The stoichiometry of peptide-heparan sulfate binding as a determinant of uptake efficiency of cell-penetrating peptides

Binding to negatively charged heparan sulfates (HS) at the cell surface is considered the first step in the internalization of cationic cell-penetrating peptides (CPPs). However, little is known about the relation of the characteristics of the HS-CPP interaction such as affinity, stoichiometry, and clustering with uptake. In this study, we investigated a collection of mutants of a cyclic CPP derived from human lactoferrin with respect to HS binding and uptake. The thermodynamic parameters of HS binding were determined by isothermal titration calorimetry, clustering of HS was investigated by dynamic light scattering, and cellular uptake by flow cytometry and confocal microscopy. Whereas mutations of non-arginine amino acids that are conserved across lactoferrins of different mammalia only had a minor effect on uptake efficiency, changes in the number of arginine residues influenced the uptake significantly. In general, introduction of arginine residues and cyclization improved the HS affinity and the ability to cluster HS. In particular, there was a strong negative correlation between stoichiometry and uptake, indicating that crosslinking of HS is the driving force for the uptake of arginine-rich CPPs. Using glycan microarrays presenting a collection of synthetic HS, we show that a minimal chain length of HS is required for peptide binding.     

Polycaprolactone Grafting of Cellulose Nanocrystals in Ionic Liquid[BMIM]CI

A polycaprolactone-grafted cellulose nanocrystal(PCL-g-CN) was prepared in ionic liquid and characterized by Fourier transform infrared spectrum(FT-IR),X-ray diffraction(XRD),and transmission electron microscopy(TEM).A peak assigned to the carbonyl group appears at 1 730 cm~(-1) in the FT-IR of PCL-g-CN,which confirms that the grafting reaction is successfully completed.The morphologies of PCL-g-CNs still maintain rod-like structure according to the TEM images.XRD results show that the crystal type of the PCL-g-CNs changed from cellulose Ⅰ to cellulose Ⅱ.The reasons for crystal transition of CNs turn out to be combined effects of anion and cation in ionic liquid with CNs.     

On a relation between modular functions and Dirichlet series: found in the estate of Adolf Hurwitz

Archive for History of Exact Sciences - Adolf Hurwitz’s estate contains a note from the early 1880s on the converse to Riemann’s proof of the functional equation for the zeta-function;...     

Activation of stress signalling pathways enhances tolerance of fungi to chemical fungicides and antifungal proteins

Fungal disease is an increasing problem in both agriculture and human health. Treatment of human fungal disease involves the use of chemical fungicides, which generally target the integrity of the fungal plasma membrane or cell wall. Chemical fungicides used for the treatment of plant disease, have more diverse mechanisms of action including inhibition of sterol biosynthesis, microtubule assembly and the mitochondrial respiratory chain. However, these treatments have limitations, including toxicity and the emergence of resistance. This has led to increased interest in the use of antimicrobial peptides for the treatment of fungal disease in both plants and humans. Antimicrobial peptides are a diverse group of molecules with differing mechanisms of action, many of which remain poorly understood. Furthermore, it is becoming increasingly apparent that stress response pathways are involved in the tolerance of fungi to both chemical fungicides and antimicrobial peptides. These signalling pathways such as the cell wall integrity and high-osmolarity glycerol pathway are triggered by stimuli, such as cell wall instability, changes in osmolarity and production of reactive oxygen species. Here we review stress signalling induced by treatment of fungi with chemical fungicides and antifungal peptides. Study of these pathways gives insight into how these molecules exert their antifungal effect and also into the mechanisms used by fungi to tolerate sub-lethal treatment by these molecules. Inactivation of stress response pathways represents a potential method of increasing the efficacy of antifungal molecules.     

Fabrication of an r-Al2Ti intermetallic matrix composite reinforced with α-Al2O3 ceramic by discontinuous mechanical milling for thermite reaction

In this study, a powder mixture with an Al/TiO2 molar ratio of 10/3 was used to form an r-Al2Ti intermetallic matrix composite (IMC) reinforced withα-Al2O3 ceramic by a novel milling technique, called ...     

Flora of the Lee Creek valley, Alberta

The floristic composition of the Lee Creek valley in southwestern Alberta, Canada, is presented. The valley flora consists of 299 species of vascular plants representing 173 genera and 46 families. The flora is dominated by forbs (73 percent), followed by grasses (24 percent), shrubs (12 percent), and trees (11 percent). The valley of Lee Creek is divided into upper and lower sections on the basis of elevational, climatic, and biotic differences. Floristic richness of the Lee Creek valley is quite evenly divided between the upper and lower valleys: 105 species limited to the upper valley, 95 to the lower valley, and 99 species shared by both upper and lower valleys.     

Programmable and autonomous computing machine made of biomolecules.

Devices that convert information from one form into another according to a definite procedure are known as automata. One such hypothetical device is the universal Turing machine, which stimulated work leading to the development of modern computers. The Turing machine and its special cases, including finite automata, operate by scanning a data tape, whose striking analogy to information-encoding biopolymers inspired several designs for molecular DNA computers. Laboratory-scale computing using DNA and human-assisted protocols has been demonstrated, but the realization of computing devices operating autonomously on the molecular scale remains rare. Here we describe a programmable finite automaton comprising DNA and DNA-manipulating enzymes that solves computational problems autonomously. The automaton's hardware consists of a restriction nuclease and ligase, the software and input are encoded by double-stranded DNA, and programming amounts to choosing appropriate software molecules. Upon mixing solutions containing these components, the automaton processes the input molecule via a cascade of restriction, hybridization and ligation cycles, producing a detectable output molecule that encodes the automaton's final state, and thus the computational result. In our implementation 1012 automata sharing the same software run independently and in parallel on inputs (which could, in principle, be distinct) in 120 microl solution at room temperature at a combined rate of 109 transitions per second with a transition fidelity greater than 99.8%, consuming less than 10-10 W.     

How 'spin ice' freezes.

The large degeneracy of states resulting from the geometrical frustration of competing interactions is an essential ingredient of important problems in fields as diverse as magnetism, protein folding and neural networks. As first explained by Pauling, geometrical frustration of proton positions is also responsible for the unusual low-temperature thermodynamics of ice and its measured 'ground state' entropy. Recent work has shown that the geometrical frustration of ice is mimicked by Dy2Ti2O7, a site-ordered magnetic material in which the spins reside on a lattice of corner-sharing tetrahedra where they form an unusual magnetic ground state known as 'spin ice'. Here we identify a cooperative spin-freezing transition leading to the spin-ice ground state in Dy2Ti2O7. This transition is associated with a very narrow range of relaxation times, and represents a new form of spin-freezing. The dynamics are analogous to those associated with the freezing of protons in ice, and they provide a means through which to study glass-like behaviour and the consequences of frustration in the limit of low disorder.     

Water capture by a desert beetle.

Some beetles in the Namib Desert collect drinking water from fog-laden wind on their backs. We show here that these large droplets form by virtue of the insect's bumpy surface, which consists of alternating hydrophobic, wax-coated and hydrophilic, non-waxy regions. The design of this fog-collecting structure can be reproduced cheaply on a commercial scale and may find application in water-trapping tent and building coverings, for example, or in water condensers and engines.