The epidemiology of pseudallescheriasis complicating transplantation: Nosocomial and community‐acquired infection

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141586/1/myc1990336296.pd

Characterization of a novel human serine protease that has extensive homology to bacterial heat shock endoprotease HtrA and is regulated by kidney ischemia.

We report the isolation and characterization of a cDNA encoding the novel mammalian serine protease Omi. Omi protein consists of 458 amino acids and has homology to bacterial HtrA endoprotease, which acts as a chaperone at low temperatures and as a proteolytic enzyme that removes denatured or damaged substrates at elevated temperatures. The carboxyl terminus of Omi has extensive homology to a mammalian protein called L56 (human HtrA), but unlike L56, which is secreted, Omi is localized in the endoplasmic reticulum. Omi has several novel putative protein-protein interaction motifs, as well as a PDZ domain and a Src homology 3-binding domain. Omi mRNA is expressed ubiquitously, and the gene is localized on human chromosome 2p12. Omi interacts with Mxi2, an alternatively spliced form of the p38 stress-activated kinase. Omi protein, when made in a heterologous system, shows proteolytic activity against a nonspecific substrate beta-casein. The proteolytic activity of Omi is markedly up-regulated in the mouse kidney following ischemia/reperfusion

Enhanced Recovery after Surgery in a Single High-Volume Surgical Oncology Unit: Details Matter

Benefits of ERAS protocol have been well documented; however, it is unclear whether the improvement stems from the protocol or shifts in expectations. Interdisciplinary educational seminars were conducted for all health professionals. However, one test surgeon adopted the protocol. 394 patients undergoing elective abdominal surgery from June 2013 to April 2015 with a median age of 63 years were included. The implementation of ERAS protocol resulted in a decrease in the length of stay (LOS) and mortality, whereas the difference in cost was found to be insignificant. For the test surgeon, ERAS was associated with decreased LOS, cost, and mortality. For the control providers, the LOS, cost, mortality, readmission rates, and complications remained similar both before and after the implementation of ERAS. An ERAS protocol on the single high-volume surgical unit decreased the cost, LOS, and mortality

Characterization of a novel and specific inhibitor for the pro-apoptotic protease Omi/HtrA2

Omi/HtrA2 is a mammalian serine protease with high homology to bacterial HtrA chaperones. Omi/HtrA2 is localized in mitochondria and is released to the cytoplasm in response to apoptotic stimuli. Omi/HtrA2 induces cell death in a caspase-dependent manner by interacting with the inhibitor of apoptosis protein as well as in a caspase-independent manner that relies on its protease activity. We describe the identification and characterization of a novel compound as a specific inhibitor of the proteolytic activity of Omi/HtrA2. This compound (ucf-101) was isolated in a high throughput screening of a combinatorial library using bacterially made Omi-(134-458) protease and fluorescein-casein as a generic substrate. ucf-101 showed specific activity against Omi/HtrA2 and very little activity against various other serine proteases. This compound has a natural fluorescence that was used to monitor its ability to enter mammalian cells. ucf-101, when tested in caspase-9 (-/-) null fibroblasts, was found to inhibit Omi/HtrA2-induced cell death

Regulation of HAX-1 anti-apoptotic protein by Omi/HtrA2 protease during cell death

Omi/HtrA2 is a nuclear-encoded mitochondrial serine protease that has a pro-apoptotic function in mammalian cells. Upon induction of apoptosis, Omi translocates to the cytoplasm and participates in caspase-dependent apoptosis by binding and degrading inhibitor of apoptosis proteins. Omi can also initiate caspase-independent apoptosis in a process that relies entirely on its ability to function as an active protease. To investigate the mechanism of Omi-induced apoptosis, we set out to isolate novel substrates that are cleaved by this protease. We identified HS1-associated protein X-1 (HAX-1), a mitochondrial anti-apoptotic protein, as a specific Omi interactor that is cleaved by Omi both in vitro and in vivo. HAX-1 degradation follows Omi activation in cells treated with various apoptotic stimuli. Using a specific inhibitor of Omi, HAX-1 degradation is prevented and cell death is reduced. Cleavage of HAX-1 was not observed in a cell line derived from motor neuron degeneration 2 mice that carry a mutated form of Omi that affects its proteolytic activity. Degradation of HAX-1 is an early event in the apoptotic process and occurs while Omi is still confined in the mitochondria. Our results suggest that Omi has a unique pro-apoptotic function in mitochondria that involves removal of the HAX-1 antiapoptotic protein. This function is distinct from its ability to activate caspase-dependent apoptosis in the cytoplasm by degrading inhibitor of apoptosis proteins

Differential Effect of Contrast Polarity Reversals in Closed Squares and Open L-Junctions

Scene segmentation depends on interaction between geometrical and photometric factors. It has been shown that reversals in contrast polarity at points of highest orientation discontinuity along closed contours significantly impair shape discrimination performance, while changes in contrast polarity at straight(er) contour segments do not have such deleterious effects (Spehar, 2002). Here we employ (semi) high resolution fMRI (1.5 mm × 1.5 mm × 1.5 mm) to investigate the neuronal substrate underlying these perception effects. Stimuli consisted of simple elements (a) squares with contrast reversals along straight segments; (b) squares with contrast reversals in the corner (highest orientation discontinuity); (c) L-Junctions with contrast reversals along the straight ends; (d) L-Junctions with contrast reversals in the corner. Element with contrast polarity reversals are easy to distinguish though appear geometrically equivalent. For squares with contrast polarity reversals only along straight lines we find significantly lower BOLD modulation compared to any of the control conditions, which show similar responses to each other. In the light of previous psychophysical work (Elder and Zucker, 1993; Spehar, 2002) we speculate that this effect is due to closure perception. We observe this across a wide range of areas on occipital cortex

Liax Is a Surrogate Marker For Cell Envelope Stress and Daptomycin Non-Susceptibility in Enterococcus Faecium

Daptomycin (DAP) is often used as a first-line therapy to treat vancomycin-resistan