Arachidin-1, a Prenylated Stilbenoid from Peanut,Induces Apoptosis in Triple-Negative Breast Cancer Cells

Triple-negative breast cancer (TNBC) is unresponsive to typical hormonal treatments, causing it to be one of the deadliest forms of breast cancer. Investigating alternative therapies to increase survival rates for this disease is essential. The goal of this study was to assess cytotoxicity and apoptosis mechanisms of prenylated stilbenoids in TNBC cells. The prenylated stilbenoids arachidin-1 (A-1) and arachidin-3 (A-3) are analogs of resveratrol (RES) produced in peanut upon biotic stress. The anticancer activity of A-1 and A-3 isolated from peanut hairy root cultures was determined in TNBC cell lines MDA-MB-231 and MDA-MB-436. After 24 h of treatment, A-1 exhibited higher cytotoxicity than A-3 and RES with approximately 11-fold and six-fold lower IC₅₀, respectively, in MDA-MB-231 cells, and nine-fold and eight-fold lower IC₅₀, respectively, in MDA-MB-436 cells. A-1 did not show significant cytotoxicity in the non-cancerous cell line MCF-10A. While A-1 blocked cell division in G2-M phases in the TNBC cells, it did not affect cell division in MCF-10A cells. Furthermore, A-1 induced caspase-dependent apoptosis through the intrinsic pathway by activating caspase-9 and PARP cleavage, and inhibiting survivin. In conclusion, A-1 merits further research as a potential lead molecule for the treatment of TNBC.     

Machine-Learning-Based Genome-Wide Association Studies for Uncovering QTL Underlying Soybean Yield and Its Components

A genome-wide association study (GWAS) is currently one of the most recommended approaches for discovering marker-trait associations (MTAs) for complex traits in plant species. Insufficient statistical power is a limiting factor, especially in narrow genetic basis species, that conventional GWAS methods are suffering from. Using sophisticated mathematical methods such as machine learning (ML) algorithms may address this issue and advance the implication of this valuable genetic method in applied plant-breeding programs. In this study, we evaluated the potential use of two ML algorithms, support-vector machine (SVR) and random forest (RF), in a GWAS and compared them with two conventional methods of mixed linear models (MLM) and fixed and random model circulating probability unification (FarmCPU), for identifying MTAs for soybean-yield components. In this study, important soybean-yield component traits, including the number of reproductive nodes (RNP), non-reproductive nodes (NRNP), total nodes (NP), and total pods (PP) per plant along with yield and maturity, were assessed using a panel of 227 soybean genotypes evaluated at two locations over two years (four environments). Using the SVR-mediated GWAS method, we were able to discover MTAs colocalized with previously reported quantitative trait loci (QTL) with potential causal effects on the target traits, supported by the functional annotation of candidate gene analyses. This study demonstrated the potential benefit of using sophisticated mathematical approaches, such as SVR, in a GWAS to complement conventional GWAS methods for identifying MTAs that can improve the efficiency of genomic-based soybean-breeding programs.     

Immunogenicity of MultiTEP-Platform-Based Recombinant Protein Vaccine,PV-1950R,Targeting Three B-Cell Antigenic Determinants of Pathological α-Synuclein

Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are characterized by the aberrant accumulation of intracytoplasmic misfolded and aggregated α-synuclein (α-Syn), resulting in neurodegeneration associated with inflammation. The propagation of α-Syn aggregates from cell to cell is implicated in the spreading of pathological α-Syn in the brain and disease progression. We and others demonstrated that antibodies generated after active and passive vaccinations could inhibit the propagation of pathological α-Syn in the extracellular space and prevent/inhibit disease/s in the relevant animal models. We recently tested the immunogenicity and efficacy of four DNA vaccines on the basis of the universal MultiTEP platform technology in the DLB/PD mouse model. The antibodies generated by these vaccines efficiently reduced/inhibited the accumulation of pathological α-Syn in the different brain regions and improved the motor deficit of immunized female mice. The most immunogenic and preclinically effective vaccine, PV-1950D, targeting three B-cell epitopes of pathological α-Syn simultaneously, has been selected for future IND-enabling studies. However, to ensure therapeutically potent concentrations of α-Syn antibodies in the periphery of the vaccinated elderly, we developed a recombinant protein-based MultiTEP vaccine, PV-1950R/A, and tested its immunogenicity in young and aged D-line mice. Antibody responses induced by immunizations with the PV-1950R/A vaccine and its homologous DNA counterpart, PV-1950D, in a mouse model of PD/DLB have been compared.     

A modified sliding-mode observer design with application to diffusion equation

In many physical systems, the system's full state cannot be measured. An observer is designed to reconstruct the state from measurements. Disturbances often contribute to the dynamics of the system, and the designed observer must account for them. In this paper, a modified sliding-mode observer (SMO), a robust observer, is proposed that combines the efficiency of a nonlinear observer with the robustness of an SMO. The estimation error is proven to converge to zero under natural assumptions. This improved observer is compared with an extended Kalman filter and an unscented Kalman filter, as well as a standard SMO for three different versions of heat equation: a linear, a quasi-linear, and a nonlinear heat equation. The comparisons are done with and without an external disturbance. The simulations show improved performance of the modified SMO over other observers.     

Density-Dependence of Surface Transport in Tellurium-Enriched Nanograined Bulk Bi2Te3

Three-dimensional topological insulators (3D TI) exhibit conventional parabolic bulk bands and protected Dirac surface states. A thorough investigation of the different transport channels provided by the bulk and surface carriers using macroscopic samples may provide a path toward accessing superior surface transport properties. Bi₂Te₃ materials make promising 3D TI models; however, due to their complicated defect chemistry, these materials have a high number of charge carriers in the bulk that dominate the transport, even as nanograined structures. To partially control the bulk charge carrier density, herein the synthesis of Te-enriched Bi₂Te₃ nanoparticles is reported. The resulting nanoparticles are compacted into nanograined pellets of varying porosity to tailor the surface-to-volume ratio, thereby emphasizing the surface transport channels. The nanograined pellets are characterized by a combination of resistivity, Hall- and magneto-conductance measurements together with (THz) time-domain reflectivity measurements. Using the Hikami-Larkin-Nagaoka (HLN) model, a characteristic coherence length of ≈200 nm is reported that is considerably larger than the diameter of the nanograins. The different contributions from the bulk and surface carriers are disentangled by THz spectroscopy, thus emphasizing the dominant role of the surface carriers. The results strongly suggest that the surface transport carriers have overcome the hindrance imposed by nanoparticle boundaries.     

Four Novel p.N385K,p.V36A,c.1033–1034insT and c.1417–1418delCT Mutations in the Sphingomyelin Phosphodiesterase 1 (SMPD1) Gene in Patients with Types A and B Niemann-Pick Disease (NPD)

Background: Types A and B Niemann-Pick disease (NPD) are autosomal-recessive lysosomal storage disorders caused by the deficient activity of acid sphingomyelinase due to mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene. Methods: In order to determine the prevalence and distribution of SMPD1 gene mutations, the genomic DNA of 15 unrelated Iranian patients with types A and B NPD was examined using PCR, DNA sequencing and bioinformatics analysis. Results: Of 8 patients with the p.G508R mutation, 5 patients were homozygous, while the other 3 were heterozygous. One patient was heterozygous for both the p.N385K and p.G508R mutations. Another patient was heterozygous for both the p.A487V and p.G508R mutations. Two patients (one homozygous and one heterozygous) showed the p.V36A mutation. One patient was homozygous for the c.1033–1034insT mutation. One patient was homozygous for the c.573delT mutation, and 1 patient was homozygous for the c.1417–1418delCT mutation. Additionally, bioinformatics analysis indicated that two new p.V36A and p.N385K mutations decreased the acid sphingomyelinase (ASM) protein stability, which might be evidence to suggest the pathogenicity of these mutations. Conclusion: with detection of these new mutations, the genotypic spectrum of types A and B NPD is extended, facilitating the definition of disease-related mutations. However, more research is essential to confirm the pathogenic effect of these mutations.     

Fabrication,characterization, and thermal property evaluation of silver nanofluids

Silver nanoparticles were successfully prepared in two different solvents using a microwave heating technique, with various irradiation times. The silver nanoparticles were dispersed in polar liquids (distilled water and ethylene glycol) without any other reducing agent, in the presence of the stabilizer polyvinylpyrrolidone (PVP). The optical properties, thermal properties, and morphology of the synthesized silver particles were characterized using ultraviolet-visible spectroscopy, photopyroelectric technique, and transmission electron microscopy. It was found that for the both solvents, the effect of microwave irradiation was mainly on the particles distribution, rather than the size, which enabled to make stable and homogeneous silver nanofluids. The individual spherical nanostructure of self-assembled nanoparticles has been formed during microwave irradiation. Ethylene glycol solution, due to its special properties, such as high dielectric loss, high molecular weight, and high boiling point, can serve as a good solvent for microwave heating and is found to be a more suitable medium than the distilled water. A photopyroelectric technique was carried out to measure thermal diffusivity of the samples. The precision and accuracy of this technique was established by comparing the measured thermal diffusivity of the distilled water and ethylene glycol with values reported in the literature. The thermal diffusivity ratio of the silver nanofluids increased up to 1.15 and 1.25 for distilled water and ethylene glycol, respectively.     

Role of hormonal and environmental factors on early incidence of breast cancer in Iran

Although the probability of having breast cancer increases with the age in general, this malignancy affects Iranian women at least one decade younger than their counterparts in other countries. However the underlying risk factors for the discrepancy have not been identified. The aryl hydrocarbon receptor (AhR) mediates the effects of many environmental endocrine disruptors and contributes to the loss of normal ovarian function in polluted environments. This study was aimed to compare the interactions between AhR and other fundamental genes (p53, K-Ras, ER, PgR) in a clinical setting. To conduct the immunohistochemical studies using appropriate monoclonal antibodies, 25 premenopausal invasive ductal carcinoma, 29 postmenopausal invasive ductal carcinoma and 30 breast fibroadenoma were selected retrospectively from 2004 to 2007 in the pathology department of Imam Khomeini hospital complex of Tehran University of Medical Sciences . Higher levels of AhR in epithelial cells of premenopausal patients and breast fibroadenoma emphasized the susceptibility of these cells to environmental-induced tumors. AhR overexpression contributed to ER-/PgR-immunophenotype in young/premenopausal patients but the same pattern was not observed in benign and postmenopausal malignant tumors. It seems that early incidence of breast cancer in Iran is the result of interactions between hormonal and environmental factors.