Miracle-dz/UniFAR-FTUs huggingface dataset:
Mas-related Gene X2 (MrgX2) Is a Novel G Protein-coupled Receptor for the Antimicrobial Peptide LL-37 in Human Mast Cells

Background: Antimicrobial peptide LL-37 activates leukocytes, mast cells, and endothelial cells. Results: LL-37 causes chemotaxis, degranulation, and chemokine production in human mast cells expressing MrgX2, but it does not induce receptor desensitization. Conclusion: MrgX2 is a novel receptor for LL-37 in human mast cells, and this receptor is resistant to regulation. Significance: This study has important implications for innate immunity and inflammation. Human LL-37 is a multifunctional antimicrobial peptide that promotes inflammation, angiogenesis, wound healing, and tumor metastasis. Most effects of LL-37 are mediated via the activation of the cell surface G protein-coupled receptor FPR2 on leukocytes and endothelial cells. Although LL-37 induces chemotaxis, degranulation, and chemokine production in mast cells, the receptor involved and the mechanism of its regulation remain unknown. MrgX2 is a member of Mas-related genes that is primarily expressed in human dorsal root ganglia and mast cells. We found that a human mast cell line LAD2 and CD34+ cell-derived primary mast cells, which natively express MrgX2, responded to LL-37 for sustained Ca2+ mobilization and substantial degranulation. However, an immature human mast cell line, HMC-1, that lacks functional MrgX2 did not respond to LL-37. shRNA-mediated knockdown of MrgX2 in LAD2 mast cell line and primary CD34+ cell-derived mast cells caused a substantial reduction in LL-37-induced degranulation. Furthermore, mast cell lines stably expressing MrgX2 responded to LL-37 for chemotaxis, degranulation, and CCL4 production. Surprisingly, MrgX2 was resistant to LL-37-induced phosphorylation, desensitization, and internalization. In addition, shRNA-mediated knockdown of the G protein-coupled receptor kinases (GRK2 and GRK3) had no effect on LL-37-induced mast cell degranulation. This study identified MrgX2 as a novel G protein-coupled receptor for the antibacterial peptide LL-37 and demonstrated that unlike most G protein-coupled receptors it is resistant to agonist-induced receptor phosphorylation, desensitization, and internalization.
Biochemical and Proteomic Characterization of Alkaptonuric Chondrocytes

Alkaptonuria (AKU) is a rare genetic disease associated with the accumulation of homogentisic acid (HGA) and its oxidized/polymerized products which leads to the deposition of melanin‐like pigments (ochronosis) in connective tissues. Although numerous case reports have described ochronosis in joints, little is known on the molecular mechanisms leading to such a phenomenon. For this reason, we characterized biochemically chondrocytes isolated from the ochronotic cartilage of AKU patients. Based on the macroscopic appearance of the ochronotic cartilage, two sub‐populations were identified: cells coming from the black portion of the cartilage were referred to as “black” AKU chondrocytes, while those coming from the white portion were referred to as “white” AKU chondrocytes. Notably, both AKU chondrocytic types were characterized by increased apoptosis, NO release, and levels of pro‐inflammatory cytokines. Transmission electron microscopy also revealed that intracellular ochronotic pigment deposition was common to both “white” and “black” AKU cells. We then undertook a proteomic and redox‐proteomic analysis of AKU chondrocytes which revealed profound alterations in the levels of proteins involved in cell defence, protein folding, and cell organization. An increased post‐translational oxidation of proteins, which also involved high molecular weight protein aggregates, was found to be particularly relevant in “black” AKU chondrocytes. J. Cell. Physiol. 227: 3333–3343, 2012. © 2011 Wiley Periodicals, Inc.
Bureaucracy and Democracy

The terms bureaucracy and democracy are usually thought of, both in the academic and the popular literature, as antithetical approaches to providing governance for a society (see EtzioniHalevey, 1983). On the one hand public bureaucracies are typically conceptualized as necessary for the effective administration of public programs, but as being legalistic and largely indifferent to the wishes and demands of individual citizens. Bureaucracies also tend to be associated with hierarchical and even authoritarian forms of governing, even though at least part of the logic for institutionalizing the bureaucratic form of governing was to ensure equal treatment of citizens, and to provide clients with records and justifications for the decisions being made about them within the public sector.
Grape Polyphenols Prevent Fructose-Induced Oxidative Stress and Insulin Resistance in First-Degree Relatives of Type 2 Diabetic Patients

OBJECTIVE To assess the clinical efficacy of nutritional amounts of grape polyphenols (PPs) in counteracting the metabolic alterations of high-fructose diet, including oxidative stress and insulin resistance (IR), in healthy volunteers with high metabolic risk. RESEARCH DESIGN AND METHODS Thirty-eight healthy overweight/obese first-degree relatives of type 2 diabetic patients (18 men and 20 women) were randomized in a double-blind controlled trial between a grape PP (2 g/day) and a placebo (PCB) group. Subjects were investigated at baseline and after 8 and 9 weeks of supplementation, the last 6 days of which they all received 3 g/kg fat-free mass/day of fructose. The primary end point was the protective effect of grape PPs on fructose-induced IR. RESULTS In the PCB group, fructose induced 1) a 20% decrease in hepatic insulin sensitivity index (P < 0.05) and an 11% decrease in glucose infusion rate (P < 0.05) as evaluated during a two-step hyperinsulinemic-euglycemic clamp, 2) an increase in systemic (urinary F2-isoprostanes) and muscle (thiobarbituric acid–reactive substances and protein carbonylation) oxidative stress (P < 0.05), and 3) a downregulation of mitochondrial genes and decreased mitochondrial respiration (P < 0.05). All the deleterious effects of fructose were fully blunted by grape PP supplementation. Antioxidative defenses, inflammatory markers, and main adipokines were affected neither by fructose nor by grape PPs. CONCLUSIONS A natural mixture of grape PPs at nutritional doses efficiently prevents fructose-induced oxidative stress and IR. The current interest in grape PP ingredients and products by the global food and nutrition industries could well make them a stepping-stone of preventive nutrition.
Analysis of Analytical Models Developed under the Uniaxial Strain Condition for Predicting Coal Permeability during Primary Depletion

The stress-dependent permeability of coal during coalbed methane production has been extensively studied both experimentally and theoretically. However, how permeability changes as a function of stress variation is somewhat unclear to date, and currently used analytical models fail to accurately predict permeability evolution with gas depletion. Considering that the role played by changes in in situ stress in permeability evolution is critical, a comprehensive theoretical study was first conducted, through which it was found that coal permeability is determined by mean effective stress. Moreover, the influence of matrix shrinkage on cleat deformation and then coal permeability was overestimated by currently used models, leading to inaccuracy of the predicted permeability. By taking both mean effective stress and the influence of matrix shrinkage on cleat deformation into account, a new permeability model was developed under the uniaxial strain condition in order to precisely estimate permeability evolution during gas depletion. An in-depth investigation and comparison among four commonly-used permeability models, the Palmer and Mansoori (PM and the accuracy of the values of initial cleat porosity and cleat compressibility, the bridges connecting permeability, and those two effects in analytical models, is extremely critical to permeability estimations. This study can shed light on improving the accuracy of analytical coal permeability models and the prediction of gas production.
Genomic Determinants of Cardiovirulence in Coxsackievirus B3 Clinical Isolates: Localization to the 5′ Nontranslated Region

Coxsackievirus B3 (CVB3) infections can cause myocarditis in humans and are implicated in the pathogenesis of dilated cardiomyopathy. The natural genetic determinants of cardiovirulence for CVB3 have not been identified, although using strains engineered in the laboratory, cardiovirulence determinants have been identified in the CVB3 5′ nontranslated region (5′NTR) and capsid. The myocarditic phenotypes of two CVB3 clinical isolates were determined using an established murine model of inflammatory heart disease. The 5′NTRs and capsid proteins of the noncardiovirulent CVB3/CO strain and cardiovirulent CVB3/AS strain were examined to determine their influence on the cardiovirulence phenotype. Six intratypic chimeric viruses were constructed in which 5′NTR and capsid sequences of the infectious cDNA copy of the cardiovirulent CVB3/20 genome were replaced by homologous sequences from CVB3/CO or CVB3/AS. Chimeric strains were tested for cardiovirulence by inoculation of C3H/HeJ mice. Sections of hearts removed at 10 days postinoculation were examined for evidence of myocarditis by light microscopy and assayed for the presence of virus. Replacement of the CVB3/20 capsid coding region by that from the homologous region of CVB3/CO resulted in no change in the cardiovirulent CVB3/20 phenotype, with virus recoverable from the heart at 10 days postinoculation. However, recombinant virus containing the CVB3/CO 5′NTR alone or the 5′NTR and capsid sequences together were not myocarditic, and infectious virus was not recovered from the myocardium. Chimeric viruses containing the CVB3/AS 5′NTR alone, capsid sequence alone, or both together preserved the myocarditic phenotype. These data support the 5′NTR as the primary site in the determination of the natural cardiovirulence phenotype of CVB3.
Does Knowledge of Predictors of Recovery and Nonrecovery Assist Outcomes After Whiplash Injury?

Study Design. Nonsystematic review. Objective. Review of prognostic indicators for outcome after whiplash injury and the implications for clinical practice and future research. Summary of Background Data. The capacity to predict outcome after whiplash injury is important to guide the management of the condition. There have now been numerous cohort studies and several systematic reviews of prognosis. It is not clear if the current knowledge of prognostic indicators is useful for clinical practice and to improve outcomes after injury. Methods. Nonsystematic review of research investigating the prediction of chronic pain/disability and psychological outcomes after whiplash injury. Results. There remains considerable uncertainty surrounding the identification of clear prognostic indicators after whiplash injury. All systematic reviews note the moderate or lower quality if primary cohort studies and only one systematic review performed meta-analysis. There have been no studies attempting validation of predictive models. At the present time, the knowledge base stands that higher initial pain levels are the most consistent predictor of poor functional recovery. Additional promising factors include physical factors of cold hyperalgesia and loss of neck range of movement, although the latter is inconsistent. Psychological factors of pain catastrophizing, symptoms of post-traumatic stress and recovery perceptions are also prognostic of poor recovery and the presence of depressed mood is inconsistent. Further research is needed to validate predictive models, investigate interactions between factors, and to determine whether modification of predictors is possible and leads to improved outcomes. Conclusion. The understanding of factors predictive of poor recovery after whiplash injury is evolving. Although more research is required to validate predictive models, some factors show consistent predictive capacity and could be used in clinical practice as potential indicators of poor recovery. It is not known if the specific targeting of modifiable prognostic indicators can be achieved or will lead to improved outcomes.
Who Leaves and Who Stays? A Review and Statistical Meta-Analysis of Hurricane Evacuation Studies

This statistical meta-analysis (SMA) examined 38 studies involving actual responses to hurricane warnings and 11 studies involving expected responses to hypothetical hurricane scenarios conducted since 1991. The results indicate official warnings, mobile home residence, risk area residence, observations of environmental (storm conditions) and social (other people’s behavior) cues, and expectations of severe personal impacts, all have consistently significant effects on household evacuation. Other variables—especially demographic variables—have weaker effects on evacuation, perhaps via indirect effects. Finally, the SMA also indicates that the effect sizes from actual hurricane evacuation studies are similar to those from studies of hypothetical hurricane scenarios for 10 of 17 variables that were examined. These results can be used to guide the design of hurricane evacuation transportation analyses and emergency managers’ warning programs. They also suggest that laboratory and Internet experiments could be used to examine people’s cognitive processing of different types of hurricane warning messages.
TEACHING VOCABULARY THROUGH SEMANTIC MAPPING AS A PRE-READING ACTIVITY ACROSS GENDERS

This study has examined the effect of semantic mapping on learning vocabulary across genders. The researchers selected 120 intermediate students after the administration of a standard proficiency test. A vocabulary test was also used to measure the students’ vocabulary knowledge. The experimental group received semantic mapping in the pre-reading stage, but the control group did not receive this treatment. The results of the study, based on statistical analysis of ANCOVA, indicated that the experimental group outperformed the control group in vocabulary learning. As for the gender differences, the results indicated no significant difference between males and females. It can be suggested that semantic mapping can be used as an efficient methodology for teaching vocabulary, a technique which is equally effective for male and female EFL
The PsaD Subunit of Photosystem I (Mutations in the Basic Domain Reduce the Level of PsaD in the Membranes)

The PsaD subunit of photosystem I (PSI) is a peripheral protein that provides a docking site for ferredoxin and interacts with the PsaB, PsaC, and PsaL subunits of PSI. We used site-directed mutagenesis to determine the function of a basic region in PsaD of the cyanobacterium Synechocystis sp. PCC 6803. We generated five mutant strains in which one or more charged residues were altered. Western blotting showed that replacement of lysine (Lys)-74 with glutamine or glutamic acid led to a substantial decrease in the level of PsaD in the membranes. The mutant PSI complexes showed reduced NADP+ photoreduction activity mediated by ferredoxin; the decrease in activity correlated with the reduced level of PsaD. Using protein synthesis inhibitors we showed that the degradation rates of the mutant and wild-type PsaD were similar, indicating a defect in the assembly of the mutant protein. Treatment of the mutant PSI complexes with a different concentration of Nal showed that the mutations decreased affinity between PsaD and the transmembrane components of PSI. With glutaraldehyde, the mutant and wild-type PsaD proteins could be cross-linked with PsaC, but the PsaD-PsaL cross-linked product was reduced drastically when arginine-72, Lys-74, and Lys-76 were mutated simultaneously. These studies demonstrate that the basic residues in the central region of PsaD, especially Lys-74, are crucial in the assembly of PsaD into the PSI complex.
The Impact of Starting Time of Treadmill Exercise on c-Fos Expression in the Hippocampus of Intracerebral Hemorrhagic Rats

The transcriptional factor c-Fos has been used as a marker of neuronal activity. Brain injury is known to induce c-Fos expression in the neurons. Intracerebral hemorrhage (ICH) is one of the most devastating types of stroke. In the present study, we investigated the impact of starting time of treadmill exercise on ICH-induced c-Fos expression in the hippocampus of rats. ICH was induced by injection of collagenase into the striatum using a stereotaxic instrument. The rats in the pre-exercise group were scheduled to run on a treadmill before ICH induction for 2 weeks. The rats in the post-exercise group were scheduled to run on a treadmill after ICH induction for 2 weeks. The rats in the pre- and post-exercise group were scheduled to run on a treadmill exercise starting 2 weeks before ICH induction until 2 weeks after ICH induction. The present results showed that c-Fos expression in the several hippocampal regions were significantly increased following ICH in rats. Treadmill exercise showed the suppressive effect on the ICH-induced c-Fos expression in the hippocampal regions. The suppression on c-Fos expression by treadmill exercise was highest in the rats of the pre- and post-exercise group. The present results suggest that treadmill exercise starting before the ICH insult and continuing after ICH insult has a potent protective effect on ICH-induced brain damage, possibly by modulating c-Fos expression in the hippocampal regions. (Korean J Str Res 2009;17:155∼161)
Oncogenic Function of DACT1 in Colon Cancer through the Regulation of β-catenin

The Wnt/β-catenin signaling pathway plays important roles in the progression of colon cancer. DACT1 has been identified as a modulator of Wnt signaling through its interaction with Dishevelled (Dvl), a central mediator of both the canonical and noncanonical Wnt pathways. However, the functions of DACT1 in the WNT/β-catenin signaling pathway remain unclear. Here, we present evidence that DACT1 is an important positive regulator in colon cancer through regulating the stability and sublocation of β-catenin. We have shown that DACT1 promotes cancer cell proliferation in vitro and tumor growth in vivo and enhances the migratory and invasive potential of colon cancer cells. Furthermore, the higher expression of DACT1 not only increases the nuclear and cytoplasmic fractions of β-catenin, but also increases its membrane-associated fraction. The overexpression of DACT1 leads to the increased accumulation of nonphosphorylated β-catenin in the cytoplasm and particularly in the nuclei. We have demonstrated that DACT1 interacts with GSK-3β and β-catenin. DACT1 stabilizes β-catenin via DACT1-induced effects on GSK-3β and directly interacts with β-catenin proteins. The level of phosphorylated GSK-3β at Ser9 is significantly increased following the elevated expression of DACT1. DACT1 mediates the subcellular localization of β-catenin via increasing the level of phosphorylated GSK-3β at Ser9 to inhibit the activity of GSK-3β. Taken together, our study identifies DACT1 as an important positive regulator in colon cancer and suggests a potential strategy for the therapeutic control of the β-catenin-dependent pathway.
Novel Type of Staphylococcal Cassette Chromosome mec Identified in Community-Acquired Methicillin-Resistant Staphylococcus aureus Strains

ABSTRACT We identified a new type of staphylococcal cassette chromosome mec (SCCmec) from two community-acquired methicillin-resistant Staphylococcus aureus (MRSA) strains. The novel element, designated type IV SCCmec, had a unique combination of the class B mec gene complex and the type 2 ccr gene complex and was much smaller in size (21 to 24 kb) than previously identified SCCmec elements of hospital-acquired MRSA. Consistent with the strains' susceptibilities to various non-β-lactam antibiotics, the type IV SCCmec was devoid of any antibiotic resistance genes other than the mecA gene.
Heat balance and cumulative heat storage during intermittent bouts of exercise.

PURPOSE The aim of this study was to investigate heat balance during thermal transients caused by successive exercise bouts. Whole-body heat loss (H x L) and changes in body heat content (Delta Hb) were measured using simultaneous direct whole-body and indirect calorimetry. METHODS Ten participants performed three successive bouts of 30-min cycling (Ex1, Ex2, and Ex3) at a constant rate of heat production of approximately 500 W, each separated by 15-min rest (R1, R2, and R3) at 30 degrees C. RESULTS Despite identical rates of heat production during exercise, the time constant (tau) of the exponential increase in H x L was greater in Ex1 (tau = 12.3 +/- 2.3 min) relative to both Ex2 (tau = 7.2 +/- 1.6 min) and Ex3 (tau = 7.1 +/- 1.6 min) (P < 0.05). Delta Hb during Ex1 (256 +/- 76 kJ) was greater than during Ex2 (135 +/- 60 kJ) and Ex3 (124 +/- 78 kJ) (P < 0.05). During recovery bouts, heat production was the same, and the tau of the exponential decrease in H L was the same during R1 (tau = 6.5 +/- 1.1 min), R2 (tau = 5.9 +/- 1.3 min), and R3 (tau = 6.0 +/- 1.2 min). Delta Hb during R1 (-82 +/- 48 kJ), R2 (-91 +/- 48 kJ), and R3 (-88 +/- 54 kJ) were the same. The cumulative Delta Hb was consequently greater at the end of Ex2 and Ex3 relative to the end of Ex1 (P < 0.05). Likewise, cumulative Delta Hb was greater at the end of R2 and R3 relative to R1 (P < 0.05). CONCLUSION The proportional decrease in the amount of heat stored in the successive exercise bouts is the result of an enhanced rate of heat dissipation during exercise and not due to a higher rate of heat loss in the recovery period. Despite a greater thermal drive with repeated exercise, the decline in the rate of total heat loss during successive recovery bouts was the same.
Sexual Racism: Intimacy as a Matter of Justice

Taking seriously the idea that the “the personal is the political,” I argue that intimacy, the opportunity to be a part of a reciprocal romantic relationship, is a matter of justice. We ought to care about the distribution of this opportunity. Justice demands as much. What has gone largely undertheorized is racial discrimination that takes place in the intimate sphere. Prioritizing individuals as romantic partners in a way that reinforces ideas of racial hierarchy or stereotypes, what I call “sexual racism,” is unjust. Sexual racism is based on nothing more than a kind of blatant, even ugly (pun intended) kind of racial favoritism or disgust. These are not benign sexual preferences but problematic conditions that structure the very formation of romantic relationships. Renegotiating the boundaries of the intimate sphere, I argue that online dating websites ought to be sites of public concern.