bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of theeaeA gene in verotoxigenicEscherichia colistrains from dairy cattle in Southwest Ontario
Authors: Sandhu K. S. , Clarke R. C. , McFadden K. , Brouwer A. , Louie M. , Wilson J. , Lior H. , Gyles C. L.
Published: May 2009

This study determined the prevalence of theeaeA gene and its relationship to serotype and type of verotoxin produced in a collection of 432 verotoxigenicEscherichia coli(VTEC) obtained from the faeces of healthy cows and calves in a systematic random survey involving 80 dairy farms in Southwest Ontario. A PCR amplification procedure involving primer pairs which target the conserved central region of the O157:H7eaeA. gene showed that 151 (35·2%) strains were positive for the eaeA gene. All isolates (9–21 for each O group) of O groups 5, 26, 69, 84, 103, 111, 145 and 157 were positive, whereas all isolates (7–34 for each O group) of O groups 113, 132, and 153 and serotype O156:NM (38 isolates) were negative foreaeA. Seventy-three percent of 130 isolates ofeaeA-positive serotypes produced VT1 only compared with 20% of 253 isolates ofeaeA-negative serotypes. We conclude that there is a strong association between certain O groups and theeaeA gene, that serotypes ofeaeA-positive and eaeA-negative VTEC implicated in human and cattle disease are present at high frequency in the faeces of healthy cattle, that VT1 is more frequently associated witheaeA-positive than witheaeA-negative serogroups, and that the eaeA gene is more frequently found in VTEC from calves compared with VTEC from adult cattle.
Phenotypic variation amongst genotypically homogeneousLegionella pneumophilaserogroup 1 isolates: implications for the investigation of outbreaks of Legionnaires' disease
Authors: Harrison T. G. , Saunders N. A. , Haththotuwa A. , Hallas G. , Birtles R. J. , Taylor A. G.
Published: May 2009

One hundred and seventy-nine isolates ofLegionella pneumophilaserogroup 1, obtained from a site associated with an outbreak of Legionnaires' disease, were examined by monoclonal antibody subgrouping, restriction fragment length polymorphism typing, restriction endonuclease analysis and plasmid content. Nine distinct phenotypes were detected but at the genotypic level all strains were closely related. The data presented indicate that phenotypic variation of a single parent strain can occur within an environmental site. The implications of these findings are discussed in relation to the investigation of outbreaks of Legionnaires' disease.
Human listeriosis in Britain, 1967–85, a summary of 722 cases: 2. Listeriosis in non-pregnant individuals, a changing pattern of infection and seasonal incidence
Authors: McLauchlin J.
Published: May 2009

Clinical information was collected on 722 cases ofListeria monocytogenesinfections in humans occurring in Britain between 1967 and 1985. This series comprised 34% (248 cases) associated with pregnancy and 66% (474 cases) in non-pregnant adults and juveniles. The cases not associated with pregnancy comprised: 76% in patients with severe underlying illness (of which 34% had central nervous system infections, and 42 % bacteraemia without involvement of the central nervous system); 21% in previously healthy individuals (of whom 18% had meningitis); and 3% in patients without bacteraemia or involvement of the central nervous system. Cases occurred most often in male patients over 40 years of age. The overall mortality was 44%.

Overall, the pattern of infection has altered to a disease of higher incidence, affecting most often susceptible non-pregnant individuals and the unborn.

An annual increase in incidence of listeriosis occurred in the autumn in all categories of patients.
Secretor status, smoking and carriage ofNeisseria meningitidis
Authors: Blackwell C. C. , Weir D. M. , James V. S. , Todd W. T. A. , Banatvala N. , Chaudhuri A. K. R. , Gray H. G. , Thomson E. J. , Fallon R. J.
Published: May 2009

A survey of ABO blood groups, secretor status and smoking habits among 389 students and staff of a school in which there was an outbreak of meningococcal disease found no difference in the distribution of the ABO blood groups but a significantly higher proportion of non-secretors (37·6%) in the population examined compared with that reported for previous surveys of the neighbouring population in Glasgow (26·2%) (P< 0·0005). There was also a significantly higher proportion of non-secretors among carriers of meningococci (47%) compared with non-carriers (32%). Increased carriage of meningococci among non-secretors might contribute to the increased susceptibility of individuals with this genetic characteristic to meningococcal disease observed in previous studies. Although passive exposure to cigarette smoke has been associated with meningococcal disease, there was no association between passive smoking and carriage. There was, however, a significant association between active smoking and carriage.
Production of IgM antibody to HHV6 in reactivation and primary infection
Authors: Fox J. D. , Ward P. , Briggs M. , Irving W. , Stammers T. G. , Tedder R. S.
Published: May 2009

The cross-reaction of HHV6 antibody with that to the other herpesviruses was studied in 96 blood donors whose sera were tested for IgG antibody to human herpesvirus type 6 (HHV6), cytomegalovirus (CMV), Epstein–Barr virus (EBV), varicella zostervirus (VZV) and herpes simplex virus (HSV). No correlation was found between IgG antibody to HHV6 and that to any of the other herpesviruses in these individuals. Antibodies to HHV6 and CMV were measured in patients undergoing documented serological responses to HHV6. Eleven cases of primary HHV6 infection associated with roseola infantum in babies, 1 of whom suffered from gastroenteritis as well as pyrexia and rash, are reported. Three cases of HHV6 reactivation, 1 in a 3-year-old child and 2 in adults, 1 of whom simultaneously underwent a primary CMV infection are also reported. Our results suggest that indirect immunofluorescence is a specific way of measuring HHV6 antibody, that HHV6 IgG and IgM can be detected in the absence of antibody to CMV and that HHV6 IgM is present both in primary HHV6 infections and in reactivations.
A competitive ELISA for the detection of group-specific antibodies to African horse sickness virus
Authors: Hamblin C. , Graham S. D. , Anderson E. C. , Crowther J. R.
Published: May 2009

A competition enzyme-linked immunosorbent assay (ELISA) has been developed for the rapid identification and quantification of antibodies against African horse sickness (AHS) in sera from solipeds. The data showed the ELISA to be sensitive, specific and reliable.

More than 1600 sera from 37 different countries were examined and results compared with those obtained by agar gel immuno-diffusion (AGID) tests. In no case did any of 775 sera from countries where AHS has never been reported and where AHS vaccines are not used, record an ELISA titre greater than 4. A titre equal to or greater than 8 was considered positive. Using this criterion, 96·3% of sera tested in both assays were in agreement. Doubtful results by AGID (1·7%) were clearly defined in terms of positivity and negativity by ELISA.

This ELISA is suited for the rapid laboratory confirmation of AHS and should be considered as a replacement for the traditional AGID test.
Trajectory analysis of winds and vesicular stomatitis in North America, 1982–5
Authors: Sellers R. F. , Maarouf A. R.
Published: May 2009

Outbreaks of vesicular stomatitis, serotype New Jersey, during epidemics in the United States and northern Mexico, 1982–5, were examined by backward trajectories of winds to investigate spread and possible sources. The outbreaks selected for analysis did not involve introduction of disease by infected animals. The findings indicate that wind could have been responsible for carrying infection from northern Mexico to Arizona and New Mexico and thence to Colorado and Utah and on to Wyoming, Idaho and Montana. The results of these analyses are consistent with the findings from T1 RNAse fingerprinting of virus isolates from outbreaks during the epidemics. The arrival of the trajectories was associated with the passage of a front and rain or passage of a front alone or rain alone. At the time of the trajectories temperatures of 10 °C and higher were recorded at heights up to 2500–3500 m.

Introduction by airborne particles would appear unlikely as it would have required a source of at least 105infectious units per minute per animal. Vesicular stomatitis virus had been isolated fromSimuliumandCulicoidesduring the epidemic with amounts of virus fromSimuliumsufficient to suggest biological transmission. The possibility ofSimuliuminfected with vesicular stomatitis virus being carried downwind to introduce disease is discussed in relation to the behaviour ofSimuliumand the pathogenesis of vesicular stomatitis in large animals.
The Blind Man and the Elephant in the Room: Robert Lieberman and the Israel Lobby
Authors: Mearsheimer John J. , Walt Stephen M.
Published: May 2009

Robert Lieberman's critique of our work on the Israel lobby is at odds with an abundance of evidence and prior scholarship describing the powerful influence that pro-Israel groups exert on U.S. Middle East policy. In addition to mischaracterizing our arguments, Lieberman claims that our methodology and research design are flawed and that our work contradicts the scholarly literature on American politics. Neither claim is true. Contrary to what he says, we did consider alternative hypotheses, and our analysis contains significant variation on both the independent and dependent variables. Given the methodological challenges involved in assessing the causal influence of any interest group, we also relied heavily on “process-tracing.” Lieberman recognizes this is an appropriate method for assessing causal impact and he concedes that this evidence supports our central argument. Moreover, we went to some lengths to avoid selection bias. Similarly, our arguments are consistent with the existing literature on interest groups, and with much of the scholarly literature on congressional decision-making, campaign financing, electoral politics, and the role of think tanks and the media. Surprisingly, after leveling a variety of false charges, Lieberman offers an “alternative” explanation for the Israel lobby's influence that is virtually identical to our own.
The Unrealism of Contemporary Realism: The Tension between Realist Theory and Realists' Practice
Authors: Oren Ido
Published: May 2009

Realist International Relations thinkers often intervene in political debates and criticize their governments' policies even as they pride themselves on theorizing politics as it “really” is. They rarely reflect on the following contradictions between their theory and their practice: if there is a “real world” impervious to political thought, why bother to try to influence it? And, is realist theory not putatively disconfirmed by the fact that realist thinkers have so often opposed existing foreign policies (e.g., the wars in Vietnam and Iraq)? I argue that these contradictions are not inherent in realism per se so much as in the commitment of contemporary realists to naturalistic methodological and epistemological postulates. I show that Hans Morgenthau and especially E. H. Carr, far from being naïve “traditionalists,” have grappled with these questions in a sophisticated manner; they have adopted non-naturalistic methodological and epistemological stances that minimize the tension between realist theory and the realities of realists' public activism. I conclude with a call for contemporary realists to adjust their theory to their practice by trading the dualism underlying their approach—subject-object; science-politics; purpose-analysis—for E. H. Carr's dictum that “political thought is itself a form of political action.”
Social Movements for Global Democracy. By Jackie Smith. Baltimore: Johns Hopkins University Press, 2008. 286p.
Authors: Spiro Peter J.
Published: May 2009

World government is once again being taken seriously. For decades the target of ridicule, some form of institutionalized global decision making may be inevitable. As the proposition wins broader acceptance, scholars are coming to more closely explore the modalities of world government and the place of democracy within it. The enhanced profile of new actors in globalization's wake has magnified the challenge. Amid conditions of deep instability, isolating elements of a new decision-making architecture is a formidable theoretical task.
Response to Peter J. Spiro's review of Social Movements for Global Democracy
Authors: Smith Jackie
Published: May 2009

Peter Spiro's portrayal of my book Beyond Citizenship illustrates the very problem we have in confronting the underlying causes of global crises and envisioning alternatives to existing models of governance. Legal scholar and activist Boaventura de Sousa Santos argued quite cogently in 2007 that the struggle for global social justice is also a struggle for global cognitive justice (“Beyond Abyssal Thinking: From Global Lines to Ecologies of Knowledges,” Eurozine, at http://eurozine.com/pdf/2007-06-29-santos-en.pdf). In order to succeed, this struggle requires a new kind of thinking. Such new thinking is apparent in many contemporary social movements, but academic training and practice inhibits our ability to appreciate the wisdom of those deemed less worthy to speak to the grand questions of our day.
Base Politics: Democratic Change and the U.S. Military Overseas. By Alexander Cooley. Ithaca, NY: Cornell University Press, 2008. 321p. $29.95.
Authors: Aldrich Daniel P.
Published: May 2009

On September 5, 1995, three United States military personnel abducted and raped a 12-year-old schoolgirl on Okinawa, an island in the Pacific that houses roughly 75% of the U.S. military facilities in Japan. After a month and a half of smaller rallies, more than 85,000 demonstrators gathered in late October that year to protest not only the crime itself but also the presence of the U.S. bases on this string of islands that sit a thousand miles south of mainland Japan. Despite the enormous tragedy of this incident, the widespread international attention it received, and the Okinawan governor's refusal afterwards to renew land to the bases, more than 48,000 U.S. military personnel, their dependents, and civilians remain today on the island, which is roughly the size of Los Angeles. Tragedies at other U.S. bases overseas have similarly not altered the bilateral contracts with the host nation. In 1998, for example, a marine airplane accidentally severed a ski-lift cable for a gondola in Cavalese, Italy, killing all 20 passengers aboard, but this incident did not negatively impact the presence of the U.S. military in that nation.
The struggle for law: some dilemmas of cultural legality
Authors: Cotterrell Roger
Published: May 2009

My title ‘The Struggle for Law’ is that of a book by the nineteenth-century German jurist Rudolf von Jhering (1915). In fact a better translation of Jhering’s original German title (Der Kampf ums Recht) might be ‘the struggle around law’ or ‘the battle for rights’. He argued that citizens owe a moral duty to themselves and their society to assert legal rights vigorously. But law itself is above the fray, not subservient to their conflicting interests. So the struggle for law is not to control it but to invigorate it – to be involved in the legal order, an active citizen living under law. Jhering presupposed a cultural unity – ‘our whole culture’ (Jhering, 1913, pp. 59, 62). Given this unity, law can respond not only to citizens’ claims but to their feelings – feelings that are understandable in the shared culture law inhabits.
Coherent sources separation based on sparsity: an application to SSR signals
Authors: Petrochilos Nicolas , Galati Gaspare , Piracci Emilio
Published: May 2009

Systems based on secondary surveillance radar (SSR) downlink signals, both with directional and with omni-directional antennae (such as in multilateration), are operational today and more and more installations are being planned. In this frame, high-density traffic leads to the reception of a mixture of several overlapping SSR replies. By nature, SSR sources are sparse,i.e.with amplitude equal to zero with significantly high probability. While in the literature several algorithms performing sources separation with anm-element antenna have been proposed, none has satisfactorily employed the full potential of sparsity for SSR signals. Most sparsity algorithms can separate only real-valued sources, although we present in this study two algorithms to separate the complex-valued SSR sources. Recorded signals in a live environment are used to demonstrate the effectiveness of the proposed techniques.
Fluid infiltration, heat transport, and healing of microcracks in the damage zone of magmatic veins: Numerical modeling
Authors: Engvik Lars , Stöckhert Bernhard , Engvik Ane K.
Published: May 2009

Alteration halos with sharp boundaries are flanking pegmatitic veins in high‐grade metamorphic and magmatic rocks of Dronning Maud Land, Antarctica. These halos are interpreted to represent the damage zone, formed as the wake of the process zone at the tip of the propagating magma‐filled fracture and infiltrated by the fluid phase liberated from the crystallizing hydrous melt. On the basis of a set of assumptions, our numerical model explores the time scales of the infiltration processes, taking into account the combined effects of fluid flow, heat transfer, and temperature‐dependent decay of interconnected porosity due to microcrack healing. Assuming an initial magma temperature of 700°C, a far field temperature in the host rock of 300°C, an initial porosity range of 0.5–2% in the damage zone, a permeability of 10−16 m2, and a pressure difference of 300 MPa, we find that the fluid infiltration into the damage zone proceeds within seconds to minutes and that the fluid flow contributes significantly to the heat transfer into the host rock. Assuming an initial microcrack aperture of 1 μm, the model predicts that the crack healing time scale is significantly longer than that of fluid infiltration in the case of thin veins with narrow damage zones; in this case, crack healing does not hinder fluid infiltration. Only for thick veins with high heat content and prolonged crystallization history does permeability become reduced by crack healing during progressive fluid infiltration. The results indicate that the formation of the alteration halos flanking pegmatitic veins may be a quasi‐instantaneous process on geological time scales.
Decreasing anthropogenic methane emissions in Europe and Siberia inferred from continuous carbon dioxide and methane observations at Alert, Canada
Authors: Worthy Douglas E. J. , Chan Elton , Ishizawa Misa , Chan Douglas , Poss Christian , Dlugokencky Edward J. , Maksyutov Shamil , Levin Ingeborg
Published: May 2009

The rate of increase in global atmospheric methane (CH4) abundance has steadily declined since the late 1980s with near zero increase from 1999 through 2006. At the Canadian Baseline Observatory at Alert, Canada (82°28′N, 62°30′W), continuous measurements of methane (CH4) and carbon dioxide (CO2) have been made since 1987. During winter, both gases are frequently highly correlated during well‐defined episodes lasting from 2 to 5 days. We observe a gradual decrease in the ratios of CH4/CO2 during these episodes from ∼16 ppb CH4 (ppm CO2)−1 to ∼12 ppb CH4 (ppm of CO2)−1 over the entire record. An atmospheric transport model with prescribed CO2 and CH4 source distributions is used to partition simulated CH4 events into contributions by region. We show that anthropogenic emissions from Europe and Siberia account for more than 85% of the CO2 and CH4 enhancements simulated at Alert, but without a change in CH4 emissions, modeled CH4/CO2 ratios remain constant. To reproduce the observed trend in the ratio of CH4/CO2, the model requires a reduction in emissions of CH4 on the order of 30 Tg (13.6 to 33.4 Tg) in Europe and Siberia over the observational period. This is about twice the drop reported by the Emission Database for Global Atmospheric Research (EDGAR) emissions inventory and large enough to account for the leveling off of the global atmospheric CH4 burden observed over the past 20 years.
Slowing of India's convergence with Eurasia since 20 Ma and its implications for Tibetan mantle dynamics
Authors: Molnar Peter , Stock Joann M.
Published: May 2009

Reconstructions of the relative positions of the India and Eurasia plates, using recently revised histories of movement between India and Somalia and between North America and Eurasia and of the opening of the East African Rift, show that India's convergence rate with Eurasia slowed by more than 40% between 20 and 10 Ma. Much evidence suggests that beginning in that interval, the Tibetan Plateau grew outward rapidly and that radially oriented compressive strain in the area surrounding Tibet increased. An abrupt increase in the mean elevation of the plateau provides a simple explanation for all of these changes. Elementary calculations show that removal of mantle lithosphere from beneath Tibet, or from just part of it, would lead to both a modest increase in the mean elevation of the plateau of ∼1 km and a substantial change in the balance of forces per unit length applied to the India and Eurasia plates.
Distinct roles of ATR and DNA‐PKcs in triggering DNA damage responses in ATM‐deficient cells
Authors: Tomimatsu Nozomi , Mukherjee Bipasha , Burma Sandeep
Published: May 2009

The cellular response to DNA double‐strand breaks involves direct activation of ataxia telangiectasia mutated (ATM) and indirect activation of ataxia telangiectasia and Rad3 related (ATR) in an ATM/Mre11/cell‐cycle‐dependent manner. Here, we report that the crucial checkpoint signalling proteins—p53, structural maintainance of chromosomes 1 (SMC1), p53 binding protein 1 (53BP1), checkpoint kinase (Chk)1 and Chk2—are phosphorylated rapidly by ATR in an ATM/Mre11/cell‐cycle‐independent manner, albeit at low levels. We observed the sequential recruitment of replication protein A (RPA) and ATR to the sites of DNA damage in ATM‐deficient cells, which provides a mechanistic basis for the observed phosphorylations. The recruitment of ATR and consequent phosphorylations do not require Mre11 but are dependent on Exo1. We show that these low levels of phosphorylation are biologically important, as ATM‐deficient cells enforce an early G2/M checkpoint that is ATR‐dependent. ATR is also essential for the late G2 accumulation that is peculiar to irradiated ATM‐deficient cells. Interestingly, phosphorylation of KRAB associated protein 1 (KAP‐1), a protein involved in chromatin remodelling, is mediated by DNA‐dependent protein kinase catalytic subunit (DNA‐PKcs) in a spatio‐temporal manner in addition to ATM. We posit that ATM substrates involved in cell‐cycle checkpoint signalling can be minimally phosphorylated independently by ATR, while a small subset of proteins involved in chromatin remodelling are phosphorylated by DNA‐PKcs in addition to ATM.
Sequoia regulates cell fate decisions in the external sensory organs of adult Drosophila
Authors: Andrews Hillary K , Giagtzoglou Nikolaos , Yamamoto Shinya , Schulze Karen L , Bellen Hugo J
Published: May 2009

The adult Drosophila external sensory organ (ESO), comprising the hair, socket, neuron, sheath and glia cells, arises through the asymmetric division of sensory organ precursor cells (SOPs). In a mosaic screen designed to identify new components in ESO development, we isolated mutations in sequoia, which encodes a putative zinc‐finger transcription factor that has previously been shown to have a role in dendritogenesis. Here, we show that adult clones mutant for seq exhibit a loss of hair cells and a gain of socket cells. We propose that the seq mutant phenotype arises, in part, owing to the loss of several crucial transcription factors known to be important in peripheral nervous system development such as D‐Pax2, Prospero and Hamlet. Thus, Sequoia is a new upstream regulator of genes that orchestrates cell fate specification during development of the adult ESO lineage.
The elastic modulus, percolation, and disaggregation of strongly interacting, intersecting antiplane cracks
Authors: Davis P. M. , Knopoff L.
Published: May 2009

We study the modulus of a medium containing a varying density of nonintersecting and intersecting antiplane cracks. The modulus of nonintersecting, strongly interacting, 2D antiplane cracks obeys a mean-field theory for which the mean field on a crack inserted in a random ensemble is the applied stress. The result of a self-consistent calculation in the nonintersecting case predicts zero modulus at finite packing, which is physically impossible. Differential self-consistent theories avoid the zero modulus problem, but give results that are more compliant than those of both mean-field theory and computer simulations. For problems in which antiplane cracks are allowed to intersect and form crack clusters or larger effective cracks, percolation at finite packing is expected when the shear modulus vanishes. At low packing factor, the modulus follows the dilute, mean-field curve, but with increased packing, mutual interactions cause the modulus to be less than the mean-field result and to vanish at the percolation threshold. The “nodes-links-blobs” model predicts a power-law approach to the percolation threshold at a critical packing factor of
p

c

= 4.426. We conclude that a power-law variation of modulus with packing, with exponent 1.3 drawn tangentially to the mean-field nonintersecting relation and passing through the percolation threshold, can be expected to be a good approximation. The approximation is shown to be consistent with simulations of intersecting rectangular cracks at all packing densities through to the percolation value for this geometry,
p

c

= 0.4072.
A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates
Authors: Chan Joyce C. Y. , Piper Derek E. , Cao Qiong , Liu Dongming , King Chadwick , Wang Wei , Tang Jie , Liu Qiang , Higbee Jared , Xia Zhen , Di Yongmei , Shetterly Susan , Arimura Ziva , Salomonis Heather , Romanow William G. , Thibault Stephen T. , Zhang Richard , Cao Ping , Yang Xiao-Ping , Yu Timothy , Lu Mei , Retter Marc W. , Kwon Gayle , Henne Kirk , Pan Oscar , Tsai Mei-Mei , Fuchslocher Bryna , Yang Evelyn , Zhou Lei , Lee Ki Jeong , Daris Mark , Sheng Jackie , Wang Yan , Shen Wenyan D. , Yeh Wen-Chen , Emery Maurice , Walker Nigel P. C. , Shan Bei , Schwarz Margrit , Jackson Simon M.
Published: May 2009

Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates serum LDL cholesterol (LDL-C) by interacting with the LDL receptor (LDLR) and is an attractive therapeutic target for LDL-C lowering. We have generated a neutralizing anti-PCSK9 antibody, mAb1, that binds to an epitope on PCSK9 adjacent to the region required for LDLR interaction. In vitro, mAb1 inhibits PCSK9 binding to the LDLR and attenuates PCSK9-mediated reduction in LDLR protein levels, thereby increasing LDL uptake. A combination of mAb1 with a statin increases LDLR levels in HepG2 cells more than either treatment alone. In wild-type mice, mAb1 increases hepatic LDLR protein levels ≈2-fold and lowers total serum cholesterol by up to 36%: this effect is not observed in LDLR
−/−
mice. In cynomolgus monkeys, a single injection of mAb1 reduces serum LDL-C by 80%, and a significant decrease is maintained for 10 days. We conclude that anti-PCSK9 antibodies may be effective therapeutics for treating hypercholesterolemia.
Predictive social factors in relation to preterm birth in a metropolitan region
Authors: BEECKMAN KATRIEN , VAN DE PUTTE SABINE , PUTMAN KOEN , LOUCKX FRED
Published: May 2009

Objective. Preterm birth is an important indicator of neonatal wellbeing. Infants born preterm are at higher risk for severe morbidity and mortality. Apart from medical risk factors, social factors are also associated with preterm birth. This study aims to provide knowledge on factors which have a predictive role in relation to preterm birth. Design. Cross‐sectional population study. Setting. The Brussels metropolitan region. Population. Women who gave birth in the Brussels metropolitan region in 2004. In total, 8,586 birth registration forms were reviewed for this study. Main outcome measures. Associations between educational level, occupation, marital status, age, and origin with preterm birth (<37 weeks). Methods. After bivariate analyses, significant correlations were explored in a stepwise logistic regression model. Odds ratios (OR) were calculated for each of the significant characteristics in the final model. Results. The risk of preterm birth was found to be associated with age, origin, and marital status. After controlling for confounding factors, the two most important social risk factors for preterm birth were being a teenage mother (OR 2.15, 95% CI: 1.31–3.53) or single mother (OR 1.49, 95% CI: 1.17–1.91). Conclusions. Being a teenage or single mother are important social risk factors for preterm birth. We hypothesize that the increased risk is related to prenatal care trajectories. To obtain a better understanding of preterm birth occurrences, further research should focus on mapping these trajectories and specifically targeting the most vulnerable groups.
Potential effects of climate change on northwest Portuguese coastal zones
Authors: Coelho Carlos , Silva Raquel , Veloso-Gomes Fernando , Taveira-Pinto Francisco
Published: May 2009

Coelho, C., Silva, R., Veloso-Gomes, F., and Taveira-Pinto, F. 2009. Potential effects of climate change on northwest Portuguese coastal zones. – ICES Journal of Marine Science, 66: 1497–1507. Coastal erosion is a common problem in Europe; a result of the dynamic nature of its coastal zones, of anthropogenic influences, such as coastal interventions and littoral occupation, and of the effects of climate change. The increase in the occurrence of extreme events, the weakening of river-sediment supplies, and the general acceleration of sea level rise (SLR) probably tends to aggravate coastal erosion on decadal time-scales. Describing vulnerability and risk patterns for energetic environmental actions is important for coastal planning and management to rationalize the decision-making process. To minimize negative effects, the various processes causing erosion must be understood to assess the possible prediction scenarios for coastal evolution in the medium to long term. This paper describes the application of a coastal (shoreline evolution) numerical model to a stretch of the Portuguese coast to determine the effects of various scenarios of wave action and SLR that might result from climate change over the next 25 years. We conclude that the effects of SLR are less important than changes in wave action. The numerical model was also applied in a generic situation to compare shoreline evolution with and without anthropogenic intervention.
Multiple Activities of the Plant Pathogen Type III Effector Proteins WtsE and AvrE Require WxxxE Motifs
Authors: Ham Jong Hyun , Majerczak Doris R. , Nomura Kinya , Mecey Christy , Uribe Francisco , He Sheng-Yang , Mackey David , Coplin David L.
Published: May 2009

The broadly conserved AvrE-family of type III effectors from gram-negative plant-pathogenic bacteria includes important virulence factors, yet little is known about the mechanisms by which these effectors function inside plant cells to promote disease. We have identified two conserved motifs in AvrE-family effectors: a WxxxE motif and a putative C-terminal endoplasmic reticulum membrane retention/retrieval signal (ERMRS). The WxxxE and ERMRS motifs are both required for the virulence activities of WtsE and AvrE, which are major virulence factors of the corn pathogen Pantoea stewartii subsp. stewartii and the tomato or Arabidopsis pathogen Pseudomonas syringae pv. tomato, respectively. The WxxxE and the predicted ERMRS motifs are also required for other biological activities of WtsE, including elicitation of the hypersensitive response in nonhost plants and suppression of defense responses in Arabidopsis. A family of type III effectors from mammalian bacterial pathogens requires WxxxE and subcellular targeting motifs for virulence functions that involve their ability to mimic activated G-proteins. The conservation of related motifs and their necessity for the function of type III effectors from plant pathogens indicates that disturbing host pathways by mimicking activated host G-proteins may be a virulence mechanism employed by plant pathogens as well.
Sir Robert William Kerr Honeycombe KBE. 2 May 1921—14 September 2007
Authors: Smallman R. E.
Published: May 2009

Although Robert Honeycombe was born in Melbourne, Australia, where he received his university education and gained valuable research experience at the Council for Scientific and Industrial Research, it was in the UK that his distinguished career developed. At Sheffield he harnessed the newly emerging technique of transmission electron microscopy to the microstructural study of alloy steels. Moving to Cambridge, he built up a world-renowned team in this area. His seminal work was the characterization of interphase precipitation at the α/γboundary interface, which had a perceptible impact on the production of micro-alloyed steels throughout the world. As Goldsmiths' Professor of Metallurgy he was the longest-serving head of the department, broadening its coverage into material science to include ceramics and polymers as well as reinforcing the traditional areas of mechanical behaviour and processing. All these activities were underpinned by state-of-the-art microstructural characterization. Robert had an open and warm personality and was a natural leader of the profession within the university, in learned societies and in government and research council bodies. Above all he was a great supporter of young researchers, not only at Cambridge but also throughout the country.
Sir Eric James Denton CBE. 30 September 1923 — 2 January 2007
Authors: Clarke Malcolm R.
Published: May 2009

Sir Eric James Denton was stimulated by his deep interest in general physics to explore his wide fascination in the fundamentals of marine animal physiology. He applied physical principles to animal design in order to analyse the utilization of ambient light, reflectance, luminescence, sound reception, signalling and buoyancy and, in the process, became the foremost exponent of marine physiology of his time.
Transcriptome response of the Pacific oyster (Crassostrea gigas) to infection withVibrio tubiashiiusing cDNA AFLP differential display
Authors: Taris N. , Lang R. P. , Reno P. W. , Camara M. D.
Published: May 2009

We used qualitative complementary DNA‐amplified fragment length polymorphism (cDNA‐AFLP) differential display analysis and real‐time, quantitative PCR (RT‐qPCR) to identify genes in the Pacific oysterCrassostrea gigas, whose transcription either changes in response to exposure to a pathogenic bacterium (Vibrio tubiashii) or varies between families known to differ in sensitivity to heat stress, before and at 12 and 36 h after bacterial exposure at a temperature of 25 °C. These conditions simulate those associated with summer mortality syndrome, a poorly understood cause of massive mortalities in cultured Pacific oysters in North America, Asia and Europe. Using 32 AFLP primer pairs, we identified 92 transcript‐derived fragments that are qualitatively differentially expressed. We then cloned and sequenced 14 of these fragments, designed fragment‐specific primers and quantified their transcription patterns using RT‐qPCR. Most of the differences in transcription patterns between stress‐tolerant and stress‐sensitive families were evident before bacterial exposure, and genes that responded to bacterial exposure did so in parallel between stress‐sensitive and stress‐tolerant families.blastsearches of sequence databases revealed that these fragments represent genes involved in immune response as well as genes related to metabolic processes. Our data support the hypothesis that family level differences in resistance to stress in Pacific oysters are largely attributable to constitutive differences in gene transcription or ‘general vigour’ that are detectable before and maintained after infection, rather than being due to induced responses at the transcriptome level.
The effect on sotrastaurin pharmacokinetics of strong CYP3A inhibition by ketoconazole
Authors: Kovarik John M. , Huang Hsun‐Lun A. , Slade Alan , Sfikas Nikos , Chandler Patricia A.
Published: May 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT?

• Sotrastaurin is an investigational protein kinase C inhibitor. This represents a new mechanism of action for immunosuppression to prevent acute rejection after organ transplantation. In vitro experiments indicate that sotrastaurin is a substrate of CYP3A4.

WHAT THIS STUDY ADDS

• This study provides clinical pharmacokinetic information to quantify the effect of the strong CYP3A4 inhibitor ketoconazole on sotrastaurin. The susceptibility of sotrastaurin to CYP3A4‐related drug interactions is placed in the context of similar information about calcineurin inhibitors (tacrolimus, ciclosporin) and T‐cell proliferation inhibitors (everolimus, sirolimus).

AIMS

Sotrastaurin is an immunosuppressant that reduces T‐lymphocyte activation via protein kinase C inhibition. The effect of CYP3A4 inhibition by ketoconazole on the pharmacokinetics of sotrastaurin, a CYP3A4 substrate, was investigated.

METHODS

This was a two‐period, single‐sequence crossover study in 18 healthy subjects. They received a single 50 mg oral dose of sotrastaurin in period 1 followed by a 14‐day inter‐treatment phase. In period 2 they received ketoconazole 200 mg twice daily for 6 days and a single 50 mg dose of sotrastaurin on the fourth day of ketoconazole administration.

RESULTS

Co‐administration of single‐dose sotrastaurin during steady‐state ketoconazole increased sotrastaurin Cmax by 2.5‐fold (90% confidence interval 2.2, 2.9) from 285 ± 128 to 678 ± 189 ng ml−1 and increased AUC by 4.6‐fold (4.1, 5.2) from 1666 ± 808 to 7378 ± 3011 ng ml−1 h. Sotrastaurin half‐life was nearly doubled from 5.9 ± 1.7 to 10.6 ± 2.5 h. The AUC of the active metabolite N‐desmethyl‐sotrastaurin was increased by 6.8‐fold. Sotrastaurin did not alter ketoconazole steady‐state predose plasma concentrations.

CONCLUSIONS

The strong CYP3A4 inhibitor ketoconazole increased sotrastaurin AUC by 4.6‐fold. A compensatory reduction in the dose of sotrastaurin is warranted when strong CYP3A4 inhibitors are co‐administered.
Intracellular ‘boosting’ of darunavir using known transport inhibitors in primary PBMC
Authors: Kwan Wai San , Janneh Omar , Hartkoorn Ruben , Chandler Becky , Khoo Saye , Back David , Owen Andrew
Published: May 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Antiretroviral protease inhibitors such as lopinavir and saquinavir have been shown to be substrates of ABCB1. Co‐administration with the potent ABCB1 and CYP3A4 inhibitor, ritonavir, has shown improved pharmacokinetics and subsequent therapeutic effects of protease inhibitors. Darunavir is a recently licensed protease inhibitor with potent antiretroviral effects but has yet to be characterized as a potential substrate for drug transporters.

WHAT THIS STUDY ADDS

• Darunavir was shown to be a substrate of ABCB1 using different in vitro models. Inhibition of ABCB1 alone does not increase cellular accumulation of darunavir in PBMCs. However, inhibition of ABCB1 and ABCCs significantly increased cellular accumulation of darunavir whereas inhibition of influx transporters significantly reduced the cellular accumulation of darunavir in PBMCs.

AIMS

ABCB1, some ABCCs and SLCOs have been reported to affect the intracellular accumulation of various protease inhibitors in vitro and ex vivo. Darunavir is the most recently licensed protease inhibitor and we sought to investigate the ability of transport inhibitors to influence its intracellular accumulation in lymphocytes from healthy volunteers.

METHODS

The intracellular accumulation of radiolabelled darunavir was assessed using CEM cells and ABCB1‐overexpressing CEMVBL cells. Apical and basolateral transport of radiolabelled darunavir through MDCKII monolayers was also studied. Finally the ability of known inhibitors to influence intracellular accumulation of darunavir in peripheral blood mononuclear cells (PBMC) was investigated.

RESULTS

CEMVBL cells (1.4 ± 0.6, P < 0.001, 95% CI for the difference = 0.46, 0.80, n= 7) had significantly lower accumulation of darunavir compared with CEM cells (5.6 ± 0.7, n= 7) and this was reversed by addition of tariquidar (30 nm, 4.6 ± 0.8, P < 0.001, 95% CI =−0.64, −0.41, n= 4). In MDCKII‐ABCBI cells, transport from the basal to the apical compartment was observed and this was also reversible with the addition of tariquidar. In PBMCs, dipyridamole (6.9 ± 1.3, P < 0.01, 95% CI for the difference =−1.16, −0.30, (n= 8) significantly increased whilst montelukast (5.7 ± 1.0, P < 0.01, 95% CI for the difference = 0.16, 0.79, n= 8) significantly decreased the intracellular accumulation of darunavir when compared with control (6.2 ± 1.1, n= 8).

CONCLUSIONS

Darunavir is a substrate for efflux and influx transporters in PBMC and intracellular concentrations can be manipulated using known inhibitors.
Generation and characterization of chicken bone marrow‐derived dendritic cells
Authors: Wu Zhiguang , Rothwell Lisa , Young John R. , Kaufman Jim , Butter Colin , Kaiser Pete
Published: May 2009

Dendritic cells (DCs) are bone marrow‐derived professional antigen‐presenting cells. The in vitro generation of DCs from either bone marrow or blood is routine in mammals. Their distinct morphology and phenotype and their unique ability to stimulate naïve T cells are used to define DCs. In this study, chicken bone marrow cells were cultured in the presence of recombinant chicken granulocyte–macrophage colony‐stimulating factor (GM‐CSF) and recombinant chicken interleukin‐4 (IL‐4) for 7 days. The cultured population showed the typical morphology of DCs, with the surface phenotype of major histocompatibility complex (MHC) class II+ (high), CD11c+ (high), CD40+ (moderate), CD1·1+ (moderate), CD86+ (low), CD83− and DEC‐205−. Upon maturation with lipopolysaccharide (LPS) or CD40L, surface expression of CD40, CD1·1, CD86, CD83 and DEC‐205 was greatly increased. Endocytosis and phagocytosis were assessed by fluorescein isothiocyanate (FITC)‐dextran uptake and fluorescent bead uptake, respectively, and both decreased after stimulation. Non‐stimulated chicken bone marrow‐derived DCs (chBM‐DCs) stimulated both allogeneic and syngeneic peripheral blood lymphocytes (PBLs) to proliferate in a mixed lymphocyte reaction (MLR). LPS‐ or CD40L‐stimulated chBM‐DCs were more effective T‐cell stimulators in MLR than non‐stimulated chBM‐DCs. Cultured chBM‐DCs could be matured to a T helper type 1 (Th1)‐promoting phenotype by LPS or CD40L stimulation, as determined by mRNA expression levels of Th1 and Th2 cytokines. We have therefore cultured functional chBM‐DCs in a non‐mammalian species for the first time.
Membrane water permeability and aquaporin expression increase during growth of maize suspension cultured cells
Authors: MOSHELION MENACHEM , HACHEZ CHARLES , YE QING , CAVEZ DAMIEN , BAJJI MOHAMMED , JUNG RUDOLF , CHAUMONT FRANÇOIS
Published: May 2009

Aquaporins (AQPs) are water channels that allow cells to rapidly alter their membrane water permeability. A convenient model for studying AQP expression and activity regulation is Black Mexican Sweet (BMS) maize cultured cells. In an attempt to correlate membrane osmotic water permeability coefficient (Pf) with AQP gene expression, we first examined the expression pattern of 33 AQP genes using macro‐array hybridization. We detected the expression of 18 different isoforms representing the four AQP subfamilies, i.e. eight plasma membrane (PIP), five tonoplast (TIP), three small basic (SIP) and two NOD26‐like (NIP) AQPs. While the expression of most of these genes was constant throughout all growth phases, mRNA levels of ZmPIP1;3, ZmPIP2;1, ZmPIP2;2, ZmPIP2;4 and ZmPIP2;6 increased significantly during the logarithmic growth phase and the beginning of the stationary phase. The use of specific anti‐ZmPIP antisera showed that the protein expression pattern correlated well with mRNA levels. Cell pressure probe and protoplast swelling measurements were then performed to determine the Pf. Interestingly, we found that the Pf were significantly increased at the end of the logarithmic growth phase and during the steady‐state phase compared to the lag phase, demonstrating a positive correlation between AQP abundance in the plasma membrane and the cell Pf.
Glucose, epithelium, and enteric nervous system: dialogue in the dark
Authors: Pfannkuche H. , Gäbel G.
Published: May 2009

The gastrointestinal epithelium is in close contact with the various components of the chymus, including nutrients, bacteria and toxins. The epithelial barrier has to decide which components are effectively absorbed and which components are extruded. In the small intestine, a nutrient like glucose is mainly absorbed by the sodium linked glucose cotransporter 1 (SGLT1) and the glucose transporter 2 (GLUT2). The expression and activity of both transport proteins is directly linked to the amount of intraluminal glucose. Besides the direct interaction between glucose and the enterocytes, glucose also stimulates different sensory mechanisms within the intestinal wall. The most important types of cells involved in the sensing of intraluminal contents are enteroendocrine cells and neurones of the enteric nervous system. Regarding glucosensing, a distinct type of enteroendocrine cells, the enterochromaffine (EC) cells are involved. Excitation of EC cells by intraluminal glucose results in the release of serotonin (5‐HT), which modulates epithelial functions and activates enteric secretomotorneurones. Enteric neurones are not only activated by 5‐HT, but also directly by glucose. The activation of different cell types and the subsequent crosstalk between these cells may trigger appropriate absorptive and secretory processes within the intestine.
Investigation into selenium requirement of growing turkeys offered a diet supplemented with two levels of vitamin E
Authors: Mueller A. S. , Fischer J. , Most E. , Pallauf J.
Published: May 2009

To evaluate dietary selenium (Se) requirement in turkeys offered a diet supplemented with two levels of vitamin E (VE), 96 newly hatched male BIG 6® chicks (58.4 ± 4.12 g) were divided into eight groups of 12 animals each and fed maize soya diets containing 0.05, 0.10, 0.20 and 0.30 mg Se/kg from sodium selenate in combination either with the natural VE content (approximately 10 IU/kg) or with a VE addition of 50 IU/kg. Animals from all the groups were highly performant and their final body weights (1746 ± 190 g) after 35 days on experiment were not significantly different. According to its dietary supply, Se concentration in the liver and plasma increased dose dependently. Independent of dietary VE, the activities of GPx3 in plasma and of GPx1 in liver and breast muscle increased to a larger extent in turkeys supplemented with 0.10 and 0.20 mg Se/kg in relation to animals with low marginal Se supply (0.05 mg/kg). Supplementation of 0.30 mg Se/kg only slightly increased further selenoprotein activities. 2‐Thiobarbituric acid reactive substances in the liver were strongly reduced by dietary VE, but not by Se. Plasma aspartate aminotransferase (AST) and creatine kinase (CK) activities did not show muscular lesions in none of the groups. Although there were no signs of muscular lesions even in turkeys with marginal Se and moderate VE supply, the activity of selenoproteins in various organs increased up to 0.30 mg Se/kg diet, independent of VE supply. It was concluded that for growing turkeys the Se supply should meet at least a level of 0.20 mg/kg diet as currently recommended by the National Research Council and Gesellschaft für Ernährungsphysiologie. Vitamin E addition confirmed the particular function of the vitamin as a lipid antioxidant and should be taken into consideration when diets with high PUFA concentrations are fed.