Magnetic domain formation in itinerant metamagnets

We examine the effects of long-range dipolar forces on metamagnetic transitions and generalize the theory of Condon domains to the case of an itinerant electron system undergoing a first-order metamagnetic transition. We demonstrate that within a finite range of the applied field, dipolar interactions induce a spatial modulation of the magnetization in the form of stripes or bubbles. Our findings are consistent with recent observations in the bilayer ruthenate Sr$_3$Ru$_2$O$_7$.Comment: 4 pages, 3 figures, minor changes, references adde

Exploring the functional domain and the target of the tetanus toxin light chain in neurohypophysial terminals

The tetanus toxin light chain blocks calcium induced vasopressin release from neurohypophysial nerve terminals. Here we show that histidine residue 233 within the putative zinc binding motif of the tetanus toxin light chain is essential for the inhibition of exocytosis, in the rat. The zinc chelating agent dipicolinic acid as well as captopril, an inhibitor of zinc-dependent peptidases, counteract the effect of the neurotoxin. Synthetic peptides, the sequences of which correspond to motifs present in the cytoplasmic domain of the synaptic vesicle membrane protein synaptobrevin 1 and 2, prevent the effect of the tetanus toxin light chain. Our results indicate that zinc bound to the zinc binding motif constitutes the active site of the tetanus toxin light chain. Moreover they suggest that cleavage of synaptobrevin by the neurotoxin causes the inhibition of exocytotic release of vasopressin from secretory granules

Botulinum neurotoxin type C protease induces apoptosis in differentiated human neuroblastoma cells

Neuroblastomas constitute a major cause of cancer-related deaths in young children. In recent years, a number of translation-inhibiting enzymes have been evaluated for killing neuroblastoma cells. Here we investigated the potential vulnerability of human neuroblastoma cells to protease activity derived from botulinum neurotoxin type C. We show that following retinoic acid treatment, human neuroblastoma cells, SiMa and SH-SY5Y, acquire a neuronal phenotype evidenced by axonal growth and expression of neuronal markers. Botulinum neurotoxin type C which cleaves neuron-specific SNAP25 and syntaxin1 caused apoptotic death only in differentiated neuroblastoma cells. Direct comparison of translation-inhibiting enzymes and the type C botulinum protease revealed one order higher cytotoxic potency of the latter suggesting a novel neuroblastoma-targeting pathway. Our mechanistic insights revealed that loss of ubiquitous SNAP23 due to differentiation coupled to SNAP25 cleavage due to botulinum activity may underlie the apoptotic death of human neuroblastoma cells

Hair cortisol concentrations in different breeds of cows: Comparison of hair from unshorn and previously shorn areas and from various regions of the body

The goals of this study were to investigate hair cortisol concentration (HCC) in seven different breeds of cows, to establish reference intervals for HCC in Brown Swiss cows and to compare cortisol concentrations of hair collected from four different areas of the body. Three groups of cows were used. Group 1 comprised 70 healthy cows representing four dairy breeds (Brown Swiss, Swiss Fleckvieh, Holstein Friesian, Water Buffalo) and three beef breeds (Raetian Grey, Limousin, Highland). Group 2 consisted of 60 healthy Brown Swiss cows in which two different hair samples were collected from the thoracic region to establish reference intervals; A samples consisted of hair that had grown for one month in a pre-clipped area, and B samples consisted of hair from a previously unshorn area. Group 3 comprised 21 healthy Brown Swiss cows, in which HCCs were measured in A and B samples from four different body regions (neck, shoulder, thorax, rump). Liquid chromatography tandem mass-spectrometry was used for cortisol measurement. In group 1, the highest HCCs were measured in Holstein Friesian cows at 1,75 pg/mg, which was significantly higher than those of the Brown Swiss, the Swiss Fleckvieh and the Water Buffalo cows. Hair cortisol concentration and daily milk yield of the 40 dairy cows were highly correlated (r = 0,57, P < 0,01). In group 2, the HCCs of 77 % of the A samples and 85 % of the B samp-les were below the laboratory's limit of quantification (LOQ) of 0,50 pg/mg and the results were expressed semiquantitatively as

Collective fields in the functional renormalization group for fermions, Ward identities, and the exact solution of the Tomonaga-Luttinger model

We develop a new formulation of the functional renormalization group (RG) for interacting fermions. Our approach unifies the purely fermionic formulation based on the Grassmannian functional integral, which has been used in recent years by many authors, with the traditional Wilsonian RG approach to quantum systems pioneered by Hertz [Phys. Rev. B 14, 1165 (1976)], which attempts to describe the infrared behavior of the system in terms of an effective bosonic theory associated with the soft modes of the underlying fermionic problem. In our approach, we decouple the interaction by means of a suitable Hubbard-Stratonovich transformation (following the Hertz-approach), but do not eliminate the fermions; instead, we derive an exact hierarchy of RG flow equations for the irreducible vertices of the resulting coupled field theory involving both fermionic and bosonic fields. The freedom of choosing a momentum transfer cutoff for the bosonic soft modes in addition to the usual band cutoff for the fermions opens the possibility of new RG schemes. In particular, we show how the exact solution of the Tomonaga-Luttinger model emerges from the functional RG if one works with a momentum transfer cutoff. Then the Ward identities associated with the local particle conservation at each Fermi point are valid at every stage of the RG flow and provide a solution of an infinite hierarchy of flow equations for the irreducible vertices. The RG flow equation for the irreducible single-particle self-energy can then be closed and can be reduced to a linear integro-differential equation, the solution of which yields the result familiar from bosonization. We suggest new truncation schemes of the exact hierarchy of flow equations, which might be useful even outside the weak coupling regime.Comment: 27 pages, 15 figures; published version, some typos correcte

Exact integral equation for the renormalized Fermi surface

The true Fermi surface of a fermionic many-body system can be viewed as a fixed point manifold of the renormalization group (RG). Within the framework of the exact functional RG we show that the fixed point condition implies an exact integral equation for the counterterm which is needed for a self-consistent calculation of the Fermi surface. In the simplest approximation, our integral equation reduces to the self-consistent Hartree-Fock equation for the counterterm.Comment: 5 pages, 1 figur

Regulation of releasable vesicle pool sizes by protein kinase A-dependent phosphorylation of SNAP-25

AbstractProtein kinase A (PKA) is a key regulator of neurosecretion, but the molecular targets remain elusive. We combined pharmacological manipulations of kinase and phosphatase activities with mutational studies on the exocytotic machinery driving fusion of catecholamine-containing vesicles from chromaffin cells. We found that constitutive PKA activity was necessary to maintain a large number of vesicles in the release-ready, so-called primed, state, whereas calcineurin (protein phosphatase 2B) activity antagonized this effect. Overexpression of the SNARE protein SNAP-25a mutated in a PKA phosphorylation site (Thr-138) eliminated the effect of PKA inhibitors on the vesicle priming process. Another, unidentified, PKA target regulated the relative size of two different primed vesicle pools that are distinguished by their release kinetics. Overexpression of the SNAP-25b isoform increased the size of both primed vesicle pools by a factor of two, and mutations in the conserved Thr-138 site had similar effects as in the a isoform

Hair cortisol measurement in older adults: Influence of demographic and physiological factors and correlation with perceived stress.

Aims This study aimed to investigate correlation between hair cortisol levels and perceived stress scale (PSS) in addition to a range of demographic and physiological factors in a sample of older adults. Experimental Hair cortisol concentrations were established from 42 older adults aged between 60 and 80 years old. Age, sex, hair colour, smoking status, employment status, daytime sleeping, medication, waist to hip ratio (WHR) and PSS scores were assessed through a questionnaire. Hair cortisol concentration was assessed through liquid chromatography coupled to tandem mass-spectrometry (LC-MS/MS). Results Amongst the older adult group there was no statistically significant correlation between hair cortisol concentration and age, employment status, daytime sleep duration, WHR or PSS. When compared to previous data assessing hair cortisol in toddlers (7 months to 3 years old), adolescents (12-17 years old) and adults (18-60 years old) it is observed that there is a trend for higher hair cortisol in older adults (60-80 years old). Hair cortisol concentrations were significantly higher in males (n = 20) than in females (n = 22) and in participants with dark brown hair (n = 8). No relationship was investigated between hair cortisol concentration and smoking status or medication intake. Conclusions The results confirm that hair samples are a useful alternative to the current mediums that are used to analyse biological cortisol. The results also validate the use of LC-MS/MS as an effective analytical method for the quantitation of hair cortisol concentrations

Loss of AP-3 function affects spontaneous and evoked release at hippocampal mossy fiber synapses

Synaptic vesicle (SV) exocytosis mediating neurotransmitter release occurs spontaneously at low intraterminal calcium concentrations and is stimulated by a rise in intracellular calcium. Exocytosis is compensated for by the reformation of vesicles at plasma membrane and endosomes. Although the adaptor complex AP-3 was proposed to be involved in the formation of SVs from endosomes, whether its function has an indirect effect on exocytosis remains unknown. Using mocha mice, which are deficient in functional AP-3, we identify an AP-3-dependent tetanus neurotoxin-resistant asynchronous release that can be evoked at hippocampal mossy fiber (MF) synapses. Presynaptic targeting of the tetanus neurotoxin-resistant vesicle soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) is lost in mocha hippocampal MF terminals, whereas the localization of synaptobrevin 2 is unaffected. In addition, quantal release in mocha cultures is more frequent and more sensitive to sucrose. We conclude that lack of AP-3 results in more constitutive secretion and loss of an asynchronous evoked release component, suggesting an important function of AP-3 in regulating SV exocytosis at MF terminals

Tiered Human Integrated Sequence Search Databases for Shotgun Proteomics.

The results of analysis of shotgun proteomics mass spectrometry data can be greatly affected by the selection of the reference protein sequence database against which the spectra are matched. For many species there are multiple sources from which somewhat different sequence sets can be obtained. This can lead to confusion about which database is best in which circumstances-a problem especially acute in human sample analysis. All sequence databases are genome-based, with sequences for the predicted gene and their protein translation products compiled. Our goal is to create a set of primary sequence databases that comprise the union of sequences from many of the different available sources and make the result easily available to the community. We have compiled a set of four sequence databases of varying sizes, from a small database consisting of only the ∼20,000 primary isoforms plus contaminants to a very large database that includes almost all nonredundant protein sequences from several sources. This set of tiered, increasingly complete human protein sequence databases suitable for mass spectrometry proteomics sequence database searching is called the Tiered Human Integrated Search Proteome set. In order to evaluate the utility of these databases, we have analyzed two different data sets, one from the HeLa cell line and the other from normal human liver tissue, with each of the four tiers of database complexity. The result is that approximately 0.8%, 1.1%, and 1.5% additional peptides can be identified for Tiers 2, 3, and 4, respectively, as compared with the Tier 1 database, at substantially increasing computational cost. This increase in computational cost may be worth bearing if the identification of sequence variants or the discovery of sequences that are not present in the reviewed knowledge base entries is an important goal of the study. We find that it is useful to search a data set against a simpler database, and then check the uniqueness of the discovered peptides against a more complex database. We have set up an automated system that downloads all the source databases on the first of each month and automatically generates a new set of search databases and makes them available for download at http://www.peptideatlas.org/thisp/