bluuebunny/crossref_metadata_2025 huggingface dataset:
Selective expansion of a subset of exhausted CD8 T cells by αPD-L1 blockade
Authors: Blackburn Shawn D. , Shin Haina , Freeman Gordon J. , Wherry E. John
Published: September 2008

Programmed death-1 (PD-1) regulates T cell exhaustion during chronic infections. Blocking the PD-1:PD-ligand (PD-L) pathway reinvigorates exhausted CD8 T cells. Exactly how blocking PD-1:PD-L interactions improves T cell immunity, however, remains unclear. PD-1:PD-L blockade could reprogram all exhausted T cells to become antiviral effectors. Alternatively, this blockade might selectively expand a subset of exhausted T cells. We have identified two subpopulations of exhausted CD8 T cells during chronic viral infection in mice. One subset of exhausted CD8 T cells is rescued by αPD-L1 blockade, whereas the other subset appears more terminally differentiated and responds poorly to PD-1:PD-L blockade. Blocking PD-1:PD-L interactions reduces spontaneous apoptosis and enhances expansion and protective immunity of the rescuable subset, but not the more terminally differentiated subset of exhausted CD8 T cells. These results have implications for predicting clinical responses to PD-1-based therapeutic interventions and for understanding T cell dynamics during persisting infections.
The mammary microenvironment alters the differentiation repertoire of neural stem cells
Authors: Booth Brian W. , Mack David L. , Androutsellis-Theotokis Andreas , McKay Ronald D. G. , Boulanger Corinne A. , Smith Gilbert H.
Published: September 2008

A fundamental issue in stem cell biology is whether adult somatic stem cells are capable of accessing alternate tissue sites and continue functioning as stem cells in the new microenvironment. To address this issue relative to neurogenic stem cells in the mouse mammary gland microenvironment, we mixed wild-type mammary epithelial cells (MECs) with bona fide neural stem cells (NSCs) isolated from WAP-
Cre
/
Rosa26R
mice and inoculated them into cleared fat pads of immunocompromised females. Hosts were bred 6–8 weeks later and examined postinvolution. This allowed for mammary tissue growth, transient activation of the WAP-
Cre
gene, recombination, and constitutive expression of LacZ. The NSCs and their progeny contributed to mammary epithelial growth during ductal morphogenesis, and the
Rosa26-LacZ
reporter gene was activated by WAP-
Cre
expression during pregnancy. Some NSC-derived LacZ
+
cells expressed mammary-specific functions, including milk protein synthesis, whereas others adopted myoepithelial cell fates. Thus, NSCs and their progeny enter mammary epithelium–specific niches and adopt the function of similarly endowed mammary cells. This result supports the conclusion that tissue-specific signals emanating from the stroma and from the differentiated somatic cells of the mouse mammary gland can redirect the NSCs to produce cellular progeny committed to MEC fates.
The “fire stick farming” hypothesis: Australian Aboriginal foraging strategies, biodiversity, and anthropogenic fire mosaics
Authors: Bliege Bird R. , Bird D. W. , Codding B. F. , Parker C. H. , Jones J. H.
Published: September 2008

Aboriginal burning in Australia has long been assumed to be a “resource management” strategy, but no quantitative tests of this hypothesis have ever been conducted. We combine ethnographic observations of contemporary Aboriginal hunting and burning with satellite image analysis of anthropogenic and natural landscape structure to demonstrate the processes through which Aboriginal burning shapes arid-zone vegetational diversity. Anthropogenic landscapes contain a greater diversity of successional stages than landscapes under a lightning fire regime, and differences are of scale, not of kind. Landscape scale is directly linked to foraging for small, burrowed prey (monitor lizards), which is a specialty of Aboriginal women. The maintenance of small-scale habitat mosaics increases small-animal hunting productivity. These results have implications for understanding the unique biodiversity of the Australian continent, through time and space. In particular, anthropogenic influences on the habitat structure of paleolandscapes are likely to be spatially localized and linked to less mobile, “broad-spectrum” foraging economies.
Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts
Authors: Lundqvist Martin , Stigler Johannes , Elia Giuliano , Lynch Iseult , Cedervall Tommy , Dawson Kenneth A.
Published: September 2008

Nanoparticles in a biological fluid (plasma, or otherwise) associate with a range of biopolymers, especially proteins, organized into the “protein corona” that is associated with the nanoparticle and continuously exchanging with the proteins in the environment. Methodologies to determine the corona and to understand its dependence on nanomaterial properties are likely to become important in bionanoscience. Here, we study the long-lived (“hard”) protein corona formed from human plasma for a range of nanoparticles that differ in surface properties and size. Six different polystyrene nanoparticles were studied: three different surface chemistries (plain PS, carboxyl-modified, and amine-modified) and two sizes of each (50 and 100 nm), enabling us to perform systematic studies of the effect of surface properties and size on the detailed protein coronas. Proteins in the corona that are conserved and unique across the nanoparticle types were identified and classified according to the protein functional properties. Remarkably, both size and surface properties were found to play a very significant role in determining the nanoparticle coronas on the different particles of identical materials. We comment on the future need for scientific understanding, characterization, and possibly some additional emphasis on standards for the surfaces of nanoparticles.
Boundaries of Dachsous Cadherin activity modulate the Hippo signaling pathway to induce cell proliferation
Authors: Willecke Maria , Hamaratoglu Fisun , Sansores-Garcia Leticia , Tao Chunyao , Halder Georg
Published: September 2008

The conserved Hippo tumor suppressor pathway is a key signaling pathway that controls organ size in
Drosophila
. To date a signal transduction cascade from the Cadherin Fat at the plasma membrane into the nucleus has been discovered. However, how the Hippo pathway is regulated by extracellular signals is poorly understood. Fat not only regulates growth but also planar cell polarity, for which it interacts with the Dachsous (Ds) Cadherin, and Four-jointed (Fj), a transmembrane kinase that modulates the interaction between Ds and Fat. Ds and Fj are expressed in gradients and manipulation of their expression causes abnormal growth. However, how Ds and Fj regulate growth and whether they act through the Hippo pathway is not known. Here, we report that Ds and Fj regulate Hippo signaling to control growth. Interestingly, we found that Ds/Fj regulate the Hippo pathway through a remarkable logic. Induction of Hippo target genes is not proportional to the amount of Ds or Fj presented to a cell, as would be expected if Ds and Fj acted as traditional ligands. Rather, Hippo target genes are up-regulated when neighboring cells express different amounts of Ds or Fj. Consistent with a model that differences in Ds/Fj levels between cells regulate the Hippo pathway, we found that artificial Ds/Fj boundaries induce extra cell proliferation, whereas flattening the endogenous Ds and Fj gradients results in growth defects. The Ds/Fj signaling system thus defines a cell-to-cell signaling mechanism that regulates the Hippo pathway, thereby contributing to the control of organ size.
Historical DNA analysis reveals living descendants of an extinct species of Galápagos tortoise
Authors: Poulakakis Nikos , Glaberman Scott , Russello Michael , Beheregaray Luciano B. , Ciofi Claudio , Powell Jeffrey R. , Caccone Adalgisa
Published: September 2008

Giant tortoises, a prominent symbol of the Galápagos archipelago, illustrate the influence of geological history and natural selection on the diversification of organisms. Because of heavy human exploitation, 4 of the 15 known species (Geochelonespp.) have disappeared. Charles Darwin himself detailed the intense harvesting of one species,G. elephantopus, which once was endemic to the island of Floreana. This species was believed to have been exterminated within 15 years of Darwin's historic visit to the Galápagos in 1835. The application of modern DNA techniques to museum specimens combined with long-term study of a system creates new opportunities for identifying the living remnants of extinct taxa in the wild. Here, we use mitochondrial DNA and microsatellite data obtained from museum specimens to show that the population on Floreana was evolutionarily distinct from all other Galápagos tortoise populations. It was demonstrated that some living individuals on the nearby island of Isabela are genetically distinct from the rest of the island's inhabitants. Surprisingly, we found that these “non-native” tortoises from Isabela are of recent Floreana ancestry and closely match the genetic data provided by the museum specimens. Thus, we show that the genetic line ofG. elephantopushas not been completely extinguished and still exists in an intermixed population on Isabela. With enough individuals to commence a serious captive breeding program, this finding may help reestablish a species that was thought to have gone extinct more than a century ago and illustrates the power of long-term genetic analysis and the critical role of museum specimens in conservation biology.
Regulation of floral organ abscission in
Arabidopsis thaliana
Authors: Cho Sung Ki , Larue Clayton T. , Chevalier David , Wang Huachun , Jinn Tsung-Luo , Zhang Shuqun , Walker John C.
Published: September 2008

Abscission is a developmental program that results in the active shedding of infected or nonfunctional organs from a plant body. Here, we establish a signaling pathway that controls abscission in
Arabidopsis thaliana
from ligand, to receptors, to downstream effectors. Loss of function mutations in
Inflorescence Deficient in Abscission
(
IDA
), which encodes a predicted secreted small protein, the receptor-like protein kinases
HAESA
(
HAE
) and
HAESA-like 2
(
HSL2
), the
Mitogen-Activated Protein Kinase Kinase 4
(
MKK4
) and
MKK5
, and a dominant-negative form of
Mitogen-Activated Protein Kinase 6
(
MPK6
) in a
mpk3
mutant background all have abscission-defective phenotypes. Conversely, expression of constitutively active MKKs rescues the abscission-defective phenotype of
hae hsl2
and
ida
plants. Additionally, in
hae hsl2
and
ida
plants, MAP kinase activity is reduced in the receptacle, the part of the stem that holds the floral organs. Plants overexpressing
IDA
in a
hae hsl2
background have abscission defects, indicating
HAE
and
HSL2
are epistatic to
IDA
. Taken together, these results suggest that the sequential action of
IDA
,
HAE
and
HSL2
, and a MAP kinase cascade regulates the programmed separation of cells in the abscission zone.
Adenosine receptor antagonists alter the stability of human epileptic GABAAreceptors
Authors: Roseti Cristina , Martinello Katiuscia , Fucile Sergio , Piccari Vanessa , Mascia Addolorata , Di Gennaro Giancarlo , Quarato Pier Paolo , Manfredi Mario , Esposito Vincenzo , Cantore Gianpaolo , Arcella Antonella , Simonato Michele , Fredholm Bertil B. , Limatola Cristina , Miledi Ricardo , Eusebi Fabrizio
Published: September 2008

We examined how the endogenous anticonvulsant adenosine might influence γ-aminobutyric acid type A (GABAA) receptor stability and which adenosine receptors (ARs) were involved. Upon repetitive activation (GABA 500 μM), GABAAreceptors, microtransplanted intoXenopusoocytes from neurosurgically resected epileptic human nervous tissues, exhibited an obvious GABAA-current (IGABA) run-down, which was consistently and significantly reduced by treatment with the nonselective adenosine receptor antagonist CGS15943 (100 nM) or with adenosine deaminase (ADA) (1 units/ml), that inactivates adenosine. It was also found that selective antagonists of A2B (MRS1706, 10 nM) or A3 (MRS1334, 30 nM) receptors reducedIGABArun-down, whereas treatment with the specific A1 receptor antagonist DPCPX (10 nM) was ineffective. The selective A2A receptor antagonist SCH58261 (10 nM) reduced or potentiatedIGABArun-down in ≈40% and ≈20% of tested oocytes, respectively. The ADA-resistant, AR agonist 2-chloroadenosine (2-CA) (10 μM) potentiatedIGABArun-down but only in ≈20% of tested oocytes. CGS15943 administration again decreasedIGABArun-down in patch-clamped neurons from either human or rat neocortex slices.IGABArun-down in pyramidal neurons was equivalent in A1 receptor-deficient and wt neurons but much larger in neurons from A2A receptor-deficient mice, indicating that, in mouse cortex, GABAA-receptor stability is tonically influenced by A2A but not by A1 receptors.IGABArun-down from wt mice was not affected by 2-CA, suggesting maximal ARs activity by endogenous adenosine. Our findings strongly suggest that cortical A2–A3 receptors alter the stability of GABAAreceptors, which could offer therapeutic opportunities.
CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS
Authors: Beers David R. , Henkel Jenny S. , Zhao Weihua , Wang Jinghong , Appel Stanley H.
Published: September 2008

Neuroinflammation, marked by gliosis and infiltrating T cells, is a prominent pathological feature in diverse models of dominantly inherited neurodegenerative diseases. Recent evidence derived from transgenic mice ubiquitously overexpressing mutant Cu
2+
/Zn
2+
superoxide dismutase (mSOD1), a chronic neurodegenerative model of inherited amyotrophic lateral sclerosis (ALS), indicates that glia with either a lack of or reduction in mSOD1 expression enhance motoneuron protection and slow disease progression. However, the contribution of T cells that are present at sites of motoneuron injury in mSOD1 transgenic mice is not known. Here we show that when mSOD1 mice were bred with mice lacking functional T cells or CD4+ T cells, motoneuron disease was accelerated, accompanied by unexpected attenuated morphological markers of gliosis, increased mRNA levels for proinflammatory cytokines and NOX2, and decreased levels of trophic factors and glial glutamate transporters. Bone marrow transplants reconstituted mice with T cells, prolonged survival, suppressed cytotoxicity, and restored glial activation. These results demonstrate for the first time in a model of chronic neurodegeneration that morphological activation of microglia and astroglia does not predict glial function, and that the presence of CD4+ T cells provides supportive neuroprotection by modulating the trophic/cytotoxic balance of glia. These glial/T-cell interactions establish a novel target for therapeutic intervention in ALS and possibly other neurodegenerative diseases.
Distinct sets of αβ TCRs confer similar recognition of tumor antigen NY-ESO-1157–165by interacting with its central Met/Trp residues
Authors: Derré Laurent , Bruyninx Marc , Baumgaertner Petra , Ferber Mathias , Schmid Daphné , Leimgruber Antoine , Zoete Vincent , Romero Pedro , Michielin Olivier , Speiser Daniel E. , Rufer Nathalie
Published: September 2008

Naturally acquired immune responses against human cancers often include CD8+T cells specific for the cancer testis antigen NY-ESO-1. Here, we studied T cell receptor (TCR) primary structure and function of 605 HLA-A*0201/NY-ESO-1157–165-specific CD8 T cell clones derived from five melanoma patients. We show that an important proportion of tumor-reactive T cells preferentially use TCR AV3S1/BV8S2 chains, with remarkably conserved CDR3 amino acid motifs and lengths in both chains. All remaining T cell clones belong to two additional sets expressing BV1 or BV13 TCRs, associated with α-chains with highly diverse VJ usage, CDR3 amino acid sequence, and length. Yet, all T cell clonotypes recognize tumor antigen with similar functional avidity. Two residues, Met-160 and Trp-161, located in the middle region of the NY-ESO-1157–165peptide, are critical for recognition by most of the T cell clonotypes. Collectively, our data show that a large number of αβ TCRs, belonging to three distinct sets (AVx/BV1, AV3/BV8, AVx/BV13) bind pMHC with equal antigen sensitivity and recognize the same peptide motif. Finally, this in-depth study of recognition of a self-antigen suggests that in part similar biophysical mechanisms shape TCR repertoires toward foreign and self-antigens.
Starting with the small words
Authors: Hunston Susan
Published: September 2008

This paper proposes a concept of ‘semantic sequences’, that is, series of meaning elements that can be demonstrated to occur
regularly either in a general corpus or in one comprising specific types of text. Semantic sequences may be identified by
examining the co-text of a lexical item such as make sure, but are also recognisable if grammatical words such as
prepositions are treated as the object of investigation. It is argued that semantic sequences are useful for characterising
discourses of particular kinds.
The ‘terroridiom’ principle between spoken and written discourse
Authors: Milizia Denise , Spinzi Cinzia
Published: September 2008

This paper focuses on phraseology used within the domain of politics, both in written and spoken discourse. We concentrate on the
lemma TERROR and on the recurrent sequences in which it is embedded, reflecting how native speakers, both American and British,
tend to use it in preferred environments making routinized blocks of language. The data come from two corpora: the spoken corpus
includes speeches of George W. Bush and Tony Blair, and the written corpus is made up of articles from The Wall Street
Journal and The Economist. Since text is nothing but phraseology of one kind or another (Sinclair
2008), our attempt here is to uncover which of the two varieties lends itself more willingly to creating phrases that are handled
like single units. The two pieces of software used to retrieve such units (n-grams and concgrams) are WordSmith Tools (Scott
2004), and ConcGram (Greaves 2005).
Translation officials of the Tang central government in medieval China
Authors: Lung Rachel
Published: September 2008

The article documents and differentiates two kinds of translation officials in the central government of the Tang dynasty (618–906 AD) in medieval China: translators in the Court of Diplomatic Reception (Yiyu 譯語) and translators in the Secretariat (Fanshu Yiyu 蕃書譯語). The distinction between them is essential because they are often mentioned in the scholarly literature indiscriminately. Given the scarcity of historical records and the absence of focused discussions about translators in Tang times, their differences were usually either toned down as minimal or misinterpreted by modern scholarship over the past decade. Although some researchers have recently made reference to the two translator titles and agreed that their translation and interpreting duties were somewhat different, the nature of these differences has not been clearly established. Analysis of standard historical records suggests that, in fact, these two types of translators had distinct job duties. Translators in the Court of Diplomatic Reception interpreted primarily for foreign envoys, while the Secretariat’s translators chiefly translated state letters from foreign envoys. This article presents evidence to substantiate this observation and explain why such an apparently straightforward categorization has not been put forward thus far.
(Non-)Sense in note-taking for consecutive interpreting
Authors: Albl-Mikasa Michaela
Published: September 2008

The paper applies cognitive theories of text and language processing, and in particular relevance theory, to the analysis of notes in consecutive interpreting. In contrast to the pre-cognitive view, in which note-taking is seen mainly as a memory-supporting technique, the process of note-taking is described as the reception and production of a notation text. Adding the relevance-theoretical constructs of explicature and implicature to the general account of cognitive text processing as coherence building and the construction of a mental representation at local and global levels, this approach allows for the comparison of source, notation and target texts with respect to the underlying propositional representation, and shows how the sense of highly fragmentary notation texts is recovered in consecutive interpreting. The paper is based on an empirical study involving consecutive interpretations (English–German) by five trainee interpreters. The analysis shows that the interpreters operate relatively closely along micropropositional lines when processing the source, notation and target texts, with the explicature regularly having the same propositional form as the corresponding proposition in the source text.
Constructing interpreting quality
Authors: Grbić Nadja
Published: September 2008

The issue of quality has attracted considerable attention recently in translation and interpreting studies. Few publications, however, seek to explore systematically the theoretical implications of the different notions of quality. The aim of this paper is to explore quality as a social construct and to examine interpretations and definitions of quality in the field of translation and interpreting studies and practice. It is evident that the notion of quality is relative, in that it depends both on the individual who is assessing quality and on the given context or specific situation, but the relativity of quality as an attribute or notion pertaining to an object also extends to the benchmarks set up in order to gauge quality. This paper will focus on the multi-perspectivity of some of the quality benchmarks that have been applied in the context of three systems within which quality discourse has developed over the years: training, professional practice and interpreting research.
Increased IL-12 inhibits B cells' differentiation to germinal center cells and promotes differentiation to short-lived plasmablasts
Authors: Kim Sun Jung , Caton Michele , Wang Chuansheng , Khalil Magi , Zhou Zhi-Jie , Hardin John , Diamond Betty
Published: September 2008

B cells activated by antigen in T cell–dependent immune responses can become short-lived plasma cells, which remain in the spleen, or germinal center–derived memory or plasma cells, which show evidence of affinity maturation and, in the case of plasma cells, migrate to the bone marrow. We show that this cell fate decision can be governed by the cytokine environment engendered by activated dendritic cells (DCs). DCs from mice lacking the Fc receptor γ chain exhibited an activated phenotype in vitro. They secreted more of the proinflammatory cytokine IL-12, which led to the preferential generation of short-lived splenic plasma cells, with ensuing low affinity antibodies and a diminished recall response. Understanding the factors that regulate antigen-activated B cell differentiation and memory cell formation has implications for both antibody-mediated autoimmune disease and protective antibody responses.
TSC–mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species
Authors: Chen Chong , Liu Yu , Liu Runhua , Ikenoue Tsuneo , Guan Kun-Liang , Liu Yang , Zheng Pan
Published: September 2008

The tuberous sclerosis complex (TSC)–mammalian target of rapamycin (mTOR) pathway is a key regulator of cellular metabolism. We used conditional deletion of Tsc1 to address how quiescence is associated with the function of hematopoietic stem cells (HSCs). We demonstrate that Tsc1 deletion in the HSCs drives them from quiescence into rapid cycling, with increased mitochondrial biogenesis and elevated levels of reactive oxygen species (ROS). Importantly, this deletion dramatically reduced both hematopoiesis and self-renewal of HSCs, as revealed by serial and competitive bone marrow transplantation. In vivo treatment with an ROS antagonist restored HSC numbers and functions. These data demonstrated that the TSC–mTOR pathway maintains the quiescence and function of HSCs by repressing ROS production. The detrimental effect of up-regulated ROS in metabolically active HSCs may explain the well-documented association between quiescence and the “stemness” of HSCs.
Chemerin reveals its chimeric nature
Authors: Yoshimura Teizo , Oppenheim Joost J.
Published: September 2008

Chemerin is a proinflammatory plasma protein that binds to the GPCR ChemR23/CMKLR1 on macrophages and plasmacytoid dendritic cells, and promotes chemotaxis. An orphan GPCR, CCRL2, has now been identified as an additional receptor for chemerin, providing a unique mechanism by which chemerin enhances inflammation. Furthermore, because recent data shows that chemerin-derived peptides possess antiinflammatory properties, chemerin may be involved in both the initiation and resolution of inflammation.
Environmental indicators: utility in meeting regulatory needs. An overview
Authors: Rees Hubert L. , Hyland Jeffrey L. , Hylland Ketil , Mercer Clarke Colleen S. L. , Roff John C. , Ware Suzanne
Published: September 2008

Rees, H. L., Hyland, J. L., Hylland, K., Mercer Clarke, C. S. L., Roff, J. C., and Ware, S. 2008. Environmental indicators: utility in meeting regulatory needs. An overview. – ICES Journal of Marine Science, 65: 1381–1386. The utility of environmental indicators in meeting regulatory needs was addressed at an international symposium held in November 2007. This paper summarizes the attributes and range of uses of indicators and highlights key points from theme sessions and a workshop on unifying concepts. The symposium attracted regulators and scientists, who supported the need to promote dialogue during the construction of indicator-based management frameworks and at key stages towards operational use. Scientists expressed willingness to engage with the wider societal context for indicator applications, which is essential to the development of ecosystem-based management. For the latter to be effective, more effort is needed to combine indicators with thresholds to guide management actions and, in the process, to assess the full range of consequences of non-compliance. There are clear benefits to periodic interdisciplinary reviews of progress in this area, and a follow-up event with a regulatory emphasis is suggested.
Understanding Fetal Alcohol Spectrum Disorders (FASDs): Toward Identification of a Behavioral Phenotype
Authors: Nash Kelly , Sheard Erin , Rovet Joanne , Koren Gideon
Published: September 2008

Fetal alcohol spectrum disorders (FASDs) currently represent the leading cause of mental retardation in North America, ahead of Down syndrome and cerebral palsy. The damaging effects of alcohol on the developing brain have a cascading impact on the social and neurocognitive profiles of affected individuals. Researchers investigating the profiles of children with FASDs have found impairments in learning and memory, executive functioning, and language, as well as hyperactivity, impulsivity, poor communication skills, difficulties with social and moral reasoning, and psychopathology. The primary goal of this review paper is to examine current issues pertaining to the identification of a behavioral phenotype in FASDs, as well as to address related screening and diagnostic concerns. We conclude that future research initiatives comparing children with FASDs to nonalcohol-exposed children with similar cognitive and socioemotional profiles should aid in uncovering the unique behavioral phenotype for FASDs.
Patterns of change in timing of spring migration in North European songbird populations
Authors: Tøttrup Anders P. , Thorup Kasper , Rahbek Carsten
Published: September 2008

From 1976 to 1997 passerines were mist‐netted and ringed on the island of Christiansø, in the Baltic Sea. Here we present analyses of phenological changes (i.e. time of arrival) for 25 species based on the entire populations of mist‐netted songbirds during spring migration. We used two approaches (least square and quantile regression) to test for changes in arrival time of first individuals and three different parts of the songbird populations (i.e. first 5%, 50% and 95% of the total number of trapped individuals corrected for trapping effort). Our results generally confirm earlier spring arrival of migratory passerines with an overall earlier arrival of 0.26 days per year. Changes in the arrival time of first individuals are often the only data available. They are typically analysed on the assumption that they are representative of their respective population. We found a unidirectional, significant change towards earlier arrival for all four measures of arrival timing which seem to support this. However, the four measures of arrival are changing at different rates. First individuals changed arrival time more rapidly than the first 5%, 50% and 95% of the spring total. Such differences are likely to be important for our understanding of population‐dynamic changes in relation to climate change. These differences may also have long‐term evolutionary consequences. Migration distance seems to affect the degree of change in arrival time, but we found no difference between species wintering in different regions of Africa.
Breeding and moulting locations and migration patterns of the Atlantic population of Steller's eiders Polysticta stelleri as determined from satellite telemetry
Authors: R. Petersen Margaret , O. Bustnes Jan , H. Systad Geir
Published: September 2008

This study was designed to determine the spring, summer, autumn, and early winter distribution, migration routes, and timing of migration of the Atlantic population of Steller's eiders Polysticta stelleri. Satellite transmitters were implanted in 20 eiders captured in April 2001 at Vadsø, Norway, and their locations were determined from 5 May 2001 to 6 February 2002. Regions where birds concentrated from spring until returning to wintering areas included coastal waters from western Finnmark, Norway, to the eastern Taymyr Peninsula, Russia. Novaya Zemlya, Russia, particularly the Mollera Bay region, was used extensively during spring staging, moult, and autumn staging; regions of the Kola, Kanin, and Gydanskiy peninsulas, Russia, were used extensively during spring and moult migrations. Steller's eiders migrated across the Barents and Kara seas and along the Kara Sea and Kola Peninsula coastal waters to nesting, moulting, and wintering areas. The majority of marked eiders (9 of 15) were flightless in near‐shore waters along the west side of Novaya Zemlya. Eiders were also flightless in northern Norway and along the Kanin and at Kola Peninsula coasts. We compare and contrast natural history characteristics of the Atlantic and Pacific populations and discuss evolutionary and ecological factors influencing their distribution.
Social factors affect the singing rates of female northern cardinals Cardinalis cardinalis
Authors: Vondrasek Joanna R.
Published: September 2008

Social factors, such as the duration of territorial occupancy or of time paired with a mate can affect the rate at which individual birds sing. This study examined the influence of duration of pair‐bond and territory occupancy as well as date on the rate of singing by male and female northern cardinals Cardinalis cardinalis. When differences in breeding status were controlled, female cardinals sang at higher rates earlier in the season. Females in newly formed pairs sang at significantly higher rates than those in pairs that had previously bred together. In contrast, male cardinals did not show significant variation in the rate of singing throughout the season. The song rates of males in newly formed and established pairs did not differ significantly. Song rates for males and females in mated pairs were not significantly correlated. This study suggests that social factors have a strong effect on the rate at which female cardinals sing. It is possible that increased intra‐sexual aggression by females when they are establishing a new territory with a new mate leads to this higher level of song output. Once females have established a territory and acquired a mate, dear‐enemy effects might diminish the need for acoustic territorial defence. Differences in the constraints of nesting or the attraction of extra‐pair mates might explain the sexual differences in male and female singing behaviour.
Contribution of the activities of CYP3A, CYP2D6, CYP1A2 and other potential covariates to the disposition of methadone in patients undergoing methadone maintenance treatment
Authors: Shiran Mohammad‐Reza , Lennard Martin S. , Iqbal Mohammad‐Zafar , Lagundoye Oldwale , Seivewright Nicholas , Tucker Geoffrey T. , Rostami‐Hodjegan Amin
Published: September 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Several cytochromes P450 (CYPs) have been implicated in the metabolism of methadone, but there is no consensus on their relative contributions to overall disposition and hence variability in response.

WHAT THIS STUDY ADDS

• Variability in CYP3A4 activity has statistically significant but nonetheless modest influence on the oral clearance of methadone and its enantiomers.

• However, CYPs 1A2 and 2D6 appear to have no impact at all.

AIMS

To investigate the influence of different cytochrome P450 (CYP) activities and other potential covariates on the disposition of methadone in patients on methadone maintenance therapy (MMT).

METHODS

Eighty‐eight patients (58 male; 21–55 years; 84 White) on MMT were studied. CYP2D6 activity [3 h plasma metabolic ratio of dextromethorphan (DEX) to dextrorphan (DOR)] was determined in 44 patients (29 male; 24–55 years), CYP1A2 activity (salivary caffeine elimination half‐life) in 44 patients (21 male; 24–55 years) and CYP3A activity (oral clearance of midazolam) in 49 patients (33 male; 23–55 years). Data on all three CYPs were obtained from 32 subjects. Total plasma concentrations of (RS)‐methadone and total and unbound plasma concentrations of both enantiomers were measured by LC/MS. Population pharmacokinetics and subsequent multiple regression analysis were used to calculate methadone oral clearance and to identify its covariates.

RESULTS

Between 61 and 68% of the overall variation in total plasma trough concentrations of (RS)‐, (R)‐ and (S)‐methadone was explained by methadone dose, duration of addiction before starting MMT, CYP3A activity and illicit morphine use. CYP3A activity explained 22, 16, 15 and 23% of the variation in unbound (R)‐, unbound (S)‐, total (RS)‐ and total (S)‐methadone clearances, respectively. Neither CYP2D6 nor CYP1A2 activity was related to methadone disposition.

CONCLUSIONS

CYP3A activity has a modest influence on methadone disposition. Inhibitors and inducers of this enzyme should be monitored in patients taking methadone.
Type‐B monogalactosyldiacylglycerol synthases are involved in phosphate starvation‐induced lipid remodeling, and are crucial for low‐phosphate adaptation
Authors: Kobayashi Koichi , Awai Koichiro , Nakamura Masanobu , Nagatani Akira , Masuda Tatsuru , Ohta Hiroyuki
Published: September 2008

Mono‐ and digalactosyldiacylglycerol (MGDG and DGDG, respectively) constitute the bulk of membrane lipids in plant chloroplasts. Mutant analyses in Arabidopsis have shown that these galactolipids are essential for chloroplast biogenesis and photoautotrophic growth. Moreover, these non‐phosphorous lipids are proposed to participate in low‐phosphate (Pi) adaptations. Under Pi‐limited conditions, a drastic accumulation of DGDG occurs concomitantly with a large reduction in membrane phospholipids, suggesting that plants substitute DGDG for phospholipids during Pi starvation. Previously, we reported that among the three MGDG synthase genes (MGD1, MGD2 and MGD3), the type‐B MGD2 and MGD3 are upregulated in parallel with DGDG synthase genes during Pi starvation. Here, we describe the identification and characterization of T‐DNA insertional mutants of Arabidopsis type‐B MGD genes. Under Pi‐starved conditions, the mgd3‐1 mutant showed a drastic reduction in DGDG accumulation, particularly in the root, indicating that MGD3 is the main isoform responsible for DGDG biosynthesis in Pi‐starved roots. Moreover, in the roots of mgd2 mgd3 plants, Pi stress‐induced accumulation of DGDG was almost fully abolished, showing that type‐B MGD enzymes are essential for membrane lipid remodeling in Pi‐starved roots. Reductions in fresh weight, root growth and photosynthetic performance were also observed in these mutants under Pi‐starved conditions. These results demonstrate that Pi stress‐induced membrane lipid remodeling is important in plant growth during Pi starvation. The widespread distribution of type‐B MGD genes in land plants suggests that membrane lipid remodeling mediated by type‐B MGD enzymes is a potent adaptation to Pi deficiency for land plants.
Photosynthesis, non‐photochemical pathways and activities of antioxidant enzymes in a resilient evergreen oak under different climatic conditions from a valley‐savanna in Southwest China
Authors: Zhu Jun‐Jie , Zhang Jiao‐Lin , Liu Hong‐Cheng , Cao Kun‐Fang
Published: September 2008

Plants in the savanna‐valleys in Southwest China are annually exposed to different combinations of multiple stresses from the hot‐rainy, to chill‐dry, and to warm‐dry seasons. This study monitored seasonal changes in photosynthesis and photoprotection in an evergreen oak (Cyclobalanopsis helferiana) from one of these valleys for four years during which usual and abnormal drought occurred. In general, during the study period with decreasing xylem water potential (Ψx), photosynthetic gas exchange, quantum yield of photosystem II (PSII) photochemistry and activities of most of the measured antioxidant enzymes decreased, while activities of the xanthophyll cycle and associated non‐photochemical energy dissipation and glutathione peroxidase (GP) (EC 1.11.1.9) increased. In a fairly severe chill period, high concentration of reactive oxygen species induced high activities of most of the antioxidant enzymes and relatively stronger decrease in gas exchange. In the most severe dry period, even when predawn Ψx decreased down to −4 MPa, considerable Pn (maximum photosynthetic rate) (4 μmol m–2 s–1) was still maintained in midmorning. At this time, most of the antioxidant enzyme activities decreased to the lowest values, whereas the xanthophyll cycle and associated non‐photochemical energy dissipation and GP activities increased to their highest levels. High predawn antheraxanthin and zeaxanthin contents were observed in the severe and very severe drought periods. Superoxide dismutase maintained high and fairly constant activity (1500–1800 U mg−1 protein) and predawn maximum photochemistry efficiency of PSII was always above 0.8 throughout the whole study period. These results indicated that the photosynthetic apparatus of the oak leaves was highly capable of maintaining its function under the multiple stresses in different seasons in the present valley‐savanna.
Hybrid breakdown and mitochondrial dysfunction in hybrids of Nasonia parasitoid wasps
Authors: ELLISON C. K. , NIEHUIS O. , GADAU J.
Published: September 2008

Male F2hybrids of the waspsNasonia giraultiandNasonia vitripennissuffer increased mortality during development. Previous studies suggested that the mitochondria may play an important role in this pattern of hybrid breakdown. The mitochondrial genome encodes 13 polypeptides, which are integral subunits of the oxidative phosphorylation enzyme complexes I, III, IV and V. We show that the mitochondrial ATP production rate and the efficacy of the enzyme complexes I, III and IV, but not that of the completely nuclear‐encoded complex II, are reduced in F2hybrid males ofN. giraultiandN. vitripennis. We hypothesize that nuclear–mitochondrial protein interactions in the oxidative phosphorylation pathway are disrupted in these hybrids, reducing energy generation capacity and potentially reducing hybrid fitness. Our results suggest that dysfunctional cytonuclear interactions could represent an under‐appreciated post‐zygotic isolation mechanism that, due to elevated evolutionary rates of mitochondrial genes, evolves very early in the speciation process.
The frequency of multiple paternity predicts variation in testes size among island populations of house mice
Authors: FIRMAN R. C. , SIMMONS L. W.
Published: September 2008

Polyandry generates selection on males through sperm competition, which has broad implications for the evolution of ejaculates and male reproductive anatomy. Comparative analyses across species and competitive mating trials within species have suggested that sperm competition can influence the evolution of testes size, sperm production and sperm form and function. Surprisingly, the intraspecific approach of comparing among population variation for investigating the selective potential of sperm competition has rarely been explored. We sampled seven island populations of house mice and determined the frequency of multiple paternity within each population. Applying the frequency of multiple paternity as an index of the risk of sperm competition, we looked for selective responses in male reproductive traits. We found that the risk of sperm competition predicted testes size across the seven island populations of house mice. However, variation in sperm traits was not explained by sperm competition risk. We discuss these findings in relation to sperm competition theory, and other intrinsic and extrinsic factors that might influence ejaculate quality.
Nice natives and mean migrants: the evolution of dispersal‐dependent social behaviour in viscous populations
Authors: EL MOUDEN C. , GARDNER A.
Published: September 2008

There has been much interest in the evolution of social behaviour in viscous populations. While low dispersal increases the relatedness of neighbours, which tends to promote the evolution of indiscriminate helping behaviour, it can also increase competition between neighbours, which tends to inhibit the evolution of helping and may even favour harming behaviour. In the simplest scenario, these two effects exactly cancel, so that dispersal rate has no impact on the evolution of helping or harming. Here, we show that dispersal rate does matter when individuals can adjust their social behaviour conditional on whether they have dispersed or whether they have remained close to their place of origin. We find that nondispersing individuals are weakly favoured to indiscriminately help their neighbours, whereas dispersing individuals are more readily favoured to indiscriminately harm their neighbours.
Investigating latitudinal clines for life history and stress resistance traits in Drosophila simulans from eastern Australia
Authors: ARTHUR A. L. , WEEKS A. R. , SGRÒ C. M.
Published: September 2008

Latitudinal clines have been demonstrated for many quantitative traits in Drosophila and are assumed to be due to climatic selection. However, clinal studies are often performed in species of Drosophila that contain common cosmopolitan inversion polymorphisms that also show clinal patterns. These inversion polymorphisms may be responsible for much of the observed clinal variation. Here, we consider latitudinal clines for quantitative traits in Drosophila simulans from eastern Australia. Drosophila simulans does not contain cosmopolitan inversion polymorphisms, so allows the study of clinal selection on quantitative traits that are not confounded by associations with inversions. Body size showed a strong linear cline for both females and males. Starvation resistance exhibited a weak linear cline in females, whereas chill‐coma recovery exhibited a significant nonlinear cline in females only. No clinal pattern was evident for development time, male chill‐coma recovery, desiccation or heat resistance. We discuss these results with reference to the role inversion polymorphisms play in generating clines in quantitative traits of Drosophila.
Male sterility, fitness gain curves and the evolution of gender specialization from distyly in Erythroxylum havanense
Authors: ROSAS F. , DOMÍNGUEZ C. A.
Published: September 2008

The evolution of dioecy from a monomorphic hermaphroditic condition requires two mutations, one producing females and one producing males. Conversely, a single mutation sterilizing one sexual function in one morph of distylous species would result in functional dioecy because such a mutation also affects the complementary function in the other morph. In this study, we tested these ideas with Erythroxylum havanense, a distylous species with morph‐biased male sterility. Based on sex allocation theory we evaluated whether the invasion of thrum females is favoured over the maintenance of this morph cosexuals. Completely male sterile thrum plants obtained higher fitness returns than hermaphrodites or partial male sterile individuals of the same morph, thus favouring the invasion of female thrum plants. We concluded that because fruit production of pin individuals depends on the pollen produced by thrum plants, the invasion of thrum females would result on the evolution of functional dioecy.
Teaching Religious Doubt with Toulmin's Model of Reasoning
Authors: Horne Milton P.
Published: September 2008

Abstract.  Teaching students to doubt, that is, to “test,” theological arguments as one might test any other kind of knowledge is challenging in that the warrant for such testing is not immediately clear. Stephen Toulmin, Richard Rieke, and Allan Janik's model of reasoning provides a conceptual framework that demonstrates the logical relationships between a claim, its grounds, warrants, and backing for warrants. Against such a model, the instructor and students may study religious claims, both biblical and theological, with the aim of analyzing the ways such claims find support or a lack of support depending upon the particular ways that claims and evidence have competing warrants. Several pedagogical benefits ensue. First, students see that the validity for theological claims rests as much upon warrants as it does upon grounding. Second, searching for ancient warrants privileges historical‐critical investigation. Third, competing warrants for contradictory theological claims summon pedagogical metaphors of process and development.
Faith in the Classroom: The Perspective of a Pastor Called to College Teaching
Authors: Martin Thomas W.
Published: September 2008

Abstract.  Can one uphold a call from an ecclesiastical body while teaching in a college classroom? This paper will argue that the dual roles of pastor and professor can be integrated by the adoption of faith development as a learning goal. This goal seems to stand at odds with three important aspects of academic teaching: the demographic reality of religious pluralism, the ethical requirement to preserve student autonomy, and the overarching goal of a university education to promote critical thinking. My argument will be that, far from violating these three areas, faith development as a broad learning goal can actually provide a valuable deepening of pluralism, autonomy, and critical thought in the educational experience of students. The method of exploration will be autobiographical. I will show how it is that in my dual roles as an ELCA pastor called to a faculty post I articulate and use faith development as an overarching learning goal in the context of (1) a theological pedagogy based on an interfaith logos theology, (2) a value‐laden pedagogy vis‐à‐vis consumerist self‐formation, and (3) an adaptation of stages of faith development to the classroom.