906 research outputs found
HilE regulates HilD by blocking DNA binding in Salmonella enterica serovar Typhimurium
ABSTRACT
The
Salmonella
type three secretion system (T3SS), encoded in the
Salmonella
pathogenicity island 1 (SPI1) locus, mediates the invasion of the host intestinal epithelium. SPI1 expression is dependent upon three AraC-like regulators: HilD, HilC, and RtsA. These regulators act in a complex feed-forward loop to activate each other and
hilA
, which encodes the activator of the T3SS structural genes. HilD has been shown to be the major integration point of most signals known to activate the expression of the SPI1 T3SS, acting as a switch to control induction of the system. HilE is a negative regulator that acts upon HilD. Here we provide genetic and biochemical data showing that HilE specifically binds to HilD but not to HilC or RtsA. This protein-protein interaction blocks the ability of HilD to bind DNA as shown by both an
in vivo
reporter system and an
in vitro
gel shift assay. HilE does not affect HilD dimerization, nor does it control the stability of the HilD protein. We also investigated the role of HilE during the infection of mice using competition assays. Although deletion of
hilE
does not confer a phenotype, the
hilE
mutation does suppress the invasion defect conferred by loss of FliZ, which acts as a positive signal controlling HilD protein activity. Together, these data suggest that HilE functions to restrict low-level HilD activity, preventing premature activation of SPI1 until positive inputs reach a threshold required to fully induce the system.
IMPORTANCE
Salmonella
is a leading cause of gastrointestinal and systemic disease throughout the world. The SPI1 T3SS is required for
Salmonella
to induce inflammatory diarrhea and to gain access to underlying tissue. A complex regulatory network controls expression of SPI1 in response to numerous physiological inputs. Most of these signals impinge primarily on HilD translation or activity. The system is triggered when HilD activity crosses a threshold that allows efficient activation of its own promoter. This threshold is set by HilE, which binds to HilD to prevent the inevitable minor fluctuations in HilD activity from inappropriately activating the system. The circuit also serves as a paradigm for systems that must integrate numerous environmental parameters to control regulatory output.
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Crystal engineering using functionalized adamantane
We performed a first principles investigation on the structural, electronic,
and optical properties of crystals made of chemically functionalized adamantane
molecules. Several molecular building blocks, formed by boron and nitrogen
substitutional functionalizations, were considered to build zincblende and
wurtzite crystals, and the resulting structures presented large bulk moduli and
cohesive energies, wide and direct bandgaps, and low dielectric constants
(low- materials). Those properties provide stability for such
structures up to room temperature, superior to those of typical molecular
crystals. This indicates a possible road map for crystal engineering using
functionalized diamondoids, with potential applications ranging from space
filling between conducting wires in nanodevices to nano-electro-mechanical
systems
Structural, Electronic, and Vibrational Properties of Amino-adamantane and Rimantadine Isomers
We performed a first principles total energy investigation on the structural,
electronic, and vibrational properties of adamantane molecules, functionalized
with amine and ethanamine groups. We computed the vibrational signatures of
amantadine and rimantadine isomers with the functional groups bonded to
different carbon sites. By comparing our results with recent infrared and Raman
spectroscopic data, we discuss the possible presence of different isomers in
experimental samples
Functionalized adamantane: fundamental building blocks for nanostructure self-assembly
We report first principles calculations on the electronic and structural
properties of chemically functionalized adamantane molecules, either in
isolated or crystalline forms. Boron and nitrogen functionalized molecules,
aza-, tetra-aza-, bora-, and tetra-bora-adamantane, were found to be very
stable in terms of energetics, consistent with available experimental data.
Additionally, a hypothetical molecular crystal in a zincblende structure,
involving the pair tetra-bora-adamantane and tetra-aza-adamantane, was
investigated. This molecular crystal presented a direct and large electronic
bandgap and a bulk modulus of 20 GPa. The viability of using those
functionalized molecules as fundamental building blocks for nanostructure
self-assembly is discussed
Atomic Layer Deposition-Based Synthesis of Photoactive TiO2 Nanoparticle Chains by Using Carbon Nanotubes as Sacrificial Templates
Highly ordered and self supported anatase TiO2 nanoparticle chains were
fabricated by calcining conformally TiO2 coated multi-walled carbon nanotubes
(MWCNTs). During annealing, the thin tubular TiO2 coating that was deposited
onto the MWCNTs by atomic layer deposition (ALD) was transformed into chains of
TiO2 nanoparticles (~12 nm diameter) with an ultrahigh surface area (137 cm2
per cm2 of substrate), while at the same time the carbon from the MWCNTs was
removed. Photocatalytic tests on the degradation of acetaldehyde proved that
these forests of TiO2 nanoparticle chains are highly photo active under UV
light because of their well crystallized anatase phase
Synthesis of a 3D network of Pt nanowires by atomic layer deposition on carbonaceous template
The formation of a 3D network composed of free standing and interconnected Pt
nanowires is achieved by a two-step method, consisting of conformal deposition
of Pt by atomic layer deposition (ALD) on a forest of carbon nanotubes and
subsequent removal of the carbonaceous template. Detailed characterization of
this novel 3D nanostructure was carried out by transmission electron microscopy
(TEM) and electrochemical impedance spectroscopy (EIS). These characterizations
showed that this pure 3D nanostructure of platinum is self-supported and offers
an enhancement of the electrochemically active surface area by a factor of 50
Outcome of postoperative critically ill patients with heparin-induced thrombocytopenia: an observational retrospective case-control study
INTRODUCTION: Heparin-induced thrombocytopenia (HIT) is described as a decrease in platelet count associated with heparin administration and is an immune-mediated adverse drug reaction that can cause both arterial and venous thromboses. It can be a life-threatening complication of heparin exposure. Little data concerning incidence, predisposing factors, or outcome in critically ill surgical patients are available. METHODS: All critically ill, postoperative patients admitted between January 1, 2000, and December 31, 2001, to a surgical intensive care unit (SICU) who tested positive by an enzyme-linked immunosorbent assay for the HIT antibody (HPIA; Diagnostica Stago, Inc., Parsippany, NJ, USA) were identified. Patient risk factors and outcomes were abstracted retrospectively from the medical record and compared with those from control patients matched for age, gender, diagnosis, severity of illness, and date of SICU admission. RESULTS: Two hundred and ten patients out of 2,046 patients (10%) admitted to the SICU had HIT assays performed. Nineteen patients (0.9% of admissions; 9% of tested individuals) had positive tests. HIT-antibody-positive patients, compared with 19 matched controls, had an increased risk of death or major thrombotic complications (37% versus 10%; P < 0.05) and prolonged length of intensive care unit (ICU) stay (20 days versus 10 days; P < 0.05). Exposure to heparin via intravascular flushes alone was sufficient to generate HIT antibodies in 12 of 19 (63%) patients. Five patients received platelet transfusions after the diagnosis of HIT was known; four of these patients died. CONCLUSION: Heparin flushes were the most common cause of HIT in this study. HIT-antibody-positive patients had an increased risk of death or major complications and a prolonged length of ICU stay. Platelet transfusions often were administered despite a positive HIT test result and were associated with a high mortality rate. Treatment algorithms that minimize exposure to heparin and contraindicate platelet transfusions merit further study
Resource partitioning among top-level piscivores in a sub-Arctic lake during thermal stratification
AbstractIn systems with multiple piscivores, co-occurrence is dependent on resource partitioning. This is pronounced in oligotrophic northern lakes, which have simple food webs and short open-water seasons. We used acoustic telemetry and stable isotopes to quantify habitat and dietary partitioning during thermal stratification among three piscivores that commonly co-occur in Canadian sub-Arctic lakes—burbot (Lota lota), lake trout (Salvelinus namaycush), and northern pike (Esox lucius). Spatial core areas and core habitat niches (space and depth) did not significantly overlap among species. Although burbot and lake trout occupied similar mean daily depths (16.2m and 13.4m, respectively), and water temperatures (5.4°C and 6.9°C, respectively), they were spatially segregated. Burbot were closely associated with the lake bottom on steep drop-offs between the offshore and nearshore zone with moderate substrate complexity, whereas lake trout were located over deep offshore basins and suspended above the lake bottom. Northern pike occupied shallow depths (5.3m) and warmer water (16.5°C) within the nearshore region and were closely associated with bottom substrate of highest complexity. Some significant overlap among spatial home ranges and broad habitat niches indicated that these species interact. However, dietary niches did not significantly overlap at either the core or broad levels, suggesting that species were utilizing spatially diverse food sources. Our results highlight the importance of including depth and space when quantifying resource partitioning among fishes and provide insight into the mechanisms that promote piscivore co-occurrence in northern lakes
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