10,791 research outputs found
The activating mutation R201C in GNAS promotes intestinal tumourigenesis in Apc(Min/+) mice through activation of Wnt and ERK1/2 MAPK pathways.
Somatically acquired, activating mutations of GNAS, the gene encoding the stimulatory G-protein Gsalpha subunit, have been identified in kidney, thyroid, pituitary, leydig cell, adrenocortical and, more recently, in colorectal tumours, suggesting that mutations such as R201C may be oncogenic in these tissues. To study the role of GNAS in intestinal tumourigenesis, we placed GNAS R201C under the control of the A33-antigen promoter (Gpa33), which is almost exclusively expressed in the intestines. The GNAS R201C mutation has been shown to result in the constitutive activation of Gsalpha and adenylate cyclase and to lead to the autonomous synthesis of cyclic adenosine monophosphate (cAMP). Gpa33(tm1(GnasR201C)Wtsi/+) mice showed significantly elevated cAMP levels and a compensatory upregulation of cAMP-specific phosphodiesterases in the intestinal epithelium. GNAS R201C alone was not sufficient to induce tumourigenesis by 12 months, but there was a significant increase in adenoma formation when Gpa33(tm1(GnasR201C)Wtsi/+) mice were bred onto an Apc(Min/+) background. GNAS R201C expression was associated with elevated expression of Wnt and extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase (ERK1/2 MAPK) pathway target genes, increased phosphorylation of ERK1/2 MAPK and increased immunostaining for the proliferation marker Ki67. Furthermore, the effects of GNAS R201C on the Wnt pathway were additive to the inactivation of Apc. Our data strongly suggest that activating mutations of GNAS cooperate with inactivation of APC and are likely to contribute to colorectal tumourigenesis
Use of ultrasound elasticity imaging to monitor the response of a primary breast cancer to neoadjuvant chemotherapy in one patient in a pilot study
Rectal cancer management during the COVID-19 pandemic (ReCaP): multicentre prospective observational study
Human rights, non-refoulement and the protection of refugees in Hong Kong
Although the 1951 Convention relating to the Status of Refugees and its 1967 Protocol do not apply to Hong Kong, asylum seekers have challenged Hong Kong's lack of an adequate refugee policy in a series of judicial review actions grounded in human rights and common law principles. This article focuses on two cases in particular in which the applicants have attempted to rely, in part, on a right to non-refoulement, derived from international and domestic law, to compel the Government to establish procedures to determine the status of refugees and other similar categories of claimants. The first, Secretary for Security v. Sakthevel Prabakar, led to the creation of a 'torture screening' mechanism based on article 3 of the Convention against Torture and other Cruel, Inhuman, or Degrading Treatment or Punishment. In the second, C v. Director of Immigration, the court considered whether a rule of non-refoulement has emerged in customary international law and, if so, whether it applies to Hong Kong and requires government-administered refugee status determination. Although the applicants failed at first instance,1 an analysis of the judgment with reference to Hong Kong's human rights obligations reveals gaps in the court's reasoning and demonstrates the potential for greater reliance on these standards as the basis for developing a more comprehensive protection framework. This examination of the Hong Kong experience may have broader comparative value, especially in the Asian region and in jurisdictions not bound by the Refugee Convention or its Protocol. © The Author (2010). Published by Oxford University Press. All rights reserved.postprin
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Equity effects of children’s physical activity interventions: a systematic scoping review
BACKGROUND: Differential effects of physical activity (PA) interventions across population sub-groups may contribute to inequalities in health. This systematic scoping review explored the state of the evidence on equity effects in response to interventions targeting children’s PA promotion. The aims were to assess and summarise the availability of evidence on differential intervention effects of children’s PA interventions across gender, body mass index, socioeconomic status, ethnicity, place of residence and religion. METHODS: Using a pre-piloted search strategy, six electronic databases were searched for controlled intervention trials, aiming to increase PA in children (6–18 years of age), that used objective forms of measurement. Screening and data extraction were conducted in duplicate. Reporting of analyses of differential effects were summarized for each equity characteristic and logistic regression analyses run to investigate intervention characteristics associated with the reporting of equity analyses. RESULTS: The literature search identified 13,052 publications and 7963 unique records. Following a duplicate screening process 125 publications representing 113 unique intervention trials were included. Although the majority of trials collected equity characteristics at baseline, few reported differential effects analyses across the equity factors of interest. All 113 included interventions reported gender at baseline with 46% of non-gender targeted interventions reporting differential effect analyses by gender. Respective figures were considerably smaller for body mass index, socioeconomic status, ethnicity, place of residence and religion. There was an increased likelihood of studying differential effects in school based interventions (OR: 2.9 [1.2–7.2]) in comparison to interventions in other settings, larger studies (per increase in 100 participants; 1.2 [1.0 – 1.4]); and where a main intervention effect on objectively measured PA was reported (3.0 [1.3–6.8]). CONCLUSIONS: Despite regularly collecting relevant information at baseline, most controlled trials of PA interventions in children do not report analyses of differences in intervention effect across outlined equity characteristics. Consequently, there is a scarcity of evidence concerning the equity effects of these interventions, particularly beyond gender, and a lack of understanding of subgroups that may benefit from, or be disadvantaged by, current intervention efforts. Further evidence synthesis and primary research is needed to effectively understand the impact of PA interventions on existing behavioural inequalities within population subgroups of children.Funding for this study and the work of all authors was supported, wholly or in part, by the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence (RES-590-28-0002). Funding from the British Heart Foundation, Department of Health, Economic and Social Research Council, Medical Research Council, and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged. Rebecca Love is funded by a Gates Cambridge Scholarship. The work of Esther M F van Sluijs was supported by the Medical Research Council (MC_UU_12015/7)
Conductivity and quasinormal modes in holographic theories
We show that in field theories with a holographic dual the retarded Green's
function of a conserved current can be represented as a convergent sum over the
quasinormal modes. We find that the zero-frequency conductivity is related to
the sum over quasinormal modes and their high-frequency asymptotics via a sum
rule. We derive the asymptotics of the quasinormal mode frequencies and their
residues using the phase-integral (WKB) approach and provide analytic insight
into the existing numerical observations concerning the asymptotic behavior of
the spectral densities.Comment: 24 pages, 3 figure
Lyman Alpha Blobs as an Observational Signature of Cold Accretion Streams into Galaxies
Recent hydrodynamic simulations of galaxy formation reveal streams of cold (T
~ 1e4 K) gas flowing into the centers of dark matter halos as massive as
1e12-1e13.5 M_sun at redshifts z~1-3. In this paper we show that if > 20% of
the gravitational binding energy of the gas is radiated away, then the
simulated cold flows are spatially extended Lyman Alpha (Lya) sources with
luminosities, Lya line widths, and number densities that are comparable to
those of observed Lya blobs. Furthermore, the filamentary structure of the cold
flows can explain the wide range of observed Lya blob morphologies. Since the
most massive halos form in dense environments, the association of Lya blobs
with overdense regions arise naturally. We argue that Lya blobs - even those
which are clearly associated with starburst galaxies or quasars - provide
direct observational support for the cold accretion mode of galaxies. We
discuss various testable predictions of this association.Comment: MNRAS in press. 13 pages, 6 figures. Discussion + references added.
Main conclusions unaffecte
Neuropsychological Deficits Are Correlated with Frontal Hypometabolism in Positron Emission Tomography Studies of Older Alcoholic Patients
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66315/1/j.1530-0277.1993.tb00750.x.pd
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