Modulations in martensitic Heusler alloys originate from nanotwin ordering.

Heusler alloys exhibiting magnetic and martensitic transitions enable applications like magnetocaloric refrigeration and actuation based on the magnetic shape memory effect. Their outstanding functional properties depend on low hysteresis losses and low actuation fields. These are only achieved if the atomic positions deviate from a tetragonal lattice by periodic displacements. The origin of the so-called modulated structures is the subject of much controversy: They are either explained by phonon softening or adaptive nanotwinning. Here we used large-scale density functional theory calculations on the Ni2MnGa prototype system to demonstrate interaction energy between twin boundaries. Minimizing the interaction energy resulted in the experimentally observed ordered modulations at the atomic scale, it explained that a/b twin boundaries are stacking faults at the mesoscale, and contributed to the macroscopic hysteresis losses. Furthermore, we found that phonon softening paves the transformation path towards the nanotwinned martensite state. This unified both opposing concepts to explain modulated martensite.

[Ways to psychosomatic rehabilitation--differential treatment selection between psychosomatic acute care and rehabilitation]. / Wege in die psychosomatische Rehabilitation--differenzielle Indikationsstellung an der Schnittstelle zwischen Krankenhaus und psychosomatischer Rehabilitationsklinik.

Consecutive admissions to the psychosomatic departments of 5 hospital units in southwest Germany registered between October 2012 and October 2013 were asked to participate in a study investigating the treatment selection process for psychosomatic rehabilitation. 527 patients were included in the study, 269 outpatients and 258 inpatients at the end of their inpatient treatment. 52 patients (10.1%) received the recommendation for rehabilitation. 47 (90.4%) could be followed up 3 months later. 22 patients had applied for a rehabilitation treatment, 11 (50%) had obtained an approval for their rehabilitation, 5 had still no answer and for 6 patients the request was refused. 4 of the latter had objected their refusal and were still waiting for an answer. Only one patient was already admitted to a rehabilitation center. Possible reasons for the low permeability at the interface between hospital care and rehabilitation are discussed.

Fam40b is required for lineage commitment of murine embryonic stem cells.

FAM40B (STRIP2) is a member of the striatin-interacting phosphatase and kinase (STRIPAK) complex that is involved in the regulation of various processes such as cell proliferation and differentiation. Its role for differentiation processes in embryonic stem cells (ESCs) is till now completely unknown. Short hairpin RNA (shRNA)-mediated silencing of Fam40b expression in ESCs and differentiating embryoid bodies (EBs) led to perturbed differentiation to embryonic germ layers and their derivatives including a complete abrogation of cardiomyogenesis. Pluripotency factors such as Nanog, Oct4 and Sox2 as well as epigenetic factors such as histone acetyltransferase type B (HAT1) and DNA (cytosine-5)-methyltransferase 3-ß (Dnmt3b) were highly upregulated in Fam40b knockdown EBs as compared with control and scrambled EBs. To examine the relevance of Fam40b for development in vivo, Fam40b was knocked down in developing zebrafish. Morpholino-mediated knockdown of Fam40b led to severe abnormalities of the cardiovascular system, including an impaired expression of ventricular myosin heavy chain (vmhc) and of cardiac myosin light chain 2 (cmlc2) in the heart. We identified the gene product of Fam40b in ESCs as a perinuclear and nucleolar protein with a molecular weight of 96 kDa. We conclude that the expression of Fam40b is essential for the lineage commitment of murine embryonic stem cells (mESCs) into differentiated somatic cells via mechanisms involving pluripotency and epigenetic networks.

Forty-eight new cases with infertility due to balanced chromosomal rearrangements: detailed molecular cytogenetic analysis of the 90 involved breakpoints.

A molecular cytogenetic study was performed on 48 infertile patients who were identified as carriers of balanced translocations (40 cases), inversions (6 cases) or insertions (2 cases) by means of banding cytogenetics. Cases with a Robertsonian translocation or pericentric inversion 2 or 9 were not included. In summary, 100 break-events occurred in these patients, and 90 different chromosomal regions were involved. Thus, this study confirmed the presence of abnormal karyotypes in a subgroup of patients seeking infertility treatment. Breaks were demonstrated to appear preferentially in GTG-light bands in these patients. Furthermore, the observed breakpoints were associated with genomic regions prone to instability due to the presence of segmental duplications. Nonetheless, further detailed molecular analysis will be necessary in the future to characterize the mechanisms and genetic basis for this phenomenon.

Tacalcitol ointment in the treatment of psoriasis vulgaris: a multicentre, placebo-controlled, double-blind study on efficacy and safety.

Tacalcitol is a vitamin D analogue which ahs been developed for the therapy of psoriasis vulgaris. The treatment with a twice daily application of 2 micrograms/g ointment is efficacious and safe in Japanese patients. The objective of this randomized, placebo-controlled, intraindividual right-left comparison was to investigate the efficacy and safety of 8 weeks' therapy with a once daily application of a 4 micrograms/g tacalcitol ointment in Caucasian psoriatics. The data on 122 male and female patients were analysed. The score sum of erythema, infiltration and desquamation was influenced significantly more by tacalcitol ointment than by placebo (P < 0.0001) at every control point, starting from week 2. With regard to the individual symptoms of desquamation, infiltration and erythema, the treatment with tacalcitol was also superior to placebo treatment beginning at week 2. Qualitatively, the same results were obtained with the preference assessment of both treated body sides and also the global assessments of efficacy and benefit. Symptoms of local skin irritation which may be related to the active compound or the ointment base were reported by 12.3% of patients. In only one patient, irritation required discontinuation of tacalcitol treatment. Laboratory criteria, including serum calcium, serum phosphate and serum levels of calcitonin, parathormone, 1 alpha, 24-dihydroxyvitamin D3 and 25-hydroxyvitamin D3, did not reveal any changes of clinical relevance during or after treatment. Furthermore, the global assessment of tolerance was good or very good in more than 90% of cases. The results of this study demonstrate that the once daily application of a 4 micrograms/g tacalcitol ointment is an efficacious therapy for psoriasis vulgaris in Caucasian patients, and that its tolerance is good, wherever the lesion is located, including on the face.

[Absorption of di-linoleoylphosphatidylcholine after oral administration]. / Resorption von Dilinoleoyl-phosphatidylcholin nach oraler Gabe.

Essentiale and Lipostabil contain "essential" phospholipids from the soybean, mainly 1,2-dilinoleoyl-phosphatidylcholine (CAS 998-06-1, DLPC) which is considered as the main active ingredient. A single oral dose of d15-DLPC loaded with deuterium 9 times in the choline and 6 times in the linoleic acid of the 1-position was given to volunteers. Sera from 11 blood samples taken within 48 h after application were examined by means of mass spectrometry with regard to d9-choline and d6-linoleic acid in the 1- and 2-position of serum phosphatidylcholines (PC) as well as in the serum triglycerides. d9-choline, i.e. the total of d15-PC and d9-PC, showed maximum values of 5.6% of the total serum PC concentration. Normally, about 1.3% of PC in the human serum is DLPC. Serum 1-linoleoyl-PC was increased by 32-40% after oral application of d15-DLPC. A minor uptake of d6-linoleic acid into the 2-position of serum PC, which is rich in linoleic acid, and into the serum triglycerides was observed with peak values of 2.3% and 6.1%, resp. The uptake of polyunsaturated PC species like DLPC and 1-linoleoyl-PC into the liver after oral application of drugs containing such species in high amounts like "essential" phospholipids with about 50% of DLPC let expect therapeutic effects on membranes into which this special species is incorporated.

Nematode test to estimate the hazard potential of solved contaminations.

The acute toxicity of lindane, pentachlorophenol and a fluortenside was examined using a recently developed ecotoxicity test with the terrestrial nematode species Panagrellus redivivus. The exposure was performed in aqueous solution over an investigation period of 96 h. For lindane a time dependent decrease of the survival rate (LC50 after 96 h: 0.4 mg/l) was observed which indicates a high cuticular permeability of the insecticide. For pentachlorophenol the LC50 (96 h) was 13 mg/l, for the fluortenside a value of 110 mg/l was determined.

Determination of formetanate hydrochloride in selected fruits by coupled-column cation exchange liquid chromatography.

A strong cation exchange (SCX) liquid chromatographic (LC) method is described for determination of formetanate hydrochloride residue in pome, citrus, and stone fruits. A test portion of fruit, homogenized with the peel left on, was blended with acidified acetonitrile and filtered. A portion of extract was finely filtered, and a 500 microL aliquot (ca 0.2 g test sample equivalent) was loaded onto an SCX solid-phase extraction (SPE) LC column, which replaced the injection loop of the LC injection valve. Cations were selectively enriched; noncations were eluted by acetonitrile in a pre-separation cleanup. Turning the valve to the inject position coupled the SPE column to an SCX analytical column for separation and detection at 250 nm. The mobile phase was 0.4M pH 3.0 ammonium phosphate buffer-water-acetonitrile (50 + 25 + 25). Formetanate cation was quantitated by peak area and regression coefficients from a 5-point linear calibration covering a 100-fold range. Recovery of duplicate fortifications of apple, pear, orange, and peach averaged 89-99% at the respective U.S. tolerances of 3, 3, 4, or 5 ppm and averaged 93-99% at one-tenth of the respective tolerance level. Peel pigments or variable peel bulk of crop varieties tested, as well as other endogenous fruit material, contributed interference that was below the 0.02 ppm limit of detection. In a 1991 limited survey comprising 15 samples, none were found violative. Residues were found in 2 samples, but only 1 measurement was quantifiable, near the 0.06 ppm limit of quantitation.

Dye ingress in molars: furcation to chamber floor.

An in vitro dye leakage study was performed to determine the incidence of patent furcal accessory canals following exposure of the pulp chamber to 5.25% sodium hypochlorite. One hundred extracted molars were labeled, endodontically opened, and irrigated for 1 h at 5-min intervals. The external furcations were exposed to 0.5% basic fuchsin for 24 h. Patency was determined by dye presence on the chamber floor. Statistical analysis revealed that first and second molars, regardless of arch position or location, demonstrated a patent accessory canal at a rate of 57% +/- 19.6% in the furcal area. It was concluded that accessory canal exposure to 5.25% sodium hypochlorite in the furcal area of molars produced patency which was demonstrable via passive methods--no vacuum or injection pressures were utilized.

The effects of xenobiotics on hepatic lipid and lipo-protein metabolism.

The liver occupies a central position in lipid and lipo-protein metabolism. Its function includes lipid and lipoprotein biosynthesis, assembly, packaging, transport, secretion, uptake and degradation of lipoproteins. In addition, enzymes synthesized and secreted by the liver into the blood stream or remaining bound to the endothelial cells in the capillaries, affect lipoprotein metabolism in the circulation. Xenobiotics may influence each of these steps. The mechanisms include more specific actions such as hormone or transmitter agonism and antagonism, membrane effects (stabilization or changes in trans-membrane gradients), influence on protein synthesis, influence on lipid metabolism by induction or inhibition of involved enzymes, or more general actions such as disturbances or damage of cellular membranes and cellular function. Some of these effects can easily be described as pharmacological actions, more or less independent of specific requirements in the chemical structure of the xenobiotics. Others are linked to specific chemical substituents such as carboxyl or alcoholic hydroxyl groups allowing the formation of lipid-xenobiotic-conjugates and/or the channeling of xenobiotics into lipid metabolism. This review will give a short overview of the mechanisms of xenobiotic-influenced hepatic lipid and lipoprotein metabolism.

Picogram level quantitation of 2,3,7,8-tetrachlorodibenzo-p-dioxin in fish extracts by capillary gas chromatography/matrix isolation/Fourier transform infrared spectrometry.

For the first time, gas chromatography/matrix isolation/Fourier transform infrared spectrometry (GC/MI/FTIR) has been reported to confirm the identity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2378-TCDD) and to quantify its level in fish extracts in the 170-220 pg range "on disk". When expressed on a fish tissue basis, analyte levels ranged from 15 to 45 pg/g. Spectroscopic identification was based on the position and relative intensity of seven absorption bands. Optical alignment as well as performance evaluation and optimization of the GC/MI/FTIR system are described. The use of [13C12]2378-TCDD as an internal standard was essential for quantitation, and quality assurance controls were used to verify system performance. GC/MI/FTIR quantitation of 2378-TCDD was compared with that independently found by GC with electron capture detection. Recovery of 2378-TCDD averaged 52% (n = 8, 30% relative standard deviation) for fish extracts.

Determination of 2,3,7,8-tetrachlorodibenzo-p-dioxin in fish, using electron capture gas chromatography with confirmation by mass spectrometry: interlaboratory study.

An interlaboratory study of the determination of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) in fish was conducted by 6 analysts in 4 laboratories using high resolution gas chromatography with electron capture detection (HRGC-EC) for quantitative screening analysis. Samples consisted of 3 Great Lakes channel catfish homogenates containing different levels of bioincurred 2,3,7,8-TCDD; 1 of these was prepared in duplicate and another was prepared both with and without standard 2,3,7,8-TCDD fortification for a total of 5 samples per set. All methods used included addition of 1,3,7,8-TCDD surrogate (to correct for procedural losses) followed by ethanolic KOH digestion and hexane extraction. Certain cleanup steps used, including sulfuric acid washing and multidimensional column liquid chromatographic procedures, varied among laboratories. Mean HRGC-EC results for the bioincurred residues were 56.6, 25.2, and 7.7 pg/g (ppt) with corresponding relative standard deviations (RSDs) of 9.1, 18.6, and 53.2%. Average determination of standard 2,3,7,8-TCDD from the fortified sample (corrected for surrogate recoveries averaging 74.6%) was 106% of the added amount (30.9 pg/g) with 11.0% RSD. HRGC-multiple ion detection mass spectrometry (MS), monitoring 12 ions, was used for confirmation. With the exception of several results from 1 analyst, HRGC-MS and HRGC-EC quantitations were in good agreement. All but 1 result reported met all of the MS identity criteria.

Ca++ antagonists and ACAT inhibitors promote cholesterol efflux from macrophages by different mechanisms. I. Characterization of cellular lipid metabolism.

The effects of the slow Ca++ channel blocker, nifedipine, and ACAT inhibitor, octimibate, on the cholesterol metabolism of cholesterol-loaded macrophages were compared. We demonstrated that apolipoprotein A-I containing high density lipoproteins (HDL) bind to specific receptor sites on macrophages, are internalized, take up cholesterol, and are then released from the cells as native lipoproteins. The ACAT inhibitor enhances HDL receptor activity and promotes HDL-mediated cholesterol efflux from cultured mouse peritoneal macrophages. In contrast, the Ca++ antagonist increases acetyl LDL-mediated cholesterol influx, abolishes the increase in HDL binding induced by cholesterol accumulation, enhances apo E synthesis, and promotes cholesterol efflux by a mechanism independent of the presence of HDL in the surrounding medium. Concomitantly, a decrease in nucleoside transporter activity, an increase in intracellular ATP hydrolysis, adenosine and cyclic AMP concentration, and a stimulation of the activities of acid and neutral cholesteryl ester hydrolase and ACAT indicated that protein kinase A-catalyzed phosphorylation reactions might be involved in the increase in cholesterol efflux. The Ca++ antagonist-induced efflux occurred only with lysosomal-associated cholesterol, while the ACAT inhibitor acted on the formation of cytoplasmic lipid droplets. The secreted lipoprotein particles contained 68% unesterified cholesterol and 21% phospholipids, 8% esterified cholesterol, and 3% triglycerides. The phospholipid components were: 72% phosphatidylcholine, 22% sphingomyelin, and 6% phosphatidylserine, phosphatidylinositol, and phosphatidylethanolamine. We conclude that macrophages release cholesterol in two ways: 1) an HDL-mediated release of unesterified cholesterol increasing upon ACAT inhibition, and 2) an HDL-independent secretion of cholesterol which can be amplified by Ca++ antagonists.

Surrogate-assisted determination of 2,3,7,8-tetrachlorodibenzo-p-dioxin in fish by electron capture capillary gas chromatography.

Surrogate spiking the sample with 1000 parts per trillion (pptr) 1,3,7,8-tetrachlorodibenzo-p-dioxin (1378-TCDD) has doubled analytical throughput in determining toxic 2378-TCDD (analyte) at the low part-per-trillion level in fish, using multicolumn high resolution liquid chromatographic cleanup before quantitation by capillary gas chromatography with electron capture detection. The 1378- and 2378-TCDD were recovered equally and were well separated by the capillary column so that the earlier-eluting surrogate did not interfere with the quantitation of levels of analyte many-fold lower. Matrix interference contributed less than 1% bias in surrogate quantitation. Using surrogate recovery to correct for analyte losses during analysis, accuracy averaged (n = 7) 105% in determining 18 or 45 pptr 2378-TCDD added to fish without detectable bioincurred analyte. Analyses of selected fish with bioincurred 2378-TCDD gave results comparable to earlier work where recovery correction required a second analysis of sample fortified with analyte. With surrogate fortification, repeatability of determination (n = 3 or 4) improved markedly to less than 5% relative standard deviation at 37-46 pptr.

Purification and characterization of a 3'-phosphoadenylylsulfate:chondroitin 6-sulfotransferase from arterial tissue.

A 3'-phosphoadenylylsulfate:chondroitin sulfotransferase (EC 2.8.2.5) was purified to homogeneity (about 760-fold) from the cytosolic fraction of calf arterial tissue by Con A-Sepharose, ion exchange and affinity chromatography. The enzyme has a molecular mass of 38000 Da, optimal activity at pH 6.0 (100%) and 7.25 (75%), requires divalent cations for maximal activity (Mn2+ greater than Mg2+, Ca2+) and exhibits specificity towards desulfated chondroitin sulfate and oligosaccharides derived therefrom. The enzyme transfers sulfate groups from [35S]phosphoadenylylsulfate exclusively to C-6 OH groups of N-acetylgalactosamine units of the acceptor substrates. Maximal sulfate transfer occurs at 2mM chondroitin disaccharide units (100%), the transfer rates decreasing with decreasing chain length in the order deca (55%), octa (17%) and hexasaccharides (4%). Lineweaver-Burk plots revealed equal maximal velocities for chondroitin, deca-, octa- and hexasaccharide, but decreasing Km values. Chondroitin 4-sulfate has 21% of the acceptor potency exhibited by chondroitin, whereas dermatan sulfate, heparan sulfate and hyaluronate and the chondroitin tetrasaccharide showed no acceptor properties. Analysis of the reaction products formed by prolonged enzymatic sulfation of a reduced chondroitin hexasaccharide [GlcA-GalNAc]2-GlcA-GalNAc-ol revealed that the preterminal N-acetylgalactosamine from the non-reducing end and the internal N-acetylgalactosamine but not the N-acetylgalactosaminitol were sulfated and that no hexasaccharide disulfate was formed by the action of chondroitin 6-sulfotransferase. Chondroitin 6-sulfotransferase is considered to possess a binding region capable of accommodating a nonsulfated oligosaccharide sequence of at least six sugars and is believed to act in the course of chondroitin sulfate synthesis in cooperation with, but shortly after, the enzymes involved in the chain elongation reaction.

Regulation of high density lipoprotein receptors in cultured macrophages: role of acyl-CoA:cholesterol acyltransferase.

The interaction of human serum high density lipoproteins (HDL) with mouse peritoneal macrophages and human blood monocytes was studied. Saturation curves for binding of apolipoprotein E-free [125I]HDL3 showed at least two components: non-specific binding and specific binding that saturated at approximately 40 micrograms HDL protein/ml. Scatchard analysis of specific binding of apo E-free [125I]-HDL3 to cultured macrophages yielded linear plots indicative of a single class of specific binding sites. Pretreatment of [125I]HDL3 with various apolipoprotein antibodies (anti apo A-I, anti apo A-II, anti apo C-II, anti apo C-III and anti apo E) and preincubation of the cells with anti-idiotype antibodies against apo A-I and apo A-II prior to the HDL binding studies revealed apolipoprotein A-I as the ligand involved in specific binding of HDL. Cellular cholesterol accumulation via incubation with acetylated LDL led to an increase in HDL binding sites as well as an increase in the activity of the cytoplasmic cholesterol esterifying enzyme acyl-CoA:cholesterol acyltransferase (ACAT). Incubation of the cholesterol-loaded cells in the presence of various ACAT inhibitors (Sandoz 58.035, Octimibate-Nattermann, progesterone) revealed a time- and dose-dependent amplification in HDL binding and HDL-mediated cholesterol efflux. It is concluded that the homeostasis of cellular cholesterol in macrophages is regulated in part by the number of HDL binding sites and that ACAT inhibitors enhance HDL-mediated cholesterol efflux from peripheral cells.

Two N-acetylgalactosaminyltransferase are involved in the biosynthesis of chondroitin sulfate.

Two N-acetylgalactosaminyltransferases, designated I and II, have been purified from the microsomal fraction of calf arterial tissue and separated on Bio-Gel A. N-Acetylgalactosaminyltransferase I was purified 450-fold. It requires Mn2+ for maximal activity and transfers N-acetylgalactosamine residues from UDP-[1-3H]GalNAc in beta-glycosidic configuration to the non-reducing terminus of the acceptor substrates GlcA(beta 1-3)Gal(beta 1-3)Gal, GlcA(beta 1-3)Gal(beta 1-4)Glc and GlcA(beta 1-3)Gal. Even-numbered chondroitin oligosaccharides serve as acceptors for N-acetylgalactosaminyltransferase II, which transfers N-acetylgalactosamine from UDP-[1-3H]GalNAc to the non-reducing glucuronic acid residues of oligosaccharide acceptor substrates. Maximum transfer rates were obtained with a decasaccharide derived from chondroitin. Longer or shorter-chain chondroitin oligosaccharides are less effective acceptor substrates. All reaction products formed by N-acetylgalactosaminyltransferases I and II are substrates of beta-N-acetylhexosaminidase, which splits off the transferred [1-3H]GalNAc completely. In the microsomal fraction N-acetylgalactosaminyltransferase II had a 300-fold higher specific activity than N-acetylgalactosaminyltransferase I. In contrast to enzyme I, enzyme II loses much of its activity during the purification procedure and undergoes rapid thermodenaturation. GlcA-Gal-Gal is a characteristic sequence of the carbohydrate-protein linkage region of proteochondrioitin sulfate. The acceptor capacity of this trisaccharide suggests that N-acetylgalactosaminyltransferase I is involved in the synthesis of the carbohydrate-protein linkage region. Since N-acetylgalactosaminyltransferase II is highly specific for chondroitin oligosaccharides, we conclude that it participates in chain elongation during chondroitin sulfate synthesis.

Purification and characterization of 3'-phosphoadenylylsulfate: N-desulfoheparan sulfate sulfotransferase from arterial tissue.

A 3'-phosphoadenylsulfate: N-desulfoheparan sulfate sulfotransferase (EC 2.8.2.12) was purified 450-fold from the microsomal fraction of calf arterial tissue and separated from 3'-phosphoadenylylsulfate:chondroitin sulfotransferase (EC 2.8.2.5) activity. The enzyme has optimal activity at neutral pH, requires divalent cations (Mn2+, Mg2+, Ca2+) for maximal activity and exhibits specificity towards N-desulfoheparan sulfate, N,O-desulfoheparan sulfate and oligosaccharides derived therefrom. N,O-desulfoheparan sulfate tetrasaccharides serve as acceptor substrates only if the nonreducing terminus is occupied by glucuronic acid (not iduronic acid). The N,O-desulfoheparan sulfate sulfotransferase transfers [35S]sulfate from 3'-phosphoadenylyl[35S]sulfate to the 2-amino groups and to the 6-hydroxy groups of glucosamine units of the acceptor substrates. The ratio of N/O-sulfation ranged between 3:1 and 2:1. O-[35S]Sulfated unsaturated disaccharides were obtained from enzymatically labelled [35S]N-desulfoheparan sulfate by heparitinase degradation and subsequent deamination. Evidence for the O-sulfation at C-6 of the glucosamine units was provided by isolation of anhydromannose [35S]monosulfate, which was formed from uronosylanhydromannose [35S]monosulfate by beta-glucuronidase treatment. An N-desulfo-N-[1-14C]lacetylheparan sulfate deacetylase activity was copurified with the N-desulfoheparan sulfate sulfotransferase.