bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Resin-Dentin Bonds Created after Caries Removal with Polymer Burs
Authors: Toledano Manuel , Cabello Inmaculada , Yamauti Monica , Osorio Raquel 
Published: May 2012

AbstractThe objective of this article was to investigate the effect of carbide and polymer burs caries removal methods on the bond strength of different adhesives to dentin. Resin restorations were performed in sound and caries-affected dentin, after using polymer or carbide burs and bonding with four different adhesive (Single bond, SB; Clearfil SE bond, SEB; FL-Bond II, FLB; and Fuji II-LC, FUJI). Microtensile bond strength (MTBS) was measured. Data were analyzed with ANOVA and Student-Newman-Keuls tests. Debonded surfaces were observed by scanning electron microscopy. Bonded interfaces were examined using light microscopy (Masson's trichrome staining). In sound dentin, MTBS was similar for SEB and SB, and higher than that of FLB and FUJI. Bond strength to carbide bur prepared dentin was similar for SB, SEB, and FLB; FUJI presented the lowest. SB applied on polymer bur excavated dentin presented similar values to those of the carbide bur group; MTBS attained by SEB, FLB, and FUJI decreased when bonding to dentin treated with polymer burs; FUJI yielded pretesting failures in all specimens. Polymer burs created a thick smear layer that was not infiltrated by tested self-etching agents. The bonding effectiveness of self-etching and glass-ionomer-like adhesives to dentin decreased when polymer burs were used.
Single scattering albedo of fine mineral dust aerosols controlled by iron concentration
Authors: Moosmüller Hans , Engelbrecht Johann P. , Skiba Michał , Frey Garrett , Chakrabarty Rajan K. , Arnott W. Patrick 
Published: May 2012

Sign and magnitude of solar aerosol direct radiative forcing are largely determined by the aerosol single scattering albedo (SSA) and the albedo of the underlying scene (e.g., surface albedo). On a global scale, mineral dust aerosol has the largest mass emission rate, average column mass burden, and average optical depth of all aerosol types. Therefore, better understanding of its optical properties with a focus on SSAis of great importance. Here, we entrain ten bulk soil samples from deserts and semi‐arid regions in the Arabian Peninsula, from locations representative of the Sahara and Sahel in North Africa, and from Northeast Africa and South‐Central Asia. We segregate the fine particle fraction (aerodynamic diameter < 2.5μm) and measure its iron content with an x‐ray fluorescence (XRF) spectrometer and its aerosolSSA and absorption, scattering, and extinction Ångström coefficients for two wavelengths (405 nm and 870 nm) with a photoacoustic instrument with integrating reciprocal nephelometer. Results show that SSA is much lower at 405 nm than at 870 nm and that SSA at both wavelengths is dominated by and linearly correlated with the iron content of the entrained mineral dust. The second result points toward potential use of SSA remote sensing to measure aerosol iron content and vice versa, measurements of iron content with simple filter sampling followed by XRF analysis, providing an assessment of SSA for aerosol radiative forcing calculations and modeling. Average Ångström coefficients were ≈3.2 for absorption, ≈−0.4 for scattering, and ≈−0.3 for extinction and showed little correlation with iron content.
Towards structure-based protein drug design
Authors: Zhang Changsheng , Lai Luhua 
Published: May 2012

Structure-based drug design for chemical molecules has been widely used in drug discovery in the last 30 years. Many successful applications have been reported, especially in the field of virtual screening based on molecular docking. Recently, there has been much progress in fragment-based as well as de novo drug discovery. As many protein–protein interactions can be used as key targets for drug design, one of the solutions is to design protein drugs based directly on the protein complexes or the target structure. Compared with protein–ligand interactions, protein–protein interactions are more complicated and present more challenges for design. Over the last decade, both sampling efficiency and scoring accuracy of protein–protein docking have increased significantly. We have developed several strategies for structure-based protein drug design. A grafting strategy for key interaction residues has been developed and successfully applied in designing erythropoietin receptor-binding proteins. Similarly to small-molecule design, we also tested de novo protein-binder design and a virtual screen of protein binders using protein–protein docking calculations. In comparison with the development of structure-based small-molecule drug design, we believe that structure-based protein drug design has come of age.
Non-homologous end-joining partners in a helical dance: structural studies of XLF–XRCC4 interactions
Authors: Wu Qian , Ochi Takashi , Matak-Vinkovic Dijana , Robinson Carol V. , Chirgadze Dimitri Y. , Blundell Tom L. 
Published: May 2012

XRCC4 (X-ray cross-complementation group 4) and XLF (XRCC4-like factor) are two essential interacting proteins in the human NHEJ (non-homologous end-joining) pathway that repairs DNA DSBs (double-strand breaks). The individual crystal structures show that the dimeric proteins are homologues with protomers containing head domains and helical coiled-coil tails related by approximate two-fold symmetry. Biochemical, mutagenesis, biophysical and structural studies have identified the regions of interaction between the two proteins and suggested models for the XLF–XRCC4 complex. An 8.5 Å (1 Å=0.1 nm) resolution crystal structure of XLF–XRCC4 solved by molecular replacement, together with gel filtration and nano-ESI (nano-electrospray ionization)–MS results, demonstrates that XLF and XRCC4 dimers interact through their head domains and form an alternating left-handed helical structure with polypeptide coiled coils and pseudo-dyads of individual XLF and XRCC4 dimers at right angles to the helical axis.
Functional studies of eppin
Authors: O'Rand Michael G. , Widgren Esther E. , Hamil Katherine G. , Silva Erick J. , Richardson Richard T. 
Published: May 2012

Our laboratory has characterized EPPIN [epididymal protease inhibitor; SPINLW1] as a novel gene on human chromosome 20q12-13.2, which encodes a cysteine-rich protein of 133 amino acids with a calculated molecular mass of 15.283 kDa, containing both Kunitz-type and WAP (whey acidic protein)-type four-disulfide core consensus sequences. Eppin is secreted by Sertoli cells in the testis and epididymal epithelial cells; it is predominantly a dimer, although multimers often exist, and in its native form eppin is found on the human sperm surface complexed with LTF (lactotransferrin) and clusterin. During ejaculation SEMG (semenogelin) from the seminal vesicles binds to the eppin protein complex, initiating a series of events that define eppin's function. Eppin's functions include (i) modulating PSA (prostate-specific antigen) enzyme activity, (ii) providing antimicrobial protection and (iii) binding SEMG thereby inhibiting sperm motility. As PSA hydrolyses SEMG in the ejaculate coagulum, spermatozoa gain progressive motility. We have demonstrated that eppin is essential for fertility because immunization of male monkeys with recombinant eppin results in complete, but reversible, contraception. To exploit our understanding of eppin's function, we are developing compounds that inhibit eppin–SEMG interaction and mimic anti-eppin, inhibiting sperm motility. These compounds should have potential as a male contraceptive.
Retinoic acid promotes proliferation of chicken primordial germ cells via activation of PI3K/Akt‐mediated NF‐κB signalling cascade
Authors: Yu Minli , Ge Chutian , Zeng Weidong , Mi Yuling , Zhang Caiqiao 
Published: May 2012

AbstractAs embryonic progenitors for the gametes, PGCs (primordial germ cells) proliferate and develop under strict regulation of numerous intrinsic and external factors. As the most active natural metabolite of vitamin A, all‐trans RA (retinoic acid) plays pivotal roles in regulating development of various cells. The proliferating action of RA on PGCs was investigated along with the intracellular PI3K (phosphoinositide 3‐kinase)/Akt (protein kinase B; also known as Akt)‐mediated NF‐κB (nuclear factor κB) signalling cascade. The results show that RA significantly promoted PGC proliferation in a dose‐ and time‐dependent manner, confirmed by BrdU (bromodeoxyuridine) incorporation and cell cycle analysis. However, this promoting effect was attenuated by sequential inhibitors of LY294002 for PI3K, KP372‐1 for Akt and SN50 for NF‐κB respectively. Western blot analysis showed increased Akt phosphorylation (Ser473) of PGCs after stimulation with RA, but this was abolished by LY294002 or KP372‐1. Treatment with RA increased expression of NF‐κB and decreased IκBα (inhibitory κBα) expression, which were inhibited by SN50. Blockade of PI3K or Akt activity inhibited NF‐κB translocation from the cytoplasm to the nucleus. Finally, mRNA expression of cell cycle regulating genes [cyclin D1 and E, CDK6 (cyclin‐dependent kinase 6) and CDK2] was up‐regulated in the RA‐treated cells. This stimulation was also markedly retarded by combined treatment with LY294002, KP372‐1 and SN50. These results suggest that RA activates the PI3K/Akt and NF‐κB signalling cascade to promote proliferation of the cultured chicken PGCs.
Movement of Radio‐Tagged Adult Pacific Lampreys during a Large‐Scale Fishway Velocity Experiment
Authors: Johnson Eric L. , Caudill Christopher C. , Keefer Matthew L. , Clabough Tami S. , Peery Christopher A. , Jepson Michael A. , Moser Mary L. 
Published: May 2012

AbstractOptimization of fishways to pass multiple species is challenging because life history, swimming ability, and behavior often differ among species. For example, high fishway water velocities designed to attract adult Pacific salmon Oncorhynchus spp. at Columbia River dams inhibit fishway entrance and passage success of adult Pacific lampreys Lampetra tridentata, a species of conservation concern. We tested whether reduced water velocities (∼1.2 m/s, 0.15 m of head) at Bonneville Dam fishway openings improved entrance efficiency and other passage metrics for radio‐tagged Pacific lampreys compared with control velocities (>1.98 m/s, 0.46 m of head) and near‐zero (“standby”) velocities. Lamprey entrance efficiencies were significantly higher in the reduced‐velocity treatment (26–29%) than in the control (13–20%) or standby (5–9%) treatment. In some years, significantly more Pacific lampreys passed through fishway collection channels and transition pools and reached the fish ladder during reduced‐velocity treatment conditions, indicating that benefits extended beyond fishway entrances. However, overall passage efficiency at the dam was relatively unchanged, suggesting that additional passage bottlenecks for Pacific lampreys exist upstream from fishway entrances. The experiment demonstrated how operational changes can improve passage performance and how exploiting behavioral differences among species can improve multispecies management.
Long‐term mortality with cardiac resynchronization therapy in the Cardiac Resynchronization‐Heart Failure (CARE‐HF) trial
Authors: Cleland John G.F. , Freemantle Nick , Erdmann Erland , Gras Daniel , Kappenberger Lukas , Tavazzi Luigi , Daubert Jean‐Claude 
Published: May 2012

AimsThe Cardiac Resynchronization‐Heart Failure (CARE‐HF) study helped establish an important role for cardiac resynchronization therapy (CRT) in the management of selected patients with heart failure. We now report the long‐term outcome during and subsequent to the randomized trial.Methods and resultsEnrolment was completed in March 2003. After reporting the main study results in 2005, investigators were asked to inform patients of the results and implant a CRT device if still appropriate. Subsequently, investigators were asked to consent patients for long‐term follow‐up until 30 September 2009. Of 813 patients originally enrolled, 343 (42%) died prior to re‐consent, 111 patients (14%) were not or could not be contacted, 50 (6%) were alive but declined to participate, and 309 (38%) consented to long‐term follow‐up. Of patients originally assigned to the control group, > 95% of survivors had received CRT by the time of re‐consent. From the time of randomization, 222 patients originally assigned to pharmacological therapy and 192 originally assigned to CRT were known to have died. The hazard ratio for mortality in patients originally assigned to CRT compared with those originally assigned to the control group was 0.77 (95% confidence interval 0.63–0.93; P = 0.007). No subgroup interactions were observed.ConclusionThe effect of CRT on mortality observed during the randomized CARE‐HF trial persisted during long‐term follow‐up. A high rate of CRT device implantation in the control group after completion of the randomized phase of the study may have prevented further divergence of the survival curves.
Impact of functional tricuspid regurgitation on heart failure and death in patients with functional mitral regurgitation and left ventricular dysfunction
Authors: Agricola Eustachio , Stella Stefano , Gullace Mariangela , Ingallina Giacomo , D'Amato Rossella , Slavich Massimo , Oppizzi Michele , Ancona Marco Bruno , Margonato Alberto 
Published: May 2012

AimsThe prognostic role of tricuspid regurgitation (TR) associated with organic left‐sided valvular heart disease is well known. However, no data are available regarding the prognostic value of functional TR (FTR) in patients with functional mitral regurgitation (FMR) and left ventricular (LV) dysfunction. The purpose of this study was to evaluate the prognostic role of FTR for occurrence of heart failure (HF) and mortality in patients with FMR.Methods and resultsWe enrolled 373 consecutive patients (mean age 68 ±11 years) with LV dysfunction and at least mild FMR and with or without FTR, both quantitated by echocardiography. The median follow‐up was 32 months (range 1–120 months); 132 (35.4%) and 97 patients developed HF or died, respectively. The incidence of HF at 3 and 6 years was 36 ±2% and 55 ±4%, respectively. Moderate to severe FTR [hazard ratio (HR) 1.4, 95% confidence interval (CI) 1.1–2.1, P = 0.01) was an independent determinant of HF. The incidence of HF was 41 ±5, 46 ±7, 57 ±7, and 65 ±8% for patients without, and with mild, moderate, and severe FTR respectively (P = 0.03). At 3 and 6 years the survival free of all‐cause mortality was 77.5 ±2% and 60 ±3%, respectively. Moderate to severe FTR (HR 1.6, 95% CI 1.2–2.1, P = 0.01) was an independent determinant of overall mortality. At 6 years, survival free of all‐cause mortality was 69 ±2.5, 67 ±2.1, 51 ±2.5, and 40 ±4.8% for patients without, and with mild, moderate, and severe FTR, respectively (P = 0.004).ConclusionsModerate or more FTR is independently associated with worse survival and a high incidence of HF episodes in patients with FMR.
The chromosomal passenger complex controls the function of endosomal sorting complex required for transport-III Snf7 proteins during cytokinesis
Authors: Capalbo Luisa , Montembault Emilie , Takeda Tetsuya , Bassi Zuni I. , Glover David M. , D'Avino Pier Paolo 
Published: May 2012

Summary

Cytokinesis controls the proper segregation of nuclear and cytoplasmic materials at the end of cell division. The chromosomal passenger complex (CPC) has been proposed to monitor the final separation of the two daughter cells at the end of cytokinesis in order to prevent cell abscission in the presence of DNA at the cleavage site, but the precise molecular basis for this is unclear. Recent studies indicate that abscission could be mediated by the assembly of filaments comprising components of the endosomal sorting complex required for transport-III (ESCRT-III). Here, we show that the CPC subunit Borealin interacts directly with the Snf7 components of ESCRT-III in both
Drosophila
and human cells. Moreover, we find that the CPC's catalytic subunit, Aurora B kinase, phosphorylates one of the three human Snf7 paralogues—CHMP4C—in its C-terminal tail, a region known to regulate its ability to form polymers and associate with membranes. Phosphorylation at these sites appears essential for CHMP4C function because their mutation leads to cytokinesis defects. We propose that CPC controls abscission timing through inhibition of ESCRT-III Snf7 polymerization and membrane association using two concurrent mechanisms: interaction of its Borealin component with Snf7 proteins and phosphorylation of CHMP4C by Aurora B.
Co‐administration of live attenuated Salmonella enterica serovar Typhimurium expressing swine interleukin‐18 and interferon‐α provides enhanced Th1‐biased protective immunity against inactivated vaccine of pseudorabies virus
Authors: Kim Seon Ju , Bum Kim Seong , Woo Han Young , Uyangaa Erdenebileg , Hyoung Kim Jin , Young Choi Jin , Kim Koanhoi , Kug Eo Seong 
Published: May 2012

ABSTRACTThe co‐administration of two or more cytokines may generate additive or synergistic effects for controlling infectious diseases. However, the practical use of cytokine combinations for the modulation of immune responses against inactivated vaccine has not been demonstrated in livestock yet, primarily due to protein stability, production, and costs associated with mass administration. In light of the current situation, we evaluated the immunomodulatory functions of the combined administration of swine interleukin‐18 (swIL‐18) and interferon‐α (swIFN‐α) against an inactivated PrV vaccine using attenuated Salmonella enterica serovar Typhimurium as a cytokine delivery system. Co‐administration of S. enterica serovar Typhimurium expressing swIL‐18 and swIFN‐α produced enhanced Th1‐biased humoral and cellular immune responses against the inactivated PrV vaccine, when compared to single administration of S. enterica serovar Typhimurium expressing either swIL‐18 or swIFN‐α. Also, enhanced immune responses in co‐administered piglets occurred rapidly after virulent PrV challenge, and piglets that received co‐administration of S. enterica serovar Typhimurium expressing swIL‐18 and swIFN‐α displayed a greater alleviation of clinical severity following the virulent PrV challenge, as determined by clinical scores and cumulative daily weight gain. Furthermore, this enhancement was confirmed by reduced nasal shedding of PrV following viral challenge. Therefore, these results suggest that oral co‐administration of S. enterica serovar Typhimurium expressing swIL‐18 and swIFN‐α provide enhanced Th1‐biased immunity against inactivated PrV vaccine to alleviate clinical signs caused by PrV challenge.
Physcomitrella patens activates reinforcement of the cell wall, programmed cell death and accumulation of evolutionary conserved defence signals, such as salicylic acid and 12‐oxo‐phytodienoic acid, but not jasmonic acid, upon Botrytis cinerea infection
Authors: PONCE DE LEÓN INÉS , SCHMELZ ERIC A. , GAGGERO CARINA , CASTRO ALEXANDRA , ÁLVAREZ ALFONSO , MONTESANO MARCOS 
Published: May 2012

SUMMARYThe moss Physcomitrella patens is an evolutionarily basal model system suitable for the analysis of plant defence responses activated after pathogen assault. Upon infection with the necrotroph Botrytis cinerea, several defence mechanisms are induced in P. patens, including the fortification of the plant cell wall by the incorporation of phenolic compounds and the induced expression of related genes. Botrytis cinerea infection also activates the accumulation of reactive oxygen species and cell death with hallmarks of programmed cell death in moss tissues. Salicylic acid (SA) levels also increase after fungal infection, and treatment with SA enhances transcript accumulation of the defence gene phenylalanine ammonia‐lyase (PAL) in P. patens colonies. The expression levels of the genes involved in 12‐oxo‐phytodienoic acid (OPDA) synthesis, including lipoxygenase (LOX) and allene oxide synthase (AOS), increase in P. patens gametophytes after pathogen assault, together with a rise in free linolenic acid and OPDA concentrations. However, jasmonic acid (JA) could not be detected in healthy or infected tissues of this plant. Our results suggest that, although conserved defence signals, such as SA and OPDA, are synthesized and are probably involved in the defence response of P. patens against B. cinerea infection, JA production appears to be missing. Interestingly, P. patens responds to OPDA and methyl jasmonate by reducing moss colony growth and rhizoid length, suggesting that jasmonate perception is present in mosses. Thus, P. patens can provide clues with regard to the evolution of different defence pathways in plants, including signalling and perception of OPDA and jasmonates in nonflowering and flowering plants.
Effects of clopidogrel and itraconazole on the disposition of efavirenz and its hydroxyl metabolites: exploration of a novel CYP2B6 phenotyping index
Authors: Jiang Fen , Desta Zeruesenay , Shon Ji‐Hong , Yeo Chang‐Woo , Kim Ho‐Sook , Liu Kwang‐Hyeon , Bae Soo‐Kyung , Lee Sang‐Seop , Flockhart David A. , Shin Jae‐Gook 
Published: May 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Cytochrome P450 (CYP) 2B6 is the enzyme primarily responsible for the metabolism of many clinically important drugs, including efavirenz, which it converts to 8‐hydroxyefavirenz and then to 8,14‐hydroxyefavirenz.• The CYP2B6*6 polymorphism influences efavirenz pharmacokinetics, but a validated phenotyping method for predicting CYP2B6 activity in human subjects is not yet available.• The disposition of 8,14‐dihydroxyefavirenz in humans in vivo is unknown.WHAT THIS STUDY ADDS• This study is the first quantitative examination of 8,14‐dihydroxyefavirenz pharmacokinetics in human subjects.• The 8,14‐dihydroxyefavirenz : efavirenz AUC(0,120 h) ratio correlates with efavirenz oral clearance and is sensitive and specific to CYP2B6 activity alterations.• The 8,14‐dihydroxyefavirenz : efavirenz AUC(0,120 h) ratio may be a useful phenotyping index for CYP2B6 activity in vivo.AIMS To evaluate the effects of clopidogrel and itraconazole on the disposition of efavirenz and its hydroxyl metabolites in relation to the CYP2B6*6 genotype and explore potential phenotyping indices for CYP2B6 activity in vivo using a low dose of oral efavirenz.METHODS We conducted a randomized three phase crossover study in 17 healthy Korean subjects pre‐genotyped for the CYP2B6*6 allele (CYP2B6*1/*1, n= 6; *1/*6, n= 6; *6/*6, n= 5). Subjects were pretreated with clopidogrel (75 mg day−1 for 4 days), itraconazole (200 mg day−1 for 6 days), or placebo and then given a single dose of efavirenz (200 mg). The plasma (0–120 h) and urine (0–24 h) concentrations of efavirenz and its metabolites (7‐ and 8‐hydroxyefavirenz and 8,14‐dihydroxyefavirenz) were determined by LC/MS/MS.RESULTS This study is the first to delineate quantitatively the full (phase I and II) metabolic profile of efavirenz and its three hydroxyl metabolites in humans. Clopidogrel pretreatment markedly decreased AUC(0,48 h), Cmax and Ae(0,24 h) for 8,14‐dihydroxyefavirenz, compared with placebo; 95% CI of the ratios were 0.55, 0.73, 0.30, 0.45 and 0.25, 0.47, respectively. The 8,14‐dihydroxyefavirenz : efavirenz AUC(0,120 h) ratio was significantly correlated with the weight‐adjusted CL/F of efavirenz (r2≈ 0.4, P < 0.05), differed with CYP2B6*6 genotype and was affected by clopidogrel pretreatment (P < 0.05) but not by itraconazole pretreatment.CONCLUSIONS The disposition of 8,14‐dihydroxy‐EFV appears to be sensitive to CYP2B6 activity alterations in human subjects. The 8,14‐dihydroxyefaviremz : efavirenz AUC(0,120 h) ratio is attractive as a candidate phenotyping index for CYP2B6 activity in vivo.