E.Coli derived camelid antibodies as a sensor for P53 in saliva

Oral squamous cell carcinoma (OSCC) is a malignant tumor with 640,000 new cases annually in the world [1]. Saliva testing is non-invasive procedure that is capable to detect potential biomarkers for OSCC. It was shown that elevated level of p53 protein was identified in OSCC patients at different stages of the disease (ibid). Camelid antibodies containing only variable regions, nanobodies (VHH) and single-chain variable regions (scFv) with VH and VL, are becoming popular in many biological studies including diagnostic applications. It was identified that VL region alone showed higher affinity to p53 than VHH, and dimerization of VL region with another one increases the affinity up to 10 folds [2]. Camelid antibodies have similar affinity to its substrate as human antibodies and can be conjugated to other proteins without functional lose. They can be expressed and secreted in many organisms including E.Coli in high amount, which reduces the cost of antibodies production. Thus, the aim of this project is to design a biosensor, based on available sequence of antibodies, to detect p53 in saliva samples for OSCC diagnosis

Resolution of dark matter problem in f(T) gravity

In this paper, we attempt to resolve the dark matter problem in f(T) gravity. Specifically, from our model we successfully obtain the flat rotation curves of galaxies containing dark matter. Further, we obtain the density profile of dark matter in galaxies. Comparison of our analytical results shows that our torsion-based toy model for dark matter is in good agreement with empirical data-based models. It shows that we can address the dark matter as an effect of torsion of the space.Comment: 14 pages, 3 figure

Identification of a Novel Class of Farnesylation Targets by Structure-Based Modeling of Binding Specificity

Farnesylation is an important post-translational modification catalyzed by farnesyltransferase (FTase). Until recently it was believed that a C-terminal CaaX motif is required for farnesylation, but recent experiments have revealed larger substrate diversity. In this study, we propose a general structural modeling scheme to account for peptide binding specificity and recapitulate the experimentally derived selectivity profile of FTase in vitro. In addition to highly accurate recovery of known FTase targets, we also identify a range of novel potential targets in the human genome, including a new substrate class with an acidic C-terminal residue (CxxD/E). In vitro experiments verified farnesylation of 26/29 tested peptides, including both novel human targets, as well as peptides predicted to tightly bind FTase. This study extends the putative range of biological farnesylation substrates. Moreover, it suggests that the ability of a peptide to bind FTase is a main determinant for the farnesylation reaction. Finally, simple adaptation of our approach can contribute to more accurate and complete elucidation of peptide-mediated interactions and modifications in the cell

Generalized Second Law of Thermodynamics in f(T)f(T) Gravity with Entropy Corrections

We study the generalized second law (GSL) of thermodynamics in $f(T)$ cosmology. We consider the universe as a closed bounded system filled with $n$ component fluids in the thermal equilibrium with the cosmological boundary. We use two different cosmic horizons: the future event horizon and the apparent horizon. We show the conditions under which the GSL will be valid in specific scenarios of the quintessence and the phantom energy dominated eras. Further we associate two different entropies with the cosmological horizons: with a logarithmic correction term and a power-law correction term. We also find the conditions for the GSL to be satisfied or violated by imposing constraints on model parameters.Comment: 17 pages, no figure, title changed, version accepted for publication in Astrophysics and Space Scienc

The Coupling of Alternative Splicing and Nonsense-Mediated mRNA Decay

Most human genes exhibit alternative splicing, but not all alternatively spliced transcripts produce functional proteins. Computational and experimental results indicate that a substantial fraction of alternative splicing events in humans result in mRNA isoforms that harbor a premature termination codon (PTC). These transcripts are predicted to be degraded by the nonsense-mediated mRNA decay (NMD) pathway. One explanation for the abundance of PTC-containing isoforms is that they represent splicing errors that are identified and degraded by the NMD pathway. Another potential explanation for this startling observation is that cells may link alternative splicing and NMD to regulate the abundance of mRNA transcripts. This mechanism, which we call "Regulated Unproductive Splicing and Translation" (RUST), has been experimentally shown to regulate expression of a wide variety of genes in many organisms from yeast to human. It is frequently employed for autoregulation of proteins that affect the splicing process itself. Thus, alternative splicing and NMD act together to play an important role in regulating gene expression

Alternatively spliced short and long isoforms of adaptor protein intersectin 1 form complexes in mammalian cells

Intersectin 1 (ITSN1) is an adaptor protein involved in membrane trafficking and cell signaling. Long and short isoforms of ITSN1 (ITSN1-L and ITSN1-S) are produced by alternative splicing. The aim of our study was to investigate whether ITSN1-L and ITSN1-S could interact in mammalian cells. Methods. During this study we employed immunoprecipitation and confocal microscopy. Results. We have shown that endogenous ITSN1-S co-precipitates with overexpressed ITSN1-L in PC12, 293 and 293T cells. Long and short isoforms of ITSN1 also co-localize in 293T cells. Conclusions. ITSN1-L and ITSN1-S form complexes in mammalian cells