Miracle-dz/UniFAR-FTUs huggingface dataset:
CB1 receptor‐mediated control of the release of endocannabinoids (as assessed by microdialysis coupled with LC/MS) in the rat hypothalamus

In the present study, we examined the occurrence and potential regulation of endocannabinoid release by cannabinoid CB1 receptors in the rat brain. To this end, we developed a highly sensitive (limit of sensitivity 30–300 amol) new analytical method, combining online brain microdialysis with solid‐phase extraction–liquid chromatography–tandem mass spectrometry, which allowed the detection in real time of trace amounts of endocannabinoids in the extracellular fluid. In the hypothalamus, anandamide and 2‐arachidonoyl‐glycerol release was stimulated following depolarization via local administration of K+, with or without addition of Ca2+, or glutamate application. Inhibition of fatty acid amide hydrolase by systemic administration of intraperitoneal (i.p.) URB597 (0.5 mg/kg) induced an increase of anandamide, but not 2‐arachidonoyl‐glycerol, outflow. The CB1 receptor antagonist rimonabant (10 mg/kg i.p.) increased, whereas the CB1 agonist WIN55,212‐2 (2.5 mg/kg i.p.) decreased, anandamide release. Interestingly, the same treatments induced opposite changes in 2‐arachidonoyl‐glycerol release. At a dose of 3 mg/kg i.p., which by itself did not affect endocannabinoid release, rimonabant fully antagonized the effect of WIN55,212‐2 (2.5 mg/kg i.p.). Taken together, these results suggest that CB1 receptors are able to control the local release of endocannabinoids in the hypothalamus via a feedback mechanism and strengthen the view that anandamide and 2‐arachidonoyl‐glycerol have distinct physiological roles.
Influences of Fanatics and Chatters on Information Diffusion on the Internet

Models that provide insight into how various behaviors of online discussants may influence information diffusion on the Internet are of great current interest. In this paper, we propose an agent based model to mimic the diffusion of online topic discussion, and study effects of different online discussants, i.e. fanatics and chatters, on the diffusion process. Simulation results show that degree distributions of fanatics and chatters play an important role in the diffusion. Increase in the number of fanatics always results in a raise in diffusion scale, while increase in the number of chatters exerts different influences on the diffusion process.
Subtype selectivity of α+β− site ligands of GABAA receptors: identification of the first highly specific positive modulators at α6β2/3γ2 receptors

GABAA receptors are the major inhibitory neurotransmitter receptors in the mammalian brain and the target of many clinically important drugs interacting with different binding sites. Recently, we demonstrated that CGS 9895 (2‐(4‐methoxyphenyl)‐2H‐pyrazolo[4,3‐c]quinolin‐3(5H)‐one) elicits a strong and subtype‐dependent enhancement of GABA‐induced currents via a novel drug‐binding site at extracellular αx+βy− (x = 1–6, y = 1–3) interfaces. Here, we investigated 16 structural analogues of CGS 9895 for their ability to modulate GABA‐induced currents of various GABAA receptor subtypes.
A Systematic Review of the Effectiveness of Interventions to Prevent and Respond to Violence Against Persons With Disabilities

Persons with disabilities make up some 15% of the world’s population and are at higher risk of violence. Yet there is currently no systematic review of the effectiveness of interventions to prevent violence against them. Thus the aim of this review was to systematically search for, appraise the quality of, and synthesize the evidence for the effectiveness of interventions to prevent and mitigate the consequences of all the main forms of interpersonal violence against people with all types of disabilities. The method used consisted of searches of eleven electronic databases, hand searches of three journals, scanning of reference lists of review articles, contact with experts, appraisal of risk of bias using the Quality Assessment Tool for Quantitative Studies, and narrative synthesis of results. This resulted in 736 titles being identified, 10 of which met the inclusion criteria and 6 and 2 addressed people with intellectual disabilities and developmental disabilities, respectively. Only one was from a low- and middle-income country. All studies received a weak rating on the quality assessment tool and none could be considered effective after taking risk of bias into account. In sum, the current evidence base offers little guidance to policy makers, program commissioners, and persons with disabilities for selecting interventions. More and higher quality research is required, particularly from low- and middle-income countries and on other forms of disability such as physical impairments, sensory impairments, and mental health conditions.
Factors Influencing Intention to Adopt Internet Banking by Postgraduate Students of the University of Ibadan, Nigeria

This study examines the factors influencing intention to adopt internet banking by postgraduate students of the University of Ibadan Nigeria. The study adopted the Technology Acceptance Model and Theory of Planned Behaviour as the theoretical framework. The survey instrument employed involved design and administration of a total of 522 survey questionnaires within the University. The results of the study reveal no significant relationship between demographic characteristics of the students and intention to adopt internet banking, while the individual factors (attitude, trust, perceived usefulness, perceived ease of use and perceived behavioural control), and social factor (subjective norms) significantly influenced intention of the students to adoption internet banking. The study concludes that even though some students are yet to adopt the use of internet banking, their attitude towards online banking is favourable. It is therefore recommended that banks should intensify efforts to improve the security of online banking platform as well as continue to educate their customers on the perceived benefits of internet banking in addition to making the platform more user-friendly and easy to use.
Improving recovery time following heart transplantation: the role of the multidisciplinary health care team

Background The care of cardiac transplant patients is complex requiring a finely orchestrated endeavor to save a patient’s life. Given the chronic and complex nature of these patients, multiple disciplines are involved in their care. Recognizing difficulties with communication among team members and striving for improved efficiencies in our pretransplant listing process and in our inpatient care, our team was prompted to change the existing approach to patient care related to heart transplantation. Methods Daily multidisciplinary rounds were instituted and the format of the weekly Multidisciplinary Review Committee (MDRC) meetings was modified with the list of attendees broadened to include a larger interdisciplinary team. Additionally, the approach to patient care was analyzed for process improvement. Results The quality improvements are improved communication and throughput, quantified in an 85% decrease in time to complete transplant evaluation, a 37% decrease in median length of stay posttransplantation, and a 33% reduction in the 30 day readmission rate. In addition, pre- and posttransplant caregivers now participate in MDRC in person or via an electronic meeting platform to support the continuum of care. Quality metrics were chosen and tracked via a transparent electronic platform allowing all involved to assess progress toward agreed upon goals. These were achieved in an 18 month time period following the recruitment of new leadership and invested team members working together as a multidisciplinary team to improve the quality of cardiac transplant care. Discussion: Implementation of daily multidisciplinary rounds and expansion of the attendees for the MDRC meetings improved care related to heart transplantation.
Acoustic correlates of perceived foreign accent in non-native English

Skilled perception of speech involves not just recognizing the words and sentences that a talker produces, but also perceiving properties imputed to the talker, such as being a foreigner. Because being perceived as foreign can have social consequences, it is important to understand the characteristics that contribute to this percept. Foreign accent perception is often studied in relation to talker characteristics, such as age of learning the second language (L2) or age of arrival in the L2-speaking country. However, listeners generally do not have direct access to such information. In order for the perception of foreign accent to be fully understood, it must be studied in relation to physical characteristics of the speech signal. This dissertation reports a series of six experiments that elicited American English monolinguals’ ratings of various properties of productions from native talkers of American English, Hindi, Korean, Mandarin, and Spanish, as well as their free classifications of talker language background. In the first four experiments, listeners heard samples of English and rated foreign accentedness or non-nativeness for each production. In the final two experiments, listeners rated non-Englishness for samples of each talker producing his or her native language (L1). Linear mixed effects regression models revealed that VOT, F1 frequency, and F2 frequency correlated with ratings of accentedness and non-nativeness for syllableand word-length stimuli. In addition, F3 frequency and F2 tilt correlated with the ratings for syllable-length stimuli, and vowel duration with the ratings for word-length
Expression of Wnt9b and activation of canonical Wnt signaling during midfacial morphogenesis in mice

Cleft lip with or without cleft palate (CLP) is the most common craniofacial birth defect in humans. Recently, mutations in the WNT3 and Wnt9b genes, encoding two members of the Wnt family of signaling molecules, were found associated with CLP in human and mice, respectively. To investigate whether Wnt3 and Wnt9b directly regulate facial development, we analyzed their developmental expression patterns and found that both Wnt3 and Wnt9b are expressed in the facial ectoderm at critical stages of midfacial morphogenesis during mouse embryogenesis. Whereas Wnt3 mRNA is mainly expressed in the maxillary and medial nasal ectoderm, Wnt9b mRNA is expressed in maxillary, medial nasal, and lateral nasal ectoderm. During lip fusion, Wnt9b, but not Wnt3, is expressed in the epithelial seam between the fusing medial and lateral nasal processes. Furthermore, we found that expression of TOPGAL, a transgenic reporter of activation of canonical Wnt signaling pathway, is specifically activated in the distal regions of the medial nasal, lateral nasal, and maxillary processes prior to lip fusion. During lip fusion, the epithelial seam between the medial and lateral nasal processes as well as the facial mesenchyme directly beneath the fusing epithelia strongly expresses TOPGAL. These data, together with the CLP lip phenotype in WNT3−/− humans and Wnt9b−/− mutant mice, indicate that Wnt3 and Wnt9b signal through the canonical Wnt signaling pathway to regulate midfacial development and lip fusion. Developmental Dynamics, 2006. © 2006 Wiley‐Liss, Inc.
Immunomodulatory effects of Aloe vera and its fractions on response of macrophages against Candida albicans

Natural products are important resources in traditional medicine and have been long used for prevention and treatment of many diseases. Medicinal plants have immunomodulatory properties. Aloe is one of the herbal medicines widely used in natural treatment and alternative therapy for various types of diseases. Aloe vera has been shown to modulate the immune response. Macrophages have been shown to play an essential role as the first line of defense against invading pathogen. Candida albicans is a communal and opportunistic pathogen in humans. In this study, we investigated the effect of A. vera extract and its fractions on infected macrophages with C. albicans. Viability of intraperitoneal macrophages was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test. Cell viability of infected macrophages was increased by the extract and dose of some isolated fractions dependently. The extract as well as R100, R50, R30, and R10 fractions of A. vera significantly increased cell viability of macrophages in most doses. R5 and F5 fractions showed no significant difference in comparison with control group. Further studies in animal models and human are necessary to clarify the modulatory effects of A. vera on macrophage function. Isolation and purification of A. vera components are also needed to find out the effective molecules.
Mutational Analysis of the Putative Fusion Domain of Ebola Virus Glycoprotein

ABSTRACT Ebola viruses contain a single glycoprotein (GP) spike, which functions as a receptor binding and membrane fusion protein. It contains a highly conserved hydrophobic region (amino acids 524 to 539) located 24 amino acids downstream of the N terminus of the Ebola virus GP2 subunit. Comparison of this region with the structural features of the transmembrane subunit of avian retroviral GPs suggests that the conserved Ebola virus hydrophobic region may, in fact, serve as the fusion peptide. To test this hypothesis directly, we introduced conservative (alanine) and nonconservative (arginine) amino acid substitutions at eight positions in this region of the GP2 molecule. The effects of these mutations were deduced from the ability of the Ebola virus GP to complement the infectivity of a vesicular stomatitis virus (VSV) lacking the receptor-binding G protein. Some mutations, such as Ile-to-Arg substitutions at positions 532 (I532R), F535R, G536A, and P537R, almost completely abolished the ability of the GP to support VSV infectivity without affecting the transport of GP to the cell surface and its incorporation into virions or the production of virus particles. Other mutations, such as G528R, L529A, L529R, I532A, and F535A, reduced the infectivity of the VSV-Ebola virus pseudotypes by at least one-half. These findings, together with previous reports of liposome association with a peptide corresponding to positions 524 to 539 in the GP molecule, offer compelling support for a fusion peptide role for the conserved hydrophobic region in the Ebola virus GP.
GJB2: The spectrum of deafness‐causing allele variants and their phenotype

Genetic testing was completed on 1,294 persons with deafness referred to the Molecular Otolaryngology Research Laboratories to establish a diagnosis of DFNB1. Exon 2 of GJB2 was screened for coding sequence allele variants by denaturing high‐performance liquid chromatography (DHPLC) complemented by bidirectional sequencing. If two deafness‐causing mutations of GJB2 (encoding Connexin 26) were identified, further screening was not performed. If only a single deafness‐causing mutation was identified, we screened for the g. 1777179_2085947del (hereafter called del(GJB6‐D13S1830); GenBank NT_024524. 13) and mutations in the noncoding region of GJB2. Phenotype–genotype correlations were evaluated by categorizing mutations as either protein truncating or nontruncating. A total of 205 persons carried two GJB2 exon 2 mutations and were diagnosed as having DFNB1; 100 persons carried only a single deafness‐causing allele variant of exon 2. A total of 37 of these persons were c.35delG carriers, and 51 carried other allele variants of GJB2. Persons diagnosed with DFNB1 segregating two truncating/nonsense mutations had a more severe phenotype than persons carrying two missense mutations, with mean hearing impairments being 88 and 37%, respectively (P < 0.05). The number of deaf c.35delG carriers was greater than expected when compared to the c.35delG carrier frequency in normal‐hearing controls (P < 0.05), suggesting the existence of at least one other mutation outside the GJB2 coding region that does not complement GJB2 deafness‐causing allele variants. Hum Mutat 24:305–311, 2004. © 2004 Wiley‐Liss, Inc.
Quality evaluation of LC‐MS/MS‐based E. coli H antigen typing (MS‐H) through label‐free quantitative data analysis in a clinical sample setup

The need for rapid and accurate H typing is evident during Escherichia coli outbreak situations. This study explores the transition of MS‐H, a method originally developed for rapid H antigen typing of E. coli using LC‐MS/MS of flagella digest of reference strains and some clinical strains, to E. coli isolates in clinical scenario through quantitative analysis and method validation.
SEROSURVEY FOR SELECTED PATHOGENS IN FREE-RANGING AMERICAN BLACK BEARS (URSUS AMERICANUS) IN MARYLAND, USA

Abstract American black bears (Ursus americanus) in Maryland, USA, live in forested areas in close proximity to humans and their domestic pets. From 1999 to 2011, we collected 84 serum samples from 63 black bears (18 males; 45 females) in five Maryland counties and tested them for exposure to infectious, including zoonotic, pathogens. A large portion of the bears had antibody to canine distemper virus and Toxoplasma gondii, many at high titers. Prevalences of antibodies to zoonotic agents such as rabies virus and to infectious agents of carnivores including canine adenovirus and canine parvovirus were lower. Bears also had antibodies to vector-borne pathogens common to bears and humans such as West Nile virus, Borrelia burgdorferi, Rickettsia rickettsii, and Anaplasma phagocytophilum. Antibodies were detected to Leptospira interrogans serovars Pomona, Icterohaemorrhagiae, Canicola, Grippotyphosa, and Bratislava. We did not detect antibodies to Brucella canis or Ehrlichia canis. Although this population of Maryland black bears demonstrated exposure to multiple pathogens of concern for humans and domesticated animals, the low levels of clinical disease in this and other free-ranging black bear populations indicate the black bear is likely a spillover host for the majority of pathogens studied. Nevertheless, bear populations living at the human–domestic-wildlife interface with increasing human and domestic animal exposure should continue to be monitored because this population likely serves as a useful sentinel of ecosystem health.
EFFECT OF ALCOHOL ON CYTOCHROME P450 ARACHIDONIC ACID METABOLISM AND BLOOD PRESSURE IN RATS AND ITS MODULATION BY RED WINE POLYPHENOLICS

1 Alcohol‐induced hypertension is well recognized with clear evidence for a direct pressor effect of chronic alcohol consumption provided by a number of intervention studies in humans. In experimental animals, the effect of alcohol on blood pressure is less consistent; however, in Sprague‐Dawley rats, alcohol feeding consistently induces a hypertensive response. The mechanism of alcohol‐induced hypertension is not clearly understood. Ethanol is known to induce certain cytochrome P450 (CYP) enzymes, particularly the 2E1 isoform, which has been shown to metabolise arachidonic acid (AA) to the 19‐hydroxy metabolite (19‐HETE), which could have prohypertensive activity; CYP4A, by comparison, is the principal AA ω‐hydroxylase in the liver. Polyphenolic compounds, such as flavonoids, have been shown to inhibit some CYPs. 2 In this study, we determined the effect of alcohol administration on blood pressure and CYP‐dependent AA metabolism in the rat and its possible modulation by red wine polyphenols. 3 Thirty male Sprague‐Dawley rats were randomly allocated to three groups, which received water, low‐dose ethanol (5% v/v) or red wine (diluted to contain 5% ethanol) for a period of 9 weeks. Bodyweight and blood pressure were measured weekly and 24h urine collected at baseline and every 2 weeks. Animals were killed at 9 weeks and blood and tissue samples were collected. The blood pressure of rats fed with alcohol increased significantly over the period of the study compared with controls (P < 0.001). The blood pressure of animals fed 5% alcohol in the form of red wine was not significantly different from controls over the study period. The urinary excretion of 20‐HETE did not differ significantly among the treatment groups over the study period and there was no effect of any treatment on the metabolism of AA by renal microsomes. Red wine, but not administration of the relatively low dose of alcohol alone, increased the expression of CYP2E1 protein in the liver and kidney and CYP4A in the kidney. Both red wine and alcohol decreased CYP4A protein levels in the liver compared with controls. 4 Our results suggest that constituents of red wine, possibly polyphenols, can attenuate the alcohol‐induced rise in blood pressure in the Sprague‐Dawley rat, although this effect does not appear to be mediated by the inhibition of CYP‐derived AA metabolism.
Characterization of a Nitrite Reductase Involved in Nitrifier Denitrification*

Background: Copper nitrite reductases convert nitrite to nitric oxide in microorganisms. Results: The copper nitrite reductase from an ammonia oxidizing bacterium is unusually oxygen tolerant and has several unique structural features. Conclusion: The structure of this copper nitrite reductase enables it to function in an aerobic environment. Significance: This enzyme plays a key role in an environmentally important pathway. Nitrifier denitrification is the conversion of nitrite to nitrous oxide by ammonia-oxidizing organisms. This process, which is distinct from denitrification, is active under aerobic conditions in the model nitrifier Nitrosomonas europaea. The central enzyme of the nitrifier dentrification pathway is a copper nitrite reductase (CuNIR). To understand how a CuNIR, typically inactivated by oxygen, functions in this pathway, the enzyme isolated directly from N. europaea (NeNIR) was biochemically and structurally characterized. NeNIR reduces nitrite at a similar rate to other CuNIRs but appears to be oxygen tolerant. Crystal structures of oxidized and reduced NeNIR reveal a substrate channel to the active site that is much more restricted than channels in typical CuNIRs. In addition, there is a second fully hydrated channel leading to the active site that likely acts a water exit pathway. The structure is minimally affected by changes in pH. Taken together, these findings provide insight into the molecular basis for NeNIR oxygen tolerance.
Effects of Na+ Channel Blockers on Extrasystolic Stimulation-evoked Changes in Ventricular Conduction and Repolarization

Abstract: Antiarrhythmic agents which belong to class Ia (quinidine) and Ic (flecainide) reportedly increase propensity to ventricular tachyarrhythmia, whereas class Ib agents (lidocaine and mexiletine) are recognized as safe antiarrhythmics. Clinically, tachyarrhythmia is often initiated by a premature ectopic beat, which increases spatial nonuniformities in ventricular conduction and repolarization thus facilitating reentry. This study examined if electrical derangements evoked by premature excitation may be accentuated by flecainide and quinidine, but unchanged by lidocaine and mexiletine, which would explain the difference in their safety profile. In perfused guinea pig hearts, a premature excitation evoked over late repolarization phase was associated with prolonged epicardial activation time, reduced monophasic action potential duration (APD), and increased transepicardial dispersion of the activation time and APD. Flecainide and quinidine increased conduction slowing evoked by extrasystolic stimulation, prolonged APD, and accentuated spatial heterogeneities in ventricular conduction and repolarization associated with premature excitation. Spontaneous episodes of nonsustained monomorphic ventricular tachycardia were observed in 50% of heart preparations exposed to drug infusion. In contrast, lidocaine and mexiletine had no effect on extrasystolic stimulation-evoked changes in ventricular conduction and repolarization or arrhythmic susceptibility. These findings suggest that flecainide and quinidine may promote arrhythmia by exaggerating electrophysiological abnormalities evoked by ectopic beats.