Predicting RNA-binding residues from evolutionary information and sequence conservation

Abstract Background RNA-binding proteins (RBPs) play crucial roles in post-transcriptional control of RNA. RBPs are designed to efficiently recognize specific RNA sequences after it is derived from the DNA sequence. To satisfy diverse functional requirements, RNA binding proteins are composed of multiple blocks of RNA-binding domains (RBDs) presented in various structural arrangements to provide versatile functions. The ability to computationally predict RNA-binding residues in a RNA-binding protein can help biologists reveal important site-directed mutagenesis in wet-lab experiments. Results The proposed prediction framework named “ProteRNA” combines a SVM-based classifier with conserved residue discovery by WildSpan to identify the residues that interact with RNA in a RNA-binding protein. Although these conserved residues can be either functionally conserved residues or structurally conserved residues, they provide clues on the important residues in a protein sequence. In the independent testing dataset, ProteRNA has been able to deliver overall accuracy of 89.78%, MCC of 0.2628, F-score of 0.3075, and F0.5-score of 0.3546. Conclusions This article presents the design of a sequence-based predictor aiming to identify the RNA-binding residues in a RNA-binding protein by combining machine learning and pattern mining approaches. RNA-binding proteins have diverse functions while interacting with different categories of RNAs because these proteins are composed of multiple copies of RNA-binding domains presented in various structural arrangements to expand the functional repertoire of RNA-binding proteins. Furthermore, predicting RNA-binding residues in a RNA-binding protein can help biologists reveal important site-directed mutagenesis in wet-lab experiments.</p

An Evolutionary Method for Financial Forecasting in Microscopic High-Speed Trading Environment

The advancement of information technology in financial applications nowadays have led to fast market-driven events that prompt flash decision-making and actions issued by computer algorithms. As a result, today’s markets experience intense activity in the highly dynamic environment where trading systems respond to others at a much faster pace than before. This new breed of technology involves the implementation of high-speed trading strategies which generate significant portion of activity in the financial markets and present researchers with a wealth of information not available in traditional low-speed trading environments. In this study, we aim at developing feasible computational intelligence methodologies, particularly genetic algorithms (GA), to shed light on high-speed trading research using price data of stocks on the microscopic level. Our empirical results show that the proposed GA-based system is able to improve the accuracy of the prediction significantly for price movement, and we expect this GA-based methodology to advance the current state of research for high-speed trading and other relevant financial applications

Accuracy of hysteroscopic biopsy, compared to dilation and curettage, as a predictor of final pathology in patients with endometrial cancer

AbstractObjectiveTo compare the methods of transcervical resectoscopy versus dilation and curettage (D&C) for endometrial biopsy and to compare these methods for the percentage of histological upgrades at the final posthysterectomy pathology findings in endometrial cancer.Materials and methodsWe retrospectively reviewed 253 cases of uterine cancer diagnosed from May 1995 to January 2014. Included in the study were patients who received transcervical resectoscopy (TCR) or D&C biopsy as the diagnostic method and underwent laparoscopic staging at our institution. The International Federation of Gynecologists and Obstetricians (FIGO) grade in the pathological report of the biopsy and final hysterectomy were recorded. The extrauterine risk was stratified using the initial FIGO grade and depth of myometrium invasion. It was compared to the actual risk using final pathological findings.ResultsWe identified 203 cases of endometrial cancer; 18 (8.9%) patients had a higher histological grade at the final hysterectomy. Among the 203 patients, 76 patients underwent TCR biopsy and 127 underwent D&C biopsy. The histological grade was upgraded in two (2.6%) patients in the TCR group. Three (3.9%) patients had positive peritoneal washings. In the D&C group, 16 (12.6%) patients with three (2.4%) positive peritoneal washings were upgraded.ConclusionTranscervical resectoscopy could provide more precise grading information, compared to D&C (2.6% vs. 12.6%). Doctors could therefore make a more accurate staging plan, based on the preoperative risk evaluation

Dedifferentiated liposarcoma can induce a leukemoid reaction

SummaryLiposarcoma is one of the most common malignant soft tissue neoplasms in adults; however, few reports of liposarcoma had been described the expression of leukocytosis and granulocyte-colony stimulating factor (G-CSF). In this report, we present the rare case of a patient who had de-differentiated liposarcoma and elevated G-CSF levels that resulted in a leukemoid reaction. The patient was a 65-year-old man who had been lame for one month due to right thigh swelling. His body temperature was slightly elevated at 38°C and leukocytosis with an elevated white blood cell (WBC) count (41500/μL) was noted. The findings of computed tomography of the lower extremities indicated the presence of a malignancy. Therefore, an incision biopsy was performed. Based on the finding of magnetic resonance imaging (MRI) and the biopsy pathology report, we diagnosed the patient with liposarcoma. Moreover, the preoperative serum G-CSF level was elevated (261.8 pg/mL). An en bloc excision including the entire biopsy pathway was performed 5 days after admission. After en bloc excision of the tumor, WBC count, C-reactive protein (CRP) level, and G-CSF expression decreased. The final pathologic report confirmed the diagnosis of de-differentiated liposarcoma. No local recurrence or distant metastasis was detected in the follow-up image study, and the patient has remained asymptomatic 2 years after surgery. The case described here is a rare type of liposarcoma that produces G-CSF, which in turn, induces leukocytosis. Liposarcoma with elevated G-CSF levels resulting in a leukemoid reaction may indicate a poorly differentiated cell type and may be associated with a poor prognosis; however, en bloc excision of the tumor remains the primary treatment for this type of tumor. Moreover, the WBC count and G-CSF serum level can be as the tools monitoring the tumor recurrence

Anserine Reverses Exercise-Induced Oxidative Stress and Preserves Cellular Homeostasis in Healthy Men

The study tested whether anserine (beta-alanyl-3-methyl-l-histidine), the active ingredient of chicken essence affects exercise-induced oxidative stress, cell integrity, and haematology biomarkers. In a randomized placebo-controlled repeated-measures design, ten healthy men ingested anserine in either a low dose (ANS-LD) 15 mg&middot;kg&minus;1&middot;bw&minus;1, high dose (ANS-HD) 30 mg&middot;kg&minus;1&middot;bw&minus;1, or placebo (PLA), following an exercise challenge (time to exhaustion), on three separate occasions. Anserine supplementation increased superoxide dismutase (SOD) by 50% (p &lt; 0.001, effect size d = 0.8 for both ANS-LD and ANS-HD), and preserved catalase (CAT) activity suggesting an improved antioxidant activity. However, both ANS-LD and ANS-HD elevated glutathione disulfide (GSSG), (both p &lt; 0.001, main treatment effect), and consequently lowered the glutathione to glutathione disulfide (GSH/GSSG) ratio compared with PLA (p &lt; 0.01, main treatment effect), without significant effects on thiobarbituric acid active reactive substances (TBARS). Exercise-induced cell damage biomarkers of glutamic-oxaloacetic transaminase (GOT) and myoglobin were unaffected by anserine. There were slight but significant elevations in glutamate pyruvate transaminase (GPT) and creatine kinase isoenzyme (CKMB), especially in ANS-HD (p &lt; 0.05) compared with ANS-LD or PLA. Haematological biomarkers were largely unaffected by anserine, its dose, and without interaction with post exercise time-course. However, compared with ANS-LD and PLA, ANS-HD increased the mean cell volume (MCV), and decreased the mean corpuscular haemoglobin concentration (MCHC) (p &lt; 0.001). Anserine preserves cellular homoeostasis through enhanced antioxidant activity and protects cell integrity in healthy men, which is important for chronic disease prevention. However, anserine temporal elevated exercise-induced cell-damage, together with enhanced antioxidant activity and haematological responses suggest an augmented exercise-induced adaptative response and recovery

Knockdown of PsbO leads to induction of HydA and production of photobiological H2 in the green alga Chlorella sp. DT

Green algae are able to convert solar energy to H2 via the photosynthetic electron transport pathway under certain conditions. Algal hydrogenase (HydA, encoded by HYDA) is in charge of catalyzing the reaction: 2H+ + 2e− ↔ H2 but usually inhibited by O2, a byproduct of photosynthesis. The aim of this study was to knockdown PsbO (encoded by psbO), a subunit concerned with O2 evolution, so that it would lead to HydA induction. The alga, Chlorella sp. DT, was then transformed with short interference RNA antisense-psbO (siRNA-psbO) fragments. The algal mutants were selected by checking for the existence of siRNA-psbO fragments in their genomes and the low amount of PsbO proteins. The HYDA transcription and the HydA expression were observed in the PsbO-knockdown mutants. Under semi-aerobic condition, PsbO-knockdown mutants could photobiologically produce H2 which increased by as much as 10-fold in comparison to the wild type

Prevention of Dental Damage and Improvement of Difficult Intubation Using a Paraglossal Technique With a Straight Miller Blade

Patients with diseased teeth, or those who are difficult to intubate, have a higher risk of dental injury during laryngoscopy. We report 3 cases of smooth endotracheal intubation using a paraglossal technique with a straight Miller blade in patients with poor dentition. Three patients with poor dentition were scheduled to undergo surgery under general anesthesia. All patients presented with extremely loose upper central incisors and had lost the other right upper teeth, while micrognathia and prominent, loose upper incisors were noted in 1 case. We elected to use a straight Miller blade using a paraglossal approach. A nasopharyngeal airway was inserted after induction of general anesthesia to facilitate mask ventilation and prevent air leakage from the mask. The Miller blade was then inserted from the right corner of the mouth, avoiding contact with the vulnerable incisors, and advanced along the groove between the tongue and tonsil. The endotracheal tube was subsequently smoothly inserted after obtaining a grade 1 Cormack and Lehane view without dental trauma in all 3 cases. Direct laryngoscopy using the paraglossal straight blade technique avoids dental damage in patients with mobile upper incisors and no right maxillary molars. It is a practical alternative method that differs from the traditional Macintosh laryngoscope in patients with a high risk of dental injury during the procedure. This technique, which provides an improved view of the larynx, might also be helpful with patients in whom intubation is difficult

T Oligo-Primed Polymerase Chain Reaction (TOP-PCR): A Robust Method for the Amplification of Minute DNA Fragments in Body Fluids.

Body fluid DNA sequencing is a powerful noninvasive approach for the diagnosis of genetic defects, infectious agents and diseases. The success relies on the quantity and quality of the DNA samples. However, numerous clinical samples are either at low quantity or of poor quality due to various reasons. To overcome these problems, we have developed T oligo-primed polymerase chain reaction (TOP-PCR) for full-length nonselective amplification of minute quantity of DNA fragments. TOP-PCR adopts homogeneous "half adaptor" (HA), generated by annealing P oligo (carrying a phosphate group at the 5' end) and T oligo (carrying a T-tail at the 3' end), for efficient ligation to target DNA and subsequent PCR amplification primed by the T oligo alone. Using DNA samples from body fluids, we demonstrate that TOP-PCR recovers minute DNA fragments and maintains the DNA size profile, while enhancing the major molecular populations. Our results also showed that TOP-PCR is a superior method for detecting apoptosis and outperforms the method adopted by Illumina for DNA amplification

Functional roles of arginine residues in mung bean vacuolar H+-pyrophosphatase

AbstractPlant vacuolar H+-translocating inorganic pyrophosphatase (V-PPase EC 3.6.1.1) utilizes inorganic pyrophosphate (PPi) as an energy source to generate a H+ gradient potential for the secondary transport of ions and metabolites across the vacuole membrane. In this study, functional roles of arginine residues in mung bean V-PPase were determined by site-directed mutagenesis. Alignment of amino-acid sequence of K+-dependent V-PPases from several organisms showed that 11 of all 15 arginine residues were highly conserved. Arginine residues were individually substituted by alanine residues to produce R→A-substituted V-PPases, which were then heterologously expressed in yeast. The characteristics of mutant variants were subsequently scrutinized. As a result, most R→A-substituted V-PPases exhibited similar enzymatic activities to the wild-type with exception that R242A, R523A, and R609A mutants markedly lost their abilities of PPi hydrolysis and associated H+-translocation. Moreover, mutation on these three arginines altered the optimal pH and significantly reduced K+-stimulation for enzymatic activities, implying a conformational change or a modification in enzymatic reaction upon substitution. In particular, R242A performed striking resistance to specific arginine-modifiers, 2,3-butanedione and phenylglyoxal, revealing that Arg242 is most likely the primary target residue for these two reagents. The mutation at Arg242 also removed F− inhibition that is presumably derived from the interfering in the formation of substrate complex Mg2+–PPi. Our results suggest accordingly that active pocket of V-PPase probably contains the essential Arg242 which is embedded in a more hydrophobic environment

E2F transcription factor 1 overexpression as a poor prognostic factor in patients with nasopharyngeal carcinomas

AbstractNasopharyngeal carcinoma (NPC) is an endemic head and neck epithelial malignancy in Southeastern Asia and Taiwan. The E2 factor (E2F) family of transcription factors is downstream targets of the retinoblastoma protein 1. The E2F family of transcription factors is the key regulator of genes involved in cell cycle progression, cell fate determination, DNA damage repair and apoptosis. E2F1 is unique in that it contributes both to the control of cellular proliferation and cellular death. However, the expression of E2F1 protein and its clinicopathological associations in patients with NPC are yet to be evaluated. Immunoexpression of E2F1 was retrospectively assessed in biopsies of 124 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. The outcomes were correlated with clinicopathological features and patient survivals. Results indicated that high E2F1 protein level (50%) was correlated with primary tumor (p < 0.001) and stage (p = 0.002; 7th American Joint Committee on Cancer). In multivariate analyses, high E2F1 expression emerged as an independent prognosticator for worse disease-specific survival (p = 0.003), distal metastasis-free survival (p = 0.003), and local recurrence-free survival (p = 0.039). In conclusion, high E2F1 protein level is common, associated with adverse prognosticators, and might confer tumor aggressiveness through tumor cell proliferation and metastasis