A Nanoscale Molecular Switch Triggered by Thermal,Light, and Guest Perturbation

Bottoms up! A discrete metallo‐supramolecular nanoball (see picture), synthesized by using “bottom‐up” methodologies, uniquely undergoes a solvent‐sensitive, physically addressable electronic spin switching. The switching occurs by thermal, light, or solvent perturbation, where importantly it can be switched “on” or “off” by green or red laser irradiation, respectively.

     

Inside Cover: A Nanoscale Molecular Switch Triggered by Thermal,Light, and Guest Perturbation (Angew. Chem. Int. Ed. 14/2009)

Continuous switching between high‐spin and low‐spin magnetic states can be accomplished by irradiation with red and green laser light, respectively. In their Communication on page 2549 ff., S. R. Batten and co‐workers report a metallo‐supramolecule that undergoes spin crossover (SCO) switching induced by temperature change or light irradiation. The SCO behavior is also dependent on the presence and nature of intercalated solvent molecules within the porous crystal structure.

     

Systems-based decomposition schemes for the approximate solution of multi-term fractional differential equations

We give a comparison of the efficiency of three alternative decomposition schemes for the approximate solution of multi-term fractional differential equations using the Caputo form of the fractional derivative. The schemes we compare are based on conversion of the original problem into a system of equations. We review alternative approaches and consider how the most appropriate numerical scheme may be chosen to solve a particular equation.     

Improved tandem mass spectrometric characterization of 3-nitrotyrosine sites in peptides

Nitrated tyrosines are easily converted into their aminotyrosine equivalents by a reduction step. We here show that this conversion can be exploited to readily discern 3-aminotyrosine peptides in a background of non-nitrated peptides. Furthermore, aminotyrosine peptides are more stable in single mass spectrometry (MS) mode rendering peptide mass maps easier to interpret. One significant caveat of both 3-nitrotyrosine and 3-aminotyrosine peptides is their lack of efficient fragmentation upon collision-induced dissociation (CID) which, in the case of the latter peptides, also produces unexpected, deviating isotopic patterns of fragment ions containing the aminotyrosine residue. The net result is that sequence database searching becomes daunting as the correct peptide is frequently missed since insufficient and/or inaccurate peptide fragments are used. We show that a simple acetylation step, blocking all amines (including aminotyrosine), produces peptides that undergo extensive backbone fragmentation by CID and are thus easily identifiable in databases. Our procedure is additionally illustrated by doubling the number of nitration events mapped in tetranitromethane-nitrated bovine serum albumin (BSA) as compared to a direct analysis of the nitrated peptides using the same amount of material. In conclusion, we here illustrate that this two-step process, heme-mediated reduction and acetylation, can be used for more efficient characterization of protein-bound nitrated tyrosines.     

Multiplexed protein detection using an affinity aptamer amplification assay

Affinity probe capillary electrophoresis (APCE) is potentially one of the most versatile technologies for protein diagnostics, offering an excellent balance between robustness, analysis speed and sensitivity. Combining the immunosensing and separating strength of capillary electrophoresis with the signal enhancement power of nucleic acid amplification, aptamers can further push the analytical limits of APCE to offer ultrasensitive, multiplexed detection of protein biomarkers, even when differences in electrophoretic mobility between the different aptamer-target complexes are limited. It is demonstrated how, through careful selection of experimental parameters, simultaneous detection of picomolar levels of three target proteins can be achieved even with aptamers that were initially selected under very different conditions and further taking into account that the aptamers need to be modified to allow successful PCR amplification. Aptamer-enhanced APCE offers limits of detection that are orders of magnitude lower than those that can be achieved through traditional capillary electrophoresis-based immunosensing. With recent developments in aptamer selection that for the first time realise the promise of aptamers as easily accessible, high affinity recognition molecules, it can therefore be envisioned that aptamer-enhanced APCE on parallel microfluidic platforms can be the basis for a truly high-throughput multiplexed proteomics platform, rivalling genetic screening for the first time.     

Ageing of enteric neurons: oxidative stress, neurotrophic factors and antioxidant enzymes

Background

??Dragon??s Blood?? (DB) has long been used as an ethnomedicine in China to invigorate blood circulation for the treatment of traumatic injuries, blood stasis and pain. To comprehensively assess the quality of DB medicine, a precise and accurate method that can rapidly separate, characterize and quantify multiple active components of DB is crucial.

Results

An ultra performance liquid chromatography (UPLC) coupled with photodiode array detection (PAD) and electrospray ionization mass spectrometry (ESI-MS) method was developed for characterization and determination of six flavonoids in DB. A comprehensive validation of the developed method was conducted, and confirmed that the method presented good sensitivity, precision and accuracy. All linear regressions were acquired with R ² > 0.99, and the limits of detection ranged from 0.06 to 0.83 ng. The relative standard deviation (RSD) values were found to be within the range 1.4?C3.8% for the method repeatability test. Recovery studies for the quantified compounds were found to be within the range 94.2?C102.8% with RSD less than 4.9%. DB samples collected from different geographical regions were analyzed by the present method, and the results demonstrated that the contents of the six flavonoids in DB samples varied significantly. Three major active components among the six flavonoids, namely dracorhodin, (2S)-5-methoxyflavan-7-ol and (2S)-5-methoxy-6-methylflavan-7-ol, are suggested as the index for DB quality evaluation.

Conclusions

Overall, the present hyphenation method is highly efficient and reliable, and hence suitable for the characterization and determination of the flavonoids of DB ethnomedicine.     

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.     

End effects influence short model peptide conformation

Previously, we derived a P(II) propensity scale using N- and C-terminally blocked host-guest peptide model AcGGXGGNH(2) (X ≠ Gly) and concluded that P(II) represents a dominant conformation in the majority of this series of 19 peptides (Shi et al. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 17964-17968). Recently, Schweitzer-Stenner and co-workers examined a series of eight short host-guest tripeptides with the sequence GXG (X = A, V, F, S, E, L, M, and K) in which both N- and C-ends were unblocked and reported major differences in P(II) content for F, V, and S compared to our scale (Hagarman et al. J. Am. Chem. Soc. 2010, 132, 540-551). We have investigated four representative amino acids (X = A, V, F, and S) in three series of peptides (GXG, AcGXGNH(2), and AcGGXGGNH(2)) as a function of pH in this study. Our data show that P(II) content in the GXG series (X = A, V, F, and S) is pH-dependent and that the conformations of each amino acid differ markedly between the GXG and AcGXGNH(2)/AcGGXGGNH(2) series. Our results indicate that P(II) scales are sequence and context dependent and the presence of proximal charged end groups exerts a strong effect on P(II) population in short model peptides.