725 research outputs found
Short-term dietary supplementation with fructose accelerates gastric emptying of a fructose but not a glucose solution
Objective
Short-term dietary glucose supplementation has been shown to accelerate the gastric emptying rate of both glucose and fructose solutions. The aim of this study was to examine gastric emptying rate responses to monosaccharide ingestion following short-term dietary fructose supplementation.
Methods
The gastric emptying rate of a fructose solution containing 36 g of fructose and an equicaloric glucose solution containing 39.6 g glucose monohydrate were measured in 10 healthy non-smoking men with and without prior fructose supplementation (water control) using a randomized crossover design. Gastric emptying rate was assessed for a period of 1 h using the [13C]breath test with sample collections at baseline and 10-min intervals following drink ingestion. Additionally, appetite ratings of hunger, fullness, and prospective food consumption were recorded at baseline and every 10 min using visual analog scales.
Results
Increased dietary fructose ingestion resulted in significantly accelerated half-emptying time of a fructose solution (mean = 48, SD = 6 versus 58, SD = 14 min control; P = 0.037), whereas the emptying of a glucose solution remained unchanged (mean = 85, SD = 31 versus 78, SD = 27 min control; P = 0.273). Time of maximal emptying rate of fructose was also significantly accelerated following increased dietary fructose intake (mean = 33, SD = 6 versus 38, SD = 9 min control; P = 0.042), while it remained unchanged for glucose (mean = 45, SD = 14 versus 44, SD = 14 min control; P = 0.757). No effects of supplementation were observed for appetite measures.
Conclusion
Three d of supplementation with 120 g/d of fructose resulted in an acceleration of gastric emptying rate of a fructose solution but not a glucose solution
Rah, rah, ROS: metabolic changes caused by loss of adhesion induce cell death
The high rate of glucose utilization by cancer cells has been well characterized. Recent data suggest that when normal mammary epithelial cells are cultured under nonadherent conditions, glucose consumption decreases, ATP levels fall, and concentrations of reactive oxygen species rise. The rise in reactive oxygen species causes death of nonadherent cells, which can be suppressed with antioxidants. Nonadherent ErbB2-transformed mammary epithelial cells maintain glucose transport and antioxidant production; however, antioxidants appear to enhance anchorage-independent growth. These findings integrate aspects of glucose metabolism, anoikis suppression and antioxidant production in tumor cell biology and suggest that antioxidant therapy could stimulate tumor survival
The Gaia-ESO Survey: Asymmetric expansion of the Lagoon Nebula cluster NGC 6530 from GES and Gaia DR2
The combination of precise radial velocities from multi-object spectroscopy and highly accurate proper motions from Gaia DR2 opens up the possibility for detailed 3D kinematic studies of young star-forming regions and clusters. Here, we perform such an analysis by combining Gaia-ESO Survey spectroscopy with Gaia astrometry for ∼900 members of the Lagoon Nebula cluster, NGC 6530. We measure the 3D velocity dispersion of the region to be 5.35+0.39 -0.34 km s-1, which is large enough to suggest the region is gravitationally unbound. The velocity ellipsoid is anisotropic, implying that the region is not sufficiently dynamically evolved to achieve isotropy, though the central part of NGC 6530 does exhibit velocity isotropy that suggests sufficient mixing has occurred in this denser part. We find strong evidence that the stellar population is expanding, though this is preferentially occurring in the declination direction and there is very little evidence for expansion in the right ascension direction. This argues against a simple radial expansion pattern, as predicted by models of residual gas expulsion. We discuss these findings in the context of cluster formation, evolution, and disruption theories.NJW acknowledges an STFC Ernest Rutherford Fellowship (grant number ST/M005569/1). RJP acknowledges support from the Royal Society in the form of a Dorothy Hodgkin Fellowship. AB acknowledges support from ICM (Iniciativa Científica Milenio) via the Núcleo Milenio de Formación Planetaria. EJA acknowledges support from the Spanish Government Ministerio de Ciencia, Innovacion y Universidades though grant AYA2016-75 931-C2-1 and from the State Agency for Research of the Spanish MCIU through the ‘Center of Excellence Severo Ochoa’ award for the Instituto de Astrofisica de Andalucia (SEV-2017-0709)
The Gaia-ESO Survey: Membership probabilities for stars in 32 open clusters from 3D kinematics
The Gaia-ESO Survey (GES) observed many open clusters as part of its
programme to spectroscopically characterise the various Milky Way populations.
GES spectroscopy and Gaia astrometry from its second data release are used here
to assign membership probabilities to targets towards 32 open clusters with
ages from 1-3800 Myr, based on maximum likelihood modelling of the 3D
kinematics of the cluster and field populations. From a parent catalogue of
14398 individual targets, 5033 stars with uniformly determined 3D velocities,
, and chemistry are assigned cluster membership with
probability , and with an average probability of 0.991. The robustness of
the membership probabilities is demonstrated using independent membership
criteria (lithium and parallax) in two of the youngest clusters. The addition
of radial velocities improves membership discrimination over proper motion
selection alone, especially in more distant clusters. The
kinematically-selected nature of the membership lists, independent of
photometry and chemistry, makes the catalogue a valuable resource for testing
stellar evolutionary models and investigating the time evolution of various
parameters
RNAi-Mediated c-Rel Silencing Leads to Apoptosis of B Cell Tumor Cells and Suppresses Antigenic Immune Response In Vivo
c-Rel is a member of the Rel/NF-κB transcription factor family and is predominantly expressed in lymphoid and myeloid cells, playing a critical role in lymphocyte proliferation and survival. Persistent activation of the c-Rel signal transduction pathway is associated with allergies, inflammation, autoimmune diseases, and a variety of human malignancies. To explore the potential of targeting c-Rel as a therapeutic agent for these disorders, we designed a small interfering RNA (siRNA) to silence c-Rel expression in vitro and in vivo. C-Rel-siRNA expression via a retroviral vector in a B cell tumor cell line leads to growth arrest and apoptosis of the tumor cells. Silencing c-Rel in primary B cells in vitro compromises their proliferative and survival response to CD40 activation signals, similar to the impaired response of c-Rel knockout B cells. Most important, in vivo silencing of c-Rel results in significant impairment in T cell-mediated immune responses to antigenic stimulation. Our study thus validates the efficacy of c-Rel-siRNA, and suggests the development of siRNA-based therapy, as well as small molecular inhibitors for the treatment of B cell tumors as well as autoimmune diseases
An exploratory randomised controlled trial of a premises-level intervention to reduce alcohol-related harm including violence in the United Kingdom
<b>Background</b><p></p>
To assess the feasibility of a randomised controlled trial of a licensed premises intervention to reduce severe intoxication and disorder; to establish effect sizes and identify appropriate approaches to the development and maintenance of a rigorous research design and intervention implementation.<p></p>
<b>Methods</b><p></p>
An exploratory two-armed parallel randomised controlled trial with a nested process evaluation. An audit of risk factors and a tailored action plan for high risk premises, with three month follow up audit and feedback. Thirty-two premises that had experienced at least one assault in the year prior to the intervention were recruited, match paired and randomly allocated to control or intervention group. Police violence data and data from a street survey of study premises’ customers, including measures of breath alcohol concentration and surveyor rated customer intoxication, were used to assess effect sizes for a future definitive trial. A nested process evaluation explored implementation barriers and the fidelity of the intervention with key stakeholders and senior staff in intervention premises using semi-structured interviews.<p></p>
<b>Results</b><p></p>
The process evaluation indicated implementation barriers and low fidelity, with a reluctance to implement the intervention and to submit to a formal risk audit. Power calculations suggest the intervention effect on violence and subjective intoxication would be raised to significance with a study size of 517 premises.<p></p>
<b>Conclusions</b><p></p>
It is methodologically feasible to conduct randomised controlled trials where licensed premises are the unit of allocation. However, lack of enthusiasm in senior premises staff indicates the need for intervention enforcement, rather than voluntary agreements, and on-going strategies to promote sustainability
New ophthalmosaurid ichthyosaurs from the European lower cretaceous demonstrate extensive ichthyosaur survival across the Jurassic–Cretaceous boundary
Background
Ichthyosauria is a diverse clade of marine amniotes that spanned most of the Mesozoic. Until recently, most authors interpreted the fossil record as showing that three major extinction events affected this group during its history: one during the latest Triassic, one at the Jurassic–Cretaceous boundary (JCB), and one (resulting in total extinction) at the Cenomanian-Turonian boundary. The JCB was believed to eradicate most of the peculiar morphotypes found in the Late Jurassic, in favor of apparently less specialized forms in the Cretaceous. However, the record of ichthyosaurs from the Berriasian–Barremian interval is extremely limited, and the effects of the end-Jurassic extinction event on ichthyosaurs remains poorly understood.
Methodology/Principal Findings
Based on new material from the Hauterivian of England and Germany and on abundant material from the Cambridge Greensand Formation, we name a new ophthalmosaurid, Acamptonectes densus gen. et sp. nov. This taxon shares numerous features with Ophthalmosaurus, a genus now restricted to the Callovian–Berriasian interval. Our phylogenetic analysis indicates that Ophthalmosauridae diverged early in its history into two markedly distinct clades, Ophthalmosaurinae and Platypterygiinae, both of which cross the JCB and persist to the late Albian at least. To evaluate the effect of the JCB extinction event on ichthyosaurs, we calculated cladogenesis, extinction, and survival rates for each stage of the Oxfordian–Barremian interval, under different scenarios. The extinction rate during the JCB never surpasses the background extinction rate for the Oxfordian–Barremian interval and the JCB records one of the highest survival rates of the interval.
Conclusions/Significance
There is currently no evidence that ichthyosaurs were affected by the JCB extinction event, in contrast to many other marine groups. Ophthalmosaurid ichthyosaurs remained diverse from their rapid radiation in the Middle Jurassic to their total extinction at the beginning of the Late Cretaceous
Spectral quantification of nonlinear behaviour of the nearshore seabed and correlations with potential forcings at Duck, N.C., U.S.A
Local bathymetric quasi-periodic patterns of oscillation are identified from
monthly profile surveys taken at two shore-perpendicular transects at the USACE
field research facility in Duck, North Carolina, USA, spanning 24.5 years and
covering the swash and surf zones. The chosen transects are the two furthest
(north and south) from the pier located at the study site. Research at Duck has
traditionally focused on one or more of these transects as the effects of the
pier are least at these locations. The patterns are identified using singular
spectrum analysis (SSA). Possible correlations with potential forcing
mechanisms are discussed by 1) doing an SSA with same parameter settings to
independently identify the quasi-periodic cycles embedded within three
potentially linked sequences: monthly wave heights (MWH), monthly mean water
levels (MWL) and the large scale atmospheric index known as the North Atlantic
Oscillation (NAO) and 2) comparing the patterns within MWH, MWL and NAO to the
local bathymetric patterns. The results agree well with previous patterns
identified using wavelets and confirm the highly nonstationary behaviour of
beach levels at Duck; the discussion of potential correlations with
hydrodynamic and atmospheric phenomena is a new contribution. The study is then
extended to all measured bathymetric profiles, covering an area of 1100m
(alongshore) by 440m (cross-shore), to 1) analyse linear correlations between
the bathymetry and the potential forcings using multivariate empirical
orthogonal functions (MEOF) and linear correlation analysis and 2) identify
which collective quasi-periodic bathymetric patterns are correlated with those
within MWH, MWL or NAO, based on a (nonlinear) multichannel singular spectrum
analysis (MSSA). (...continued in submitted paper)Comment: 50 pages, 3 tables, 8 figure
Extragalactic Results from the Infrared Space Observatory
More than a decade ago the IRAS satellite opened the realm of external
galaxies for studies in the 10 to 100 micron band and discovered emission from
tens of thousands of normal and active galaxies. With the 1995-1998 mission of
the Infrared Space Observatory the next major steps in extragalactic infrared
astronomy became possible: detailed imaging, spectroscopy and
spectro-photometry of many galaxies detected by IRAS, as well as deep surveys
in the mid- and far- IR. The spectroscopic data reveal a wealth of detail about
the nature of the energy source(s) and about the physical conditions in
galaxies. ISO's surveys for the first time explore the infrared emission of
distant, high-redshift galaxies. ISO's main theme in extragalactic astronomy is
the role of star formation in the activity and evolution of galaxies.Comment: 106 pages, including 17 figures. Ann.Rev.Astron.Astrophys. (in
press), a gzip'd pdf file (667kB) is also available at
http://www.mpe.mpg.de/www_ir/preprint/annrev2000.pdf.g
Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.
Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies
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