic poly(9,9-dyoctilfluorene) (PFO) surface and a PEDOT:PSS bubble or dome was built as an interfacial layer. The barrier heights of PEDOT:PSS and PFO in the two-unit tandem OLED induced a charge accumulation at the interface in the heterojunction and thereby created exciton recombination at a much higher level than in the one-unit reference. This effect was confirmed in both the hole only and the electron only devices. (c) 2008 American Institute of Physicsopen8

The impact of sMICA/sMICB on immunochemotherapy outcomes in newly diagnosed diffuse large B-cell lymphoma

IntroductionSoluble MHC class I-related chain A (sMICA) and B (sMICB) play a critical role tumor evolution and poor prognosis through an immune evasion mechanism. Thus, this study determines the interaction between sMICA/sMICB and the tumor immune environment in newly diagnosed diffuse large B-cell lymphoma (ND-DLBCL).MethodsWe analyzed sMICA/sMICB, cytokine in serum, and macrophage polarization analysis in tissue samples before the first chemotherapy administration. This research was performed to investigate the correlation between sMICA/sMICB expression and treatment outcomes as well as their influence on the immune system within ND-DLBCL.ResultsOf the 262 patients, 47.3% (n = 124) presented stage III or IV at diagnosis and 50.8% (n = 133) had a high International Prognostic Index (IPI ≥ 3). The patients with high (p = 0.034 and 0.004), elevated lactate dehydrogenase (p = 0.002 and 0.030), advanced stage (p = 0.003 and 0.012), and higher IPI risk (p = 0.009, and 0.032) correlated with the detection of sMICA or sMICB. The median progression-free survival (PFS) of patients with sMICA (p = 0.006) or sMICB (p =0.032) was inferior. Among the patients with advanced-stage or high IPI, those with sMICA or sMICB presented an inferior PFS and OS compared to those without. TNF-a, a pro-inflammatory cytokine, showed statistical significance with detected sMICA (p = 0.035) or sMICB (p = 0.044). Among anti-inflammatory cytokines, IL-1RA (P-value = 0.013) and IL-10 (p = 0.005) were associated with detecting sMICB, but not sMICA. In tissue samples, sMICA or sMICB detection did not correlate with the CD68/CD163 ratio.DiscussionConclusively, the identification of sMICA/sMICB presented unfavorable immunochemotherapy outcomes, and it was assumed that sMICA or sMICB and various cytokines interact, but the relationship with macrophage differentiation is unclear. Therefore, further research is needed to determine the relationship between sMICA/sMICB and tumor microenvironment in DLBCL

α-amylase and α-glucosidase inhibition effects of Korean edible brown, green, and red seaweed extracts

The control of intestinal α-amylase and α-glucosidase is an effective therapeutic strategy for prevention of post-prandial hyperglycemia associated with diabetes mellitus. The objective of this study was to evaluate the anti-diabetes activities of Korean edible seaweed against α-amylase and α-glucosidase, two carbolytic enzymes involved in serum glucose regulation. Of the 41 species initially screened, Cladophora wrightiana var. minor, Eisenia bicyclis, Ecklonia cava, Ishige foliacea, and Ishige okamurae exhibited the strongest inhibitory activities from brown seaweeds. Asparagopsis taxiformis showed the strongest inhibitory effects from red seaweeds. The results of this study suggest that the crude brown seaweed extracts (C. wrightiana var. minor, E. bicyclis, E. cava, I. foliacea, and I. okamurae) and crude red seaweed extracts (A. taxiformis) may have beneficial effects suppressing the rise in postprandial hyperglycemia through the inhibition of α-amylase and α-glucosidase

Characteristics, Outcomes and Predictors of Long-Term Mortality for Patients Hospitalized for Acute Heart Failure: A Report From the Korean Heart Failure Registry

BACKGROUND AND OBJECTIVES: Acute heart failure (AHF) is associated with a poor prognosis and it requires repeated hospitalizations. However, there are few studies on the characteristics, treatment and prognostic factors of AHF. The aims of this study were to describe the clinical characteristics, management and outcomes of the patients hospitalized for AHF in Korea. SUBJECTS AND METHODS: We analyzed the clinical data of 3,200 hospitalization episodes that were recorded between June 2004 and April 2009 from the Korean Heart Failure (KorHF) Registry database. The mean age was 67.6±14.3 years and 50% of the patients were female. RESULTS: Twenty-nine point six percent (29.6%) of the patients had a history of previous HF and 52.3% of the patients had ischemic heart disease. Left ventricular ejection fraction (LVEF) was reported for 89% of the patients. The mean LVEF was 38.5±15.7% and 26.1% of the patients had preserved systolic function (LVEF ≥50%), which was more prevalent in the females (34.0% vs. 18.4%, respectively, p<0.001). At discharge, 58.6% of the patients received beta-blockers (BB), 53.7% received either angiotensin converting enzyme-inhibitors or angiotensin receptor blockers (ACEi/ARB), and 58.4% received both BB and ACEi/ARB. The 1-, 2-, 3- and 4-year mortality rates were 15%, 21%, 26% and 30%, respectively. Multivariate analysis revealed that advanced age {hazard ratio: 1.023 (95% confidence interval: 1.004-1.042); p=0.020}, a previous history of heart failure {1.735 (1.150-2.618); p=0.009}, anemia {1.973 (1.271-3.063); p=0.002}, hyponatremia {1.861 (1.184-2.926); p=0.007}, a high level of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) {3.152 (1.450-6.849); p=0.004} and the use of BB at discharge {0.599 (0.360-0.997); p=0.490} were significantly associated with total death. CONCLUSION: We present here the characteristics and prognosis of an unselected population of AHF patients in Korea. The long-term mortality rate was comparable to that reported in other countries. The independent clinical risk factors included age, a previous history of heart failure, anemia, hyponatremia, a high NT-proBNP level and taking BB at discharge.ope

Controlling Ferromagnetic Easy Axis in a Layered MoS2 Single Crystal

We report the effective methods to induce weak ferromagnetism in pristine MoS2 persisting up to room temperature with the improved transport property, which would lead to new spintronics devices. The hydrogenation of MoS2 by heating at 300 degrees C for 1 h leads to the easy axis out of plane, while the irradiation of proton with a dose of 1 x 10(13) P/cm(2) leads to the easy axis in plane. The theoretical modeling supports such magnetic easy axes.open16

Light triggers the miRNA-biogenetic inconsistency for de-etiolated seedling survivability in Arabidopsis thaliana

The shift of dark-grown seedlings into light causes enormous transcriptome changes followed by a dramatic developmental transition. Here, we show that miRNA biogenesis also undergoes regulatory changes during de-etiolation. Etiolated seedlings maintain low levels of primary-miRNAs (pri-miRNAs) and miRNA processing core proteins, such as Dicer-like 1 (DCL1), SERRATE (SE) and HYPONASTIC LEAVES 1 (HYL1), whereas during de-etiolation, both pri-miRNAs and the processing components accumulated to high levels. However, most miRNA levels did not notably increase in response to light. To reconcile this inconsistency, we demonstrate that an unknown suppressor decreases miRNA-processing activity and light-induced SMALL RNA DEGRADING NUCLEASE 1 (SDN1) shortens the half-life of several miRNAs in de-etiolated seedlings. Taken together, we suggest a novel mechanism, miRNA-biogenetic inconsistency, which accounts for the intricacy of miRNA biogenesis during de-etiolation. This mechanism is essential for the survival of de-etiolated seedlings after long-term skotomorphogenesis and their optimal adaptation to ever-changing light conditions

Controlling ferromagnetic easy axis in a layered MoS2 single crystal

We report the effective methods to induce weak ferromagnetism in pristine MoS2 persisting up to room temperature with the improved transport property, which would lead to new spintronics devices. The hydrogenation of MoS2 by heating at 300 degrees C for 1 h leads to the easy axis out of plane, while the irradiation of proton with a dose of 1 x 10(13) P/cm(2) leads to the easy axis in plane. The theoretical modeling supports such magnetic easy axes.open116160Nsciescopu