bluuebunny/crossref_metadata_2025 huggingface dataset:
A 2680 year volcanic record from the DT‐401 East Antarctic ice core
Authors: Ren Jiawen , Li Chuanjin , Hou Shugui , Xiao Cunde , Qin Dahe , Li Yuansheng , Ding Minghu
Published: June 2010

Volcanic signals recorded in the Antarctic and Greenland ice cores can provide useful information on past explosive volcanism and its impact. In this study, we carried out a continuous sulfate analysis of a 102.65 m East Antarctic ice core (DT‐401, dated as 2682 years) and identified 36 extensive volcanic eruption signals using Cole‐Dai's method, which gives an average of 1.4 eruptions per century, consistent with the results from the Plateau Remote (PR‐B) ice core. When the record is divided into three parts, the latest millennium (1999–1000 A.D.), the middle millennium (999–1 A.D.), and the earliest 682 years (0 A.D. to 682 B.C.), it is found that there were more volcanic eruptions that occurred during the latest millennium (19 eruptions) than during the middle millennium (10 eruptions) of the record and that the intensities of the eruptions in the latest millennium are markedly larger than those in the middle one. There were only seven events recorded in the earliest 682 years, but their intensities were greater, and nearly half of the eruptions had a similar intensity to Tambora's (1815 A.D.), which differs from the PR‐B record. It is also found that volcanism and its average accumulation rate were lower during the “Little Ice Age” than during the “Medieval Warm Period.” Comparison of volcanic records between DT‐401 and other Antarctica ice cores (PR‐B, Dome C, DT‐263, and Byrd) show that in the East Antarctica area with its lower accumulation rates, postdepositional effects may play an important role in the deposition of the sulfate.
A method for including mesoscale and synoptic‐scale information in scatterometer wind retrievals
Authors: Patoux Jérôme , Foster Ralph C. , Brown Robert A.
Published: June 2010

A method for improving scatterometer wind retrievals based on the mesoscale and synoptic‐scale structure of the flow field is presented and evaluated. The large‐scale structure of the flow is inferred from the sea‐level pressure (SLP) field derived from the scatterometer winds using a planetary boundary layer model. The wind vectors derived from this SLP field can be used to either (1) inform the ambiguity selection, (2) correct the direction of the scatterometer wind vectors, in all cases or above a certain threshold, or (3) replace the scatterometer winds. The methodology is demonstrated with QuikSCAT (QS) scatterometer wind vectors. The new wind vector set is evaluated statistically by comparison with buoy measurements, with numerical weather prediction model analyses, and by spectral analysis. It is found that the new wind vectors are particularly valuable at nadir and in rain‐contaminated areas, and that their spectral behavior is closer to a power law than are the uncorrected QS winds.
Uncoupling of Endothelial Nitric Oxide Synthase after Experimental Subarachnoid Hemorrhage
Authors: Sabri Mohammed , Ai Jinglu , Knight Britta , Tariq Asma , Jeon Hyojin , Shang Xueyuan , Marsden Philip Anthony , Macdonald Robert Loch
Published: June 2010

We studied whether endothelial nitric oxide synthase (eNOS) is upregulated and uncoupled in large cerebral arteries after subarachnoid hemorrhage (SAH) and also whether this causes cerebral vasospasm in a mouse model of anterior circulation SAH. Control animals underwent injection of saline instead of blood ( n=16 SAH and n=16 controls). There was significant vasospasm of the middle cerebral artery 2 days after SAH (lumen radius/wall thickness ratio 4.3±1.3 for SAH, 23.2±2.1 for saline, P<0.001). Subarachnoid hemorrhage was associated with terminal deoxynucleotidyl transferase dUTP nick-end labeling, cleaved caspase-3, and Fluoro-Jade-positive neurons in the cortex and with CA1 and dentate regions in the hippocampus. There were multiple fibrinogen-positive microthromboemboli in the cortex and hippocampus after SAH. Transgenic mice expressing lacZ under control of the eNOS promoter had increased X-gal staining in large arteries after SAH, and this was confirmed by the increased eNOS protein on western blotting. Evidence that eNOS was uncoupled was found in that nitric oxide availability was decreased, and superoxide and peroxynitrite concentrations were increased in the brains of mice with SAH. This study suggests that artery constriction by SAH upregulates eNOS but that it is uncoupled and produces peroxynitrite that may generate microemboli that travel distally and contribute to brain injury.
Effect of glypican‐1 gene on the pulp cells during the reparative dentine process
Authors: Masuda Murakami Yoshiko , Wang Xiaogu , Yokose Satoshi , Yamada Yoshishige , Kimura Yuichi , Okano Tomohiro , Matsumoto Koukichi
Published: June 2010

GPC‐1 (glypican‐1) is a cell surface heparan sulfate proteoglycan that acts as a co‐receptor for heparin‐binding growth factors and members of the TGF‐β (transforming growth factor beta‐1) family. The function of cell‐surface proteoglycans in the reparative dentine process has been under investigation. Gpc‐1 was detected with similar frequency as tgf‐β1 in the cDNA library using mRNA from the odontoblast‐like cell‐enriched pulp of rat incisors. The aim of this study was to test our hypothesis that gpc‐1 may be related to reparative dentine formation. We examined the expression of this gene during the reparative dentine process, as well as the effect of gpc‐1 on odontoblast‐like cell differentiation using siRNA (small interfering RNA) to down‐regulate gpc‐1 expression. Immunohistological examination showed that GPC‐1 was expressed in pulp cells entrapped by fibrodentine and odontoblast‐like cells as well as TGF‐β1. The mRNAs for gpc‐1, ‐3 and ‐4, except for gpc‐2, were expressed during odontoblast‐like cell differentiation in pulp cells. The relative levels of gpc‐1 mRNA were increased prior to the differentiation stages and were decreased during the secretory and maturation stages of pulp cells. Down‐regulation of gpc‐1 expression resulted in a 3.9‐fold increase in tgf‐β1 expression in pulp cells and a 0.3‐fold decrease in dspp (dentine sialophosphoprotein) expression compared with control. These results suggested that gpc‐1 and tgfβ‐1 expression are necessary for the onset of differentiation, but should be down‐regulated before other molecules are implicated in the formation of reparative dentine. In conclusion, gpc‐1 expression in odontoblast‐like cells is associated with the early differentiation but not with the formation of reparative dentine.
What You Might Not Find in a Typical Transition Plan! Some Important Lessons From Adults Who Rely on Augmentative and Alternative Communication
Authors: Bryen Diane Nelson , Chung Yoosun , Lever Sarah
Published: June 2010

Increasingly, parents of students with complex communication needs have high expectations for life after school. To respond to these high expectations, professionals must ensure that, among other skills, these students have three key supports: (a) access to needed socially-valued adult vocabulary, (b) rich social networks, and (c) strategies to increase personal safety and to reduce the risk of becoming a victim of a crime. This paper provides both first-person accounts, as well as descriptions of the results of innovative strategies for the acquisition of skills needed for living full, active, and socially valued adult lives.
Business: Developing a Marketing Plan: Initial Considerations
Authors: DeRuiter Mark
Published: June 2010

Marketing might not be a topic that speech-language pathologists (SLPs) find themselves thinking about on a daily basis. However, marketing impacts our profession in a variety of ways. Marketing entails more than just advertising. Successful marketing involves four factors commonly known as the four “Ps” of marketing (product, price, place, promotion). Developing a marketing plan takes time, talent, and consistent energy. This article invites clinicians across different professional environments to consider their services through a framework used by many marketing consultants as they develop a marketing plan. The four “Ps” of marketing, as well as their relationship to each other and the profession, will be explored. Thoughtful questions are posited and myths regarding the practice of marketing are addressed.
Current Issues: Incorporating Counseling Into Graduate Education
Authors: Millar Diane C. , Harrow Kori L. , Morgan Ashley A.
Published: June 2010

Counseling is considered a critical component of effective clinical practice. As such, speech-language pathologists and audiologists should receive explicit preparation in counseling as part of their graduate education. However, counseling is often a neglected area of instruction in many graduate programs. A research study was designed to assess perceptions of the effectiveness of a set of counseling strategies (i.e., nonverbal approaches) that have been described in the literature. Interestingly, preliminary data suggest that individuals may have differing opinions on effective counseling approaches. In part, these differences may be based on experiences and education. Implications for improving counseling skills of professionals and service delivery effectiveness are discussed.
Supervision: Supervision to Mentoring: Practical Considerations
Authors: Livingston Amy , Hudson Melanie
Published: June 2010

As students transition from graduate programs to their Clinical Fellowship Experience, there is a corresponding shift in their autonomy and level of supervision. Supervisors of student clinicians and mentors of Clinical Fellows share many of the same roles and responsibilities as key figures in the professional development of the new clinician. Mentors are appropriately less directive than supervisors as part of a collaborative process with the Clinical Fellow. The mentor is charged with facilitating and promoting reflective practice techniques while giving consideration to influence and power; interpersonal skills; issues of race, culture, gender, and age; and professional ethics.
Corticobasal Ganglionic Degeneration and Progressive Supranuclear Palsy: Clinical and Speech-Language Characteristics
Authors: Strand Edythe A.
Published: June 2010

Purpose: The purpose of this article is to present a brief description of the neuroanatomical correlates, pathophysiology, and clinical presentation of corticobasal ganglionic degeneration, (often referred to as corticobasal degeneration, or CBD) and progressive supranuclear palsy (PSP).

Methods: Descriptions of the clinical characteristics of the two degenerative syndromes are presented, including a discussion of the similarities and differences. The speech and language disorders associated with each are described, including progressive aphasia, progressive non-fluent aphasia (PNFA), progressive apraxia of speech (AOS), and dysarthria.

Results and Conclusions: CBD and PSP have a number of commonalities in clinical characteristics and in pathology. Both progressive aphasia and apraxia of speech have been associated with CBD and PSP. Clinicians who evaluate patients exhibiting a progressive neurologic disease and who identify either progressive aphasia, PNFA and/or progressive AOS should consider CBD or PSP as a possible medical diagnosis.
The Development of ICF Core Sets for Hearing Loss
Authors: Granberg Sarah , Danermark Berth , Gagné Jean-Pierre
Published: June 2010

The International Classification of Functioning, Disability and Health (ICF), adopted by the World Health Organization (WHO) in 2001, offers a framework for a comprehensive understanding of health. One of the main goals of the ICF is to provide a conceptual framework of health that can be applied both for research purposes and in clinical settings. In order to promote the use of the ICF in clinical settings, the WHO initiated the Core Sets project. Core Sets, targeting a specific health condition, consist of a set of ICF categories that can serve as minimal standards (Brief ICF Core Set) or as standards for comprehensive assessment (Comprehensive ICF Core Set). In 2009, a process of developing ICF Core Sets for Hearing Loss was initiated. This process involves three phases of development. In the first phase, four scientific studies are conducted to collect evidence for relevant ICF categories to be used in the Core Sets. In phase two, a consensus conference is held to establish relevant ICF categories, and in the third phase, the Core Sets that are retained are tested and validated. This paper describes the process of developing ICF Core Sets for Hearing Loss as well as an invitation to participate in the project.
Audiology Service Models in a Family Physician Practice Setting
Authors: Krishnamurti Sridhar
Published: June 2010

This article illustrates the potential of placing audiology services in a family physician’s practice setting to increase referrals of geriatric and pediatric patients to audiologists. The primary focus of family practice physicians is the diagnosis/intervention of critical systemic disorders (e.g., cardiovascular disease, diabetes, cancer). Hence concurrent hearing/balance disorders are likely to be overshadowed in such patients. If audiologists get referrals from these physicians and have direct access to diagnose and manage concurrent hearing/balance problems in these patients, successful audiology practice patterns will emerge, and there will be increased visibility and profitability of audiological services. As a direct consequence, audiological services will move into the mainstream of healthcare delivery, and the profession of audiology will move further towards its goals of early detection and intervention for hearing and balance problems in geriatric and pediatric populations.
Perspectives on Preparing Graduate Students To Provide Services to Diverse Populations in Schools
Authors: Lazewnik Rochel , Creaghead Nancy , Combs Sandra , Raisor-Becker Lesley
Published: June 2010

In today's school settings, speech-language pathologists are likely to engage in assessment, intervention, and consultation for students from culturally and linguistically diverse populations. Therefore, speech-language pathology graduate programs must make changes that will prepare monolingual and bilingual graduate students to meet the needs of these children. Graduate students can learn information about cultural and linguistic diversity through independent courses and when these topics are incorporated into all courses. Practicum placements and experiences with children from culturally and linguistically diverse populations in the community can provide the necessary skills. When practicum experiences with diverse children are not available, faculty may consider simulated experiences, as well as experiences with typical speakers from other linguistic and cultural backgrounds.
A 21st Century Communication Sciences and Disorders Program
Authors: Montgomery Judy K. , Dodd Janet L. , Giess SallyAnn , Barnes Kamica
Published: June 2010

The focus of graduate programs in communication sciences and disorders has changed greatly in the last decade to reflect changes in society in general. Newly formed graduate programs must account for these societal changes as they prepare students for practice in the 21st century. This article will discuss what is expected of new graduates, how teaching philosophies influence course content, and how a new graduate program in communication sciences and disorders came to be.
Correction orthodontique du plan d’occlusion avec des mini-vis
: cas clinique
Authors: Walter Andy
Published: June 2010

Une patiente en denture permanente, hors croissance, consulte exclusivement pour
améliorer l’esthétique de son sourire. Elle présente une occlusion de classe I avec une
légère asymétrie faciale et une bascule frontale du plan d’occlusion se traduisant par une
différence de hauteur des molaires de 4 à 5 mm. Un traitement orthodontique a été réalisé
avec deux mini-vis vestibulaires et un appareil fixe aux deux arcades pendant 14 mois. Une
analyse correcte du sourire et des problèmes dentaires est indispensable pour atteindre
l’objectif esthétique.
L’information de l’adolescent dans le cadre d’un traitement
orthodontique multibague
Authors: Ceada Julien , Hamel Olivier , Marchal-Sixou Christine
Published: June 2010

Une interrogation sur la réalité du consentement de l’adolescent est proposée. Cette
réflexion, de nature éthique, confronte le volet médico-légal du contrat de soins,
spécifique lorsqu’il s’agit d’un mineur, avec le volet psychologique si particulier
lorsqu’il s’agit d’un adolescent. Comment traitons-nous le mineur adolescent ? Au-delà du
questionnement quasi-philosophique sur la relation interhumaine de soins, nous proposons
des éléments de réponses très pratiques.
Choix chirurgico-prothétiques dans la gestion alvéolaire des
séquelles de fentes labio-maxillo-palatines
Authors: Molé Christian , Simon Étienne , Billiotte Christophe , Stricker Michel
Published: June 2010

En fin de croissance, après une succession de traitements chirurgicaux, orthopédiques et
orthodontiques visant à l’obtention d’un équilibre esthétique et fonctionnel, se pose,
pour les patients porteurs de fentes labio-maxillo-palatines (FLMP), le problème crucial
de la fin de traitement et de la réhabilitation prothétique d’usage. Lorsqu’un espace
édenté a été maintenu ou recréé entre les dents proximales de chaque fragment, deux types
d’orientation du plan de traitement se présentent au praticien odontologiste:
l’implantation ou la prothèse conjointe traditionnelle. Quatre problématiques sont
évoquées pour décrire les difficultés liées à cette prise de décision thérapeutique:
l’affrontement des berges, le déficit osseux résiduel, les dents bordant la fente et la
place de l’odontologiste dans la prise en charge globale du patient. Le choix du contexte
chirurgico-prothétique final doit s’inscrire dans une démarche d’analyse multifactorielle
et être intégré suffisamment tôt dans la stratégie thérapeutique multidisciplinaire. Ainsi
pourra-t-il s’inscrire dans le cadre d’une bonne acceptation psychologique et dans la
recherche rationnelle d’une finalité esthétique durable.
Coupled
182
W-
142
Nd constraint for early Earth differentiation
Authors: Moynier Frederic , Yin Qing-Zhu , Irisawa Keita , Boyet Maud , Jacobsen Benjamin , Rosing Minik T.
Published: June 2010

Recent high precision
142
Nd isotope measurements showed that global silicate differentiation may have occurred as early as 30–75 Myr after the Solar System formation [Bennett V, et al. (2007)
Science
318:1907–1910]. This time scale is almost contemporaneous with Earth’s core formation at ∼30 Myr [Yin Q, et al. (2002)
Nature
418:949–952]. The
182
Hf-
182
W system provides a powerful complement to the
142
Nd results for early silicate differentiation, because both core formation and silicate differentiation fractionate Hf from W. Here we show that eleven terrestrial samples from diverse tectonic settings, including five early Archean samples from Isua, Greenland, of which three have been previously shown with
142
Nd anomalies, all have a homogeneous W isotopic composition, which is ∼2
ε
-unit more radiogenic than the chondritic value. By using a 3-stage model calculation that describes the isotopic evolution in chondritic reservoir and core segregation, as well as silicate differentiation, we show that the W isotopic composition of terrestrial samples provides the most stringent time constraint for early core formation (27.5–38 Myr) followed by early terrestrial silicate differentiation (38–75 Myr) that is consistent with the terrestrial
142
Nd anomalies.
Structural requirements of bitter taste receptor activation
Authors: Brockhoff Anne , Behrens Maik , Niv Masha Y. , Meyerhof Wolfgang
Published: June 2010

An important question in taste research is how 25 receptors of the human TAS2R family detect thousands of structurally diverse compounds. An answer to this question may arise from the observation that TAS2Rs in general are broadly tuned to interact with numerous substances. Ultimately, interaction with chemically diverse agonists requires architectures of binding pockets tailored to combine flexibility with selectivity. The present study determines the structure of hTAS2R binding pockets. We focused on a subfamily of closely related hTAS2Rs exhibiting pronounced amino acid sequence identities but unique agonist activation spectra. The generation of chimeric and mutant receptors followed by calcium imaging analyses identified receptor regions and amino acid residues critical for activation of hTAS2R46, -R43, and -R31. We found that the carboxyl-terminal regions of the investigated receptors are crucial for agonist selectivity. Intriguingly, exchanging two residues located in transmembrane domain seven between hTAS2R46, activated by strychnine, and hTAS2R31, activated by aristolochic acid, was sufficient to invert agonist selectivity. Further mutagenesis revealed additional positions involved in agonist interaction. The transfer of functionally relevant amino acids identified in hTAS2R46 to the corresponding positions of hTAS2R43 and -R31 resulted in pharmacological properties indistinguishable from the parental hTAS2R46. In silico modeling of hTAS2R46 allowed us to visualize the putative mode of interaction between agonists and hTAS2Rs. Detailed structure-function analyses of hTAS2Rs may ultimately pave the way for the development of specific antagonists urgently needed for more sophisticated analyses of human bitter taste perception.
Structural basis for Rab GTPase recognition and endosome tethering by the C
2
H
2
zinc finger of Early Endosomal Autoantigen 1 (EEA1)
Authors: Mishra Ashwini , Eathiraj Sudharshan , Corvera Silvia , Lambright David G.
Published: June 2010

Regulation of endosomal trafficking by Rab GTPases depends on selective interactions with multivalent effectors, including EEA1 and Rabenosyn-5, which facilitate endosome tethering, sorting, and fusion. Both EEA1 and Rabenosyn-5 contain a distinctive N-terminal C
2
H
2
zinc finger that binds Rab5. How these C
2
H
2
zinc fingers recognize Rab GTPases remains unknown. Here, we report the crystal structure of Rab5A in complex with the EEA1 C
2
H
2
zinc finger. The binding interface involves all elements of the zinc finger as well as a short N-terminal extension but is restricted to the switch and interswitch regions of Rab5. High selectivity for Rab5 and, to a lesser extent Rab22, is observed in quantitative profiles of binding to Rab family GTPases. Although critical determinants are identified in both switch regions, Rab4-to-Rab5 conversion-of-specificity mutants reveal an essential requirement for additional substitutions in the proximal protein core that are predicted to indirectly influence recognition through affects on the structure and conformational stability of the switch regions.
Reconstructing early 17th century estuarine drought conditions from Jamestown oysters
Authors: Harding Juliana M. , Spero Howard J. , Mann Roger , Herbert Gregory S. , Sliko Jennifer L.
Published: June 2010

Oysters (
Crassostrea virginica
) were a central component of the Chesapeake Bay ecosystem in 1607 when European settlers established Jamestown, VA, the first permanent English settlement in North America. These estuarine bivalves were an important food resource during the early years of the James Fort (Jamestown) settlement while the colonists were struggling to survive in the face of inadequate supplies and a severe regional drought. Although oyster shells were discarded as trash after the oysters were eaten, the environmental and ecological data recorded in the bivalve geochemistry during shell deposition remain intact over centuries, thereby providing a unique window into conditions during the earliest Jamestown years. We compare oxygen isotope data from these 17th century oyster shells with modern shells to quantify and contrast estuarine salinity, season of oyster collection, and shell provenance during Jamestown colonization (1609–1616) and the 21st century. Data show that oysters were collected during an extended drought between fall 1611 and summer 1612. The drought shifted the 14 psu isohaline above Jamestown Island, facilitating individual oyster growth and extension of oyster habitat upriver toward the colony, thereby enhancing local oyster food resources. Data from distinct well layers suggest that the colonists also obtained oysters from reefs near Chesapeake Bay to augment oyster resources near Jamestown Island. The oyster shell season of harvest reconstructions suggest that these data come from either a 1611 well with a very short useful period or an undocumented older well abandoned by late 1611.
Quaternary organization of a phytochrome dimer as revealed by cryoelectron microscopy
Authors: Li Hua , Zhang Junrui , Vierstra Richard D. , Li Huilin
Published: June 2010

Phytochromes are a collection of dimeric photoreceptors that direct a diverse array of responses in plants and microorganisms through photoconversion between a red light-absorbing ground state Pr, and a far-red light-absorbing photoactivated state Pfr. Photoconversion from Pr to Pfr is initiated by a light-driven rotation within the covalently attached bilin, which then triggers a series of protein conformational changes in the binding pocket. These movements ultimately affect an appended output module, which often has reversible protein kinase activity. Propagation of the light signal from the bilin to the output module likely depends on the dimerization interface but its architecture and response to phototransformation remain unclear. Here, we used single particle cryoelectron microscopy to determine the quaternary arrangement of the phytochrome dimer as Pr, using the bacteriophytochrome (BphP) from
Deinococcus radiodurans
. Contrary to the long-standing view that the two monomers are held together solely via their C-terminal region, we provide unambiguous evidence that the N-terminal bilin-binding region of BphP also provides a dimerization interface with the C-terminal kinase domain appearing as a more flexible appendage. The BphP monomers dimerize in parallel with the polypeptides intimately twisting around each other in a right-handed fashion. Based on this electron microscopic picture, we propose that the light-driven conformational changes transmitted from the chromophore to the output module along the spine of this extensive dimer interface is the central feature underpinning phytochrome signaling.
Influenza A virus-generated small RNAs regulate the switch from transcription to replication
Authors: Perez Jasmine T. , Varble Andrew , Sachidanandam Ravi , Zlatev Ivan , Manoharan Muthiah , García-Sastre Adolfo , tenOever Benjamin R.
Published: June 2010

The discovery of regulatory small RNAs continues to reshape paradigms in both molecular biology and virology. Here we describe examples of influenza A virus-derived small viral RNAs (svRNAs). svRNAs are 22–27 nt in length and correspond to the 5′ end of each of the viral genomic RNA (vRNA) segments. Expression of svRNA correlates with the accumulation of vRNA and a bias in RNA-dependent RNA polymerase (RdRp) activity from transcription toward genome replication. Synthesis of svRNA requires the RdRp, nucleoprotein and the nuclear export protein NS2. In addition, svRNA is detectable during replication of various influenza A virus subtypes across multiple host species and associates physically with the RdRp. We demonstrate that depletion of svRNA has a minimal impact on mRNA and complementary vRNA (cRNA) but results in a dramatic loss of vRNA in a segment-specific manner. We propose that svRNA triggers the viral switch from transcription to replication through interactions with the viral polymerase machinery. Taken together, the discovery of svRNA redefines the mechanistic switch of influenza virus transcription/replication and provides a potential target for broad-range, anti-influenza virus-based therapeutics.
Structure of the Qβ replicase, an RNA-dependent RNA polymerase consisting of viral and host proteins
Authors: Kidmose Rune T. , Vasiliev Nikita N. , Chetverin Alexander B. , Andersen Gregers Rom , Knudsen Charlotte R.
Published: June 2010

The RNA-dependent RNA polymerase core complex formed upon infection of
Escherichia coli
by the bacteriophage Qβ is composed of the viral catalytic β-subunit as well as the host translation elongation factors EF-Tu and EF-Ts, which are required for initiation of RNA replication. We have determined the crystal structure of the complex between the β-subunit and the two host proteins to 2.5-Å resolution. Whereas the basic catalytic machinery in the viral subunit appears similar to other RNA-dependent RNA polymerases, a unique C-terminal region of the β-subunit engages in extensive interactions with EF-Tu and may contribute to the separation of the transient duplex formed between the template and the nascent product to allow exponential amplification of the phage genome. The evolution of resistance by the host appears to be impaired because of the interactions of the β-subunit with parts of EF-Tu essential in recognition of aminoacyl-tRNA.
Neural correlates of anchoring-and-adjustment during mentalizing
Authors: Tamir Diana I. , Mitchell Jason P.
Published: June 2010

Recent studies have suggested that the medial prefrontal cortex (MPFC) contributes both to understanding the mental states of others and to introspecting about one's own mind. This finding has suggested that perceivers might use their own thoughts and feelings as a starting point for making inferences about others, consistent with “simulation” or “self-projection” views of social cognition. However, perceivers cannot simply assume that others think and feel exactly as they do; social cognition also must include processes that adjust for perceived differences between self and other. Recent cognitive work has suggested that such correction occurs through a process of “anchoring-and-adjustment” by which perceivers serially tune their inferences from an initial starting point based on their own introspections. Here, we used functional MRI to test two predictions derived from this anchoring-and-adjustment view. Participants (
n
= 64) used a Likert scale to judge the preferences of another person and to indicate their own preferences on the same items, allowing us to calculate the discrepancy between the participant's answers for self and other. Whole-brain parametric analyses identified a region in the MPFC in which activity was related linearly to this self–other discrepancy when inferring the mental states of others. These findings suggest both that the self serves as an important starting point from which to understand others and that perceivers customize such inferences by serially adjusting away from this anchor.
Metal-induced conformational changes in ZneB suggest an active role of membrane fusion proteins in efflux resistance systems
Authors: De Angelis Fabien , Lee John K. , O'Connell Joseph D. , Miercke Larry J. W. , Verschueren Koen H. , Srinivasan Vasundara , Bauvois Cédric , Govaerts Cédric , Robbins Rebecca A. , Ruysschaert Jean-Marie , Stroud Robert M. , Vandenbussche Guy
Published: June 2010

Resistance nodulation cell division (RND)-based efflux complexes mediate multidrug and heavy-metal resistance in many Gram-negative bacteria. Efflux of toxic compounds is driven by membrane proton/substrate antiporters (RND protein) in the plasma membrane, linked by a membrane fusion protein (MFP) to an outer-membrane protein. The three-component complex forms an efflux system that spans the entire cell envelope. The MFP is required for the assembly of this complex and is proposed to play an important active role in substrate efflux. To better understand the role of MFPs in RND-driven efflux systems, we chose ZneB, the MFP component of the ZneCAB heavy-metal efflux system from
Cupriavidus metallidurans
CH34. ZneB is shown to be highly specific for Zn
2+
alone. The crystal structure of ZneB to 2.8 Å resolution defines the basis for metal ion binding in the coordination site at a flexible interface between the β-barrel and membrane proximal domains. The conformational differences observed between the crystal structures of metal-bound and apo forms are monitored in solution by spectroscopy and chromatography. The structural rearrangements between the two states suggest an active role in substrate efflux through metal binding and release.
Protein folded states are kinetic hubs
Authors: Bowman Gregory R. , Pande Vijay S.
Published: June 2010

Understanding molecular kinetics, and particularly protein folding, is a classic grand challenge in molecular biophysics. Network models, such as Markov state models (MSMs), are one potential solution to this problem. MSMs have recently yielded quantitative agreement with experimentally derived structures and folding rates for specific systems, leaving them positioned to potentially provide a deeper understanding of molecular kinetics that can lead to experimentally testable hypotheses. Here we use existing MSMs for the villin headpiece and NTL9, which were constructed from atomistic simulations, to accomplish this goal. In addition, we provide simpler, humanly comprehensible networks that capture the essence of molecular kinetics and reproduce qualitative phenomena like the apparent two-state folding often seen in experiments. Together, these models show that protein dynamics are dominated by stochastic jumps between numerous metastable states and that proteins have heterogeneous unfolded states (many unfolded basins that interconvert more rapidly with the native state than with one another) yet often still appear two-state. Most importantly, we find that protein native states are hubs that can be reached quickly from any other state. However, metastability and a web of nonnative states slow the average folding rate. Experimental tests for these findings and their implications for other fields, like protein design, are also discussed.
Reprogramming the posttranslational code of SRC-3 confers a switch in mammalian systems biology
Authors: York Brian , Yu Chundong , Sagen Jørn V. , Liu Zhaoliang , Nikolai Bryan C. , Wu Ray-Chang , Finegold Milton , Xu Jianming , O'Malley Bert W.
Published: June 2010

Here we demonstrate that reprogramming steroid receptor coactivator-3 (SRC-3) function by changing its posttranslational modification (PTM) code drastically influences systems biology. These findings support the physiological importance of PTMs in directing in vivo functions of a master coregulator. We previously reported that the transactivation potential of SRC-3 is controlled in part by PTMs, although this data emanated from in vitro studies. To test the physiological implications of PTMs on SRC-3, we developed a knock-in mouse model containing mutations at four conserved phosphorylation sites. These mice displayed a systems biology phenotype with increased body weight and adiposity, coupled with reduced peripheral insulin sensitivity. Collectively, these phenotypes result from increased IGF1 signaling, due to elevated IGFBP3 levels. We provide convincing evidence that these mutations in SRC-3 promoted enhanced transcription of the IGFBP3 gene and globally influenced growth and metabolism. Consequently, these mice displayed increased liver tumorigenesis, which likely results from elevated IGF1 signaling.
Colorimetric detection of DNA, small molecules, proteins, and ions using unmodified gold nanoparticles and conjugated polyelectrolytes
Authors: Xia Fan , Zuo Xiaolei , Yang Renqiang , Xiao Yi , Kang Di , Vallée-Bélisle Alexis , Gong Xiong , Yuen Jonathan D. , Hsu Ben B. Y. , Heeger Alan J. , Plaxco Kevin W.
Published: June 2010

We have demonstrated a novel sensing strategy employing single-stranded probe DNA, unmodified gold nanoparticles, and a positively charged, water-soluble conjugated polyelectrolyte to detect a broad range of targets including nucleic acid (DNA) sequences, proteins, small molecules, and inorganic ions. This nearly “universal” biosensor approach is based on the observation that, while the conjugated polyelectrolyte specifically inhibits the ability of single-stranded DNA to prevent the aggregation of gold-nanoparticles, no such inhibition is observed with double-stranded or otherwise “folded” DNA structures. Colorimetric assays employing this mechanism for the detection of hybridization are sensitive and convenient—picomolar concentrations of target DNA are readily detected with the naked eye, and the sensor works even when challenged with complex sample matrices such as blood serum. Likewise, by employing the binding-induced folding or association of aptamers we have generalized the approach to the specific and convenient detection of proteins, small molecules, and inorganic ions. Finally, this new biosensor approach is quite straightforward and can be completed in minutes without significant equipment or training overhead.
Protein interface conservation across structure space
Authors: Zhang Qiangfeng Cliff , Petrey Donald , Norel Raquel , Honig Barry H.
Published: June 2010

With the advent of Systems Biology, the prediction of whether two proteins form a complex has become a problem of increased importance. A variety of experimental techniques have been applied to the problem, but three-dimensional structural information has not been widely exploited. Here we explore the range of applicability of such information by analyzing the extent to which the location of binding sites on protein surfaces is conserved among structural neighbors. We find, as expected, that interface conservation is most significant among proteins that have a clear evolutionary relationship, but that there is a significant level of conservation even among remote structural neighbors. This finding is consistent with recent evidence that information available from structural neighbors, independent of classification, should be exploited in the search for functional insights. The value of such structural information is highlighted through the development of a new protein interface prediction method, PredUs, that identifies what residues on protein surfaces are likely to participate in complexes with other proteins. The performance of PredUs, as measured through comparisons with other methods, suggests that relationships across protein structure space can be successfully exploited in the prediction of protein-protein interactions.
Diabetogenic T cells recognize insulin bound to IAg7in an unexpected, weakly binding register
Authors: Stadinski Brian D. , Zhang Li , Crawford Frances , Marrack Philippa , Eisenbarth George S. , Kappler John W.
Published: June 2010

A peptide derived from the insulin B chain contains a major epitope for diabetogenic CD4+T cells in the NOD mouse model of type 1 diabetes (T1D). This peptide can fill the binding groove of the NOD MHCII molecule, IAg7, in a number of ways or “registers.” We show here that a diverse set of NOD anti-insulin T cells all recognize this peptide bound in the same register. Surprisingly, this register results in the poorest binding of peptide to IAg7. The poor binding is due to an incompatibility between the p9 amino acid of the peptide and the unique IAg7p9 pocket polymorphisms that are strongly associated with susceptibility to T1D. Our findings suggest that the association of autoimmunity with particular MHCII alleles may be do to poorer, rather than more favorable, binding of the critical self-epitopes, allowing T-cell escape from thymic deletion.
Variation in the Type and Frequency of Postoperative Invasive Staphylococcus aureus Infections According to Type of Surgical Procedure
Authors: Anderson Deverick J. , Arduino Jean Marie , Reed Shelby D. , Sexton Daniel J. , Kaye Keith S. , Grussemeyer Chelsea A. , Peter Senaka A. , Hardy Chantelle , Choi Yong II , Friedman Joelle Y. , Fowler Vance G.
Published: June 2010

Objective.

To determine the epidemiological characteristics of postoperative invasive Staphylococcus aureus infection following 4 types of major surgical procedures.

Design.

Retrospective cohort study.

Setting.

Eleven hospitals (9 community hospitals and 2 tertiary care hospitals) in North Carolina and Virginia.

Patients.

Adults undergoing orthopedic, neurosurgical, cardiothoracic, and plastic surgical procedures.

Methods.

We used previously validated, prospectively collected surgical surveillance data for surgical site infection and microbiological data for bloodstream infection. The study period was 2003 through 2006. We defined invasive S. aureus infection as either nonsuperficial incisional surgical site infection or bloodstream infection. Nonparametric bootstrapping was used to generate 95% confidence intervals (CIs). P values were generated using the Pearson x2 test, Student t test, or Wilcoxon rank-sum test, as appropriate.

Results.

In total, 81,267 patients underwent 96,455 procedures during the study period. The overall incidence of invasive S. aureus infection was 0.47 infections per 100 procedures (95% CI, 0.43–0.52); 227 (51%) of 446 infections were due to methicillin-resistant S. aureus. Invasive S. aureus infection was more common after cardiothoracic procedures (incidence, 0.79 infections per 100 procedures [95% CI, 0.62–0.97]) than after orthopedic procedures (0.37 infections per 100 procedures [95% CI, 0.32–0.42]), neurosurgical procedures (0.62 infections per 100 procedures [95% CI, 0.53–0.72]), or plastic surgical procedures (0.32 infections per 100 procedures [95% CI, 0.17¬0.47]) (P < .001). Similarly, S. aureus bloodstream infection was most common after cardiothoracic procedures (incidence, 0.57 infections per 100 procedures [95% CI, 0.43–0.72]; P < .001, compared with other procedure types), comprising almost three-quarters of the invasive S. aureus infections after these procedures. The highest rate of surgical site infection was observed after neurosurgical procedures (incidence, 0.50 infections per 100 procedures [95% CI, 0.42–0.59]; P < .001, compared with other procedure types), comprising 80% of invasive S. aureus infections after these procedures.

Conclusion.

The frequency and type of postoperative invasive S. aureus infection varied significantly across procedure types. The highest risk procedures, such as cardiothoracic procedures, should be targeted for ongoing preventative interventions.
Theoretical Study of Mechanism and Regioselectivity of 1,3-dipolar Cycloaddition of N-[methyl]-C-[5-nitro-2-furyl] Nitrilimine with Dimethyl 7-oxabicyclo[2,2,1]hepta-2,5-diene-2,3-dicarboxylate
Authors: Moeinpour Farid
Published: June 2010

The mechanism and regioselectivity of 1,3-dipolar cycloaddition of N-[methyl]-C-[5-nitro-2-furyl] nitrilimine with dimethyl 7-oxabicyclo[2,2,1]hepta-2,5-diene-2,3-dicarboxylate were investigated using activation energy calculations and density functional theory-based reactivity indexes. The reaction proceeds by an asynchronous concerted mechanism. The calculations are performed at the B3LYP/6–31G(d) level of theory and the obtained results are in agreement with experimental outcome.
Ligand Size Effect on PdLnOxidative Addition with Aryl Bromide: A DFT Study
Authors: Sun Wen-jing , Chu Wei , Yu Liang-jun , Jiang Cheng-fa
Published: June 2010

The process and mechanism of the ligand volume controlled Pd(PR3)2 (PR3 = PH3, PMe3, and PtBu3) oxidative addition with aryl bromide were investigated, using density functional theory method with the conductor-like screening model. Association pathway and dissociation pathway were investigated by the comparison of several energies. The cleavage energy of Pd(PR3)2 complex was calculated, as well as the oxidative addition reaction barrier energy of Pd(PR3)n (n = 1, 2) with aryl bromide in N,N-dimethylformamide solvent. This study proved that the ligands volume possessed a great impact on the mechanism of oxidative addition: less bulky ligand palladium associated with aryl bromide via two donor ligands, but larger bulky ligand palladium coordinated via monoligand.
Effects of Single Vacancy on Electronic and Optical Properties for γ-Si3N4
Authors: Ding Ying-chun , Xiang An-ping , He Xiu-jun , Zhu Xing-hua , Hu Xiao-fei
Published: June 2010

The energetics, electronic structures, and optical properties of several neutral vacancies for γ-Si3N4 are studied based on density function theory within the generalized gradient approximation. The binding and formation energies of nitrogen vacancy are smaller than that of silicon vacancies, implying that nitrogen vacancy can be easily formed in γ-Si3N4. Corresponding density of states of different point vacancies is analyzed. We concluded that the neutral silicon vacancies introduce the p-type carriers into the system, whereas single nitrogen vacancy leads to an n-type semiconductor. The results show indirect semiconductor of nitrogen vacancy for γ-Si3N4. The effects of optical properties are discussed on single vacancies for γ-Si3N4. For silicon vacancies, the materials have much higher static dielectric constants than these of nitrogen vacancy and perfect γ-Si3N4. The single nitrogen vacancy for γ-Si3N4 has no effects on absorption and reflection in visible and infrared light. For silicon vacancy, it is significantly increased.
Preparation and Characterization of Polypyrrole Microbelt via Cotton Template
Authors: Li Qiao-ling , Zhang Cui-rui , Xue Zheng-shan , Li Jian-qiang
Published: June 2010

Polypyrrole (PPY) microbelts are synthesized via the absorbent cotton template for the first time. PPY microbelts are characterized by Fourier transform infrared spectroscopy. The stability, the morphology and electrical conductivity of such microbelts are evaluated by means of scanning electron microscope, thermo-gravimetric analysis and four-probe conductivity. A possible mechanism for the formation of PPY microbelts are proposed. The conductivity is measured, and the conductivity variation mechanism of the PPY microbelts with the pyrrole monomer concentrations is analyzed.
Efficient Thickness of Solid Oxide Fuel Cell Composite Electrode
Authors: Jiang Zhi-yi , Xia Chang-rong , Chen Fang-lin
Published: June 2010

The efficient thickness of a composite electrode for solid oxide fuel cells was directly calculated by developing a physical model taking into account of the charge transfer process, the oxygen ion and electron transportation, and the microstructure characteristics of the electrode. The efficient thickness, which is defined as the electrode thickness corresponding to the minimum electrode polarization resistance, is formulated as a function of charge transfer resistivity, effective resistivity to ion and electron transport, and three-phase boundary length per unit volume. The model prediction is compared with the experimental reports to check the validity. Simulation is performed to show the effect of microstructure, intrinsic material properties, and electrode reaction mechanism on the efficient thickness. The results suggest that when an electrode is fabricated, its thickness should be controlled regarding its composition, particle size of its components, the intrinsic ionic and electronic conductivities, and its reaction mechanisms as well as the expected operation temperatures. The sensitivity of electrode polarization resistance to its thickness is also discussed.