Comparison of urinary creatine with other biomarkers for the detection of 2-methoxyethanol-induced testicular damage

This study has compared different biomarkers of testicular damage, in particular evaluating urinary creatine as a non-invasive marker. Male rats were exposed to various doses of 2-methoxyethanol, a known testicular toxicant. Pathological damage, testis weight, urinary creatine and creatinine, serum lactate dehydrogenase, isozyme C4 (LDH-C4), and serum testosterone were determined. 2-Methoxyethanol caused dose-dependent pathological damage to the testes which was detectable at the lowest dose (100 mg kg^-1). Urinary creatine excretion was significantly raised at all doses but testis weight was only significantly decreased at the highest two doses (500, 750 mg kg^-1). Serum testosterone was only significantly decreased at 500 mg kg^-1 and LDH-C4 was not significantly increased at any dose. Therefore urinary creatine was the most sensitive marker of 2-methoxethanol-induced testicular damage and dysfunction.     

Imaginal disc development in a non-pupariating lethal mutant inDrosophila melanogaster

Summary Imaginal disc development in the non-pupariating lethall(1)npr-1, a mutant that maps to an ecdysone early puff site, is studied in situ, in vitro and in transplanted discs. Disc development is slightly abnormal from the middle of the third instar with severe abnormalities appearing after the rise in 20-hydroxyecdysone that triggers metamorphosis. The mutant discs only partly evaginate and do not undergo any of the detailed morphological changes characteristic of metamorphosis. Treatment of the mutant dises in vitro with colcemid and trypsin facilitates evagination but the appendages remain morphologically abnormal. A number of differentiative processes occur in mutant discs in situ and in discs transplanted into wild type hosts in spite of the absence of normal morphogenesis. Implications of the observations for normal disc development are discussed. Possible modes of action of thel(1)npr-1 gene are also discussed in light of the observation that the mutant gene maps to a locus which is thought to have a regulatory function in development.     

A Macrophyte-Based Rapid Biosurvey of Stream Water Quality: Restoration at the Watershed Scale

The restoration of chemically degraded rivers, lakes, and estuaries with large watersheds and pollution sources that are primarily diffuse in nature requires the grading of thousands of kilometers of tributary streams. Many population-and community-oriented biomonitoring methods have been developed that avoid the cost limitations of chemical/biomarker/bioassay approaches and the serious limitations of single-factor analysis as related to complex systems. In this study of the coastal plain and piedmont geomorphologic provinces of the Chesapeake Bay watershed, we have demonstrated a set of quantitative measures based on analysis of macrophyte populations that provide statistically significant separation of streams in accordance with their state-issued water quality rating. Macrophytes can be abundant and diverse in lower-order streams, and they demonstrate patterns of community structure and diversity similar to those of other organisms developed for biomonitoring of stream degradation. Unlike organisms previously and extensively used in biomonitoring techniques, however, macrophytes are considerably easier to identify and quantify. In addition, macrophyte techniques provide a range of measures of increasing sensitivity from species numbers at a few sites, to the presence/absence and abundance of indicator species, and, finally, to a diversity analysis based on easily identified species at an extended number of sites. We suggest that the ease of utilization of this methodology will allow repeated surveys of all streams in large watersheds with the invertebrate, fish and diatom biomonitoring to biomarking and chemical bioassays and finally analytical chemistry, progressively applied to verify and then identify specific pollution sources (“hot spots”) in a more limited number of problem streams.     

Dihydrotestosterone promotes fighting behavior of female mice

Female mice injected once with dihydrotestosterone (DHT) or testosterone propionate (TP) on the day of birth fought sooner following the commencement of chronic exposure to testosterone in adult life than did animals administered only the oil vehicle at birth. Also, adult nonperinatally androgenized females fought in response to chronic exposure to DHT or TP. It appears that DHT shares with TP the ability both to sensitize the perinatal CNS to testosterone and to activate fighting behavior in the adult.     

Secondary structure spatial conformation footprint: a novel method for fast protein structure comparison and classification

Background  

Recently a new class of methods for fast protein structure comparison has emerged. We call the methods in this class projection methods as they rely on a mapping of protein structure into a high-dimensional vector space. Once the mapping is done, the structure comparison is reduced to distance computation between corresponding vectors. As structural similarity is approximated by distance between projections, the success of any projection method depends on how well its mapping function is able to capture the salient features of protein structure. There is no agreement on what constitutes a good projection technique and the three currently known projection methods utilize very different approaches to the mapping construction, both in terms of what structural elements are included and how this information is integrated to produce a vector representation.     

Bacterial defenses against a natural antibiotic promote collateral resilience to clinical antibiotics

Bacterial opportunistic human pathogens frequently exhibit intrinsic antibiotic tolerance and resistance, resulting in infections that can be nearly impossible to eradicate. We asked whether this recalcitrance could be driven by these organisms’ evolutionary history as environmental microbes that engage in chemical warfare. Using Pseudomonas aeruginosa as a model, we demonstrate that the self-produced antibiotic pyocyanin (PYO) activates defenses that confer collateral tolerance specifically to structurally similar synthetic clinical antibiotics. Non-PYO-producing opportunistic pathogens, such as members of the Burkholderia cepacia complex, likewise display elevated antibiotic tolerance when cocultured with PYO-producing strains. Furthermore, by widening the population bottleneck that occurs during antibiotic selection and promoting the establishment of a more diverse range of mutant lineages, PYO increases apparent rates of mutation to antibiotic resistance to a degree that can rival clinically relevant hypermutator strains. Together, these results reveal an overlooked mechanism by which opportunistic pathogens that produce natural toxins can dramatically modulate the efficacy of clinical antibiotics and the evolution of antibiotic resistance, both for themselves and other members of clinically relevant polymicrobial communities.

This study shows that pyocyanin, a toxin secreted by the opportunistic pathogen Pseudomonas aeruginosa, induces defense responses that decrease the efficacy of structurally-similar clinical antibiotics and accelerate the evolution of antibiotic resistance, both in the producer and in other members of clinically-relevant polymicrobial communities.