Self-complementary circular codes in coding theory

Self-complementary circular codes are involved in pairing genetic processes. A maximal \(C^3\) self-complementary circular code X of trinucleotides was identified in genes of bacteria, archaea, eukaryotes, plasmids and viruses (Michel in Life 7(20):1–16 2017, J Theor Biol 380:156–177, 2015; Arquès and Michel in J Theor Biol 182:45–58 1996). In this paper, self-complementary circular codes are investigated using the graph theory approach recently formulated in Fimmel et al. (Philos Trans R Soc A 374:20150058, 2016). A directed graph \(\mathcal {G}(X)\) associated with any code X mirrors the properties of the code. In the present paper, we demonstrate a necessary condition for the self-complementarity of an arbitrary code X in terms of the graph theory. The same condition has been proven to be sufficient for codes which are circular and of large size \(\mid X \mid \ge 18\) trinucleotides, in particular for maximal circular codes (\(\mid X \mid = 20\) trinucleotides). For codes of small-size \(\mid X \mid \le 16\) trinucleotides, some very rare counterexamples have been constructed. Furthermore, the length and the structure of the longest paths in the graphs associated with the self-complementary circular codes are investigated. It has been proven that the longest paths in such graphs determine the reading frame for the self-complementary circular codes. By applying this result, the reading frame in any arbitrary sequence of trinucleotides is retrieved after at most 15 nucleotides, i.e., 5 consecutive trinucleotides, from the circular code X identified in genes. Thus, an X motif of a length of at least 15 nucleotides in an arbitrary sequence of trinucleotides (not necessarily all of them belonging to X) uniquely defines the reading (correct) frame, an important criterion for analyzing the X motifs in genes in the future.     

Competition between phytoplankton and bacteria: exclusion and coexistence

Resource-based competition between microorganisms species in continuous culture has been studied extensively both experimentally and theoretically, mostly for bacteria through Monod and Contois “constant yield” models, or for phytoplankton through the Droop “variable yield” models. For homogeneous populations of N bacterial species (Monod) or N phytoplanktonic species (Droop), with one limiting substrate and under constant controls, the theoretical studies indicated that competitive exclusion occurs: only one species wins the competition and displaces all the others (Armstrong and McGehee in Am Nat 115:151, 1980; Hsu and Hsu in SIAM J Appl Math 68:1600–1617, 2008). The winning species expected from theory is the one with the lowest “substrate subsistence concentration” \(s^{\star }\), such that its corresponding equilibrium growth rate is equal to the dilution rate \(D\). This theoretical result was validated experimentally with phytoplankton (Tilman and Sterner in Oecologia 61(2):197–200, 1984) and bacteria (Hansen and Hubell in Science 207(4438):1491–1493, 1980), and observed in a lake with microalgae (Tilman in Ecology 58(22):338–348, 1977). On the contrary for aggregating bacterial species described by a Contois model, theory predicts coexistence between several species (Grognard et al. in Discrete Contin Dyn Syst Ser B 8(1):73–93, 2007). In this paper we present a generalization of these results by studying a competition between three different types of microorganisms: planktonic (or free) bacteria (represented by a generalized Monod model), aggregating bacteria (represented by a Contois model) and free phytoplankton (represented by a Droop model). We prove that the outcome of the competition is a coexistence between several aggregating bacterial species with a free species of bacteria or phytoplankton, all the other free species being washed out. This demonstration is based mainly on the study of the substrate concentration’s evolution caused by competition; it converges towards the lowest subsistence concentration \(s^{\star }\), leading to three different types of competition outcomes: (1) the best free bacteria or phytoplankton competitor excludes all other species; (2) only some aggregating bacterial species coexist in the chemostat; (3) A coexistence between the single best free species, with one or several aggregating species.     

Persistence in Stochastic Lotka–Volterra Food Chains with Intraspecific Competition

This paper is devoted to the analysis of a simple Lotka–Volterra food chain evolving in a stochastic environment. It can be seen as the companion paper of Hening and Nguyen (J Math Biol 76:697–754, 2018b) where we have characterized the persistence and extinction of such a food chain under the assumption that there is no intraspecific competition among predators. In the current paper, we focus on the case when all the species experience intracompetition. The food chain we analyze consists of one prey and \(n-1\) predators. The jth predator eats the \(j-1\)st species and is eaten by the \(j+1\)st predator; this way each species only interacts with at most two other species—the ones that are immediately above or below it in the trophic chain. We show that one can classify, based on the invasion rates of the predators (which we can determine from the interaction coefficients of the system via an algorithm), which species go extinct and which converge to their unique invariant probability measure. We obtain stronger results than in the case with no intraspecific competition because in this setting we can make use of the general results of Hening and Nguyen (Ann Appl Probab 28:1893–1942, 2018a). Unlike most of the results available in the literature, we provide an in-depth analysis for both non-degenerate and degenerate noise. We exhibit our general results by analyzing trophic cascades in a plant–herbivore–predator system and providing persistence/extinction criteria for food chains of length \(n\le 4\).     

Mathematical Model of Bone Remodeling Captures the Antiresorptive and Anabolic Actions of Various Therapies

A better understanding of the molecular pathways regulating the bone remodeling process should help in the development of new antiresorptive regulators and anabolic regulators, that is, regulators of bone resorption and of bone formation. Understanding the mechanisms by which parathyroid hormone (PTH) influences bone formation and how it switches from anabolic to catabolic action is important for treating osteoporosis (Poole and Reeve in Curr Opin Pharmacol 5:612–617, 2005). In this paper we describe a mathematical model of bone remodeling that incorporates, extends, and integrates several models of particular aspects of this biochemical system (Cabal et al. in J Bone Miner Res 28(8):1830–1836, 2013; Lemaire et al. in J Theor Biol 229:293–309, 2004; Peterson and Riggs in Bone 46:49–63, 2010; Raposo et al. in J Clin Endocrinol Metab 87(9):4330–4340, 2002; Ross et al. in J Disc Cont Dyn Sys Series B 17(6):2185–2200, 2012). We plan to use this model as a bone homeostasis platform to develop anabolic and antiresorptive compounds. The model will allow us to test hypotheses about the dynamics of compounds and to test the potential benefits of combination therapies. At the core of the model is the idealized account of osteoclast and osteoblast signaling given by Lemaire et al. (J Theor Biol 229:293–309, 2004). We have relaxed some of their assumptions about the roles of osteoprotegerin, transforming growth factor \(\upbeta \), and receptor activator of nuclear factor \(\upkappa \)B ligand; we have devised more detailed models of the interactions of these species. We have incorporated a model of the effect of calcium sensing receptor antagonists on remodeling (Cabal et al. in J Bone Miner Res 28(8):1830–1836, 2013). We have also incorporated a basic model of the effects of vitamin D on calcium homeostasis. We have included a simple model of the mechanism proposed by Bellido et al. (2003), Ross et al. (J Disc Cont Dyn Sys Series B 17(6):2185–2200, 2012), of the influence of PTH on osteoblast apoptosis, a mechanism that accounts for the anabolic response to pulsatile PTH administration. Finally, we have devised a simple model of the administration and effects of bisphosphonates. The biomarkers in the model are procollagen type 1 amino-terminal propeptide and C-terminal telopeptide. Bone mineral density is the model’s principal endpoint.     

A Mathematical Model Supports a Key Role for Ae4 (Slc4a9) in Salivary Gland Secretion

We develop a mathematical model of a salivary gland acinar cell with the objective of investigating the role of two \(\mathrm{Cl}^-/\mathrm{HCO}_3^-\) exchangers from the solute carrier family 4 (Slc4), Ae2 (Slc4a2) and Ae4 (Slc4a9), in fluid secretion. Water transport in this type of cell is predominantly driven by \(\mathrm{Cl}^-\) movement. Here, a basolateral \(\mathrm{Na}^+/ \mathrm{K}^+\) adenosine triphosphatase pump (NaK-ATPase) and a \(\mathrm{Na}^+\)–\(\mathrm{K}^+\)–\(2 \mathrm{Cl}^-\) cotransporter (Nkcc1) are primarily responsible for concentrating the intracellular space with \(\mathrm{Cl}^-\) well above its equilibrium potential. Gustatory and olfactory stimuli induce the release of \(\mathrm{Ca}^{2+}\) ions from the internal stores of acinar cells, which triggers saliva secretion. \(\mathrm{Ca}^{2+}\)-dependent \(\mathrm{Cl}^-\) and \(\mathrm{K}^+\) channels promote ion secretion into the luminal space, thus creating an osmotic gradient that promotes water movement in the secretory direction. The current model for saliva secretion proposes that \(\mathrm{Cl}^-/ \mathrm{HCO}_3^-\) anion exchangers (Ae), coupled with a basolateral \(\mathrm{Na}^+/\hbox {proton}\) (\(\hbox {H}^+\)) (Nhe1) antiporter, regulate intracellular pH and act as a secondary \(\mathrm{Cl}^-\) uptake mechanism (Nauntofte in Am J Physiol Gastrointest Liver Physiol 263(6):G823–G837, 1992; Melvin et al. in Annu Rev Physiol 67:445–469, 2005.  https://doi.org/10.1146/annurev.physiol.67.041703.084745). Recent studies demonstrated that Ae4 deficient mice exhibit an approximate \(30\%\) decrease in gland salivation (Peña-Münzenmayer et al. in J Biol Chem 290(17):10677–10688, 2015). Surprisingly, the same study revealed that absence of Ae2 does not impair salivation, as previously suggested. These results seem to indicate that the Ae4 may be responsible for the majority of the secondary \(\mathrm{Cl}^-\) uptake and thus a key mechanism for saliva secretion. Here, by using ‘in-silico’ Ae2 and Ae4 knockout simulations, we produced mathematical support for such controversial findings. Our results suggest that the exchanger’s cotransport of monovalent cations is likely to be important in establishing the osmotic gradient necessary for optimal transepithelial fluid movement.     

Fitting alignment tensor components to experimental RDCs,CSAs and RQCs

Residual dipolar couplings, chemical shift anisotropies and quadrupolar couplings provide information about the orientation of inter-spin vectors and the anisotropic contribution of the local environment to the chemical shifts of nuclei, respectively. Structural interpretation of these observables requires parameterization of their angular dependence in terms of an alignment tensor. We compare and evaluate two algorithms for generating the optimal alignment tensor for a given molecular structure and set of experimental data, namely SVD (Losonczi et al. in J Magn Reson 138(2):334–342, 1999), which scales as \({{\mathcal {O}}(n^2)}\), and the linear least squares algorithm (Press et al. in Numerical recipes in C. The art of scientific computing, 2nd edn. Cambridge University Press, Cambridge, 1997), which scales as \({{\mathcal {O}}(n)}\).     

Superbubbles revisited

Background

Superbubbles are distinctive subgraphs in direct graphs that play an important role in assembly algorithms for high-throughput sequencing (HTS) data. Their practical importance derives from the fact they are connected to their host graph by a single entrance and a single exit vertex, thus allowing them to be handled independently. Efficient algorithms for the enumeration of superbubbles are therefore of important for the processing of HTS data. Superbubbles can be identified within the strongly connected components of the input digraph after transforming them into directed acyclic graphs. The algorithm by Sung et al. (IEEE ACM Trans Comput Biol Bioinform 12:770–777, 2015) achieves this task in \(\mathcal {O}(m~log(m))\)-time. The extraction of superbubbles from the transformed components was later improved to by Brankovic et al. (Theor Comput Sci 609:374–383, 2016) resulting in an overall \(\mathcal {O}(m+n)\)-time algorithm.

Results

A re-analysis of the mathematical structure of superbubbles showed that the construction of auxiliary DAGs from the strongly connected components in the work of Sung et al. missed some details that can lead to the reporting of false positive superbubbles. We propose an alternative, even simpler auxiliary graph that solved the problem and retains the linear running time for general digraph. Furthermore, we describe a simpler, space-efficient \(\mathcal {O}(m+n)\)-time algorithm for detecting superbubbles in DAGs that uses only simple data structures.

Implementation

We present a reference implementation of the algorithm that accepts many commonly used formats for the input graph and provides convenient access to the improved algorithm. https://github.com/Fabianexe/Superbubble.

     

Use of CD40L immunoconjugates to overcome the defective immune response to vaccines for infections and cancer in the aged

Multiple investigators have reported thepresence of defects in the immune response of the elderly [Castle In: Clin Infect Dis 31:578, 2000; Ortqvist et al. In: Eur Respir J 30:414–422, 2007; Saurwein-Teissl et al. In: J Immunol 168:5893, 2002; Haynes et al. In: Proc Natl Acad Sci USA 100:15053–15058, 2003]. These defects reduce the magnitude of the immune response to infection and to vaccination. In individuals greater than 55 years of age, the probability of developing a fully protective neutralizing antibody response to the yearly multivalent particle inactivated influenza vaccine is less than 20% [Jefferson et al. In: Lancet 264:1165–1174, 2005; Goodwin et al. In: Vaccine 24:1159–1169, 2006; Jackson et al. In: Lancet 372:398–405, 2008; Simonsen and Taylor In: Lancet 7:658–666, 2007]. The defects in the aged immune system that are responsible for this limited response to vaccination in the older age groups include functional defects of the antigen presenting cells, functional defects in CD4 helper CD4 T cells and monocytes, and an altered microenvironment [Eaton et al. In: J Exp Med 200:1613–1622, 2004; Dong et al. In: J Gen Virol 84:1623–1628, 2003; Deng et al. In: Immunology 172:3437–3446, 2004; Cella et al. In: J Exp Med 184:747–752, 1996]. Starting at puberty, the involution of the thymus and the consequent reduction of the export of naïve T cells specific to neo-antigens leads to the reduction of the ratio of antigen naïve to memory cells as chronological age advances [Prelog In: AutoimmunRev 5:136–139, 2006; McElhaney et al. In: J Immunology 176:6333–6339, 2006]. Changes in glycosylation of T cells and target antigens acquired during the aging process and the antibodies to these new glycopeptides and glycoproteins may also contribute to a reduction in the functioning of the adaptive immune response [Ishii et al. In: J Clin Neurosci 14:110–115, 2007; Shirai et al. In: Clin Exp Immunol 12:455–464, 1972; Adkins and Riley In: Mech AgeingDev 103:147–164, 1998; Ben-Yehuda and Weksler In: Cancer Investigation 10:525–531, 1992]. One of the more interesting examples of the functional defects in the cells of the adaptive immune response is a reduced level of expression in the surface cytoadhesion and activation receptor molecules on CD4 helper T cells undergoing activation during vaccination. Upon infection or vaccination, CD40L is typically increased on the surface of CD4 helper T cells during activation, and this increased expression is absolutely essential to the CD40L promotion of expansion of antigen-specific B cells and CD 8 effector T cells in response to infection or vaccination [Singh et al. In: Protein Sci 7:1124–1135, 1998; Grewal and Flavell In: Immunol Res 16: 59–70, 1997; Kornbluth In: J Hematother Stem Cell Res 11:787–801, 2002; Garcia de Vinuesa et al. In: Eur J Immunol 29:3216–3224, 1999]. In aged human beings and mice, the reduced levels of expression of CD40 ligand (CD40L) in activated CD4 helper T cells is dramatically reduced [Eaton et al. In: J Exp Med 200:1613–1622, 2004; Dong et al. In: J Gen Virol 84:1623–1628, 2003]. To circumvent the reduction in CD40L expression and the subsequent reduction in immune response in the elderly, we have developed a chimeric vaccine comprised of the CD40L linked to the target antigen, in a replication incompetent adenoviral vector and in booster protein. This review will discuss the implementation the potential use of this approach for the vaccination of the older populations for cancer and infection.     

Segmental isotopic labeling of HIV-1 capsid protein assemblies for solid state NMR

Recent studies of noncrystalline HIV-1 capsid protein (CA) assemblies by our laboratory and by Polenova and coworkers (Protein Sci 19:716–730, 2010; J Mol Biol 426:1109–1127, 2014; J Biol Chem 291:13098–13112, 2016; J Am Chem Soc 138:8538–8546, 2016; J Am Chem Soc 138:12029–12032, 2016; J Am Chem Soc 134:6455–6466, 2012; J Am Chem Soc 132:1976–1987, 2010; J Am Chem Soc 135:17793–17803, 2013; Proc Natl Acad Sci USA 112:14617–14622, 2015; J Am Chem Soc 138:14066–14075, 2016) have established the capability of solid state nuclear magnetic resonance (NMR) measurements to provide site-specific structural and dynamical information that is not available from other types of measurements. Nonetheless, the relatively high molecular weight of HIV-1 CA leads to congestion of solid state NMR spectra of fully isotopically labeled assemblies that has been an impediment to further progress. Here we describe an efficient protocol for production of segmentally labeled HIV-1 CA samples in which either the N-terminal domain (NTD) or the C-terminal domain (CTD) is uniformly ¹⁵N,¹³C-labeled. Segmental labeling is achieved by trans-splicing, using the DnaE split intein. Comparisons of two-dimensional solid state NMR spectra of fully labeled and segmentally labeled tubular CA assemblies show substantial improvements in spectral resolution. The molecular structure of HIV-1 assemblies is not significantly perturbed by the single Ser-to-Cys substitution that we introduce between NTD and CTD segments, as required for trans-splicing.     

Analysis of gene copy number changes in tumor phylogenetics

Backgound

Evolution of cancer cells is characterized by large scale and rapid changes in the chromosomal  landscape. The fluorescence in situ hybridization (FISH) technique provides a way to measure the copy numbers of preselected genes in a group of cells and has been found to be a reliable source of data to model the evolution of tumor cells. Chowdhury et al. (Bioinformatics 29(13):189–98, 23; PLoS Comput Biol 10(7):1003740, 24) recently develop a computational model for tumor progression driven by gains and losses in cell count patterns obtained by FISH probes. Their model aims to find the rectilinear Steiner minimum tree (RSMT) (Chowdhury et al. in Bioinformatics 29(13):189–98, 23) and the duplication Steiner minimum tree (DSMT) (Chowdhury et al. in PLoS Comput Biol 10(7):1003740, 24) that describe the progression of FISH cell count patterns over its branches in a parsimonious manner. Both the RSMT and DSMT problems are NP-hard and heuristics are required to solve the problems efficiently.

Methods

In this paper we propose two approaches to solve the RSMT problem, one inspired by iterative methods to address the “small phylogeny” problem (Sankoff et al. in J Mol Evol 7(2):133–49, 27; Blanchette et al. in Genome Inform 8:25–34, 28), and the other based on maximum parsimony phylogeny inference. We further show how to extend these heuristics to obtain solutions to the DSMT problem, that models large scale duplication events.

Results

Experimental results from both simulated and real tumor data show that our methods outperform previous heuristics (Chowdhury et al. in Bioinformatics 29(13):189–98, 23; Chowdhury et al. in PLoS Comput Biol 10(7):1003740, 24) in obtaining solutions to both RSMT and DSMT problems.

Conclusion

The methods introduced here are able to provide more parsimony phylogenies compared to earlier ones which are consider better choices.

     

The phylotypic stage as a boundary of modular memory: non mechanistic perspective

The concept of the phylotypic stage has been strongly integrated into developmental biology, thanks mostly to drawings presented by Haeckel (Anthropogenie oder Entwicklungsgeschichte des Menschen, 1874). They are printed in every textbook as proof of the existence of the phylotypic stage and the fact of its conservation, albeit many times criticized as misleading and simplifying (Richardson in Develop Biol 172:412–421, 1995, Richardson et al. in Anat Embryo 196:91–106, 1997; Bininda-Emons et al. in Proc R Soc Lond 270:341–346, 2003). Although generally accepted by modern biology, doubt still exists concerning the very existence or the usefulness of the concept. What kind of evolutionary and developmental horizons does it open indeed? This article begins with the history of the concept, discusses its validity and draws this into connotation with the idea of a memory activated throughout the development. Barbieri (The organic codes. An introduction to semantic biology, 2003) considers the phylotypic stage to be a crucial boundary when the genetic program ceases to suffice for further development of the embryo, and supracellular memory of the body plan is activated. This moment clearly coincides with the commencing of the modular development of the embryo. In this article the nature of such putative memory will be discussed.     

What is behind “centromere repositioning”?

An increasing number of observations suggest an evolutionary switch of centromere position on monocentric eukaryotic chromosomes which otherwise display a conserved sequence of genes and markers. Such observations are particularly frequent for primates and equidae (for review see Heredity 108:59–67, 2012) but occur also in marsupials (J Hered 96:217–224, 2005) and in plants (Chromosome Res 25:299–311, 2017 and references therein). The actual mechanism(s) behind remained unclear in many cases (Proc Natl Acad Sci USA 101:6542–6547, 2004; Trends Genet 30:66–74, 2014). The same is true for de novo centromere formation on chromosomes lacking an active centromere. This article focuses on recent reports on centromere repositioning and possible mechanisms behind and addresses open questions.     

Metabolite targeting: development of a comprehensive targeted metabolomics platform for the assessment of diabetes and its complications

Biomarker studies for metabolic disorders like diabetes mellitus (DM) are an important approach towards a better understanding of the underlying pathophysiological mechanisms of diseases (Roberts and Gerszten in Cell Metab 18:43–50, 2013; Wilson et al. in Proteome Res 4:591–598, 2005). Furthermore, screening of potential metabolic biomarkers opens the opportunity of early diagnosis as well as therapy and drug monitoring of metabolic disorders (Rhee et al. in J Clin Invest 10:1–10, 2011; Wang et al. in Nat Med 17:448–458, 2011; Wenk in Nat Rev Drug Discov 4:594–610, 2005). The aim of the present study was to develop methods for the quantitative determination of 74 potential metabolite biomarkers for DM and diabetic nephropathy (DN) in serum. Several studies have shown that the concentrations of many polar metabolites like amino or organic acids are changed in subjects suffering from diabetes (Wang et al. in Nat Med 17:448–458, 2011; Yuan et al. in J Chromatogr B 813:53–58, 2007). Analyzing polar analytes presents a challenge in liquid chromatography (LC) coupled with ESI–MS/MS (Gika et al. in J Sep Sci 31:1598–1608, 2008; Spagou et al. in J Sep Sci 33:716–727, 2010). Considering those reasons we decided to develop a specific HILIC–ESI–QqQ–MS/MS-method for quantitative determination of these polar metabolites. A subsequent method validation was carried out for both HILIC and RP chromatography with respect to the guidelines of the Food and Drug Administration (FDA in Food and Drug Administration: Guidance for industry, bioanalytical method validation, 2001). The HILIC and RP LC–MS methods were successfully validated. Furthermore, the HILIC method presented here was applied to serum samples of GIPR^dn transgenic mice, a diabetic strain developing DN, and non transgenic littermate controls. Significant, diabetes-associated changes were observed for the concentrations of 21 out of 62 metabolites. The new methods described here accurately quantify 74 metabolites known to be regulated in diabetes, allowing for direct comparison between studies and laboratories. Thus, these methods may be highly adoptable in clinical research, providing a starting point for early diagnosis and metabolic screening.     

First-principle investigation on growth patterns and properties of cobalt-doped lithium nanoclusters

A systematic theoretical investigation on cobalt lithium clusters Li_nCo [1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12] was performed with a DFT approach. The location of global minima and structural evolution were carried out using the partical swarm optimization method. Li₆Co is the transition structure in going from low-coordinated structures to three-dimensional torispherical structures with a cobalt atom enclosed by lithium atoms. Maxima of ?₂ E and E _b for Li_nCo were found at n?=?3, 6, 8, 10, indicating that these clusters possess higher relative stability than their neighbors. In comparison with small clusters, n?=?1–6, the greater electron transfer from Li-2s to Co-3d within cage-like clusters Li_nCo (n?=?7–12) strengthens the bonding effect between Li_n and Co, which is reflected in the Wiberg bond index of Co and atomic binding energy analysis. AdNDP analysis verified the presence of both Lewis bonding elements (1c–2e objects) and delocalized bonding elements (6c–2e, 9c–2e and 10c–2e bonds). It is hoped that this theoretical work will provide favorable information to help understand the influence of dopant transition metal atoms on the properties of lithium-based materials.     

Plant individuality: a solution to the demographer’s dilemma

The problem of plant individuality is something which has vexed botanists throughout the ages, with fashion swinging back and forth from treating plants as communities of individuals (Darwin 1800; Braun and Stone 1853; Münch 1938) to treating them as organisms in their own right, and although the latter view has dominated mainstream thought most recently (Harper 1977; Cook 1985; Ariew and Lewontin 2004), a lively debate conducted mostly in Scandinavian journals proves that the issues are far from being resolved (Tuomi and Vuorisalo 1989b; Fagerström 1992; Pan and Price 2001). In this paper I settle the matter once and for all, by showing which elements of each side are correct.     

A representation of a compressed de Bruijn graph for pan-genome analysis that enables search

Background

Recently, Marcus et al. (Bioinformatics 30:3476–83, 2014) proposed to use a compressed de Bruijn graph to describe the relationship between the genomes of many individuals/strains of the same or closely related species. They devised an \(O(n\log g)\) time algorithm called splitMEM that constructs this graph directly (i.e., without using the uncompressed de Bruijn graph) based on a suffix tree, where n is the total length of the genomes and g is the length of the longest genome. Baier et al. (Bioinformatics 32:497–504, 2016) improved their result.

Results

In this paper, we propose a new space-efficient representation of the compressed de Bruijn graph that adds the possibility to search for a pattern (e.g. an allele—a variant form of a gene) within the pan-genome. The ability to search within the pan-genome graph is of utmost importance and is a design goal of pan-genome data structures.

     

Lexical splits within periphrasis: mixed perfective auxiliation systems in Italo-Romance

This paper addresses the phenomenon of mixed paradigms, i.e. mixed perfective auxiliation systems, attested in a wide range of Italo-Romance varieties (cf. Loporcaro 2001, 2007a, 2014; Manzini and Savoia 2005, among others). In these varieties, two auxiliary verbs, esse and habere, alternate within one and the same (sub)paradigm, displaying various patterns which can range from morphosyntactically motivated to apparently unmotivated distributions (here termed ‘morphomic’). I propose that, in these varieties, auxiliary selection is no longer a syntactically driven phenomenon, but becomes morphologized. I draw on the notion of ‘lexical split’ (cf. Corbett 2013, 2015, 2016) and describe the attested splits induced by intraparadigmatic auxiliary alternation. Following Bonami (2015), I put forward a typology of such splits. It is shown that, apart from motivated distributions, some morphomic patterns can also be found. The typology becomes more complex insofar as patterns with free variation between both auxiliaries are taken into account, as well as patently morphomic patterns which also seem to display external syntactic relevance (cf. Corbett 2013: 174–176). The phenomena reviewed and discussed in this paper are of major interest because they demonstrate the existence of competing exponence strategies within periphrasis, thus enriching the notion of ‘possible lexeme’ (cf. Corbett 2015: 146).     

From possessive suffix to affective demonstrative suffix in Hungarian: a grammaticalization analysis

The non-possessive uses of possessive morphology in Uralic languages have been a topic of intense debate (Fraurud 2001; Nikolaeva 2003; Gerland 2014; Janda 2015; É. Kiss and Tánczos to appear). In this paper, I focus on a special use of the poss.3sg suffix in Hungarian constructions such as a hülyéje (the stupid-poss.3sg): lit. ‘its stupid’, meaning ‘that total idiot’. My main claim is that this suffix is an affective demonstrative suffix (Lakoff 1974; Liberman 2008; Potts and Schwarz 2010), and that it has developed as a result of grammaticalization from a full-fledged possessive construction of the form a világ hülyéje (the world stupid-poss.3sg): lit. ‘the world’s stupid’, meaning: ‘the biggest idiot in the world’. I will show that this gradual process can be reconstructed fairly accurately using historical and contemporary corpora. I also claim that this grammaticalization pathway is very natural as it is based on a set-element relationship which is often expressed by possessive constructions cross-linguistically. I also identify two parameters which facilitate this grammaticalization process: the availability of (silent) pro possessors and the lack of gender agreement on the possessive suffix. Since Uralic languages in general have these parameters, I will argue that this grammaticalization pathway should at least be considered as one of the possible sources of the demonstrative (and definiteness marking) uses of poss.3sg suffixes in Uralic languages. Finally, my results are also an important contribution to the debate on whether demonstratives can be derived from other functional elements through grammaticalization (Plank 1979; Traugott 1982; Himmelmann 1997).     

Multiple feature affixation in Seenku plural formation

Nominal plural formation in Seenku involves two surface changes: fronting of the final vowel and raising of the final tone. Diachronically, the plural patterns likely derive from a suffix *- Open image in new window , which has been obscured through the loss of falling sonority diphthongs. By comparing plural formation to other morphophonological processes in Seenku, this paper argues that the plural suffix has been restructured as a featural suffix consisting of two features: the vocalic feature [+front], resulting in vowel fronting, and the tonal feature [+raised], resulting in tone raising. Given the atomic nature of the morphosyntactic feature plural, Seenku plural formation represents a strong case of multiple feature affixation, albeit a case that can be accounted for through Max constraints on feature values (Lombardi 2001, etc.) and Realize-Morpheme (van Oostendorp 2005; Trommer 2012) rather than the constraint Max-Flt argued for by Wolf (2007). A level-ordered approach retaining the vocalic suffix is also considered but is shown to suffer from a number of shortcomings, particularly with respect to tone and a challenging class of nasal stems. In short, this paper explores how the synchronic grammar copes with the vestiges of affixal morphology in a language that has undergone heavy reduction.     

Inheritance by recruitment

Doolittle (Biol Philos 28(2):351–378, 2013) and Ereshefsky and Pedroso (Proc Natl Acad Sci 112:10126–10132, 2013) argue that selection can act at the level of biofilms and other microbial communities. Clarke (Biol Philos 191–212, 2016) is skeptical and argues that selection acts on microbial cells rather than microbial communities. Her main criticism is that biofilms lack one of the ingredients required for selection to operate: heritability. This paper replies to her concern by elaborating how biofilm-level traits can be inheritable