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The Himalayan–Tibetan orogen is the world's largest active orogen with the thickest continental crust on Earth. However, the timing of crustal thickening of this orogen remains controversial. In recent years, magmatic rocks with adakitic affinities have been widely used to constrain the crustal thickness. Here, we present zircon U–Pb ages, geochemical and Sr–Nd–Pb–Hf isotopic data for the Dala two‐mica granites (eastern Tethyan Himalaya) that may shed light on this issue. Zircon U–Pb dating shows that the Dala two‐mica granites were emplaced at ca. 43 Ma. The granites display adakitic signatures, including high SiO2, Al2O3 and Sr contents, low Y and Yb contents with high Sr/Y (27−67) and La/Yb (35−99) ratios. High K2O and Th contents, low Nb/U, Ce/Pb, Ti/Eu and Nd/Sm ratios and low MgO, Mg#, Cr and Ni contents suggest that the Dala two‐mica granites were derived from partial melting of a thickened lower crust. Low negative zircon εHf(t) values (−10.4 to −0.5) with old two‐stage Hf model ages (1.1–1.8 Ga), high (87Sr/86Sr)i (0.715861–0.717665) with low εNd(t) (−12.5 to −11.3) and high Pb isotopes [(206Pb/204Pb)i=18.783–18.861, (207Pb/204Pb)i=18.783–18.861 and (208Pb/204Pb)i=39.052–39.285], together with previous literature data, indicate that the magma source for the Eocene granites in the Yardoi area was composed of ancient lower crust consisting mainly of garnet‐amphibolite and probably subordinate metapelites of the High Himalayan Crystalline Sequence. The residual mineral assemblage of garnet + rutile + plagioclase ± amphibole in the source region demonstrates that the crust beneath the Himalaya could have been thickened to ﹥50 km in the Eocene. Combining with previous studies, we propose that the Eocene magmatic rocks in the Tethyan Himalaya (e.g. ca. 43 Ma old Dala two‐mica granites) can be best interpreted as the consequence of breakoff of the Neo‐Tethyan oceanic slab. [ABSTRACT FROM AUTHOR]

5-Aminolevulinic acid (5-ALA) is an amino acid derivative and a precursor of protoporphyrin IX (PpIX). The photophysical feature of PpIX is clinically used in photodynamic diagnosis (PDD) and photodynamic therapy (PDT). These clinical applications are potentially based on in vitro cell culture experiments. Thus, conducting a systematic review and meta-analysis of in vitro 5-ALA PDT experiments is meaningful and may provide opportunities to consider future perspectives in this field. We conducted a systematic literature search in PubMed to summarize the in vitro 5-ALA PDT experiments and calculated the effectiveness of 5-ALA PDT for several cancer cell types. In total, 412 articles were identified, and 77 were extracted based on our inclusion criteria. The calculated effectiveness of 5-ALA PDT was statistically analyzed, which revealed a tendency of cancer-classification-dependent sensitivity to 5-ALA PDT, and stomach cancer was significantly more sensitive to 5-ALA PDT compared with cancers of different origins. Based on our analysis, we suggest a standardized in vitro experimental protocol for 5-ALA PDT.

Abstract: Intranasal phototherapy has been found to be effective for the treatment of nasal polyposis (NP) therefore the aim was to investigate the apoptosis inducing effect of phototherapy in NP. In this ex vivo study nasal polyp tissue was surgically collected from 21 consecutive patients with chronic rhinosinusitis (CRS) associated with NP. The removed polyps were cut into pieces and tissue samples were irradiated in vitro by different doses of combined ultraviolet and visible light (UV/VIS: 280–650nm) and by selective ultraviolet and visible light (sUV/VIS: 295–650nm). Photodynamic therapy (PDT) was performed by presensitizing tissue samples with 5-delta-aminolevulinic acid (DALA) then irradiated with visible light (VIS: 395–650nm). Tunel assay was applied to detect apoptosis of epithelial and inflammatory cells in irradiated and control nasal polyp tissue samples. UV/VIS light significantly increased epithelial cell and subepithelial leukocyte apoptosis compared to control groups. PDT treatment showed the highest surface epithelial cell as well as subepithelial leukocyte apoptosis compared to all other groups. Intranasal phototherapy may serve as a new potential therapeutical method in treatment of NP. [Copyright &y& Elsevier]

Abstract: Recent studies have shown that the opioid enkephalin (ENK), acting in part through the hypothalamic paraventricular nucleus (PVN), can stimulate consumption of a high-fat diet. The objective of the present study was to examine sub-populations of Sprague–Dawley rats naturally prone to overconsuming a high-fat diet and determine whether endogenous ENK, in different brain regions, is altered in these animals and possibly contributes to their behavioral phenotype. An animal model, involving a measure of initial high-fat diet intake during a few days of access that predicts long-term intake, was designed to classify rats at normal weight that are either high-fat consumers (HFC), which ingest 35% more calories of the high-fat than low-fat chow diet, or controls, which consume similar calories of these two diets. Immediately after their initial access to the diet, the HFC compared to control rats exhibited significantly greater expression of ENK mRNA, in the PVN, nucleus accumbens and central nucleus of the amygdala, but not the arcuate nucleus or basolateral amygdala. This site-specific increase in ENK persisted even when the HFC rats were maintained on a chow diet, suggesting that it reflects an inherent characteristic that can be expressed independently of the diet. It was also accompanied by a greater responsiveness of the HFC rats to the stimulatory effect of a PVN-injected, ENK analogue, D-ala2-met-enkephalinamide, compared to saline on consumption of the high-fat diet. Thus, normal-weight rats predicted to overconsume a fat-rich diet exhibit disturbances in endogenous ENK expression and functioning that may contribute to their long-term, behavioral phenotype. [ABSTRACT FROM AUTHOR]

Abstract: The experimental question is whether hypothalamic opioids, known to stimulate consummatory behavior, control a link to the nucleus accumbens (NAc). It was hypothesized that opioids injected in the hypothalamic paraventricular nucleus (PVN) alter the balance of dopamine (DA) and acetylcholine (ACh) in the NAc in a manner that fosters appetite for food or ethanol. Rats were implanted with two guide shafts, one in the NAc to measure extracellular DA and ACh by microdialysis and the other in the PVN for microinjection of opioid μ- and δ-agonists, an antagonist, or saline vehicle. The compounds tested were morphine, the μ-receptor agonist [d-Ala2,N-Me-Phe4,Gly5-ol]-Enkephalin (DAMGO), the δ-receptor agonist d-Ala-Gly-Phe-Met-NH2 (DALA), and the opioid antagonist naloxone methiodide (m-naloxone). Morphine in the PVN increased the release of accumbens DA (+41%) and decreased ACh (−35%). Consistent with this, the opioid antagonist m-naloxone decreased DA (−24%) and increased ACh (+19%). In terms of receptor involvement, DAMGO dose-dependently increased DA to up to 209% of baseline. Simultaneously, ACh levels were markedly decreased to 55% of baseline. The agonist DALA produced a smaller but significant, 34% increase in DA, without affecting ACh. In contrast, control injections of saline had no significant effect. These results demonstrate that μ- and δ-opioids in the PVN contribute to the control of accumbens DA and ACh release and suggest that this circuit from the PVN to the NAc may be one of the mechanisms underlying opiate-induced ingestive behavior as well as naltrexone therapy for overeating and alcoholism. [Copyright &y& Elsevier]

Abstract: The nucleus accumbens (NAc) participates in the control of both motivation and addiction. To test the possibility that opioids in the NAc can cause rats to select ethanol in preference to food, Sprague–Dawley rats with ethanol, food, and water available, were injected with two doses each of morphine, the μ-receptor agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-Enkephalin (DAMGO), the δ-receptor agonist D-Ala-Gly-Phe-Met-NH2 (DALA), the k-receptor agonist (±)-trans-U-50488 methanesulfonate (U-50,488H), or the opioid antagonist naloxone methiodide (m-naloxone). As an anatomical control for drug reflux, injections were also made 2mm above the NAc. The main result was that morphine in the NAc significantly increased ethanol and food intake, whereas m-naloxone reduced ethanol intake without affecting food or water intake. Of the selective receptor agonists, DALA in the NAc increased ethanol intake in preference to food. This is in contrast to DAMGO, which stimulated food but not ethanol intake, and the k-agonist U-50,488H, which had no effect on intake. When injected in the anatomical control site 2mm dorsal to the NAc, the opioids had no effects on ethanol intake. These results demonstrate that ethanol intake produced by morphine in the NAc is driven in large part by the δ-receptor. In light of other studies showing ethanol intake to increase enkephalin expression in the NAc, the present finding of enkephalin-induced ethanol intake suggests the existence of a positive feedback loop that fosters alcohol abuse. Naltrexone therapy for alcohol abuse may then act, in part, in the NAc by blocking this opioid-triggered cycle of alcohol intake. [Copyright &y& Elsevier]

In the present study, the foraging behaviour of ewes from three common Norwegian sheep breeds; the long-tailed Dala sheep, and the two short-tailed breeds Spæl sheep and Norwegian Fur sheep was studied. Based on difference in body size and digestive anatomy, we expected the lighter short-tailed ewes to browse more on woody plants than the Dala ewes. The experiments were conducted during two consecutive summers within the flocks’ usual grazing areas, and we sampled the proportion of grazing time that ewes spent feeding on woody plant species. We tested the hypothesis by applying generalized linear mixed models to the feeding behaviour data. As predicted, the short-tailed ewes spent substantially more of their grazing time browsing on trees, bushes and heather compared to the Dala ewes. We discuss the results in the context of maintaining the, now threatened, pastoral landscapes of mountainous regions of Norway; short-tailed breeds should be more effective than the Dala breed in reducing tree and bush encroachment, but more detailed studies are needed to quantify the breed differences in this respect. [ABSTRACT FROM AUTHOR]

With high variation in environmental conditions, especially during the extensive grazing season, genotype by environment interaction is potentially important to lamb production in Norway. Using breed as an indicator of genotype, the interaction between breed and environment, i.e. production level of farm and year calculated as solutions of a random farm*year variable, on 52 farms keeping both long-tailed Dala and short-tailed Spæl during 1989-98 was studied. The dataset included 48,946 Dala lambs and 38,299 Spæl lambs. The breed by environment interaction affected lamb autumn weights, and though Dala lambs were always heavier, the difference was substantially smaller at lower than at higher production levels: 1 kg increase in production level was related to Dala lambs' weights increasing 0.09 kg more than the Spæl lambs' weights. The results indicate that breed by environment interaction may be of importance, and potential bias in the data and need for further research is discussed. [ABSTRACT FROM AUTHOR]

There is evidence to suggest an antagonistic interaction between the anxiogenic peptide, cholecystokinin (CCK) and the anxiolytic opioid peptide, enkephalin in mesolimbic sites following stressor applications in humans and animals which may define specific behavioral symptom subsets and alter the course of anxiety-like behavior. Locomotor and rearing behavior were decreased following a central CCK-8S (50 ng) injection among independent groups of mice relative to saline-treated animals. Central administration of DALA not only ameliorated the CCK-induced behavioral deficits but exaggerated behavioral activity of CCK and saline control mice (SAL). Locomotor activity and rearing behavior were depressed 24 h following DALA administration yet returned to basal values 168 h following drug applications. Eighteen days following the initial 50 ng CCK-8S and intervening DALA challenge, mice were administered 5 ng CCK-8S. An intervening dose of DALA in mice following the original 50 ng CCK-8S administration on Day 1 was associated with elevated locomotor activity in mice in response to the 5 ng CCK-8S challenge on Day 18. In contrast to locomotor activity, mice administered DALA following the original 50 ng CCK-8S administration on Day 1 demonstrated decreased rearing behavior to both 5 ng CCK-8S challenge and SAL on Day 18. Moreover, administration of 5 ng CCK-8S on Day 18 was associated with decreased rearing behavior in mice previously administered SAL on Day 1. These data imply that while CCK induces relatively protracted behavioral disturbances, μ/δ receptor activation may change the course of psychopathology. [Copyright &y& Elsevier]

We investigated the relationship between reproductive performance in Norwegian domestic sheep at the age of 12 months and autumn body weights (i.e., pre-oestrus condition), among primiparous females in two different populations, Buskerud and Nordland. We hypothesized the existence of a threshold weight below which lambing either does not occur, or the probability of lambing is very low. We also expected heavier females to have higher probabilities of successful lambing. Using mixed-effects logistic regression analyses, we observed spatio-temporal variability in lambing success of primiparous sheep. The proportion of primiparous females giving birth between 1993 and 1999 varied from 87.4 to 92.75% (mean=91%) and from 82.02 to 90.53% (mean=87%) in Buskerud and Nordland, respectively. As expected, higher autumn weight increased the probability of lambing in the first year of life, even after accounting for the random variability between year and farm. We were unable to find a threshold weight necessary for successful lambing, probably as a result of varying management practices. We conclude that juvenile weight before oestrus is, among others, a good predictor of the probability of successful lambing in primiparous sheep. [ABSTRACT FROM AUTHOR]

The effects of bilateral nucleus accumbens microinjections of d-ala-met-enkephalinamide (DALA) were assessed in behavioral activation and lateral hypothalamic self-stimulation (LHSS) rate-frequency curve-shift paradigms in normal and accumbens 6-OHDA (4.0 µg) treated rats. Microinjections of DALA (2.5 µg/µl) in the behavioral activation paradigm had little effect on normal activity; however, DALA administered to 6-OHDA treated rats produced a significant overall increase in locomotion. The 6-OHDA DALA-induced locomotion effect peaked at 2 weeks after 6-OHDA treatment and then returned to baseline levels by week 5 posttreatment. Using LHSS, DALA tested over a range of doses (2.5, 5, 10, 20 µg/µl) displayed a weak biphasic reward effect only at the highest dose, which was characterized by an initial suppression followed by an elevation. DALA significantly depressed initial operant motor/performance in LHSS in a dose dependent fashion. Micro-injections of the normally ineffective low dose of DALA (2.5 µg/µl) following accumbens 6-OHDA treatment produced a significant LHSS reward decrease 2 weeks posttreatment, while LHSS motor/performance was relatively unaffected. Results are discussed in terms of opiate-dopamine and limbic-motor interactions. [ABSTRACT FROM AUTHOR]

5-Aminolevulinic acid (5-ALA) is an amino acid derivative and a precursor of protoporphyrin IX (PpIX). The photophysical feature of PpIX is clinically used in photodynamic diagnosis (PDD) and photodynamic therapy (PDT). These clinical applications are potentially based on in vitro cell culture experiments. Thus, conducting a systematic review and meta-analysis of in vitro 5-ALA PDT experiments is meaningful and may provide opportunities to consider future perspectives in this field. We conducted a systematic literature search in PubMed to summarize the in vitro 5-ALA PDT experiments and calculated the effectiveness of 5-ALA PDT for several cancer cell types. In total, 412 articles were identified, and 77 were extracted based on our inclusion criteria. The calculated effectiveness of 5-ALA PDT was statistically analyzed, which revealed a tendency of cancer-classification-dependent sensitivity to 5-ALA PDT, and stomach cancer was significantly more sensitive to 5-ALA PDT compared with cancers of different origins. Based on our analysis, we suggest a standardized in vitro experimental protocol for 5-ALA PDT. [ABSTRACT FROM AUTHOR]