Successful Amelioration of Mitochondrial Optic Neuropathy Using the Yeast NDI1 Gene in a Rat Animal Model

Background: Leber’s hereditary optic neuropathy (LHON) is a maternally inherited disorder with point mutations in mitochondrial DNA which result in loss of vision in young adults. The majority of mutations reported to date are within the genes encoding the subunits of the mitochondrial NADH-quinone oxidoreductase, complex I. Establishment of animal models of LHON should help elucidate mechanism of the disease and could be utilized for possible development of therapeutic strategies. Methodology/Principal Findings: We established a rat model which involves injection of rotenone-loaded microspheres into the optic layer of the rat superior colliculus. The animals exhibited the most common features of LHON. Visual loss was observed within 2 weeks of rotenone administration with no apparent effect on retinal ganglion cells. Death of retinal ganglion cells occurred at a later stage. Using our rat model, we investigated the effect of the yeast alternative NADH dehydrogenase, Ndi1. We were able to achieve efficient expression of the Ndi1 protein in the mitochondria of all regions of retinal ganglion cells and axons by delivering the NDI1 gene into the optical layer of the superior colliculus. Remarkably, even after the vision of the rats was severely impaired, treatment of the animals with the NDI1 gene led to a complete restoration of the vision to the normal level. Control groups that received either empty vector or the GFP gene had no effects

Necrotrophism Is a Quorum-Sensing-Regulated Lifestyle in Bacillus thuringiensis

How pathogenic bacteria infect and kill their host is currently widely investigated. In comparison, the fate of pathogens after the death of their host receives less attention. We studied Bacillus thuringiensis (Bt) infection of an insect host, and show that NprR, a quorum sensor, is active after death of the insect and allows Bt to survive in the cadavers as vegetative cells. Transcriptomic analysis revealed that NprR regulates at least 41 genes, including many encoding degradative enzymes or proteins involved in the synthesis of a nonribosomal peptide named kurstakin. These degradative enzymes are essential in vitro to degrade several substrates and are specifically expressed after host death suggesting that Bt has an active necrotrophic lifestyle in the cadaver. We show that kurstakin is essential for Bt survival during necrotrophic development. It is required for swarming mobility and biofilm formation, presumably through a pore forming activity. A nprR deficient mutant does not develop necrotrophically and does not sporulate efficiently in the cadaver. We report that necrotrophism is a highly regulated mechanism essential for the Bt infectious cycle, contributing to spore spreading

The PlcR Virulence Regulon of Bacillus cereus

PlcR is a Bacillus cereus transcriptional regulator, which activates gene expression by binding to a nucleotidic sequence called the ‘PlcR box’. To build a list of all genes included in the PlcR regulon, a consensus sequence was identified by directed mutagenesis. The reference strain ATCC14579 sequenced genome was searched for occurrences of this consensus sequence to produce a virtual regulon. PlcR control of these genes was confirmed by comparing gene expression in the reference strain and its isogenic Δ-plcR strain using DNA microarrays, lacZ fusions and proteomics methods. The resulting list included 45 genes controlled by 28 PlcR boxes. Forty of the PlcR controlled proteins were exported, of which 22 were secreted in the extracellular medium and 18 were bound or attached to cell wall structures (membrane or peptidoglycan layer). The functions of these proteins were related to food supply (phospholipases, proteases, toxins), cell protection (bacteriocins, toxins, transporters, cell wall biogenesis) and environment-sensing (two-component sensors, chemotaxis proteins, GGDEF family regulators). Four genes coded for cytoplasmic regulators. The PlcR regulon appears to integrate a large range of environmental signals, including food deprivation and self cell-density, and regulate the transcription of genes designed to overcome obstacles that hinder B. cereus growth within the host: food supply, host barriers, host immune defenses, and competition with other bacterial species. PlcR appears to be a key component in the efficient adaptation of B. cereus to its host environment

The Secret Life of the Anthrax Agent Bacillus anthracis: Bacteriophage-Mediated Ecological Adaptations

Ecological and genetic factors that govern the occurrence and persistence of anthrax reservoirs in the environment are obscure. A central tenet, based on limited and often conflicting studies, has long held that growing or vegetative forms of Bacillus anthracis survive poorly outside the mammalian host and must sporulate to survive in the environment. Here, we present evidence of a more dynamic lifecycle, whereby interactions with bacterial viruses, or bacteriophages, elicit phenotypic alterations in B. anthracis and the emergence of infected derivatives, or lysogens, with dramatically altered survival capabilities. Using both laboratory and environmental B. anthracis strains, we show that lysogeny can block or promote sporulation depending on the phage, induce exopolysaccharide expression and biofilm formation, and enable the long-term colonization of both an artificial soil environment and the intestinal tract of the invertebrate redworm, Eisenia fetida. All of the B. anthracis lysogens existed in a pseudolysogenic-like state in both the soil and worm gut, shedding phages that could in turn infect non-lysogenic B. anthracis recipients and confer survival phenotypes in those environments. Finally, the mechanism behind several phenotypic changes was found to require phage-encoded bacterial sigma factors and the expression of at least one host-encoded protein predicted to be involved in the colonization of invertebrate intestines. The results here demonstrate that during its environmental phase, bacteriophages provide B. anthracis with alternatives to sporulation that involve the activation of soil-survival and endosymbiotic capabilities

Magnetic properties of perovskites Pr0.9_{0.9}Sr0.1_{0.1}Mn0.93+_{0.9}^{3+}Mn0.14+_{0.1}^{4+}O3_{3}: Monte Carlo simulations and experiments

This work presents the remarkable experimental magnetocaloric properties of the perovskites Pr$_{0.9}$Sr$_{0.1}$Mn$_{0.9}^{3+}$Mn$_{0.1}^{4+}$O$_{3}$, including the magnetic entropy change $|\Delta S_m|$ and the Relative Cooling Power (RCP). To understand these striking properties,we elaborate in this paper a model and use Monte Carlo (MC) simulations to study it for comparison. For the model, we take into account nearest-neighbor (NN) interactions between magnetic ions Mn$^{3+}$($S=2$) and Mn$^{4+}$($S=3/2$) and the interactions between these Mn ions with the magnetic Pr ions. The crystal is a body-centered tetragonal lattice where the corner sites are occupied by Mn ions and the center sites by Pr and Sr ions in their respective concentrations given in the compound formula. We use an Ising-like spin model describing a strong anisotropy on the $z$ axis. We show that pairwise interactions between ions cannot reproduce the large plateau of the magnetization experimentally observed below the phase-transition temperature. By introducing for the first time a many-spin interaction between Mn ions, we obtain an excellent agreement with experiments. Fitting the experimental Curie temperature $T_C$ with the MC transition temperature, we estimate the value of the effective exchange interaction in the system. From this value, we estimate various exchange interactions between ions: the dominant one is that between Mn$^{3+}$ and Mn$^{4+}$ which is at the origin of the ferromagnetic ordering below $T_C$. We also studied the applied-field effect on the magnetization in the region below and above $T_C$. The obtained MC results for $|\Delta S_m|$ are in agreement with experiments performed for applied fields from 1 to 5 Tesla. MC results of RCP are also shown and compared to experimental ones. Various other physical quantities obtained from MC simulations including internal energy and specific heat, versus temperature are also shown and discussed

Structural, magnetic, magnetocaloric and critical exponents of oxide manganite La0.7Sr0.3Mn0.95Fe0.05O3

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Cytospora paraplurivora sp. nov. isolated from orchards with fruit tree decline syndrome in Ontario, Canada

A new species of Cytospora was isolated from cankered wood of Prunus spp. during a survey of orchards exhibiting symptoms of fruit tree decline syndrome in southern Ontario, Canada. We found isolates that are morphologically similar to species in the Cytosporaceae family, which is characterized by single or labyrinthine locules, filamentous conidiophores or clavate to elongate obovoid asci and allantoid, hyaline conidia. Multi-gene phylogenetic analysis of ITS, LSU, act and tef1- α showed that the isolates form a distinct clade, sister to Cytospora plurivora. Morphologically, our isolates showed differences in the length of conidia and culture characteristics compared to C. plurivora, suggesting the establishment of a new species. The species is described as Cytospora paraplurivora sp. nov. and placed in the family Cytosporaceae of Diaporthales. Additionally, we sequenced, assembled and characterized the genome of the representative isolate for this new species. The phylogenomic analysis confirms the species order and family level classification. C. paraplurivora sp. nov. has the potential to severely affect stone fruits production, causing cankers and dieback in stressed trees, and eventually leads to tree decline. Pathogenicity tests show that the species is pathogenic to Prunus persica var. persica