Generalization of entropy based divergence measures for symbolic sequence analysis

Entropy based measures have been frequently used in symbolic sequence analysis. A symmetrized and smoothed form of Kullback-Leibler divergence or relative entropy, the Jensen-Shannon divergence (JSD), is of particular interest because of its sharing properties with families of other divergence measures and its interpretability in different domains including statistical physics, information theory and mathematical statistics. The uniqueness and versatility of this measure arise because of a number of attributes including generalization to any number of probability distributions and association of weights to the distributions. Furthermore, its entropic formulation allows its generalization in different statistical frameworks, such as, non-extensive Tsallis statistics and higher order Markovian statistics. We revisit these generalizations and propose a new generalization of JSD in the integrated Tsallis and Markovian statistical framework. We show that this generalization can be interpreted in terms of mutual information. We also investigate the performance of different JSD generalizations in deconstructing chimeric DNA sequences assembled from bacterial genomes including that of E. coli, S. enterica typhi, Y. pestis and H. influenzae. Our results show that the JSD generalizations bring in more pronounced improvements when the sequences being compared are from phylogenetically proximal organisms, which are often difficult to distinguish because of their compositional similarity. While small but noticeable improvements were observed with the Tsallis statistical JSD generalization, relatively large improvements were observed with the Markovian generalization. In contrast, the proposed Tsallis-Markovian generalization yielded more pronounced improvements relative to the Tsallis and Markovian generalizations, specifically when the sequences being compared arose from phylogenetically proximal organisms.publishedVersionFil: Ré, Miguel Ángel. Universidad Tecnológica Nacional. Facultad Regional Córdoba. Centro de Investigación en Informática para la Ingeniería. Departamento de Ciencias Básicas; Argentina.Fil: Ré, Miguel Ángel. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Azad, Rajeev K. University of North Texas. College of Science. Department of Biological Sciences; Estados Unidos de América.Fil: Azad, Rajeev K. University of North Texas. College of Science. Department of Mathematics; Estados Unidos de América.Ciencias de la Información y Bioinformática (desarrollo de hardware va en 2.2 "Ingeniería Eléctrica, Electrónica y de Información" y los aspectos sociales van en 5.8 "Comunicación y Medios"

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Similarities and differences in the autonomic control of airway and urinary bladder smooth muscle

The airways and the urinary bladder are both hollow organs serving very different functions, i.e. air flow and urine storage, respectively. While the autonomic nervous system seems to play only a minor if any role in the physiological regulation of airway tone during normal breathing, it is important in the physiological regulation of bladder smooth muscle contraction and relaxation. While both tissues share a greater expression of M2 than of M3 muscarinic receptors, smooth muscle contraction in both is largely mediated by the smaller M3 population apparently involving phospholipase C activation to only a minor if any extent. While smooth muscle in both tissues can be relaxed by β-adrenoceptor stimulation, this primarily involves β2-adrenoceptors in human airways and β3-adrenoceptors in human bladder. Despite activation of adenylyl cyclase by either subtype, cyclic adenosine monophosphate plays only a minor role in bladder relaxation by β-agonists; an important but not exclusive function is known in airway relaxation. While airway β2-adrenoceptors are sensitive to agonist-induced desensitization, β3-adrenoceptors are generally considered to exhibit much less if any sensitivity to desensitization. Gene polymorphisms exist in the genes of both β2- and β3-adrenoceptors. Despite being not fully conclusive, the available data suggest some role of β2-adrenoceptor polymorphisms in airway function and its treatment by receptor agonists, whereas the available data on β3-adrenoceptor polymorphisms and bladder function are too limited to allow robust interpretation. We conclude that the distinct functions of airways and urinary bladder are reflected in a differential regulation by the autonomic nervous system. Studying these differences may be informative for a better understanding of each tissue

Sustained favorable long-term outcome in the treatment of schizophrenia: a 3-year prospective observational study

<p>Abstract</p> <p>Background</p> <p>This study of chronically ill patients with schizophrenia aimed to identify patients who achieve sustained favorable long-term outcome - when the outcome incorporates severity of symptoms, level of functioning, and use of acute care services - and to identify the best baseline predictors of achieving this sustained favorable long-term outcome.</p> <p>Methods</p> <p>Using data from the United States Schizophrenia Care and Assessment Program (US-SCAP) (N = 2327), a large 3-year prospective, multisite, observational study of individuals treated for schizophrenia in the US, a hierarchical cluster analysis was performed to group patients based upon baseline symptom severity. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS) scores, level of functioning, and use of acute care services. Level of functioning reflected patient-reported productivity and clinician-rated occupational role functioning. Use of acute care services reflected self-reported psychiatric hospitalization and emergency service use. Change of health state was determined over the 3-year period. A patient was classified as having a sustained favorable long-term outcome if their health state values had the closest distance to the defined "best baseline cluster" at each point over the length of the study. Stepwise logistic regression was used to determine baseline predictors of sustained favorable long-term outcome.</p> <p>Results</p> <p>At baseline, 5 distinct health state clusters were identified, ranging from "best" to "worst." Of 1635 patients with sufficient data, only 157 (10%) experienced sustained favorable long-term outcome during the 2-years postbaseline. The baseline predictors associated with sustained favorable long-term outcome included better quality of life, more daily activities, patient-reported clearer thinking from medication, better global functioning, being employed, not being a victim of a crime, not having received individual therapy, and not having received help with shopping and leisure activities.</p> <p>Conclusions</p> <p>Only a small percentage of patients achieved sustained favorable long-term outcome in this study, suggesting there continues to be a great need for improvement in the treatment of schizophrenia. Findings suggest that clinicians could make early projections of health states and identify those patients more likely to achieve favorable long-term outcomes enabling early therapeutic interventions to enhance benefits for patients.</p

Understanding hereditary diseases using the dog and human as companion model systems

Animal models are requisite for genetic dissection of, and improved treatment regimens for, human hereditary diseases. While several animals have been used in academic and industrial research, the primary model for dissection of hereditary diseases has been the many strains of the laboratory mouse. However, given its greater (than the mouse) genetic similarity to the human, high number of naturally occurring hereditary diseases, unique population structure, and the availability of the complete genome sequence, the purebred dog has emerged as a powerful model for study of diseases. The major advantage the dog provides is that it is afflicted with approximately 450 hereditary diseases, about half of which have remarkable clinical similarities to corresponding diseases of the human. In addition, humankind has a strong desire to cure diseases of the dog so these two facts make the dog an ideal clinical and genetic model. This review highlights several of these shared hereditary diseases. Specifically, the canine models discussed herein have played important roles in identification of causative genes and/or have been utilized in novel therapeutic approaches of interest to the dog and human

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Site-specific labeling of nucleotides for making RNA for high resolution NMR studies using an E. coli strain disabled in the oxidative pentose phosphate pathway

Escherichia coli (E. coli) is a versatile organism for making nucleotides labeled with stable isotopes (13C, 15N, and/or 2H) for structural and molecular dynamics characterizations. Growth of a mutant E. coli strain deficient in the pentose phosphate pathway enzyme glucose-6-phosphate dehydrogenase (K10-1516) on 2-13C-glycerol and 15N-ammonium sulfate in Studier minimal medium enables labeling at sites useful for NMR spectroscopy. However, 13C-sodium formate combined with 13C-2-glycerol in the growth media adds labels to new positions. In the absence of labeled formate, both C5 and C6 positions of the pyrimidine rings are labeled with minimal multiplet splitting due to 1JC5C6 scalar coupling. However, the C2/C8 sites within purine rings and the C1′/C3′/C5′ positions within the ribose rings have reduced labeling. Addition of 13C-labeled formate leads to increased labeling at the base C2/C8 and the ribose C1′/C3′/C5′ positions; these new specific labels result in two- to three-fold increase in the number of resolved resonances. This use of formate and 15N-ammonium sulfate promises to extend further the utility of these alternate site specific labels to make labeled RNA for downstream biophysical applications such as structural, dynamics and functional studies of interesting biologically relevant RNAs

The HIV Tat protein affects processing of ribosomal RNA precursor

<p>Abstract</p> <p>Background</p> <p>Inside the cell, the HIV Tat protein is mainly found in the nucleus and nucleolus. The nucleolus, the site of ribosome biogenesis, is a highly organized, non-membrane-bound sub-compartment where proteins with a high affinity for nucleolar components are found. While it is well known that Tat accumulates in the nucleolus via a specific nucleolar targeting sequence, its function in this compartment it still unknown.</p> <p>Results</p> <p>To clarify the significance of the Tat nucleolar localization, we induced the expression of the protein during oogenesis in <it>Drosophila melanogaster </it>strain transgenic for HIV-<it>tat </it>gene. Here we show that Tat localizes in the nucleoli of <it>Drosophila </it>oocyte nurse cells, where it specifically co-localizes with fibrillarin. Tat expression is accompanied by a significant decrease of cytoplasmic ribosomes, which is apparently related to an impairment of ribosomal rRNA precursor processing. Such an event is accounted for by the interaction of Tat with fibrillarin and U3 snoRNA, which are both required for pre-rRNA maturation.</p> <p>Conclusion</p> <p>Our data contribute to understanding the function of Tat in the nucleolus, where ribosomal RNA synthesis and cell cycle control take place. The impairment of nucleolar pre-rRNA maturation through the interaction of Tat with fibrillarin-U3snoRNA complex suggests a process by which the virus modulates host response, thus contributing to apoptosis and protein shut-off in HIV-uninfected cells.</p

Aboveground Herbivory Shapes the Biomass Distribution and Flux of Soil Invertebrates

Contains fulltext : 72659.pdf ( ) (Open Access)Background Living soil invertebrates provide a universal currency for quality that integrates physical and chemical variables with biogeography as the invertebrates reflect their habitat and most ecological changes occurring therein. The specific goal was the identification of “reference” states for soil sustainability and ecosystem functioning in grazed vs. ungrazed sites. Methodology/Principal Findings Bacterial cells were counted by fluorescent staining and combined direct microscopy and automatic image analysis; invertebrates (nematodes, mites, insects, oligochaetes) were sampled and their body size measured individually to allow allometric scaling. Numerical allometry analyses food webs by a direct comparison of weight averages of components and thus might characterize the detrital soil food webs of our 135 sites regardless of taxonomy. Sharp differences in the frequency distributions are shown. Overall higher biomasses of invertebrates occur in grasslands, and all larger soil organisms differed remarkably. Conclusions/Significance Strong statistical evidence supports a hypothesis explaining from an allometric perspective how the faunal biomass distribution and the energetic flux are affected by livestock, nutrient availability and land use. Our aim is to propose faunal biomass flux and biomass distribution as quantitative descriptors of soil community composition and function, and to illustrate the application of these allometric indicators to soil systems.7 p

RNAcentral 2021: secondary structure integration, improved sequence search and new member databases

RNAcentral is a comprehensive database of non-coding RNA (ncRNA) sequences that provides a single access point to 44 RNA resources and >18 million ncRNA sequences from a wide range of organisms and RNA types. RNAcentral now also includes secondary (2D) structure information for >13 million sequences, making RNAcentral the world’s largest RNA 2D structure database. The 2D diagrams are displayed using R2DT, a new 2D structure visualization method that uses consistent, reproducible and recognizable layouts for related RNAs. The sequence similarity search has been updated with a faster interface featuring facets for filtering search results by RNA type, organism, source database or any keyword. This sequence search tool is available as a reusable web component, and has been integrated into several RNAcentral member databases, including Rfam, miRBase and snoDB. To allow for a more fine-grained assignment of RNA types and subtypes, all RNAcentral sequences have been annotated with Sequence Ontology terms. The RNAcentral database continues to grow and provide a central data resource for the RNA community. RNAcentral is freely available at https://rnacentral.org