bluuebunny/crossref_metadata_2025 huggingface dataset:
What Makes You Think You're so Smart?
Authors: Visser Beth A. , Ashton Michael C. , Vernon Philip A.
Published: January 2008

Abstract. This study examined the correlates of self-estimated levels of the eight abilities of Gardner's (1983) “multiple intelligences” framework. Participants (N = 200) estimated their own levels of the eight abilities, completed two maximum performance tests of each ability, and provided self-ratings of their personality characteristics. As observed in previous research, most participants tended to overestimate their levels of ability in most of the intelligence domains. Self-estimated ability levels were generally only modestly correlated with measured levels of the same ability, and tended to show equally strong correlations with personality variables. Sex differences were observed for self-estimates of some abilities, and these sex differences were largely independent of measured ability and personality. It was concluded that high levels of self-estimated ability were related to being male, having high measured ability, and being high in Conscientiousness, Extraversion, and Openness to Experience, and low in Emotionality.
Awards for Best Geoscience Publications
Authors: Showstack Randy
Published: January 2008

Four Earth science publications were honored by the Geoscience Information Society (GSIS) at its meeting held in conjunction with the 2007 meeting of the Geological Society of America. The four‐volume Encyclopedia of Quaternary Science, published by Elsevier in 2007, received the Mary B. Ansari Best Reference Work Award as an outstanding reference work in the field of geoscience information published during the previous 3 years. Lura E. Joseph, associate professor of administration and geology librarian at the University of Illinois at Urbana‐Champaign, received the GSIS Best Paper Award for her article, “Image and figure quality: A study of Elsevier's Earth and Planetary Sciences electronic journal back file package,” published in the September–December 2006 issue of Library Collections, Acquisitions, and Technical Services. The Best Guidebook Award recognized two books: Geology of the Chama Basin, published by the New Mexico Geological Society in 2005, and 1906 San Francisco Earthquake Centennial Field Guides, published by the Geological Society of America in 2006.
Drilling of the Mjølnir Structure, the Barents Sea: Workshop on Marine Impacts and Environmental Consequences; Longyearbyen, Norway, 10–13 September 2007
Authors: Dypvik Henning , Claeys Philippe , Deutsch Alex , Kyte Frank T. , Matsui Takafumi , Smelror Morten
Published: January 2008

In September 2007, thirty‐three scientists attended an international workshop in Norway to discuss impacts into marine targets and prepare the drilling of the 142‐million‐year‐old Mjølnir impact structure in the Barents Sea. The workshop focused on (1) mechanisms of marine impact cratering, including ejecta distribution, geothermal reactions, and tsunami production, and (2) environmental effects of marine impacts and potential links to the Jurassic/Cretaceous boundary (about 145 to 140 million years ago). A field trip visited the ejecta layer in Svalbard's Janusfjellet mountain.

Impacts, particularly in marine environments, can significantly affect Earth's geological and biological evolution. However, detailed knowledge of the marine impact cratering process is still limited. Among the 170 terrestrial craters, Mjølnir and its proximal ejecta deposits are unique: It is one of few marine impacts, and since the proximal ejecta always remained under water in calm conditions, it is most likely very well preserved. Today, the crater's central uplift is buried under ∼50 meters of postimpact sediments and 350 meters of water.
Mao Receives 2007 Inge Lehmann Medal
Authors: Hemley Russell J. , Mao Ho‐Kwang
Published: January 2008

The Inge Lehmann Medal is awarded in recognition of “outstanding contributions to the understanding of the structure, composition, and dynamics of the Earth's mantle and core.” When Ho‐kwang (Dave) Mao completed his Ph.D. in 1968 at the University of Rochester and moved to the Geophysical Laboratory, a revolution in how we could achieve that understanding was in the making.

Over the following four decades, Dave Mao redefined solid Earth geophysics, demonstrating that the mantle and core are accessible in the laboratory through direct study of their components at high pressures and temperatures. Through diverse, ingenious experimentation, this journey to the center of the planet has revealed the many dramatic ways that Earth materials transform under extreme conditions and established a materials‐based understanding of the deep interior.
Modern Perspectives on Measuring and Interpreting Seafloor Heat Flux: The Future of Marine Heat Flow: Defining Scientific Goals and Experimental Needs for the 21st Century; Salt Lake City, Utah, 6–7 September 2007
Authors: Harris Robert N. , Fisher Andrew , Ruppel Carolyn , Martinez Fernando
Published: January 2008

There has been a resurgence of interest in marine heat flow in the past 10–15 years, coinciding with fundamental achievements in understanding the Earth's thermal state and quantifying the dynamics and impacts of material and energy fluxes within and between the lithosphere and hydrosphere. At the same time, technical capabilities have dwindled to the point that no U.S. academic institution currently operates a seagoing heat flow capacity.

In September 2007, a workshop was convened in Salt Lake City with sponsorship from the U.S. National Science Foundation (NSF) and participation by scientists and engineers from North America, Europe, and Asia. The primary goals of the workshop were to (1) assess high‐priority scientific and technical needs and (2) to evaluate options for developing and maintaining essential capabilities in marine heat flow for the U.S. scientific community.
AGU Position Statements: Evolution and Nuclear‐Test‐Ban Treaty
Authors: Von Holle Kate
Published: January 2008

At its 14 December meeting, the AGU Council adopted four position statements, after months of work by panels of experts that also included input from the AGU membership. AGU formulates and maintains a number of position statements that reflect the concerns of the Union, and none of these position statements extends beyond the range of available geophysical data or the norms of legitimate scientific debate. Two of the four adopted statements— “Biological Evolution and the History of the Earth Are Foundations of Science” and “Capability to Monitor the Comprehensive Nuclear‐Test‐Ban Treaty”—have been released.
Development of a cell‐based assay for screening of phosphodiesterase 10A (PDE10A) inhibitors using a stable recombinant HEK‐293 cell line expressing high levels of PDE10A
Authors: Bora Roop Singh , Gupta Dikshi , Malik Renu , Chachra Sonia , Sharma Pratibha , Saini Kulvinder Singh
Published: January 2008

cDNA encoding PDE10A (phosphodiesterase 10A) was cloned and a stable recombinant HEK‐293 (human embryonic kidney‐293) cell line expressing high levels of PDE10A was generated. Transient transfection of pCRE‐Luc plasmid, harbouring the luciferase reporter gene under the control of CRE (cAMP‐response element)‐binding sequence, into the stable recombinant cell line, followed by treatment with PDE10 inhibitor, resulted in a dose‐dependent increase in luciferase activity. This method provides a simple and sensitive cell‐based assay for screening of PDE10 inhibitors for development of novel therapeutics for the treatment of neurological disorders.
Preparation of Silver - Gold Alloy Nanoparticles at Higher Concentration Using Sodium Dodecyl Sulfate
Authors: Pal Angshuman , Shah Sunil , Devi Surekha
Published: January 2008

Highly stable gold–silver alloy nanoparticles with varying mole fractions were prepared in aqueous sodium dodecyl sulfate solution by simultaneous reduction of chloroauric acid (HAuCl4) and silver nitrate (AgNO3) using sodium citrate. The formation of alloy nanoparticles was confirmed by UV-visible spectroscopy and transmission electron microscopy. Particle size distribution was measured by dynamic light scattering. The surface plasmon absorption band of the Au–Ag alloy nanoparticles shows linear bathochromic shift with increasing Au content. Appearance of a single absorption peak in the visible region and lack of apparent core-shell structures in the transmission electron microscope images confirm the formation of homogeneous gold–silver alloy nanoparticles.
The logic of indirect speech
Authors: Pinker Steven , Nowak Martin A. , Lee James J.
Published: January 2008

When people speak, they often insinuate their intent indirectly rather than stating it as a bald proposition. Examples include sexual come-ons, veiled threats, polite requests, and concealed bribes. We propose a three-part theory of indirect speech, based on the idea that human communication involves a mixture of cooperation and conflict. First, indirect requests allow for plausible deniability, in which a cooperative listener can accept the request, but an uncooperative one cannot react adversarially to it. This intuition is supported by a game-theoretic model that predicts the costs and benefits to a speaker of direct and indirect requests. Second, language has two functions: to convey information and to negotiate the type of relationship holding between speaker and hearer (in particular, dominance, communality, or reciprocity). The emotional costs of a mismatch in the assumed relationship type can create a need for plausible deniability and, thereby, select for indirectness even when there are no tangible costs. Third, people perceive language as a digital medium, which allows a sentence to generate common knowledge, to propagate a message with high fidelity, and to serve as a reference point in coordination games. This feature makes an indirect request qualitatively different from a direct one even when the speaker and listener can infer each other's intentions with high confidence.
Sex-specific perceptual spaces for a vertebrate basal social aggregative behavior
Authors: Engeszer Raymond E. , Wang George , Ryan Michael J. , Parichy David M.
Published: January 2008

Loose aggregations of fishes, or shoals, are a basal social organization of vertebrates and offer a valuable opportunity to determine how individual perceptions influence group formation. We used zebrafish,Danio rerio, to comprehensively investigate the preference space for shoaling related to adult pigment pattern variation, presented in the form of 17 zebrafish pigment pattern mutants or closely related species. We examined all combinations of these phenotypes in 2,920 initial and replicated preference tests, and used as subjects both domesticated laboratory stocks and wild-caught fish. By using multidimensional scaling and other approaches, we show that laboratory and wild zebrafish exhibit similar preferences, yet, unexpectedly, these preferences differ markedly between sexes, and also from how human observers perceive the same pigment patterns. Whereas zebrafish males respond to two traits (species and stripe patterning) in deciding whether to join a shoal, zebrafish female preferences do not correlate witha prioriidentifiable traits, and neither perceptual world is correlated with that of human observers. The observed zebrafish sex differences run counter to the most commonly accepted explanations for the individual selective advantages gained by shoaling. More generally, these data describe very different perceptual worlds between sexes and reveal the importance of sex differences in social group formation, as well as the critical importance of defining species specificity in visual signaling.
High-confidence prediction of global interactomes based on genome-wide coevolutionary networks
Authors: Juan David , Pazos Florencio , Valencia Alfonso
Published: January 2008

Interacting or functionally related protein families tend to have similar phylogenetic trees. Based on this observation, techniques have been developed to predict interaction partners. The observed degree of similarity between the phylogenetic trees of two proteins is the result of many different factors besides the actual interaction or functional relationship between them. Such factors influence the performance of interaction predictions. One aspect that can influence this similarity is related to the fact that a given protein interacts with many others, and hence it must adapt to all of them. Accordingly, the interaction or coadaptation signal within its tree is a composite of the influence of all of the interactors. Here, we introduce a new estimator of coevolution to overcome this and other problems. Instead of relying on the individual value of tree similarity between two proteins, we use the whole network of similarities between all of the pairs of proteins within a genome to reassess the similarity of that pair, thereby taking into account its coevolutionary context. We show that this approach offers a substantial improvement in interaction prediction performance, providing a degree of accuracy/coverage comparable with, or in some cases better than, that of experimental techniques. Moreover, important information on the structure, function, and evolution of macromolecular complexes can be inferred with this methodology.
Direct transfer of starter substrates from type I fatty acid synthase to type III polyketide synthases in phenolic lipid synthesis
Authors: Miyanaga Akimasa , Funa Nobutaka , Awakawa Takayoshi , Horinouchi Sueharu
Published: January 2008

Alkylresorcinols and alkylpyrones, which have a polar aromatic ring and a hydrophobic alkyl chain, are phenolic lipids found in plants, fungi, and bacteria. In the Gram-negative bacterium
Azotobacter vinelandii
, phenolic lipids in the membrane of dormant cysts are essential for encystment. The aromatic moieties of the phenolic lipids in
A. vinelandii
are synthesized by two type III polyketide synthases (PKSs), ArsB and ArsC, which are encoded by the
ars
operon. However, details of the synthesis of hydrophobic acyl chains, which might serve as starter substrates for the type III polyketide synthases (PKSs), were unknown. Here, we show that two type I fatty acid synthases (FASs), ArsA and ArsD, which are members of the
ars
operon, are responsible for the biosynthesis of C
22
–C
26
fatty acids from malonyl-CoA.
In vivo
and
in vitro
reconstitution of phenolic lipid synthesis systems with the Ars enzymes suggested that the C
22
–C
26
fatty acids produced by ArsA and ArsD remained attached to the ACP domain of ArsA and were transferred hand-to-hand to the active-site cysteine residues of ArsB and ArsC. The type III PKSs then used the fatty acids as starter substrates and carried out two or three extensions with malonyl-CoA to yield the phenolic lipids. The phenolic lipids in
A. vinelandii
were thus found to be synthesized solely from malonyl-CoA by the four members of the
ars
operon. This is the first demonstration that a type I FAS interacts directly with a type III PKS through substrate transfer.
Micromechanical properties of keratin intermediate filament networks
Authors: Sivaramakrishnan Sivaraj , DeGiulio James V. , Lorand Laszlo , Goldman Robert D. , Ridge Karen M.
Published: January 2008

Keratin intermediate filaments (KIFs) form cytoskeletal KIF networks that are essential for the structural integrity of epithelial cells. However, the mechanical properties of the
in situ
network have not been defined. Particle-tracking microrheology (PTM) was used to obtain the micromechanical properties of the KIF network in alveolar epithelial cells (AECs), independent of other cytoskeletal components, such as microtubules and microfilaments. The storage modulus (
G′
) at 1 Hz of the KIF network decreases from the perinuclear region (335 dyn/cm
2
) to the cell periphery (95 dyn/cm
2
), yielding a mean value of 210 dyn/cm
2
. These changes in
G′
are inversely proportional to the mesh size of the network, which increases ≈10-fold from the perinuclear region (0.02 μm
2
) to the cell periphery (0.3 μm
2
). Shear stress (15 dyn/cm
2
for 4 h) applied across the surface of AECs induces a more uniform distribution of KIF, with the mesh size of the network ranging from 0.02 μm
2
near the nucleus to only 0.04 μm
2
at the cell periphery. This amounts to a 40% increase in the mean
G′
. The storage modulus of the KIF network in the perinuclear region accurately predicts the shear-induced deflection of the cell nucleus to be 0.87 ± 0.03 μm. The high storage modulus of the KIF network, coupled with its solid-like rheological behavior, supports the role of KIF as an intracellular structural scaffold that helps epithelial cells to withstand external mechanical forces.
PPARα agonist fenofibrate suppresses tumor growth through direct and indirect angiogenesis inhibition
Authors: Panigrahy Dipak , Kaipainen Arja , Huang Sui , Butterfield Catherine E. , Barnés Carmen M. , Fannon Michael , Laforme Andrea M. , Chaponis Deviney M. , Folkman Judah , Kieran Mark W.
Published: January 2008

Angiogenesis and inflammation are central processes through which the tumor microenvironment influences tumor growth. We have demonstrated recently that peroxisome proliferator-activated receptor (PPAR)α deficiency in the host leads to overt inflammation that suppresses angiogenesis via excess production of thrombospondin (TSP)-1 and prevents tumor growth. Hence, we speculated that pharmacologic activation of PPARα would promote tumor growth. Surprisingly, the PPARα agonist fenofibrate potently suppressed primary tumor growth in mice. This effect was not mediated by cancer-cell-autonomous antiproliferative mechanisms but by the inhibition of angiogenesis and inflammation in the host tissue. Although PPARα-deficient tumors were still susceptible to fenofibrate, absence of PPARα in the host animal abrogated the potent antitumor effect of fenofibrate. In addition, fenofibrate suppressed endothelial cell proliferation and VEGF production, increased TSP-1 and endostatin, and inhibited corneal neovascularization. Thus, both genetic abrogation of PPARα as well as its activation by ligands cause tumor suppression via overlapping antiangiogenic pathways. These findings reveal the potential utility of the well tolerated PPARα agonists beyond their use as lipid-lowering drugs in anticancer therapy. Our results provide a mechanistic rationale for evaluating the clinical benefits of PPARα agonists in cancer treatment, alone and in combination with other therapies.
From proper name to primary interjection
Authors: Gehweiler Elke
Published: January 2008

This paper is concerned with interjections that have evolved from nouns. Looking at a subclass of interjections, so-called expletives like gee!, jeeze!, gosh!, crikey!, it will be shown how primary interjections regularly evolve from religious names (here Jesus, God, Christ) via secondary interjections (Jesus!, God!, Christ!). Four stages can be distinguished:

I proper name Jesus

II secondary interjection Jesus!

III phonological modification of Jesus!

IV primary interjection gee!

The “standard” model for subjectification in grammaticalization, Traugott and Dasher’s Invited Inferencing Theory of Semantic Change (2002), which focuses on the speaker as initiator of change, suffices to explain the gradual process through which the secondary interjection Jesus! has evolved through the repeated use of Jesus in invocations, oaths and prayers. Moreover it is claimed that the syntactic position of Jesus in these uses — sentence-initial and separated from the rest of the sentence — played a crucial role in the emergence of the interjection.

Invited inferencing, however, fails to explain the emergence of gee!. It will be shown with corpus data that gee! emerged rather abruptly. The meaning of gee! is different from the meaning of Jesus! from its very beginning, and — in contrast to the process through which the secondary interjection Jesus! emerged — there are no transitional stages attested where both the meaning of Jesus! and the meaning of gee! can be inferred. It will be argued that this change was hearer-based and that semantic stability and relationships between words are determined by aspects of phonological transparency. As a result of the clipping of Jesus! (speakers did not want to “take the name of the Lord in vain”), which yielded gee!, the semantic base of gee! became phonologically obscured. Accordingly the hearer had to infer the meaning of gee! from the context of its occurrence alone — consequently gee! differed in meaning from Jesus! straightaway.

The OED will be used as a corpus for the diachronic study (cf. Fischer 1992 and Hoffmann 2004 for a discussion of how the OED can be used as a historical corpus). The synchronic use of the forms discussed will be illustrated with examples from the British National Corpus and from the GoogleGroups newsgroups (cf. Bergh 2005 for a discussion of whether and how the Internet can be used as corpus).
Distinct Chromatin Modulators Regulate the Formation of Accessible and Repressive Chromatin at the Fission Yeast Recombination Hotspotade6-M26
Authors: Hirota Kouji , Mizuno Ken-ichi , Shibata Takehiko , Ohta Kunihiro
Published: January 2008

Histone acetyltransferases (HATs) and ATP-dependent chromatin remodeling factors (ADCRs) regulate transcription and recombination via alteration of local chromatin configuration. The ade6-M26 allele of Schizosaccharomyces pombe creates a meiotic recombination hotspot that requires a cAMP-responsive element (CRE)-like sequence M26, the Atf1/Pcr1 heterodimeric ATF/CREB transcription factor, the Gcn5 HAT, and the Snf22 SWI2/SNF2 family ADCR. Chromatin alteration occurs meiotically around M26, leading to the activation of meiotic recombination. We newly report the roles of other chromatin remodeling factors that function positively and negatively in chromatin alteration at M26: two CHD-1 family ADCRs (Hrp1 and Hrp3), a Spt-Ada-Gcn5 acetyltransferase component (Ada2), and a member of Moz-Ybf2/Sas3-Sas2-Tip60 family (Mst2). Ada2, Mst2, and Hrp3 are required for the full activation of chromatin changes around M26 and meiotic recombination. Acetylation of histone H3 around M26 is remarkably reduced in gcn5Δ, ada2Δ and snf22Δ, suggesting cooperative functions of these HAT complexes and Snf22. Conversely, Hrp1, another CHD-1 family ADCR, maintains repressive chromatin configuration at ade6-M26. Interestingly, transcriptional initiation site is shifted to a site around M26 from the original initiation sites, in couple with the histone acetylation and meiotic chromatin alteration induced around 3′ region of M26, suggesting a collaboration between these chromatin modulators and the transcriptional machinery to form accessible chromatin. These HATs and ADCRs are also required for the regulation of transcription and chromatin structure around M26 in response to osmotic stress. Thus, we propose that multiple chromatin modulators regulate chromatin structure reversibly and participate in the regulation of both meiotic recombination and stress-induced transcription around CRE-like sequences.
Different Effects ofTetrahymena IFT172Domains on Anterograde and Retrograde Intraflagellar Transport
Authors: Tsao Che-Chia , Gorovsky Martin A.
Published: January 2008

Intraflagellar transport (IFT) particles are multiprotein complexes that move bidirectionally along the cilium/flagellum. The Tetrahymena IFT172 gene encodes a protein with an N-terminal WD domain (WDD) and a C-terminal repeat domain (RPD). Epitope-tagged Ift172p localized to the basal body and in cilia along the axoneme, and IFT172 knockout cells lost cilia and motility. Using serial deletion constructs to rescue the knockout cells, we found that neither the WDD nor the RPD alone is sufficient to assemble cilia. Ift172p containing only the WDD or the RPD failed to enter cilia. Constructs with a partial truncation of the RPD still rescued although cilia were assembled less efficiently, indicating that the WDD and a part of the RPD are sufficient for anterograde transport. Partial truncation of the RPD caused the accumulation of truncated Ift172p itself and of Ift88p at ciliary tips, suggesting that IFT turnaround or retrograde transport was affected. These results implicate different regions of Ift172p in different steps of the IFT process.
The Primate-specific Protein TBC1D3 Is Required for Optimal Macropinocytosis in a Novel ARF6-dependent Pathway
Authors: Frittoli Emanuela , Palamidessi Andrea , Pizzigoni Alessandro , Lanzetti Letizia , Garrè Massimiliano , Troglio Flavia , Troilo Albino , Fukuda Mitsunori , Di Fiore Pier Paolo , Scita Giorgio , Confalonieri Stefano
Published: January 2008

The generation of novel genes and proteins throughout evolution has been proposed to occur as a result of whole genome and gene duplications, exon shuffling, and retrotransposition events. The analysis of such genes might thus shed light into the functional complexity associated with highly evolved species. One such case is represented by TBC1D3, a primate-specific gene, harboring a TBC domain. Because TBC domains encode Rab-specific GAP activities, TBC-containing proteins are predicted to play a major role in endocytosis and intracellular traffic. Here, we show that the TBC1D3 gene originated late in evolution, likely through a duplication of the RNTRE locus, and underwent gene amplification during primate speciation. Despite possessing a TBC domain, TBC1D3 is apparently devoid of Rab-GAP activity. However, TBC1D3 regulates the optimal rate of epidermal growth factor–mediated macropinocytosis by participating in a novel pathway involving ARF6 and RAB5. In addition, TBC1D3 binds and colocalize to GGA3, an ARF6-effector, in an ARF6-dependent manner, and synergize with it in promoting macropinocytosis, suggesting that the two proteins act together in this process. Accordingly, GGA3 siRNA-mediated ablation impaired TBC1D3-induced macropinocytosis. We thus uncover a novel signaling pathway that appeared after primate speciation. Within this pathway, a TBC1D3:GGA3 complex contributes to optimal propagation of signals, ultimately facilitating the macropinocytic process.
The Human Spindle Assembly Checkpoint Protein Bub3 Is Required for the Establishment of Efficient Kinetochore–Microtubule Attachments
Authors: Logarinho Elsa , Resende Tatiana , Torres Cláudia , Bousbaa Hassan
Published: January 2008

The spindle assembly checkpoint monitors the status of kinetochore–microtubule (K-MT) attachments and delays anaphase onset until full metaphase alignment is achieved. Recently, the role of spindle assembly checkpoint proteins was expanded with the discovery that BubR1 and Bub1 are implicated in the regulation of K-MT attachments. One unsolved question is whether Bub3, known to form cell cycle constitutive complexes with both BubR1 and Bub1, is also required for proper chromosome-to-spindle attachments. Using RNA interference and high-resolution microscopy, we analyzed K-MT interactions in Bub3-depleted cells and compared them to those in Bub1- or BubR1-depleted cells. We found that Bub3 is essential for the establishment of correct K-MT attachments. In contrast to BubR1 depletion, which severely compromises chromosome attachment and alignment, we found Bub3 and Bub1 depletions to produce defective K-MT attachments that, however, still account for significant chromosome congression. After Aurora B inhibition, alignment defects become severer in Bub3- and Bub1-depleted cells, while partially rescued in BubR1-depleted cells, suggesting that Bub3 and Bub1 depletions perturb K-MT attachments distinctly from BubR1. Interestingly, misaligned chromosomes in Bub3- and Bub1-depleted cells were found to be predominantly bound in a side-on configuration. We propose that Bub3 promotes the formation of stable end-on bipolar attachments.
The Ubiquitin-like Protein PLIC-2 Is a Negative Regulator of G Protein-coupled Receptor Endocytosis
Authors: N'Diaye Elsa-Noah , Hanyaloglu Aylin C. , Kajihara Kimberly K. , Puthenveedu Manojkumar A. , Wu Ping , von Zastrow Mark , Brown Eric J.
Published: January 2008

The activity of many signaling receptors is regulated by their endocytosis via clathrin-coated pits (CCPs). For G protein-coupled receptors (GPCRs), recruitment of the adaptor protein arrestin to activated receptors is thought to be sufficient to drive GPCR clustering in CCPs and subsequent endocytosis. We have identified an unprecedented role for the ubiquitin-like protein PLIC-2 as a negative regulator of GPCR endocytosis. Protein Linking IAP to Cytoskeleton (PLIC)-2 overexpression delayed ligand-induced endocytosis of two GPCRs: the V2 vasopressin receptor and β-2 adrenergic receptor, without affecting endocytosis of the transferrin or epidermal growth factor receptor. The closely related isoform PLIC-1 did not affect receptor endocytosis. PLIC-2 specifically inhibited GPCR concentration in CCPs, without affecting membrane recruitment of arrestin-3 to activated receptors or its cellular levels. Depletion of cellular PLIC-2 accelerated GPCR endocytosis, confirming its regulatory function at endogenous levels. The ubiquitin-like domain of PLIC-2, a ligand for ubiquitin-interacting motifs (UIMs), was required for endocytic inhibition. Interestingly, the UIM-containing endocytic adaptors epidermal growth factor receptor protein substrate 15 and Epsin exhibited preferential binding to PLIC-2 over PLIC-1. This differential interaction may underlie PLIC-2 specific effect on GPCR endocytosis. Identification of a negative regulator of GPCR clustering reveals a new function of ubiquitin-like proteins and highlights a cellular requirement for exquisite regulation of receptor dynamics.
Phosphorylation by c-Jun NH2-terminal Kinase 1 Regulates the Stability of Transcription Factor Sp1 during Mitosis
Authors: Chuang Jian-Ying , Wang Yi-Ting , Yeh Shiu-Hwa , Liu Yi-Wen , Chang Wen-Chang , Hung Jan-Jong
Published: January 2008

The transcription factor Sp1 is ubiquitously expressed in different cells and thereby regulates the expression of genes involved in many cellular processes. This study reveals that Sp1 was phosphorylated during the mitotic stage in three epithelial tumor cell lines and one glioma cell line. By using different kinase inhibitors, we found that during mitosis in HeLa cells, the c-Jun NH2-terminal kinase (JNK) 1 was activated that was then required for the phosphorylation of Sp1. In addition, blockade of the Sp1 phosphorylation via inhibition JNK1 activity in mitosis resulted in the ubiquitination and degradation of Sp1. JNK1 phosphorylated Sp1 at Thr278/739. The Sp1 mutated at Thr278/739 was unstable during mitosis, possessing less transcriptional activity for the 12(S)-lipoxygenase expression and exhibiting a decreased cell growth rate compared with wild-type Sp1 in HeLa cells. In N-methyl-N-nitrosourea–induced mammary tumors, JNK1 activation provided a potential relevance with the accumulation of Sp1. Together, our results indicate that JNK1 activation is necessary to phosphorylate Sp1 and to shield Sp1 from the ubiquitin-dependent degradation pathway during mitosis in tumor cell lines.
Activation of Heat Shock and Antioxidant Responses by the Natural Product Celastrol: Transcriptional Signatures of a Thiol-targeted Molecule
Authors: Trott Amy , West James D. , Klaić Lada , Westerheide Sandy D. , Silverman Richard B. , Morimoto Richard I. , Morano Kevin A.
Published: January 2008

Stress response pathways allow cells to sense and respond to environmental changes and adverse pathophysiological states. Pharmacological modulation of cellular stress pathways has implications in the treatment of human diseases, including neurodegenerative disorders, cardiovascular disease, and cancer. The quinone methide triterpene celastrol, derived from a traditional Chinese medicinal herb, has numerous pharmacological properties, and it is a potent activator of the mammalian heat shock transcription factor HSF1. However, its mode of action and spectrum of cellular targets are poorly understood. We show here that celastrol activates Hsf1 in Saccharomyces cerevisiae at a similar effective concentration seen in mammalian cells. Transcriptional profiling revealed that celastrol treatment induces a battery of oxidant defense genes in addition to heat shock genes. Celastrol activated the yeast Yap1 oxidant defense transcription factor via the carboxy-terminal redox center that responds to electrophilic compounds. Antioxidant response genes were likewise induced in mammalian cells, demonstrating that the activation of two major cell stress pathways by celastrol is conserved. We report that celastrol's biological effects, including inhibition of glucocorticoid receptor activity, can be blocked by the addition of excess free thiol, suggesting a chemical mechanism for biological activity based on modification of key reactive thiols by this natural product.
Roles of Greatwall Kinase in the Regulation of Cdc25 Phosphatase
Authors: Zhao Yong , Haccard Olivier , Wang Ruoning , Yu Jiangtao , Kuang Jian , Jessus Catherine , Goldberg Michael L.
Published: January 2008

We previously reported that immunodepletion of Greatwall kinase prevents Xenopus egg extracts from entering or maintaining M phase due to the accumulation of inhibitory phosphorylations on Thr14 and Tyr15 of Cdc2. M phase–promoting factor (MPF) in turn activates Greatwall, implying that Greatwall participates in an MPF autoregulatory loop. We show here that activated Greatwall both accelerates the mitotic G2/M transition in cycling egg extracts and induces meiotic maturation in G2-arrested Xenopus oocytes in the absence of progesterone. Activated Greatwall can induce phosphorylations of Cdc25 in the absence of the activity of Cdc2, Plx1 (Xenopus Polo-like kinase) or mitogen-activated protein kinase, or in the presence of an activator of protein kinase A that normally blocks mitotic entry. The effects of active Greatwall mimic in many respects those associated with addition of the phosphatase inhibitor okadaic acid (OA); moreover, OA allows cycling extracts to enter M phase in the absence of Greatwall. Taken together, these findings support a model in which Greatwall negatively regulates a crucial phosphatase that inhibits Cdc25 activation and M phase induction.
Anti‐microbial Activity of Urine after Ingestion of Cranberry: A Pilot Study
Authors: Lee Yee Lean , Najm Wadie I. , Owens John , Thrupp Laurie , Baron Sheryl , Shanbrom Edward , Cesario Thomas
Published: January 2008

We explore the anti‐microbial activity of urine specimens after the ingestion of a commercial cranberry preparation. Twenty subjects without urinary infection, off antibiotics and all supplements or vitamins were recruited. The study was conducted in two phases: in phase 1, subjects collected the first morning urine prior to ingesting 900 mg of cranberry and then at 2, 4 and 6 h. In phase 2, subjects collected urine on 2 consecutive days: on Day 1 no cranberry was ingested (control specimens), on Day 2, cranberry was ingested. The pH of all urine specimens were adjusted to the same pH as that of the first morning urine specimen. Aliquots of each specimen were independently inoculated with Escherichia coli, Klebsiella pneumoniae or Candida albicans. After incubation, colony forming units/ml (CFU ml−1) in the control specimen was compared with CFU ml−1 in specimens collected 2, 4 and 6 h later. Specimens showing ≥50% reduction in CFU ml−1 were considered as having ‘activity’ against the strains tested. In phase 1, 7/20 (35%) subjects had anti‐microbial activity against E. coli, 13/20 (65%) against K. pneumoniae and 9/20 (45%) against C. albicans in specimens collected 2–6 h after ingestion of cranberry. In phase 2, 6/9 (67%) of the subjects had activity against K. pneumoniae. This pilot study demonstrates weak anti‐microbial activity in urine specimens after ingestion of a single dose of commercial cranberry. Anti‐microbial activity was noted only against K. pneumoniae 2–6 h after ingestion of the cranberry preparation.
Complementary and Alternative Medicine Familiarization: What′s happening in Medical Schools in Wales?
Authors: Taylor Natalie , Blackwell Anona
Published: January 2008

Despite recommendations that complementary and alternative medicine (CAM) familiarization should be offered to UK medical students, in Wales little such teaching was offered. We decided to assess medical students’ knowledge of CAMs, perceived training needs in CAMs, their view of its role in the National Health Service (NHS) and current teaching given. Analysis of data from a questionnaire given to medical students and direct questioning of senior academic medical school staff in Cardiff and Swansea Medical Schools was carried out. The participants comprised 78 first year medical students in the undergraduate entry program in Cardiff and 58 first year medical students from the graduate entry program in Swansea. Senior academic medical school staff at Cardiff and Swansea Medical Schools were asked about current CAM teaching. Results revealed that 32% of undergraduate entry students (UGES) had previous knowledge of CAMs compared with 51% of graduate entry students (GES). Of the UGES, 62% believed they should be taught about CAM′s compared with 94% of GES. Of UGES 31% felt that CAMs have a role in the NHS compared with 50% of GES. None of the students had received teaching about CAMs and little formal CAM teaching is currently included in the curricula at each site. The majority of medical students in Wales would like to receive CAM teaching and significant numbers support a role for CAMs in the NHS. Little formal teaching is currently provided.
Chromosomal inversion between rrn operons among Streptococcus mutans serotype c oral and blood isolates
Authors: Huang Wen-Chuan , Chen Yi-Ywan M. , Teng Lee-Jene , Lien Huwei-Ting , Chen Jen-Yang , Chia Jean-San
Published: January 2008

Streptococcus mutanscauses dental caries and infective endocarditis. The aim of this study was to determine genomic diversity among serotypec S. mutanslaboratory and clinical strains and to characterize the genetic events involved. A genome-based approach using PFGE coupled with Southern hybridization was employed to examine a total of 58 serotypecoral and blood isolates and seven laboratory strains and to compare them withS. mutansUA159. No significant differences were found in the phenotypic characteristics of the strains tested, except that some of the strains exhibited smooth rather than rough colony morphology. In contrast, PFGE profiles of clinical isolates, from either diseased or healthy subjects, exhibited diverse patterns, suggesting that recombination or point mutations occurred frequentlyin vivo. Diverse PFGE patterns, with various lengths of insertions and deletions, could be detected even within a localized chromosomal region between rRNA operons. Comparative analysis using Southern hybridization with specific markers revealed that a large chromosomal inversion had also occurred betweenrrnoperons in 25 strains.
Bacteraemia associated with a vancomycin-resistant Enterococcus gallinarum strain harbouring both the vanA and vanC1 genes
Authors: Merquior Vânia Lúcia Carreira , Gonçalves Neves Felipe Piedade , Ribeiro Rachel Leite , Duarte Rafael Silva , de Andrade Marques Elizabeth , Teixeira Lúcia Martins
Published: January 2008

A case of a post-surgical patient who developed a fatal bloodstream infection caused by high-level vancomycin-resistant Enterococcus gallinarum is reported. The isolate was found to carry both the vanC1 and vanA genes. This is the first report of an invasive infection associated with a vanA E. gallinarum isolate in Brazil.
Necrotizing fasciitis with ruminococcus
Authors: Livaoğlu Murat , Yilmaz Gürdal , Kerimoğlu Servet , Aydin Kemalettin , Karacal Naci
Published: January 2008

Necrotizing fasciitis is a life- and limb-threatening soft tissue infection. Due to its underlying predisposition and rapid progression, treatment should be started quickly using antibiotherapy and surgical intervention. Although necrotizing fasciitis is mainly caused by streptococci and staphylococci, it may also be polymicrobial. Other peptostreptococci have been reported as necrotizing fasciitis agents in the literature, though we encountered no cases of necrotizing fasciitis caused by Ruminococcus productus. Here, we describe a case of necrotizing fasciitis caused by R. productus, a Gram-positive, obligatory anaerobe.
Mycobacterium tuberculosis strains disrupted in mce3 and mce4 operons are attenuated in mice
Authors: Senaratne Ryan H. , Sidders Ben , Sequeira Patricia , Saunders Grainne , Dunphy Kathleen , Marjanovic Olivera , Reader J. Rachel , Lima Patricia , Chan Stephen , Kendall Sharon , McFadden Johnjoe , Riley Lee W.
Published: January 2008

The Mycobacterium tuberculosis genome contains four copies of an operon called mce (mce1–4). Previously we reported that M. tuberculosis disrupted in the mce1 operon is more virulent than wild-type M. tuberculosis in mice. We generated single deletion mutants in mce3 (Δmce3) and mce4 (Δmce4) operons and a double deletion mutant (Δmce3/4). Similar doubling times and growth characteristics were observed for all mutants and the wild-type (parent) M. tuberculosis H37Rv strain in culture and in macrophages. In addition, similar bacterial burdens were detected in organs from mice infected with Δmce3 and the parent strain. However, the bacterial burdens of mice infected with Δmce4 and Δmce 3/4 were less than those of mice infected with the parent strain. The median survival times of mice infected with wild-type M. tuberculosis, Δmce3, Δmce4 and Δmce3/4 were 40.5, 46, 58 and 62 weeks, respectively. Histopathological examination of lungs at 15 weeks post-infection showed that the extent of the lung lesions was less prominent in mice infected with Δmce4 and Δmce 3/4 mutants than in mice infected with the other two strains. These observations suggest that the mce3 and mce4 operons have a role distinct from that of mce1 for in vivo survival of M. tuberculosis.
Functional association between the Helicobacter pylori virulence factors VacA and CagA
Authors: Argent Richard H. , Thomas Rachael J. , Letley Darren P. , Rittig Michael G. , Hardie Kim R. , Atherton John C.
Published: January 2008

The Helicobacter pylori virulence factors CagA and VacA are implicated in the development of gastroduodenal diseases. Most strains possessing CagA also possess the more virulent vacuolating form of VacA. This study assessed the significance of possession of both virulence factors in terms of their effect on gastric epithelial cells, using a set of minimally passaged, isogenic VacA, CagA and CagE mutants in H. pylori strains 60190 and 84-183. The cagA and cagE mutants were found to significantly increase VacA-induced vacuolation of epithelial cells, and the vacA mutants significantly increased CagA-induced cellular elongations, compared with wild-type strains, indicating that CagA reduces vacuolation and VacA reduces hummingbird formation. Although epithelial cells incubated with the wild-type H. pylori strains may display both vacuolation and hummingbird formation, it was found that (i) hummingbird length was significantly reduced in vacuolated cells compared with those without vacuolation; (ii) the number of vacuoles was significantly reduced in vacuolated cells with hummingbird formation compared with those without hummingbirds; and (iii) cells displaying extensive vacuolation did not subsequently form hummingbirds and vice versa. VacA did not affect the phosphorylation of CagA. These data show that VacA and CagA downregulate each other's effects on epithelial cells, potentially allowing H. pylori interaction with cells whilst avoiding excessive cellular damage.
Prevalence and risk factors for nasopharyngeal carriage of Streptococcus pneumoniae among adolescents
Authors: Cardozo Déa M. , Nascimento-Carvalho Cristiana M. , Andrade Ana-Lúcia S. S. , Silvany-Neto Anníbal M. , Daltro Carla H. C. , Brandão Maria-Angélica S. , Brandão Angela P. , Brandileone Maria-Cristina C.
Published: January 2008

Data on the prevalence of pneumooccal nasopharyngeal carriage and its risk factors among adolescents are scarce. The aim of this study was to provide such information. A cross-sectional, population-based prospective study was conducted. Participants were 1013 adolescents (age range 10–19 years) randomly recruited in 22 public schools. Those schools were randomly chosen among 307 public schools from 11 Sanitary Districts of Salvador, Brazil. Nasopharyngeal samples were assessed by standard procedures to recover and identify Streptococcus pneumoniae. Data on potential risk factors were gathered by confidential interview based on a standardized questionnaire. Pneumococci were recovered from 8.2 % [83/1013, 95 % confidence interval (CI) 6.6–10.0]. By stepwise logistic regression, pneumococcal colonization was independently associated with younger age [odds ratio (OR) 0.85, 95 % CI 0.77–0.94, P=0.001], being male (OR 1.78, 95 % CI 1.11–2.85, P=0.02), exposure to passive smoke in the household (OR 1.76, 95 % CI 1.10–2.79, P=0.02), having an upper respiratory infection during recruitment (OR 2.67, 95 % CI 1.67–4.28, P<0.001) and having a history involving an episode of acute asthma during the last year (OR 2.89, 95 % CI 1.18–7.08, P=0.03). The estimated probability of pneumococcal colonization decreased with age (χ
2 for trend=8.52, P=0.003). These findings provide tools for increasing the use of prevention strategies for pneumococcal diseases, such as pneumococcal vaccination among asthmatic patients and public health measures to stop smoking.
A new phylogenetic group of Propionibacterium acnes
Authors: McDowell Andrew , Perry Alexandra L. , Lambert Peter A. , Patrick Sheila
Published: January 2008

Immunofluorescence microscopy-based identification of presumptivePropionibacterium acnesisolates, using theP. acnes-specific mAb QUBPa3, revealed five organisms with an atypical cellular morphology. Unlike the coryneform morphology seen withP. acnestypes I and II, these isolates exhibited long slender filaments (which formed large tangled aggregates) not previously described inP. acnes. No reaction with mAbs that labelP. acnestypes IA (QUBPa1) and II (QUBPa2) was observed. Nucleotide sequencing of the 16S rRNA gene (1484 bp) revealed the isolates to have between 99.8 and 99.9 % identity to the 16S rRNA gene of theP. acnestype IA, IB and II strains NCTC 737, KPA171202 and NCTC 10390, respectively. Analysis of therecAhousekeeping gene (1047 bp) did reveal, however, a greater number of conserved nucleotide polymorphisms between the sequences from these isolates and those from NCTC 737 (98.9 % identity), KPA171202 (98.9 % identity) and NCTC 10390 (99.1 % identity). Phylogenetic investigations demonstrated that the isolates belong to a novelrecAcluster or lineage distinct fromP. acnestypes I and II. We now propose this new grouping asP. acnestype III. The prevalence and clinical importance of this novelrecAlineage amongst isolates ofP. acnesremains to be determined.