bluuebunny/crossref_metadata_2025 huggingface dataset:
Socio-economic perspectives on the conservation of Critically Endangered vultures in South Asia: an empirical study from Nepal
Authors: Baral Nabin , Gautam Ramji
Published: May 2007

Following the catastrophic decline in populations of three species of South Asian Gyps vultures, we conducted a study to explore socio-economic variables that could facilitate conservation efforts. A questionnaire survey was carried out in 103 randomly selected households in the Rampur valley, one of the Important Bird Areas of Nepal, during 2004. Among respondents, 38% were female, 62% male, 28% illiterate and 72% literate. Households belonged to three ethno-religious groups (Hindu castes, ethnic groups and Muslim) and 96% of households had some parcels of registered land to farm. About 90% of households reared one or more types of livestock while the mean Livestock Size Unit was 3.32 per household. Livestock diseases and ailments were common and usually treated with diclofenac. Livestock carcass disposal practices were favourable to vultures because 60% of households dumped carcasses in open fields. Diclofenac is lethal to vultures; 3% of diclofenac-contaminated carcasses were available annually. The majority (78%) of respondents had favourable attitudes towards the concept of vulture conservation. Diclofenac contamination and the destruction of nesting habitat were two major threats to vultures. Ensuring healthy food through economic incentives, inculcating new values through environmental education and soliciting popular participation for habitat conservation are recommended.
Junk ingestion and nestling mortality in a reintroduced population of California Condors Gymnogyps californianus
Authors: Mee Allan , Rideout Bruce A. , Hamber Janet A. , Todd J. Nick , Austin Greg , Clark Mike , Wallace Michael P.
Published: May 2007

Ingestion of foreign anthropogenic material, here called junk, has been documented in many avian taxa but has become especially problematic in some Old World Gyps vulture populations within the last 30 years. Here, we document the effects of ingested junk on a reintroduced population of the Critically Endangered California Condor Gymnogyps californianus in southern California, U.S.A. Of 13 breeding attempts to date (2001–2005), only one has resulted in successful fledging. Of nests where either the nest substrate was sifted (n = 10) or nestlings (n = 8) were examined, all but one held junk. Nine nestlings hatched in the wild between 2002 and 2005; of these six died at or near nests and two were removed from the wild for health reasons. Four dead nestlings and two removed from the wild held substantial quantities of junk. In two cases, junk ingestion was determined to be the cause of death. Five of six dead nestlings had elevated hepatic copper levels (150–531 ppm dry weight) although the significance of this, if any, remains undetermined. In comparison with historic condor nests (n = 69), junk was more prevalent and of greater size and quantity in reintroduced condor nests. To date, junk ingestion has been the primary cause of nest failure in the reintroduced condor population and threatens the reestablishment of a viable breeding population in southern California.
Genetic structure among wild populations of Elliot's Pheasant Syrmaticus ellioti in China from mitochondrial DNA analyses
Authors: Jiang Ping Ping , Ge Yun Fa , Lang Qiu Lei , Ding Ping
Published: May 2007

Genetic structure among five populations of Elliot's Pheasant sampled from five different provinces – Anhui (AH), Zhejiang (ZJ), Fujian (FJ), Hunan (HN) and Guizhou (GZ) – was assayed using mitochondrial control region sequences from 33 individuals. Using AMOVA, we found a high level of haplotype variation within populations, and a degree of genetic structure among groups (GZ population relative to all others pooled). However, this difference was not statistically significant and little geographical structure was indicated among the remaining populations. Furthermore, using a rooted maximum parsimony tree, we found the sequences of the GZ population were largely grouped in their own branch, while sequences of the other four populations were interspersed among branches. We identified a lower level of gene flow between the GZ population and all others, a finding supported by significant FST values. Conversely, we identified a larger amount of gene flow between the remaining four populations, particularly among the three easternmost populations (AH, ZJ and FJ). Given our results, further study should be focused on the GZ population and on management units for the purpose of maintaining the genetic structure of the species in the west of China.
Philippine bird taxonomy and conservation: a commentary on Peterson (2006)
Authors: Collar N. J.
Published: May 2007

A review by Peterson (2006) claims that a new species-level taxonomy leads to improved conservation insights for Philippine birds. However, it does not report how borderline taxonomic cases were dealt with, how many taxa and specimens were examined, how closely the evaluations were made, why four key museums were omitted from the survey, and why certain taxa were omitted despite their presence in museums visited. It provides no conclusive or accurate diagnoses in more than 40% of taxa on the first two pages of the Appendix, and overlooks another 16% that have already achieved species-level recognition. It unjustifiably asserts that work was hampered by lack of material, and inappropriately calls for the collection of a highly threatened taxon. It employs one unstable diagnostic method but preaches the virtue of another, entirely different but equally unstable. All these shortcomings undermine confidence in the paper's rigour; and reference to the recent conservation literature shows that in any case no new conservation insights have resulted.
Philippine bird taxonomy and conservation, a response to Collar
Authors: Peterson A. Townsend
Published: May 2007

Collar (2007) attacked a recent paper of mine (Peterson 2006) on a number of grounds; he raised some valid points, and detected some errors in detail. Here, I respond to his criticisms, clarify misunderstandings, and urge the field to move beyond the status quo to consider the need for new taxonomic viewpoints to benefit bird conservation globally.
Recurrence with affine level mappings is P-time decidable for CLP
Authors: MESNARD FRED , SEREBRENIK ALEXANDER
Published: May 2007

In this paper we introduce a class of constraint logic programs such that their termination can be proved by using affine level mappings. We show that membership to this class is decidable in polynomial time.
Summer surface waters in the Gulf of California: Prime habitat for biological N2 fixation
Authors: White Angelicque E. , Prahl Fredrick G. , Letelier Ricardo M. , Popp Brian N.
Published: May 2007

We report significant rates of dinitrogen (N2) fixation in the central basins of the Gulf of California (GC) during July–August 2005. Mixing model estimates based upon δ15N values of particulate matter in the surface mixed layer indicate that N2 fixation provides as much as 35% to 48% of the phytoplankton‐based nitrogen demand in the central Guaymas and Carmen basins. Microscopic analyses identify the responsible genera as the N2‐fixing endosymbiont, Richelia intracellularis, with lesser contributions from the large nonheterocystous diazotroph Trichodesmium. Analyses of remotely sensed chlorophyll a and sea surface temperature indicate that primary production levels are elevated in regions of the GC where oceanographic conditions are ideal in summertime for the growth of N2‐fixing organisms. These findings suggest that biological N2 fixation must be taken into account when assessing past and present nitrogen dynamics in this environmentally important region.
Global biofuel use, 1850–2000
Authors: Fernandes Suneeta D. , Trautmann Nina M. , Streets David G. , Roden Christoph A. , Bond Tami C.
Published: May 2007

This paper presents annual, country‐level estimates of biofuel use for the period 1850–2000. We estimate that global biofuel consumption rose from about 1000 Tg in 1850 to 2460 Tg in 2000, an increase of 140%. In the late 19th century, biofuel consumption in North America was very high, ∼220–250 Tg/yr, because widespread land clearing supplied plentiful fuelwood. At that time biofuel use in Western Europe was lower, ∼180–200 Tg/yr. As fossil fuels became available, biofuel use in the developed world fell. Compensating changes in other parts of the world, however, caused global consumption to remain remarkably stable between 1850 and 1950 at ∼1200 ± 200 Tg/yr. It was only after World War II that biofuel use began to increase more rapidly in response to population growth in the developing world. Between 1950 and 2000, biofuel use in Africa, South Asia, and Southeast Asia grew by 170%, 160%, and 130%, respectively.
Spatiotemporal evolution of radio wave pump‐induced ionospheric phenomena near the fourth electron gyroharmonic
Authors: Ashrafi M. , Kosch M. J. , Kaila K. , Isham B.
Published: May 2007

On 12 November 2001, the European Incoherent Scatter (EISCAT) high‐frequency (HF) radio wave transmitter facility, operating in O‐mode at 5.423 MHz with 550 MW effective radiated power, produced artificial optical rings which appeared immediately at transmitter turn‐on and collapsed into blobs after ∼60 s while descending in altitude. A similar descent in altitude was observed in the EISCAT ultra high frequency (UHF) ion line enhancements. Likewise, the stimulated electromagnetic emission (SEE) spectra changed as the pump frequency approached the fourth electron gyroharmonic due to pump‐induced variations in electron concentration. Optical recordings were made from Skibotn at 630.0 and 557.7 nm and from Ramfjord in white light. The altitude of the initial optical ring and steady state blob has been estimated by triangulation. The evolution in altitude of the optical emissions, ion line enhancements, and SEE spectra all show a similar morphology but are generally not at exactly the same height. Typically, the optical height is close to and a few kilometers below that of the radar backscatter but sometimes above it, both of which are above the SEE generation altitude. There is evidence that upper hybrid (UH) waves, which propagate perpendicular to the magnetic field line, and Langmuir (L) waves, which propagate parallel to the magnetic field line, act simultaneously to accelerate electrons even in the steady state.
Influences of urban fabric on pyroclastic density currents at Pompeii (Italy): 1. Flow direction and deposition
Authors: Gurioli L. , Zanella E. , Pareschi M. T. , Lanza R.
Published: May 2007

To assess ways in which the products of explosive eruptions interact with human settlements, we performed volcanological and rock magnetic analyses on the deposits of the A.D. 79 eruption at the Pompeii excavations (Italy). During this eruption the Roman town of Pompeii was covered by 2.5 m of fallout pumice and then partially destroyed by pyroclastic density currents (PDCs). Anisotropy of magnetic susceptibility measurements performed on the fine matrix of the deposits allowed the quantification of the variations in flow direction and emplacement mechanisms of the parental PDCs that entered the town. These results, integrated with volcanological field investigations, revealed that the presence of buildings, still protruding through the fallout deposits, strongly affected the distribution and accumulation of the erupted products. All of the PDCs that entered the town, even the most dilute ones, were density stratified currents in which interaction with the urban fabric occurred in the lower part of the current. The degree of interaction varied mainly as a function of obstacle height and density stratification within the current. For examples, the lower part of the EU4pf current left deposits up to 3 m thick and was able to interact with 2‐ to 4‐m‐high obstacles. However, a decrease in thickness and grain size of the deposits across the town indicates that even though the upper portion of the current was able to decouple from the lower portion, enabling it to flow over the town, it was not able to fully restore the sediment supply to the lower portion in order to maintain the deposition observed upon entry into the town.
Evaluation of calibrated salinity from profiling floats with high resolution conductivity‐temperature‐depth data in the East/Japan Sea
Authors: Park Jong Jin , Kim Kuh
Published: May 2007

The East/Japan Sea is an ideal region for the assessment of the quality of calibrated profiling float salinity data due to the availability of recent shipboard conductivity‐temperature‐depth (CTD) observations, dense spatial occupation by profiling floats, and its unique water mass structure. More than 5000 salinity profiles obtained from the profiling floats have been corrected with respect to two calibration methods, and their qualities have been evaluated using 787 high‐resolution CTD profiles. In this paper, we suggest not only a method for the real‐ and non‐real‐time quality control of the float salinity data acquired in the East/Japan Sea (EJS) but also the uncertainty in the quality‐controlled salinity estimated from a statistical comparison with independent high‐resolution measurements. After applying the scientific quality control (Wong et al., 2003, hereafter referred to as WJO), the salinity data exhibit 1 standard deviation uncertainty of 0.003 psu which is comparable to the manufacturer's accuracy. However, the scientific calibration in the EJS provides a significant bias error of about 0.002 psu in the float salinity profiles adjusted to historical CTD data over the last 7 years. The WJO method could produce a bias error in the calibrated salinity for an open ocean where recent hydrographic data are insufficient and if significant salinity trends exist. Since the deep salinity change in the North Atlantic is two times larger than that in the EJS, the bias problem of the calibrated float salinity could be more serious in the North Atlantic.
Effects of El Niño–Southern Oscillation on sea level anomalies along the Gulf of Mexico coast
Authors: Kennedy Andrew J. , Griffin Melissa L. , Morey Steven L. , Smith Shawn R. , O'Brien James J.
Published: May 2007

Analyses of daily sea level data show the impacts of El Niño–Southern Oscillation (ENSO) in the Gulf of Mexico (GOM). Data from three stations (St. Petersburg, Florida, Pensacola, Florida, and Galveston, Texas), all of which have at least 50 years of daily observations, are processed to identify the interannual signals. Although low frequency (interannual) signals in the sea level anomaly time series are not clearly evident, a low frequency modulation of the extreme anomaly events (upper 10% or lower 10% of the distributions) is identified. Results show that sea level variability is seasonally dependent at all stations, with maximum variability in the winter months. In the eastern GOM, low sea level events in the winter months are more frequent during El Niño (warm phase) conditions when compared to a neutral ENSO phase. This is consistent with ENSO‐related changes in the location where extratropical atmospheric low pressure systems form and in the tracks of these weather systems. The impacts of tropical systems in the summer through early fall months on coastal sea level in the GOM are shown by infrequent extreme high and low anomalies coinciding with individual storms. However, the number of storms affecting the data record from a particular sea level station is too small to confirm ENSO‐related variability. Statistical methods are employed to demonstrate a significant link between extreme sea level anomalies in the GOM and ENSO during the October to March period.
Tropical wave‐induced oceanic eddies at Cabo Corrientes and the María Islands, Mexico
Authors: Zamudio Luis , Hurlburt Harley E. , Metzger E. Joseph , Tilburg Charles E.
Published: May 2007

TOPEX/Poseidon and ERS‐2 satellite altimeter observations and the 1/16° Naval Research Laboratory (NRL) Layered Ocean Model (NLOM) show the existence of anticyclonic eddies in the Cabo Corrientes – María Islands region off the Mexican West Coast. Analysis of the results demonstrates that: (1) The Cabo Corrientes ‐ María Islands region is characterized by mean poleward coastal currents, driven by local wind forcing. (2) The local currents are intensified by the arrival of baroclinic downwelling coastally trapped waves (CTWs), generated in the equatorial Pacific. (3) Anticyclonic eddies are generated as the intensified local currents pass cape‐like features in the coastline or shelf‐break geometry. (4) From 1979 to 2001 the CTWs generated an average of 2.35 (2.5) Cabo Corrientes (María Islands) anticyclonic eddies per year. (5) The formation of eddies varies interannually, increasing (decreasing) during El Niño (La Niña) years. Comparison of a variety of numerical simulations, which include different dynamics and/or different wind forcing and/or different topographic effects, suggests that bottom topography, local wind, and baroclinic instabilities are not essential for the eddy generation. It is (a) the capes at Cabo Corrientes and the María Islands and (b) the strong transient events associated with the CTWs that are essential to the formation of these newly recognized eddies.
Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) on Mars Reconnaissance Orbiter (MRO)
Authors: Murchie S. , Arvidson R. , Bedini P. , Beisser K. , Bibring J.‐P. , Bishop J. , Boldt J. , Cavender P. , Choo T. , Clancy R. T. , Darlington E. H. , Des Marais D. , Espiritu R. , Fort D. , Green R. , Guinness E. , Hayes J. , Hash C. , Heffernan K. , Hemmler J. , Heyler G. , Humm D. , Hutcheson J. , Izenberg N. , Lee R. , Lees J. , Lohr D. , Malaret E. , Martin T. , McGovern J. A. , McGuire P. , Morris R. , Mustard J. , Pelkey S. , Rhodes E. , Robinson M. , Roush T. , Schaefer E. , Seagrave G. , Seelos F. , Silverglate P. , Slavney S. , Smith M. , Shyong W.‐J. , Strohbehn K. , Taylor H. , Thompson P. , Tossman B. , Wirzburger M. , Wolff M.
Published: May 2007

The Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) is a hyperspectral imager on the Mars Reconnaissance Orbiter (MRO) spacecraft. CRISM consists of three subassemblies, a gimbaled Optical Sensor Unit (OSU), a Data Processing Unit (DPU), and the Gimbal Motor Electronics (GME). CRISM's objectives are (1) to map the entire surface using a subset of bands to characterize crustal mineralogy, (2) to map the mineralogy of key areas at high spectral and spatial resolution, and (3) to measure spatial and seasonal variations in the atmosphere. These objectives are addressed using three major types of observations. In multispectral mapping mode, with the OSU pointed at planet nadir, data are collected at a subset of 72 wavelengths covering key mineralogic absorptions and binned to pixel footprints of 100 or 200 m/pixel. Nearly the entire planet can be mapped in this fashion. In targeted mode the OSU is scanned to remove most along‐track motion, and a region of interest is mapped at full spatial and spectral resolution (15–19 m/pixel, 362–3920 nm at 6.55 nm/channel). Ten additional abbreviated, spatially binned images are taken before and after the main image, providing an emission phase function (EPF) of the site for atmospheric study and correction of surface spectra for atmospheric effects. In atmospheric mode, only the EPF is acquired. Global grids of the resulting lower data volume observations are taken repeatedly throughout the Martian year to measure seasonal variations in atmospheric properties. Raw, calibrated, and map‐projected data are delivered to the community with a spectral library to aid in interpretation.
Mars Reconnaissance Orbiter Radio Science Gravity Investigation
Authors: Zuber Maria T. , Lemoine Frank G. , Smith David E. , Konopliv Alex S. , Smrekar Suzanne E. , Asmar Sami W.
Published: May 2007

The objectives of the Mars Reconnaissance Orbiter (MRO) Radio Science Gravity Investigation are to improve knowledge of the static structure and characterize the temporal variability of the Martian gravitational field relevant to the planet's internal dynamics, the structure and dynamics of the atmosphere, and the orbital evolution of spacecraft at Mars. The investigation will utilize range rate and range measurements from X‐band and, when available, Ka‐band tracking systems of the MRO spacecraft. MRO will enable a considerable improvement in the spatial resolution and quality of Mars' global gravity field. The low orbital periapsis of MRO (∼255 km) will yield gravity maps suitable for study of regional (∼102 km) structure of the crust and lithosphere. The addition of tracking data from the Mars Global Surveyor and Mars Odyssey spacecraft, also currently orbiting Mars, will be useful in decorrelating errors in spherical harmonic coefficients of the gravity field that will improve the quality of the static field. Studies of the low‐degree gravity field combined with measurements of rotational dynamics will permit insight about the structure of Mars' deep interior. Changes in the low‐degree spherical harmonic coefficients of the Martian gravity field and in polar mass anomalies will be used to track the seasonal cycle of CO2 exchange with the surface. Measurements of spacecraft drag will be used to estimate density variations in the atmosphere relevant to weather patterns and aerobraking of future spacecraft. Tracking observations will also be used to improve the ephemeris of Mars and the masses of the Martian moons.
Relief threshold for eolian sand transport on alluvial fans
Authors: Cook Joseph P. , Pelletier Jon D.
Published: May 2007

Many arid alluvial‐fan terraces downwind from eolian sand sources exhibit an abrupt increase in eolian epipedon thickness and sand content below a critical elevation which varies from fan to fan. Above this elevation, sand accumulates locally and is not transported across the fan. Below this elevation eolian sand from nearby playa and channel sources is readily transported across the distal fan. Here we test the hypothesis that these distal‐fan eolian “corridors” are controlled by a threshold fan‐surface relief. We propose that when along‐strike relief falls below a critical threshold value, an eolian surface of transportation or “corridor” develops. To test this hypothesis, we measured multiple along‐strike topographic profiles and eolian epipedon textures on two piedmonts in the Ivanpah Valley and adjacent Hidden Valley in Clark County, Nevada. Both piedmonts are located near sand‐dominated playas and exhibit clear evidence of eolian transport across their distal fan regions. The near‐surface boundary layer flow above each topographic profile was quantified using the multispectral finite difference (MSFD) numerical model. This model predicts the surface shear stress above complex terrain for any wind condition assuming neutrally stable flow. The minimum shear stress calculated by MSFD for each profile during extreme wind conditions was compared to the shear‐velocity threshold necessary to initiate saltation. Model results showed that in proximal fan areas, along‐strike relief was large enough to prevent eolian transport of all but fine sand particles. In distal fan profiles within the eolian corridor, model results predict shear stresses everywhere above threshold for both fine and coarse sand.
Reactive transport of trace elements and isotopes in the Eutaw coastal plain aquifer, Alabama
Authors: Lee Ming‐Kuo , Griffin James , Saunders James , Wang Yang , Jean Jiin‐Shuh
Published: May 2007

We integrate groundwater geochemistry, mineralogy, and numerical modeling techniques to study the reactive transport of heavy metals and isotopes in the Eutaw coastal plain aquifer, Alabama. Geochemical data show that the elevated concentrations of Fe, Mn, and Sr can be correlated with high pH and alkalinity. These geochemical correlations suggest that that elevated metal concentrations may be derived from bacterial iron and manganese reduction. Geochemical modeling of bacterial Fe(III) and Mn(IV) reduction shows that the biotransformation of iron and manganese minerals could control mobility and concentrations of Fe and Mn in coastal plain aquifers. Petrographic, SEM, and EDAX studies of sediments show the formation of biogenic siderite, rhodochrosite, and pyrite in sediments associated with Fe‐ and Mn‐rich groundwater. Rhodochrosite and siderite occur together as spheroids (≈1.0 mm) in which rhodochrosite forms the center and siderite forms an outer rind, which is consistent with the redox sequence of mineral precipitation predicted by the geochemical modeling. The low δ13C ratios of siderite and rhodochrosite (−14.4 to −15.4‰, PDB) and groundwater DIC (−20.6 to −14.1‰, PDB) imply carbon of biogenic origin. Higher DIC‐δ13C levels are found to be correlated with elevated Fe and Mn concentrations and high pH values of groundwater. This unexpected result implies novel carbon isotopic fractionation processes associated with bacterial Fe(III) reduction. We used 36Cl/Cl ratios of groundwater and isotope transport modeling to calculate the residence time of regional groundwater in the Eutaw aquifer. The calculation considering the natural decay only would yield 36Cl levels that are significantly higher than field data, suggesting that a significant mixing with Cl‐rich, older groundwater at depth is an important reason for substantial 36Cl depletion along flow path.
Pathways of the Greenland Sea warming
Authors: Walczowski Waldemar , Piechura Jan
Published: May 2007

Progressive warming of the West Spitsbergen Current (WSC) has been observed since 2004. During summer 2006 temperature and salinity of the core of Atlantic Water (AW) reached the highest ever observed by the Institute of Oceanology Polish Academy of Sciences (IOPAS) values. The structure of the WSC, the heat content and the extent of AW in the Fram Strait (FS) region has also changed. Temperature changes resulted from the upstream warming of the Norwegian‐Atlantic Current (NwAC); the structure of the WSC and its heat content were modified by the northward advection of large mesoscale eddies observed within the western branch of the WSC in summer 2005. These changes may have large impacts on the Arctic Ocean (AO) climate and ecosystem.
Different profiles of Ca2+ responses to endothelin‐1 and PDGF in liver myofibroblasts during the process of cell differentiation
Authors: Kojima N , Hori M , Murata T , Morizane Y , Ozaki H
Published: May 2007

Background and purpose:

Hepatic stellate cells play an important role in liver fibrosis but little is known about liver myofibroblasts located around the central vein and in the portal area. In this study, intracellular Ca2+ concentration ([Ca2+]i) was measured to assess the response to endothelin‐1 (ET‐1), platelet derived growth factor (PDGF) and ATP in rat liver myofibroblasts.

Experimental approach:

Rat liver myofibroblasts were compared in ‘quiescent’ (cultured on Matrigel‐coated dishes) and ‘activated’ (cultured on non‐coated plastic dishes) conditions. [Ca2+]i was measured with the fluorescent dye fura‐2 and mRNA for ET‐1, PDGF and their receptors by RT‐PCR.

Key results:

ET‐1 increased [Ca2+]i in quiescent cells but not in activated cells, whereas PDGF‐BB increased [Ca2+]i in activated cells but not in quiescent cells. However, there was no difference between responses to ATP in quiescent or activated cells. ET‐1 (in quiescent cells), PDGF‐BB (in activated cells) and ATP (in both cells) all induced transient increases in [Ca2+]i in the absence of extracellular Ca2+ (with EGTA), indicating the involvement of Ca2+ release from intracellular Ca2+ stores. The sustained increase in [Ca2+]i in the presence of external Ca2+ in activated cells (ATP and PDGF) was significantly reduced by nicardipine, a L‐type Ca2+ channel blocker, but not in quiescent cells (ATP and ET‐1).

Conclusions and implications:

The different pharmacological profiles of [Ca2+]i‐response in quiescent and activated myofibroblasts suggest that ET‐1 and PDGF contribute differently to myofibroblast activation during the process of liver fibrosis.

British Journal of Pharmacology (2007) 151, 816–827; doi:10.1038/sj.bjp.0707269
Neuroprotection with or without erythropoiesis; sometimes less is more
Authors: Torup L
Published: May 2007

Erythropoietin (EPO) is a pleiotropic cytokine with a therapeutic potential that goes well beyond the treatment of anaemia. The study by Wang et al (2007b) examined the protective effects of EPO in a rat model of embolic stroke. The efficacy and haematological side effects of EPO were compared to those of a carbamylated EPO variant (CEPO). Treatment with EPO dose‐dependently reduced infarct volume and improved long‐term functional outcome. However, an increase in hematocrit was seen even for doses of EPO that did not offer neuroprotection. These data do not suggest the existence of a therapeutic window between effect and side effect for treatment with EPO. Treatment with CEPO was without haematological side effects.

British Journal of Pharmacology (2007) 151, 1141–1142; doi:10.1038/sj.bjp.0707287
Achieving signalling selectivity of ligands for the corticotropin‐releasing factor type 1 receptor by modifying the agonist's signalling domain
Authors: Beyermann M , Heinrich N , Fechner K , Furkert J , Zhang W , Kraetke O , Bienert M , Berger H
Published: May 2007

Background and purpose:

Most of the pharmaceuticals target G‐protein‐coupled receptors (GPCRs) which can generally activate different signalling events. The aim of this study was to achieve functional selectivity of corticotropin‐releasing factor receptor type 1 (CRF1) ligands.

Experimental approach:

We systematically substituted urocortin, a natural peptide agonist of CRF1, with bulky amino acids (benzoyl‐phenylalanine, naphthylalanine) and determined the effect of the analogues on coupling of CRF1 to Gs‐ and Gi‐protein in human embryonic kidney cells, using receptor binding, [35S]‐GTPγS binding stimulation, and cAMP accumulation assays.

Key results:

Native ligands stimulated Gs and Gi activation through CRF1, resulting in stimulation and then inhibition of cAMP accumulation. Single replacements in urocortin at positions 6–15 led, dependent on the position and nature of the substituent, to ligands that conserved Gs activity, but were devoid of Gi activity, only stimulating cAMP accumulation, and competitively antagonized the Gi activation by sauvagine. In contrast, analogues with substitutions outside this sequence non‐selectively activated Gs and Gi, as urocortin did.

Conclusions and implications:

Modifications in a specific region, which we have called the signalling domain, in the polypeptide agonist urocortin resulted in analogues that behaved as agonists and, at the same time, antagonists for the activation of different G‐proteins by CRF1. This finding implies significant differences between active conformations of the receptor when coupled to different G‐proteins. A similar structural encoding of signalling information in other polypeptide hormone receptor ligands would result in a general concept for the development of signalling‐selective drug candidates.

British Journal of Pharmacology (2007) 151, 851–859; doi:10.1038/sj.bjp.0707293
Dexrazoxane prevents doxorubicin‐induced long‐term cardiotoxicity and protects myocardial mitochondria from genetic and functional lesions in rats
Authors: Lebrecht D , Geist A , Ketelsen U‐P , Haberstroh J , Setzer B , Walker U A
Published: May 2007

Background and purpose:

Doxorubicin causes a chronic cardiomyopathy in which reactive oxygen species (ROS) accumulate over time and are associated with genetic and functional lesions of mitochondria. Dexrazoxane is a cardioprotective iron chelator that interferes with ROS production. We aim to analyze the effects of dexrazoxane on mitochondria in the prevention of doxorubicin‐induced chronic myocardial lesions.

Experimental approach:

Wistar rats (11 weeks of age) were injected with intravenous doxorubicin (0.8 mg kg‐1 weekly for 7 weeks) with or without simultaneous dexrazoxane (8 mg kg‐1). Animals were killed at 48 weeks. Cardiomyopathy was scored clinically and histologically and cardiac mitochondria were analyzed.

Key results:

Compared to control rats receiving saline, rats treated with doxorubicin alone developed a clinical, macroscopic, histological and ultrastructural cardiomyopathy with low cytochrome c‐oxidase (COX) activity (26% of controls). The expression of the mtDNA‐encoded COX II subunit was reduced (64% of controls). Myocardia exhibited a high production of ROS (malondialdehyde 338% and superoxide 787% of controls). Mitochondria were depleted of mitochondrial DNA (mtDNA copy number 46% of controls) and contained elevated levels of mtDNA deletions. Dexrazoxane co‐administration prevented all these effects of doxorubicin on mitochondria, except that hearts co‐exposed to doxorubicin and dexrazoxane had a slightly lower mtDNA content (81% of controls) and mtDNA deletions at low frequency.

Conclusions and Implications:

Dexrazoxane prevented doxorubicin induced late‐onset cardiomyopathy and also protected the cardiac mitochondria from acquired ultrastructural, genetic and functional damage.

British Journal of Pharmacology (2007) 151, 771–778; doi:10.1038/sj.bjp.0707294
Kisspeptins: a multifunctional peptide system with a role in reproduction, cancer and the cardiovascular system
Authors: Mead E J , Maguire J J , Kuc R E , Davenport A P
Published: May 2007

Orphan G‐protein‐coupled receptors that have recently been paired with their cognate ligand are an often untapped resource for novel drug development. The KISS1 receptor (previously designated GPR54) has been paired with biologically active cleavage peptides of the KiSS‐1 gene product, the kisspeptins (KP). The focus of this review is the emerging pharmacology and physiology of the KP. Genetic linkage analysis in humans revealed that mutations in KISS1 (GPR54, AXOR12 or hOT7T175) result in idiopathic hypogonadotrophic hypogonadism and knockout mouse studies confirmed this finding. Identification of KISS1 (GPR54) as a molecular switch for puberty subsequently led to the discovery that KP activate the GnRH cascade. Prior to the role of KISS1 (GPR54) in puberty being described, KP had been shown to be inhibitors of tumour metastasis across a range of cancers. Subsequently the mechanism of this inhibition has been suggested to be via altered cell motility and adhesiveness. PCR detected highest expression of KP and KISS1 (GPR54) in placenta, and changes in KP levels throughout pregnancy and expression in trophoblasts suggests a role in placentation. Placentation and metastasis are invasive processes that require angiogenesis. Investigation of KISS1 (GPR54) and KP in vasculature revealed discrete localisation of KISS1 (GPR54) to blood vessels prone to atherosclerosis and a potent vasoconstrictor action. A role for KP has also been shown in whole body homeostasis. KP are multifunctional peptides and further investigation is required to fully elucidate the complex pathways regulated by these peptides and how these pathways integrate in the whole body system.

British Journal of Pharmacology (2007) 151, 1143–1153; doi:10.1038/sj.bjp.0707295
Size‐fractionated heparins have differential effects on human neutrophil function in vitro
Authors: Lever R , Lo W T , Faraidoun M , Amin V , Brown R A , Gallagher J , Page C P
Published: May 2007

Background and purpose:

Heparin is known to possess a range of activities, other than effects on blood coagulation, many of which are anti‐inflammatory. Effects with potential anti‐inflammatory applications include the inhibition of elastase release from neutrophils, as well as the adhesion of these cells to vascular endothelium. In the present study we aimed to investigate whether fractionation of heparin may yield molecules with enhanced or specific effects on human neutrophil function.

Experimental approach:

Fractions of defined molecular size were obtained from heparin by different methods and assessed for their effects on elastase release induced by formyl Met‐Leu‐Phe (fMLP), from neutrophils, in some cases following the priming of these cells with tumour necrosis factor‐α (TNF‐α). Effects of the fractions on neutrophil adhesion to interleukin‐1β (IL‐β)‐stimulated human umbilical vein endothelial cells (HUVECs) were also examined.

Key results:

Elastase release was inhibited by very low molecular weight fractions of heparin, with an apparent minimum chain length of 10 saccharides required for full effect. In contrast, neutrophil‐endothelial adhesion was unaffected by these fractionated heparins, suggesting that certain non‐anticoagulant actions of heparin may be lost by such an approach.

Conclusions and implications:

These data suggest that an optimum chain length of heparin possibly exists for certain non‐anticoagulant actions of heparin, which may prove to be useful in the design of novel drugs with specific anti‐inflammatory actions.

British Journal of Pharmacology (2007) 151, 837–843; doi:10.1038/sj.bjp.0707298
Chemogenomic approaches to rational drug design
Authors: Rognan D
Published: May 2007

Paradigms in drug design and discovery are changing at a significant pace. Concomitant to the sequencing of over 180 several genomes, the high‐throughput miniaturization of chemical synthesis and biological evaluation of a multiple compounds on gene/protein expression and function opens the way to global drug‐discovery approaches, no more focused on a single target but on an entire family of related proteins or on a full metabolic pathway. Chemogenomics is this emerging research field aimed at systematically studying the biological effect of a wide array of small molecular‐weight ligands on a wide array of macromolecular targets. Since the quantity of existing data (compounds, targets and assays) and of produced information (gene/protein expression levels and binding constants) are too large for manual manipulation, information technologies play a crucial role in planning, analysing and predicting chemogenomic data. The present review will focus on predictive in silico chemogenomic approaches to foster rational drug design and derive information from the simultaneous biological evaluation of multiple compounds on multiple targets. State‐of‐the‐art methods for navigating in either ligand or target space will be presented and concrete drug design applications will be mentioned.

British Journal of Pharmacology (2007) 152, 38–52; doi:10.1038/sj.bjp.0707307
Influence of dietary fats on ecstasy‐induced hyperthermia
Authors: Mills E M , Weaver K L , Abramson E , Pfeiffer M , Sprague J E
Published: May 2007

Background and purpose:

Studies were designed to examine the effects of dietary fats on metabolic effects of 3,4‐methylenedioxymethamphetamine (MDMA, Ecstasy). These effects included hyperthermia, expression of uncoupling protein (UCP1 and 3) in brown adipose tissue or skeletal muscle and plasma free fatty acid (FFA) levels.

Experimental approach:

Male Sprague‐Dawley rats were fed either a high‐fat diet (HFD, 60% kcal) or a lower fat isocaloric controlled diet (LFD, 10% kcal) for 28 days before MDMA challenge.

Key results:

No significant differences were observed between LFD and HFD groups in terms of body weight, plasma thyroxine (T4) levels and expression of brown fat UCP1 or skeletal muscle UCP3 protein. HFD significantly raised levels of circulating FFA and potentiated the thermogenesis induced by MDMA (10 mg kg−1, s.c.), compared to the effects of the LFD. Moreover, 30 and 60 min after MDMA administration, plasma FFA levels decreased in HFD animals, but were markedly elevated in the LFD group.

Conclusions and implications:

These results indicate that high‐fat feeding regulates MDMA‐induced thermogenesis by augmenting the activation of UCP rather than its expression.

British Journal of Pharmacology (2007) 151, 1103–1108; doi:10.1038/sj.bjp.0707312
Use of gene profiling to describe a niche for dendritic cell development
Authors: Despars Geneviève , O'Neill Terence J , O'Neill Helen C
Published: May 2007

Gene profiling provides a multitude of data on individual gene expression. The view is expressed here that unreplicated data can be used in a descriptive way to compare cell populations in terms of their lineage characteristics and function. In these studies, the aim is to provide a snapshot of gene expression or its absence as a reflection of cell lineage or type, rather than gain a reliable expression measure for all genes expressed. The data set used in this analysis represents gene expression in the splenic stroma STX3 supportive of dendritic cell hematopoiesis and the lymph node stroma 2RL22, which is non‐supportive. These were obtained by hybridization of Affymetrix U74Av2 genechips. The use of P‐value selection to identify genes with a high probability of differential expression has been used effectively to detect differentially expressed genes. Genes that relate to a niche environment for hematopoiesis have been selected for further study to make predictions about the cell types of supportive stroma.
In Pursuit of Distinction: The Method of the Non-Proprietary Name
Authors: Fidelino R. John
Published: May 2007

This is an update to a paper that appeared in the very first issue of the Journal of Generic Medicines in October 2003. Over the past few years, pharmaceutical manufacturers have started to diversify their portfolios to include generic medicines as a way to maximise their investment in patented drugs. With this dynamic as context, understanding the development and construction of a generic name may be helpful both to the manufacturer of patented drugs who wants to support the perception of distinctiveness among competition, as well as to the generics marketer who wants to leverage the legacy of previously patented drugs. This paper intends to define generic names, explain their purpose and the challenges they pose to manufacturers, provide some guidance on their development, and identify how the non-proprietary name can support marketing opportunities.
Ca2+-dependent Inactivation of CaV1.2 Channels Prevents Gd3+ Block: Does Ca2+ Block the Pore of Inactivated Channels?
Authors: Babich Olga , Matveev Victor , Harris Andrew L. , Shirokov Roman
Published: May 2007

Lanthanide gadolinium (Gd3+) blocks CaV1.2 channels at the selectivity filter. Here we investigated whether Gd3+ block interferes with Ca2+-dependent inactivation, which requires Ca2+ entry through the same site. Using brief pulses to 200 mV that relieve Gd3+ block but not inactivation, we monitored how the proportions of open and open-blocked channels change during inactivation. We found that blocked channels inactivate much less. This is expected for Gd3+ block of the Ca2+ influx that enhances inactivation. However, we also found that the extent of Gd3+ block did not change when inactivation was reduced by abolition of Ca2+/calmodulin interaction, showing that Gd3+ does not block the inactivated channel. Thus, Gd3+ block and inactivation are mutually exclusive, suggesting action at a common site. These observations suggest that inactivation causes a change at the selectivity filter that either hides the Gd3+ site or reduces its affinity, or that Ca2+ occupies the binding site at the selectivity filter in inactivated channels. The latter possibility is supported by previous findings that the EEQE mutation of the selectivity EEEE locus is void of Ca2+-dependent inactivation (Zong Z.Q., J.Y. Zhou, and T. Tanabe. 1994. Biochem. Biophys. Res. Commun. 201:1117–11123), and that Ca2+-inactivated channels conduct Na+ when Ca2+ is removed from the extracellular medium (Babich O., D. Isaev, and R. Shirokov. 2005. J. Physiol. 565:709–717). Based on these results, we propose that inactivation increases affinity of the selectivity filter for Ca2+ so that Ca2+ ion blocks the pore. A minimal model, in which the inactivation “gate” is an increase in affinity of the selectivity filter for permeating ions, successfully simulates the characteristic U-shaped voltage dependence of inactivation in Ca2+.
Female extrapair mate choice in a cooperative breeder: trading sex for help and increasing offspring heterozygosity
Authors: Rubenstein Dustin R
Published: May 2007

Sexual conflict between males and females over mating is common. Females that copulate with extrapair mates outside the pair-bond may gain (i) direct benefits such as resources or increased paternal care, (ii) indirect genetic benefits for their offspring, or (iii) insurance against infertility in their own social mate. Few studies have been able to demonstrate the different contexts in which females receive varying types of benefits from extrapair mates. Here, I examined sexual conflict, female extrapair mate choice, and patterns of extrapair paternity in the cooperatively breeding superb starlingLamprotornis superbususing microsatellite markers. Although extrapair paternity was lower than many other avian cooperative breeders (14% of offspring and 25% of nests), females exhibited two distinct mating patterns: half of the extrapair fertilizations were with males from inside the group, whereas half were with males from outside the group. Females with few potential helpers copulated with extrapair mates from within their group and thereby gained direct benefits in the form of additional helpers at the nest, whereas females paired to mates that were relatively less heterozygous than themselves copulated with extrapair mates from outside the group and thereby gained indirect genetic benefits in the form of increased offspring heterozygosity. Females did not appear to gain fertility insurance from copulating with extrapair mates. This is the first study to show that individuals from the same population mate with extrapair males and gain both direct and indirect benefits, but that they do so in different contexts.
Chronic exposure in vivo to thyrotropin receptor stimulating monoclonal antibodies sustains high thyroxine levels and thyroid hyperplasia in thyroid autoimmunity‐prone HLA‐DRB1*0301 transgenic mice
Authors: Flynn Jeffrey C. , Gilbert Jacqueline A. , Meroueh Chady , Snower Daniel P. , David Chella S. , Kong Yi‐chi M. , Paul Banga J.
Published: May 2007

We have examined the induction of autoimmunity and the maintenance of sustained hyperthyroidism in autoimmunity‐prone human leucocyte antigen (HLA) DR3 transgenic non‐obese diabetic (NOD) mice following chronic stimulation of the thyrotropin receptor (TSHR) by monoclonal thyroid‐stimulating autoantibodies (TSAbs). Animals received weekly injections over the course of 9 weeks of monoclonal antibodies (mAbs) with strong thyroid‐stimulating properties. Administration of the mAbs KSAb1 (IgG2b) or KSAb2 (IgG2a), which have similar stimulating properties but different TSH‐binding blocking activity, resulted in significantly elevated serum thyroxine (T4) levels and thyroid hyperplasia. After the first injection, an initial surge then fall in serum T4 levels was followed by sustained elevated levels with subsequent injections for at least 63 days. Examination of KSAb1 and KSAb2 serum bioactivity showed that the accumulation of the TSAbs in serum was related to their subclass half‐lives. The thyroid glands were enlarged and histological examination showed hyperplastic follicles, with minimal accompanying thyroid inflammation. Our results show that chronic in vivo administration of mAbs with strong thyroid‐stimulating activity resulted in elevated T4 levels, suggesting persistent stimulation without receptor desensitization, giving a potential explanation for the sustained hyperthyroid status in patients with Graves' disease. Moreover, despite the presence of HLA disease susceptibility alleles and the autoimmune prone NOD background genes, chronic stimulation of the thyroid gland did not lead to immune cell‐mediated follicular destruction, suggesting the persistence of immunoregulatory influences to suppress autoimmunity.