Log canonical thresholds of Del Pezzo Surfaces in characteristic p

The global log canonical threshold of each non-singular complex del Pezzo surface was computed by Cheltsov. The proof used Koll\'ar-Shokurov's connectedness principle and other results relying on vanishing theorems of Kodaira type, not known to be true in finite characteristic. We compute the global log canonical threshold of non-singular del Pezzo surfaces over an algebraically closed field. We give algebraic proofs of results previously known only in characteristic $0$. Instead of using of the connectedness principle we introduce a new technique based on a classification of curves of low degree. As an application we conclude that non-singular del Pezzo surfaces in finite characteristic of degree lower or equal than $4$ are K-semistable.Comment: 21 pages. Thorough rewrite following referee's suggestions. To be published in Manuscripta Mathematic

Techniques for the study of singularities with applications to resolution of 2-dimensional schemes

We give an overview of invariants of algebraic singularities over perfect fields. We then show how they lead to a synthetic proof of embedded resolution of singularities of 2-dimensional schemes.Comment: 26 pages; minor changes have been adde

Listeria monocytogenes Invades the Epithelial Junctions at Sites of Cell Extrusion

Listeria monocytogenes causes invasive disease by crossing the intestinal epithelial barrier. This process depends on the interaction between the bacterial surface protein Internalin A and the host protein E-cadherin, located below the epithelial tight junctions at the lateral cell-to-cell contacts. We used polarized MDCK cells as a model epithelium to determine how L. monocytogenes breaches the tight junctions to gain access to this basolateral receptor protein. We determined that L. monocytogenes does not actively disrupt the tight junctions, but finds E-cadherin at a morphologically distinct subset of intercellular junctions. We identified these sites as naturally occurring regions where single senescent cells are expelled and detached from the epithelium by extrusion. The surrounding cells reorganize to form a multicellular junction that maintains epithelial continuity. We found that E-cadherin is transiently exposed to the lumenal surface at multicellular junctions during and after cell extrusion, and that L. monocytogenes takes advantage of junctional remodeling to adhere to and subsequently invade the epithelium. In intact epithelial monolayers, an anti-E-cadherin antibody specifically decorates multicellular junctions and blocks L. monocytogenes adhesion. Furthermore, an L. monocytogenes mutant in the Internalin A gene is completely deficient in attachment to the epithelial apical surface and is unable to invade. We hypothesized that L. monocytogenes utilizes analogous extrusion sites for epithelial invasion in vivo. By infecting rabbit ileal loops, we found that the junctions at the cell extrusion zone of villus tips are the specific target for L. monocytogenes adhesion and invasion. Thus, L. monocytogenes exploits the dynamic nature of epithelial renewal and junctional remodeling to breach the intestinal barrier

HadA is an atypical new multifunctional trimeric coiled-coil adhesin of Haemophilus influenzae biogroup aegyptius, which promotes entry into host cells.

Summary The Oca (Oligomeric coiled-coil adhesin) family is a subgroup of the bacterial trimeric autotrans- porter adhesins, which includes structurally related proteins, such as YadA of Yersinia entero- colitica and NadA of Neisseria meningitidis. In this study, we searched in silico for novel members of this family in bacterial genomes and identified HadA (Haemophilus adhesin A), a trimeric autotransporter expressed only by Haemophilus influenzae biogroup aegyptius causing Brazilian purpuric fever (BPF), a fulminant septicemic disease of children. By comparative genomics and sequence analysis we predicted that the hadA gene is harboured on a mobile genetic element unique to BPF isolates. Biological analysis of HadA in the native background was limited because this organism is not amenable to genetic manipulation. Alternatively, we demonstrated that expression of HadA confers to a non-invasive Escherichia coli strain the ability to adhere to human cells and to extracellular matrix proteins and to induce in vitro bacterial aggregation and microcolony formation. Intriguingly, HadA is pre- dicted to lack the typical N-terminal head domain of Oca proteins generally associated with cellular receptor binding. We propose here a structural model of the HadA coiled-coil stalk and show that the N-terminal region is still responsible of the binding activity and a KGD motif plays a role. Interestingly, HadA promotes bacterial entry into mammalian cells. Our results show a cytoskeleton re-arrangement and an involvement of clathrin in the HadA-mediated internalization. These data give new insights on the structure-function relationship of oligomeric coiled-coil adhesins and suggest a potential role of this protein in the pathogenesis of BPF

Sequence Profile of the Parallel β Helix in the Pectate Lyase Superfamily

The parallel β helix structure found in the pectatelyasesuperfamily has been analyzed in detail. A comparative analysis of known structures has revealed a unique sequenceprofile, with a strong positional preference for specific amino acids oriented toward the interior of the parallel β helix. Using the unique sequenceprofile, search patterns have been constructed and applied to the sequence databases to identify a subset of proteins that are likely to fold into the parallel β helix. Of the 19 families identified, 39% are known to be carbohydrate-binding proteins, and 50% belong to a broad category of proteins with sequences containing leucine-rich repeats (LRRs). The most striking result is the sequence match between the search pattern and four contiguous segments of internalin A, a surface protein from the bacterial pathogenListeria monocytogenes.A plausible model of the repetitive LRR sequences of internalin A has been constructed and favorable 3D–1D profile scores have been calculated. Moreover, spectroscopic features characteristic of the parallel β helix topology in the pectate lyases are present in the circular dichroic spectrum of internalin A. Altogether, the data support the hypothesis that sequence search patterns can be used to identify proteins, including a subset of LRR proteins, that are likely to fold into the parallel β helix

Sequence Profile of the Parallel β Helix in the Pectate Lyase Superfamily

The parallel β helix structure found in the pectatelyasesuperfamily has been analyzed in detail. A comparative analysis of known structures has revealed a unique sequenceprofile, with a strong positional preference for specific amino acids oriented toward the interior of the parallel β helix. Using the unique sequenceprofile, search patterns have been constructed and applied to the sequence databases to identify a subset of proteins that are likely to fold into the parallel β helix. Of the 19 families identified, 39% are known to be carbohydrate-binding proteins, and 50% belong to a broad category of proteins with sequences containing leucine-rich repeats (LRRs). The most striking result is the sequence match between the search pattern and four contiguous segments of internalin A, a surface protein from the bacterial pathogenListeria monocytogenes.A plausible model of the repetitive LRR sequences of internalin A has been constructed and favorable 3D–1D profile scores have been calculated. Moreover, spectroscopic features characteristic of the parallel β helix topology in the pectate lyases are present in the circular dichroic spectrum of internalin A. Altogether, the data support the hypothesis that sequence search patterns can be used to identify proteins, including a subset of LRR proteins, that are likely to fold into the parallel β helix

Characterisation of a new VUV beamline at the Daresbury SRS using a dispersed fluorescence apparatus incorporating CCD detection

The design and performance of a new normal incidence monochromator at the Daresbury Synchrotron Radiation Source, optimised for experiments requiring high flux of vacuum-UV radiation, are described. The re-developed beamline 3.1, based on the Wadsworth design of monochromator, is the source of tunable vacuum-UV photons in the range 4 – 31 eV, providing over two orders of magnitude more flux than the vacuum-UV, Seya monochromator in its previous manifestation. The undispersed and dispersed fluorescence spectra resulting from photoexcitation of N$_2$, CO$_2$, CF$_4$ and C$_6$F$_6$ are presented. Emitting species observed were N$_2^+$ B$^2\Sigma_u^+$ - X$^2\Sigma_g^+$, CO$_2^+$ A$^2\Pi_u$ - X$^2\Pi_g$ and B$^2\Sigma_u^+$ - X$^2\Pi_g$, CF$_4$$^+$ C$^2$T$_2$ - X$^2$T$_1$ and C$^2$T$_2$ - A$^2$T$_2$, CF$_3$* $^2$A$^’_2$ - $^2$A$^”_2$, and C$_6$F$_6^+$ B$^2$A$_{2u}$ - X$^2$E$_{1g}$. A CCD multi-channel detector has significantly reduced the time period needed to record dispersed fluorescence spectra with a comparable signal-to-noise ratio

Sequence learning in Associative Neuronal-Astrocytic Network

The neuronal paradigm of studying the brain has left us with limitations in both our understanding of how neurons process information to achieve biological intelligence and how such knowledge may be translated into artificial intelligence and its most brain-derived branch, neuromorphic computing. Overturning our fundamental assumptions of how the brain works, the recent exploration of astrocytes is revealing that these long-neglected brain cells dynamically regulate learning by interacting with neuronal activity at the synaptic level. Following recent experimental evidence, we designed an associative, Hopfield-type, neuronal-astrocytic network and analyzed the dynamics of the interaction between neurons and astrocytes. We show that astrocytes were sufficient to trigger transitions between learned memories in the neuronal component of the network. Further, we mathematically derived the timing of the transitions that was governed by the dynamics of the calcium-dependent slow-currents in the astrocytic processes. Overall, we provide a brain-morphic mechanism for sequence learning that is inspired by, and aligns with, recent experimental findings. To evaluate our model, we emulated astrocytic atrophy and showed that memory recall becomes significantly impaired after a critical point of affected astrocytes was reached. This brain-inspired and brain-validated approach supports our ongoing efforts to incorporate non-neuronal computing elements in neuromorphic information processing.Comment: 8 pages, 5 figure

Comparative transcriptomics of pathogenic and non-pathogenic Listeria species

Comparative RNA-seq analysis of two related pathogenic and non-pathogenic bacterial strains reveals a hidden layer of divergence in the non-coding genome as well as conserved, widespread regulatory structures called ‘Excludons', which mediate regulation through long non-coding antisense RNAs

Theory of Interaction of Memory Patterns in Layered Associative Networks

A synfire chain is a network that can generate repeated spike patterns with millisecond precision. Although synfire chains with only one activity propagation mode have been intensively analyzed with several neuron models, those with several stable propagation modes have not been thoroughly investigated. By using the leaky integrate-and-fire neuron model, we constructed a layered associative network embedded with memory patterns. We analyzed the network dynamics with the Fokker-Planck equation. First, we addressed the stability of one memory pattern as a propagating spike volley. We showed that memory patterns propagate as pulse packets. Second, we investigated the activity when we activated two different memory patterns. Simultaneous activation of two memory patterns with the same strength led the propagating pattern to a mixed state. In contrast, when the activations had different strengths, the pulse packet converged to a two-peak state. Finally, we studied the effect of the preceding pulse packet on the following pulse packet. The following pulse packet was modified from its original activated memory pattern, and it converged to a two-peak state, mixed state or non-spike state depending on the time interval