Impact of Changing Water Levels and Weather on <Emphasis Type="Italic">Oncomelania hupensis hupensis</Emphasis> Populations,the Snail Host of <Emphasis Type="Italic">Schistosoma japonicum</Emphasis>, Downstream of the Three Gorges Dam

Increasing evidence indicates that dams impact riverine ecosystems and human diseases. Poyang Lake, one of the largest schistosomiasis endemic environments in China, will change due to the construction of the Yangtze River Three Gorges Dam. We assess changes in Oncomelania hupensis hupensis, the snail host for Schistosoma japonicum, in response to changing water levels and weather from 1998 to 2002. In the 5 years following the major flooding of Poyang Lake in 1998, seasonal water levels have gradually decreased, concomitant with decreases in mean and variance of fall snail densities. Nonlinear relationships suggest that the highest spring density is associated with current, 2-, and 3-month prior temperatures of 18°, 9.1°, and 5.8°C, while the highest fall density is associated with 2- and 3-month prior water levels of 17 and 18 m, respectively. This suggests that lower, more stable water levels downstream of the dam may result in a reduction in mean fall densities and their variance. However, additional data are needed to determine whether snail populations that are typically destroyed by seasonal floods may live longer in more stable environments created by the dam.     

ABO(H) blood group A and B glycosyltransferases recognize substrate via specific conformational changes

The final step in the enzymatic synthesis of the ABO(H) blood group A and B antigens is catalyzed by two closely related glycosyltransferases, an alpha-(1-->3)-N-acetylgalactosaminyltransferase (GTA) and an alpha-(1-->3)-galactosyltransferase (GTB). Of their 354 amino acid residues, GTA and GTB differ by only four "critical" residues. High resolution structures for GTB and the GTA/GTB chimeric enzymes GTB/G176R and GTB/G176R/G235S bound to a panel of donor and acceptor analog substrates reveal "open," "semi-closed," and "closed" conformations as the enzymes go from the unliganded to the liganded states. In the open form the internal polypeptide loop (amino acid residues 177-195) adjacent to the active site in the unliganded or H antigen-bound enzymes is composed of two alpha-helices spanning Arg(180)-Met(186) and Arg(188)-Asp(194), respectively. The semi-closed and closed forms of the enzymes are generated by binding of UDP or of UDP and H antigen analogs, respectively, and show that these helices merge to form a single distorted helical structure with alternating alpha-3(10)-alpha character that partially occludes the active site. The closed form is distinguished from the semi-closed form by the ordering of the final nine C-terminal residues through the formation of hydrogen bonds to both UDP and H antigen analogs. The semi-closed forms for various mutants generally show significantly more disorder than the open forms, whereas the closed forms display little or no disorder depending strongly on the identity of residue 176. Finally, the use of synthetic analogs reveals how H antigen acceptor binding can be critical in stabilizing the closed conformation. These structures demonstrate a delicately balanced substrate recognition mechanism and give insight on critical aspects of donor and acceptor specificity, on the order of substrate binding, and on the requirements for catalysis.     

Rapid microRNA (miRNA) detection and classification via surface-enhanced Raman spectroscopy (SERS)

microRNAs (miRNA) are recognized as regulators of gene expression during development and cell differentiation as well as biomarkers of disease. Development of rapid and sensitive miRNA profiling methods is essential for evaluating the pattern of miRNA expression that varies across normal and diseased states. The ability to identify miRNA expression patterns is limited to cumbersome assays that often lack sensitivity and specificity to distinguish between different miRNA families and members. We evaluated a surface-enhanced Raman scattering (SERS) platform for detection and classification of miRNAs. The strength of the SERS-based sensor is its sensitivity to detect extremely low levels of analyte and specificity to provide the molecular fingerprint of the analyte. We show that the SERS spectra of related and unrelated miRNAs can be detected in near-real time, that detection is sequence dependent, and that SERS spectra can be used to classify miRNA patterns with high accuracy.     

A gene for speed: contractile properties of isolated whole EDL muscle from an alpha-actinin-3 knockout mouse

The actin-binding protein -actinin-3 is one of the two isoforms of -actinin that are found in the Z-discs of skeletal muscle. -Actinin-3 is exclusively expressed in fast glycolytic muscle fibers. Homozygosity for a common polymorphism in the ACTN3 gene results in complete deficiency of -actinin-3 in about 1 billion individuals worldwide. Recent genetic studies suggest that the absence of -actinin-3 is detrimental to sprint and power performance in elite athletes and in the general population. In contrast, -actinin-3 deficiency appears to be beneficial for endurance athletes. To determine the effect of -actinin-3 deficiency on the contractile properties of skeletal muscle, we studied isolated extensor digitorum longus (fast-twitch) muscles from a specially developed -actinin-3 knockout (KO) mouse. -Actinin-3-deficient muscles showed similar levels of damage to wild-type (WT) muscles following lengthening contractions of 20% strain, suggesting that the presence or absence of -actinin-3 does not significantly influence the mechanical stability of the sarcomere in the mouse. -Actinin-3 deficiency does not result in any change in myosin heavy chain expression. However, compared with -actinin-3-positive muscles, -actinin-3-deficient muscles displayed longer twitch half-relaxation times, better recovery from fatigue, smaller cross-sectional areas, and lower twitch-to-tetanus ratios. We conclude that -actinin-3 deficiency results in fast-twitch, glycolytic fibers developing slower-twitch, more oxidative properties. These changes in the contractile properties of fast-twitch skeletal muscle from -actinin-3-deficient individuals would be detrimental to optimal sprint and power performance, but beneficial for endurance performance. extensor digitorum longus     

Induction of normal levels of genetic transformation in a class of endonuclease-defective mutants of Pneumococci.

Pneumococcal mutants were isolated that showed no zones of DNA hydrolysis around the bacterial colonies, even after prolonged incubation on the surface of agar plates containing DNA and methylgreen. Lysates of such mutants contained only very low levels of endonuclease activity; the mutants were also defective in genetic transformation even though they could still bind DNA to their surface. However, the same mutants could be made to undergo normal, high frequency genetic transformation by treatment with the activator protein, under appropriate conditions. The same treatment caused no detectable increase in the endonuclease level. Poor transformability of these mutants seems to be related to an inhibitory factor(s) released into the growth medium. Activation in the presence of this factor(s) leads to an abnormal (non-productive) DNA adsorption-both in mutant and in wild type pneumococci.     

The Assignment of the 13C-NMR Spectrum of Lysocellin and Its Biosynthesis

The complete ¹⁸C-NMR assignment of lysocellin sodium salt has been obtained based on the ¹³C-¹³C double labeling method and comparison with its retroaldol degradation product as well as a structurally related polyether antibiotic, lasalocid A.

In parallel, the biosynthesis of lysocellin was investigated by feeding ¹³C-labeled precursors followed by analyzing the resulting labeling patterns of the ¹³C-NMR spectra; a pathway to the antibiotic molecule is suggested which proceeds through condensation of two butyrate, eight propionate and one acetate units.

In addition, a conversion of butyrate to propionate during the metabolic process has been disclosed.     

X-ray study on egg-yolk lecithin: Unit cell data and electron density profile

The unit cell dimensions and space group of egg-yolk lecithin (l-α-phosphatidylcholine) in the crystalline state were obtained from a set of X-ray fibre diagrams recorded from specimens oriented in two different axes; $\text{a = 8.84}\text{A}\text{?}\text{± 0.05}\text{A}\text{?}\text{, b = 10.07}\text{A}\text{?}\text{± 0.05}\text{A}\text{?}\text{, c = 54.69}\text{A}\text{?}\text{± 0.05}\text{A}\text{?}$, with space group P2₁2₁2, and four molecules per unit cell. From the 00l reflexions up to the 25th order, an electron density profile is obtained which is consistent with a probable structure of the molecule.     

Genetic Transformation in a Synchronous Culture of Streptococcus pneumoniae

Cultures of synchronized Streptococcus pneumoniae cells were prepared by amino acid starvation followed by refeeding, and the cellular reactivity towards the competence-activator for genetic transformation, i.e., competence induction on the addition of the activator, was investigated. Cyclical fluctuation in the level of competence was observed during the cell cycle. Especially, cells at division showed reduced cellular ability to develop competence. It was also observed that deprivation of nutritionally required amino acids had quite diiferent effects on the induction of competence, depending upon the amino acid removed: glutamine or serine starvation caused a significant reduction in the level of competence induced by the activator, whereas deprivation of other amino acids (histidine, leucine, isoleucine, valine, arginine and cysteine) did not.