EDIN-B Promotes the Translocation of Staphylococcus aureus to the Bloodstream in the Course of Pneumonia

It is crucial to define risk factors that contribute to host invasion by Staphylococcus aureus. Here, we demonstrate that the chromosomally encoded EDIN-B isoform from S. aureus contributes to the onset of bacteremia during the course of pneumonia. Deletion of edinB in a European lineage community-acquired methicillin resistant S. aureus (CA-MRSA) strain (ST80-MRSA-IV) dramatically decreased the frequency and magnitude of bacteremia in mice suffering from pneumonia. This deletion had no effect on the bacterial burden in both blood circulation and lung tissues. Re-expression of wild-type EDIN-B, unlike the catalytically inactive mutant EDIN-R185E, restored the invasive characteristics of ST80-MRSA-IV.     

The genome of Bacillus coahuilensis reveals adaptations essential for survival in the relic of an ancient marine environment

The Cuatro Ciénegas Basin (CCB) in the central part of the Chihuahan desert (Coahuila, Mexico) hosts a wide diversity of microorganisms contained within springs thought to be geomorphological relics of an ancient sea. A major question remaining to be answered is whether bacteria from CCB are ancient marine bacteria that adapted to an oligotrophic system poor in NaCl, rich in sulfates, and with extremely low phosphorus levels (<0.3 μM). Here, we report the complete genome sequence of Bacillus coahuilensis, a sporulating bacterium isolated from the water column of a desiccation lagoon in CCB. At 3.35 Megabases this is the smallest genome sequenced to date of a Bacillus species and provides insights into the origin, evolution, and adaptation of B. coahuilensis to the CCB environment. We propose that the size and complexity of the B. coahuilensis genome reflects the adaptation of an ancient marine bacterium to a novel environment, providing support to a “marine isolation origin hypothesis” that is consistent with the geology of CCB. This genomic adaptation includes the acquisition through horizontal gene transfer of genes involved in phosphorous utilization efficiency and adaptation to high-light environments. The B. coahuilensis genome sequence also revealed important ecological features of the bacterial community in CCB and offers opportunities for a unique glimpse of a microbe-dominated world last seen in the Precambrian.     

Regulation of indoleamine 2,3-dioxygenase and tryptophanyl-tRNA-synthetase by CTLA-4-Fc in human CD4+ T cells

Indoleamine-2,3-dioxygenase (IDO) and tryptophanyl-tRNA-synthetase (TTS) are interferon-gamma (IFN-gamma)-inducible enzymes that are responsible for tryptophan degradation and for its use in protein synthesis, respectively. IFN-gamma-induced IDO has immunomodulatory properties in murine and human models. A concomitant increase of TTS has been postulated to protect the IDO-expressing cells from tryptophan catabolism. IDO can be induced in dendritic cells (DCs) by recombinant soluble cytotoxic T lymphocyte antigen-4 (CTLA-4-Fc). We investigated the effects of CTLA-4-Fc on IDO and TTS mRNA expression in human peripheral blood mononuclear cells (PBMCs) and isolated leukocyte subsets. CTLA-4-Fc exposure induced increased IDO and TTS expression in unseparated PBMCs, as well as in monocyte-derived mature DCs. CD4(+) T cells isolated from CTLA-4-Fc-treated PBMCs showed increased IDO and TTS compared with untreated cells. CD8(+) T cells from CTLA-4-Fc-treated PBMCs expressed increased levels of TTS but not IDO. Pretreatment of PBMCs with CTLA-4-Fc inhibited the activation of CD4(+) T cells induced by influenza A virus (Flu) or phytohemagglutinin A (PHA), but had no effect on CD8(+) T cells. This is the first report of IDO and TTS regulation by the CTLA-4-B7 system in human CD4(+) and CD8(+) T cells, and raises the possibility that these 2 tryptophan-modulating enzymes provide an important mechanism for regulating immune responses.     

Effect of bracing or surgical treatments on balance control in idiopathic scoliosis: three case studies

Scoliosis is the most frequent spinal deformity among adolescents. In 80 % of cases, it is defined as idiopathic as no individual cause has been identified. However, several factors linked to Adolescent Idiopathic Scoliosis (AIS) have been identified and are under investigation. One of these factors is neurological dysfunction. Increase in body sway has been observed either during or following sensory manipulation in AIS patients. It is believed that impairment in sensory processing could be related to scoliosis onset. Impairment in sensory processing could induce a body schema distortion. The aim of this case series was to evaluate if conventional orthopaedic treatments could improve balance control thus implying a better body representation. Although, no strong conclusion can be drawn from a case series, results suggest that alteration in body representation should be investigated in future studies.     

Non-Gaussian water diffusion in aging white matter

Age-associated white matter degeneration has been well documented and is likely an important mechanism contributing to cognitive decline in older adults. Recent work has explored a range of noninvasive neuroimaging procedures to differentially highlight alterations in the tissue microenvironment. Diffusional kurtosis imaging (DKI) is an extension of diffusion tensor imaging (DTI) that accounts for non-Gaussian water diffusion and can reflect alterations in the distribution and diffusion properties of tissue compartments. We used DKI to produce whole-brain voxel-based maps of mean, axial, and radial diffusional kurtoses, quantitative indices of the tissue microstructure's diffusional heterogeneity, in 111 participants ranging from the age of 33 to 91 years. As suggested from prior DTI studies, greater age was associated with alterations in white-matter tissue microstructure, which was reflected by a reduction in all 3 DKI metrics. Prominent effects were found in prefrontal and association white matter compared with relatively preserved primary motor and visual areas. Although DKI metrics co-varied with DTI metrics on a global level, DKI provided unique regional sensitivity to the effects of age not available with DTI. DKI metrics were additionally useful in combination with DTI metrics for the classification of regions according to their multivariate “diffusion footprint”, or pattern of relative age effect sizes. It is possible that the specific multivariate patterns of age-associated changes measured are representative of different types of microstructural pathology. These results suggest that DKI provides important complementary indices of brain microstructure for the study of brain aging and neurologic disease.