Effects of estrogen and progesterone on the escalation of cocaine self-administration in female rats during extended access.

Estrogen increases and progesterone decreases the acquisition and reinstatement of cocaine-seeking behavior in female rats. Here estrogen and progesterone were studied for their effects on the escalation of cocaine self-administration in female rats. The rats received ovariectomy (OVX) or sham (SH) surgery and were treated with estradiol benzoate (0.05 mg/kg sc) and/or progesterone (0.5 mg/kg) or vehicle (indicated by E, P, and V), resulting in 5 groups: SH+V, SH+P, OVX+V, OVX+E, OVX+E+P. Rats self-administered intravenous cocaine (0.4 mg/kg) under a fixed ratio 1 (FR 1) schedule during 2-hr sessions and were then given 6-hr sessions (long access; LgA) (FR 1) for 21 days. After LgA, self-administration was reassessed with 2-hr sessions under the FR 1 and a progressive ratio schedule with 4 cocaine doses. There were no differences among the 5 groups in cocaine self-administration during initial 2-hr sessions. During LgA, the SH+V, OVX+E, and OVX+V groups escalated their cocaine self-administration, whereas the OVX+E+P and SH+P groups did not. Estradiol increased escalation in the OVX+E group compared with the OVX+V group, and progesterone (SH+P) reduced escalation compared with the SH+V group. When estrogen and progesterone were both administered in OVX rats (OVX+E+P), escalation was significantly lower than in the OVX+E group. Cocaine infusions during the 2-hr sessions were significantly higher after escalation than before in all groups except the progesterone-treated groups (SH+P and OVX+E+P). Estrogen promoted and progesterone inhibited escalation of cocaine self-administration, illustrating the importance of female gonadal hormones in drug-seeking behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Structural features of the hemicellulose polymers of apples

The hemicellulose extract from apples, obtained by alkaline extraction of depectinized apple alcohol-insoluble solids, was fractionated by ion-exchange chromatography on DEAE cellulose and gel filtration chromatography before and after treatment with pure 1,4--d-glucan glucanohydrolase. The sugar and glycosyl linkage composition of various fractions obtained were established. The results of this study indicate that the apple hemicellulose extract consists of fucogalactoxyloglucans, pectic arabinans and galactans, (gluco-)mannans, (arabino-)xylans, and 1,3 linked glucans. Fucogalaktoxyloglucans and pectic arabinans and galactans were isolated as such, and in complexes with each other and with (arabino-)xylans. The major part of the mannans is not linked to other hemicellulose polymers.

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Strukturkennzeichen der Hemicellulose-Polysaccharide von Äpfeln

Zusammenfassung Es wurde ein Hemicellulose-Extrakt aus Äpfeln durch alkalische Extraktion der entpectinisierten alkoholunlöslichen Substanz gewonnen. Dieser Extrakt wurde fraktioniert mittels Ionenaustausch-Chromatographie und Gelfiltration vor und nach Behandlung mit einer reinen 1,4--d-Glucanglucanohydrolase. Die Zusammensetzung der verschiedenen Fraktionen an Zuckerbausteinen und den glykosidischen Bindungen wurde bestimmt. Die Resultate deuten darauf hin, daß der Hemicellulose-Extrakt von Äpfeln Fucogalaktoxyloglucane, pektinassoziierte Arabane und Galaktane (Gluko)-Mannane, (Arabino)-Xylane und 1,3-Glucane enthält. Die Fucogalaktoxyloglucane und die Arabane und Galaktane wurden als solche und als Komplexe miteinander und mit (Arabino)-Xylanen isoliert. Der größte Teil der Mannane war nicht an andere Hemicellulosen gebunden.

     

A Magnetoresistance Induced by a Nonzero Berry Phase in GeTe/Sb2Te3 Chalcogenide Superlattices

The chalcogenide alloy Ge–Sb–Te (GST) has not only been used in rewritable digital versatile discs, but also in nonvolatile electrical phase change memory as a key recording material. Although GST has been believed for a long time not to show magnetic properties unless doped with magnetic impurities, it has recently been reported that superlattices (SLs) with the structure [(GeTe)_L(Sb₂Te₃)_M]_N (where L, M, and N are usually integers) have a large magnetoresistance at room temperature for particular combinations of L and M. Here it is reported that when [(GeTe)_L(Sb₂Te₃)_M]_N chalcogenide SL films are thermally annealed at 470 K and cooled down to room temperature under an external magnetic field accompanied by current pulse injections, a large magnetoresistance change (>2500 Ω) is induced. This study shows that the phenomenon has a strong correlation with the GeTe thickness and the periodic structure of the SL films, and that it is induced by the structural phase transition between electrically nonpolar and polar phases in the GeTe layers in the SLs. This study proposes that the relationship between the polar (ferroelectric) phase and the Berry curvature in the SLs is responsible for the magnetoresistance change.     

The Somatic Mutation Paradigm in Congenital Malformations: Hirschsprung Disease as a Model

Patients with Hirschsprung disease (HSCR) do not always receive a genetic diagnosis after routine screening in clinical practice. One of the reasons for this could be that the causal mutation is not present in the cell types that are usually tested—whole blood, dermal fibroblasts or saliva—but is only in the affected tissue. Such mutations are called somatic, and can occur in a given cell at any stage of development after conception. They will then be present in all subsequent daughter cells. Here, we investigated the presence of somatic mutations in HSCR patients. For this, whole-exome sequencing and copy number analysis were performed in DNA isolated from purified enteric neural crest cells (ENCCs) and blood or fibroblasts of the same patient. Variants identified were subsequently validated by Sanger sequencing. Several somatic variants were identified in all patients, but causative mutations for HSCR were not specifically identified in the ENCCs of these patients. Larger copy number variants were also not found to be specific to ENCCs. Therefore, we believe that somatic mutations are unlikely to be identified, if causative for HSCR. Here, we postulate various modes of development following the occurrence of a somatic mutation, to describe the challenges in detecting such mutations, and hypothesize how somatic mutations may contribute to ‘missing heritability’ in developmental defects.     

Multi-Omics Profiling in Marfan Syndrome: Further Insights into the Molecular Mechanisms Involved in Aortic Disease

Thoracic aortic aneurysm is a potentially life-threatening disease with a strong genetic contribution. Despite identification of multiple genes involved in aneurysm formation, little is known about the specific underlying mechanisms that drive the pathological changes in the aortic wall. The aim of our study was to unravel the molecular mechanisms underlying aneurysm formation in Marfan syndrome (MFS). We collected aortic wall samples from FBN1 variant-positive MFS patients (n = 6) and healthy donor hearts (n = 5). Messenger RNA (mRNA) expression levels were measured by RNA sequencing and compared between MFS patients and controls, and between haploinsufficient (HI) and dominant negative (DN) FBN1 variants. Immunohistochemical staining, proteomics and cellular respiration experiments were used to confirm our findings. FBN1 mRNA expression levels were highly variable in MFS patients and did not significantly differ from controls. Moreover, we did not identify a distinctive TGF-β gene expression signature in MFS patients. On the contrary, differential gene and protein expression analysis, as well as vascular smooth muscle cell respiration measurements, pointed toward inflammation and mitochondrial dysfunction. Our findings confirm that inflammatory and mitochondrial pathways play important roles in the pathophysiological processes underlying MFS-related aortic disease, providing new therapeutic options.     

Weekly Treatment of 2-Hydroxypropyl-β-cyclodextrin Improves Intracellular Cholesterol Levels in LDL Receptor Knockout Mice

Recently, the importance of lysosomes in the context of the metabolic syndrome has received increased attention. Increased lysosomal cholesterol storage and cholesterol crystallization inside macrophages have been linked to several metabolic diseases, such as atherosclerosis and non-alcoholic fatty liver disease (NAFLD). Two-hydroxypropyl-β-cyclodextrin (HP-B-CD) is able to redirect lysosomal cholesterol to the cytoplasm in Niemann-Pick type C1 disease, a lysosomal storage disorder. We hypothesize that HP-B-CD ameliorates liver cholesterol and intracellular cholesterol levels inside Kupffer cells (KCs). Hyperlipidemic low-density lipoprotein receptor knockout (Ldlr^−/−) mice were given weekly, subcutaneous injections with HP-B-CD or control PBS. In contrast to control injections, hyperlipidemic mice treated with HP-B-CD demonstrated a shift in intracellular cholesterol distribution towards cytoplasmic cholesteryl ester (CE) storage and a decrease in cholesterol crystallization inside KCs. Compared to untreated hyperlipidemic mice, the foamy KC appearance and liver cholesterol remained similar upon HP-B-CD administration, while hepatic campesterol and 7α-hydroxycholesterol levels were back increased. Thus, HP-B-CD could be a useful tool to improve intracellular cholesterol levels in the context of the metabolic syndrome, possibly through modulation of phyto- and oxysterols, and should be tested in the future. Additionally, these data underline the existence of a shared etiology between lysosomal storage diseases and NAFLD.     

Implicit theories about interrelations of anger components in 25 countries.

We were interested in the cross-cultural comparison of implicit theories of the interrelations of eight anger components (antecedents, body sensations, cognitive reactions, verbal expressions, nonverbal expressions, interpersonal responses, and primary and secondary self-control). Self-report scales of each of these components were administered to a total of 5,006 college students in 25 countries. Equivalence of the scales was supported in that scales showed acceptable congruence coefficients in almost all comparisons. A multigroup confirmatory factor model with three latent variables (labeled internal processes, behavioral outcomes, and self-control mechanisms) could well account for the interrelations of the eight observed variables; measurement and structural weights were invariant. Behavioral outcomes and self-control mechanisms were only associated through their common dependence on internal processes. Verbal expressions and cognitive reactions showed the largest cross-cultural differences in means, whereas self-control mechanisms scales showed the smallest differences. Yet, cultural differences between the countries were small. It is concluded that anger, as measured by these scales, shows more pronounced cross-cultural similarities than differences in terms of both interrelations and mean score levels. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Texture and morphology variations in (In,Ga)2Se3 and Cu(In,Ga)Se2 thin films grown with various Se source conditions

Texture and morphology variations in co‐evaporated (In,Ga)₂Se₃ and Cu(In,Ga)Se₂ (CIGS) films grown with various Se source conditions during growth were studied. The Se species of simply evaporated, large molecular Se (E‐Se, low‐sticking coefficient), and RF‐plasma cracked atomic Se (R‐Se, high sticking coefficient) were used in the present work. (In,Ga)₂Se₃ precursor films, which were prepared during the first stage of CIGS film growth by the three‐stage process, showed systematic variations in texture and Na distribution profile with varying evaporative Se (E‐Se) flux. The properties of CIGS films and solar cells also showed systematic variations, and the open‐circuit voltage (V_oc) and fill factor were found to be especially sensitive to the E‐Se flux. R‐Se grown (In,Ga)₂Se₃ precursor films featured granular morphology with strong (105) and (301) peaks in the diffraction pattern, and the texture was very similar to an E‐Se grown film fabricated with a Se to group III metal (In + Ga) flux ratio (P_{[Se]/[In + Ga]}) of about 6, although the nominal P_{[Se]/[In + Ga]} used for an R‐Se source was very small and less than 0.5. The R‐Se grown CIGS films displayed, however, highly dense surfaces and larger grain sizes than E‐Se grown CIGS films. The controllability of film morphology and the Na diffusion profile in (In,Ga)₂Se₃ and CIGS films with various Se source conditions are discussed. Copyright © 2011 John Wiley & Sons, Ltd.     

Feasibility of a novel system to prestress externally bonded reinforcement

The strengthening of concrete structures with externally bonded prestressed reinforcement has advantages compared to a passive system. The load bearing capacity is increased as well as the flexural stiffness. Prestressing allows to exploit the high tensile strength of the fibres of the external reinforcement. A number of systems are already commercially available, however their use is restricted as they are more expensive and show some practical inconveniences in use. In this paper, a novel system is presented and a feasibility study is carried out. The novel system aims to overcome the inconveniences of existing prestressing systems. The system has a reduced number of necessary operations and keeps a small distance between the concrete surface and the laminate. In the initial study presented, feasibility tests are carried out on simplified test systems and the design of the anchorage to the concrete and of the clamping system are discussed.     

Effects of annealing on CuInSe2 films grown by molecular beam epitaxy

CuInSe₂ (CIS) thin films with a range of Cu/In ratios were grown by molecular beam epitaxy on GaAs (0 0 1) at substrate temperatures of T_s = 450–500°C and the effects of annealing under various atmospheres have been investigated. Photoluminescence spectra obtained from an ex-situ vacuum annealed CIS film at a temperature of T_A = 350°C showed a red-shift and a broadening of an emission peak (peak c) which originally appeared at 0.970 eV before annealing and the red-shifted peak c was found to consist of two overlapping peaks. The excitation power dependence of these overlapping peaks indicated the radiative recombination processes associated with the emissions to be a conduction band to acceptor transition (peak at 0.970 eV) and a transition due to donor-acceptor pairs (peak at 0.959 eV), indicating the formation of a shallow donor-type defect during the vacuum annealing process. The origin of this defect has tentatively been attributed to Se vacancies. On the other hand, the molar fraction of oxygen increased with increasing annealing temperature in dry-air. An epitaxially grown In₂O₃ phase was found both in Cu-rich and In-rich films annealed at T_A 350°C, which was not observed in the films annealed in Ar atmosphere. Thermodynamic calculations based on the Cu---In---Se---O---N system showed In₂O₃ to be the most stable phase in good agreement with the experimental results.