Circular cut codes in genetic information.

In this work we present an analysis of the dinucleotide occurrences in the three codon sites 1-2, 2-3 and 1-3, based on a computation of the codon usage of three large sets of bacterial, archaeal and eukaryotic genes using the same method that identified a maximal C3 self-complementary trinucleotide circular code X in genes of bacteria and eukaryotes in 1996 (Arquès and Michel, 1996). Surprisingly, two dinucleotide circular codes are identified in the codon sites 1-2 and 2-3. Furthermore, these two codes are shifted versions of each other. Moreover, the dinucleotide code in the codon site 1-3 is circular, self-complementary and contained in the projection of X onto the 1st and 3rd bases, i.e. by cutting the middle base in each codon of X. We prove several results showing that the circularity and the self-complementarity of trinucleotide codes is induced by the circularity and the self-complementarity of its dinucleotide cut codes. Finally, we present several evolutionary approaches for an emergence of trinucleotide codes from dinucleotide codes.

Circular code in introns.

A massive statistical analysis based on the autocorrelation function of the circular code X observed in genes is performed on the (eukaryotic) introns. Surprisingly, a circular code periodicity 0 modulo 3 is identified in 5 groups of introns: birds, ascomycetes, basidiomycetes, green algae and land plants. This circular code periodicity, which is a property of retrieving the reading frame in (protein coding) genes, may suggest that these introns have a coding property. In a well-known way, a periodicity 1 modulo 2 is observed in 6 groups of introns: amphibians, fishes, mammals, other animals, reptiles and apicomplexans. A mixed periodicity modulo 2 and 3 is found in the introns of insects. Astonishing, a subperiodicity 3 modulo 6 is a common statistical property in these 3 classes of introns. When the particular trinucleotides N1N2N1 of the circular code X are not considered, the circular code periodicity 0 modulo 3, hidden by the periodicity 1 modulo 2, is now retrieved in 5 groups of introns: amphibians, fishes, other animals, reptiles and insects. Thus, 10 groups of introns, taxonomically different, out of 12 have a coding property related to the reading frame retrieval. The trinucleotides N1N2N1 are analysed in the 216 maximal C3 self-complementary trinucleotide circular codes. A hexanucleotide code (words of 6 letters) is proposed to explain the periodicity 3 modulo 6. It could be a trace of more general circular codes at the origin of the circular code X.

Prospective Assessment of Treatment-Induced Liver Injury as a Cause of Diffuse Pathologic Hepatic Enhancement in Contrast-Enhanced Ultrasound.

OBJECTIVE: A hypo-enhancement of the liver in contrast-enhanced ultrasound (CEUS), pathologic one-minute hepatic enhancement (pOMHE), was recently observed in 70% of allogeneic hematopoietic stem cell transplantation patients with a high-risk profile for veno-occlusive disease (VOD). Whether pOMHE was a pre-clinical sign of VOD or an unspecific feature of liver damage secondary to intensive chemotherapy is unclear. METHODS: To investigate this, we studied CEUS patterns in patients receiving high-dose chemotherapy prior to autologous hematopoietic stem cell transplantation (auto-HSCT) or intensive induction therapy (IT) for the treatment of acute leukemia. From April 2020 to May 2021, patients undergoing auto-HSCT (n = 20) or acute leukemia patients prior to IT (n = 20) were included. All patients underwent a B-mode ultrasound and CEUS of the liver and spleen before treatment (d0) and on day 10 (d10) after therapy start. The one-minute hepatic enhancement was quantified. An optical density of liver enhancement less than 90% compared with the spleen was considered pathologic (pOMHE). Clinical and laboratory parameters used to assess a drug-induced liver injury (DILI) were documented. RESULTS: The OMHE was normal (d0 and d10) in 36 (90%) patients. After IT, 2 of 20 patients had a pOMHE. A DILI grade IV was diagnosed in one case and hyperfibrinolysis in the second case. In 2 of 20 (5%) auto-HSCT patients a pOMHE was observed at d10 without clinical symptoms. CONCLUSION: Chemotherapy-induced effects are not the cause of a pathologic liver enhancement. In contrast, severe DILI or hyperfibrinolysis can be associated with pOMHE.

Circular mixed sets.

In this article, we introduce the new mathematical concept of circular mixed sets of words over an arbitrary finite alphabet. These circular mixed sets may not be codes in the classical sense and hence allow a higher amount of information to be encoded. After describing their basic properties, we generalize a recent graph theoretical approach for circularity and apply it to distinguish codes from sets (i.e. non-codes). Moreover, several methods are given to construct circular mixed sets. Finally, this approach allows us to propose a new evolution model of the present genetic code that could have evolved from a dinucleotide world to a trinucleotide world via circular mixed sets of dinucleotides and trinucleotides.

Copredication and Complexity Revisited: Reply to Murphy's Reply.

In Löhr and Michel (2022), we proposed a neurocognitive model within the predictive processing paradigm for acceptability intuitions about copredication sentences. We also addressed "predicate order effects," the phenomenon that the acceptability of copredication sentences can vary with the order in which the predicates occur. We discussed Murphy's interpretation of order preferences based on a hierarchy of semantic complexity and tried to motivate that other interpretations are worthwhile pursuing. In a reply letter, Murphy (2022) takes issue with our approach, putting forward several purported methodological and conceptual issues with our paper. In this reply, we first clarify where exactly we agree and disagree. Second, we focus on a crucial equivocation and some misrepresentations of our proposal by Murphy.

Reading Frame Retrieval of Genes: A New Parameter of Codon Usage Based on the Circular Code Theory.

Based on the circular code theory, we define a new function f that quantifies the property of reading frame retrieval (RFR) of genes from their codon usage. This RFR function f is computed on a massive scale in genes of genomes of bacteria, eukaryotes and archaea. By expressing f as a function of the mean number [Formula: see text] of codons per gene, a "universal" property is identified, whatever the kingdom: the reading frame retrieval is enhanced in large genes. By investigating this property according to the theory developed, a Spearman's rank correlation with a strong negative coefficient is observed between the codon usage dispersion d (from the uniform codon distribution [Formula: see text]) and the RFR function f, whatever the kingdom (p-values [Formula: see text] in bacteria, [Formula: see text] in eukaryotes and [Formula: see text] in archaea). Thus, the reading frame retrieval is enhanced with the codon usage dispersion. Furthermore, this approach identifies a "genome centre" from which emerge two distinct "genome arms": an upper arm and a lower arm, respectively, above and below the linear regression. The RFR function by itself or combined with classical methods (alignment, phylogeny) could also be a new approach to classify the genomes in the future.

Safety of AFM11 in the treatment of patients with B-cell malignancies: findings from two phase 1 studies.

BACKGROUND: The prognosis for patients with relapsed and/or refractory (R/R) non-Hodgkin's lymphoma (NHL) or acute lymphoblastic leukaemia (ALL) remains poor, with existing treatments having significant side effects. Developed for the treatment of these cancers, AFM11 is a tetravalent, bispecific humanised recombinant antibody construct (TandAb®) designed to bind to human CD19 and CD3 and lead to the activation of T cells inducing apoptosis and killing of malignant B cells. METHODS: Two open-label, multicentre, dose-escalation phase 1 studies evaluated the safety, pharmacokinetics and activity of AFM11 in patients with R/R CD19-positive B cell NHL (AFM11-101) and in patients with CD19 + B-precursor Philadelphia-chromosome negative ALL (AFM11-102). Adverse events (AEs) were assessed and recorded; imaging (NHL) or bone marrow assessment (ALL) were used to evaluate response. Additional pharmacodynamic assays undertaken included cytokine release analysis and B-cell and T-cell depletion. RESULTS: In AFM11-101, 16 patients with R/R NHL received AFM11 in five different dose cohorts. Of which, 14 experienced drug-related treatment-emergent AEs (TEAEs) [including five serious AEs (SAEs)], five patients experienced dose-limiting toxicity (DLT) and ten patients discontinued the study. The high number of neurological events led to a decrease in infusion frequency during the study. No objective response to treatment was observed. In AFM11-102, 17 patients with R/R ALL received AFM11 in six different dose cohorts. Thirteen patients experienced drug-related TEAEs (including four SAEs), DLTs occurred in two patients and five patients discontinued the study. An objective response was recorded in three patients. The maximum tolerated dose could not be determined in either study due to early termination. CONCLUSIONS: AFM11 treatment was associated with frequent neurological adverse reactions that were severe in some patients. In ALL, some signs of activity, albeit short-lived, were observed whereas no activity was observed in patients with NHL; therefore, further clinical development was terminated. TRIAL REGISTRATION: NCT02106091 . Safety Study to Assess AFM11 in Patients With Relapsed and/or Refractory CD19 Positive B-cell NHL. Registered April 2014. NCT02848911 . Safety Study to Assess AFM11 in Patients With Relapsed or Refractory Adult B-precursor ALL. Registered July 2016.

Publicly available framework for simulating and experimentally validating clinical PET systems.

BACKGROUND: Monte Carlo (MC) simulations are a powerful tool to model medical imaging systems. However, before simulations can be considered the ground truth, they have to be validated with experiments. PURPOSE: To provide a pipeline that models a clinical positron emission tomography (PET)/CT system using MC simulations after extensively validating the results against experimental measurements. METHODS: A clinical four-ring PET imaging system was modeled using Geant4 application for tomographic emission (v. 9.0). To validate the simulations, PET images were acquired of a cylindrical phantom, point source, and image quality phantom with the modeled system and the simulations of the experimental procedures. For the purpose of validating the quantification capabilities and image quality provided by the simulation pipeline, the simulations were compared against the measurements in terms of their count rates and sensitivity as well as their image uniformity, resolution, recovery coefficients (RCs), coefficients of variation, contrast, and background variability. RESULTS: When compared to the measured data, the number of true detections in the MC simulations was within 5%. The scatter fraction was found to be 30.0% ± 2.2% and 28.8% ± 1.7% in the measured and simulated scans, respectively. Analyzing the measured and simulated sinograms, the sensitivities were found to be 8.2 and 7.8 cps/kBq, respectively. The fraction of random coincidences were 19% in the measured data and 25% in the simulation. When calculating the image uniformity within the axial slices, the measured image exhibited a uniformity of 0.015 ± 0.005, whereas the simulated image had a uniformity of 0.029 ± 0.011. In the axial direction, the uniformity was measured to be 0.024 ± 0.006 and 0.040 ± 0.015 for the measured and simulated data, respectively. Comparing the image resolution, an average percentage difference of 2.9% was found between the measurements and simulations. The RCs calculated in both the measured and simulated images were found to be within the EARL ranges, except for that of the simulation of the smallest sphere. The coefficients of variation for the measured and simulated images were found to be 12% and 13%, respectively. Lastly, the background variability was consistent between the measurements and simulations, whereas the average percentage difference in the sphere contrasts was found to be 8.8%. CONCLUSION: The clinical PET/CT system was modeled and validated to provide a simulation pipeline for the community. The pipeline and the validation procedures have been made available (https://github.com/teaghan/PET_MonteCarlo).

Loss of SUV420H2-Dependent Chromatin Compaction Drives Right-Sided Colon Cancer Progression.

BACKGROUND & AIMS: Epigenetic processes regulating gene expression contribute markedly to epithelial cell plasticity in colorectal carcinogenesis. The lysine methyltransferase SUV420H2 comprises an important regulator of epithelial plasticity and is primarily responsible for trimethylation of H4K20 (H4K20me3). Loss of H4K20me3 has been suggested as a hallmark of human cancer due to its interaction with DNMT1. However, the role of Suv4-20h2 in colorectal cancer is unknown. METHODS: We examined the alterations in histone modifications in patient-derived colorectal cancer organoids. Patient-derived colorectal cancer organoids and mouse intestinal organoids were genetically manipulated for functional studies in patient-derived xenograft and orthotopic transplantation. Gene expression profiling, micrococcal nuclease assay, and chromatin immunoprecipitation were performed to understand epigenetic regulation of chromatin states and gene expression in patient-derived and mouse intestinal organoids. RESULTS: We found that reduced H4K20me3 levels occurred predominantly in right-sided patient-derived colorectal cancer organoids, which were associated with increased chromatin accessibility. Re-compaction of chromatin by methylstat, a histone demethylase inhibitor, resulted in reduced growth selectively in subcutaneously grown tumors derived from right-sided cancers. Using mouse intestinal organoids, we confirmed that Suv4-20h2-mediated H4K20me3 is required for maintaining heterochromatin compaction and to prevent R-loop formation. Cross-species comparison of Suv4-20h2-depleted murine organoids with right-sided colorectal cancer organoids revealed a large overlap of gene signatures involved in chromatin silencing, DNA methylation, and stemness/Wnt signaling. CONCLUSIONS: Loss of Suv4-20h2-mediated H4K20me3 drives right-sided colorectal tumorigenesis through an epigenetically controlled mechanism of chromatin compaction. Our findings unravel a conceptually novel approach for subtype-specific therapy of this aggressive form of colorectal cancer.

Comparative transcriptional profiling of regenerating damaged knee joints in two animal models of the newt Notophthalmus viridescens strengthens the role of candidate genes involved in osteoarthritis.

Objectives: To compare joint regeneration in adult newts (N. viridescens) upon both newly established surgical removal and previously reported enzymatic destruction of articular cartilage to identify molecular factors and functionally analyze potentially important regulators involved in osteoarthritis (OA). Methods: Damage of knee cartilage was induced by either intra-articular injection of collagenase or by surgical removal of articular cartilage as a novel additional approach. Changes over time were clinically and histologically analyzed and studied by cDNA microarray analysis, real-time quantitative PCR, immunohistochemistry and functional assays to identify relevant candidate genes and determine their impact on regeneration. Results: Several genes were found to be up-regulated during regeneration, including extracellular matrix components and mediators of cell-matrix interactions, genes encoding for cellular components, for cell and tissue homeostasis and tissue remodelling, for cellular processes as well as signalling molecules. A high activity and diversity of transcription was detected on days 10 and 20, especially in the surgical model. 10 candidate genes were further analyzed. The matricellular protein tenascin C (TN-C) attracted our particular attention due to its prominent up-regulation during regeneration in both models and at different time points. Conclusions: Newts are able to regenerate OA-like articular cartilage damage ad integrum both after enzymatic and mechanical injury. Most of the genes involved in amphibians are also known to be operative in humans and other mammals, especially matricellular factors interfering with optimized matrix remodelling. Our results stress the necessity to elucidate mechanistic differences in different species potentially using identical molecules but with different functional results.

Alcohol Consumption in the Specific Socio-Professional Context of the French Public Service: Qualitative Study Protocol.

Alcohol, a psychoactive substance with addictive potential, has major consequences on the population and public health. In France, alcohol use disorder affects approximately 3.5 million people, and 41,000 persons died in 2015. Alcohol consumption is significantly correlated to the workplace. Thus, the workplace is an area of opportunity to change risky behaviors and must play a key role in the prevention of alcohol misuse. To do this, it is essential to understand the consumption framework and to identify specific environmental risk factors. This qualitative study aims to describe the framework of alcohol consumption in the French public service. A focus group will be organized in France from November to January 2023. The participants will be: (i) representatives of the Local Health Insurance; (ii) over 18 years old; (iii) active or retired civil servants; (iv) mutualist activists; and (v) representatives of the Union of Health Prevention for the Obligatory System of the Public Service. The exclusion criteria for the study will be: (i) lack of consent form; (ii) inability to participate in the focus group, and (iii) early departure during the focus group. The focus groups will be supervised by two researchers following an interview guide. The data will be analyzed using the methodological framework, which consists in carrying out a thematic analysis. This will allow for an understanding of the sources of usage behaviors, and the identification of the most appropriate intervention functions for suitable prevention actions in order to reduce the risk of a transition to alcohol use disorder.

Presentation of Chloromas in B-Mode Ultrasound and Contrast-Enhanced Ultrasound.

Chloromas, also referred to as myeloid sarcomas, describe rare extramedullary tumor aggregates of malignant myeloid progenitor cells. The aim of this study was investigate the diagnostic features and characteristics of chloromas using contrast-enhanced ultrasound (CEUS). Between July 2007 and April 2021, 15 patients with 20 myeloid neoplasms and suspected chloroma manifestations were examined using B-mode US (B-US) and CEUS. Clinical data and B-US (echogenicity, border, size) and CEUS (hyper-, iso-, hypo- or complex enhancement) characteristics were retrospectively analyzed. Absolute and relative frequencies were determined. In B-US, the chloromas were most frequently hypo-echoic (n = 15, 75%). In addition, a hyperechoic (n = 2, 10%) or echocomplex (n = 3, 15%) presentation was observed. On CEUS, 7 chloromas (35%) had an arterial hyperenhancement, 8 (40%) an iso-enhancement and 3 (15%) a complex enhancement. Two chloromas (10%) did not exhibit any enhancement. We describe for the first time CEUS and B-US patterns of chloromas. They are typically hypo-echoic on B-US and have a strong iso- or hyperenhancement on CEUS, which may help in the differential diagnosis of some unclear masses (e.g., hematoma, abscess) in patients with myeloid neoplasias. Nevertheless, histology is necessary for a reliable diagnosis.

Copredication in Context: A Predictive Processing Approach.

We propose a cognitive-psychological model of linguistic intuitions about copredication statements. In copredication statements, like "The book is heavy and informative," the nominal denotes two ontologically distinct entities at the same time. This has been considered a problem for standard truth-conditional semantics. In this paper, we discuss two questions that have so far received less attention: What kinds of word representations and cognitive mechanisms are responsible for judgments about the felicitousness of copredication statements? Relatedly, why can similar copredication statements have different degrees of felicitousness? We first propose a cognitive-computational model of copredication within the predictive processing framework. We then suggest that certain asymmetries in felicitousness judgments can be modeled in terms of a set of expectations that are influenced by higher-order priors associated with discourse context and world knowledge.

Trinucleotide k-circular codes I: Theory.

A code X is (⩾k)-circular if every concatenation of words from X that admits, when read on a circle, more than one partition into words from X, must contain at least k+1 words. In other words, the reading frame retrieval is guaranteed for any concatenation of up to k words from X. A code that is (⩾k)-circular for all integers k is said to be circular. Any code is (⩾0)-circular and it turns out that a code of trinucleotides is circular as soon as it is (⩾4)-circular. A code is k-circular if it is (⩾k)-circular and not (⩾k+1)-circular. Due to the explosive combinatorics of trinucleotide k-circular codes, we developed three classes of algorithms based on: (i) the smallest directed cycles (directed girth) in graphs; (ii) the eigenvalues of matrices; and (iii) the files that incrementally save partial results. These different approaches also allow us to verify the computational results obtained. We determine here the growth functions of trinucleotide k-circular codes, k varying between 0 and 4, in the general case and in various particular cases: minimum, minimal, maximum, self-complementary k-, (k,k,k)- and self-complementary (k,k,k)-circular.

Trinucleotide k-circular codes II: Biology.

A code X is (⩾k)-circular if every concatenation of words from X that admits, when read on a circle, more than one partition into words from X, must contain at least k+1 words. In other words, the reading frame retrieval is guaranteed for any concatenation of up to k words from X. A code that is (⩾k)-circular for all integers k is said to be circular. Any code is (⩾0)-circular and it turns out that a code of trinucleotides is circular as soon as it is (⩾4)-circular. A code is k-circular if it is (⩾k)-circular and not (⩾k+1)-circular. The theoretical aspects of trinucleotide k-circular codes have been developed in a companion article (Michel et al., 2022). Trinucleotide circular codes always retrieve the reading frame, leaving no ambiguous sequences. On the contrary, trinucleotide k-circular codes, for k∈{0,1,2,3} all have ambiguous sequences, for which the reading frame cannot always be retrieved. However, such a trinucleotide k-circular code is still able to retrieve the reading frame for a number of sequences, thereby exhibiting a partial circularity property. We describe this combinatorial property for each class of trinucleotide k-circular codes with k∈{0,1,2,3}. The circularity, i.e. the reading frame retrieval, is an ordinary property in genes. In order to consider the different cases of ambiguous sequences, we derive a new and general formula to measure the reading frame loss, whatever the trinucleotide k-circular code. This formula allows us to study the evolution of any trinucleotide k-circular code of (maximal) cardinality 20 to the genetic code, based on the reading frame retrieval property. We apply this approach to analyse the evolution of the trinucleotide circular code X observed in genes to the genetic code. The (⩾1)-circular codes of maximal size 20 necessarily have the same number of each nucleotide, specifically 15=3⋅20/4. This balanceness property can also be achieved by trinucleotide codes of cardinality 4,8,12 and 16. We call such trinucleotide codes balanced. We develop a general mathematical method to compute the number of balanced trinucleotide codes of each size, which also applies to self-complementary trinucleotide codes. We establish and quantify a relation between this balanceness property and the self-complementarity property. The combinatorial hierarchy of trinucleotide k-circular codes is updated with the growth function results. The numbers of amino acids coded by the trinucleotide k-circular codes are given for the cases maximal, minimal, self-complementary k-, (k,k,k)- and self-complementary (k,k,k)-circular.

Assessment of Early Therapy Response of Non-Hodgkin's and Hodgkin's Lymphoma Using B-Mode Ultrasound and Dynamic Contrast-Enhanced Ultrasound.

OBJECTIVES: Here we asked, whether contrast enhanced ultrasound (CEUS) enables to judge early treatment response in malignant lymphoma as a potential guidance for further treatment. METHODS: From May 2017 to May 2018, 21 patients with histologically confirmed diagnosis of lymphoma were examined by B-mode ultrasound (B-US) and CEUS at fixed early time points after commencing therapy (days [d] 0, 15 and 30 after therapy start) and contrast enhancement patterns in target lymphoma lesions were quantified using Bracco-VUE Box® (DCE-US). To estimate the potential value of CEUS-enhancement patterns for early response prediction, patients were grouped according to their best achieved actual response into complete remission (CR) patients, partial remission (PR) patients or progressive disease (PD) patients. RESULTS: Between d0, d15 and d30, CR-patients showed a median lymphoma shrinking by 34% in B-US. PD-patients experienced a median lymphoma size reduction by 44% on day 15, but lymphoma mass again increased by 20% between d15 and d30. In contrast, the median CEUS enhancement intensity, as assessed by the area under the curve (AUC) was increasing at d15 in CR and PD patients (CR to 152%, PD: to 126%), but decreased at d30 to 14% in CR patients and 22% in PD patients. CONCLUSIONS: While early response assessment using B-US might be useful to predict treatment response in lymphoma, CEUS and DCE-US-although often feasible-do not provide additional value in this regard.

Combination of a Hydraulic Device and Nanohydroxylapatite Paste for Minimally Invasive Transcrestal Sinus Floor Elevation: Procedure and 4-Year Results.

PURPOSE: The objectives of this retrospective study were to describe a transcrestal sinus floor elevation technique combining the use of a hydraulic device and a nanohydroxylapatite paste and to report on 4-year clinical and radiographic outcomes. MATERIALS AND METHODS: The sinus floor elevation procedure used a specially designed drill (SinusJet) to start sinus membrane unsticking and a nanohydroxylapatite paste (Ostim) for further sinus membrane elevation and bone augmentation. It was performed as a one-step procedure with immediate implant placement or a two-step procedure with delayed implant placement 9 months later. Implant survival rate, sinus membrane perforation, postoperative complications, and the level of intraoperative and postoperative patient comfort using a visual analog scale were analyzed retrospectively. A nonparametric Wilcoxon matched-pairs test and parametric paired t test were used to identify significant differences. RESULTS: One hundred thirty-six sinus floor elevations were performed in 110 patients at two dental clinics in Belgium with a mean follow-up period of 48 months. In the one-step procedure, the mean 6-month elevation was 8.5 ± 2.7 mm; 194 implants were placed. In the two-step procedure, the mean 9-month elevation was 9.5 ± 2.4 mm; 8 implants were placed. The osteotomy, sinus membrane elevation, and bone grafting typically took less than 3 minutes. Sinus membrane perforation was observed in 2.9% (n = 4/136). The 4-year implant survival rate was 97% (n = 196/202), with six early implant losses. 96.4% of patients reported either no or minimal discomfort. CONCLUSION: This minimally invasive transcrestal sinus floor elevation procedure that combines a hydraulic device and nanohydroxylapatite paste appears to be safe and predictable. However, further randomized controlled studies are needed to validate the results of this retrospective observational study.

Genes on the circular code alphabet.

The X motifs, motifs from the circular code X, are enriched in the (protein coding) genes of bacteria, archaea, eukaryotes, plasmids and viruses, moreover, in the minimal gene set belonging to the three domains of life, as well as in tRNA and rRNA sequences. They allow to retrieve, maintain and synchronize the reading frame in genes, and contribute to the regulation of gene expression. These results lead here to a theoretical study of genes based on the circular code alphabet. A new occurrence relation of the circular code X under the hypothesis of an equiprobable (balanced) strand pairing is given. Surprisingly, a statistical analysis of a large set of bacterial genes retrieves this relation on the circular code alphabet, but not on the DNA alphabet. Furthermore, the circular code X has the strongest balanced circular code pairing among 216 maximal C3 self-complementary trinucleotide circular codes, a new property of this circular code X. As an application of this theory, different tRNAs studied on the circular code alphabet reveal an unexpected stem structure. Thus, the circular code X would have constructed a coding stem in tRNAs as an outline of the future gene structure and the future DNA double helix.

Potential role of the X circular code in the regulation of gene expression.

The X circular code is a set of 20 trinucleotides (codons) that has been identified in the protein-coding genes of most organisms (bacteria, archaea, eukaryotes, plasmids, viruses). It has been shown previously that the X circular code has the important mathematical property of being an error-correcting code. Thus, motifs of the X circular code, i.e. a series of codons belonging to X and called X motifs, allow identification and maintenance of the reading frame in genes. X motifs are significantly enriched in protein-coding genes, but have also been identified in many transfer RNA (tRNA) genes and in important functional regions of the ribosomal RNA (rRNA), notably in the peptidyl transferase center and the decoding center. Here, we investigate the potential role of X motifs as functional elements of protein-coding genes. First, we identify the codons of the X circular code which are frequent or rare in each domain of life (archaea, bacteria, eukaryota) and show that, for the amino acids with the highest codon bias, the preferred codon is often an X codon. We also observe a correlation between the 20 X codons and the optimal codons/dicodons that have been shown to influence translation efficiency. Then, we examined recently published experimental results concerning gene expression levels in diverse organisms. The approach used is the analysis of X motifs according to their density ds(X), i.e. the number of X motifs per kilobase in a gene sequence s. Surprisingly, this simple parameter identifies several unexpected relations between the X circular code and gene expression. For example, the X motifs are significantly enriched in the minimal gene set belonging to the three domains of life, and in codon-optimized genes. Furthermore, the density of X motifs generally correlates with experimental measures of translation efficiency and mRNA stability. Taken together, these results lead us to propose that the X motifs may represent a genetic signal contributing to the maintenance of the correct reading frame and the optimization and regulation of gene expression.

Mediastinal Masses in Contrast-Enhanced Ultrasound - Retrospective Analysis of 58 Cases.

OBJECTIVES: To determine contrast enhancing features of mediastinal masses (ML) using transcutaneous contrast-enhanced ultrasound (CEUS). METHODS: Retrospective analysis of n = 58 patients with histologically confirmed ML, which were examined in the period from October 2005 to February 2018 using transcutaneous B-mode ultrasound and CEUS. In n = 29 (50%) histological confirmation was performed by ultrasound guided core-needle biopsy. The lesions were evaluated using CEUS in regard to the enhancement pattern (hyper-, iso-, hypoenhancement, non-enhancement, homogenous, inhomogenous) compared to enhancement of the spleen as an in vivo reference. RESULTS: N = 53 (91.4%) of ML were malignant (m) (lymphoma n = 36, metastasis n = 11, thymoma n = 2, teratoma n = 1, sarcoma n = 2, seminoma n = 1). In n = 5 (8.6%) cases there was a benign (b) histology (thyroid tissue n = 2, thymus residue n = 1, ganglioneurinoma n = 1, scar tissue: n = 1). In ultrasound, n = 53 (91.4%; (48 = m, 5 = b)) were hypoechoic, n = 5 (8.6%, (5 = m,0 = b)) hyperechoic. In CEUS, n = 35 lesions presented an arterial isoenhancement (60.3%; 33 = m, 2 = b). An arterial hypoenhancement had n = 21 (36.2%, (20 = m,1 = b)), and no enhancement showed n = 2 (3.5%, (0 = m, 2 = b) of the ML. A parenchymal isoenhancement was observed in n = 1 (1.7%, (1 = m, 0 = b)), a hypoenhancement in n = 54 (93.1%; 51 = m, 3 = b) of the patients and almost no enhancement in n = 3 ML (5.2%, (1 = m, 2 = b).) The enhancement was homogeneous in n = 26 (44.8%, (25 = m,1 = b)) cases, in n = 31 (53.5%, (28 = m,3 = b)) inhomogeneous and n = 1 (1.7%) benign lesion was exclusively cystic. CONCLUSION: In CEUS, mediastinal tumor formations showed variable arterial enhancement, followed by parenchymal hypoenhancement (wash-out).