19 research outputs found

    Deep learning predicts short non-coding RNA functions from only raw sequence data.

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    Small non-coding RNAs (ncRNAs) are short non-coding sequences involved in gene regulation in many biological processes and diseases. The lack of a complete comprehension of their biological functionality, especially in a genome-wide scenario, has demanded new computational approaches to annotate their roles. It is widely known that secondary structure is determinant to know RNA function and machine learning based approaches have been successfully proven to predict RNA function from secondary structure information. Here we show that RNA function can be predicted with good accuracy from a lightweight representation of sequence information without the necessity of computing secondary structure features which is computationally expensive. This finding appears to go against the dogma of secondary structure being a key determinant of function in RNA. Compared to recent secondary structure based methods, the proposed solution is more robust to sequence boundary noise and reduces drastically the computational cost allowing for large data volume annotations. Scripts and datasets to reproduce the results of experiments proposed in this study are available at: https://github.com/bioinformatics-sannio/ncrna-deep

    Case report: Ponatinib as a bridge to CAR-T cells and subsequent maintenance in a patient with relapsed/refractory Philadelphia-like acute lymphoblastic leukemia

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    Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) constitutes a heterogeneous subset of ALL with a uniformly unfavorable prognosis. The identification of mutations amenable to treatment with tyrosine kinase-inhibitors (TKIs) represents a promising field of investigation. We report the case of a young patient affected by relapsed/refractory Ph-like ALL treated with chimeric antigen receptor T (CAR-T) cells after successful bridging with compassionate-use ponatinib and low-dose prednisone. We restarted low-dose ponatinib maintenance three months later. Twenty months later, measurable residual disease negativity and B-cell aplasia persist. To the best of our knowledge, this is the first case reporting the use of ponatinib in Ph-like ALL as a bridge to and maintenance after CAR-T cell therapy

    Loss of circadian rhythmicity in bdnf knockout zebrafish larvae

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    Brain-derived neurotrophic factor (BDNF) plays a pivotal role in neuronal growth and differentiation, neuronal plasticity, learning, and memory. Using CRISPR/Cas9 technology, we generated a vital Bdnf null mutant line in zebrafish and carried out its molecular and behavioral characterization. Although no defects are evident on a morphological inspection, 66% of coding genes and 37% of microRNAs turned out to be differentially expressed in bdnf−/− compared with wild type sibling embryos. We deeply investigated the circadian clock pathway and confirmed changes in the rhythmic expression of clock (arntl1a, clock1a and clock2) and clock-controlled (aanat2) genes. The modulatory role of Bdnf on the zebrafish circadian clock was then validated by behavioral tests highlighting the absence of circadian activity rhythms in bdnf−/− larvae. The circadian behavior was partially rescued by pharmacological treatment. The bdnf−/− zebrafish line presented here is the first valuable and stable vertebrate model for the study of BDNF-related neurodevelopmental disease

    Detection of long non–coding RNA homology, a comparative study on alignment and alignment–free metrics

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    Abstract Background Long non-coding RNAs (lncRNAs) represent a novel class of non-coding RNAs having a crucial role in many biological processes. The identification of long non-coding homologs among different species is essential to investigate such roles in model organisms as homologous genes tend to retain similar molecular and biological functions. Alignment–based metrics are able to effectively capture the conservation of transcribed coding sequences and then the homology of protein coding genes. However, unlike protein coding genes the poor sequence conservation of long non-coding genes makes the identification of their homologs a challenging task. Results In this study we compare alignment–based and alignment–free string similarity metrics and look at promoter regions as a possible source of conserved information. We show that promoter regions encode relevant information for the conservation of long non-coding genes across species and that such information is better captured by alignment–free metrics. We perform a genome wide test of this hypothesis in human, mouse, and zebrafish. Conclusions The obtained results persuaded us to postulate the new hypothesis that, unlike protein coding genes, long non-coding genes tend to preserve their regulatory machinery rather than their transcribed sequence. All datasets, scripts, and the prediction tools adopted in this study are available at https://github.com/bioinformatics-sannio/lncrna-homologs

    Multicentre survey of post-surgical infections in Campania (Italy)

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    The aim of the study was to evaluate the incidence of post-surgical infections and to assess the way of managing antibiotic surgical prophylaxis. The survey was carried out by means of a questionnaire in order to obtain diverse information such as demographics, length of pre- and post-operative hospitalization, type of surgery, intervention duration, possible antibiotic prophylaxis and onset of post-surgical infections also monitored by post-discharge ambulatory controls. Four General Surgery and five Obstetrics and Gynaecology Departments in Campania (southern Italy) participated in the study, which was carried out in the period December 2001-January 2002. Overall, 410 questionnaires were collected referring to as many patients; antibiotic prophylaxis was performed in 385 (93.9%) patients. Antibiotic prophylaxis was generally managed not according to the general principles suggested by the international guidelines either for timing or for its duration or for the route of administration. Substantial differences were also noted in patient selection and antibiotic choice. Surgical site infections were recorded in 0.6% of patients undergoing clean surgery, in 5.3% of patients undergoing clean-contaminated surgery and in 3.2% of those undergoing contaminated surgery. Distant infections occurred in 1.8% and 6.5% in clean-contaminated and contaminated surgery, respectively. The results of the present study suggest the need of a continuous and accurate monitoring of post-surgical infections and the need to adopt appropriate guidelines to improve the management of surgical prophylaxis

    The Effect of Removable Orthodontic Appliances on Oral Microbiota: A Systematic Review

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    Background (1): Removable orthodontic appliances may favor plaque accumulation and oral microbe colonization. This might be associated with intraoral adverse effects on enamel or periodontal tissues. The proposed systematic review was carried out to evaluate qualitatively and quantitatively the microbiological changes occurring during orthodontic therapy with removable orthodontic appliances. Methods (2): PubMed, Cochrane Library, Embase, Web of Science, Scopus, Ovid Medline, and Dentistry and Oral Sciences Source were searched. The research included every article published up to January 2020. The Preferred Reporting Items for Reporting Systematic reviews and Meta Analyses (PRISMA) protocol and the “Swedish Council on Technology Assessment in Health Care Criteria for Grading Assessed Studies” (SBU) method were adopted to conduct this systematic review. Results (3): The current study has a moderate evidence, demonstrating that removable appliances do influence the oral microbiota. Significant alterations occur just 15 days after the beginning of therapy, independently from the type of appliance. Furthermore, the levels of oral pathogens decrease significantly or even returned to pre-treatment levels several months later the therapy end. Conclusions (4): This review suggests that orthodontic treatment with removable appliances induces changes to oral microflora, but these alterations might not be permanent

    Surveillance of post-operative infections and management of antibiotic surgical prophylaxis in an Italian region

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    The aim of the study was to evaluate the incidence of post-surgical infections and to assess management of antibiotic surgical prophylaxis. The survey was carried out by means of a questionnaire in order to obtain diverse information such as demographics, length of pre- and post-operative hospitalization, type of surgery, intervention duration, possible antibiotic prophylaxis and onset of post-surgical infections also monitored by post-discharge ambulatory controls. Four General Surgery and five Obstetrics and Gynecology Departments in Campania (southern Italy) participated in the study, which was carried out from December 2001-January 2002. Overall, 410 questionnaires were collected, referring to as many patients; antibiotic prophylaxis was performed in 385 (93.9%) patients. Antibiotic prophylaxis was generally managed not according to the general principles suggested by the international guidelines either for timing, for its duration or for the route of administration. Substantial differences were also noted in patient selection and antibiotic choice. Surgical site infections were recorded in 0.9% of patients undergoing clean surgery and in 3.6% of patients undergoing clean-contaminated surgery. Distant infections occurred in 1.5% in clean-contaminated surgery. The results of the present study suggest the need for continuous and accurate monitoring of post-surgical infections and the need to adopt appropriate guidelines to improve the management of surgical prophylaxis
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