Irritable bowel syndrome : the role of gut neuroendocrine peptides

Irritable bowel syndrome (IBS) is a common chronic disorder with a prevalence ranging from 5 to 10 % of the world's population. This condition is characterised by abdominal discomfort or pain, altered bowel habits, and often bloating and abdominal distension. IBS reduces quality of life in the same degree of impairment as major chronic diseases such as congestive heart failure and diabetes and the economic burden on the health care system and society is high. Abnormalities have been reported in the neuroendocrine peptides/amines of the stomach, small- and large intestine in patients with IBS. These abnormalities would cause disturbances in digestion, gastrointestinal motility and visceral hypersensitivity, which have been reported in patients with IBS. These abnormalities seem to contribute to the symptom development and appear to play a central role in the pathogenesis of IBS. Neuroendocrine peptides/amines are potential tools in the treatment and diagnosis of IBS. In particular, the cell density of duodenal chromogranin A expressing cells appears to be a good histopathological marker for the diagnosis of IBS with high sensitivity and specificity.

The location of Ti atom in sodium alanate : an ab initio spin-polarised study

In this work, ab initio spin-polarised Density Functional Theory (DFT) calculations are performed to study the interaction of a Ti atom with a NaAlH4(001) surface. We confirm that an interstitially located Ti atom in the NaAlH4 subsurface is the most energetically favoured configuration as recently reported (Chem. Comm. (17) 2006, 1822). On the NaAlH4(001) surface, the Ti atom is most stable when adsorbed between two sodium atoms with an AlH4 unit beneath. A Ti atom on top of an Al atom is also found to be an important structure at low temperatures. The diffusion of Ti from the Al-top site to the Na-bridging site has a low activation barrier of 0.20 eV and may be activated at the experimental temperatures (∼323 K). The diffusion of a Ti atom into the energetically favoured subsurface interstitial site occurs via the Na-bridging surface site and is essentially barrierless.

Vacancy mediated desorption of hydrogen from a sodium alanate surface : An ab initio spin-polarized study

Ab initio spin-polarized density functional theory calculations are performed to explore the effect of single Na vacancy on NaAlH4(001) surface on the initial dehydrogenation kinetics. The authors found that two Al–H bond lengths become elongated and weakened due to the presence of a Na vacancy on the NaAlH4(001) surface. Spontaneous recombination from the surface to form molecular hydrogen is observed in the spin-polarized ab initio molecular dynamics simulation. The authors’ results indicate that surface Na vacancies play a critical role in accelerating the dehydrogenation kinetics in sodium alanate. The understanding gained here will aid in the rational design and development of complex hydride materials for hydrogen storage

Spin-polarization and ferromagnetism of graphitic carbon nitride materials

Polymeric graphitic carbon nitride materials have attracted increasing attention in recent years owning to their potential applications in energy conversion, environment protection, and so on. Here, from first-principles calculations, we report the electronic structure modification of graphitic carbon nitride (g-C3N4) in response to carbon doping. We showed that each dopant atom can induce a local magnetic moment of 1.0 μB in non-magnetic g-C3N4. At the doping concentration of 1/14, the local magnetic moments of the most stable doping configuration which has the dopant atom at the center of heptazine unit prefer to align in a parallel way leading to long-range ferromagnetic (FM) ordering. When the joint N atom is replaced by C atom, the system favors an antiferromagnetic (AFM) ordering at unstrained state, but can be tuned to ferromagnetism (FM) by applying biaxial tensile strain. More interestingly, the FM state of the strained system is half-metallic with abundant states at the Fermi level in one spin channel and a band gap of 1.82 eV in another spin channel. The Curie temperature (Tc) was also evaluated using a mean-field theory and Monte Carlo simulations within the Ising model. Such tunable electron spin-polarization and ferromagnetism are quite promising for the applications of graphitic carbon nitride in spintronics.

Spin-coated carbon

We describe a novel and facile approach to covalently graft molecules containing stable free radicals onto carbon surfaces including graphene, carbon nanotubes, glassy carbon and carbon fibres. The new technique employs a stable aryl nitroxide radical diazonium tetrafluoroborate salt. The salt may be isolated and added to carbon surfaces in solution, suspension or electrochemically and represents a convenient, versatile and highly efficient means to adorn graphitic materials with large numbers of free radical spin systems

Photodissociation of TEMPO-modified peptides: New approaches to radical-directed dissociation of biomolecules

Radical-directed dissociation of gas phase ions is emerging as a powerful and complementary alternative to traditional tandem mass spectrometric techniques for biomolecular structural analysis. Previous studies have identified that coupling of 2-[(2,2,6,6-tetramethylpiperidin-1-oxyl)methyl] benzoic acid (TEMPO-Bz) to the N-terminus of a peptide introduces a labile oxygen-carbon bond that can be selectively activated upon collisional activation to produce a radical ion. Here we demonstrate that structurally-defined peptide radical ions can also be generated upon UV laser photodissociation of the same TEMPO-Bz derivatives in a linear ion-trap mass spectrometer. When subjected to further mass spectrometric analyses, the radical ions formed by a single laser pulse undergo identical dissociations as those formed by collisional activation of the same precursor ion, and can thus be used to derive molecular structure. Mapping the initial radical formation process as a function of photon energy by photodissociation action spectroscopy reveals that photoproduct formation is selective but occurs only in modest yield across the wavelength range (300-220 nm), with the photoproduct yield maximised between 235 and 225 nm. Based on the analysis of a set of model compounds, structural modifications to the TEMPO-Bz derivative are suggested to optimise radical photoproduct yield. Future development of such probes offers the advantage of increased sensitivity and selectivity for radical-directed dissociation. © 2014 the Owner Societies.

Ion-molecule reactions reveal facile radical migration in peptides

Ion-molecule reactions between molecular oxygen and peptide radicals in the gas phase demonstrate that radical migration occurs easily within large biomolecules without addition of collisional activation energy.

Soluble laminin and arginine-glycine-aspartic acid containing peptides differentially regulate type IV collagenase messenger RNA, activation, and localization in testicular cell culture

Rat testicular cells in culture produce several metalloproteinases including type IV collagenases (Sang et al. Biol Reprod 1990; 43:946-955, 956-964). We have now investigated the regulation of testicular cell type IV collagenase and other metalloprotemases in vitro. Soluble laminin stimulated Sertoli cell type IV collagenase mRNA levels. However, three peptides corresponding to different domains of the laminin molecule (CSRAKQAASIKVASADR, FALRGDNP, CLQDGDVRV) did not influence type IV collagenase mENA levels. Zyniographic analysis of medium collected from these cultures revealed that neither soluble laminin nor any of the peptides influenced 72-Wa type IV collagenase protein levels. However, peptide FALRGDNP resulted in both, a selective increase in two higher molecular-weight metalloprotemnases (83 kDa and 110 Wa and in an activation of the 72-Wa rat type IV collagenase. Interleukin-1, phorbol ester, testosterone, and FSH did not affect collagenase activation, lmmunocytochemical studies demonstrated that the addition of soluble laminin resulted in a redistribution of type IV collagenase from intracellular vesicles to the cell-substrate region beneath the cells. Peptide FALRGDNP induced a change from a vesicular to peripheral plasma membrane type of staining pattern. Zymography of plasma membrane preparations demonstrated triton-soluble gelatinases of 76 Wa, 83 Wa, and 110 Wa and a triton-insoluble gelatinase of 225 Wa, These results indicate that testicular cell type IV collagenase mRNA levels, enzyme activation, and distribution are influenced by laminin and RGD-containing peptides.

Analysis of albumin-associated peptides and proteins from ovarian cancer patients

Albumin binds low–molecular-weight molecules, including proteins and peptides, which then acquire its longer half-life, thereby protecting the bound species from kidney clearance. We developed an experimental method to isolate albumin in its native state and to then identify [mass spectrometry (MS) sequencing] the corresponding bound low–molecular-weight molecules. We used this method to analyze pooled sera from a human disease study set (high-risk persons without cancer, n= 40; stage I ovarian cancer, n = 30; stage III ovarian cancer, n = 40) to demonstrate the feasibility of this approach as a discovery method. Methods Albumin was isolated by solid-phase affinity capture under native binding and washing conditions. Captured albumin-associated proteins and peptides were separated by gel electrophoresis and subjected to iterative MS sequencing by microcapillary reversed-phase tandem MS. Selected albumin-bound protein fragments were confirmed in human sera by Western blotting and immunocompetition. Results In total, 1208 individual protein sequences were predicted from all 3 pools. The predicted sequences were largely fragments derived from proteins with diverse biological functions. More than one third of these fragments were identified by multiple peptide sequences, and more than one half of the identified species were in vivo cleavage products of parent proteins. An estimated 700 serum peptides or proteins were predicted that had not been reported in previous serum databases. Several proteolytic fragments of larger molecules that may be cancer-related were confirmed immunologically in blood by Western blotting and peptide immunocompetition. BRCA2, a 390-kDa low-abundance nuclear protein linked to cancer susceptibility, was represented in sera as a series of specific fragments bound to albumin. Conclusion Carrier-protein harvesting provides a rich source of candidate peptides and proteins with potential diverse tissue and cellular origins that may reflect important disease-related information.

Semantic context and visual feature effects in object naming : an fMRI study using arterial spin labeling

Previous behavioral studies reported a robust effect of increased naming latencies when objects to be named were blocked within semantic category, compared to items blocked between category. This semantic context effect has been attributed to various mechanisms including inhibition or excitation of lexico-semantic representations and incremental learning of associations between semantic features and names, and is hypothesized to increase demands on verbal self-monitoring during speech production. Objects within categories also share many visual structural features, introducing a potential confound when interpreting the level at which the context effect might occur. Consistent with previous findings, we report a significant increase in response latencies when naming categorically related objects within blocks, an effect associated with increased perfusion fMRI signal bilaterally in the hippocampus and in the left middle to posterior superior temporal cortex. No perfusion changes were observed in the middle section of the left middle temporal cortex, a region associated with retrieval of lexical-semantic information in previous object naming studies. Although a manipulation of visual feature similarity did not influence naming latencies, we observed perfusion increases in the perirhinal cortex for naming objects with similar visual features that interacted with the semantic context in which objects were named. These results provide support for the view that the semantic context effect in object naming occurs due to an incremental learning mechanism, and involves increased demands on verbal self-monitoring.

One-step macroscopic alignment of conjugated polymer systems by epitaxial crystallization during spin-coating

The one-step preparation of highly anisotropic polymer semiconductor thin films directly from solution is demonstrated. The conjugated polymer poly(3-hexylthiophene) (P3HT) as well as P3HT:fullerene bulk-heterojunction blends can be spin-coated from a mixture of the crystallizable solvent 1,3,5-trichlorobenzene (TCB) and a second carrier solvent such as chlorobenzene. Solidification is initiated by growth of macroscopic TCB spherulites followed by epitaxial crystallization of P3HT on TCB crystals. Subsequent sublimation of TCB leaves behind a replica of the original TCB spherulites. Thus, highly ordered thin films are obtained, which feature square-centimeter-sized domains that are composed of one spherulite-like structure each. A combination of optical microscopy and polarized photoluminescence spectroscopy reveals radial alignment of the polymer backbone in case of P3HT, whereas P3HT:fullerene blends display a tangential orientation with respect to the center of spherulite-like structures. Moreover, grazing-incidence wide-angle X-ray scattering reveals an increased relative degree of crystallinity and predominantly flat-on conformation of P3HT crystallites in the blend. The use of other processing methods such as dip-coating is also feasible and offers uniaxial orientation of the macromolecule. Finally, the applicability of this method to a variety of other semi-crystalline conjugated polymer systems is established. Those include other poly(3-alkylthiophene)s, two polyfluorenes, the low band-gap polymer PCPDTBT, a diketopyrrolopyrrole (DPP) small molecule as well as a number of polymer:fullerene and polymer:polymer blends. Macroscopic spherulite-like structures of the conjugated polymer poly(3-hexylthiophene) (P3HT) grow directly during spin-coating. This is achieved by processing P3HT or P3HT:fullerene bulk heterojunction blends from a mixture of the crystallizable solvent 1,3,5-trichlorobenzene and a second carrier solvent such as chlorobenzene. Epitaxial growth of the polymer on solidified solvent crystals gives rise to circular-symmetric, spherulite-like structures that feature a high degree of anisotropy.

Iron(II) spin transition complexes with dendritic ligands, Part I

The ligands G1- and G2-oligo (benzyl ether) (PBE) dendrons and their iron(II) complexes [Fe(Gn-PBE)3]A2·xH2O (with n = 1, 2 and A = triflate, tosylate) were prepared. The magnetic properties of the complexes were investigated by a SQUID magnetometer. All complexes exhibit gradual spin transition below room temperature. At very low temperatures the magnetic behaviour reflects zero-field splitting (ZFS) effects. 57Fe-Mössbauer spectroscopy was performed to distinguish between ZFS of high spin species and spin state conversion into the low spin state. Further characterisation was carried out by thermogravimetric analysis (TGA) and FT-IR spectroscopy. Structural features have been determined by powder XRD measurements.

Iron(II) spin-transition complexes with dendritic ligands, part II

The dendritic triazole-based complexes \[Fe(G1-BOC)3](triflate) 2·xH2O (1; G1-BOC = tert-butyl {3-\[3-(3-tert- butoxycarbonylaminopropyl)-5-(\[1,2,4]triazol-4-ylcarbamoyl)-phenyl]propyl} carbamate, triflate = CF3SO3-), \[Fe(G1-BOC) 3]-(tosylate)2·xH2O(2;tosylate = p-CH3PhSO3-),\[Fe(G1-DPBE)3]-(triflate) 2·xH2O {3; G1-DPBE = 3,5-bis(3,5- didodecaoxybenzyloxy)-N-\[1,2,4]triazol-4-ylbenzamide}, \[Fe(G1-DPBE) 3]-(tosylate)2·xH2O (4) and \[Fe(G1-DPBE)3](BF4)2·xH2O (5) were designed and synthesized. Magnetic and thermal properties of these novel complexes were characterized by magnetic susceptibility measurements, 57Fe Mössbauer spectroscopy and thermogravimetric analysis or differential scanning calorimetry, respectively. All dendritic complexes under study show different spin-transition behaviour with respect to the nature of different dendritic ligands and counteranions. Complexes 1 and 2 have pronounced effects of a spin-state change during the first heating process and gradual spintransition properties for further temperature treatments, whereas 3 and 4 exhibited a very sharp spin-state change in the first heating procedures. Complex 5 showed a gradual spin-transition curve. In this paper, we report how the magnetic properties of these complexes are correlated with noncoordinated water molecules and their effects on spin states.

Spin polarized DFT calculations of metal borides

The metal borides, in particular the diborides and hexaborides, contain stoichiometric forms that include insulators, semiconductors and superconductors. In addition, their end-member structures have high symmetry and two atoms although, in general, substitution(s) of multi-valent ions into the metal site occurs consistent with Vegard’s law. These characteristics allow for fundamental comparison of important physical properties such as superconductivity and insulation within a relatively simple structure type. Our early work1,2 has demonstrated this for the hexaborides and this work compares similar attributes across a broader suite of boride structures. In all cases, theoretical calculations are referenced to structures determined via high resolution neutron or X-ray diffraction experiments.