IsoPlotter(+): A Tool for Studying the Compositional Architecture of Genomes.

Eukaryotic genomes, particularly animal genomes, have a complex, nonuniform, and nonrandom internal compositional organization. The compositional organization of animal genomes can be described as a mosaic of discrete genomic regions, called "compositional domains," each with a distinct GC content that significantly differs from those of its upstream and downstream neighboring domains. A typical animal genome consists of a mixture of compositionally homogeneous and nonhomogeneous domains of varying lengths and nucleotide compositions that are interspersed with one another. We have devised IsoPlotter, an unbiased segmentation algorithm for inferring the compositional organization of genomes. IsoPlotter has become an indispensable tool for describing genomic composition and has been used in the analysis of more than a dozen genomes. Applications include describing new genomes, correlating domain composition with gene composition and their density, studying the evolution of genomes, testing phylogenomic hypotheses, and detect regions of potential interbreeding between human and extinct hominines. To extend the use of IsoPlotter, we designed a completely automated pipeline, called IsoPlotter(+) to carry out all segmentation analyses, including graphical display, and built a repository for compositional domain maps of all fully sequenced vertebrate and invertebrate genomes. The IsoPlotter(+) pipeline and repository offer a comprehensive solution to the study of genome compositional architecture. Here, we demonstrate IsoPlotter(+) by applying it to human and insect genomes. The computational tools and data repository are available online

A Comparative Study and a Phylogenetic Exploration of the Compositional Architectures of Mammalian Nuclear Genomes

For the past four decades the compositional organization of the mammalian genome posed a formidable challenge to molecular evolutionists attempting to explain it from an evolutionary perspective. Unfortunately, most of the explanations adhered to the “isochore theory,” which has long been rebutted. Recently, an alternative compositional domain model was proposed depicting the human and cow genomes as composed mostly of short compositionally homogeneous and nonhomogeneous domains and a few long ones. We test the validity of this model through a rigorous sequence-based analysis of eleven completely sequenced mammalian and avian genomes. Seven attributes of compositional domains are used in the analyses: (1) the number of compositional domains, (2) compositional domain-length distribution, (3) density of compositional domains, (4) genome coverage by the different domain types, (5) degree of fit to a power-law distribution, (6) compositional domain GC content, and (7) the joint distribution of GC content and length of the different domain types. We discuss the evolution of these attributes in light of two competing phylogenetic hypotheses that differ from each other in the validity of clade Euarchontoglires. If valid, the murid genome compositional organization would be a derived state and exhibit a high similarity to that of other mammals. If invalid, the murid genome compositional organization would be closer to an ancestral state. We demonstrate that the compositional organization of the murid genome differs from those of primates and laurasiatherians, a phenomenon previously termed the “murid shift,” and in many ways resembles the genome of opossum. We find no support to the “isochore theory.” Instead, our findings depict the mammalian genome as a tapestry of mostly short homogeneous and nonhomogeneous domains and few long ones thus providing strong evidence in favor of the compositional domain model and seem to invalidate clade Euarchontoglires

'Genome order index' should not be used for defining compositional constraints in nucleotide sequences - a case study of the Z-curve

Background: The Z-curve is a three dimensional representation of DNA sequences proposed over a decade ago and has been extensively applied to sequence segmentation, horizontal gene transfer detection, and sequence analysis. Based on the Z-curve, a “genome order index,” was proposed, which is defined as S = a2 + c 2 +t 2 +g2 , where a, c, t, and g are the nucleotide frequencies of A, C, T, and G, respectively. This index was found to be smaller than 1/3 for almost all tested genomes, which was taken as support for the existence of a constraint on genome composition. A geometric explanation for this constraint has been suggested. Each genome was represented by a point P whose distance from the four faces of a regular tetrahedron was given by the frequencies a, c, t, and g. They claimed that an inscribed sphere of radius r = 1/ 3 contains almost all points corresponding to various genomes, implying that S < r 2 . The distribution of the points P obtained by S was studied using the Z-curve. Results: In this work, we studied the basic properties of the Z-curve using the “genome order index” as a case study. We show that (1) the calculation of the radius of the inscribed sphere of a regular tetrahedron is incorrect, (2) the S index is narrowly distributed, (3) based on the second parity rule, the S index can be derived directly from the Shannon entropy and is, therefore, redundant, and (4) the Z-curve suffers from over dimensionality, and the dimension stands for GC content alone suffices to represent any given genome. Conclusion: The “genome order index” S does not represent a constraint on nucleotide composition. Moreover, S can be easily computed from the Gini-Simpson index and be directly derived from entropy and is redundant. Overall, the Z-curve and S are over-complicated measures to GC content and Shannon H index, respectively. Reviewers: This article was reviewed by Claus Wilke, Joel Bader, Marek Kimmel and Uladzislau Hryshkevich (nominated by Itai Yanai)

Universality of Long-Range Correlations in Expansion-Randomization Systems

We study the stochastic dynamics of sequences evolving by single site mutations, segmental duplications, deletions, and random insertions. These processes are relevant for the evolution of genomic DNA. They define a universality class of non-equilibrium 1D expansion-randomization systems with generic stationary long-range correlations in a regime of growing sequence length. We obtain explicitly the two-point correlation function of the sequence composition and the distribution function of the composition bias in sequences of finite length. The characteristic exponent $\chi$ of these quantities is determined by the ratio of two effective rates, which are explicitly calculated for several specific sequence evolution dynamics of the universality class. Depending on the value of $\chi$, we find two different scaling regimes, which are distinguished by the detectability of the initial composition bias. All analytic results are accurately verified by numerical simulations. We also discuss the non-stationary build-up and decay of correlations, as well as more complex evolutionary scenarios, where the rates of the processes vary in time. Our findings provide a possible example for the emergence of universality in molecular biology.Comment: 23 pages, 15 figure

Mapping biodiversity value worldwide: combining higher-taxon richness from different groups

Maps of large-scale biodiversity are urgently needed to guide conservation, and yet complete enumeration of organisms is impractical at present. One indirect approach is to measure richness at higher taxonomic ranks, such as families. The difficulty is how to combine information from different groups on numbers of higher taxa, when these taxa may in effect have been defined in different ways, particularly for more distantly related major groups. In this paper, the regional family richness of terrestrial and freshwater seed plants, amphibians, reptiles and mammals is mapped worldwide by combining: (i) absolute family richness; (ii) proportional family richness; and (iii) proportional family richness weighted for the total species richness in each major group. The assumptions of the three methods and their effects on the results are discussed, although for these data the broad pattern is surprisingly robust with respect to the method of combination. Scores from each of the methods of combining families are used to rank the top five richness hotspots and complementary areas, and hotspots of endemism are mapped by unweighted combination of range-size rarity scores

LATE-TIME PHOTOMETRY OF TYPE IA SUPERNOVA SN 2012cg REVEALS THE RADIOACTIVE DECAY OF Co-57

Seitenzahl et al. have predicted that roughly three years after its explosion, the light we receive from a Type Ia supernova (SN Ia) will come mostly from reprocessing of electrons and X-rays emitted by the radioactive decay chain 57Co → 57Fe, instead of positrons from the decay chain 56Co → 56Fe that dominates the SN light at earlier times. Using the Hubble Space Telescope, we followed the light curve of the SN Ia SN 2012cg out to 1055 days after maximum light. Our measurements are consistent with the light curves predicted by the contribution of energy from the reprocessing of electrons and X-rays emitted by the decay of 57Co, offering evidence that 57Co is produced in SN Ia explosions. However, the data are also consistent with a light echo ∼14 mag fainter than SN 2012cg at peak. Assuming no light-echo contamination, the mass ratio of 57Ni and 56Ni produced by the explosion, a strong constraint on any SN Ia explosion models, is 0.043 0.011 0.012 - + , roughly twice Solar. In the context of current explosion models, this value favors a progenitor white dwarf with a mass near the Chandrasekhar limit

Laparoscopic rectal resections: practical aspects

Abordul laparoscopic in chirurgia cancerului de rect este o considerat standardul de aur ce ofera rezultate oncologice similar cu o recuperare postoperatorie imbunatatita, si o rata minimala de complicatii. Pe fondul complexitatii crescute, cu toate astea, abordul laparoscopic ar trebui efectuat in centre tertiare, fiind rezervat chirurgilor cu o curba de invatare adecvata. O selectie atenta a cazurilor si o planificare adecvata ar trebui luata in considerare in cadrul acestui abord. Prezentarea de fata surprinde aspectele practice de baza precum si variatii tatice in cadrul rezectiilor de rect laparoscopice, precum si pasii potentiali in atingerea curbei de invatare.Laparoscopic approach is an already established procedure in rectal cancer which offers a similar oncological outcome, with improved postoperative recovery and fewer complications. Due to its increased complexity, however, the laparoscopic approach should be reserved for high-volume centers and for experienced surgeons with an adequate learning curve. Appropriate patient selection and planning must be carefully considered when opting for this approach. In this presentation, the primary practical aspects as well as certain tactical approaches will be covered regarding the laparoscopic rectal resections as well as the potential steps in achieving the learning curve

Classic vs laparoscopic approach in colorectal cancer. Experience of a tertiary center, Surgery No 3 Clinic, Cluj-Napoca

Clinica Chirurgie 3, Cluj-Napoca, România, Al XIII-lea Congres al Asociației Chirurgilor „Nicolae Anestiadi” și al III-lea Congres al Societății de Endoscopie, Chirurgie miniminvazivă și Ultrasonografie ”V.M.Guțu” din Republica MoldovaIntroducere: Cancerul colorectal este unul dintre cele mai frecvente cancere și cu tendință în creștere la nivel global. Majoritatea studiilor recente au demonstrat non inferioritatea și chiar o ușoară superioritate în abordul laparoscopic prin prisma rezultatelor obținute și a supraviețuirii la distanță. Material și metode: Au fost selectate retrospectiv 2186 de cazuri din baza de date completată prospectiv a Clinicii Chirurgie 3 pentru perioada ian 2013-dec 2018 (6 ani). Din acestea s-au exclus 76 cazuri laparoscopie/laparotomie exploratorie, 154 cazuri colostomii, 51 derivații interne; în final au fost analizate 1905 cazuri de cancer colorectal. Rezultate: Din 1905 cazuri s-au efectuat rezecții laparoscopice la un număr de 310 (16.27%) și clasice la un număr de 1595 cazuri (83.73%). Au fost analizați între cele două loturi următorii parametri: pregătire preoperatorie, durata operației, pierderi sangvine, complicații postoperatorii (fistulă, abces, hemoragie, ocluzie, complicații generale), supurații de plagă, zile spitalizare, necesar antibiotic, mobilizare postoperatorie, mortalitate. Concuzii: Abordul laparoscopic prezintă avantaje privind recuperarea postoperatorie, pierderi sangvine, zile spitalizare, necesar antialgice/antibiotic, lipsa supurațiilor de plagă. Dezavantajele sunt curba de învățare, aparatura specifică și dificultatea păstrării principiilor oncologice.Introduction: Colorectal cancer remains one of the most frequently diagnosed malignant pathologies with a continuously increasing rate worldwide. Most of the recent studies have shown the non-inferiority and slight superiority in the laparoscopic approach through obtained results. Material and methods: 2186 cases were selected retrospectively from a prospectively completed database of the Surgical no 3 Clinic in Cluj-Napoca over the course of 6 years (ian 2013 – dec 2018). Out of these cases, 76 cases were excluded for exploratory laparoscopy/laparotomy, 154 which underwent only colostomy, and 51 which underwent internal derivation. At the end of the study, 1905 cases were eligible. Results: Out of 1905 cases, 310 underwent a laparoscopic approach (16.27%) and 1595 cases underwent a classic approach (83.73%). Between the two approaches, a series of parameters were analyzed: preoperative care, duration of the surgery, intraoperative blood loss, postoperative complications (fistula, abscess, hemorrhage, occlusion, general complications), antibiotic necessity, postoperative mobilization, mortality, prevalence of surgical site infection. Conclusions: The laparoscopic approach proves many advantages regarding postoperative care, blood loss, hospitalization care, necessity of antibiotics and painkillers, and surgical site infection, cosmetic advantages. Disadvantages are the learning curve, specific instruments requirements, difficulty of maintaining the oncology principles

Supernovae in the Subaru Deep Field: the rate and delay-time distribution of Type Ia supernovae out to redshift 2

The Type Ia supernova (SN Ia) rate, when compared to the cosmic star formation history (SFH), can be used to derive the delay-time distribution (DTD; the hypothetical SN Ia rate versus time following a brief burst of star formation) of SNe Ia, which can distinguish among progenitor models. We present the results of a supernova (SN) survey in the Subaru Deep Field (SDF). Over a period of 3 years, we have observed the SDF on four independent epochs with Suprime-Cam on the Subaru 8.2-m telescope, with two nights of exposure per epoch, in the R, i′and z′ bands. We have discovered 150 SNe out to redshift z≈ 2. Using 11 photometric bands from the observer-frame far-ultraviolet to the near-infrared, we derive photometric redshifts for the SN host galaxies (for 24 we also have spectroscopic redshifts). This information is combined with the SN photometry to determine the type and redshift distribution of the SN sample. Our final sample includes 28 SNe Ia in the range 1.0 1, most of the events found in this range are likely SNe Ia. Our SN Ia rate measurements are consistent with those derived from the Hubble Space Telescope (HST) Great Observatories Origins Deep Survey (GOODS) sample, but the overall uncertainty of our 1.5 2

Lack of self-averaging in neutral evolution of proteins

We simulate neutral evolution of proteins imposing conservation of the thermodynamic stability of the native state in the framework of an effective model of folding thermodynamics. This procedure generates evolutionary trajectories in sequence space which share two universal features for all of the examined proteins. First, the number of neutral mutations fluctuates broadly from one sequence to another, leading to a non-Poissonian substitution process. Second, the number of neutral mutations displays strong correlations along the trajectory, thus causing the breakdown of self-averaging of the resulting evolutionary substitution process.Comment: 4 pages, 2 figure