Enhanced development of mouse single blastomeres into blastocysts via the simultaneous inhibition of TGF‐β and ERK pathways in microdroplet culture

Optimization of an in vitro culture that supports blastocyst (BL) development from single blastomeres (SBs) is essential to generate additional embryos for farm animals and humans and unravel the mechanisms that underlie totipotency. In this study, we have examined BL development from SBs that were derived from 2‐cell and 4‐cell mouse embryos in different media. Moreover, BLs were assessed for inner cell mass (ICM) by staining with Oct4. We found that BL development was improved in a lower volume of medium (1 µL) compared with a higher volume (5 µL). Furthermore, the supplementation of medium with the inhibitors of ERK1/2 and TGFβ (R2i) signaling pathways in 1 µL droplets of T6 medium improved BL development. The co‐culture of SBs with intact embryos in the presence of R2i showed more BL development and ICM to trophectoderm cell number ratio in comparison with SB culture and SB group culture. We also observed reduced total cell number, ICM, and trophectoderm cell numbers in all of the SB culture conditions versus intact embryo development. These findings might facilitate the successful generation of additional embryos for biomedical applications and elucidate the mechanisms that underlie totipotency.     

Terrestrial venomous animals,the envenomings they cause,and treatment perspectives in the Middle East and North Africa

The Middle East and Northern Africa, collectively known as the MENA region, are inhabited by a plethora of venomous animals that cause up to 420,000 bites and stings each year. To understand the resultant health burden and the key variables affecting it, this review describes the epidemiology of snake, scorpion, and spider envenomings primarily based on heterogenous hospital data in the MENA region and the pathologies associated with their venoms. In addition, we discuss the venom composition and the key medically relevant toxins of these venomous animals, and, finally, the antivenoms that are currently in use to counteract them. Unlike Asia and sub-Saharan Africa, scorpion stings are significantly more common (approximately 350,000 cases/year) than snakebites (approximately 70,000 cases/year) and present the most significant contributor to the overall health burden of envenomings, with spider bites being negligible. However, this review also indicates that there is a substantial lack of high-quality envenoming data available for the MENA region, rendering many of these estimates speculative. Our understanding of the venoms and the toxins they contain is also incomplete, but already presents clear trends. For instance, the majority of snake venoms contain snake venom metalloproteinases, while sodium channel–binding toxins and potassium channel–binding toxins are the scorpion toxins that cause most health-related challenges. There also currently exist a plethora of antivenoms, yet only few are clinically validated, and their high cost and limited availability present a substantial health challenge. Yet, some of the insights presented in this review might help direct future research and policy efforts toward the appropriate prioritization of efforts and aid the development of future therapeutic solutions, such as next-generation antivenoms.     

N-terminally fusion of Her2/neu to HSP70 decreases efficiency of Her2/neu DNA vaccine

DNA vaccines consisted of tumor-associated antigen (TAA) are well suited for immunotherapy against tumor. The construct can contain TAA fused to an appropriate molecule (biologic adjuvant) to improve the efficacy of anti-tumor immune response. Heat shock protein 70 (HSP70) has been shown to be an excellent candidate, capable of cross-priming TAA by antigen presenting cells leading to a robust T-cell response. However, the relationship between strong T-cell responses and tumor rejection is not always mutually exclusive, for which TAA loss or activation of suppressive mechanisms may occur. HSP70 fused to downstream of Her2/neu as DNA vaccine has been shown to be efficient against Her2-expressing tumors. In this study, we examined if N-terminally fusion of Her2/neu to HSP70 could also improve efficiency of Her2/neu DNA vaccine. Therefore, mice with an established Her2/neu expressing tumor were immunized with DNA vaccine consisting of extracellular and trans-membrane domain (EC+TM) of rat Her2/neu alone or N-terminally fused to HSP70 and immune response was evaluated. Administration of rat Her2/neu led to partial control of tumor progression. Surprisingly, fusion of HSP70 to N-terminal of rat Her2/neu led to tumor progression. Our result proposes that fusion direction of biologic adjuvant is an important consideration when Her2/neu is used.     

Investigating the Effect of Heavy Metals on Developmental Stages of Anther and Pollen in <Emphasis Type="Italic">Chenopodium botrys</Emphasis> L. (Chenopodiaceae)

Excessive amounts of heavy metals adversely affect plant growth and development. Whereas some regions naturally contain high levels of heavy metals, anthropogenic release of heavy metals into the environment continuously increases soil contamination. Preliminary studies have shown that Chenopodium botrys can grow in some heavy metal contaminated soils and is a high accumulator plant species for Cu and moderately accumulator plant species for Fe, Mn, and Zn, thus, was considered as an important species in this study. Based on that, in this species, we studied the individual effects of heavy metals on the formation, development, and structure of anther and pollen. To achieve this purpose, surrounding area of Hame-Kasi iron and copper mine (Hamedan, Iran) was chosen as a polluted area where the amount of some heavy metals was several times higher than the natural soils. Flowers and young pods were removed from non-polluted and polluted plants, fixed in FAA 70, and subjected to developmental studies. Analysis of anther development in plants from contaminated sites showed general similarities in the pattern of pollen formation with those from non-polluted ones, but also deviation from typical form of major stages of anther and pollen development was seen in plants from polluted ones. Stabilizing of tapetum layer, increasing in tapetum layer numbers, thickening callose wall in the microspore mother cell stage, changing the anther shape, and decreasing the size of anther were the effects of heavy metals. Reduction of pollen number was also seen in the plants collected from polluted area.     

All-Optical Tunable Plasmonic Biosensor Made of Graphene and Metamaterial

Plasmonics - We demonstrate a novel, label-free and real-time tunable infrared biosensor by employing surface-plasmon polaritons in asymmetric Mach–Zehnder interferometer. The waveguides...     

Effect of Leukemia Inhibitory Factor on the Myelinogenic Ability of Schwann-Like Cells Induced from Human Adipose-Derived Stem Cells

The Schwann cells (SCs) may be obtain from nerve biopsies for autologous transplantation. However, it is difficult to obtain sufficient amount of SCs for clinical applications. Human adipose-derived stem cells (ADSCs) can be induced to differentiate into Schwann-like cells (S-like cells) and used for autologous transplantation. However, effect of leukemia inhibitory factor (LIF) on the myelinogenic ability of SC-like cells induced from human ADSC is not investigated yet. The aim of this study was to evaluate of the effect of exogenous LIF on myelinogenic potential of differentiated cells in vitro. ADSCs were harvested from human fat tissue and characterized using flow cytometry. Human ADSCs were treated for sphere formation and LIF was added to terminal differentiation medium. GFAP/S100β and MBP markers were used to confirm differentiation of human ADSCs, and myelinogenic ability of SC-like cells, respectively, using both immunostaining and real-time RT-PCR analysis. The analysis for GFAP⁺/S100β⁺ revealed that LIF can increase both differentiated cells rates and the percentage of myelinating SC-like cells (p < 0.05). Our data showed that SC-like cells induced from human ADSCs were able to generate myelin when exposed to LIF and these cells could be a potential source for the treatment of peripheral and central axonal injuries.     

Fabrication of an Electrochemical Sensor Based on Gold Nanoparticles/Carbon Nanotubes as Nanocomposite Materials: Determination of Myricetin in Some Drinks

In this paper, the electrochemical behavior of myricetin on a gold nanoparticle/ethylenediamine/multi-walled carbon-nanotube modified glassy carbon electrode (AuNPs/en/MWCNTs/GCE) has been investigated. Myricetin effectively accumulated on the AuNPs/en/MWCNTs/GCE and caused a pair of irreversible redox peaks at around 0.408 V and 0.191 V (vs. Ag/AgCl) in 0.1 mol L⁻¹ phosphate buffer solution (pH 3.5) for oxidation and reduction reactions respectively. The heights of the redox peaks were significantly higher on AuNPs/en/MWNTs/GCE compare with MWCNTs/GC and there was no peak on bare GC. The electron-transfer reaction for myricetin on the surface of electrochemical sensor was controlled by adsorption. Some parameters including pH, accumulation potential, accumulation time and scan rate have been optimized. Under the optimum conditions, anodic peak current was proportional to myricetin concentration in the dynamic range of 5.0×10⁻⁸ to 4.0×10⁻⁵ mol L⁻¹ with the detection limit of 1.2×10⁻⁸ mol L⁻¹. The proposed method was successfully used for the determination of myricetin content in tea and fruit juices.     

Adjuvant activity of GP96 C-terminal domain towards Her2/neu DNA vaccine is fusion direction-dependent

The Her2 is one of tumor-associated antigens (TAA), regarded as an ideal target of immunotherapy. DNA encoding full-length or truncated rat Her2/neu have shown protective and therapeutics potentials against Her2/neu-expressing mammary tumors. However, the efficacy of active vaccination is limited since Her2 is a self-tolerated antigen. Hence, new strategies are required to enhance both the quality and quantity of the immune response against Her2-expressing tumors. Many studies have used Her2/neu gene with cytokine or other molecules involved in regulation of immune response to enhance the potency of Her2/neu DNA vaccines. Some studies fused adjuvant gene to C-terminal domain of Her2/neu gene, while others fused the adjuvant gene N-terminally to Her2/neu gene, but no comparison on how direction of fusion could affect efficiency of DNA vaccine has ever been made. Based on previous reports demonstrating potent adjuvant activity of gp96 C-terminal domain, we chose it as adjuvant. The aim of this study was to investigate if direction of fusion could affect adjuvant activity of gp96 C-terminal domain or potency of Her2/neu DNA vaccination. To do so, we fused C-terminal domain of gp96 to downstream or C-terminal end of transmembrane and extracellular domain (TM+ECD) of rat Her2/neu and resultant immune response to DNA vaccination was evaluated. The results were compared with that of N-terminally fusion of gp96 C-terminal domain to TM+ECD of rat Her2/neu. Our results revealed that adjuvant activity of gp96 C-terminal domain is enhanced when fused N-terminally to TM+ECD of rat Her2/neu. It suggests that adjuvant activity of gp96 C-terminal domain towards Her2/neu is fusion direction-dependent.     

C-curve: A novel 3D graphical representation of DNA sequence based on codons

In this paper, a novel 3D graphical representation of DNA sequence based on codons is proposed. Since there is not loss of information due to overlapping and containing loops, this representation will be useful for comparison of different DNA sequences. This 3D curve will be convenient for DNA mutations comparison specially. In continues we give a numerical characterization of DNA sequences based on the new 3D curve. This characterization facilitates quantitative comparisons of similarities/dissimilarities analysis of DNA sequences based on codons.