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Metabolites linked to changes in choline kinase-α (CK-α) expression and drug resistance, which contribute to survival and autophagy mechanisms, are attractive targets for breast cancer therapies. We previously reported that autophagy played a causative role in driving tamoxifen (TAM) resistance of breast cancer cells (BCCs) and was also promoted by CK-α knockdown, resulting in the survival of TAM-resistant BCCs. There is no comparative study yet about the metabolites resulting from BCCs with TAM-resistance and CK-α knockdown. Therefore, the aim of this study was to explore the discriminant metabolic biomarkers responsible for TAM resistance as well as CK-α expression, which might be linked with autophagy through a protective role. A total of 33 intracellular metabolites, including a range of amino acids, energy metabolism-related molecules and others from cell extracts of the parental cells (MCF-7), TAM-resistant cells (MCF-7/TAM) and CK-α knockdown cells (MCF-7/shCK-α, MCF-7/TAM/shCK-α) were analyzed by proton nuclear magnetic resonance spectroscopy (1H-NMRS). Principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) revealed the existence of differences in the intracellular metabolites to separate the 4 groups: MCF-7 cells, MCF-7/TAM cells, MCF-7-shCK-α cells, and MCF-7/TAM/shCK-α cells. The metabolites with VIP>1 contributed most to the differentiation of the cell groups, and they included fumarate, UA (unknown A), lactate, myo-inositol, glycine, phosphocholine, UE (unknown E), glutamine, formate, and AXP (AMP/ADP/ATP). Our results suggest that these altered metabolites would be promising metabolic biomarkers for a targeted therapeutic strategy in BCCs that exhibit TAM-resistance and aberrant CK-α expression, which triggers a survival and drug resistance mechanism.

Background: Invasive infections due to foodborne pathogens, including Salmonella enterica serovar Typhimurium, are prevalent and life-threatening. This study aimed to evaluate the effects of ginsenoside Rg3 (Rg3) on the adhesion, invasion, and intracellular survival of S. Typhimurium. Methods: The impacts of Rg3 on bacterial growth and host cell viability were determined using the time kill and the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays, respectively. Gentamicin assay and confocal microscopic examination were undertaken to determine the effects of Rg3 on the adhesive and invasive abilities of S. Typhimurium to Caco-2 and RAW 264.7 cells. Quantitative reverse transcription polymerase chain reaction was performed to assess the expression of genes correlated with the adhesion, invasion, and virulence of S. Typhimurium. Results: Subinhibitory concentrations of Rg3 significantly reduced (p < 0.05) the adhesion, invasion, and intracellular survival of S. Typhimurium. Rg3 considerably reduced (p < 0.05) the bacterial motility as well as the release of nitrite from infected macrophages in a concentration-dependent manner. The expression of genes related to the adhesion, invasion, quorum sensing, and virulence of S. Typhimurium including cheY, hilA, OmpD, PrgK, rsgE, SdiA, and SipB was significantly reduced after Rg3 treatment. Besides, the compound downregulated rac-1 and Cdc-42 that are essential for actin remodeling and membrane ruffling, thereby facilitating Salmonella entry into host cells. This report is the first to describe the effects of Rg3 on “trigger” entry mechanism and intracellular survival S. Typhimurium. Conclusion: Rg3 could be considered as a supplement agent to prevent S. Typhimurium infection.

AbstractThe scale‐eating cichlid fish, Perissodus microlepis, from Lake Tanganyika are a well‐known example of an asymmetry dimorphism because the mouth/head is either left‐bending or right‐bending. However, how strongly its pronounced morphological laterality is affected by genetic and environmental factors remains unclear. Using quantitative assessments of mouth asymmetry, we investigated its origin by estimating narrow‐sense heritability (h2) using midparent–offspring regression. The heritability estimates [field estimate: h2 = 0.22 ± 0.06, P = 0.013; laboratory estimate: h2 = 0.18 ± 0.05, P = 0.004] suggest that although variation in laterality has some additive genetic component, it is strongly environmentally influenced. Family‐level association analyses of a putative microsatellite marker that was claimed to be linked to gene(s) for laterality revealed no association of this locus with laterality. Moreover, the observed phenotype frequencies in offspring from parents of different phenotype combinations were not consistent with a previously suggested single‐locus two‐allele model, but they neither were able to reject with confidence a random asymmetry model. These results reconcile the disputed mechanisms for this textbook case of mouth asymmetry where both genetic and environmental factors contribute to this remarkable case of morphological asymmetry.

Advantageous numerical methods for solving the Dirac equations are derived. They are based on different stochastic optimization techniques, namely the Genetic algorithms, the Particle Swarm Optimization and the Simulated Annealing method, their use of which is favored fromintuitive, practical, and theoretical arguments. Towards this end, we optimize appropriate parametric expressions representing the radial Dirac wave functions by employing methods that minimize multi parametric expressions in several physical applications. As a concrete application, we calculate the small (bottom) and large (top) components of the Dirac wave function for a bound muon orbiting around a very heavy (complex) nuclear system (the 208Pb nucleus), but the new approach may effectively be applied in other complex atomic, nuclear and molecular systems.Program summaryProgram Title: DiracSolverProgram Files doi: http://dx.doi.org/10.17632/7hv9mtdvmp.1Licensing provisions: GPLv3Programming language: GNU-C++Nature of problem: The software tackles the problem of solving the Dirac equation using stochastic optimization methods.Solution method: The software utilizes three stochastic optimization methods for the solution of Dirac equation in the form of neural networks. The used methods are: genetic algorithm, particle swarm optimization and simulated annealing.

Abstract Azaspiracids (AZAs) are a group of lipophilic polyether toxins implicated in incidents of shellfish poisoning in humans, particularly in northern Europe, which are produced by the small marine dinoflagellate Azadinium spinosum . Other related species/strains of the Amphidomataceae have not been proven to date to contain any of the known azaspiracids. Closer analyses of these species/strains by triple quadrupole mass spectrometry in the precursor and product ion mode now revealed four new compounds with high similarity to azaspiracids, all of them with a characteristic m / z 348 fragment but with absence of the m / z 362 fragment. These compounds were detected in three species/strains, i.e. in North Sea isolates of Azadinium poporum (molecular mass: 845.5 Da), in a Korean isolate which has been designated as A. cf. poporum (molecular mass: 857.5 Da) and in Amphidoma languida isolated from Bantry Bay, Ireland (molecular masses: 815.5 and 829.5 Da). Cell quotas of roughly 2–20 fg per cell were in the same range as found for AZA-1/-2 in A. spinosum . Structures for all compounds were proposed by interpretation of fragmentation patterns and high resolution mass measurements using Fourier transform ion cyclotron resonance-mass spectrometry (FTICR-MS).

Two new species of Triconia in Oncaeidae, including both sexes of Triconia constricta n. sp. and females of Triconia pararedacta n. sp., are described from south of Jeju Island in the East China Sea. Triconia constricta belongs to the dentipes-subgroup of Triconia characterized by the absence of integumental pockets on the anterior surface of the labrum. It is distinguished from the closely related species of this subgroup, T dentipes (Giesbrecht, 1891), T elongata Bottger-Schnack, 1999, and T giesbrechti Bottger-Schnack, 1999, by the following combination of morphological features in females: 1) lateral margins of genital double-somite in dorsal view slightly constricted at midlength; 2) P5 with very long outer basal seta, reaching beyond paired secretory pores on posterior part of genital doublesomite, as well as distinctive length ratios of exopodal setae; in both sexes; 3) length ratios of caudal setae, and 4) relative spine lengths on distal endopodal segments of swimming legs 2 to 4. Triconia pararedacta is a member of the conifera-subgroup characterized by a dorsal projection on the second pedigerous somite in the female. It differs from females of other species of this subgroup in the following: 1) very small-sized dorsal projection on second pedigerous somite, 2) different length to width ratio of P5 exopod, 3) relative lengths of outer basal seta and exopodal setae of P5, and 4) different length ratio of outer distal spine to distal spine on endopods of P2-P4. Additional character states are proposed for defining the dentipes-subgroup within Triconia and for recognizing three sets of species within the conifera-subgroup.

DNA is considered as a useful building bio-material, and it serves as an efficient template to align functionalized nanomaterials. Riboflavin (RF)-doped synthetic double-crossover DNA (DX-DNA) lattices and natural salmon DNA (SDNA) thin films were constructed using substrate-assisted growth and drop-casting methods, respectively, and their topological, chemical and electro-optical characteristics were evaluated. The critical doping concentrations of RF ([RF]C, approx. 5 mM) at given concentrations of DX-DNA and SDNA were obtained by observing the phase transition (from crystalline to amorphous structures) of DX-DNA and precipitation of SDNA in solution above [RF]C. [RF]Care verified by analysing the atomic force microscopy images for DX-DNA and current, absorbance and photoluminescence (PL) for SDNA. We study the physical characteristics of RF-embedded SDNA thin films, using the Fourier transform infrared spectrum to understand the interaction between the RF and DNA molecules, current to evaluate the conductance, absorption to understand the RF binding to the DNA and PL to analyse the energy transfer between the RF and DNA. The current and UV absorption band of SDNA thin films decrease up to [RF]Cfollowed by an increase above [RF]C. By contrast, the PL intensity illustrates the reverse trend, as compared to the current and UV absorption behaviour as a function of the varying [RF]. Owing to the intense PL characteristic of RF, the DNA lattices and thin films with RF might offer immense potential to develop efficient bio-sensors and useful bio-photonic devices.