Miracle-dz/UniFAR-FTUs huggingface dataset:
K+ channels of stomatal guard cells: bimodal control of the K+ inward-rectifier evoked by auxin.

The influence of the auxins indole-3-acetic acid (IAA) and 1-napthylene acetic acid (NAA) on K+ channels and their control was examined in stomatal guard cells of Vicia faba L. intact guard cells were impaled with multibarrelled microelectrodes to record membrane potentials and to monitor K+ channel currents under voltage clamp during exposures to 0.1-100 microM IAA and NAA. Following impalements, challenge with either IAA or NAA in the presence of 10 mM KCl resulted in the concerted modulation of at least four different currents with distinct kinetic characteristics and concentration dependencies. Equivalent concentrations of benzoic acid were wholly without effect. Most striking, current carried by inward-rectifying K+ channels (IK,in) exhibited a bimodal response to both IAA and NAA which was reversed on washing the auxins from the bathing medium. The steady-state current was augmented 1.3- to 2-fold at concentrations between 0.1 and 10 microM and antagonized at concentrations near 30 microM and above. Auxin agonism of IK,in was time- and voltage-independent. By contrast, IK,in inactivation at the higher auxin concentrations was marked by a voltage-dependence and slowing of the kinetics for current activation. Inactivation of IK,in by the auxins was relieved when cytoplasmic pH (pHi) was clamped near 7.0 in the presence of 30 mM Na(+)-butyrate. In addition to the control of IK,in, current carried by a second class of (outward-rectifying) K+ channels rose in a monotonic and largely voltage-independent manner with auxin concentrations about 10 microM and above, and IAA and NAA also activated an inward-going current with a voltage dependence characteristic of guard cell anion channels. Further changes in background current were consistent with a limited activation of the H(+)-ATPase. Over the concentration range examined, the auxins evoked membrane hyperpolarizations and depolarizations of up to +/- 12-19 mV, depending on the free-running membrane potential prevailing before auxin additions. Prolonging exposures to 100 microM auxin beyond 3-5 min frequently elicited rapid transitions to voltages near EK as well as regenerative action potentials. However, in every case the voltage response was a predictable consequence of auxin action on the K+ channels and, at 100 microM auxin, on the anion current. (ABSTRACT TRUNCATED AT 400 WORDS)
Sequence signals for generation of antigenic peptides by the proteasome: implications for proteasomal cleavage mechanism.

Proteasomal cleavage of proteins is the first step in the processing of most antigenic peptides that are presented to cytotoxic T cells. Still, its specificity and mechanism are not fully understood. To identify preferred sequence signals that are used for generation of antigenic peptides by the proteasome, we performed a rigorous analysis of the residues at the termini and flanking regions of naturally processed peptides eluted from MHC class I molecules. Our results show that both the C terminus (position P1 of the cleavage site) and its immediate flanking position (P1') possess significant signals. The N termini of the peptides show these signals only weakly, consistent with previous findings that antigenic peptides may be cleaved by the proteasome with N-terminal extensions. Nevertheless, we succeed to demonstrate indirectly that the N-terminal cleavage sites contain the same preferred signals at position P1'. This reinforces previous findings regarding the role of the P1' position of a cleavage site in determining the cleavage specificity, in addition to the well-known contribution of position P1. Our results apply to the generation of antigenic peptides and bare direct implications for the mechanism of proteasomal cleavage. We propose a model for proteasomal cleavage mechanism by which both ends of cleaved fragments are determined by the same cleavage signals, involving preferred residues at both P1 and P1' positions of a cleavage site. The compatibility of this model with experimental data on protein degradation products and generation of antigenic peptides is demonstrated.
Prognostic factors for bacterial cultures positive for Propionibacterium acnes and other organisms in a large series of revision shoulder arthroplasties performed for stiffness, pain, or loosening.

BACKGROUND Propionibacterium acnes has been grown on culture in half of the reported cases of chronic infection associated with shoulder arthroplasty. The presence of this organism can be overlooked because its subtle presentation may not suggest the need for culture or because, in contrast to many orthopaedic infections, multiple tissue samples and weeks of culture incubation are often necessary to recover this organism. Surgical decisions regarding implant revision and antibiotic therapy must be made before the results of intraoperative cultures are known. In the present study, we sought clinically relevant prognostic evidence that could help to guide treatment decisions. METHODS We statistically correlated preoperative and intraoperative observations on 193 shoulder arthroplasty revisions that were performed because of pain, loosening, or stiffness with the results of a Propionibacterium acnes-specific culture protocol. Regression models were used to identify factors predictive of a positive culture for Propionibacterium acnes. RESULTS One hundred and eight of the 193 revision arthroplasties were associated with positive cultures; 70% of the positive cultures demonstrated growth of Propionibacterium acnes. The rate of positive cultures per shoulder increased with the number of culture specimens obtained from each shoulder. Fifty-five percent of the positive cultures required observation for more than one week. Male sex, humeral osteolysis, and cloudy fluid were each associated with significant increases of ≥ 600% in the likelihood of obtaining a positive Propionibacterium acnes culture. Humeral loosening, glenoid wear, and membrane formation were associated with significant increases of >300% in the likelihood of obtaining a positive Propionibacterium acnes culture. CONCLUSIONS Preoperative and intraoperative factors can be used to help to predict the risk of a positive culture for Propionibacterium acnes. This evidence is clinically relevant to decisions regarding prosthesis removal or retention and the need for immediate antibiotic therapy at the time of revision shoulder arthroplasty before the culture results become available. LEVEL OF EVIDENCE Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
Pulmonary , gastrointestinal and urogenital pharmacology Effects of Buscopan on human gastrointestinal smooth muscle activity in an ex vivo model : Are there any differences for various sections ?

Hyoscine butylbromide (Buscopan ) is clinically used as an anticholinergic antispasmodic for the treatment of abdominal cramping or visceral pain associated with cramps. However, the spasmolytic efficacy on contractile activity of human gastrointestinal smooth muscle from various sections remains unclear. We aimed to investigate the potentially selective actions of Buscopan on different bowel segments, as well as muscular layers and contractile states. Human smooth muscle tissues of the esophagus, gastric corpus and antrum, jejunum, ileum and colon were obtained. Isometric measurements of circular and longitudinal muscle strips were performed to determine effects of Buscopan on spontaneous activity and induced-contractions by 30 mM KCl, 10 μM bethanechol and electrical field stimulation (EFS). Buscopan concentration-dependently (10 –10 5 M) inhibited smooth muscle activity, particularly in spasticity evoked by bethanechol and EFS but not high Kþ . The inhibiting effects were mainly responsible for the antagonism on muscarinic M2 and M3 receptors (IC50 values: 3.1 10 5 M vs. 0.9 10 5 M). The sensitivity toward Buscopan revealed a tendency of increasing from the esophagus, gastric corpus and antrum to the colon, jejunum and ileum. There was a reversed gradient of mRNA and protein expression of muscarinic M2 and M3 receptors from the blocking effects of Buscopan, which could be ascribed to the fact that a higher concentration of Buscopan was needed to antagonize the spastic contraction to reach the equipotent inhibitory rate in the region with higher muscarinic receptor activity. The findings of different inhibitory effectiveness on various parts of the gastrointestinal tract provide a potential guideline for the clinical application. & 2016 Elsevier B.V. All rights reserved.
Health Evaluation of Volatile Organic Compound (VOC) Emissions from Wood and Wood-Based Materials

Abstract In this study, the authors describe a method for evaluation of material emissions. The study was based on chemical analysis of emissions from 23 materials representing solid wood and wood-based materials commonly used in furniture, interior furnishings and building products in Denmark in the 1990s. The authors used the emission chamber testing method to examine the selected materials with a qualitative screening and quantitative determination of volatile organic compounds. The authors evaluated the toxicological effects of all substances identified with chamber testing. Lowest concentration of interest and standard room concentrations were assessed and the authors calculated an S-value for each wood and wood-based material. The authors identified 144 different chemical substances with the screening analyses and a total of 84 individual substances were quantified with chamber measurements. The irritative effects dominated at low exposure levels; therefore, the lowest concentration of interest and the S-value were based predominantly on these effects. The S-values were very low for solid ash, oak and beech. For solid spruce and pine, the determining substances for size of the S-value were Δ3-carene, α-pinene and limonene. For the surface-treated wood materials, the S-value reflected the emitted substances from the surface treatment.
Proliferation of microglia, but not photoreceptors, in the outer nuclear layer of the rd-1 mouse.

PURPOSE To establish whether photoreceptor apoptosis in the rd-1 mouse is accompanied by cell cycle progression. Studies of cell cycle proteins in other models of neuronal death provide consistent evidence that a repertoire of proliferative markers accompanies apoptosis. METHODS The spatiotemporal progression of photoreceptor loss in rd-1 and control mice at postnatal days (PN)8, -10, -12, -15, and -18 was correlated with markers of G(1)- and S-phase progression. Photoreceptor death was detected by using morphology and terminal dUTP transferase nick end labeling (TUNEL). Cell-cycle-associated markers consisted of bromodeoxyuridine (BrdU) uptake, and immunolabeling for proliferating cell nuclear antigen (PCNA), Ki-67, and cyclin-dependent kinases-2 and -4. The identity of proliferating cells in the outer nuclear layer was established by double immunolabeling with PCNA and either F4/80 or recoverin. RESULTS A population of proliferating cells in the outer nuclear layer accompanies photoreceptor death along a central to peripheral gradient in rd-1 retinas. Double immunolabeling for PCNA and F4/80 readily identified these as microglial cells originating from the inner retina. Cell cycle progression in photoreceptors could not be demonstrated. CONCLUSIONS These findings confirm that in rd-1, a preexisting condition for cell cycle progression does not exist as it does in other neurodegenerative conditions. Therefore, in this model, evidence of photoreceptor cell cycle progression in retinas exposed to neurotrophic factors is likely to result from the therapy itself. In addition, the results confirmed that proliferating microglial cells are intimately associated with the degenerative process in rd-1.
Interaction between Chlamydia pneumoniae seropositivity, inflammation and risk factors for atherosclerosis in patients with severe coronary stenosis

Objective. To investigate whether Chlamydia pneumoniae (Cpn) seropositivity in patients with suspected coronary artery disease (CAD) (n = 81) is associated with increases in markers of inflammation, the severity of coronary atherosclerosis, and traditional risk factors for cardiovascular events. Material and methods. The severity of coronary atherosclerosis was ranked by Gensini score. Inflammation and endothelial dysfunction were evaluated using white blood cell counts and levels of high‐sensitivity C‐reactive protein (hs‐CRP), ferritin, tumour necrosis factor‐α (TNF‐α), interleukins 1β and 6 (IL‐1β, IL‐6), soluble intercellular adhesion molecule‐1 (sICAM‐1), E‐selectin and oxidized LDL (oxLDL), and these were compared between Cpn‐seropositive and seronegative individuals. Results. IgA and IgG Cpn seropositivity were significantly associated with the presence of CAD (p = 0.005) and were independent predictive factors for the severity of coronary atherosclerosis (p = 0.005). Elevated levels of IL‐6 (p = 0.027) and triglyceride (p = 0.038) and low levels of high‐density lipoprotein cholesterol (HDL‐C) (p = 0.038) were significantly predicted by Cpn IgA and IgG seropositivity. Conclusions. Seropositivity for Cpn is a risk factor for patients with significant angiographically documented coronary stenosis. Additionally, Cpn seropositivity was significantly associated with dyslipidemia and elevated IL‐6, known risk factors for CAD. These observations indicate that Cpn infection may be one entry point to the causal or contributory pathways that lead to atherosclerosis and its clinical manifestations.
Financial Markets and Agricultural Commodities: Volatility Impulse Response Analysis

The recent global food crisis has caused an increase in agricultural market volatility, raising important questions on the determinants of this instability. Many studies have analyzed this issue focusing on main factors affecting price volatility, as past volatility and trends, transmission across prices, oil price volatility, export concentration, stock levels and yields (Balcombe, 2010). Existing empirical literature identifies different drivers of volatility; among them, financialization and speculation are by far one of the most important. Indeed, with the introduction of agricultural commodity as an alternative asset class in investment portfolios, and the consequent increasing integration between commodity markets and major financial markets, there has been a growing convergence of risk-adjusted returns on assets class across markets, and an increase in the risk of volatility spillovers from outside to commodity markets due to portfolio rebalancing of institutional investors (Adams and Gluck, 2015). Since the beginning of the new millennium, in fact, there has been a steady flows of financial investments in commodities. As reported by Irwin and Sanders (2011), commodity investments have grown between 2003 and 2009 from 15 billion to 250 billions of dollars. Investments in these markets is made through different financial instruments, driven by different motivations: in futures, both for hedging and speculative purposes, and also in commodity index funds and hedge funds, mainly for portfolio diversification purposes. Increase in investing in the latter two types of investments, however, has been much stronger, compared to the past (Cheng et al. 2014). This process of massive increase in investments in commodities through financial instruments, knows as “commodity finanziarization”, has generated a gradual integration between commodities market and financial markets which, in turn, has risen spillover volatility between markets due to investors’ rebalancing of portfolio’s asset classes.
Metabolic Activation of trans-4-Hydroxy-2-nonenal, a Toxic Product of Membrane Lipid Peroxidation and Inhibitor of P450 Cytochromes*

Lipid peroxidation in biological membranes is known to yield reactive aldehydes, of whichtrans-4-hydroxy-2-nonenal (HNE) is particularly cytotoxic. This laboratory previously reported that purified liver microsomal P450 cytochromes are directly inactivated to varying extents by HNE. We have now found a mechanism-based reaction in which P450s are inactivated by HNE in the presence of molecular oxygen, NADPH, and NADPH-cytochrome P450 reductase. The sensitivity of the various isozymes in the two pathways is different as follows: P450 2B4 and the orthologous 2B1 are inactivated to the greatest extent and 2C3, 1A2, 2E1, and 1A1 to a somewhat lesser extent by the pathway in which HNE undergoes metabolic activation. In contrast, 2B4 and 2B1 are insensitive to direct inactivation, and the reductase is unaffected by HNE by either route. Recent studies on the catalytic activities of the T302A mutant of P450 2B4 have shown that the rate of oxidation of a variety of xenobiotic aldehydes to carboxylic acids is decreased, but the rates of aldehyde deformylation and mechanism-based inactivation of the cytochrome are stimulated over those of the wild-type enzyme (Raner, G. M., Vaz, A. D. N., and Coon, M. J. (1997) Biochemistry36, 4895–4902). Inactivation by those aldehydes apparently occurs by homolytic cleavage of a peroxyhemiacetal intermediate to yield formate and an alkyl radical that reacts with the heme. In sharp contrast, the rate of mechanism-based inactivation by HNE is decreased with the T302A mutant relative to that of the wild-type P450 2B4, and mass spectral analysis of the heme adduct formed shows that deformylation does not occur. We therefore propose that the metabolic activation of HNE involves formation of an acyl carbon radical that leads to the carboxylic acid or alternatively reacts with the heme.
Validity and reliability of the Nursing Minimum Data Set for the Netherlands (NMDSN).

UNLABELLED The Nursing Minimum Data Set for the Netherlands (NMDSN) describes nursing care based on nursing phenomena, interventions and outcomes. The validity and reliability of its data collection has not been tested yet. PURPOSE To report about the discriminative validity and the interrater reliability of the NMDSN. DESIGN Data were collected in an intensive care ward, in a nursing home and in a residential home. The unit of measurement and analysis is the 'patient day'. The analysis for validity consisted of ridits calculations, and their graphical representations. Interrater reliability was measured by percentage agreement and Cohen's kappa. RESULTS Graphs illustrate the differences on most nursing phenomena and interventions as expected beforehand. The percentage agreements for the residential home vary from 60.4 to 100%, and the kappa statistics from -0.09 to 0.85, indicating a poor to almost perfect interrater reliability. CONCLUSION Intensive care patients and patients in the nursing home have more problems and need more nursing interventions compared with general hospital patients, while the patients in the residential home have lesser of both. This illustrates the discriminative validity of the NMDSN. The kappa values for various NMDSN variables are sufficient. A similar test in the general hospital is recommended.
Fas Signal Promotes the Immunosuppressive Function of Regulatory Dendritic Cells via the ERK/β-Catenin Pathway*

Background: Regulatory DCs are important in tolerance maintenance, whereas the mechanisms for maintaining their immunosuppressive function in immune microenvironment remain unclear. Results: Fas signal enhances the immunosuppressive function of splenic stroma-educated regulatory DCs via the ERK/β-catenin pathway. Conclusion: Fas signal, at least from activated T cells, enhances regulatory function of regulatory DCs. Significance: This study provides new mechanistic insight for immune homeostasis. Dendritic cells (DCs) play important roles in the initiation of immune response and also in the maintenance of immune tolerance. Now, many kinds of regulatory DCs with different phenotypes have been identified to suppress immune response and contribute to the control of autoimmune diseases. However, the mechanisms by which regulatory DCs can be regulated to exert the immunosuppressive function in the immune microenvironment remain to be fully investigated. In addition, how T cells, once activated, can feedback affect the function of regulatory DCs during immune response needs to be further identified. We previously identified a unique subset of CD11bhiIalow regulatory DCs, differentiated from mature DCs or hematopoietic stem cells under a stromal microenvironment in spleen and liver, which can negatively regulate immune response in a feedback way. Here, we show that CD11bhiIalow regulatory DCs expressed high level of Fas, and endothelial stromal cell-derived TGF-β could induce high expression of Fas on regulatory DCs via ERK activation. Fas ligation could promote regulatory DCs to inhibit CD4+ T cell proliferation more significantly. Furthermore, Fas ligation preferentially induced regulatory DCs to produce IL-10 and IP-10 via ERK-mediated inactivation of GSK-3 and subsequent up-regulation of β-catenin. Interestingly, activated T cells could promote regulatory DCs to secrete more IL-10 and IP-10 partially through FasL. Therefore, our results demonstrate that Fas signal, at least from the activated T cells, can promote the immunosuppressive function of Fas-expressing regulatory DCs, providing a new manner for the regulatory DCs to regulate adaptive immunity.
Apomorphine in the treatment of Parkinson disease and other movement disorders

Background: Apomorphine, a medication that has been studied intensively over the years, is available in the US as intermittent subcutaneous injections for treatment of ‘off’ motor states in Parkinson disease. Objective: The clinical literature is summarized with particular focus on randomized controlled studies of apomorphine in the treatment of Parkinson disease. Methods: After reviewing the pharmacologic properties of apomorphine, the English language literature is summarized with particular attention on articles resulting from a Medline search of apomorphine and Parkinson disease limited to randomized controlled studies. Other formulations and indications for treatment of movement disorders are also discussed. Results/conclusion: Subcutaneous apomorphine is well tolerated when co-administered with trimethobenzamide or domperidone premedication. It has a unique efficacy as a ‘rescue’ medication owing to its rapid onset of action. Subcutaneous infusion, although not an approved route of administration in the US, provides more continuous dopaminergic stimulation and, therefore, ameliorates dyskinesia and motor fluctuations.