bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipocalin‐type prostaglandin D synthase as a marker for the proliferative potential of melanocyte‐lineage cells in the human skin
Authors: SHIMANUKI Miwa , TAKEDA Kazuhisa , KAWAGUCHI Masakazu , SUZUKI Tamio , SHIBAHARA Shigeki 
Published: February 2012

AbstractMelanocytes in the human epidermis actively produce and secrete various substances, thereby contributing to the maintenance of the skin homeostasis. Lipocalin‐type prostaglandin D synthase (L‐PGDS) that catalyzes the formation of prostaglandin D2 (PGD2) may be one of such secreted molecules. Once secreted, L‐PGDS functions as a transporter for lipophilic ligands, including all‐trans retinoic acid (RA). L‐PGDS, therefore, may possess pleiotropic functions in the skin through PGD2 and RA. We aimed to identify the cell types that express L‐PGDS in human skin and to explore the role of L‐PGDS in the growth potential of melanocyte‐lineage cells. Immunohistochemical analysis for L‐PGDS expression was performed with the tissue sections that were prepared from five malignant melanomas, six nevus cell nevi and one Spitz nevus. Normal skin tissues adjacent to the excised melanoma tissues were also analyzed. L‐PGDS is expressed in epidermal melanocytes but its expression is undetectable in keratinocytes. Moreover, L‐PGDS is undetectable in most benign nevus cells, which may reflect the marginally accelerated proliferation of nevus cells. In contrast, L‐PGDS is overexpressed in malignant melanomas, although the frequency of L‐PGDS‐positive cells was variable (15–50%), depending on the specimens. Lastly, RNA interference analysis against human L‐PGDS was performed with short interfering RNA. Knockdown of L‐PGDS expression with short interfering RNA in cultured cells suggests that L‐PGDS may restrict cell proliferation through RA. In conclusion, L‐PGDS expression may contribute to the restricted proliferation of epidermal melanocytes, but conversely its overexpression may reflect the dysregulated proliferation of melanoma cells.
Effects of large sea‐level variations in connected basins: theDacian–Black Sea system of theEasternParatethys
Authors: Munteanu I. , Matenco L. , Dinu C. , Cloetingh S. 
Published: February 2012

AbstractSea‐level changes provide an important control on the interplay between accommodation space and sediment supply, in particular, for shallow‐water basins where the available space is limited. Sediment exchange between connected basins separated by a subaqueous sill (bathymetric threshold) is still not well understood. When sea‐level falls below the bathymetric level of this separating sill, the shallow‐water basin evolution is controlled by its erosion and rapid fill. Once this marginal basin is filled, the sedimentary depocenter shifts to the open marine basin (outward shift). With new accommodation space created during the subsequent sea‐level rise, sediment depocenter shifts backwards to the marginal basin (inward shift). This new conceptual model is tested here in the context of LateMiocene toQuaternary evolution of the open connection betweenDacian andBlack Sea basins. By the means of seismic sequence stratigraphic analysis of theMiocene‐Pliocene evolution of this EasternParatethys domain, this case study demonstrates these shifts in sedimentary depocenter between basins. An outward shift occurs with a delay that corresponds to the time required to fill the remaining accommodation space in theDacian Basin below the sill that separates it from the Black Sea. This study provides novel insight on the amplitude and sedimentary geometry of the Messinian Salinity Crisis (MSC) event in theBlack Sea. A large (1.3–1.7 km) sea‐level drop is demonstrated by quantifying coeval sedimentation patterns that change to mass‐flows and turbiditic deposits in the deep‐sea part of this main sink. The post‐MSCsediment routing continued into the present‐day pattern ofBlack Sea rivers discharge.
Effect of the ethinylestradiol/levonorgestrel combined oral contraceptive on the activity of cytochrome P4503A in obese women
Authors: Edelman Alison , Munar Myrna , Elman Miriam R. , Koop Dennis , Cherala Ganesh 
Published: February 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Obesity is known to suppress CYP3A4/5 activity.• Use of combined oral contraceptives (COC) has been shown to suppress CYP3A4/5 activity in non‐obese women.• However, the effect of COC on CYP3A4/5 activity is unknown in obese women who constitute 50% of women of reproductive age.WHAT THIS STUDY ADDS• Although we hypothesized that obesity exposure might amplify the impact on CYP3A4/5 activity in COC users, we found that this was not the case.• This finding is reassuring regarding potential additional drug–drug interactions in obese COC users as CYP3A4/5 is a major player in the metabolism of many marketed drugs.AIM(S) While it is known that CYP3A4/5 activity is decreased with combined oral contraceptive (COC) use and obesity suppresses CYP expression, the combined effects of obesity and COC use on CYP3A4/5 activity are unclear. Therefore, our aim was to examine the effect of COC usage on CYP3A4/5 activity in obese women.METHODS Thirty‐four, obese (body mass index, BMI > 30 kg m−2) women of reproductive age (18–35 years old) were placed on a COC pill containing 20 µg ethinylestradiol/100 µg levonorgestrel for 21 days starting at the onset of menses. A midazolam pharmacokinetic study was conducted prior to initiation and after 21 days of COC treatment. Serial blood samples were collected and plasma concentrations of midazolam were measured using liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were estimated using a non‐compartmental method.RESULTS Midazolam clearance, a surrogate measure of CYP3A4/5 activity, was significantly decreased upon COC use (63.3 l h−1vs. 53.9 l h−1, P < 0.05). A median decrease of 5.6 l h−1 (95% CI −4.1, 13.3 l h−1) was observed. However, the magnitude of change was similar to that reported in women with normal BMI.CONCLUSIONS Although we hypothesized that obesity might amplify the impact on CYP3A4/5 activity in COC users, we found that this was not the case. This finding is reassuring regarding potential additional drug−drug interactions in obese COC users as CYP3A4/5 is a major enzyme in the metabolism of many marketed drugs.
Growth factor‐associated graft‐versus‐host disease and mortality 10 years after allogeneic bone marrow transplantation
Authors: Ringdén Olle , Labopin Myriam , Gorin Norbert‐Claude , Volin Liisa , Torelli Giovanni F. , Attal Michel , Jouet Jean P. , Milpied Noel , Socié Gerard , Cordonnier Catherine , Michallet Mauricette , Atienza Arturo I. , Hermine Olivier , Mohty Mohamad ,   for the Acute Leukaemia Working Party of the European Group for Blood and Marrow Transplantation
Published: February 2012

SummaryThis study analysed the effects of growth factor on outcome after haematopoietic stem‐cell transplantation (HSCT) with >9 years follow‐up. Of 1887 adult patients with acute leukaemia who received bone marrow from human leucocyte antigen (HLA)‐identical siblings and were treated with myeloablative conditioning, 459 (24%) were treated with growth factor. Growth factor hastened engraftment of neutrophils (P < 0·0001), but reduced platelet counts (P = 0·0002). Graft‐versus‐host disease (GVHD)‐free survival (no acute GVHD grade II–IV or chronic GVHD) at 10 years was 12 ± 2% (±SE) in the growth factor group, as opposed to 17 ± 2% in the controls [hazard ratio (HR) 0·81, P = 0·001]. Similar differences in GVHD‐free survival were seen in patients with or without conditioning with total body irradiation (TBI). Non‐relapse mortality (NRM) was higher in the growth factor group irrespective of whether or not TBI conditioning was included [HR = 1·48; 95% confidence interval (CI): 1·15–1·9; P = 0·002; HR = 1·59; 95% CI: 1·07–2·37; P = 0·02, respectively]. Both groups had similar probabilities of leukaemic relapse (HR = 0·96; 95% CI: 0·78–1·18; P = 0·71). Leukaemia‐free survival (LFS) at 10 years was 35 ± 2% in those receiving growth factor prophylaxis, as opposed to 44 ± 1% in the controls (HR = 0·70; 95% CI: 0·60–0·82; P = 0·00001). Prophylaxis with growth factor increases the risk of GVHD, does not affect relapse, increases NRM and reduces LFS > 10 years after HSCT, regardless of conditioning with TBI.
Tumour necrosis factor-mediated macrophage activation in the target organ is critical for clinical manifestation of uveitis
Authors: Khera T K , Copland D A , Boldison J , Lait P J P , Szymkowski D E , Dick A D , Nicholson L B 
Published: February 2012

SummaryClinically available anti-tumour necrosis factor (TNF) biologics, which inhibit both soluble (sTNF) and transmembrane forms (tmTNF) of TNF, eliminating all TNF signalling, have successfully treated autoimmune diseases including uveitis. These have potentially serious side effects such as reactivation of latent Mycobacterium tuberculosis and, therefore, more specific inhibition of TNF signalling pathways may maintain clinical efficacy while reducing adverse effects. To determine the effects of specific pharmacological inhibition of sTNF on macrophage activation and migration, we used a mouse model of uveitis (experimental autoimmune uveoretinitis; EAU). We show that selective inhibition of sTNF is sufficient to suppress EAU by limiting inflammatory CD11b+ macrophages and CD4+ T cell migration into the eye. However, inhibition of both sTNF and tmTNF is required to inhibit interferon-γ-induced chemokine receptor 2, CD40, major histocompatibility complex class II and nitric oxide (NO) up-regulation, and signalling via tmTNF is sufficient to mediate tissue damage. In confirmation, intravitreal inhibition of sTNF alone did not suppress disease, and inflammatory cells that migrated into the eye were activated, generating NO, thus causing structural damage to the retina. In contrast, intravitreal inhibition of both sTNF and tmTNF suppressed macrophage activation and therefore disease. We conclude that sTNF is required for inflammatory cell infiltration into target tissue, but at the tissue site inhibition of both sTNF and tmTNF is required to inhibit macrophage activation and to protect from tissue damage.
Full waveform inversion and distance separated simultaneous sweeping: a study with a land seismic data set
Authors: Plessix René‐Édouard , Baeten Guido , de Maag Jan Willem , ten Kroode Fons , Rujie Zhang 
Published: February 2012

ABSTRACTDense, wide‐aperture and broad frequency band acquisition improves seismic imaging and potentially allows the use of full waveform inversion for velocity model building. The cost of dense acquisitions however limits its applicability. Blended or simultaneous shooting could lead to a good compromise between cost and dense acquisition, although the cross‐talk between simultaneous sweeps may reduce imaging capabilities. Onshore, a compromise is achieved with distance separated simultaneous sweeping acquisition, because the shots are easily separated when the processing focuses on pre‐critical reflected events. Full waveform inversion for velocity model building however relies on post‐critical reflected, refracted and diving events. These events can interfere in a distance separated simultaneous sweeping acquisition. By using a single vibrator, single receiver data set recorded in Inner Mongolia, China, a distance separated simultaneous sweeping data set is created to study the robustness of full waveform inversion in this acquisition context. This data set is well suited for full waveform inversion since it contains frequencies down to 1.5 Hz and offsets up to 25 km. Full waveform inversion after a crude deblending of the distance separated simultaneous sweeping data set leads to a result very similar to the one obtained from the single vibrator, single receiver data set. The inversion of the blended data set gives a slightly less good result because of the cross‐talk but it is still quite satisfactory.
Reduced variability in range‐edge butterfly populations over three decades of climate warming
Authors: Oliver Tom H. , Roy David B. , Brereton Tom , Thomas Jeremy A. 
Published: February 2012

AbstractPopulations at the high latitude edge of species’ geographical ranges are thought to show larger interannual population fluctuations, with subsequent higher local extinction risk, than those within the ‘core’ climatic range. As climate envelopes shift northward under climate warming, however, we would expect populations to show dampened variability. We test this hypothesis using annual abundance indices from 19 butterfly species across 79British monitoring sites between 1976 and 2009, a period of climatic warming. We found that populations in the latter (warmer) half of the recording period show reduced interannual population variability. Species with more southerlyEuropean distributions showed the greatest dampening in population variability over time. Our results suggest that increases in population variability occur towards climatic range boundaries.British sites, previously existing at the margins of suitable climate space, now appear to fall closer to the core climatic range for many butterfly species.
Chronic kidney disease stressors influence choice of dialysis modality
Authors: Harwood Lori , Wilson Barbara , Sontrop Jessica , Clark Alexander M. 
Published: February 2012

harwood l., wilson b., sontrop j. & clark a.m. (2012) Chronic kidney disease stressors influence choice of dialysis modality. Journal of Advanced Nursing68(11), 2454–2465.AbstractAim.  This article is a report of a study examining the relationships between chronic kidney disease stressors and coping strategies with dialysis modality.Background.  People with chronic kidney disease are given information to enable dialysis modality choice. This education increases awareness and may alleviate concerns and stress. Disease‐related stressors and coping may affect dialysis selection. Understanding the influence of stress and coping on dialysis choices will assist in providing responsive programmes. Reducing stress and encouraging coping may increase home dialysis which, despite economic and patient benefits, remains underused.Design.  A prospective correlational design was used.Methods.  Information was obtained from the Chronic Kidney Disease Stress Inventory and the Jalowiec Coping Scale in 223 individuals not on dialysis between the years 2005–2007. Data were recorded with respect to modality at dialysis initiation (n = 76) from 2005–2010. The effects of stress, coping and patient parameters on modality selection were compared using bivariate and multivariate analyses.Results.  Individuals on home dialysis vs. in‐centre haemodialysis reported significantly fewer pre‐dialysis stressors. Coping was not associated with dialysis modality. Individuals on in‐centre haemodialysis had a lower serum creatinine, less advanced kidney disease and weighed more than those who started on a home therapy. Physiological stressors were most common and are amenable to interventions.Conclusion.  Pre‐dialysis stress levels predicted dialysis modality. Interventional studies are recommended to address chronic kidney disease stressors with the outcome of improving home‐dialysis usage.
Current SEM techniques for de‐ and re‐construction of centromeres to determine 3D CENH3 distribution in barley mitotic chromosomes
Authors: SCHROEDER‐REITER E. , SANEI M. , HOUBEN A. , WANNER G. 
Published: February 2012

SummaryCombined light microscopic (LM) and field emission scanning electron microscopic (FESEM) techniques with FluoroNanogold labelling allowed quantification and high resolution analysis of 3D distribution of the centromere‐specific histone H3 variant CENH3 in barley mitotic chromosomes. Chromosomes were investigated with fluorescence LM, conventional FESEM, low‐voltage FESEM and combined FIB/FESEM techniques for unprecedented comprehensive analysis to determine chromatin distribution patterns in the centromere. Using data from FIB/FESEM sectioning of centromeric regions of chromosomes, it was possible to render 3D reconstruction of the CENH3 distribution with highest resolution achieved to date. Complementary data derived from each approach show that CENH3 localizes not only to the primary constriction, but also in the pericentric regions and is distributed exclusively in the interior, rather than on the surface, of the centromere. This is relevant for understanding kinetochore assembly and digresses from current models of centromere structure. We emphasize here this broad microscopic approach, focusing on technical aspects of combined FESEM techniques, for which advantages and limitations are discussed, providing a relevant example—in the field of centromeric research—for application to investigations of other subcellular biological structures.
Soil sampling and isolation of extracellular DNA from large amount of starting material suitable for metabarcoding studies
Authors: TABERLET PIERRE , PRUD’HOMME SOPHIE M. , CAMPIONE ETIENNE , ROY JULIEN , MIQUEL CHRISTIAN , SHEHZAD WASIM , GIELLY LUDOVIC , RIOUX DELPHINE , CHOLER PHILIPPE , CLÉMENT JEAN‐CHRISTOPHE , MELODELIMA CHRISTELLE , POMPANON FRANÇOIS , COISSAC ERIC 
Published: February 2012

AbstractDNA metabarcoding refers to the DNA‐based identification of multiple species from a single complex and degraded environmental sample. We developed new sampling and extraction protocols suitable for DNA metabarcoding analyses targeting soil extracellular DNA. The proposed sampling protocol has been designed to reduce, as much as possible, the influence of local heterogeneity by processing a large amount of soil resulting from the mixing of many different cores. The DNA extraction is based on the use of saturated phosphate buffer. The sampling and extraction protocols were validated first by analysing plant DNA from a set of 12 plots corresponding to four plant communities in alpine meadows, and, second, by conducting pilot experiments on fungi and earthworms. The results of the validation experiments clearly demonstrated that sound biological information can be retrieved when following these sampling and extraction procedures. Such a protocol can be implemented at any time of the year without any preliminary knowledge of specific types of organisms during the sampling. It offers the opportunity to analyse all groups of organisms using a single sampling/extraction procedure and opens the possibility to fully standardize biodiversity surveys.
A network of enzymes involved in repair of oxidative DNA damage in Neisseria meningitidis
Authors: Nagorska Krzysztofa , Silhan Jan , Li Yanwen , Pelicic Vladimir , Freemont Paul S. , Baldwin Geoff S. , Tang Christoph M. 
Published: February 2012

SummaryAlthough oxidative stress is a key aspect of innate immunity, little is known about how host‐restricted pathogens successfully repair DNA damage. Base excision repair is responsible for correcting nucleobases damaged by oxidative stress, and is essential for bloodstream infection caused by the human pathogen, Neisseria meningitidis. We have characterized meningococcal base excision repair enzymes involved in the recognition and removal of damaged nucleobases, and incision of the DNA backbone. We demonstrate that the bi‐functional glycosylase/lyases Nth and MutM share several overlapping activities and functional redundancy. However, MutM and other members of the GO system, which deal with 8‐oxoG, a common lesion of oxidative damage, are not required for survival of N. meningitidis under oxidative stress. Instead, the mismatch repair pathway provides back‐up for the GO system, while the lyase activity of Nth can substitute for the meningococcal AP endonuclease, NApe. Our genetic and biochemical evidence shows that DNA repair is achieved through a robust network of enzymes that provides a flexible system of DNA repair. This network is likely to reflect successful adaptation to the human nasopharynx, and might provide a paradigm for DNA repair in other prokaryotes.
RcsB‐BglJ activates the Escherichia coli leuO gene, encoding an H‐NS antagonist and pleiotropic regulator of virulence determinants
Authors: Stratmann Thomas , Pul Ümit , Wurm Reinhild , Wagner Rolf , Schnetz Karin 
Published: February 2012

SummaryThe LysR‐type transcription factor LeuO is involved in regulation of pathogenicity determinants and stress responses in Enterobacteriaceae, and acts as antagonist of the global repressor H‐NS. Expression of the leuO gene is repressed by H‐NS, and it is upregulated in stationary phase and under amino acid starvation conditions. Here, we show that the heterodimer of the FixJ/NarL‐type transcription regulators RcsB and BglJ strongly activates expression of leuO and that RcsB‐BglJ regulates additional loci. Activation of leuO by RcsB‐BglJ is independent of the Rcs phosphorelay system. RcsB‐BglJ binds to the leuO promoter region and activates one of two leuO promoters mapped in vivo. Moreover, LeuO antagonizes activation of leuO by RcsB‐BglJ and acts as negative autoregulator in vivo and in vitro. Further, the H‐NS paralogue StpA causes repression of leuO in addition to H‐NS. Together, our data suggest a complex arrangement of regulatory elements and they indicate a feedback control mechanism of leuO expression.
Depletion of leaf‐type ferredoxin‐NADP+ oxidoreductase results in the permanent induction of photoprotective mechanisms in Arabidopsis chloroplasts
Authors: Lintala Minna , Lehtimäki Nina , Benz J. Philipp , Jungfer Andreas , Soll Jürgen , Aro Eva‐Mari , Bölter Bettina , Mulo Paula 
Published: February 2012

SummaryArabidopsis thaliana contains two photosynthetically competent chloroplast‐targeted ferredoxin‐NADP+ oxidoreductase (FNR) isoforms that are largely redundant in their function. Nevertheless, the FNR isoforms also display distinct molecular phenotypes, as only the FNR1 is able to directly bind to the thylakoid membrane. We report the consequences of depletion of FNR in the F1 (fnr1 × fnr2) and F2 (fnr1 fnr2) generation plants of the fnr1 and fnr2 single mutant crossings. The fnr1 × fnr2 plants, with a decreased total content of FNR, showed a small and pale green phenotype, accompanied with a marked downregulation of photosynthetic pigment‐protein complexes. Specifically, when compared with the wild type (WT), the quantum yield of photosystem II (PSII) electron transport was lower, non‐photochemical quenching (NPQ) was higher and the rate of P700+ re‐reduction was faster in the mutant plants. The slight over‐reduction of the plastoquinone pool detected in the mutants resulted in the adjustment of the reactive oxygen species (ROS) scavenging systems, as both the content and de‐epoxidation state of xanthophylls, as well as the content of α‐tocopherol, were higher in the leaves of the mutant plants when compared with the WT. The fnr1 fnr2 double mutant plants, which had no detectable FNR and possessed an extremely downregulated photosynthetic machinery, survived only when grown heterotrophically in the presence of sucrose. Intriguingly, the fnr1 fnr2 plants were still capable of sustaining the biogenesis of a few malformed chloroplasts.