AaTs-1: A Tetrapeptide from Androctonus australis Scorpion Venom,Inhibiting U87 Glioblastoma Cells Proliferation by p53 and FPRL-1 Up-Regulations

Glioblastoma is an aggressive cancer, against which medical professionals are still quite helpless, due to its resistance to current treatments. Scorpion toxins have been proposed as a promising alternative for the development of effective targeted glioblastoma therapy and diagnostic. However, the exploitation of the long peptides could present disadvantages. In this work, we identified and synthetized AaTs-1, the first tetrapeptide from Androctonus australis scorpion venom (Aa), which exhibited an antiproliferative effect specifically against human glioblastoma cells. Both the native and synthetic AaTs-1 were endowed with the same inhibiting effect on the proliferation of U87 cells with an IC₅₀ of 0.56 mM. Interestingly, AaTs-1 was about two times more active than the anti-glioblastoma conventional chemotherapeutic drug, temozolomide (TMZ), and enhanced its efficacy on U87 cells. AaTs-1 showed a significant similarity with the synthetic peptide WKYMVm, an agonist of a G-coupled formyl-peptide receptor, FPRL-1, known to be involved in the proliferation of glioma cells. Interestingly, the tetrapeptide triggered the dephosphorylation of ERK, p38, and JNK kinases. It also enhanced the expression of p53 and FPRL-1, likely leading to the inhibition of the store operated calcium entry. Overall, our work uncovered AaTs-1 as a first natural potential FPRL-1 antagonist, which could be proposed as a promising target to develop new generation of innovative molecules used alone or in combination with TMZ to improve glioblastoma treatment response. Its chemical synthesis in non-limiting quantity represents a valuable advantage to design and develop low-cost active analogues to treat glioblastoma cancer.     

High sensitivity and ultra-compact optical biosensor for detection of UREA concentration

In this paper, we suggest two-dimensional photonic crystal based biosensors for measurement of urea concentration in urine by means of refractive index detecting. In case of variation of urea concentration in urine, both the output peak intensity and the resonant peak center wavelength will shift. Two different structure dimensions are used to analyze the sensing characteristics of urine. The first sensor consists of a novel square ring joined to a simple waveguide with rods in air configuration. The second sensor is schemed by use of two-dimensional photonic crystals based on air hole in slab with elliptical resonant cavity in the middle of a photonic crystal waveguide. To realize sensing in both cases, we fill air area by urine sample. A high sensitivity is observed in small structures. In addition, we demonstrated a high quality factor, which is superior to those reported in recently published work discussing urine components based on photonic crystal, with small size sensors and fast response times.     

Optimal observable analysis for the decay $$b \rightarrow s$$ plus missing energy

The decay \(b\rightarrow s\nu {\bar{\nu }}\) has received comparatively less attention than the semileptonic decay \(b\rightarrow s\ell ^+\ell ^-\), because neutrinos pass undetected and hence the process offers lesser number of observables. We show how the decay \(b\rightarrow s~+\) invisible(s) can shed light, even with a limited number of observables, on possible new physics beyond the Standard Model and also show, quantitatively, the reach of future B factories like SuperBelle to uncover such new physics. Depending on the operator structure of new physics, different channels may act as the best possible probe. We show, using the optimal observable technique, how almost the entire parameter space allowed till now can successfully be probed at a high-luminosity B factory.     

Strengthening Anti-Glioblastoma Effect by Multi-Branched Dendrimers Design of a Scorpion Venom Tetrapeptide

Glioblastoma is the most aggressive and invasive form of central nervous system tumors due to the complexity of the intracellular mechanisms and molecular alterations involved in its progression. Unfortunately, current therapies are unable to stop its neoplastic development. In this context, we previously identified and characterized AaTs-1, a tetrapeptide (IWKS) from Androctonus autralis scorpion venom, which displayed an anti-proliferative effect against U87 cells with an IC₅₀ value of 0.57 mM. This peptide affects the MAPK pathway, enhancing the expression of p53 and altering the cytosolic calcium concentration balance, likely via FPRL-1 receptor modulation. In this work, we designed and synthesized new dendrimers multi-branched molecules based on the sequence of AaTs-1 and showed that the di-branched (AaTs-1-2B), tetra-branched (AaTs-1-4B) and octo-branched (AaTs-1-8B) dendrimers displayed 10- to 25-fold higher effects on the proliferation of U87 cells than AaTs-1. We also found that the effects of the newly designed molecules are mediated by the enhancement of the ERK1/2 and AKT phosphorylated forms and by the increase in p53 expression. Unlike AaTs-1, AaTs-1-8B and especially AaTs-1-4B affected the migration of the U87 cells. Thus, the multi-branched peptide synthesis strategy allowed us to make molecules more active than the linear peptide against the proliferation of U87 glioblastoma cells.     

Stability of nonlinear time-varying perturbed differential equations

The goal of this paper is twofold. The first part presents a converse Lyapunov theorem for the notion of uniform practical exponential stability of nonlinear differential equations in presence of small perturbation. This class of nonlinear differential equations can be viewed as parametric differential equations. The second part provides the classical perturbation method of seeking an approximate solution as a finite Taylor expansion of the exact solution. The practical asymptotic validity on the approximate is established on infinite-time interval. Finally, we give a numerical example to prove the validity of our methods.