On the general theory of the origins of retroviruses

<p>Abstract</p> <p>Background</p> <p>The order retroviridae comprises viruses based on ribonucleic acids (RNA). Some, such as HIV and HTLV, are human pathogens. Newly emerged human retroviruses have zoonotic origins. As far as has been established, both repeated infections (themselves possibly responsible for the evolution of viral mutations <b>(Vm) </b>and host adaptability <b>(Ha)</b>); along with interplay between <it>inhibitors </it>and <it>promoters </it>of cell tropism, are needed to effect retroviral cross-species transmissions. However, the exact <it>modus operadi </it>of intertwine between these factors at molecular level remains to be established. Knowledge of such intertwine could lead to a better understanding of retrovirology and possibly other infectious processes. This study was conducted to derive the mathematical equation of a general theory of the origins of retroviruses.</p> <p>Methods and results</p> <p>On the basis of an arbitrarily non-Euclidian geometrical "thought experiment" involving the cross-species transmission of simian foamy virus (sfv) from a non-primate species <it>Xy </it>to <it>Homo sapiens </it>(<it>Hs</it>), initially excluding all social factors, the following was derived. At the port of exit from <it>Xy </it>(where the species barrier, SB, is defined by the <it>Index of Origin</it>, IO), sfv shedding is (1) enhanced by two transmitting tensors <b>(Tt)</b>, (i) virus-specific immunity (VSI) and (ii) evolutionary defenses such as APOBEC, RNA interference pathways, and (when present) expedited therapeutics (denoted e²D); and (2) opposed by the five accepting scalars <b>(At)</b>: (a) genomic integration hot spots, gIHS, (b) nuclear envelope transit <b>(</b>NMt) vectors, (c) virus-specific cellular biochemistry, VSCB, (d) virus-specific cellular receptor repertoire, VSCR, and (e) pH-mediated cell membrane transit, (↓_pHCMat). Assuming <b>As </b>and <b>Tt </b>to be independent variables, <b>IO = Tt/As</b>. The same forces acting in an opposing manner determine SB at the port of sfv entry (defined here by the <it>Index of Entry</it>, <b>IE = As/Tt</b>). Overall, If sfv encounters no unforeseen effects on transit between X<it>y </it>and <it>Hs</it>, then the square root of the combined index of sfv transmissibility (√<b>|RTI|) </b>is proportional to the product IO* IE (or ~Vm* Ha* ∑Tt*∑As*<b>Ω</b>), where <b>Ω </b>is the retrovirological constant and ∑ is a function of the ratio Tt/As or As/Tt for sfv transmission from <it>Xy </it>to <it>Hs</it>.</p> <p>Conclusions</p> <p>I present a mathematical formalism encapsulating the general theory of the origins of retroviruses. It summarizes the choreography for the intertwined interplay of factors influencing the probability of retroviral cross-species transmission: <b>Vm, Ha, Tt, As, </b>and <b>Ω</b>.</p

Whole Genome Resequencing Reveals Natural Target Site Preferences of Transposable Elements in Drosophila melanogaster

Transposable elements are mobile DNA sequences that integrate into host genomes using diverse mechanisms with varying degrees of target site specificity. While the target site preferences of some engineered transposable elements are well studied, the natural target preferences of most transposable elements are poorly characterized. Using population genomic resequencing data from 166 strains of Drosophila melanogaster, we identified over 8,000 new insertion sites not present in the reference genome sequence that we used to decode the natural target preferences of 22 families of transposable element in this species. We found that terminal inverted repeat transposon and long terminal repeat retrotransposon families present clade-specific target site duplications and target site sequence motifs. Additionally, we found that the sequence motifs at transposable element target sites are always palindromes that extend beyond the target site duplication. Our results demonstrate the utility of population genomics data for high-throughput inference of transposable element targeting preferences in the wild and establish general rules for terminal inverted repeat transposon and long terminal repeat retrotransposon target site selection in eukaryotic genomes

Panmixia in a fragmented and unstable environment: the hydrothermal shrimp Rimicaris exoculata disperses extensively along the Mid-Atlantic ridge

Dispersal plays a fundamental role in the evolution and persistence of species, and especially for species inhabiting extreme, ephemeral and highly fragmented habitats as hydrothermal vents. The Mid-Atlantic Ridge endemic shrimp species Rimicaris exoculata was studied using microsatellite markers to infer connectivity along the 7100-Km range encompassing the sampled sites. Astonishingly, no genetic differentiation was found between individuals from the different geographic origins, supporting a scenario of widespread large-scale dispersal despite the habitat distance and fragmentation. We hypothesize that delayed metamorphosis associated to temperature differences or even active directed migration dependent on physical and/or chemical stimuli could explain these results and warrant further studies on adaptation and dispersal mechanisms

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Elevated extracellular HSP70 (HSPA1A) level as an independent prognostic marker of mortality in patients with heart failure

Predicting the survival of a patient with heart failure (HF) is a complex problem in clinical practice. Our previous study reported that extracellular HSP70 (HSPA1A) correlates with markers of heart function and disease severity in HF, but the predictive value of HSP70 is unclear. The goal of this study was to analyze extracellular HSP70 as predictive marker of mortality in HF. One hundred ninety-five patients with systolic heart failure were enrolled and followed up for 60 months. By the end of follow-up, 85 patients were alive (survivors) and 110 died (nonsurvivors). HSP70 (measured by ELISA in the serum) was elevated in nonsurvivors, compared with survivors (0.39 [0.27-0.59] vs. 0.30 [0.24-0.43] ng/ml, respectively, p = 0.0101). In Kaplan-Meier survival analysis higher HSP70 levels above median were associated with a significantly increased mortality. In multivariable survival models, we show that HSP70 level above the median is an age-, sex-, body mass index-, creatinine-, and NT-proBNP-independent predictor of 5-year mortality in HF. Extracellular HSP70 could prove useful for estimating survival in patients with HF