Cryo-EM structure of the ancient eukaryotic ribosome from the human parasite Giardia lamblia

Giardiasis is a disease caused by the protist Giardia lamblia. As no human vaccines have been approved so far against it, and resistance to current drugs is spreading, new strategies for combating giardiasis need to be developed. The G. lamblia ribosome may provide a promising therapeutic target due to its distinct sequence differences from ribosomes of most eukaryotes and prokaryotes. Here, we report the cryo-electron microscopy structure of the G. lamblia (WB strain) ribosome determined at 2.75 Å resolution. The ribosomal RNA is the shortest known among eukaryotes, and lacks nearly all the eukaryote-specific ribosomal RNA expansion segments. In contrast, the ribosomal proteins are typically eukaryotic with some species-specific insertions/extensions. Most typical inter-subunit bridges are maintained except for one missing contact site. Unique structural features are located mainly at the ribosome’s periphery. These may be exploited as target sites for the design of new compounds that inhibit selectively the parasite’s ribosomal activity.     

Pseudo-fi+ I-Like Sex Factor, R62(I), Selective for Increased Pilus Synthesis

An I-like R factor, R62(I), inhibits F-like pilus synthesis and selects for mutant sex factors with a greatly increased capacity for pilus production.     

Atropine lowers blood pressure in normotensive rats through blockade of α-adrenergic receptors

Atropine sulfate elicited a dose-dependent decrease in blood pressure in normotensive rats at doses higher than needed to cause muscarinic blockade. This hypotensive effect was not altered by pretreatment with ganglionic or β-adrenergic blockers, but was fully abolished by α-adrenergic blockers. In addition, atropine inhibited the pressor response to α-agonists in a dose-dependent manner. The time course for hypotension and α-blockade were the same (onset < 1 minute; duration < 20 minutes). $\text{In vitro}$, atropine was found to be 200 times more potent in displacing the α₁-adrenergic receptor ligand ([³H] WB-4101) than the α₂-ligand ([³H] clonidine). Thus the observed hypotensive effect is apparently due to α-blockade as demonstrated $\text{in vivo}$ and $\text{in vitro}$.     

Brain-gonad axis and photoperiodically-stimulated sexual maturation in the slug,Limax maximus

Summary Physiological and endocrine mechanisms mediating long-day (LD 168) triggered sexual maturation were studied in the terrestrial slug,Limax maximus. Our findings were: (1) Maturation was induced in immature slugs seeing only short days (LD 816) after implantation of whole brains from maturing donors, but no development was found in sham-operated control slugs or in animals receiving implants of muscle from mature donors (Table 1). (2) Removal of the optic tentacles did not block maturation in LD 168 or promote maturation in LD 816 (Fig. 1). (3) Gonadectomy (castration) abolished penis development in 9 of 11 slugs exposed to LD 168 for periods of up to 31 weeks (Table 2). The results are consistent with a model forLimax reproductive tract development in which the perception of long days by extraocular receptors results in the secretion of a maturation hormone by the brain followed by the production of a separate male-phase sex hormone by the developing gonad.Abbreviations ASO accessory sex organs - DB dorsal bodies - FPSH female-phase sex hormone - MH maturation hormone - MPSH male-phase sex hormone This work was supported in part by grants from NSF (BNS 78-01408) and NIH (MH 27948) to P.G.S. The assistance of Mr. T.M. Gordon, Mr. J.L. Broyles, and Mr. M. Bullock is gratefully acknowledged.     

Comparison of the MSRV method with an in-house conventional method for the detection of Salmonella in various high and low moisture foods

In this trial an in-house conventional method was compared with the MSRV method for Salmonella detection. Various high and low moisture foodstuffs (121 and 116 samples respectively), some either artificially or naturally contaminated, were examined.
Eleven different serotypes of Salmonella were used to inoculate samples and no significant difference was observed in the sensitivity of any of the media used. Significantly lower numbers of false-positive results were obtained with the MSRV agar when compared to MLCB agar.
This work suggests that the MSRV method as used here, could be used to replace conventional Salmonella detection methods for both high and low moisture foodstuffs.     

Leader of the pack: gene mapping in dogs and other model organisms

The domestic dog offers a unique opportunity to explore the genetic basis of disease, morphology and behaviour. We share many diseases with our canine companions, including cancer, diabetes and epilepsy, making the dog an ideal model organism for comparative disease genetics. Using newly developed resources, whole-genome association in dog breeds is proving to be exceptionally powerful. Here, we review the different trait-mapping strategies, some key biological findings emerging from recent studies and the implications for human health. We also discuss the development of similar resources for other vertebrate organisms.     

Scaling of xylem vessels and veins within the leaves of oak species

General models of plant vascular architecture, based on scaling of pipe diameters to remove the length dependence of hydraulic resistance within the xylem, have attracted strong interest. However, these models have neglected to consider the leaf, an important hydraulic component; they assume all leaves to have similar hydraulic properties, including similar pipe diameters in the petiole. We examine the scaling of the leaf xylem in 10 temperate oak species, an important hydraulic component. The mean hydraulic diameter of petiole xylem vessels varied by 30% among the 10 oak species. Conduit diameters narrowed from the petiole to the midrib to the secondary veins, consistent with resistance minimization, but the power function scaling exponent differed from that predicted for stems. Leaf size was an organizing trait within and across species. These findings indicate that leaf vasculature needs to be included in whole-plant scaling models, for these to accurately reflect and predict whole-plant transport and its implications for performance and ecology.     

Behaviors in rhesus monkeys (Macaca mulatta) associated with activity counts measured by accelerometer

There are large individual differences in the daily pattern and level of physical activity in humans and other species. As it is becoming apparent that activity plays an integral role in a number of physiological processes including arousal, attention, cardiovascular health and body weight regulation, there is an increased interest in quantifying activity. Nonhuman primates are particularly useful experimental models for such studies in that they exhibit a repertoire of activity more similar to humans than the activity of animals such as rodents and domestic animals. Recent studies measuring activity in nonhuman primates have used omnidirectional accelerometers, often worn on collars; however, the exact behaviors and movements detected by monkeys wearing these devices have not yet been characterized. To test the hypothesis that collar-worn accelerometers primarily detect movements that involve movement of the whole body, 16 adult female rhesus monkeys, housed individually in stainless steel cages, wore loose-fitting collars with an attached small metal box housing an activity monitor (Actical omnidirectional accelerometer; MiniMitter Inc., Bend, OR) and behavior was videotaped. Videotaped behaviors were analyzed by frame-by-frame analysis. There was a significant correlation between total (all) movement revealed by videotape analysis and activity counts detected by the accelerometers (r(s)=0.612, P=0.012), primarily reflecting a strong correlation between whole body movement and activity counts (r(s)=0.647, P=0.007). In contrast, arm movement (r(s)=-0.221, P=0.412) and head/neck movement (r(s)=0.193, P=0.474) were not correlated with activity counts. These findings support the hypothesis that activity monitor placement on a collar allows for effective quantification of whole body movement in monkeys, and indicate that behaviors such as chewing and arm movement do not significantly influence activity recorded by collar-mounted accelerometers.     

Microchip placement for identification of birds

Individual identification is important for both laboratory and pet birds. This column gives instructions for placement of microchips in birds and discusses the advantages and disadvantages of this method of identification.     

Ribosome-binding and anti-microbial studies of the mycinamicins, 16-membered macrolide antibiotics from Micromonospora griseorubida

Macrolides have been effective clinical antibiotics for over 70 years. They inhibit protein biosynthesis in bacterial pathogens by narrowing the nascent protein exit tunnel in the ribosome. The macrolide class of natural products consist of a macrolactone ring linked to one or more sugar molecules. Most of the macrolides used currently are semi-synthetic erythromycin derivatives, composed of a 14- or 15-membered macrolactone ring. Rapidly emerging resistance in bacterial pathogens is among the most urgent global health challenges, which render many antibiotics ineffective, including next-generation macrolides. To address this threat and advance a longer-term plan for developing new antibiotics, we demonstrate how 16-membered macrolides overcome erythromycin resistance in clinically isolated Staphylococcus aureus strains. By determining the structures of complexes of the large ribosomal subunit of Deinococcus radiodurans (D50S) with these 16-membered selected macrolides, and performing anti-microbial studies, we identified resistance mechanisms they may overcome. This new information provides important insights toward the rational design of therapeutics that are effective against drug resistant human pathogens.