Screening and identification of novel compounds with potential anti-proliferative effects on gallium-resistant lung cancer through an AXL kinase pathway

The clinical application of gallium compounds as anticancer agents is hampered by development of resistance. As a potential strategy to overcome the limitation, eight series of compounds were identified through virtual screening of AXL kinase homology model. Anti-proliferative studies were carried using gallium-sensitive (S) and gallium-resistant (R) human lung adenocarcinoma (A549) cells. Compounds 5476423 and 7919469 were identified as leads. The IC₅₀ values from treating R-cells showed compounds 5476423 and 7919469 had 80 fold and 13 fold increased potency, respectively, compared to gallium acetylacetonate (GaAcAc). The efficacy of GaAcAc against R-cells was increased 2 fold and 1.2 fold when combined with compounds 5476423 and 7919469, respectively. Compared with S-cells, R-cells showed elevated expression of AXL protein, which was significantly suppressed through treatments with the lead compounds. It is anticipated that the lead compounds could be applied in virtual screening programs to identify novel scaffolds for new therapeutic agents as well as combinatorial therapy agents in gallium resistant lung cancer.     

Divergent growth of Norway spruce on Babia Góra Mountain in the western Carpathians

Growth divergence – i.e. the expression of divergent growth trends of neighboring trees – has certain implications for dendrochronological research, for instance in the context of climate reconstructions but also in terms of estimating net ecosystem productivity. Thus, understanding the underlying mechanisms is essential to extend our fundamental dendroecological knowledge. In this context, the Picea genus plays an important role since several of its species were reported to exhibit growth divergence. Here, we investigate a well sampled Norway spruce (Picea abies (L.) Karst) data set for growth divergence comprising ring-width and Blue Intensity measurements from seven sites on Babia Góra Mountain, at the border between Poland and Slovakia. By means of Principal Component Gradient Analysis, inter-series correlations, and climate growth relationships, we are able to show that I) Norway spruce on Babia Góra expressed growth divergence since the 1970s, II) the definition of groups increased the strength of population signals and the stability of climate-growth relationships, and III) Blue Intensity appeared as a more robust proxy for environmental conditions. We discuss soil heterogeneity, genetics, and air pollution as possible underlying mechanisms, thereby indicating further research avenues to obtain a better understanding of growth divergence.     

Virtual traumatology of pregnant women: The PRegnant car Occupant Model for Impact Simulations (PROMIS)

This study report documents the development of a finite element (FE) model for analyzing trauma in pregnant women involved in road accidents and help the design of a specific safety device. The model is representative of a 50th percentile pregnant woman at 26 weeks of pregnancy in sitting position. To achieve this, the HUMOS 2 model, which has been validated in a wide range of dynamic tests, was scaled to the morphology of a woman in the 50th percentile and coupled with a model of gravid uterus. During scaling, special attention was paid to the pelvic region which is known to differ considerably in morphological terms between men and women. The gravid uterus model includes a placenta, a fetus, uterosacral ligaments and the amniotic fluid by means of fluid structure interaction formulation. The uterus and the female model were coupled using an original method whereby the growth of an uterus was simulated to compress the abdominal organs in a realistic manner. The model was validated based on experimental tests described in the literature. Additional tests based on abdominal loadings with a seatbelt on Post Mortem Human Surrogates (PMHS) coupled to silicone uterus were also performed.     

Discovering Precise Temporal Patterns in Large-Scale Neural Recordings through Robust and Interpretable Time Warping

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Genetic and allelopathic differences between populations of daisy fleabane Erigeron annuus (L.) Pers. (Asteraceae) from disturbed and stable habitats

The interactions between invasive plants and their habitats may vary at different phases of the invasion process and depend on the phenotypic plasticity or local adaptations of each species. In this study, we investigated whether habitat changes during the invasion process are related to variations in the physiological traits (allelopathic properties) and genetic differentiation of daisy fleabane (Erigeron annuus (L.) Pers.). E. annuus is a winter annual invasive species that originated in North America and is now distributed throughout Europe. Genetic and genotypic diversity analyses were performed for 37 populations of E. annuus based on inter simple sequence repeat (ISSR) polymorphisms. In total, 684 plants were analyzed; 342 were from stable habitats and 342 were from disturbed habitats. The genetic differences among the populations from the different habitats were studied using a Bayesian cluster analysis and an analysis of molecular variance (AMOVA) and by calculating the genetic and genotypic diversity parameters. A germination test using the juglone index was employed to examine the potential allelopathic properties of the plants from the different habitats. Bayesian cluster analysis, AMOVA and allelopathic effects evaluation revealed differences in the allelopathic potential and genetic structure of the E. annuus populations from the disturbed and stable habitats. This differentiation of populations could be associated with founder effects or with different selection pressures among habitats.     

Genetic diversity and population structure of food-borne Staphylococcus carnosus strains

The species Staphylococcus carnosus is a non-pathogenic representative of the coagulase negative staphylococci. Specific strains are applied as meat starter cultures. The species consists of two subspecies, S. carnosus ssp. carnosus and S. carnosus ssp. utilis. In order to place S. carnosus strains, characterized in former studies, in a genetic background that allows a typing of candidates for starter cultures, a Multilocus Sequence Typing (MLST) scheme was developed. Internal fragments of the genes tpiA, xprT, dat, gmk, glpK, narG, cstA, encoding triosephosphate isomerase, xanthine phosphoribosyltransferase, d-amino acid aminotransferase, guanylate kinase, glycerol kinase, the α-chain of the respiratory nitrate reductase, and a carbon starvation protein where chosen. Genes were selected based on their equal distribution in the genome, taxonomic value in subspecies differentiation and metabolic function. This MLST was applied to 44 S. carnosus strains, most of them previously analyzed for their suitability as starter cultures.The number of alleles varied between zero (tpiA) and five (cstA) and allowed the definition of nine sequence types (ST). ST1 was most abundant (18 strains), followed by ST2 (8) and ST4 (6). The nine STs confirmed a close relationship of all strains despite their isolation source and year, but lacked correlation with physiological activities relevant for starter cultures. The low amount of STs in the strain set lets us suggest that recombination between strains is rare. Thus, it is hypothesized that evolutionary events seem to be due to single point mutations rather than intrachromosomal recombination, and that the species possesses a clonal population structure.     

Low mtDNA Cytb diversity and shallow population structure of Eleutheronema tetradactylum in the East China Sea and the South China Sea

Eleutheronema tetradactylum is an economically important fish species in China water. To investigate the genetic diversity and describe population structure of it, an 1151 base pair (bp) fragment of the mitochondrial DNA Cytb sequence was analyzed in 120 individuals from four populations in the East China Sea and the South China Sea. A total of 16 haplotypes were defined by 24 variable nucleotide sites. High level of haplotype diversity and low nucleotide diversity were observed in all populations. The results of AMOVA detected that 89.44% of the genetic variation occurred within populations. Significant genetic differentiations were detected among populations (0.05097, P < 0.05), but no large-scale regional differences were detected. Analysis of neutral evolution and mismatch distribution suggested no recent population expansion happened. The present results provided new information for genetic assessment, fishery management and conservation of this species.     

Genetic diversity and population structure of Korean wild soybean (Glycine soja Sieb. and Zucc.) inferred from microsatellite markers

Korea is considered one of the centers of genetic diversity for cultivated as well as wild soybeans. Natural habitats of wild soybeans are distributed across the Korean mainland and the islands surrounding the Korean peninsula. In this study, the genetic diversity of 100 mainland Korean wild soybean accessions was evaluated by using 42 simple sequence repeat markers covering 17 soybean chromosomes. All analyzed loci were polymorphic and a total of 114 alleles were found. The observed average genetic diversity was low (0.4). The results showed that the 100 selected accessions did not exactly follow the geographical distribution. These results were further confirmed by the phylogeny inferred from five morphological characteristics (i.e., leaf shape, leaf area, plant shape, seed area, and 100-seed weight). Together, the genetic and morphological evaluations suggested conclusively that the selected population did not follow the geographical distribution pattern. The present study could provide useful information for the ex situ conservation and exploitation of wild soybean accessions in soybean improvement stratagems, and will aid in further understanding about the phylogeography of the species in the Korean center of diversity.     

Finite time blow-up in some models of chemotaxis

We consider a class of models of chemotactic bacterial populations, introduced by Keller-Segel. For those models, we investigate the possibility of chemotactic collapse, in other words, the possibility that in finite time the population of predators aggregates to form a delta-function. To study this phenomenon, we construct self-similar solutions, which may or may not blow-up (in finite time), depending on the relative strength of three mechanisms in competition: (i) the chemotactic attraction of bacteria towards regions of high concentration in substrate (ii) the rate of consumption of the substrate by the bacteria and (iii) (possibly) the diffusion of bacteria. The solutions we construct are radially symmetric, and therefore have no relation with the classical traveling wave solutions. Our scaling can be justified by a dimensional analysis. We give some evidence of numerical stability.