bluuebunny/crossref_metadata_2025_split huggingface dataset:
EGF and amphiregulin differentially regulate Cbl recruitment to endosomes and EGF receptor fate
Authors: Stern Kathryn A. , Place Trenton L. , Lill Nancy L. 
Published: February 2008

EGF-R [EGF (epidermal growth factor) receptor] ligands can promote or inhibit cell growth. The biological outcome of receptor activation is dictated, at least in part, by ligand-specified patterns of endocytic trafficking. EGF-R trafficking downstream of the ligands EGF and TGF-α (transforming growth factor-α) has been investigated extensively. However, less is known about EGF-R fates induced by the ligands BTC (betacellulin) and AR (amphiregulin). We undertook comparative analyses to identify ligand-specific molecular events that regulate EGF-R trafficking and degradation. EGF (17 nM) and BTC (8.5 nM) induced significant EGF-R degradation, with or without ectopic expression of the ubiquitin ligase Cbl. Human recombinant AR (17 nM) failed to affect receptor degradation in either case. Notably, levels of ligand-induced EGF-R ubiquitination did not correlate strictly with receptor degradation. Dose–response experiments revealed that AR at a saturating concentration was a partial agonist at the EGF-R, with approx. 40% efficacy (relative to EGF) at inducing receptor tyrosine phosphorylation, ubiquitination and association with Cbl. EGF-R down-regulation and degradation also were compromised upon cell stimulation with AR (136 nM). These outcomes correlated with decreased degradation of the Cbl substrate and internalization inhibitor hSprouty2. Downstream of the hSprouty2 checkpoint in AR-stimulated cells, Cbl-free EGF-R was incorporated into endosomes from which Cbl–EGF-R complexes were excluded. Our results suggest that the AR-specific EGF-R fate results from decreased hSprouty2 degradation and reduced Cbl recruitment to underphosphorylated EGF-R, two effects that impair EGF-R trafficking to lysosomes.
The Hsp90 molecular chaperone: an open and shut case for treatment
Authors: Pearl Laurence H. , Prodromou Chrisostomos , Workman Paul 
Published: February 2008

The molecular chaperone Hsp90 (90 kDa heat-shock protein) is a remarkably versatile protein involved in the stress response and in normal homoeostatic control mechanisms. It interacts with ‘client proteins’, including protein kinases, transcription factors and others, and either facilitates their stabilization and activation or directs them for proteasomal degradation. By this means, Hsp90 displays a multifaceted ability to influence signal transduction, chromatin remodelling and epigenetic regulation, development and morphological evolution. Hsp90 operates as a dimer in a conformational cycle driven by ATP binding and hydrolysis at the N-terminus. The cycle is also regulated by a group of co-chaperones and accessory proteins. Here we review the biology of the Hsp90 molecular chaperone, emphasizing recent progress in our understanding of structure–function relationships and the identification of new client proteins. In addition we describe the exciting progress that has been made in the development of Hsp90 inhibitors, which are now showing promise in the clinic for cancer treatment. We also identify the gaps in our current understanding and highlight important topics for future research.
A modelling study of developmental stage and environmental variability effects on copepod foraging
Authors: Wiggert Jerry D. , Hofmann Eileen E. , Paffenhöfer Gustav-Adolf 
Published: February 2008

Abstract
Wiggert, J. D., Hofmann, E. E., and Paffenhöfer, G-A. 2008. A modelling study of developmental stage and environmental variability effects on copepod foraging. – ICES Journal of Marine Science, 65: 379–398. We used a stochastic Lagrangian model to study how behaviour contributes to copepod grazing success. The model simulates distinct foraging behaviours of Clausocalanus furcatus, Paracalanus aculeatus, and Oithona plumifera. Three sets of simulations were performed to investigate the effects of (a) prey-size preference; (b) variation in prey-size spectra; and (c) turbulence intensity on these species’ grazing rates. The size preference simulations demonstrate that, compared with copepodites, mature females have cell ingestion rates that are an order of magnitude lower, while carbon uptake is reduced by 35%. A prey spectrum that is skewed towards cells <6 µm promotes copepodite success because the basal metabolic needs of the adult females require a prey concentration of 850–1000 cells ml−1. Variations in turbulence intensity reveal distinct ecological niches, with stronger mixing favouring O. plumifera and stable conditions favouring C. furcatus. Differences in theoretically derived and simulated prey-encounter rates demonstrate that the hopping behaviour of O. plumifera provides an order of magnitude increase in prey encounter, whereas the feeding behaviour of C. furcatus can result in localized depletion of prey. These simulations highlight the importance of species-specific feeding behaviour in defining oceanic copepod distributions.
Basin‐wide mass‐wasting complexes as markers of the Oligo‐Miocene foredeep‐accretionary wedge evolution in the Northern Apennines, Italy
Authors: Lucente Claudio Corrado , Pini Gian Andrea 
Published: February 2008

ABSTRACTSedimentary bodies emplaced by mass‐wasting processes and exceeding tens of metres of thickness and a hundred of square kilometres in area are widespread in the Cretaceous–Pleistocene marine successions of the Northern Apennines of Italy. At least 10 such bodies are present in the stratigraphic record of the Oligo‐Miocene foredeep during the northeastern, time‐transgressive migration of the accretionary wedge‐foredeep system. The term mass‐wasting complex (MWC) is here adopted for these bodies to emphasize their multistory emplacement mechanism and polymictic composition with variously deformed slabs of different lithology, age and provenance. As one of the more intriguing features, their occurrence was associated with changes in turbidite deposition from basin plain to slope. Wide sectors of the internal margin of the basin (lobe‐fan) and even of the basin plain become a slope at the front of the accretionary wedge for a limited period of time (temporary slope). The temporary slope supplied the intrabasinal components of the MWCs, whereas the diffused extrabasinal components came from the front of the accretionary wedge. Therefore, an enhanced instability of the entire foredeep‐wedge system occurred systematically and cyclically. As a consequence, many variously consolidated sediments were transferred into the foredeep basin invading the depocentre and forcing the turbidite deposition towards the foreland, in a more northeasterly position. The presence of such MWCs therefore conditioned basin size and geometry in an analogous way as that reported for some modern convergent margins, as in the case of Costa Rica. Normal sedimentation was restored on top of the MWC only after the levelling of topographic irregularities.
Thermal modelling of magmatic intrusions in the Gjallar Ridge, Norwegian Sea: implications for vitrinite reflectance and hydrocarbon maturation
Authors: Fjeldskaar W. , Helset H. M. , Johansen H. , Grunnaleite I. , Horstad I. 
Published: February 2008

ABSTRACTExtensive magmatic activity took place in the Vøring Basin, offshore Norway, related to the Early Cenozoic rifting. The break‐up of the North‐Atlantic at the Palaeocene–Eocene transition induced strong volcanism. There are numerous magmatic sills below 3 km depth in the area. They are predominantly layer parallel and thin compared with their lateral extent. Igneous intrusions, sills and dykes affected the temperature history, and thus need to be taken into account in petroleum prospect analysis. We have calculated the temperature and maturity effects in the sedimentary layers in the Gjallar area associated with the emplacement of single sill and sill complexes. A 120‐m‐thick sill produces a theoretical vitrinite reflectance (%R0) 0.8% higher than normal at a distance of 100 m from the sill. Vitrinite reflectance changes caused by a swarm of seven sills varying from 8 to 80 m in thickness were calculated. It is shown that the calculated thermal profile can account for the observed shift in vitrinite reflectance in the well. A two‐dimensional section crossing the Gjallar Ridge, consisting of numerous magmatic intrusions, is also modelled. The modelled geological development and temperature history over the profile show that there are significant maturation effects in the interval under investigation. Based on this work, the sill swarm observed in the area could more than double the fraction of the kerogen that has been transformed to petroleum at the (present) depth of 4 km.
Expanding forests and changing growth forms of Siberian larch at the Polar Urals treeline during the 20th century
Authors: DEVI NADEZHDA , HAGEDORN FRANK , MOISEEV PAVEL , BUGMANN HARALD , SHIYATOV STEPAN , MAZEPA VALERIE , RIGLING ANDREAS 
Published: February 2008

AbstractThe ongoing climatic changes potentially affect plant growth and the functioning of temperature‐limited high‐altitude and high‐latitude ecosystems; the rate and magnitude of these biotic changes are, however, uncertain. The aim of this study was to reconstruct stand structure and growth forms of Larix sibirica (Ledeb.) in undisturbed forest–tundra ecotones of the remote Polar Urals on a centennial time scale. Comparisons of the current ecotone with historic photographs from the 1960s clearly document that forests have significantly expanded since then. Similarly, the analysis of forest age structure based on more than 300 trees sampled along three altitudinal gradients reaching from forests in the valleys to the tundra indicate that more than 70% of the currently upright‐growing trees are <80 years old. Because thousands of more than 500‐year‐old subfossil trees occur in the same area but tree remnants of the 15–19th century are lacking almost entirely, we conclude that the forest has been expanding upwards into the formerly tree‐free tundra during the last century by about 20–60 m in altitude. This upward shift of forests was accompanied by significant changes in tree growth forms: while 36% of the few trees that are more than 100 years old were multi‐stem tree clusters, 90% of the trees emerging after 1950 were single‐stemmed. Tree‐ring analysis of horizontal and vertical stems of multi‐stemmed larch trees showed that these trees had been growing in a creeping form since the 15th century. In the early 20th century, they started to grow upright with 5–20 stems per tree individual. The incipient vertical growth led to an abrupt tripling in radial growth and thus, in biomass production. Based on above‐ and belowground biomass measurements of 33 trees that were dug out and the mapping of tree height and diameter, we estimated that forest expansion led to a biomass increase by 40–75 t ha−1 and a carbon accumulation of approximately 20–40 g C m−2 yr−1 during the last century. The forest expansion and change in growth forms coincided with significant summer warming by 0.9 °C and a doubling of winter precipitation during the 20th century. In summary, our results indicate that the ongoing climatic changes are already leaving a fingerprint on the appearance, structure, and productivity of the treeline ecotone in the Polar Urals.
Dexamethasone transforms lipopolysaccharide‐stimulated human blood myeloid dendritic cells into myeloid dendritic cells that prime interleukin‐10 production in T cells
Authors: Bosma Brenda M. , Metselaar Herold J. , Nagtzaam Nicole M. A. , De Haan Roel , Mancham Shanta , Van Der Laan Luc J. W. , Kuipers Ernst J. , Kwekkeboom Jaap 
Published: February 2008

SummaryMyeloid dendritic cells (MDC) play an important role in antigen‐specific immunity and tolerance. In transplantation setting donor‐derived MDC are a promising tool to realize donor‐specific tolerance. Current protocols enable generation of tolerogenic donor MDC from human monocytes during 1‐week cultures. However, for clinical application in transplantation medicine, a rapidly available source of tolerogenic MDC is desired. In this study we investigated whether primary human blood MDC could be transformed into tolerogenic MDC using dexamethasone (dex) and lipopolysaccharide (LPS). Human blood MDC were cultured with dex and subsequently matured with LPS in the presence or absence of dex. Activation of MDC with LPS after pretreatment with dex did not prevent maturation into immunostimulatory MDC. In contrast, simultaneous treatment with dex and LPS yielded tolerogenic MDC, that had a reduced expression of CD86 and CD83, that poorly stimulated allogeneic T‐cell proliferation and production of T helper 1 (Th1) cytokines, and primed production of the immunoregulatory cytokine interleukin‐10 (IL‐10) in T cells. In vitro, however, these tolerogenic MDC did not induce permanent donor‐specific hyporesponsiveness in T cells. Importantly, tolerogenic MDC obtained by LPS stimulation in the presence of dex did not convert into immunostimulatory MDC after subsequent activation with different maturation stimuli. In conclusion, these findings demonstrate that combined treatment with dex and LPS transforms primary human blood MDC into tolerogenic MDC that are impaired to stimulate Th1 cytokines, but strongly prime the production of the immunoregulatory cytokine IL‐10 in T cells, and are resistant to maturation stimuli. This strategy enables rapid generation of tolerogenic donor‐derived MDC for immunotherapy in clinical transplantation.
Evidence for habitat fragmentation altering within‐population processes in wombats
Authors: WALKER FAITH M. , SUNNUCKS PAUL , TAYLOR ANDREA C. 
Published: February 2008

AbstractHabitat fragmentation and associated reduced dispersal of wildlife can lead to an accumulation of related individuals in fragments. The altered kin interactions and amplified chance of inbred matings has profound implications for mating and social systems, and ultimately population persistence. Nonetheless, within‐fragment population processes are rarely studied. With this aim, we examined relatedness structure in two candidate isolated populations (Kulpara and Scrubby Peak) of southern hairy‐nosed wombats (Lasiorhinus latifrons). Wombats were sampled by remote hair‐trapping for genotyping at 14 microsatellite loci, enabling individual identification and estimation of space‐use and associative behaviour with respect to relatedness. Genetic data indicated that Scrubby Peak was not strongly isolated, against predictions from landscape structure and history. In isolated Kulpara, inhibited female dispersal (normally the dispersing sex) was associated with high population density and altered kin relationships. First, female relatives preferentially coexisted, a radical departure from the previously reported active avoidance of female relatives in continuous habitat. This is consistent with females in altered habitat interacting with more‐ rather than less‐related females to minimize the cost:benefit ratio of proximity to other wombats. Second, inbreeding avoidance appeared to be stronger at Kulpara than in conspecific populations with natural population structures. Although these adaptive behaviours may have contributed to persistence of the Kulpara population in the short term, they are unlikely to ensure its long‐term viability in the face of ongoing isolation because they can act only to slow the rate of inbreeding and mitigate some of its negative impacts.
The role of vicariance vs. dispersal in shaping genetic patterns in ocellated lizard species in the western Mediterranean
Authors: PAULO O. S. , PINHEIRO J. , MIRALDO A. , BRUFORD M. W. , JORDAN W. C. , NICHOLS R. A. 
Published: February 2008

AbstractThe schism between North Africa and Southern Europe caused by the opening of the Strait of Gibraltar and the consequent refilling of the Mediterranean basin at the end of Messinian salinity crisis (MSC), 5.33 million years ago, has been advocated as the main event shaping biogeographical patterns in the western Mediterranean as exemplified by the distribution of species and subspecies and genetic variation within the ocellated lizard group. To reassess the role of the MSC, partial sequences of three mitochondrial DNA genes (cytochrome b, 12S and 16S ribosomal RNA) and two nuclear genes (β‐fibrinogen and C‐mos) from species of the ocellated lizard group were analysed. Three alternative hypotheses were tested: that divergence was initiated (i) by post‐MSC vicariance as the basin filled, (ii) when separate populations established either side of the strait by pre‐MSC overseas dispersal, and (iii) by post‐MSC overseas dispersal. The pattern and level of divergence detected clearly refute the post‐MSC vicariance hypothesis, and support a model of divergence initiated by earlier overseas dispersal. Indeed, our best estimate is that the basal Euro‐African divergence predates the MSC event by several million years. The estimated divergence times among the populations in former Miocene Mediterranean islands, the current Betic and Rifian mountains, from adjacent mainland populations suggest overseas dispersal for the former and overland dispersal, or perhaps vicariance, for the latter. These results suggest that the MSC may have played a much less important role in shaping the current western Mediterranean biogeographical patterns than might have been anticipated from the dramatic nature of the episode.
Reproductive skew and relatedness in social groups of European badgers, Meles meles
Authors: DUGDALE HANNAH L. , MACDONALD DAVID W. , POPE LISA C. , JOHNSON PAUL J. , BURKE TERRY 
Published: February 2008

AbstractReproductive skew is a measure of the proportion of individuals of each sex that breed in a group and is a valuable measure for understanding the evolution and maintenance of sociality. Here, we provide the first quantification of reproductive skew within social groups of European badgers Meles meles, throughout an 18‐year study in a high‐density population. We used 22 microsatellite loci to analyse within‐group relatedness and demonstrated that badger groups contained relatives. The average within‐group relatedness was high (R = 0.20) and approximately one‐third of within‐group dyads were more likely to represent first‐order kin than unrelated pairs. Adult females within groups had higher pairwise relatedness than adult males, due to the high frequency of extra‐group paternities, rather than permanent physical dispersal. Spatial clustering of relatives occurred among neighbouring groups, which we suggest was due to the majority of extra‐group paternities being attributable to neighbouring males. Reproductive skew was found among within‐group candidate fathers (B = 0.26) and candidate mothers (B = 0.07), but not among breeding individuals; our power to detect skew in the latter was low. We use these results to evaluate reproductive skew models. Although badger society best fits the assumptions of the incomplete‐control models, our results were not consistent with their predictions. We suggest that this may be due to female control of paternity, female–female reproductive suppression occurring only in years with high food availability resulting in competition over access to breeding sites, extra‐group paternity masking the benefits of natal philopatry, and/or the inconsistent occurrence of hierarchies that are linear when established.
Promoter specificity for 6S RNA regulation of transcription is determined by core promoter sequences and competition for region 4.2 of σ70
Authors: Cavanagh Amy T. , Klocko Andrew D. , Liu Xiaochun , Wassarman Karen M. 
Published: February 2008

Summary6S RNA binds σ70‐RNA polymerase and downregulates transcription at many σ70‐dependent promoters, but others escape regulation even during stationary phase when the majority of the transcription machinery is bound by the RNA. We report that core promoter elements determine this promoter specificity; a weak −35 element allows a promoter to be 6S RNA sensitive, and an extended −10 element similarly determines 6S RNA inhibition except when a consensus −35 element is present. These two features together predicted that hundreds of mapped Escherichia coli promoters might be subject to 6S RNA dampening in stationary phase. Microarray analysis confirmed 6S RNA‐dependent downregulation of expression from 68% of the predicted genes, which corresponds to 49% of the expressed genes containing mapped E. coli promoters and establishes 6S RNA as a global regulator in stationary phase. We also demonstrate a critical role for region 4.2 of σ70 in RNA polymerase interactions with 6S RNA. Region 4.2 binds the −35 element during transcription initiation; therefore we propose one mechanism for 6S RNA regulation of transcription is through competition for binding region 4.2 of σ70.
Long-term optical spectra variability of BL Lacertae object OJ 287
Authors: Zheng Y. G. , Zhang X. , Bi X. W. , Hao J. M. , Zhang H. J. 
Published: February 2008

Abstract
Based on the long-term data in the literature, we present evidence for long-term optical spectral index variability behaviour for BL Lacertae object OJ 287. First we find that the optical spectral index variability period of BL Lacertae object OJ 287 is in agreement with the optical flux variability period of about 11.96 yr. It is considered that different processes induce optical variability, and each process should have a definite signature in the spectral index, thus leading to the periodicity of the spectral index. We also find that the time lag between the optical spectral index and the optical flux density is half of the optical flux variability period. This result tends to support the argument that when the brightness of the long-term variations increases, the optical spectra become bluer. These variations can be explained by energy loss of the electrons during the outburst. We show that the spectral index is different during the flares compared with outside the flares; between the first and second flare peaks of the superflares, the spectrum shapes are different. Disparate processes possibly induce the two peaks of OJ 287.
NKG2D Ligands Expression and NKG2D‐Mediated Cytotoxicity in Human Laryngeal Squamous Carcinoma Cells
Authors: Chen X. M. , Xu X. Q. , Sun K. , Hallett W. H. D. , Zhao J. D. , Zhang D. L. 
Published: February 2008

AbstractThe NKG2D is an activating immunoreceptor expressed by NK cells and CD8+ T cells. Engagement of NKG2D by its ligands is critical for both innate and adoptive immunity. While the overexpression of NKG2D ligands on certain tumour cells has previously been demonstrated, little is known about NKG2D ligand expression on human laryngeal tumour cells. In this study, we first verified that the interaction between NKG2D and its ligands was critical for NK cell‐based immune response to human laryngeal squamous carcinoma cells Hep‐2. This NKG2D‐mediated effect was observed by transfecting the recombinant eukaryotic expression vector pEGFP‐N1/NKG2D as well as the NKG2D blockade. The mRNA and protein expression of NKG2D ligands, MHC class I‐related chain molecules A (MICA) and UL16‐binding proteins (ULBPs), in human laryngeal carcinoma cell line Hep‐2 and fresh tumour tissues were evaluated. Compared with non‐tumour tissues of vocal cords polyps, MICA and ULBP‐3 were strongly overexpressed on both the human laryngeal carcinoma cell line Hep‐2 and fresh human laryngeal carcinoma tissues. The mechanism and impact of NKG2D ligands overexpression on NK cell‐mediated anti‐laryngeal cancer immune response would require further investigation.