Abstract Presently, there is no convenient method to measure 24-h urinary Na excretion, which is an important index of daily Na intake, and 24-h urine collection involves a complex process. However, the Na-to-creatinine ratio (NCR) in spot urine has the potential to evaluate 24-h Na excretion and is useful for point-of-care testing. Thus, this study aimed to realize a near-infrared spectroscopic system to assess NCR in spot urine: (1) We attempted to estimate Na concentration using...
Abstract This study investigated the accuracy, drift, and clinical usefulness of a new optical transcutaneous oxygen tension (tcPO2) measuring technique, combined with a conventional electrochemical transcutaneous carbon dioxide (tcPCO2) measurement and reflectance pulse oximetry in the novel transcutaneous OxiVenT™ Sensor. In vitro gas studies were performed to measure accuracy and drift of tcPO2 and tcPCO2. Clinical usefulness for tcPO2 and tcPCO2 monitoring was assessed in neonates....
Abstract The aim of this study was the analysis of the mechanical behaviour of a partially porous lumbar custom-made cage by means of a subject-specific finite element analysis (FEA). The cage, made of Ti6Al4V ELI alloy, was produced via electron beam melting (EBM) process and surgically implanted in a female subject, 50 years old. The novelty of this study was the customized design of the cage and of its internal structure, which is impossible to obtain with the traditional production...
Abstract In this work, the IEEE 802.11af technology–based wireless sensor network for health data monitoring with priority classes is proposed. In IEEE 802.11af technology, a White Space Device (WSD), a Station (STA), and an Access Point (AP) communicate through television white spectrum opportunistically without causing any harmful interference to licensed` services. In the proposed network; WSDs, STA, and AP employ Frequency Division Multiple Access (FDMA) technique with the...
Experimental validation of adaptive pedicle screws—a novel implant concept using shape memory alloys
Abstract Pedicle screw fixation is a standard procedure in spine surgery. A secure anchoring in deficient (e.g., osteoporotic) bone or in a secondary supply after a revision is a major challenge. This study aimed to test the primary stability of a new self-expanding shape memory actuator screw concept with the traditional screw design. The actuator part braces itself against the osseous environment after implantation by heating to body temperature. Thirty screws and twenty-four...
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Cancers, Vol. 11, Pages 1815: Nucleocytoplasmic Shuttling of STATs. A Target for Intervention? Cancers doi: 10.3390/cancers11111815 Authors: Sabrina Ernst Gerhard Müller-Newen Signal transducer and activator of transcription (STAT) proteins are transcription factors that in the latent state are located predominantly in the cytoplasm. Activation of STATs through phosphorylation of a single tyrosine residue results in nuclear translocation. The requirement of tyrosine phosphorylation...
Cancers, Vol. 11, Pages 1814: A Novel Calcium-Mediated EMT Pathway Controlled by Lipids: An Opportunity for Prostate Cancer Adjuvant Therapy Cancers doi: 10.3390/cancers11111814 Authors: Figiel Bery Chantôme Fontaine Pasqualin Maupoil Domingo Guibon Bruyère Potier-Cartereau Vandier Fromont Mahéo The composition of periprostatic adipose tissue (PPAT) has been shown to play a role in prostate cancer (PCa) progression. We recently reported...
Cancers, Vol. 11, Pages 1813: Evaluation of the Accuracy of Liquid-Based Oral Brush Cytology in Screening for Oral Squamous Cell Carcinoma Cancers doi: 10.3390/cancers11111813 Authors: Deuerling Gaida Neumann Remmerbach This study evaluates the accuracy of the results of liquid-based oral brush cytology and compares it to the histology and/or the clinical follow-ups of the respective patients. A total of 1352 exfoliated specimens were collected with an Orcellex brush from...
Cancers, Vol. 11, Pages 1812: Synergistic Autophagy Effect of miR-212-3p in Zoledronic Acid-Treated In Vitro and Orthotopic In Vivo Models and in Patient-Derived Osteosarcoma Cells Cancers doi: 10.3390/cancers11111812 Authors: Ju Yeon Oh Eun Ho Kim Yeon-Joo Lee Sei Sai Sun Ha Lim Jang Woo Park Hye Kyung Chung Joon Kim Guillaume Vares Akihisa Takahashi Youn Kyoung Jeong Mi-Sook Kim Chang-Bae Kong Osteosarcoma (OS) originates from osteoid bone tissues...
Cancers, Vol. 11, Pages 1810: The Gasdermin E gene Potential as a Pan-Cancer Biomarker, While Discriminating between Different Tumor Types Cancers doi: 10.3390/cancers11111810 Authors: Joe Ibrahim Ken Op de Beeck Erik Fransen Marc Peeters Guy Van Camp Due to the elevated rates of incidence and mortality of cancer, early and accurate detection is crucial for achieving optimal treatment. Molecular biomarkers remain important screening and detection tools, especially in light...
Cancers, Vol. 11, Pages 1809: Bulk and Single-Cell Next-Generation Sequencing: Individualizing Treatment for Colorectal Cancer Cancers doi: 10.3390/cancers11111809 Authors: Ioannis D. Kyrochristos Demosthenes E. Ziogas Anna Goussia Georgios K. Glantzounis Dimitrios H. Roukos The increasing incidence combined with constant rates of early diagnosis and mortality of colorectal cancer (CRC) over the past decade worldwide, as well as minor overall survival improvements in the...
Cancers, Vol. 11, Pages 1808: hENT1 Testing in Pancreatic Ductal Adenocarcinoma: Are We Ready? A Multimodal Evaluation of hENT1 Status Cancers doi: 10.3390/cancers11111808 Authors: Jerome Raffenne Remy Nicolle Francesco Puleo Delphine Le Corre Camille Boyez Raphael Marechal Jean François Emile Peter Demetter Armelle Bardier Pierre Laurent-Puig Louis de Mestier Valerie Paradis Anne Couvelard Jean Luc VanLathem John R. MacKey Jean-Baptiste Bachet...
Cancers, Vol. 11, Pages 1811: Mitigating Effect of 1-Palmitoyl-2-Linoleoyl-3-Acetyl-Rac-Glycerol (PLAG) on a Murine Model of 5-Fluorouracil-Induced Hematological Toxicity Cancers doi: 10.3390/cancers11111811 Authors: Jinseon Jeong Yong-Jae Kim Do Young Lee Ki-Young Sohn Sun Young Yoon Jae Wha Kim 5-Fluorouracil (5-FU) is an antimetabolite chemotherapy widely used for the treatment of various cancers. However, many cancer patients experience hematological side effects following...
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Purpose. To investigate the pachymetry distribution of central cornea and morphologic changes in subclinical keratoconus with normal biomechanics and determine their potential benefit for the screening of very early keratoconus. Methods. This retrospective comparative study was performed in 33 clinically unaffected eyes with normal topography and biomechanics from 33 keratoconus patients with very asymmetric ectasia (VAE-NTB; Corvis Biomechanical Index defined) and 70 truly normal eyes from 70 age-matched...
Several computational approaches for predicting subcellular localization have been developed and proposed. These approaches provide diverse performance because of their different combinations of protein features, training datasets, training strategies, and computational machine learning algorithms. In some cases, these tools may yield inconsistent and conflicting prediction results. It is important to consider such conflicting or contradictory predictions from multiple prediction programs during...
Hepatocellular carcinoma (HCC) is one of the most common and lethal malignancies. Recent studies reveal that tumor microenvironment (TME) components significantly affect HCC growth and progression, particularly the infiltrating stromal and immune cells. Thus, mining of TME-related biomarkers is crucial to improve the survival of patients with HCC. Public access of The Cancer Genome Atlas (TCGA) database allows convenient performance of gene expression-based analysis of big data, which contributes...
Purpose. To investigate factors with a significant relationship with the absence of musculoskeletal disease (MSD: osteoporosis, knee osteoarthritis (K-OA), and lumbar spondylosis (L-OA)) in elderly people ≥70 years old. Methods. The subjects were 279 people (134 males, 145 females, mean age: 75.2 years) who attended an annual health checkup and were prospectively included in the study. Osteoporosis was defined as %YAM ≤70%, K-OA as Kellgren–Lawrence grade ≥2, and L-OA as osteophytes of Nathan class...
The islands of Sardinia, Crete, and Cyprus are hosting the last native insular griffon populations in the Mediterranean basin. Their states have been evaluated from “vulnerable” to “critically endangered”. The sequence analysis of molecular markers, particularly the mtDNA D-loop region, provides useful information in studying the evolution of closely related taxa and the conservation of endangered species. Therefore, a study of D-loop region sequence was carried out to estimate the genetic diversity...
Animal gut microbiota begins to colonize after birth and is functionally indispensable for maintaining the health of the host. It has been reported that gender and age influence the composition of the intestinal microbiome. However, the effects of gender and age on the intestinal microorganism of forest musk deer (FMD) remain unclear. The aim of this study was to establish the relationship between the structure and composition of fecal microbiota of male and female forest musk deer with age. Here,...
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Journal of Adolescent and Young Adult Oncology, Ahead of Print.
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Thyroid, Volume 29, Issue 11, Page 1545-1557, November 2019.
Thyroid, Volume 29, Issue 11, Page 1708-1709, November 2019.
Thyroid, Volume 29, Issue 11, Page 1634-1645, November 2019.
Thyroid, Volume 29, Issue 11, Page 1615-1622, November 2019.
Thyroid, Volume 29, Issue 11, Page 1704-1707, November 2019.
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AbstractAir pollution has been linked to poor olfactory function in human adults. Among pollutants, particulate matter (PM) is especially relevant, as it may contain toxic metal ions that can reach the brain via olfactory pathways. Our purpose was to investigate the relation between atmospheric PM and olfactory identification performance in children. Using a validated method, we tested the olfactory identification performance of 120 children, 6–12 years old, from two locations in Mexico City; a focal...
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Alternative Splicing Coupled with Transcript Degradation Modulates OAS1g Antiviral Activity [Report]
At the heart of an innate immune response lies a tightly regulated gene expression program. This precise regulation is crucial because small changes can shift the balance from protective to destructive immunity. Here we identify a frequently used alternative splice site in the gene oligoadenylate synthetase 1g (Oas1g), a key component of the 2-5A antiviral system. Usage of this splice site leads to the generation of a transcript subject to decay, and removal of the site leads to increased expression...
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Purpose To determine whether second-line therapy with capecitabine and temozolomide was superior to irinotecan, leucovorin and fluorouracil (FOLFIRI) in patients with RAS mutated, MGMT methylated metastatic colorectal cancer. Experimental design In this randomized, phase 2 trial, we enrolled patients with RAS mutated, MGMT methylated mCRC after failure of oxaliplatin-based regimen. Patients with centrally confirmed MGMT methylation were stratified by first-line progression-free survival and prior...
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British Journal of Cancer, Published online: 19 November 2019; doi:10.1038/s41416-019-0633-0TRIP13 promotes the cell proliferation, migration and invasion of glioblastoma through the FBXW7/c-MYC axis
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Oncogenesis, Published online: 18 November 2019; doi:10.1038/s41389-019-0177-4Long non-coding RNA GAS5 acts as proliferation “brakes” in CD133+ cells responsible for tumor recurrence
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Journal of the American Chemical SocietyDOI: 10.1021/jacs.9b10763
Journal of the American Chemical SocietyDOI: 10.1021/jacs.9b10741
Journal of the American Chemical SocietyDOI: 10.1021/jacs.9b08776
Journal of the American Chemical SocietyDOI: 10.1021/jacs.9b09367
Journal of the American Chemical SocietyDOI: 10.1021/jacs.9b07632
Journal of the American Chemical SocietyDOI: 10.1021/jacs.9b10376
Journal of the American Chemical SocietyDOI: 10.1021/jacs.9b10875
Journal of the American Chemical SocietyDOI: 10.1021/jacs.9b10507
Journal of the American Chemical SocietyDOI: 10.1021/jacs.9b09721
Journal of the American Chemical SocietyDOI: 10.1021/jacs.9b10579
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Exp Clin Endocrinol DiabetesDOI: 10.1055/a-1032-8369Thyroid hormones (TH) pass through the plasma membrane into the target cells via transporter proteins. Thyroid hormone transporters that have been identified until now belong to two different solute carrier (SLC) subfamilies i) the major facilitator superfamily (MFS) and ii) the amino acid polyamine-organocation (APC) superfamily. Both are comprised by 12 transmembrane helices, however with different structural topology. The TH transporter MCT8,...
Exp Clin Endocrinol DiabetesDOI: 10.1055/a-1038-3883Chronic obstructive pulmonary disease (COPD) is a common disease with an increasing prevalence, characterised by persistent respiratory symptoms and airflow limitation. Apart from cigarette smoking, certain occupational and environmental exposures, low socioeconomic status and genetic factors may contribute to the pathogenesis of COPD. Comorbidities, e. g. diabetes mellitus (DM), can negatively affect quality of life, COPD outcomes and cardiovascular...
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Analytical ChemistryDOI: 10.1021/acs.analchem.9b03021
Analytical ChemistryDOI: 10.1021/acs.analchem.9b03402
Analytical ChemistryDOI: 10.1021/acs.analchem.9b03448
Analytical ChemistryDOI: 10.1021/acs.analchem.9b04333
Analytical ChemistryDOI: 10.1021/acs.analchem.9b04503
Analytical ChemistryDOI: 10.1021/acs.analchem.9b03598
Analytical ChemistryDOI: 10.1021/acs.analchem.9b03824
Analytical ChemistryDOI: 10.1021/acs.analchem.9b04708
Analytical ChemistryDOI: 10.1021/acs.analchem.9b03805
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Sprache Stimme GehörDOI: 10.1055/a-0949-7863© Georg Thieme Verlag KG Stuttgart · New YorkArticle in Thieme eJournals:Table of contents | Full text
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Laryngo-Rhino-Otol 2019; 98: 755-755DOI: 10.1055/a-0954-7752© Georg Thieme Verlag KG Stuttgart · New YorkArticle in Thieme eJournals:Table of contents | Full text
Laryngo-Rhino-Otol 2019; 98: 826-829DOI: 10.1055/a-0954-7877© Georg Thieme Verlag KG Stuttgart · New YorkArticle in Thieme eJournals:Table of contents | Full text
Laryngo-Rhino-Otol 2019; 98: 760-761DOI: 10.1055/a-0898-8562Tzelnick S et al. Long-Term Outcomes of Tonsillectomy for Recurrent Tonsillitis in Adults. Laryngoscope 2019; 9999: 1–4. doi:10.1002/lary.27928 Ein Cochrane Review von 2014 beantwortete die Frage nach der Effektivität von Tonsillektomien bei Erwachsenen nicht abschließend, sprach aber für einen positiven Einfluss auf die Lebensqualität. Die retrospektive Studie aus Israel belegt nun eine deutliche Reduktion der Tonsillitis-Episoden...
Laryngo-Rhino-Otol 2019; 98: 815-823DOI: 10.1055/a-0896-9572Die Sialolithiasis als eine der häufigsten Speicheldrüsenerkrankungen betrifft die Glandula submandibularis im Vergleich zur Glandula parotis deutlich häufiger. Im Verlauf der Erkrankung kommt es in vielen Fällen zu rezidivierenden Sialadenitiden. Durch verbesserte Diagnostik besteht neben der Submandibulektomie auch die Möglichkeit einer drüsenerhaltenden Therapie, z. B. mittels Miniaturendoskopie (Sialendoskopie).[...]© Georg Thieme Verlag...
Laryngo-Rhino-Otol 2019; 98: 761-761DOI: 10.1055/a-0996-6580Omidvar S et al. Association Between Tinnitus and Temporomandibular Disorders: A Systematic Review and Meta-Analysis. Ann Otol Rhinol Laryngol 2019; 128: 662–675 Tinnitus ist eines der häufigsten otologischen Symptome bei Patienten mit Kiefergelenkserkrankungen. Iranische Ärzte durchsuchten die Literatur, um den möglichen Zusammenhang zwischen Tinnitus und der temporomandibulären Dysfunktion (TMD) darzustellen. ...
Laryngo-Rhino-Otol 2019; 98: 776-788DOI: 10.1055/a-0960-6616Ziel des auf einer PubMed-Recherche basierenden Übersichtsartikels ist es, die Schlafphysiologie und die pathophysiologischen Zusammenhänge von rheumatologischen Erkrankungen und primären sowie sekundären Schlafstörungen darzustellen. Dabei werden die somnologische Diagnostik und Therapie als ergänzende Verfahren in die rheumatologische Behandlungsstrategie eingebunden. Epidemiologie 70 % aller Rheumapatienten berichten über einen...
Laryngo-Rhino-Otol 2019; 98: 762-763DOI: 10.1055/a-0954-7785© Georg Thieme Verlag KG Stuttgart · New YorkArticle in Thieme eJournals:Table of contents | Full text
Laryngo-Rhino-Otol 2019; 98: 812-814DOI: 10.1055/a-0954-7807© Georg Thieme Verlag KG Stuttgart · New YorkArticle in Thieme eJournals:Table of contents | Full text
Laryngo-Rhino-Otol 2019; 98: 764-775DOI: 10.1055/a-0960-6553Die eosinophile Ösophagitis gilt heute als eine der häufigsten Erkrankungen der Speiseröhre und eine der häufigsten Ursachen für Dysphagie und Bolusobstruktion bei Kindern und Erwachsenen. Die zunehmende Bedeutung dieser Erkrankung und neue klinisch-wissenschaftliche Erkenntnisse erforderten eine Aktualisierung der bis dato existierenden internationalen Leitlinien. Die europäische Studiengruppe Eosinophile Ösophagitis (EUREOS) hat daher,...
Laryngo-Rhino-Otol 2019; 98: 824-825DOI: 10.1055/a-0954-7819© Georg Thieme Verlag KG Stuttgart · New YorkArticle in Thieme eJournals:Table of contents | Full text
Laryngo-Rhino-Otol 2019; 98: 806-811DOI: 10.1055/a-0841-9713© Georg Thieme Verlag KG Stuttgart · New YorkArticle in Thieme eJournals:Table of contents | Full text
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Despite recent taxonomic diversification in studies linking genotype with phenotype, follow-up studies aimed at understanding the molecular processes of such genotype-phenotype associations remain rare. The age at which an individual reaches sexual maturity is an important fitness trait in many wild species. However, the molecular mechanisms regulating maturation timing processes remain obscure. A recent genome-wide association study in Atlantic salmon (Salmo salar) identified large-effect age-at-maturity-associated...
Gene regulatory networks and their evolution are important in the study of animal development. In the nematode, Caenorhabditis elegans, the endoderm (gut) is generated from a single embryonic precursor, E. Gut is specified by the maternal factor SKN-1, which activates the MED -> END-1,3 -> ELT-2,7 cascade of GATA transcription factors. In this work, genome sequences from over two dozen species within the Caenorhabditis genus are used to identify MED and END-1,3 orthologues. Predictions are...
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Abstract Purpose In Y90 radioembolization, the number of microspheres infused varies by more than a factor of 20 over the shelf-life of the glass radioembolization device. We investigated the effect of the number of Y90 microspheres on normal liver tissue. Method Healthy pigs received lobar radioembolization with glass Y90 microspheres at 4, 8, 12, and 16...
Abstract Introduction This study aims to reveal the feasibility and potential of molecular connectivity based on neurotransmission in comparison with the metabolic connectivity with an application to dopaminergic pathways. For this purpose, we propose to compare the neurotransmission connectivity findings using 123I-FP-CIT SPECT and 18F-FDOPA PET with the metabolic connectivity findings using 18F-FDG PET. ...
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Cow’s milk allergy is very common affecting between 2% and 3%, and in some reports up to 7%, of young infants and children1. It has been found that approximately 75% of cow’s milk allergic children are able to tolerate heated cow’s milk, such as in baked goods, while remaining reactive to unheated milk2-4. In addition, regular consumption of heated cow’s milk may hasten the development of tolerance to unheated cow’s milk in a proportion of cow’s milk allergic children5.
Guidelines recommend prompt use of intramuscular epinephrine as first-line treatment for anaphylaxis 1-5. Patients at-risk of anaphylaxis are generally couselled by medical professionals to carry epinephrine in the form of an epinephrine auto-injector (EAI) to treat a severe allergic reaction. Despite its critical role as a life-saving medication, availability of EAIs differs around the world. Shortages of EAIs have compounded this problem.
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Abstract Objectives The present study was designed to investigate the effects of microRNA‐21 (miR‐21) on orthodontic tooth movement. Methods The orthodontic tooth movement model was established in C57BL/6 and miR‐21‐/‐ mice with or without implantation of activated T cells. Histological and histomorphometrical analyses were performed by hematoxylin‐eosin staining. Tartrate‐resistant acid phosphate staining was used to analyze the osteoclast numbers during tooth movement. Enzyme‐linked immunosorbent...
Abstract Objective The serotype b of Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) induces higher cytokine production in dendritic cells (DCs) compared with the other serotypes. However, this increased immuno‐stimulatory potential was modified when DCs were co‐infected with the other A. actinomycetemcomitans serotypes. This study aimed to analyze whether the production of interferon‐gamma (IFN‐γ), C‐reactive protein (CRP), matrix metalloproteinase (MMP)‐2, and MMP‐9, as well...
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Circular RNAs (circRNAs) are abundant in eukaryotic transcriptomes and have been linked to various human disorders. However, understanding genetic control of circular RNA expression is in the early stages. Here we present the first integrated analysis of circRNAs and genome sequence variation from lymphoblastoid cell lines of the 1000 Genomes Project. We identified thousands of circRNAs in the RNA-seq data and show their association with local single-nucleotide polymorphic sites, referred to as circQTLs,...
Differential gene isoform expression is a ubiquitous mechanism to enhance proteome diversity and maintain cell homeostasis. Mechanisms such as splicing that drive gene isoform variability are highly dynamic and responsive to changes in cell signaling pathways. Wnt/β-catenin signaling has profound effects on cell activity and cell fate and is known to modify several splicing events by altering the expression of individual splicing factors. However, a global assessment of how extensively Wnt signaling...
The RNA world hypothesis relies on the ability of ribonucleic acids to spontaneously acquire complex structures capable of supporting essential biological functions. Multiple sophisticated evolutionary models have been proposed for their emergence, but they often assume specific conditions. In this work, we explore a simple and parsimonious scenario describing the emergence of complex molecular structures at the early stages of life. We show that at specific GC content regimes, an undirected replication...
Genetic robustness, the preservation of evolved phenotypes against genotypic mutations, is one of the central concepts in evolution. In recent years a large body of work has focused on the origins, mechanisms, and consequences of robustness in a wide range of biological systems. In particular, research on ncRNAs studied the ability of sequences to maintain folded structures against single-point mutations. In these studies, the structure is merely a reference. However, recent work revealed evidence...
The primary oncogenic event in ~85% of Ewing sarcomas is a chromosomal translocation that generates a fusion oncogene encoding an aberrant transcription factor. The exact genomic breakpoints within the translocated genes, EWSR1 and FLI1, vary; however, in EWSR1, breakpoints typically occur within introns 7 or 8. We previously found that in Ewing sarcoma cells harboring EWSR1 intron 8 breakpoints, the RNA-binding protein HNRNPH1 facilitates a splicing event that excludes EWSR1 exon 8 from the EWS–FLI1...
Circular RNAs (circRNAs), with their crucial roles in gene regulation and disease development, have become rising stars in the RNA world. To understand the regulatory function of circRNAs, many studies focus on the interactions between circRNAs and RNA-binding proteins (RBPs). Recently, the abundant CLIP-seq experimental data has enabled the large-scale identification and analysis of circRNA–RBP interactions, whereas, as far as we know, no computational tool based on machine learning has been proposed...
Exon size and sequence conservation improves identification of splice-altering nucleotides [ARTICLE]
Pre-mRNA splicing is regulated through multiple trans-acting splicing factors. These regulators interact with the pre-mRNA at intronic and exonic positions. Given that most exons are protein coding, the evolution of exons must be modulated by a combination of selective coding and splicing pressures. It has previously been demonstrated that selective splicing pressures are more easily deconvoluted when phylogenetic comparisons are made for exons of identical size, suggesting that exon size–filtered...
The nadA motif is a riboswitch candidate present in various Acidobacteria species that was previously identified by bioinformatic analysis of bacterial DNA data sets. More than 100 unique representatives have been identified exclusively upstream of nadA genes, which code for an enzyme in the biosynthetic pathway of the ubiquitous coenzyme NAD+. The architecture of nadA motif RNAs suggests they use structurally similar tandem ligand-binding aptamer domains to control translation initiation. Biochemical...
Protein–RNA recognition is highly affinity-driven and regulates a wide array of cellular functions. In this study, we have curated a binding affinity data set of 40 protein–RNA complexes, for which at least one unbound partner is available in the docking benchmark. The data set covers a wide affinity range of eight orders of magnitude as well as four different structural classes. On average, we find the complexes with single-stranded RNA have the highest affinity, whereas the complexes with the duplex...
The origin of the genetic code remains enigmatic five decades after it was elucidated, although there is growing evidence that the code coevolved progressively with the ribosome. A number of primordial codes were proposed as ancestors of the modern genetic code, including comma-free codes such as the RRY, RNY, or GNC codes (R = G or A, Y = C or T, N = any nucleotide), and the X circular code, an error-correcting code that also allows identification and maintenance of the reading frame. It was demonstrated...
Human mitochondrial ribonuclease P (mtRNase P) is an essential three-protein complex that catalyzes the 5' end maturation of mitochondrial precursor tRNAs (pre-tRNAs). Mitochondrial RNase P Protein 3 (MRPP3), a protein-only RNase P (PRORP), is the nuclease component of the mtRNase P complex and requires a two-protein S-adenosyl-methionine (SAM)-dependent methyltransferase MRPP1/2 subcomplex to function. Dysfunction of mtRNase P is linked to several human mitochondrial diseases, such as mitochondrial...
A new paradigm has emerged that coding regions can regulate mRNA stability in model organisms. Here, due to differences in cognate tRNA abundance, synonymous codons are translated at different speeds, and slow codons then stimulate mRNA decay. To ask if this phenomenon also occurs in humans, we isolated RNA stability effects due to coding regions using the human ORFeome collection. We find that many open reading frame (ORF) characteristics, such as length and secondary structure, fail to provide...
Brefeldin A resistance factor 1 (Bfr1p) is a nonessential RNA-binding protein and multicopy suppressor of brefeldin A sensitivity in Saccharomyces cerevisiae. Deletion of BFR1 leads to multiple defects, including altered cell shape and size, change in ploidy, induction of P-bodies and chromosomal missegregation. Bfr1p has been shown to associate with polysomes, binds to several hundred mRNAs, and can target some of them to P-bodies. Although this implies a role of Bfr1p in translational control of...
U6 RNA contains a 1 x 2-nt internal loop that folds and unfold during spliceosomal assembly and activation. The 1 x 2 loop consists of a C67•A79 base pair that forms an additional hydrogen bond upon protonation, C67•A+79, and uracil (U80) that coordinates the catalytically essential magnesium ions. We designed a series of RNA and DNA constructs with a 1 x 2 loop sequence contained in the ISL, and its modifications, to measure the thermodynamic effects of protonation and magnesium binding using UV-visible...
Most eukaryotic messenger RNA precursors must undergo 3'-end cleavage and polyadenylation for maturation. We and others recently reported the structure of the AAUAAA polyadenylation signal (PAS) in complex with the protein factors CPSF-30, WDR33, and CPSF-160, revealing the molecular mechanism for this recognition. Here we have characterized in detail the interactions between the PAS RNA and the protein factors using fluorescence polarization experiments. Our studies show that AAUAAA is recognized...
There is a pressing need for nucleic acid–based assays that are capable of rapidly and reliably detecting pathogenic organisms. Many of the techniques available for the detection of pathogenic RNA possess one or more limiting factors that make the detection of low-copy RNA challenging. Although RT-PCR is the most commonly used method for detecting pathogen-related RNA, it requires expensive thermocycling equipment and is comparatively slow. Isothermal methods promise procedural simplicity but have...
NEAT1 is one of the most studied lncRNAs, in part because its silencing in mice causes defects in mammary gland development and corpus luteum formation and protects them from skin cancer development. Moreover, depleting NEAT1 in established cancer cell lines reduces growth and sensitizes cells to DNA damaging agents. However, NEAT1 produces two isoforms and because the short isoform, NEAT1_1, completely overlaps the 5' part of the long NEAT1_2 isoform; the respective contributions of each of the...
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