A new rodent species of the genus Mus (Rodentia: Muridae) confirms the biogeographical uniqueness of the isolated forests of southern Ethiopia

Organisms Diversity & Evolution - The Ethiopian highlands represent the largest part of the Eastern Afromontane Biodiversity Hotspot (EAMBH). Their fauna and flora are largely unique....     

Drivers of temporal changes in temperate forest plant diversity vary across spatial scales

Global biodiversity is affected by numerous environmental drivers. Yet, the extent to which global environmental changes contribute to changes in local diversity is poorly understood. We investigated biodiversity changes in a meta‐analysis of 39 resurvey studies in European temperate forests (3988 vegetation records in total, 17–75 years between the two surveys) by assessing the importance of (i) coarse‐resolution (i.e., among sites) vs. fine‐resolution (i.e., within sites) environmental differences and (ii) changing environmental conditions between surveys. Our results clarify the mechanisms underlying the direction and magnitude of local‐scale biodiversity changes. While not detecting any net local diversity loss, we observed considerable among‐site variation, partly explained by temporal changes in light availability (a local driver) and density of large herbivores (a regional driver). Furthermore, strong evidence was found that presurvey levels of nitrogen deposition determined subsequent diversity changes. We conclude that models forecasting future biodiversity changes should consider coarse‐resolution environmental changes, account for differences in baseline environmental conditions and for local changes in fine‐resolution environmental conditions.     

Stereoselective pharmacokinetics and metabolism of flobufen in guinea pigs

Stereoselective aspects of pharmacokinetics and metabolism of a chiral nonsteroidal antiinflammatory drug, flobufen, 4-(2', 4'-difluorobiphenyl-4-yl)-2-methyl-4-oxobutanoic acid, were studied in male guinea pigs after p.o. administration of racemic flobufen (rac-flobufen) at a dose of 10 mg/kg. Blood samples were collected at intervals over 16 h after the administration of rac-flobufen for the quantification of flobufen enantiomers and their respective metabolites in plasma by chiral high-performance liquid chromatography (HPLC). Compartmental pharmacokinetic analysis was used to determine pharmacokinetic parameters of R- and S-flobufen. The plasma concentrations of the S- and R-enantiomers differed significantly during the experimental period. The S/R-enantiomeric ratio in 7plasma reached a maximum value of 10.1 at 240 min postdose. The oral clearance value of R-flobufen was five times higher than S-flobufen. The other pharmacokinetic parameters (K(e), T(1/2), V(SS)/F, MRT) of the enantiomers also differed substantially. All four stereoisomers of the dihydrometabolite of flobufen were detected in plasma with varying concentrations. Metabolite 17203 [4-(2,4-difluorophenyl)-phenylacetic acid] exhibited a relatively longer residence time compared to that noted for the enantiomers of the parent compound. Pharmacokinetics of the flobufen enantiomers were stereoselective in guinea pigs. The metabolism of flobufen was complex. However, metabolite 17203 seemed to be the main metabolite of flobufen that may be responsible for its relatively long-lasting antiphlogistic and immunomodulatory effects.     

Does a linear position transducer placed on a stick and belt provide sufficient validity and reliability of countermovement jump performance outcomes?

Manufacturers recommend that linear position transducers (LPTs) should be placed on the side of a barbell (or wooden dowel) to measure countermovement jump (CMJ) height, but the validity and reliability of this placement have not been compared to other attachment sites. Since this recommended attachment site is far from the centre of mass, a belt attachment where the LPT is placed between the feet may increase the validity and reliability of CMJ data. Thirty-six physical education students participated in the study (24.6 ± 4.3 years; 177.0 ± 7.7 cm; 77.2 ± 9.0 kg). Parameters from the two LPT attachments (barbell and belt) were simultaneously validated to force plate data, where the nature of bias was analysed (systematic vs random). The within-session and between-session reliability of both attachment sites were compared to force plate data using a test-retest protocol of two sets of 5 CMJs separated by 7 days. The LPT provided highly reliable and valid measures of peak force, mean force, mean power, and jump height, where the bias was mostly systematic (r² > 0.7; ICC > 0.9). Peak velocity, mean velocity, and peak power were in very good agreement with the force plate and were highly reliable (r² > 0.5; ICC > 0.7). Therefore, both attachment sites produced similar results with a systematic bias compared to force plate data. Thus, both attachment sites seem to be valid for assessing CMJs when the measuring tool and site remain consistent across measurements. However, if LPT data are to be compared to force plate data, recalculation equations should be used.     

Inhibition of enzymatic reactions. A rapid method to determine the index pI50

The activity of every substance I inhibiting an enzymatic reaction can be approximately evaluated by the index PI50. This paper describes a simple and fast method of estimate and/ or determination of this index. The method is based on the linearity of the dependence of the ratio of reaction rates of uninhibited and inhibited reaction vs. concentration of the inhibitor at constant initial substrate and enzyme concentrations for fully competitive, noncompetitive, uncompetitive and mixed type of inhibition by the one inhibitor. The validity of the method is demonstrated by four inhibitors of hydrolysis of acetylthiocholine by butyrylcholine esterase.     

Sucking and allosucking duration in farmed red deer (Cervus elaphus)

Sucking duration in ungulates does not only mean milk transfer, but is also associated with maternal care in general. It seems to be a reflection of offspring demand rather than solely milk transfer rate. Thus, the objective of this study was to discriminate between sucking and allosucking (i.e. sucking non-maternal hind) behaviour in red deer according to the sucking duration.We hypothesized that: (1) calves should suck longer from their mothers than allosuck from non-maternal hinds; (2) sucking duration of calves frequently nursed by a particular non-maternal hind should be longer than that of calves occasionally allonursed; (3) sucking duration should be longer for bouts including one calf than two or more calves sucking simultaneously; (4) male calves should suck and allosuck longer than female calves; and (5) primiparous hinds should nurse and allonurse longer than multiparous hinds. We observed sucking behaviour of 25 hinds and their 38 calves (from birth until the youngest calf reached one month of age) in two seasons. We recorded 1730 sucking bouts, of which 11.62% in the first season and 4.37% in the second season were non-filial. The duration of filial sucking was significantly longer than non-filial sucking. A large individual variance in the incidence of non-filial sucking in both the calves and hinds was found. Therefore, the non-filial hind–calf pairs were categorized in two clusters according to the frequency of nursing non-filial calves for one hind in relationship to all nursing events for this hind by a cluster analysis (PROC CLUSTER, SAS). We used a general linear mixed model, GLMM (PROC MIXED, SAS) to test the influence of hind relationship to the nursed calf (filial, frequently allosucking non-filial, or occasionally allosucking non-filial pair). Sucking duration of occasionally allosucking non-filial calves was only marginally different from that of filial calves. There was no difference between the two groups of non-filial calves. Multiple sucking bouts were shorter than those with one calf. Male calves sucked longer than female calves; however, the greatest difference was recorded between frequently allosucking non-filial pairs of both sexes. Frequently allosucking non-filial males sucked the longest and differently from occasionally allosucking non-filial males. Frequently allosucking non-filial females sucked the shortest and differently from filial calves of both sexes. It is more likely that allosucking seems to be more important for male rather than female calves.Therefore, it is concluded that allosucking calves differ in their sucking behaviour and two types of allosuckers (frequent and occasional) should be taken into account when analyzing allosuckling behaviour.     

Identifying new sex-linked genes through BAC sequencing in the dioecious plant Silene latifolia

Background

Silene latifolia represents one of the best-studied plant sex chromosome systems. A new approach using RNA-seq data has recently identified hundreds of new sex-linked genes in this species. However, this approach is expected to miss genes that are either not expressed or are expressed at low levels in the tissue(s) used for RNA-seq. Therefore other independent approaches are needed to discover such sex-linked genes.

Results

Here we used 10 well-characterized S. latifolia sex-linked genes and their homologs in Silene vulgaris, a species without sex chromosomes, to screen BAC libraries of both species. We isolated and sequenced 4 Mb of BAC clones of S. latifolia X and Y and S. vulgaris genomic regions, which yielded 59 new sex-linked genes (with S. vulgaris homologs for some of them). We assembled sequences that we believe represent the tip of the Xq arm. These sequences are clearly not pseudoautosomal, so we infer that the S. latifolia X has a single pseudoautosomal region (PAR) on the Xp arm. The estimated mean gene density in X BACs is 2.2 times lower than that in S. vulgaris BACs, agreeing with the genome size difference between these species. Gene density was estimated to be extremely low in the Y BAC clones. We compared our BAC-located genes with the sex-linked genes identified in previous RNA-seq studies, and found that about half of them (those with low expression in flower buds) were not identified as sex-linked in previous RNA-seq studies. We compiled a set of ~70 validated X/Y genes and X-hemizygous genes (without Y copies) from the literature, and used these genes to show that X-hemizygous genes have a higher probability of being undetected by the RNA-seq approach, compared with X/Y genes; we used this to estimate that about 30 % of our BAC-located genes must be X-hemizygous. The estimate is similar when we use BAC-located genes that have S. vulgaris homologs, which excludes genes that were gained by the X chromosome.

Conclusions

Our BAC sequencing identified 59 new sex-linked genes, and our analysis of these BAC-located genes, in combination with RNA-seq data suggests that gene losses from the S. latifolia Y chromosome could be as high as 30 %, higher than previous estimates of 10-20 %.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1698-7) contains supplementary material, which is available to authorized users.     

Olomoucine II,but Not Purvalanol A,Is Transported by Breast Cancer Resistance Protein (ABCG2) and P-Glycoprotein (ABCB1)

Purine cyclin-dependent kinase inhibitors have been recognized as promising candidates for the treatment of various cancers; nevertheless, data regarding interaction of these substances with drug efflux transporters is still lacking. Recently, we have demonstrated inhibition of breast cancer resistance protein (ABCG2) by olomoucine II and purvalanol A and shown that these compounds are able to synergistically potentiate the antiproliferative effect of mitoxantrone, an ABCG2 substrate. In this follow up study, we investigated whether olomoucine II and purvalanol A are transported by ABCG2 and ABCB1 (P-glycoprotein). Using monolayers of MDCKII cells stably expressing human ABCB1 or ABCG2, we demonstrated that olomoucine II, but not purvalanol A, is a dual substrate of both ABCG2 and ABCB1. We, therefore, assume that pharmacokinetics of olomoucine II will be affected by both ABCB1 and ABCG2 transport proteins, which might potentially result in limited accumulation of the compound in tumor tissues or lead to drug-drug interactions. Pharmacokinetic behavior of purvalanol A, on the other hand, does not seem to be affected by either ABCG2 or ABCB1, theoretically favoring this drug in the potential treatment of efflux transporter-based multidrug resistant tumors. In addition, we observed intensive sulfatation of olomoucine II in MDCKII cell lines with subsequent active efflux of the metabolite out of the cells. Therefore, care should be taken when performing pharmacokinetic studies in MDCKII cells, especially if radiolabeled substrates are used; the generated sulfated conjugate may largely contaminate pharmacokinetic analysis and result in misleading interpretation. With regard to chemical structures of olomoucine II and purvalanol A, our data emphasize that even drugs with remarkable structure similarity may show different pharmacokinetic behavior such as interactions with ABC transporters or biotransformation enzymes.