Miracle-dz/UniFAR-FTUs huggingface dataset:
Radiation Metabolomics. 2. Dose- and Time-Dependent Urinary Excretion of Deaminated Purines and Pyrimidines after Sublethal Gamma-Radiation Exposure in Mice

Abstract Tyburski, J. B. , Patterson, A. D. , Krausz, K. W. , Slavík, J., Fornace, A. J. Jr., Gonzalez, F. J. and Idle, J. R. Radiation Metabolomics. 2. Dose- and Time-Dependent Urinary Excretion of Deaminated Purines and Pyrimidines after Sublethal Gamma-Radiation Exposure in Mice. Radiat. Res. 172, 42-57 (2009). Gamma-radiation exposure of humans is a major public health concern as the threat of terrorism and potential hostile use of radiological devices increases worldwide. We report here the effects of sublethal γ-radiation exposure on the mouse urinary metabolome determined using ultra-performance liquid chromatography-coupled time-of-flight mass spectrometry-based metabolomics. Five urinary biomarkers of sublethal radiation exposure that were statistically significantly elevated during the first 24 h after exposure to doses ranging from 1 to 3 Gy were unequivocally identified by tandem mass spectrometry. These are deaminated purine and pyrimidine derivatives, namely, thymidine, 2′-deoxyuridine, 2′-deoxyxanthosine, xanthine and xanthosine. Furthermore, the aminopyrimidine 2′-deoxycytidine appeared to display reduced urinary excretion at 2 and 3 Gy. The elevated biomarkers displayed a time-dependent excretion, peaking in urine at 8–12 h but returning to baseline by 36 h after exposure. It is proposed that 2′-deoxyuridine and 2′-deoxyxanthosine arise as a result of γ irradiation by nitrosative deamination of 2′-deoxycytidine and 2′-deoxyguanosine, respectively, and that this further leads to increased synthesis of thymidine, xanthine and xanthosine. The urinary excretion of deaminated purines and pyrimidines, at the expense of aminopurines and aminopyrimidines, appears to form the core of the urinary radiation metabolomic signature of mice exposed to sublethal doses of ionizing radiation.
Peripherally Administered Angiotensin II AT1 Receptor Antagonists Are Anti‐stress Compounds in Vivo

Angiotensin II AT1 receptor blockers (ARBs) are commonly used in the clinical treatment of hypertension. Subcutaneous or oral administration of the ARB candesartan inhibits brain as well as peripheral AT1 receptors, indicating transport across the blood–brain barrier. Pretreatment with candesartan profoundly modifies the response to stress. The ARB prevents the peripheral and central sympathetic activation characteristic of isolation stress and abolishes the activation of the hypothalamic‐pituitary‐adrenal axis during isolation. In addition, candesartan prevents the isolation‐induced decrease in cortical corticotropin‐releasing factor 1 and benzodiazepine receptors induced by isolation. When administered before cold‐restraint stress, candesartan totally prevents the production of gastric ulcerations. This preventive effect of candesartan is the consequence of profound anti‐inflammatory effects, reduction of sympathetic stimulation, and preservation of blood flow to the gastric mucosa. The ARB does not reduce the hypothalamic‐pituitary‐adrenal axis stimulation during cold restraint. Preservation of the effects of endogenous glucocorticoids is essential for protection of the gastric mucosa during cold restraint. Administration of the ARB to nonstressed rats decreases anxiety in the elevated plus‐maze. Our results demonstrate that Angiotensin II, through AT1 receptor stimulation, is a major stress hormone, and that ARBs, in addition to their antihypertensive effects, may be considered for the treatment of stress‐related disorders.
Priorities of Low-Income Urban Residents for Interventions to Address the Socio-Economic Determinants of Health

Objectives. To determine the priorities of low-income urban residents for interventions that address the socio-economic determinants of health. Methods. We selected and estimated the cost of 16 interventions related to education, housing, nutrition, employment, health care, healthy behavior, neighborhood improvement, and transportation. Low-income residents of Washington, D.C. (N=431) participated in decision exercises to prioritize these interventions. Results. Given a budget valued at approximately twice an estimated cost of medical and dental care ($885), the interventions ultimately prioritized by the greatest percentage of individuals were: health insurance (95%), housing vouchers (82%) dental care (82%), job training (72%), adult education (63%), counseling (68%), healthy behavior incentives (68%), and job placement (67%). The percentages of respondents who received support for housing, adult education, and job training and placement were far less than the percentage who prioritized these interventions. Conclusions. Poor and low-income residents' priorities may usefully inform allocation of social services that affect health.
Reproductive factors, hormone use and gastric cancer risk: The Singapore Chinese Health Study

Gastric cancer incidence varies greatly worldwide, but is consistently twice as high in men than in women. The hormone‐related factors hypothesized to be associated with lower risk of gastric cancer in women have not been fully explored in populations with a high background risk of gastric cancer. The Singapore Chinese Health Study (SCHS) is a prospective cohort study in which 34,022 of the participants enrolled between 1993 and 1998 were women between 45 and 74 years of age. Information on reproductive histories, hormone replacement therapy (HRT) and oral contraceptive (OC) use was collected through in‐person interviews at baseline. As of December 31, 2013, 269 incident gastric cancer cases were identified. Multivariable‐adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate gastric cancer risk associations. Older age at natural menopause (≥55 versus <45 years: HR = 0.50, 95% CI: 0.25–0.99), type of menopause (other versus natural: HR = 0.48, 95% CI: 0.27–0.87) and greater years of menstrual cycling (fourth versus first quartile: HR = 0.67, 95% CI: 0.46–0.96) were associated with a decreased risk of gastric cancer. Ever use of OCs and HRT was also associated with reduced risk of gastric cancer; the multivariable‐adjusted HRs (95% CIs) were 0.40 (0.17–0.90) for use of HRT >3 years and 0.67 (0.47–0.94) for ever use of OCs, compared with never use. Reproductive factors associated with a longer window of fertility and the use of exogenous hormones were shown to reduce gastric cancer development in a cohort of Chinese women with a high background risk of gastric cancer.
Integrin ligands at a glance

Integrins are one of the major families of cell adhesion receptors ([Humphries, 2000][1]; [Hynes, 2002][2]). All integrins are non-covalently linked, heterodimeric molecules containing an α and a β subunit. Both subunits are type I transmembrane proteins, containing large extracellular domains and
Binding and release of cholesterol in the Osh4 protein of yeast

Sterols have been shown experimentally to bind to the Osh4 protein (a homolog of the oxysterol binding proteins) of Saccharomyces cerevisiae within a binding tunnel, which consists of antiparallel β‐sheets that resemble a β‐barrel and three α‐helices of the N‐terminus. This and other Osh proteins are essential for intracellular transport of sterols and ultimately cell life. Molecular dynamics (MD) simulations are used to study the binding of cholesterol to Osh4 at the atomic level. The structure of the protein is stable during the course of all MD simulations and has little deviation from the experimental crystal structure. The conformational stability of cholesterol within the binding tunnel is aided in part by direct or water‐mediated interactions between the 3‐hydroxyl (3‐OH) group of cholesterol and Trp46, Gln96, Tyr97, Asn165, and/or Gln181 as well as dispersive interactions with Phe42, Leu24, Leu39, Ile167, and Ile203. These residues along with other nonpolar residues in the binding tunnel and lid contribute nearly 75% to the total binding energy. The strongest and most populated interaction is between Gln96 and 3‐OH with a cholesterol/Gln96 interaction energy of −4.5 ± 1.0 kcal/mol. Phe42 has a similar level of attraction to cholesterol with −4.1 ± 0.3 kcal/mol. A MD simulation without the N‐terminus lid that covers the binding tunnel resulted in similar binding conformations and binding energies when compared with simulations with the full‐length protein. Steered MD was used to determine details of the mechanism used by Osh4 to release cholesterol to the cytoplasm. Phe42, Gln96, Asn165, Gln181, Pro211, and Ile206 are found to direct the cholesterol as it exits the binding tunnel as well as Lys109. The mechanism of sterol release is conceptualized as a molecular ladder with the rungs being amino acids or water‐mediated amino acids that interact with 3‐OH. Proteins 2009. Published 2008 Wiley‐Liss, Inc.
Complexity of MS management in the current treatment era

Prodigious progress in the treatment of multiple sclerosis (MS) has occurred over the last 20 years, with the licensing of more than 15 novel and highly effective disease-modifying therapies (DMTs) to treat the disease. In this new complex scenario, an update of the previous therapeutic guidelines published by the American Academy of Neurology (AAN) in 2002 is needed for an appropriate and effective use of the old and new agents in clinical practice.
Effects of risperidone on conduct and disruptive behavior disorders in children with subaverage IQs.

OBJECTIVE To determine whether risperidone is effective in reducing symptoms of disruptive behaviors (such as aggression, impulsivity, defiance of authority figures, and property destruction) associated with conduct disorder, oppositional defiant disorder, and disruptive behavior disorder-not otherwise specified in children with subaverage IQs. METHOD The trial consisted of a 1-week, single-blind, placebo run-in period and was followed by a 6-week, double-blind, placebo-controlled period. One hundred ten children (aged 5-12 years inclusive) with an IQ of 36-84 with a disruptive behavior disorder and a score of at least 24 on the Conduct Problem subscale of the Nisonger Child Behavior Rating Form (NCBRF) were enrolled. Eighty percent of subjects had comorbid attention-deficit/hyperactivity disorder (ADHD). Risperidone doses ranged from 0.02 to 0.06 mg/kg per day. Subjects were rated on the NCBRF, Aberrant Behavior Checklist, Behavior Problems Inventory, Clinical Global Impressions (CGI), modified California Verbal Learning Test (CVLT), and a continuous performance task (CPT). RESULTS The intention-to-treat analysis of risperidone-treated subjects showed a significant (p < .001) reduction in mean scores (from 33.4 at baseline to 17.6 at end point; 47.3% reduction) versus placebo-treated subjects (mean baseline of 32.6 to 25.8 at end point; 20.9% reduction) on the Conduct Problem subscale of the NCBRF. Between-group differences in favor of risperidone were seen as early as week 1 and were significant at all post-baseline visits. Other subscales showed significant improvement with risperidone compared with placebo. CGI scale ratings of improvement showed highly significant gains for risperidone over placebo. A subanalysis demonstrated that the effect of risperidone was unaffected by diagnosis, presence/absence of ADHD, psychostimulant use, IQ status, and somnolence. Risperidone produced no changes on the cognitive variables (CPT/modified CVLT). The most common side effects included somnolence, headache, appetite increase, and dyspepsia. Side effects related to extrapyramidal symptoms were reported in 7 (13.2%) and 3 (5.3%) of the subjects in the risperidone and placebo groups, respectively (p = .245). CONCLUSIONS Risperidone appears to be an adequately tolerated and effective treatment in children with subaverage IQs and severe disruptive behaviors such as aggression and destructive behavior.
Content popularity based fast content transmission in the wireless environment

Human behaviors may change over time, but people always tend to preserve their preference. People typically like similar types of contents, for example, movies that they watch in regular intervals with the same amount of interests. On the other hand, the Internet is moving towards a content-oriented structure from the host-oriented structure. Content-Centric Networking (CCN), a content-oriented paradigm, is being considered as a suitable way for the efficient and fast delivery of the requested content. The rapid increase in the usage of the smart mobile devices implies that a vast amount of contents is generated, which was not foreseen in the past. The contents generated by those devices should be cached in an efficient and proper manner so that they can be accessed quickly when needed. In this paper, we propose a content popularity identification mechanism to manage the contents properly. This mechanism ensures that less cache miss will occur and the overall content delivery time will decrease. Performance evaluation results are also provided to show the feasibility of the proposed mechanism.
Nitric Oxide Controls Fat Deposition in Dystrophic Skeletal Muscle by Regulating Fibro‐Adipogenic Precursor Differentiation

Duchenne muscular dystrophy (DMD) is an hereditary disease characterized by loss of muscle fibers and their progressive substitution by fat and fibrous tissue. Mesenchymal fibro‐adipogenic progenitors (FAPs) expressing the platelet‐derived growth factor receptor alpha (PDGFRα) are an important source of fibrosis and adipogenesis in dystrophic skeletal muscle. Among the therapies suggested for dystrophy are those based on nitric oxide (NO) donating drugs, the administration of which slows disease progression. NO has been shown to act by enhancing the regenerative potential of the diseased muscle. Whether it acts also by inhibiting fibrosis and adipogenesis was not known. Here, we show in vitro that NO regulates FAP fate through inhibition of their differentiation into adipocytes. In mdx mice, an animal model of DMD, treatment with the NO donating drug molsidomine reduced the number of PDGFRα+ cells as well as the deposition of both skeletal muscle fat and connective tissues. Inhibition of adipogenesis was due to NO‐induced increased expression of miR‐27b leading to downregulation of peroxisome proliferator‐activated receptors gamma (Pparγ1) expression in a pathway independent of cGMP generation. These findings reveal an additional effect of NO in dystrophic muscle that conceivably synergizes with its known effects on regeneration improvement and explain why NO‐based therapies appear effective in the treatment of muscular dystrophy. Stem Cells 2014;32:874–885
THE COOL PLUME:

Matrix-assisted laser desorption (MALD) as a soft volatilization and ionization technique was introduced three years ago? ’ Since then it acquired a reputation as a strong candidate for the analysis of high-molecular weight biopolymers. MALD remained in competition with electrospray ionization for the availability of a similar mass range and for their comparable detection limits. In other respects (e.g., the problem of interferences and coupling to separation techniques) they are considered to be complementary methods. However I in the atmosphere of excitement caused by the vast field of potential new applications, not too much attention has been paid to answering basic questions concerning the mechanism of the volatilization and ionization phenomena. The experiment itself is relatively simple. Solutions of the large (guest) molecules and of the matrix (host) material are mixed, providing 1:lOOO to 1:lO 000 molar ratios. A droplet of this mixture is dried on metallic substrate and excited by.a laser pulse in vacuum. The generated ions are typically analyzed by a time-offlight mass spectrometer. The astonishing finding was that extremely large molecules jmolecular weight exceeding 100 000 Da)’ could be transferred to the gas phase and ionized by this method. Some early efforts were directed toward broadening the range of applicable matrices and laser wavelengths and resulted in a rough outline of required matrix material properties? A promising candidate for a successful matrix should exhibit the following features:
Essential and Conditionally-Essential Nutrients in Clinical Nutrition

Glutamine and urea salvage . trauma . A R G I N I N E . O R N I T H I N E ~ K E T O G L U T A R A T E (OKG) . N U C L E I C A C I D S . P U R I N E A N D P Y R I M I D I N E BIOSYNTHESIS, S A L V A G E A N D C A T A B O L I S M . R E L A T I V E R A T E S O F S A L V A G E A N D D E NOVO S Y N T H E S I S O F P U R I N E S A N D P Y R I M I D I N E S . N U C L E O T I D E R E Q U I R E M E N T S F O R C E L L U L A R G R O W T H . E X O G E N O U S N U C L E O T I D E S I N G R O W T H E S S E N T I A L O R N O T ? E V I D E N C E F O R A P O S I T I V E R O L E F O R D I E T A R Y N U C L E O T I D E S I N C L I N I C A L N U T R I T I O N . Infection and immune function . Liver regeneration. Intestinal repair .
Mesleki Tükenmişlik ve Duygusal

The purpose of this study is to draw applicable conclusions based upon the analysis of data informing an understanding of the relationship between the variables from the theory of emotional intelligence and the variables known from occupational or professional burnout. For this aim, first theoretical framework about occupational burnout and emotional intelligence is drawn. Results of the application, which was held on 122 managers of 68 organizations, showed that there exists a negative correlation between occupational burnout and emotional intelligence.
Hidden danger: the raw facts about hepatitis E virus.

In 1980, hepatitis E was the last of the 5 recognized types of human hepatitis to be discovered; in 1990, the genome of the etiologic agent of hepatitis E, hepatitis E virus (HEV), was cloned and serological tests were developed [1]. It proved to be the most or second-most important cause of acute clinical hepatitis among adults throughout much of Asia, the Middle East, and Africa [2]. In contrast, HEV was rarely identified in industrialized countries, and the few reported cases of infection were usually in someone who had recently traveled to an endemic region. In the past few years this pattern has changed, as cases of endemic or autochthonous hepatitis E have been diagnosed with increasing frequency in individuals who have not traveled abroad.
Synaptic pathology in retinoschisis knockout (Rs1-/y) mouse retina and modification by rAAV-Rs1 gene delivery.

PURPOSE At an early age, the retinoschisin knockout (Rs1-KO) mouse retina has progressive photoreceptor degeneration with severe disruption of the outer plexiform layer (OPL) that decreases at older ages. The electroretinogram (ERG) undergoes parallel changes. The b-wave amplitude from bipolar cells is reduced disproportionately to the photoreceptor a-wave at young but not at older ages. The protein expression and morphology of the OPL in Rs1-KO mice was investigated at different ages, to explore the role of the synaptic layer in these ERG changes. METHODS Retinas of wild-type (Wt) and Rs1-KO mice from postnatal day (P)7 to 12 months were evaluated by light and electron microscopy (EM) and biochemistry. PSD95 (postsynaptic density protein), mGluR6 (metabotropic glutamate receptor subtype 6), retinoschisin (Rs1), the Müller cell proteins glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS), the bipolar cell marker protein kinase C alpha (PKCalpha), and the horizontal cell marker calbindin were localized by immunofluorescence and immuno-EM. Levels of PSD95 and mGluR6 were determined by quantitative Western blot. Rs1-KO mice treated by intravitreous injection of rAAV(2/2)-CMV-Rs1 in one eye at P14 were evaluated at 8 months by full-field scotopic ERG responses and retinal immunohistochemistry. RESULTS Rs1 was associated with the outer surface of synaptic membranes in wild-type (Wt) retinas. PSD95 and mGluR6 were juxtaposed in the OPL of the Rs1-KO retinas by P14, implying that synaptic structures are formed. Light microscopic retinal morphology was similar in Wt and Rs1-KO at P14, but by P21, the OPL was disrupted in Rs1-KO, and some PSD95 and mGluR6 was mislocalized in the outer nuclear layer (ONL). GFAP expression spanned all retinal layers. EM showed synaptic structures adjacent to photoreceptor nuclei. PSD95 and mGluR6 levels were normal at 1 month on Western blot but declined to 59% (P < 0.001) and 55% (P < 0.05) of Wt, respectively, by 4 months. Levels thereafter showed no further reduction out to 12 months. Eyes injected with AAV-Rs1 were studied at 8 months by immunohistochemistry and had higher expression of PSD95 and mGluR6 and less GFAP expression compared with fellow untreated eyes. CONCLUSIONS In the Rs1-KO mouse, retinal layer formation and synaptic protein expression in the OPL is normal up to P14, implying normal development of synaptic connections. Aberrant localization of synaptic proteins by P21 indicates that displacement of developing and/or mature synapses contributes to the b-wave reduction at young ages, when photoreceptor numbers and synaptic protein levels are normal. The subsequent decline in PSD95 and mGluR6 between 1 and 12 months in Rs1-KO retina mirrors the course of b-wave change and provides evidence of causal relationship between the ERG and OPL changes. These findings and the improved structural integrity of the OPL and b-wave amplitude after Rs1 gene transfer therapy provide a cellular and molecular basis for interpreting the changes in retinal signaling in this model.
Link prediction in complex networks: A local naïve Bayes model

The common-neighbor–based method is simple yet effective to predict missing links, which assume that two nodes are more likely to be connected if they have more common neighbors. In the traditional method, each common neighbor of two nodes contributes equally to the connection likelihood. In this letter, we argue that different common neighbors may play different roles and thus contributes differently, and propose a local naïve Bayes model. Extensive experiments were carried out on nine real networks. Compared with the traditional method, the present method can provide more accurate predictions.