Pilot Safety Evaluation of Varenicline for the Treatment of Methamphetamine Dependence.

Despite the worldwide extent of methamphetamine dependence, no medication has been shown to effectively treat afflicted individuals. One relatively unexplored approach is modulation of cholinergic system function. Animal research suggests that enhancement of central cholinergic activity, possibly at nicotinic acetylcholine receptors (nAChRs), can reduce methamphetamine-related behaviors. Further, preliminary findings indicate that rivastigmine, a cholinesterase inhibitor, may reduce craving for methamphetamine after administration of the drug in human subjects. We therefore performed a double-blind, placebo-controlled, crossover pilot study of the safety and tolerability of varenicline in eight methamphetamine-dependent research subjects. Varenicline is used clinically to aid smoking cessation, and acts as a partial agonist at α4β2 nAChRs with full agonist properties at α7 nAChRs. Oral varenicline dose was titrated over 1 week to reach 1 mg bid, and then was co-administered with 30 mg methamphetamine, delivered in ten intravenous infusions of 3 mg each. Varenicline was found to be safe in combination with IV methamphetamine, producing no cardiac rhythm disturbances or alterations in vital sign parameters. No adverse neuropsychiatric sequelae were detected either during varenicline titration or following administration of methamphetamine. The results suggest that varenicline warrants further investigation as a potential treatment for methamphetamine dependence

The SDGs in the EU Cultural Policies: an institutional communication perspective

The main goal of this research is to analyze the experts’ opinions on cultural sustainability and the importance of sustainable development in the EU cultural policies. Besides, the research analyses how institutional communication may contribute to the introduction of the sustainable development, and, specifically, of the SDGs in the European Union cultural policies’ definition. In order to achieve these objectives, we share a survey with several experts in EU cultural policies. The experts’ conclusions show that the SDGs need to be explicitly included in the cultural policies, adding a more practical perspective through specific projects and action plans. Institutional communication is a strategic factor for the success of sustainable development in terms of cultural policies and cultural sustainability in the European Union

Multiple Continental Radiations and Correlates of Diversification in Lupinus (Leguminosae): Testing for Key Innovation with Incomplete Taxon Sampling

Replicate radiations provide powerful comparative systems to address questions about the interplay between opportunity and innovation in driving episodes of diversification and the factors limiting their subsequent progression. However, such systems have been rarely documented at intercontinental scales. Here, we evaluate the hypothesis of multiple radiations in the genus Lupinus (Leguminosae), which exhibits some of the highest known rates of net diversification in plants. Given that incomplete taxon sampling, background extinction, and lineage-specific variation in diversification rates can confound macroevolutionary inferences regarding the timing and mechanisms of cladogenesis, we used Bayesian relaxed clock phylogenetic analyses as well as MEDUSA and BiSSE birth-death likelihood models of diversification, to evaluate the evolutionary patterns of lineage accumulation in Lupinus. We identified 3 significant shifts to increased rates of net diversification (r) relative to background levels in the genus (r = 0.18-0.48 lineages/myr). The primary shift occurred approximately 4.6 Ma (r = 0.48-1.76) in the montane regions of western North America, followed by a secondary shift approximately 2.7 Ma (r = 0.89-3.33) associated with range expansion and diversification of allopatrically distributed sister clades in the Mexican highlands and Andes. We also recovered evidence for a third independent shift approximately 6.5 Ma at the base of a lower elevation eastern South American grassland and campo rupestre clade (r = 0.36-1.33). Bayesian ancestral state reconstructions and BiSSE likelihood analyses of correlated diversification indicated that increased rates of speciation are strongly associated with the derived evolution of perennial life history and invasion of montane ecosystems. Although we currently lack hard evidence for "replicate adaptive radiations” in the sense of convergent morphological and ecological trajectories among species in different clades, these results are consistent with the hypothesis that iteroparity functioned as an adaptive key innovation, providing a mechanism for range expansion and rapid divergence in upper elevation regions across much of the New Worl

Accelerated placental aging in early onset preeclampsia pregnancies identified by DNA methylation.

Aim: To determine whether dynamic DNA methylation changes in the human placenta can be used to predict gestational age. Materials & methods: Publicly available placental DNA methylation data from 12 studies, together with our own dataset, using Illumina Infinium Human Methylation BeadChip arrays. Results & conclusion: We developed an accurate tool for predicting gestational age of placentas using 62 CpG sites. There was a higher predicted gestational age for placentas from early onset preeclampsia cases, but not term preeclampsia, compared with their chronological age. Therefore, early onset preeclampsia is associated with placental aging. Gestational age acceleration prediction from DNA methylation array data may provide insight into the molecular mechanisms of pregnancy disorders.Benjamin T Mayne, Shalem Y Leemaqz, Alicia K Smith, James Breen, Claire T Roberts, Tina Bianco-Miott

Spectroscopic and Theoretical Study of CuI Binding to His111 in the Human Prion Protein Fragment 106-115

The ability of the cellular prion protein (PrPC) to bind copper in vivo points to a physiological role for PrPC in copper transport. Six copper binding sites have been identified in the nonstructured N-terminal region of human PrPC. Among these sites, the His111 site is unique in that it contains a MKHM motif that would confer interesting CuI and CuII binding properties. We have evaluated CuI coordination to the PrP(106-115) fragment of the human PrP protein, using NMR and X-ray absorption spectroscopies and electronic structure calculations. We find that Met109 and Met112 play an important role in anchoring this metal ion. CuI coordination to His111 is pH-dependent: at pH >8, 2N1O1S species are formed with one Met ligand; in the range of pH 5-8, both methionine (Met) residues bind to CuI, forming a 1N1O2S species, where N is from His111 and O is from a backbone carbonyl or a water molecule; at pH <5, only the two Met residues remain coordinated. Thus, even upon drastic changes in the chemical environment, such as those occurring during endocytosis of PrPC (decreased pH and a reducing potential), the two Met residues in the MKHM motif enable PrPC to maintain the bound CuI ions, consistent with a copper transport function for this protein. We also find that the physiologically relevant CuI-1N1O2S species activates dioxygen via an inner-sphere mechanism, likely involving the formation of a copper(II) superoxide complex. In this process, the Met residues are partially oxidized to sulfoxide; this ability to scavenge superoxide may play a role in the proposed antioxidant properties of PrPC. This study provides further insight into the CuI coordination properties of His111 in human PrPC and the molecular mechanism of oxygen activation by this site.Fil: Arcos López, Trinidad. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzado; MéxicoFil: Qayyum, Munzarin. University of Stanford; Estados UnidosFil: Rivillas Acevedo, Lina. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzado; MéxicoFil: Miotto, Marco César. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina. Max Planck Laboratory for Structural Biology; ArgentinaFil: Grande Aztatzi, Rafael. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzado; MéxicoFil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina. Max Planck Laboratory for Structural Biology; ArgentinaFil: Hedman, Britt. University of Stanford; Estados UnidosFil: Hodgson, Keith O.. University of Stanford; Estados UnidosFil: Vela, Alberto. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzado; MéxicoFil: Solomon, Edward I.. University of Stanford; Estados UnidosFil: Quintanar, Liliana. Instituto Politécnico Nacional. Centro de Investigación y de Estudios Avanzado; Méxic

ALTERNATIVE DESIGN AND ECONOMIC FEASIBILITY OF AN EXPERIMENTAL WHR FOR INTAKE AIR CONDITIONING OF A LARGE INTERNAL COMBUSTION ENGINE

This work presents an alternative design for an experimental waste heat recovery thermal system to be coupled to a large turbocharged internal combustion engine for combustion air conditioning. The goal is to carry out a design of a new thermal system under restricted economic requirements for one of the generators set of Luiz Oscar Rodrigues de Melo Thermoelectric Power Plant. Thereby, a comparison with the original proposal from previous works is also developed in order to demonstrate the differences in terms of thermo-economic design parameters. The waste recovery thermal system produces sufficient chilled water through a single-effect absorption chiller, powered by hot water which is produced by recovering the exhaust gases residual heat to supply cooling applications on the combustion air. The results showed a significant reduction for the chiller capacity demand, from 550 to 185 RT, that would be enough to provide chilled water for 98.72% of the analyzed operation historical period. The economic feasibility indicators reveal the proposal for the alternative waste heat recovery system as the best financial option, presenting a lower investment cost (US$316,793.27 of savings) and a time for capital recovery of 2.14 years, 1.61 years shorter when compared with the initial WHR system

Large scale gene expression meta-analysis reveals tissue-specific, sex-biased gene expression in humans

The severity and prevalence of many diseases are known to differ between the sexes. Organ specific sex-biased gene expression may underpin these and other sexually dimorphic traits. To further our understanding of sex differences in transcriptional regulation, we performed meta-analyses of sex biased gene expression in multiple human tissues. We analyzed 22 publicly available human gene expression microarray data sets including over 2500 samples from 15 different tissues and 9 different organs. Briefly, by using an inverse-variance method we determined the effect size difference of gene expression between males and females. We found the greatest sex differences in gene expression in the brain, specifically in the anterior cingulate cortex, (1818 genes), followed by the heart (375 genes), kidney (224 genes), colon (218 genes), and thyroid (163 genes). More interestingly, we found different parts of the brain with varying numbers and identity of sex-biased genes, indicating that specific cortical regions may influence sexually dimorphic traits. The majority of sex-biased genes in other tissues such as the bladder, liver, lungs, and pancreas were on the sex chromosomes or involved in sex hormone production. On average in each tissue, 32% of autosomal genes that were expressed in a sex-biased fashion contained androgen or estrogen hormone response elements. Interestingly, across all tissues, we found approximately two-thirds of autosomal genes that were sex-biased were not under direct influence of sex hormones. To our knowledge this is the largest analysis of sex-biased gene expression in human tissues to date. We identified many sex-biased genes that were not under the direct influence of sex chromosome genes or sex hormones. These may provide targets for future development of sex-specific treatments for diseases.Benjamin T. Mayne, Tina Bianco-Miotto, Sam Buckberry, James Breen, Vicki Clifton, Cheryl Shoubridge and Claire T. Robert

Características da carcaça de Tourinhos Nelore x Limousin alimentados com dietas contendo gérmen de milho integral.

Foram avaliadas as características quantitativas das carcaças de 24 tourinhos Nelore X Limousin submetidos a dietas contendo 0%, 15% e 45% de gérmen de milho integral (GMI), terminados em confinamento, com peso e idade média inicial de 321,25 kg e vinte meses, respectivamente

Value of various PSA parameters for diagnosing prostate cancer in men with normal digital rectal examination

OBJECTIVES: The risks of identifying prostate cancer (PCa) in patients with serum total PSA (tPSA) between 4 and 10 ng/dl are between 25 and 35%. There are no data in Brazil showing the incidence of disease when all variables for PSA assessment are considered altogether, specifically tPSA, free fraction, PSA velocity and PSA stratified by age. The objective in this work was to define the incidence of disease in a population of men with abnormal values of PSA variables and normal digital rectal examination. MATERIALS AND METHODS: Between 1998 and 2003, 273 prostate biopsies were performed by the same radiologist and analyzed by the same pathologist. All patients had a normal digital rectal examination and biopsy had been indicated due to tPSA above 4 ng/dl or free-to-total PSA ratio (F/T PSA) below 15% or PSA velocity higher than 25% per year or a PSA level regarded as high for the age range. The relationship between these parameters and the positivity for prostate caner was determined. RESULTS: Patients' mean age was 63.8 years, and PCa was identified in 135 cases (49.5%). The incidence of PCa, related to unitary variations in tPSA, ranged from the limits of 33 to 80%, respectively, in tPSA < 3 and PSA between 15.1 to 20. When the other PSA parameters were assessed (free PSA, PSA according to age, rise velocity) PCa was detected in more than 25.3% of cases. CONCLUSION: When patients with normal digital rectal examination are selected for prostate biopsy due to tPSA levels above 4 or F/T PSA ratio lower than 15% or PSA velocity higher than 25% per year or high PSA for the age range, the incidence of PCa is quite higher than that observed in a population selected exclusively with basis on total PSA value.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Division of UrologyUNIFESP, EPM, Division of UrologySciEL

Twitter-based analysis of the dynamics of collective attention to political parties

Large-scale data from social media have a significant potential to describe complex phenomena in real world and to anticipate collective behaviors such as information spreading and social trends. One specific case of study is represented by the collective attention to the action of political parties. Not surprisingly, researchers and stakeholders tried to correlate parties' presence on social media with their performances in elections. Despite the many efforts, results are still inconclusive since this kind of data is often very noisy and significant signals could be covered by (largely unknown) statistical fluctuations. In this paper we consider the number of tweets (tweet volume) of a party as a proxy of collective attention to the party, identify the dynamics of the volume, and show that this quantity has some information on the elections outcome. We find that the distribution of the tweet volume for each party follows a log-normal distribution with a positive autocorrelation of the volume over short terms, which indicates the volume has large fluctuations of the log-normal distribution yet with a short-term tendency. Furthermore, by measuring the ratio of two consecutive daily tweet volumes, we find that the evolution of the daily volume of a party can be described by means of a geometric Brownian motion (i.e., the logarithm of the volume moves randomly with a trend). Finally, we determine the optimal period of averaging tweet volume for reducing fluctuations and extracting short-term tendencies. We conclude that the tweet volume is a good indicator of parties' success in the elections when considered over an optimal time window. Our study identifies the statistical nature of collective attention to political issues and sheds light on how to model the dynamics of collective attention in social media.Comment: 16 pages, 7 figures, 3 tables. Published in PLoS ON