Symmetry groupoids and admissible vector fields for coupled cell networks

The space of admissible vector fields, consistent with the structure of a network of coupled dynamical systems, can be specified in terms of the network's symmetry groupoid. The symmetry groupoid also determines the robust patterns of synchrony in the network – those that arise because of the network topology. In particular, synchronous cells can be identified in a canonical manner to yield a quotient network. Admissible vector fields on the original network induce admissible vector fields on the quotient, and any dynamical state of such an induced vector field can be lifted to the original network, yielding an analogous state in which certain sets of cells are synchronized. In the paper, necessary and sufficient conditions are specified for all admissible vector fields on the quotient to lift in this manner. These conditions are combinatorial in nature, and the proof uses invariant theory for the symmetric group. Also the symmetry groupoid of a quotient is related to that of the original network, and it is shown that there is a close analogy with the usual normalizer symmetry that arises in group-equivariant dynamics

Physical and biological characteristics of multi drug resistance (MDR): an integral approach considering pH and drug resistance in cancer

The role of the Warburg effect in cancer remains to be elucidated with a resurgence in research efforts over the past decade. Why a cancer cell would prefer to use energy inefficient glycolysis, leading to an alteration of pH both inside and outside of the cell, remains to be uncovered. The development of MDR represents a major challenge in the treatment of cancer and it is explained, so far, by the over expression of drug transporters such as the well-known and archetypal P-glycoprotein (Pgp). However, controversies exist regarding the function of Pgp in multi-drug resistance. We suggest here that Pgp-mediated MDR relies fundamentally on pH alterations mediated by the Warburg effect. Furthermore, we propose that the use of proton pump and/or transporters inhibitors (PPIs/PTIs) in cancer are key to controlling both MDR, i.e. sensitize tumors to antineoplastic agents, and drug-related adverse effects

A molecular biology and phase II trial of lapatinib in children with refractory CNS malignancies: a pediatric brain tumor consortium study.

High expression of ERBB2 has been reported in medulloblastoma and ependymoma; EGFR is amplified and over-expressed in brainstem glioma suggesting these proteins as potential therapeutic targets. We conducted a molecular biology (MB) and phase II study to estimate inhibition of tumor ERBB signaling and sustained responses by lapatinib in children with recurrent CNS malignancies. In the MB study, patients with recurrent medulloblastoma, ependymoma, and high-grade glioma (HGG) undergoing resection were stratified and randomized to pre-resection treatment with lapatinib 900 mg/m(2) dose bid for 7-14 days or no treatment. Western blot analysis of ERBB expression and pathway activity in fresh tumor obtained at surgery estimated ERBB receptor signaling inhibition in vivo. Drug concentration was simultaneously assessed in tumor and plasma. In the phase II study, patients, stratified by histology, received lapatinib continuously, to assess sustained response. Eight patients, on the MB trial (four medulloblastomas, four ependymomas), received a median of two courses (range 1-6+). No intratumoral target inhibition by lapatinib was noted in any patient. Tumor-to-plasma ratios of lapatinib were 10-20 %. In the 34 patients (14 MB, 10 HGG, 10 ependymoma) in the phase II study, lapatinib was well-tolerated at 900 mg/m(2) dose bid. The median number of courses in the phase II trial was two (range 1-12). Seven patients (three medulloblastoma, four ependymoma) remained on therapy for at least four courses range (4-26). Lapatinib was well-tolerated in children with recurrent or CNS malignancies, but did not inhibit target in tumor and had little single agent activity.Fil: Fouladi, Maryam. St. Jude Children’s Research Hospital; Estados UnidosFil: Stewart, Clinton F.. St. Jude Children’s Research Hospital; Estados UnidosFil: Blaney, Susan M.. Baylor College of Medicine. Texas Children’s Cancer Center; Estados UnidosFil: Onar Thomas, Arzu. St. Jude Children’s Research Hospital; Estados UnidosFil: Schaiquevich, Paula Susana. St. Jude Children’s Research Hospital; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Packer, Roger J.. Children’s National Medical Center; Estados UnidosFil: Goldman, Stewart. Anne and Robert H. Lurie Children’s Hospital of Chicago; Estados UnidosFil: Geyer, J. Rusell. Children’s Hospital and Regional Medical Center; Estados UnidosFil: Gajjar, Amar. St. Jude Children’s Research Hospital; Estados UnidosFil: Kun, Larry E.. St. Jude Children’s Research Hospital; Estados UnidosFil: Boyett, James M.. St. Jude Children’s Research Hospital; Estados UnidosFil: Gilbertson, Richard J.. St. Jude Children’s Research Hospital; Estados Unido

Perspectives on environment and human health:an editorial

Human health and wellbeing are intimately linked to the state of the environment [...]</jats:p

Systematic reviews of and integrated report on the quantitative, qualitative and economic evidence base for the management of obesity in men

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Obesity increases the risk of many serious illnesses such as coronary heart disease, type 2 diabetes and osteoarthritis. More men than women are overweight or obese in the UK but men are less likely to perceive their weight as a problem and less likely to engage with weight-loss services.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Objective&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The aim of this study was to systematically review evidence-based management strategies for treating obesity in men and investigate how to engage men in obesity services by integrating the quantitative, qualitative and health economic evidence base.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Data sources&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Electronic databases including MEDLINE, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials, the Database of Abstracts of Reviews of Effects and the NHS Economic Evaluation Database were searched from inception to January 2012, with a limited update search in July 2012. Subject-specific websites, reference lists and professional health-care and commercial organisations were also consulted.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Review methods&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Six systematic reviews were conducted to consider the clinical effectiveness, cost-effectiveness and qualitative evidence on interventions for treating obesity in men, and men in contrast to women, and the effectiveness of interventions to engage men in their weight reduction. Randomised controlled trials (RCTs) with follow-up data of at least 1 year, or any study design and length of follow-up for UK studies, were included. Qualitative and mixed-method studies linked to RCTs and non-randomised intervention studies, and UK-based, men-only qualitative studies not linked to interventions were included. One reviewer extracted data from the included studies and a second reviewer checked data for omissions or inaccuracies. Two reviewers carried out quality assessment. We undertook meta-analysis of quantitative data and a realist approach to integrating the qualitative and quantitative evidence synthesis.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt;&lt;p&gt;&lt;/p&gt; From a total of 12,764 titles reviewed, 33 RCTs with 12 linked reports, 24 non-randomised reports, five economic evaluations with two linked reports, and 22 qualitative studies were included. Men were more likely than women to benefit if physical activity was part of a weight-loss programme. Reducing diets tended to produce more favourable weight loss than physical activity alone (mean weight change after 1 year from a reducing diet compared with an exercise programme -3.2 kg, 95% CI -4.8 kg to -1.6 kg). The type of reducing diet did not affect long-term weight loss. A reducing diet plus physical activity and behaviour change gave the most effective results. Low-fat reducing diets, some with meal replacements, combined with physical activity and behaviour change training gave the most effective long-term weight change in men [-5.2 kg (standard error 0.2 kg) after 4 years]. Such trials may prevent type 2 diabetes in men and improve erectile dysfunction. Although fewer men joined weight-loss programmes, once recruited they were less likely to drop out than women (difference 11%, 95% CI 8% to 14%). The perception of having a health problem (e.g. being defined as obese by a health professional), the impact of weight loss on health problems and desire to improve personal appearance without looking too thin were motivators for weight loss amongst men. The key components differ from those found for women, with men preferring more factual information on how to lose weight and more emphasis on physical activity programmes. Interventions delivered in social settings were preferred to those delivered in health-care settings. Group-based programmes showed benefits by facilitating support for men with similar health problems, and some individual tailoring of advice assisted weight loss in some studies. Generally, men preferred interventions that were individualised, fact-based and flexible, which used business-like language and which included simple to understand information. Preferences for men-only versus mixed-sex weight-loss group programmes were divided. In terms of context, programmes which were cited in a sporting context where participants have a strong sense of affiliation showed low drop out rates and high satisfaction. Although some men preferred weight-loss programmes delivered in an NHS context, the evidence comparing NHS and commercial programmes for men was unclear. The effect of family and friends on participants in weight-loss programmes was inconsistent in the evidence reviewed - benefits were shown in some cases, but the social role of food in maintaining relationships may also act as a barrier to weight loss. Evidence on the economics of managing obesity in men was limited and heterogeneous.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Limitations&lt;/b&gt;&lt;p&gt;&lt;/p&gt; The main limitations were the limited quantity and quality of the evidence base and narrow outcome reporting, particularly for men from disadvantaged and minority groups. Few of the studies were undertaken in the UK.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Weight reduction for men is best achieved and maintained with the combination of a reducing diet, physical activity advice or a physical activity programme, and behaviour change techniques. Tailoring interventions and settings for men may enhance effectiveness, though further research is needed to better understand the influence of context and content. Future studies should include cost-effectiveness analyses in the UK setting

Caprine PRNP polymorphisms N146S and Q222K are associated with proteolytic cleavage of PrPC

Abstract Expression of the cellular prion protein (PrPC) is crucial for the development of prion diseases. Amino acid changes in PrPC or a reduced amount of PrPC may modulate disease resistance. The relative abundance of C1, a natural α-cleavage fragment of PrPC, was previously found to be associated with a resistant PRNP genotype in sheep. Goats are another small ruminant where classical scrapie susceptibility is under strong genetic control. In this study, we assessed PrPC in goats for the existence of similar associations between PrPC fragments and genotype. Brain tissue homogenates from scrapie-free goats with wild type PRNP or polymorphisms (I142M, H143R, N146S, or Q222K) were deglycosylated prior to immunoblot for assessment of the relative abundance of the C1 fragment of PrPC. The presence of K222 or S146 alleles demonstrated significantly different relative levels of C1 compared to that observed in wild type goats, which suggests that the genotype association with C1 is neither unique to sheep nor exclusive to the ovine Q171R dimorphism

Perspectives on environment and human health: an editorial

Human health and wellbeing are intimately linked to the state of the environment [...]This editorial work received from the European Union through the European Regional Development Fund based on COMPETE 2020 (Programa Operacional da Competitividade e Internacionalização) and projects ICT UIDB/04683/2020 and UIDP/04683/2020

Water use and yield of soybean under various irrigation regimes and severe water stress. Application of AquaCrop and SIMDualKc models

Data relative to two soybean seasons, several irrigation scheduling treatments, including moderate and severe deficit irrigation, and rain-fed cropping were used to parameterize and assess the performance of models AquaCrop and SIMDualKc, the latter combined with the Stewart’s yield model. SIMDualKc applies the FAO56 dual crop coefficient approach for computing and partitioning evapotranspiration (ET) into actual crop transpiration (Tc act) and soil evaporation (Es), while AquaCrop uses an approach that depends on the canopy cover curve. The calibration-validations of models were performed by comparing observed and predicted soil water content (SWC) and grain yield. SIMDualKc showed good accuracy for SWC estimations, with normalized root mean square error (NRMSE) 7.6%. AquaCrop was less accurate, with NRMSE 9.2%. Differences between models regarding the water balance terms were notable, and the ET partition revealed a trend for under-estimation of Tc act by AquaCrop, mainly under severe water stress. Yield predictions with SIMDualKc-Stewart models produced NRMSE < 15% while predictions with AquaCrop resulted in NRMSE 23% due to under-estimation of Tc act, particularly for water stressed treatments. Results show the appropriateness of SIMDualKc to support irrigation scheduling and assessing impacts on yield when combined with Stewart’s modelinfo:eu-repo/semantics/publishedVersio

Experimental Bovine Spongiform Encephalopathy in Squirrel Monkeys:The Same Complex Proteinopathy Appearing after Very Different Incubation Times

Incubation periods in humans infected with transmissible spongiform encephalopathy (TSE) agents can exceed 50 years. In humans infected with bovine spongiform encephalopathy (BSE) agents, the effects of a “species barrier,” often observed when TSE infections are transmitted from one species to another, would be expected to increase incubation periods compared with transmissions of same infectious agents within the same species. As part of a long-term study investigating the susceptibility to BSE of cell cultures used to produce vaccines, we inoculated squirrel monkeys (Saimiri sp., here designated SQ) with serial dilutions of a bovine brain suspension containing the BSE agent and monitored them for as long as ten years. Previously, we showed that SQ infected with the original “classical” BSE agent (SQ-BSE) developed a neurological disease resembling that seen in humans with variant CJD (vCJD). Here, we report the final characterization of the SQ-BSE model. We observed an unexpectedly marked difference in incubation times between two animals inoculated with the same dilution and volume of the same C-BSE bovine brain extract on the same day. SQ-BSE developed, in addition to spongiform changes and astrogliosis typical of TSEs, a complex proteinopathy with severe accumulations of protease-resistant prion protein (PrP(TSE)), hyperphosphorylated tau (p-tau), ubiquitin, and α-synuclein, but without any amyloid plaques or β-amyloid protein (Aβ) typical of Alzheimer’s disease. These results suggest that PrP(TSE) enhanced the accumulation of several key proteins characteristically seen in human neurodegenerative diseases. The marked variation in incubation periods in the same experimental TSE should be taken into account when modeling the epidemiology of human TSEs

Conformational insights and vibrational study of a promising anticancer agent: the role of the ligand in Pd(ii)–amine complexes

This study reports the first complete vibrational analysis of a dinuclear polyamine-based compound displaying antitumour properties.</p