bluuebunny/crossref_metadata_2025 huggingface dataset:
Putting the ‘bio’ into bioinformatics
Authors: Bromham Lindell
Published: April 2009

Bioinformatic analyses have grown rapidly in sophistication and efficiency to accommodate the vast increase in available data. One of the major challenges has been to incorporate the growing appreciation of the complexity of molecular evolution into new analytical methods. As the reliance on molecular data in biology and medicine increases, we need to be confident that these methods adequately reflect the underlying processes of genome change. This special issue focuses on the way that patterns and processes of molecular evolution are influenced by features of populations of whole organisms, such as selection pressure, population size and life history. The advantage of this approach to molecular evolution is that it views genomic change not simply as a biochemical or stochastic process, but as the result of a complex series of interactions that shape the kinds of genomic changes that can and do happen.
Social implications of the battle of the sexes: sexual harassment disrupts female sociality and social recognition
Authors: Darden Safi K. , James Richard , Ramnarine Indar W. , Croft Darren P.
Published: April 2009

Across sexually reproducing species, males and females are in conflict over the control of reproduction. At the heart of this conflict in a number of taxa is male harassment of females for mating opportunities and female strategies to avoid this harassment. One neglected consequence that may result from sexual harassment is the disruption of important social associations. Here, we experimentally manipulate the degree of sexual harassment that wild female guppies (
Poecilia reticulata
) experience by establishing replicated, semi-natural pools with different population sex ratios. We quantify the effects of sexual harassment on female social structure and the development of social recognition among females. When exposed to sexual harassment, we found that females had more disparate social networks with limited repeated interactions when compared to females that did not experience male harassment. Furthermore, females that did not experience harassment developed social recognition with familiar individuals over an 8-day period, whereas females that experienced harassment did not, an effect we suggest is due to disruption of association patterns. These results show that social network structure and social recognition can be affected by sexual harassment, an effect that will be relevant across taxonomic groups and that we predict will have fitness consequences for females.
Tensioning the helix: a mechanism for force generation in twining plants
Authors: Isnard Sandrine , Cobb Alexander R. , Holbrook N.Michele , Zwieniecki Maciej , Dumais Jacques
Published: April 2009

Twining plants use their helical stems to clasp supports and to generate a squeezing force, providing stability against gravity. To elucidate the mechanism that allows force generation, we measured the squeezing forces exerted by the twinerDioscorea bulbiferawhile following its growth using time-lapse photography. We show that the development of the squeezing force is accompanied by stiffening of the stem and the expansion of stipules at the leaf base. We use a simple thin rod model to show that despite their small size and sparse distribution, stipules impose a stem deformation sufficient to account for the measured squeezing force. We further demonstrate that tensioning of the stem helix, although counter-intuitive, is the most effective mechanism for generating large squeezing forces in twining plants. Our observations and model point to a general mechanism for the generation of the twining force: a modest radial stem expansion during primary growth, or the growth of lateral structures such as leaf bases, causes a delayed stem tensioning that creates the squeezing forces necessary for twining plants to ascend their supports. Our study thus provides the long-sought answer to the question of how twining plants ascend smooth supports without the use of adhesive or hook-like structures.
Bile acid signaling pathways increase stability of Small Heterodimer Partner (SHP) by inhibiting ubiquitin–proteasomal degradation
Authors: Miao Ji , Xiao Zhen , Kanamaluru Deepthi , Min Gyesik , Yau Peter M. , Veenstra Timothy D. , Ellis Ewa , Strom Steve , Suino-Powell Kelly , Xu H. Eric , Kemper Jongsook Kim
Published: April 2009

Small Heterodimer Partner (SHP) inhibits activities of numerous transcription factors involved in diverse biological pathways. As an important metabolic regulator, SHP plays a key role in maintaining cholesterol and bile acid homeostasis by inhibiting cholesterol conversion to bile acids. While SHP gene induction by increased bile acids is well established, whether SHP activity is also modulated remains unknown. Here, we report surprising findings that SHP is a rapidly degraded protein via the ubiquitin–proteasomal pathway and that bile acids or bile acid-induced intestinal fibroblast growth factor 19 (FGF19) increases stability of hepatic SHP by inhibiting proteasomal degradation in an extracellular signal-regulated kinase (ERK)-dependent manner. SHP was ubiquitinated at Lys122 and Lys123, and mutation of these sites altered its stability and repression activity. Tandem mass spectrometry revealed that upon bile acid treatment, SHP was phosphorylated at Ser26, within an ERK motif in SHP, and mutation of this site dramatically abolished SHP stability. Surprisingly, SHP stability was abnormally elevated in ob/ob mice and diet-induced obese mice. These results demonstrate an important role for regulation of SHP stability in bile acid signaling in normal conditions, and that abnormal stabilization of SHP may be associated with metabolic disorders, including obesity and diabetes.
A role for ubiquitin in the clearance of nonfunctional rRNAs
Authors: Fujii Kotaro , Kitabatake Makoto , Sakata Tomoko , Miyata Atsumi , Ohno Mutsuhito
Published: April 2009

Quality control mechanisms operate in various steps of ribosomal biogenesis to ensure the production of functional ribosome particles. It was reported previously that mature ribosome particles containing nonfunctional mutant rRNAs are also recognized and selectively removed by a cellular quality control system (nonfunctional rRNA decay [NRD]). Here, we show that the NRD of 25S rRNA requires a ubiquitin E3 ligase component Rtt101p and its associated protein Mms1p, identified previously as factors involved in DNA repair. We revealed that a group of proteins associated with nonfunctional ribosome particles are ubiquitinated in a Rtt101–Mms1-dependent manner. 25S NRD was disrupted when ubiquitination was inhibited by the overexpression of modified ubiquitin molecules, demonstrating a direct role for ubiquitin in this pathway. These results uncovered an unexpected connection between DNA repair and the quality control of rRNAs. Our findings support a model in which responses to DNA and rRNA damages are triggered by a common ubiquitin ligase complex during genotoxic stress harmful to both molecules.
Mechanisms that regulate localization of a DNA double-strand break to the nuclear periphery
Authors: Oza Pranav , Jaspersen Sue L. , Miele Adriana , Dekker Job , Peterson Craig L.
Published: April 2009

DNA double-strand breaks (DSBs) are among the most deleterious forms of DNA lesions in cells. Here we induced site-specific DSBs in yeast cells and monitored chromatin dynamics surrounding the DSB using Chromosome Conformation Capture (3C). We find that formation of a DSB within G1 cells is not sufficient to alter chromosome dynamics. However, DSBs formed within an asynchronous cell population result in large decreases in both intra- and interchromosomal interactions. Using live cell microscopy, we find that changes in chromosome dynamics correlate with relocalization of the DSB to the nuclear periphery. Sequestration to the periphery requires the nuclear envelope protein, Mps3p, and Mps3p-dependent tethering delays recombinational repair of a DSB and enhances gross chromosomal rearrangements. Furthermore, we show that components of the telomerase machinery are recruited to a DSB and that telomerase recruitment is required for its peripheral localization. Based on these findings, we propose that sequestration of unrepaired or slowly repaired DSBs to the nuclear periphery reflects a competition between alternative repair pathways.
Yeast telomerase and the SUN domain protein Mps3 anchor telomeres and repress subtelomeric recombination
Authors: Schober Heiko , Ferreira Helder , Kalck Véronique , Gehlen Lutz R. , Gasser Susan M.
Published: April 2009

Telomeres form the ends of linear chromosomes and protect these ends from being recognized as DNA double-strand breaks. Telomeric sequences are maintained in most cells by telomerase, a reverse transcriptase that adds TG-rich repeats to chromosome ends. In budding yeast, telomeres are organized in clusters at the nuclear periphery by interactions that depend on components of silent chromatin and the telomerase-binding factor yeast Ku (yKu). In this study, we examined whether the subnuclear localization of telomeres affects end maintenance. A telomere anchoring pathway involving the catalytic yeast telomerase subunits Est2, Est1, and Tlc1 is shown to be necessary for the perinuclear anchoring activity of Yku80 during S phase. Additionally, we identify the conserved Sad1–UNC-84 (SUN) domain protein Mps3 as the principal membrane anchor for this pathway. Impaired interference with Mps3 anchoring through overexpression of the Mps3 N terminus in a tel1 deletion background led to a senescence phenotype and to deleterious levels of subtelomeric Y′ recombination. This suggests that telomere binding to the nuclear envelope helps protect telomeric repeats from recombination. Our results provide an example of a specialized structure that requires proper spatiotemporal localization to fulfill its biological role, and identifies a novel pathway of telomere protection.
The origin of embryonic and fetal myoblasts: a role of Pax3 and Pax7: Figure 1.
Authors: Messina Graziella , Cossu Giulio
Published: April 2009

Skeletal muscle is a heterogeneous tissue composed of individual muscle fibers, diversified in size, shape, and contractile protein content, to fulfill the different functional needs of the vertebrate body. This heterogeneity derives from and depends at least in part on distinct classes of myogenic progenitors; i.e., embryonic and fetal myoblasts and satellite cells whose origin and lineage relationship have been elusive so far. In this issue of Genes & Development, Hutcheson and colleagues (pp. 997–1013) provide a first answer to this question.
Active destruction of defective ribosomes by a ubiquitin ligase involved in DNA repair: Figure 1.
Authors: Hinnebusch Alan G.
Published: April 2009

Progression of DNA replication forks through damaged DNA requires a ubiquitin ligase comprised of the cullin Rtt101, the RING finger protein Hrt1, and the adaptor protein Mms1. Rtt101 and Mms1 were implicated recently by Fujii and colleagues (pp. 963–974) in the degradation of catalytically inactive mutant 25S ribosomal RNAS (rRNAs) in mature 60S ribosomal subunits, a process that requires ubiquitin and is accompanied by ubiquitination of 60S components. It now seems likely that the same ubiquitin ligase is enlisted to deal with defective rRNA and damaged DNA.
Expression Level ofABERRANT PANICLE ORGANIZATION1Determines Rice Inflorescence Form through Control of Cell Proliferation in the Meristem
Authors: Ikeda-Kawakatsu Kyoko , Yasuno Naoko , Oikawa Tetsuo , Iida Shigeru , Nagato Yasuo , Maekawa Masahiko , Kyozuka Junko
Published: April 2009

Two types of branches, rachis branches (i.e. nonfloral) and spikelets (i.e. floral), are produced during rice (Oryza sativa) inflorescence development. We previously reported that the ABERRANT PANICLE ORGANIZATION1 (APO1) gene, encoding an F-box-containing protein orthologous to Arabidopsis (Arabidopsis thaliana) UNUSUAL FLORAL ORGANS, suppresses precocious conversion of rachis branch meristems to spikelets to ensure generation of certain number of spikelets. Here, we identified four dominant mutants producing an increased number of spikelets and found that they are gain-of-function alleles of APO1. The APO1 expression levels are elevated in all four mutants, suggesting that an increase of APO1 activity caused the delay in the program shift to spikelet formation. In agreement with this result, ectopic overexpression of APO1 accentuated the APO1 gain-of-function phenotypes. In the apo1-D dominant alleles, the inflorescence meristem starts to increase in size more vigorously than the wild type when switching to the reproductive development phase. This alteration in growth rate is opposite to what is observed with the apo1 mutants that have a smaller inflorescence meristem. The difference in meristem size is caused by different rates of cell proliferation. Collectively, these results suggest that the level of APO1 activity regulates the inflorescence form through control of cell proliferation in the meristem.
The Effects on Lignin Structure of Overexpression of Ferulate 5-Hydroxylase in Hybrid Poplar1
Authors: Stewart Jaclyn J. , Akiyama Takuya , Chapple Clint , Ralph John , Mansfield Shawn D.
Published: April 2009

Poplar (Populus tremula × alba) lignins with exceedingly high syringyl monomer levels are produced by overexpression of the ferulate 5-hydroxylase (F5H) gene driven by a cinnamate 4-hydroxylase (C4H) promoter. Compositional data derived from both standard degradative methods and NMR analyses of the entire lignin component (as well as isolated lignin fraction) indicated that the C4H∷F5H transgenic's lignin was comprised of as much as 97.5% syringyl units (derived from sinapyl alcohol), the remainder being guaiacyl units (derived from coniferyl alcohol); the syringyl level in the wild-type control was 68%. The resultant transgenic lignins are more linear and display a lower degree of polymerization. Although the crucial β-ether content is similar, the distribution of other interunit linkages in the lignin polymer is markedly different, with higher resinol (β-β) and spirodienone (β-1) contents, but with virtually no phenylcoumarans (β-5, which can only be formed from guaiacyl units). p-Hydroxybenzoates, acylating the γ-positions of lignin side chains, were reduced by >50%, suggesting consequent impacts on related pathways. A model depicting the putative structure of the transgenic lignin resulting from the overexpression of F5H is presented. The altered structural features in the transgenic lignin polymer, as revealed here, support the contention that there are significant opportunities to improve biomass utilization by exploiting the malleability of plant lignification processes.
Reactive Oxygen Species Are Involved in Brassinosteroid-Induced Stress Tolerance in Cucumber
Authors: Xia Xiao-Jian , Wang Yan-Jie , Zhou Yan-Hong , Tao Yuan , Mao Wei-Hua , Shi Kai , Asami Tadao , Chen Zhixiang , Yu Jing-Quan
Published: April 2009

Brassinosteroids (BRs) induce plant tolerance to a wide spectrum of stresses. To study how BR induces stress tolerance, we manipulated the BR levels in cucumber (Cucumis sativus) through a chemical genetics approach and found that BR levels were positively correlated with the tolerance to photo-oxidative and cold stresses and resistance to Cucumber mosaic virus. We also showed that BR treatment enhanced NADPH oxidase activity and elevated H2O2 levels in apoplast. H2O2 levels were elevated as early as 3 h and returned to basal levels 3 d after BR treatment. BR-induced H2O2 accumulation was accompanied by increased tolerance to oxidative stress. Inhibition of NADPH oxidase and chemical scavenging of H2O2 reduced BR-induced oxidative and cold tolerance and defense gene expression. BR treatment induced expression of both regulatory genes, such as RBOH, MAPK1, and MAPK3, and genes involved in defense and antioxidant responses. These results strongly suggest that elevated H2O2 levels resulting from enhanced NADPH oxidase activity are involved in the BR-induced stress tolerance.
Auxin-Responsive Genes AIR12 Code for a New Family of Plasma Membrane b-Type Cytochromes Specific to Flowering Plants
Authors: Preger Valeria , Tango Nunzio , Marchand Christophe , Lemaire Stéphane D. , Carbonera Donatella , Di Valentin Marilena , Costa Alex , Pupillo Paolo , Trost Paolo
Published: April 2009

We report here on the identification of the major plasma membrane (PM) ascorbate-reducible b-type cytochrome of bean (Phaseolus vulgaris) and soybean (Glycine max) hypocotyls as orthologs of Arabidopsis (Arabidopsis thaliana) AIR12 (for auxin induced in root cultures). Soybean AIR12, which is glycosylated and glycosylphosphatidylinositol-anchored to the external side of the PM in vivo, was expressed in Pichia pastoris in a recombinant form, lacking the glycosylphosphatidylinositol modification signal and purified from the culture medium. Recombinant AIR12 is a soluble protein predicted to fold into a β-sandwich domain and belonging to the DOMON (for dopamine β-monooxygenase N terminus) domain superfamily. It is shown to be a b-type cytochrome with a symmetrical α-band at 561 nm, fully reduced by ascorbate, and fully oxidized by monodehydroascorbate radical. AIR12 is a high-potential cytochrome b showing a wide bimodal dependence from the redox potential between +80 mV and +300 mV. Optical absorption and electron paramagnetic resonance analysis indicate that AIR12 binds a single, highly axial low-spin heme, likely coordinated by methionine-91 and histidine-76, which are strongly conserved in AIR12 sequences. Phylogenetic analyses reveal that the auxin-responsive genes AIR12 represent a new family of PM b-type cytochromes specific to flowering plants. Circumstantial evidence suggests that AIR12 may interact with other redox partners within the PM to constitute a redox link between cytoplasm and apoplast.
Two Cys or Not Two Cys? That Is the Question; Alternative Oxidase in the Thermogenic Plant Sacred Lotus
Authors: Grant Nicole , Onda Yoshihiko , Kakizaki Yusuke , Ito Kikukatsu , Watling Jennifer , Robinson Sharon
Published: April 2009

Sacred lotus (Nelumbo nucifera) regulates temperature in its floral chamber to 32°C to 35°C across ambient temperatures of 8°C to 40°C with heating achieved through high alternative pathway fluxes. In most alternative oxidase (AOX) isoforms, two cysteine residues, Cys1 and Cys2, are highly conserved and play a role in posttranslational regulation of AOX. Further control occurs via interaction of reduced Cys1 with α-keto acids, such as pyruvate. Here, we report on the in vitro regulation of AOX isolated from thermogenic receptacle tissues of sacred lotus. AOX protein was mostly present in the reduced form, and only a small fraction could be oxidized with diamide. Cyanide-resistant respiration in isolated mitochondria was stimulated 4-fold by succinate but not pyruvate or glyoxylate. Insensitivity of the alternative pathway of respiration to pyruvate and the inability of AOX protein to be oxidized by diamide suggested that AOX in these tissues may lack Cys1. Subsequently, we isolated two novel cDNAs for AOX from thermogenic tissues of sacred lotus, designated as NnAOX1a and NnAOX1b. Deduced amino acid sequences of both confirmed that Cys1 had been replaced by serine; however, Cys2 was present. This contrasts with AOXs from thermogenic Aroids, which contain both Cys1 and Cys2. An additional cysteine was present at position 193 in NnAOX1b. The significance of the sequence data for regulation of the AOX protein in thermogenic sacred lotus is discussed and compared with AOXs from other thermogenic and nonthermogenic species.
The movement of wild sea trout, Salmo trutta L., smolts through a river estuary
Authors: MOORE A. , POTTER E.C.E.
Published: April 2009

Abstract  The movement of sea trout. Salmo trutta L., smolts through the estuary of the River Avon, southern England was studied using miniature 300 kHz acoustic transmitters and an array of strategically placed acoustic sonar buoys. Sea trout smolts were trapped 3.25 km above the head of tide as they moved downstream and the transmitters were surgically implanted into the peritoneal cavity of the fish. Subsequent movement of the smolts through the estuary was predominantly nocturnal and occurred mainly during an ebb tide or the period of slack water between two high waters. During the hours of darkness the ground speed of the smolts through the estuary was similar to that of passively drifting objects. However, where movement did occur during daylight hours ground speeds of smolts were significantly slower. Vertical salinity profile measurements of the estuary indicated that individual smolts may have experienced salinities ranging from fresh to 100% sea water during their migration. The behaviour of the smolts is discussed in relation to the possible environmental and physiological cues controlling the estuarine migration.
International management of Atlantic salmon, Salmo salar L., by the North Atlantic Salmon Conservation Organization, 1984–1994
Authors: WINDSOR M.L. , HUTCHINSON P.
Published: April 2009

Abstract  The development of distant water fisheries at West Greenland and in the Northern Norwegian Sea during the 1960s and, more recently, in the Faroese zone, led to the establishment, in 1984, of the North Atlantic Salmon Conservation Organization (NASCO). This paper summarizes the progress made in the 10 years since this Organization was established towards achieving its goals of conservation, restoration, enhancement and rational management of salmon, Salmo salar L., stocks. Agreements on regulatory measures have reduced the proportion of the total catch taken by the distant water fisheries and, in the case of the West Greenland fishery, management is now firmly based on scientific advice. The stability created by these regulations has allowed NASCO to address the broader areas of conservation called for under the Convention and international action has been taken to address a number of threats to the resource, including the impacts of aquaculture, introductions and transfers, and fishing in international waters by non‐contracting parties. These actions are described and the paper concludes that NASCO has a significant role to play in the future, both through continued regulation of the fisheries and by promoting international cooperation to address these broader threats to the resource.
Fyke‐netting and coarse fisheries in lowland Britain: practical advice for fishery owners and managers
Authors: NAISMITH I.A. , KNIGHTS B.
Published: April 2009

Abstract  The by‐catches of fish, mammals and birds from a fyke‐net survey of eel, Anguilla angilla (L.), stocks (total effort 1593 end days) at 45 sites in rivers and lakes in the Thames catchment and tidal river were examined. Sizes and compositions of by‐catches varied between sites, yielding a total of 21 fish species representative of the types of water body sampled. The largest catches were of shoaling juvenile perch (especially in lakes). Small roach, perch and ruffe were also fairly frequent in running waters (especially the tidal and non‐tidal Thames). Carp, tench and pike were less frequently caught (mainly in still waters and upper tributaries). Juvenile flounders and smelt were fairly common in the tidal Thames. Salmonids were rarely caught and fish mortalities overall were very low. Few mammals, wildfowl or crustaceans were trapped, but it is important that nets are set below water level to avoid trapping birds swimming on the surface, and the use of otter guards is recommended. Fouling of fishing tackle was rare. Recommendations are made for practical steps that can be taken to minimize undesirable impacts of commercial fyke‐netting, whilst realizing the potential financial and management benefits. The cost‐effective uses of fyke‐nets for sampling and culling fish for management purposes are discussed.
Has the introduction of brown trout altered disease patterns in native New Zealand fish?
Authors: KELLY D. W. , PATERSON R. A. , TOWNSEND C. R. , POULIN R. , TOMPKINS D. M.
Published: April 2009

1. It is well recognised that non‐indigenous species (NIS) can affect native communities via the ‘spillover’ of introduced parasites. However, two other potentially important processes, the ‘spillback’ of native parasites from a competent NIS host, where the latter acts as a reservoir leading to amplified infection in native hosts, and the ‘dilution’ of parasitism by a NIS host acting as a sink for native parasites, have either not been tested or largely overlooked.

2. We surveyed the helminth parasite fauna of native New Zealand fish in Otago streams that varied in the abundance of introduced brown troutSalmo trutta, to look for evidence of spillback and/or dilution. Spillover is not an issue in this system, with trout introduced as parasite‐free eggs.

3. Seven native parasite species were present across 12 sites; significant inverse relationships with an index of trout abundance (i.e. dilution) were documented for three species infecting the native upland bullyGobiomorphus breviceps, and one species infecting the native roundhead galaxiasGalaxias anomalus.

4. An inverse relationship between bully energy status and infection intensity of one parasite species suggests that parasite dilution could have positive effects on bully populations. Our failure to detect similar relationships for the other parasites does not preclude the possibility that dilution is beneficial to native fish, since parasites may have subtle or unmeasured impacts.

5. The parasite dilution patterns reported are compelling in that they occurred across several native host and parasite species; as such they have important implications for invasion ecology, providing an interesting contrast to the largely negative impacts reported for NIS. Mechanisms potentially responsible for the patterns observed are discussed.
Age‐related gestation length adjustment in a large iteroparous mammal at northern latitude
Authors: Mysterud Atle , Røed Knut H. , Holand Øystein , Yoccoz Nigel G. , Nieminen Mauri
Published: April 2009

There is considerable interest in patterns of age‐dependent reproductive effort and reproductive timing of large iteroparous mammals living in strongly seasonal environments. Due to lack of data on both timing of mating and birth, there is generally little insight into whether variation in gestation length play a role for life‐history patterns observed for large mammals at northern latitudes.

Based on data on both timing of mating and birth of 88 female reindeer (and paternity confirmed with DNA fingerprinting), we explore the view that adjustment of gestation length plays a role in the reproductive tactic.

Observed gestation lengths of reindeer varied between 211 and 229 days (mean of 221 days). Consistent with a dynamic view of gestation length, variation could be predicted from life‐history traits. Gestation length was longer for male than female offspring, which is expected in polygynous species where males benefit more from extra allocation of maternal resources. Gestation length increased with maternal age both due to direct effects and indirect effects linked to earlier mating of older, heavier females. Early mating females increased gestation length. A relatively small effect of female age on birth mass operated through variation in gestation length.

Our analysis supports the view that adjustment of gestation length is a part of the reproductive tactic of large mammals in northern environments.
The effects of mowing and agricultural landscape management on population movements of the common quail
Authors: Rodríguez‐Teijeiro José Domingo , Sardà‐Palomera Francesc , Nadal Jesús , Ferrer Xavier , Ponz Carolina , Puigcerver Manel
Published: April 2009

Aim  Information on the movements of bird populations in extensive landscapes is needed to assess environmental effects and conservation strategies over appropriate temporal and spatial scales. The common quail (Coturnix coturnix) is a game bird that breeds mainly in dense cereal crops. These crops cover huge areas of the Iberian Peninsula. The aim of this work is to relate cereal mowing, which causes rapid and massive habitat loss for the common quail, to population movements of the species during its breeding season.

Location  Spain, southern Europe.

Methods  We used ring recoveries to analyse, using circular statistics, the orientation of movements by male common quails in the northern half of Spain. Forward stepwise multiple regressions were applied to correlate (1) the Julian day of cereal harvesting at 770 locations with the respective latitude, longitude and elevation, and (2) the number of hunted birds with hunting pressure, breeding densities and mean mowing date by province. Finally, data concerning the number of quails hunted at the end of the breeding season were compared by province and year using two‐way ANOVA.

Results  Our results show that during the breeding season in the northern half of Spain, male quails orient their movements towards higher areas, and mainly to the northern Castilian Plateau. These are the areas of Spain where cereals are harvested latest. Moreover, records show that the number of quails hunted is significantly higher in these areas than in other areas of the country, independently of hunting pressure and breeding densities, and it is extremely high in the northern Castilian Plateau.

Main conclusions  Cereal mowing combined with some Spanish geographical characteristics acts as a funnel, forcing quail populations to concentrate in certain areas of Spain at the end of the breeding season. This implies that the number of quails hunted in these areas may be high, and that they therefore constitute priority conservation areas.
The European Prader–Willi Syndrome Clinical Research Database: an aid in the investigation of a rare genetically determined neurodevelopmental disorder
Authors: Holland A. , Whittington J. , Cohen O. , Curfs L. , Delahaye F. , Dudley O. , Horsthemke B. , Lindgren A.‐C. , Nourissier C. , Sharma N. , Vogels A.
Published: April 2009

Background  Prader–Willi Syndrome (PWS) is a rare genetically determined neurodevelopmental disorder with a complex phenotype that changes with age. The rarity of the syndrome and the need to control for different variables such as genetic sub‐type, age and gender limits clinical studies of sufficient size in any one country. A clinical research database has been established to structure data collection and to enable multinational investigations into the development of children and adults with PWS.

Methods  As part of a joint basic science and clinical study of PWS funded through Framework 6 of the European Union (EU), an expert multidisciplinary group was established that included clinicians involved in PWS research and clinical practice, expert database software developers, and representatives from two national PWS Associations. This group identified the key issues that required resolution and the data fields necessary for a comprehensive database to support PWS research.

Results  The database consists of six ‘index’ entry points and branching panels and sub‐panels and over 1200 data ‘fields’. It is Internet‐based and designed to support multi‐site clinical research in PWS. An algorithm ensures that participant data are anonymous. Access to data is controlled in a manner that is compatible with EU and national laws. The database determines the assessments to be used to collect data thereby enabling the combining of data from different groups under specifically agreed conditions. The data collected at any one time will be determined by individual research groups, who retain control of the data. Over time the database will accumulate data on participants with PWS that will support future research by avoiding the need for repeat data collection of fixed data and it will also enable longitudinal studies and treatment trials.

Conclusion  The development of the database has proved to be complex with various administrative and ethical issues to be addressed. At an early stage, it was important to clarify the exact function of the database. It was agreed that it was primarily to support grant‐funded research rather than clinical practice. The most complex issues that had to be addressed were concerned with data ownership and establishing the rules for data entry, retrieval and sharing that are compatible with data protection laws, and which are likely to be acceptable to participants and their families and to individual research groups.
Community management of intellectual disabilities in Pakistan: a mixed methods study
Authors: Mirza I. , Tareen A. , Davidson L. L. , Rahman A.
Published: April 2009

Background  Pakistan has one of the highest reported rates of childhood intellectual disabilities (ID) in the world. Prevalence estimates vary from 19.1/1000 for serious ID to 65/1000 for mild ID.

Methods  We surveyed carers of persons with ID (n = 100) using quantitative and qualitative instruments. We conducted in‐depth interviews of carers (n = 16) and key primary health providers (n = 10). We also carried out focus groups (n = 7). Data were triangulated and interpreted in light of peer reviewed literature.

Results  There was a delay of 2.92 (95% CI 1.9 to 3.94) to 4.17 (95% CI 2.34 to 6.01) years between detection and seeking of care. Parental stress associated with caring for these children was high (mean Self‐Reporting Questionnaire score 8.4; 95% CI 6.80 to 9.91). Home management consisted mainly of physical containment. Stigma associated with ID contributed to decreased opportunity for these children and families to participate in community activities. There was a lack of knowledge about causation and effective interventions for ID.

Conclusions  Our findings suggest that there is significant delay in detection of ID especially in rural setting where more than 70% of population of Pakistan resides. This missed opportunity for rehabilitation in early formative years is a cause of significant distress for the caregivers who rarely receive valid information about course, prognosis and what remedial action to take. There is a need to develop feasible, cost‐effective, community level interventions, which can be integrated into existing healthcare systems.
Role of two nutritional hepatic markers (insulin‐like growth factor 1 and transthyretin) in the clinical assessment and follow‐up of acute intermittent porphyria patients
Authors: Delaby C. , To‐Figueras J. , Deybach J. C. , Casamitjana R , Puy H. , Herrero C.
Published: April 2009

Objective.  Acute intermittent porphyria (AIP) is caused by a deficiency of hydroxymethylbilane synthase. Clinical manifestations are abdominal pain and neurovisceral symptoms, accompanied by overproduction of heme‐precursors in the liver, which frequently remains long‐lasting in AIP patients. We tested the hypothesis that this condition may be associated with alterations of hepatic proteins known to be either increased or decreased in serum according to diverse pathological conditions including malnutrition, inflammation or liver disease.

Design.  Serum proteins were analyzed in 26 biochemically active AIP patients that were classified according to the EPI (European Porphyria Initiative) guidelines as follows: (i) patients who presented a single acute attack having remained so far free of clinical symptoms; (ii) patients who present recurrent attacks or chronic symptoms associated with exacerbations of AIP.

Results.  Most of the serum proteins were within normal limits, however insulin‐like growth factor 1 (IGF‐1) was decreased in 53.8% of AIP patients (z‐score = −2.86 ± 0.37) and transthyretin (prealbumin) was found significantly decreased in 38.5% of them. The IGF‐1 z‐score was lower in group B versus group A patients (−2.66 vs. −1.43; P = 0.024). The coincident decrease of both IGF‐1 and transthyretin was associated with worsening of the clinical condition.

Conclusions.  This first study in humans suggests that the clinical expression AIP is associated with a state of under‐nutrition and/or with hepatic inflammation due to the sustained accumulation of heme‐precursors. We propose the use of both IGF‐1 and transthyretin as biomarkers of disease morbidity/severity for the clinical follow‐up of AIP patients.
Serum amyloid A is independently associated with metabolic risk factors but not with early atherosclerosis: the Cardiovascular Risk in Young Finns Study
Authors: Jylhävä J. , Haarala A. , Eklund C. , Pertovaara M. , Kähönen M. , Hutri‐Kähönen N. , Levula M. , Lehtimäki T. , Huupponen R. , Jula A. , Juonala M. , Viikari J. , Raitakari O. , Hurme M.
Published: April 2009

Background.  Serum amyloid A (SAA) is a sensitive marker of inflammation and its elevation has been implicated in obesity and in cardiovascular disease, yet data on its regulation in young adults or on its role in early atherosclerosis is scarce. We investigated which factors explain the variation in SAA and analysed whether SAA could be associated with preclinical atherosclerosis.

Methods.  Serum amyloid A levels were measured in participants of the Cardiovascular Risk in Young Finns Study (n = 2280, n = 1254 women, n = 1026 men). Correlates and determinants of SAA were analysed and the effect of SAA on subclinical atherosclerosis, measured as intima‐media thickness (IMT) and carotid artery compliance, was evaluated with risk‐factor adjusted models.

Results.  Serum amyloid A correlated directly and independently of BMI with C‐reactive protein (CRP), waist circumference and leptin in both sexes, with total cholesterol, LDL cholesterol and ApolipoproteinA1 (ApoA1) in women and with triglycerides, insulin levels and insulin resistance in men. Use of combined oral contraceptives and intrauterine device was also associated with SAA levels. Determinants for SAA included CRP, leptin and ApoA1 in women, and CRP, leptin and HDL cholesterol in men. SAA levels correlated with carotid compliance in both sexes and with IMT in men, yet SAA had no independent effect on IMT or carotid compliance in multivariable analysis.

Conclusions.  Serum amyloid A was associated with several metabolic risk factors but was not an independent predictor of IMT or carotid artery compliance. Further longitudinal studies will show whether SAA holds a prognostic value as a risk marker, analogously to CRP.
Natural killer cell‐based immunotherapy in cancer: current insights and future prospects
Authors: Sutlu T. , Alici E.
Published: April 2009

As our understanding of the molecular mechanisms governing natural killer (NK) cell activity increases, their potential in cancer immunotherapy is growing increasingly prominent. This review analyses the currently available preclinical and clinical data regarding NK cell‐based immunotherapeutic approaches in cancer starting from a historical background and an overview of molecular mechanisms taking part in NK cell responses. The status of NK cells in cancer patients, currently investigated clinical applications such as in vivo modulation of NK cell activity, ex vivo purification/expansion and adoptive transfer as well as future possibilities such as genetic modifications are discussed in detail.
Kidney function and discrimination of cardiovascular risk in middle‐aged men
Authors: Soveri I. , Ärnlöv J. , Berglund L. , Lind L. , Fellström B. , Sundström J.
Published: April 2009

Objective.  To define the optimal glomerular filtration rate (GFR) cut off for discriminating the risk of myocardial infarction or cardiovascular death.

Design.  Prospective longitudinal observational study.

Setting.  A community‐based cohort.

Participants.  A total of 2176 nondiabetic 50‐year‐old men without cardiovascular disease.

Methods.  The men were followed until age 70. GFR was estimated at baseline using the Cockcroft–Gault formula. The optimal GFR cut‐off points for discriminating risk of a fatal or nonfatal myocardial infarction and cardiovascular death were defined as the GFR levels maximizing integrated discrimination improvement (IDI).

Main outcome measures.  Fatal or nonfatal myocardial infarction, cardiovascular death.

Results.  During follow‐up, 264 men experienced a fatal or nonfatal myocardial infarction, and 218 died of cardiovascular disease. The IDI‐defined optimal GFR cut offs in this study were 98 mL min−1 for discriminating myocardial infarction risk and 92 mL min−1 for discriminating risk of cardiovascular death. In Cox proportional hazard models adjusting for established risk factors, the myocardial infarction risk was substantially higher in men with GFR below versus above 98 mL min−1 [hazard ratio (HR) 1.7, 95% confidence interval (CI) 1.3–2.3, P < 0.001], and the risk of cardiovascular death was doubled in men with GFR below versus above 92 mL min−1 (HR 2.1, 95% CI 1.5–3.0, P < 0.001).

Conclusion.  The GFR cut‐off point for optimal discrimination of cardiovascular risk in the general population may be higher than previously suggested.
Prevalence and extent of calcification over aorta, coronary and carotid arteries in patients with rheumatoid arthritis
Authors: Wang S. , Yiu K.‐H. , Mok M.‐Y. , Ooi G. C. , Khong P.‐L. , Mak K.‐F. H. , Lau C.‐P. , LAM K.‐F. , Lau C.‐S. , Tse H.‐F.
Published: April 2009

Objective.  To evaluate the prevalence and pattern of arterial calcification in patients with rheumatoid arthritis (RA).

Background.  Patients with RA are prone to premature atherosclerosis; nonetheless the prevalence and extent of atherosclerosis in different vascular beds and their relationship to each other remain unknown.

Methods.  We studied the distribution and extent of arterial calcification in 85 RA patients and 85 age‐and sex‐matched controls. Arterial calcification as determined by calcium score (CS) were measured using multi‐detector computed tomography in thoracic aorta, coronary and carotid arteries.

Results.  Compared with controls, RA patients had a significantly higher average CS and prevalence of CS > 0 in aorta, coronary and carotid arteries and overall arteries (all P < 0.05). After adjusting for age and sex, RA patients had a significantly higher relative risk of developing calcification in the aorta [Odds Ratio (OR) = 19.5, 95% Confidence Interval (CI): 8.0–47.6], followed by the carotid arteries (OR = 5.7, 95% CI:1.7–18.7) and coronary arteries (OR = 5.0, 95% CI:2.2–11.1) compared with controls (all P < 0.01). Amongst RA patients aged >60, 90% had diffuse arterial calcification, especially over the thoracic aorta, compared with 55% of controls who had arterial calcification clustered in the coronary arteries (P < 0.05). RA patients with total CS > 0 were older with a higher urea level and C‐reactive protein than those without arterial calcification, no factor was found to be independently predictive for arterial calcification (all P > 0.05).

Conclusions.  Our results demonstrated that RA patients had earlier onset, more diffuse arterial calcification over multiple vascular beds and more preferential involvement of thoracic aorta, rather than coronary artery when compared with control.
A relict bank vole lineage highlights the biogeographic history of the Pyrenean region in Europe
Authors: DEFFONTAINE VALÉRIE , LEDEVIN RONAN , FONTAINE MICHAËL C. , QUÉRÉ JEAN‐PIERRE , RENAUD SABRINA , LIBOIS ROLAND , MICHAUX JOHAN R.
Published: April 2009

The Pyrenean region exhibits high levels of endemism suggesting a major contribution to the phylogeography of European species. But, to date, the role of the Pyrenees and surrounding areas as a glacial refugium for temperate species remains poorly explored. In the current study, we investigated the biogeographic role of the Pyrenean region through the analyses of genetic polymorphism and morphology of a typical forest‐dwelling small mammal, the bank vole (Myodes glareolus). Analyses of the mitochondrial cytochrome b gene and the third upper molar (M3) show a complex phylogeographic structure in the Pyrenean region with at least three distinct lineages: the Western European, Spanish and Basque lineages. The Basque lineage in the northwestern (NW) Pyrenees was identified as a new clearly differentiated and geographically localized bank vole lineage in Europe. The average M3 shape of Basque bank voles suggests morphological differentiation but also restricted genetic exchanges with other populations. Our genetic and morphological results as well as palaeo‐environmental and fossils records support the hypothesis of a new glacial refugium in Europe situated in the NW Pyrenees. The permissive microclimatic conditions that prevailed for a long time in this region may have allowed the survival of temperate species, including humans. Moreover, local differentiation around the Pyrenees is favoured by the opportunity for populations to track the shift of the vegetation belt in altitude rather than in latitude. The finding of the Basque lineage is in agreement with the high level of endemic taxa reported in the NW Pyrenees.
Transalpine colonisation and partial phylogeographic erosion by dispersal in the common vole (Microtus arvalis)
Authors: BRAAKER SONJA , HECKEL GERALD
Published: April 2009

The colonisation history and genetic structure of the common vole (Microtus arvalis) was investigated in the region of the Alps by analysing the mitochondrial cytochrome b gene (mtDNA) and 19 microsatellite loci (nucDNA) for 137 voles from 52 localities. mtDNA data provided a much refined distribution of three highly divergent evolutionary lineages in the region compared to previous studies. Although high mountain ranges are widely accepted to be barriers for colonisation processes for many organisms and especially small terrestrial mammals, our phylogeographic analyses showed clear evidence of four transalpine colonisation events by the common vole. Individual‐based phylogenetic analyses of nucDNA and two alternative Bayesian‐clustering approaches revealed a deep genetic structure analogous to mtDNA. Incongruence between nucDNA and mtDNA at the individual level was restricted to the regions of contact between the lineages. mtDNA patterns and strong female philopatry in M. arvalis suggest that the crossings of the Alps occurred during the colonisation of the region when it was free from ice after the last glaciation. nucDNA patterns suggest that some of the transalpine elements of this phylogeographic pattern were subsequently eroded by male‐biased gene flow. We conclude that the combination of phylogeography and landscape genetics at the individual level can provide very detailed insights into colonisation events and may even allow differentiation between historical and more recent processes.
Health researchers’ attitudes towards public involvement in health research
Authors: Thompson Jill , Barber Rosemary , Ward Paul R. , Boote Jonathan D. , Cooper Cindy L. , Armitage Christopher J. , Jones Georgina
Published: April 2009

Objective  To investigate health researchers’ attitudes to involving the public in research.

Background  Public involvement in research is encouraged by the Department of Health in the UK. Despite this, the number of health researchers actively involving the public in research appears to be limited. There is little research specifically addressing the attitudes of health researchers towards involving the public: how they interpret the policy, what motivates and de‐motivates them and what their experiences have been to date.

Design  A qualitative research design, using semi‐structured telephone interviews.

Setting and participants  Fifteen purposively sampled UK‐based University health researchers were the participants. Interviews were conducted over the telephone.

Findings  The participants suggested varying constructions of public involvement in research. Arguments based on moral and political principles and consequentialist arguments for involving the public in research were offered and most participants highlighted the potential benefits of involving the public. However, feelings of apprehension expressed by some participants imply that a number of researchers may still be uncomfortable with involving the public, as it presents a different way of working.