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41.
Some disciplines in the social sciences rely heavily on collecting survey responses to detect empirical relationships among variables. We explored whether these relationships were a priori predictable from the semantic properties of the survey items, using language processing algorithms which are now available as new research methods. Language processing algorithms were used to calculate the semantic similarity among all items in state-of-the-art surveys from Organisational Behaviour research. These surveys covered areas such as transformational leadership, work motivation and work outcomes. This information was used to explain and predict the response patterns from real subjects. Semantic algorithms explained 60–86% of the variance in the response patterns and allowed remarkably precise prediction of survey responses from humans, except in a personality test. Even the relationships between independent and their purported dependent variables were accurately predicted. This raises concern about the empirical nature of data collected through some surveys if results are already given a priori through the way subjects are being asked. Survey response patterns seem heavily determined by semantics. Language algorithms may suggest these prior to administering a survey. This study suggests that semantic algorithms are becoming new tools for the social sciences, opening perspectives on survey responses that prevalent psychometric theory cannot explain.  相似文献   
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Much of our current knowledge about the physiological and pathophysiological role of gap junctions is based on experiments where coupling has been reduced by either chemical agents or genetic modification. This has brought evidence that gap junctions are important in many physiological processes. In a number of cases, gap junctions have been implicated in the initiation and progress of disease, and experimental uncoupling has been used to investigate the exact role of coupling. The inverse approach, i.e., to increase coupling, has become possible in recent years and represents a new way of testing the role of gap junctions. The aim of this review is to summarize the current knowledge obtained with agents that selectively increase gap junctional intercellular coupling. Two approaches will be reviewed: increasing coupling by the use of antiarrhythmic peptide and its synthetic analogs and by interfering with the gating of gap junctional channels.  相似文献   
44.
Lysophosphatidic acid (LPA) is a natural bioactive lipid that acts through six different G protein-coupled receptors (LPA1–6) with pleiotropic activities on multiple cell types. We have previously demonstrated that LPA is necessary for successful in vitro osteoclastogenesis of bone marrow cells. Bone cells controlling bone remodeling (i.e. osteoblasts, osteoclasts, and osteocytes) express LPA1, but delineating the role of this receptor in bone remodeling is still pending. Despite Lpar1−/− mice displaying a low bone mass phenotype, we demonstrated that bone marrow cell-induced osteoclastogenesis was reduced in Lpar1−/− mice but not in Lpar2−/− and Lpar3−/− animals. Expression of LPA1 was up-regulated during osteoclastogenesis, and LPA1 antagonists (Ki16425, Debio0719, and VPC12249) inhibited osteoclast differentiation. Blocking LPA1 activity with Ki16425 inhibited expression of nuclear factor of activated T-cell cytoplasmic 1 (NFATc1) and dendritic cell-specific transmembrane protein and interfered with the fusion but not the proliferation of osteoclast precursors. Similar to wild type osteoclasts treated with Ki16425, mature Lpar1−/− osteoclasts had reduced podosome belt and sealing zone resulting in reduced mineralized matrix resorption. Additionally, LPA1 expression markedly increased in the bone of ovariectomized mice, which was blocked by bisphosphonate treatment. Conversely, systemic treatment with Debio0719 prevented ovariectomy-induced cancellous bone loss. Moreover, intravital multiphoton microscopy revealed that Debio0719 reduced the retention of CX3CR1-EGFP+ osteoclast precursors in bone by increasing their mobility in the bone marrow cavity. Overall, our results demonstrate that LPA1 is essential for in vitro and in vivo osteoclast activities. Therefore, LPA1 emerges as a new target for the treatment of diseases associated with excess bone loss.  相似文献   
45.
Arginine has been demonstrated to enhance glucose and lipid oxidation in mammals through activation of polyamine turnover. We aimed to investigate how arginine affects energy utilization through polyamine metabolism and whether this effect is time dependent. Primary liver cells were isolated from Atlantic salmon (2.2 kg body weight) fed diets containing 25.5 (low arginine, LA) or 36.1 (high arginine, HA) g arginine/kg dry matter for 12 weeks, to investigate the effect of long-term arginine supplementation. The cells were cultured for 24 h in L-15 medium to which either alpha-difluoromethylornithine (DFMO) or N 1,N 11-diethylnorspermine (DENSPM) was added. Analysis of the medium by nuclear magnetic resonance revealed significant differences between the two dietary groups as well as between cells exposed to DFMO and DENSPM, with decreased glucose, fumarate and lactate concentrations in media of the HA cells. Liver cells from fish fed the HA diet had higher spermidine/spermine-N1-acetyltransferase protein abundance and lower adenosine triphosphate concentration as compared to the LA-fed fish, while gene expression was not affected by either diet or treatment. Primary liver cells isolated from salmon fed a commercial diet and cultured in L-15 media with or without arginine supplementation (1.82 or 3.63 mM) for 48 h, representing short-term effect of arginine supplementation, showed differential expression of genes for apoptosis and polyamine synthesis due to arginine supplementation or inhibition by DFMO. Overall, arginine concentration and exposure time affected energy metabolism and gene regulation more than inhibition or activation of key enzymes of polyamine metabolism, suggesting a polyamine-independent influence of arginine on cellular energy metabolism and survival.  相似文献   
46.
Expression of the mammalian enzyme methionine sulfoxide reductase B1 (MsrB1) in Escherichia coli growing in cobalt-containing media resulted in the reproducible appearance of the stable cobalt-containing protein MsrB1-Co. NMR studies and biocomputing using the programs AnisoFit and Amber allowed us to generate a structure of MsrB1-Co sharing the overall fold with the native zinc-containing protein MsrB1-Zn. Our data suggest that the N-terminus containing resolving cysteine tends to be closer to the protein’s catalytic center than was previously reported. It is argued that this proximity supports the proposed catalytic mechanism and ensures high catalytic efficiency of MsrB1. Functional studies showed that both MsrB1-Zn and MsrB1-Co exhibit similar levels of activity, in agreement with the structural studies performed. The proposed metal ion substitution approach may have a methodological significance in determining whether methionine sulfoxide reductase B proteins contain a metal ion.  相似文献   
47.

Background/Objectives

White matter hyperintensities (WMH) in magnetic resonance imaging (MRI) scans of the brain, and orthostatic hypotension (OH) are both common in older people. We tested the hypothesis that OH is associated with WMH.

Design

Cross-sectional study.

Setting

Secondary care outpatient clinics in geriatric medicine and old age psychiatry in western Norway.

Participants

160 older patients with mild dementia, diagnosed according to standardised criteria.

Measurements

OH was diagnosed according to the consensus definition, measuring blood pressure (BP) in the supine position and within 3 minutes in the standing position. MRI scans were performed according to a common protocol at three centres, and the volumes of WMH were quantified using an automated method (n = 82), followed by manual editing. WMH were also quantified using the visual Scheltens scale (n = 139). Multiple logistic regression analyses were applied, with highest vs. lowest WMH quartile as response.

Results

There were no significant correlations between WMH volumes and systolic or diastolic orthostatic BP drops, and no significant correlations between Scheltens scores of WMH and systolic or diastolic BP drops. In the multivariate analyses, only APOEε4 status remained a significant predictor for WMH using the automated method (p = 0.037, OR 0.075 (0.007–0.851)), whereas only age remained a significant predictor for WMH scores (p = 0.019, OR 1.119 (1.018–1.230)).

Conclusion

We found no association between OH and WMH load in a sample of older patients with mild dementia.  相似文献   
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49.
Finding effective ways of conserving large carnivores is widely recognised as a priority in conservation. However, there is disagreement about the most effective way to do this, with some favouring top‐down ‘command and control’ approaches and others favouring collaboration. Arguments for coercive top‐down approaches have been presented elsewhere; here we present arguments for collaboration. In many parts of the developed world, flexibility of approach is built into the legislation, so that conservation objectives are balanced with other legitimate goals. In the developing world, limited resources, poverty and weak governance mean that collaborative approaches are likely to play a particularly important part in carnivore conservation. In general, coercive policies may lead to the deterioration of political legitimacy and potentially to non‐compliance issues such as illegal killing, whereas collaborative approaches may lead to psychological ownership, enhanced trust, learning, and better social outcomes. Sustainable hunting/trapping plays a crucial part in the conservation and management of many large carnivores. There are many different models for how to conserve carnivores effectively across the world, research is now required to reduce uncertainty and examine the effectiveness of these approaches in different contexts.  相似文献   
50.
Direct observation was used to measure feeding rates of the flagellate Spumella on three sizes of bacteria plus 0.3 µm latex beads using video microscopy. Feeding rate was maximum on the intermediate-sized bacteria. Maximum ingestion rates (Im) for the large- (0.53 µm3), intermediate- (0.08 µm3) and small-sized (0.02 µm3) bacteria and 0.014 µm3 latex beads were 11, 38 and 14 bacteria and 9 beads flagellate–1 h–1, respectively. The growth rates of Spumella sp. feeding on monoxenic cultures of the large- vs. the intermediate-sized bacteria were indistinguishable but Spumella sp. could not sustain its population density when feeding on the small bacterium as the sole food source. Our data are consistent with the hypothesis that Spumella sp., and possibly other flagellate protozoa, tend to feed selectively on larger prey. One consequence of this hypothesis is that differential grazing by bactivores may select for small bacteria in natural waters.  相似文献   
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