1,862 research outputs found
Field-induced quantum fluctuations in the heavy fermion superconductor CeCu2Ge2
Quantum-mechanical fluctuations in strongly correlated electron systems cause
unconventional phenomena such as non-Fermi liquid behavior, and arguably high
temperature superconductivity. Here we report the discovery of a field-tuned
quantum critical phenomenon in stoichiometric CeCu2Ge2, a spin density wave
ordered heavy fermion metal that exhibits unconventional superconductivity
under ~ 10 GPa of applied pressure. Our finding of the associated quantum
critical spin fluctuations of the antiferromagnetic spin density wave order,
dominating the local fluctuations due to single-site Kondo effect, provide new
information about the underlying mechanism that can be important in
understanding superconductivity in this novel compound.Comment: Heavy Fermion, Quantum Critical Phenomeno
Combined In Silico, In Vivo, and In Vitro Studies Shed Insights into the Acute Inflammatory Response in Middle-Aged Mice
We combined in silico, in vivo, and in vitro studies to gain insights into age-dependent changes in acute inflammation in response to bacterial endotoxin (LPS). Time-course cytokine, chemokine, and NO2-/NO3- data from "middle-aged" (6-8 months old) C57BL/6 mice were used to re-parameterize a mechanistic mathematical model of acute inflammation originally calibrated for "young" (2-3 months old) mice. These studies suggested that macrophages from middle-aged mice are more susceptible to cell death, as well as producing higher levels of pro-inflammatory cytokines, vs. macrophages from young mice. In support of the in silico-derived hypotheses, resident peritoneal cells from endotoxemic middle-aged mice exhibited reduced viability and produced elevated levels of TNF-α, IL-6, IL-10, and KC/CXCL1 as compared to cells from young mice. Our studies demonstrate the utility of a combined in silico, in vivo, and in vitro approach to the study of acute inflammation in shock states, and suggest hypotheses with regard to the changes in the cytokine milieu that accompany aging. © 2013 Namas et al
Perturbation with Intrabodies Reveals That Calpain Cleavage Is Required for Degradation of Huntingtin Exon 1
Background:
Proteolytic processing of mutant huntingtin (mHtt), the protein that causes Huntington's disease (HD), is critical for mHtt toxicity and disease progression. mHtt contains several caspase and calpain cleavage sites that generate N-terminal fragments that are more toxic than full-length mHtt. Further processing is then required for the degradation of these fragments, which in turn, reduces toxicity. This unknown, secondary degradative process represents a promising therapeutic target for HD.
Methodology/Principal Findings: We have used intrabodies, intracellularly expressed antibody fragments, to gain insight into the mechanism of mutant huntingtin exon 1 (mHDx-1) clearance. Happ1, an intrabody recognizing the proline-rich region of mHDx-1, reduces the level of soluble mHDx-1 by increasing clearance. While proteasome and macroautophagy inhibitors reduce turnover of mHDx-1, Happ1 is still able to reduce mHDx-1 under these conditions, indicating Happ1-accelerated mHDx-1 clearance does not rely on these processes. In contrast, a calpain inhibitor or an inhibitor of lysosomal pH block Happ1-mediated acceleration of mHDx-1 clearance. These results suggest that mHDx-1 is cleaved by calpain, likely followed by lysosomal degradation and this process regulates the turnover rate of mHDx-1. Sequence analysis identifies amino acid (AA) 15 as a potential calpain cleavage site. Calpain cleavage of recombinant mHDx-1 in vitro yields fragments of sizes corresponding to this prediction. Moreover, when the site is blocked by binding of another intrabody, V_L12.3, turnover of soluble mHDx-1 in living cells is blocked.
Conclusions/Significance:
These results indicate that calpain-mediated removal of the 15 N-terminal AAs is required for the degradation of mHDx-1, a finding that may have therapeutic implications
Alcohol consumption and body composition in a population-based sample of elderly Australian men
Background: Alcohol is calorie dense, and impacts activity, appetite and lipid processing. The aim of this study was to therefore investigate the association between alcohol consumption and components of body composition including bone, fat and lean tissue.Methods: Participants were recruited from a randomly selected, population-based sample of 534 men aged 65 years and older enrolled in the Geelong Osteoporosis Study. Alcohol intake was ascertained using a food frequency questionnaire and the sample categorised as nondrinkers or alcohol users who consumed B2, 3–4 or C5 standard drinks on a usual drinking day. Bone mineral density (BMD), lean body mass and body fat mass were measured using dual energy X-ray absorptiometry; overall adiposity (%body fat), central adiposity (%truncal fat) and body mass index (BMI) were calculated. Bone quality was determined by quantitative heel ultrasound (QUS).Results: There were 90 current non-drinkers (16.9 %), 266 (49.8 %) consumed 1–2 drinks/day, 104 (19.5 %) 3–4 drinks/day and 74 (13.8 %) C5 drinks/day. Those consuming C5 drinks/day had greater BMI (?4.8 %), fat mass index (?20.1 %), waist circumference (?5.0 %), %body fat (?15.2 %) and proportion of trunk fat (?5.3 %) and lower lean mass (-5.0 %) than non-drinkers after adjustment for demographic and lifestyle factors. Furthermore, they were more likely to be obese than non-drinkers according to criteria based on BMI (OR = 2.83, 95 %CI 1.10–7.29) or waist circumference (OR = 3.36, 95 %CI 1.32–8.54). There was an inverse relationship between alcohol consumption and QUS parameters and BMD at the mid forearm site; no differences were detected for BMD at other skeletal sites.Conclusion: Higher alcohol intake was associated with greater total and central adiposity and reduced bone quality.<br /
Parental transfer of the antimicrobial protein LBP/BPI protects Biomphalaria glabrata eggs against oomycete infections
Copyright: © 2013 Baron et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by ANR (ANR-07-BLAN-0214 and ANR-12-EMMA-00O7-01), CNRS and INRA. PvW was financially supported by the BBSRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD
What we talk about when we talk about "global mindset": managerial cognition in multinational corporations
Recent developments in the global economy and in multinational corporations have placed significant emphasis on the cognitive orientations of managers, giving rise to a number of concepts such as âglobal mindsetâ that are presumed to be associated with the effective management of multinational corporations (MNCs). This paper reviews the literature on global mindset and clarifies some of the conceptual confusion surrounding the construct. We identify common themes across writers, suggesting that the majority of studies fall into one of three research perspectives: cultural, strategic, and multidimensional. We also identify two constructs from the social sciences that underlie the perspectives found in the literature: cosmopolitanism and cognitive complexity and use these two constructs to develop an integrative theoretical framework of global mindset. We then provide a critical assessment of the field of global mindset and suggest directions for future theoretical and empirical research
Partial complementation of Sinorhizobium meliloti bacA mutant phenotypes by the Mycobacterium tuberculosis BacA protein
The Sinorhizobium meliloti BacA ABC transporter protein plays an important role in its nodulating symbiosis with the legume alfalfa (Medicago sativa). The Mycobacterium tuberculosis BacA homolog was found to be important for the maintenance of chronic murine infections, yet its in vivo function is unknown. In the legume plant as well as in the mammalian host, bacteria encounter host antimicrobial peptides (AMPs). We found that the M. tuberculosis BacA protein was able to partially complement the symbiotic defect of an S. meliloti BacA-deficient mutant on alfalfa plants and to protect this mutant in vitro from the antimicrobial activity of a synthetic legume peptide, NCR247, and a recombinant human \u3b2-defensin 2 (HBD2). This finding was also confirmed using an M. tuberculosis insertion mutant. Furthermore, M. tuberculosis BacA-mediated protection of the legume symbiont S. meliloti against legume defensins as well as HBD2 is dependent on its attached ATPase domain. In addition, we show that M. tuberculosis BacA mediates peptide uptake of the truncated bovine AMP, Bac71-16. This process required a functional ATPase domain. We therefore suggest that M. tuberculosis BacA is important for the transport of peptides across the cytoplasmic membrane and is part of a complete ABC transporter. Hence, BacA-mediated protection against host AMPs might be important for the maintenance of latent infections
Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors
Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects
Perineal discomfort in prostatic adenocarcinoma
We highlight the risk of missing a high-grade\ud
(Gleason Grade 7/8) transition zone adenocarcinoma\ud
in a patient presenting with perineal discomfort\ud
on sitting
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