bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of the Distribution of the Central-Government Budgetary Grants in Turkey
Authors: Tekeli Recep , Kaplan Muhittin
Published: September 2008

Intergovernmental grants are the main revenue source of local governments. In the fiscal decentralization literature it has been argued that fiscal disparities across the regions are accounted for in the central-government grant distribution. However, some argue that grants are given to localities to increase the reelection chances of the incumbent or to increase the votes at election. To compete with the opposition parties the incumbent party may try to allocate the grants to aligned local governments. In this paper we analyze the grant allocation in Turkey. We test empirically whether central-government's budgetary transfers to the municipalities were made on the basis of economic criteria or in accordance with the political interest of politicians, and hence the coalition government. To test the hypothesis we followed the literature but we used additional variables. Using municipal data in sixty-one provinces, we find that the desire to secure reelection motivates politicians.
Employment Changes in Italy in the 1990s: A Comparison between Large Enterprise Areas and Industrial Districts
Authors: Dei Ottati Gabi , Grassini Laura
Published: September 2008

We examine the uneven employment changes in the Italian local labour systems (LLSs) in the 1990s. Using the 1991 and 2001 economic census data, we intend to compare the performance of different types of LLS, and particularly those of the industrial districts (IDs) and the large enterprise systems (LESs). The originality of the study lies in the territorial unit of analysis chosen: the 784 Italian LLSs. The analysed data show that, in the 1990s, the Italian IDs proved to be the country's most dynamic local systems. Moreover, the shift-and-share analysis demonstrates that the local effect in the IDs was positive enough to more than compensate for the negative industry mix. Conversely, in the LESs the local effect was so negative as to determine a total negative effect, despite the positive industry mix. We conclude with an overview of the present situation and the corresponding policy implications.
Adaptive changes in the transcription factor HoxA-11 are essential for the evolution of pregnancy in mammals
Authors: Lynch Vincent J. , Tanzer Andrea , Wang Yajun , Leung Frederick C. , Gellersen Birgit , Emera Deena , Wagner Gunter P.
Published: September 2008

Evolutionary change in gene regulation can result from changes in
cis
-regulatory elements, leading to differences in the temporal and spatial expression of genes or in the coding region of transcription factors leading to novel functions or both. Although there is a growing body of evidence supporting the importance of
cis
-regulatory evolution, examples of protein-mediated evolution of novel developmental pathways have not been demonstrated. Here, we investigate the evolution of prolactin (PRL) expression in endometrial cells, which is essential for placentation/pregnancy in eutherian mammals and is a direct regulatory target of the transcription factor HoxA-11. Here, we show that (
i
) endometrial PRL expression is a derived feature of placental mammals, (
ii
) the PRL regulatory gene HoxA-11 experienced a period of strong positive selection in the stem-lineage of eutherian mammals, and (
iii
) only HoxA-11 proteins from placental mammals, including the reconstructed ancestral eutherian gene, are able to up-regulate PRL from the promoter used in endometrial cells. In contrast, HoxA-11 from the reconstructed therian ancestor, opossum, platypus, and chicken are unable to up-regulate PRL expression. These results demonstrate that the evolution of novel gene expression domains is not only mediated by the evolution of
cis
-regulatory elements but can also require evolutionary changes of transcription factor proteins themselves.
Evolutionary linkage between eukaryotic cytokinesis and chloroplast division by dynamin proteins
Authors: Miyagishima Shin-ya , Kuwayama Hidekazu , Urushihara Hideko , Nakanishi Hiromitsu
Published: September 2008

Chloroplasts have evolved from a cyanobacterial endosymbiont and been retained for more than 1 billion years by coordinated chloroplast division in multiplying eukaryotic cells. Chloroplast division is performed by ring structures at the division site, encompassing both the inside and the outside of the two envelopes. A part of the division machinery is derived from the cyanobacterial cytokinetic activity based on the FtsZ protein. In contrast, other parts of the division machinery involve proteins specific to eukaryotes, including a member of the dynamin family. Each member of the dynamin family is involved in the division or fusion of a distinct eukaryotic membrane system. To gain insight into the kind of ancestral dynamin protein and eukaryotic membrane activity that evolved to regulate chloroplast division, we investigated the functions of the dynamin proteins that are most closely related to chloroplast division proteins. These proteins in the amoeba
Dictyostelium discoideum
and
Arabidopsis thaliana
localize at the sites of cell division, where they are involved in cytokinesis. Our results suggest that the dynamin for chloroplast division is derived from that involved in eukaryotic cytokinesis. Therefore, the chloroplast division machinery is a mixture of bacterial and eukaryotic cytokinesis components, with the latter a key factor in the synchronization of endosymbiotic cell division with host cell division, thus helping to establish the permanent endosymbiotic relationship.
Discovery of posttranslational maturation by self-subunit swapping
Authors: Zhou Zhemin , Hashimoto Yoshiteru , Shiraki Kentaro , Kobayashi Michihiko
Published: September 2008

Several general mechanisms of metallocenter biosynthesis have been reported and reviewed, and in all cases, the components or subunits of an apoprotein remain in the final holoprotein. Here, we first discovered that one subunit of an apoenzyme did not remain in the functional holoenzyme. The cobalt-containing low-molecular-mass nitrile hydratase (L-NHase) of
Rhodococcus rhodochrous
J1 consists of β- and α-subunits encoded by the
nhlBA
genes, respectively. An ORF,
nhlE
, just downstream of
nhlBA
, was found to be necessary for L-NHase activation. In contrast to the cobalt-containing L-NHase (holo-L-NHase containing Cys-SO
2
−
and Cys-SO
−
metal ligands) derived from
nhlBAE
, the gene products derived from
nhlBA
were cobalt-free L-NHase (apo-L-NHase lacking oxidized cysteine residues). We discovered an L-NHase maturation mediator, NhlAE, consisting of NhlE and the cobalt- and oxidized cysteine-containing α-subunit of L-NHase. The incorporation of cobalt into L-NHase was shown to depend on the exchange of the nonmodified cobalt-free α-subunit of apo-L-NHase with the cobalt-containing cysteine-modified α-subunit of NhlAE. This is a posttranslational maturation process different from general mechanisms of metallocenter biosynthesis known so far: the unexpected behavior of a protein in a protein complex, which we named “self-subunit swapping.”
Equatorial convergence of India and early Cenozoic climate trends
Authors: Kent Dennis V. , Muttoni Giovanni
Published: September 2008

India's northward flight and collision with Asia was a major driver of global tectonics in the Cenozoic and, we argue, of atmospheric CO
2
concentration (
p
CO
2
) and thus global climate. Subduction of Tethyan oceanic crust with a carpet of carbonate-rich pelagic sediments deposited during transit beneath the high-productivity equatorial belt resulted in a component flux of CO
2
delivery to the atmosphere capable to maintain high
p
CO
2
levels and warm climate conditions until the decarbonation factory shut down with the collision of Greater India with Asia at the Early Eocene climatic optimum at ≈50 Ma. At about this time, the India continent and the highly weatherable Deccan Traps drifted into the equatorial humid belt where uptake of CO
2
by efficient silicate weathering further perturbed the delicate equilibrium between CO
2
input to and removal from the atmosphere toward progressively lower
p
CO
2
levels, thus marking the onset of a cooling trend over the Middle and Late Eocene that some suggest triggered the rapid expansion of Antarctic ice sheets at around the Eocene-Oligocene boundary.
Neanderthal exploitation of marine mammals in Gibraltar
Authors: Stringer C. B. , Finlayson J. C. , Barton R. N. E. , Fernández-Jalvo Y. , Cáceres I. , Sabin R. C. , Rhodes E. J. , Currant A. P. , Rodríguez-Vidal J. , Giles-Pacheco F. , Riquelme-Cantal J. A.
Published: September 2008

Two coastal sites in Gibraltar, Vanguard and Gorham's Caves, located at Governor's Beach on the eastern side of the Rock, are especially relevant to the study of Neanderthals. Vanguard Cave provides evidence of marine food supply (mollusks, seal, dolphin, and fish). Further evidence of marine mammal remains was also found in the occupation levels at Gorham's Cave associated with Upper Paleolithic and Mousterian technologies [Finlayson C,
et al.
(2006)
Nature
443:850–853]. The stratigraphic sequence of Gibraltar sites allows us to compare behaviors and subsistence strategies of Neanderthals during the Middle Paleolithic observed at Vanguard and Gorham's Cave sites. This evidence suggests that such use of marine resources was not a rare behavior and represents focused visits to the coast and estuaries.
Unconscious processing dissociates along categorical lines
Authors: Almeida Jorge , Mahon Bradford Z. , Nakayama Ken , Caramazza Alfonso
Published: September 2008

Visual object recognition is subserved by ventral temporal and occipital regions of the brain. Regions comprising the dorsal visual pathway have not been considered relevant for object recognition, despite strong categorical biases for tool-related information in those regions. Here, we show that dorsal stream processes influence object categorization. We used two techniques to render prime pictures invisible: continuous flash suppression (CFS), which obliterates input into ventral temporal regions, but leaves dorsal stream processes largely unaffected, and backward masking (BM), which allows suppressed information to reach both ventral and dorsal stream structures. Categorically congruent primes suppressed under CFS facilitate categorization of tools but have no effect on nonmanipulable objects; in contrast, primes rendered invisible through BM facilitate target categorization for both tools and nonmanipulable things. Our findings demonstrate that information computed by the dorsal stream is used in object categorization, but only for a category of manipulable objects.
piRNA-mediated nuclear accumulation of retrotransposon transcripts in the
Drosophila
female germline
Authors: Chambeyron Séverine , Popkova Anna , Payen-Groschêne Geneviève , Brun Christine , Laouini Dorsaf , Pelisson Alain , Bucheton Alain
Published: September 2008

Germline silencing of transposable elements is essential for the maintenance of genome integrity. Recent results indicate that this repression is largely achieved through a RNA silencing pathway that involves Piwi-interacting RNAs (piRNAs). However the repressive mechanisms are not well understood. To address this question, we used the possibility to disrupt the repression of the
Drosophila
I element retrotransposon by hybrid dysgenesis. We show here that the repression of the functional I elements that are located in euchromatin requires proteins of the piRNA pathway, and that the amount of ovarian I element piRNAs correlates with the strength of the repression in the female germline. Antisense RNAs, which are likely used to produce antisense piRNAs, are transcribed by heterochromatic defective I elements, but efficient production of these antisense small RNAs requires the presence in the genome of euchromatic functional I elements. Finally, we demonstrate that the piRNA-induced silencing of the functional I elements is at least partially posttranscriptional. In a repressive background, these elements are still transcribed, but some of their sense transcripts are kept in nurse cell nuclear foci together with those of the Doc retrotransposon. In the absence of I element piRNAs, either in dysgenic females or in mutants of the piRNA silencing pathway, sense I element transcripts are transported toward the oocyte where retrotransposition occurs. Our results indicate that piRNAs are involved in a posttranscriptional gene-silencing mechanism resulting in RNA nuclear accumulation.
Sequence and genetic map of
Meloidogyne hapla
: A compact nematode genome for plant parasitism
Authors: Opperman Charles H. , Bird David M. , Williamson Valerie M. , Rokhsar Dan S. , Burke Mark , Cohn Jonathan , Cromer John , Diener Steve , Gajan Jim , Graham Steve , Houfek T. D. , Liu Qingli , Mitros Therese , Schaff Jennifer , Schaffer Reenah , Scholl Elizabeth , Sosinski Bryon R. , Thomas Varghese P. , Windham Eric
Published: September 2008

We have established
Meloidogyne hapla
as a tractable model plant-parasitic nematode amenable to forward and reverse genetics, and we present a complete genome sequence. At 54 Mbp,
M. hapla
represents not only the smallest nematode genome yet completed, but also the smallest metazoan, and defines a platform to elucidate mechanisms of parasitism by what is the largest uncontrolled group of plant pathogens worldwide. The
M. hapla
genome encodes significantly fewer genes than does the free-living nematode
Caenorhabditis elegans
(most notably through a reduction of odorant receptors and other gene families), yet it has acquired horizontally from other kingdoms numerous genes suspected to be involved in adaptations to parasitism. In some cases, amplification and tandem duplication have occurred with genes suspected of being acquired horizontally and involved in parasitism of plants. Although
M. hapla
and
C. elegans
diverged >500 million years ago, many developmental and biochemical pathways, including those for dauer formation and RNAi, are conserved. Although overall genome organization is not conserved, there are areas of microsynteny that may suggest a primary biological function in nematodes for those genes in these areas. This sequence and map represent a wealth of biological information on both the nature of nematode parasitism of plants and its evolution.
Disulfide locking a sodium channel voltage sensor reveals ion pair formation during activation
Authors: DeCaen Paul G. , Yarov-Yarovoy Vladimir , Zhao Yong , Scheuer Todd , Catterall William A.
Published: September 2008

The S4 transmembrane segments of voltage-gated ion channels move outward on depolarization, initiating a conformational change that opens the pore, but the mechanism of S4 movement is unresolved. One structural model predicts sequential formation of ion pairs between the S4 gating charges and negative charges in neighboring S2 and S3 transmembrane segments during gating. Here, we show that paired cysteine substitutions for the third gating charge (R3) in S4 and D60 in S2 of the bacterial sodium channel NaChBac form a disulfide bond during activation, thus “locking” the S4 segment and inducing slow inactivation of the channel. Disulfide locking closely followed the kinetics and voltage dependence of activation and was reversed by hyperpolarization. Activation of D60C:R3C channels is favored compared with single cysteine mutants, and mutant cycle analysis revealed strong free-energy coupling between these residues, further supporting interaction of R3 and D60 during gating. Our results demonstrate voltage-dependent formation of an ion pair during activation of the voltage sensor in real time and suggest that this interaction catalyzes S4 movement and channel activation.
T antigen mutations are a human tumor-specific signature for Merkel cell polyomavirus
Authors: Shuda Masahiro , Feng Huichen , Kwun Hyun Jin , Rosen Steven T. , Gjoerup Ole , Moore Patrick S. , Chang Yuan
Published: September 2008

Merkel cell polyomavirus (MCV) is a virus discovered in our laboratory at the University of Pittsburgh that is monoclonally integrated into the genome of ≈80% of human Merkel cell carcinomas (MCCs). Transcript mapping was performed to show that MCV expresses transcripts in MCCs similar to large T (LT), small T (ST), and 17kT transcripts of SV40. Nine MCC tumor-derived LT genomic sequences have been examined, and all were found to harbor mutations prematurely truncating the MCV LT helicase. In contrast, four presumed episomal viruses from nontumor sources did not possess this T antigen signature mutation. Using coimmunoprecipitation and origin replication assays, we show that tumor-derived virus mutations do not affect retinoblastoma tumor suppressor protein (Rb) binding by LT but do eliminate viral DNA replication capacity. Identification of an MCC cell line (MKL-1) having monoclonal MCV integration and the signature LT mutation allowed us to functionally test both tumor-derived and wild type (WT) T antigens. Only WT LT expression activates replication of integrated MCV DNA in MKL-1 cells. Our findings suggest that MCV-positive MCC tumor cells undergo selection for LT mutations to prevent autoactivation of integrated virus replication that would be detrimental to cell survival. Because these mutations render the virus replication-incompetent, MCV is not a “passenger virus” that secondarily infects MCC tumors.
Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics
Authors: Cideciyan Artur V. , Aleman Tomas S. , Boye Sanford L. , Schwartz Sharon B. , Kaushal Shalesh , Roman Alejandro J. , Pang Ji-jing , Sumaroka Alexander , Windsor Elizabeth A. M. , Wilson James M. , Flotte Terence R. , Fishman Gerald A. , Heon Elise , Stone Edwin M. , Byrne Barry J. , Jacobson Samuel G. , Hauswirth William W.
Published: September 2008

The
RPE65
gene encodes the isomerase of the retinoid cycle, the enzymatic pathway that underlies mammalian vision. Mutations in
RPE65
disrupt the retinoid cycle and cause a congenital human blindness known as Leber congenital amaurosis (LCA). We used adeno-associated virus-2-based
RPE65
gene replacement therapy to treat three young adults with
RPE65
-LCA and measured their vision before and up to 90 days after the intervention. All three patients showed a statistically significant increase in visual sensitivity at 30 days after treatment localized to retinal areas that had received the vector. There were no changes in the effect between 30 and 90 days. Both cone- and rod-photoreceptor-based vision could be demonstrated in treated areas. For cones, there were increases of up to 1.7 log units (i.e., 50 fold); and for rods, there were gains of up to 4.8 log units (i.e., 63,000 fold). To assess what fraction of full vision potential was restored by gene therapy, we related the degree of light sensitivity to the level of remaining photoreceptors within the treatment area. We found that the intervention could overcome nearly all of the loss of light sensitivity resulting from the biochemical blockade. However, this reconstituted retinoid cycle was not completely normal. Resensitization kinetics of the newly treated rods were remarkably slow and required 8 h or more for the attainment of full sensitivity, compared with <1 h in normal eyes. Cone-sensitivity recovery time was rapid. These results demonstrate dramatic, albeit imperfect, recovery of rod- and cone-photoreceptor-based vision after
RPE65
gene therapy.
NF-IL6 (C/EBPβ) induces HIV-1 replication by inhibiting cytidine deaminase APOBEC3G
Authors: Kinoshita Shigemi M. , Taguchi Shizuka
Published: September 2008

T cell activation is crucial for the productive HIV-1 infection of primary T cells; however, little is known about the host molecules involved in this process. We show that the host transcription factor NF-IL6 (also called C/EBPβ) renders primary CD4+T cells highly permissive for HIV-1 replication. NF-IL6 facilitates reverse transcription of the virus by binding to and inhibiting the antiviral cytidine deaminase APOBEC3G. A mutation in NF-IL6 at Ser-288 weakened its binding to APOBEC3G and strongly inhibited HIV-1 replication. NF-IL6 also induced the replication of a Vif-deficient strain of HIV-1 in nonpermissive HUT78 cells. These data indicate that NF-IL6 is a natural inhibitor of APOBEC3G that facilitates HIV-1 replication. Host factors, such as NF-IL6, that are involved in early HIV-1 replication are potential targets for anti-HIV-1 therapy. Our findings shed light on the activation of HIV-1 replication by T cell host molecules and reveal a unique regulation of DNA deamination by APOBEC3G and NF-IL6.
Loss of p120 catenin and links to mitotic alterations, inflammation, and skin cancer
Authors: Perez-Moreno Mirna , Song Weimin , Pasolli H. Amalia , Williams Scott E. , Fuchs Elaine
Published: September 2008

Tumor formation involves epigenetic modifications and microenvironmental changes as well as cumulative genetic alterations encompassing somatic mutations, loss of heterozygosity, and aneuploidy. Here, we show that conditional targeting of
p120 catenin
in mice leads to progressive development of skin neoplasias associated with intrinsic NF-κB activation. We find that, similarly, squamous cell carcinomas in humans display altered p120 and activated NF-κB. We show that epidermal hyperproliferation arising from p120 loss can be abrogated by IκB kinase 2 inhibitors. Although this underscores the importance of this pathway, the role of NF-κB in hyperproliferation appears rooted in its impact on epidermal microenvironment because as p120-null keratinocytes display a growth-arrested phenotype in culture. We trace this to a mitotic defect, resulting in unstable, binucleated cells
in vitro
and
in vivo
. We show that the abnormal mitoses can be ameliorated by inhibiting RhoA, the activity of which is abnormally high. Conversely, we can elicit such mitotic defects in control keratinocytes by elevating RhoA activity. The ability of p120 deficiency to elicit mitotic alterations and chronic inflammatory responses, that together may facilitate the development of genetic instability
in vivo
, provides insights into why it figures so prominently in skin cancer progression.
New insights into cadherin function in epidermal sheet formation and maintenance of tissue integrity
Authors: Tinkle Christopher L. , Pasolli H. Amalia , Stokes Nicole , Fuchs Elaine
Published: September 2008

Co-expression and gene linkage have hampered elucidating the physiological relevance of cadherins in mammalian tissues. Here, we combine conditional gene ablation and transgenic RNA interference to uncover new roles for E- and P-cadherins in epidermal sheet formation
in vitro
and maintenance of epidermal integrity
in vivo
. By devising skin-specific RNAi technology, we demonstrate that cadherin inhibition
in vivo
impairs junction formation and intercellular adhesion and increases apoptosis. These defects compromise epidermal barrier function and tissue integrity.
In vitro
, with only E-cadherin missing, epidermal sheet formation is delayed, but when both cadherins are suppressed, defects extend to adherens junctions, desmosomes, tight junctions and cortical actin dynamics. Using different rescue strategies, we show that cadherin level rather than subtype is critical. Finally, by comparing conditional loss-of-function studies of epidermal catenins and cadherins, we dissect cadherin-dependent and independent roles of adherens junction components in tissue physiology.
Ancient origin of the gene encoding involucrin, a precursor of the cross-linked envelope of epidermis and related epithelia
Authors: Vanhoutteghem Amandine , Djian Philippe , Green Howard
Published: September 2008

The cross-linked (cornified) envelope is a characteristic product of terminal differentiation in the keratinocyte of the epidermis and related epithelia. This envelope contains many proteins of which involucrin was the first to be discovered and shown to become cross-linked by a cellular transglutaminase. Involucrin has evolved greatly in placental mammals, but retains the glutamine repeats that make it a good substrate for the transglutaminase. Until recently, it has been impossible to detect involucrin outside the placental mammals, but analysis of the GenBank and Ensembl databases that have become available since 2006 reveals the existence of involucrin in marsupials and birds. We describe here the properties of these involucrins and the ancient history of their evolution.
Melting of ice under pressure
Authors: Schwegler Eric , Sharma Manu , Gygi François , Galli Giulia
Published: September 2008

The melting of ice under pressure is investigated with a series of first-principles molecular dynamics simulations. In particular, a two-phase approach is used to determine the melting temperature of the ice-VII phase in the range of 10–50 GPa. Our computed melting temperatures are consistent with existing diamond anvil cell experiments. We find that for pressures between 10 and 40 GPa, ice melts as a molecular solid. For pressures above ≈45 Gpa, there is a sharp increase in the slope of the melting curve because of the presence of molecular dissociation and proton diffusion in the solid before melting. The onset of significant proton diffusion in ice-VII as a function of increasing temperature is found to be gradual and bears many similarities to that of a type-II superionic solid.
Emphasizers in spoken and written academic discourse
Authors: Diani Giuliana
Published: September 2008

The role played by mitigation in academic discourse has been the subject of intense scholarly interest over the last two decades,
but interest in the role played by intensifying textual elements expressing evaluation and stance — emphasizers — is a more recent
turn. This paper presents a preliminary attempt at capturing the uses of the adverb really across spoken and
written academic registers. The adverb really is examined with an eye to how its frequencies, meanings and uses
vary across spoken and written academic discourse. The findings will also be interpreted in terms of variation across genres and
disciplines. A quantitative analysis of this adverb reveals significant distributional trends across both academic genres and
disciplines, and a qualitative analysis of concordance lines confirms that these trends are motivated by genre-specific purposes
and disciplinary-specific practices, respectively.
N-grams in comparable specialized corpora
Authors: Forchini Pierfranca , Murphy Amanda
Published: September 2008

This paper investigates the idiom principle realized as four-word phrases (4-grams) headed by prepositions in specialized corpora
in English and Italian. Concentrating on at the end of, it reports that the collocates of at the end
of regard time, and that apparently synonymic 4-grams are not used in the same contexts. It then explores
realizations of at the end of in a specialized comparable corpus of Italian. Two findings emerge: firstly, that
the most obvious equivalent, alla fine d*, occurs more frequently than in the English corpus;
secondly, this n-gram is frequently used, but has weaker collocational relations, and several synonymic 3-grams share its
collocates. This invites contrastive research on lexical variation and repetition and on the strength of collocations of
multi-word units in English and Italian. Lastly, the paper recounts an experiment with students who gained awareness of language
by concentrating on phraseology in comparable corpora.
From phraseology to culture
Authors: Manca Elena
Published: September 2008

This paper aims to describe the phraseology associated with adjectives in the language of tourism. The adjectives appearing in the
word list of a British farmhouse holidays corpus were grouped into three different semantic fields (‘description of rooms’,
‘description of surroundings’, and ‘description of food’) and from which their collocational profiles were then identified. In
order to compare and contrast the Italian and the British languages of tourism, we searched an Italian comparable agriturismi
corpus for items that are used to describe rooms, food, and surroundings. The results are discussed with reference to Sinclair’s
theories on the influence of context and register on language choices (Sinclair 1991), and Hall’s theory of high vs. low context
cultures (Hall 1976, 1989; Katan 2003). This analysis shows that the language of tourism is highly phraseological. It also gives
insights into some differences and similarities between English and Italian in terms of ‘language systems’ and cultural
orientations.
The p110δ of PI3K plays a critical role in NK cell terminal maturation and cytokine/chemokine generation
Authors: Guo Hailong , Samarakoon Asanga , Vanhaesebroeck Bart , Malarkannan Subramaniam
Published: September 2008

Phosphatidylinositol 3-kinases (PI3Ks) play a critical role in regulating B cell receptor– and T cell receptor–mediated signaling. However, their role in natural killer (NK) cell development and functions is not well understood. Using mice expressing p110δD910A, a catalytically inactive p110δ, we show that these mice had reduced NK cellularity, defective Ly49C and Ly49I NK subset maturation, and decreased CD27High NK numbers. p110δ inactivation marginally impaired NK-mediated cytotoxicity against tumor cells in vitro and in vivo. However, NKG2D, Ly49D, and NK1.1 receptor–mediated cytokine and chemokine generation by NK cells was severely affected in these mice. Further, p110δD910A/D910A NK cell–mediated antiviral responses through natural cytotoxicity receptor 1 were reduced. Analysis of signaling events demonstrates that p110δD910A/D910A NK cells had a reduced c-Jun N-terminal kinase 1/2 phosphorylation in response to NKG2D-mediated activation. These results reveal a previously unrecognized role of PI3K-p110δ in NK cell development and effector functions.
Dissecting T cell lineage relationships by cellular barcoding
Authors: Schepers Koen , Swart Erwin , van Heijst Jeroen W.J. , Gerlach Carmen , Castrucci Maria , Sie Daoud , Heimerikx Mike , Velds Arno , Kerkhoven Ron M. , Arens Ramon , Schumacher Ton N.M.
Published: September 2008

T cells, as well as other cell types, are composed of phenotypically and functionally distinct subsets. However, for many of these populations it is unclear whether they develop from common or separate progenitors. To address such issues, we developed a novel approach, termed cellular barcoding, that allows the dissection of lineage relationships. We demonstrate that the labeling of cells with unique identifiers coupled to a microarray-based detection system can be used to analyze family relationships between the progeny of such cells. To exemplify the potential of this technique, we studied migration patterns of families of antigen-specific CD8+ T cells in vivo. We demonstrate that progeny of individual T cells rapidly seed independent lymph nodes and that antigen-specific CD8+ T cells present at different effector sites are largely derived from a common pool of precursors. These data show how locally primed T cells disperse and provide a technology for kinship analysis with wider utility.
Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein
Authors: Cheng Pingyan , Corzo Cesar A. , Luetteke Noreen , Yu Bin , Nagaraj Srinivas , Bui Marylin M. , Ortiz Myrna , Nacken Wolfgang , Sorg Clemens , Vogl Thomas , Roth Johannes , Gabrilovich Dmitry I.
Published: September 2008

Accumulation of myeloid-derived suppressor cells (MDSCs) associated with inhibition of dendritic cell (DC) differentiation is one of the major immunological abnormalities in cancer and leads to suppression of antitumor immune responses. The molecular mechanism of this phenomenon remains unclear. We report here that STAT3-inducible up-regulation of the myeloid-related protein S100A9 enhances MDSC production in cancer. Mice lacking this protein mounted potent antitumor immune responses and rejected implanted tumors. This effect was reversed by administration of wild-type MDSCs from tumor-bearing mice to S100A9-null mice. Overexpression of S100A9 in cultured embryonic stem cells or transgenic mice inhibited the differentiation of DCs and macrophages and induced accumulation of MDSCs. This study demonstrates that tumor-induced up-regulation of S100A9 protein is critically important for accumulation of MDSCs and reveals a novel molecular mechanism of immunological abnormalities in cancer.
Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia
Authors: El-Osta Assam , Brasacchio Daniella , Yao Dachun , Pocai Alessandro , Jones Peter L. , Roeder Robert G. , Cooper Mark E. , Brownlee Michael
Published: September 2008

The current goal of diabetes therapy is to reduce time-averaged mean levels of glycemia, measured as HbA1c, to prevent diabetic complications. However, HbA1c only explains <25% of the variation in risk of developing complications. Because HbA1c does not correlate with glycemic variability when adjusted for mean blood glucose, we hypothesized that transient spikes of hyperglycemia may be an HbA1c–independent risk factor for diabetic complications. We show that transient hyperglycemia induces long-lasting activating epigenetic changes in the promoter of the nuclear factor κB (NF-κB) subunit p65 in aortic endothelial cells both in vitro and in nondiabetic mice, which cause increased p65 gene expression. Both the epigenetic changes and the gene expression changes persist for at least 6 d of subsequent normal glycemia, as do NF-κB–induced increases in monocyte chemoattractant protein 1 and vascular cell adhesion molecule 1 expression. Hyperglycemia-induced epigenetic changes and increased p65 expression are prevented by reducing mitochondrial superoxide production or superoxide-induced α-oxoaldehydes. These results highlight the dramatic and long-lasting effects that short-term hyperglycemic spikes can have on vascular cells and suggest that transient spikes of hyperglycemia may be an HbA1c–independent risk factor for diabetic complications.
Dockground protein–protein docking decoy set
Authors: Liu Shiyong , Gao Ying , Vakser Ilya A.
Published: September 2008

Summary: A protein–protein docking decoy set is built for the Dockground unbound benchmark set. The GRAMM-X docking scan was used to generate 100 non-native and at least one near-native match per complex for 61 complexes. The set is a publicly available resource for the development of scoring functions and knowledge-based potentials for protein docking methodologies.

Availability: The decoys are freely available for download at http://dockground.bioinformatics.ku.edu/UNBOUND/decoy/decoy.php

Contact:  vakser@ku.edu
Interactions between the South American sea lion (Otaria flavescens) and the artisanal fishery off Coquimbo, northern Chile
Authors: Goetz Sabine , Wolff Matthias , Stotz Wolfgang , Villegas Mario J.
Published: September 2008

Goetz, S., Wolff, M., Stotz, W., and Villegas, M. J. 2008. Interactions between the South American sea lion (Otaria flavescens) and the artisanal fishery off Coquimbo, northern Chile. – ICES Journal of Marine Science, 65: 1739–1746. The South American sea lion (Otaria flavescens) forages in coastal waters, where it interacts with fisheries and causes considerable economic loss by removing some catch and damaging gear. This study describes for the fishery region of Coquimbo (Chile) where, when, and with what type of gear interactions occur, characterizes the animals involved (group size, sex, and age), and derives some management recommendations. The study was based on 55 interviews with fishers and observations aboard fishing vessels in the main fishing sectors between October 2003 and March 2004. Interactions were primarily at night (88% of interviewees fished at night), in the bay (“Bahía”) of Coquimbo (81% of interviewees fished in this sector), where shoaling fish were abundant, and with purse-seines (100% of interviewees used this gear). Although some large groups of sea lions were seen, most comprised 1–10 animals. Most animals that interacted with the fishing gear were males (67%), probably because of the different feeding strategies of the two sexes. Management options discussed include the adjustment of fisheries to foraging behaviour of sea lions, and the controlled elimination of conflicting animals.
Contribution of patient and physician factors to cardiac rehabilitation enrollment: a prospective multilevel study
Authors: Grace Sherry L. , Gravely-Witte Shannon , Brual Janette , Monette George , Suskin Neville , Higginson Lyall , Alter David A. , Stewart Donna E.
Published: September 2008

Background

Cardiac rehabilitation (CR) is an established means of reducing mortality, yet is grossly underutilized. This is due to both health system and patient-level factors; issues that have yet to be investigated concurrently. This study utilized a hierarchical design to examine physician and patient-level factors affecting verified CR enrollment.

Design

A prospective multisite study, using a multilevel design of 1490 coronary artery disease outpatients nested within 97 Ontario cardiology practices (mean 15 per cardiologist).

Methods

Cardiologists completed a survey regarding CR attitudes. Outpatients were surveyed prospectively to assess factors affecting CR enrollment. Patients were mailed a follow-up survey 9 months later to self-report CR enrollment This was verified with 40 CR sites.

Results

Five hundred and fifty (43.4%) outpatients were referred, and 469 (37.0%) enrolled in CR. In mixed logistic regression analyses, factors affecting verified CR enrollment were greater strength of physician endorsement ( P = 0.005), shorter distance to CR ( P = 0.001), being married ( P = 0.01), and fewer perceived CR barriers ( P = 0.03).

Conclusion

Both physician and patient factors play a part in CR enrollment. Patient CR barriers should be addressed during referral discussions, and reasons why physicians fail to uniformly endorse CR exploration. Although distance to CR was related to patient enrollment patterns, greater access to home-based CR services should be provided.
Atherosclerotic and pleural calcifications are related among asbestos-exposed workers
Authors: Vehmas Tapio , Hiltunen Asta , Kivisaari Leena , Leino-Arjas Päivi
Published: September 2008

Methods

We studied the relationship between calcified chest atherosclerosis and pleural plaques among 505 construction workers with computed tomography. The extent and thickness of pleural plaques and the score of visceral pleural thickening were estimated, as was calcification of both pleural disease and chest atherosclerosis.

Results

Adjusted for age, BMI, smoking, and asbestos exposure, pleural calcification was associated with calcification in coronary arteries ( P < 0.001) and in the aorta ( P < 0.001).

Conclusion

These associations may be due to susceptibility factors common to both conditions. Calcification in pleural plaques may be a hint of atherosclerosis at least among asbestos-exposed people.
Three‐Dimensional Imaging in Measuring Facial Aesthetic Outcomes
Authors: Lin Samuel J. , Patel Neel , O'Shaughnessy Kristina , Fine Neil A.
Published: September 2008

Objectives/Hypothesis: Medical imaging techniques have continually improved. However, measuring esthetic outcomes using conventional two‐dimensional photography has inherent limitations visualizing in three dimensions such as the face.

Study Design: This study used three‐dimensional imaging to visualize facial images preoperatively and postoperatively in patients undergoing Contour threadlift procedures.

Methods: In patients undergoing Contour threadlift placement for midfacial rejuvenation, we prospectively imaged and photographed patients preoperatively and postoperatively. From three‐dimensional images, we measured three‐axis vector movement of the facial soft tissue in millimeters. Three control subjects (n = 6, bilateral sides) who had not undergone any procedure were a control group to confirm stability of the images over time. Patients also completed a questionnaire regarding their results and overall experience.

Results: We studied 6 (n = 12, bilateral procedures) undergoing Contour thread placement. Analyzed images revealed a trend of midface soft tissue flattening of nasolabial contour over 3 months. Average nasolabial flattening or tightening was 2.3 mm (P > .05) in the Contour patient group. The flattening of the midfacial region returned to baseline postprocedure at 90 days. Three‐dimensional imaging for the control subjects demonstrate less than 0.2 mm change (P < .05) in the nasolabial region weekly over a period of 3 weeks.

Conclusions: After 3 months, patients undergoing Contour thread placement had three‐dimensional imaging measurements suggesting a return to baseline values. Three‐dimensional imaging may increase accuracy in quantifying change after surgery specifically with contour differences; film and digital photography capture in only two dimensions. The use of three‐dimensional imaging may be applicable to numerous clinical settings.
High dispersal potential has maintained long-term population stability in the North Atlantic copepodCalanus finmarchicus
Authors: Provan Jim , Beatty Gemma E , Keating Sianan L , Maggs Christine A , Savidge Graham
Published: September 2008

The cool-water copepodCalanus finmarchicusis a key species in North Atlantic marine ecosystems since it represents an important food resource for the developmental stages of several fish of major economic value. Over the last 40 years, however, data from the Continuous Plankton Recorder survey have highlighted a 70 per cent reduction inC. finmarchicusbiomass, coupled with a gradual northward shift in the species's distribution, which have both been linked with climate change. To determine the potential forC. finmarchicusto track changes in habitat availability and maintain stable effective population sizes, we have assessed levels of gene flow and dispersal in current populations, as well as using a coalescent approach together with palaeodistribution modelling to elucidate the historical population demography of the species over previous changes in Earth's climate. Our findings indicate high levels of dispersal and a constant effective population size over the period 359 000–566 000 BP and suggest thatC. finmarchicuspossesses the capacity to track changes in available habitat, a feature that may be of crucial importance to the species's ability to cope with the current period of global climate change.
Constraining free riding in public goods games: designated solitary punishers can sustain human cooperation
Authors: O'Gorman Rick , Henrich Joseph , Van Vugt Mark
Published: September 2008

Much of human cooperation remains an evolutionary riddle. Unlike other animals, people frequently cooperate with non-relatives in large groups. Evolutionary models of large-scale cooperation require not just incentives for cooperation, but also a credible disincentive for free riding. Various theoretical solutions have been proposed and experimentally explored, including reputation monitoring and diffuse punishment. Here, we empirically examine an alternative theoretical proposal: responsibility for punishment can be borne by one specific individual. This experiment shows that allowing a single individual to punish increases cooperation to the same level as allowing each group member to punish and results in greater group profits. These results suggest a potential key function of leadership in human groups and provides further evidence supporting that humans will readily and knowingly behave altruistically.
Wonderful Mira
Authors: Wareing Christopher John
Published: September 2008

Since being named ‘wonderful’ in the seventeenth century for its peculiar brightness variability, Mira A has been the subject of extensive research and become the prototype for a whole class of ‘Mira’ variable stars. The primary star in a binary system, Mira A is reaching the end of its life and currently undergoing an extended period of enhanced mass loss. Recent observations have revealed a surrounding arc-like structure and a stream of material stretching 12 light years away in opposition to the arc. In this article, I review recent modelling of this cometary appearance as a bow shock with an accompanying tail of material ram pressure stripped from the head of the bow shock, place Mira in an evolutionary context, predict its future with reference to the similar star R Hya and planetary nebula Sh 2-188, and speculate some avenues of research both on Mira itself and on other ‘Mira-like’ stars with bow shocks and tails. I also discuss the implications of this discovery for our own star, the Sun.
Atmospheric dynamics of tidally synchronized extrasolar planets
Authors: Cho James Y.-K
Published: September 2008

Tidally synchronized planets present a new opportunity for enriching our understanding of atmospheric dynamics on planets. Subject to an unusual forcing arrangement (steady irradiation on the same side of the planet throughout its orbit), the dynamics on these planets may be unlike that on any of the Solar System planets. Characterizing the flow pattern and temperature distribution on the extrasolar planets is necessary for reliable interpretation of data currently being collected, as well as for guiding future observations. In this paper, several fundamental concepts from atmospheric dynamics, likely to be central for characterization, are discussed. Theoretical issues that need to be addressed in the near future are also highlighted.
Introduction. Progress in astronomy: from gravitational waves to space weather
Authors: Thompson J. Michael T
Published: September 2008

This brief paper introduces and reviews the ‘visions of the future’ articles prepared by leading young scientists throughout the world for the first of two Christmas 2008 Triennial issues of
Phil. Trans. R. Soc. A
, devoted, respectively, to astronomy and Earth science. Contributions in astronomy include the very topical gamma-ray bursts, new ideas on stellar collapse and the unusual atmospheres of synchronized planets orbiting nearby stars.
On the acceleration of ultra-high-energy cosmic rays
Authors: Fraschetti Federico
Published: September 2008

Ultra-high-energy cosmic rays (UHECRs) hit the Earth's atmosphere with energies exceeding 10
18
 eV. This is the same energy as carried by a tennis ball moving at 100 km h
−1
, but concentrated on a subatomic particle. UHECRs are so rare (the flux of particles with
E
>10
20
 eV is 0.5 km
−2
per century) that only a few such particles have been detected over the past 50 years. Recently, the HiRes and Auger experiments have reported the discovery of a high-energy cut-off in the UHECR spectrum, and Auger has found an apparent clustering of the highest energy events towards nearby active galactic nuclei. Consensus is building that the highest energy particles are accelerated within the radio-bright lobes of these objects, but it remains unclear how this actually happens, and whether the cut-off is due to propagation effects or reflects an intrinsically physical limitation of the acceleration process. The low event statistics presently allows for many different plausible models; nevertheless observations are beginning to impose strong constraints on them. These observations have also motivated suggestions that new physics may be implicated. We present a review of the key theoretical and observational issues related to the processes of propagation and acceleration of UHECRs and proposed solutions.