Composition and Variation of the Human Milk Microbiota Are Influenced by Maternal and Early-Life Factors

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Comparison of Hindlimb Muscle Architecture Properties in Small-Bodied,Generalist Mammals Suggests Similarity in Soft Tissue Anatomy

Journal of Mammalian Evolution - For the first 100+?million years of their evolutionary history, the majority of mammals were very small, and many exhibited relatively generalized locomotor...     

A three-fluorophore FRET assay for high-throughput screening of small-molecule inhibitors of ribosome assembly

In one of the first steps of prokaryotic ribosome assembly, the ribosomal protein S15 binds to a three-way junction in the central domain of the 16S rRNA. Binding causes a conformational change that is required for subsequent binding events. Using a novel fluorescence resonance energy transfer assay with three fluorophores, two on the RNA and one on the S15 protein, small-molecule libraries can be screened for potential inhibitors of this initial step in ribosome assembly. The employment of three fluorophores allows both the conformational change of the RNA and the binding of S15 to be monitored in a single assay.     

Glyco-optimization of aminoglycosides: new aminoglycosides as novel anti-infective agents

Glyco-optimization (OPopS) of aminoglycosides has been performed by replacing the existing sugar moiety with a variety of sugar derivatives. Glycosylation of the 6-position of nebramine provided a library of novel 4,6-linked aminoglycosides (AMGs). Among them, compounds 8b,g,i,l, and 8u with 2"-amino, 2",3"-diamino, 2",4"-diamino, 3",4"-diamino, 3"-amino groups, respectively, showed significant antimicrobial activity against Gram-(+) and -(-) bacteria. Several were particularly potent against Pseudomonus aeruginosa with MICs in the 1-2 microg/mL range.     

Temperature, growth rate, and body size in ectotherms: fitting pieces of a life-history puzzle

The majority of ectotherms grow slower but mature at a larger body size in colder environments. This phenomenon has puzzled biologists because classic theories of life-history evolution predict smaller sizes at maturity in environments that retard growth. During the last decade, intensive theoretical and empirical research has generated some plausible explanations based on nonadaptive or adaptive plasticity. Nonadaptive plasticity of body size is hypothesized to result from thermal constraints on cellular growth that cause smaller cells at higher temperatures, but the generality of this theory is poorly supported. Adaptive plasticity is hypothesized to result from greater benefits or lesser costs of delayed maturation in colder environments. These theories seem to apply well to some species but not others. Thus, no single theory has been able to explain the generality of temperature-size relationships in ectotherms. We recommend a multivariate theory that focuses on the coevolution of thermal reaction norms for growth rate and size at maturity. Such a theory should incorporate functional constraints on thermal reaction norms, as well as the natural covariation between temperature and other environmental variables.     

The monarch butterfly controversy: scientific interpretations of a phenomenon

The future development and use of agricultural biotechnology has been challenged by two preliminary studies indicating potential risk to monarch butterfly populations by pollen from corn engineered to express proteins from Bacillus thuringiensis. Likewise, these studies have also challenged the way in which science should be performed, published in scientific journals and communicated to the public at large. Herein, we provide a history of the monarch controversy to date. We believe a retrospective view may be useful for providing insights into the proper roles and responsibilities of scientists, the media and public agencies and the consequences when they go awry.     

Multiple substrate growth kinetics of Leptothrix discophora SP-6

The growth parameters of Leptothrix discophora SP-6 were quantified on the basis of the steady-state concentrations and utilization rates of pyruvate, dissolved oxygen, and concentration of microorganisms in a chemostat operated at 25 degrees C, pH 7.2, and an agitation rate of 350 rpm. The results showed that the microbial growth was limited by both pyruvate and dissolved oxygen. A combined growth kinetics model using Monod growth kinetics for pyruvate and Tessier growth kinetics for oxygen showed the best correlation with the experimental data when analyzed using an interactive multiple substrate model. The growth kinetics parameters and the respective confidence limits, estimated using the Monte Carlo simulation, were mu(max) = 0.576 +/- 0.021 h(-1), K(sMp) = 38.81 +/- 4.24 mg L(-1), K(sTo) = 0.39 +/- 0.04 mg L(-1), Y(X/p) = 0.150 (mg microorganism mg(-1) pyruvate), Y(X/o) = 1.24 (mg microorganism mg(-1) oxygen), the maintenance factors for pyruvate and oxygen were m(p) = 0.129 (mg pyruvate consumed mg(-1) microorganism h(-1)) and m(o) = 0.076 (mg oxygen consumed mg(-1) microorganism h(-1)), respectively.     

Solution structures of antimalarial drug-heme complexes

Paramagnetic metal centers [such as Fe(III) found within ferriprotoporphyrin IX heme (FPIX)] exert through space effects on the relaxation rate of nearby proton spins that depend critically on the metal-proton distance. We have measured these effects for all protons of several antimalarial drugs that bind to FPIX by systematically varying the drug:heme molar ratio in high field NMR experiments. These measurements allow us to determine precise FPIX Fe-drug H distances for the solution structures of noncovalent complexes formed between FPIX mu-oxo dimers and the antimalarial drugs chloroquine (CQ), quinine (QN), and quinidine (QD). Using these distances, we then performed distance restraint calculations to determine the lowest-energy solution structures of these complexes. Structures were solved for neutral, monoprotic (+1), and diprotic (+2) forms of the drugs. Analysis of these structures allows us to visualize for the first time the stereospecific differences between QN and QD binding to FPIX and the differences in populations of QN and QD solution structures upon changes in digestive vacuolar pH for drug resistant malarial parasites [Dzekunov, S. M., et al. (2000) Mol. Biochem. Parasitol. 110, 107-124]. The data indicate a previously unrecognized key role for the CQ aliphatic chain in stabilizing FPIX-CQ complexes, and suggest how lengthening or shortening the chain might perturb stability. We also define FPIX:drug stoichiometries of 2:1 for the complexes formed at physiological FPIX concentrations, in contrast to the 4:1 and 5:1 stoichiometries previously determined at higher FPIX concentrations [Dorn, A., et al. (1998) Biochem. Pharmacol. 55, 727-736]. These atomic resolution antimalarial drug-heme structures should help elucidate how these drugs inhibit formation of hemozoin during metabolism of heme within the malarial parasite Plasmodium falciparum and assist ongoing development of strategies for circumventing antimalarial drug resistance.     

Oxalic acid, a pathogenicity factor for Sclerotinia sclerotiorum, suppresses the oxidative burst of the host plant

Effective pathogenesis by the fungus Sclerotinia sclerotiorum requires the secretion of oxalic acid. Studies were conducted to determine whether oxalate aids pathogen compatibility by modulating the oxidative burst of the host plant. Inoculation of tobacco leaves with an oxalate-deficient nonpathogenic mutant of S. sclerotiorum induced measurable oxidant biosynthesis, but inoculation with an oxalate-secreting strain did not. Oxalate inhibited production of H(2)O(2) in tobacco and soybean cultured cell lines with a median inhibitory concentration of approximately 4 to 5 mM, a concentration less than that measured in preparations of the virulent fungus. Several observations also indicate that the inhibitory effects of oxalate are largely independent of both its acidity and its affinity for Ca(2)+. These and other data demonstrate that oxalate may inhibit a signaling step positioned upstream of oxidase assembly/activation but downstream of Ca(2)+ fluxes into the plant cell cytosol.