The crystal structures of three vancomycin complexes with two vancomycin-sensitive cell-wall precursor analogs (diacetyl-Lys-d-Ala-d-Ala and acetyl-d-Ala-d-Ala) and a vancomycin-resistant cell-wall ...precursor analog (diacetyl-Lys-d-Ala-d-lactate) were determined at atomic resolutions of 1.80 Å, 1.07 Å, and 0.93 Å, respectively. These structures not only reconfirm the “back-to-back” dimerization of vancomycin monomers and the ligand-binding scheme proposed by previous experiments but also show important structural features of strategies for the generation of new glycopeptide antibiotics. These structural features involve a water-mediated antibiotic–ligand interaction and supramolecular structures such as “side-by-side” arranged dimer-to-dimer structures, in addition to ligand-mediated and “face-to-face” arranged dimer-to-dimer structures. In the diacetyl-Lys-d-Ala-d-lactate complex, the interatomic O⋯O distance between the carbonyl oxygen of the fourth residue of the antibiotic backbone and the ester oxygen of the d-lactate moiety of the ligand is clearly longer than the corresponding N–H⋯O hydrogen-bonding distance observed in the two other complexes due to electrostatic repulsion. In addition, two neighboring hydrogen bonds are concomitantly lengthened. These observations provide, at least in part, a molecular basis for the reduced antibacterial activity of vancomycin toward vancomycin-resistant bacteria with cell-wall precursors terminating in –d-Ala-d-lactate.
Staphylococcus aureus is one of the major causes of community-acquired and hospital-acquired infections. It produces numerous toxins including superantigens that cause unique disease entities such as ...toxic-shock syndrome and staphylococcal scarlet fever, and has acquired resistance to practically all antibiotics. Whole genome analysis is a necessary step towards future development of countermeasures against this organism.
Whole genome sequences of two related
S aureus strains (N315 and Mu50) were determined by shot-gun random sequencing. N315 is a meticillin-resistant
S aureus (MRSA) strain isolated in 1982, and Mu50 is an MRSA strain with vancomycin resistance isolated in 1997. The open reading frames were identified by use of GAMBLER and GLIMMER programs, and annotation of each was done with a BLAST homology search, motif analysis, and protein localisation prediction.
The
Staphylococcus genome was composed of a complex mixture of genes, many of which seem to have been acquired by lateral gene transfer. Most of the antibiotic resistance genes were carried either by plasmids or by mobile genetic elements including a unique resistance island. Three classes of new pathogenicity islands were identified in the genome: a toxic-shock-syndrome toxin island family, exotoxin islands, and enterotoxin islands. In the latter two pathogenicity islands, clusters of exotoxin and enterotoxin genes were found closely linked with other gene clusters encoding putative pathogenic factors. The analysis also identified 70 candidates for new virulence factors.
The remarkable ability of
S aureus to acquire useful genes from various organisms was revealed through the observation of genome complexity and evidence of lateral gene transfer. Repeated duplication of genes encoding superantigens explains why
S aureus is capable of infecting humans of diverse genetic backgrounds, eliciting severe immune reactions. Investigation of many newly identified gene products, including the 70 putative virulence factors, will greatly improve our understanding of the biology of staphylococci and the processes of infectious diseases caused by
S aureus.
Background:
Type II tibial spine avulsion (TSA) fractures have traditionally been managed by first attempting to achieve closed reduction with extension and immobilization, with surgical indications ...reserved for those who fail to reduce within 3 mm. However, the frequency with which appropriate reduction can be achieved is largely unknown.
Purpose:
To evaluate changes in displacement of type II TSA fractures by comparing magnetic resonance imaging (MRI) scans obtained with the knee in flexion and in extension.
Study Design:
Case series; Level of evidence, 4.
Methods:
Ten patients with type II TSA fractures were identified. Fracture displacement was measured using 3 images for each patient: (1) initial lateral view radiography, (2) sagittal-plane MRI of the knee in resting flexion, and (3) sagittal-plane MRI of the knee in passive extension. Maximum displacement of the bony fragment was measured in the 2 MRI studies for all patients, and the corresponding change in displacement was calculated. Displacement in flexion was compared with displacement in extension using a paired-sample t test. Statistical significance was set at P < .05.
Results:
The displacement distance of the bony fragment was reduced by a mean of 0.97 mm on MRI when the knee was in extension compared with flexion in patients with type II TSA fractures (P = .02). Mean displacement with extension was 6.14 mm, with no fractures reduced below 4 mm. The largest reduction observed was 2.80 mm. The displacement distance increased in 2 knees with extension. The intermeniscal ligament (IML) was entrapped in 4 of 10 patients; however, the amount of reduction achieved did not differ based on the presence of IML entrapment (P = .85).
Conclusion:
While the amount of tibial spine displacement warranting surgical treatment can be debated, the study findings suggest that knee extension is not reliable in obtaining adequate closed reduction for type II TSA fractures. Management decisions may need to be based on the initial displacement distance of the fracture, with a lower threshold for operative treatment than previously recognized.
Late-onset hemorrhagic cystitis (LHC) after hematopoietic stem cell transplantation (HSCT) is mainly caused by viral infections. We retrospectively analyzed the records of 141 Japanese adult patients ...who underwent a first allogeneic HSCT from 1995 to 2002. In all, 19 patients developed LHC a median of 51 days after HSCT. Adenovirus (AdV) was detected in the urine of 10 LHC patients, of whom eight had AdV type 11. Five of the six available serum samples from these patients were also positive for AdV type 11, but the detection of AdV in serum was not associated with a worse outcome. Male sex and the development of grade II-IV acute graft-versus-host disease were identified as independent significant risk factors for LHC. Male predominance was detected in LHC after HSCT, as has been previously shown in children with AdV-induced acute HC. The detection of AdV DNA in serum did not predict a poor outcome.
X-ray diffraction study of solid CO(2) at room temperature has shown that the powder pattern of the high-pressure phase, which supersedes the low-pressure cubic Pa3 phase at about 10 gigapascals, is ...consistently interpreted in terms of an orthorhombic Cmca structure. The orthorhombic cell at 11.8 gigapascals has dimensions of 4.330 +/- 0.015, 4.657 +/- 0.005, 5.963 +/- 0.009 angstroms for its a, b, and c faces, respectively, and a volume of 120.3 +/- 0.5 cubic angstroms. Four molecules contained in the unit cell are located at the base-centered positions with their molecular axes inclined at about 52 degrees with respect to the crystallographic c axis. The volume change associated with the Pa3-Cmca transition is close to zero. The structural dimensions obtained for the high-pressure crystalline phase of CO(2) are of great importance for a theoretical understanding of the role of intermolecular interactions, including quadrupole-quadrupole interactions, in molecular condensation.
ABSTRACT We present near-infrared spectroscopy of the host galaxy of the dark gamma-ray burst (GRB) 080325 using Subaru/Multi-Object Infrared Camera and Spectrograph. The obtained spectrum provides a ...clear detection of H emission and marginal Niiλ6584. The host is a massive (M* ∼ 1011 M ), dusty ( ) star-forming galaxy at z = 1.78. The extinction-corrected star formation rate (SFR) calculated from the H luminosity (35.6-47.0 M yr−1) is typical among GRB host galaxies (and star-forming galaxies generally) at z 1; however, the specific SFR is lower than for normal star-forming galaxies at redshift ∼1.6, in contrast to the high specific SFR measured for many of other GRB hosts. The metallicity of the host is estimated to be 12 + log(O/H)KK04 = 8.88. We emphasize that this is one of the most massive host galaxies at z for which metallicity is measured with emission-line diagnostics. The metallicity is fairly high among GRB hosts, however, this is still lower than the metallicity of normal star-forming galaxies of the same mass at z ∼ 1.6. The metallicity offset from normal star-forming galaxies is close to a typical value of other GRB hosts and indicates that GRB host galaxies are uniformly biased toward low metallicity over a wide range of redshifts and stellar masses. The low-metallicity nature of the GRB 080325 host likely cannot be attributed to the fundamental metallicity relation of star-forming galaxies because it is a metal-poor outlier from the relation and has a low specific star formation rate. Thus, we conclude that metallicity is important to the mechanism that produced this GRB.
Glycans, or carbohydrate sugar chains, which play a number of important roles in the development and functioning of multicellular organisms, can be regarded as labeled ordered trees. A recent ...increase in the documentation of glycan structures, especially in the form of database curation, has made mining glycans important for the understanding of living cells. We propose a probabilistic model for mining labeled ordered trees, and we further present an efficient learning algorithm for this model, based on an EM algorithm. The time and space complexities of this algorithm are rather favorable, falling within the practical limits set by a variety of existing probabilistic models, including stochastic context-free grammars. Experimental results have shown that, in a supervised problem setting, the proposed method outperformed five other competing methods by a statistically significant factor in all cases. We further applied the proposed method to aligning multiple glycan trees, and we detected biologically significant common subtrees in these alignments where the trees are automatically classified into subtypes already known in glycobiology.
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