SubCons: a new ensemble method for improved human subcellular localization predictions.

MOTIVATION: Knowledge of the correct protein subcellular localization is necessary for understanding the function of a protein. Unfortunately large-scale experimental studies are limited in their accuracy. Therefore, the development of prediction methods has been limited by the amount of accurate experimental data. However, recently large-scale experimental studies have provided new data that can be used to evaluate the accuracy of subcellular predictions in human cells. Using this data we examined the performance of state of the art methods and developed SubCons, an ensemble method that combines four predictors using a Random Forest classifier. RESULTS: SubCons outperforms earlier methods in a dataset of proteins where two independent methods confirm the subcellular localization. Given nine subcellular localizations, SubCons achieves an F1-Score of 0.79 compared to 0.70 of the second best method. Furthermore, at a FPR of 1% the true positive rate (TPR) is over 58% for SubCons compared to less than 50% for the best individual predictor. AVAILABILITY AND IMPLEMENTATION: SubCons is freely available as a webserver (http://subcons.bioinfo.se) and source code from https://bitbucket.org/salvatore_marco/subcons-web-server. The golden dataset as well is available from http://subcons.bioinfo.se/pred/download. CONTACT: arne@bioinfo.se. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Genome-wide analysis of salinity-stress induced DNA methylation alterations in cotton (Gossypium hirsutum L.) using the Me-DIP sequencing technology.

Cytosine DNA methylation is a significant form of DNA modification closely associated with gene expression in eukaryotes, fungi, animals, and plants. Although the reference genomes of cotton (Gossypium hirsutum L.) have been publically available, the salinity-stress-induced DNA methylome alterations in cotton are not well understood. Here, we constructed a map of genome-wide DNA methylation characteristics of cotton leaves under salt stress using the methylated DNA immunoprecipitation sequencing method. The results showed that the methylation reads on chromosome 9 were most comparable with those on the other chromosomes, but the greatest changes occurred on chromosome 8 under salt stress. The DNA methylation pattern analysis indicated that a relatively higher methylation density was found in the upstream2k and downstream2k elements of the CDS region and CG-islands. Almost 94% of the reads belonged to LTR-gspsy and LTR-copia, and the number of methylation reads in LTR-gypsy was four times greater than that in LTR-copia in both control and stressed samples. The analysis of differentially methylated regions (DMRs) showed that the gene elements upstream2k, intron, and downstream2k were hypomethylated, but the CDS regions were hypermethylated. The GO (Gene Ontology) analysis suggested that the methylated genes were most enriched in cellular processes, metabolic processes, cell parts and catalytic activities, which might be closely correlated with response to NaCl stress. In this study, we completed a genomic DNA methylation profile and conducted a DMR analysis under salt stress, which provided valuable information for the better understanding of epigenetics in response to salt stress in cotton.

The SubCons webserver: A user friendly web interface for state-of-the-art subcellular localization prediction.

SubCons is a recently developed method that predicts the subcellular localization of a protein. It combines predictions from four predictors using a Random Forest classifier. Here, we present the user-friendly web-interface implementation of SubCons. Starting from a protein sequence, the server rapidly predicts the subcellular localizations of an individual protein. In addition, the server accepts the submission of sets of proteins either by uploading the files or programmatically by using command line WSDL API scripts. This makes SubCons ideal for proteome wide analyses allowing the user to scan a whole proteome in few days. From the web page, it is also possible to download precalculated predictions for several eukaryotic organisms. To evaluate the performance of SubCons we present a benchmark of LocTree3 and SubCons using two recent mass-spectrometry based datasets of mouse and drosophila proteins. The server is available at http://subcons.bioinfo.se/.

Brain MRI Characteristics of Patients with Anti-N-Methyl-D-Aspartate Receptor Encephalitis and Their Associations with 2-Year Clinical Outcome.

BACKGROUND AND PURPOSE: Anti-N-methyl-D-aspertate receptor encephalitis is an autoimmune-mediated disease without specific brain MRI features. Our aim was to investigate the brain MR imaging characteristics of anti-N-methyl-D-aspartate receptor encephalitis and their associations with clinical outcome at a 2-year follow-up. MATERIALS AND METHODS: We enrolled 53 patients with anti-N-methyl-D-aspartate receptor encephalitis and performed 2-year follow-up. Brain MRIs were acquired for all patients at the onset phase. The brain MR imaging manifestations were classified into 4 types: type 1: normal MR imaging findings; type 2: only hippocampal lesions; type 3: lesions not involving the hippocampus; and type 4: lesions in both the hippocampus and other brain areas. The modified Rankin Scale score at 2-year follow-up was assessed, and the association between the mRS and onset brain MR imaging characteristics was evaluated. RESULTS: Twenty-eight (28/53, 53%) patients had normal MR imaging findings (type 1), and the others (25/53, 47%) had abnormal MRI findings: type 2: 7 patients (13%); type 3: seven patients (13%); and type 4: eleven patients (21%). Normal brain MRI findings were more common in female patients (P = .02). Psychiatric and behavioral abnormalities were more common in adults (P = .015), and autonomic symptoms (P = .025) were more common in pediatric patients. The presence of hippocampal lesions (P = .008, OR = 9.584; 95% CI, 1.803-50.931) and relapse (P = .043, OR = 0.111; 95% CI, 0.013-0.930) was associated with poor outcome. CONCLUSIONS: Normal brain MRI findings were observed in half of the patients. Lesions in the hippocampus were the most common MR imaging abnormal finding. The presence of hippocampal lesions is the main MR imaging predictor for poor prognosis in patients with anti-N-methyl-D-aspartate receptor encephalitis.

Right ventricular dilatation and remodeling the first year after an initial transmural wall left ventricular myocardial infarction.

Left ventricular (LV) remodeling after LV myocardial infarction was described previously. Little is known regarding concomitant adaptation, if any, in right ventricular (RV) volumes after LV infarction. To examine this issue, cine-computed tomography was used to determine serial changes in absolute global LV and RV volumes in 27 patients without clinical heart failure during the first year after an initial Q-wave myocardial infarction (14 anterior and 13 inferior). The patient group with anterior wall LV infarction showed progressive increases in LV and RV volumes from hospital discharge to 1 year (end-diastolic volumes +25 and +13%, respectively; and end-systolic volumes +35 and +15%, respectively). In patients with inferior wall LV infarction, both LV end-diastolic and end-systolic volumes increased significantly during the study period (+13 and +15%, respectively). Despite a trend for RV end-diastolic volume to be increased at 1 year, neither end-diastolic nor end-systolic volume increased significantly after hospital discharge following inferior wall LV infarction. Absolute RV end-diastolic volume was not significantly different between the infarct groups at any time after infarction. In conclusion, global changes occur in both LV and RV volumes during the first year after an initial infarction regardless of infarct location. The magnitude of these changes was greater after anterior than inferior wall LV infarction.

Sensory neurons regenerate more dominantly than motoneurons during the initial stage of the regenerating process after peripheral axotomy.

This study was designed to determine whether sensory neurons or motoneurons were dominant during the earlier stage of the regeneration process after peripheral axotomy. After transection of the right sciatic nerves of rats, epineurial end neurorrhaphy was performed. At 5, 7 and 14 days postoperatively, the nerves were re-transected at the positive pinch site, and their proximal stumps were exposed to the retrograde neurotracer, Fluoro-Gold (F-G). Seventy-two hours later, the lumbar spinal cords and the L4 and L5 dorsal root ganglia (DRG) were harvested and evaluated. The incidence and the intensity of F-G labelling in DRG were significantly higher than in anterior horns (AH). These results demonstrated that sensory neurons were more dominant than motoneurons in nerve regeneration.

Examination of geniculate ganglion cells contributing sensory fibers to the rat facial 'motor' nerve.

Using a method to visualize HRP-containing cells in the geniculate ganglion (GG) in situ after decalcifying surrounding bone, we found that about 30% of the total (about 1000) GG cells contributed sensory fibers to the posterior auricular branch of the facial motor nerve. These cells are relatively large for GG cells in general. The remaining facial motor nerve branches, including those involved in vibrissal movement, contained few sensory afferent fibers originating from GG cells.

Effectiveness of an insole with a lateral wedge for idiopathic osteonecrosis of the knee.

For the purpose of investigating the effect of an insole with a lateral wedge, we studied 30 patients (31 knees) aged from 46 to 78 years with idiopathic osteonecrosis of the knee for at least three years. The 18 knees treated with an insole (group I) were matched by age, gender, obesity index, area of lesion, femorotibial angle, stage, and clinical evaluation with 13 treated conservatively without an insole (group II). The clinical results, as rated by a knee score, improved significantly more in group I than in group II. Radiologically, the necrotic area and ratio decreased in group I, whereas in group II they increased. In advanced cases, with stage 4 or a femorotibial angle of more than 180 degrees, the use of an insole did not improve the clinical or radiological findings. The insole is a valuable method of conservative treatment for the early stages of osteonecrosis of the medial femoral condyle.

Expression of cytokines after meniscal rasping to promote meniscal healing.

PURPOSE: We have developed a new surgical procedure of rasping a meniscal surface to repair a tear in the avascular zone. This procedure stimulates vascular induction to the tear, resulting in meniscal healing. The purpose of this study was to elucidate the mechanism of vascular induction and meniscal healing. TYPE OF STUDY: Randomized trial. METHODS: A full-thickness longitudinal tear of 5 mm in length was created in the avascular zone of the anterior segment of both medial menisci of rabbits. Meniscal rasping of about 0.5 mm in depth was then done on the femoral surface of the left meniscus from the parameniscal synovium to the inner portion including the longitudinal tear, and the right meniscus was left untreated as a control. After surgery, at 1, 7, 14, 28, 56, and 112 days, 4 rabbits were killed, both medial menisci were resected, and immunohistochemical staining with monoclonal antibodies was used to quantify expression of interleukin-1alpha (IL-1alpha), transforming growth factor-beta1 (TGF-beta1), platelet-derived growth factor (PDGF), and proliferating-cell nuclear antigen (PCNA) on the femoral surface of the menisci. A positive ratio of immunostaining was encountered. RESULTS: The positive ratio of IL-1alpha, TGF-beta1, PDGF, and PCNA on the rasped surface area reached its peak at 1, 7, 14, and 7 days, respectively, after surgery, and thereafter gradually declined. Although the time course of the positive ratio was different among these cytokines, the positive ratio on the rasped surface was significantly higher than that on the control surface at the early stage of the observation period. CONCLUSIONS: The cytokine network on the rasped meniscal surface appears to be the key to explaining the mechanism of vascular induction and meniscal healing by meniscal rasping.

A case of superficial peroneal nerve injury during ankle arthroscopy.

We report a case of superficial peroneal nerve (SPN) injury caused by ankle arthroscopy. A 20-year-old woman underwent arthroscopy on her right ankle because of chronic ankle pain after a sprain. After arthroscopy, the patient complained of pain on the dorsum of her right foot and felt a radiating pain from the anterolateral portal to the dorsomedial aspect of her foot. Eight months after arthroscopy, we found that a neuroma had developed on the intermediate dorsal cutaneous nerve, and performed neurolysis of the SPN. Her symptoms gradually decreased after surgery, and had disappeared by 45 months. To avoid such an injury of the SPN, the safest placement of the anterolateral portal is necessary and is, according to our previous anatomic study, 2 mm lateral to the peroneus tertius tendon.

Bandage distraction technique for ankle arthroscopy.

In ankle arthroscopy, the joint space of the talocrural joint is often too narrow for insertion of the scope and instruments. Various distraction devices for this procedure have been used to widen the joint space. Bandage distraction is effective and noninvasive, but it is difficult to extend the posterior joint space sufficiently for insertion of the scope. Here we describe a new bandage distraction method that can extend the posterior joint space adequately. Using our method, the anterior and posterior joint spaces on direct lateral radiographs were measured after adding the distraction force in nine healthy volunteers (18 ankles; three men and 6 women). This was compared to a previously reported method. The posterior joint space was widened a greater amount when our new bandage distraction technique was used.

Control of preweaning diarrhea in piglets by acupuncture and Chinese medicine.

Preweaning diarrhea in piglets is a very common disease. Even thought vaccination and antibiotics are used widely for controlling the disease nowadays, it is still a serious production problem. Therefore, the search for a new medication that is both cheaper and more effective is of major importance. During the last year, acupuncture and Chinese medicine have been evaluated for this purpose. The results are summarized as follows: 1) Oral administration of 0.5 g of Ko-ken-huang-lien-huang-chin-tang (pueraria, coptis, scute and licorice combination) to piglets at 1 day old was effective in reducing incidence of infection (P less than 0.1) and increasing the body weight gain (P less than 0.05) during the first 10 days of life. Gentamycin or aqua-acupuncture at day 1 of life had no prophylactic value. 2) Piglets with preweaning diarrhea were treated by aqua-acupuncture at Chang-Chiang point (VG 1, or so called Chiao-Chao in traditional pig charts) with 0.2 ml of 3% saline, or by oral administration of 0.5 g of Ko-ken-huang-lien-huang-chin-tang or by injection of gentamycin (10 mg/piglet) twice a day for 1-3 days. These treatments significantly reduced the duration of illness (P less than 0.01) when compared with the control groups which received 0.5 g lactose orally. These results indicate that both acupuncture treatment and Chinese medicine have a high clinical value for controlling piglet diarrhea.

Adverse effects of saline neurolysis on a chronically compressed rat sciatic nerve.

We have evaluated the effect of saline neurolysis compared with a simple decompression procedure on chronically compressed sciatic nerves in rats. Eight months after the initiation of nerve compression within a silicone tube, rats were divided into three groups of 35. In group I, saline was injected subepineurially at the compressed segment of the nerve after removal of the tube (decompression plus saline neurolysis). The nerves in group II were treated by removal of the tube only (simple decompression). In group III the tubes were left in place. Adding saline neurolysis to decompression provided no histological, morphometric, electrophysiological, or vascular advantages up to four months, and even gave worse results than simple decompression. We conclude that saline neurolysis has no beneficial effect on a chronically compressed nerve and it is not recommended for clinical use.

Atypical compression of the deep branch of the ulnar nerve in Guyon's canal by a ganglion. Case report.

A 61-year-old woman with an ulnar claw-finger deformity but no sensory loss had a cystic lesion excised from Guyon's canal. The ganglion was in zone 1 of the canal, which is associated with both motor and sensory deficit, but on this occasion it caused motor dysfunction alone.

[The effect of neurolysis on the recovery of experimentally induced entrapment neuropathy].

While chronic entrapment neuropathy is a common problem in orthopaedic practice, controversy remains over which is the most appropriate surgical procedures. There have been few experimental studies addressing this problem. This study was undertaken to compare the effects, as well as the risks, of various surgical procedures on experimentally induced chronic entrapment neuropathy in rat. Ninety adult male Wistar rats (250-300 g) were used as the experimental animals. The sciatic nerves were wrapped by silastic tubes each 10 mm long with an internal diameter of 1.5 mm. At eight months later, after the nerves had demonstrated changes compatible with clinical chronic entrapment neuropathy, the tubes were removed and simple decompression, external or internal neurolysis was carried out on the entrapped nerve. Nerves at 1, 2, 4 and 6 months after surgery were morphologically and functionally examined. Electrophysiological and histological changes were gradually ameliorated after simple decompression. The externally neurolysed nerve showed improvements in the normal nerve functions. Internal neurolysis on chronically entrapped nerves produced a deterioration in the nerve functions, as well as in the nerve structures. We concluded that more favorable results were achieved by the external neurolysis, whereas internal neurolysis was a very harmful procedure for chronic entrapment neuropathy.

A fast computed tomographic imaging method for myocardial perfusion.

Fast x-ray computed tomography can be used to generate indicator dilution curves in perfused tissues following intravascular injection of roentgen contrast agent. These curves can be used to estimate regional parenchymal perfusion, intravascular blood volume, heterogeneity of these two parameters, and vascular bed transfer function.

Recurrent acute encephalopathy due to fatty acid metabolic defect--report of two cases.

An increasing number of reports indicate that patients with some inherited metabolic diseases may have symptoms resembling those of Reye's syndrome. We describe 2 patients who developed Reye-like syndrome at the age of 7 months respectively. Conscious disturbance, hepatomegaly, impaired liver function, hyperammonemia, and nonketotic hypoglycemia were noted during acute episode. Blood lactate level was normal in both cases. Liver and muscle biopsy of both patients showed macrovesicular fatty change. Increased density of matrix in hepatocyte mitochondria was noted in patient 1. Stacking of cristae was shown in patient 2. The first patient had another episode of hyperammonemia at 2 years of age. The second patient was admitted three more times due to recurrent vomiting and conscious change at the age of 7 months, 10 months and 13 months respectively. Fatty acid metabolic defect should be considered in children or infants with recurrent Reye-like syndrome.