Two clinically-important beta-lactam antibiotics, cephalothin and cefotaxime, have been observed by X-ray crystallography bound to the reactive Ser62 of the D-alanyl-D-alanine ...carboxypeptidase/transpeptidase of Streptomyces sp. R61. Refinement of the two crystal structures produced R factors for 3 sigma (F) data of 0.166 (to 1.8 A) and 0.170 (to 2.0 A) for the cephalothin and cefotaxime complexes, respectively. In each complex, a water molecule is within 3.1 and 3.6 A of the acylated beta-lactam carbonyl carbon atom, but is poorly activated by active site residues for nucleophilic attack and deacylation. This apparent lack of good stereochemistry for facile hydrolysis is in accord with the long half-lives of cephalosporin intermediates in solution (20-40 h) and the efficacy of these beta-lactams as inhibitors of bacterial cell wall synthesis. Different hydrogen binding patterns of the two cephalosporins to Thr301 are consistent with the low cefotaxime affinity of an altered penicillin-binding protein, PBP-2x, reported in cefotaxime-resistant strains of Streptococcus pneumoniae, and with the ability of mutant class A beta-lactamases to hydrolyze third-generation cephalosporins.
White-tailed deer (Odocoileus virginianus) population management is important because of this species' popularity for sport hunting and the ecological and economic damage deer can cause. ...Relationships between various physical condition metrics, most commonly body mass and antler measures, and estimates of absolute density have been used to develop harvest-management decision models. However, biases in estimating densities among different populations and differences in herd productivity may limit their wide-scale application. We developed models relating 3 commonly used physical parameters (yearling male body mass, yearling female body mass, and antler measures) to relative density (density/K-carrying capacity). We used these models to examine condition and density relationships among 8 populations: 1 in the midwestern and 7 in the southeastern United States. The populations studied spanned several physiographic provinces, had long-term (15- to 31-yr duration, median = 26 yr) harvest data, and varying densities (3–32 deer/km2). Population model slopes were similar with no apparent pattern along a presumed habitat-quality gradient, suggesting that food resources, the range of relative densities, and local genetic variation may be overriding influences. However, slight variation in slopes for yearling male body mass (all between 2% and 4% change in relative density for each 0.4-kg change in mass) among populations suggests that relative density models could have general applicability in the southeastern United States.
The structure of the class C ampC beta -lactamase (cephalosporinase) from Enterobacter cloacae strain P99 has been established by x-ray crystallography to 2-angstrom resolution and compared to a ...class A beta -lactamase (penicillinase) structure. The binding site for beta -lactam antibiotics is generally more open than that in penicillinases, in agreement with the ability of the class C beta -lactamases to better bind third-generation cephalosporins. Four corresponding catalytic residues (Ser-64/70, Lys-67/73, Lys-315/234, and Tyr-150/Ser-130 in class C/A) lie in equivalent positions within 0.4 angstrom. Significant differences in positions and accessibilities of Arg-349/244 may explain the inability of clavulanate-type inhibitors to effectively inactivate the class C beta -lactamases. Glu-166, required for deacylation of the beta -lactamoyl intermediate in class A penicillinases, has no counterpart in this cephalosporinase; the nearest candidate, Asp-217, is 10 angstrom from the reactive Ser-64. A comparison of overall tertiary folding shows that the cephalosporinase, more than the penicillinase, is broadly similar to the ancestral beta -lactam-inhibited enzymes of bacterial cell wall synthesis. On this basis, it is proposed that the cephalosporinase is the older of the two beta -lactamases, and, therefore, that a local refolding in the active site, rather than a simple point mutation, was required for the primordial class C beta -lactamase to evolve to the class A beta -lactamase having an improved ability to catalyze the deacylation step of beta -lactam hydrolysis.
In response to the accumulation of evidence implicating the importance of psychosocial factors in subsequent recovery after acute myocardial infarction, the ENhancing Recovery In Coronary Heart ...Disease (ENRICHD) trial was initiated. ENRICHD is a multicenter, randomized, clinical trial designed to evaluate the effects of a psychosocial intervention on cardiovascular morbidity and mortality in post-AMI patients exhibiting clinical depression and social isolation.
The problems of controlling and ultimately eradicating pertussis are addressed in the face of the apparent impermanence of vaccine immunity, and the limited protection offered while it lasts. ...Interactions between partial immunity, reduced infectiousness, responses to a superimposed natural infection, changing mean ages of infection and alternative rates of transmission before the vaccine was introduced, are considered in an integrated manner. Mathematical expressions were developed for these different components, from which a computer program was constructed for predicting the levels of control to be expected from different vaccination strategies. The most important of the parameters determining outcomes are those relating to levels of uptake, the choice of a one-course or two-course policy, and the specification of the vaccine itself. As might be expected, high levels of uptake and a two-course policy are necessary for high levels of control, but they will not necessarily succeed. The detailed specification of the type of protection to be offered by a vaccine is also crucial. The most important necessity is for a vaccine immunity with a low rate of decay; but in the presence of decay (which greatly reduces the feasibility of eradication) it is important that the vaccine should protect against the clinical disease without preventing the child from being infected with the organism, and thus attaining permanent immunity.
In Pterostylis concinna individual pollen grains all possess an outer exine wall, pollinia are mealy, and they fall apart easily. In contrast, Dendrobium spp. have hard pollinia in which only pollen ...grains on the outer surface have an exine, inner pollinium pollen grains being enveloped only by intine. Different types of tapetally derived pollen-coat material bind each kind of pollinium together. Pollen-coat material covers only the outer surface in Dendrobium, is released after microspore mitosis, and polymerizes following anthesis. In Pterostylis, pollen coat is released before microspore mitosis and covers every pollen grain. At microspore mitosis the cytoplasmic channels between adjacent microspores in each tetrad close and extensive sheets of ER replace strands of tubular ER. The generative cell has no apparent callose wall and is surrounded by its own plasma membrane and that of the inner vegetative cell.