The complexity of the list homomorphism problem for graphs

We completely classify the computational complexity of the list H-colouring problem for graphs (with possible loops) in combinatorial and algebraic terms: for every graph H the problem is either NP-complete, NL-complete, L-complete or is first-order definable; descriptive complexity equivalents are given as well via Datalog and its fragments. Our algebraic characterisations match important conjectures in the study of constraint satisfaction problems.Comment: 12 pages, STACS 201

Alginates along the filament of the brown alga Ectocarpus help cells cope with stress

International audienceEctocarpus is a filamentous brown alga, which cell wall is composed mainly of alginates and fucans (80%), two non-crystalline polysaccharide classes. Alginates are linear chains of epimers of 1,4-linked uronic acids, β-d-mannuronic acid (M) and α-l-guluronic acid (G). Previous physico-chemical studies showed that G-rich alginate gels are stiffer than M-rich alginate gels when prepared in vitro with calcium. In order to assess the possible role of alginates in Ectocarpus, we first immunolocalised M-rich or G-rich alginates using specific monoclonal antibodies along the filament. As a second step, we calculated the tensile stress experienced by the cell wall along the filament, and varied it with hypertonic or hypotonic solutions. As a third step, we measured the stiffness of the cell along the filament, using cell deformation measurements and atomic force microscopy. Overlapping of the three sets of data allowed to show that alginates co-localise with the stiffest and most stressed areas of the filament, namely the dome of the apical cell and the shanks of the central round cells. In addition, no major distinction between M-rich and G-rich alginate spatial patterns could be observed. Altogether, these results support that both M-rich and G-rich alginates play similar roles in stiffening the cell wall where the tensile stress is high and exposes cells to bursting, and that these roles are independent from cell growth and differentiation

Alginates along the filament of the brown alga Ectocarpus help cells cope with stress.

Ectocarpus is a filamentous brown alga, which cell wall is composed mainly of alginates and fucans (80%), two non-crystalline polysaccharide classes. Alginates are linear chains of epimers of 1,4-linked uronic acids, β-D-mannuronic acid (M) and α-L-guluronic acid (G). Previous physico-chemical studies showed that G-rich alginate gels are stiffer than M-rich alginate gels when prepared in vitro with calcium. In order to assess the possible role of alginates in Ectocarpus, we first immunolocalised M-rich or G-rich alginates using specific monoclonal antibodies along the filament. As a second step, we calculated the tensile stress experienced by the cell wall along the filament, and varied it with hypertonic or hypotonic solutions. As a third step, we measured the stiffness of the cell along the filament, using cell deformation measurements and atomic force microscopy. Overlapping of the three sets of data allowed to show that alginates co-localise with the stiffest and most stressed areas of the filament, namely the dome of the apical cell and the shanks of the central round cells. In addition, no major distinction between M-rich and G-rich alginate spatial patterns could be observed. Altogether, these results support that both M-rich and G-rich alginates play similar roles in stiffening the cell wall where the tensile stress is high and exposes cells to bursting, and that these roles are independent from cell growth and differentiation

A gene-expression profiling score for prediction of outcome in patients with follicular lymphoma: a retrospective training and validation analysis in three international cohorts

Patients with follicular lymphoma (FL) have heterogeneous outcomes. Predictor models able to distinguish, at diagnosis, patients at high versus low risk of progression are still needed. A training set of fresh-frozen tumour biopsies was prospectively obtained from 160 untreated patients with high-tumour-burden follicular lymphoma enrolled in the phase 3 randomised PRIMA trial, in which rituximab maintenance was evaluated after rituximab plus chemotherapy induction (median follow-up 6·6 years [IQR 6·0-7·0]). RNA of sufficient quality was obtained for 149 of 160 cases, and Affymetrix U133 Plus 2.0 microarrays were used for gene-expression profiling. We did a multivariate Cox regression analysis to identify genes with expression levels associated with progression-free survival independently of maintenance treatment in a subgroup of 134 randomised patients. Expression levels from 95 curated genes were then determined by digital expression profiling (NanoString technology) in 53 formalin-fixed paraffin-embedded samples of the training set to compare the technical reproducibility of expression levels for each gene between technologies. Genes with high correlation (>0·75) were included in an L2-penalised Cox model adjusted on rituximab maintenance to build a predictive score for progression-free survival. The model was validated using NanoString technology to digitally quantify gene expression in 488 formalin-fixed, paraffin-embedded samples from three independent international patient cohorts from the PRIMA trial (n=178; distinct from the training cohort), the University of Iowa/Mayo Clinic Lymphoma SPORE project (n=201), and the Barcelona Hospital Clinic (n=109). All tissue samples consisted of pretreatment diagnostic biopsies and were confirmed as follicular lymphoma grade 1-3a. The patients were all treated with regimens containing rituximab and chemotherapy, possibly followed by either rituximab maintenance or ibritumomab-tiuxetan consolidation. We determined an optimum threshold on the score to predict patients at low risk and high risk of progression. The model, including the multigene score and the threshold, was initially evaluated in the three validation cohorts separately. The sensitivity and specificity of the score for the prediction of the risk of lymphoma progression at 2 years were assessed on the combined validation cohorts. FINDINGS: In the training cohort, the expression levels of 395 genes were associated with a risk of progression. 23 genes reflecting both B-cell biology and tumour microenvironment with correlation coefficients greater than 0·75 between the two technologies and sample types were retained to build a predictive model that identified a population at an increased risk of progression (p<0·0001). In a multivariate Cox model for progression-free survival adjusted on rituximab maintenance treatment and Follicular Lymphoma International Prognostic Index 1 (FLIPI-1) score, this predictor independently predicted progression (adjusted hazard ratio [aHR] of the high-risk group compared with the low-risk group 3·68, 95% CI 2·19-6·17 [p<0·0001]). The 5-year progression-free survival was 26% (95% CI 16-43) in the high-risk group and 73% (64-83) in the low-risk group. The predictor performances were confirmed in each of the individual validation cohorts (aHR comparing high-risk to low-risk groups 2·57 [95% CI 1·65-4·01] in cohort 1; 2·12 [1·32-3·39] in cohort 2; and 2·11 [1·01-4·41] in cohort 3). In the combined validation cohort, the median progression-free survival was 3·1 years (95% CI 2·4-4·8) in the high-risk group and 10·8 years (10·1-not reached) in the low-risk group (p<0·0001). The risk of lymphoma progression at 2 years was 38% (95% CI 29-46) in the high-risk group and 19% (15-24) in the low-risk group. In a multivariate analysis, the score predicted progression-free survival independently of anti-CD20 maintenance treatment and of the FLIPI score (aHR for the combined cohort 2·30, 95% CI 1·72-3·07). INTERPRETATION: We developed and validated a robust 23-gene expression-based predictor of progression-free survival that is applicable to routinely available formalin-fixed, paraffin-embedded tumour biopsies from patients with follicular lymphoma at time of diagnosis. Applying this score could allow individualised therapy for patients according to their risk category

Extensive and Intimate Association of the Cytoskeleton with Forming Silica in Diatoms: Control over Patterning on the Meso- and Micro-Scale

BACKGROUND: The diatom cell wall, called the frustule, is predominantly made out of silica, in many cases with highly ordered nano- and micro-scale features. Frustules are built intracellularly inside a special compartment, the silica deposition vesicle, or SDV. Molecules such as proteins (silaffins and silacidins) and long chain polyamines have been isolated from the silica and shown to be involved in the control of the silica polymerization. However, we are still unable to explain or reproduce in vitro the complexity of structures formed by diatoms. METHODS/PRINCIPAL FINDING: In this study, using fluorescence microscopy, scanning electron microscopy, and atomic force microscopy, we were able to compare and correlate microtubules and microfilaments with silica structure formed in diversely structured diatom species. The high degree of correlation between silica structure and actin indicates that actin is a major element in the control of the silica morphogenesis at the meso and microscale. Microtubules appear to be involved in the spatial positioning on the mesoscale and strengthening of the SDV. CONCLUSIONS/SIGNIFICANCE: These results reveal the importance of top down control over positioning of and within the SDV during diatom wall formation and open a new perspective for the study of the mechanism of frustule patterning as well as for the understanding of the control of membrane dynamics by the cytoskeleton

Symmetric Datalog and constraint satisfaction problems in Logspace

We introduce symmetric Datalog, a syntactic restriction of linear Datalog and show that its expressive power is exactly that of restricted symmetric monotone Krom SNP. The deep result of Reingold [17] on the complexity of undirected connectivity suffices to show that symmetric Datalog queries can be evaluated in logarithmic space. We show that for a number of constraint languages Γ, the complement of the constraint satisfaction problem CSP(Γ) can be expressed in symmetric Datalog. In particular, we show that if CSP(Γ) is first-order definable and Λ is a finite subset of the relational clone generated by Γ then ¬CSP(Λ) is definable in symmetric Datalog. Over the two-element domain and under a standard complexity-theoretic assumption, expressibility of ¬CSP(Γ) in symmetric Datalog corresponds exactly to the class of CSPs solvable in logarithmic space. Finally, we describe a fairly general subclass of implicational (or 0/1/all) constraints for which the complement of the corresponding CSP is also definable in symmetric Datalog. Our results provide preliminary evidence that symmetric Datalog may be a unifying explanation for families of CSPs lying in L

Characterization and Localization of Insoluble Organic Matrices Associated with Diatom Cell Walls: Insight into Their Roles during Cell Wall Formation

<div><p>Organic components associated with diatom cell wall silica are important for the formation, integrity, and function of the cell wall. Polysaccharides are associated with the silica, however their localization, structure, and function remain poorly understood. We used imaging and biochemical approaches to describe in detail characteristics of insoluble organic components associated with the cell wall in 5 different diatom species. Results show that an insoluble organic matrix enriched in mannose, likely the diatotepum, is localized on the proximal surface of the silica cell wall. We did not identify any organic matrix embedded within the silica. We also identified a distinct material consisting of glucose polymer with variable localization depending on the species. In some species this component was directly involved in the morphogenesis of silica structure while in others it appeared to be only a structural component of the cell wall. A novel glucose-rich structure located between daughter cells during division was also identified. This work for the first time correlates the structure, composition, and localization of insoluble organic matrices associated with diatom cell walls. Additionally we identified a novel glucose polymer and characterized its role during silica structure formation.</p></div

<i>N. curvilineata</i> silica structure and organic matrix.

<p>a; SEM micrograph of the proximal side of the valve (scale bar 1 µm). b–h; AFM micrographs and height profiles. Arrows in a and b show the fibulae (black) and the location of the raphe slit (white). b and d; Organic matrix associated with the valves. c; organic matrix associated with the valve and girdle bands (GB). e; organic matrix associated with the GB and corresponding height profile (F). g; Silicified GB and corresponding profile (h). AFM scan sizes are 5, 20×9, 2, 3.1 and 2.7 µm for b–e and g, respectively).</p

Raphe formation in <i>Nitzschia curvilineata.</i>

<p>a and b) SEM of forming raphe showing and earlier (a) and later (b) stage of development of the fibulae which span the raphe fissure; r =  raphe, and f =  one of several fibulae. c and c′) Actin and silica localization during raphe formation. c) Actin alone, c′) Actin plus silica. Mra  =  mother cell raphe actin, Dra  =  daughter cell raphe actin, DSa  =  daughter cell SDV actin. d and d′) Higher magnification image of actin and silica localization during raphe formation. d) Actin alone, d′) Actin plus silica. Actin is seen to completely surround the silica.</p

<i>C. radiatus</i> silica structure and organic matrix.

<p>a; SEM micrograph of the valve matrix deposited on a filter (scale bar 5 µm). b; SEM micrograph of the proximal surface of the valve (scale bar 1 µm). c–e; AFM micrographs of the organic matrix associated with the valves, c) shows the organization of material corresponding to the foramen, d) shows a high resolution image of material corresponding to a single foramen, e) shows the fibrous nature of the material between foramen, and f) shows a height profile of the line in e. g and h; organic material associated with the girdle bands. The arrow in g points at the higher edge and in h shows nodules filling the pores in the silica structure (scan size for AFM images: 9.3x8.1, 2, 1.2, 10 and 2 µm respectively).</p