Growth on Chitin Impacts the Transcriptome and Metabolite Profiles of Antibiotic-Producing Vibrio coralliilyticus S2052 and Photobacterium galatheae S2753

Members of the Vibrionaceae family are often associated with chitin-containing organisms, and they are thought to play a major role in chitin degradation. The purpose of the present study was to determine how chitin affects the transcriptome and metabolome of two bioactive Vibrionaceae strains, Vibrio coralliilyticus and Photobacterium galatheae. We focused on chitin degradation genes and secondary metabolites based on the assumption that these molecules in nature confer an advantage to the producer. Growth on chitin caused upregulation of genes related to chitin metabolism and of genes potentially involved in host colonization and/or infection. The expression of genes involved in secondary metabolism was also significantly affected by growth on chitin, in one case being 34-fold upregulated. This was reflected in the metabolome, where the antibiotics andrimid and holomycin were produced in larger amounts on chitin. Other polyketide synthase/ nonribosomal peptide synthetase (PKS-NRPS) clusters in P. galatheae were also strongly upregulated on chitin. Collectively, this suggests that both V. coralliilyticus and P. galatheae have a specific lifestyle for growth on chitin and that their secondary metabolites likely play a crucial role during chitin colonization. IMPORTANCE The bacterial family Vibrionaceae (vibrios) is considered a major player in the degradation of chitin, the most abundant polymer in the marine environment; however, the majority of studies on the topic have focused on a small number of Vibrio species. In this study, we analyzed the genomes of two vibrios to assess their genetic potential for the degradation of chitin. We then used transcriptomics and metabolomics to demonstrate that chitin strongly affects these vibrios at both the transcriptional and metabolic levels. We observed a strong increase in production of secondary metabolites, suggesting an ecological role for these molecules during chitin colonization in the marine environment

Allelic Lineages of the Ficolin Genes (FCNs) Are Passed from Ancestral to Descendant Primates

The ficolins recognize carbohydrates and acetylated compounds on microorganisms and dying host cells and are able to activate the lectin pathway of the complement system. In humans, three ficolin genes have been identified: FCN1, FCN2 and FCN3, which encode ficolin-1, ficolin-2 and ficolin-3, respectively. Rodents have only two ficolins designated ficolin-A and ficolin-B that are closely related to human ficolin-1, while the rodent FCN3 orthologue is a pseudogene. Ficolin-2 and ficolin-3 have so far only been observed in humans. Thus, we performed a systematic investigation of the FCN genes in non-human primates. The exons and intron-exon boundaries of the FCN1-3 genes were sequenced in the following primate species: chimpanzee, gorilla, orangutan, rhesus macaque, cynomolgus macaque, baboon and common marmoset. We found that the exon organisation of the FCN genes was very similar between all the non-human primates and the human FCN genes. Several variations in the FCN genes were found in more than one primate specie suggesting that they were carried from one species to another including humans. The amino acid diversity of the ficolins among human and non-human primate species was estimated by calculating the Shannon entropy revealing that all three proteins are generally highly conserved. Ficolin-1 and ficolin-2 showed the highest diversity, whereas ficolin-3 was more conserved. Ficolin-2 and ficolin-3 were present in non-human primate sera with the same characteristic oligomeric structures as seen in human serum. Taken together all the FCN genes show the same characteristics in lower and higher primates. The existence of trans-species polymorphisms suggests that different FCN allelic lineages may be passed from ancestral to descendant species

The reaction γp→π∘γ′p\gamma p \to \pi^\circ \gamma^\prime p and the magnetic dipole moment of the Δ+(1232)\Delta^+(1232) resonance

The reaction $\gamma p \to \pi^\circ \gamma^\prime p$ has been measured with the TAPS calorimeter at the Mainz Microtron accelerator facility MAMI for energies between $\sqrt{s}$ = 1221--1331 MeV. Cross sections differential in angle and energy have been determined for all particles in the final state in three bins of the excitation energy. This reaction channel provides access to the magnetic dipole moment of the $\Delta^{+}(1232)$ resonance and, for the first time, a value of $\mu_{\Delta^+} = (2.7_{-1.3}^{+1.0}(stat.) \pm 1.5 (syst.) \pm 3(theo.)) \mu_N$ has been extracted

Photoproduction of eta-mesic 3He

The photoproduction of eta-mesic 3He has been investigated using the TAPS calorimeter at the Mainz Microtron accelerator facility MAMI. The total inclusive cross section for the reaction gamma+3He->eta+X has been measured for photon energies from threshold to 820 MeV. The total and angular differential coherent eta cross sections have been extracted up to energies of 745 MeV. A resonance-like structure just above the eta production threshold with an isotropic angular distribution suggests the existence of a resonant quasi-bound state. This is supported by studies of a competing decay channel of such a quasi-bound eta-mesic nucleus into pi^0+p+X. A binding energy of (-4.4+-4.2) MeV and a width of (25.6+-6.1) MeV is deduced for the quasi-bound eta-mesic state in 3He.Comment: v1: 4 pages, 4 figures, submitted to PRL; v2: minor revisions and corrections, new figure added, 4 pages, 5 figs; v3: minor change

In-medium modifications of the ππ\pi\pi interaction in photon-induced reactions

Differential cross sections of the reactions $(\gamma,\pi^\circ\pi^\circ)$ and $(\gamma,\pi^\circ\pi^++\pi^\circ\pi^-)$ have been measured for several nuclei ($^1$H,$^{12}$C, and $^{\rm nat}$Pb) at an incident-photon energy of $E_{\gamma}$=400-460 MeV at the tagged-photon facility at MAMI-B using the TAPS spectrometer. A significant nuclear-mass dependence of the $\pi\pi$ invariant-mass distribution is found in the $\pi^\circ\pi^\circ$ channel. This dependence is not observed in the $\pi^\circ\pi^{+/-}$ channel and is consistent with an in-medium modification of the $\pi\pi$ interaction in the $I$=$J$=0 channel. The data are compared to $\pi$-induced measurements and to calculations within a chiral-unitary approach

From Relational Data to Graphs: Inferring Significant Links using Generalized Hypergeometric Ensembles

The inference of network topologies from relational data is an important problem in data analysis. Exemplary applications include the reconstruction of social ties from data on human interactions, the inference of gene co-expression networks from DNA microarray data, or the learning of semantic relationships based on co-occurrences of words in documents. Solving these problems requires techniques to infer significant links in noisy relational data. In this short paper, we propose a new statistical modeling framework to address this challenge. It builds on generalized hypergeometric ensembles, a class of generative stochastic models that give rise to analytically tractable probability spaces of directed, multi-edge graphs. We show how this framework can be used to assess the significance of links in noisy relational data. We illustrate our method in two data sets capturing spatio-temporal proximity relations between actors in a social system. The results show that our analytical framework provides a new approach to infer significant links from relational data, with interesting perspectives for the mining of data on social systems.Comment: 10 pages, 8 figures, accepted at SocInfo201

Identification of a Classical Mutant in the Industrial Host <i>Aspergillus niger</i> by Systems Genetics: LaeA Is Required for Citric Acid Production and Regulates the Formation of Some Secondary Metabolites

The asexual filamentous fungus Aspergillus niger is an important industrial cell factory for citric acid production. In this study, we genetically characterized a UV-generated A. niger mutant that was originally isolated as a nonacidifying mutant, which is a desirable trait for industrial enzyme production. Physiological analysis showed that this mutant did not secrete large amounts of citric acid and oxalic acid, thus explaining the nonacidifying phenotype. As traditional complementation approaches to characterize the mutant genotype were unsuccessful, we used bulk segregant analysis in combination with high-throughput genome sequencing to identify the mutation responsible for the nonacidifying phenotype. Since A. niger has no sexual cycle, parasexual genetics was used to generate haploid segregants derived from diploids by loss of whole chromosomes. We found that the nonacidifying phenotype was caused by a point mutation in the laeA gene. LaeA encodes a putative methyltransferase-domain protein, which we show here to be required for citric acid production in an A. niger lab strain (N402) and in other citric acid production strains. The unexpected link between LaeA and citric acid production could provide new insights into the transcriptional control mechanisms related to citric acid production in A. niger. Interestingly, the secondary metabolite profile of a ΔlaeA strain differed from the wild-type strain, showing both decreased and increased metabolite levels, indicating that LaeA is also involved in regulating the production of secondary metabolites. Finally, we show that our systems genetics approach is a powerful tool to identify trait mutations

Heat shock protein amplification improves cerebellar myelination in the Npc1nih mouse model.

BACKGROUND: Niemann-Pick disease type C (NPC) is a rare prematurely fatal lysosomal lipid storage disease with limited therapeutic options. The prominent neuropathological hallmarks include hypomyelination and cerebellar atrophy. We previously demonstrated the efficacy of recombinant human heat shock protein 70 (rhHSP70) in preclinical models of the disease. It reduced glycosphingolipid levels in the central nervous system (CNS), improving cerebellar myelination and improved behavioural phenotypes in Npc1nih (Npc1-/-) mice. Furthermore, treatment with arimoclomol, a well-characterised HSP amplifier, attenuated lysosomal storage in NPC patient fibroblasts and improved neurological symptoms in Npc1-/- mice. Taken together, these findings prompted the investigation of the effects of HSP amplification on CNS myelination. METHODS: We administered bimoclomol daily or rhHSP70 6 times per week to Npc1-/- (BALB/cNctr-Npc1m1N/J, also named Npc1nih) mice by intraperitoneal injection from P7 through P34 to investigate the impact on CNS myelination. The Src-kinase inhibitor saracatinib was administered with/without bimoclomol twice daily to explore the contribution of Fyn kinase to bimoclomol's effects. FINDINGS: Treatment with either bimoclomol or rhHSP70 improved myelination and increased the numbers of mature oligodendrocytes (OLs) as well as the ratio of active-to-inactive forms of phosphorylated Fyn kinase in the cerebellum of Npc1-/- mice. Additionally, treatment with bimoclomol preserved cerebellar weight, an effect that was abrogated when co-administered with saracatinib, an inhibitor of Fyn kinase. Bimoclomol-treated mice also exhibited increased numbers of immature OLs within the cortex. INTERPRETATION: These data increase our understanding of the mechanisms by which HSP70 regulates myelination and provide further support for the clinical development of HSP-amplifying therapies in the treatment of NPC. FUNDING: Funding for this study was provided by Orphazyme A/S (Copenhagen, Denmark) and a Pathfinder Award from The Wellcome Trust

Photoproduction of pi0-mesons from nuclei

Photoproduction of neutral pions from nuclei (carbon, calcium, niobium, lead) has been studied for incident photon energies from 200 MeV to 800 MeV with the TAPS detector using the Glasgow photon tagging spectrometer at the Mainz MAMI accelerator. Data were obtained for the inclusive photoproduction of neutral pions and the partial channels of quasifree single pi0, double pi0, and pi0pi+/- photoproduction. They have been analyzed in terms of the in-medium behavior of nucleon resonances and the pion - nucleus interaction. They are compared to earlier measurements from the deuteron and to the predictions of a Boltzmann-Uehling-Uhlenbeck (BUU) transport model for photon induced pion production from nuclei.Comment: 15 pages, 22 figures, accepted for publication in EPJ