A Single Nucleotide Change Affects Fur-Dependent Regulation of sodB in H. pylori

Helicobacter pylori is a significant human pathogen that has adapted to survive the many stresses found within the gastric environment. Superoxide Dismutase (SodB) is an important factor that helps H. pylori combat oxidative stress. sodB was previously shown to be repressed by the Ferric Uptake Regulator (Fur) in the absence of iron (apo-Fur regulation) [1]. Herein, we show that apo regulation is not fully conserved among all strains of H. pylori. apo-Fur dependent changes in sodB expression are not observed under iron deplete conditions in H. pylori strains G27, HPAG1, or J99. However, Fur regulation of pfr and amiE occurs as expected. Comparative analysis of the Fur coding sequence between G27 and 26695 revealed a single amino acid difference, which was not responsible for the altered sodB regulation. Comparison of the sodB promoters from G27 and 26695 also revealed a single nucleotide difference within the predicted Fur binding site. Alteration of this nucleotide in G27 to that of 26695 restored apo-Fur dependent sodB regulation, indicating that a single base difference is at least partially responsible for the difference in sodB regulation observed among these H. pylori strains. Fur binding studies revealed that alteration of this single nucleotide in G27 increased the affinity of Fur for the sodB promoter. Additionally, the single base change in G27 enabled the sodB promoter to bind to apo-Fur with affinities similar to the 26695 sodB promoter. Taken together these data indicate that this nucleotide residue is important for direct apo-Fur binding to the sodB promoter

Metal-responsive gene regulation and metal transport in Helicobacter species

Helicobacter species are among the most successful colonizers of the mammalian gastrointestinal and hepatobiliary tract. Colonization is usually lifelong, indicating that Helicobacter species have evolved intricate mechanisms of dealing with stresses encountered during colonization of host tissues, like restriction of essential metal ions. The recent availability of genome sequences of the human gastric pathogen Helicobacter pylori, the murine enterohepatic pathogen Helicobacter hepaticus and the unannotated genome sequence of the ferret gastric pathogen Helicobacter mustelae has allowed for comparitive genome analyses. In this review we present such analyses for metal transporters, metal-storage and metal-responsive regulators in these three Helicobacter species, and discuss possible contributions of the differences in metal metabolism in adaptation to the gastric or enterohepatic niches occupied by Helicobacter species

Oceanization starts at depth during continental rupturing in the Northern Red Sea

We present here 3D seismic reflection and gravity data obtained from an off-axis area of the NW Red Sea, as well as results of a study of gabbroic rocks recovered in the same area both from an oil well below a thick evaporitic-sedimentary sequence, and from a layered mafic complex exposed on the Brothers Islets. These new data provide constraints on the composition, depth of emplacement and age of early syn-rift magma intrusions into the deep crust. The Brothers are part of a series of sub-parallel NW-striking topographic highs associated with SW-dipping extensional fault blocks with significant footwall uplift during rifting that brought early syn-rift deep crustal rocks up to the seafloor. Assuming an important role played by magmatism in the evolution of narrow rifts helps to solve the controversy on the nature of the crust in the northern/central Red Sea (i.e., the crust outside the axial oceanic cells is either oceanic or it consists of melt-intruded extended continental crust). Gabbros show petrologic and geochemical signatures similar to those of MORB-type gabbroic cumulates and are compatible with their having been emplaced either in a continental or in an oceanic context. We explored the different hypotheses proposed to explain the lack of magnetic anomalies in the presence of oceanic crust in the northern Red Sea. Our results, combined with a review of all the geophysical and geological data in the area, suggest a stretched and thinned continental crust with few isolated sites of basaltic injections, in line with a model whereby asthenospheric melt intrusions contribute to weaken the lower crust enabling some decoupling between upper and lower crust, protracting upper crust extension and delaying crustal breakup. Our findings show that continental rupture in the northern Red Sea is preceded by intrusion of basaltic melts with MORB-type elemental and isotopic signature, that cooled forming gabbros at progressively shallower crustal depths as rifting progressed toward continental separation

Osteonecrosis is not a predictor of poor outcomes in primary total hip arthroplasty: a systematic literature review

The primary goals of this critical literature review were to determine whether revision rates of primary total hip arthroplasty in patients with osteonecrosis differ based on the underlying associated risk factors and diagnoses, whether the outcomes of this procedure have improved over the past two decades, and to compare outcomes based on study level of evidence. A systematic literature review yielded 67 reports representing 3,277 hips in 2,593 patients who had a total hip arthroplasty for osteonecrosis of the femoral head. Stratification of outcomes by associated risk factors or diagnoses revealed significantly lower revision rates in patients with idiopathic disease, systemic lupus erythematosus, and after heart transplant, and significantly higher rates in patients with sickle cell disease, Gaucher disease, or after renal failure and/or transplant. There was a significant decrease in revision rates between patients operated upon before 1990 versus those in 1990 or later, with rates of 17% and 3%, respectively. The results for arthroplasties performed in 1990 or later were similar to those for all hips in publicly reported national joint registries. Certain risk factors were associated with higher revision rates in patients with osteonecrosis who were treated by total hip arthroplasty. However, most patients (82%) do not have these associated negative risk factors. Overall, this critical literature review provides evidence that osteonecrosis itself, or when associated with the most common risk factors and/or diagnoses, is not associated with poor outcomes in total hip arthroplasty

SAS Weekly Rounds: Avascular Necrosis

Osteonecrosis of the femoral head is a condition that affects upwards of 10,000 individuals in the USA each year. The peak incidence is in the fourth decade of life, and overall, there is a male preponderance. The condition accounts for up to 12% of total hip arthroplasties performed in developed countries. The etiology can be traumatic or non-traumatic, with 90% of atraumatic cases attributed to corticosteroid therapy or excess alcohol consumption. Osteonecrosis of the femoral head reflects the final common pathway of a range of insults to the blood supply and ultimately results in femoral head collapse, acetabular involvement, and secondary osteoarthritis. Currently, conservative treatment options, which aim to correct pathophysiologic features allowing revascularization and new bone formation, appear to be able to delay but not halt the progression of this condition. As a consequence of femoral head osteonecrosis, many individuals undergo surgical treatments including: core decompression, osteotomy, non-vascularized bone matrix grafting, free vascularized fibular grafts, limited femoral resurfacing, total hip resurfacing, and total hip arthroplasty