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Dysregulation of the PI3K/AKT pathway is a common occurrence in high‐grade serous ovarian carcinoma (HGSOC), with the loss of the tumour suppressor PTEN in HGSOC being associated with poor prognosis. The cellular mechanisms of how PTEN loss contributes to HGSOC are largely unknown. We here utilise time‐lapse imaging of HGSOC spheroids coupled to a machine learning approach to classify the phenotype of PTEN loss. PTEN deficiency induces PI(3,4,5)P3‐rich and ‐dependent membrane protrusions into the extracellular matrix (ECM), resulting in a collective invasion phenotype. We identify the small GTPase ARF6 as a crucial vulnerability of HGSOC cells upon PTEN loss. Through a functional proteomic CRISPR screen of ARF6 interactors, we identify the ARF GTPase‐activating protein (GAP) AGAP1 and the ECM receptor β1‐integrin (ITGB1) as key ARF6 interactors in HGSOC regulating PTEN loss‐associated invasion. ARF6 functions to promote invasion by controlling the recycling of internalised, active β1‐integrin to maintain invasive activity into the ECM. The expression of the CYTH2‐ARF6‐AGAP1 complex in HGSOC patients is inversely associated with outcome, allowing the identification of patient groups with improved versus poor outcome. ARF6 may represent a therapeutic vulnerability in PTEN‐depleted HGSOC. Synopsis: Loss of the tumor suppressor PTEN is associated with poor prognosis in high‐grade serous ovarian carcinoma (HGSOC) but its cellular role remains unclear. Here, PTEN deficiency is shown to drive PI(3,4,5)P3‐dependent cancer cell invasion via enhancing recycling of pro‐invasive endocytic cargos. PTEN depletion in three‐dimensional HGSOC spheroids induces PI(3,4,5)P3‐rich membrane protrusions in an ARF6‐dependent manner.A CYTH2‐ARF6‐AGAP1 module regulates PTEN loss‐associated invasion, with GEF CYTH2 being PI(3,4,5)P3‐responsive.The CYTH2‐ARF6‐AGAP1 module localises to PI(3,4,5)P3‐rich protrusion tips, supporting recycling of β1‐integrin and extracellular matrix invasion.Expression of the ARF6 complex in HGSOC patients is inversely correlated with outcome. [ABSTRACT FROM AUTHOR]

Patient‐derived organoids and cellular spheroids recapitulate tissue physiology with remarkable fidelity. We investigated how engagement with a reconstituted basement membrane in three dimensions (3D) supports the polarized, stress resilient tissue phenotype of mammary epithelial spheroids. Cells interacting with reconstituted basement membrane in 3D had reduced levels of total and actin‐associated filamin and decreased cortical actin tension that increased plasma membrane protrusions to promote negative plasma membrane curvature and plasma membrane protein associations linked to protein secretion. By contrast, cells engaging a reconstituted basement membrane in 2D had high cortical actin tension that forced filamin unfolding and endoplasmic reticulum (ER) associations. Enhanced filamin‐ER interactions increased levels of PKR‐like ER kinase effectors and ER‐plasma membrane contact sites that compromised calcium homeostasis and diminished cell viability. Consequently, cells with decreased cortical actin tension had reduced ER stress and survived better. Consistently, cortical actin tension in cellular spheroids regulated polarized basement membrane membrane deposition and sensitivity to exogenous stress. The findings implicate cortical actin tension‐mediated filamin unfolding in ER function and underscore the importance of tissue mechanics in organoid homeostasis. Synopsis: How three‐dimensional spheroid cultures of mammary epithelial cells retain superior long‐term viability and stress resilience remains unclear. This work uncovers coupling between extracellular matrix (ECM) topology, cortical actin tension and endoplasmic reticulum (ER) function, which serves to safeguard protein secretion and cellular stress response. High cortical actin tension in 2D mammary epithelial cell cultures facilitates filamin‐PERK interaction and compromises ER function.In 3D spheroid cultures, mammary epithelial cell ‐ ECM interactions reduce cortical actin tension and filamin binding to PERK, maintaining ER homeostasis.Reduced cortical actin tension increases plasma membrane protrusion size and duration, favoring recruitment of negative curvature‐binding proteins that facilitate protein secretion. [ABSTRACT FROM AUTHOR]

Triple‐negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with poor prognosis and high rates of relapse. The lack of actionable targets for TNBC has contributed to the high mortality rates of this disease, and new candidate molecules for potential manipulation are urgently required. Here, we show that macrophage‐stimulating protein (MSP) and its tyrosine kinase receptor, Recepteur d'origine nantais (RON), are potent drivers of cancer cell growth and tumor progression in a mouse model of TNBC driven by the loss of Trp53 and Brca1. After comparison of two genetically engineered mouse models of TNBC, we found that mammary tumors from K14‐Cre;Brca1F/F;Trp53F/F (KB1P) mice exhibit high endogenous levels of MSP and RON expression. We show that MSP stimulates serine/threonine kinase 1 and extracellular regulated MAPK activation as well as cancer cell growth in cell lines derived from the two mouse models, while genetic and pharmacological inhibition of RON prevents these effects. Similarly, KB1P tumor progression in mice was robustly attenuated by treatment with a RON inhibitor with accompanied reduction in the proliferation marker, Ki‐67. Analysis of human gene expression data confirmed that the genes encoding MSP and RON are robustly expressed in human TNBC as well as other subsets of breast cancer. Our findings uncover a mouse model where MSP expression and RON expression are naturally increased, and they provide evidence that this receptor and its ligand are viable candidate molecules for targeted treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Abstract: Bio‐based and bio‐degradable plastics such as polybutylene succinate (PBS) have the potential to become sustainable alternatives to petrochemical‐based plastics. Polybutylene succinate can be produced from bio‐based succinic acid and 1,4‐butanediol using first‐generation (1G) or second‐generation (2G) sugars. A cradle‐to‐grave environmental assessment was performed for PBS products in Europe to investigate the non‐renewable energy use (NREU) and greenhouse gas (GHG) impacts. The products investigated are single‐use trays and agricultural film, with incineration, industrial composting and degradation on agricultural land as end‐of‐life scenarios. Both end products manufactured from fully bio‐based PBS and from partly bio‐based PBS (made from bio‐based succinic acid and fossil fuel‐based 1,4 butanediol) were analysed. We examine corn (1G) as well as corn stover, wheat straw, miscanthus and hardwood as 2G feedstocks. For the cradle‐to‐grave system, 1G fully bio‐based PBS plastic products were found to have environmental impacts comparable with their petrochemical incumbents, while 2G fully bio‐based PBS plastic products allow to reduce NREU and GHG by around one third under the condition of avoidance of concentration of sugars and energy integration of the pretreatment process with monomer production. Without energy integration and with concentration of sugars (i.e., separate production), the impacts of 2G fully bio‐based PBS products are approximately 15–20% lower than those of 1G fully bio‐based PBS products. The environmental analysis of PBS products supports the value proposition related to PBS products while also pointing out areas requiring further research and development. © 2018 Society of Chemical Industry and John Wiley & Sons, Ltd [ABSTRACT FROM AUTHOR]

Abstract: Recent studies have suggested that spatial patterns of intraspecific diversity can be influenced by density‐dependent processes, which can inhibit effective migration of new lineages to established populations. How mechanisms such as dispersal and disturbance influence these processes is, however, still poorly understood. We hypothesised that (1) species with leptokurtic dispersal (frequent on small scales but rare on larger scales) would show no spatial structure on small scales and strong structure on large scales, and (2) disturbance would influence the chance of genetic turnover in a population. We tested these hypotheses using empirical genetic (mtDNA) data from field observations of a model taxon (the buoyant, forest‐forming kelp Durvillaea, which exhibits leptokurtic dispersal distribution), and by conducting simulation analyses. Our data supported the first hypothesis, with no spatial structure detected on fine (metres) scales despite evidence of strong structure on larger (tens to hundreds of kilometres) scales. The second hypothesis was also supported, with simulations showing that disturbance increased the rate at which structure developed, and reduced the time to fixation (monopolisation by a single lineage). The chance of any lineage reaching fixation was directly related to its initial proportion in the population, and this relationship was unaffected by changes in disturbance size or dispersal capacity. We conclude that, in the absence of selection, extirpation is typically a prerequisite for population‐genetic “turnover”, with remnant (refugial) individuals otherwise outnumbering immigrants. Synthesis. Disturbance plays a critical role in releasing density‐dependent blocks to colonisation, and thus enables lineage turnover within species. Our results indicate that although both disturbance size and dispersal capacity play important roles in the formation of spatial structure within species, unless a population is totally extirpated, establishment of genetic lineages from elsewhere (turnover) is unlikely even for species that can disperse well. [ABSTRACT FROM AUTHOR]

Natural grasslands in southern Australia commonly exist in altered states. One widespread altered state is grassland pasture dominated by cool-season (C3) native grasses maintained by ongoing grazing. This study explores the consequences of removing grazing and introducing fire as a conservation management tool for such a site. We examined the abundance of two native and three exotic species, across a mosaic of fire regimes that occurred over a three-year period: unburnt, summer wild-fire (>2 years previous), autumn management fire (<1 year previously) and burnt in both fires. Given that one aim of conservation management is to increase native species at the expense of exotics, the impacts of the fires were largely positive. Native grasses were at higher cover levels in the fire-managed vegetation than in the unburnt vegetation. Of the three exotic species, one was consistently at lower density in the burnt plots compared to the unburnt plots, while the others were lower only in those plots burnt in summer. The results show that the response of a species varies significantly between different fire events, and that the effects of one fire can persist through subsequent fires. Importantly, some of the effects were large, with changes in the density of plants of over 100-fold. Fire is potentially a cost-effective tool to assist the ecological restoration of retired grassland pastures at large scales. [ABSTRACT FROM AUTHOR]

Tumor progression alters the composition and physical properties of the extracellular matrix. Particularly, increased matrix stiffness has profound effects on tumor growth and metastasis. While endothelial cells are key players in cancer progression, the influence of tumor stiffness on the endothelium and the impact on metastasis is unknown. Through quantitative mass spectrometry, we find that the matricellular protein CCN1/ CYR61 is highly regulated by stiffness in endothelial cells. We show that stiffness-induced CCN1 activates β-catenin nuclear translocation and signaling and that this contributes to upregulate N-cadherin levels on the surface of the endothelium, in vitro. This facilitates N-cadherin-dependent cancer cell-endothelium interaction. Using intravital imaging, we show that knockout of Ccn1 in endothelial cells inhibits melanoma cancer cell binding to the blood vessels, a critical step in cancer cell transit through the vasculature to metastasize. Targeting stiffness-induced changes in the vasculature, such as CCN1, is therefore a potential yet unappreciated mechanism to impair metastasis. [ABSTRACT FROM AUTHOR]

The formation of distinct subdomains of the cell surface is crucial for multicellular organism development. The most striking example of this is apical-basal polarization. What is much less appreciated is that underpinning an asymmetric cell surface is an equally dramatic intracellular endosome rearrangement. Here, we review the interplay between classical cell polarity proteins and membrane trafficking pathways, and discuss how this marriage gives rise to cell polarization. We focus on those mechanisms that regulate apical polarization, as this is providing a number of insights into how membrane traffic and polarity are regulated at the tissue level. [ABSTRACT FROM AUTHOR]

Haplotype networks are an intuitive method for visualising relationships between individual genotypes at the population level., Here, we present popart, an integrated software package that provides a comprehensive implementation of haplotype network methods, phylogeographic visualisation tools and standard statistical tests, together with publication-ready figure production., popart also provides a platform for the implementation and distribution of new network-based methods - we describe one such new method, integer neighbour-joining., The software is open source and freely available for all major operating systems. [ABSTRACT FROM AUTHOR]

With the increasing use of massively parallel sequencing approaches in evolutionary biology, the need for fast and accurate methods suitable to investigate genetic structure and evolutionary history is more important than ever. We propose new distance measures for estimating genetic distances between individuals when allelic variation, gene dosage and recombination could compromise standard approaches., We present four distance measures based on single nucleotide polymorphisms (SNP) and evaluate them against previously published measures using coalescent-based simulations. Simulations were used to test (i) whether the measures give unbiased and accurate distance estimates, (ii) whether they can accurately identify the genomic mixture of hybrid individuals and (iii) whether they give precise (low variance) estimates. The effect of rate variation among genes and recombination was also investigated., The results showed that the SNP-based genpofad distance we propose appears to work well in the widest range of circumstances. It was the most accurate and precise method for estimating genetic distances and is also relatively good at estimating the genomic mixture of hybrid individuals., Our simulations provide benchmarks to compare the performance of different methods that estimate genetic distances between organisms. [ABSTRACT FROM AUTHOR]

Plant production systems globally must be optimized to produce stable high yields from limited land under changing and variable climates. Demands for food, animal feed, and feedstocks for bioenergy and biorefining applications, are increasing with population growth, urbanization and affluence. Low-input, sustainable, alternatives to petrochemical-derived fertilizers and pesticides are required to reduce input costs and maintain or increase yields, with potential biological solutions having an important role to play. In contrast to crops that have been bred for food, many bioenergy crops are largely undomesticated, and so there is an opportunity to harness beneficial plant-microbe relationships which may have been inadvertently lost through intensive crop breeding. Plant-microbe interactions span a wide range of relationships in which one or both of the organisms may have a beneficial, neutral or negative effect on the other partner. A relatively small number of beneficial plant-microbe interactions are well understood and already exploited; however, others remain understudied and represent an untapped reservoir for optimizing plant production. There may be near-term applications for bacterial strains as microbial biopesticides and biofertilizers to increase biomass yield from energy crops grown on land unsuitable for food production. Longer term aims involve the design of synthetic genetic circuits within and between the host and microbes to optimize plant production. A highly exciting prospect is that endosymbionts comprise a unique resource of reduced complexity microbial genomes with adaptive traits of great interest for a wide variety of applications. [ABSTRACT FROM AUTHOR]

Intertidal habitats provide important feeding areas for migratory shorebirds. Anthropogenic developments along coasts can increase ambient light levels at night across adjacent inter-tidal zones. Here, we report the effects of elevated nocturnal light levels upon the foraging strategy of a migratory shorebird (common redshank Tringa totanus) overwintering on an industrialised estuary in Northern Europe., To monitor behaviour across the full intertidal area, individuals were located by day and night using VHF transmitters, and foraging behaviour was inferred from inbuilt posture sensors. Natural light was scored using moon-phase and cloud cover information and nocturnal artificial light levels were obtained using geo-referenced DMSP/ OLS night-time satellite imagery at a 1-km resolution., Under high illumination levels, the commonest and apparently preferred foraging behaviour was sight-based. Conversely, birds feeding in areas with low levels of artificial light had an elevated foraging time and fed by touch, but switched to visual rather than tactile foraging behaviour on bright moonlit nights in the absence of cloud cover. Individuals occupying areas which were illuminated continuously by lighting from a large petrochemical complex invariably exhibited a visually based foraging behaviour independently of lunar phase and cloud cover., We show that ambient light levels affect the timing and distribution of foraging opportunities for redshank. We argue that light emitted from an industrial complex improved nocturnal visibility. This allowed sight-based foraging in place of tactile foraging, implying both a preference for sight-feeding and enhanced night-time foraging opportunities under these conditions. The study highlights the value of integrating remotely sensed data and telemetry techniques to assess the effect of anthropogenic change upon nocturnal behaviour and habitat use. [ABSTRACT FROM AUTHOR]

Safeners enhance the selectivity of graminicidal herbicides such as fenoxaprop ethyl in cereals, by increasing their rates of detoxification in the crop. While studying the selectivity of fenoxaprop ethyl in wheat, we determined that the safeners mefenpyr diethyl and fenchlorazole ethyl also enhanced herbicide tolerance in the competing weed black-grass ( Alopecurus myosuroides). Fenoxaprop ethyl was detoxified by conjugation with glutathione in both wheat and black-grass, with the resulting metabolites processed to the respective cysteine derivatives, which were then N-glycosylated. In black-grass, these detoxification pathways were only slightly enhanced by safeners, suggesting that metabolism alone was unlikely to account for increased herbicide tolerance. Instead, it was determined that safening was associated with an accumulation of glutathione and hydroxymethylglutathione and enzymes with antioxidant functions including phi and lambda glutathione transferases, active as glutathione peroxidases and thiol transferases respectively. These safener-induced changes closely mirrored those determined in two independent black-grass populations that had acquired multiple herbicide resistance (MHR) in the field. In addition to enhanced glutathione metabolism, both safener treatment and MHR resulted in elevated levels of flavonoids in the foliage of black-grass plants, notably flavone- C-glycosides and anthocyanins. Our results demonstrate that safening in a grass weed is associated with an inducible activation in antioxidant and secondary metabolism which mirrors the biochemical phenotype exhibited in plants that are resistant to multiple classes of herbicides. [ABSTRACT FROM AUTHOR]

We examined the influence of warming and supplemental precipitation on plant production and abundance of the dominant microarthropod, the springtail Cryptopygus antarcticus (Collembola), in tundra dominated by the vascular plants Colobanthus quitensis and Deschampsia antarctica along the Antarctic Peninsula. Tundra cores were placed in plots near Palmer Station where they were warmed with infrared heaters in combination with receiving supplemental precipitation. Diel canopy air and soil temperatures and air vapor pressure deficits in warmed plots were elevated 0.8 °C, 2.2 °C and 0.13 kPa, respectively. After two growing seasons, total aboveground plant production was greater under warming as a result of enhanced production by C. quitensis, which more than offset declines in moss biomass. Total aboveground plant production was also greater under supplemental precipitation primarily as a result of enhanced moss production. Total aboveground plant production was greatest under the combination of warming and supplemental precipitation, primarily as a result of enhanced C. quitensis production. C. antarcticus were more abundant in cores receiving supplemental precipitation and there was a strong treatment interaction; these springtails were most abundant in warmed cores receiving supplemental precipitation. Over 50% of the variability in the abundance of C. antarcticus could be explained by differences in aboveground plant biomass. However, plant production did not appear directly responsible for differences in C. antarcticus abundance; when we examined C. antarcticus abundance per unit of aboveground plant biomass, differences in its abundance among treatments were still apparent implying these differences were not the direct result of plant biomass. The responses of C. antarcticus were consistent with its known moisture and thermal preferences, suggesting that abiotic factors played a dominant role in controlling its abundance. Precipitation regime had large impacts on warming responses and these were species specific, illustrating the importance of future precipitation regimes in predicting system responses to warming. [ABSTRACT FROM AUTHOR]

In multicellular epithelial tissues, the orientation of polarity of each cell must be coordinated. Previously, we reported that for Madin–Darby canine kidney cells in three-dimensional collagen gel culture, blockade of β1-integrin by the AIIB2 antibody or expression of dominant-negative Rac1N17 led to an inversion of polarity, such that the apical surfaces of the cells were misorientated towards the extracellular matrix. Here, we show that this process results from the activation of RhoA. Knockdown of RhoA by short hairpin RNA reverses the inverted orientation of polarity, resulting in normal cysts. Inhibition of RhoA downstream effectors, Rho kinase (ROCK I) and myosin II, has similar effects. We conclude that the RhoA–ROCK I–myosin II pathway controls the inversion of orientation of epithelial polarity caused by AIIB2 or Rac1N17. These results might be relevant to the hyperactivation of RhoA and disruption of normal polarity frequently observed in human epithelial cancers. [ABSTRACT FROM AUTHOR]

In three experiments, subjects learned to classify simulated aircraft using four probabilistic cues then classified test sets designed to contrast predictions of several compensatory and non-compensatory heuristics. Results indicated that a proportion of subjects appeared to use a non-compensatory fast and frugal heuristic but that significant proportions used less frugal compensatory decision rules. The relative proportions of subjects exhibiting responses consistent with the fast and frugal heuristic versus other decision rules was largely unaffected by manipulations of time pressure and perceived cue uncertainty. An extreme time constraint, however, did result in significant differences in the proportions of subjects who preferred non-compensatory to compensatory decision rules. These results suggest that it is possible to model multi-attribute decision tasks like threat assessment with a fast and frugal heuristic although no single heuristic is a general model for the simulated threat assessment task. Copyright © 2006 Crown in the right of Canada. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Measurements of the energy costs of individual behaviours provide insights into how animals trade-off resource allocation and energy acquisition decisions. The energetic costs while resting on water are poorly known for seabirds but could comprise a substantial proportion of their daily energy expenditure. We measured the cost of resting on water in Black-legged Kittiwakes Rissa tridactyla, a species which does not fly during the night and for which estimating energy expenditure while resting on the water is therefore important. Their resting metabolic rate on water at 12.5 °C was at least 40% higher compared with resting at the same temperature in air. This indicates that, at comparable temperatures, metabolic costs are elevated for birds resting at sea compared with on land. We argue that Kittiwakes meet much of this extra thermoregulatory demand by dedicated metabolic activity. During the winter months, their costs are likely to be even higher owing to lower sea temperatures. Accordingly, we suggest that migration to milder latitudes, following breeding, will provide enhanced benefits, particularly to seabirds such as Kittiwakes which rest on the sea surface during darkness. [ABSTRACT FROM AUTHOR]

Different phases of the annual cycle in birds and mammals are often associated with characteristic and recurrent foraging behaviours. The extent to which stage-dependent changes in foraging behaviour are caused by intrinsic or extrinsic factors is unclear. We controlled for the effects of extrinsic factors by synchronising groups of incubating and chick-rearing black-legged kittiwakes Rissa tridactyla. Synchrony amongst incubators and rearers was achieved experimentally by switching eggs between nests. Behavioural responses to the treatment varied between the sexes. Male kittiwakes with prolonged-incubation made fewer foraging trips but of greater duration compared to those rearing chicks resulting in no change in the time spent on trips between the two groups. Females with prolonged-incubation carried out fewer trips than those rearing chicks but trip duration did not differ between the two stages which resulted in prolonged-incubating birds spending a lower percentage time on trips. In contrast, foraging ranges did not differ between prolonged-incubation and chick-rearing birds for either sex. This suggests that extrinsic factors, such as food availability and distribution determine kittiwake foraging locations and ranges, whereas intrinsic factors, reflected in parental duties, constrain nest attendance. Female prolonged-incubators invested lower levels of parental effort, in terms of daily energy expenditure, compared to chick-rearers whereas males did not show stage-related differences in energy expenditure. This provides evidence that incubation could be an energetically cheaper stage although under normal conditions this difference may be masked by temporal variation in environmental factors. We conclude that while conditions differ between the incubation and chick rearing stages for kittiwakes at this colony, they are not the main factors prompting changes in stage-related foraging patterns. Intrinsic factors such as sex differences, or behaviours required for each stage of the annual cycle, rather than extrinsic factors related to seasonal environments, are likely to be the main proximate cause of recurring changes in behaviour between breeding stages. [ABSTRACT FROM AUTHOR]

Birds might form eggs from stored nutrients, from current food intake or from both. We examined whether stored nutrients were a substantial resource for egg production in an aerial insectivore, which had a variable food supply, but for which there was likely to be a cost for carrying additional mass. The mass changes of female barn swallows Hirundo rustica during the egg formation period were most simply explained by changes in the mass of the eggs and oviduct. Fat score and body mass excluding the eggs and oviduct did not vary systematically during egg formation. Egg production stopped altogether during particularly bad weather. The normal range in environmental conditions before and during laying had little influence on clutch size. Our results suggest that swallows form eggs primarily from current food intake, although our data do not exclude use of micronutrients from reserves. [ABSTRACT FROM AUTHOR]

1. Given the increasing threat of ‘emerging infectious diseases’ (EIDs), and the vulnerability of small inbred populations to such novel challenges (at least partly through compromised immunity), a degree of interspecific hybridization may improve the viability of endangered species by enriching depauperate gene pools. 2. To investigate this hypothesis, we quantified indicators of the strength of both innate and cell-mediated immunity in wild populations of hybridizing parakeets on the Chatham Islands, New Zealand. 3. We show that both measures of immune function are markedly higher in the cosmopolitan red-crowned parakeet Cyanoramphus novaezelandiae than in the island endemic Forbes’ parakeet C. forbesi, as is to be expected when comparing relatively outbred vs. relatively inbred species. 4. In addition, we show that both measures of immune function are higher in Forbes’× red-crowned parakeet hybrids than in the Forbes’ parakeet. Even those individuals with few red-crowned characteristics, suggesting they are the products of matings between hybrids and Forbes’ parakeets, have significantly higher measures of immune function. 5. As at least one of the immune indicators measured correlates directly with both survivorship and the viability of small bird populations, this study reveals a potential management option for hybridizing species of conservation concern, where an increase in resilience to novel disease challenges could outweigh some loss of genetic integrity. [ABSTRACT FROM AUTHOR]

The nuclear localization of a number of growth factors, cytokine ligands and their receptors has been reported in various cell lines and tissues. These include members of the fibroblast growth factor (FGF), epidermal growth factor and growth hormone families. Accordingly, a number of nuclear functions have begun to emerge for these protein families. The demonstration of functional interactions of these proteins with the nuclear import machinery has further supported their functions as nuclear signal transducers. Here, we review the membrane- trafficking machinery and pathways demonstrated to regulate this cell surface to nucleus-trafficking event and highlight the many remaining unanswered questions. We focus on the FGF family, which is providing many of the clues as to the process of this unusual phenomenon. [ABSTRACT FROM AUTHOR]

We used the doubly-labelled water technique to measure daily energy expenditure (DEE) of a free-living uniparental incubator, the white-throated dipper Cinclus cinclus , in Scotland. DEE was 205±8 (s.e.m.) kJ d-1 for 17 females incubating their natural clutch sizes, equivalent to 3.2±0.1×basal metabolic rate (BMR). To investigate the influence of clutch size on the energy budget, we measured the DEE of 14 females with clutches increased or reduced by a single egg. Birds with reduced clutch sizes had an energy expenditure with a mean and variance that did not differ from those of birds with unmanipulated clutches. Enlarging the clutch led to an increase in energy expenditure to over 4×BMR for some individuals but not for others, resulting in greater variance in energy expenditure for birds with enlarged clutches. Individual variation in energy expenditure could not be fully explained by environmental conditions, by patterns of behaviour or clutch size. Incubating females received a maximum of only 4 kJ d-1 (2% of DEE) from provisioning by the male, and mobilised up to 6 kJ d-1 (3% of DEE) from reserves. Females spent 2.9±0.2 h (n=20) away from the nest each day, so a foraging rate of 95 kJ h-1 was required during incubation recesses to balance DEE. This ‘required foraging rate’ is double previous estimates of the maximum rates of energy acquisition for birds of this size. We suggest that the greater likelihood of a raised energy expenditure associated with larger clutches, combined with the difficulties in maintaining energy supplies, may constitute a constraint on avian clutch size. [ABSTRACT FROM AUTHOR]

Summary 1. There is continuing debate about the impact of agricultural practices on farmland wildlife. In particular, it has been postulated that a general decline in insect abundance linked with intensification of agriculture may have contributed to farmland bird decline. While some autecological studies have supported this hypothesis, larger-scale and long-term studies are needed. 2. Suction traps mounted on 12·2-m towers (Rothamsted-type) have been sampling aerial insects for nearly 40 years throughout the UK. Their catches are correlated over large spatial scales. We analysed insect catch data from a single suction trap run for 27 years in a rural location in Scotland, and showed that insect numbers have changed significantly over time, although non-linearly. The multivariate data set (numbers from the 12 common arthropod groups) was summarized using principal components analysis (PCA) to extract three components explaining 62% of the variation. 3. We also used PCA to describe agricultural change, using published agricultural data for eight measures of farming in Scotland. Arthropod abundance and principal component (PC) scores were significantly related to the agricultural PC scores as well to summary climatic measures. 4. Using Scottish data from the British Trust for Ornithology Common Birds Census, we extracted three PC to describe the time-dependent average densities of 15 common farmland birds in Scotland. Measures of bird density were significantly related to insect abundance and PC scores and, independently, to measures of agriculture and climate. 5. These data from a broad suite of species provide support for linked temporal change between farmland birds, invertebrate numbers and agricultural practice in Scotland. Although entirely correlative, the results are consistent with the view that agricultural change has influenced birds through changes in food quality or quantity. The work also shows how large-scale invertebrate sampling, in this case... [ABSTRACT FROM AUTHOR]

Measures the field metabolic rate of nesting Northern Fulmars using the doubly labeled water technique. Behavior of labeled birds; At-sea metabolism; Effects of win on FMR; Wingbeat frequency.

1. The puffin, a long-lived seabird, was studied on the Isle of May, East Scotland between 1990 and 1992. During two of these years, parental effort was experimentally decreased by supplementary feeding of young. This aimed to identify inter-year reproductive costs, and show whether they took the form of reduced adult survival, reduced fledging success and/or a reduction in the ‘quality’ of offspring in the following year. 2. The feeding treatment significantly reduced the daily number of feeds delivered by experimental parents by 67% in 1990 and 87% in 1991. 3. The proportions of experimental and control parents returning to the colony in the year following manipulation did not differ significantly, although in 1991, 2·5 times as many controls (young unfed) as experimental birds (young fed) failed to return. 4. The fledging success of experimental pairs in the year following manipulation (68%) was significantly higher than that of controls (24%). 5. Experimental pairs raised young with significantly higher body condition (Residual Peak Mass) than that of controls in the year following manipulation (1992). 6. Experimental parents did not differ from controls in their body condition (Lipid Reserve Mass) or rate of reserve depletion, either in the year of manipulation or in the following breeding season; hence there was no evidence for a role of the measured component of body condition in the cost mechanism. 7. The study demonstrated inter-year reproductive costs for puffins and supported the hypothesis that long-lived species reduce the ‘quality’ of their offspring or abandon a breeding attempt rather than compromise their survival and future opportunities to reproduce. [ABSTRACT FROM AUTHOR]

Assesses the ability of critical load exceedance estimates to predict the abundance of an indicator species, Cinclus cinclus in Scotland. Derivation of two predictive models of dipper density based on altitude and gradient; Regression model applied to analyze altitude and gradient.

A recently developed technique for examining thermal sensitivity during sleep was used to assess whether skin and core temperature responses to thermal stimulation were altered by sleep state. the technique was designed to probe thermal responsivity without altering core body temperature or inducing awakening. Twenty-seven young men and women were studied during a sleep deprivation night and a sleep night three nights later. Cold water stimulation of the face alternated with an equal period of rewarming across a 40-min cycle throughout the night. Skin temperature from the finger and rectal temperature were continuously assessed. Sleep continuity and architecture were largely uninfluenced by the thermal stimulation. Finger skin temperature decreased during cold facial stimulation in both sleep and waking states. Skin temperature changes during sleep were approximately one-fifth the magnitude of those during waking. Core temperature was minimally influenced. REM sleep was associated with a greater amplitude decrease in finger temperature than was non-REM (NREM) sleep. The results support the utility of the technique as a probe of thermal responsivity during sleep and suggest a reduction of thermal responsivity during sleep and, more tentatively, an altered responsivity during REM versus NREM sleep. [ABSTRACT FROM AUTHOR]

Details the growth of giant cell fibroma (GCF) on the tongue of a ten year old girl. Emphasis on GCF as benign tumor of the oral cavity; Concerns on wrongful identification of a wart; Result of biopsy.