Designing probiotic therapies with broad-spectrum activity against a wildlife pathogen

Host-associated microbes form an important component of immunity that protect against infection by pathogens. Treating wild individuals with these protective microbes, known as probiotics, can reduce rates of infection and disease in both wild and captive settings. However, the utility of probiotics for tackling wildlife disease requires that they offer consistent protection across the broad genomic variation of the pathogen that hosts can encounter in natural settings. Here we develop multi-isolate probiotic consortia with the aim of effecting broad-spectrum inhibition of growth of the lethal amphibian pathogen Batrachochytrium dendrobatidis (Bd) when tested against nine Bd isolates from two distinct lineages. Though we achieved strong growth inhibition between 70 and 100% for seven Bd isolates, two isolates appeared consistently resistant to inhibition, irrespective of probiotic strategy employed. We found no evidence that genomic relatedness of the chytrid predicted similarity of inhibition scores, nor that increasing the genetic diversity of the bacterial consortia could offer stronger inhibition of pathogen growth, even for the two resistant isolates. Our findings have important consequences for the application of probiotics to mitigate wildlife diseases in the face of extensive pathogen genomic variation

Equilibrium states and their entropy densities in gauge-invariant C*-systems

A gauge-invariant C*-system is obtained as the fixed point subalgebra of the infinite tensor product of full matrix algebras under the tensor product unitary action of a compact group. In the paper, thermodynamics is studied on such systems and the chemical potential theory developed by Araki, Haag, Kastler and Takesaki is used. As a generalization of quantum spin system, the equivalence of the KMS condition, the Gibbs condition and the variational principle is shown for translation-invariant states. The entropy density of extremal equilibrium states is also investigated in relation to macroscopic uniformity.Comment: 20 pages, revised in March 200

Off-Diagonal Long-Range Order: Meissner Effect and Flux Quantization

There has been a proof by Sewell that the hypothesis of off-diagonal long-range order in the reduced density matrix $\rho _2$ implies the Meissner effect. We present in this note an elementary and straightforward proof that not only the Meissner effect but also the property of magnetic flux quantization follows from the hypothesis. It is explicitly shown that the two phenomena are closely related, and phase coherence is the origin for both.Comment: 11 pages, Latex fil

Off-Diagonal Long-Range Order in Bose Liquids: Irrotational Flow and Quantization of Circulation

On the basis of gauge invariance, it is proven in an elementary and straightforward manner, but without invoking any {\it ad hoc} assumption, that the existence of off-diagonal long-range order in one-particle reduced density matrix in Bose liquids implies both the irrotational flow in a simply connected region and the quantization of circulation in a multiply connected region, the two fundamental properties of a Bose superfluid. The origin for both is the phase coherence of condensate wave-functions. Some relevant issues are also addressed.Comment: Revtex, 4 pages, no figure

Developmental patterning in the Caenorhabditis elegans hindgut

AbstractDevelopmental pattern formation allows cells within a tissue or organ to coordinate their development and establish cell types in relationship to one another. To better characterize the developmental patterning events within one organ, the C. elegans hindgut, we have analyzed the expression pattern of several genes using green fluorescent protein-based reporter transgenes. In wild-type animals, these genes are expressed in subsets of hindgut cells rather than in individual cell types. In mutant animals, we find that some, but not all, genes expressed in cells with altered development exhibit a corresponding alteration of gene expression. The results are consistent with a model where a combination of factors contribute to each cell's fate, and address how developmental information converges to specify cell types

A Comment on the Geometric Entropy and Conical Space

It has been recently pointed out that a definition of the geometric entropy using the partition function in a conical space does not in general lead to a positive definite quantity. For a scalar field model with a non-minimal coupling we clarify the origin of the anomalous behavior from the viewpoint of the canonical formulation.Comment: No Figures. To appear in Classical and Quantum Gravit

On the Question of Temperature Transformations under Lorentz and Galilei Boosts

We provide a quantum statistical thermodynamical solution of the long standing problem of temperature transformations of uniformly moving bodies. Our treatment of this question is based on the well established quantum statistical result that the thermal equilibrium conditions demanded by both the Zeroth and Second Laws of Thermodynamics are precisely those of Kubo, Martin and Schwinger (KMS). We prove that, in both the special relativistic and nonrelativistic settings, a state of a body cannot satisfy these conditions for different inertial frames with non-zero relative velocity. Hence a body that serves as a thermal reservoir, in the sense of the Zeroth Law, in an inertial rest frame cannot do so in a laboratory frame relative to which it moves with non-zero uniform velocity. Consequently, there is no law of temperature transformation under either Lorentz or Galilei boosts, and so the concept of temperature stemming from the Zeroth Law is restricted to states of bodies in their rest frames.Comment: A few minor corrections have been made. The article will be published in J. Phys.

Non-random distribution of azole resistance across the global population of Aspergillus fumigatus

The emergence of azole resistance in the pathogenic fungus Aspergillus fumigatus has continued to increase, with the dominant resistance mechanisms, consisting of a 34-nucleotide tandem repeat (TR34)/L98H and TR46/Y121F/T289A, now showing a structured global distribution. Using hierarchical clustering and multivariate analysis of 4,049 A. fumigatus isolates collected worldwide and genotyped at nine microsatellite loci using analysis of short tandem repeats of A. fumigatus (STRAf), we show that A. fumigatus can be subdivided into two broad clades and that cyp51A alleles TR34/L98H and TR46/Y121F/T289A are unevenly distributed across these two populations. Diversity indices show that azole-resistant isolates are genetically depauperate compared to their wild-type counterparts, compatible with selective sweeps accompanying the selection of beneficial mutations. Strikingly, we found that azole-resistant clones with identical microsatellite profiles were globally distributed and sourced from both clinical and environmental locations, confirming that azole resistance is an international public health concern. Our work provides a framework for the analysis of A. fumigatus isolates based on their microsatellite profile, which we have incorporated into a freely available, user-friendly R Shiny application (AfumID) that provides clinicians and researchers with a method for the fast, automated characterization of A. fumigatus genetic relatedness. Our study highlights the effect that azole drug resistance is having on the genetic diversity of A. fumigatus and emphasizes its global importance upon this medically important pathogenic fungus. IMPORTANCE Azole drug resistance in the human-pathogenic fungus Aspergillus fumigatus continues to emerge, potentially leading to untreatable aspergillosis in immunosuppressed hosts. Two dominant, environmentally associated resistance mechanisms, which are thought to have evolved through selection by the agricultural application of azole fungicides, are now distributed globally. Understanding the effect that azole resistance is having on the genetic diversity and global population of A. fumigatus will help mitigate drug-resistant aspergillosis and maintain the azole class of fungicides for future use in both medicine and crop protection

Holography and SL(2,\bR) symmetry in 2D Rindler spacetime

It is shown that it is possible to define quantum field theory of a massless scalar free field on the Killing horizon of a 2D-Rindler spacetime. Free quantum field theory on the horizon enjoys diffeomorphism invariance and turns out to be unitarily and algebraically equivalent to the analogous theory of a scalar field propagating inside Rindler spacetime, nomatter the value of the mass of the field in the bulk. More precisely, there exists a unitary transformation that realizes the bulk-boundary correspondence under an appropriate choice for Fock representation spaces. Secondly, the found correspondence is a subcase of an analogous algebraic correspondence described by injective *-homomorphisms of the abstract algebras of observables generated by abstract quantum free-field operators. These field operators are smeared with suitable test functions in the bulk and exact 1-forms on the horizon. In this sense the correspondence is independent from the chosen vacua. It is proven that, under that correspondence the ``hidden'' SL(2,\bR) quantum symmetry found in a previous work gets a clear geometric meaning, it being associated with a group of diffeomorphisms of the horizon itself.Comment: Title changed, further minor changes, references added, accepted for publication in J. Math. Phy