Terpene chemodiversity of relict conifers Picea omorika, Pinus heldreichii, and Pinus peuce, endemic to Balkan

Terpenes are often used as ecological and chemotaxonomic markers of plant species, as well as for estimation of geographic variability. Essential oils of relic and Balkan endemic/subendemic conifers, Picea omorika, Pinus heldreichii, and P. peuce, in central part of Balkan Peninsula (Serbia and Montenegro), on the level of terpene classes and common terpene compounds were investigated. In finding terpene combinations, which could show the best diversity between species and their natural populations, several statistical methods were applied. Apart from the content of different terpene classes (P. omorika has the most abundant O-containing monoterpenes and sesquiterpenes; P. heldreichii and P. peuce have the largest abundance of sesquiterpene and monoterpene hydrocarbons, resp.), the species are clearly separated according to terpene profile with 22 common compounds. But, divergences in their populations were established only in combination of several compounds (specific for each species), and they were found to be the results of geomorphologic, climatic, and genetic factors. We found similarities between investigated species and some taxa from literature with respect to terpene composition, possibly due to hybridization and phylogenetic relations. Obtained results are also important regarding to chemotaxonomy, biogeography, phylogeny, and evolution of these taxa.     

Synchronization properties of networks of electrically coupled neurons in the presence of noise and heterogeneities

We investigate how synchrony can be generated or induced in networks of electrically coupled integrate-and-fire neurons subject to noisy and heterogeneous inputs. Using analytical tools, we find that in a network under constant external inputs, synchrony can appear via a Hopf bifurcation from the asynchronous state to an oscillatory state. In a homogeneous net work, in the oscillatory state all neurons fire in synchrony, while in a heterogeneous network synchrony is looser, many neurons skipping cycles of the oscillation. If the transmission of action potentials via the electrical synapses is effectively excitatory, the Hopf bifurcation is supercritical, while effectively inhibitory transmission due to pronounced hyperpolarization leads to a subcritical bifurcation. In the latter case, the network exhibits bistability between an asynchronous state and an oscillatory state where all the neurons fire in synchrony. Finally we show that for time-varying external inputs, electrical coupling enhances the synchronization in an asynchronous network via a resonance at the firing-rate frequency.

Chemodiversity of Nonacosan‐10‐ol and n‐Alkanes in the Needle Wax of Pinus heldreichii

This is the first report of individual variability and population diversity of the contents of nonacosan‐10‐ol and n‐alkanes in the needle cuticular waxes of Bosnian pines originated from Montenegro, regarded as Pinus heldreichii var. leucodermis, and from Serbia, regarded as P. heldreichii var. pan?i?i. The amount of nonacosan‐10‐ol varied individually from 27.4 to 73.2% (55.5% in average), but differences between the four investigated populations were not statistically confirmed. The size of the n‐alkanes ranged from C₁₈ to C₃₃. The most abundant n‐alkanes were C₂₃, C₂₇, and C₂₅ (12.2, 11.2, and 10.8% in average, resp.). The carbon preference index (CPI) of the n‐alkanes ranged from 0.8 to 3.1 (1.6 in average), while the average chain length (ACL) ranged from 20.9 to 26.5 (24.4 in average). Long‐chain and mid‐chain n‐alkanes prevailed (49.6 and 37.9% in average, resp.). It was also found that the populations of P. heldreichii var. leucodermis had predominantly a narrower range of n‐alkanes (C₁₈? C₃₁) than the trees of the variety pan?i?i (C₁₈? C₃₃). Differences between the varieties were also significant for most of the other characteristics of the n‐alkane pattern (e.g., most abundant n‐alkanes, CPI, ACL, and relative proportion of short‐, mid‐, and long‐chain n‐alkanes). The principle component and cluster analyses of eleven n‐alkanes confirmed the significant diversity of these two varieties.     

Spatial fiber type distribution in normal human muscle: Histochemical and tensiomyographical evaluation

The variability of fiber type distribution in nine limb muscles was examined with histochemical and tensiomyographical (TMG) methods in two groups of 15 men aged between 17 and 40 years. The aim of this study was to determine the extent to which the relative occurrence of different fiber types and subtypes varies within human limb muscles in function to depth and to predict fiber type proportions with a non-invasive TMG method.

The distribution of different fiber types varied within the muscles, as a function of depth, with a predominance of type 2b fibers at the surface and type 1 fibers in deeper regions of the muscle. For all the analyzed muscles the contraction times measured at stimulus intensity 10% of supramaximal stimulus (10% MS) were significantly (p<0.05) shorter than the contraction times measured at 50% of supramaximal stimulus intensity (50% MS). The Pearson's correlation coefficient between percentage of type 1 muscle fibers measured at the surface of the muscle and contraction time at 10% MS, obtained by TMG was statistically significant (r=0.76,P<0.01). Also the Pearson's correlation coefficient between percentage of type 1 muscle fibers measured in the deep region of the muscle and contraction time at 50% MS obtained by TMG was also statistically significant (r=0.90,P<0.001).

These findings suggest that the contraction time obtained by TMG may be useful for non-invasive examining of muscle fiber types spatial distribution in humans.     

The patients with clinically isolated syndrome and relapsing remitting multiple sclerosis show different levels of advanced protein oxidation products and total thiol content in plasma and CSF

Advanced oxidation protein products (AOPP) and total thiol (SH) groups levels in plasma and CSF were studied in a cohort of 50 clinically isolated syndrome (CIS) and 57 relapsing remittent multiple sclerosis (RRMS) patients related to 20 control group (CG) patients’ values. The obtained results were compared regarding patients demographic, biochemical, clinical (EDSS) and MRI features (total T2 weighted lesions number and Gd enhancement lesion volume).     

β-Lactam and glycopeptide antibiotics: first and last line of defense?

Most infections are caused by bacteria, many of which are ever-evolving and resistant to nearly all available antibiotics. β-Lactams and glycopeptides are used to combat these infections by inhibiting bacterial cell-wall synthesis. This mechanism remains an interesting target in the search for new antibiotics in light of failed genomic approaches and the limited input of major pharmaceutical companies. Several strategies have enriched the pipeline of bacterial cell-wall inhibitors; examples include combining screening strategies with lesser-explored microbial diversity, or reinventing known scaffolds based on structure-function relationships. Drugs developed using novel strategies will contribute to the arsenal in fight against the continued emergence of bacterial resistance.     

Composition of n‐Alkanes in Natural Populations of Pinus nigra from Serbia – Chemotaxonomic Implications

This is the first report on the composition and variability of the needle‐wax n‐alkanes in natural populations of Pinus nigra in Serbia. Samples of 195 trees from seven populations belonging to several infraspecific taxa (ssp. nigra, var. gocensis, ssp. pallasiana, and var. banatica) were analyzed. In general, the size of the n‐alkanes ranged from C₁₆ to C₃₃, with the exception of ssp. nigra, for which it ranged from C₁₈ to C₃₃. The most abundant were C₂₃‐, C₂₅‐, C₂₇‐, and C₂₉‐alkanes. The needle waxes of Populations I–III and V were characterized by a higher content of C₂₃‐, C₂₅‐, and C₂₇‐alkanes and a lower content of C₂₄‐, C₂₆‐, C₂₈‐, and C₃₀‐alkanes, compared to the other populations, and the trees of these populations could be assigned to ssp. nigra. The samples of Population VI were characterized by higher amounts of C₂₂‐, C₂₄‐, C₃₀‐, and C₃₂‐alkanes and lower amounts of C₂₅‐ and C₂₇‐alkanes, and the trees could be considered as ssp. pallasiana. The samples of Population VII, consisting of trees belonging to var. banatica, were richer in C₂₉‐, C₃₁‐, and C₃₃‐alkanes. The wax compositions of Populations IV and V, both composed of trees previously determined as P. nigra var. gocensis, showed a tendency of splitting. Indeed, the alkane composition of Population IV was closer to that of ssp. pallasiana pines, while that of Population V was more similar to that of ssp. nigra pines. From the results presented here, it is obvious that in the central part of the Balkan Peninsula, significant diversification and differentiation of the populations of black pine exists, and these populations could be defined as different intraspecific taxa. Our results also indicate the validity of n‐alkanes as chemotaxonomic characters within this aggregate.     

Combinations of Genetic Data Present in Bipolar Patients,but Absent in Control Persons

The main objective of the study was to find combinations of genetic variants significantly associated with bipolar disorder. In a previous study of bipolar disorder, combinations of three single nucleotide polymorphism (SNP) genotypes taken from 803 SNPs were analyzed, and four clusters of combinations were found to be significantly associated with bipolar disorder. In the present study, combinations of four SNP genotypes taken from the same 803 SNPs were analyzed, and one cluster of combinations was found to be significantly associated with bipolar disorder. Combinations from the new cluster and from the four previous clusters were identified in the genomes of 209 of the 607 patients in the study whereas none of the 1355 control participants had any of these combinations in their genome.     

The genetic structure of cattle populations (Bos taurus) in northern Eurasia and the neighbouring Near Eastern regions: implications for breeding strategies and conservation

We investigated the genetic structure and variation of 21 populations of cattle (Bos taurus) in northern Eurasia and the neighbouring Near Eastern regions of the Balkan, the Caucasus and Ukraine employing 30 microsatellite markers. By analyses of population relationships, as well as by a Bayesian-based clustering approach, we identified a genetic distinctness between populations of modern commercial origin and those of native origin. Our data suggested that northern European Russia represents the most heavily colonized area by modern commercial cattle. Further genetic mixture analyses based on individual assignment tests found that native Red Steppe cattle were also employed in the historical breeding practices in Eastern Europe, most probably for incorporating their strong and extensive adaptability. In analysis of molecular variance, within-population differences accounted for approximately 90% of the genetic variation. Despite some correspondence between geographical proximity and genetic similarity, genetic differentiation was observed to be significantly associated with the difference in breeding purpose among the European populations (percentage of variance among groups and significance: 2.99%, P = 0.02). Our findings give unique genetic insight into the historical patterns of cattle breeding practices in the former Soviet Union. The results identify the neighbouring Near Eastern regions such as the Balkan, the Caucasus and Ukraine, and the isolated Far Eastern Siberia as areas of 'genetic endemism', where cattle populations should be given conservation priority. The results will also be of importance for cost-effective management of their future utilization.     

Synthesis and anti-aromatase activity of some new steroidal D-lactones

Starting from D-seco derivatives of 5-androstene 1-3, the D-homo lactones, 4 and 5, were synthesized. By the Oppenauer oxidation and/or by dehydration of 4 and 5 with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) or 2,3,5,6-tetrachloro-1,4-benzoquinone (chloranil), the corresponding D-lactones 6-12 were obtained. The structures of 6 and 10 were unambiguously proved by the appropriate X-ray structural analysis. Anti-aromatase assay showed that tested compounds possess inhibition potency, however, two to four times smaller (IC50 from 0.2 to 0.7 microM, respectively) in comparison to aminoglutethimide (AG).