The Parameterized Complexity of Centrality Improvement in Networks

The centrality of a vertex v in a network intuitively captures how important v is for communication in the network. The task of improving the centrality of a vertex has many applications, as a higher centrality often implies a larger impact on the network or less transportation or administration cost. In this work we study the parameterized complexity of the NP-complete problems Closeness Improvement and Betweenness Improvement in which we ask to improve a given vertex' closeness or betweenness centrality by a given amount through adding a given number of edges to the network. Herein, the closeness of a vertex v sums the multiplicative inverses of distances of other vertices to v and the betweenness sums for each pair of vertices the fraction of shortest paths going through v. Unfortunately, for the natural parameter "number of edges to add" we obtain hardness results, even in rather restricted cases. On the positive side, we also give an island of tractability for the parameter measuring the vertex deletion distance to cluster graphs

Sp6 and Sp8 transcription factors control AER formation and dorsal-ventral patterning in limb development

The formation and maintenance of the apical ectodermal ridge (AER) is critical for the outgrowth and patterning of the vertebrate limb. The induction of the AER is a complex process that relies on integrated interactions among the Fgf, Wnt, and Bmp signaling pathways that operate within the ectoderm and between the ectoderm and the mesoderm of the early limb bud. The transcription factors Sp6 and Sp8 are expressed in the limb ectoderm and AER during limb development. Sp6 mutant mice display a mild syndactyly phenotype while Sp8 mutants exhibit severe limb truncations. Both mutants show defects in AER maturation and in dorsal-ventral patterning. To gain further insights into the role Sp6 and Sp8 play in limb development, we have produced mice lacking both Sp6 and Sp8 activity in the limb ectoderm. Remarkably, the elimination or significant reduction in Sp6;Sp8 gene dosage leads to tetra-amelia; initial budding occurs, but neither Fgf8 nor En1 are activated. Mutants bearing a single functional allele of Sp8 (Sp6-/-;Sp8+/-) exhibit a split-hand/foot malformation phenotype with double dorsal digit tips probably due to an irregular and immature AER that is not maintained in the center of the bud and on the abnormal expansion of Wnt7a expression to the ventral ectoderm. Our data are compatible with Sp6 and Sp8 working together and in a dose-dependent manner as indispensable mediators of Wnt/βcatenin and Bmp signaling in the limb ectoderm. We suggest that the function of these factors links proximal-distal and dorsal-ventral patterning

Genome-wide screens identify Toxoplasma gondii determinants of parasite fitness in IFNγ-activated murine macrophages

Macrophages play an essential role in the early immune response against Toxoplasma and are the cell type preferentially infected by the parasite in vivo. Interferon gamma (IFNγ) elicits a variety of anti-Toxoplasma activities in macrophages. Using a genome-wide CRISPR screen we identify 353 Toxoplasma genes that determine parasite fitness in naїve or IFNγ-activated murine macrophages, seven of which are further confirmed. We show that one of these genes encodes dense granule protein GRA45, which has a chaperone-like domain, is critical for correct localization of GRAs into the PVM and secretion of GRA effectors into the host cytoplasm. Parasites lacking GRA45 are more susceptible to IFNγ-mediated growth inhibition and have reduced virulence in mice. Together, we identify and characterize an important chaperone-like GRA in Toxoplasma and provide a resource for the community to further explore the function of Toxoplasma genes that determine fitness in IFNγ-activated macrophages

Polymorphisms in the p53 pathway are enriched in cancer susceptibility loci and share characteristics with somatic pathway mutations

Commonly inherited genetic variants, such as single nucleotide polymorphisms (SNPs) hold great promise as easily obtainable and measurable biomarkers. Over one thousand SNPs associate with cancer in genome-wide association studies (GWAS). However, the limited understanding of the biology behind these associations has restricted their utility

Polymorphisms in the p53 pathway are enriched in cancer susceptibility loci and share characteristics with somatic pathway mutations

Commonly inherited genetic variants, such as single nucleotide polymorphisms (SNPs) hold great promise as easily obtainable and measurable biomarkers. Over one thousand SNPs associate with cancer in genome-wide association studies (GWAS). However, the limited understanding of the biology behind these associations has restricted their utility

The Fe-rich clay microsystems in basalt-komatiite lavas: importance of Fe-smectites for pre-biotic molecule catalysis during the Hadean Eon

During the Hadean to early Archean period (4.5–3.5 Ga), the surface of the Earth’s crust was predominantly composed of basalt and komatiite lavas. The conditions imposed by the chemical composition of these rocks favoured the crystallization of Fe-Mg clays rather than that of Al-rich ones (montmorillonite). Fe-Mg clays were formed inside chemical microsystems through sea weathering or hydrothermal alteration, and for the most part, through post-magmatic processes. Indeed, at the end of the cooling stage, Fe-Mg clays precipitated directly from the residual liquid which concentrated in the voids remaining in the crystal framework of the mafic-ultramafic lavas. Nontronite-celadonite and chlorite-saponite covered all the solid surfaces (crystals, glass) and are associated with tiny pyroxene and apatite crystals forming the so-called “mesostasis”. The mesostasis was scattered in the lava body as micro-settings tens of micrometres wide. Thus, every square metre of basalt or komatiite rocks was punctuated by myriads of clay-rich patches, each of them potentially behaving as a single chemical reactor which could concentrate the organics diluted in the ocean water. Considering the high catalytic potentiality of clays, and particularly those of the Fe-rich ones (electron exchangers), it is probable that large parts of the surface of the young Earth participated in the synthesis of prebiotic molecules during the Hadean to early Archean period through innumerable clay-rich micro-settings in the massive parts and the altered surfaces of komatiite and basaltic lavas. This leads us to suggest that Fe,Mg-clays should be preferred to Al-rich ones (montmorillonite) to conduct experiments for the synthesis and the polymerisation of prebiotic molecules

Retention of Sm-Nd isotopic ages in garnets subjected to high-grade thermal reworking: implications for diffusion rates of major and rare earth elements and the Sm-Nd closure temperature in garnet

Accepted: 21 June 2009. Published online: 10 July 2009Garnet is a vital mineral for determining constrained P–T–t paths as it can give both the P–T and t information directly. However, estimates of the closure temperature of the Sm–Nd system in garnet vary considerably leading to significant uncertainties in the timing of peak conditions. In this study, five igneous garnets from an early Proterozoic 2414 ± 6 Ma garnet—cordierite bearing s-type granite—which was subjected to high-T reworking have been dated to examine their diffusional behaviour in the Sm–Nd system. Garnets 8, 7, 6 and 2.5 mm in diameter were compositionally profiled and then dated, producing two-point Sm–Nd isochron ages of 2412 ± 10, 2377 ± 5, 2370 ± 5 and 2365 ± 8 and 2313 ± 11 Ma, respectively. A direct correlation exists between grain size and amount of resetting highlighting the effect of grain size on closure temperature. Major element EMPA and LA-ICPMS REE traverses reveal homogenous major element profiles and relict igneous REE profiles. The retention of REE zoning and homogenisation of major element zoning suggest that diffusion rates of REEs are considerably slower than that of the major cations. The retention of REE zoning and the lack of resetting in the largest grains suggest that Sm–Nd closure temperature in garnet is a function of grain size, thermal history and REE zoning in garnetRian Dutch and Martin Han