MicroRNAs: shortcuts in dealing with molecular complexity?

Recent studies from Clarke's group published in the journal Cell indicate that miRNAs may be the elusive universal stem cell markers that the field of cancer stem cell biology has been seeking. Distinct profiles of miRNAs appear to reflect the state of cell differentiation not only in breast cancer cells, but also in normal mammary epithelial cells. Moreover, they are conserved across tissues and species. The authors of this work also show evidence that downregulation of miRNA-200c in normal and malignant breast stem cells and in embryonal carcinoma cells has functional relevance, being responsible for the proliferative potential of these cells in vitro and in vivo

Garden varieties: how attractive are recommended garden plants to butterflies?

One way the public can engage in insect conservation is through wildlife gardening, including the growing of insect-friendly flowers as sources of nectar. However, plant varieties differ in the types of insects they attract. To determine which garden plants attracted which butterflies, we counted butterflies nectaring on 11 varieties of summer-flowering garden plants in a rural garden in East Sussex, UK. These plants were all from a list of 100 varieties considered attractive to British butterflies, and included the five varieties specifically listed by the UK charity Butterfly Conservation as best for summer nectar. A total of 2659 flower visits from 14 butterfly and one moth species were observed. We performed a principal components analysis which showed contrasting patterns between the species attracted to Origanum vulgare and Buddleia davidii. The “butterfly bush” Buddleia attracted many nymphalines, such as the peacock, Inachis io, but very few satyrines such as the gatekeeper, Pyronia tithonus, which mostly visited Origanum. Eupatorium cannibinum had the highest Simpson’s Diversity score of 0.75, while Buddleia and Origanum were lower, scoring 0.66 and 0.50 respectively. No one plant was good at attracting all observed butterfly species, as each attracted only a subset of the butterfly community. We conclude that to create a butterfly-friendly garden, a variety of plant species are required as nectar sources for butterflies. Furthermore, garden plant recommendations can probably benefit from being more precise as to the species of butterfly they attract

Some investigations into non passive listening

Our knowledge of the function of the auditory nervous system is based upon a wealth of data obtained, for the most part, in anaesthetised animals. More recently, it has been generally acknowledged that factors such as attention profoundly modulate the activity of sensory systems and this can take place at many levels of processing. Imaging studies, in particular, have revealed the greater activation of auditory areas and areas outside of sensory processing areas when attending to a stimulus. We present here a brief review of the consequences of such non-passive listening and go on to describe some of the experiments we are conducting to investigate them. In imaging studies, using fMRI, we can demonstrate the activation of attention networks that are non-specific to the sensory modality as well as greater and different activation of the areas of the supra-temporal plane that includes primary and secondary auditory areas. The profuse descending connections of the auditory system seem likely to be part of the mechanisms subserving attention to sound. These are generally thought to be largely inactivated by anaesthesia. However, we have been able to demonstrate that even in an anaesthetised preparation, removing the descending control from the cortex leads to quite profound changes in the temporal patterns of activation by sounds in thalamus and inferior colliculus. Some of these effects seem to be specific to the ear of stimulation and affect interaural processing. To bridge these observations we are developing an awake behaving preparation involving freely moving animals in which it will be possible to investigate the effects of consciousness (by contrasting awake and anaesthetized), passive and active listening

Do female association preferences predict the likelihood of reproduction?

Sexual selection acting on male traits through female mate choice is commonly inferred from female association preferences in dichotomous mate choice experiments. However, there are surprisingly few empirical demonstrations that such association preferences predict the likelihood of females reproducing with a particular male. This information is essential to confirm association preferences as good predictors of mate choice. We used green swordtails (<i>Xiphophorus helleri</i>) to test whether association preferences predict the likelihood of a female reproducing with a male. Females were tested for a preference for long- or short-sworded males in a standard dichotomous choice experiment and then allowed free access to either their preferred or non-preferred male. If females subsequently failed to produce fry, they were provided a second unfamiliar male with similar sword length to the first male. Females were more likely to reproduce with preferred than non-preferred males, but for those that reproduced, neither the status (preferred/non-preferred) nor the sword length (long/short) of the male had an effect on brood size or relative investment in growth by the female. There was no overall preference based on sword length in this study, but male sword length did affect likelihood of reproduction, with females more likely to reproduce with long- than short-sworded males (independent of preference for such males in earlier choice tests). These results suggest that female association preferences are good indicators of female mate choice but that ornament characteristics of the male are also important

Accurate non-invasive diagnosis and staging of non-alcoholic fatty liver disease using the urinary steroid metabolome

Background: The development of accurate, non-invasive markers to diagnose and stage non-alcoholic fatty liver disease (NAFLD) is critical to reduce the need for an invasive liver biopsy and to identify patients who are at the highest risk of hepatic and cardio-metabolic complications.Aim(s): As the liver represents the main site of steroid hormone metabolism, and disruption of specific pathways has been described in patients with NAFLD, we hypothesised that assessment of the urinary steroid metabolome may provide a novel, non-invasive biomarker strategy to stage NAFLD.Methods: We analysed the urinary steroid metabolome in 275 subjects (121 with biopsy-proven NAFLD, 48 with alcohol-related cirrhosis, 106 controls), using gas chromatography-mass spectrometry (GC-MS) coupled with machine learning-based generalised matrix learning vector quantisation (GMLVQ) analysis.Results: GMLVQ analysis achieved excellent separation of early (F0-F2) from advanced (F3-F4) fibrosis (AUC ROC: 0.92 [0.91-0.94]). Furthermore, there was near perfect separation of controls from patients with advanced fibrotic NAFLD (AUC ROC=0.99 [0.98-0.99]) and from those with NAFLD cirrhosis (AUC ROC=1.0 [1.0-1.0]). This approach was also able to distinguish patients with NAFLD cirrhosis from those with alcohol-related cirrhosis (AUC ROC=0.83 [0.81-0.85]).Conclusions: Unbiased GMLVQ analysis of the urinary steroid metabolome offers excellent potential as a non-invasive biomarker approach to stage NAFLD fibrosis as well as to screen for NAFLD. A highly sensitive and specific urinary biomarker is likely to have clinical utility both in secondary care and in the broader general population within primary care and could significantly decrease the need for liver biopsy

Finding Your Mate at a Cocktail Party: Frequency Separation Promotes Auditory Stream Segregation of Concurrent Voices in Multi-Species Frog Choruses

Vocal communication in crowded social environments is a difficult problem for both humans and nonhuman animals. Yet many important social behaviors require listeners to detect, recognize, and discriminate among signals in a complex acoustic milieu comprising the overlapping signals of multiple individuals, often of multiple species. Humans exploit a relatively small number of acoustic cues to segregate overlapping voices (as well as other mixtures of concurrent sounds, like polyphonic music). By comparison, we know little about how nonhuman animals are adapted to solve similar communication problems. One important cue enabling source segregation in human speech communication is that of frequency separation between concurrent voices: differences in frequency promote perceptual segregation of overlapping voices into separate “auditory streams” that can be followed through time. In this study, we show that frequency separation (ΔF) also enables frogs to segregate concurrent vocalizations, such as those routinely encountered in mixed-species breeding choruses. We presented female gray treefrogs (Hyla chrysoscelis) with a pulsed target signal (simulating an attractive conspecific call) in the presence of a continuous stream of distractor pulses (simulating an overlapping, unattractive heterospecific call). When the ΔF between target and distractor was small (e.g., ≤3 semitones), females exhibited low levels of responsiveness, indicating a failure to recognize the target as an attractive signal when the distractor had a similar frequency. Subjects became increasingly more responsive to the target, as indicated by shorter latencies for phonotaxis, as the ΔF between target and distractor increased (e.g., ΔF = 6–12 semitones). These results support the conclusion that gray treefrogs, like humans, can exploit frequency separation as a perceptual cue to segregate concurrent voices in noisy social environments. The ability of these frogs to segregate concurrent voices based on frequency separation may involve ancient hearing mechanisms for source segregation shared with humans and other vertebrates

Testing the theory of immune selection in cancers that break the rules of transplantation

Modification of cancer cells likely to reduce their immunogenicity, including loss or down-regulation of MHC molecules, is now well documented and has become the main support for the concept of immune surveillance. The evidence that these modifications, in fact, result from selection by the immune system is less clear, since the possibility that they may result from reorganized metabolism associated with proliferation or from cell de-differentiation remains. Here, we (a) survey old and new transplantation experiments that test the possibility of selection and (b) survey how transmissible tumours of dogs and Tasmanian devils provide naturally evolved tests of immune surveillance

Nut production in Bertholletia excelsa across a logged forest mosaic: implications for multiple forest use

Although many examples of multiple-use forest management may be found in tropical smallholder systems, few studies provide empirical support for the integration of selective timber harvesting with non-timber forest product (NTFP) extraction. Brazil nut (Bertholletia excelsa, Lecythidaceae) is one of the world’s most economically-important NTFP species extracted almost entirely from natural forests across the Amazon Basin. An obligate out-crosser, Brazil nut flowers are pollinated by large-bodied bees, a process resulting in a hard round fruit that takes up to 14 months to mature. As many smallholders turn to the financial security provided by timber, Brazil nut fruits are increasingly being harvested in logged forests. We tested the influence of tree and stand-level covariates (distance to nearest cut stump and local logging intensity) on total nut production at the individual tree level in five recently logged Brazil nut concessions covering about 4000 ha of forest in Madre de Dios, Peru. Our field team accompanied Brazil nut harvesters during the traditional harvest period (January-April 2012 and January-April 2013) in order to collect data on fruit production. Three hundred and ninety-nine (approximately 80%) of the 499 trees included in this study were at least 100 m from the nearest cut stump, suggesting that concessionaires avoid logging near adult Brazil nut trees. Yet even for those trees on the edge of logging gaps, distance to nearest cut stump and local logging intensity did not have a statistically significant influence on Brazil nut production at the applied logging intensities (typically 1–2 timber trees removed per ha). In one concession where at least 4 trees ha-1 were removed, however, the logging intensity covariate resulted in a marginally significant (0.09) P value, highlighting a potential risk for a drop in nut production at higher intensities. While we do not suggest that logging activities should be completely avoided in Brazil nut rich forests, when a buffer zone cannot be observed, low logging intensities should be implemented. The sustainability of this integrated management system will ultimately depend on a complex series of socioeconomic and ecological interactions. Yet we submit that our study provides an important initial step in understanding the compatibility of timber harvesting with a high value NTFP, potentially allowing for diversification of forest use strategies in Amazonian Perù

A simple rule to determine which insolation cycles lead to interglacials

The pacing of glacial–interglacial cycles during the Quaternary period (the past 2.6 million years) is attributed to astronomically driven changes in high-latitude insolation. However, it has not been clear how astronomical forcing translates into the observed sequence of interglacials. Here we show that before one million years ago interglacials occurred when the energy related to summer insolation exceeded a simple threshold, about every 41,000 years. Over the past one million years, fewer of these insolation peaks resulted in deglaciation (that is, more insolation peaks were ‘skipped’), implying that the energy threshold for deglaciation had risen, which led to longer glacials. However, as a glacial lengthens, the energy needed for deglaciation decreases. A statistical model that combines these observations correctly predicts every complete deglaciation of the past million years and shows that the sequence of interglacials that has occurred is one of a small set of possibilities. The model accounts for the dominance of obliquity-paced glacial–interglacial cycles early in the Quaternary and for the change in their frequency about one million years ago. We propose that the appearance of larger ice sheets over the past million years was a consequence of an increase in the deglaciation threshold and in the number of skipped insolation peaks.P.C.T. acknowledges funding from a Leverhulme Trust Research Project Grant (RPG-2014-417). M.C. and T.M. acknowledge support from the Belgian Policy Office under contract BR/121/A2/STOCHCLIM. E.W.W. is funded under a Royal Society Research Professorship and M.C. is a senior research scientist with the Belgian National Fund of Scientific Research