Miracle-dz/UniFAR-FTUs huggingface dataset:
How Inflammation Changes Neuromuscular Function and Its Relevance to Symptoms in Diverticular Disease

Diverticulosis is largely asymptomatic but recent evidence suggests that episodes of acute diverticulitis double the risk of subsequently suffering from recurrent noninflammatory pain. Numerous animal models demonstrate how inflammation is followed by circular muscle hypertrophy, abnormalities of innervation, and increased sensitivity to cholinergic agents. There is also an impairment of norepinephrine and acetylcholine release and damage to nitrergic neurons. These changes are also associated with visceral hypersensitivity. Many of the features, including visceral hypersensitivity are also seen in symptomatic patients with diverticulosis. The trinitrobenzene sulfonic acid colitis model demonstrates that inflammation is followed by long lasting increases in tachykinin and other neuropeptide immunoreactivity. These changes occur both in the mucosa and myenteric plexus and parallel changes seen in resections and mucosal biopsies in diverticular patients. These neural abnormalities may be responsible for the visceral hypersensitivity, which explains why symptoms correlate poorly with objective abnormalities such as intraluminal pressure or motor patterns. Treatment of visceral hypersensitivity might be more effective than current therapies that often leave pain unaltered.
Nine members of the myomodulin family of peptide cotransmitters at the B16-ARC neuromuscular junction of Aplysia.

1. Neuromodulation by multiple related peptides with different spectra of physiological effects appears an effective way to integrate complex physiological functions. A good opportunity to examine this issue occurs in the accessory radula closer (ARC) neuromuscular circuit of Aplysia, where, extensive previous work has shown, acetylcholine-induced contractions of the muscle are variously modulated by several families of peptide cotransmitters released under appropriate behavioral circumstances from the muscle's own two motor neurons. 2. In this work we focused on the myomodulins (MMs) released from motor neuron B16. Previous work has characterized MMA (PMSMLRLamide) and MMB (GSYRMMRLamide). We now similarly purified from ARC neuromuscular material and sequenced MMC (GWSMLRLamide), MMD (GLSMLRLamide), MME (GLQMLRLamide), and MMF (SLNMLRLamide). Three additional MMs, MMG (TLSMLRLamide), MMH (GLHMLRLamide), and MMI (SLSMLRLamide), are encoded by a known MM gene. B16 probably synthesizes, and coreleases, all nine MMs. Further MMs have been found in other mollusks. All evidence indicates that the MMs are a major, widely distributed family of molluscan neuropeptides important as neuromuscular modulators and probably also central transmitters or modulators. 3. MM effects on motor neuron B16-elicited ARC muscle contractions were best analyzed as the sum of three distinct actions: potentiation, depression of the amplitude of the contractions, and acceleration of their relaxation rate. We compared the effectiveness of all nine MMs in these respects. We correlated this with their effectiveness in enhancing the L-type Ca current and activating a specific K current in voltage-clamped dissociated ARC muscle fibers, effects we previously proposed to underlie, respectively, the potentiation and the depression of contractions. 4. All nine MMs were similarly effective in enhancing the Ca current and, as far as it was possible to determine, potentiating the amplitude as well as accelerating the relaxation rate of the contractions. 5. In contrast, the MMs' ability to activate the K current and depress the contractions varied greatly. MMB and MMC, in particular, were weak, whereas the other seven MMs were considerably more effective in both respects. 6. Altogether, we were able to explain the potentiating and depressing strengths of the MMs by the magnitude of their modulation of the Ca and K currents, providing further support for our hypothesis that the effects on contraction amplitude are mediated by the effects on the two currents. 7. The net effect on contraction amplitude was determined by the balance between the potentiation and depression. Although most MM concentrations had both potentiating and depressing actions, potentiated contractions predominated at low and depressed contractions (but with accelerated relaxation rate) at high concentrations. (ABSTRACT TRUNCATED AT 400 WORDS)
Does nitric oxide allow endothelial cells to sense hypoxia and mediate hypoxic vasodilatation?in vivo and in vitro studies

Hypoxia‐evoked vasodilatation is a fundamental regulatory mechanism that is often attributed to adenosine. The identity of the O2 sensor is unknown. Nitric oxide (NO) inhibits endothelial mitochondrial respiration and ATP generation by competing with O2 for its binding site on cytochrome oxidase. We proposed that in vivo this interaction allows endothelial cells to release adenosine when O2 tension falls or NO concentration increases. Using anaesthetised rats, we confirmed that the increase in femoral vascular conductance (FVC, hindlimb vasodilatation) evoked by systemic hypoxia is attenuated by NO synthesis blockade with l‐NAME, but restored when baseline FVC is restored by infusion of NO donor. This ‘restored’ hypoxic response, like the control hypoxic response, is inhibited by the adenosine A1 receptor antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine. Similarly, the FVC increase evoked by adenosine infusion was attenuated by l‐NAME but restored by infusion of NO donor. However, when baseline FVC was restored after l‐NAME with 8‐bromo‐cGMP, the FVC increase evoked by adenosine infusion was restored, but not in response to systemic hypoxia, suggesting that adenosine was no longer released by hypoxia. Infusion of NO donor at a given rate after treatment with l‐NAME evoked a greater FVC increase during systemic hypoxia than during normoxia, both responses being reduced by 8‐cyclopentyl‐1,3‐dipropylxanthine. Finally, both bradykinin and NO donor released adenosine from superfused endothelial cells in vitro; l‐NAME attenuated only the former response. We propose that in vivo, shear‐released NO increases the apparent Km of endothelial cytochrome oxidase for O2, allowing the endothelium to act as an O2 sensor, releasing adenosine in response to moderate falls in O2.
Restoring lost cognitive function

A prosthetic device that functions in a biomimetic manner to replace information transmission between cortical brain regions is considered. In such a prosthesis, damaged CNS neurons is replaced with a biomimetic system comprised of silicon neurons. The replacement silicon neurons would have functional properties specific to those of the damaged neurons and would both receive as inputs and send as outputs electrical activity to regions of the brain with which the damaged region previously communicated. Thus, the class of prosthesis proposed is one that would replace the computational function of the damaged brain and restore the transmission of that computational result to other regions of the nervous system.
Reduction of 1,4-quinone and Ubiquinones by Hydrogen Atom Transfer under UVA Irradiation

1,4-Benzoquinone, coenzyme Q 0 and Q 10 were reacted with a series of hydrogen donors in the ESR cavity in the presence or absence of UVA irradiation. The signals of the radicals generated from the hydrogen donors or of those of the semiquinones were detected. The reaction mechanism was interpreted by a hydrogen atom transfer instead of the usual electron transfer mechanism on the basis of the redox potentials of the reactants and the Marcus theory. The hydrogen atom transfer is explained by the excited triplet state of quinones, which, on the basis of quantum mechanic calculations, may be reached even under visible light. In some cases, hydrogen atom transfer was also observed without irradiation, although to a lesser extent.
Modeling Life Expectancy for Multi-Population: A Cointegration Approach

The continuous improvements in mortality rates and life expectancy from the last century have been giving particular attention from academics, life insurers, financial engineers and pension planners, particularly in developped countries. Mortality-linked securities such as longevity bonds (EIB & BNP as well as Swiss Re bonds), survivor swaps or mortality forward (q-forward) have appeared recently in the industry to help operators hegding such risks. A classical survivor bond has been proposed in literature with coupons payment linked to life time of the last survivor in insurance reference portfolio. It appears therefore to be crucial to improve the accuracy of future life expectancy. In this paper, we investigate time varying dependency associated with common trends which drive regional life expectancy within Canada. We aim to compare the three main models appeared recently in literature such as Autoregressive Integrated Moving Average (ARIMA), Vector Autoregressive model (VAR) and Vector Error Correction Model (VECM), to analyse the common factors that have determined a progressive shift of life expectancy in six Canadian regions. The latter shows better performance over VAR and ARIMA in terms of backtesting and its ability to capture the dynamics of common life expectancy. Findings from these analysis are useful for local insurers and demographers in their goal to project life expectancy improvements and also to forecast future trends.
Characterization of the gene encoding serine acetyltransferase, a regulated enzyme of cysteine biosynthesis from the protist parasites Entamoeba histolytica and Entamoeba dispar. Regulation and possible function of the cysteine biosynthetic pathway in Entamoeba.

The enteric protist parasites Entamoeba histolytica and Entamoeba dispar possess a cysteine biosynthetic pathway, unlike their mammalian host, and are capable of de novo production of L-cysteine. We cloned and characterized cDNAs that encode the regulated enzyme serine acetyltransferase (SAT) in this pathway from these amoebae by genetic complementation of a cysteine-auxotrophic Escherichia coli strain with the amoebic cDNA libraries. The deduced amino acid sequences of the amoebic SATs exhibited, within the most conserved region, 36-52% identities with the bacterial and plant SATs. The amoebic SATs contain a unique insertion of eight amino acids, also found in the corresponding region of a plasmid-encoded SAT from Synechococcus sp. , which showed the highest overall identities to the amoebic SATs. Phylogenetic reconstruction also revealed a close kinship of the amoebic SATs with cyanobacterial SATs. Biochemical characterization of the recombinant E. histolytica SAT revealed several enzymatic features that distinguished the amoebic enzyme from the bacterial and plant enzymes: 1) inhibition by L-cysteine in a competitive manner with L-serine; 2) inhibition by L-cystine; and 3) no association with cysteine synthase. Genetically engineered amoeba strains that overproduced cysteine synthase and SAT were created. The cysteine synthase-overproducing amoebae had a higher level of cysteine synthase activity and total thiol content and revealed increased resistance to hydrogen peroxide. These results indicate that the cysteine biosynthetic pathway plays an important role in antioxidative defense of these enteric parasites.
X-ray microtomography assessment of Carisolv and Papacarie effect on dentin mineral density and amount of removed tissue

Abstract Objective: The aim of the present study was to directly compare Carisolv and Papacarie regarding the volume of removed tissue (RT) and dentin mineral density (DMD) after excavation. Materials and Methods: Twenty permanent molars were randomized into two groups where caries was excavated using Carisolv or Papacarie followed by removal of softened tissue by a blunt instrument. X-ray microtomography was used to scan teeth before and after excavation generating two- and three-dimensional images that were used to calculate the percentage of RT relative to baseline tooth tissue volume and DMD that was categorized into sound dentin (>1.11 g/cm3) and residual caries (≤1.11 g/cm3). The two groups were compared using t-test Fisher exact test. Results: DMD was higher after Papacarie than Carisolv (mean = 1.70 and 1.14, p = .14) with higher percentage of cases with sound dentin (70 and 60%, p = 1.00). The percentage of RT was lower after Papacarie than Carisolv (7.40 and 8.95%, p = .31) with 22.95% less RT in cases that ended with sound dentin after excavation. Conclusions: There was higher DMD, more sound dentin and less RT when Papacarie was used compared to Carisolv.
Metformin as an antitumor agent in cancer prevention and treatment

Recent epidemiological investigations conducted in diabetic cohorts and cancer patients have found that metformin users have lower risks for cancer than those using insulin or insulin secretagogues. Studies conducted in various animal tumor models and cancer cell lines have demonstrated that metformin prevents tumor development or inhibits cell proliferation. In addition, a recent clinical trial has shown that short‐term use of metformin reduces aberrant crypt foci (ACF) formation in non‐diabetic patients with ACF. The antitumor activity of metformin may be mediated through its regulatory effect on hormonal, metabolic, and immune functions. Metformin achieves glycemic control by reducing hepatic glucose production and increasing the muscle intake of glucose, thus lowering levels of circulating glucose and, consequently, insulin. The major molecular targets of metformin are the liver kinase B1 (LKB1)–AMP‐activated protein kinase (AMPK) signaling and mammalian target of rapamycin (mTOR) pathways, which are central in the regulation of cellular energy homeostasis and play a crucial role in the control of cell division and cell proliferation. Metformin has been shown to improve endothelial function, decrease inflammatory activity, and regulate immune function. Increasing experimental evidence provides a strong biological rationale for metformin as an antitumor and chemopreventive agent. Metformin is being tested as an adjuvant cancer therapy in clinical settings, and metformin is recommended for all cases of Type 2 diabetes without contraindications. As described in this review, the chemopreventive value of metformin is not restricted to diabetic or obese individuals.
Chemopreventive Effects of Nonsteroidal Anti-Inflammatory Drugs on 1,2-Dimethylhydrazine-Induced Colon Carcinogenesis in Rats

ABSTRACT The anticancer efficacy of two different classes of NSAIDs, the nonspecific cyclooxygenase (COX) inhibitor aspirin and the specific COX-2 inhibitor celecoxib, was examined at their therapeutic anti-inflammatory doses during 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis in a rat model. Eight to 10-week-old male rats of Sprague strain were divided into four groups. While group 1 served as control and received the vehicle of the drugs, groups 2, 3, and 4 were administered freshly prepared DMH in 1 mM EDTA saline (pH 7.0) (30 mg/kg body weight/week, subcutaneously). Groups 3 and 4 were also given a daily treatment of aspirin (60 mg/kg body weight, orally) and celecoxib (6 mg/kg body weight, orally), respectively, both prepared in carboxy-methyl cellulose. Animals were sacrificed at the end of 12 weeks and colons from different groups were subjected to macroscopic and histopathological studies, enzymatic activities of superoxide dismutase (SOD) and catalase (CAT), and determination of lipid peroxide level. The maximum number of raised mucosal lesions in proximal, middle, and distal regions of the colon was found in the DMH group alone, and the lowest number was found in the celecoxib-treated DMH group. Histological studies also showed the highest occurrence of dysplastic aberrant crypt foci (ACF) associated with enlarged lymphoid follicles in all the three portions of colon (i.e., proximal, middle, and distal). The aspirin-administered DMH group had lesser ACF in the proximal and middle portions and no ACF in the distal region. The celecoxib-administered DMH group showed no ACF in the middle region of the rat colon. DMH treatment induced lipid peroxidation and inhibited the activities of SOD and CAT. Both the aspirin- and celecoxib-treated DMH groups showed a marked lowering of the lipid peroxide level along with a significant enhancement of CAT activity when compared with the DMH-treated group. The results show that celecoxib was found to be more effective in reducing the ACF occurrence and aggregates of lymphoid tissue than the nonselective COX inhibitor aspirin, and suggests a possible chemoprevention modality in colon cancer. This may have important implications as COX-2 selective drugs at anti-inflammatory doses are better tolerated clinically than standard NSAIDs, thus making them potentially better chemopreventive agents in colon cancer.
Association of sleep-related problems with CKD in the United States, 2005-2008.

BACKGROUND Sleep-related problems, which have been associated with poor health outcomes, have not been investigated thoroughly in people with chronic kidney disease (CKD). We examined the prevalence of a variety of sleep-related problems in persons with and without CKD. STUDY DESIGN National cross-sectional survey (National Health and Nutrition Examination Survey 2005-2008). SETTING & PARTICIPANTS Community-based survey of 9,110 noninstitutionalized US civilian residents 20 years or older. PREDICTOR CKD, defined as estimated glomerular filtration rate (eGFR) of 15-59 mL/min/1.73 m(2) (stages 3 and 4) or eGFR ≥60 mL/min/1.73 m(2) and albumin-creatinine ratio ≥30 mg/g (stages 1 and 2). OUTCOME Sleep quality, defined using self-report in a multi-item sleep questionnaire including items from previously validated instruments. MEASUREMENTS Albuminuria and eGFR assessed from urine and blood samples; sleep, demographics, and comorbid conditions assessed using a standardized questionnaire. RESULTS Inadequate sleep (≤6 hours per night) differed by CKD severity (37.4%, 43.0%, and 30.9% for no CKD, CKD stages 1 and 2, and CKD stages 3 and 4, respectively; P = 0.003). Frequent sleeping pill use (8.4%, 9.9%, and 16.6%), leg symptoms (39.2%, 48.0%, and 50.9%), and nocturia (20.9%, 35.2%, and 43.6%; P < 0.001 for all) also differed by CKD severity. After adjustment for age, sex, race/ethnicity, obesity, diabetes, and cardiovascular disease, the prevalence of these sleep-related problems remained higher in people with CKD stages 1 and 2 relative to no CKD. Most other measures of sleep quality, disorder, and functional outcomes did not differ by CKD. LIMITATIONS Inability to establish causality and possible unmeasured confounding. CONCLUSION Providers should be aware of early sleep-related CKD manifestations, including inadequate sleep, leg symptoms, and nocturia, and of the high rate of reported sleep medication use in this population.
The Compleat Economic Voter: New Theory and British Evidence

Almost all the prolific work done on economic voting has been based on the classic reward–punishment model, which treats the economy as a valence issue. The economy is a valence issue, but it is much more than that. This article explores two other dimensions of economic voting – position and patrimony. Investigating a 2010 British survey containing relevant measures on these three dimensions, the authors estimate their impact on vote intention, using a carefully specified system of equations. According to the evidence reported, each dimension of economic voting has its own independent effect. Moreover, together, they reveal a ‘compleat’ economic voter, who wields considerable power over electoral choice in Britain. This new result confirms and extends recent work on American and French elections.
An Investigation of Computer Satisfaction in Mexico

Abstract The effects of computerization in Mexico are receiving growing attention in the U.S. This study investigates user information satisfaction among employees of organizations in northern Mexico. Results indicate that Mexican computer users have positive attitudes toward and are generally satisfied with their employers' information systems. On a subfactor assessment level, Mexican computer users are especially satisfied with their IT staff and services and least satisfied with the level of user training they receive.
A System for Real-Time Multimodal Analysis of Nonverbal Affective Social Interaction in User-Centric Media

This paper presents a multimodal system for real-time analysis of nonverbal affective social interaction in small groups of users. The focus is on two major aspects of affective social interaction: the synchronization of the affective behavior within a small group and the emergence of functional roles, such as leadership. A small group of users is modeled as a complex system consisting of single interacting components that can auto-organize and show global properties. Techniques are developed for computing quantitative measures of both synchronization and leadership. Music is selected as experimental test-bed since it is a clear example of interactive and social activity, where affective nonverbal communication plays a fundamental role. The system has been implemented as software modules for the EyesWeb XMI platform (http://www.eyesweb.org). It has been used in experimental frameworks (a violin duo and a string quartet) and in real-world applications (in user-centric applications for active music listening). Further application scenarios include entertainment, edutainment, therapy and rehabilitation, cultural heritage, and museum applications. Research has been carried out in the framework of the EU-ICT FP7 Project SAME (http://www.sameproject.eu).
Identification of a Rat Oltipraz-inducible UDP-glucuronosyltransferase (UGT1A7) with Activity Towards Benzo(a)pyrene-7,8-dihydrodiol*

Previous work has shown that polycyclic aromatic hydrocarbons and oltipraz both induce an unidentified rat liver UDP-glucuronosyltransferase with activity toward benzo(a)pyrene-7,8-diol, the proximate carcinogenic form of benzo(a)pyrene. Here we report the isolation of a benzo(a)pyrene-7,8-diol transferase-encoding cDNA, LC14, from an adult rat hepatocyte-derived cell line (RALA255-10G LCS-3). The predicted amino acid sequence of LC14 is nearly identical (5 differences out of 531 residues) to that deduced from UGT1A7, recently cloned at the genomic DNA level (Emi, Y., Ikushiro, S., and Kyanagi, T. (1995) J. Biochem. (Tokyo) 117, 392-399). Northern analysis of RNA from female F344 rat liver and LCS-3 cells revealed over a 40-fold and 4.4-fold enhancement by oltipraz treatment, respectively. Benzo(a)pyrene-7,8-diol glucuronidating activity was detected (0.4 nmol/106 cells/16 h) in AHH-1 cells transfected with the LC14 expression vector, pMF6-LC14-3. The LC14-encoded transferase exhibited even higher activity toward certain benzo(a)pyrene phenols, including the major 3- and 9-phenol metabolites (4.1 and 2.8 nmol/106 cells/16 h, respectively). The Km of the enzyme for (−)-trans benzo(a)pyrene-7,8-diol and 3-OH-BP was 15.5 and 12.3 μM, respectively. Northern analyses of total RNA revealed expression of LC14 or LC14-like RNA in all extrahepatic tissues tested. Marked inducibility by oltipraz was observed only in liver and (to a lesser extent) intestine. The results suggest that induction of UGT1A7 may explain the increased glucuronidating activities toward benzo(a)pyrene-7,8-diol and other metabolites that occur following treatment with polycyclic aromatic hydrocarbon-type inducing agents and oltipraz. UGT1A7 appears to represent an important cellular chemoprotective enzyme which mediates conjugation and elimination of toxic benzo(a)pyrene metabolites.