Algorithmic and Hardness Results for the Colorful Components Problems

In this paper we investigate the colorful components framework, motivated by applications emerging from comparative genomics. The general goal is to remove a collection of edges from an undirected vertex-colored graph $G$ such that in the resulting graph $G'$ all the connected components are colorful (i.e., any two vertices of the same color belong to different connected components). We want $G'$ to optimize an objective function, the selection of this function being specific to each problem in the framework. We analyze three objective functions, and thus, three different problems, which are believed to be relevant for the biological applications: minimizing the number of singleton vertices, maximizing the number of edges in the transitive closure, and minimizing the number of connected components. Our main result is a polynomial time algorithm for the first problem. This result disproves the conjecture of Zheng et al. that the problem is $NP$-hard (assuming $P \neq NP$). Then, we show that the second problem is $APX$-hard, thus proving and strengthening the conjecture of Zheng et al. that the problem is $NP$-hard. Finally, we show that the third problem does not admit polynomial time approximation within a factor of $|V|^{1/14 - \epsilon}$ for any $\epsilon > 0$, assuming $P \neq NP$ (or within a factor of $|V|^{1/2 - \epsilon}$, assuming $ZPP \neq NP$).Comment: 18 pages, 3 figure

Algorithms for Cut Problems on Trees

We study the {\sc multicut on trees} and the {\sc generalized multiway Cut on trees} problems. For the {\sc multicut on trees} problem, we present a parameterized algorithm that runs in time $O^{*}(\rho^k)$, where $\rho = \sqrt{\sqrt{2} + 1} \approx 1.555$ is the positive root of the polynomial $x^4-2x^2-1$. This improves the current-best algorithm of Chen et al. that runs in time $O^{*}(1.619^k)$. For the {\sc generalized multiway cut on trees} problem, we show that this problem is solvable in polynomial time if the number of terminal sets is fixed; this answers an open question posed in a recent paper by Liu and Zhang. By reducing the {\sc generalized multiway cut on trees} problem to the {\sc multicut on trees} problem, our results give a parameterized algorithm that solves the {\sc generalized multiway cut on trees} problem in time $O^{*}(\rho^k)$, where $\rho = \sqrt{\sqrt{2} + 1} \approx 1.555$ time

From cat scratch disease to endocarditis, the possible natural history of Bartonella henselae infection

BACKGROUND: Most patients with infectious endocarditis (IE) due to Bartonella henselae have a history of exposure to cats and pre-existing heart valve lesions. To date, none of the reported patients have had a history of typical cat scratch disease (CSD) which is also a manifestation of infection with B. henselae. CASE PRESENTATION: Here we report the case of a patient who had CSD and six months later developed IE of the mitral valve caused by B. henselae. CONCLUSION: Based on this unique case, we speculate that CSD represents the primary-infection of B. henselae and that IE follows in patients with heart valve lesions

A nested-PCR with an Internal Amplification Control for the detection and differentiation of Bartonella henselae and B. clarridgeiae: An examination of cats in Trinidad

BACKGROUND: Bartonella species are bacterial blood parasites of animals capable of causing disease in both animals and man. Cat-Scratch Disease (CSD) in humans is caused mainly by Bartonella henselae and is acquired from the cat, which serves as a reservoir for the bacteria. A second species, B. clarridgeiae is also implicated in the disease. Diagnosis of Bartonellosis by culture requires a week or more of incubation on enriched media containing blood, and recovery is often complicated by faster growing contaminating bacteria and fungi. PCR has been explored as an alternative to culture for both the detection and species identification of Bartonella, however sensitivity problems have been reported and false negative reactions due to blood inhibitors have not generally been addressed in test design. METHODS: A novel, nested-PCR was designed for the detection of Bartonella henselae and B. clarridgeiae based on the strategy of targeting species-specific size differences in the 16S-23S rDNA intergenic regions. An Internal Amplification Control was used for detecting PCR inhibition. The nested-PCR was utilized in a study on 103 blood samples from pet and stray cats in Trinidad. RESULTS: None of the samples were positive by primary PCR, but the Nested-PCR detected Bartonella in 32/103 (31%) cats where 16 were infected with only B. henselae, 13 with only B. clarridgeiae and 3 with both species. Of 22 stray cats housed at an animal shelter, 13 (59%) were positive for either or both species, supporting the reported increased incidence of Bartonella among feral cats. CONCLUSION: The usefulness of a single PCR for the detection of Bartonella henselae and B. clarridgeiae in the blood of cats is questionable. A nested-PCR offers increased sensitivity over a primary PCR and should be evaluated with currently used methods for the routine detection and speciation of Bartonella henselae and B. clarridgeiae. In Trinidad, B. henselae and B. clarridgeiae are the predominant species in cats and infection appears highest with stray cats, however B. clarridgeiae may be present at levels similar to that of B. henselae in the pet population

Beneficial effect of Sparassis crispa on stroke through activation of Akt/eNOS pathway in brain of SHRSP

Sparassis crispa (S. crispa) is a mushroom used as a natural medicine that recently became cultivatable in Japan. In this study, we investigated not only the preventive effects of S. crispa against stroke and hypertension in stroke-prone spontaneously hypertensive rats (SHRSP) but also the mechanism involved by using studies of the cerebral cortex at a young age. Six-week-old male SHRSP were divided into 2 groups, a control group and an S. crispa group administered 1.5% S. crispa in feed, and we then observed their survival. In addition, rats of the same age were treated with 1.5% S. crispa for 4 weeks and we measured body weight, blood pressure, blood flow from the tail, NOx production, and the levels of expression of several proteins in the cerebral cortex by western blot analysis. Our results showed that the S. crispa group had a delayed incidence of stroke and death and significantly decreased blood pressure and increased blood flow after the administration. Moreover, the quantity of urinary excretion and the nitrate/nitrite concentration in cerebral tissue were higher than those of control SHRSP rats. In the cerebral cortex, phosphor-eNOS (Ser1177) and phosphor-Akt (Ser473) in S. crispa-treated SHRSP were increased compared with those of control SHRSP rats. In conclusion, S. crispa could ameliorate cerebrovascular endothelial dysfunction by promoting recovery of Akt-dependent eNOS phosphorylation and increasing NO production in the cerebral cortex. S. crispa may be useful for preventing stroke and hypertension

Functional Conservation of Cis-Regulatory Elements of Heat-Shock Genes over Long Evolutionary Distances

Transcriptional control of gene regulation is an intricate process that requires precise orchestration of a number of molecular components. Studying its evolution can serve as a useful model for understanding how complex molecular machines evolve. One way to investigate evolution of transcriptional regulation is to test the functions of cis-elements from one species in a distant relative. Previous results suggested that few, if any, tissue-specific promoters from Drosophila are faithfully expressed in C. elegans. Here we show that, in contrast, promoters of fly and human heat-shock genes are upregulated in C. elegans upon exposure to heat. Inducibility under conditions of heat shock may represent a relatively simple “on-off” response, whereas complex expression patterns require integration of multiple signals. Our results suggest that simpler aspects of regulatory logic may be retained over longer periods of evolutionary time, while more complex ones may be diverging more rapidly

Differential Pharmacological Actions of Methadone and Buprenorphine in Human Embryonic Kidney 293 Cells Coexpressing Human μ-Opioid and Opioid Receptor-Like 1 Receptors

Methadone and buprenorphine are used in maintenance therapy for heroin addicts. In this study, we compared their effects on adenylate cyclase (AC) activity in human embryonic kidney (HEK) 293 cells stably overexpressing human μ-opioid receptor (MOR) and nociceptin/opioid receptor-like 1 receptor (ORL1) simultaneously. After acute exposure, methadone inhibited AC activity; however, buprenorphine induced compromised AC inhibition. When naloxone was introduced after 30 min incubation with methadone, the AC activity was enhanced. This was not observed in the case of buprenorphine. Enhancement of the AC activity was more significant when the incubation lasted for 4 h, and prolonged exposure to buprenorphine elevated the AC activity as well. The removal of methadone and buprenorphine by washing also obtained similar AC superactivation as that revealed by naloxone challenge. The study demonstrated that methadone and buprenorphine exert initially different yet eventually convergent adaptive changes of AC activity in cells coexpressing human MOR and ORL1 receptors

The Gene Regulatory Cascade Linking Proneural Specification with Differentiation in Drosophila Sensory Neurons

Temporal expression profiling of sensory precursor cells reveals how the atonal proneural transcription factor regulates a specialized neuronal differentiation pathway

Conserved molecular interactions in centriole-to-centrosome conversion.

Centrioles are required to assemble centrosomes for cell division and cilia for motility and signalling. New centrioles assemble perpendicularly to pre-existing ones in G1-S and elongate throughout S and G2. Fully elongated daughter centrioles are converted into centrosomes during mitosis to be able to duplicate and organize pericentriolar material in the next cell cycle. Here we show that centriole-to-centrosome conversion requires sequential loading of Cep135, Ana1 (Cep295) and Asterless (Cep152) onto daughter centrioles during mitotic progression in both Drosophila melanogaster and human. This generates a molecular network spanning from the inner- to outermost parts of the centriole. Ana1 forms a molecular strut within the network, and its essential role can be substituted by an engineered fragment providing an alternative linkage between Asterless and Cep135. This conserved architectural framework is essential for loading Asterless or Cep152, the partner of the master regulator of centriole duplication, Plk4. Our study thus uncovers the molecular basis for centriole-to-centrosome conversion that renders daughter centrioles competent for motherhood.J.F., Z.L., S.S. and N.S.D. are supported from Programme Grant to D.M.G. from Cancer Research UK. H.R. is supported from MRC Programme Grant to D.M.G. J.F. thank the British Academy and the Royal Society for Newton International Fellowship and Z.L. thanks the Federation of European Biochemical Societies for the Long-Term postdoctoral Fellowship. The authors thank Nicola Lawrence and Alex Sossick for assistance with 3D-SIM.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ncb327