Cleavage of Müllerian inhibiting substance activates antiproliferative effects in vivo

Müllerian inhibiting substance (MIS), an inhibitor of growth and development of the female reproductive ducts in male fetuses, requires precise proteolytic cleavage to yield its biologically active species. Human plasmin is now used to cleave and, thereby, activate immunoaffinity-purified recombinant human MIS at its monobasic arginine-serine site at residues 427-428. To avoid the need for exogenous enzymatic cleavage and to simplify purification, we created an arginine-arginine dibasic cleavage site (MIS RR) using site-directed mutagenesis to change the serine at position 428 (AGC) to an arginine (cGC). The mutant cDNA was then stably transfected into a MIS-responsive ocular melanoma cell line, OM431, followed by cloning for amplified expression to test its biological activity in vitro and in vivo. Media from each clone were assayed for production of MIS RR by a sensitive ELISA for holo-MIS, and high- and low-producing clones were selected for further study. Media from the highest MIS RR producer caused Müllerian duct regression in an organ culture bioassay. Other transfections were done with an empty vector (pcDNAI Neo) or a construct lacking the leader sequence and thus failing to secrete MIS, to serve as controls. The OM431 clones containing the MIS RR mutant were growth inhibited in monolayer culture. The high- and low-producing MIS RR OM431 clones, along with transfected OM431 controls, were injected into the tail veins of immunosuppressed severe combined immunodeficiency mice for in vivo analyses. Four to 6 weeks later, pulmonary metastases were counted in uniformly inflated lungs. OM431 clones containing the more easily cleaved MIS RR displayed a significant dose-dependent reduction in pulmonary metastases when compared to the lungs of animals given injections of OM431 clones containing empty vector, leaderless MIS, or wild-type MIS that requires activation by plasmin cleavage. Since the purification protocol of MIS RR is less complicated than that for wild-type MIS, which requires subsequent enzymatic activation, MIS RR can be used for scale-up production with increased yields for further therapeutic trials against MIS-sensitive tumors.     

Wear of graphite anodes during electrolysis of add sulphate solutions

Graphite electrodes were prepared by mixing calcined coke and coal tar pitch. They were pressed under 250 kg cm^–2 and heat treated up to 2800° C. Rectangles measuring 70 mm x 40 mm x 8 mm were anodically polarized under galvanostatic and potentiostatic conditions. Electrolyses were conducted at 10–50 mA cm^–2 for periods ranging from 10–120 hours in Na₂SO₄ solutions acidified with sulphuric acid to various pH values. The wear of graphite anodes increased with decreasing bath temperature, increasing acid concentration, decreasing pH of the electrolyte and increasing current density. A model is suggested which assumes that corrosion takes place via the formation of a lamellar crystal compound with the formula (C ₈ ⁰ O)(OH)₃HSO ₄ ^– ·2H₂SO₄.The compound is unstable at higher temperatures when corrosion is effected by oxidation of graphite by atomic oxygen. The formation of the carbon ions was found to be a necessary precondition for the formation of the complex.     

Developmental stages in experimental liver metastases: relation to invasiveness

We have previously reported that an invasive morphotype can be evoked in a rat colon carcinoma by transplanting it into pre-induced subcutaneous granulation tissue. We have now studied the interaction of the same tumor with liver tissue, which is extremely poor in connective tissue in comparison with the subcutaneous site. Tumor cells were injected into the portal system and the resulting experimental liver metastases were examined by electron microscopy and immunohistochemistry. Early metastases consisted of well-differentiated acini, fully surrounded by connective tissue that was derived from the periportal stroma. In a later stage, this connective tissue was overgrown by tumor cells and, almost immediately, acinar differentiation was lost. Most metastases eventually reached the liver capsule, which reacted by forming a layer of granulation tissue. Only in this layer, we observed invasion by thin tumor cell strands, which were often intimately associated with fibroblasts or with blood capillaries. The tumor cells remained smooth and rounded during this process. After fully penetrating the granulation tissue, the tumor cell strands reached the liver surface, where they formed poorly structured papillary masses that were nearly devoid of stroma. Our observations indicate that, even in a relatively homogeneous organ like the liver, the tumor-host interaction is highly complex and dynamic. They also confirm the notion that granulation tissue stimulates tumor invasiveness. Finally, they show that tumor cells can actively invade host tissues without exhibiting a "fibroblastic" morphology.     

Exploring the relationship between Internet ethics in university students and the big five model of personality

The widespread use of the Internet and the convenient mechanism it provides, such as easy access, easy downloads, and easy copy and paste functions have made many types of unethical behaviors easier, particularly those involving students in academic settings. Among the issues in ethics within the academic environment that can be triggered by the Internet are fraudulence, plagiarism, falsification, delinquency, unauthorized help, and facility misuse. Given these issues, the study seeks to investigate the extent to which students at a public university in Malaysia engage in such unethical behavior and their relationship with the big five personality model. This study was conducted using a survey method of 252 students in three different academic faculties. The results of factor analyses confirm and refine the reliability of the scales for both big five personality variables and unethical Internet behaviors as conceptualized through Internet triggered academic dishonesty (ITADS). The findings indicate that personality traits such as (1) agreeableness, (2) conscientiousness and (3) emotional stability are significantly and negatively correlated with unethical Internet behavior in university students. Significant differences in facility misuse are also observed between the three academic faculties investigated. This research should provide significant contributions to educators in designing the computer ethics curriculum and in allowing for educational institutions as well as other organizations in developing relevant policies and guidelines on matters pertaining to academic conduct, utilization of computers and Internet, and recruitment exercises.     

Ultrastructure of nerve plexus in flatworms. III. The infra-epithelial nervous system

In addition to a submuscular and subepithelial nerve plexus an infra-epithelial nerve-net also occurs in Notoplana acticola. It contains naked nerve cells which lie between the bases of epithelial cells. Individual neurites occur separately or in small tracts. Synapses contain clear spherical vesicles and are polarized. Post-synaptic neurites tend to be flat and ribbon-like. Rhabdite and mucus secreting cells in the epithelium have synapses associated with them. Neurites ending on the rhabdites appear to originate in the subepithelial plexus. The "sensory-free nerve endings" of earlier workers are reinterpreted as being motor terminals on epithelial secretory cells.     

Electric-field induced fluctuations in laser generated plasma plume

The effect of an external electric field on laser-generated plasma has been studied. It is observed that the laser-generated plasma can be used for the ignition of a spark in the presence of a low voltage external electric field. An eight-fold emission intensity enhancement in Cu Ⅰ spectral lines are measured as compared to the signal intensity in the absence of an external electric field.The plasma parameters remain the same initially, up to a few microseconds after the generation of plasma, and this feature makes it more interesting for the quantitative analysis of any sample using laser induced breakdown spectroscopy(LIBS). In the presence of an external electric field,fluctuations(contraction and expansion) in the laser-generated plasma are observed which increase the plasma decay time and consequently result in enhanced signal intensity.     

Synthesis and Physical Properties of Mn Doped ZnO Dilute Magnetic Semiconductor Nanostructures

Mn doped ZnO nanostructures have been prepared using low temperature simple, quick, and versatile synthesis approach. The structural, microstructural, and vibrational investigations reveal that as prepared nanostructures with low Mn doping concentration have single hexagonal phase and are grown along the preferred c-axis. The X-rays photoelectron spectroscopy demonstrates that the Mn ions are in mixed oxidation states for high doping concentration of Mn, while are in 2+ oxidation state for low concentration into ZnO lattice. The photoluminescence spectrum (PL) exhibits a significant red-shift of 22 nm in the optical band gap of doped ZnO and shows the improved luminescence properties, which makes it potential for its use in the photocatalyst, optoelectronics and solar cell nanodevices. Furthermore, the magnetic measurement of Mn doped ZnO nanostructures exhibits the ferromagnetism at room temperature.     

The effect of some alloying elements on the corrosion resistance of lead-antimony alloys — II. Silver

The effect of Ag on the stationary and non-stationary anodic corrosion rates of PbSbCd and PbSb alloys in H₂SO₄ has been studied. Anodic polarization curves were constructed under galvanostatic and potentiostatic conditions. Optical microscopic examination and microprobe analysis of the alloys were conducted. The beneficial effect of Ag was ascribed to a delay in closure of pores in the initial PbSO₄ film. The leaching out of Sb from the outermost layers and the simultaneous nucleation of PbSO₄ and Ag₂SO₄ from supersaturated solutions in the pores is thus made possible.     

Atomic-Resolution Structures and Mode of Action of Clinically Relevant Antimicrobial Peptides

Global rise of infections and deaths caused by drug-resistant bacterial pathogens are among the unmet medical needs. In an age of drying pipeline of novel antibiotics to treat bacterial infections, antimicrobial peptides (AMPs) are proven to be valid therapeutics modalities. Direct in vivo applications of many AMPs could be challenging; however, works are demonstrating encouraging results for some of them. In this review article, we discussed 3-D structures of potent AMPs e.g., polymyxin, thanatin, MSI, protegrin, OMPTA in complex with bacterial targets and their mode of actions. Studies on human peptide LL37 and de novo-designed peptides are also discussed. We have focused on AMPs which are effective against drug-resistant Gram-negative bacteria. Since treatment options for the infections caused by super bugs of Gram-negative bacteria are now extremely limited. We also summarize some of the pertinent challenges in the field of clinical trials of AMPs.