SNARE derived peptide mimic inducing membrane fusion

SNARE proteins mediate membrane fusion between synaptic vesicles and the plasma membrane. A minimized peptide SNARE model system with reduced complexity was introduced combining the native SNARE transmembrane (TMD) and linker domains with artificial coiled-coil forming peptides. Specific membrane fusion initiated by coiled-coil recognition was shown by lipid and content mixing vesicle assays.     

Polymorphism of sorbitol

The polymorphism of sorbitol was investigated, confirming the existence of four anhydrous crystalline phases plus the hydrate. The crystallised melt (CM), the alpha form, and the gamma form were obtained via a dry route. The CM was confirmed to be a crystalline state with a spherulite morphology. The alpha form was obtained via direct conversion from the CM, in contrast to more complicated routes previously reported, and was found to have a very high crystallinity. Gamma crystals were obtained by seeding the melt at high temperature; however, crystallinity was clearly less than for alpha crystals.     

Approximate Central Limit Theorems

We refine the classical Lindeberg–Feller central limit theorem by obtaining asymptotic bounds on the Kolmogorov distance, the Wasserstein distance, and the parameterized Prokhorov distances in terms of a Lindeberg index. We thus obtain more general approximate central limit theorems, which roughly state that the row-wise sums of a triangular array are approximately asymptotically normal if the array approximately satisfies Lindeberg’s condition. This allows us to continue to provide information in nonstandard settings in which the classical central limit theorem fails to hold. Stein’s method plays a key role in the development of this theory.     

Introduction: Vagueness and Ontology

The article introduces a special issue of the journal Metaphysica on vagueness and ontology. The conventional view has it that all vagueness is semantic or representational. Russell, Dummett, Evans and Lewis, inter alia, have argued that the notion of “ontic” or “metaphysical” vagueness is not even intelligible. In recent years, a growing minority of philosophers have tried to make sense of the notion and have spelled it out in various ways. The article gives an overview and relates the idea of ontic vagueness to the unquestioned phenomenon of fuzzy spatiotemporal boundaries and to the associated “problem of the many”. It briefly discusses the question of whether ontic vagueness can be spelled out in terms of “vague identity”, emphasizes the often neglected role of the difference between sortal and non-sortal ontologies and suggests a deflationary answer to the ill-conceived question of whether the “ultimate source” of vagueness lies either in language or in the world.     

Linear solvation energy relationships of anionic dimeric surfactants in micellar electrokinetic chromatography I. Effect of the length of a hydrophobic spacer

The influence of the length of a flexible hydrophobic spacer on the selectivity of anionic dimeric surfactants was investigated. Disodium 1,omega-bis(decyloxymethyl)-dioxa alkane-1,omega disulfates with a spacer containing an ethylene, butylene, hexylene, octylene, decylene or dodecylene group were synthesized, and four of these were evaluated for use in micellar electrokinetic chromatography (MEKC) via linear solvation energy relationships (LSERs). There were no significant differences in the system constants of these surfactants, indicating that their micelles all have a very similar interface with the aqueous phase, regardless of the length of the hydrophobic spacer. Compared to sodium dodecylsulfate (SDS), these dimeric surfactants are slightly more cohesive, interact better with polarizable compounds, and are somewhat better hydrogen bond acceptors and worse hydrogen bond donors, while there is no difference in dipolarity. The critical micelle concentrations (CMCs) of these surfactants were in the order of 1mM, except for the dimeric surfactant with a spacer containing an ethylene group, which had a CMC <0.03 mM.     

Protein Functionalization Revised: N‐tert‐butoxycarbonylation as an Elegant Tool to Circumvent Protein Crosslinking

The protection of primary amines available in proteins holds great potential to introduce a plethora of diverse functionalities along the protein backbone (e.g., via its carboxylic acid or alcohol moieties) while circumventing the crosslinking issue using conventional approaches. This paper reports on a straightforward and efficient proof‐of‐concept including the chemoselective N‐tert‐butyloxycarbonylation of the primary amines in the protein gelatin (gel‐NH‐BOC), followed by introducing crosslinkable methacrylamide moieties. The reaction is performed successfully under relatively mild conditions (50 °C). Following selective protein functionalization, the deprotection is realized by adding a catalytic amount of an aqueous hydrogen chloride solution. The present communication illustrates the occurrence of a straightforward and selective deprotection procedure, which is typically required to circumvent the occurrence of acidic hydrolysis of the protein backbone. The results hold promise for a large range of biomedical applications in which the presence of primary amines is essential for preserving the biological activity.

     

Single-cell recording and stimulation with a 16k micro-nail electrode array integrated on a 0.18 μm CMOS chip

To cope with the growing needs in research towards the understanding of cellular function and network dynamics, advanced micro-electrode arrays (MEAs) based on integrated complementary metal oxide semiconductor (CMOS) circuits have been increasingly reported. Although such arrays contain a large number of sensors for recording and/or stimulation, the size of the electrodes on these chips are often larger than a typical mammalian cell. Therefore, true single-cell recording and stimulation remains challenging. Single-cell resolution can be obtained by decreasing the size of the electrodes, which inherently increases the characteristic impedance and noise. Here, we present an array of 16,384 active sensors monolithically integrated on chip, realized in 0.18 μm CMOS technology for recording and stimulation of individual cells. Successful recording of electrical activity of cardiac cells with the chip, validated with intracellular whole-cell patch clamp recordings are presented, illustrating single-cell readout capability. Further, by applying a single-electrode stimulation protocol, we could pace individual cardiac cells, demonstrating single-cell addressability. This novel electrode array could help pave the way towards solving complex interactions of mammalian cellular networks.