Obesity and triple‐negative‐breast‐cancer: Is apelin a new key target?

Epidemiological studies have shown that obese subjects have an increased risk of developing triple‐negative breast cancer (TNBC) and an overall reduced survival. However, the relation between obesity and TNBC remains difficult to understand. We hypothesize that apelin, an adipokine whose levels are increased in obesity, could be a major factor contributing to both tumour growth and metastatization in TNBC obese patients. We observed that development of obesity under high‐fat diet in TNBC tumour‐bearing mice significantly increased tumour growth. By showing no effect of high‐fat diet in obesity‐resistant mice, we demonstrated the necessity to develop obesity‐related disorders to increase tumour growth. Apelin mRNA expression was also increased in the subcutaneous adipose tissue and tumours of obese mice. We further highlighted that the reproduction of obesity‐related levels of apelin in lean mice led to an increased TNBC growth and brain metastases formation. Finally, injections of the apelinergic antagonist F13A to obese mice significantly reduced TNBC growth, suggesting that apelinergic system interference could be an interesting therapeutic strategy in the context of obesity and TNBC.     

Comparison of X‐ray and NMR structures: Is there a systematic difference in residue contacts between X‐ray‐ and NMR‐resolved protein structures?

We have compared structures of 78 proteins determined by both NMR and X-ray methods. It is shown that X-ray and NMR structures of the same protein have more differences than various X-ray structures obtained for the protein, and even more than various NMR structures of the protein. X-ray and NMR structures of 18 of these 78 proteins have obvious large-scale structural differences that seem to reflect a difference of crystal and solution structures. The other 60 pairs of structures have only small-scale differences comparable with differences between various X-ray or various NMR structures of a protein; we have analyzed these structures more attentively. One of the main differences between NMR and X-ray structures concerns the number of contacts per residue: (1) NMR structures presented in PDB have more contacts than X-ray structures at distances below 3.0 A and 4.5-6.5 A, and fewer contacts at distances of 3.0-4.5 A and 6.5-8.0 A; (2) this difference in the number of contacts is greater for internal residues than for external ones, and it is larger for beta-containing proteins than for all-alpha proteins. Another significant difference is that the main-chain hydrogen bonds identified in X-ray and NMR structures often differ. Their correlation is 69% only. However, analogous difference is found for refined and rerefined NMR structures, allowing us to suggest that the observed difference in interresidue contacts of X-ray and NMR structures of the same proteins is due mainly to a difference in mathematical treatment of experimental results.     

Perovskite Solar Cells: Can We Go Organic‐Free,Lead‐Free,and Dopant‐Free?

Having demonstrated incredibly fast progress in power conversion efficiency, rising to a level comparable with that of crystalline silicon cells, lead‐based organic–inorganic hybrid perovskite solar cells are now facing the stability tests needed for industrialization. Poor thermal stability (<150 °C) owing to organic constituents and interlayer diffusion of materials (dopants), and environmental incompatibility due to Pb has surged the development of organic‐free, Pb‐free perovskites and dopant‐free hole transport materials (HTMs). The recent rapid increase in efficiency of cells based on inorganic perovskites, crossing 18%, demonstrates the great potential of inorganic perovskites as thermally stable and high‐efficiency cells. Although all kinds of Pb‐free perovskites lag in efficiency in comparison to the hybrid and inorganic perovskites, they also demonstrate better structural and environmental stability. The performance of dopant‐free HTMs matching/surpassing dopant‐containing HTMs makes the former a better choice for stability. Even though the efforts to enhance the stability of Pb‐based hybrid perovskites should continue by different techniques, organic‐free and lead‐free perovskites, and dopant‐free HTMs must be pursued with greater interest for the future. This review describes the present issues and possible strategies to address them, and thus will help to improve the overall performance of robust organic‐free, Pb‐free, and dopant‐free perovskite solar cells.     

Do weaver ants affect arthropod diversity and the natural‐enemy‐to‐pest ratio in horticultural systems?

High biodiversity is an important component of sustainable agricultural systems, and previous studies have found that increases in the diversity of the natural enemies of pests are associated with decreases in pest populations. Weaver ants are well known for their highly territorial and aggressive behaviour and for their control efficiency of many insect pests in tropical crop trees. Because of this, the ants have been used as a key component in integrated pest management (IPM) programmes for tropical crop trees. In implementing the IPM programmes, we received a number of enquiries related to whether weaver ants have negative effects on arthropod diversity and other natural enemies in orchard systems due to their aggressive behaviour. To answer these questions, we regularly sampled canopy arthropods in cashew and mango orchards in the Northern Territory of Australia in 1996, 2002 and 2003. We sampled, using a vacuum sampler, orchards with and without weaver ants. Cashew and mango plots with abundant weaver ants had similar or higher canopy arthropod and natural enemy diversity and similar ratios of natural enemies to insect pests, compared with plot where the weaver ant was absent. The study also showed that the application of insecticides reduced arthropod diversity and the ratio of natural enemies to insect pests in a mango orchard. However, insecticide spray did not affect natural enemy diversity and abundance, which may be related to a high immigration rate of natural enemies in small plots surrounded by areas that were not sprayed.     

Are nutrient availability and acidity‐alkalinity gradients related in Sphagnum‐dominated peatlands?

Abstract. Gradients in acidity‐alkalinity and nutrient availability were studied in 2 Sphagnum‐dominated peatlands on the southeastern Italian Alps. Decreasing concentrations of most mineral elements (Ca²⁺, Mg²⁺, Mn²⁺, Al³⁺ and Si⁴⁺) in pore water indicated a progressively lower influx of mineral‐soil water from the slightly minerotrophic conditions in the peatland margins to ombrogenous conditions in the central part of the peatlands. This was paralleled by decreasing concentrations of ash, bulk density, Ca, Fe and, partly, Mn in the peat. The nutrient gradient, as defined by pore water concentrations of N and P, was largely independent of the acidity‐ alkalinity gradient: NO^3‐ and PO₄^3‐ had similar concentrations throughout the gradient, whereas NH₄⁺ concentrations increased with increasing pore‐water pH. In contrast, the peat nutrient gradient coincided with the acidity‐alkalinity gradient, with total concentrations of N and P decreasing from the margin to the centre. Bryophytes and vascular plants had different responses along the acidity‐alkalinity gradient and the nutrient gradient. Bryophyte distribution reflected the acidity‐alkalinity gradient both in pore water and in peat. Vascular plant distribution was mainly influenced by variations in nutrient availability.     

Mammals,agri‐environment schemes and set‐aside – what are the putative benefits?

• 1 The impacts of agricultural intensification on farmland wildlife have been the subject of increasing concern, particularly over the last two decades. Population declines have occurred for a number of mammalian species, sometimes drastically so, and changes in farming practice are believed to be significant contributory factors.
• 2 The major policy instruments for delivering environmental benefits on farmland are agri‐environment schemes. These encourage farmers to adopt more environmentally sensitive farming practices to promote farmland biodiversity. Additionally, compulsory set‐aside, which reduces agricultural surplus, could also have positive impacts on wildlife. In this paper we consider some of the putative benefits of agri‐environment schemes and set‐aside for mammals.
• 3 We review how establishment and management options within agri‐environment schemes and set‐aside might affect habitat resources for mammals. For example, conservation headlands increase plant and invertebrate resources within the crop edge for mammals such as wood mice. Grassy field margins can support communities of smaller mammals, and hedgerows may act as important commuting and hunting routes. Their potential will depend on factors such as seed mixtures used, timing and severity of cutting, and length of time they have been in place.
• 4 At a farm level, habitat heterogeneity may be increased through organic agriculture, which is supported by some agri‐environment schemes. Studies suggest significant benefits to mammals, including wood mice and bats. However, it is increasingly recognized that effective conservation of farmland mammals must seek solutions at the landscape scale, addressing such issues as habitat connectivity between farms. One approach may be the better targeting of scheme agreements.
• 5 We suggest that agri‐environment schemes and set‐aside can contribute to the conservation of mammals on farmland. Recent policy changes are likely to have further positive impacts on farmland wildlife but appropriate mammal monitoring programmes must be developed rigorously to assess their effects.

     

Genomic‐scale comparison of sequence‐ and structure‐based methods of function prediction: Does structure provide additional insight?

A function annotation method using the sequence-to-structure-to-function paradigm is applied to the identification of all disulfide oxidoreductases in the Saccharomyces cerevisiae genome. The method identifies 27 sequences as potential disulfide oxidoreductases. All previously known thioredoxins, glutaredoxins, and disulfide isomerases are correctly identified. Three of the 27 predictions are probable false-positives. Three novel predictions, which subsequently have been experimentally validated, are presented. Two additional novel predictions suggest a disulfide oxidoreductase regulatory mechanism for two subunits (OST3 and OST6) of the yeast oligosaccharyltransferase complex. Based on homology, this prediction can be extended to a potential tumor suppressor gene, N33, in humans, whose biochemical function was not previously known. Attempts to obtain a folded, active N33 construct to test the prediction were unsuccessful. The results show that structure prediction coupled with biochemically relevant structural motifs is a powerful method for the function annotation of genome sequences and can provide more detailed, robust predictions than function prediction methods that rely on sequence comparison alone.     

Above‐ and Belowground Trophic Interactions on Creeping Thistle (Cirsium arvense) in High‐ and Low‐Diversity Plant Communities: Potential for Biotic Resistance?

The capacity of local communities to control introduced plants is called biotic resistance. Biotic resistance has been almost exclusively tested for plant competition and above ground herbivores and pathogens, while neglecting root herbivores and soil pathogens. Here, we present biotic resistance by above- and below ground herbivores in concert, and relate the abundance of the plant enemies to the species diversity of the local plant communities. The study was carried out in a 7-year-old biodiversity field experiment. We used creeping thistle (Cirsium arvense) as a model, and quantified sap-sucking herbivores: above ground aphids, their antagonists, and root-feeding nematodes. As plant diversity treatments, we used field plots sown with high (15 plant species, HSD) or low (4 plant species, LSD) diverse seed mixtures in 1996 and that were not weeded. Creeping thistle became established spontaneously at the start of the experiment. In 2002, in HSD plots, 90 % of the plant community was made up by 11 species, compared to seven species in LSD plots. No differences were found for C. arvense abundance or biomass. Above ground, three aphid species were found on C. arvense-Uroleucon cirsii, Aphis fabae, and Macrosiphum euphorbiae, but the latter was found only in low densities. Significantly more aphid species were found on individual plants in HSD plots. Moreover, in HSD plots, on average 10 % of aphids were parasitized, while no parasitism was observed in LSD plots. In the root zone of C. arvense, significantly more nematodes were found in HSD than in LSD plots, and a significantly higher proportion of those nematodes were plant parasites. The dominant plant parasitic nematode in both treatments was Paratylenchus. We conclude that biotic resistance by natural enemies may be enhanced by plant species diversity, but that above- and below ground sap-sucking herbivores do not necessarily have to respond similarly to the diversity of the surrounding plant community.     

A gene for speed? The evolution and function of α‐actinin‐3

The alpha-actinins are an ancient family of actin-binding proteins that play structural and regulatory roles in cytoskeletal organisation and muscle contraction. alpha-actinin-3 is the most-highly specialised of the four mammalian alpha-actinins, with its expression restricted largely to fast glycolytic fibres in skeletal muscle. Intriguingly, a significant proportion ( approximately 18%) of the human population is totally deficient in alpha-actinin-3 due to homozygosity for a premature stop codon polymorphism (R577X) in the ACTN3 gene. Recent work in our laboratory has revealed a strong association between R577X genotype and performance in a variety of athletic endeavours. We are currently exploring the function and evolutionary history of the ACTN3 gene and other alpha-actinin family members. The alpha-actinin family provides a fascinating case study in molecular evolution, illustrating phenomena such as functional redundancy in duplicate genes, the evolution of protein function, and the action of natural selection during recent human evolution.     

Retromer and the cation‐independent mannose 6‐phosphate receptor—Time for a trial separation?

The retromer cargo‐selective complex (CSC) comprising Vps35, Vps29 and Vps26 mediates the endosome‐to‐Golgi retrieval of the cation‐independent mannose 6‐phosphate receptor (CIMPR). Or does it? Recently published data have questioned the validity of this long‐established theory. Here, the evidence for and against a role for the retromer CSC in CIMPR endosome‐to‐Golgi retrieval is examined in the light of the new data that the SNX‐BAR dimer is actually responsible for CIMPR retrieval.      

Home or away? Differences between home‐ and clinic‐based dental examinations for older people

Objective: To determine whether home‐based and clinic‐based dental examinations of older people are comparable. Background: Despite a number of studies which have examined the concordance between different examiners or examination circumstances, none has directly compared an oral examination conducted at home with one conducted in an appropriate clinical setting. Materials and methods: Dentate participants (n = 61) aged between 65 and 74 years underwent two clinical examinations, one in a conventional dental clinic and the other in the person’s home. Kappa statistics, intra‐class correlation coefficients and ‘Difference against mean’ plots were used to determine the nature and extent of any bias. Results: The summary estimates for missing teeth and dental caries were close, although the home‐based examinations resulted in a lower estimate of the mean number of decayed teeth and of untreated coronal decay. The lowest reliability statistics were observed with respect to the prevalence of untreated coronal caries, filled root surfaces and root surface (Decayed or Filled Surfaces) DFS. The periodontitis prevalence estimates were closer, but the reliability statistics were relatively low. The extent of bleeding on probing was relatively under‐estimated in the home‐based examinations. ‘Difference against mean’ plots indicated that, overall, the clinic‐based examinations detected more disease (although this was not observed for all clinical parameters which were measured). Conclusion: While clinic‐based examinations will remain the preferred option, the potential loss of information associated with home‐based examinations is unlikely to be great enough to preclude using them where required, although surveys with larger samples (and therefore more accurate estimates) should restrict their proportion of home‐based examinations to no more than 10%. As they are less precise, surveys with samples of 300 or fewer can safely accommodate up to about one‐third of their examinations being conducted in participants’ homes.     

PARP‐mediated proteasome activation: A co‐ordination of DNA repair and protein degradation?

During the evolution of aerobic life, antioxidant defence systems developed that either directly prevent oxidative modifications of the cellular constituents or remove the modified components. An example of the latter is the proteasome, which removes cytosolic oxidised proteins. Recently, a novel mechanism of activation of the nuclear 20S proteasome was discovered: automodified poly-(ADP-ribose) polymerase-1 (PARP-1) activates the proteasome to facilitate selective degradation of oxidatively damaged histones. Since activation of the PARP-1 itself is induced by DNA damage and is supposed to play a role in DNA repair, these new results suggest a joint role of PARP-1 in the removal of oxidised nucleoproteins and in DNA repair. We hypothesise that PARP-1 could provide a co-ordinative link between two nuclear antioxidant defence systems, whose concerted activation would produce a fast and efficient restoration of the native chromatin structure following oxidative stress.     

Why are birds' eggs colourful? Eggshell pigments co‐vary with life‐history and nesting ecology among British breeding non‐passerine birds

The colourful appearance of bird eggshells has long fascinated biologists and considerable research effort has focused on the structure and biochemistry of the avian eggshell matrix. The presence of tetrapyrrole pigments was identified nearly a century ago. Surprisingly, how the concentrations of avian eggshell pigments vary among related species, and whether this variability is associated with either eggshell appearance and/or species life‐history traits, remains poorly understood. We quantified the concentrations of the two key eggshell pigments, protoporphyrin IX and biliverdin, from a diverse sample of eggshells stored at the Natural History Museum, Tring, UK. We explicitly tested how these two pigments are associated with physical measures of eggshell coloration and whether the pigment concentrations and colour diversity co‐vary with phylogenetic affiliations among species. We also tested a series of comparative hypotheses regarding the association between the concentrations of the two pigments and specific life‐history and breeding ecology traits. Across species, the average concentrations of protoporphyrin and biliverdin were positively correlated, and both strongly co‐varied with phylogenetic relatedness. Controlling for phylogeny, protoporphyrin concentration was associated with a higher likelihood of cavity nesting and ground nesting, whereas biliverdin concentration was associated with a higher likelihood of non‐cavity nesting habit and bi‐parental provisioning. Although unlikely to be explained by a single function, the breeding ecology and life history‐dependence of eggshell pigment concentrations in these comparative analyses implies that related species share pigment strategies, and that those strategies relate to broad adaptive roles in the evolution of variation in avian eggshell coloration and its underlying mechanisms. © 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, 106 , 657–672.     

Air‐core fiber or photonic‐crystal rod,which is more suitable for energetic femtosecond pulse generation and three‐photon microscopy at the 1700‐nm window?

Energetic femtosecond pulses at the 1700‐nm window are a prerequisite for deep‐tissue three‐photon microscopy (3PM). Soliton self‐frequency shift (SSFS) in photonic‐crystal (PC) rod has been the only technique to generate such pulses suitable for 3PM. Here we demonstrate through SSFS in an air‐core fiber, we can generate most energetic femtosecond soliton pulses at the 1700‐nm window, 5.2 times higher than that from PC rod. However, the air‐core soliton pulse width is 5.9 times longer than that of PC rod soliton. Based on comparative 3PM excited with both air‐core and PC rod solitons, we propose the more suitable source for 3PM. We further elucidate the challenge of generating shorter soliton pulses from air‐core fibers through numerical simulation.     

Could co‐transplantation of iPS cells derived hepatocytes and MSCs cure end‐stage liver disease?

Orthotopic liver transplantation is, to date, the only proven effective treatment for end-stage liver disease. However, it suffers from lack of donors and immunorejection. Here, we speculate that co-transplantation of induced pluripotent stem (iPS) cells derived hepatocytes and mesenchymal stem cells (MSCs) may offer an alternative way to treat patients with end-stage liver disease. Recently, progress on iPS cells, homogeneous differentiation of hepatocyte-like cells from embryonic stem cells (ESCs), and paracrine effects by MSCs highlight the possibility. Safe, efficient and rapid generation of iPS cells has been reliably produced by several experimental laboratories. Methods for highly efficient and homogeneous differentiation of ESCs into functional hepatocytes have been established as well. Moreover, paracrine effects by MSCs have been proven to play an important role in liver regeneration and repair, and the effects can be used as an enhancer for engraftment. All of these remarkable developments lead to this hypothesis which may offer a novel therapeutic strategy for treatment of patients with end-stage liver disease, though some issues about safety and efficacy need to be further guaranteed.     

How efficiently do corn‐ and soybean‐based cropping systems use water? A systems modeling analysis

Agricultural systems are being challenged to decrease water use and increase production while climate becomes more variable and the world's population grows. Low water use efficiency is traditionally characterized by high water use relative to low grain production and usually occurs under dry conditions. However, when a cropping system fails to take advantage of available water during wet conditions, this is also an inefficiency and is often detrimental to the environment. Here, we provide a systems‐level definition of water use efficiency (sWUE) that addresses both production and environmental quality goals through incorporating all major system water losses (evapotranspiration, drainage, and runoff). We extensively calibrated and tested the Agricultural Production Systems sIMulator (APSIM) using 6 years of continuous crop and soil measurements in corn‐ and soybean‐based cropping systems in central Iowa, USA. We then used the model to determine water use, loss, and grain production in each system and calculated sWUE in years that experienced drought, flood, or historically average precipitation. Systems water use efficiency was found to be greatest during years with average precipitation. Simulation analysis using 28 years of historical precipitation data, plus the same dataset with ± 15% variation in daily precipitation, showed that in this region, 430 mm of seasonal (planting to harvesting) rainfall resulted in the optimum sWUE for corn, and 317 mm for soybean. Above these precipitation levels, the corn and soybean yields did not increase further, but the water loss from the system via runoff and drainage increased substantially, leading to a high likelihood of soil, nutrient, and pesticide movement from the field to waterways. As the Midwestern United States is predicted to experience more frequent drought and flood, inefficiency of cropping systems water use will also increase. This work provides a framework to concurrently evaluate production and environmental performance of cropping systems.     

Macro and Microhabitat Associations of the Peter's Tent‐Roosting Bat (Uroderma bilobatum): Human‐Induced Selection and Colonization?

Understanding species‐specific habitat selection is essential to identify how natural systems are assembled and maintained, and how emerging natural and anthropogenic disturbances will affect ecosystem function. In the Neotropics, Peter's tent‐roosting bat (Uroderma bilobatum), known to roost in forests, has become abundant in human‐modified areas. To understand how habitat characteristics in both intact forest and human‐modified areas influence the presence and density of U. bilobatum, we characterized habitat use at two scales (macrohabitat and microhabitat) and used logistic and poisson regressions to determine which habitat characteristics best predicted the presence and density of U. bilobatum within each scale. Moreover, we performed a redundancy analysis to determine which habitat scale explained more variation. As these bats are obligate tent roosters, we used tent as a surrogate for bat presence and density. We found that both macrohabitat and microhabitat scales explained variation in presence and density. Characteristics of the microhabitat scale, however, had higher predictive power, revealing that U. bilobatum preferentially inhabits areas with high density of coconut palms. Coconut palms were introduced recently in the Neotropics and are found only in human‐modified areas. Therefore, we hypothesize that U. bilobatum is expanding its range into these areas following the expanded distribution of this exotic plant species.     

Are Normal‐Weight Americans Over‐Fat?

Data from National Health and Nutrition Examination Surveys (NHANES) 1999-2004 have recently shown the percent body fat of American adults. Average American men and women have ~28 and 40% body fat. When categorized by BMI and age, the data also show high percent body fat values, particularly in lower BMI categories. These data should make one reflect on the health status of Americans in all BMI categories and the use of these data for public health recommendations.     

Who Is the King? The α‐Hydroxy‐β‐oxo‐α,β‐enone Moiety or the Catechol B Ring: Relationship between the Structure of Quercetin Derivatives and Their Pro‐Oxidative Abilities

Quercetin and other flavonoids have been reported to exhibit both antioxidant and pro‐oxidant properties. Most studies about the pro‐oxidative ability were conducted in the presence of metal ions, and the essential functional moiety of quercetin responsible for the pro‐oxidative effect is still unclear. In this study, we evaluated the pro‐oxidative abilities in the absence of metal ions of two quercetin derivatives, i.e., quercetin‐3′‐O‐β‐D ‐glucoside ( 1 ) and quercetin‐3‐O‐β‐D ‐glucoside ( 2 ), by assessing DNA cleavage and HO^.‐radical production. The binding mode between these compounds and DNA was studied by fluorescence and viscometric titrations. The results showed that 1 can efficiently induce oxidative damage to plasmid DNA, while 2 shows poor activity. Both 1 and 2 bind to DNA via groove‐binding. These results proved that the α‐hydroxy‐β‐oxo‐α,β‐enone moiety contributes to the pro‐oxidative activity of quercetin.     

Ecological filtering or random extinction? Beta‐diversity patterns and the importance of niche‐based and neutral processes following habitat loss

Although both niche‐based and neutral processes are involved in community assembly, most models on the effects of habitat loss are stochastic, assuming neutral communities mainly affected by ecological drift and random extinction. Given that habitat loss is considered the most important driver of the current biodiversity crisis, unraveling the processes underlying the effects of habitat loss is critical from both a theoretical and an applied perspective. Here we unveil the importance of niche‐based and neutral processes to species extinction and community assembly across a gradient of habitat loss, challenging the predictions of neutral models. We draw on a large dataset containing the distribution of 3653 individuals of 42 species, representing 35% of the small mammal species of the Atlantic Forest hotspot, obtained in 68 sites across three continuously‐forested landscapes and three adjacent 10 000‐ha fragmented landscapes differing in the amount of remaining forest (50%, 30% and 10%). By applying a null‐model approach, we investigated β‐diversity patterns by detecting deviations of observed community similarity from the similarity between randomly assembled communities. Species extinction following habitat loss was decidedly non‐random, in contrast to the notion that fragmented communities are mainly driven by ecological drift. Instead, habitat loss led to a strong biotic homogenization. Moreover, species composition changed abruptly at the same level of landscape‐scale habitat loss that has already been associated with a drastic decline in species richness. Habitat loss, as other anthropogenic disturbances, can thus be seen as a strong ecological filter that increases (rather than decreases) the importance of deterministic processes in community assembly. As such, critical advances for the development of conservation science lie on the incorporation of the relevant niche traits associated with extinction proneness into models of habitat loss. The results also underscore the fundamental importance of pro‐active measures to prevent human‐modified landscapes surpassing critical ecological thresholds.