Multiway analysis applied to time‐resolved chemiluminescence for simultaneous determination of paracetamol and codeine in pharmaceuticals

This method is based on the enhancing effect of codeine (COD) and paracetamol (PAR) on the chemiluminescence (CL) reaction of Ru(phen)₃²⁺ with Ce(IV). In the batch mode, COD gives a relatively sharp peak with the highest CL intensity at 4.0 s, whereas the maximum CL intensity of the PAR appears at ~60 s after injection of Ce(IV) solution. Whole CL time profiles allowed use of the time‐resolved CL data in combination with multiway calibration techniques, as multiway partial least squares (N‐PLS), for the quantitative determination of both COD and PAR in binary mixtures. In this work, we found that the impact of Ce(IV) concentration on the CL intensity was different for COD and PAR. Therefore, a Ce(IV) concentration mode was added to the time and sample modes to obtain 3D data. The percent relative standard deviation (%RSD) values for 10 determinations of 1.0 × 10^?5 mol/L of COD and 1.0 × 10^?4 mol/L of PAR were 6.1% and 8.7%, respectively. The limit of detection (LOD) values (S/N = 3) were 0.9 × 10^?8 mol/L and 1.0 × 10^?6 mol/L for COD and PAR, respectively. The proposed method was successfully applied to the determination of PAR and COD in commercial pharmaceutical formulations. Acceptable recoveries (90–110%) were obtained for the quantification of these drugs in the real samples. Copyright © 2016 John Wiley & Sons, Ltd.     

Can Lionel Messi’s brain slow down time passing?

It seems that seeing others in slow-motion by heroes does not belong only to movies. When Lionel Messi plays football, you can hardly see anything from him that other players cannot do. Then why he is not stoppable really? It seems the answer may be that opponents do not have enough time to do what they want; because in Messi’s neural system, time passes slower. In differential equations that model a single neuron, this speed can be generated by multiplying an equal term in all equations. Or maybe interactions between neurons and the structure of neural networks play this role.     

Technical reproducibility of genotyping SNP arrays used in genome-wide association studies

During the last several years, high-density genotyping SNP arrays have facilitated genome-wide association studies (GWAS) that successfully identified common genetic variants associated with a variety of phenotypes. However, each of the identified genetic variants only explains a very small fraction of the underlying genetic contribution to the studied phenotypic trait. Moreover, discordance observed in results between independent GWAS indicates the potential for Type I and II errors. High reliability of genotyping technology is needed to have confidence in using SNP data and interpreting GWAS results. Therefore, reproducibility of two widely genotyping technology platforms from Affymetrix and Illumina was assessed by analyzing four technical replicates from each of the six individuals in five laboratories. Genotype concordance of 99.40% to 99.87% within a laboratory for the sample platform, 98.59% to 99.86% across laboratories for the same platform, and 98.80% across genotyping platforms was observed. Moreover, arrays with low quality data were detected when comparing genotyping data from technical replicates, but they could not be detected according to venders' quality control (QC) suggestions. Our results demonstrated the technical reliability of currently available genotyping platforms but also indicated the importance of incorporating some technical replicates for genotyping QC in order to improve the reliability of GWAS results. The impact of discordant genotypes on association analysis results was simulated and could explain, at least in part, the irreproducibility of some GWAS findings when the effect size (i.e. the odds ratio) and the minor allele frequencies are low.     

Reversing the trend of wildlife crime in Tanzania: challenges and opportunities

Wildlife crime is increasingly gaining prominence in global environmental debates. The crime, generating huge financial returns to few individuals, has far reaching implications on ecology, economy and global security. The seriousness of these implications provides sufficient rationale for reconsidering and intensifying efforts to combat this crime. However, these efforts are compromised by a number of challenges, though opportunities for success exist. This paper presents some of these challenges and opportunities available for reversing the trend of wildlife crime in Tanzania. The challenges presented include poverty, high profit associated with illicit trade on wildlife, poor governance and corruption, minimal budget and inadequate institutional support, political interference and low employee morale, minimal benefits to local communities, human population growth, climate change and HIV/AIDS pandemic. Opportunities identified include increased public awareness, growing global political concern and commitment, presence of relevant policies, programmes and strategies along with international agreements supportive to species protection. Before embarking on challenges and opportunities, the paper provides an overview of Tanzania’s wildlife resources, status and trend of this crime. In conclusion, the paper underscores the gravity of the problem and its implications and offers some recommendations for improving the situation.     

Trends in the Design and Development of Specific Aptamers Against Peptides and Proteins

Aptamers are single stranded oligonucleotides, comparable to monoclonal antibodies (mAbs) in selectivity and affinity and have significant strategic properties in design, development and applications more than mAbs. Ease of design and development, simple chemical modification and the attachment of functional groups, easily handling and more adaptability with analytical methods, small size and adaptation with nanostructures are the valuable characteristics of aptamers in comparison to large protein based ligands. Among a broad range of targets that their specific aptamers developed, proteins and peptides have significant position according to the number of related studies performed so far. Since proteins control many of important physiological and pathological incidents in the living organisms, particularly human beings and because of the benefits of aptamers in clinical and analytical applications, aptamer related technologies in the field of proteins and peptides are under progress, exclusively. Currently, there is only one FDA approved therapeutic aptamer in the pharmaceutical market, which is specific to vascular endothelial growth factor and is prescribed for age related macular degenerative disease. Additionally, there are several aptamers in the different phases of clinical trials. Almost all of these aptamers are specific to clinically important peptide or protein targets. In addition, the application of protein specific aptamers in the design and development of targeted drug delivery systems and diagnostic biosensors is another intersting field of aptamer technology. In this review, significant efforts related to development and applications of aptamer technologies in proteins and peptides sciences were considered to emphasis on the importance of aptamers in medicinal and clinical applications.     

A multiscale cell‐based model of tumor growth for chemotherapy assessment and tumor‐targeted therapy through a 3D computational approach

ObjectivesComputational modeling of biological systems is a powerful tool to clarify diverse processes contributing to cancer. The aim is to clarify the complex biochemical and mechanical interactions between cells, the relevance of intracellular signaling pathways in tumor progression and related events to the cancer treatments, which are largely ignored in previous studies.Materials and MethodsA three‐dimensional multiscale cell‐based model is developed, covering multiple time and spatial scales, including intracellular, cellular, and extracellular processes. The model generates a realistic representation of the processes involved from an implementation of the signaling transduction network.ResultsConsidering a benign tumor development, results are in good agreement with the experimental ones, which identify three different phases in tumor growth. Simulating tumor vascular growth, results predict a highly vascularized tumor morphology in a lobulated form, a consequence of cells'' motile behavior. A novel systematic study of chemotherapy intervention, in combination with targeted therapy, is presented to address the capability of the model to evaluate typical clinical protocols. The model also performs a dose comparison study in order to optimize treatment efficacy and surveys the effect of chemotherapy initiation delays and different regimens.ConclusionsResults not only provide detailed insights into tumor progression, but also support suggestions for clinical implementation. This is a major step toward the goal of predicting the effects of not only traditional chemotherapy but also tumor‐targeted therapies.     

Expression of anti human IL-4 and IL-6 scFvs in transgenic tobacco plants

The two murine single-chain Fv (scFv) genes against human interleukin IL-4 and IL-6 cytokines were cloned in a plant expression vector (pGEJAE1) and mobilized to Agrobacterium tumefaciens. Tobacco leaf discs were co-cultured with Agrobacterium and transferred to selective media for regeneration. The tobacco in vitro plants produced scFvs against human IL-4 and IL-6. Only 8% of transformed plants expressing anti-IL-4 scFv were obtained versus 76% of transformed plants expressing anti-IL-6 scFv. In addition, some plants producing anti-IL-4 and anti-IL-6 scFvs aged more rapidly in in vitro conditions and in greenhouse pots than did control plants. Western blot analysis showed that the transformed Nicotiana tabacum plants contained proteins with an apparent molecular mass on electrophoresis of ca. 32 kDa, corresponding to the predicted size of the scFvs. As entire plant root seemed to accumulate more scFv than did leaves, we decided to continue working with isolated roots. Anti-IL-6 scFvs were detected in cultivated roots and their culture media. Functional anti-IL-6 scFv accounted for 0.16–0.18% of total soluble proteins. The affinity of the anti-IL-6 scFv produced in plants and measured by Biacore was similar to that of scFv produced in Escherichia coli. The high levels of antibody accumulation in isolated roots and secretion into the medium demonstrate the potential for producing recombinant protein in bioreactor systems.these authors contributed equally to this workthese authors contributed equally to this work     

Membrane Anchoring by a C-terminal Tryptophan Enables HIV-1 Vpu to Displace Bone Marrow Stromal Antigen 2 (BST2) from Sites of Viral Assembly

The restriction factor BST2 (tetherin) prevents the release of enveloped viruses from the host cell and is counteracted by HIV-1 Vpu. Vpu and BST2 interact directly via their transmembrane domains. This interaction enables Vpu to induce the surface down-regulation and the degradation of BST2, but neither of these activities fully accounts for the ability of Vpu to enhance virion release. During a study of naturally occurring Vpu proteins, we found that a tryptophan residue near the Vpu C terminus is particularly important for enhancing virion release. Vpu proteins with a W76G polymorphism degraded and down-regulated BST2 from the cell surface, yet they inefficiently stimulated virion release. Here we explore the mechanism of this anomaly. We find that Trp-76 is critical for the ability of Vpu to displace BST2 from sites of viral assembly in the plane of the plasma membrane. This effect does not appear to involve a general reorganization of the membrane microdomains associated with virion assembly, but rather is a specific effect of Vpu on BST2. Using NMR spectroscopy, we find that the cytoplasmic domain of Vpu and Trp-76 specifically interact with lipids. Moreover, paramagnetic relaxation enhancement studies show that Trp-76 inserts into the lipid. These data are consistent with a model whereby Trp-76 anchors the C terminus of the cytoplasmic tail of Vpu to the plasma membrane, enabling the movement of Vpu-bound BST2 away from viral assembly sites.