bluuebunny/crossref_metadata_2025 huggingface dataset:
Anaphase promoting complex–dependent degradation of transcriptional repressors Nrm1 and Yhp1 inSaccharomyces cerevisiae
Authors: Ostapenko Denis , Solomon Mark J.
Published: May 2011

The anaphase-promoting complex/cyclosome (APC/C) is an essential ubiquitin ligase that targets cell cycle proteins for proteasome-mediated degradation in mitosis and G1. The APC regulates a number of cell cycle processes, including spindle assembly, mitotic exit, and cytokinesis, but the full range of its functions is still unknown. To better understand cellular pathways controlled by the APC, we performed a proteomic screen to identify additional APC substrates. We analyzed cell cycle–regulated proteins whose expression peaked during the period when other APC substrates were expressed. Subsequent analysis identified several proteins, including the transcriptional repressors Nrm1 and Yhp1, as authentic APC substrates. We found that APCCdh1targeted Nrm1 and Yhp1 for degradation in early G1 through Destruction-box motifs and that the degradation of these repressors coincided with transcriptional activation of MBF and Mcm1 target genes, respectively. In addition, Nrm1 was stabilized by phosphorylation, most likely by the budding yeast cyclin–dependent protein kinase, Cdc28. We found that expression of stabilized forms of Nrm1 and Yhp1 resulted in reduced cell fitness, due at least in part to incomplete activation of G1-specific genes. Therefore, in addition to its known functions, APC-mediated targeting of Nrm1 and Yhp1 coordinates transcription of multiple genes in G1 with other cell cycle events.
Model-based gene set analysis for Bioconductor
Authors: Bauer Sebastian , Robinson Peter N. , Gagneur Julien
Published: May 2011

Summary: Gene Ontology and other forms of gene-category analysis play a major role in the evaluation of high-throughput experiments in molecular biology. Single-category enrichment analysis procedures such as Fisher's exact test tend to flag large numbers of redundant categories as significant, which can complicate interpretation. We have recently developed an approach called model-based gene set analysis (MGSA), that substantially reduces the number of redundant categories returned by the gene-category analysis. In this work, we present the Bioconductor package mgsa, which makes the MGSA algorithm available to users of the R language. Our package provides a simple and flexible application programming interface for applying the approach.

Availability: The mgsa package has been made available as part of Bioconductor 2.8. It is released under the conditions of the Artistic license 2.0.

Contact:  peter.robinson@charite.de; julien.gagneur@embl.de
Apocalypse in world fisheries? The reports of their death are greatly exaggerated
Authors: Daan Niels , Gislason Henrik , Pope John G. , Rice Jake C.
Published: May 2011

Daan, N., Gislason, H., Pope, J. G., and Rice, J. C. 2011. Apocalypse in world fisheries? The reports of their death are greatly exaggerated. – ICES Journal of Marine Science, 68: 1375–1378. The catch-based methods underlying the forecast that by 2048 all commercially exploited stocks will have collapsed have been severely criticized, and a recent and more-elaborate analysis by a group of scientists that included the lead author of the original article has led to a quite different interpretation. Nonetheless, the 2006 forecast of a forthcoming apocalypse in the oceans is still uncritically referred to by critics of current management and fisheries science. In the title, the quote by Mark Twain is paraphrased to underline the fact that this prediction is both technically and conceptually flawed: (i) any series of random numbers subjected to the algorithm underlying the prediction will show a pattern similar to that observed in catch statistics; (ii) this pattern should be accounted for in making predictions; and (iii) interpreting the period of maximum harvest in a time-series as generally reflecting a period during which a stock was fully exploited is incorrect, because history often has shown that these maximum yields were taken during a period of overexploitation and could not have been sustainable.
Involvement of Tuberomamillary Histaminergic Neurons in Isoflurane Anesthesia
Authors: Luo Tao , Leung L. Stan
Published: May 2011

Background

The brain histaminergic system plays a critical role in maintenance of arousal. Previous studies suggest that histaminergic neurotransmission might be a potential mediator of general anesthetic actions. However, it is not clear whether histaminergic tuberomamillary nucleus (TMN) is necessarily involved in the sedative/hypnotic effects of general anesthetics.

Methods

Male Long Evans rats underwent either TMN orexin-saporin/sham lesion or implantation of intracerebroventricular cannula 2 weeks before the experiment. The behavioral endpoint of loss of righting reflex was used to assess the hypnotic property of isoflurane, propofol, pentobarbital, and ketamine in animals. Histaminergic cell loss was assessed by adenosine deaminase expression in the TMN using immunohistochemistry.

Results

Rats with bilateral TMN orexin-saporin lesion induced an average 72% loss of histaminergic cells compared with sham-lesion rats. TMN orexin-saporin lesion or intracerebroventricular administration of triprolidine (an H1 receptor antagonist) decreased the 50% effective concentration for loss of righting reflex value and prolonged emergence time to isoflurane anesthesia. However, TMN orexin-saporin lesion had no significant effect on the anesthetic sensitivity to propofol, pentobarbital, and ketamine.

Conclusions

These findings suggest a role of the TMN histaminergic neurons in modulating isoflurane anesthesia and that the neural circuits for isoflurane-induced hypnosis may differ from those of γ-aminobutyric acid-mediated anesthetics and ketamine.
CD209/DC-SIGN mediates efficient infection of monocyte-derived dendritic cells by clinical adenovirus 2C isolates in the presence of bovine lactoferrin
Authors: Günther Patrick S. , Mikeler Elfriede , Hamprecht Klaus , Schneider-Schaulies Jürgen , Jahn Gerhard , Dennehy Kevin M.
Published: May 2011

Adenovirus often causes respiratory infection in immunocompromised patients, but relevant attachment receptors have largely not been defined. We show that the antiviral protein bovine lactoferrin enhances infection of monocyte-derived dendritic cells (MDDC) by adenovirus species C serotype 2 (2C) isolates. Under the same conditions infection of MDDC by human cytomegalovirus was reduced. Adenoviral infection was prominently enhanced by bovine but not human lactoferrin, and was not prominently enhanced using blood monocyte-derived macrophages, suggesting that the relevant receptor is expressed on MDDC. Infection of MDDC in the presence of bovine lactoferrin was blocked by mannan, and an antibody to CD209/DC-SIGN but not isotype control or CD46 antibodies. Lastly, U937 macrophages ectopically expressing CD209/DC-SIGN, but not parental U937 cells, were efficiently infected by adenovirus 2C in the presence of bovine lactoferrin. These results may provide a tool, given the high efficiency of infection, to dissect responses by myeloid cells to clinical adenovirus isolates.
Characterization of new small ruminant lentivirus subtype B3 suggests animal trade within the Mediterranean Basin
Authors: Bertolotti L. , Mazzei M. , Puggioni G. , Carrozza M. L. , Dei Giudici S. , Muz D. , Juganaru M. , Patta C. , Tolari F. , Rosati S.
Published: May 2011

Small ruminant lentiviruses (SRLVs) represent a group of viruses infecting sheep and goats worldwide. Despite the high heterogeneity of genotype A strains, which cluster into as many as ten subtypes, genotype B was believed to be less complex and has, so far, been subdivided into only two subtypes. Here, we describe two novel full-length proviral sequences isolated from Sarda sheep in two Italian regions. Genome sequence as well as the main linear epitopes clearly placed this cluster into genotype B. However, owing to long-standing segregation of this sheep breed, the genetic distances that are clearly >15 % with respect to B1 and B2 subtypes suggest the designation of a novel subtype, B3. Moreover the close relationship with a gag sequence obtained from a Turkish sheep adds new evidence to historical data that suggest an anthropochorous dissemination of hosts (small ruminants) and their pathogens (SRLV) during the colonization of the Mediterranean from the Middle East.
Characterization of the interaction between the influenza A virus polymerase subunit PB1 and the host nuclear import factor Ran-binding protein 5
Authors: Hutchinson Edward C. , Orr Olivia E. , Man Liu Sai , Engelhardt Othmar G. , Fodor Ervin
Published: May 2011

The influenza A virus RNA polymerase is a heterotrimer that transcribes and replicates the viral genome in the cell nucleus. Newly synthesized RNA polymerase subunits must therefore be imported into the nucleus during an infection. While various models have been proposed for this process, the consensus is that the polymerase basic protein PB1 and polymerase acidic protein PA subunits form a dimer in the cytoplasm and are transported into the nucleus by the beta-importin Ran-binding protein 5 (RanBP5), with the PB2 subunit imported separately to complete the trimeric complex. In this study, we characterized the interaction of PB1 with RanBP5 further and assessed its importance for viral growth. In particular, we found that the N-terminal region of PB1 mediates its binding to RanBP5 and that basic residues in a nuclear localization signal are required for RanBP5 binding. Mutating these basic residues to alanines does not prevent PB1 forming a dimer with PA, but does reduce RanBP5 binding. RanBP5-binding mutations reduce, though do not entirely prevent, the nuclear accumulation of PB1. Furthermore, mutations affecting RanBP5 binding are incompatible with or severely attenuate viral growth, providing further support for a key role for RanBP5 in the influenza A virus life cycle.
To what extent are the dietary compositions of three abundant, co‐occurring labrid species different and related to latitude, habitat, body size and season?
Authors: Lek E. , Fairclough D. V. , Platell M. E. , Clarke K. R. , Tweedley J. R. , Potter I. C.
Published: May 2011

This study demonstrated that the dietary composition of each of three abundant reef‐associated labrid species in temperate Western Australia differed significantly with latitude and changed with increasing body size and almost invariably differed among those species when they co‐occurred. These results were derived from comparisons and multivariate analyses of volumetric dietary data, obtained from the foregut contents of Coris auricularis, Notolabrus parilus and Ophthalmolepis lineolatus from the Jurien Bay Marine Park (JBMP) and waters off Perth, 250 km to the south. Latitudinal differences in the dietary compositions of each species in exposed reefs typically reflected greater contributions by large crustaceans, bivalve molluscs, echinoids and annelids to the diets in the waters off Perth than in the JBMP, whereas the reverse was true for gastropods and small crustaceans. The diet of each species exhibited similar, but not identical, quantitative changes with increasing body size, with the contributions of small crustaceans declining and those of large crustaceans and echinoids increasing, while that of gastropods underwent little change. Within the JBMP, the dietary compositions of both C. auricularis and N. parilus were similar in exposed and sheltered reefs and the same was true for N. parilus in the sheltered reefs and interspersed areas of seagrass. The latter similarity demonstrated that, in both of those divergent habitat types, N. parilus feeds on prey associated with either the sand or the macrophytes that cover and lie between the reefs. Although the main dietary components of each species were the same, i.e. gastropods, small crustaceans (mainly amphipods and isopods), large crustaceans (particularly penaeids and brachyuran crabs) and echinoids, their contributions varied among those species, which accounts for the significant interspecific differences in diet. Coris auricularis had the most distinct diet, due mainly to an ingestion of greater volumes of small crustaceans, e.g. amphipods and isopods, and lesser volumes of large crustaceans, e.g. brachyuran crabs, which was associated with a relatively narrower mouth and smaller teeth and the absence of prominent canines at the rear of the jaw. The above intra and interspecific differences in dietary composition would reduce, on the south‐west coast of Australia, the potential for competition for food among and within these three abundant labrids, each of which belongs to different genera within the Julidine clade.
The life histories of endangered hammerhead sharks (Carcharhiniformes, Sphyrnidae) from the east coast of Australia
Authors: Harry A. V. , Macbeth W. G. , Gutteridge A. N. , Simpfendorfer C. A.
Published: May 2011

The life histories of two globally endangered hammerhead sharks,Sphyrna lewiniandSphyrna mokarran, were examined using samples collected from a range of commercial fisheries operating along the east coast of Australia. The catch ofS. lewiniwas heavily biased towards males, and there were significant differences in von Bertalanffy growth parameters (L∞andk) and maturity [stretched total length (LST) and age (A) at which 50% are mature,LST50andA50] between those caught in the tropics (L∞= 2119 mm,k= 0·163,LST50= 1471 mm,A50= 5·7 years) and those caught in temperate waters (L∞= 3199 mm,k= 0·093,LST50= 2043 mm,A50= 8·9 years). The best‐fit estimates for a three‐parameter von Bertalanffy growth curve fit to both sexes wereL∞= 3312 mm,L0= 584 mm andk= 0·076. Males attained a maximum age of 21 years and grew to at least 2898 mmLST. The longevity, maximum length and maturity of females could not be estimated as mature animals could not be sourced from any fishery. Length at birth inferred from neonates with open umbilical scars was 465–563 mmLST. There was no significant difference in length and age at maturity of male and femaleS. mokarran, which reached 50% maturity at 2279 mmLSTand 8·3 years.Sphyrna mokarrangrew at a similar rate toS. lewiniand the best‐fit estimates for a two‐parameter von Bertalanffy equation fit to length‐at‐age data for sexes combined with an assumed mean length‐at‐birth of 700 mm wereL∞= 4027 mm andk= 0·079. Females attained a maximum age of 39·1 years and grew to at least 4391 mmLST. The oldest maleS. mokarranwas 31·7 years old and 3691 mmLST. Validation of annual growth‐band deposition inS. mokarranwas achieved through a mark, tag and recapture study.
Calpain regulates thymidylate synthase–5‐fluoro‐dUMP complex levels associated with response to 5‐fluorouracil in gastric cancer cells
Authors: Nabeya Yoshihiro , Suzuki Takao , Furuya Aki , Koide Naoki , Ohkoshi Motohiro , Takiguchi Masaki , Ochiai Takenori , Matsubara Hisahiro , Hiwasa Takaki
Published: May 2011

Thymidylate synthase (TS) plays a major role in the response to 5‐fluorouracil (5‐FU) by binding directly to the 5‐FU metabolite, 5‐fluoro‐dUMP (FdUMP). The change in the TS expression levels after 5‐FU administration was examined in parallel to 5‐FU responsiveness in six human gastric adenocarcinoma cell lines to elucidate the source of variability of 5‐FU sensitivity. MKN‐1, SH‐10‐TC and MKN‐74 cells were more resistant to 5‐FU than MKN‐28, KATO III and MKN‐45 cells. Western blotting analysis revealed that the 5‐FU sensitivity of these cells did not correlate with the basal TS expression levels but did correlate with rapid detection of the TS‐FdUMP complex after exposure to 5‐FU. In 5‐FU‐resistant cells, very low levels of the TS‐FdUMP complex early after 5‐FU exposure were elevated by pretreatment with calpain inhibitors such as benzyloxycarbonyl‐leucyl‐leucinal (ZLLH), benzyloxycarbonyl‐leucyl‐leucyl‐leucinal (ZLLLH) and ALLN, but not by other protease inhibitors. In contrast, ONO‐3403, which causes calpain activation, stimulated downregulation of the TS‐FdUMP complex in 5‐FU‐sensitive cells. The expression levels of calpastatin, an endogenous calpain inhibitor, were higher in 5‐FU‐sensitive cells than in 5‐FU‐resistant cells. ZLLH increased the 5‐FU sensitivity of 5‐FU‐resistant cells, whereas ONO‐3403 decreased the sensitivity of 5‐FU‐sensitive cells. In addition, knockdown of m‐calpain by siRNA increased the 5‐FU sensitivity in 5‐FU‐resistant cells, while knockdown of calpastatin reduced the sensitivity in 5‐FU‐sensitive cells. These results suggest that calpain might reduce the chemosensitivity of human gastric cancer cells to 5‐FU possibly by rapid degradation of the TS‐FdUMP complex, a finding that is considered to have novel therapeutic implications. (Cancer Sci 2011; 102: 1509–1515)
Enhanced antitumor efficacy by blocking activation of the phosphatidylinositol 3‐kinase/Akt pathway during anti‐angiogenesis therapy
Authors: Zhao Yu Wei , Jin Lu , Li Zhi Mian , Zhao Cheng Jian , Wei Yu Quan , Yang Han Shuo
Published: May 2011

Anti‐angiogenesis has been a promising strategy for cancer therapy. However, many signal pathways are activated during anti‐angiogenic treatment to counteract the therapeutic efficacy. Among these pathways, evidence has directly pointed to the phosphatidylinositol 3‐kinase/Akt (PI3K/Akt) pathway, whose activation resulted in tolerance to the absence of nutrients and oxygen when tumor angiogenesis has been inhibited. In the present study, we investigated the effects of blocking activation of the PI3K/Akt pathway on cell survival in vitro and tumor growth in vivo during anti‐angiogenesis therapy. In modeled microenvironments in vitro, we observed that the phosphorylation of Akt in tumor cells was increased gradually in the absence of serum and oxygen in a time‐dependent manner. The specific inhibitors of PI3K inhibited the proliferation of tumor cells in a dose‐dependent manner in vitro. Moreover, inhibition was enhanced gradually with increased serum deprivation and/or hypoxia. In a mouse tumor model, we found the phosphorylation of Akt obviously increased following anti‐angiogenic therapy using plasmids encoding soluble vascular endothelial growth factor receptor‐2, but significantly reduced after treatment with LY294002. Consequently, the combinational treatment exhibited better antitumor effects compared with single treatments, presenting larger necrosis‐like areas, more apoptotic cells, less microvessel density and less phosphorylated Akt in tumors. These results suggest that blocking activation of the PI3K/Akt pathway during anti‐angiogenesis therapy could enhance antitumor efficacy. Thus, targeting the PI3K/Akt pathway might be a promising strategy to reverse tumor resistance to anti‐angiogenesis therapy. (Cancer Sci 2011; 102: 1469–1475)
Primary gastrointestinal follicular lymphoma involving the duodenal second portion is a distinct entity: A multicenter, retrospective analysis in Japan
Authors: Takata Katsuyoshi , Okada Hiroyuki , Ohmiya Naoki , Nakamura Shotaro , Kitadai Yasuhiko , Tari Akira , Akamatsu Taiji , Kawai Hiroki , Tanaka Shu , Araki Hiroshi , Yoshida Takashi , Okumura Hirokazu , Nishisaki Hogara , Sagawa Tamotsu , Watanabe Norihiko , Arima Nobuyoshi , Takatsu Noritaka , Nakamura Masanao , Yanai Shunichi , Kaya Hiroyasu , Morito Toshiaki , Sato Yasuharu , Moriwaki Hisataka , Sakamoto Choitsu , Niwa Yasumasa , Goto Hidemi , Chiba Tsutomu , Matsumoto Takayuki , Ennishi Daisuke , Kinoshita Tomohiro , Yoshino Tadashi
Published: May 2011

We conducted a multicenter, retrospective study to determine the anatomical distribution and prognostic factors of gastrointestinal (GI) follicular lymphoma (FL). This study included 125 patients with stage I and II1 GI–FL. Of the 125 patients, the small intestine was examined in 70 patients, with double‐balloon endoscopy and/or capsule endoscopy. The most frequently involved GI–FL site was the duodenal second portion (DSP) (81%), followed by the jejunum (40%); 85% of patients with involvement of the DSP also had jejunal or ileal lesions. The absence of abdominal symptoms and macroscopic appearance of multiple nodules were significantly present in the DSP‐positive group. During a median follow up of 40 months, six patients showed disease progression. Patients with involvement of the DSP had better progression‐free survival (PFS) than those without such involvement (P = 0.001). A multivariate analysis revealed that male sex, the presence of abdominal symptoms, and negative involvement of the DSP were independently associated with poor PFS. In conclusion, most patients with GI–FL have duodenal lesions associated with multiple jejunal or ileal lesions. Gastrointestinal follicular lymphomas involving the DSP might be a distinct entity showing a favorable clinical course. (Cancer Sci 2011; 102: 1532–1536)
Performance of gastric cancer screening by endoscopy testing through the National Cancer Screening Program of Korea
Authors: Choi Kui Son , Jun Jae Kwan , Lee Hoo‐Yeon , Park Sohee , Jung Kyu Won , Han Mi Ah , Choi Il Ju , Park Eun‐Cheol
Published: May 2011

Recent reports have proposed endoscopy as an alternative strategy to radiography for gastric cancer (GC) screening. The current study presents the first reported population‐based data from a large GC screening program that provided endoscopic examinations. A retrospective population‐based study was conducted using the National Cancer Screening Program (NCSP) database. We evaluated GC detection rates, sensitivity, specificity, and the positive predictive value of an endoscopic screening program for the average‐risk Korean population, aged 40 years and older, who underwent the NCSP from 2002 to 2005. The detection rates of GC by endoscopy in the first and subsequent rounds were 2.71 and 2.14 per 1000 examinations, respectively. Localized cancer accounted for 45.7% of screen‐detected GC cases. The sensitivity of endoscopy was 69% (95% confidence interval [CI]: 66.3–71.8). The endoscopic screening was less sensitive for the detection of localized GC (65.7%, 95% CI = 61.8–69.5) than for regional or distant GC (73.6%, 95% CI = 67.4–79.8). In the multiple logistic models for localized GC and all combined GC, the odds ratio (OR) of sensitivity for the undifferentiated type was statistically significantly higher than that for the differentiated type, whereas the OR of sensitivity for the mixed type was lower than that for the differentiated type. The sensitivity of the endoscopic test in a population‐based screening was slightly higher for the detection of regional or distant GC than for localized GC. Further evaluation of the impact of endoscopic screening should take into account the balance of cost and mortality reduction. (Cancer Sci 2011; 102: 1559–1564)
Resistance to activated protein C is a risk factor for pregnancy‐related venous thrombosis in the absence of the F5 rs6025 (factor V Leiden) polymorphism
Authors: Bergrem Astrid , Dahm Anders Erik Astrup , Jacobsen Anne Flem , Mowinckel Marie‐Christine , Sandvik Leiv , Sandset Per Morten
Published: May 2011

Resistance to activated protein C (aPC) is most commonly due to the F5 rs6025 (factor V Leiden) polymorphism, which increases the risk of venous thrombosis. In the present population‐based study of 313 cases and 353 controls, we investigated whether reduced sensitivity to aPC was associated with a history of pregnancy‐related venous thrombosis. Calibrated automated thrombography was used to determine the sensitivity to aPC, and normalized aPC sensitivity ratio (n‐aPC‐sr) was calculated. Pregnant women and women using oral contraceptives and/or anticoagulants were excluded due to the effect on the n‐aPC‐sr. In women without the F5 rs6025 polymorphism, free tissue factor pathway inhibitor (TFPI), free protein S and protein C activity were associated with n‐aPC‐sr. Unadjusted odds ratio for venous thrombosis for women with n‐aPC‐sr in the 4th quartile as compared with n‐aPC‐sr below the 4th quartile was 2·4 (95% confidence interval 1·7–3·6). Adjusting for free protein S, free TFPI and age did not influence the odds ratios. Also in carriers of the F5 rs6025 polymorphism the risk for venous thrombosis was increased for women with higher n‐aPC‐sr. Our findings substantiate the importance of the aPC resistant phenotype as a risk factor for pregnancy‐related venous thrombosis.
Attainment of complete/very good partial response following rituximab‐based therapy is an important determinant to progression‐free survival, and is impacted by polymorphisms in FCGR3A in Waldenstrom macroglobulinaemia
Authors: Treon Steven P. , Yang Guang , Hanzis Christine , Ioakimidis Leukothea , Verselis Sigitas J. , Fox Edward A. , Xu Lian , Hunter Zachary R. , Tseng Hsiuyi , Manning Robert J. , Patterson Christopher J. , Sheehy Patricia , Turnbull Barry
Published: May 2011

The incorporation of rituximab into various regimens has improved depth of response in Waldenstrom macroglobulinaemia (WM), though the impact of achieving better responses remains to be determined. We examined response depth on progression‐free survival (PFS) in 159 rituximab‐naïve WM patients who received rituximab‐based therapy. The median follow‐up was 33·5 months, and categorical responses were as follows: complete response (CR, 8·8%); very good partial response (VGPR, 13·2%); partial response (50%); minor response (18·9%); Non‐Responders (8·8%). Sequencing for polymorphic variants of FCGR2A, FCGR2B, and FCGR3A was performed, and impact on response depth determined. Achievement of better categorical responses was incrementally associated with improved PFS (P < 0·0001). No separation was observed between CR and VGPR, and attainment of at least a VGPR was associated with improved time‐to‐progression. Neither age, serum IgM, haematocrit, platelet count, serum β2microglobulin, WM International Prognostic Scoring System score, and treatment group predicted for CR/VGPR. Polymorphisms at FCGR3A‐48 and ‐158 were associated with improved categorical responses, particularly attainment of CR/VGPR (P ≤ 0·03). The attainment of CR/VGPR was associated with significantly longer PFS in rituximab‐naïve WM patients undergoing rituximab‐based therapy, and was predicted by polymorphisms in FCGR3A.
Carbon sequestration potential of tropical pasture compared with afforestation in Panama
Authors: WOLF SEBASTIAN , EUGSTER WERNER , POTVIN CATHERINE , TURNER BENJAMIN L. , BUCHMANN NINA
Published: May 2011

Tropical forest ecosystems play an important role in regulating the global climate, yet deforestation and land‐use change mean that the tropical carbon sink is increasingly influenced by agroecosystems and pastures. Despite this, it is not yet fully understood how carbon cycling in the tropics responds to land‐use change, particularly for pasture and afforestation. Thus, the objectives of our study were: (1) to elucidate the environmental controls and the impact of management on gross primary production (GPP), total ecosystem respiration (TER) and net ecosystem CO2 exchange (NEE); (2) to estimate the carbon sequestration potential of tropical pasture compared with afforestation; and (3) to compare eddy covariance‐derived carbon budgets with biomass and soil inventory data. We performed comparative measurements of NEE in a tropical C4 pasture and an adjacent afforestation with native tree species in Sardinilla (Panama) from 2007 to 2009. Pronounced seasonal variation in GPP, TER and NEE were closely related to radiation, soil moisture, and C3 vs. C4 plant physiology. The shallow rooting depth of grasses compared with trees resulted in a higher sensitivity of the pasture ecosystem to water limitation and seasonal drought. During 2008, substantial amounts of carbon were sequestered by the afforestation (–442 g C m–2, negative values denote ecosystem carbon uptake), which was in agreement with biometric observations (–450 g C m–2). In contrast, the pasture ecosystem was a strong carbon source in 2008 and 2009 (261 g C m–2), associated with seasonal drought and overgrazing. In addition, soil carbon isotope data indicated rapid carbon turnover after conversion from C4 pasture to C3 afforestation. Our results clearly show the potential for considerable carbon sequestration of tropical afforestation and highlight the risk of carbon losses from pasture ecosystems in a seasonal tropical climate.
The role of BLIMP1 and its putative downstream target TFAP2C in germ cell development and germ cell tumours
Authors: Schäfer S. , Anschlag J. , Nettersheim D. , Haas N. , Pawig L. , Schorle H.
Published: May 2011

During the past years, much information has been gathered regarding the genetic and epigenetic programmes leading to the specification and maintenance of primordial germ cells. Expression of the transcriptional regulator BLIMP1 (PRDM1) is regarded as the main event in germ cell specification. BLIMP1 induces a set of target genes, one of them being transcription factor TFAP2C (AP‐2γ, Tcfap2c). In murine loss of function models Blimp1 and Tcfap2c share an identical phenotype, strengthening the assumption that they act in the same pathway. One major role of this pathway is the inhibition of somatic differentiation in germ cells. BLIMP1 and TFAP2C are also expressed in carcinoma in situ (CIS, IGCNU, TIN) and in seminoma. As pointed out herein, the presence of both proteins helps to explain the undifferentiated nature of these germ cell tumours. In addition, we performed a meta‐analysis of high‐throughput datasets searching for TFAP2C/Tcfap2c target genes. This analysis leads us to suggest Nanos3, Dmrt1 and Dnmt3b as potential TFAP2C/Tcfap2c target genes with relevance to germ cell development and germ cell tumours.
The effects of leadership and ward factors on job satisfaction in nursing homes: a multilevel approach
Authors: Havig Anders K , Skogstad Anders , Veenstra Marijke , Romøren Tor I
Published: May 2011

Aims and objectives.  To examine (1) the relationships between job satisfaction and task‐ and relationship‐oriented leadership and (2) the direct and moderating effects on job satisfaction of three ward‐level factors: workload, use of teams and staff stability.

Background.  Job satisfaction in nursing homes is vital to meeting the challenges related to recruitment and turnover.

Design.  Cross‐sectional design.

Method.  A multilevel analysis approach was used to recognise a hierarchal structure of determined factors and to capture variation in job satisfaction at the individual and ward level. A questionnaire was sent to 444 registered nurses, auxiliary nurses and unskilled nursing assistants. Structured interviews were administered to 40 ward managers and 13 directors, and 900 hours of field observations was conducted in 40 nursing home wards throughout Norway.

Results.  We found a significant relationship between job satisfaction and task‐oriented and relationship‐oriented leadership styles, with a stronger effect for task orientation. The effect of the two leadership styles varied significantly across wards. Furthermore, staff stability had both a significant positive direct effect and a moderating effect on job satisfaction, whereas the two other ward‐level predictors yielded no significant contributions.

Conclusion.  The relatively stronger effect of task‐oriented leadership on job satisfaction, particularly in wards with low staff stability, is in contrast to most previous studies and suggests that there may be specific conditions in nursing homes that favour the use of this leadership style. The varying effect of both leadership styles indicates that staff in different nursing home wards could benefit from the use of different leadership styles.

Relevance to clinical practice.  The study highlights the importance of using different leadership behaviour and the importance of high staff stability to ensure job satisfaction among nursing home personnel.
Attitudes to organ donation among Swedish ICU nurses
Authors: Flodén Anne , Persson Lars‐Olof , Rizell Magnus , Sanner Margareta , Forsberg Anna
Published: May 2011

Aims and objectives.  To present data on Swedish ICU nurses’ attitudes to brain death and organ donation and to test a questionnaire designed to explore these issues in terms of validity and reliability.

Background.  Previous studies have identified various barriers to organ donation. The single most important factor was the attitude of ICU staff.

Design.  A 34‐item instrument was developed to explore attitudes and experiences of organ donation.

Method.  The questionnaire was sent to 50% of ICU nurses in Sweden (n = 1013) and the response rate was 69% (n = 702). The expected scale dimensionality was examined both by explorative principal component analysis and confirmatory multi‐trait analysis. Scale reliability was further estimated using Cronbach’s alpha. Chi‐squared test was used to compare proportions between ICU specialities and Pearson correlations were calculated to investigate relationships between each of the factors verified and the single items.

Results.  The main findings were that less than half of the ICU nurses trusted clinical diagnosis of brain death without a confirmatory cerebral angiography. Twenty‐five percent of the respondents indicated that mechanical ventilation was withdrawn to reduce the possible suffering of a person assumed to be clinically dead, without the issue of organ donation being raised. A total of 39% had experienced occasions when the question about organ donation was never raised with the relatives. Four factors were verified and labelled: personal attitudes to organ donation as a situation; Organisational attitudes to organ donation as a phenomenon; Environmental resources; and Personal wish to donate, which accounted for 70% of the variance.

Conclusions.  Swedish ICU nurses reported several barriers to organ donation. An action plan including education in brain death diagnostics, interpersonal relationships and interaction with relatives as well as regular follow‐up regarding donation issues in various ICU settings would be useful.

Relevance to clinical practice.  All nurses working in ICUs are obliged to participate in organ donation and are therefore included in these results.
Selective Oestrogen Receptor Modulators Decrease the Inflammatory Response of Glial Cells
Authors: Arevalo M. A. , Diz‐Chaves Y. , Santos‐Galindo M. , Bellini M. J. , Garcia‐Segura L. M.
Published: May 2011

Neuroinflammation comprises a feature of many neurological disorders that is accompanied by the activation of glial cells and the release of pro‐inflammatory cytokines and chemokines. Such activation is a normal response oriented to protect neural tissue and it is mainly regulated by microglia and astroglia. However, excessive and chronic activation of glia may lead to neurotoxicity and may be harmful for neural tissue. The ovarian hormone oestradiol exerts protective actions in the central nervous system that, at least in part, are mediated by a reduction of reactive gliosis. Several selective oestrogen receptor modulators may also exert neuroprotective effects by controlling glial inflammatory responses. Thus, tamoxifen and raloxifene decrease the inflammatory response caused by lipopolysaccharide, a bacterial endotoxin, in mouse and rat microglia cells in vitro. Tamoxifen and raloxifene are also able to reduce microglia activation in the brain of male and female rats in vivo after the peripheral administration of lipopolysaccharide. In addition, tamoxifen decreases the microglia inflammatory response induced by irradiation. Furthermore, treatment with tamoxifen and raloxifene resulted in a significant reduction of the number of reactive astrocytes in the hippocampus of young, middle‐aged and older female rats after a stab wound injury. Tamoxifen, raloxifene and the new selective oestrogen receptor modulators ospemifene and bazedoxifene decrease the expression and release of interleukine‐6 and interferon‐γ inducible protein‐10 in cultured astrocytes exposed to lipopolysaccharide. Ospemifene and bazedoxifene exert anti‐inflammatory effects in astrocytes by a mechanism involving classical oestrogen receptors and the inhibition of nuclear factor‐kappa B p65 transactivation. These data suggest that oestrogenic compounds are candidates to counteract brain inflammation under neurodegenerative conditions by targeting the production and release of pro‐inflammatory molecules by glial cells.
Mutations in the nucleotide binding pocket of MreB can alter cell curvature and polar morphology in Caulobacter
Authors: Dye Natalie A. , Pincus Zachary , Fisher Isabelle C. , Shapiro Lucy , Theriot Julie A.
Published: May 2011

The maintenance of cell shape in Caulobacter crescentus requires the essential gene mreB, which encodes a member of the actin superfamily and the target of the antibiotic, A22. We isolated 35 unique A22‐resistant Caulobacter strains with single amino acid substitutions near the nucleotide binding site of MreB. Mutations that alter cell curvature and mislocalize the intermediate filament crescentin cluster on the back surface of MreB's structure. Another subset have variable cell widths, with wide cell bodies and actively growing thin extensions of the cell poles that concentrate fluorescent MreB. We found that the extent to which MreB localization is perturbed is linearly correlated with the development of pointed cell poles and variable cell widths. Further, we find that a mutation to glycine of two conserved aspartic acid residues that are important for nucleotide hydrolysis in other members of the actin superfamily abolishes robust midcell recruitment of MreB but supports a normal rate of growth. These mutant strains provide novel insight into how MreB's protein structure, subcellular localization, and activity contribute to its function in bacterial cell shape.
The combined actions of the copper‐responsive repressor CsoR and copper‐metallochaperone CopZ modulate CopA‐mediated copper efflux in the intracellular pathogen Listeria monocytogenes
Authors: Corbett David , Schuler Stephanie , Glenn Sarah , Andrew Peter W. , Cavet Jennifer S. , Roberts Ian S.
Published: May 2011

We have characterized the csoR‐copA‐copZ copper resistance operon of the important human intracellular pathogen Listeria monocytogenes. Transcription of the operon is specifically induced by copper, and mutants lacking the P1‐type ATPase CopA have reduced copper tolerance and over‐accumulate copper relative to wild type. The copper‐responsive repressor CsoR autoregulates transcription by binding to a single 32 bp site spanning the −10 and −35 elements of the promoter. Copper co‐ordination by CsoR derepresses transcription of the operon and alters CsoR:DNA complex assembly as determined by DNase I footprinting and electrophoretic mobility shift assays, with some DNA‐binding capacity being retained in the presence of 2 mole equivalents of copper. Analysis of the CsoR copper sensory site demonstrated that substitution of Cys42 with Ala generated a CsoR variant that was unresponsive to copper. Importantly, in the absence of CopZ, copper responsiveness of csoR‐copA‐copZ expression is substantially increased, implying that CopZ reduces the access of CsoR to copper. Furthermore, CopZ is shown to confer copper resistance in mutants lacking copper‐inducible csoR‐copA‐copZ expression, thus providing protection from the deleterious effects of copper within the cytoplasm.
Rate and synchronicity of environmental changes on a shallow carbonate platform (Late Oxfordian, Swiss Jura Mountains)
Authors: STRASSER ANDRÉ , VÉDRINE STÉPHANIE , STIENNE NOÉMIE
Published: May 2011

Recent global change occurs within decades and leaves a significant imprint on shallow carbonate platforms. To what extent can rate and synchronicity of environmental changes in the past be evaluated in order to allow comparisons with the processes and products of today? Sections of a carbonate‐dominated platform of Late Oxfordian age have been logged in detail in the Swiss Jura Mountains. The time frame, based on ammonite biostratigraphy and the hierarchical stacking of the sedimentary sequences, suggests that these formed by low‐amplitude, high‐frequency sea‐level changes in tune with the orbital cycles. The smallest unit, the elementary sequence, can thus be attributed to the 20 kyr precession cycle. By identifying sequence‐stratigraphic elements such as maximum‐flooding surfaces within an elementary sequence, an even higher time resolution can be obtained and reconstructions of changes in water depth and sea‐level are attempted. Sedimentation rates were highly irregular and discontinuity surfaces are common. Correlation of such surfaces from one section to the other is tentative because they could also have formed locally and are not necessarily synchronous. On the scale of elementary sequences, the vertical facies evolution permits interpretation of changes in water depth, which were produced by eustatic sea‐level changes (allocyclic) and/or by autocyclic processes. The distribution of clay minerals indicates changes of sea‐level, as well as of rainfall in the hinterland. Biotic changes were controlled by water depth and water quality, and also by nutrient and clay input. Carbon and oxygen isotopes do not show significant shifts within the elementary sequences. The original ecological, mineralogical and geochemical signals have partly been homogenized because of time‐averaging through bioturbation and through reworking by storms, and because of diagenetic modifications. Consequently, there is potential to interpret environmental changes on the studied carbonate platform but the time resolution is not better than a few thousand years. The rates and the synchronicity of the processes leading to the observed environmental changes can thus be estimated only within this time frame.
Evolution and sedimentology of a channel fill in the sandy braided South Saskatchewan River and its comparison to the deposits of an adjacent compound bar
Authors: ASHWORTH PHILIP J. , SAMBROOK SMITH GREGORY H. , BEST JAMES L. , BRIDGE JOHN S. , LANE STUART N. , LUNT IAN. A. , REESINK ARNOLD J. H. , SIMPSON CHRISTOPHER J. , THOMAS ROBERT E.
Published: May 2011

The depositional stratigraphy of within‐channel deposits in sandy braided rivers is dominated by a variety of barforms (both singular ‘unit’ bars and complex ‘compound’ bars), as well as the infill of individual channels (herein termed ‘channel fills’). The deposits of bars and channel fills define the key components of facies models for braided rivers and their within‐channel heterogeneity, knowledge of which is important for reservoir characterization. However, few studies have sought to address the question of whether the deposits of bars and channel fills can be readily differentiated from each other. This paper presents the first quantitative study to achieve this aim, using aerial images of an evolving modern sandy braided river and geophysical imaging of its subsurface deposits. Aerial photographs taken between 2000 and 2004 document the abandonment and fill of a 1·3 km long, 80 m wide anabranch channel in the sandy braided South Saskatchewan River, Canada. Upstream river regulation traps the majority of very fine sediment and there is little clay (< 1%) in the bed sediments. Channel abandonment was initiated by a series of unit bars that stalled and progressively blocked the anabranch entrance, together with dune deposition and stacking at the anabranch entrance and exit. Complete channel abandonment and subsequent fill of up to 3 m of sediment took approximately two years. Thirteen kilometres of ground‐penetrating radar surveys, coupled with 18 cores, were obtained over the channel fill and an adjacent 750 m long, 400 m wide, compound bar, enabling a quantitative analysis of the channel and bar deposits. Results show that, in terms of grain‐size trends, facies proportions and scale of deposits, there are only subtle differences between the channel fill and bar deposits which, therefore, renders them indistinguishable. Thus, it may be inappropriate to assign different geometric and sedimentological attributes to channel fill and bar facies in object‐based models of sandy braided river alluvial architecture.
PCR–DGGE method for in planta detection and identification of Phytophthora species
Authors: Rytkönen A. , Lilja A. , Hantula J.
Published: May 2011

We have developed a method to detect multiple species of Phytophthora directly in infected plant tissues. The method is based on the polymerase chain reaction and uses Phytopththora‐specific primers and denaturing gradient gel electrophoresis (PCR–DGGE). The method distinguished most of the 16 Phytophthora species tested. Very closely related species might not, however, be identified using the method. The detection efficiency was high and successful in eight different plant tissues tested. The PCR–DGGE detection tool developed here will be a fast and inexpensive method suitable for pathogen surveys and research programmes.
Two cases of pregnancy involving conjoined twins, with details of management after opting for live birth
Authors: Takae Seido , Izuchi Shinichiro , Murayama Kimie , Kondo Haruhiro , Kobayashi Yoichi , Ishizuka Bunpei
Published: May 2011

Conjoined twinning is a unique complication of monochorionic pregnancy. This report describes the clinical findings in two cases of conjoined twins, and discusses their management. One case involved thoracopagus complicating a triplet pregnancy, and the other involved cephalothoracopagus, in which the outcome was intrauterine fetal death due to abruptio placentae after amniocentesis. Recent improvements in ultrasound imaging have facilitated the diagnosis of conjoined twins as early as the first trimester. Although many mothers opt to terminate pregnancy when conjoined twins are diagnosed, a few do not, as in the cases described. In such cases, pregnancy management, including accurate determination of the degree of organ fusion and psychological follow up, are important. On the basis of the two present cases, we present a systematic flow diagram for management of conjoined twin pregnancy from the time of diagnosis until delivery.
Acute acalculous cholecystitis due to dengue hemorrhagic fever during pregnancy
Authors: Marasinghe Jeevan P. , Sriyasinghe Radhika Y. , Wijewantha Vidyani I. , Gunaratne Kumbalathara A. R. C. W. , Wijeyaratne Chandrika N.
Published: May 2011

A 29‐year‐old pregnant woman presented with fever, right hypochondrial pain and fatigability at 29 weeks of gestation. Dengue hemorrhagic fever was diagnosed based on clinical, hematological and serological features. However, ultrasound scanning was suggestive of acute acalculous cholecystitis. The patient was managed symptomatically and made a good recovery 8 days following onset of fever. This is the first case of acute acalculous cholecystitis coinciding with dengue hemorrhagic fever reported during pregnancy from an endemic country in Asia. The possible viral and host factors for the development of such a severe form of disease and preventive measures are discussed.
The State of the Art in Topology‐Based Visualization of Unsteady Flow
Authors: Pobitzer Armin , Peikert Ronald , Fuchs Raphael , Schindler Benjamin , Kuhn Alexander , Theisel Holger , Matković Krešimir , Hauser Helwig
Published: May 2011

Vector fields are a common concept for the representation of many different kinds of flow phenomena in science and engineering. Methods based on vector field topology are known for their convenience for visualizing and analysing steady flows, but a counterpart for unsteady flows is still missing. However, a lot of good and relevant work aiming at such a solution is available. We give an overview of previous research leading towards topology‐based and topology‐inspired visualization of unsteady flow, pointing out the different approaches and methodologies involved as well as their relation to each other, taking classical (i.e. steady) vector field topology as our starting point. Particularly, we focus on Lagrangian methods, space–time domain approaches, local methods and stochastic and multifield approaches. Furthermore, we illustrate our review with practical examples for the different approaches.