bluuebunny/crossref_metadata_2025 huggingface dataset:
CX3CR1 is a gatekeeper for intestinal barrier integrity in mice: Limiting steatohepatitis by maintaining intestinal homeostasis
Authors: Schneider Kai Markus , Bieghs Veerle , Heymann Felix , Hu Wei , Dreymueller Daniela , Liao Lijun , Frissen Mick , Ludwig Andreas , Gassler Nikolaus , Pabst Oliver , Latz Eicke , Sellge Gernot , Penders John , Tacke Frank , Trautwein Christian
Published: July 2015

Nonalcoholic fatty liver disease is seen as the hepatic manifestation of the metabolic syndrome and represents the most common liver disease in Western societies. The G protein–coupled chemokine receptor CX3CR1 plays a central role in several metabolic syndrome–related disease manifestations and is involved in maintaining intestinal homeostasis. Because diet‐induced intestinal dysbiosis is a driver for nonalcoholic fatty liver disease, we hypothesized that CX3CR1 may influence the development of steatohepatitis. In two independent models of diet‐induced steatohepatitis (high‐fat diet and methionine/choline‐deficient diet), CX3CR1 protected mice from excessive hepatic steatosis and inflammation, as well as systemic glucose intolerance. Lack of Cx3cr1 expression was associated with significantly altered intestinal microbiota composition, which was linked to an impaired intestinal barrier. Concomitantly, endotoxin levels in portal serum and inflammatory macrophages in liver were increased in Cx3cr1
–/– mice, indicating an increased inflammatory response. Depletion of intestinal microbiota by administration of broad‐spectrum antibiotics suppressed the number of infiltrating macrophages and promoted macrophage polarization in liver. Consequently, antibiotic‐treated mice demonstrated a marked improvement of steatohepatitis. Conclusion: Microbiota‐mediated activation of the innate immune responses through CX3CR1 is crucial for controlling steatohepatitis progression, which recognizes CX3CR1 as an essential gatekeeper in this scenario. (Hepatology 2015;62:1405–1416)
Prediction of short‐ and long‐term outcome in patients with autoimmune hepatitis
Authors: Kirstein Martha M. , Metzler Frauke , Geiger Elena , Heinrich Eyk , Hallensleben Michael , Manns Michael P. , Vogel Arndt
Published: July 2015

Autoimmune hepatitis (AIH) is a chronic inflammatory disease characterized by a loss of tolerance toward the hepatocellular epithelium. Liver transplantation (LT) represents the ultimate therapeutic option for a fulminant course or end‐stage liver disease. The aim of this study was to elucidate the clinical, serological, and genetic features of remission, relapse, and overall and LT‐free survival. Between 2000 and 2014, 354 AIH patients from Hannover Medical School were included. Clinical, laboratory, and histological reports were analyzed. DRB1 allele analyses were performed in 264 AIH and 399 non‐AIH patients. Cox's regression analysis was performed to identify factors significantly associated with survival. Patients diagnosed in childhood were at higher risk for relapses (P = 0.003), requirement for LTs (P = 0.014, log rank), and had a reduced life expectancy (P < 0.001, log rank). Detection of soluble liver antigen/liver pancreas antigen (SLA/LP) antibodies was significantly associated with reduced overall and LT‐free survival (P = 0.037; P = 0.021). Cirrhosis, which was evident in 25% at first diagnosis, was found to be a predictor of poor survival and requirement for LT (P = 0.003; P = 0.009). DRB1*04:01‐positive phenotype was associated with a higher rate of complete remissions and with a lower frequency of cirrhosis and LTs. There were no significant differences for subsequent relapses or survival in patients achieving either partial or complete remission. Conclusion: Diagnosis <18 years, histological cirrhosis at first diagnosis and SLA/LP antibodies are major risk factors for a poor short‐ and long‐term outcome. These patients are in need of high surveillance. Separating patients with positive SLA/LP antibodies into a third group may be reconsidered. DRB1*04:01 positivity has been identified in association with a favorable clinical outcome. (Hepatology 2015;62:1524–1535)
The Aminopropenal‐ and Aminopentadienal Rearrangement
Authors: Neuenschwander Markus
Published: July 2015

Scope and mechanism of the aminopropenal rearrangement are reviewed: Various 3‐acyloxy‐3‐dialkylaminopropenals (2, formed by addition of acids to ‘push‐pull’‐acetylenes 1) rearranged quantitatively to give 3‐acyloxyacrylic amides (3, Schemes 1 and 22). Since these activated enol esters reacted very selectively with amino groups of polyfunctional amino acids, ‘push‐pull’‐acetylenes are versatile peptide reagents.

Similarly, 5‐X‐5‐dialkylaminopentadienals (38, formed by addition of acids to ‘push‐pull’‐enynes 37) could be rearranged (aminopentadienal rearrangement). In this case, the rearrangement 38→40→42 (Schemes 16 and 22) normally stopped at the level of the quite stable 2‐dialkylamino‐pyrylium salts 40. Ring opening 40→42 of these intermediates was quite tricky, but could be realized in several cases.
Synthesis of Two Natural Furan‐Cyclized Diarylheptanoids via 2‐Furaldehyde
Authors: Seçinti Hatice , Seçen Hasan
Published: July 2015

Two natural diarylheptanoids, 2‐benzyl‐5‐(2‐phenylethyl)furan (1) and 2‐methoxy‐4‐{[5‐(2‐phenylethyl)furan‐2‐yl]methyl}phenol (2), were synthesized starting from 2‐furaldehyde. A Wittig reaction of 2‐furaldehyde with benzyltriphenylphosphonium bromide followed by reduction of the alkene CC bond with Mg gave 2‐(2‐phenylethyl)furan (5). Lithiation of 5 with BuLi at −78° followed by alkylation with benzyl bromide gave natural product 1. In another approach, FriedelCrafts acylation of compound 5 with benzoyl chloride followed by deoxygenation of the CO group afforded 1. The natural product 2 was also synthesized by acylation of 5 with 4‐acetoxy‐3‐methoxybenzoyl chloride (16) followed by deoxygenation and deacetylation.
Two New Eudesmanolides from the Flowers of Achillea millefolium
Authors: Zhang Chun‐Bao , Ni Zhi‐Yu , Wang Jin , Qing Xia , Yan Hui‐Min , Shi Qing‐Wen , Sauriol Françoise , Gu Yu‐Cheng , Wu Yi‐Bing
Published: July 2015

Two new eudesmanolides, 3β‐acetoxy‐1β,4α‐dihydroxy‐11αH‐eudesman‐12,6α‐olide (1) and 3β‐acetoxy‐1β‐hydroxy‐11αH‐eudesman‐4(15)‐en‐12,6α‐olide (2), were isolated from the flowers of Achillea millefolium, their structures were established on the basis of spectral analysis.
Diterpene Glycosides from the Dry Fronds of Conyza japonica
Authors: Hu Jiang , Song Yan , Li Hui , Mao Xia , Shi Xiaodong , Liu Zhiming
Published: July 2015

Phytochemical investigation of the 95% EtOH extract of the dry fronds of Conyza japonica (Thunb.) Less. resulted in the isolation of three new labdane diterpene glycosides, (3β,13S)‐13‐O‐α‐L‐rhamnopyranosyllabda‐8(17),14‐dien‐3‐yl α‐L‐rhamnopyranoside (1), (3β,13S)‐13‐O‐α‐L‐rhamnopyranosyllabda‐8(17),14‐diene‐3‐yl 2‐O‐acetyl‐α‐L‐rhamnopyranoside (2), and (3β,13S)‐13‐O‐α‐L‐rhamnopyranosylabda‐8(17),14‐dien‐3‐yl 6‐O‐acetyl‐β‐D‐glucopyranosyl‐(1→2)‐α‐L‐rhamnopyranoside (3), together with their aglycone, (13S)‐labda‐8(17),14‐diene‐3,13‐diol (4). Their structures were characterized by spectroscopic analyses and chemical correlations, including 1D‐ and 2D‐NMR, and HR‐ESI‐MS. Furthermore, compounds 1–3 appeared to be promising as active agents against the tested pathogen fungi and oral pathogens as they possessed moderate cytotoxic properties.
Two New Sesquiterpenes from the Resin of Toxicodendron vernicifluum
Authors: He Jiang‐Bo , Lu Qing , Cheng Yong‐Xian
Published: July 2015

A phytochemical investigation of the resin of Toxicodendron vernicifluum resulted in the isolation of two new sesquiterpenoids, toxicodenanes D (1), endowed with a new carbon skeleton, and E (2), along with six known sesquiterpenoids (Fig. 1). Their structures were determined by spectroscopic analysis, including 1D‐ and 2D‐NMR and mass spectrometry.
An Efficient Enantioselective Synthesis of Natural Gingerols, the Active Principles of Ginger
Authors: Ramesh Reddy A. , Wadavrao Sachin B. , Yadav J. S. , Venkat Narsaiah A.
Published: July 2015

A straightforward synthesis of (S)‐gingerols 1–3 has been described. The requisite stereogenic center in the target molecules was introduced by Sharpless asymmetric dihydroxylation using a chiral complex, AD‐mix β. This route is simple and efficient to prepare the products in very good yields.
Novel 1,2,3,4‐Tetrahydroquinazolinones via Reaction of 2‐Amino‐N‐substituted Benzamides and Dimethyl Acetylenedicarboxylate
Authors: Nahavandian Semiramis , Allameh Sadegh , Saeedi Mina , Ansari Shirin , Mahdavi Mohammad , Foroumadi Alireza , Shafiee Abbas
Published: July 2015

Reaction of 2‐amino‐N‐substituted benzamides and dimethyl acetylenedicarboxylate (DMAD) in the presence of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) in H2O at room temperature led to the formation of novel 1,2,3,4‐tetrahydroquinazolinones.
Serological response to Helicobacter pylori infection among Latin American populations with contrasting risks of gastric cancer
Authors: Camargo M. Constanza , Beltran Mauricio , Conde‐Glez Carlos J. , Harris Paul R. , Michel Angelika , Waterboer Tim , Carolina Flórez Astrid , Torres Javier , Ferreccio Catterina , Sampson Joshua N. , Pawlita Michael , Rabkin Charles S.
Published: July 2015

Gastric cancer is a rare outcome of chronic Helicobacter pylori infection. Serologic profiles may reveal bacterial, environmental and/or host factors associated with cancer risk. We therefore compared specific anti‐H. pylori antibodies among populations with at least twofold differences in gastric cancer mortality from Mexico, Colombia and Chile. Our study included 1,776 adults (mean age 42 years) from three nationally representative surveys, equally divided between residents of high‐ and low‐risk areas. Antibodies to 15 immunogenic H. pylori antigens were measured by fluorescent bead‐based multiplex assays; results were summarized to identify overall H. pylori seropositivity. We used logistic regression to model associations between antibody seroreactivity and regional cancer risk (high vs. low), adjusting for country, age and sex. Both risk areas had similar H. pylori seroprevalence. Residents in high‐ and low‐risk areas were seroreactive to a similar number of antigens (means 8.2 vs. 7.9, respectively; adjusted odds ratio, OR: 1.02, p = 0.05). Seroreactivities to Catalase and the known virulence proteins CagA and VacA were each significantly (p < 0.05) associated with residence in high‐risk areas, but ORs were moderate (1.26, 1.42 and 1.41, respectively) and their discriminatory power was low (area under the curve < 0.6). The association of Catalase was independent from effects of either CagA or VacA. Sensitivity analyses for antibody associations restricted to H. pylori‐seropositive individuals generally replicated significant associations. Our findings suggest that humoral responses to H. pylori are insufficient to distinguish high and low gastric cancer risk in Latin America. Factors determining population variation of gastric cancer burden remain to be identified.
Circulating tumor cells in breast cancer beyond the genotype of primary tumor for tailored therapy
Authors: Ren Chuanli , Han Chongxu , Fu Deyuan , Wang Daxin , Chen Hui , Chen Yong , Shen Ming
Published: July 2015

Although TNM staging based on tumor, node lymph status and metastasis status—is the most widely used method in the clinic to classify breast cancer (BC) and assess prognosis, it offers limited information for different BC subgroups. Circulating tumor cells (CTCs) are regarded as minimal residual disease and are proven to have a strong relationship with BC. Detection of ≥5 CTCs per 7.5 mL in peripheral blood predicts poor prognosis in metastatic BC irrespective of other clinical parameters, whereas, in early‐stage BC, detection of CK19+ CTCs are also associated with poor prognosis. Increasing data and clinical trials show that CTCs can improve prognostic accuracy and help tailor treatment for patients with BC. However, heterogeneous CTCs in the process of an epithelial‐mesenchymal transition (EMT) in BC makes it a challenge to detect these rare cells. Moreover, the genotypic and phenotypic features of CTCs are different from primary BC tumors. Molecular analysis of CTCs in BC may benefit patients by identifying those amenable to tailored therapy. We propose that CTCs should be used alongside the TNM staging system and the genotype of primary tumor to guide tailored BC diagnosis and treatment.
A rescue act: Translesion DNA synthesis past N2‐deoxyguanosine adducts
Authors: Nair Deepak T. , Kottur Jithesh , Sharma Rahul
Published: July 2015

Genomic DNA is continually subjected to a number of chemical insults that result in the formation of modified nucleotides—termed as DNA lesions. The N2‐atom of deoxyguanosine is particularly reactive and a number of chemicals react at this site to form different kinds of DNA adducts. The N2‐deoxyguanosine adducts perturb different genomic processes and are particularly deleterious for DNA replication as they have a strong tendency to inhibit replicative DNA polymerases. Many organisms possess specialized dPols—generally classified in the Y‐family—that serves to rescue replication stalled at N2‐dG and other adducts. A review of minor groove N2‐adducts and the known strategies utilized by Y‐family dPols to replicate past these lesions will be presented here. © 2015 IUBMB Life, 67(7):564–574, 2015
Error Correction Testing in Panels with Common Stochastic Trends
Authors: Gengenbach Christian , Urbain Jean‐Pierre , Westerlund Joakim
Published: July 2015

This paper develops panel data tests for the null hypothesis of no error correction in a model with common stochastic trends. The asymptotic distributions of the new test statistics are derived and simulation results are provided to suggest that they perform well in small samples. Copyright © 2015 John Wiley & Sons, Ltd.
Replication of unconditional Quantile Regressions by Firpo, Fortin and Lemieux (2009)
Authors: Baltagi Badi H. , Ghosh Pallab Kumar
Published: July 2015

This paper is a narrow replication of Firpo, Fortin and Lemieux (Unconditional quantile regressions. Econometrica 2009; 77(3): 953–973), who propose a new estimation method, called ‘unconditional quantile regressions’. Using their empirical example, we confirm their results for the effects of unionization on US wage inequality during the period 1983–1985 for both conditional and unconditional quantile regressions. In addition, this paper applies the proposed estimation method to another paper by Autor, Katz and Kearney (Trends in US wage inequality: revising the revisionists. Review of Economics and Statistics 2008; 90(2): 300–323). The latter paper looks at measures of wage inequality in the US labor market data over the period 1963–2005. Copyright © 2015 John Wiley & Sons, Ltd.
The comparative toxicity of a reduced, crude comfrey (Symphytum officinale) alkaloid extract and the pure, comfrey‐derived pyrrolizidine alkaloids, lycopsamine and intermedine in chicks (Gallus gallus domesticus)
Authors: Brown Ammon W. , Stegelmeier Bryan L. , Colegate Steven M. , Gardner Dale R. , Panter Kip E. , Knoppel Edward L. , Hall Jeffery O.
Published: July 2015

Comfrey (Symphytum officinale), a commonly used herb, contains dehydropyrrolizidine alkaloids that, as a group of bioactive metabolites, are potentially hepatotoxic, pneumotoxic, genotoxic and carcinogenic. Consequently, regulatory agencies and international health organizations have recommended comfrey be used for external use only. However, in many locations comfrey continues to be ingested as a tisane or as a leafy vegetable. The objective of this work was to compare the toxicity of a crude, reduced comfrey alkaloid extract to purified lycopsamine and intermedine that are major constituents of S. officinale. Male, California White chicks were orally exposed to daily doses of 0.04, 0.13, 0.26, 0.52 and 1.04 mmol lycopsamine, intermedine or reduced comfrey extract per kg bodyweight (BW) for 10 days. After another 7 days chicks were euthanized. Based on clinical signs of poisoning, serum biochemistry, and histopathological analysis the reduced comfrey extract was more toxic than lycopsamine and intermedine. This work suggests a greater than additive effect of the individual alkaloids and/or a more potent toxicity of the acetylated derivatives in the reduced comfrey extract. It also suggests that safety recommendations based on purified compounds may underestimate the potential toxicity of comfrey. Published 2015. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
Biodegradation, biocompatibility, and osteoconduction evaluation of collagen‐nanohydroxyapatite cryogels for bone tissue regeneration
Authors: Salgado Christiane Laranjo , Grenho Liliana , Fernandes Maria Helena , Colaço Bruno Jorge , Monteiro Fernando Jorge
Published: July 2015

Designing biomimetic biomaterials inspired by the natural complex structure of bone and other hard tissues is still a challenge nowadays. The control of the biomineralization process onto biomaterials should be evaluated before clinical application. Aiming at bone regeneration applications, this work evaluated thein vitrobiodegradation and interaction between human bone marrow stromal cells (HBMSC) cultured on different collagen/nanohydroxyapatite cryogels. Cell proliferation, differentiation, morphology, and metabolic activity were assessed through different protocols. All the biocomposite materials allowed physiologic apatite deposition after incubation in simulated body fluid and the cryogel with the highest nanoHA content showed to have the highest mechanical strength (DMA). The study clearly showed that the highest concentration of nanoHA granules on the cryogels were able to support cell type's survival, proliferation, and individual functionality in a monoculture system, for 21 days. In fact, the biocomposites were also able to differentiate HBMSCs into osteoblastic phenotype. The composites behavior was also assessedin vivothrough subcutaneous and bone implantation in rats to evaluate its tissue‐forming ability and degradation rate. The cryogels Coll/nanoHA (30 : 70) promoted tissue regeneration and adverse reactions were not observed on subcutaneous and bone implants. The results achieved suggest that scaffolds of Coll/nanoHA (30 : 70) should be considered promising implants for bone defects that present a grotto like appearance with a relatively small access but a wider hollow inside. This material could adjust to small dimensions and when entering into the defect, it could expand inside and remain in close contact with the defect walls, thus ensuring adequate osteoconductivity. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 57–70, 2016.
Neonatal High Bone Mass With First Mutation of the NF-κB Complex: Heterozygous De Novo Missense (p.Asp512Ser) RELA (Rela/p65)
Authors: Frederiksen Anja L , Larsen Martin J , Brusgaard Klaus , Novack Deborah V , Knudsen Peter Juel Thiis , Schrøder Henrik Daa , Qiu Weimin , Eckhardt Christina , McAlister William H , Kassem Moustapha , Mumm Steven , Frost Morten , Whyte Michael P
Published: July 2015

Heritable disorders that feature high bone mass (HBM) are rare. The etiology is typically a mutation(s) within a gene that regulates the differentiation and function of osteoblasts (OBs) or osteoclasts (OCs). Nevertheless, the molecular basis is unknown for approximately one-fifth of such entities. NF-κB signaling is a key regulator of bone remodeling and acts by enhancing OC survival while impairing OB maturation and function. The NF-κB transcription complex comprises five subunits. In mice, deletion of the p50 and p52 subunits together causes osteopetrosis (OPT). In humans, however, mutations within the genes that encode the NF-κB complex, including the Rela/p65 subunit, have not been reported. We describe a neonate who died suddenly and unexpectedly and was found at postmortem to have HBM documented radiographically and by skeletal histopathology. Serum was not available for study. Radiographic changes resembled malignant OPT, but histopathological investigation showed morphologically normal OCs and evidence of intact bone resorption excluding OPT. Furthermore, mutation analysis was negative for eight genes associated with OPT or HBM. Instead, accelerated bone formation appeared to account for the HBM. Subsequently, trio-based whole exome sequencing revealed a heterozygous de novo missense mutation (c.1534_1535delinsAG, p.Asp512Ser) in exon 11 of RELA encoding Rela/p65. The mutation was then verified using bidirectional Sanger sequencing. Lipopolysaccharide stimulation of patient fibroblasts elicited impaired NF-κB responses compared with healthy control fibroblasts. Five unrelated patients with unexplained HBM did not show a RELA defect. Ours is apparently the first report of a mutation within the NF-κB complex in humans. The missense change is associated with neonatal osteosclerosis from in utero increased OB function rather than failed OC action. These findings demonstrate the importance of the Rela/p65 subunit within the NF-κB pathway for human skeletal homeostasis and represent a new genetic cause of HBM. © 2015 American Society for Bone and Mineral Research.
Inhibition of Notch Signaling During Mouse Incisor Renewal Leads to Enamel Defects
Authors: Jheon Andrew H , Prochazkova Michaela , Meng Bo , Wen Timothy , Lim Young-Jun , Naveau Adrien , Espinoza Ruben , Cox Timothy C , Sone Eli D , Ganss Bernhard , Siebel Christian W , Klein Ophir D
Published: July 2015

The continuously growing rodent incisor is an emerging model for the study of renewal of mineralized tissues by adult stem cells. Although the Bmp, Fgf, Shh, and Wnt pathways have been studied in this organ previously, relatively little is known about the role of Notch signaling during incisor renewal. Notch signaling components are expressed in enamel-forming ameloblasts and the underlying stratum intermedium (SI), which suggested distinct roles in incisor renewal and enamel mineralization. Here, we injected adult mice with inhibitory antibodies against several components of the Notch pathway. This blockade led to defects in the interaction between ameloblasts and the SI cells, which ultimately affected enamel formation. Furthermore, Notch signaling inhibition led to the downregulation of desmosome-specific proteins such as PERP and desmoplakin, consistent with the importance of desmosomes in the integrity of ameloblast-SI attachment and enamel formation. Together, our data demonstrate that Notch signaling is critical for proper enamel formation during incisor renewal, in part by regulating desmosome-specific components, and that the mouse incisor provides a model system to dissect Jag-Notch signaling mechanisms in the context of mineralized tissue renewal. © 2015 American Society for Bone and Mineral Research.
Effect of methylation on relative energies of tautomers and on the intramolecular proton transfer barriers of protonated nitrosamine: A MR‐CISD study
Authors: de Andrade Railton Barbosa , Vieira Leitão Ezequiel Fragoso , de Souza Miguel Angelo Fonseca , Ventura Elizete , do Monte Silmar Andrade
Published: July 2015

MR‐CISD, MR‐CISD+Q, and MR‐AQCC calculations have been performed on the minima and transition states (corresponding to intramolecular proton transfer between the protonation sites) of the ground state of protonated nitrosamine and N,N‐dimethylnitrosamine. Our highest level results (MR‐AQCC/cc‐pVTZ) for the smaller system indicate that protonation on the N amino (2a) is practically as favorable as the most favorable protonation on the O atom (1a). They also suggest that protonation on the nitroso N atom (2c) is ∼14.5 kcal/mol less favorable than 1a. Results obtained at the MR‐CISD+Q/cc‐pVTZ level indicate that the effect of methylation on the relative energies of the tautomers is, in order of importance, 2a > 2c and increases their energies by ∼17.5 and 4.8 kcal/mol, respectively. They also indicate that methylation alters significantly the intramolecular proton transfer barriers. The largest differences between the common geometric parameters of both systems have been found for 2a. © 2015 Wiley Periodicals, Inc.
Effect of food or proton pump inhibitor treatment on the bioavailability of dacomitinib in healthy volunteers
Authors: Ruiz‐Garcia Ana , Masters Joanna C. , Mendes da Costa Laure , LaBadie Robert R. , Liang Yali , Ni Grace , Ellery Craig A. , Boutros Tanya , Goldberg Zelanna , Bello Carlo L.
Published: July 2015

This phase 1, open‐label crossover study evaluated the relative bioavailability of dacomitinib in healthy volunteers under fed and fasted conditions and following coadministration with rabeprazole, a potent acid‐reducing proton pump inhibitor (PPI). Twenty‐four male subjects received a single dacomitinib 45‐mg dose under 3 different conditions separated by washout periods of ≥16 days: coadministered with rabeprazole 40 mg under fasting conditions; alone under fasting conditions; and alone after a high‐fat, high‐calorie meal. Increased peak exposure of 23.7% (90% confidence interval [CI], 5.3%–45.2%) was detected with dacomitinib taken after food versus fasting. The adjusted geometric mean ratio (fed/fasted) for area under the plasma concentration−time curve from time zero to infinity (AUCinf) was 114.2% (90%CI, 104.7%–124.5%) and not considered clinically meaningful. In the fasted state, a decrease in dacomitinib AUCinf was observed following rabeprazole versus dacomitinib alone (PPI+fasted/fasted alone): 71.1% (90%CI, 61.7%–81.8%). Dacomitinib was generally well tolerated. Dacomitinib may be taken with or without food. Use of long‐acting acid‐reducing agents, such as PPIs with dacomitinib should be avoided if possible. Shorter‐acting agents such as antacids and H2‐receptor antagonists may have lesser impact on dacomitinib exposure and may be preferable to PPIs if acid reduction is clinically required.
Spherical activated carbon modified by polymerized ionic liquid for the removal of ibuprofen from water
Authors: Xu Xiao , An Xiaoning
Published: July 2015

BACKGROUND

The adsorption capacity of activated carbon has been found to improve through modification with ionic liquids. However, ionic liquids tend to separate from the activated carbon when exposed to water even for a relatively short period.

RESULTS

Characterization of spherical activated carbon (SAC) modified with poly(1‐vinyl‐3‐butylimidazolium hexafluorophosphate) (PIL) showed that 1‐vinyl‐3‐butylimidazolium hexafluorophosphate (IL) was adsorbed and polymerized on SAC. Stability studies of PIL‐SAC in water demonstrated that it was more stable against IL desorption in water than the non‐polymerized IL‐SAC. The adsorption data showed that the modification improved the adsorption capacity of SAC at least 2‐fold. The results also indicated that although the pH and ionic strength of the solution played a significant role in the adsorption process, there was no significant influence on the adsorption capacity. Moreover, PIL‐SAC could be reused at least five times with only minor losses in its adsorption capacity.

CONCLUSION

The activated carbon modified with PIL produces a remarkable increase in the ibuprofen adsorption capacity and strongly decreases undesirable desorption of ionic liquids. © 2015 Society of Chemical Industry
Exploring laccase and mediators behavior during saccharification and fermentation of steam‐exploded wheat straw for bioethanol production
Authors: Moreno Antonio D , Ibarra David , Alvira Pablo , Tomás‐Pejó Elia , Ballesteros Mercedes
Published: July 2015

BACKGROUND

Laccases represent a very powerful tool to improve biorefining processes from lignocellulosic feedstocks. These enzymes are being investigated not only for potential use as pretreatment agents in bioethanol production, mainly as a delignifying agent, but also as a biotechnological tool for removal of inhibitors (mainly phenols) of subsequent fermentation processes.

RESULTS

In this work, the treatment of the water insoluble solids (WIS) fraction from steam‐exploded wheat straw with Pycnoporus cinnabarinus laccase and different laccase‐mediator systems (LMS) did not decrease the lignin content, resulting in lower glucose recoveries during the subsequent saccharification. In combination with an alkaline extraction, the treatment with laccase/LMS produced no synergistic effect enhancing the delignification or saccharification of WIS. In contrast, laccase reduced the soluble phenols (95% of the total phenols identified) of the whole slurry from steam‐exploded wheat straw, improving the yeast performance during the fermentation and enhancing the ethanol yields.

CONCLUSIONS

The efficiency of P. cinnabarinus laccase with or without mediators as a delignifying agent on steam‐exploded wheat straw for bioethanol production was not observed, whereas its detoxification ability was shown. Thus, new laccases or designing laccases with ability to delignify and detoxify simultaneously needs to be explored in order to produce major ethanol global yields. © 2015 Society of Chemical Industry
The effect of maternal obesity on sonographic fetal weight estimation and perinatal outcome in pregnancies complicated by fetal growth restriction
Authors: Cody Fiona , Unterscheider Julia , Daly Sean , Geary Michael P. , Kennelly Mairead M. , McAuliffe Fionnuala M. , O'Donoghue Keelin , Hunter Alyson , Morrison John J. , Burke Gerard , Dicker Patrick , Tully Elizabeth C. , Malone Fergal D.
Published: July 2015

Purpose

Maternal obesity represents a challenge in the sonographic (US) assessment of fetal weight, and is a recognized risk factor for adverse pregnancy outcome. The objective of this secondary analysis of data from the Prospective Observational Trial to Optimize Pediatric Health in fetal growth restriction (FGR) Study (PORTO) was to describe the effect of maternal obesity on the accuracy of US in determining the estimated fetal weight (EFW) and the perinatal outcome of pregnancies affected by FGR.

Methods

Between 2010 and 2012, 1,116 women with nonanomalous singleton pregnancies with an EFW in less than the tenth centile were recruited for the PORTO study. Maternal body mass index (BMI) was divided into five subcategories: normal (BMI < 24.9 kg/m2), overweight (25–29.9), obese class 1 (30–34.9), obese class 2 (35–39.9), and obese class 3 (>40). The accuracy of the EFW was determined in women who delivered within 2 weeks of their last US scan. Perinatal outcomes were analyzed by BMI subcategory.

Results

Of the 1,074 patients with complete records, 691 (64%) were of normal weight, 258 (24%) were overweight, 93 (9%) were in obese class 1, 32 (3%) were in obese class 2, and none were in obese class 3. Overall, the EFW determined prior to delivery was within 6% of the actual birth weight in all BMI subcategories. Overweight and obese women delivered more commonly by cesarean section and at earlier gestational ages than did women with a normal BMI (p = 0.0008), resulting in lower birth weights (p = 0.0031) and significantly increased composite perinatal morbidity (p < 0.0001) and mortality (p = 0.0215) rates.

Conclusions

US examination is reliable for assessing the weight of fetuses with FGR in overweight women. Maternal obesity, however, has a significant adverse effect on perinatal outcomes. Thus, health education should focus on awareness of this adverse effect, with optimization of prepregnancy weight as its main goal. © 2015 Wiley Periodicals, Inc. J Clin Ultrasound 44:34–39, 2016
Varying patterns of brachial artery flow‐mediated dilatation in women with polycystic ovary syndrome and controls: An application of the group‐based trajectory modeling
Authors: Meyer Michelle L. , Tepper Ping G. , Barinas‐Mitchell Emma , Korytkowski Mary T. , Talbott Evelyn O.
Published: July 2015

Purpose

To identify changing patterns of absolute change in brachial artery lumen diameter (LD) after reactive hyperemia in women with polycystic ovary syndrome (PCOS) and controls and to quantify the association of PCOS status and participants' factors with these patterns.

Methods

Brachial flow‐mediated dilation was measured in 128 women with PCOS and 148 controls aged 30–60 years. Group‐based trajectory modeling was used to investigate absolute change in LD every 30 seconds for 2 minutes after occluding cuff deflation. Multinomial logistic regression was used to identify factors associated with trajectories.

Results

Three patterns emerged, namely nondilators (42.2%), dilators (44.6%), and enhanced dilators (13.0%). The proportion of women with PCOS did not differ across groups. Independently of age and PCOS status, larger baseline LD (odds ratio; 95% confidence interval: 2.51; 1.29, 4.89) and lower insulin levels (0.70; 0.52, 0.93) were associated with nondilators rather than with dilators. Higher total cholesterol was associated with dilators in women with PCOS but with nondilators in controls.

Conclusions

Trajectory modeling identified distinct patterns of change in LD and factors associated with the endothelial response. This method may be a useful tool to understand the brachial flow‐mediated vasodilator response. © 2015 Wiley Periodicals, Inc. J Clin Ultrasound 44:46–54, 2016
Revival of the use of ultrasound in screening for appendicitis in young adult men
Authors: Pare Joseph R. , Langlois Breanne K. , Scalera Sushama A. , Husain Lubna Farooq , Douriez Carole , Chiu Helen , Carmody Kristin
Published: July 2015

Purpose

Our primary aim was to evaluate the use of ultrasound (US) as an initial screening test for diagnosing appendicitis in young adult men. Secondary exploratory analyses included the effects of using US for initial screening in these patients, compared with the use of CT, on radiation exposure, length of stay (LOS), and cost of imaging.

Methods

We retrospectively gathered data from the records of male patients 18–39 years old who had been admitted with appendicitis between June 2006 and September 2011. We investigated the diagnostic tests performed, the patients' characteristics, and the pathologic testing findings and compared the results obtained on US with those obtained on CT.

Results

Of 451 included patients, 86 had undergone US initially. Its sensitivity was only 57% (95% confidence interval, 46–67.6), but its positive predictive value was 98% (95% confidence interval, 93.8–100). The mean LOS was significantly shorter for patients who had undergone US only (214 minutes) than it was for those who had undergone CT only (276 minutes; p < 0.001). We estimated a 57% reduction in CT use and radiation exposure if US were to be performed initially; this would lead to a 45% decrease in imaging costs at our institution.

Conclusions

Screening US should be considered first for diagnosing appendicitis because of its high positive predictive value, but even if US results are negative for appendicitis, one should not exclude the possible existence of pathology because US has poor sensitivity in this situation. We speculate that the use of screening US can decrease radiation exposure, imaging costs, and LOS. © 2015 Wiley Periodicals, Inc. J Clin Ultrasound 44:3–11, 2016
Temporal bone thickness and texture are major determinants of the high rate of insonation failures of transcranial doppler in amerindians (the Atahualpa Project)
Authors: Del Brutto Oscar H. , Mera Robertino M. , de la Luz Andrade María , Espinosa Verónica , Castillo Pablo R. , Zambrano Mauricio , Nader Juan A.
Published: July 2015

Purpose

To assess the role of temporal bone characteristics in transcranial Doppler (TCD) insonation failures in Amerindians living in rural Ecuador.

Methods

We evaluated thickness and texture of temporal bones in community‐dwelling Amerindians ≥65 years old undergoing TCD. Using receiver operator characteristics curve analysis and generalized estimating equations, we investigated factors associated with insonation failures.

Results

Of 65 participants (mean age 74.7 ± 6.7 years, 60% women), 32 (49%) had uni‐ or bilateral insonation failure through temporal windows. Considering temporal bones independently, 57 of 130 (44%) had poor insonation. Mean thickness was higher (4.7 ± 1.2 versus 2.7 ± 0.9, p < 0.0001), and texture more often heterogeneous (93% versus 22%, p < 0.0001) in bones with poor acoustic windows. Thickness, better predicting poor insonation, was ≥3.6 mm if used alone, and ≥2.7 mm if used together with heterogeneous texture. For every millimeter of increase in thickness, subjects were 2.9 times more likely to have insonation failures. Per se, heterogeneous texture increased by 3.2 times the odds for poor insonation. In all models, being woman increased the odds for poor insonation by six to nine times.

Conclusions

Temporal bone thickness and texture are independent predictors of TCD insonation failure in Amerindians. © 2015 Wiley Periodicals, Inc. J Clin Ultrasound 44:55–60, 2016
The implications of different criteria for grading carotid artery stenosis by duplex ultrasound
Authors: Gray Cleona , Murray Sorcha A. , Connolly Mary , O'Donohoe Martin K. , McDonnell Ciaran O. , Badger Stephen A.
Published: July 2015

Purpose

Duplex ultrasound is the first‐line mode of investigation for carotid stenosis, whose severity could be graded according to NASCET or St. Mary's ratio criteria. The aim of this study was to compare these two methods and review the literature.

Methods

All patients who had carotid duplex ultrasound in a 1‐month period were included. The reports and images were retrospectively reviewed, and the grade of carotid artery stenosis was then recalculated using the St. Mary's Ratio.

Results

A total of 245 (160 men) patients with a mean age 70.4 years (±11.5) were assessed, and 469 extracranial carotid systems were analyzed. Pearson's Coefficient revealed strong correlation (r = 0.79, p = 0.05) between the two methods. In 114 (24.3%) internal carotid arteries, results were different. Of these, 26 (22.8%) would have gone for surgery had they been assessed using the St. Mary's Ratio and not the NASCET grading criteria. Conversely, two internal carotid arteries (1.75%) went for surgery using the NASCET grading criteria that would not have had to should the St. Mary's Ratio been used.

Conclusions

Although there is a strong level of correlation between the two criteria, choosing one or the other would have a significant impact on the patient' selection for surgery. © 2015 Wiley Periodicals, Inc. J Clin Ultrasound 43:563–566, 2015
Hybrid origin of gynogenetic clones and the introgression of their mitochondrial genome into sexual diploids through meiotic hybridogenesis in the loach, Misgurnus anguillicuadatus
Authors: Yamada Aya , Kodo Yukihiro , Murakami Masaru , Kuroda Masamichi , Aoki Takao , Fujimoto Takafumi , Arai Katsutoshi
Published: July 2015

In a few Japanese populations of the loach Misgurnus anguillicaudatus (Teleostei: Cobitidae), clonal diploid lineages produce unreduced diploid eggs that normally undergo gynogenetic reproduction; however the origin of these clones remains elusive. Here, we show the presence of two diverse clades, A and B, within this loach species from sequence analyses of two nuclear genes RAG1 (recombination activating gene 1) and IRBP2 (interphotoreceptor retinoid‐binding protein, 2) and then demonstrate heterozygous genotypes fixed at the two loci as the evidence of the hybrid nature of clonal lineages. All the clonal individuals were identified by clone‐specific mitochondrial DNA haplotypes, microsatellite genotypes, and random amplified polymorphic DNA fingerprints; they commonly showed two alleles, one from clade A and another from clade B, whereas other wild‐type diploids possessed alleles from either clade A or B. However, we also found wild‐type diploids with clone‐specific mitochondrial DNA and nuclear genes from clade B. One possible explanation is an introgression of a clone‐specific mitochondrial genome from clonal to these wild‐type loaches. These individuals likely arose by a cross between haploid sperm from bisexual B clade males and haploid eggs with clone‐specific mtDNA and clade B nuclear genome, produced by meiotic hybridogenesis (elimination of unmatched A genome followed by meiosis after preferential pairing between two matched B genomes) in clone‐origin triploid individual (ABB). J. Exp. Zool. 323A: 593–606, 2015. © 2015 Wiley Periodicals, Inc.
Cortisol stimulates arginine vasotocin and isotocin release from the hypothalamo‐pituitary complex of round goby (Neogobius melanostomus): Probable mechanisms of action
Authors: Kalamarz‐Kubiak Hanna , Kleszczyńska Agnieszka , Kulczykowska Ewa
Published: July 2015

There were two aims of this in vitro perfusion study. Firstly, to determine which class of receptors, glucocorticoid (GRs) or mineralocorticoid (MRs), are involved in cortisol regulation of arginine vasotocin (AVT) and isotocin (IT) release from the hypothalamo‐pituitary (H–P) complex of round goby (Neogobius melanostomus). Secondly, to determine which pathways, genomic or non‐genomic, are involved in the aformentioned process.The H–P explants were perfused with cortisol (1.4 × 10−7 M, 2.8 × 10−7 M, 0.4 × 10−6 M); only the highest dose significantly increased a release of both nonapeptides. In the perfusion of H–P explants, we used cortisol (0.4 × 10−6 M) in combination with GRs antagonist RU486 (0.3 × 10−6 M) or MRs antagonist C03DA01 (0.36 × 10−6 M) or transcription inhibitor Actinomycin D (1 × 10−7 M). All inhibitors were also tested seperately. The contents of AVT and IT in the perfusion media was determined by high‐performance liquid chromatography (HPLC) with UV detection. This study suggested that different mechanisms were involved in the regulation of AVT and IT release from H–P complex in round goby. Apparently it was GRs but not MRs that were involved in cortisol regulation of AVT and IT release. In the case of AVT, our data points to both genomic and non‐genomic pathways mediating the effect of cortisol; in the case of IT, it is only the non‐genomic pathway. This study presents the first feasible mechanisms of cortisol action on AVT and IT release from the H–P complex in round goby. J. Exp. Zool. 323A: 616–626, 2015. © 2015 Wiley Periodicals, Inc.
Rapid changes in ovarian mRNA induced by brief photostimulation in Siberian hamsters (Phodopus sungorus)
Authors: Shahed Asha , McMichael Carling F. , Young Kelly A.
Published: July 2015

This study sought to characterize the rapid intraovarian mRNA response of key folliculogenic factors that may contribute to the restoration of folliculogenesis during 2–10 days of photostimulation in Siberian hamsters. Adult hamsters were exposed to short photoperiod (8L:16D) for 14 weeks (SD). A subset were then transferred to long photoperiod (16L:8D) for 2 (PT day‐2), 4 (PT day‐4), or 10 days (PT day‐10). Quantitative real‐time PCR was used to measure intraovarian mRNA expression of: gonadotropin releasing hormone (GnRH), follicle stimulating hormone β‐subunit (FSHβ‐subunit), luteinizing hormone β‐subunit (LHβ‐subunit), FSH and LH receptors, estrogen receptors α and β (Esr1 and Esr2), matrix metalloproteinase (MMP)‐2 and ‐9, anti‐Müllerian hormone (AMH), inhibin‐α subunit, fibroblast growth factor‐2 (FGF‐2) and proliferating cell nuclear antigen (PCNA). Compared to SD, plasma FSH concentrations increased on PT day‐4 and the number of antral follicles and corpora lutea increased on PT day‐10. FSHR and inhibin‐α mRNA expression also increased on PT day‐4, whereas LHR and proliferation marker PCNA both increased on PT day‐10 as compared to SD. Esr1 mRNA increased on PT day‐2 and remained significantly increased as compared to SD, whereas Esr1 mRNA increased only on PT day‐2, similar to FGF‐2 and MMP‐2 results. No differences were observed in mRNA expression in ovarian GnRH, FSHβ‐ and LHβ‐subunits, AMH, and MMP‐9 mRNA with 2–10 days of photostimulation. Rapid increases in intraovarian FSHR and inhibin‐α mRNA and antral follicle/corpora lutea numbers suggest that the ovary is primed to react quickly to the FSH released in response to brief periods of photostimulation. J. Exp. Zool. 323A: 627–636, 2015. © 2015 Wiley Periodicals, Inc.
Character trees from transcriptome data: Origin and individuation of morphological characters and the so‐called “species signal”
Authors: Musser Jacob M. , Wagner Günter P.
Published: July 2015

We elaborate a framework for investigating the evolutionary history of morphological characters. We argue that morphological character trees generated by phylogenetic analysis of transcriptomes provide a useful tool for identifying causal gene expression differences underlying the development and evolution of morphological characters. They also enable rigorous testing of different models of morphological character evolution and origination, including the hypothesis that characters originate via divergence of repeated ancestral characters. Finally, morphological character trees provide evidence that character transcriptomes undergo concerted evolution. We argue that concerted evolution of transcriptomes can explain the so‐called “species signal” found in several recent comparative transcriptome studies. The species signal is the phenomenon that transcriptomes cluster by species rather than character type, even though the characters are older than the respective species. We suggest the species signal is a natural consequence of concerted gene expression evolution resulting from mutations that alter gene regulatory network interactions shared by the characters under comparison. Thus, character trees generated from transcriptomes allow us to investigate the variational independence, or individuation, of morphological characters at the level of genetic programs. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 588–604, 2015. © 2015 Wiley Periodicals, Inc.
Phylogenetic uncertainty can bias the number of evolutionary transitions estimated from ancestral state reconstruction methods
Authors: Duchêne Sebastian , Lanfear Robert
Published: July 2015

Ancestral state reconstruction (ASR) is a popular method for exploring the evolutionary history of traits that leave little or no trace in the fossil record. For example, it has been used to test hypotheses about the number of evolutionary origins of key life‐history traits such as oviparity, or key morphological structures such as wings. Many studies that use ASR have suggested that the number of evolutionary origins of such traits is higher than was previously thought. The scope of such inferences is increasing rapidly, facilitated by the construction of very large phylogenies and life‐history databases. In this paper, we use simulations to show that the number of evolutionary origins of a trait tends to be overestimated when the phylogeny is not perfect. In some cases, the estimated number of transitions can be several fold higher than the true value. Furthermore, we show that the bias is not always corrected by standard approaches to account for phylogenetic uncertainty, such as repeating the analysis on a large collection of possible trees. These findings have important implications for studies that seek to estimate the number of origins of a trait, particularly those that use large phylogenies that are associated with considerable uncertainty. We discuss the implications of this bias, and methods to ameliorate it. J. Exp. Zool. (Mol. Dev. Evol.) 324B: 517–524, 2015. © 2015 Wiley Periodicals, Inc.
Simple and Efficient Synthesis of 2‐Oxo‐2H‐Pyrido[1,2‐a]Pyrimidin‐3(4H)‐Ylidene)Acetic Acid and Its Rearrangement in Presence of Acid Media
Authors: Venugopal Sharulatha , Sundaram Sivakamasundari
Published: July 2015

A highly efficient one‐pot simple synthesis of 2‐[2‐oxo‐2H‐pyrido[1,2‐a]pyridmidn‐3(4H)‐ylidene)]acetic acid is described. The rearrangement of 2‐[2‐oxo‐2H‐pyrido[1,2‐a]pyridmidn‐3(4H)‐ylidene)]acetic acid in the presence of polyphosphoric acid (PPA) yielded a seven‐membered diazepine with decarboxylation and ring expansion.