bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognitive complaints in a general population of older adults: Prevalence, association with pain and the influence of concurrent affective disorders
Authors: Westoby Catherine J. , Mallen Christian D. , Thomas Elaine
Published: December 2008

Previous studies examining the associations between pain and cognitive complaints have been in pain clinic outpatients; there has been no research in the general population setting. A cross‐sectional postal survey of 7878 older adults, aged 50 years and over, registered with three general practices (n=11230) in North Staffordshire using self‐complete questionnaires was conducted. The questionnaire included the Alertness Behaviour Subscale from the Sickness Impact Profile to measure cognitive complaint, a full‐body manikin to record presence and location of any recent pain (past 4 weeks) and the Hospital Anxiety and Depression Scale. The prevalence of any cognitive complaint was 46.5%; this increased with age (41.6% in 50–59 year olds to 63.4% in 80–100 year olds) and was higher in females than males (48.6% vs. 43.8%). Reporting recent pain was associated with a statistically significant increase in also reporting any cognitive complaint (odds ratio: 2.49; 95% confidence interval: 2.2, 2.8) and altered little after adjusting for age and gender. A dose‐response relationship was seen when examining the association between pain and degree of cognitive complaint. Statistically significant associations between cognitive complaints and pain were seen across all anxiety and depression status. Cognitive complaints are common in a general population of older adults and are strongly related to the reporting of pain; a relationship which is independent of the presence of concurrent affective disorders. Taken together with previous work suggesting that subjective memory complaints are strongly correlated to risk of future cognitive decline, these results have implication for clinical practice in an aging population.
Characterization of chemoreceptive protein binding to an oviposition stimulant using a fluorescent micro‐binding assay in a butterfly
Authors: Tsuchihara Kazuko , Wazawa Tetsuichi , Ishii Yoshiharu , Yanagida Toshio , Nishida Ritsuo , Zheng Xiang-Guo , Ishiguro Masaji , Yoshihara Kazuo , Hisatomi Osamu , Tokunaga Fumio
Published: December 2008

A native female‐specific chemoreceptive protein of a swallowtail butterfly [oviposition stimulant binding protein (OSBP)] was shown to specifically bind to aristolochic acid, a main stimulant for oviposition from its host plant. Oviposition stimulants are recognized by chemoreceptive organs of insects. OSBP isolated previously from the chemoreceptive organs was assumed to bind to an oviposition stimulant. Using a highly sensitive fluorescent micro‐binding assay, we clarified OSBP bound to aristolochic acid. Three‐dimensional molecular modeling revealed the structure of the OSBP‐aristolochic acid complex. This is the first report of a native chemoreceptive protein binding to an oviposition stimulant as a ligand in insects.
Down‐regulation of adenine nucleotide translocase 3 and its role in camptothecin‐induced apoptosis in human hepatoma QGY7703 cells
Authors: Hu Zhenlin , Guo Xueqing , Yu Qi , Qiu Lei , Li Jianzhong , Ying Kang , Guo Cheng , Zhang Junping
Published: December 2008

Adenine nucleotide translocase (ANT) is known as a core component of the mitochondrial permeability transition pore (MPTP) and a key player in cell death. However, its role in camptothecin (CPT)‐induced apoptosis has not been examined. We showed that CPT‐induced apoptosis in QGY7703 cells and down‐regulated the expression of ANT3. Using ANT3 knock‐out and overexpression experiments, we provide further evidence that ANT3 plays a contributive role in CPT‐induced apoptosis through induction of MPTP. We speculate that the down‐regulation of ANT3 upon stimulation with CPT may be part of the molecular basis underlying the mechanism of acquired resistance to CPT.
The resetting of the circadian rhythm by Prostaglandin J2 is distinctly phase‐dependent
Authors: Koinuma Satoshi , Yagita Kazuhiro , Fujioka Atsuko , Takashima Naoyuki , Takumi Toru , Shigeyoshi Yasufumi
Published: December 2008

The circadian rhythm can be reset by a variety of substances. Prostaglandin J2 (PGJ2) is one such substance and resets the circadian rhythm in fibroblasts. In our current study, we examined the phase‐dependent phase shift following PGJ2 treatment using a real‐time luciferase luminescence monitoring system. In the phase response curves, we observed 12 h differences in the times of peaks in comparison with the same analysis for forskolin. Quantification of clock gene mRNAs following PGJ2 administration additionally revealed a rapid decrease in the Per1, Rev‐erbAα and Dbp levels. Our current findings thus suggest that PGJ2 resets the peripheral circadian clock via a mechanism that is distinct from that used by forskolin (FK).
Effects of (+)‐methamphetamine on path integration and spatial learning, but not locomotor activity or acoustic startle, align with the stress hyporesponsive period in rats
Authors: Vorhees Charles V. , Skelton Matthew R. , Grace Curtis E. , Schaefer Tori L. , Graham Devon L. , Braun Amanda A. , Williams Michael T.
Published: December 2008

Rats treated with (+)‐methamphetamine (MA) on postnatal days (P) 11–20 exhibit long‐term spatial and path integration (Morris water maze (MWM) and Cincinnati water maze (CWM)) learning deficits whereas those treated on P1–10 do not. MA treatment increases corticosterone release in an age‐dependent U‐shaped pattern that corresponds to the stress hyporesponsive period (SHRP; P4–15). Here we tested the hypothesis that the cognitive effects induced by MA are associated with treatment that begins within the SHRP. Three treatment regimens were compared, P1–10, P6–15, and P11–20. One male/female pair/litter received 0, 10, or 25 mg/kg MA/dose (four doses/day at 2 h intervals given s.c. with 19–21 litters/regimen). Locomotor activity and acoustic startle were tested as behaviors not predicted to be associated with the SHRP. Cincinnati and Morris water maze findings were consistent with the hypothesis in that MA‐treated animals exposed from P6–15 or P11–20 showed impaired learning compared to those exposed from P1–10; however, on probe trials in the Morris water maze, MA‐induced memory impairments were not regimen‐specific and were contributed to by all treatment regimens. All MA treatment regimens induced reductions in locomotor activity and acoustic startle facilitation as expected. No differential effect on prepulse trials was seen suggesting no impairment in sensory gating. Cognitive deficits from neonatal MA treatment are associated with the SHRP and may be the product of hypothalamic–pituitary–adrenal (HPA) axis dysregulation during critical periods of brain development.
‘Tackling cancer in the EU: The role of innovation’
Authors: Andrejevs Georgs , Celis Julio E. , Guidi Guido , Peterle Alojz , Sullivan Richard , Wilson Roger
Published: December 2008

The objective of the workshop was to examine what Cancer Innovation in Europe means and what it should be standing for in the future. The panel discussion brought together patients, researchers, politicians and industry in order to examine what cancer innovation represents to them, what the challenges are to innovation, and how innovation in this research area can be encouraged and developed in the EU.
Two stages of high-pressure metamorphism in the Main Uralian Fault area (northern Urals)
Authors: Petrov G.A. , Ronkin Yu.L. , Popov N.V. , Tristan N.I. , Kozlov P.S.
Published: December 2008

Metamorphism in the northern sector of the Main Uralian Fault (MUF) area, northern Urals, is considered by the example of the Salatim glaucophane-schist and Belokamenka kyanite-staurolite complexes. New isotope-geochronological dates for metamorphic rocks of the MUF area are presented. The obtained data evidence the existence of two metamorphic events, of Early and Late Devonian ages, which apparently correspond to the wedging-up of subduction paleozones.
Paleomagnetism of granites from the Angara-Kan basement inlier, Siberian craton
Authors: Didenko A.N. , Kozakov I.K. , Dvorova A.V.
Published: December 2008

We report a new paleomagnetic determination of Paleoproterozoic rocks from the Siberian craton which showed a positive baked contact test and a stable age of the high-temperature NRM component. The mean paleomagnetic pole of Siberia for ∼1730 Ma located at 42.9° S, 109.6° E (α95 = 5.3°) is compatible with the pole positions obtained recently for the middle and late Early Proterozoic.
Ensemble reforecasts of recent warm‐season weather: Impacts of a dynamic vegetation parameterization
Authors: Beltrán‐Przekurat Adriana , Marshall Curtis H. , Pielke Roger A.
Published: December 2008

The impact of dynamic vegetation on ensemble re‐forecasts of recent warm‐season weather over the continental U.S. was assessed using the Regional Atmospheric Modeling System (RAMS) and a fully coupled dynamic vegetation version of RAMS, the General Energy and Mass Transfer–RAMS (GEMRAMS). Two 10‐member ensembles were produced for the June‐August periods of 2000 and 2001. For each period, one of the members used the standard RAMS, and the other the GEMRAMS version. Initial and lateral boundary conditions were provided by a re‐forecast produced with the NCEP Seasonal Forecast Model (SFM). In addition, a pair of “baseline” simulations was produced using the NCEP Reanalysis, the “perfect” global forecast, as initial and lateral boundary conditions. Precipitation in the regional ensembles was largely controlled by the driving large‐scale forcing. A large precipitation bias exists over the regional domain in the SFM itself that is amplified in the simulations. For the time periods and model set‐up considered in this work, under an explicitly predictive model configuration, the use of a more complex parameterization of land‐surface processes with dynamic vegetation added little value to the skill of the seasonal forecast over the regional domain. This is a consequence of the strong dependence of the regional model results on the lateral boundary conditions provided by the parent global model. Even the use of an ensemble of predictions does not remove all of the biases that are inherent in the parent global model.
A comprehensive evaluation of the errors inherent in the use of a two‐dimensional shell for modeling the ionosphere
Authors: Smith Dru A. , Araujo‐Pradere Eduardo A. , Minter Cliff , Fuller‐Rowell Tim
Published: December 2008

Accurately modeling the ionosphere is a critical component to many radionavigation applications. However, in a significant number of cases, these models assume the ionosphere is compacted into a thin shell surrounding the Earth, rather than a full three‐dimensional field. While such models allow for ease of use and small storage needs, they are necessarily lacking in detailed information on the actual three‐dimensional distribution of electrons in the ionosphere. This paper attempts to quantify all geometric and numerical errors made through the use of a shell model. Such errors can reach as high as 14% on days of no strong ionosphere activity. Ultimately, this paper concludes that the highest levels of accuracy require the total electron content of the ionosphere be modeled three‐dimensionally. However, for those who must continue to use a shell model, a new mapping function has been derived which removes as much as 50% of the total errors seen using the previous, standard mapping function for shell models.
Dust aerosol impact on regional precipitation over western Africa, mechanisms and sensitivity to absorption properties
Authors: Solmon Fabien , Mallet Marc , Elguindi Nellie , Giorgi Filippo , Zakey Ashraf , Konaré Abdourahamane
Published: December 2008

We investigate the climatic impact of shortwave and longwave radiative forcing of Saharan dust on the West African monsoon and Sahel precipitation using a regional climate model (RCM) interactively coupled to a dust model and running for the period 1996–2006. Two competing effects are found. First a reduction of monsoon intensity in the lower troposphere induced by the dust surface cooling causes a reduction of precipitation, and second an ‘elevated heat pump effect’ in the higher troposphere induced by the dust diabatic warming causes an increase of precipitation. In the standard model configuration, the net impact of these effects is a reduction of precipitation over most of the Sahelian region (by about 8% on average) except over a Northern Sahel ‐ Southern Sahara band, where precipitation increases. These patterns are very sensitive to the dust absorbing properties, which modulate the intensity of the patterns and the boundary between enhanced and decreased precipitation areas. Finally we show that taking into account dust in the RCM could reduce the model bias compared to available observations.
What controls the isotopic composition of the African monsoon precipitation? Insights from event‐based precipitation collected during the 2006 AMMA field campaign
Authors: Risi Camille , Bony Sandrine , Vimeux Francoise , Descroix Luc , Ibrahim Boubacar , Lebreton Eric , Mamadou Ibrahim , Sultan Benjamin
Published: December 2008

The stable isotopic composition of the tropical precipitation constitutes a useful tool for paleoclimate reconstructions and to better constrain the water cycle. To better understand what controls the isotopic composition of tropical precipitation, we analyze the δ18O and deuterium‐excess of the precipitation of individual events collected in the Niamey area (Niger) during the monsoon season, as part of the 2006 AMMA field campaign. During the monsoon onset, the abrupt increase of convective activity over the Sahel is associated with an abrupt change in the isotopic composition. Before the onset, when convective activity is scarce, the rain composition records the intensity and the organization of individual convective systems. After the onset, on the contrary, it records a regional‐scale intra‐seasonal variability over the Sahel, by integrating convective activity both spatially and temporally over the previous days.
Observations of swell influence on ocean surface roughness
Authors: Hwang Paul A.
Published: December 2008

Field measurements of the ocean surface wave spectrum focusing on the slope‐contributing components are used to construct a spectral model of the ocean surface roughness. The spectral parameterization is established with the observed empirical power law relation between the dimensionless wave spectral density and wind speed. The power law parameters (proportionality coefficient and exponent) are shown to be modified by swell. Discussions are presented on the swell effects of spectral properties, including their wind speed dependence and swell modification of roughness components characterizing Bragg resonance and surface tilting in radar application. Several notable results include the following: (1) With increasing swell intensity, the spectral density increases in the long‐wave portion and decreases in the short‐wave portion of the intermediate‐scale waves. (2) There is a nodal point with respect to swell impact in the wave number dependence of the coefficient and exponent of the spectral parameterization function in the vicinity of wave number near 3 rad/m, suggesting that waves about a couple of meters long are insensitive to swell influence. (3) Spectral density in the decimeter length scale becomes less sensitive to wind speed variation as swell intensity increases. (4) Increasing swell influence shifts wave breaking toward shorter and broader scales.
Effect of atmospheric water vapor on modification of stable isotopes in near‐surface snow on ice sheets
Authors: Town Michael S. , Warren Stephen G. , Walden Von P. , Waddington Edwin D.
Published: December 2008

A Rayleigh fractionation model is developed to investigate postdepositional modification of stable isotopes of water in the near‐surface snow of East Antarctica. The processes of forced ventilation, pore‐space diffusion, and intra‐ice‐grain diffusion are parameterized through characteristic time constants. Routine meteorological observations, their derived products, and general glaciological conditions from the South Pole are used to simulate the δ18O of near‐surface snow as it evolves in time. The sensitivity of δ18O of near‐surface snow to wind speed, surface temperature, and accumulation rate is tested through model experiments. A steady wind of 5–10 m s−1 results in annual mean δ18O enrichment of 3–7‰. Enrichment of the heavy isotope occurs predominantly in buried winter snow layers during summer. However, in many simulations, there is a slight depletion of δ18O summer layers that occurs as atmospheric water vapor is deposited within the snow during winter. Postdepositional modification of water stable isotopes in near‐surface snow also depends on the snow accumulation rate; high accumulation rates quickly advect snow layers away from the influence of the atmosphere, preventing significant modification. Low accumulation rates (e.g., at Vostok and Dome C) allow significant postdepositional modification because the near‐surface snow is exposed to forced ventilation for several annual cycles. Postdepositional modification during the Last Glacial Maximum (LGM) at Summit, Greenland is estimated to be greater than the present‐day postdepositional modification. Therefore the temperature difference for LGM may be larger than that previously inferred from the δ18O record. However, because of the compensating effects of lower temperatures and smaller accumulation during the LGM in Antarctica, the postdepositional enrichment in East Antarctica may be approximately the same for LGM as for the modern climate.
Global distribution of atmospheric waves in the equatorial upper troposphere and lower stratosphere: COSMIC observations of wave mean flow interactions
Authors: Alexander S. P. , Tsuda T. , Kawatani Y. , Takahashi M.
Published: December 2008

Temperature profiles derived from Constellation Observing System for Meteorology, Ionosphere and Climate Global Positioning System Radio Occultation satellite constellation data are used to study equatorial gravity wave potential energy associated with waves having vertical wavelengths of less than 7 km and their interaction with the background quasi‐biennial oscillation (QBO) wind. The data are binned into grids of size 20° in longitude and 5° in latitude. Results show evidence of vertically propagating convectively generated gravity waves interacting with the background mean flow. Enhancements in potential energy around the descending 0 m s−1 QBO eastward shear phase line are observed. Equatorially trapped Kelvin waves and Mixed Rossby Gravity Waves with zonal wave numbers s ≤ 9 are obtained by bandpass filtering wave number‐frequency temperature spectra. Their temporal, spatial and vertical structures, propagation and wave‐mean flow interactions are examined with respect to the background mean flow. Equatorial waves observed by COSMIC are compared with those seen in OLR data, with differences discussed.
A three‐dimensional model study on the production of BrO and Arctic boundary layer ozone depletion
Authors: Zhao T. L. , Gong S. L. , Bottenheim J. W. , McConnell J. C. , Sander R. , Kaleschke L. , Richter A. , Kerkweg A. , Toyota K. , Barrie L. A.
Published: December 2008

A three‐dimensional model (GEM‐AQ/Arctic) was developed to study the chemistry and processes involved in the ozone depletion events (ODEs) in the Arctic boundary layer (ABL), which included a comprehensive mechanism of multiphase halogen chemistry in the ABL and our current understanding of the ODEs. Assuming that frost flower‐derived aerosols were the primary halogen source, the areas potentially covered by frost flowers were determined. The carbonate precipitation scheme was taken into account for triggering the bromine explosions in the model. A comparison of the simulations with GOME satellite measurements in springs of 2000 and 2001 showed that the spatial structure and temporal evolution of tropospheric BrO clouds were well predicted by the model. The majority of the springtime ODEs observed at three arctic stations was reasonably reproduced. An analysis on the model results indicated that most periods of simulated ozone depletion (O3 < 1 nmol mol−1) occurred in a layer 300 to 400 m deep at the Arctic sites. It is found that the halogen chemistry in the marine boundary layer (MBL) contributed substantially to the spring time ODEs, but atmospheric temperature and circulations as well as the transported air pollution in the ABL were also responsible for the ODEs. For springs of 2000 and 2001, two source regions with low surface O3 levels were identified: the Siberian/Beaufort Arctic and the Canadian Arctic, broadly corresponding to areas of enhanced BrO levels and accompanied by the Arctic anticyclones. Dominant trans‐Arctic transport pathways were also investigated for the ODEs at Alert, Barrow and Zeppelinfjellet.
Elevated sulfate reduction in metal‐contaminated freshwater lake sediments
Authors: Gough Heidi L. , Dahl Amy L. , Tribou Erik , Noble Peter A. , Gaillard Jean‐François , Stahl David A.
Published: December 2008

Although sulfate‐reducing prokaryotes have long been studied as agents of metals bioremediation, impacts of long‐term metals exposure on biologically mediated sulfur cycling in natural systems remains poorly understood. The effects of long‐term exposure to metal stress on the freshwater sulfur cycle were studied, with a focus on biologic sulfate reduction using a combination of microbial and chemical methods. To examine the effects after decades of adaptation time, a field‐based experiment was conducted using multiple study sites in a natural system historically impacted by a nearby zinc smelter (Lake DePue, Illinois). Rates were highest at the most metals‐contaminated sites (∼35 μmol/cm3/day) and decreased with decreased pore water zinc and arsenic contamination levels, while other environmental characteristics (i.e., pH, nutrient concentrations and physical properties) showed little between‐site variation. Correlations were established using an artificial neural network to evaluate potentially non‐linear relationships between sulfate reduction rates (SRR) and measured environmental variables. SRR in Lake DePue were up to 50 times higher than rates previously reported for lake sediments and the chemical speciation of Zn was dominated by the presence of ZnS as shown by X‐ray Absorption Spectroscopy (XAS). These results suggest that long‐term metal stress of natural systems might alter the biogeochemical cycling of sulfur by contributing to higher rates of sulfate reduction.
Onset of “Hudson Strait” Heinrich events in the eastern North Atlantic at the end of the middle Pleistocene transition (∼640 ka)?
Authors: Hodell David A. , Channell James E. T. , Curtis Jason H. , Romero Oscar E. , Röhl Ursula
Published: December 2008

Heinrich events are well documented for the last glaciation, but little is known about their occurrence in older glacial periods of the Pleistocene. Here we report scanning XRF and bulk carbonate δ18O results from Integrated Ocean Drilling Program Site U1308 (reoccupation of Deep Sea Drilling Project Site 609) that are used to develop proxy records of ice‐rafted detritus (IRD) for the last ∼1.4 Ma. Ca/Sr is used as an indicator of IRD layers that are rich in detrital carbonate (i.e., Heinrich layers), whereas Si/Sr reflects layers that are poor in biogenic carbonate and relatively rich in detrital silicate minerals. A pronounced change occurred in the composition and frequency of IRD at ∼640 ka during marine isotope stage (MIS) 16, coinciding with the end of the middle Pleistocene transition. At this time, “Hudson Strait” Heinrich layers suddenly appeared in the sedimentary record of Site U1308, and the dominant period of the Si/Sr proxy shifted from 41 ka prior to 640 ka to 100 ka afterward. The onset of Heinrich layers during MIS 16 represents either the initiation of surging of the Laurentide Ice Sheet (LIS) off Hudson Strait or the first time icebergs produced by this process survived the transport to Site U1308. We speculate that ice volume (i.e., thickness) and duration surpassed a critical threshold during MIS 16 and activated the dynamical processes responsible for LIS instability in the region of Hudson Strait. We also observe a strong coupling between IRD proxies and benthic δ13C variation at Site U1308 throughout the Pleistocene, supporting a link between iceberg discharge and weakening of thermohaline circulation in the North Atlantic.
Trophic cascades promote threshold-like shifts in pelagic marine ecosystems
Authors: Casini Michele , Hjelm Joakim , Molinero Juan-Carlos , Lövgren Johan , Cardinale Massimiliano , Bartolino Valerio , Belgrano Andrea , Kornilovs Georgs
Published: December 2008

Fisheries can have a large impact on marine ecosystems, because the effects of removing large predatory fish may cascade down the food web. The implications of these cascading processes on system functioning and resilience remain a source of intense scientific debate. By using field data covering a 30-year period, we show for the Baltic Sea that the underlying mechanisms of trophic cascades produced a shift in ecosystem functioning after the collapse of the top predator cod. We identified an ecological threshold, corresponding to a planktivore abundance of ≈17 × 10
10
individuals, that separates 2 ecosystem configurations in which zooplankton dynamics are driven by either hydroclimatic forces or predation pressure. Abundances of the planktivore sprat above the threshold decouple zooplankton dynamics from hydrological circumstances. The current strong regulation by sprat of the feeding resources for larval cod may hinder cod recovery and the return of the ecosystem to a prior state. This calls for the inclusion of a food web perspective in management decisions.
Reprogramming of murine and human somatic cells using a single polycistronic vector
Authors: Carey Bryce W. , Markoulaki Styliani , Hanna Jacob , Saha Kris , Gao Qing , Mitalipova Maisam , Jaenisch Rudolf
Published: December 2008

Directed reprogramming of somatic cells by defined factors provides a novel method for the generation of patient-specific stem cells with the potential to bypass both the practical and ethical concerns associated with somatic cell nuclear transfer (SCNT) and human embryonic stem (hES) cells. Although the generation of induced pluripotent stem (iPS) cells has proven a robust technology in mouse and human, a major impediment to the use of iPS cells for therapeutic purposes has been the viral-based delivery of the reprogramming factors because multiple proviral integrations pose the danger of insertional mutagenesis. Here we report a novel approach to reduce the number of viruses necessary to reprogram somatic cells by delivering reprogramming factors in a single virus using 2A “self-cleaving” peptides, which support efficient polycistronic expression from a single promoter. We find that up to four reprogramming factors (Oct4, Sox2, Klf4, and c-Myc) can be expressed from a single virus to generate iPS cells in both embryonic and adult somatic mouse cells and we show that a single proviral copy is sufficient to generate iPS cells from mouse embryonic fibroblasts. In addition we have generated human induced pluripotent stem (hiPS) cell lines from human keratinocytes, demonstrating that a single polycistronic virus can reprogram human somatic cells.
GINS Inactivation Phenotypes Reveal Two Pathways for Chromatin Association of Replicative α and ε DNA Polymerases in Fission Yeast
Authors: Pai Chen Chun , García Ignacio , Wang Shao Win , Cotterill Sue , MacNeill Stuart A. , Kearsey Stephen E.
Published: December 2008

The tetrameric GINS complex, consisting of Sld5-Psf1-Psf2-Psf3, plays an essential role in the initiation and elongation steps of eukaryotic DNA replication, although its biochemical function is unclear. Here we investigate the function of GINS in fission yeast, using fusion of Psf1 and Psf2 subunits to a steroid hormone-binding domain (HBD) to make GINS function conditional on the presence of β-estradiol. We show that inactivation of Psf1-HBD causes a tight but rapidly reversible DNA replication arrest phenotype. Inactivation of Psf2-HBD similarly blocks premeiotic DNA replication and leads to loss of nuclear localization of another GINS subunit, Psf3. Inactivation of GINS has distinct effects on the replication origin association and chromatin binding of two of the replicative DNA polymerases. Inactivation of Psf1 leads to loss of chromatin binding of DNA polymerase ε, and Cdc45 is similarly affected. In contrast, chromatin association of the catalytic subunit of DNA polymerase α is not affected by defective GINS function. We suggest that GINS functions in a pathway that involves Cdc45 and is necessary for DNA polymerase ε chromatin binding, but that a separate pathway sets up the chromatin association of DNA polymerase α.
SPE-39 Family Proteins Interact with the HOPS Complex and Function in Lysosomal Delivery
Authors: Zhu Guang-dan , Salazar Gloria , Zlatic Stephanie A. , Fiza Babar , Doucette Michele M. , Heilman Craig J. , Levey Allan I. , Faundez Victor , L'Hernault Steven W.
Published: December 2008

Yeast and animal homotypic fusion and vacuole protein sorting (HOPS) complexes contain conserved subunits, but HOPS-mediated traffic in animals might require additional proteins. Here, we demonstrate that SPE-39 homologues, which are found only in animals, are present in RAB5-, RAB7-, and RAB11-positive endosomes where they play a conserved role in lysosomal delivery and probably function via their interaction with the core HOPS complex. Although Caenorhabditis elegans spe-39 mutants were initially identified as having abnormal vesicular biogenesis during spermatogenesis, we show that these mutants also have disrupted processing of endocytosed proteins in oocytes and coelomocytes. C. elegans SPE-39 interacts in vitro with both VPS33A and VPS33B, whereas RNA interference of VPS33B causes spe-39–like spermatogenesis defects. The human SPE-39 orthologue C14orf133 also interacts with VPS33 homologues and both coimmunoprecipitates and cosediments with other HOPS subunits. SPE-39 knockdown in cultured human cells altered the morphology of syntaxin 7-, syntaxin 8-, and syntaxin 13-positive endosomes. These effects occurred concomitantly with delayed mannose 6-phosphate receptor-mediated cathepsin D delivery and degradation of internalized epidermal growth factor receptors. Our findings establish that SPE-39 proteins are a previously unrecognized regulator of lysosomal delivery and that C. elegans spermatogenesis is an experimental system useful for identifying conserved regulators of metazoan lysosomal biogenesis.
Health‐related quality of life in patients with gastro‐oesophageal reflux disease under routine care: 5‐year follow‐up results of the ProGERD study
Authors: NOCON M. , LABENZ J. , JASPERSEN D. , LEODOLTER A. , RICHTER K. , VIETH M. , LIND T. , MALFERTHEINER P. , WILLICH S. N.
Published: December 2008

Background  Gastro‐oesophageal reflux disease (GERD) is a common disorder associated with substantial reductions in health‐related quality of life (HRQL).

Aim  To describe patterns of change in HRQL during 5 years of follow‐up in a large population of GERD patients.

Methods  In 2000, a total of 6215 GERD patients were enrolled in the Progression of GERD (ProGERD) study. During follow‐up, patients received any medication considered necessary. HRQL was assessed yearly with the Short‐Form 36 and the Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaires. Associations between patient characteristics and changes in HRQL were analysed using multiple logistic regression models.

Results  After 5 years, data on HRQL were available for 4597 (74%) patients. Both generic and disease‐specific HRQL improved after baseline and remained well above baseline levels in the following years. A clinically relevant decrease in QOLRAD scores was reported by 3–5% of patients. According to our multivariate analysis, a decrease in HRQL was associated with a higher reflux symptom load and the presence of night‐time heartburn.

Conclusions  Only a small minority of the ProGERD population reported a clinically relevant decrease in HRQL, which was associated most strongly with nocturnal heartburn.
International validation of a health‐related quality of life questionnaire in patients with erosive gastro‐oesophageal reflux disease
Authors: HOLTMANN G. , CHASSANY O. , DEVAULT K. R. , SCHMITT H. , GEBAUER U. , DOERFLER H. , MALAGELADA J. R.
Published: December 2008

Background Although erosive gastro‐oesophageal reflux disease (GERD) is a highly prevalent condition, there is no specific, valid, reliable and sensitive questionnaire that allows evaluating treatment‐induced changes in health‐related quality of life (HRQoL).

Aim To design a self‐administered questionnaire, theGERDAnalyzer(GERDyzer), for use in clinical studies.

Methods The GERDyzer comprises 10 dimensions each illustrated by pictogram‐like drawings, simplifying communication with the patients. Self‐assessment is performed by 100 mm Visual Analogue Scales. For validation, a 5‐week clinical trial involving 395 patients (per‐protocol) with oesophagitis was conducted. Patients were treated with pantoprazole (40 mg o.d.) for 28 days. Psychometric analyses included internal consistency, test–retest reliability, responsiveness and construct validity.

Results Factor analysis showed consistency of the dimensions and no reduction was necessary. Validation of GERDyzer indicated high internal consistency (Cronbach’s α = 0.95) and test–retest reliability (intraclass correlation coefficient =0.91). Responsiveness of the total score expressed by nonparametric effect size was 1.38. Comparison of scores with other questionnaires resulted in logical correlation levels depending on the respected concepts measured.

Conclusions GERDyzer proved to be highly valid, reproducible and responsive. It allows reliably assessing treatment‐induced changes in HRQoL in erosive GERD.
Haemophilia care in children – benefits of early prophylaxis for inhibitor prevention
Authors: MANCUSO M. E. , GRACA L. , AUERSWALD G. , SANTAGOSTINO E.
Published: December 2008

Summary.  Haemophilia therapy is aimed at treating and preventing bleeding episodes and related complications and clinical studies have shown that regular prophylaxis, started at an early age, is able to reduce physical impairment from haemophilic arthropathy. Today, the development of anti‐Factor VIII (FVIII) inhibitors is the most serious treatment‐related complication of haemophilia therapy and a number of genetic and environmental risk factors have been identified in the past years. Clinical data show that early start of prophylaxis and the avoidance of intensive treatment periods may protect patients from inhibitor development. The mechanisms are not completely understood; yet, recent experimental data suggest that pro‐inflammatory or ‘danger signals’ may be involved in inducing tolerance vs. an effector immune response. So, exposure to a factor concentrate by itself may not be enough to trigger an immune response, while an intensive exposure to FVIII in the presence of such ‘danger signals’ can activate antigen‐presenting cells, up‐regulating co‐stimulatory signals for T lymphocytes and ultimately enhancing antibody production. The ‘optimal’ regimen for primary prophylaxis is still not identified and barriers to prophylaxis implementation remain relevant. Key issues include the optimal age at prophylaxis onset, the optimal dosage/schedule, the proper clinical and laboratory monitoring and patients’ compliance. Practical approaches to early prophylaxis as implemented in the haemophilia centres in Milan and Bremen are discussed in this respect.
Seromucinous hamartomas: a clinicopathological study of a sinonasal glandular lesion lacking myoepithelial cells
Authors: Weinreb Ilan , Gnepp Douglas R , Laver Nora M , Hoschar Aaron P , Hunt Jennifer L , Seethala Raja R , Barnes E Leon , Chetty Runjan , Perez‐Ordoñez Bayrdo
Published: December 2008

Aims:  To describe seven cases of sinonasal seromucinous hamartoma.

Materials and results:  The clinicopathological and immunohistochemical features of seven seromucinous hamartomas were analysed. There were four men and three women. Six lesions involved the posterior nasal septum and one the lateral wall. Size ranged from 6 to 40 mm. Four patients had no recurrences. One patient had local recurrences 24 and 60 months after diagnosis. The masses were covered by respiratory epithelium. Their stroma was oedematous to fibrous and contained invaginated respiratory epithelium forming glands and cysts, cysts with cuboidal to flat epithelium, and small serous glands, ducts and tubules with lobular and irregular haphazard patterns. One case had numerous glands surrounded by hyalinized basement membrane with features of respiratory epithelial adenomatoid hamartoma (REAH). One case had focal REAH‐like changes. Both respiratory and serous components were positive for cytokeratin (CK) 7 and CK19. The serous component lacked myoepithelial cells when stained for CK14, p63, calponin and muscle‐specific antigen in five cases.

Conclusions:  Seromucinous hamartomas show a broader histopathological appearance than previously reported. The serous proliferation in these lesions lacks myoepithelial cells. The presence of occasional REAH‐like features and common location in the posterior nasal septum suggest a spectrum from pure seromucinous hamartoma to REAH.
Multigenerational analysis of spatial structure in the terrestrial, food‐deceptive orchid Orchis mascula
Authors: Jacquemyn Hans , Wiegand Thorsten , Vandepitte Katrien , Brys Rein , Roldán‐Ruiz Isabel , Honnay Olivier
Published: December 2008

In long‐lived, terrestrial orchids, strong aggregation of adults and recruits within populations and pronounced spatial association between recruits and adults can be expected when seed dispersal is limited, probabilities of seed germination decrease with increasing distance from mother plants and/or not all mother plants contribute to future generations. When individuals are distributed evenly across life‐history stages, these processes can also be expected to result in a significant fine‐scale spatial genetic structure in recruits that will persist into the adult‐stage class.

We combined detailed spatial genetic and point pattern analyses across different generations with parentage analyses to elucidate the role of the diverse processes that might determine spatial structure in Orchis mascula.

Analyses of spatial point patterns showed a significant association between adults and recruits and similar clustering patterns for both. Weak, but highly significant spatial genetic structure was observed in adults and recruits, but no significant differences were observed across life stages, indicating that the spatial genetic structure present in recruits persists into the adult stage.

Parentage analyses highlighted relatively short seed dispersal distances (median offspring‐recruitment distance: 1.55 and 1.70 m) and differential contribution of mother plants to future generations.

Persistence of fine‐scale spatial genetic structure from seedlings into the adult stage class is consistent with the life history of O. mascula, whereas relatively large dispersal distances of both pollen and seeds compared to the fine‐scale clustering of adults and seedlings suggest overlapping seed shadows and mixing of genotypes within populations as the major factors explaining the observed weak spatial genetic structure.

Nonetheless, comparison of the spatial association between recruits and adults with the genetic analysis of offspring‐parent distances suggests that the tight clustering of recruits around adults was probably caused by decreasing probabilities of seed germination with increasing distance from mother plants.

Synthesis. This study shows that the approach presented here, which combines spatial genetic and spatial pattern analyses with parentage analyses, may be broadly applied to other plant species to elucidate the processes that determine spatial structure within their populations.
Phylogeny, biogeography and evolution of clutch size in South American lizards of the genusKentropyx(Squamata: Teiidae)
Authors: WERNECK FERNANDA DE P. , GIUGLIANO LILIAN G. , COLLEVATTI ROSANE G. , COLLI GUARINO R.
Published: December 2008

The lizard genusKentropyx(Squamata: Teiidae) comprises nine species, which have been placed in three species groups (calcaratagroup, associated to forests ecosystems;paulensisandstriatagroups, associated to open ecosystems). We reconstructed phylogenetic relationships ofKentropyxbased on morphology (pholidosis and coloration) and mitochondrial DNA data (12S and 16S), using maximum parsimony and Bayesian methods, and evaluated biogeographic scenarios based on ancestral areas analyses and molecular dating by Bayesian methods. Additionally, we tested the life‐history hypothesis that species ofKentropyxinhabiting open ecosystems (under seasonal environments) produce larger clutches with smaller eggs and that species inhabiting forest ecosystems (under aseasonal conditions) produce clutches with fewer and larger eggs, using Stearns’ phylogenetic‐subtraction method and canonical phylogenetic ordination to take in to account the effects of phylogeny. Our results showed thatKentropyxcomprises three monophyletic groups, withK.striataoccupying a basal position in opposition to previous suggestions of relationships. Additionally, Bayesian analysis of divergence time showed thatKentropyxmay have originated at the Tertiary (Eocene/Oligocene) and the ‘Pleistocene Refuge Hypothesis’ may not explain the species diversification. Based on ancestral reconstruction and molecular dating, we argued that a savanna ancestor is more likely and that historical events during the Tertiary of South America promoted the differentiation of the genus, coupled with recent Quaternary events that were important as dispersion routes and for the diversification at populational levels. Clutch size and egg volume were not significantly different between major clades and ecosystems of occurrence, even accounting for the phylogenetic effects. Finally, we argue that phylogenetic constraints and phylogenetic inertia might be playing essential roles in life history evolution ofKentropyx.
Thermal structure of a fossil subduction wedge in the Western Alps
Authors: Gabalda S. , Beyssac O. , Jolivet L. , Agard P. , Chopin C.
Published: December 2008

New peak metamorphic temperatures are obtained by Raman spectroscopy of Carbonaceous Material to document the thermal structure of the central Western Alps with high sampling resolution. We show that peak metamorphic T gradually increases eastward from <330 to 350 °C (ultra‐Dauphinois to subbriançonnais units), ∼350 to more than 400 °C (Briançonnais domain including the Zone Houillère where metamorphic index minerals are rare) and from 350 to more than 500 °C (Liguro–Piemontese domain). Combined with other constraints on the metamorphic evolution, this dataset reveals a good preservation of the overall thermal structure of the fossil subduction wedge, with no particular thermal overprint during collision. However, local confrontation with P–T estimates and radiometric ages reveals more subtle variations within tectonic units and across the main contacts that are linked to the past activity of the major thrusts and extensional shear zones during subduction and exhumation.
Prostate cancer: a serious disease suitable for prevention
Authors: Fitzpatrick John M. , Schulman Claude , Zlotta Alexandre R. , Schröder Fritz H.
Published: December 2008

Prostate cancer is among the most common causes of death from cancer in men, and accounts for 10% of all new male cancers worldwide. The diagnosis and treatment of prostate cancer place a substantial physical and emotional burden on patients and their families, and have considerable financial implications for healthcare providers and society. Given that the risk of prostate cancer continues to increase with age, the burden of the disease is likely to increase in line with population life‐expectancy. Reducing the risk of prostate cancer has gained increasing coverage in recent years, with proof of principle shown in the Prostate Cancer Prevention Trial with the type 2 5α‐reductase (5AR) inhibitor, finasteride. The long latency period, high disease prevalence, and significant associated morbidity and mortality make prostate cancer a suitable target for a risk‐reduction approach. Several agents are under investigation for reducing the risk of prostate cancer, including selenium/vitamin E and selective oestrogen receptors modulators (e.g. toremifene). In addition, the Reduction by Dutasteride of Prostate Cancer Events trial, involving >8000 men, is evaluating the effect of the dual 5AR inhibitor, dutasteride, on the risk of developing prostate cancer. A successful risk‐reduction strategy might decrease the incidence of the disease, as well as the anxiety, cost and morbidity associated with its diagnosis and treatment.
Examining the Interaction between Saving and Contributions to Personal Pension Plans: Evidence from the BHPS*
Authors: Rossi Mariacristina
Published: December 2008

This paper analyses the effects of social security reforms on saving in Britain. We use the British Household Panel Survey to investigate the interactions between voluntary additional contributions to personal pension plans (PPP) and saving in conventional forms. In particular, we test whether contributions to the PPP crowd out saving or constitute additional saving. Results suggest that not only have private pension schemes not crowded out private saving, but actually they have increased it too.
Ear acupuncture or local anaesthetics as pain relief during postpartum surgical repair: a randomised controlled trial
Authors: Kindberg S , Klünder L , Strøm J , Henriksen TB
Published: December 2008

Objective  To evaluate two methods of pain relief during postpartum surgical repair in regard to effectiveness, wound healing and patient evaluation.

Design  A randomised controlled trial testing a pragmatic set‐up of brief training of clinicians.

Setting  Delivery ward at a Danish district hospital with approximately 1600 annual deliveries.

Population  Primiparous women with a vaginal delivery at term who needed surgical repair of lacerations to the labia or the vagina, perineal lacerations of first or second degree or mediolateral episiotomies.

Methods  The trial was set up to evaluate the effect of a brief 2‐hour hands‐on training in the use of ear acupuncture. All midwives (n = 36) in the department had previous experience in using acupuncture for obstetric pain relief. Pain and wound healing were evaluated using validated scores. Data collection was performed by research assistants blinded towards treatment allocation. Randomisation was computer assisted. A total of 207 women were randomised to receive ear acupuncture (105) and local anaesthetics (102), respectively.

Main outcome measures  The primary outcome was pain during surgical repair. Secondary outcomes were wound healing at 24–48 hours and 14 days postpartum, participant satisfaction, revision of wound or dyspareunia reported 6 months postpartum.

Results  Pain during surgical repair was more frequently reported by participants allocated to ear acupuncture compared with participants receiving local anaesthetics (89 versus 54%, P < 0.01). Pain intensity during surgical repair was also reported higher (Visual Analogue Scale score 3.5 versus 1.5, P < 0.01). The ear acupuncture group received more additional pain relief during repair (53 versus 19%, P < 0.01). No difference was observed in wound healing at 24–48 hours or 14 days postpartum. Revision of wounds was rare, and no difference occurred in this trial. Comparable proportions of participants reported dyspareunia at 6 months. Patient satisfaction with the allocated pain‐relief method was lower in the ear acupuncture group (69 versus 91%, P < 0.01) and fewer women would recommend the method to a friend (74 versus 91%, P < 0.01).

Conclusions  Ear acupuncture as used in this trial was less effective for pain relief compared with a local anaesthetic. No difference was observed in wound healing, need for revision of wound or dyspareunia. Patient satisfaction with allocated pain‐relief method was lower in the ear acupuncture group.