Maximum Independent Sets in Subcubic Graphs: New Results

The maximum independent set problem is known to be NP-hard in the class of subcubic graphs, i.e. graphs of vertex degree at most 3. We present a polynomial-time solution in a subclass of subcubic graphs generalizing several previously known results

Improved FPT algorithms for weighted independent set in bull-free graphs

Very recently, Thomass\'e, Trotignon and Vuskovic [WG 2014] have given an FPT algorithm for Weighted Independent Set in bull-free graphs parameterized by the weight of the solution, running in time $2^{O(k^5)} \cdot n^9$. In this article we improve this running time to $2^{O(k^2)} \cdot n^7$. As a byproduct, we also improve the previous Turing-kernel for this problem from $O(k^5)$ to $O(k^2)$. Furthermore, for the subclass of bull-free graphs without holes of length at most $2p-1$ for $p \geq 3$, we speed up the running time to $2^{O(k \cdot k^{\frac{1}{p-1}})} \cdot n^7$. As $p$ grows, this running time is asymptotically tight in terms of $k$, since we prove that for each integer $p \geq 3$, Weighted Independent Set cannot be solved in time $2^{o(k)} \cdot n^{O(1)}$ in the class of $\{bull,C_4,\ldots,C_{2p-1}\}$-free graphs unless the ETH fails.Comment: 15 page

Tryptophan depletion disinhibits punishment but not reward prediction: implications for resilience

Item does not contain fulltextRATIONALE: We have previously shown that tryptophan depletion enhances punishment but not reward prediction (Cools et al. in Neuropsychopharmacology 33:2291-2299, 2008b). This provided evidence for a valence-specific role of serotonin (which declines under depleted tryptophan) in aversive processing. Recent theoretical (Dayan and Huys in PLoS Comput Biol 4:e4, 2008) and experimental (Crockett et al. in J Neurosci 29:11993-11999, 2009) approaches have, however, further specified this role by showing that serotonin is critical for punishment-induced inhibition. OBJECTIVES: We sought to examine the role of serotonin in punishment-induced inhibition. We also examined the impact of induced mood on this effect to assess whether effects of tryptophan depletion on affective inhibition are moderated by mood. METHODS: Healthy females consumed a balanced amino acid mixture with (N = 20) or without (N = 21) the serotonin precursor tryptophan. Each subject completed either negative or neutral mood induction. All subjects completed the reward and punishment reversal learning task adopted in the previous study. RESULTS: We demonstrate a punishment prediction impairment in individuals who consumed tryptophan which was absent in individuals who were depleted of tryptophan. This effect was impervious to mood state. CONCLUSIONS: Our results suggest that serotonin promotes the inhibition of responses to punishing outcomes. This may lead to reduced punishment prediction accuracy in the presence of tryptophan and may contribute to resilience to affective disorders. Reduction of serotonin via tryptophan depletion then removes this inhibition. As such, we highlight a mechanism by which reduced serotonin can contribute to disorders of impulsivity and compulsivity as well as disorders of emotion.1 januari 201

Token Jumping in minor-closed classes

Given two $k$-independent sets $I$ and $J$ of a graph $G$, one can ask if it is possible to transform the one into the other in such a way that, at any step, we replace one vertex of the current independent set by another while keeping the property of being independent. Deciding this problem, known as the Token Jumping (TJ) reconfiguration problem, is PSPACE-complete even on planar graphs. Ito et al. proved in 2014 that the problem is FPT parameterized by $k$ if the input graph is $K_{3,\ell}$-free. We prove that the result of Ito et al. can be extended to any $K_{\ell,\ell}$-free graphs. In other words, if $G$ is a $K_{\ell,\ell}$-free graph, then it is possible to decide in FPT-time if $I$ can be transformed into $J$. As a by product, the TJ-reconfiguration problem is FPT in many well-known classes of graphs such as any minor-free class

Maximum Independent Sets in Subcubic Graphs: New Results

International audienceWe consider the complexity of the classical Independent Set problem on classes of subcubic graphs characterized by a finite set of forbidden induced subgraphs. It is well-known that a necessary condition for Independent Set to be tractable in such a class (unless P=NP) is that the set of forbidden induced subgraphs includes a subdivided star S k,k,k , for some k. Here, S k,k,k is the graph obtained by taking three paths of length k and identifying one of their endpoints. It is an interesting open question whether this condition is also sufficient: is Independent Set tractable on all hereditary classes of subcu-bic graphs that exclude some S k,k,k ? A positive answer to this question would provide a complete classification of the complexity of Independent Set on all classes of subcubic graphs characterized by a finite set of forbidden induced subgraphs. The best currently known result of this type is tractability for S2,2,2-free graphs. In this paper we generalize this result by showing that the problem remains tractable on S 2,k,k-free graphs, for any fixed k. Along the way, we show that subcubic Independent Set is tractable for graphs excluding a type of graph we call an "apple with a long stem", generalizing known results for apple-free graphs

Whole-genome association analysis of treatment response in obsessive-compulsive disorder.

Up to 30% of patients with obsessive-compulsive disorder (OCD) exhibit an inadequate response to serotonin reuptake inhibitors (SRIs). To date, genetic predictors of OCD treatment response have not been systematically investigated using genome-wide association study (GWAS). To identify specific genetic variations potentially influencing SRI response, we conducted a GWAS study in 804 OCD patients with information on SRI response. SRI response was classified as 'response' (n=514) or 'non-response' (n=290), based on self-report. We used the more powerful Quasi-Likelihood Score Test (the MQLS test) to conduct a genome-wide association test correcting for relatedness, and then used an adjusted logistic model to evaluate the effect size of the variants in probands. The top single-nucleotide polymorphism (SNP) was rs17162912 (P=1.76 × 10(-8)), which is near the DISP1 gene on 1q41-q42, a microdeletion region implicated in neurological development. The other six SNPs showing suggestive evidence of association (P<10(-5)) were rs9303380, rs12437601, rs16988159, rs7676822, rs1911877 and rs723815. Among them, two SNPs in strong linkage disequilibrium, rs7676822 and rs1911877, located near the PCDH10 gene, gave P-values of 2.86 × 10(-6) and 8.41 × 10(-6), respectively. The other 35 variations with signals of potential significance (P<10(-4)) involve multiple genes expressed in the brain, including GRIN2B, PCDH10 and GPC6. Our enrichment analysis indicated suggestive roles of genes in the glutamatergic neurotransmission system (false discovery rate (FDR)=0.0097) and the serotonergic system (FDR=0.0213). Although the results presented may provide new insights into genetic mechanisms underlying treatment response in OCD, studies with larger sample sizes and detailed information on drug dosage and treatment duration are needed

Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS.

Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1065 families (containing 1406 patients with OCD), combined with population-based samples (resulting in a total sample of 5061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at single-nucleotide polymorphism (SNP) and gene levels (via a hybrid approach that allowed for combined analyses of the family- and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P=4.13 × 10(-)(7)). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of genome-wide association study (GWAS) signals from a previously published OCD study identified significant enrichment (P=0.0176). Secondary analyses of high-confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P=0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2 and PTPRD. Analyses at the gene level revealed association of IQCK and C16orf88 (both P<1 × 10(-)(6), experiment-wide significant), as well as OFCC1 (P=6.29 × 10(-)(5)). The suggestive findings in this study await replication in larger samples

Transmembrane helix dynamics of bacterial chemoreceptors supports a piston model of signalling.

Transmembrane α-helices play a key role in many receptors, transmitting a signal from one side to the other of the lipid bilayer membrane. Bacterial chemoreceptors are one of the best studied such systems, with a wealth of biophysical and mutational data indicating a key role for the TM2 helix in signalling. In particular, aromatic (Trp and Tyr) and basic (Arg) residues help to lock α-helices into a membrane. Mutants in TM2 of E. coli Tar and related chemoreceptors involving these residues implicate changes in helix location and/or orientation in signalling. We have investigated the detailed structural basis of this via high throughput coarse-grained molecular dynamics (CG-MD) of Tar TM2 and its mutants in lipid bilayers. We focus on the position (shift) and orientation (tilt, rotation) of TM2 relative to the bilayer and how these are perturbed in mutants relative to the wildtype. The simulations reveal a clear correlation between small (ca. 1.5 Å) shift in position of TM2 along the bilayer normal and downstream changes in signalling activity. Weaker correlations are seen with helix tilt, and little/none between signalling and helix twist. This analysis of relatively subtle changes was only possible because the high throughput simulation method allowed us to run large (n = 100) ensembles for substantial numbers of different helix sequences, amounting to ca. 2000 simulations in total. Overall, this analysis supports a swinging-piston model of transmembrane signalling by Tar and related chemoreceptors

A new pathway of glucocorticoid action for asthma treatment through the regulation of PTEN expression

<p>Abstract</p> <p>Background</p> <p>"Phosphatase and tensin homolog deleted on chromosome 10" (PTEN) is mostly considered to be a cancer-related gene, and has been suggested to be a new pathway of pathogenesis of asthma. The purpose of this study was to investigate the effects of the glucocorticoid, dexamethasone, on PTEN regulation.</p> <p>Methods</p> <p>OVA-challenged mice were used as an asthma model to investigate the effect of dexamethasone on PTEN regulation. Immunohistochemistry was used to detect expression levels of PTEN protein in lung tissues. The human A549 cell line was used to explore the possible mechanism of action of dexamethasone on human PTEN regulation <it>in vitro</it>. A luciferase reporter construct under the control of PTEN promoter was used to confirm transcriptional regulation in response to dexamethasone.</p> <p>Results</p> <p>PTEN protein was found to be expressed at low levels in lung tissues in asthmatic mice; but the expression was restored after treatment with dexamethasone. In A549 cells, human PTEN was up-regulated by dexamethasone treatment. The promoter-reporter construct confirmed that dexamethasone could regulate human PTEN transcription. Treatment with the histone deacetylase inhibitor, TSA, could increase PTEN expression in A549 cells, while inhibition of histone acetylase (HAT) by anacardic acid attenuated dexamethasone-induced PTEN expression.</p> <p>Conclusions</p> <p>Based on the data a new mechanism is proposed where glucocorticoids treat asthma partly through up-regulation of PTEN expression. The <it>in vitro </it>studies also suggest that the PTEN pathway may be involved in human asthma.</p