bluuebunny/crossref_metadata_2025 huggingface dataset:
Conservation status and biogeography of Australia's terrestrial mammals
Authors: Burbidge Andrew A. , McKenzie N. L. , Brennan K. E. C. , Woinarski J. C. Z. , Dickman C. R. , Baynes A. , Gordon G. , Menkhorst P. W. , Robinson A. C.
Published: March 2009

This paper attempts to identify and explain patterns in the biogeography of Australia’s indigenous terrestrial mammals at the time of European settlement (before modern extinctions), and also compares species’ pre-European and current status by region. From subfossil, historical and contemporary sources, we compiled data on the past geographic range and present status of mammals for Australia’s 85 biogeographic regions. Of the 305 indigenous species originally present, 91 have disappeared from at least half of the bioregions in which they occurred before European settlement. Thirty-nine extant species ‘persist’ in less than 25% of their original bioregions; 28 of these are marsupials and 11 are rodents. Twenty-two of the original 305 species are extinct, a further eight became restricted to continental islands, and 100 have become extinct in at least one bioregion. Over the same period, 26 species of exotic mammals established wild populations and now occupy from one to 85 bioregions. When we classified the bioregions in terms of their original species composition, the 3-group level in the dendrogram approximated the Torresian, Eyrean and Bassian subregions proposed by Spencer in 1898, while the 4-group level separated southern semiarid Eyrean bioregions, including those in south-west Australia, from the arid Eyrean bioregions. The classification dendrogram showed geographically (and statistically) discrete clustering down to the 19-group level, suggesting that all four subregions can be further divided on the basis of their mammal faunas. Variation partitioning showed 66% of the biogeographical pattern can be explained by environmental factors (related to temperature and precipitation), the spatial position of each bioregion (a third-order polynomial of latitude and longitude), the area of each bioregion, and the richness of species in each bioregion. In addition to the marked distributional changes that indigenous mammals have experienced over the last 200 years, the 49% of variation explainable by temperature and precipitation implies further shifts with global climate change.
A phylogeny and timescale for the living genera of kangaroos and kin (Macropodiformes:Marsupialia) based on nuclear DNA sequences
Authors: Meredith Robert W. , Westerman Michael , Springer Mark S.
Published: March 2009

Kangaroos and kin (Macropodiformes) are the most conspicuous elements of the Australasian marsupial fauna. The approximately 70 living species can be divided into three families: (1) Hypsiprymnodontidae (the musky rat kangaroo); (2) Potoroidae (potoroos and bettongs); and (3) Macropodidae (larger kangaroos, wallabies, banded hare wallaby and pademelons). Here we examine macropodiform relationships using protein-coding portions of the ApoB, BRCA1, IRBP, Rag1 and vWF genes via maximum parsimony, maximum likelihood and Bayesian methods. We estimate times of divergence using two different relaxed molecular clock methods to present a timescale for macropodiform evolution and reconstruct ancestral states for grades of dental organisation. We find robust support for a basal split between Hypsiprymnodontidae and the other macropodiforms, potoroid monophyly and macropodid monophyly, with Lagostrophus as the sister-taxon to all other macropodids. Our divergence estimates suggest that kangaroos diverged from Phalangeroidea in the early Eocene, that crown-group Macropodiformes originated in the late Eocene or early Oligocene and that the potoroid–macropodid split occurred in the late Oligocene or early Miocene followed by rapid cladogenesis within these families 5 to 15 million years ago. These divergence estimates coincide with major geological and ecological changes in Australia. Ancestral state reconstructions for grades of dental organisation suggest that the grazer grade evolved independently on two different occasions within Macropodidae.
Biogeographical effects on body mass of native Australian and introduced mice, Pseudomys hermannsburgensis and Mus domesticus: an inquiry into Bergmann's Rule
Authors: Tomlinson Sean , Withers Philip C.
Published: March 2009

We investigated interactions of body mass with geographical location, and five climatic measures for two Australian rodents, the native Australian sandy inland mouse (Pseudomys hermannsburgensis) and the introduced house mouse (Mus domesticus). Correlation and regression analyses identified interactions of body mass with latitude, longitude, average highest maximum and lowest minimum temperatures, average annual rainfall, rainfall variability, and aridity. There was a significant correlation of body mass with latitude and longitude for Mus domesticus and P. hermannsburgensis. House mice were heavier in the south and east, and sandy inland mice were heavier in the north and east. M. domesticus conforms to Bergmann’s Rule, while P. hermannsburgensis does not. Maximum temperature, aridity and rainfall variability significantly influenced body mass of M. domesticus, which was heavier at cooler maxima, in less arid areas, and in areas of greater rainfall variability. Only aridity significantly influenced body mass of P. hermannsburgensis, which was heavier in more arid areas. Temperature did not interact significantly with body mass. After accounting for climatic variables, there was still a significant relationship between the residuals of body mass with locality for both species, with a negative influence of latitude and a positive influence of longitude in both; the latitudinal interaction for both species was converse to Bergmann’s Rule. We suggest that latitude, ambient temperature and other selection pressures (such as aridity or productivity) can act in opposing directions, and speculate that the influence of other factors, such as food availability or sociality, may be more important than latitude or ambient temperature.
Theoretical predictions strongly support decision accuracy as a major driver of ecological specialization
Authors: Tosh Colin R. , Krause Jens , Ruxton Graeme D.
Published: March 2009

We examine the proposal that the high levels of ecological specialization seen in many animals has been driven by benefits in decision accuracy that accrue from this resource-use strategy. Using artificial analogs of real neural processing (artificial neural networks), we examine the relationship between decision accuracy, level of ecological specialization/generalization, and the punishment/reward for selecting non-host resources. We demonstrate that specialists make more accurate resource-use decisions than generalists when the consequences of using a non-host are neutral or positive but not very positive. Pronounced unsuitability of non-host resources in fact promotes higher decision accuracy in generalists. These unusual predictions can be explained by the special properties of neural processing systems and are entirely consistent with patterns of performance of many specialists in nature, where non-used resources are, curiously, often quite suitable for growth and reproduction. They potentially reconcile the long-observed discrepancy between the presence of high levels of ecological specialization in many animal groups and the absence of strong negative fitness correlations across resources. The strong theoretical support obtained here, and the equally good support in experimental studies elsewhere, should bring the “neural limitations” hypothesis to the forefront of research on the evolutionary determinants of ecological range.
Larval dispersal connects fish populations in a network of marine protected areas
Authors: Planes Serge , Jones Geoffrey P. , Thorrold Simon R.
Published: March 2009

Networks of no-take marine protected areas (MPAs) have been widely advocated for the conservation of marine biodiversity. But for MPA networks to be successful in protecting marine populations, individual MPAs must be self-sustaining or adequately connected to other MPAs via dispersal. For marine species with a dispersive larval stage, populations within MPAs require either the return of settlement-stage larvae to their natal reserve or connectivity among reserves at the spatial scales at which MPA networks are implemented. To date, larvae have not been tracked when dispersing from one MPA to another, and the relative magnitude of local retention and connectivity among MPAs remains unknown. Here we use DNA parentage analysis to provide the first direct estimates of connectivity of a marine fish, the orange clownfish (
Amphiprion percula
), in a proposed network of marine reserves in Kimbe Bay, Papua New Guinea. Approximately 40% of
A. percula
larvae settling into anemones in an island MPA at 2 different times were derived from parents resident in the reserve. We also located juveniles spawned by Kimbe Island residents that had dispersed as far as 35 km to other proposed MPAs, the longest distance that marine larvae have been directly tracked. These dispersers accounted for up to 10% of the recruitment in the adjacent MPAs. Our findings suggest that MPA networks can function to sustain resident populations both by local replenishment and through larval dispersal from other reserves. More generally, DNA parentage analysis provides a direct method for measuring larval dispersal for other marine organisms.
Recent speciation ofCapsella rubellafromCapsella grandiflora, associated with loss of self-incompatibility and an extreme bottleneck
Authors: Guo Ya-Long , Bechsgaard Jesper S. , Slotte Tanja , Neuffer Barbara , Lascoux Martin , Weigel Detlef , Schierup Mikkel H.
Published: March 2009

Flowering plants often prevent selfing through mechanisms of self-incompatibility (S.I.). The loss of S.I. has occurred many times independently, because it provides short-term advantages in situations where pollinators or mates are rare. The genusCapsella, which is closely related toArabidopsis, contains a pair of closely related diploid species, the self-incompatibleCapsella grandifloraand the self-compatibleCapsella rubella. To elucidate the transition to selfing and its relationship to speciation ofC. rubella, we have made use of comparative sequence information. Our analyses indicate thatC. rubellaseparated fromC. grandiflorarecently (≈30,000–50,000 years ago) and that breakdown of S.I. occurred at approximately the same time. Contrasting the nucleotide diversity patterns of the 2 species, we found thatC. rubellahas only 1 or 2 alleles at most loci, suggesting that it originated through an extreme population bottleneck. Our data are consistent with diploid speciation by a single, selfing individual, most likely living in Greece. The new species subsequently colonized the Mediterranean by Northern and Southern routes, at a time that also saw the spread of agriculture. The presence of phenotypic diversity within modernC. rubellasuggests that this species will be an interesting model to understand divergence and adaptation, starting from very limited standing genetic variation.
Glucocorticoid regulation of preproglucagon transcription and RNA stability during stress
Authors: Zhang Rong , Packard Benjamin A. , Tauchi Miyuki , D'Alessio David A. , Herman James P.
Published: March 2009

Stress elicits a synchronized response of the endocrine, sympathetic, and central nervous systems to preserve homeostasis and well-being. Glucagon-like peptide-1 (GLP-1), a primary posttranslational product of the preproglucagon (PPG) gene, activates both physical and psychological stress responses. The current study examined mechanisms regulating expression of PPG gene products in the hindbrain. Our results indicate that PPG mRNA decreases rapidly after exposure to acute stressors of multiple modalities. Reduced mRNA levels are accompanied by reduced GLP-1 immunoreactivity in the paraventricular nucleus of hypothalamus, suggesting release at PPG terminals. Stress-induced decrements in PPG mRNA were attenuated in adrenalectomized-corticosterone-replaced rats, suggesting that mRNA down-regulation is due at least in part to glucocorticoid secretion. In contrast, acute stress increased levels of PPG heteronuclear RNA (hnRNA) in a glucocorticoid-dependent manner, suggesting that decreases in PPG mRNA are due to increased degradation rather than reduced transcription. Glucocorticoid administration to unstressed rats is sufficient to cause decrements in PPG mRNA and increments in PPG hnRNA. These findings suggest that glucocorticoids deplete the pool of transcribed PPG mRNA and concurrently stimulate PPG gene transcription, with the latter allowing a mechanism for replenishment of PPG mRNA after stress cessation. The combination of rapid PPG mRNA depletion and initiation of PPG transcription within 30 min is consistent with a rapid action of glucocorticoids on GLP-1 bioavailability, resulting in a transient reduction in the capacity for neuropeptidergic excitation of stress responses.
Posttranscriptional regulation of interleukin-10 expression by hsa-miR-106a
Authors: Sharma Amit , Kumar Manish , Aich Jyotirmoi , Hariharan Manoj , Brahmachari Samir K. , Agrawal Anurag , Ghosh Balaram
Published: March 2009

IL-10 is a key regulator of the immune system that critically determines health and disease. Its expression is finely tuned both at the transcriptional and posttranscriptional levels. Although the importance of posttranscriptional regulation of IL-10 has been previously shown, understanding the underlying mechanisms is still in its infancy. In this study, using a combination of bioinformatics and molecular approaches, we report that microRNA (hsa-miR-106a) regulates IL-10 expression. The hsa-miR-106a binding site in the 3′ UTR of
IL10
has been identified by site-directed mutagenesis studies. Also, the involvement of transcription factors, Sp1 and Egr1, in the regulation of hsa-miR-106a expression and concomitant decrease in the IL-10 expression, has also been demonstrated. In summary, our results showed that IL-10 expression may be regulated by miR-106a, which is in turn transcriptionally regulated by Egr1 and Sp1.
Adult deafness induces somatosensory conversion of ferret auditory cortex
Authors: Allman Brian L. , Keniston Leslie P. , Meredith M. Alex
Published: March 2009

In response to early or developmental lesions, responsiveness of sensory cortex can be converted from the deprived modality to that of the remaining sensory systems. However, little is known about capacity of the adult cortex for cross-modal reorganization. The present study examined the auditory cortices of animals deafened as adults, and observed an extensive somatosensory conversion within as little as 16 days after deafening. These results demonstrate that cortical cross-modal reorganization can occur after the period of sensory system maturation.
The capillarity of nanometric water menisci confined inside closed-geometry viral cages
Authors: Carrasco C. , Douas M. , Miranda R. , Castellanos M. , Serena P. A. , Carrascosa J. L. , Mateu M. G. , Marqués M. I. , de Pablo P. J.
Published: March 2009

We present an investigation of water menisci confined in closed geometries by studying the structural effects of their capillary forces on viruses during the final stage of desiccation. We used individual particles of the bacteriophage ϕ29 and the minute virus of mice. In both cases the genomic DNA was ejected from the capsid. However, although the structural integrity of the minute virus of mice was essentially preserved, the ϕ29 capsid underwent a wall-to-wall collapse. We provide evidence that the capillary forces of water confined inside the viruses are mainly responsible for these effects. Moreover, by performing theoretical simulations with a lattice gas model, we found that some structural differences between these 2 viruses may be crucial to explain the different ways in which they are affected by water menisci forces confined at the nanoscale.
The endometrium responds differently to cloned versus fertilized embryos
Authors: Bauersachs Stefan , Ulbrich Susanne E. , Zakhartchenko Valeri , Minten Megan , Reichenbach Myriam , Reichenbach Horst-Dieter , Blum Helmut , Spencer Thomas E. , Wolf Eckhard
Published: March 2009

Although somatic cell nuclear transfer (SCNT) cloning is more efficient in cattle than in any other species tested so far, there is a high rate of pregnancy failure that has been linked to structural and functional abnormalities of the placenta. We tested the hypothesis that these changes may originate from disturbed embryo–maternal interactions in the peri-implantation period. Therefore, we evaluated the response of the endometrium to SCNT embryos (produced from 7 different fetal fibroblast cell lines) as compared with embryos derived from in vitro fertilization (IVF). SCNT embryos and IVF embryos were cultured under identical conditions to the blastocyst stage (day 7) and were transferred to corresponding recipients, which were slaughtered at day 18 of pregnancy. The mRNA profiles of endometrium samples were obtained using a custom cDNA microarray enriched for transcripts differentially expressed in the endometrium and/or oviduct epithelium during the estrous cycle and/or early pregnancy. Overall, the variation in mRNA profiles was greater in the SCNT group than in the IVF group. Furthermore, 58 transcripts were differentially abundant in endometria from SCNT and IVF pregnancies. Prominent examples are orphan nuclear receptor COUP-TFII and connexin 43, both known to play important roles in uterine receptivity and conceptus placentation. These findings suggest that placental failure in bovine clone pregnancies may originate from abnormal embryo–maternal communication that develops during the peri-implantation period. Endometrium transcriptome profiles may serve as a tool to evaluate SCNT embryos for their ability to establish pregnancy and develop a functional placenta.
Model of mouth-to-mouth transfer of bacterial lipoproteins through inner membrane LolC, periplasmic LolA, and outer membrane LolB
Authors: Okuda Suguru , Tokuda Hajime
Published: March 2009

Outer membrane-specific lipoproteins in
Escherichia coli
are released from the inner membrane by an ATP-binding cassette transporter, the LolCDE complex, which causes the formation of a soluble complex with a periplasmic molecular chaperone, LolA. LolA then transports lipoproteins to the outer membrane where an outer membrane receptor, LolB, incorporates lipoproteins into the outer membrane. The molecular mechanisms underlying the Lol-dependent lipoprotein sorting have been clarified in detail. However, it remained unclear how Lol factors interact with each other to conduct very efficient lipoprotein transfer in the periplasm where ATP is not available. To address this issue, a photo-reactive phenylalanine analogue,
p
-benzoyl-phenylalanine, was introduced at various positions of LolA and LolB, of which the overall structures are very similar and comprise an incomplete β-barrel with a hydrophobic cavity inside. Cells expressing LolA or LolB derivatives containing the above analogue were irradiated with UV for in vivo photo-cross-linking. These analyses revealed a hot area in the same region of LolA and LolB, through which LolA and LolB interact with each other. This area is located at the entrance of the hydrophobic cavity. Moreover, this area in LolA is involved in the interaction with a membrane subunit, LolC, whereas no cross-linking occurs between LolA and the other membrane subunit, LolE, or ATP-binding subunit LolD, despite the structural similarity between LolC and LolE. The hydrophobic cavities of LolA and LolB were both found to bind lipoproteins inside. These results indicate that the transfer of lipoproteins through Lol proteins occurs in a mouth-to-mouth manner.
Interference of mismatch and base excision repair during the processing of adjacent U/G mispairs may play a key role in somatic hypermutation
Authors: Schanz Silvia , Castor Dennis , Fischer Franziska , Jiricny Josef
Published: March 2009

In eukaryotic mismatch repair (MMR), degradation of the error-containing strand initiates at nicks or gaps that can be up to a kilobase away from the mispair. These discontinuities may be the ends of Okazaki fragments or the 3′-termini of the leading strands during replication, whereas the termini of invading strands may fulfill this role during recombination. Here we show that, in extracts of human cells, MMR can initiate also at sites of ongoing base excision repair. Although unlikely under normal circumstances, this situation may arise in vivo during somatic hypermutation (SHM) and class switch recombination of Ig genes, where activation-induced cytidine deaminase (AID) generates multiple U/G mismatches in the variable or switch regions. Uracil should normally be excised by base excision repair (BER), but we show here that MMR proteins activated by a nearby mismatch interfere with uracil processing to generate long single-stranded gaps. We postulate that, in a subset of the repair events, filling-in of the MMR-generated gaps might be catalyzed by the error-prone polymerase-η, rather than by the high-fidelity polymerase-δ. Because polymerase-η has a propensity to misinsertions opposite adenine residues, the above mechanism would help explain why SHM affects not only C/G, but also A/T base pairs.
A membrane interferometer
Authors: Ganesan Prasad V. , Boxer Steven G.
Published: March 2009

Freestanding phospholipid bilayers have been assembled spanning shallow, micrometer-sized wells etched into a Si wafer substrate so that the bilayers are near (within hundreds of nanometers) but not in contact with the wafer surface. The proximity of the bilayers to the highly reflective Si/SiO
2
interface allows them to be probed by using fluorescence-interference techniques. These interferometry measurements show that the bilayers are curved and that the curvature can be varied by changes in osmotic pressure. Furthermore, the ionophore gramicidin can be incorporated into the bilayers, making them selectively permeable to monovalent cations. This freestanding architecture may overcome surface-interaction problems that occur when cell membrane proteins are introduced into solid supported bilayers, while also allowing for high-precision measurements of changes in fluorophore position by interferometry.
Smoking worsens the prognosis of mild abnormalities in cervical cytology
Authors: GUARISI RENATA , SARIAN LUIS OTAVIO , HAMMES LUCIANO SERPA , LONGATTO‐FILHO ADHEMAR , DERCHAIN SOPHIE F.M. , ROTELI‐MARTINS CECÍLIA , NAUD PAULO , ERŽEN MOJCA , BRANCA MARGHERITA , TATTI SÍLVIO , COSTA SILVANO , SYRJÄNEN STINA , BRAGANÇA JOANA F. , SYRJÄNEN KARI
Published: March 2009

Objective. To examine the effect of smoking on the incidence of low‐ and high‐grade cervical intraepithelial neoplasia (CIN) in women with a baseline Pap smear of atypical squamous cells (ASC) or a low‐grade squamous intraepithelial lesion (LSIL). Design. Prospective study in which a cohort of women with normal colposcopy and ASC/LSIL at baseline were followed at 6‐month intervals of up to 36 months. Women were grouped in post‐hoc analysis according to their smoking behavior: never (or past) smokers and current smokers. Setting. This report was based on data from the Latin American Screening Study, conducted in São Paulo, Campinas, Porto Alegre (Brazil) and Buenos Aires (Argentina). Population. A subset of 150 women derived from a cohort of 1,011 women. Methods. Multivariate Cox analysis and Kaplan–Meier curves were used. Main outcome measures. Low‐ and high‐grade CIN during follow‐up. Results. The only factor related to an increased risk of developing CIN was the positive high‐risk (hr) HPV status (hazard ratio (HR) = 3.42; 95% CI: 1.11–9.43). A total of 21 cases of incident CIN were detected during follow‐up. Of these, 11 appeared in the group of 67 smokers and 10 among the 83 non‐smoker women (log‐rank, p = 0.33). Smoking status was not associated with the risk of developing CIN (HR = 0.73; 95% CI: 0.40–1.33). However, when restricting the analysis to high‐grade CIN only (11 cases), the probability of developing the disease was significantly higher among smokers (p = 0.04). Conclusions. Smoking contributes additional risk for developing high‐grade CIN in women with ASC or LSIL cytology but normal colposcopy.
Optimization of computed tomography urography protocol, 1997 to 2008: Effects on radiation dose
Authors: Dahlman P. , Jangland L. , Segelsjö M. , Magnusson A.
Published: March 2009

Background: Since computed tomography (CT) urography began to replace excretory urography as the primary imaging technique in uroradiology, the collective radiation dose to the patients has increased.

Purpose: To examine the changes in the CT urography protocol for investigating suspected urinary tract malignancy between the years 1997 and 2008, and how these changes have influenced the mean effective dose.

Material and Methods: The study was based on 102 patients (mean age 66.1±14.8 years, range 31–89 years; 30 female, 72 male) divided into five groups (groups A–E) corresponding to the time points at which changes were made to the CT urography protocol. The mean effective doses were estimated using the ImPACT CT Patient Dosimetry Calculator.

Results: The number of scan phases at CT urography was reduced from four to three in 1999, resulting in a reduction of the mean effective dose from 29.9/22.5 (female [F]/male [M]) mSv (group A) to 26.1/18.9 (F/M) mSv (group B). In 2001, mAs settings were adapted to patient size, and the mean effective dose was reduced to 16.8/12.0 (F/M) mSv (group C). In 2005, scans were performed with a multidetector-row CT equipped with automatic tube current modulation in the x- and y-axis (CARE Dose). The effective mAs was also lowered in the unenhanced and excretory phase, yet the mean effective dose increased to 18.2/13.1 (F/M) mSv (group D), since the effective mAs had to be increased in the corticomedullary phase to maintain image quality. In 2008, as tube current modulation in the x-, y-, and z-axis was introduced (CARE Dose4D), the mean effective dose was reduced to 11.7/8.8 (F/M) mSv (group E).

Conclusion: This study shows that the individual mean effective dose to patients undergoing CT urography has decreased by 60%, from 29.9/22.5 (F/M) mSv in 1997 to 11.7/8.8 (F/M) mSv in 2008.
Magnetic resonance coronary angiography: Comparison between a Gd-BOPTA- and a Gd-DTPA-enhanced spoiled gradient-echo sequence and a non-contrast-enhanced steady-state free-precession sequence
Authors: Nassenstein K. , Breuckmann F. , Hunold P. , Barkhausen J. , Schlosser T.
Published: March 2009

Background: Several studies have demonstrated that the administration of contrast agents is advantageous in magnetic resonance coronary angiography (MRCA).

Purpose: To compare a non-contrast-enhanced steady-state free-precession (SSFP) with a contrast-enhanced inversion recovery spoiled gradient-echo (IR-GE) sequence using two different contrast agents for MRCA.

Material and Methods: Eight healthy volunteers were examined on a 1.5T MR scanner. For non-contrast-enhanced MRCA, a breath-hold three-dimensional (3D) SSFP sequence (repetition/echo time [TR/TE] 3.9/1.7 ms, flip angle [FA] 65°) was used. Contrast-enhanced MRCA was performed repetitively in two imaging sessions over 30 min after injection of 0.2 mmol/kg body weight gadobenate dimeglumine (Gd-BOPTA) or gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) using a breath-hold 3D IR-GE sequence (TR/TE 4.1/1.7 ms, FA 15°). The signal-to-noise ratios (SNR) of the coronary arteries, as well as the contrast-to-noise ratios (CNR) between coronary arteries and perivascular tissue, were calculated for all images. Blood T1 values were repetitively estimated over 30 min using an SSFP sequence with incrementally increasing inversion times (TR/TE 2.4/1.0 ms, FA 50°).

Results: Gd-BOPTA-enhanced images showed significantly ( P<0.05) higher SNR and CNR compared to Gd-DTPA-enhanced images for all times after contrast injection (SNR: 1 min post injection [PI] 26.4±4.2 vs. 16.2±3.1; CNR: 1 min PI 21.4±3.7 vs. 13.2±2.6). Compared to the SSFP images, the Gd-BOPTA-enhanced images showed higher CNR values for all times after injection (1 min PI 21.4±3.7 vs. 13.8±5.5; P<0.05), whereas the Gd-DTPA-enhanced images did not (1 min PI 13.2±2.6 vs. 13.8±5.5; P>0.05). Blood T1 estimates were not significantly different for either agent 1 min after administration ( P>0.05), but they were significantly lower for Gd-BOPTA ( P<0.05) from 7 to 25 min after injection.

Conclusion: Compared to non-contrast-enhanced SSFP images, only Gd-BOPTA-enhanced images show a significantly improved contrast between the coronary arteries and the surrounding tissue.
Protection by Glycyrrhizin against Warm Ischemia‐Reperfusion–Induced Cellular Injury and Derangement of the Microcirculatory Blood Flow in the Rat Liver
Authors: MABUCHI AYAKO , WAKE KENJIRO , MARLINI MUHAMAD , WATANABE HITOMI , WHEATLEY ANTONY M.
Published: March 2009

Background/Aim: The mechanism by which ischemia‐reperfusion (I/R)‐induced derangement of the hepatic microcirculation leads to tissue injury is not fully understood. We postulated that alterations to the hepatic microcirculation, including hemodynamic derangement and increased leukocyte‐endothelium interaction, play a role, and that glycyrrhizin exerts its hepatoprotective effects, in part, by reducing these microcirculatory changes. Materials and Methods: Wistar rats were subjected to 30–60 minutes segmental hepatic ischemia, followed by 120 minutes of reperfusion. Glycyrrhizin was administered prior to ischemia. Using intravital fluorescence microscopy, the administration of fluorescein isothiocyanate–conjugated erythrocytes allowed the measurement of erythrocyte‐velocity (RBCvel), lobular, and sinusoidal perfusion. Bleb formation was observed by electron microscopy. Blood and tissue were taken for the assessment of liver injury. Results: Glycyrrhizin reduced I/R‐induced liver injury (histology, liver enzymes) and reduced hepatocyte apoptosis (TUNEL, caspase‐3 activity). Glycyrrhizin inhibited hepatocyte bleb formation and reversed the I/R‐induced reductions in lobular perfusion and RBCvel. Leukocyte rolling and adherence in postsinusoidal venules and neutrophil infiltration were reduced by glycyrrhizin. I/R‐induced elevation in HMGB1 was prevented by glycyrrhizin. Conclusions: Early bleb formation with deranged microcirculatory flow and leukocyte‐endothelium interaction would appear to contribute to I/R‐induced hepatocellular injury. Glycyrrhizin exerts its hepatoprotective effect by preventing these changes, in addition to a direct cellular effect.
New Joint Design to Create a More Natural and Efficient Biped
Authors: Gini Giuseppina , Scarfogliero Umberto , Folgheraiter Michele
Published: March 2009

This paper presents a human‐oriented approach to design the mechanical architecture and the joint controller for a biped robot. Starting from the analysis of the human lower limbs, we figured out which features of the human legs are fundamental for a correct walking motion, and can be adopted in the mechanical design of a humanoid robot. We focus here on the knee, designed as a compliant human‐like knee instead of a classical pin‐joint, and on the foot, characterised by the mobility and lightness of the human foot. We implemented an elastic actuator, with a simple position control paradigm that sets the joint stiffness in real time, and developed the basic controller. Results in simulation are discussed. In our approach the robot gains in adaptability and energetic efficiency, which are the most challenging issues for a biped robot.
A role for human skin–resident T cells in wound healing
Authors: Toulon Antoine , Breton Lionel , Taylor Kristen R. , Tenenhaus Mayer , Bhavsar Dhaval , Lanigan Caroline , Rudolph Ross , Jameson Julie , Havran Wendy L.
Published: March 2009

Epidermal T cells have been shown to play unique roles in tissue homeostasis and repair in mice through local secretion of distinct growth factors in the skin. Human epidermis contains both αβ+ and γδ+ T cells whose functional capabilities are not understood. We demonstrate that human epidermal T cells are able to produce insulin-like growth factor 1 (IGF-1) upon activation and promote wound healing in a skin organ culture model. Moreover, an analysis of the functional capabilities of T cells isolated from acute versus chronic wounds revealed a striking difference. Both αβ+ and Vδ1+ T cells isolated from acute wounds actively produced IGF-1, demonstrating that they are activated during tissue damage to participate in wound repair. In contrast, IGF-1 production could not be detected in T cells isolated from chronic wounds. In fact, skin T cells isolated from chronic wounds were refractory to further stimulation, suggesting an unresponsive state. Collectively, these results define a novel role for human epidermis–resident T cells in wound healing and provide new insight into our understanding of chronic wound persistence.
Transcriptional complexes formed by NFAT dimers regulate the induction of T cell tolerance
Authors: Soto-Nieves Noemi , Puga Irene , Abe Brian T. , Bandyopadhyay Sanmay , Baine Ian , Rao Anjana , Macian Fernando
Published: March 2009

In T cells, anergy can be induced after T cell receptor engagement in the absence of costimulation. Under these conditions, the expression of a specific set of anergy-associated genes is activated. Several lines of evidence suggest that nuclear factor of activated T cells (NFAT) proteins may regulate the expression of many of those genes; however, the nature of the complexes responsible for the induction of this new program of gene expression is unknown. Here, we show that transcriptional complexes formed by NFAT homodimers are directly responsible for the activation of at least two anergy-inducing genes, Grail and Caspase3. Our data shows that Grail expression is activated by direct binding of NFAT dimers to the Grail promoter at two different sites. Consequently, a mutant NFAT protein with impaired ability to dimerize is not able to induce an unresponsive state in T cells. Our results not only identify a new biological function for NFAT dimers but also reveal the different nature of NFAT-containing complexes that induce anergy versus those that are activated during a productive immune response. These data also establish a basis for the design of immunomodulatory strategies that specifically target each type of complex.
Statistical model for whole genome sequencing and its application to minimally invasive diagnosis of fetal genetic disease
Authors: Chu Tianjiao , Bunce Kimberly , Hogge W. Allen , Peters David G.
Published: March 2009

There is currently great interest in the development of methods for the minimally invasive diagnosis of fetal genetic disease using cell-free DNA from maternal plasma samples obtained in the first trimester of pregnancy. With the rapid development of high-throughput sequencing technology, the possibility of detecting the presence of trisomy fetal genomes in the maternal plasma DNA sample has recently been explored. The major concern of this whole genome sequencing approach is that, while detecting the karyotype of the fetal genome from the maternal plasma requires extremely high accuracy of copy number estimation, the majority of the available high-throughput sequencing technologies require polymerase chain reaction (PCR) and are subject to the substantial bias that is inherent to the PCR process. We introduce a novel and sophisticated statistical model for the whole genome sequencing data, and based on this model, develop a highly sensitive method of Minimally Invasive Karyotyping (MINK) for the diagnosis of the fetal genetic disease. Specifically we demonstrate, by applying our statistical method to ultra high-throughput whole sequencing data, that trisomy 21 can be detected in a minor (‘fetal’) genome when it is mixed into a major (‘maternal’) background genome at frequencies as low as 5%. This observation provides additional proof of concept and justification for the further development of this method towards its eventual clinical application. Here, we describe the statistical and experimental methods that illustrate this approach and discuss future directions for technical development and potential clinical applications.

Contact:  dgp6@pitt.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Evolutionary Trace Annotation Server: automated enzyme function prediction in protein structures using 3D templates
Authors: Matthew Ward R. , Venner Eric , Daines Bryce , Murray Stephen , Erdin Serkan , Kristensen David M. , Lichtarge Olivier
Published: March 2009

Summary:The Evolutionary Trace Annotation (ETA) Server predicts enzymatic activity. ETA starts with a structure of unknown function, such as those from structural genomics, and with no prior knowledge of its mechanism uses the phylogenetic Evolutionary Trace (ET) method to extract key functional residues and propose a function-associated 3D motif, called a 3D template. ETA then searches previously annotated structures for geometric template matches that suggest molecular and thus functional mimicry. In order to maximize the predictive value of these matches, ETA next applies distinctive specificity filters—evolutionary similarity, function plurality and match reciprocity. In large scale controls on enzymes, prediction coverage is 43% but the positive predictive value rises to 92%, thus minimizing false annotations. Users may modify any search parameter, including the template. ETA thus expands the ET suite for protein structure annotation, and can contribute to the annotation efforts of metaservers.

Availability:The ETA Server is a web application available at http://mammoth.bcm.tmc.edu/eta/.

Contact:  lichtarge@bcm.edu
KEGGgraph: a graph approach to KEGG PATHWAY in R and bioconductor
Authors: Zhang Jitao David , Wiemann Stefan
Published: March 2009

Motivation: KEGG PATHWAY is a service of Kyoto Encyclopedia of Genes and Genomes (KEGG), constructing manually curated pathway maps that represent current knowledge on biological networks in graph models. While valuable graph tools have been implemented in R/Bioconductor, to our knowledge there is currently no software package to parse and analyze KEGG pathways with graph theory.

Results: We introduce the software package KEGGgraph in R and Bioconductor, an interface between KEGG pathways and graph models as well as a collection of tools for these graphs. Superior to existing approaches, KEGGgraph captures the pathway topology and allows further analysis or dissection of pathway graphs. We demonstrate the use of the package by the case study of analyzing human pancreatic cancer pathway.

Availability:KEGGgraph is freely available at the Bioconductor web site (http://www.bioconductor.org). KGML files can be downloaded from KEGG FTP site (ftp://ftp.genome.jp/pub/kegg/xml).

Contact:  j.zhang@dkfz-heidelberg.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
SBML2LaTEX: Conversion of SBML files into human-readable reports
Authors: Dräger Andreas , Planatscher Hannes , Motsou Wouamba Dieudonné , Schröder Adrian , Hucka Michael , Endler Lukas , Golebiewski Martin , Müller Wolfgang , Zell Andreas
Published: March 2009

Summary: The XML-based Systems Biology Markup Language (SBML) has emerged as a standard for storage, communication and interchange of models in systems biology. As a machine-readable format XML is difficult for humans to read and understand. Many tools are available that visualize the reaction pathways stored in SBML files, but many components, e.g. unit declarations, complex kinetic equations or links to MIRIAM resources, are often not made visible in these diagrams. For a broader understanding of the models, support in scientific writing and error detection, a human-readable report of the complete model is needed. We present SBML2LaTEX, a Java-based stand-alone program to fill this gap. A convenient web service allows users to directly convert SBML to various formats, including DVI, LaTEX and PDF, and provides many settings for customization.

Availability: Source code, documentation and a web service are freely available at http://www.ra.cs.uni-tuebingen.de/software/SBML2LaTeX.

Contact:  andreas.draeger@uni-tuebingen.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Some topics on a new class of elastic bodies
Authors: Bustamante Roger
Published: March 2009

In this paper, we study the problem of prescribing deformation as a function of stresses. For the particular case of small deformations, we find a weak formulation, from which we define the constitutive equation of a
Green-like
material, where an
energy
function that depends on the Cauchy stress tensor is proposed. Constraints on the deformation are studied for this new class of elastic bodies.
Signals of recent positive selection in a worldwide sample of human populations
Authors: Pickrell Joseph K. , Coop Graham , Novembre John , Kudaravalli Sridhar , Li Jun Z. , Absher Devin , Srinivasan Balaji S. , Barsh Gregory S. , Myers Richard M. , Feldman Marcus W. , Pritchard Jonathan K.
Published: March 2009

Genome-wide scans for recent positive selection in humans have yielded insight into the mechanisms underlying the extensive phenotypic diversity in our species, but have focused on a limited number of populations. Here, we present an analysis of recent selection in a global sample of 53 populations, using genotype data from the Human Genome Diversity-CEPH Panel. We refine the geographic distributions of known selective sweeps, and find extensive overlap between these distributions for populations in the same continental region but limited overlap between populations outside these groupings. We present several examples of previously unrecognized candidate targets of selection, including signals at a number of genes in the NRG–ERBB4 developmental pathway in non-African populations. Analysis of recently identified genes involved in complex diseases suggests that there has been selection on loci involved in susceptibility to type II diabetes. Finally, we search for local adaptation between geographically close populations, and highlight several examples.
Cathepsin D activity protects against development of type AA amyloid fibrils
Authors: Van Der Hilst J. C. H. , Kluve‐Beckerman B. , Van Der Meer J. W. M. , Simon A.
Published: March 2009

Background  The extracellular, fibrillar deposits of reactive (secondary) amyloidosis are composed of amyloid A (AA) protein, a proteolytically derived fragment of the acute phase protein serum amyloid A (SAA). While complete degradation of SAA precludes amyloid formation, limited cleavage which generates AA protein is considered part of the pathogenic mechanism.

Materials and methods  In this study, we investigated SAA degradation by lysosomal enzymes cathepsins B, D, and K, and assessed the impact of cathepsin activity on AA amyloid formation in a cell culture model using peripheral blood mononuclear cells from healthy volunteers.

Results  Lysates of human mononuclear cells were capable of degrading SAA. Degradation was significantly reduced by inhibition of cathepsin D with pepstatin A. Inhibition of cathepsin B or cathepsin K, however, had no effect. The SAA fragment pattern generated by mononuclear cell lysates was similar to that produced by incubating SAA with purified human cathepsin D. Consistent with in vitro findings, amyloid formation in human monocyte cultures was increased by 43% when cathepsin D was inhibited, but remained unaffected by inhibition of cathepsin B or cathepsin K.

Conclusion  These data provide evidence that cathepsin D but not cathepsin B or cathepsin K is physiologically important in SAA degradation and hence in preventing SAA from accumulating and serving as precursor of AA amyloid fibrils.
Characterization and utilization of microsatellite loci in the New World screwworm fly, Cochliomyia hominivorax
Authors: GRIFFITHS A. M. , EVANS L. M. , STEVENS J. R.
Published: March 2009

Abstract New World screwworm populations in North and Central America have been the targets of virtually continuous eradication attempts by sterile insect technique (SIT) since the 1950s. Nevertheless, in some areas, such as Jamaica, SIT control programmes have failed. Reasons for the failure of SIT‐based control programmes in some locations are unknown, but it has been hypothesized that failure may be related to mating incompatibility between sterile and wild fly populations or to the existence of sexually incompatible cryptic species. This paper outlines the development of a suite of four new microsatellite loci which can be used to study intra‐specific relationships between populations of Cochliomyia hominivorax from the Caribbean and South America, which represent those populations involved in, or earmarked for, forthcoming SIT control. Cross‐amplification with the secondary screwworm, Cochliomyia macellaria, was also successful with three of the new loci. We present results which suggest that populations from Trinidad and Jamaica form distinct groupings of flies and that C. hominivorax from Trinidad appears particularly distinct.
Phylogeography and recent emergence of the Old World screwworm fly, Chrysomya bezziana, based on mitochondrial and nuclear gene sequences
Authors: READY P. D. , TESTA J. M. , WARDHANA A. H. , AL‐IZZI M. , KHALAJ M. , HALL M. J. R.
Published: March 2009

Abstract A previous study had identified an African and an Asian race of the Old World screwworm fly, Chrysomya bezziana Villeneuve (Diptera: Calliphoridae), based on the 3′ terminal 279 basepairs (bp) of the mitochondrial cytochrome b gene. The current study improved the phylogeographic resolution of cytochrome b for this species by characterizing more of the gene (the 3′ terminal 715 bp) and by sampling more geographical populations, including Oman, Iran, Hong Kong and the Indonesian islands of Sulawesi and East Sumba. Strong support was found for recognizing an African race, but not for a monophyletic Asian race. The cladistic and genealogical relationships among the Asian populations were complex. There was sufficient genetic homogeneity throughout separate regions (mainland Asia and each Indonesian island) to suggest that there are no reproductive barriers within each region that might necessitate the production of more than one strain for control by the sterile insect technique (SIT). Primers were designed for the amplification by polymerase chain reaction of two nuclear loci, the highly conserved elongation factor‐1αgene and the less conserved white gene, and the preliminary results indicated that these genes showed the same pattern of small‐scale regional variation as cytochrome b. The cytochrome b haplotypes are useful markers for identifying the geographical origins of any emerging infestations of the species: the absence of Indonesian and African haplotypes in the Middle East demonstrates that the large‐scale transport of livestock is not spreading Old World screwworm.