bluuebunny/crossref_metadata_2025 huggingface dataset:
Egg consumption, serum total cholesterol concentrations and coronary heart disease incidence: Japan Public Health Center-based prospective study
Authors: Nakamura Yasuyuki , Iso Hiroyasu , Kita Yoshikuni , Ueshima Hirotsugu , Okada Katsutoshi , Konishi Masafumi , Inoue Manami , Tsugane Shoichiro ,   Japan Public Health Center-based prospective study group
Published: February 2008

Limited egg consumption is often recommended to reduce serum cholesterol concentration for the prevention of CHD. We examined the association of egg consumption and total cholesterol concentration with the risk of CHD. A total of 90 735 subjects (19 856 men and 21 408 women, aged 40–59 years in cohort I; 23 463 men and 26 008 women, aged 40–69 years in cohort II) were followed from 1990–4 to the end of 2001 under the Japan Public Health Center-based prospective study. Total cholesterol was obtained in 36 % of the subjects. Men and women were combined for the analyses. The subjects were categorised into four groups according to egg consumption. Subjects with total cholesterol ≥2200 mg/l were less frequent in frequent egg consumption groups in both cohorts (trendP<0·0001). Subjects with <1 d/week of egg consumption were more likely to avoid a cholesterol-rich diet. Egg consumption was not associated with the risk of CHD, although total cholesterol was significantly related to the risk of CHD. The multivariate hazard ratio of CHD in subjects with total cholesterol ≥2400v.<1800 mg/l was 2·17 (95 % CI 1·22, 3·85; trendP=0·0018). In conclusion, eating eggs more frequently, up to almost daily, was not associated with an increase in CHD incidence for middle-aged Japanese men and women. Subjects with hypercholesterolaemia were less frequently in frequent egg consumption groups, probably because they avoided eating eggs.
Sarcopenia is predictive of nosocomial infection in care of the elderly
Authors: Cosquéric Gaëlle , Sebag Aline , Ducolombier Cyril , Thomas Caroline , Piette François , Weill-Engerer Sébastien
Published: February 2008

Protein–energy malnutrition and nosocomial infection (NI) are frequent in elderly patients, and a causal link between the two has often been suggested. The aim of the present study was to identify the nutritional parameters predictive of NI in elderly patients. We assessed on admission 101 patients (sixty-six women, thirty-five men, aged over 65 years) admitted to an acute care of the elderly department. Sarcopenia was detected by dual-energy X-ray absorptiometry, with appendicular skeletal muscle mass expressed with respect to body area. Weight, BMI, albuminaemia, serum transthyretin and C-reactive protein values were also determined on admission, and known risk factors, such as functional dependence and invasive biomedical material, were also evaluated. After up to 3 weeks of hospitalisation, patients were classified according to whether they had developed an NI. After 3 weeks of hospitalisation, we found that twenty-nine patients had suffered an NI, occurring after a mean of 16·1 d. Patients who were sarcopenic on admission had a significantly higher risk of contracting an NI (relative risk 2·1, 95 % CI 1·1, 3·8). None of the other morphometric or biological parameters differed significantly between the two groups of patients on admission. Patients who experienced an NI were also more likely, on admission, to have a medical device (P=0·02 to P=0·001 depending on the device), to have swallowing problems (P=0·002) or to have restricted autonomy (P<0·01). Sarcopenia on admission to an acute care of the elderly unit, as measured by X-ray absorptiometry, was therefore associated with a doubled risk of NI during the first 3 weeks of hospitalisation.
MACROECONOMICS OF SUBSISTENCE POINTS
Authors: RAVN MORTEN O. , SCHMITT-GROHÉ STEPHANIE , URIBE MARTÍN
Published: February 2008

This paper explores the macroeconomic consequences of preferences displaying a subsistence point. It departs from the existing related literature by assuming that subsistence points are specific to each variety of goods rather than to the composite consumption good. We show that this simple feature makes the price elasticity of demand for individual goods procyclical. As a result, markups behave countercyclically in equilibrium. This implication is in line with the available empirical evidence.
A new GPS‐acoustic method for measuring ocean floor crustal deformation: Application to the Nankai Trough
Authors: Ikuta Ryoya , Tadokoro Keiichi , Ando Masataka , Okuda Takashi , Sugimoto Shingo , Takatani Kazunori , Yada Kazuyuki , Besana Glenda M.
Published: February 2008

We developed a new geodetic method of monitoring crustal deformation on the ocean floor. The measurements were conducted at two sites beneath the Pacific Ocean, near the Nankai Trough, where the Philippine Sea plate subducts into the Pacific plate. The first site was at a depth of 700 m in Suruga Bay, and the second one was at a depth of 2000 m in the Kumano Basin. At each survey site, three seafloor transponders, whose positions were repetitively measured, were deployed to define a benchmark unit. An ultrasonic signal was generated from a surface vessel drifting over the benchmark unit that was transmitting and receiving the signal and the replies from the transponders. Both sound speed structure and the benchmark unit positions were determined simultaneously using a tomographic technique. We repeatedly carried out measurements over the two sites. For the Kumano Basin we made six measurements from July 2004 to August 2005. The benchmark unit location's horizontal precision was 5 cm, and its vertical precision was 10 cm. For Suruga Bay we made five measurements, and the positions were less accurate, with horizontal variation of 7 cm and vertical variation of 16 cm. We investigated the reason for the decreased precision in Suruga Bay with a numerical experiment, and the results revealed that the geometry of the measurement, that is, the vessel's path, is one of the most important variables in our method. At the Kumano Basin a 21.5‐cm southward displacement of the benchmark unit was detected just below the site before and after a large earthquake (Mw 7.5). Our observation system therefore proved itself capable of detecting seafloor crustal deformation associated with crustal activities in offshore areas.
Impact pressures and flow regimes in dense snow avalanches observed at the Vallée de la Sionne test site
Authors: Sovilla Betty , Schaer M. , Kern M. , Bartelt P.
Published: February 2008

A fundamental problem in avalanche engineering is to determine the impact pressures exerted on structures. This task is complicated because snow avalanches flow in a variety of regimes, primarily depending on snow temperature and moisture content. In this paper we address this problem by analyzing measured impact pressures, flow velocities, and flow depths of five Vallée de la Sionne avalanches. The measurements are made on a 20 m high tubular pylon instrumented with high‐frequency pressure transducers and optoelectronic velocity sensors. In the observed avalanches, we find both subcritical and supercritical flow regimes. Typical Froude numbers were smaller than 6. The subcritical regime (Fr < 1) is characterized by a flow plug riding above a highly sheared basal layer. The measured pressures are large and velocity‐independent in contradiction to calculation procedures. Pressure fluctuations increase with flow depth, indicating a kinematic stick‐slip phenomena which is largest at the basal layer. Supercritical flow regimes (1 < Fr < 6) are characterized by a sheared flow all over the avalanche depth. In this regime the impact pressure is velocity‐dependent. We derive relationships governing impact pressure as a function of the Froude number, and therefore flow regime, encompassing all the observed avalanches.
Carbon and oxygen fluxes from a small pond to the atmosphere: Temporal variability and the CO2/O2 imbalance
Authors: Torgersen T. , Branco B.
Published: February 2008

Because of the relative strength of sediment processes compared to water column processes, natural and anthropogenic ponds represent an important component of the terrestrial hydrologic cycle and a site for recycling carbon to the atmosphere. Over 250 d of dissolved oxygen and carbon dioxide concentrations were measured on the 0.5 h timescale in a small Connecticut pond. Using approximately 8000 half‐hour time intervals, Mirror Lake (Storrs, Connecticut) exhibits net annual fluxes for 2002 and 2003 of 80 and 86 mmol CO2 m−2 d−1 (±26%) and 25 and −7.5 mmol O2 m−2 d−1 (±20%), respectively (positive flux is to the atmosphere). The instantaneous (0.5 h) fluxes of both CO2 and O2 to the atmosphere exhibit a standard deviation in the flux (measured every 0.5 h) of the order 100%, indicating a high degree of daily, weekly, and seasonal variability in the controlling processes, and the two gases rarely follow Redfield ratio stoichiometry. This net carbon flux to the atmosphere agrees with the range of carbon fluxes from various shallow inland aquatic waters. Using CO2 and O2 mass balances, the minimum bacterial production of CO2 in the pond is estimated to be 100 and 81mmol CO2 m−2 d−1 for 2002 and 2003 (same order as the net CO2 flux from the pond), indicating the importance of the bacterial processes in pond carbon dynamics. Bacterial pathways that utilize NO3−1 or fermentation strongly favor CO2 production relative to O2 consumption and may provide a mechanistic explanation for the (instantaneous to annual) CO2 to O2 imbalance relative to the Redfield ratio. Thus, while natural and man‐made ponds do provide advantages for flood control, sediment settling, and some degree of contaminant removal, ponds may also provide a locus for the processing of terrestrial carbon into a CO2 source to the atmosphere. Given the number of small ponds and their location in the hydrologic cycle, pond systems represent a coupling of hydrology and the carbon cycle worthy of greater investigation.
Relative paleointensity record during the last 800 ka from the equatorial Indian Ocean: Implication for relationship between inclination and intensity variations
Authors: Suganuma Y. , Yamazaki T. , Kanamatsu T. , Hokanishi N.
Published: February 2008

Paleomagnetic and rock magnetic investigations were carried out on three sediment cores taken from the Ninetyeast Ridge, the eastern equatorial Indian Ocean. The cores are 4.1–10.2 m long and cover the last 270–790 ka with average sedimentation rates of 1.3–1.9 cm/ka. Generally stable demagnetization behaviors and relatively uniform rock magnetic characteristics allowed us to reconstruct relative paleointensity records (NRM30mT/IRM30mT) for each core. The relative paleointensity records showed a beneficial agreement with each other except for the uppermost parts of the cores, and patterns similar to the Sint‐800 paleointensity stack and other relative paleointensity records. Spectral analyses of the relative paleointensity records revealed a dominant periodicity at about 100 ka, but not for the normalizer and other rock magnetic proxies. These results suggested that the 100 ka periodicity in the paleointensity records during the Brunhes Chron would not be caused by sedimentological effects. The mean inclination values of the three cores were close to the expected hypothetical geocentric axial dipole (GAD) direction, which implies that ∼5–10° of negative inclination anomaly (ΔI) is centered at the western equatorial Pacific Ocean, and not extended to the eastern equatorial Indian Ocean. A comparison between the relative paleointensity variation and ΔI amplitude between the eastern equatorial Indian Ocean and the western equatorial Pacific Ocean suggests that changes of the GAD intensity control the relative contribution of the persistent nondipole components and produces the inclination variation.
Gravitational separation of major atmospheric components of nitrogen and oxygen in the stratosphere
Authors: Ishidoya Shigeyuki , Sugawara Satoshi , Morimoto Shinji , Aoki Shuji , Nakazawa Takakiyo
Published: February 2008

To investigate the gravitational separation of atmospheric components in the stratosphere, air samples collected over Japan, the Arctic and the Antarctic were analyzed for δ15N of N2 and δ18O of O2. The gravitational separation is a function of latitude, showing the largest effect inside the polar vortex over the Arctic. The relationship between the gravitational separation (calculated using a steady‐state 1‐dimensional eddy‐diffusion/molecular‐diffusion model) and the CO2 age (calculated using a 1‐dimensional time dependent eddy‐diffusion model) suggests that the observed gravitational separation is fundamentally a result of diffusive separation but modified by meridional circulation of air in the stratosphere. We also obtain a compact relationship between the gravitational separation and the N2O concentration. By comparing the gravitational separations at two height intervals with the N2O concentrations >125 ppb and <45 ppb, the effect of descending air is found to be more significant over the Arctic than over Japan. The variation in the gravitational separation with height is found to be weaker in region with the N2O concentrations between 45 and 125 ppb than in other regions.
First ground‐based FTIR observations of the seasonal variation of carbon monoxide in the tropics
Authors: Petersen A. K. , Warneke T. , Lawrence M. G. , Notholt J. , Schrems O.
Published: February 2008

We present the first ground‐based solar absorption Fourier Transform Infrared (FTIR) spectrometric measurements in the inner tropics over several years. The FTIR observations agree well with satellite data from the MOPITT instrument. MATCH‐MPIC model simulations reproduce the mean vertical structure of the FTIR observations. The model is generally not able to reproduce the extreme enhancements seen during the specific biomass burning events by both observation instruments. Nevertheless, the model indicates that beyond the background source of CO from methane oxidation, the main contributions to the CO mixing ratios are the episodic convective injection of NMHCs and CO from South American biomass burning into the upper troposphere, along with long range transport of African biomass burning CO, particularly during spring. In future studies with more extensive observed time series, observations such as these will be valuable for evaluating ongoing improvements in global chemistry transport models.
Gravitational separation suggested by O2/N2, δ15N of N2, δ18O of O2, Ar/N2 observed in the lowermost part of the stratosphere at northern middle and high latitudes in the early spring of 2002
Authors: Ishidoya Shigeyuki , Morimoto Shinji , Sugawara Satoshi , Watai Tomonori , Machida Toshinobu , Aoki Shuji , Nakazawa Takakiyo , Yamanouchi Takashi
Published: February 2008

Lower stratospheric O2/N2 ratios (δ(O2/N2)) at northern middle and high latitudes were measured by analyzing aircraft air samples collected between Nagoya, Japan and Svalbard Islands in the Arctic during the early spring of 2002. The measured values of δ(O2/N2) are relatively uniform horizontally in the lowermost part of the stratosphere but increase with height. Vertical distributions of δ(O2/N2) and the CO2 concentration observed over Svalbard Islands and Barrow, Alaska are negatively correlated. By examining the rates of change in δ(O2/N2) and δ13C of CO2 relative to the CO2 concentration, such a correlation observed is mainly attributable to upward propagation of their seasonal cycles produced on the ground surface for the troposphere and height‐dependent air age for the stratosphere. However, from the vertical profiles of δ15N of N2, δ18O of O2 and δ(Ar/N2) measured in the lowermost part of the stratosphere over Svalbard Islands, it is suggested that the relationship between δ(O2/N2) and the CO2 concentration is affected by the gravitational separation. By correcting the measured δ(O2/N2) and δ13C values for this gravitational separation, the relationships of δ(O2/N2) and δ13C with the CO2 concentration are consistent with those expected from their secular trends in the troposphere.
Identifying the processes controlling the distribution of H2O2 in surface waters along a meridional transect in the eastern Atlantic
Authors: Steigenberger S. , Croot P. L.
Published: February 2008

Hydrogen peroxide (H2O2) is an important oxidant for many bio‐relevant trace metals and organic compounds and has potential as a tracer for mixing in near surface waters. In this study we combine H2O2 and bio‐optical measurements with satellite data for a meridional transect from 46°N to 26°S in the eastern Atlantic in order to determine the key processes affecting its distribution. Surface H2O2 ranged from 21–123 nmol L−1, with maximum inventories (0–200 m) of 5.5–5.9 mmol m−2 found at 30°N and 25°S. Analyses showed a strong positive correlation of surface H2O2 with daily irradiances and recent precipitation, though poor correlations with CDOM suggest sunlight is the limiting reactant for H2O2 formation. Vertical distributions of H2O2 were controlled by a combination of mixing processes and phytoplankton activity. The present study highlights processes controlling global H2O2 distributions and points towards the development of parameterization schemes for prediction via satellite data.
How winding is the coast of Britain? Conformal invariance of rocky shorelines
Authors: Boffetta G. , Celani A. , Dezzani D. , Seminara A.
Published: February 2008

We show that rocky shorelines with fractal dimension 4/3 are conformally invariant curves by measuring the statistics of their winding angles from global high‐resolution data. Such coastlines are thus statistically equivalent to the outer boundary of the random walk and of percolation clusters. A simple model of coastal erosion gives an explanation for these results. Conformal invariance allows also to predict the highly intermittent spatial distribution of the flux of pollutant diffusing ashore.
The annual cycle of particulate organic carbon export in Franklin Bay (Canadian Arctic): Environmental control and food web implications
Authors: Forest Alexandre , Sampei Makoto , Makabe Ryosuke , Sasaki Hiroshi , Barber David G. , Gratton Yves , Wassmann Paul , Fortier Louis
Published: February 2008

As part of the Canadian Arctic Shelf Exchange Study (CASES), we assessed the importance of new production and resuspension in determining the nature and magnitude of the deep (210 m) particulate organic carbon (POC) flux from October 2003 to September 2004 in central Franklin Bay. In spring and summer, phytoplankton production was nutrient‐limited in the stratified surface layer and the initial spring bloom evolved into a subsurface chlorophyll maximum (SCM) at the nutricline. Large herbivorous calanoid copepods intercepted little of the initial bloom but grazed intensely on the SCM. The phytoplankton and fecal pellet fluxes culminated simultaneously in July–August (24 and 23 mg C m−2 d−1, respectively). The detrital POC flux peaked in September (52 mg C m−2 d−1), coincident with wind‐induced resuspension of recently settled POC. In the fall, detrital POC fluxes increased again to 22 mg C m−2 d−1, following the off‐shelf transport of terrigenous POC carried by the Mackenzie River plume and POC resuspended by wind on the shelf. In winter, the relatively weak POC fluxes (2–7 mg C m−2 d−1, detrital at 90%) resulted from the settling down of resuspended sediments. We propose a conceptual model in which the ecosystem of Franklin Bay shifts from an algal to a detrital mode according to seasonal changes in the relative importance of fresh and old POC supplies. On the basis of this model, the ecosystem of southeastern Beaufort Sea could evolve toward a less productive equilibrium dominated by sediment resuspension in response to the ongoing reduction of the ice cover.
Surface heat fluxes from the NCEP/NCAR and NCEP/DOE reanalyses at the Kuroshio Extension Observatory buoy site
Authors: Kubota Masahisa , Iwabe Noriyasu , Cronin Meghan F. , Tomita Hiroyuki
Published: February 2008

Surface heat fluxes from the Kuroshio Extension Observatory (KEO) buoy are compared with surface heat fluxes from the National Centers for Environmental Prediction (NCEP)/National Center for Atmospheric Research reanalysis (NRA1) and NCEP/Department of Energy reanalysis (NRA2). KEO surface measurements include downward solar and longwave radiation, wind speed and direction, relative humidity, rain rate, and air and sea surface temperature. For solar radiation, NRA2 had better agreement with KEO than NRA1. Both reanalyses underestimated shortwave radiation in summer and slightly overestimated it in winter. Turbulent surface heat fluxes are estimated with the KEO surface data using the Coupled Ocean‐Atmosphere Response Experiment (COARE) version 3.0 bulk algorithm. Both NRA1 and NRA2 latent heat flux (LHF) are larger than KEO LHF, consistent with previous studies. However, the comparison shows larger errors than previously thought. Indeed, the latent heat flux bias for NRA1 is 41 W m−2 and for NRA2 is 62 W m−2 (indicating that the bias between NRA1 and NRA2 is 21 W m−2). For latent heat flux, the large bias is caused primarily by the NRA bulk flux algorithm, while the root mean square (RMS) error is caused primarily by errors in the NRA meteorological variables. The combination of the biases for each heat flux is such that total NRA heat transfer from the ocean to the atmosphere is considerably larger than observed by KEO. These results highlight the importance of maintaining in situ observations for monitoring surface heat fluxes in the Kuroshio/Kuroshio Extension regions.
Integrated summer insolation forcing and 40,000‐year glacial cycles: The perspective from an ice‐sheet/energy‐balance model
Authors: Huybers Peter , Tziperman Eli
Published: February 2008

Although the origins of the 40,000‐year glacial cycles during the early Pleistocene are readily attributed to changes in Earth's obliquity (also having a 40,000‐year period), the lack of ice‐volume variability at precession periods (20,000 years) is difficult to reconcile with most parameterizations of the insolation forcing. It was recently proposed that precession's influence on glaciation is muted because variations in the intensity of summer insolation are counterbalanced by changes in the duration of the summertime, but no climate model has yet been shown to generate obliquity period glacial cycles in response to the seasonal insolation forcing. Here we present a coupled ice‐sheet/energy‐balance model that reproduces the seasonal cycle and, when run over long time periods, generates glacial variability in response to changes in Earth's orbital configuration. The model is forced by the full seasonal cycle in insolation, and its response can be understood within the context of the integrated summer insolation forcing. The simple fact that obliquity's period is roughly twice as long as that of precession results in a larger amplitude glacial response to obliquity. However, for the model to generate almost exclusively obliquity period glacial variability, two other conditions must be met. First, the ice sheet's ablation zone must reside poleward of ∼60°N because insolation intensity is more sensitive to changes in Earth's obliquity at high latitudes. Second, the ablation season must be long enough for precession's opposing influences on summer and fall insolation intensity to counterbalance one another. These conditions are consistent with a warm climate and a thin ice sheet, where the latter is simulated as a response to subglacial sediment deformation. If a colder climate is prescribed, or in the absence of basal motion, ice sheets tend to be larger and undergo greater precession period variability, in keeping with proxy observations of late Pleistocene glaciation.
Mitochondrial non-syndromic sensorineural hearing loss: a clinical, audiological and pathological study from Italy, and revision of the literature
Authors: Berrettini Stefano , Forli Francesca , Passetti Susanna , Rocchi Anna , Pollina Luca , Cecchetti Denise , Mancuso Michelangelo , Siciliano Gabriele
Published: February 2008

Over the last decade, a number of distinct mutations in the mtDNA (mitochondrial DNA) have been found to be associated with both syndromic and non-syndromic forms of hearing impairment. Their real incidence as a cause of deafness is poorly understood and generally underestimated. Among the known mtDNA mutations, the A1555G mutation in the 12S gene has been identified to be one of the most common genetic cause of deafness, and it has been described to be both associated to non-syndromic progressive SNHL (sensorineural hearing loss) and to aminoglycoside-induced SNHL. In the present study, we have investigated the presence of mtDNA alterations in patients affected by idiopathic non-syndromic SNHL, both familiar and sporadic, in order to evaluate the frequency of mtDNA alterations as a cause of deafness and to describe the audiological manifestations of mitochondrial non-syndromic SNHL. In agreement with previous studies, we found the A1555G mutation to be responsible for a relevant percentage (5.4%) of cases affected with isolated idiopathic sensorineural hearing impairment.
Immunological and clinical aspects of lymphocytic hypophysitis
Authors: De Bellis Annamaria , Ruocco Giuseppe , Battaglia Marina , Conte Marisa , Coronella Concetta , Tirelli Gilda , Bellastella Antonio , Pane Elena , Sinisi Antonio Agostino , Bizzarro Antonio , Bellastella Giuseppe
Published: February 2008

LYH (lymphocytic hypophysitis) is an autoimmune disease of the pituitary gland which can present with varying degrees of pituitary hormonal impairment and/or with symptoms related to pituitary enlargement. In this review, we provide an overview of the epidemiology, diagnosis, pathogenesis, treatment, and the role of organ-specific and antipituitary antibodies as potential markers of LYH. In addition, although the mechanisms underlying LYH are not completely understood, the role of prolactin, which plays an important part in maintaining immune system homoeostasis and is increased in the disease, is considered.
Derivation of the distensibility coefficient using tissue Doppler as a marker of arterial function
Authors: Haluska Brian A. , Jeffriess Leanne , Brown Joseph , Downey Melodie , Carlier Stephane G. , Marwick Thomas H.
Published: February 2008

To date, the main cardiovascular application of TDI (tissue Doppler imaging) has been in myocardial evaluation. In the present study, we investigated the feasibility and reproducibility of assessing arterial elasticity using the DC (distensibility coefficient) measured by TDI, the correlation of this with the DC obtained by other methods and the DC in patients with various degrees of cardiovascular risk. We studied 450 subjects (256 men; age, 51±10 years) with and without risk factors of cardiovascular disease. Arterial displacement was measured from TDI, and B-mode and M-mode images of the common carotid artery in the longitudinal plane, and the DC with each method was compared. Linear regression showed a good correlation between all three methods. The results for TDI and B-mode were comparable [(21±10) compared with (21±10)×10−3/kPa respectively; P=not significant], but there were significant differences between TDI and M-mode [(21±10) compared with (31±13)×10−3/kPa respectively; P<0.0001] and between B-mode and M-mode [(21±10) compared with (31±13)×10−3/kPa respectively; P<0.0001]. Similarly, Bland–Altman analysis showed the least variability in the DC between TDI and B-mode, and there were no significant differences between the average measurements. The TDI DC also had the lowest paired difference for inter-observer variability [(−0.1±1.1)×10−3/kPa; P=not significant]. In conclusion, the results of the present study suggest that TDI of the carotid arteries is feasible, comparable with B-mode measurements, more robust than M-mode and less variable than the other methods.
Cardiac magnetic resonance findings predict increased resource utilization in elective coronary artery bypass grafting
Authors: Berry Colin , Zimmerli Lukas U. , Steedman Tracey , Foster John E. , Dargie Henry J. , Berg Geoffrey A. , Dominiczak Anna F. , Delles Christian
Published: February 2008

Morbidity following CABG (coronary artery bypass grafting) is difficult to predict and leads to increased healthcare costs. We hypothesized that pre-operative CMR (cardiac magnetic resonance) findings would predict resource utilization in elective CABG. Over a 12-month period, patients requiring elective CABG were invited to undergo CMR 1 day prior to CABG. Gadolinium-enhanced CMR was performed using a trueFISP inversion recovery sequence on a 1.5 tesla scanner (Sonata; Siemens). Clinical data were collected prospectively. Admission costs were quantified based on standardized actual cost/day. Admission cost greater than the median was defined as ‘increased’. Of 458 elective CABG cases, 45 (10%) underwent pre-operative CMR. Pre-operative characteristics [mean (S.D.) age, 64 (9) years, mortality (1%) and median (interquartile range) admission duration, 7 (6–8) days] were similar in patients who did or did not undergo CMR. In the patients undergoing CMR, eight (18%) and 11 (24%) patients had reduced LV (left ventricular) systolic function by CMR [LVEF (LV ejection fraction) <55%] and echocardiography respectively. LE (late enhancement) with gadolinium was detected in 17 (38%) patients. The average cost/day was $2723. The median (interquartile range) admission cost was $19059 ($10891–157917). CMR LVEF {OR (odds ratio), 0.93 [95% CI (confidence interval), 0.87–0.99]; P=0.03} and SV (stroke volume) index [OR 1.07 (95% CI, 1.00–1.14); P=0.02] predicted increased admission cost. CMR LVEF (P=0.08) and EuroScore tended to predict actual admission cost (P=0.09), but SV by CMR (P=0.16) and LV function by echocardiography (P=0.95) did not. In conclusion, in this exploratory investigation, pre-operative CMR findings predicted admission duration and increased admission cost in elective CABG surgery. The cost-effectiveness of CMR in risk stratification in elective CABG surgery merits prospective assessment.
Assessment of glycosaminoglycan concentration
in vivo
by chemical exchange-dependent saturation transfer (gagCEST)
Authors: Ling Wen , Regatte Ravinder R. , Navon Gil , Jerschow Alexej
Published: February 2008

Glycosaminogycans (GAGs) are involved in numerous vital functions in the human body. Mapping the GAG concentration
in vivo
is desirable for the diagnosis and monitoring of a number of diseases such as osteoarthritis, which affects millions of individuals. GAG loss in cartilage is typically an initiating event in osteoarthritis. Another widespread pathology related to GAG is intervertebral disk degeneration. Currently existing techniques for GAG monitoring, such as delayed gadolinium-enhanced MRI contrast (dGEMRIC),
T
1
ρ
, and
23
Na MRI, have some practical limitations. We show that by exploiting the exchangeable protons of GAG one may directly measure the localized GAG concentration
in vivo
with high sensitivity and therefore obtain a powerful diagnostic MRI method.
Mutations in
FN1
cause glomerulopathy with fibronectin deposits
Authors: Castelletti Federica , Donadelli Roberta , Banterla Federica , Hildebrandt Friedhelm , Zipfel Peter F. , Bresin Elena , Otto Edgar , Skerka Christine , Renieri Alessandra , Todeschini Marta , Caprioli Jessica , Caruso Rosa Maria , Artuso Rosangela , Remuzzi Giuseppe , Noris Marina
Published: February 2008

Glomerulopathy with fibronectin (FN) deposits (GFND) is an autosomal dominant disease with age-related penetrance, characterized by proteinuria, microscopic hematuria, hypertension, and massive glomerular deposits of FN that lead to end-stage renal failure. The genetic abnormality underlying GFND was still unknown. We hypothesized that mutations in
FN1
, which encodes FN, were the cause of GFND. In a large Italian pedigree with eight affected subjects, we found linkage with GFND at the
FN1
locus at 2q32. We sequenced the
FN1
in 15 unrelated pedigrees and found three heterozygous missense mutations, the W1925R, L1974R, and Y973C, that cosegregated with the disease in six pedigrees. The mutations affected two domains of FN (Hep-II domain for the W1925R and the L1974R, and Hep-III domain for the Y973C) that play key roles in FN–cell interaction and in FN fibrillogenesis. Mutant recombinant Hep-II fragments were expressed, and functional studies revealed a lower binding to heparin and to endothelial cells and podocytes compared with wild-type Hep-II and an impaired capability to induce endothelial cell spreading and cytoskeletal reorganization. Overall dominant mutations in
FN1
accounted for 40% of cases of GFND in our study group. These findings may help understanding the pathogenesis of proteinuria and glomerular FN deposits in GFND and possibly in more common renal diseases such as diabetic nephropathy, IgA nephropathy, and lupus nephritis. To our knowledge no
FN1
mutation causing a human disease was previously reported.
Hydrophobicity of protein surfaces: Separating geometry from chemistry
Authors: Giovambattista Nicolas , Lopez Carlos F. , Rossky Peter J. , Debenedetti Pablo G.
Published: February 2008

To better understand the role of surface chemical heterogeneity in natural nanoscale hydration, we study via molecular dynamics simulation the structure and thermodynamics of water confined between two protein-like surfaces. Each surface is constructed to have interactions with water corresponding to those of the putative hydrophobic surface of a melittin dimer, but is flattened rather than having its native “cupped” configuration. Furthermore, peripheral charged groups are removed. Thus, the role of a rough surface topography is removed, and results can be productively compared with those previously observed for idealized, atomically smooth hydrophilic and hydrophobic flat surfaces. The results indicate that the protein surface is less hydrophobic than the idealized counterpart. The density and compressibility of water adjacent to a melittin dimer is intermediate between that observed adjacent to idealized hydrophobic or hydrophilic surfaces. We find that solvent evacuation of the hydrophobic gap (cavitation) between dimers is observed when the gap has closed to sterically permit a single water layer. This cavitation occurs at smaller pressures and separations than in the case of idealized hydrophobic flat surfaces. The vapor phase between the melittin dimers occupies a much smaller lateral region than in the case of the idealized surfaces; cavitation is localized in a narrow central region between the dimers, where an apolar amino acid is located. When that amino acid is replaced by a polar residue, cavitation is no longer observed.
Sharply increased insect herbivory during the Paleocene–Eocene Thermal Maximum
Authors: Currano Ellen D. , Wilf Peter , Wing Scott L. , Labandeira Conrad C. , Lovelock Elizabeth C. , Royer Dana L.
Published: February 2008

The Paleocene–Eocene Thermal Maximum (PETM, 55.8 Ma), an abrupt global warming event linked to a transient increase in
p
CO
2
, was comparable in rate and magnitude to modern anthropogenic climate change. Here we use plant fossils from the Bighorn Basin of Wyoming to document the combined effects of temperature and
p
CO
2
on insect herbivory. We examined 5,062 fossil leaves from five sites positioned before, during, and after the PETM (59–55.2 Ma). The amount and diversity of insect damage on angiosperm leaves, as well as the relative abundance of specialized damage, correlate with rising and falling temperature. All reach distinct maxima during the PETM, and every PETM plant species is extensively damaged and colonized by specialized herbivores. Our study suggests that increased insect herbivory is likely to be a net long-term effect of anthropogenic
p
CO
2
increase and warming temperatures.
Receptor determinants of zoonotic transmission of New World hemorrhagic fever arenaviruses
Authors: Radoshitzky Sheli R. , Kuhn Jens H. , Spiropoulou Christina F. , Albariño César G. , Nguyen Dan P. , Salazar-Bravo Jorge , Dorfman Tatyana , Lee Amy S. , Wang Enxiu , Ross Susan R. , Choe Hyeryun , Farzan Michael
Published: February 2008

Transferrin receptor 1 (TfR1) is a cellular receptor for the New World hemorrhagic fever arenaviruses Machupo (MACV), Junín (JUNV), and Guanarito (GTOV). Each of these viruses is specifically adapted to a distinct rodent host species, but all cause human disease. Here we compare the ability of these viruses to use various mammalian transferrin receptor 1 (TfR1) orthologs, including those of the South American rodents that serve as reservoirs for MACV, JUNV, and GTOV (
Calomys callosus
,
Calomys musculinus
, and
Zygodontomys brevicauda
, respectively). Retroviruses pseudotyped with MACV and JUNV but not GTOV glycoproteins (GPs) efficiently used
C. callosus
TfR1, whereas only JUNV GP could use
C. musculinus
TfR1. All three viruses efficiently used
Z. brevicauda
TfR1. TfR1 orthologs from related rodents, including house mouse (
Mus musculus
) and rat (
Rattus norvegicus
), did not support entry of these viruses. In contrast, these viruses efficiently used human and domestic cat TfR1 orthologs. We further show that a local region of the human TfR1 apical domain, including tyrosine 211, determined the efficiency with which MACV, JUNV, and GTOV used various TfR1 orthologs. Our data show that these New World arenaviruses are specifically adapted to the TfR1 orthologs of their respective rodent hosts and identify key commonalities between these orthologs and human TfR1 necessary for efficient transmission of these viruses to humans.
Lifespan and reproduction in
Drosophila
: New insights from nutritional geometry
Authors: Lee Kwang Pum , Simpson Stephen J. , Clissold Fiona J. , Brooks Robert , Ballard J. William O. , Taylor Phil W. , Soran Nazaneen , Raubenheimer David
Published: February 2008

Modest dietary restriction (DR) prolongs life in a wide range of organisms, spanning single-celled yeast to mammals. Here, we report the use of recent techniques in nutrition research to quantify the detailed relationship between diet, nutrient intake, lifespan, and reproduction in
Drosophila melanogaster
. Caloric restriction (CR) was not responsible for extending lifespan in our experimental flies. Response surfaces for lifespan and fecundity were maximized at different protein–carbohydrate intakes, with longevity highest at a protein-to-carbohydrate ratio of 1:16 and egg-laying rate maximized at 1:2. Lifetime egg production, the measure closest to fitness, was maximized at an intermediate P:C ratio of 1:4. Flies offered a choice of complementary foods regulated intake to maximize lifetime egg production. The results indicate a role for both direct costs of reproduction and other deleterious consequences of ingesting high levels of protein. We unite a body of apparently conflicting work within a common framework and provide a platform for studying aging in all organisms.
Remodeling of ryanodine receptor complex causes “leaky” channels: A molecular mechanism for decreased exercise capacity
Authors: Bellinger Andrew M. , Reiken Steven , Dura Miroslav , Murphy Peter W. , Deng Shi-Xian , Landry Donald W. , Nieman David , Lehnart Stephan E. , Samaru Mahendranauth , LaCampagne Alain , Marks Andrew R.
Published: February 2008

During exercise, defects in calcium (Ca
2+
) release have been proposed to impair muscle function. Here, we show that during exercise in mice and humans, the major Ca
2+
release channel required for excitation–contraction coupling (ECC) in skeletal muscle, the ryanodine receptor (RyR1), is progressively PKA-hyperphosphorylated,
S
-nitrosylated, and depleted of the phosphodiesterase PDE4D3 and the RyR1 stabilizing subunit calstabin1 (FKBP12), resulting in “leaky” channels that cause decreased exercise tolerance in mice. Mice with skeletal muscle-specific calstabin1 deletion or PDE4D deficiency exhibited significantly impaired exercise capacity. A small molecule (S107) that prevents depletion of calstabin1 from the RyR1 complex improved force generation and exercise capacity, reduced Ca
2+
-dependent neutral protease calpain activity and plasma creatine kinase levels. Taken together, these data suggest a possible mechanism by which Ca
2+
leak via calstabin1-depleted RyR1 channels leads to defective Ca
2+
signaling, muscle damage, and impaired exercise capacity.
Genome evolution in cyanobacteria: The stable core and the variable shell
Authors: Shi Tuo , Falkowski Paul G.
Published: February 2008

Cyanobacteria are the only known prokaryotes capable of oxygenic photosynthesis, the evolution of which transformed the biology and geochemistry of Earth. The rapid increase in published genomic sequences of cyanobacteria provides the first opportunity to reconstruct events in the evolution of oxygenic photosynthesis on the scale of entire genomes. Here, we demonstrate the overall phylogenetic incongruence among 682 orthologous protein families from 13 genomes of cyanobacteria. However, using principal coordinates analysis, we discovered a core set of 323 genes with similar evolutionary trajectories. The core set is highly conserved in amino acid sequence and contains genes encoding the major components in the photosynthetic and ribosomal apparatus. Many of the key proteins are encoded by genome-wide conserved small gene clusters, which often are indicative of protein–protein, protein–prosthetic group, and protein–lipid interactions. We propose that the macromolecular interactions in complex protein structures and metabolic pathways retard the tempo of evolution of the core genes and hence exert a selection pressure that restricts piecemeal horizontal gene transfer of components of the core. Identification of the core establishes a foundation for reconstructing robust organismal phylogeny in genome space. Our phylogenetic trees constructed from 16S rRNA gene sequences, concatenated orthologous proteins, and the core gene set all suggest that the ancestral cyanobacterium did not fix nitrogen and probably was a thermophilic organism.
Structural and biochemical insights into the dicing mechanism of mouse Dicer: A conserved lysine is critical for dsRNA cleavage
Authors: Du Zhihua , Lee John K. , Tjhen Richard , Stroud Robert M. , James Thomas L.
Published: February 2008

Dicer, an RNase III enzyme, initiates RNA interference by processing precursor dsRNAs into mature microRNAs and small-interfering RNAs. It is also involved in loading and activation of the RNA-induced silencing complex. Here, we report the crystal structures of a catalytically active fragment of mouse Dicer, containing the RNase IIIb and dsRNA binding domains, in its apo and Cd
2+
-bound forms, at 1.68- and 2.8-Å resolution, respectively. Models of this structure with dsRNA reveal that a lysine residue, highly conserved in Dicer RNase IIIa and IIIb domains and in Drosha RNase IIIb domains, has the potential to participate in the phosphodiester bond cleavage reaction by stabilizing the transition state and leaving group of the scissile bond. Mutational and enzymatic assays confirm the importance of this lysine in dsRNA cleavage, suggesting that this lysine represents a conserved catalytic residue of Dicers. The structures also reveals a ≈45-aa region within the RNase IIIb domain that harbors an α-helix at the N-terminal half and a flexible loop at the C-terminal half, features not present in previously reported structures of homologous RNase III domains from either bacterial RNase III enzymes or
Giardia
Dicer. N-terminal residues of this α-helix have the potential to engage in minor groove interaction with dsRNA substrates.
Dissection of the insulin signaling pathway via quantitative phosphoproteomics
Authors: Krüger Marcus , Kratchmarova Irina , Blagoev Blagoy , Tseng Yu-Hua , Kahn C. Ronald , Mann Matthias
Published: February 2008

The insulin signaling pathway is of pivotal importance in metabolic diseases, such as diabetes, and in cellular processes, such as aging. Insulin activates a tyrosine phosphorylation cascade that branches to create a complex network affecting multiple biological processes. To understand the full spectrum of the tyrosine phosphorylation cascade, we have defined the tyrosine-phosphoproteome of the insulin signaling pathway, using high resolution mass spectrometry in combination with phosphotyrosine immunoprecipitation and stable isotope labeling by amino acids in cell culture (SILAC) in differentiated brown adipocytes. Of 40 identified insulin-induced effectors, 7 have not previously been described in insulin signaling, including SDR, PKCδ binding protein, LRP-6, and PISP/PDZK11, a potential calcium ATPase binding protein. A proteomic interaction screen with PISP/PDZK11 identified the calcium transporting ATPase SERCA2, supporting a connection to calcium signaling. The combination of quantitative phosphoproteomics with cell culture models provides a powerful strategy to dissect the insulin signaling pathways in intact cells.
Extraordinary intraspecific diversity in oyster sperm bindin
Authors: Moy G. W. , Springer S. A. , Adams S. L. , Swanson W. J. , Vacquier V. D.
Published: February 2008

In free-spawning invertebrates sperm–egg incompatibility is a barrier to mating between species, and divergence of gamete recognition proteins (GRPs) can result in reproductive isolation. Of interest are processes that create reproductive protein diversity within species, because intraspecific variants are potentially involved in mate choice and early speciation. Sperm acrosomes of the Pacific oyster
Crassostrea gigas
contain the protein bindin that bonds sperm to egg during fertilization. Oyster bindin is a single-copy gene encoding a diversity of protein variants. Oyster bindins have a conserved N-terminal region followed by one to five tandem fucose-binding lectin (F-lectin) domains. These repeats have diversified by positive selection at eight sites clustered on the F-lectin's fucose binding face. Additional bindin variants result from recombination in an intron in each F-lectin repeat. Males also express alternatively spliced bindin cDNAs with one to five repeats, but typically translate only one or two isoforms into protein. Thus, positive selection, alternative splicing, and recombination can create thousands of bindin variants within
C. gigas
. Models of sexual conflict predict high male diversity when females are diverse and sexual conflict is strong. The amount of intraspecific polymorphism in male GRPs may be a consequence of the relative efficiency of local (molecular recognition) and global (electrical, cortical, and physical) polyspermy blocks that operate during fertilization.
Commensal microbiota is fundamental for the development of inflammatory pain
Authors: Amaral F. A. , Sachs D. , Costa V. V. , Fagundes C. T. , Cisalpino D. , Cunha T. M. , Ferreira S. H. , Cunha F. Q. , Silva T. A. , Nicoli J. R. , Vieira L. Q. , Souza D. G. , Teixeira M. M.
Published: February 2008

The ability of an individual to sense pain is fundamental for its capacity to adapt to its environment and to avoid damage. The sensation of pain can be enhanced by acute or chronic inflammation. In the present study, we have investigated whether inflammatory pain, as measured by hypernociceptive responses, was modified in the absence of the microbiota. To this end, we evaluated mechanical nociceptive responses induced by a range of inflammatory stimuli in germ-free and conventional mice. Our experiments show that inflammatory hypernociception induced by carrageenan, lipopolysaccharide, TNF-α, IL-1β, and the chemokine CXCL1 was reduced in germ-free mice. In contrast, hypernociception induced by prostaglandins and dopamine was similar in germ-free or conventional mice. Reduction of hypernociception induced by carrageenan was associated with reduced tissue inflammation and could be reversed by reposition of the microbiota or systemic administration of lipopolysaccharide. Significantly, decreased hypernociception in germ-free mice was accompanied by enhanced IL-10 expression upon stimulation and could be reversed by treatment with an anti-IL-10 antibody. Therefore, these results show that contact with commensal microbiota is necessary for mice to develop inflammatory hypernociception. These findings implicate an important role of the interaction between the commensal microbiota and the host in favoring adaptation to environmental stresses, including those that cause pain.