Brain Activation by Visual Food-Related Stimuli and Correlations with Metabolic and Hormonal Parameters: A fMRI Study

Regional brain activity in 15 healthy, normal weight males during processing of visual food stimuli in a satiated and a hungry state was examined and correlated with neuroendocrine factors known to be involved in hunger and satiated states. Two functional Magnetic Resonance Imaging (fMRI) sessions were performed with a one week interval, after overnight fasting or 1 hour after a standardized meal. Blood samples and appetite assessment were obtained after each fMRI session. Main effects of processing food versus non-food stimuli were observed in the ventral visual stream, including the fusiform gyrus and hippocampal areas bilaterally, significantly more in the fasting state. Leptin concentration correlated negatively with activity in the left hippocampal area and right insula during the satiation condition. A positive correlation between ghrelin and "thought of food" hunger scores were found. The positive correlation between ghrelin and food related activation in the insula areas and the right hippocampus during fasting did not reach significance. Conclusion: The increased activation of food vs non-food pictures in the ventral visual stream reflects increased salience of food pictures when subjects are hungry. Leptin was associated with activations in areas involved in processing of new information and emotion. © Jakobsdottir et al

Interpretation of Genetic Association Studies: Markers with Replicated Highly Significant Odds Ratios May Be Poor Classifiers

Recent successful discoveries of potentially causal single nucleotide polymorphisms (SNPs) for complex diseases hold great promise, and commercialization of genomics in personalized medicine has already begun. The hope is that genetic testing will benefit patients and their families, and encourage positive lifestyle changes and guide clinical decisions. However, for many complex diseases, it is arguable whether the era of genomics in personalized medicine is here yet. We focus on the clinical validity of genetic testing with an emphasis on two popular statistical methods for evaluating markers. The two methods, logistic regression and receiver operating characteristic (ROC) curve analysis, are applied to our age-related macular degeneration dataset. By using an additive model of the CFH, LOC387715, and C2 variants, the odds ratios are 2.9, 3.4, and 0.4, with p-values of 10−13, 10−13, and 10−3, respectively. The area under the ROC curve (AUC) is 0.79, but assuming prevalences of 15%, 5.5%, and 1.5% (which are realistic for age groups 80 y, 65 y, and 40 y and older, respectively), only 30%, 12%, and 3% of the group classified as high risk are cases. Additionally, we present examples for four other diseases for which strongly associated variants have been discovered. In type 2 diabetes, our classification model of 12 SNPs has an AUC of only 0.64, and two SNPs achieve an AUC of only 0.56 for prostate cancer. Nine SNPs were not sufficient to improve the discrimination power over that of nongenetic predictors for risk of cardiovascular events. Finally, in Crohn's disease, a model of five SNPs, one with a quite low odds ratio of 0.26, has an AUC of only 0.66. Our analyses and examples show that strong association, although very valuable for establishing etiological hypotheses, does not guarantee effective discrimination between cases and controls. The scientific community should be cautious to avoid overstating the value of association findings in terms of personalized medicine before their time

Of three sharks and one chimaera: varied habitat preferences across a latitudinal range revealed by coastal and offshore surveys

Using national and international research survey data and applying a combination of models and mapping tools, this study revealed temperature and depth as the crucial environmental drivers of both the distribution and the abundance of four benthopelagic chondrichthyans inhabiting Norwegian and Icelandic waters: rabbitfish (Chimaera monstrosa), velvet-belly lanternshark (Etmopterus spinax), blackmouth catshark (Galeus melastomus) and spurdog (Squalus acanthias). C. monstrosa and E. spinax seem to prefer similar spatial and ecological habitats, that is deep and cold waters. In contrast, G. melastomus and S. acanthias both prefer similar ecological habitats, that is warmer and shallower waters; nonetheless, they exhibit a different spatial distribution pattern. The species' varied habitat and spatial preferences may lead to different levels of exposure to fishing activities and associated by-catch risks. Findings of the species' spatial distributions and their driving forces are expected to inform the sustainable management of these species and the ecosystems they inhabit.publishedVersio

Dense seismic network provides new insight into the 2007 Upptyppingar dyke intrusion

Factors such as network geometry, network size and phase-picking accuracy have significant\ud effects on the precision of seismic hypocentre locations. In turn, the precision of the hypocentral locations\ud dictates the degree to which morphological details within seismic swarms may be resolved. The Icelandic\ud national seismic network (SIL) is designed to monitor seismic activity across large expanses of Iceland in realtime\ud using automated earthquake detection and location software. Here we examine the performance of the\ud SIL network relative to a much denser, local network of seismometers deployed around the Askja volcano in\ud the Northern Volcanic Zone. A subset of earthquakes from the 2007–2008 dyke intrusion beneath Mt. Upptyppingar\ud is used to compare single- and multi-event hypocentral locations. Specifically, we highlight 288, high\ud signal-to-noise ratio events that occurred during an intensive sequence of earthquakes from 6–24 July 2007,\ud when the temporary Askja network was active. A careful refinement of phase onsets recorded by our wellconfigured,\ud dense network of receivers reveals hypocentres clustered tightly on a planar structure, interpreted\ud as a dyke dipping at 49. The root-mean-square (RMS) misfit to the plane (114 m) is only slightly greater than\ud the uncertainties in relative locations of the earthquakes themselves, and constitutes a three-fold reduction in\ud RMS misfit over SIL relative locations. The improved precision, facilitated predominantly by a more favourable\ud network size and configuration, permits a more detailed analysis of the intrusion

A new way to rapidly create functional, fluorescent fusion proteins: random insertion of GFP with an in vitro transposition reaction

BACKGROUND: The jellyfish green fluorescent protein (GFP) can be inserted into the middle of another protein to produce a functional, fluorescent fusion protein. Finding permissive sites for insertion, however, can be difficult. Here we describe a transposon-based approach for rapidly creating libraries of GFP fusion proteins. RESULTS: We tested our approach on the glutamate receptor subunit, GluR1, and the G protein subunit, α(s). All of the in-frame GFP insertions produced a fluorescent protein, consistent with the idea that GFP will fold and form a fluorophore when inserted into virtually any domain of another protein. Some of the proteins retained their signaling function, and the random nature of the transposition process revealed permissive sites for insertion that would not have been predicted on the basis of structural or functional models of how that protein works. CONCLUSION: This technique should greatly speed the discovery of functional fusion proteins, genetically encodable sensors, and optimized fluorescence resonance energy transfer pairs

Crustal structure beneath western and eastern Iceland from surface waves and receiver functions

We determine the crustal structures beneath 14 broad-band seismic stations, deployed in western, eastern, central and southern Iceland, using surface wave dispersion curves and receiver functions. We implement a method to invert receiver functions using constraints obtained from genetic algorithm inversion of surface waves. Our final models satisfy both data sets. The thickness of the upper crust, as defined by the velocity horizon Vs= 3.7 km s−1, is fairly uniform at ∼6.5–9 km beneath the Tertiary intraplate areas of western and eastern Iceland, and unusually thick at 11 km beneath station HOT22 in the far south of Iceland. The depth to the base of the lower crust, as defined by the velocity horizon Vs= 4.1 km s−1 is ∼20–26 km in western Iceland and ∼27–33 km in eastern Iceland. These results agree with those of explosion profiles that detect a thinner crust beneath western Iceland than beneath eastern Iceland. An earlier report of a substantial low-velocity zone beneath the Middle Volcanic Zone in the lower crust is confirmed by a similar observation beneath an additional station there. As was found in previous receiver function studies, the most reliable feature of the results is the clear division into an upper sequence that is a few kilometres thick where velocity gradients are high, and a lower, thicker sequence where velocity gradients are low. The transition to typical mantle velocities is variable, and may range from being very gradational to being relatively sharp and clear. A clear Moho, by any definition, is rarely seen, and there is thus uncertainty in estimates of the thickness of the crust in many areas. Although a great deal of seismic data are now available constraining the structures of the crust and upper mantle beneath Iceland, their geological nature is not well understood

APOBEC3 mutational signatures are associated with extensive and diverse genomic instability across multiple tumour types

Background: The APOBEC3 (apolipoprotein B mRNA editing enzyme catalytic polypeptide 3) family of cytidine deaminases is responsible for two mutational signatures (SBS2 and SBS13) found in cancer genomes. APOBEC3 enzymes are activated in response to viral infection, and have been associated with increased mutation burden and TP53 mutation. In addition to this, it has been suggested that APOBEC3 activity may be responsible for mutations that do not fall into the classical APOBEC3 signatures (SBS2 and SBS13), through generation of double strand breaks.Previous work has mainly focused on the effects of APOBEC3 within individual tumour types using exome sequencing data. Here, we use whole genome sequencing data from 2451 primary tumours from 39 different tumour types in the Pan-Cancer Analysis of Whole Genomes (PCAWG) data set to investigate the relationship between APOBEC3 and genomic instability (GI). Results and conclusions: We found that the number of classical APOBEC3 signature mutations correlates with increased mutation burden across different tumour types. In addition, the number of APOBEC3 mutations is a significant predictor for six different measures of GI. Two GI measures (INDELs attributed to INDEL signatures ID6 and ID8) strongly suggest the occurrence and error prone repair of double strand breaks, and the relationship between APOBEC3 mutations and GI remains when SNVs attributed to kataegis are excluded. We provide evidence that supports a model of cancer genome evolution in which APOBEC3 acts as a causative factor in the development of diverse and widespread genomic instability through the generation of double strand breaks. This has important implications for treatment approaches for cancers that carry APOBEC3 mutations, and challenges the view that APOBECs only act opportunistically at sites of single stranded DNA

Formation of Short-Chain Fatty Acids, Excretion of Anthocyanins, and Microbial Diversity in Rats Fed Blackcurrants, Blackberries, and Raspberries

Introduction. Berries contain high amounts of dietary fibre and flavonoids and have been associated with improved metabolic health. The mechanisms are not clear but the formation of SCFAs, especially propionic and butyric acids, could be important. The potent antioxidant and antimicrobial properties of flavonoids could also be a factor, but little is known about their fate in the gastrointestinal tract. Aim. To compare how blackcurrants, blackberries, raspberries, and Lactobacillus plantarum HEAL19 affect formation of SCFAs, inflammatory status, caecal microbial diversity, and flavonoids. Results and Conclusions. Degradation of the dietary fibre, formation of SCFAs including propionic and butyric acids, the weight of the caecal content and tissue, and the faecal wet and dry weight were all higher in rats fed blackcurrants rather than blackberries or raspberries. However, the microbial diversity of the gut microbiota was higher in rats fed raspberries. The high content of soluble fibre in blackcurrants and the high proportion of mannose-containing polymers might explain these effects. Anthocyanins could only be detected in urine of rats fed blackcurrants, and the excretion was lower with HEAL19. No anthocyanins or anthocyanidins were detected in caecal content or blood. This may indicate uptake in the stomach or small intestine

Changes in Insulin-Like Growth Factor-I and -II Associated with Fat but not Lean Mass in Early Old Age

Objective: To test the hypothesis that insulin-like growth factors-I and II (IGF-I and II) decline during late midlife and that greater declines are related to higher fat mass and lower lean mass. Methods: A total of 1,542 men and women in a British birth cohort study had IGF-I and II measured by immunoassay of blood samples at age 53 and/or 60-64 years. Fat mass, android:gynoid fat ratio, and appendicular lean mass were measured at 60-64 years using dual-energy X-ray absorptiometry (DXA). Associations between changes in IGF-I or II and body composition outcomes were examined using conditional change linear regression models. Results: Mean IGF-I and IGF-II concentrations were lower at 60-64 than at 53 years, by 12.8% for IGF-I and by 12.5% for IGF-II. Larger declines in either IGF-I or II were associated with higher fat mass at 60-64 years. Although higher IGF-I at 53 years was associated with higher lean mass, there was little evidence linking changes in IGF-I or II to lean mass. Conclusions: The findings suggest that IGF-I and II concentrations decline with age, and greater declines are associated with higher fat mass levels. These results provide some evidence for the suggested roles of IGF-I and II in regulating fat mass but not lean mass in older age