Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T(reg) cells

Although immune mechanisms can suppress tumour growth, tumours establish potent, overlapping mechanisms that mediate immune evasion. Emerging evidence suggests a link between angiogenesis and the tolerance of tumours to immune mechanisms. Hypoxia, a condition that is known to drive angiogenesis in tumours, results in the release of damage-associated pattern molecules, which can trigger the rejection of tumours by the immune system. Thus, the counter-activation of tolerance mechanisms at the site of tumour hypoxia would be a crucial condition for maintaining the immunological escape of tumours. However, a direct link between tumour hypoxia and tolerance through the recruitment of regulatory cells has not been established. We proposed that tumour hypoxia induces the expression of chemotactic factors that promote tolerance. Here we show that tumour hypoxia promotes the recruitment of regulatory T (T(reg)) cells through induction of expression of the chemokine CC-chemokine ligand 28 (CCL28), which, in turn, promotes tumour tolerance and angiogenesis. Thus, peripheral immune tolerance and angiogenesis programs are closely connected and cooperate to sustain tumour growth.     

Fractional-order model of the disease Psoriasis: A control based mathematical approach

Autoimmune diseases are generated through irregular immune response of the human body. Psoriasis is one type of autoimmune chronic skin diseases that is differentiated by T-Cells mediated hyper-proliferation of epidermal Keratinocytes. Dendritic Cells and CD8⁺ T-Cells have a significant role for the occurrence of this disease. In this paper, the authors have developed a mathematical model of Psoriasis involving CD4⁺ T-Cells, Dendritic Cells, CD8⁺ T-Cells and Keratinocyte cell populations using the fractional differential equations with the effect of Cytokine release to observe the impact of memory on the cell-biological system. Using fractional calculus, the authors try to explore the suppressed memory, associated with the cell-biological system and to locate the position of Keratinocyte cell population as fractional derivative possess non-local property. Thus, the dynamics of Psoriasis can be predicted in a better way using fractional differential equations rather than its corresponding integer order model. Finally, the authors introduce drug into the system to obstruct the interaction between CD4⁺ T-Cells and Keratinocytes to restrict the disease Psoriasis. The authors derive the Euler-Lagrange conditions for the optimality of the drug induced system. Numerical simulations are made through Matlab by developing iterative schemes.     

Transvascular delivery of small interfering RNA to the central nervous system

A major impediment in the treatment of neurological diseases is the presence of the blood-brain barrier, which precludes the entry of therapeutic molecules from blood to brain. Here we show that a short peptide derived from rabies virus glycoprotein (RVG) enables the transvascular delivery of small interfering RNA (siRNA) to the brain. This 29-amino-acid peptide specifically binds to the acetylcholine receptor expressed by neuronal cells. To enable siRNA binding, a chimaeric peptide was synthesized by adding nonamer arginine residues at the carboxy terminus of RVG. This RVG-9R peptide was able to bind and transduce siRNA to neuronal cells in vitro, resulting in efficient gene silencing. After intravenous injection into mice, RVG-9R delivered siRNA to the neuronal cells, resulting in specific gene silencing within the brain. Furthermore, intravenous treatment with RVG-9R-bound antiviral siRNA afforded robust protection against fatal viral encephalitis in mice. Repeated administration of RVG-9R-bound siRNA did not induce inflammatory cytokines or anti-peptide antibodies. Thus, RVG-9R provides a safe and noninvasive approach for the delivery of siRNA and potentially other therapeutic molecules across the blood-brain barrier.     

A threshold model for the French franc/deutschmark exchange rate

The behaviour of the French franc/deutschmark exchange rate is examined in this paper. During the time period studied, these currencies were constrained to lie within prescribed bands relative to one another and the usual random walk explanation of the exchange rate may not be appropriate. The data are examined for evidence of non-linear structure and it is shown that a piecewise linear SETAR model provides a better explanation and superior forecasting performance than a random walk.