Can sequence determine function?

The functional annotation of proteins identified in genome sequencing projects is based on similarities to homologs in the databases. As a result of the possible strategies for divergent evolution, homologous enzymes frequently do not catalyze the same reaction, and we conclude that assignment of function from sequence information alone should be viewed with some skepticism.     

Eye-hand coordination: eye to hand or hand to eye?

Single-unit recording has revealed both hand and eye movement-related activity in the parietal cortex of the macaque monkey. These experiments, as well as neuropsychological studies, are unravelling the complex nature of how the eye and the hand work together in the control of visually guided movements.     

Can edible grasshoppers and silkworm pupae be tasted by humans when prevented to see and smell these insects?

Out of 26 students (11 male, 15 female) that were blindfolded and held their noses, 14 correctly identified the taste of insects when given pieces of cheese, dried fish, beondaegi (commercially available Korean Bombyx mori silkworm pupae), inago (commercially available Japanese Oxya yezoensis grasshoppers) and white bread to taste. Eight identified one of the food insects and four failed to detect any. Of 11 students given a choice between beondaegi, inago and hachinoko (larval wasps of Vespula flaviceps) most students preferred the inago grasshoppers, three ranked the commercially available hachinoko first and one gave the top position to the beondaegi silkworm pupae. It is concluded that insects, per se, are not terribly easy to identify by taste alone. Given the well documented aversion of especially people of western cultural backgrounds to insects in food, our results suggest that insects processed into flour or pastes have a greater chance to be accepted by the consumer (as they cannot easily be identified by taste alone) than food that displays insect images on its packing.

Can We Depend on Investigators to Identify and Register Randomized Controlled Trials?

Purpose

To reduce publication bias, systematic reviewers are advised to search conference abstracts to identify randomized controlled trials (RCTs) conducted in humans and not published in full. We assessed the information provided by authors to aid identification of RCTs for reviews.

Methods

We handsearched the Association for Research in Vision and Ophthalmology (ARVO) meeting abstracts for 2004 to 2009 to identify reports of RCTs. We compared our classification with that of authors (requested by ARVO 2004–2006), and authors’ report of trial registration (required by ARVO 2007–2009).

Results

Authors identified their study as a clinical trial for 169/191 (88%; 95% CI, 84–93) RCTs we identified for 2004, 174/212 (82%; 95% CI, 77–87) for 2005 and 162/215 (75%; 95% CI, 70–81) for 2006. Authors provided registration information for 107/172 (62%; 95% CI, 55–69) RCTs for 2007, 103/153 (67%; 95% CI, 60–75) for 2008, and 126/171 (74%; 95% CI, 67–80) for 2009. Most RCT authors providing a trial register name specified ClinicalTrials.gov (276/312; 88%; 95% CI, 85–92) and provided a valid ClinicalTrials.gov registration number (261/276; 95%; 95% CI, 92–97). Based on information provided by authors, trial registration information would be accessible for 48% (83/172) (95% CI, 41–56) of all ARVO abstracts describing RCTs in 2007, 63% (96/153) (95% CI, 55–70) in 2008, and 70% in 2009 (118/171) (95% CI, 62–76).

Conclusions

Authors of abstracts describing RCTs frequently did not classify them as clinical trials nor comply with reporting trial registration information, as required by the conference organizers. Systematic reviewers cannot rely on authors to identify relevant unpublished trials or report trial registration, if present.     

Can we optimise the exercise training prescription to maximise improvements in mitochondria function and content?

Background

While there is agreement that exercise is a powerful stimulus to increase both mitochondrial function and content, we do not know the optimal training stimulus to maximise improvements in mitochondrial biogenesis.

Scope of review

This review will focus predominantly on the effects of exercise on mitochondrial function and content, as there is a greater volume of published research on these adaptations and stronger conclusions can be made.

Major conclusions

The results of cross-sectional studies, as well as training studies involving rats and humans, suggest that training intensity may be an important determinant of improvements in mitochondrial function (as determined by mitochondrial respiration), but not mitochondrial content (as assessed by citrate synthase activity). In contrast, it appears that training volume, rather than training intensity, may be an important determinant of exercise-induced improvements in mitochondrial content. Exercise-induced mitochondrial adaptations are quickly reversed following a reduction or cessation of physical activity, highlighting that skeletal muscle is a remarkably plastic tissue. Due to the small number of studies, more research is required to verify the trends highlighted in this review, and further studies are required to investigate the effects of different types of training on the mitochondrial sub-populations and also mitochondrial adaptations in different fibre types. Further research is also required to better understand how genetic variants influence the large individual variability for exercise-induced changes in mitochondrial biogenesis.

General significance

The importance of mitochondria for both athletic performance and health underlines the importance of better understanding the factors that regulate exercise-induced changes in mitochondrial biogenesis. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research.     

How does onchocerciasis-related skin and eye disease in Africa depend on cumulative exposure to infection and mass treatment?

BackgroundOnchocerciasis (river-blindness) in Africa is targeted for elimination through mass drug administration (MDA) with ivermectin. Onchocerciasis may cause various types of skin and eye disease. Predicting the impact of MDA on onchocercal morbidity is useful for future policy development. Here, we introduce a new disease module within the established ONCHOSIM model to predict trends over time in prevalence of onchocercal morbidity.MethodsWe developed novel generic model concepts for development of symptoms due to cumulative exposure to dead microfilariae, accommodating both reversible (acute) and irreversible (chronic) symptoms. The model was calibrated to reproduce pre-control age patterns and associations between prevalences of infection, eye disease, and various types of skin disease as observed in a large set of population-based studies. We then used the new disease module to predict the impact of MDA on morbidity prevalence over a 30-year time frame for various scenarios.ResultsONCHOSIM reproduced observed age-patterns in disease and community-level associations between infection and disease reasonably well. For highly endemic settings with 30 years of annual MDA at 60% coverage, the model predicted a 70% to 89% reduction in prevalence of chronic morbidity. This relative decline was similar with higher MDA coverage and only somewhat higher for settings with lower pre-control endemicity. The decline in prevalence was lowest for mild depigmentation and visual impairment. The prevalence of acute clinical manifestations (severe itch, reactive skin disease) declined by 95% to 100% after 30 years of annual MDA, regardless of pre-control endemicity.ConclusionWe present generic model concepts for predicting trends in acute and chronic symptoms due to history of exposure to parasitic worm infections, and apply this to onchocerciasis. Our predictions suggest that onchocercal morbidity, in particular chronic manifestations, will remain a public health concern in many epidemiological settings in Africa, even after 30 years of MDA.     

Can calmodulin function without binding calcium?

Calmodulin is a small Ca(2+)-binding protein proposed to act as the intracellular Ca2+ receptor that translates Ca2+ signals into cellular responses. We have constructed mutant yeast calmodulins in which the Ca(2+)-binding loops have been altered by site-directed mutagenesis. Each of the mutant proteins has a dramatically reduced affinity for Ca2+; one does not bind detectable levels of 45Ca2+ either during gel filtration or when bound to a solid support. Furthermore, none of the mutant proteins change conformation even in the presence of high Ca2+ concentrations. Surprisingly, yeast strains relying on any of the mutant calmodulins not only survive but grow well. In contrast, yeast strains deleted for the calmodulin gene are not viable. Thus, calmodulin is required for growth, but it can perform its essential function without the apparent ability to bind Ca2+.     

Can you still see the cochlea for the molecules?

It is now established that the mammalian cochlea uses active amplification of incoming sound to achieve sensitivity. Cellular details are emerging slowly. Recent studies of sensory hair cells have highlighted the possible molecular bases for amplification and the components of sensitivity regulation within the cochlea: a synthesis is likely to depend on effective and physiologically informed modelling.     

Can glutathione-S-transferases function as intracellular heme carriers?

The possibility that glutathione-S-transferases can serve as heme carriers in cells was studied via the following two characteristics: the ability to bind hemin reversibly and the coordination between heme and glutathione-S-transferases level in the cell. two erythroleukemic cell lines that can be induced to synthesize hemoglobin were studied, K-562 and Friend murine erythroleukemia cells. It was found that hemin-associated glutathione-S-transferase tends to lose its native structure as expressed by partial irreversible inhibition of glutathione conjugation activity. In K-562 cells, a small increase in heme synthesis was induced, but under no condition could glutathione-S-transferase be elevated. In addition, introduction of high hemin from without caused large hemoglobin production but did not induce changes in the glutathione-S-transferase content. Dimethyl sulfoxide-induced Friend murine erythroleukemia cells synthesized a large amount of endogenous hemin that had to be transported from the mitochondria for hemoglobin synthesis. Although a concomitant increase in glutathione-S-transferase level (20-40%) was observed, it was only short-lived, unlike hemin, which continued to increase. These data indicate a lack of correlation between glutathione-S-transferase and hemin or hemoglobin levels. Finally, dimethyl sulfoxide-induced cells were treated with succinyl acetone to inhibit heme synthesis. These cells showed the same increased levels and time-dependent pattern of glutathione-S-transferase as untreated cells. A similar phenomenon was observed when different substrates were used to measure the activities of glutathione-S-transferases. These results raise doubts about the possibility of glutathione-S-transferases functioning as heme carriers in cells.     

Can ultraviolet cues function as aposematic signals?

The fact that birds are sensitive to ultraviolet light (UV,320-400 nm) has been largely ignored by previous studies ofaposematism. Therefore, in the present article we investigatedwhether great tits preferred ultraviolet-reflecting colorscompared to colors without UV reflection and whether UV cuesalone could function as aposematic signals. We were able to manipulate prey visibility in UV light by changing the UV reflectanceof prey items as well as altering the lighting conditions.In order to perform a preference experiment we used three pairsof colors (green+UV vs. green, gray+UV vs. gray, yellow+UVvs. yellow) on a black background. The birds ate both UV typesequally for all three colors. Thus, there was no avoidance of the UV-reflecting prey. Next we tested the possibility thatUV reflection may affect avoidance learning. We used eithergreen or green+UV as a signal for unpalatability. In this set-upthe difference in UV did not allow avoidance learning to occur.Our experiment with great tits does not support the hypothesisthat UV cues alone might work effectively as aposematic signals.     

Can roadside habitat lead monarchs on a route to recovery?

The Eastern North American monarch butterfly population has severely declined over the past decade. The decreasing availability of larval host plants (milkweeds) due to the use of herbicide-tolerant crops has been implicated in this decline. Roadsides could provide additional habitat for monarchs. In this study we document the occurrence of milkweed and monarchs on roadsides, and discuss whether roadsides are appropriate targets for monarch habitat restoration. We sampled roadside rights-of-way in the Upper Midwestern U.S. during the summer of 2015 to estimate the abundance, distribution, and diversity of milkweeds and the extent to which monarchs use these milkweeds. We then compared monarch densities in roadsides to other habitat types and modelled immature monarch densities based on several site characteristics. Our findings suggest that roadsides have conservation potential for monarchs, especially when other habitat is scarce and if wildlife-friendly management practices are enacted. Milkweeds were found on ~60% of roadside transects. Asclepias syriaca was the most common of the seven species encountered, occurring on 97% of transects with milkweed. Immature monarchs were observed in roadsides, but in lower densities than other habitats during the same time period. At lower milkweed densities, immature monarch density per unit area is positively correlated with milkweed density. However, milkweed density weakens as a predictor of immature monarch density over ~0.6 plants per m², possibly indicating a saturation effect.     

How Can Research on Plants Contribute to Promoting Human Health?

One of the most pressing challenges for the next 50 years is to reduce the impact of chronic disease. Unhealthy eating is an increasing problem and underlies much of the increase in mortality from chronic diseases that is occurring worldwide. Diets rich in plant-based foods are strongly associated with reduced risks of major chronic diseases, but the constituents in plants that promote health have proved difficult to identify with certainty. This, in turn, has confounded the precision of dietary recommendations. Plant biochemistry can make significant contributions to human health through the identification and measurement of the many metabolites in plant-based foods, particularly those known to promote health (phytonutrients). Plant genetics and metabolic engineering can be used to make foods that differ only in their content of specific phytonutrients. Such foods offer research tools that can provide significant insight into which metabolites promote health and how they work. Plant science can reduce some of the complexity of the diet-health relationship, and through building multidisciplinary interactions with researchers in nutrition and the pathology of chronic diseases, plant scientists can contribute novel insight into which foods reduce the risk of chronic disease and how these foods work to impact human health.