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Supermassive black holes (SMBHs) play[-105pt]Kindly check and confirm the Article Title. fundamental roles in the evolution of galaxies, groups, and clusters. The fossil record of supermassive black hole outbursts is seen through the cavities and shocks that are imprinted on these gas-rich systems. For M87, the central galaxy in the Virgo cluster, deep Chandra observations illustrate the physics of AGN feedback in hot, gas-rich atmospheres and allow measurements of the age, duration, and power of the outburst from the supermassive black hole in M87 that produced the observed cavities and shocks in the hot X-ray atmosphere.

Thin synchrotron-emitting filaments are increasingly seen in the intracluster medium (ICM). We present the first example of a direct interaction between a magnetic filament, a radio jet, and a dense ICM clump in the poor cluster Abell 194. This enables the first exploration of the dynamics and possible histories of magnetic fields and cosmic rays in such filaments. Our observations are from the MeerKAT Galaxy Cluster Legacy Survey and the LOFAR Two Metre Sky Survey. Prominent 220 kpc long filaments extend east of radio galaxy 3C40B, with very faint extensions to 300 kpc, and show signs of interaction with its northern jet. They curve around a bend in the jet and intersect the jet in Faraday depth space. The X-ray surface brightness drops across the filaments; this suggests that the relativistic particles and fields contribute significantly to the pressure balance and evacuate the thermal plasma in a $\sim$35 kpc cylinder. We explore whether the relativistic electrons could have streamed along the filaments from 3C40B, and present a plausible alternative whereby magnetized filaments are a) generated by shear motions in the large-scale, post-merger ICM flow, b) stretched by interactions with the jet and flows in the ICM, amplifying the embedded magnetic fields, and c) perfused by re-energized relativistic electrons through betatron-type acceleration or diffusion of turbulently accelerated ICM cosmic ray electrons. We use the Faraday depth measurements to reconstruct some of the 3D structures of the filaments and of 3C40A and B., Accepted for publication in ApJ. 32 pages, 28 figures. Each of the last four figures has a corresponding movie file (mpeg), available under the Ancillary Files associated with this preprint

We present deep and high fidelity images of the merging galaxy cluster Abell 2256 at low frequencies, using the upgraded Giant Metrewave Radio Telescope (uGMRT) and LOw-Frequency ARray (LOFAR). This cluster hosts one of the most prominent known relics, with a remarkably spectacular network of filamentary substructures. The new uGMRT (300-850 MHz) and LOFAR (120-169 MHz) observations, combined with the archival Karl G. Jansky Very Large Array (VLA; 1-4 GHz) data, allowed us to carry out the first spatially resolved spectral analysis of the exceptional relic emission down to 6 arcsec resolution over a broad range of frequencies. Our new sensitive radio images confirm the presence of complex filaments of magnetized relativistic plasma also at low frequencies. We find that the integrated spectrum of the relic is consistent with a single power law, without any sign of spectral steepening, at least below 3 GHz. Unlike previous claims, the relic shows an integrated spectral index of $-1.07\pm0.02$ between 144 MHz and 3 GHz, which is consistent with the (quasi)stationary shock approximation. The spatially resolved spectral analysis suggests that the relic surface very likely traces the complex shock front, with a broad distribution of Mach numbers propagating through a turbulent and dynamically active intracluster medium. Our results show that the northern part of the relic is seen edge-on and the southern part close to face-on. We suggest that the complex filaments are regions where higher Mach numbers dominate the (re-)acceleration of electrons that are responsible for the observed radio emission., Comment: 27 pages, 14 Figures, accepted for publication in ApJ

We currently face significant, anthropogenic, global environmental challenges, and the role of ecologists in mitigating these challenges is arguably more important than ever. Consequently there is an urgent need to recruit and train future generations of ecologists, both those whose main area is ecology, but also those involved in the geological, biological, and environmental sciences.Here we present the results of a horizon scanning exercise that identified current and future challenges facing the teaching of ecology, through surveys of teachers, students, and employers of ecologists. Key challenges identified were grouped in terms of the perspectives of three groups: students, for example the increasing disconnect between people and nature; teachers, for example the challenges associated with teaching the quantitative skills that are inherent to the study of ecology; and society, for example poor societal perceptions of the field of ecology.In addition to the challenges identified, we propose a number of solutions developed at a workshop by a team of ecology teaching experts, with supporting evidence of their potential to address many of the problems raised. These proposed solutions include developing living labs, teaching students to be ecological entrepreneurs and influencers, embedding skills‐based learning and coding in the curriculum, an increased role for learned societies in teaching and learning, and using new technology to enhance fieldwork studies including virtual reality, artificial intelligence and real‐time spoken language translation.Our findings are focused towards UK higher education, but they should be informative for students and teachers of a wide range of educational levels, policy makers and professional ecologists worldwide.

The Western European Hedgehog (Erinaceous europaeus) is a nocturnal animal that is in decline in much of Europe, but the monitoring of this species is subjective, prone to error, and an inadequate basis for estimating population trends. Here, we report the use of Crenosoma striatum, a parasitic nematode specific to hedgehogs as definitive hosts, to detect hedgehog presence in the natural environment. This is achieved through collecting and sampling the parasites within their intermediate hosts, gastropoda, a group much simpler to locate and sample in both urban and rural habitats. C. striatum and Crenosoma vulpis were collected post-mortem from the lungs of hedgehogs and foxes, respectively. Slugs were collected in two sessions, during spring and autumn, from Skomer Island (n = 21), which is known to be free of hedgehogs (and foxes), and Pennard, Swansea (n = 42), known to have a healthy hedgehog population. The second internal transcribed spacer of parasite ribosomal DNA was used to develop a highly specific, novel, PCR based multiplex assay. Crenosoma striatum was found only at the site known to be inhabited by hedgehogs, at an average prevalence in gastropods of 10% in spring and autumn. The molecular test was highly specific: One mollusc was positive for both C. striatum and C. vulpis, and differentiation between the two nematode species was clear. This study demonstrates proof of principle for using detection of specific parasite DNA in easily sampled intermediate hosts to confirm the presence of an elusive nocturnal definitive host species. The approach has great potential as an adaptable, objective tool to supplement and support existing ecological survey methods.

The XXL survey currently covers two 25 sq. deg. patches with XMM observations of ~10ks. We summarise the scientific results associated with the first release of the XXL data set, that occurred mid 2016. We review several arguments for increasing the survey depth to 40 ks during the next decade of XMM operations. X-ray (z 1 cluster density. It will eventually constitute a reference study and an ideal calibration field for the upcoming eROSITA and Euclid missions.

Pollination is a key ecosystem service for agriculture and wider ecosystem function. However, most pollination studies focus on Hymenoptera, with hoverflies (Syrphidae) frequently treated as a single functional group. We tested this assumption by investigating pollen carried by eleven species of hoverfly in five genera, Cheilosia, Eristalis, Rhingia, Sericomyia and Volucella, using DNA metabarcoding. Hoverflies carried pollen from 59 plant taxa, suggesting they visit a wider number of plant species than previously appreciated. Most pollen recorded came from plant taxa frequently found at our study sites, predominantly Apiaceae, Cardueae, Calluna vulgaris, Rubus fruticosus agg., and Succisa pratensis, with hoverflies transporting pollen from 40% of entomophilous plant species present. Overall pollen transport network structures were generalised, similar to other pollination networks elsewhere. All hoverfly species were also generalised with few exclusive plant/hoverfly interactions. However, using the Jaccard Index, we found significant differences in the relative composition of pollen loads between hoverfly genera, except for Volucella, demonstrating some degree of functional complementarity. Eristalis and Sericomyia species had significant differences in relative pollen load composition compared to congeners. Our results demonstrate the range of pollens transported by hoverflies and the potential pollination function undertaken within this ecologically and morphologically diverse guild.

Pollination by insects is a key ecosystem service and important to wider ecosystem function. Most species‐level pollination networks studied have a generalised structure, with plants having several potential pollinators, and pollinators in turn visiting a number of different plant species. This is in apparent contrast to a plant's need for efficient conspecific pollen transfer.The aim of this study was to investigate the structure of pollen transport networks at three levels of biological hierarchy: community, species and individual. We did this using hoverflies in the genus Eristalis, a key group of non‐Hymenopteran pollinators.We constructed pollen transport networks using DNA metabarcoding to identify pollen. We captured hoverflies in conservation grasslands in west Wales, UK, removed external pollen loads, sequenced the pollen DNA on the Illumina MiSeq platform using the standard plant barcode rbcL, and matched sequences using a pre‐existing plant DNA barcode reference library.We found that Eristalis hoverflies transport pollen from 65 plant taxa, more than previously appreciated. Networks were generalised at the site and species level, suggesting some degree of functional redundancy, and were more generalised in late summer compared to early summer. In contrast, pollen transport at the individual level showed some degree of specialisation. Hoverflies defined as “single‐plant visitors” varied from 40% of those captured in early summer to 24% in late summer. Individual hoverflies became more generalised in late summer, possibly in response to an increase in floral resources. Rubus fruticosus agg. and Succisa pratensis were key plant species for hoverflies at our sitesOur results contribute to resolving the apparent paradox of how generalised pollinator networks can provide efficient pollination to plant species. Generalised hoverfly pollen transport networks may result from a varied range of short‐term specialised feeding bouts by individual insects. The generalisation and functional redundancy of Eristalis pollen transport networks may increase the stability of the pollination service they deliver.

This study tested the ‘silver spoon’ hypothesis which posits that individuals that develop under favourable conditions should enjoy a fitness advantage later in life because they are more likely to recognize and settle in high-quality habitats. Atlantic salmon Salmo salar of two age classes (0+ and 1+ years) were reared in environmentally enriched or standard hatchery tanks for a short period (c. 10 weeks), were then released into a natural river and sampled on repeated occasions to test for silver-spoon effects. Compared with controls, enriched fish had a 6·4% higher recapture rate and settled in higher velocity habitats when they were stocked as 0+ year fry, but not when they were stocked as 1+ year parr. The opportunity for selection was generally higher for environmentally enriched fish than for controls, and also higher for 0+ than for 1+ year fish. Selection favoured individuals with high condition factor, extensive fat reserves and longer than average pectoral fins in both age classes but favoured a small body size in 1+ year and a large body size in 0+ year releases. Stomach analysis showed that enriched fish ate more, and adapted quicker to natural prey than controls. These results provide support for silver-spoon effects in fish and indicate that enrichment can improve post-release performance in conservation programmes, but seemingly only if fish are not kept in captivity for too long.

Pollination is a key ecosystem service, and appropriate management, particularly in agricultural systems, is essential to maintain a diversity of pollinator guilds. However, management recommendations frequently focus on maintaining plant communities, with the assumption that associated invertebrate populations will be sustained. We tested whether plant community, flower resources, and soil moisture would influence hoverfly (Syrphidae) abundance and species richness in floristically‐rich seminatural and floristically impoverished agricultural grassland communities in Wales (U.K.) and compared these to two Hymenoptera genera, Bombus, and Lasioglossum. Interactions between environmental variables were tested using generalized linear modeling, and hoverfly community composition examined using canonical correspondence analysis. There was no difference in hoverfly abundance, species richness, or bee abundance, between grassland types. There was a positive association between hoverfly abundance, species richness, and flower abundance in unimproved grasslands. However, this was not evident in agriculturally improved grassland, possibly reflecting intrinsically low flower resource in these habitats, or the presence of plant species with low or relatively inaccessible nectar resources. There was no association between soil moisture content and hoverfly abundance or species richness. Hoverfly community composition was influenced by agricultural improvement and the amount of flower resource. Hoverfly species with semiaquatic larvae were associated with both seminatural and agricultural wet grasslands, possibly because of localized larval habitat. Despite the absence of differences in hoverfly abundance and species richness, distinct hoverfly communities are associated with marshy grasslands, agriculturally improved marshy grasslands, and unimproved dry grasslands, but not with improved dry grasslands. Grassland plant community cannot be used as a proxy for pollinator community. Management of grasslands should aim to maximize the pollinator feeding resource, as well as maintain plant communities. Retaining waterlogged ground may enhance the number of hoverflies with semiaquatic larvae.

The importance of the marine environment to Eurasian otters is currently poorly understood. Wales is one of the few countries where coastal activity has been recorded and an increase in marine otter sightings could indicate remarkable developments within Welsh populations. The trophic niche of coastal otter populations around Pembrokeshire was investigated over a 12-month period. Marine activity was more widespread than previously thought and marine prey formed the largest component of otter diet, although, otters also consumed freshwater and terrestrial prey throughout the year. Otter diet was very diverse compared to other European coastal populations and a spring contraction in trophic niche width coincided with the estimated timing of breeding activity. Seasonal variation in prey composition was predominantly due to differences in the consumption of alternate prey types. In areas where wetlands are fragmented and populations of freshwater fish are declining, the marine environment may become an increasingly important habitat for otters. It is necessary to define the historical importance of coastal populations to otter conservation. Coastal areas are often subject to pressure from human activities, so the impact of disturbance needs to be assessed. Importantly, there is no verified otter survey method for coastal areas, so the use of marine habitat is likely to be underestimated.

Protein kinase C delta (PKCdelta) modulates cell survival and apoptosis in diverse cellular systems. We recently reported that PKCdelta functions as a critical anti-apoptotic signal transducer in cells containing activated p21(Ras) and results in the activation of AKT, thereby promoting cell survival. How PKCdelta is regulated by p21(Ras), however, remains incompletely understood. In this study, we show that PKCdelta, as a transducer of anti-apoptotic signals, is activated by phosphotidylinositol 3' kinase/phosphoinositide-dependent kinase 1 (PI(3)K-PDK1) to deliver the survival signal to Akt in the environment of activated p21(Ras). PDK1 is upregulated in cells containing an activated p21Ras. Knock-down of PDK1, PKCdelta, or AKT forces cells containing activated p21(Ras) to undergo apoptosis. PDK1 regulates PKCdelta activity, and constitutive expression of PDK1 increases PKCdelta activity in different cell types. Conversely, expression of a kinase-dead (dominant-negative) PDK1 significantly suppresses PKCdelta activity. p21(Ras)-mediated survival signaling is therefore regulated by via a PI(3)K-AKT pathway, which is dependent upon both PDK1 and PKCdelta, and PDK1 activates and regulates PKCdelta to determine the fate of cells containing a mutated, activated p21(Ras).

Androgen antagonists or androgen deprivation is a primary therapeutic modality for the treatment of prostate cancer. Invariably, however, the disease becomes progressive and unresponsive to androgen ablation therapy (hormone refractory). The molecular mechanisms by which the androgen antagonists inhibit prostate cancer proliferation are not fully defined. In this report, we demonstrate that sirtuin 1 (SIRT1), a nicotinamide adenosine dinucleotide-dependent histone deacetylase (HDAC) linked to the regulation of longevity, is required for androgen antagonist-mediated transcriptional repression and growth suppression. Androgen antagonist-bound androgen receptor (AR) recruits SIRT1 and nuclear receptor corepressor to AR-responsive promoters and deacetylates histone H3 locally at the prostate-specific antigen promoter. Furthermore, SIRT1 down-regulation by small interfering RNA or by pharmacological means increased the sensitivity of androgen-responsive genes to androgen stimulation, enhanced the sensitivity of prostate cancer cell proliferative responses to androgens, and decreased the sensitivity of prostate cancer cells to androgen antagonists. In this study, we demonstrate the ligand-dependent recruitment of a class III HDAC into a corepressor transcriptional complex and a necessary functional role for a class III HDAC as a transcriptional corepressor in AR antagonist-induced transcriptional repression. Collectively, these findings identify SIRT1 as a corepressor of AR and elucidate a new molecular pathway relevant to prostate cancer growth and approaches to therapy.

Inhibition of protein kinase C (PKC) activity in transformed cells and tumor cells containing activated p21(RAS) results in apoptosis. To investigate the pro-apoptotic pathway induced by the p21(RAS) oncoprotein, we first identified the specific PKC isozyme necessary to prevent apoptosis in the presence of activated p21(RAS). Dominant-negative mutants of PKC, short interfering RNA vectors, and PKC isozyme-specific chemical inhibitors directed against the PKCdelta isozyme demonstrated that PKCdelta plays a critical role in p21(RAS)-mediated apoptosis. An activating p21(RAS) mutation, or activation of the phosphatidylinositol 3-kinase (PI3K) Ras effector pathway, increased the levels of PKCdelta protein and activity in cells, whereas inhibition of p21(RAS) activity decreased the expression of the PKCdelta protein. Activation of the Akt survival pathway by oncogenic Ras required PKCdelta activity. Akt activity was dramatically decreased after PKCdelta suppression in cells containing activated p21(RAS). Conversely, constitutively activated Akt rescued cells from apoptosis induced by PKCdelta inhibition. Collectively, these findings demonstrate that p21(RAS), through its downstream effector PI3K, induces PKCdelta expression and that this increase in PKCdelta activity, acting through Akt, is required for cell survival. The p21(RAS) effector molecule responsible for the initiation of the apoptotic signal after suppression of PKCdelta activity was also determined to be PI3K. PI3K (p110(C)(AAX), where AA is aliphatic amino acid) was sufficient for induction of apoptosis after PKCdelta inhibition. Thus, the same p21(RAS) effector, PI3K, is responsible for delivering both a pro-apoptotic signal and a survival signal, the latter being mediated by PKCdelta and Akt. Selective suppression of PKCdelta activity and consequent induction of apoptosis is a potential strategy for targeting of tumor cells containing an activated p21(RAS).

1. Time-depth data recorders (TDRs) have been widely used to explore the behaviour of relatively large, deep divers. However, little is known about the dive behaviour of small, shallow divers such as semi-aquatic mammals. 2. We used high-resolution TDRs to record the diving behaviour of American mink Mustela vison (weight of individuals 580-1275 g) in rivers in Oxfordshire (UK) between December 2005 and March 2006. 3. Dives to0.2 m were measured in all individuals (n = 6). Modal dive depth and duration were 0.3 m and 10 s, respectively, although dives up to 3 m and 60 s in duration were recorded. Dive duration increased with dive depth. 4. Temperature data recorded by TDRs covaried with diving behaviour: they were relatively cold (modal temperature 4-6 degrees C across individuals) when mink were diving and relatively warm (modal temperature 24-36 degrees C across individuals) when mink were not diving. 5. Individuals differed hugely in their use of rivers, reflecting foraging plasticity across both terrestrial and aquatic environments. For some individuals there was1 dive per day while for others there was100 dives per day. 6. We have shown it is now possible to record the diving behaviour of small free-living animals that only dive a few tens of centimetres, opening up the way for a new range of TDR studies on shallow diving species.

SUMMARYThe nematode Angiostrongylus vasorum is becoming more widely recorded globally, and is of increasing concern as a cause of disease in dogs. Apparent geographic spread is difficult to confirm due to a lack of standardized disease recording systems, increasing awareness among veterinary clinicians, and recent improvements in diagnostic technologies. This study examines the hypothesis that A. vasorum has spread in recent years by repeating the methods of a previous survey of the fox population. The hearts and lungs of 442 foxes from across Great Britain were collected and examined by dissection and flushing of the pulmonary circulation and microscopic inspection of tracheal scrapes. Sampling and parasite extraction methods were identical to an earlier survey in 2005 to ensure comparability. Prevalence of A. vasorum was 18·3% (exact binomial confidence bounds 14·9–22·3), compared with 7·3% previously (5·3–9·9, n = 546), and had increased significantly in most regions, e.g. 7·4% in the Northern UK (previously zero) and 50·8% in the south-east (previously 23·2%). Other nematodes identified were Crenosoma vulpis (prevalence 10·8%, CI 8·1–14·2) and Eucoleus aerophilus (31·6%, CI 27·3–36·2). These data support the proposal that A. vasorum has increased in prevalence and has spread geographically in Great Britain.

Remote, non-intrusive monitoring of elusive mammals remains problematic, particularly in running waters. The utility of using submerged infrared counters for monitoring non-intrusively the activity of Eurasian otters Lutra lutra was assessed in three tributaries of the River Dee (Beltie, Cattie, Feardar; Scotland) during 2003–2004. Otters passing through the infrared counters were strongly nocturnal and displayed a bimodal diel activity pattern. Seasonal activity indices varied fourfold between tributaries and peaked during the salmonid breeding season. The median time elapsing between consecutive night visits was 2.02 0.79 days and did not differ between tributaries. The median head–body length of adult otters was estimated at 75.0 1.1 cm, whereas median upstream swimming speed was calculated at 0.97 0.01 m s 1 . Minimum census estimates revealed the activity of at least two adults in the Beltie, two adults and three juveniles in the Cattie, and two adults with one juvenile in the Feardar. Our study indicates that, under suitable conditions, infrared technology can be used effectively to examine non-intrusively the activity of free-ranging otters in running waters, offering some advantages over previous, more intrusive techniques that relied on the collection of spraints, the use of radioisotopes or the tracking of marked individuals.

Intra-specific aggression was investigated in a wild colony of Water voles between 1999 and 2004 in South Wales, UK. The occurrence and location (i.e. on the head, neck, body or tail) of bite wounds were recorded for adult and juvenile male and female voles. The greatest (33%) incidence of bite wounds were recorded on juvenile females and the lowest (18%) in adult females. Seasonal analysis of wound data in adults revealed that females were more likely to be bitten during the breeding season whereas bite patterns in males did not vary seasonally. Analysis of bite pattern topography revealed that most Water voles seemingly attempt to bite vulnerable target areas of the body (namely the head and tail). This is in contrast with studies on rats and mice where competitive forms of attack (particularly involving males) largely avoid these areas of the attacked animal's body. Targeting vulnerable areas is normally a characteristic of defensive modes of attack. Patterns of bite topography and agonistic behaviour in this species seem to reflect competitive interactions between individuals, particularly between territorial females and their female offspring, over access to essential resources. Aggr. Behav. 32:599–603. 2006. © 2006 Wiley-Liss, Inc.

Females of some bird species “steal“ the parental care of other breeding individuals by laying eggs parasitically in their nests. In most populations, conspecific brood parasites lay parasitically before laying in their own nests. By contrast, in a young and expanding Common Moorhen (Gallinula chloropus) population, 17.4% (n = 8) of brood parasites laid parasitically when their own clutches were currently being incubated, and 13.1% (n = 6) laid parasitically when they were tending to their young. This result differs from previous data on conspecific brood parasitism in this (and other) avian species and suggests that sitespecific ecological conditions exert differing selective influences on the behavioral development of populations. The behavior adopted by individual vertebrate species may not, therefore, be rigidly fixed throughout their geographic range.

Sensitive surveys of the X-ray universe have been limited to small areas of the sky due to the intrinsically small field of view of Wolter-1 X-ray optics. High angular resolution is needed to achieve a low background per source, minimize source confusion, and distinguish point from extended objects. WFXT consists of three co-aligned wide field X-ray telescopes with a 1 degrees field of view and a less than or similar to 10 '' (goal of 5 '') angular resolution (HEW) over the full field. Total effective area at 1 keV will be > 5000 cm(-2). WFXT will perform three extragalactic surveys that will cover most of the sky to 100-1000 times the sensitivity of the ROSAT All Sky Survey, greater than or similar to 2000 deg(2) to deep Chandra or XMM-Newton sensitivity, and greater than or similar to 100 deg(2) to the deepest Chandra sensitivity. WFXT will generate a legacy X-ray dataset of a half million clusters and groups of galaxies to z approximate to 2, also characterizing the physics of the intracluster gas for a significant fraction of them, thus providing an unprecedented data set for cosmological applications; it will detect > 10(7) AGN to z > 6, again obtaining spectra for a substantial fraction, to study the growth of supermassive black holes; it will detect > 10(5) normal/starburst galaxies; and it will detect and characterize star formation regions across the Galaxy. WFXT is the only X-ray survey mission that will match, in area and sensitivity, the next generation of wide-area optical, IR and radio surveys.

Ligand-induced PDGF-type beta receptor (PDGFbeta-R) autophosphorylation is profoundly suppressed in cells transformed by activated p21(Ras). We report here that the integrity of the actin cytoskeleton is a critical regulator of PDGFbeta-R function in the presence of p21(Ras). Morphological reversion of Balb cells expressing a constitutively activated p21(Ras), with re-formation of actin stress fibers and cytoskeletal architecture, rendering them phenotypically similar to untransformed fibroblasts, allowed recovery of ligand-dependent PDGFbeta-R autophosphorylation. Conversely, disruption of the actin cytoskeleton in Balb/c-3T3 cells obliterated the normal ligand-induced phosphorylation of the PDGFbeta-R. The Rho family GTPases Rac and Rho are activated by p21(Ras) and are critical mediators of cell motility and morphology via their influence on the actin cytoskeleton. Transient expression of wild-type or constitutively active mutant forms of RhoA suppressed ligand-dependent PDGFbeta-R autophosphorylation and downstream signal transduction. These studies demonstrate the necessary role of Rho in the inhibition of PDGFbeta-R autophosphorylation in cells containing activated p21(Ras) and also demonstrate the importance of cell context and the integrity of the actin cytoskeleton in the regulation of PDGFbeta-R ligand-induced autophosphorylation.

This study tested the 'silver spoon' hypothesis which posits that individuals that develop under favourable conditions should enjoy a fitness advantage later in life because they are more likely to recognize and settle in high-quality habitats. Atlantic salmon Salmo salar of two age classes (0+ and 1+ years) were reared in environmentally enriched or standard hatchery tanks for a short period (c. 10 weeks), were then released into a natural river and sampled on repeated occasions to test for silver-spoon effects. Compared with controls, enriched fish had a 6.4% higher recapture rate and settled in higher velocity habitats when they were stocked as 0+ year fry, but not when they were stocked as 1+ year parr. The opportunity for selection was generally higher for environmentally enriched fish than for controls, and also higher for 0+ than for 1+ year fish. Selection favoured individuals with high condition factor, extensive fat reserves and longer than average pectoral fins in both age classes but favoured a small body size in 1+ year and a large body size in 0+ year releases. Stomach analysis showed that enriched fish ate more, and adapted quicker to natural prey than controls. These results provide support for silver-spoon effects in fish and indicate that enrichment can improve post-release performance in conservation programmes, but seemingly only if fish are not kept in captivity for too long.

The product of the ras proto-oncogene has been implicated as an essential signal transducer, involved in a variety of biological or pathological activities, including apoptosis. The aim of this investigation was to further explore the mechanisms of apoptosis triggered by Ras. Stable expression of constitutively-activated (v)-Ki-Ras in Balb/c-3T3 mouse fibroblasts resulted in a loss of G1 arrest in response to treatments which induced cell cycle arrest in the parental Balb/c-3T3 cells, accompanied by decreased expression of the p53 tumor suppressor protein and the GADD45 gene, the product of which is involved in DNA repair, and deregulated expression of the MDM-2 gene, the product of which can regulate p53 expression. Ki-Ras expression also increased the frequency of PALA-selectable CAD gene amplification, and paradoxically the susceptibility to PALA-induced apoptosis. After persistent serum-starvation, cells expressing the activated ras gene lost clonogenic potential, indicating impaired capability for genetic repair in the cells. Taken together, these data suggest that activated Ki-ras may confer genetic instabilty upon cells, possibly through interference with tumor suppressors, such as p53. While this instability may facilitate adaptation to environmental stresses, this instability in the genome also renders cells containing activated ras genes intrinsically more susceptible to programmed cell death, possibly by accumulation of undesirable or lethal genetic events during the process of tumor development.

We present a catalog of 200 clusters of galaxies serendipitously detected in 647 ROSAT PSPC pointings covering 158 square degrees. This is one of the largest X-ray selected cluster samples, comparable in size only to the ROSAT All-Sky Survey sample of nearby clusters (Ebeling et al. 1997). We detect clusters in the inner 17.5 arcmin of the ROSAT PSPC field of view using the spatial extent of their X-ray emission. Cluster X-ray luminosities range from 10^42 erg/s to ~5x10^44 erg/s, i.e. from poor groups to rich clusters. The cluster redshifts range from z=0.015 to z>0.5. The catalog lists X-ray fluxes, core-radii, spectroscopic redshifts for 73 clusters and photometric redshifts for the remainder. We have optically confirmed 200 of 223 X-ray sources as clusters of galaxies. Of the remaining 23 sources, 18 are likely false detections arising from blends of unresolved point X-ray sources, and for 5 we have not obtained deep CCD images. Above a flux of 2e-13 erg/s/cm**2, 98\% of extended X-ray sources are optically confirmed clusters. The log N-log S relation derived from our catalog shows excellent agreement with previous results: EMSS and ROSAT All-Sky survey BCS in teh bright end and WARPS at intermediate fluxes. Our cluster counts appear to be systematically higher than those from a 50 deg^2 survey of Rosati et al. (1998). In particular, at a flux of 2e-13 erg/s/cm**2, we find a surface density of clusters of 0.57+/-0.07 per square degree, which is a factor of 1.3 more than found by Rosati et al. This difference is marginally significant at the ~2 sigma level. The large area of our survey makes it possible to study the evolution of the X-ray luminosity function in the high luminosity range inaccessible with other, smaller area ROSAT surveys.

Background Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, which may result from alteration of the gastrointestinal microbiota following gastrointestinal infection, or with intestinal dysbiosis or small intestinal bacterial overgrowth. This may be treated with antibiotics, but there is concern that widespread antibiotic use might lead to antibiotic resistance. Some herbal medicines have been shown to be beneficial, but their mechanism(s) of action remain incompletely understood. To try to understand whether antibacterial properties might be involved in the efficacy of these herbal medicines, and to investigate potential new treatments for IBS, we have conducted a preliminary study in vitro to compare the antibacterial activity of the essential oils of culinary and medicinal herbs against the bacterium, Esherichia coli. Methods Essential oils were tested for their ability to inhibit E. coli growth in disc diffusion assays and in liquid culture, and to kill E. coli in a zone of clearance assay. Extracts of coriander, lemon balm and spearmint leaves were tested for their antibacterial activity in the disc diffusion assay. Disc diffusion and zone of clearance assays were analysed by two-tailed t tests whereas ANOVA was performed for the turbidometric assays. Results Most of the oils exhibited antibacterial activity in all three assays, however peppermint, lemon balm and coriander seed oils were most potent, with peppermint and coriander seed oils being more potent than the antibiotic rifaximin in the disc diffusion assay. The compounds present in these oils were identified by gas chromatography mass spectrometry. Finally, extracts were made of spearmint, lemon balm and coriander leaves with various solvents and these were tested for their antibacterial activity against E. coli in the disc diffusion assay. In each case, extracts made with ethanol and methanol exhibited potent antibacterial activity. Conclusions Many of the essential oils had antibacterial activity in the three assays, suggesting that they would be good candidates for testing in clinical trials. The observed antibacterial activity of ethanolic extracts of coriander, lemon balm and spearmint leaves suggests a mechanistic explanation for the efficacy of a mixture of coriander, lemon balm and mint extracts against IBS in a published clinical trial.

Prostate cancer represents approximately 10 percent of all cancer cases in men and accounts for more than a quarter of all cancer types. Advances in understanding the molecular mechanisms of prostate cancer progression, however, have not translated well to the clinic. Patients with metastatic and hormone-refractory disease have only palliative options for treatment, as chemotherapy seldom produces durable or complete responses, highlighting the need for novel therapeutic approaches. T-oligo, a single-stranded deoxyribonucleic acid with partial sequence homology to human telomeric DNA, has elicited cytostatic and/or cytotoxic effects in multiple cancer cell types. In contrast, normal primary cells of varying tissue types are resistant to cytotoxic actions of T-oligo, underscoring its potential utility as a novel targeted cancer therapeutic. Mechanistically, T-oligo is hypothesized to interfere with normal telomeric structure and form G-quadruplex structures, thereby inducing genomic stress in addition to aberrant upregulation of DNA damageresponse pathways. Here, we present data demonstrating the enhanced effectiveness of a deoxyguanosine-enriched sequence of T-oligo, termed (GGTT)4, which elicits robust cytotoxic effects in prostate cancer cells at lower concentrations than the most recent T-oligo sequence (5′-pGGT TAG GTG TAG GTT T 3′) described to date and used for comparison in this study, while exerting no cytotoxic actions on nontransformed human prostate epithelial cells. Additionally, we provide evidence supporting the T-oligo induced activation of cJun N-terminal kinase (JNK) signaling in prostate cancer cells consistent with G-quadruplex formation, thereby significantly advancing the understanding of the T-oligo mechanism of action.

Assessing and monitoring populations of elusive species frequently rely on the identification of indirect signs such as faeces. The absence of signs does not necessarily denote the absence of a species, thus, the ability to determine the presence/absence is susceptible to false negative results. The probability of detection is central to the interpretation and utility of data from field sign surveys. A low probability of detection may introduce considerable error into distribution patterns, resulting in inaccurate ecological conclusions. We used a systematic resampling approach, based on sequential spatial replication of spraint surveys, to investigate the probability of detecting Eurasian otters (Lutra lutra L.) with different survey designs. This included the standard otter transect survey methodology, which is widely used in conservation and scientific studies. In particular, we focus on the impact of applying broad scale population assessment techniques at smaller spatial scales. Fortnightly catchment-level otter surveys were undertaken on four lowland rivers in South Wales, over a period of two years. GIS was used to construct binary vectors for each survey, denoting the presence (1) or absence (0) of otters at each 50 m section of river. Vectors from all study rivers were pooled and resampled to test the different survey designs. The mean probability of detecting otters based on the standard protocol of a single 600 m transect survey was very low (0.26 ± 0.01 SE). The best way of obtaining a detection probability of 0.8 was to undertake three repeat surveys at two separate sites, using a transect of 800–1000 m. We demonstrate how sequentially collected spatial data can be analysed to determine the reliability of field sign surveys. Increasing the number of visits and study sites was a more efficient means of improving detection power than increasing transect length alone. The study emphasises the importance of determining detection probabilities and designing field sign surveys according to study scale and objectives. Our findings question the value of survey designs that aim to provide an instantaneous assessment of species presence/absence.

A novel scaffold system for the generation of diversity libraries has been designed which allows for rapid modification not only of functional groups, but their spatial arrangements as well. The biphenyl scaffold allows for display of three or four diverse functional groups in a wide variety of spatial arrangements depending on the substitution pattern selected. The libraries are generated by a combination of solution and solid-phase chemistries and are cleaved off the solid-support for screening.

This paper describes the application of low-cost radar technology for the detection and analysis of the Doppler signatures of wild life, in particular birds and bats. We demonstrate the ability to extract the wing beat frequency in real-time. Such processing affords a method of readily discriminating between animals and other flying objects such as micro-unmanned aerial vehicles. The timing waveforms used for sampling and integration can have a significant impact on the fidelity of the data that can be captured and on the response time of the system to detect and analyse animals in motion. This work paves the way for future research in support of target classification and conservation ecology.

The function of mos protein in somatic cells, the mechanisms underlying its ability to transform cells, and its relationship to growth factor autonomy and growth factor-mediated signal transduction are not well defined. This report demonstrates that the expression of transforming mos (v-mos) can block the stimulation of growth-related gene expression mediated by the platelet-derived growth factor (PDGF-BB). This blockade by v-mos of PDGF-BB signal transduction occurs very early in the signalling pathway, at the level of PDGF type-beta receptor autophosphorylation. Although the expression of PDGF type-beta receptor, as detected by Western blot with anti-PDGF type-beta receptor antibody,was not diminished in v-mos transformed BALB/c-3T3 murine fibroblasts, the autophosphorylation of PDGF-beta receptor in response to ligand (recombinant PDGF-BB homodimer) stimulation was profoundly suppressed. This same phenomenon of v-mos-mediated PDGF type-beta receptor autophosphorylation inhibition was also demonstrated in NIH-3T3 fibroblasts. A v-mos mutant gene, which was incapable of binding ATP and was kinase-defective, did not block ligand-mediated receptor autophosphorylation. Factor(s) present in v-mos expressing fibroblasts, and found in the membrane fractions of these cells, dominantly inhibit the autophosphorylation of the PDGF type-beta receptor obtained from normal fibroblasts. This trans-acting factor does not appear to be a protein-tyrosine phosphatase. These findings suggest a role for mos, or a similar serine/threonine kinase, as a control mechanism in one of the earliest steps of the PDGF signal transduction pathway, and may provide a model for the functional interaction of mos with growth factor receptors.

The concept of targeting cancer therapeutics toward specific mutations or abnormalities in tumor cells, which are not found in normal tissues, has the potential advantages of high selectivity for the tumor and correspondingly low secondary toxicities. Many human malignancies display activating mutations in the Ras family of signal-transducing genes or over-activity of p21Ras-signaling pathways. Carcinoid and other neuroendocrine tumors have been similarly demonstrated to have activation of Ras signaling directly by mutations in Ras, indirectly by loss of Ras-regulatory proteins, or via constitutive activation of upstream or downstream effector pathways of Ras, such as growth factor receptors or PI3-kinase and Raf/mitogen-activated protein kinases. We previously reported that aberrant activation of Ras signaling sensitizes cells to apoptosis when the activity of the PKCδ isozyme is suppressed and that PKCδ suppression is not toxic to cells with normal levels of p21Rassignaling. We demonstrate here that inhibition of PKCδ by a number of independent means, including genetic mechanisms (shRNA) or small-molecule inhibitors, is able to efficiently and selectively repress the growth of human neuroendocrine cell lines derived from bronchopulmonary, foregut, or hindgut tumors. PKCδ inhibition in these tumors also efficiently induced apoptosis. Exposure to small-molecule inhibitors of PKCδ over a period of 24 h is sufficient to significantly suppress cell growth and clonogenic capacity of these tumor cell lines. Neuroendocrine tumors are typically refractory to conventional therapeutic approaches. This Ras-targeted therapeutic approach, mediated through PKCδ suppression, which selectively takes advantage of the very oncogenic mutations that contribute to the malignancy of the tumor, may hold potential as a novel therapeutic modality.

Methylation of CpG repeats in the upstream/promoter regions of genes is an established mechanism of gene silencing in many cell types. DNA methylation results in the recruitment of histone deacetylases (HDACs) to promoter regions, thereby repressing expression of genes. General inhibitors of class I and II HDACs (HDACi), such as sodium butyrate and suberoylanilide hydroxamic acid, suppress the growth of prostate cancer cells in vitro and in vivo. In this study, we investigated the mechanism of re-expression of silenced cell cycle inhibitors and retinoic acid receptor B2 (RARB2). HDACi inhibited cell cycle progression, and reversed promoter methylation and silencing of three tumor suppressor genes: RARB2 and the cell cycle regulating cyclin-dependent kinase inhibitors p16 and p21. HDACi repressed MAP kinase I (ERK) activation and down-regulated DNA (cytosine-5-)-methyltransferase 1 (DNMT1) levels. Direct inhibition of ERK activity similarly decreased DNMT1 protein levels and reversed the basal hypermethylation of the promoters and silencing of the RARB2, p21 and p16 tumor suppressor genes. Suppression of DNMT1 level by siRNA also reversed methylation of these tumor suppressor genes with similar kinetics. Collectively, these data demonstrate that HDACi, by inhibiting ERK activity, regulate DNMT1 and ultimately DNA methylation. These results demonstrate that HDACs regulate gene methylation, in addition to the established and reciprocal ability of CpG methylation to recruit HDACs to repress transcription.