Two novel loci underlie natural differences in Caenorhabditis elegans abamectin responses

Parasitic nematodes cause a massive worldwide burden on human health along with a loss of livestock and agriculture productivity. Anthelmintics have been widely successful in treating parasitic nematodes. However, resistance is increasing, and little is known about the molecular and genetic causes of resistance for most of these drugs. The free-living roundworm Caenorhabditis elegans provides a tractable model to identify genes that underlie resistance. Unlike parasitic nematodes, C. elegans is easy to maintain in the laboratory, has a complete and well annotated genome, and has many genetic tools. Using a combination of wild isolates and a panel of recombinant inbred lines constructed from crosses of two genetically and phenotypically divergent strains, we identified three genomic regions on chromosome V that underlie natural differences in response to the macrocyclic lactone (ML) abamectin. One locus was identified previously and encodes an alpha subunit of a glutamate-gated chloride channel (glc-1). Here, we validate and narrow two novel loci using near-isogenic lines. Additionally, we generate a list of prioritized candidate genes identified in C. elegans and in the parasite Haemonchus contortus by comparison of ML resistance loci. These genes could represent previously unidentified resistance genes shared across nematode species and should be evaluated in the future. Our work highlights the advantages of using C. elegans as a model to better understand ML resistance in parasitic nematodes.     

Testis size,epididymis weight,and sperm competition in rhesus macaques

The intensity of sperm competition is often measured using the gonadosomatic index (testes/body weight). But sperm competition could be mediated more by size of the epididymis than by size of the testicles, and little information is available on the relationship between testicular and epididymal size. We found that both organs were positively correlated in size among male rhesus macaques. Body weight accounted for over 70% of the variance in testicle size and volumetric estimates of testicle size accurately reflected testicle weight. We conclude that methods for ascertaining testicle size are accurate, but the covariation in size between testicles and epididymis will hamper understanding of the physiological mechanisms involved in sperm competition in primates. © 1993 Wiley-Liss, Inc.     

Effect of oxygen and air flow on xylanolytic and cellulolytic activity from bacterial cultures grown on bagasse pith

Summary The xylanolytic and cellulolytic activity fromCellulomanas were reduced by high O₂ concentrations in continous culture as well as by an air flow passed trough the samples, suggesting an inhibition or inactivation of enzymes in such conditions.     

Impact of vaginal microbiome communities on HIV antiretroviral-based pre-exposure prophylaxis (PrEP) drug metabolism

Despite the efficacy of antiretroviral-based pre-exposure prophylactics (PrEP) in men who have sex with men, studies in women have produced widely varying outcomes. Recent evidence demonstrates that vaginal microbial communities are associated with increased HIV acquisition risk and may impact PrEP efficacy. Here, we investigate the mechanisms underlying how vaginal bacteria alter PrEP drug levels and impact HIV infection rates ex vivo. Using cervicovaginal lavages (CVLs) from women with or without bacterial vaginosis (BV), we identified microbial metabolism of PrEP drugs in BV samples through LC-MS/MS analysis of soluble drug levels and metabolite formation in dual T-cell cultures. CVL samples were assessed for microbiome analysis using sequencing of bacterial 16S rRNA genes. We also observed non-Lactobacillus bacteria that are associated with BV may potentially impact PrEP efficacy through increased HIV infection rates in co-cultures containing Lactobacillus or BV bacteria, PrEP drugs, CEM-GFP cells, and HIV-1_LAI virus. Finally, we used these data to develop a novel predictive mathematical simulation modeling system to predict these drug interactions for future trials. These studies demonstrate how dysbiotic vaginal microbiota may impact PrEP drugs and provides evidence linking vaginal bacteria to PrEP efficacy in women.     

Chrysonila sitophila (TFB-27441): A hyperlignolytic strain

Summary C. sitophila strain TFB-27441 showed 2–3 times higher lignolytic activity thanPhanerochaete chrysosporium (BKM-F-1767 strain). Lignin had a marked effect on the ligninase activity indicating that some induction or activation mechanism is involved in lignin degradation byC. sitophila.     

Taste systems of the petrosal ganglion of the rat glossopharyngeal nerve

Single unit recordings were taken from sensory ganglion cellsin the petrosal ganglion (PG) of the glossopharyngeal nerveof the rat. These taste units were examined with respect tospontaneous and evoked discharge patterns and responsivenessto a wide variety of chemical compounds, most of natural occurrence.Spontaneous activity patterns, with few exceptions, tended tobe extremely irregular with both bursting (clusters of 2–3spikes) and grouping (large groups of spikes as in evoked discharges).Most interspike interval histograms of spontaneous activitywere multimodal, similar to rat geniculate ganglion (GG) units.Evoked discharges usually displayed grouping of spikes, andlong latencies of onset and persistence of discharge after rinsewere sometimes seen. Little response was shown to nucleotidesor salts. Units responsive to amino acids tended to show largedischarge to only one or two amino acids; and the most responsiveamino acid usually varied from cell to cell. Units responsiveto alkaloids only responded to a few alkaloids with atropineand quinine being the most stimulatory. Units responsive toacids only discharged to a few of the acids tested and oftenacids of low pH elicited no discharge. Saccharin activated unitsresponsive to both sugar and alkaloids. A few units highly responsiveto both sugar and alkaloids were seen. The units were placedinto four clusters on the basis of chemicals activating themand certain neurophysiological characteristics: PG salt units,PG acid units and, tentatively, amino acid (sugar) units andX (alkaloid and alkaloid plus) units. The PG salt units didnot show the exclusive sensitivity to sodium and lithium compoundsas did the GG salt units. The PG acid units could also be differentiatedfrom the GG acid units. The petrosal amino acid and X units,on the other hand, could not be differentiated from similarunits in the rat GG.     

Structure of the precursor to an enzyme mediating COOH-terminal amidation in peptide biosynthesis

Many bioactive peptides terminate with an amino acid alpha-amide at their COOH terminus. The enzyme responsible for this essential posttranslational modification is known as peptidyl-glycine alpha-amidating monooxygenase or PAM. We identified cDNAs encoding the enzyme by using antibodies to screen a bovine intermediate pituitary lambda gt11 expression library. Antibodies to a beta-galactosidase/PAM fusion protein removed PAM activity from bovine pituitary homogenates. The 108,207 dalton protein predicted by the complete cDNA is approximately twice the size of purified PAM. An NH2-terminal signal sequence and short propeptide precede the NH2 terminus of purified PAM. The sequences of several PAM cyanogen bromide peptides were localized in the NH2-terminal half of the predicted protein. The cDNA encodes an additional 430 amino acid intragranular domain followed by a putative membrane spanning domain and a hydrophilic cytoplasmic domain. The forms of PAM purified from bovine neurointermediate pituitary may be generated by endoproteolytic cleavage at a subset of the 10 pairs of basic amino acids in the precursor. High levels of PAM mRNA were found in bovine pituitary and cerebral cortex. In corticotropic tumor cells, levels of PAM mRNA and pro-ACTH/endorphin mRNA were regulated in parallel by glucocorticoids and CRF.     

Quantitative assessment of vaginal microflora during use of tampons of various compositions.

Although the effect of vaginal tampons on the microbial flora during menstruation has recently been studied by several investigators, quantitative effects attributable to particular tampon fibers have received less attention. The purposes of the present study were (i) to determine and then to compare the effects of polyacrylate rayon tampons and viscose rayon tampons on the normal vaginal flora, (ii) to compare quantitative bacterial counts obtained from these tampons with those obtained from concomitant vaginal swabs, and (iii) to determine whether either of these tampon types alters the vaginal microflora when compared with the microflora in the same women using all-cotton tampons or external catamenial pads. Tampon and swab samples were obtained at predetermined times from 18 women for an average of seven menstrual cycles. Samples consisting of swabs from women wearing menstrual pads were compared with swab and tampon samples taken at predetermined times during the menstrual cycle from women using cotton, polyacrylate rayon, or viscose rayon tampons. Samples were analyzed for total aerobic, facultative, and anaerobic bacterial counts. Statistical evaluation of the results indicated that, on the whole, total bacterial counts decreased during menstruation and that the numbers of bacteria in tampons tended to be lower than those in swab samples taken at the same time. The tampon type had little effect on the vaginal microflora.