Are cultured human myotubes far from home?

Satellite cells can be isolated from skeletal muscle biopsies, activated to proliferating myoblasts and differentiated into multinuclear myotubes in culture. These cell cultures represent a model system for intact human skeletal muscle and can be modulated ex vivo. The advantages of this system are that the most relevant genetic background is available for the investigation of human disease (as opposed to rodent cell cultures), the extracellular environment can be precisely controlled and the cells are not immortalized, thereby offering the possibility of studying innate characteristics of the donor. Limitations in differentiation status (fiber type) of the cells and energy metabolism can be improved by proper treatment, such as electrical pulse stimulation to mimic exercise. This review focuses on the way that human myotubes can be employed as a tool for studying metabolism in skeletal muscles, with special attention to changes in muscle energy metabolism in obesity and type 2 diabetes.     

Transcription profiling during the cell cycle shows that a subset of Polycomb-targeted genes is upregulated during DNA replication

Genome-wide gene expression analyses of the human somatic cell cycle have indicated that the set of cycling genes differ between primary and cancer cells. By identifying genes that have cell cycle dependent expression in HaCaT human keratinocytes and comparing these with previously identified cell cycle genes, we have identified three distinct groups of cell cycle genes. First, housekeeping genes enriched for known cell cycle functions; second, cell type-specific genes enriched for HaCaT-specific functions; and third, Polycomb-regulated genes. These Polycomb-regulated genes are specifically upregulated during DNA replication, and consistent with being epigenetically silenced in other cell cycle phases, these genes have lower expression than other cell cycle genes. We also find similar patterns in foreskin fibroblasts, indicating that replication-dependent expression of Polycomb-silenced genes is a prevalent but unrecognized regulatory mechanism.     

Adding parasites to the guppy-predation story: insights from field surveys

Studies of phenotypic variation in nature often consider only a single potential selective agent. In such cases, it remains an open question as to whether variation attributed to that single measured agent might be influenced by some other unmeasured agent. Previous research has shown that phenotypic variation in the Trinidadian guppy (Poecilia reticulata) is strongly influenced by predation regime, and we here ask whether parasitism might represent an additional important selective agent shaping this variation. We performed a field survey of 26 natural guppy populations of known predation regime in northern Trinidad. We quantified levels of parasitism of guppies by the monogenean ecotoparasite, Gyrodactylus, and examined whether this parasite was associated with guppy body size or male colour. Spatial variation in Gyrodactylus parasitism was consistent between years, and parasite prevalence was generally, but not always, higher at high-predation sites than at low-predation sites. Consistent with previous work, predation regime was related to guppy size and some aspects of male colour, whereas parasitism showed few and only minor associations with the same traits. Moreover, a consideration of parasitism did not alter any interpretations regarding associations between guppy traits and predation regimes. These results suggest that parasitism, at least as quantified in the present study, does not play a major role in shaping variation in guppy body size or colour. Nevertheless, considerable variation in these traits, even within a predation regime, suggests the likely importance of other selective agents beyond just predation regime.     

The age of terrestrial carbon export and rainfall intensity in a temperate river headwater system

Riverine dissolved organic carbon (DOC) supports the production of estuaries and coastal ecosystems, constituting one of the most actively recycled pools of the global carbon cycle. A substantial proportion of DOC entering oceans is highly aged, but its origins remain unclear. Significant fluxes of old DOC have never been observed in temperate headwaters where terrestrial imports take place. Here, we studied the radiocarbon age of DOC in three streams draining forested headwater catchments of the river Mulde (Ore Mountains, Germany). In a 4 week summer precipitation event DOC aged at between 160 and 270 years was delivered into the watershed. In one stream, the DOC was modern but depleted in radiocarbon compared to other hydrological conditions. The yield was substantial and corresponded to 20–52 % of the annual DOC yields in wet and dry years, respectively. The analysis of long-term data suggested that the DOC export in extreme precipitation events added to the annual yield and was not compensated for by lower exports in remaining periods. We conclude that climate change, along with additional processes associated with human activities, channels old soil carbon into more rapidly cycled carbon pools of the hydrosphere.     

Experimental elimination of parasites in nature leads to the evolution of increased resistance in hosts

A reduction in the strength of selection is expected to cause the evolution of reduced trait expression. Elimination of a parasite should thus cause the evolution of reduced resistance to that parasite. To test this prediction in nature, we studied the fourth- and eighth-generation descendants of guppies (Poecilia reticulata) introduced into four natural streams following experimental elimination of a common and deleterious parasite (Gyrodactylus spp.). After two generations of laboratory rearing to control for plasticity and maternal effects, we infected individual fish to assess their resistance to the parasite. Contrary to theoretical expectations, the introduced guppy populations had rapidly and repeatably evolved increased resistance to the now-absent parasite. This evolution was not owing to a resistance-tolerance trade-off, nor to differences in productivity among the sites. Instead, a leading candidate hypothesis is that the rapid life-history evolution typical in such introductions pleiotropically increases parasite resistance. Our study adds a new dimension to the growing evidence for contemporary evolution in the wild, and also points to the need for a re-consideration of simple expectations from host–parasite theory. In particular, our results highlight the need for increased consideration of multiple sources of selection and pleiotropy when studying evolution in natural contexts.     

TRPV1 antagonist with high analgesic efficacy: 2-Thio pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides

A series of 2-thio pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides were investigated as hTRPV1 antagonists. Among them, compound 24S showed stereospecific and excellent TRPV1 antagonism of capsaicin-induced activation. Further, it demonstrated strong anti-allodynic in a rat neuropathic pain model. Consistent with its action in vitro being through TRPV1, compound 24S blocked capsaicin-induced hypothermia in mice. Docking analysis of 24S with our hTRPV1 homology model was performed to identify its binding mode.     

Requirements for a minimum standard of care for phenylketonuria: the patients’ perspective

Phenylketonuria (PKU, ORPHA716) is an inherited disorder that affects about one in every 10,000 children born in Europe. Early and continuous application of a modified diet is largely successful in preventing the devastating brain damage associated with untreated PKU. The management of PKU is inconsistent: there are few national guidelines, and these tend to be incomplete and implemented sporadically. In this article, the first-ever pan- European patient/carer perspective on optimal PKU care, the European Society for Phenylketonuria and Allied Disorders (E.S.PKU) proposes recommendations for a minimum standard of care for PKU, to underpin the development of new pan-European guideline for the management of PKU. New standards of best practice should guarantee equal access to screening, treatment and monitoring throughout Europe. Screening protocols and interpretation of screening results should be standardised. Experienced Centres of Expertise are required, in line with current European Union policy, to guarantee a defined standard of multidisciplinary treatment and care for all medical and social aspects of PKU. Women of childbearing age require especially intensive management, due to the risk of severe risks to the foetus conferred by uncontrolled PKU. All aspects of treatment should be reimbursed to ensure uniform access across Europe to guideline-driven, evidence-based care. The E.S.PKU urges PKU healthcare professionals caring for people with PKU to take the lead in developing evidence based guidelines on PKU, while continuing to play an active role in serving as the voice of patients and their families, whose lives are affected by the condition.     

The Effect of New Zealand Kanuka,Manuka and Clover Honeys on Bacterial Growth Dynamics and Cellular Morphology Varies According to the Species

Treatment of chronic wounds is becoming increasingly difficult due to antibiotic resistance. Complex natural products with antimicrobial activity, such as honey, are now under the spotlight as alternative treatments to antibiotics. Several studies have shown honey to have broad-spectrum antibacterial activity at concentrations present in honey dressings, and resistance to honey has not been attainable in the laboratory. However not all honeys are the same and few studies have used honey that is well defined both in geographic and chemical terms. Here we have used a range of concentrations of clover honey and a suite of manuka and kanuka honeys from known geographical locations, and for which the floral source and concentration of methylglyoxal and hydrogen peroxide potential were defined, to determine their effect on growth and cellular morphology of four bacteria: Bacillus subtilis, Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. While the general trend in effectiveness of growth inhibition was manuka>manuka-kanuka blend>kanuka>clover, the honeys had varying and diverse effects on the growth and cellular morphology of each bacterium, and each organism had a unique response profile to these honeys. P. aeruginosa showed a markedly different pattern of growth inhibition to the other three organisms when treated with sub-inhibitory concentrations of honey, being equally sensitive to all honeys, including clover, and the least sensitive to honey overall. While hydrogen peroxide potential contributed to the antibacterial activity of the manuka and kanuka honeys, it was never essential for complete growth inhibition. Cell morphology analysis also showed a varied and diverse set of responses to the honeys that included cell length changes, cell lysis, and alterations to DNA appearance. These changes are likely to reflect the different regulatory circuits of the organisms that are activated by the stress of honey treatment.     

Squares of different sizes: effect of geographical projection on model parameter estimates in species distribution modeling

In species distribution analyses, environmental predictors and distribution data for large spatial extents are often available in long‐lat format, such as degree raster grids. Long‐lat projections suffer from unequal cell sizes, as a degree of longitude decreases in length from approximately 110 km at the equator to 0 km at the poles. Here we investigate whether long‐lat and equal‐area projections yield similar model parameter estimates, or result in a consistent bias. We analyzed the environmental effects on the distribution of 12 ungulate species with a northern distribution, as models for these species should display the strongest effect of projectional distortion. Additionally we choose four species with entirely continental distributions to investigate the effect of incomplete cell coverage at the coast. We expected that including model weights proportional to the actual cell area should compensate for the observed bias in model coefficients, and similarly that using land coverage of a cell should decrease bias in species with coastal distribution. As anticipated, model coefficients were different between long‐lat and equal‐area projections. Having progressively smaller and a higher number of cells with increasing latitude influenced the importance of parameters in models, increased the sample size for the northernmost parts of species ranges, and reduced the subcell variability of those areas. However, this bias could be largely removed by weighting long‐lat cells by the area they cover, and marginally by correcting for land coverage. Overall we found little effect of using long‐lat rather than equal‐area projections in our analysis. The fitted relationship between environmental parameters and occurrence probability differed only very little between the two projection types. We still recommend using equal‐area projections to avoid possible bias. More importantly, our results suggest that the cell area and the proportion of a cell covered by land should be used as a weight when analyzing distribution of terrestrial species.