63 research outputs found
Metabolic effects of diets differing in glycaemic index depend on age and endogenous GIP
Aims/hypothesis
High- vs low-glycaemic index (GI) diets unfavourably affect body fat mass and metabolic markers in rodents. Different effects of these diets could be age-dependent, as well as mediated, in part, by carbohydrate-induced stimulation of glucose-dependent insulinotrophic polypeptide (GIP) signalling.
Methods
Young-adult (16 weeks) and aged (44 weeks) male wild-type (C57BL/6J) and GIP-receptor knockout (Gipr â/â ) mice were exposed to otherwise identical high-carbohydrate diets differing only in GI (20â26 weeks of intervention, nâ=â8â10 per group). Diet-induced changes in body fat distribution, liver fat, locomotor activity, markers of insulin sensitivity and substrate oxidation were investigated, as well as changes in the gene expression of anorexigenic and orexigenic hypothalamic factors related to food intake.
Results
Body weight significantly increased in young-adult high- vs low-GI fed mice (two-way ANOVA, pâ<â0.001), regardless of the Gipr genotype. The high-GI diet in young-adult mice also led to significantly increased fat mass and changes in metabolic markers that indicate reduced insulin sensitivity. Even though body fat mass also slightly increased in high- vs low-GI fed aged wild-type mice (pâ<â0.05), there were no significant changes in body weight and estimated insulin sensitivity in these animals. However, aged Gipr â/â vs wild-type mice on high-GI diet showed significantly lower cumulative net energy intake, increased locomotor activity and improved markers of insulin sensitivity.
Conclusions/interpretation
The metabolic benefits of a low-GI diet appear to be more pronounced in younger animals, regardless of the Gipr genotype. Inactivation of GIP signalling in aged animals on a high-GI diet, however, could be beneficial
Effect of photon flux densities on regulation of carotenogenesis and cell viability of Haematococcus pluvialis (Chlorophyceae)
The green alga Haematococcus pluvialis produces large amounts of the pink carotenoid astaxanthin under high photon flux density (PFD) and other oxidative stress conditions. However, the regulation and physiological role of carotenogenesis leading to astaxanthin formation is not well understood. Comparative transcriptional expression of five carotenoid genes along with growth and pigment composition as a function of PFD was studied using a wild-type and an astaxanthin-overproduction mutant of H. pluvialis NIES144. The results indicate that astaxanthin biosynthesis was mainly under transcriptional control of the gene encoding carotenoid hydroxylase, and to a lesser extent, the genes encoding isopentenyl isomerase and phytoene desaturase, and to the least extent, the genes encoding phytoene synthase and carotenoid oxygenase. The expression of a plastid terminal oxidase (PTOX) gene ptox2 underwent transient up-regulation under elevated PFDs, suggesting that PTOX may be functionally coupled with phytoene desaturase through the plastoquinone pool and may play a role in reducing redox-potential-dependent and oxygen-concentration-dependent formation of reactive oxygen species in the chloroplast. Over-expression of both the carotenogenic and PTOX genes confers to the astaxanthin-overproduction mutant more effective photoprotective capability than that of the wild type under photooxidative stress
Developmental malformation of the corpus callosum: a review of typical callosal development and examples of developmental disorders with callosal involvement
This review provides an overview of the involvement of the corpus callosum (CC) in a variety of developmental disorders that are currently defined exclusively by genetics, developmental insult, and/or behavior. I begin with a general review of CC development, connectivity, and function, followed by discussion of the research methods typically utilized to study the callosum. The bulk of the review concentrates on specific developmental disorders, beginning with agenesis of the corpus callosum (AgCC)âthe only condition diagnosed exclusively by callosal anatomy. This is followed by a review of several genetic disorders that commonly result in social impairments and/or psychopathology similar to AgCC (neurofibromatosis-1, Turner syndrome, 22q11.2 deletion syndrome, Williams yndrome, and fragile X) and two forms of prenatal injury (premature birth, fetal alcohol syndrome) known to impact callosal development. Finally, I examine callosal involvement in several common developmental disorders defined exclusively by behavioral patterns (developmental language delay, dyslexia, attention-deficit hyperactive disorder, autism spectrum disorders, and Tourette syndrome)
Estimates of ozone return dates from Chemistry-Climate Model Initiative simulations
We analyse simulations performed for the
Chemistry-Climate Model Initiative (CCMI) to estimate the
return dates of the stratospheric ozone layer from depletion
caused by anthropogenic stratospheric chlorine and bromine.
We consider a total of 155 simulations from 20 models, including
a range of sensitivity studies which examine the impact
of climate change on ozone recovery. For the control
simulations (unconstrained by nudging towards analysed meteorology)
there is a large spread (±20 DU in the global average)
in the predictions of the absolute ozone column. Therefore,
the model results need to be adjusted for biases against
historical data. Also, the interannual variability in the model
results need to be smoothed in order to provide a reasonably
narrow estimate of the range of ozone return dates. Consistent
with previous studies, but here for a Representative
Concentration Pathway (RCP) of 6.0, these new CCMI simulations
project that global total column ozone will return to
1980 values in 2049 (with a 1Ï uncertainty of 2043â2055).
At Southern Hemisphere mid-latitudes column ozone is projected
to return to 1980 values in 2045 (2039â2050), and at
Northern Hemisphere mid-latitudes in 2032 (2020â2044). In
the polar regions, the return dates are 2060 (2055â2066) in
the Antarctic in October and 2034 (2025â2043) in the Arctic
in March. The earlier return dates in the Northern Hemisphere
reflect the larger sensitivity to dynamical changes.
Our estimates of return dates are later than those presented
in the 2014 Ozone Assessment by approximately 5â17 years,
depending on the region, with the previous best estimates
often falling outside of our uncertainty range. In the tropics
only around half the models predict a return of ozone to
1980 values, around 2040, while the other half do not reach
the 1980 value. All models show a negative trend in tropical
total column ozone towards the end of the 21st century. The
CCMI models generally agree in their simulation of the time
evolution of stratospheric chlorine and bromine, which are
the main drivers of ozone loss and recovery. However, there
are a few outliers which show that the multi-model mean results
for ozone recovery are not as tightly constrained as possible.
Throughout the stratosphere the spread of ozone return
dates to 1980 values between models tends to correlate with
the spread of the return of inorganic chlorine to 1980 values.
In the upper stratosphere, greenhouse gas-induced cooling
speeds up the return by about 10â20 years. In the lower
stratosphere, and for the column, there is a more direct link
in the timing of the return dates of ozone and chlorine, especially
for the large Antarctic depletion. Comparisons of total
column ozone between the models is affected by different
predictions of the evolution of tropospheric ozone within
the same scenario, presumably due to differing treatment
of tropospheric chemistry. Therefore, for many scenarios,
clear conclusions can only be drawn for stratospheric ozone
columns rather than the total column. As noted by previous
studies, the timing of ozone recovery is affected by the evolution
of N2O and CH4. However, quantifying the effect in the
simulations analysed here is limited by the few realisations
available for these experiments compared to internal model
variability. The large increase in N2O given in RCP 6.0 extends
the ozone return globally by ⌠15 years relative to N2O
fixed at 1960 abundances, mainly because it allows tropical
column ozone to be depleted. The effect in extratropical latitudes
is much smaller. The large increase in CH4 given in the
RCP 8.5 scenario compared to RCP 6.0 also lengthens ozone
return by ⌠15 years, again mainly through its impact in the
tropics. Overall, our estimates of ozone return dates are uncertain
due to both uncertainties in future scenarios, in particular
those of greenhouse gases, and uncertainties in models.
The scenario uncertainty is small in the short term but increases
with time, and becomes large by the end of the century.
There are still some modelâmodel differences related
to well-known processes which affect ozone recovery. Efforts
need to continue to ensure that models used for assessment
purposes accurately represent stratospheric chemistry
and the prescribed scenarios of ozone-depleting substances,
and only those models are used to calculate return dates. For
future assessments of single forcing or combined effects of
CO2, CH4, and N2O on the stratospheric column ozone return
dates, this work suggests that it is more important to
have multi-member (at least three) ensembles for each scenario
from every established participating model, rather than
a large number of individual models
Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes
BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events
Large expert-curated database for benchmarking document similarity detection in biomedical literature search
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term FrequencyâInverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research
Arabidopsis cell expansion is controlled by a photothermal switch
In Arabidopsis, the seedling hypocotyl has emerged as an exemplar model system to study light and temperature control of cell expansion. Light sensitivity of this organ is epitomized in the fluence rate response where suppression of hypocotyl elongation increases incrementally with light intensity. This finely calibrated response is controlled by the photoreceptor, phytochrome B, through the deactivation and proteolytic destruction of phytochrome-interacting factors (PIFs). Here we show that this classical light response is strictly temperature dependent: a shift in temperature induces a dramatic reversal of response from inhibition to promotion of hypocotyl elongation by light. Applying an integrated experimental and mathematical modelling approach, we show how light and temperature coaction in the circuitry drives a molecular switch in PIF activity and control of cell expansion. This work provides a paradigm to understand the importance of signal convergence in evoking different or non-intuitive alterations in molecular signalling
Transcriptional regulatory networks controlling woolliness in peach in response to preharvest gibberellin application and cold storage
Genetically Engineered Mesenchymal Stem Cells as a Proposed Therapeutic for Huntingtonâs Disease
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