bluuebunny/crossref_metadata_2025 huggingface dataset:
Demography and elasticity of the diamond stingray, Dasyatis dipterura: parameter uncertainty and resilience to fishing pressure
Authors: Smith Wade D. , Cailliet Gregor M. , Cortés Enric
Published: July 2008

Despite their abundance in near-shore tropical and subtropical marine environments, which support much of the world’s elasmobranch fisheries, population dynamics and impacts of fisheries on stingrays are poorly documented. Age-structured demographic models were developed using empirical estimates of fecundity, longevity and maturity to project population growth parameters and potential responses to fishing mortality of Dasyatis dipterura from the Bahía Magdalena lagoon complex, México. Monte Carlo simulation was incorporated to include uncertainty in life history parameters into model projections. Six models were developed using deterministic and probabilistic approaches under unexploited and exploited (fishing mortality = 0.05 year–1) conditions. Mean annual population growth rates (λ) of 1.05–1.06 (5–6% increase), net reproductive rates of 2.3–2.4 and generation times of 14.9–16.5 years were projected from simulations. The introduction of a low fishing mortality into probabilistic models produced λ of 1.01 year–1. Elasticity analysis indicated that population growth rates for D. dipterura are more strongly influenced by the survival of juvenile and adult stages than by survival of neonates or changes in fecundity. Demographic analyses indicated that D. dipterura has a low intrinsic growth potential and limited resilience to fishing pressure. Localised depletion or population collapses are therefore likely to occur through unrestricted, unmonitored fishing effort.
Invasive character of the brine shrimp Artemia franciscana Kellogg 1906 (Branchiopoda: Anostraca) and its potential impact on Australian inland hypersaline waters
Authors: Ruebhart David R. , Cock Ian E. , Shaw Glen R.
Published: July 2008

Brine shrimp (Artemia species) are a major faunal element in many hypersaline biotopes throughout the world and are used extensively in aquaculture, the aquarium trade, solar salt fields and in toxicity bioassays. Commercially available brine shrimp are generally Artemia franciscana cysts, primarily harvested from Great Salt Lake, Utah, USA. The invasive potential of this species raises concerns about its presence in Australia. We reviewed recent overseas reports of the occurrence of A. franciscana populations and confirm that the use of this species has extended its natural geographic range through both deliberate and inadvertent releases. In Australia, Artemia species have been previously identified as being a threat to ecosystem health and biodiversity; however, the specific recognition of A. franciscana was not made. In reviewing the biogeography of Artemia species in Australia, we provide a collation of the reported populations of A. franciscana. The biological attributes of this species contributing to its invasive success are also compiled. The implications of further releases and increases in the range of this species to Australian inland waters are discussed. We appeal for increased vigilance regarding the importation and use of this potentially highly invasive species and monitoring for its presence.
Corrigendum to: Temporal patterns of gastropod egg mass deposition on southeastern Australian shores
Authors: Przeslawski Rachel
Published: July 2008

Spawning of marine invertebrates may be affected by environmental factors (e.g. food availability, environmental stress) or intrinsic factors (e.g. phylogenetic constraints, developmental mode); intrinsic factors may obscure environmental effects. Two-year surveys of gastropod egg mass deposition were conducted at two rocky intertidal sites in south-eastern Australia to test the following hypotheses: (1) temporal patterns of spawning are more similar within taxonomic order than across orders; and (2) species with planktotrophic larvae are more likely to spawn in seasons coinciding with maximum food availability. There were no discernible effects of either order or developmental mode on spawning patterns, suggesting that spawning behaviour is unrelated to taxonomic order or larval food availability. Alternatively, low numbers of species in certain groups may have increased the risk of not detecting significant effects (type II error). Comparisons with anecdotal data from other regions suggest that developmental mode may indeed play a role in marine gastropod spawning. Criteria are provided for future comparative studies, including a direct focus on specific families and the inclusion of similar latitudes and habitats to those used here. Such studies will help to determine the roles of developmental mode, food availability and environmental stress in the evolution of egg mass deposition.
Effects of sewage discharges on microbial components in tropical coastal waters (Senegal, West Africa)
Authors: Bouvy Marc , Briand Enora , Boup Maimouna M. , Got Patrice , Leboulanger Christophe , Bettarel Yvan , Arfi Robert
Published: July 2008

Coastal ecosystems are frequently submitted to anthropogenic pressure but little is known about how the dynamics of aquatic communities can be altered. The impact of urban and industrial discharges on microbial plankton was studied in Hann Bay near Dakar (Senegal) on the Atlantic Ocean. Spatial patterns were studied using three transects, with a total of 20 stations, during two periods in May and November (before and after the seasonal upwelling), revealing a clear contrast between near shore stations and the intermediate and seaward stations. In November, phytoplankton were associated with dissolved nutrient availability (e.g. with nitrate, r = 0.76) whereas in May, phytoplankton were more correlated with microbial variables (e.g. with heterotrophic nanoflagellates, r = 0.63). Most samples (40) failed to meet the quality levels for the faecal indicator bacteria (FIB) defined by the European Union bathing water quality directive. The topography plays a major role in water circulation explaining the presence of FIB at the seaward stations. The high prevalence of FIB during the two periods suggests chronic pollution and a potential risk to recreational swimmers and fish consumers in Hann Bay. Thus, as demonstrated in various temperate systems, the decline of water quality constitutes a serious problem in many West African countries.
Global cost estimates of reducing carbon emissions through avoided deforestation
Authors: Kindermann Georg , Obersteiner Michael , Sohngen Brent , Sathaye Jayant , Andrasko Kenneth , Rametsteiner Ewald , Schlamadinger Bernhard , Wunder Sven , Beach Robert
Published: July 2008

Tropical deforestation is estimated to cause about one-quarter of anthropogenic carbon emissions, loss of biodiversity, and other environmental services. United Nations Framework Convention for Climate Change talks are now considering mechanisms for avoiding deforestation (AD), but the economic potential of AD has yet to be addressed. We use three economic models of global land use and management to analyze the potential contribution of AD activities to reduced greenhouse gas emissions. AD activities are found to be a competitive, low-cost abatement option. A program providing a 10% reduction in deforestation from 2005 to 2030 could provide 0.3–0.6 Gt (1 Gt = 1 × 105g) CO2·yr−1in emission reductions and would require $0.4 billion to $1.7 billion·yr−1for 30 years. A 50% reduction in deforestation from 2005 to 2030 could provide 1.5–2.7 Gt CO2·yr−1in emission reductions and would require $17.2 billion to $28.0 billion·yr−1. Finally, some caveats to the analysis that could increase costs of AD programs are described.
In vivo
selection of genetically modified erythroblastic progenitors leads to long-term correction of β-thalassemia
Authors: Miccio Annarita , Cesari Rossano , Lotti Francesco , Rossi Claudia , Sanvito Francesca , Ponzoni Maurilio , Routledge Samantha J. E. , Chow Cheok-Man , Antoniou Michael N. , Ferrari Giuliana
Published: July 2008

Gene therapy for β-thalassemia requires stable transfer of a β-globin gene into hematopoietic stem cells (HSCs) and high and regulated hemoglobin expression in the erythroblastic progeny. We developed an erythroid-specific lentiviral vector driving the expression of the human β-globin gene from a minimal promoter/enhancer element containing two hypersensitive sites from the β-globin locus control region. Transplantation of transduced HSCs into thalassemic mice leads to stable and long-term correction of anemia with all red blood cells expressing the transgene. A frequency of 30–50% of transduced HSCs, harboring an average vector copy number per cell of 1, was sufficient to fully correct the thalassemic phenotype. In the mouse model of Cooley's anemia transplantation of transduced cells rescues lethality, leading to either a normal or a thalassemia intermedia phenotype. We show that genetically corrected erythroblasts undergo
in vivo
selection with preferential survival of progenitors harboring proviral integrations in genome sites more favorable to high levels of vector-derived expression. These data provide a rationale for a gene therapy approach to β-thalassemia based on partially myeloablative transplantation protocols.
Triggering receptor expressed on myeloid cell-like transcript 2 (TLT-2) is a counter-receptor for B7-H3 and enhances T cell responses
Authors: Hashiguchi Masaaki , Kobori Hiroko , Ritprajak Patcharee , Kamimura Yosuke , Kozono Haruo , Azuma Miyuki
Published: July 2008

The B7 family member B7-H3 (CD276) plays important roles in immune responses. However, the function of B7-H3 remains controversial. We found that murine B7-H3 specifically bound to Triggering receptor expressed on myeloid cells (TREM)-like transcript 2 (TLT-2, TREML2). TLT-2 was expressed on CD8
+
T cells constitutively and on activated CD4
+
T cells. Stimulation with B7-H3 transfectants preferentially up-regulated the proliferation and IFN-γ production of CD8
+
T cells. Transduction of TLT-2 into T cells resulted in enhanced IL-2 and IFN-γ production via interactions with B7-H3. Blockade of the B7-H3:TLT-2 pathway with a mAb against B7-H3 or TLT-2 efficiently inhibited contact hypersensitivity responses. Our results demonstrate a direct interaction between B7-H3 and TLT-2 that preferentially enhances CD8
+
T cell activation.
Genetic control of floral zygomorphy in pea (
Pisum sativum
L.)
Authors: Wang Zheng , Luo Yonghai , Li Xin , Wang Liping , Xu Shilei , Yang Jun , Weng Lin , Sato Shusei , Tabata Satoshi , Ambrose Mike , Rameau Catherine , Feng Xianzhong , Hu Xiaohe , Luo Da
Published: July 2008

Floral zygomorphy (flowers with bilateral symmetry) has multiple origins and typically manifests two kinds of asymmetries, dorsoventral (DV) and organ internal (IN) asymmetries in floral and organ planes, respectively, revealing the underlying key regulators in plant genomes that generate and superimpose various mechanisms to build up complexity and different floral forms during plant development. In this study, we investigate the loci affecting these asymmetries during the development of floral zygomorphy in pea (
Pisum sativum
L.). Two genes,
LOBED STANDARD 1
(
LST1
) and
KEELED WINGS
(
K
), were cloned that encode TCP transcription factors and have divergent functions to constitute the DV asymmetry. A previously undescribed regulator,
SYMMETRIC PETALS 1
(
SYP1
), has been isolated as controlling IN asymmetry. Genetic analysis demonstrates that DV and IN asymmetries could be controlled independently by the two kinds of regulators in pea, and their interactions help to specify the type of zygomorphy. Based on the genetic analysis in pea, we suggest that variation in both the functions and interactions of these regulators could give rise to the wide spectrum of floral symmetries among legume species and other flowering plants.
Molecular and cellular signatures of human vaccine adjuvants
Authors: Mosca F. , Tritto E. , Muzzi A. , Monaci E. , Bagnoli F. , Iavarone C. , O'Hagan D. , Rappuoli R. , De Gregorio E.
Published: July 2008

Oil-in-water emulsions are potent human adjuvants used for effective pandemic influenza vaccines; however, their mechanism of action is still unknown. By combining microarray and immunofluorescence analysis, we monitored the effects of the adjuvants MF59 oil-in-water emulsion, CpG, and alum in the mouse muscle. MF59 induced a time-dependent change in the expression of 891 genes, whereas CpG and alum regulated 387 and 312 genes, respectively. All adjuvants modulated a common set of 168 genes and promoted antigen-presenting cell recruitment. MF59 was the stronger inducer of cytokines, cytokine receptors, adhesion molecules involved in leukocyte migration, and antigen-presentation genes. In addition, MF59 triggered a more rapid influx of CD11b+ blood cells compared with other adjuvants. The early biomarkers selected by microarray, JunB and Ptx3, were used to identify skeletal muscle as a direct target of MF59. We propose that oil-in-water emulsions are the most efficient human vaccine adjuvants, because they induce an early and strong immunocompetent environment at the injection site by targeting muscle cells.
Generation ofmTert-GFP mice as a model to identify and study tissue progenitor cells
Authors: Breault David T. , Min Irene M. , Carlone Diana L. , Farilla Loredana G. , Ambruzs Dana M. , Henderson Daniel E. , Algra Selma , Montgomery Robert K. , Wagers Amy J. , Hole Nicholas
Published: July 2008

Stem cells hold great promise for regenerative medicine, but remain elusive in many tissues in part because universal markers of “stemness” have not been identified. The ribonucleoprotein complex telomerase catalyzes the extension of chromosome ends, and its expression is associated with failure of cells to undergo cellular senescence. Because such resistance to senescence is a common characteristic of many stem cells, we hypothesized that telomerase expression may provide a selective biomarker for stem cells in multiple tissues. In fact, telomerase expression has been demonstrated within hematopoietic stem cells. We therefore generated mouse telomerase reverse transcriptase (mTert)-GFP-transgenic mice and assayed the ability ofmTert-driven GFP to mark tissue stem cells in testis, bone marrow (BM), and intestine.mTert-GFP mice were generated by using a two-step embryonic stem cell-based strategy, which enabled primary and secondary screening of stably transfected clones before blastocyst injection, greatly increasing the probability of obtainingmTertreporter mice with physiologically appropriate regulation of GFP expression. Analysis of adult mice showed that GFP is expressed in differentiating male germ cells, is enriched among BM-derived hematopoietic stem cells, and specifically marks long-term BrdU-retaining intestinal crypt cells. In addition, telomerase-expressing GFP+BM cells showed long-term, serial, multilineage BM reconstitution, fulfilling the functional definition of hematopoietic stem cells. Together, these data provide direct evidence thatmTert-GFP expression marks progenitor cells in blood and small intestine, validating these mice as a useful tool for the prospective identification, isolation, and functional characterization of progenitor/stem cells from multiple tissues.
The redox activity of ERp57 is not essential for its functions in MHC class I peptide loading
Authors: Peaper David R. , Cresswell Peter
Published: July 2008

ERp57 is an oxidoreductase that, in conjunction with calnexin and calreticulin, assists disulfide bond formation in folding glycoproteins. ERp57 also forms a mixed disulfide with the MHC class I-specific chaperone tapasin, and this dimeric conjugate edits the peptide repertoire bound by MHC class I molecules. In cells unable to form the conjugate, because of tapasin mutation in human studies or ERp57 deletion in mouse studies, peptide loading is impeded. Subtle differences between the mouse and human systems have been observed. Here, we address these differences and expand the analysis to investigate the role of ERp57 redox functions in MHC class I peptide loading. We show in human cells that in the absence of conjugate formation MHC class I recruitment and/or stabilization in the MHC class I peptide-loading complex is impaired, similar to observations in mouse cells. However, we found no role for the enzymatic activities of either theaora′domain redox sites of ERp57 in peptide loading. Our data argue that the function of ERp57 in peptide loading is likely caused by other ERp57 functional domains or a combinatorial feature of the tapasin–ERp57 conjugate.
Infant‐Directed Speech Is Modulated by Infant Feedback
Authors: Smith Nicholas A. , Trainor Laurel J.
Published: July 2008

When mothers engage in infant‐directed (ID) speech, their voices change in a number of characteristic ways, including adopting a higher overall pitch. Studies have examined these acoustical cues and have tested infants' preferences for ID speech. However, little is known about how these cues change with maternal sensitivity to infant feedback in the context of interaction. In this study, each mother watched her infant (located in an adjacent sound booth) on a video screen and talked to him or her through a microphone. The mother believed that her infant could hear her voice and she attempted to make her infant happy through her vocalizations. In reality, the infant could not hear her voice. The mother's ID speech was analyzed in real time for changes in mean pitch. For half of the infant–mother dyads an experimenter surreptitiously positively engaged the infant when the voice analysis revealed a rise in pitch, thereby producing positive reinforcement to the mother for natural higher pitched ID speech. The other half were reinforced for lower pitched ID speech. Mothers raised their pitch significantly more in the former than the latter condition, illustrating that the pitch of ID speech is dynamically affected by feedback from the infant.
Comparison at 32–37 Weeks Postconception of Infants Born 1983–1989 and 1995–2004 on the Neurobehavioral Assessment of the Preterm Infant
Authors: Brown Josephine V. , Bakeman Roger , Sampers Jackie S. , Korner Anneliese F. , Constantinou Janet C. , Anand K. J. S.
Published: July 2008

In spite of numerous recent outcome studies of extremely low birth weight (ELBW) infants, no data exist on their development prior to term. In this study we traced and compared the neurobehavioral development of 251 ELBW (< 1,000 g) and 240 low birth weight (LBW; 1,000 g–2,500 g) preterms born between 1995 and 2004 from 32 to 37 weeks postconceptional age (PCA), using the Neurobehavioral Assessment of the Preterm Infant (NAPI Korner & Thom, 1990). Compared to the original NAPI cohort of 521 infants (born 1983–1989), the ELBW and LBW infants were at higher medical risk, displayed weaker motor development, a tighter scarf sign and popliteal angle at all or most PCAs, and a weaker cry at older PCAs; they did not differ in irritability and percent asleep ratings. Few differences were noted between the ELBW and LBW groups. Research is now needed to determine whether the 1995 to 2004 NAPI values of ELBW and LBW infants at 32 to 37 weeks PCA are predictive of later outcome of high‐risk preterms.
How Mothers Encourage and Discourage Infants' Motor Actions
Authors: Karasik Lana B. , Tamis‐LeMonda Catherine S. , Adolph Karen E. , Dimitropoulou Katherine A.
Published: July 2008

The content of mothers' emotional, verbal, and gestural communication to their infants was examined under conditions of potential physical risk in a laboratory motor task. Mothers encouraged and discouraged their 12‐ and 18‐month‐old infants to crawl or walk down a sloping walkway. Mothers expressed positive affect on nearly every trial. They rarely expressed purely negative affect in their faces and voices, even when discouraging. Instead, they discouraged infants with a mixture of positive and negative expressions. In both encourage and discourage conditions, mothers coupled their emotional messages with rich verbal and gestural information to elicit infants' attention, regulate their location, guide their actions, and describe the situation and potential consequences of their actions. The content of mothers' communication was attuned to infants' age and locomotor experience.
Changes in the Ability to Detect Ordinal Numerical Relationships Between 9 and 11 Months of Age
Authors: Suanda Sumarga H. , Tompson Whitney , Brannon Elizabeth M.
Published: July 2008

When are the precursors of ordinal numerical knowledge first evident in infancy? Brannon (2002) argued that by 11 months of age, infants possess the ability to appreciate the greater than and less than relations between numerical values but that this ability experiences a sudden onset between 9 and 11 months of age. Here we present 5 experiments that explore the changes that take place between 9 and 11 months of age in infants' ability to detect reversals in the ordinal direction of a sequence of arrays. In Experiment 1, we replicate the finding that 11‐ but not 9‐month‐old infants detect a numerical ordinal reversal. In Experiment 2 we rule out an alternative hypothesis that 11‐month‐old infants attended to changes in the absolute numerosity of the first stimulus in the sequence rather than a reversal in ordinal direction. In Experiment 3, we demonstrate that 9‐month‐old infants are not aided by additional exposure to each numerosity stimulus in a sequence. In Experiment 4 we find that 11‐month‐old but not 9‐month‐old infants succeed at detecting the reversal in a nonnumerical size or area‐based rule, casting doubt on Brannon's prior claim that what develops between 9 and 11 months of age is a specifically numerical ability. In Experiment 5 we demonstrate that 9‐month‐old infants are capable of detecting a reversal in ordinal direction but only when there are multiple converging cues to ordinality. Collectively these data indicate that at 11 months of age infants can represent ordinal relations that are based on number, size, or cumulative area, whereas at 9 months of age infants are unable to use any of these dimensions in isolation but instead require a confluence of cues.
Mother–Infant Person‐ and Object‐Directed Interactions in Latino Immigrant Families: A Comparative Approach
Authors: Cote Linda R. , Bornstein Marc H. , Haynes O. Maurice , Bakeman Roger
Published: July 2008

Cultural variation in durations, relations, and contingencies of mother–infant person‐and object‐directed behaviors were examined for 121 nonmigrant Latino mother–infant dyads in South America, Latina immigrants from South America and their infants living in the United States, and European American mother–infant dyads. Nonmigrant Latina mothers and infants engaged in person‐directed behaviors longer than Latino immigrant or European American mothers and infants. Mother and infant person‐directed behaviors were positively related; mother and infant object‐related behaviors were related for some cultural groups but not others. Nearly all mother and infant behaviors were mutually contingent. Mothers were more responsive to infants' behaviors than infants were to mothers. Some cultural differences in responsiveness emerged. Immigrant status has a differentiated role in mother–infant interactions.
The Cat is out of the Bag: The Joint Influence of Previous Experience and Looking Behavior on Infant Categorization
Authors: Kovack‐Lesh Kristine A. , Horst Jessica S. , Oakes Lisa M.
Published: July 2008

We examined the effect of 4‐month‐old infants' previous experience with dogs, cats, or both and their online looking behavior on their learning of the adult‐defined category ofcatin a visual familiarization task. Four‐month‐old infants' (N= 123) learning in the laboratory was jointly determined by whether or not they had experience with pets at home and how much they shifted their gaze back and forth between the stimuli during familiarization. Specifically, only infants with pets at home who also exhibited high levels of switching during familiarization remembered the individual cat exemplars or formed a summary representation of those cats. These results are consistent with recent theorizing about the processes of how infants' categorical representations are formed, and provide new understanding into how infants' categorization unfolds over time.
MNL1Regulates Weak Acid–induced Stress Responses of the Fungal PathogenCandida albicans
Authors: Ramsdale Mark , Selway Laura , Stead David , Walker Jan , Yin Zhikang , Nicholls Susan M. , Crowe Jonathan , Sheils Emma M. , Brown Alistair J.P.
Published: July 2008

MNL1, the Candida albicans homologue of an orphan Msn2-like gene (YER130c in Saccharomyces cerevisiae) has no known function. Here we report that MNL1 regulates weak acid stress responses. Deletion of MNL1 prevents the long-term adaptation of C. albicans cells to weak acid stresses and compromises their global transcriptional response under these conditions. The promoters of Mnl1-dependent genes contain a novel STRE-like element (SLE) that imposes Mnl1-dependent, weak acid stress–induced transcription upon a lacZ reporter in C. albicans. The SLE (HHYYCCCCTTYTY) is related to the Nrg1 response element (NRE) element recognized by the transcriptional repressor Nrg1. Deletion of NRG1 partially restores the ability of C. albicans mnl1 cells to adapt to weak acid stress, indicating that Mnl1 and Nrg1 act antagonistically to regulate this response. Molecular, microarray, and proteomic analyses revealed that Mnl1-dependent adaptation does not occur in cells exposed to proapoptotic or pronecrotic doses of weak acid, suggesting that Ras-pathway activation might suppress the Mnl1-dependent weak acid response in dying cells. Our work defines a role for this YER130c orthologue in stress adaptation and cell death.
A Mitotic GlcNAcylation/Phosphorylation Signaling Complex Alters the Posttranslational State of the Cytoskeletal Protein Vimentin
Authors: Slawson Chad , Lakshmanan T. , Knapp Spencer , Hart Gerald W.
Published: July 2008

O-linked β-N-acetylglucosamine (O-GlcNAc) is a highly dynamic intracellular protein modification responsive to stress, hormones, nutrients, and cell cycle stage. Alterations in O-GlcNAc addition or removal (cycling) impair cell cycle progression and cytokinesis, but the mechanisms are not well understood. Here, we demonstrate that the enzymes responsible for O-GlcNAc cycling, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) are in a transient complex at M phase with the mitotic kinase Aurora B and protein phosphatase 1. OGT colocalized to the midbody during telophase with Aurora B. Furthermore, these proteins coprecipitated with each other in a late mitotic extract. The complex was stable under Aurora inhibition; however, the total cellular levels of O-GlcNAc were increased and the localization of OGT was decreased at the midbody after Aurora inhibition. Vimentin, an intermediate filament protein, is an M phase substrate for both Aurora B and OGT. Overexpression of OGT or OGA led to defects in mitotic phosphorylation on multiple sites, whereas OGT overexpression increased mitotic GlcNAcylation of vimentin. OGA inhibition caused a decrease in vimentin late mitotic phosphorylation but increased GlcNAcylation. Together, these data demonstrate that the O-GlcNAc cycling enzymes associate with kinases and phosphatases at M phase to regulate the posttranslational status of vimentin.
Direct Interaction between a Myosin V Motor and the Rab GTPases Ypt31/32 Is Required for Polarized Secretion
Authors: Lipatova Zhanna , Tokarev Andrei A. , Jin Yui , Mulholland Jon , Weisman Lois S. , Segev Nava
Published: July 2008

Rab GTPases recruit myosin motors to endocytic compartments, which in turn are required for their motility. However, no Ypt/Rab GTPase has been shown to regulate the motility of exocytic compartments. In yeast, the Ypt31/32 functional pair is required for the formation of trans-Golgi vesicles. The myosin V motor Myo2 attaches to these vesicles through its globular-tail domain (GTD) and mediates their polarized delivery to sites of cell growth. Here, we identify Myo2 as an effector of Ypt31/32 and show that the Ypt31/32–Myo2 interaction is required for polarized secretion. Using the yeast-two hybrid system and coprecipitation of recombinant proteins, we show that Ypt31/32 in their guanosine triphosphate (GTP)-bound form interact directly with Myo2-GTD. The physiological relevance of this interaction is shown by colocalization of the proteins, genetic interactions between their genes, and rescue of the lethality caused by a mutation in the Ypt31/32-binding site of Myo2-GTD through fusion with Ypt32. Furthermore, microscopic analyses show a defective Myo2 intracellular localization in ypt31Δ/32ts and in Ypt31/32-interaction–deficient myo2 mutant cells, as well as accumulation of unpolarized secretory vesicles in the latter mutant cells. Together, these results indicate that Ypt31/32 play roles in both the formation of trans-Golgi vesicles and their subsequent Myo2-dependent motility.
Cranberry and Grape Seed Extracts Inhibit the Proliferative Phenotype of Oral Squamous Cell Carcinomas
Authors: Chatelain Kourt , Phippen Spencer , McCabe Jonathan , Teeters Christopher A. , O′Malley Susan , Kingsley Karl
Published: July 2008

Proanthocyanidins, compounds highly concentrated in dietary fruits, such as cranberries and grapes, demonstrate significant cancer prevention potential against many types of cancer. The objective of this study was to evaluate cranberry and grape seed extracts to quantitate and compare their anti‐proliferative effects on the most common type of oral cancer, oral squamous cell carcinoma. Using two well‐characterized oral squamous cell carcinoma cell lines, CAL27 and SCC25, assays were performed to evaluate the effects of cranberry and grape seed extract on phenotypic behaviors of these oral cancers. The proliferation of both oral cancer cell lines was significantly inhibited by the administration of cranberry and grape seed extracts, in a dose‐dependent manner. In addition, key regulators of apoptosis, caspase‐2 and caspase‐8, were concomitantly up‐regulated by these treatments. However, cranberry and grape seed extracts elicited differential effects on cell adhesion, cell morphology, and cell cycle regulatory pathways. This study represents one of the first comparative investigations of cranberry and grape seed extracts and their anti‐proliferative effects on oral cancers. Previous findings using purified proanthocyanidin from grape seed extract demonstrated more prominent growth inhibition, as well as apoptosis‐inducing, properties on CAL27 cells. These observations provide evidence that cranberry and grape seed extracts not only inhibit oral cancer proliferation but also that the mechanism of this inhibition may function by triggering key apoptotic regulators in these cell lines. This information will be of benefit to researchers interested in elucidating which dietary components are central to mechanisms involved in the mediation of oral carcinogenesis and progression.
The effect of surface tension on localized free-surface oscillations about surface-piercing bodies
Authors: Harter Robert , Simon Michael J , Abrahams I.David
Published: July 2008

It is well known that the inclusion of surface tension in the linear water-wave problem introduces an additional term in the free-surface boundary condition. Furthermore, if the fluid contains one or more partially immersed bodies, edge conditions describing the motion of the fluid at each contact line need to be applied. In this paper, an inverse procedure is used to construct examples of two-dimensional, surface-piercing trapping structures for non-zero values of surface tension. The problem is considered with two separate edge conditions that are appropriate for investigations involving trapped modes. The first edge condition fixes each contact line and the procedure used forces the bodies to be horizontal at the contact points; it is shown that results can be found for all values of surface tension. The second condition forces the free-surface slope to be zero at the contact points, and results are obtained for a restricted range of surface tension values.
Mathematical analysis of spark ignition engine operation via the combination of the first and second laws of thermodynamics
Authors: Sezer İsmet , Bilgin Atilla
Published: July 2008

This study aims at the theoretical exergetic evaluation of spark ignition engine operation. For this purpose, a two-zone quasi-dimensional cycle model was installed, not considering the complex calculation of fluid motions. The cycle simulation consists of compression, combustion and expansion processes. The combustion phase is simulated as a turbulent flame propagation process. Intake and exhaust processes are also computed by a simple approximation method. The results of the model were compared with experimental data to demonstrate the validation of the model. Principles of the second law are applied to the model to perform the exergy (or availability) analysis. In the exergy analysis, the effects of various operational parameters, i.e. fuel–air equivalence ratio, engine speed and spark timing on exergetic terms have been investigated. The results of exergy analysis show that variations of operational parameters examined have considerably affected the exergy transfers, irreversibilities and efficiencies. For instance, an increase in equivalence ratio causes an increase in irreversibilities, while it decreases the first and also the second law efficiencies. The irreversibilities have minimum values for the specified engine speed and optimum spark timing, while the first and second law efficiencies reach a maximum at the same engine speed and optimum spark timing.
Global Analysis of Arabidopsis Gene Expression Uncovers a Complex Array of Changes Impacting Pathogen Response and Cell Cycle during Geminivirus Infection
Authors: Ascencio-Ibáñez José Trinidad , Sozzani Rosangela , Lee Tae-Jin , Chu Tzu-Ming , Wolfinger Russell D. , Cella Rino , Hanley-Bowdoin Linda
Published: July 2008

Geminiviruses are small DNA viruses that use plant replication machinery to amplify their genomes. Microarray analysis of the Arabidopsis (Arabidopsis thaliana) transcriptome in response to cabbage leaf curl virus (CaLCuV) infection uncovered 5,365 genes (false discovery rate <0.005) differentially expressed in infected rosette leaves at 12 d postinoculation. Data mining revealed that CaLCuV triggers a pathogen response via the salicylic acid pathway and induces expression of genes involved in programmed cell death, genotoxic stress, and DNA repair. CaLCuV also altered expression of cell cycle-associated genes, preferentially activating genes expressed during S and G2 and inhibiting genes active in G1 and M. A limited set of core cell cycle genes associated with cell cycle reentry, late G1, S, and early G2 had increased RNA levels, while core cell cycle genes linked to early G1 and late G2 had reduced transcripts. Fluorescence-activated cell sorting of nuclei from infected leaves revealed a depletion of the 4C population and an increase in 8C, 16C, and 32C nuclei. Infectivity studies of transgenic Arabidopsis showed that overexpression of CYCD3;1 or E2FB, both of which promote the mitotic cell cycle, strongly impaired CaLCuV infection. In contrast, overexpression of E2FA or E2FC, which can facilitate the endocycle, had no apparent effect. These results showed that geminiviruses and RNA viruses interface with the host pathogen response via a common mechanism, and that geminiviruses modulate plant cell cycle status by differentially impacting the CYCD/retinoblastoma-related protein/E2F regulatory network and facilitating progression into the endocycle.
Predator population dynamics under a cyclic prey regime: numerical responses, demographic parameters and growth rates
Authors: Millon Alexandre , Bretagnolle Vincent
Published: July 2008

The consequences of cyclic fluctuations in abundance of prey species on predator continue to improve our understanding of the mechanisms behind population regulation. Among predators, vole‐eating raptors usually respond to changes in prey abundance with no apparent time‐lag and therefore contradict predictions from the predator–prey theory. In such systems, the interplay between demographic traits and population growth rate in relation to prey abundance remains poorly studied, yet it is crucial to characterize the link between ecological processes and population changes. Using a mechanistic approach, we assessed the demographic rates associated to the direct and indirect numerical responses of a specialist raptor (Montagu's harrier) to its cyclic prey (common vole), using long term data from two adjacent study sites in France. First‐year survival rates were weakly affected by vole abundance, probably due to the fact that Montagu's harriers are trans‐Saharan migrants and thus escape the vole collapse occurring in autumn–winter. Recruitment of yearling as well as breeding propensity of experienced adult females were strongly affected by vole abundance and at least partially shaped the trajectory of the breeding population. We argued that the strong density dependent signal detected in predator time series was mostly the phenomenological consequence of the positive direct numerical response of harriers to vole abundance. Accounting for this, we proposed a method to assess density dependence in predator relying on a cyclic prey. Finally, the variation in Montagu's harrier population growth rates was best explained by overwinter growth rates of the prey population and to a lesser extent by previous residual predator density.
Inhibition of flucloxacillin tubular renal secretion by piperacillin
Authors: Landersdorfer Cornelia B. , Kirkpatrick Carl M. J. , Kinzig Martina , Bulitta Jürgen B. , Holzgrabe Ulrike , Sörgel Fritz
Published: July 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Most β‐lactams are excreted by filtration and to a greater extent by tubular secretion, which is a capacity‐limited saturable pathway.

• Pharmacokinetic interactions between co‐administered β‐lactams have been frequently reported; however, their mechanism and possible clinical benefits are not well defined.

• We are not aware of the interaction between piperacillin and flucloxacillin being reported in the literature.

WHAT THIS STUDY ADDS

• Piperacillin inhibits the renal and nonrenal elimination of flucloxacillin to a clinically significant extent, but not vice versa.

• Modelling suggests that the mechanism for the decrease of renal clearance of flucloxacillin is probably competitive inhibition of renal tubular secretion by piperacillin.

• Piperacillin has a 15‐times higher affinity for the renal transporter than flucloxacillin based on the molar ratio.

AIMS

To explore the extent, time course, site(s), mechanism and possible clinical relevance of the pharmacokinetic (PK) interaction between piperacillin and flucloxacillin.

METHODS

A single‐dose, randomized, six‐way crossover study in 10 healthy volunteers where all subjects received all of the following as 5‐min intravenous infusions: (i) 1.5 g piperacillin, (ii) 0.5 g flucloxacillin, (iii) 1.5 g piperacillin + 0.5 g flucloxacillin, (iv) 3 g piperacillin, (v) 1 g flucloxacillin, and (vi) 3 g piperacillin + 1 g flucloxacillin. Drug concentrations in plasma and urine were determined by high‐performance liquid chromatography. WinNonlin® was used for PK modelling and statistics.

RESULTS

Piperacillin significantly decreased the renal clearance of flucloxacillin from 5.44 to 2.29 l h−1(medians,P < 0.01) and the nonrenal clearance of flucloxacillin from 2.67 to 1.80 l h−1(P < 0.01). The renal clearance of flucloxacillin was reduced to 45% (point estimate, 90% confidence interval 40 to 50%) and the nonrenal clearance to 66% (59, 73). The extent of interaction was larger at the higher doses. Competitive inhibition of tubular secretion by piperacillin was identified as the most likely mechanism for the decreased renal clearance of flucloxacillin. Piperacillin had a 15‐times higher affinity for the renal transporter than flucloxacillin based on the molar ratio. Piperacillin PK was only slightly affected by flucloxacillin.

CONCLUSIONS

Piperacillin inhibits renal and nonrenal elimination of flucloxacillin. This interaction seems clinically significant, as total clearance was reduced by a factor of 1.5 for the lower and 2.1 for the higher doses. PK interactions, especially with piperacillin, are likely to occur also with other β‐lactam combinations and might be useful to improve the effectiveness of antibacterial treatment.
Ibudilast in healthy volunteers: safety, tolerability and pharmacokinetics with single and multiple doses
Authors: Rolan Paul , Gibbons Jacqueline A. , He Lin , Chang Eppie , Jones Drew , Gross Matthew I. , Davidson Jennifer Bahr , Sanftner Laura M. , Johnson Kirk W.
Published: July 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Ibudilast is an oral drug approved in Asia for asthma.

• Tolerability of 10‐mg regimens has been described previously.

• Published pharmacokinetics (PK) are limited: single or 7‐day repeat oral administration of 10 mg in healthy male Asian volunteers.

WHAT THIS STUDY ADDS

• Safety/tolerability and PK of a single 30‐mg dose and a 30‐mg twice daily (b.i.d.) 2‐week regimen in male and female healthy volunteers.

• Higher‐dose regimens are relevant for testing in new neurological indications.

• LC‐MS/MS analytics for quantification of plasma and urine levels of ibudilast parent and its primary metabolite (6,7‐dihydrodiol‐ibudilast).

AIMS

To investigate the safety, tolerability and pharmacokinetics (PK) of ibudilast after a single‐dose and a multiple‐dose regimen.

METHODS

Healthy adult male (n = 9) and female (n = 9) volunteers were evaluated over a 17‐day stay in a Phase 1 unit. Subjects were randomized 1 : 3 to either oral placebo or ibudilast at 30‐mg single administration followed by 14 days of 30 mg b.i.d. Complete safety analyses were performed and, for PK, plasma and urine samples were analysed for ibudilast and its major metabolite.

RESULTS

Ibudilast was generally well tolerated. No serious adverse events occurred. Treatment‐related adverse events included hyperhidrosis, headache and nausea. Two subjects discontinued after a few days at 30 mg b.i.d. because of vomiting. Although samples sizes were too small to rule out a sex difference, PK were similar in men and women. The mean half‐life for ibudilast was 19 h and median Tmax was 4–6 h. Mean (SD) steady‐state plasma Cmax and AUC0–24 were 60 (25) ng ml−1 and 1004 (303) ng h ml−1, respectively. Plasma levels of 6,7‐ dihydrodiol‐ibudilast were approximately 30% of the parent.

CONCLUSIONS

Ibudilast is generally well tolerated in healthy adults when given as a single oral dose of 30 mg followed by 30 mg b.i.d. (60 mg day−1) for 14 days. Plasma PK reached steady state within 2 days of starting the b.i.d. regimen. Exposure to ibudilast was achieved of a magnitude comparable to that associated with efficacy in rat chronic pain models.
The effects and safety of dexibuprofen compared with ibuprofen in febrile children caused by upper respiratory tract infection
Authors: Yoon Jong Seo , Jeong Dae‐Chul , Oh Jae‐Won , Lee Keun Young , Lee Hyun Seung , Koh Young Yull , Kim Jin Tack , Kang Jin Han , Lee Joon Sung
Published: July 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The analgesic and anti‐inflammatory efficacy of dexibuprofen compared with ibuprofen in adults with osteoarthritis, rheumatoid arthritis and dental pain.

WHAT THIS STUDY ADDS

• Dexibuprofen is as effective and tolerable as ibuprofen, and a dose of 5 mg kg−1 of dexibuprofen would be sufficient to control fever caused by upper respiratory tract infection in children.

AIM

To evaluate the antipyretic efficacy and tolerability of dexibuprofen compared with ibuprofen in children with fever caused by upper respiratory tract infection (URTI).

METHODS

The study population consisted of children aged 6 months to 14 years. At the time of visit to the hospital, the children had fever; the cause of fever was determined to be URTI by a paediatrician based on history taking and physical examination. The study was a multicentre, randomized, double‐blind, controlled parallel group, comparative, Phase 3 clinical trial, conducted at three hospitals. By using a computer‐based random assignment program, the subjects were allocated to the following three groups: 5 mg kg−1 dexibuprofen group, 7 mg kg−1 dexibuprofen group, and 10 mg kg−1 ibuprofen group.

RESULTS

In the clinical trial of the antipyretic action of dexibuprofen in patients with fever caused by URTI, there was no statistically significant difference in maximal decrease of temperature and mean time to become apyrexial among the 5 mg kg−1 dexibuprofen, 7 mg kg−1 dexibuprofen and 10 mg kg−1 ibuprofen groups (P > 0.05). There also was no significant difference in adverse drug reaction (P > 0.05).

CONCLUSIONS

Dexibuprofen is as effective and tolerable as ibuprofen. A dose of 5 mg kg−1 and 7 mg kg−1 dexibuprofen in place of 10 mg kg−1 ibuprofen would be sufficient to control fever caused by URTI in children.
Phenotypic changes and reduced genetic diversity have accompanied the rapid decline of the garden tiger moth (Arctia caja) in the U.K.
Authors: ANDERSON SARAH J. , CONRAD KELVIN F. , GILLMAN MIKE P. , WOIWOD IAN P. , FREELAND JOANNA R.
Published: July 2008

Abstract 1. Previous studies have quantified the recent decline of numerous Lepidopteran species in the U.K., including the garden tiger moth (Arctia caja), in which abundance has decreased by 85% over the past 30 years. At the same time that overall numbers have been falling, the distribution of abundance of this species has been moving northwards. In this study, morphological and genetic data were used to investigate the possibility that these changes in abundance and distribution have been accompanied by microevolutionary changes.

2. A comparison of wing size and shape in current and historical moth samples revealed that wing shape has altered significantly over the past century, resulting in longer, narrower hindwings and narrower forewings for a given forewing length. Habitat fragmentation and increased suitability of northerly sites provide a plausible explanation for the selection of increasingly dispersive individuals.

3. Mitochondrial DNA revealed no phylogeographic structuring either before or after the population decline. However, a comparison of mtDNA haplotypes from current and museum specimens indicated that the recent population decline across the U.K. has been accompanied by a significant loss of genetic diversity.

4. The changes in wing shape suggest recent adaptation to environmental change, whereas a loss of genetic diversity may limit the ability of garden tiger moths to adapt to future environmental change.
Colour morph related performance in the meadow grasshopper Chorthippus parallelus (Orthoptera, Acrididae)
Authors: UNSICKER SYBILLE B. , KÖHLER GÜNTER , LINZ JEANINE , STEIN CLAUDIA , WEISSER WOLFGANG W.
Published: July 2008

Abstract 1. Polymorphism has been described for a number of herbivorous insects, but little is known about whether differences in body colour cause fitness differences. In Chorthippus parallelus, three main colour morphs occur, namely brown, green, and dorsally striped.

2. The present study examined colour morph abundances and morph‐related differences in body size, oviposition rate, and offspring numbers in females of C. parallelus collected in 15 montane grasslands. The study also examined the effect of plant species richness, composition, community productivity, and solar radiation on colour morph frequency and fitness.

3. The relative frequencies of the three colour morphs was 31.7% (brown), 33.1% (green), and 35.2% (dorsally striped), but the morphs were not evenly distributed across the 15 sites.

4. There was no effect of the habitat variables on the distribution of the green and the striped morph in the study sites, however 80% of the variation in the abundances of the brown morph was explained by plant species richness and composition.

5. Grasshopper size was equal among the morphs. Brown females laid significantly more egg pods than the green and dorsally striped morphs. There were no significant differences in offspring numbers among the colour morphs.

6. Body colour in C. parallelus seems to be a fitness‐relevant trait, raising the question of the evolutionary maintenance of polymorphism.