Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteolytic processing of SDF-1α reveals a change in receptor specificity mediating HIV-associated neurodegeneration

Proteolytic cleavage of constitutively expressed proteins can generate peptides with novel bioactive properties. Matrix metalloproteinase (MMP)-2 cleaves the 4 amino-terminal residues of the chemokine, stromal cell-derived factor (SDF)-1α, yielding a highly neurotoxic molecule, SDF(5-67), which fails to bind to its cognate receptor, CXCR4. Herein, we detected SDF(5-67) in brain monocytoid cells of HIV-infected persons, particularly in those with HIV-associated dementia. SDF(5-67) activated cell type-specific expression of proinflammatory genes including IL-1β, TNFα, indoleamine 2′,3′-dioxygenase (IDO), and IL-10 in both astrocytic and monocytoid cells (P < 0.05). Unlike SDF-1α, SDF(5-67) caused neuronal membrane perturbations with ensuing neurotoxicity and apoptosis (P < 0.05) through engagement of an inducible receptor. CXCR3 antagonists and siRNA-mediated knockdown of CXCR3 inhibited SDF(5-67)-stimulated neurophysiological changes, neuronal death, and neuroimmune activation (P < 0.05). Moreover SDF(5-67) bound directly to CXCR3 in a competitive manner, mediated by its amino terminus. In vivo neuroinflammation, neuronal loss, and neurobehavioral abnormalities caused by SDF(5-67) (P < 0.05) were prevented by a CXCR3 antagonist. These studies reveal additive neuropathogenic properties exerted by a proteolytically cleaved chemokine as consequences of a change in receptor specificity, culminating in neurodegeneration.
Obstructive sleep apnea: Should all children with Down syndrome be tested?

OBJECTIVES To determine the incidence of obstructive sleep apnea syndrome in children aged 2 to 4 years with Down syndrome and to determine parents' ability to predict sleep abnormalities in this patient population. DESIGN Prospective cohort study. SETTING Tertiary care pediatric referral center. PATIENTS Sixty-five children participating in a 5-year longitudinal study in which the otolaryngologic problems seen in Down syndrome were evaluated. Fifty-six completed overnight polysomnography (PSG) between 4 and 63 months of age (mean age, 42 months). INTERVENTIONS Overnight PSG was performed. Parents also completed a questionnaire regarding their impressions of their child's sleep patterns before PSG. MAIN OUTCOME MEASURES Polysomnograms were classified as abnormal if the obstructive index was greater than 1, if the carbon dioxide level was greater than 45 mm Hg for more than two thirds of the study or greater than 50 mm Hg for more than 10% of the study, and/or if there was unexpected hypoxemia less than 92% during sleep or repeated intermittent desaturations less than 90%. We also identified a group of children whose PSGs findings were normal except for an arousal index greater than 10 and were associated with increased work of breathing. RESULTS The PSGs revealed that 57% of the children had abnormal results and evidence of obstructive sleep apnea syndrome. If we also include an elevated arousal index, 80% of the PSGs had abnormal results. Sixty-nine percent of parents reported no sleep problems in their children, but in this group, 54% of PSGs had abnormal results. Of the parents who reported sleep problems in their children, only 36% had abnormal sleep study results. CONCLUSION Because of the high incidence of obstructive sleep apnea syndrome in young children with Down syndrome, and the poor correlation between parental impressions of sleep problems and PSG results, baseline PSG is recommended in all children with Down syndrome at age 3 to 4 years.
A Life Cycle Model of Continuous Clinical Process Innovation

EXECUTIVE SUMMARY The changing healthcare environment has created a sense of urgency for continuous innovation in clinical care processes. Managers and clinicians are investing unprecedented funds and energy in the development of various clinical process innovations (CPI) such as clinical pathways, electronic workstations, and various forms of information technology. While increasing attention has been paid to the development of such initiatives, our understanding of how best to disseminate and ensure their use is limited. In this first of two articles dealing with the dissemination and use of CPI in integrated delivery systems, we present a “life cycle” model of the dissemination process and suggest opportunities for managing CPI. The management of CPI requires more than just an understanding of the factors that may facilitate or impede its implementation and use. Managers require an understanding of the actual process so that they can assess the specific implementation stage at which the organization is presently operating, and design appropriate interventions that can affect the process. A furture article will identify the factors that facilitate and inhibit the process and suggest some intervention strategies.
Identification of a Moraxella catarrhalis Outer Membrane Protein Exhibiting Both Adhesin and Lipolytic Activities

ABSTRACT The UspA1 and Hag proteins have previously been shown to be involved in the ability of the Moraxella catarrhalis wild-type strain O35E to bind to human Chang and A549 cells, respectively. In an effort to identify novel adhesins, we generated a plasmid library of M. catarrhalis DNA fragments, which was introduced into a nonadherent Escherichia coli strain. Recombinant E. coli bacteria were subsequently enriched for clones that gained the ability to bind to Chang and A549 cells, yielding the plasmid pELFOS190. Transposon mutagenesis of this plasmid identified the potential adhesin gene mcaP (M. catarrhalis adherence protein). Sequence analysis revealed that McaP is related to autotransporter proteins and has substantial similarity with the GDSL family of lipolytic enzymes, particularly the Moraxella bovis phospholipase B. Expression of the mcaP gene product by E. coli increased adherence to Chang, A549, and 16HBE14o− polarized human bronchial cells 50- to 100-fold. Spectrophotometric assays with p-nitrophenol derivatives also demonstrated that McaP is an esterase. Furthermore, thin-layer chromatography revealed that McaP cleaves both phosphatidylcholine and lysophosphatidylcholine. McaP releases fatty acids and glycerophosphorylcholine upon cleavage of phosphatidylcholine, thus exhibiting phospholipase B activity. The construction and characterization of isogenic M. catarrhalis O35E mutants demonstrated that the lack of McaP expression abolishes esterase activity and considerably decreases adherence to several human cell lines.
CB1 cannabinoid receptor-mediated increases in cyclic AMP accumulation are correlated with reduced Gi/o function

Abstract Background: CB1 cannabinoid receptors (CB1Rs) stimulate Gi/o-dependent signaling pathways. CB1R-mediated cAMP increases were proposed to result from Gs activation, but CB1R-stimulated GTPγS binding to Gs has not heretofore been investigated. Methods: Three models of CB1R-stimulated cAMP production were tested: pertussis toxin disruption of Gi/o in N18TG2 cells; L341A/A342L-CB1R expressed in Chinese hamster ovary (CHO) cells; and CB1 and D2 dopamine receptors endogenously co-expressed in MN9D cells. cAMP was assayed by [3H]cAMP binding competition. G protein activation was assayed by the antibody-targeted scintillation proximity assay. Results: In L341A/A342L-CB1-CHO cells, cannabinoid agonists significantly stimulated cAMP accumulation over vehicle; (–)-3-[2-hydroxyl-4-(1,1-dimethylheptyl)phenyl]-4-[3-hydroxyl propyl] cyclohexan-1-ol (CP55940)-stimulated [35S]GTPγS binding to Gi1/2/3 was reversed, whereas binding to Gs was not different from CB1R. In MN9D cells, CB1 agonist HU210 or D2 agonist quinpirole alone inhibited forskolin-activated cAMP accumulation, whereas HU210 plus quinpirole increased cAMP accumulation above basal. HU210 alone stimulated [35S]GTPγS binding to Gi1/2/3, whereas co-stimulation with quinpirole reversed HU210-stimulated [35S]GTPγS binding to Gi1/2/3. Conclusions: CB1R couples to Gs but with low efficacy compared to Gi/o. The L341A/A342L mutation in CB1R reversed CP55940 activation of Gi to an inhibition, but had no effect on Gs. Combined CB1 plus D2 agonists in MN9D cells converted the CB1 agonist-mediated activation of Gi to inhibition of Gi. In these models, the CB1 agonist response was converted to an inverse agonist response at Gi activation. Cannabinoid agonist-stimulated cAMP accumulation can be best explained as reduced activation of Gi, thereby attenuating the tonic inhibitory influence of Gi on the major isoforms of adenylyl cyclase.
TAA1-Regulated Local Auxin Biosynthesis in the Root-Apex Transition Zone Mediates the Aluminum-Induced Inhibition of Root Growth in Arabidopsis[C][W][OPEN]

Al toxicity is a major constraint to crop production in acidic soil worldwide. This study elucidates how Al may regulate root growth inhibition through mediating local auxin biosynthesis and signaling in the root-apex transition zone and provides insights into how environmental cues affect root growth plasticity through influencing local auxin biosynthesis and signaling. The transition zone (TZ) of the root apex is the perception site of Al toxicity. Here, we show that exposure of Arabidopsis thaliana roots to Al induces a localized enhancement of auxin signaling in the root-apex TZ that is dependent on TAA1, which encodes a Trp aminotransferase and regulates auxin biosynthesis. TAA1 is specifically upregulated in the root-apex TZ in response to Al treatment, thus mediating local auxin biosynthesis and inhibition of root growth. The TAA1-regulated local auxin biosynthesis in the root-apex TZ in response to Al stress is dependent on ethylene, as revealed by manipulating ethylene homeostasis via the precursor of ethylene biosynthesis 1-aminocyclopropane-1-carboxylic acid, the inhibitor of ethylene biosynthesis aminoethoxyvinylglycine, or mutant analysis. In response to Al stress, ethylene signaling locally upregulates TAA1 expression and thus auxin responses in the TZ and results in auxin-regulated root growth inhibition through a number of auxin response factors (ARFs). In particular, ARF10 and ARF16 are important in the regulation of cell wall modification–related genes. Our study suggests a mechanism underlying how environmental cues affect root growth plasticity through influencing local auxin biosynthesis and signaling.
Studying the Integration of Damascus Securities Exchange with Selected Stock Markets

This study aims to examine the integration of Damascus Securities Exchange (DSE) with some Arab and international financial markets, which are (Jordan, Iraq, Germany, and France). The study used monthly data of each stock market index during the period 2010-2015. To achieve the objectives of the study, five tests are used. Namely, Unit Root Test, Johansen Cointegration Test, Vector Error Model, Vector Autoregressive Models (Impulse Response Function and Variance Decomposition) and finally Granger Causality. The findings show a long-run relationship between DSE and other studied markets. Consequently, markets move together in a long-term. No evidence is found about short-term relationship. In addition, DSE seems to respond slowly to changes in the other markets; as a result, shocks on these markets do not explain the variation on DSE index. Finally, Granger Causality test reveals absence of causality among these markets. Thus, investors can benefit from diversifying their portfolios in short-term, but not in the long-term.
Involvement of an Alkane Hydroxylase System of Gordonia sp. Strain SoCg in Degradation of Solid n-Alkanes

ABSTRACT Enzymes involved in oxidation of long-chain n-alkanes are still not well known, especially those in Gram-positive bacteria. This work describes the alkane degradation system of the n-alkane degrader actinobacterium Gordonia sp. strain SoCg, which is able to grow on n-alkanes from dodecane (C12) to hexatriacontane (C36) as the sole C source. SoCg harbors in its chromosome a single alk locus carrying six open reading frames (ORFs), which shows 78 to 79% identity with the alkane hydroxylase (AH)-encoding systems of other alkane-degrading actinobacteria. Quantitative reverse transcription-PCR showed that the genes encoding AlkB (alkane 1-monooxygenase), RubA3 (rubredoxin), RubA4 (rubredoxin), and RubB (rubredoxin reductase) were induced by both n-hexadecane and n-triacontane, which were chosen as representative long-chain liquid and solid n-alkane molecules, respectively. Biotransformation of n-hexadecane into the corresponding 1-hexadecanol was detected by solid-phase microextraction coupled with gas chromatography-mass spectrometry (SPME/GC-MS) analysis. The Gordonia SoCg alkB was heterologously expressed in Escherichia coli BL21 and in Streptomyces coelicolor M145, and both hosts acquired the ability to transform n-hexadecane into 1-hexadecanol, but the corresponding long-chain alcohol was never detected on n-triacontane. However, the recombinant S. coelicolor M145-AH, expressing the Gordonia alkB gene, was able to grow on n-triacontane as the sole C source. A SoCg alkB disruption mutant that is completely unable to grow on n-triacontane was obtained, demonstrating the role of an AlkB-type AH system in degradation of solid n-alkanes.
Prevalence of attempting weight loss and strategies for controlling weight.

CONTEXT Overweight and obesity are increasing in the United States. Changes in diet and physical activity are important for weight control. OBJECTIVES To examine the prevalence of attempting to lose or to maintain weight and to describe weight control strategies among US adults. DESIGN The Behavioral Risk Factor Surveillance System, a random-digit telephone survey conducted in 1996 by state health departments. Setting The 49 states (and the District of Columbia) that participated in the survey. PARTICIPANTS Adults aged 18 years and older (N = 107 804). MAIN OUTCOME MEASURES Reported current weights and goal weights, prevalence of weight loss or maintenance attempts, and strategies used to control weight (eating fewer calories, eating less fat, or using physical activity) by population subgroup. RESULTS The prevalence of attempting to lose and maintain weight was 28.8% and 35.1 % among men and 43.6% and 34.4% among women, respectively. Among those attempting to lose weight, a common strategy was to consume less fat but not fewer calories (34.9% of men and 40.0% of women); only 21.5% of men and 19.4% of women reported using the recommended combination of eating fewer calories and engaging in at least 150 minutes of leisure-time physical activity per week. Among men trying to lose weight, the median weight was 90.4 kg with a goal weight of 81.4 kg. Among women, the median weight was 70.3 kg with a goal weight of 59.0 kg. CONCLUSIONS Weight loss and weight maintenance are common concerns for US men and women. Most persons trying to lose weight are not using the recommended combination of reducing calorie intake and engaging in leisure-time physical activity 150 minutes or more per week.
French Complementary Currency Systems : Exploring Contributions to Promote Social Currency in Argentina

textabstractSince 2010 there has been an increasing proliferation of complementary currency systems (CCS) in France and other countries of Europe facing the Euro crisis. These CCS are shaped by the interest in a civic reclaim of the currency and the aspiration for a full-citizenship in which two principles stand out: participation and autonomy. The aims resonated with the expectations of the community currencies in Argentina between 1995 and 2005. This research studied the French CCS with the goal of rethinking the dynamics of social currencies in present Argentina. The study presents a brief overview of the present CCS in Argentina and France, on which fieldwork was done between April and May 2013. Despite differences in the macroeconomic structures and context, the present Argentine CCS may find inspiration in the French experiences, namely the inclusion of various state and financial sector organisations and the strong civic dynamics of the 'consom-acteur'.
The impact of the metabolic syndrome on the patients with acute coronary syndrome.

BACKGROUND The subjects with metabolic syndrome are an increased risk for the development of diabetes mellitus and cardiovascular disease as well as an increased mortality for cardiovascular disease in all causes. The prevalence of the metabolic syndrome after acute coronary syndrome has not been studied yet. We aimed to evaluate the prevalence of the metabolic syndrome and to evaluate its cardiovascular risk potential using the National Cholesterol Education Program's Adult Treatment Panel III (NCEP-ATP III) criteria. METHODS We performed a cross sectional study in 256 patients with acute coronary syndrome. The definition of the metabolic syndrome was based on NCEP-ATP III criteria. The cardiovascular risk factors that define the metabolic syndrome and their correlation with the cardiovascular risk were evaluated by descriptive and interferential statistical methods. RESULTS The prevalence of metabolic syndrome was 47.26%, as assessed by criteria of the NCEP-ATP III. The presence of the metabolic syndrome has been positively correlated with the cardiovascular risk (OR 1.29; 95% CI, 1.05-1.54, p=0.047). The cardiovascular risk has significantly correlated with the increasing of the components number that defines the metabolic syndrome. Among the components of the metabolic syndrome, HDL-Cholesterol was the most significantly correlated with the cardiovascular risk in the patients with acute coronary syndrome (OR 3.60; 95% CI 2.14-5.06; p=0.002). CONCLUSION The prevalence of the metabolic syndrome according to the NCEP-ATP III criteria was high, and positively correlated with the cardiovascular risk in the patients with acute coronary syndrome. The cardiovascular risk rises proportionally with the number of metabolic components.
A Capacitance Sensor for Gas/Oil Two-Phase Flow Measurement: Exciting Frequency Analysis and Static Experiment

A capacitance sensor with high sensitivity was applied to oil–gas two-phase measurement based on a modeling and experimental studies. A model of the electric behavior of the material system between electrodes, comprising fluids and pipe, was developed to choose the optimum working frequency using two types of electrode configurations: double ring and concave, which differ in terms of linearity of response, sensitivity, and phase distribution dependence. According to the model, medium frequencies, 800–1000 KHz, is the best choice for gas–oil ratio measurement. Subsequently, a capacitance sensor was designed and constructed using electrodes mounted at the outside of the wall of a polyester tube in a static test bench to measuring gas–oil ratio. The model and experimental results show better sensitivity of ring configuration, whereas concave one presented better linearity of response. Moreover, ring configuration is less affected by air/oil distribution, although both electrodes showed dependence on flow pattern. The experimental results confirm reducing in sensitivity of both electrodes by increasing the frequency. The gas–oil ratio was determined directly from the output voltage changes instead of measuring the capacitance as void fraction indicator.
Akt3 controls vascular endothelial growth factor secretion and angiogenesis in ovarian cancer cells

The PI3 kinase/Akt pathway is commonly deregulated in human cancers, functioning in such processes as proliferation, glucose metabolism, survival and motility. We have previously described a novel function for one of the Akt isoforms (Akt3) in primary endothelial cells: the control of VEGF‐induced mitochondrial biogenesis. We sought to determine if Akt3 played a similar role in carcinoma cells. Because the PI3 kinase/Akt pathway has been strongly implicated as a key regulator in ovarian carcinoma, we tested the role of Akt3 in this tumor type. Silencing of Akt3 by shRNA did not cause an overt reduction in mitochondrial gene expression in a series of PTEN positive ovarian cancer cells. Rather, we find that blockade of Akt3, results in smaller, less vascularized tumors in a xenograft mouse model that is correlated with a reduction in VEGF expression. We find that blockade of Akt3, but not Akt1, results in a reduction in VEGF secretion and retention of VEGF protein in the endoplasmic reticulum (ER). The reduction in secretion under conditions of Akt3 blockade is, at least in part, due to the down regulation of the resident golgi protein and reported tumor cell marker, RCAS1. Conversely, over‐expression of Akt3 results in an increase in RCAS1 expression and in VEGF secretion. Silencing of RCAS1 using siRNA inhibits VEGF secretion. These findings suggest an important role for Akt3 in the regulation of RCAS1 and VEGF secretion in ovarian cancer cells.
When Do Leaders Free-Ride? Business Experience and Contributions to Collective Defense

The logic of free-riding expects that individuals will under-invest in public goods, but people often behave in ways that are inconsistent with this prediction. Why do we observe variation in free-riding behavior? This study addresses this question by examining contributions to an important international public good - collective defense in military alliances. It develops a behavioral theory of free-riding in which the beliefs of world leaders are important for explaining investments in public goods. The argument holds that leaders with business experience make smaller contributions to collective defense because they are egoistic and more comfortable relying on a powerful ally for their defense. An analysis of defense expenditures in 17 non-US members of the North Atlantic Treaty Organization (NATO) from 1952 to 2014 provides evidence consistent with the theory. The findings suggest that leaders with business experience are more likely than other heads of government to act as self-interested utility maximizers.
Calpain 2‐dependent IκBα degradation mediates CPT‐11 secondary resistance in colorectal cancer xenografts

CPT‐11 (irinotecan), the first‐line chemotherapy for advanced stage colorectal cancer, remains inactive in about half of patients (primary chemoresistance) and almost all initial responders develop secondary resistance after several courses of treatment (8 months on average). Nude mice bearing HT‐29 colon cancer xenografts were treated with CPT‐11 and/or an NF‐κB inhibitor for two courses. We confirm that NF‐κB inhibition potentiated CPT‐11 anti‐tumoural effect after the first course of treatment. However, tumours grew again at the end of the second course of treatment, generating resistant tumours. We observed an increase in the basal NF‐κB activation in resistant tumours and in two resistant sublines, either obtained from resistant HT‐29 tumours (HT‐29R cells) or generated in vitro (RSN cells). The decrease of NF‐κB activation in HT‐29R and RSN cells by stable transfections with the super‐repressor form of IκBα augmented their sensitivity to CPT‐11. Comparing gene expression profiles of HT‐29 and HT‐29R cells, we identified the S100A10/Annexin A2 complex and calpain 2 as over‐expressed potential NF‐κB inducers. SiRNA silencing of calpain 2 but not of S100A10 and/or annexin A2, resulted in a decrease in NF‐κB activation, an increase in cellular levels of IκBα and a partial restoration of the CPT‐11 sensitivity in both HT‐29R and RSN cells, suggesting that calpain 2‐dependent IκBα degradation mediates CPT‐11 secondary resistance. Thus, targeted therapies directed against calpain 2 may represent a novel strategy to enhance the anti‐cancer efficacy of CPT‐11. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.