878 research outputs found
Ventricular assist device implantation in the elderly
BACKGROUND:
Dramatic advances in ventricular assist device (VAD) design and patient management have made mechanical circulatory support an attractive therapeutic option for the growing pool of elderly heart failure patients.
METHODS:
A literature review of all relevant studies was performed. No time or language restrictions were imposed, and references of the selected studies were checked for additional relevant citations.
RESULTS:
In concordance with the universal trend in mechanical circulatory support, continuous flow devices appear to have particular benefits in the elderly. In addition, the literature suggests that early intervention before the development of cardiogenic shock, important in all patients, is particularly paramount in older patients.
CONCLUSIONS:
The ongoing refinement of patient selection, surgical technique, and post-operative care will continue to improve surgical outcomes, and absolute age may become a less pivotal criterion for mechanical circulatory support. However, clear guidelines for the use of mechanical circulatory support in the elderly remain undefined
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Twin RNA Polymerase–associated Proteins Control Virulence Gene Expression in Francisella tularensis
The MglA protein is the only known regulator of virulence gene expression in Francisella tularensis, yet it is unclear how it functions. F. tularensis also contains an MglA-like protein called SspA. Here, we show that MglA and SspA cooperate with one another to control virulence gene expression in F. tularensis. Using a directed proteomic approach, we show that both MglA and SspA associate with RNA polymerase (RNAP) in F. tularensis, and that SspA is required for MglA to associate with RNAP. Furthermore, bacterial two-hybrid and biochemical assays indicate that MglA and SspA interact with one another directly. Finally, through genome-wide expression analyses, we demonstrate that MglA and SspA regulate the same set of genes. Our results suggest that a complex involving both MglA and SspA associates with RNAP to positively control virulence gene expression in F. tularensis. The F. tularensis genome is unusual in that it contains two genes encoding different α subunits of RNAP, and we show here that these two α subunits are incorporated into RNAP. Thus, as well as identifying SspA as a second critical regulator of virulence gene expression in F. tularensis, our findings provide a framework for understanding the mechanistic basis for virulence gene control in a bacterium whose transcription apparatus is unique
X-Ray and UV Orbital Phase Dependence in LMC X-3
The black-hole binary LMC X-3 is known to be variable on time scales of days
to years. We investigate X-ray and ultraviolet variability in the system as a
function of the 1.7 day binary phase using a 6.4 day observation with the Rossi
X-ray Timing Explorer (RXTE) from December 1998. An abrupt 14% flux decrease,
lasting nearly an entire orbit, is followed by a return to previous flux
levels. This behavior occurs twice, at nearly the same binary phase, but it is
not present in consecutive orbits. When the X-ray flux is at lower intensity, a
periodic amplitude modulation of 7% is evident in data folded modulo the
orbital period. The higher intensity data show weaker correlation with phase.
This is the first report of X-ray variability at the orbital period of LMC X-3.
Archival RXTE observations of LMC X--3 during a high flux state in December
1996 show similar phase dependence. An ultraviolet light curve obtained with
the High Speed Photometer aboard the Hubble Space Telescope shows orbital
modulation consistent with that in the optical, caused by the ellipsoidal
variation of the spatially deformed companion.
The X-ray spectrum of LMC X-3 can be acceptably represented by a
phenomenological disk-black-body plus a power law. Changes in the spectrum of
LMC X-3 during our observations are compatible with earlier observations during
which variations in the 2-10 keV flux are tracked closely by the disk geometry
spectral model parameter.Comment: 11 pages, 7 figures, ApJ in pres
Novel cyclic di-GMP effectors of the YajQ protein family control bacterial virulence
Bis-(3 ',5 ') cyclic di-guanylate (cyclic di-GMP) is a key bacterial second messenger that is implicated in the regulation of many critical processes that include motility, biofilm formation and virulence. Cyclic di-GMP influences diverse functions through interaction with a range of effectors. Our knowledge of these effectors and their different regulatory actions is far from complete, however. Here we have used an affinity pull-down assay using cyclic di-GMP-coupled magnetic beads to identify cyclic di-GMP binding proteins in the plant pathogen Xanthomonas campestris pv. campestris (Xcc). This analysis identified XC_3703, a protein of the YajQ family, as a potential cyclic di-GMP receptor. Isothermal titration calorimetry showed that the purified XC_3703 protein bound cyclic di-GMP with a high affinity (K-d similar to 2 mu M). Mutation of XC_3703 led to reduced virulence of Xcc to plants and alteration in biofilm formation. Yeast two-hybrid and far-western analyses showed that XC_3703 was able to interact with XC_2801, a transcription factor of the LysR family. Mutation of XC_2801 and XC_3703 had partially overlapping effects on the transcriptome of Xcc, and both affected virulence. Electromobility shift assays showed that XC_3703 positively affected the binding of XC_2801 to the promoters of target virulence genes, an effect that was reversed by cyclic di-GMP. Genetic and functional analysis of YajQ family members from the human pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia showed that they also specifically bound cyclic di-GMP and contributed to virulence in model systems. The findings thus identify a new class of cyclic di-GMP effector that regulates bacterial virulence
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