bluuebunny/crossref_metadata_2025 huggingface dataset:
Facile Recoding of Selenocysteine in Nature
Authors: Mukai Takahito , Englert Markus , Tripp H. James , Miller Corwin , Ivanova Natalia N. , Rubin Edward M. , Kyrpides Nikos C. , Söll Dieter
Published: March 2016

Selenocysteine (Sec or U) is encoded by UGA, a stop codon reassigned by a Sec‐specific elongation factor and a distinctive RNA structure. To discover possible code variations in extant organisms we analyzed 6.4 trillion base pairs of metagenomic sequences and 24 903 microbial genomes for tRNASec species. As expected, UGA is the predominant Sec codon in use. We also found tRNASec species that recognize the stop codons UAG and UAA, and ten sense codons. Selenoprotein synthesis programmed by UAG in Geodermatophilus and Blastococcus, and by the Cys codon UGU in Aeromonas salmonicida was confirmed by metabolic labeling with 75Se or mass spectrometry. Other tRNASec species with different anticodons enabled E. coli to synthesize active formate dehydrogenase H, a selenoenzyme. This illustrates the ease by which the genetic code may evolve new coding schemes, possibly aiding organisms to adapt to changing environments, and show the genetic code is much more flexible than previously thought.
Synthesis of Chiral 1,4‐Benzodioxanes and Chromans by Enantioselective Palladium‐Catalyzed Alkene Aryloxyarylation Reactions
Authors: Hu Naifu , Li Ke , Wang Zheng , Tang Wenjun
Published: March 2016

A highly enantioselective alkene aryloxyarylation led to the high‐yielding formation of a series of 1,4‐benzodioxanes, 1,4‐benzooxazines, and chromans containing quaternary stereocenters with excellent enantioselectivity. The sterically bulky and conformationally well defined chiral monophosphorus ligand L4 or L5 was responsible for the high reactivity and enantioselectivity of these transformations. The application of this method to the synthesis of the chiral chroman backbone of α‐tocopherol was demonstrated.
H2‐Fueled ATP Synthesis on an Electrode: Mimicking Cellular Respiration
Authors: Gutiérrez‐Sanz Óscar , Natale Paolo , Márquez Ileana , Marques Marta C. , Zacarias Sonia , Pita Marcos , Pereira Inês A. C. , López‐Montero Iván , De Lacey Antonio L. , Vélez Marisela
Published: March 2016

ATP, the molecule used by living organisms to supply energy to many different metabolic processes, is synthesized mostly by the ATPase synthase using a proton or sodium gradient generated across a lipid membrane. We present evidence that a modified electrode surface integrating a NiFeSe hydrogenase and a F1F0‐ATPase in a lipid membrane can couple the electrochemical oxidation of H2 to the synthesis of ATP. This electrode‐assisted conversion of H2 gas into ATP could serve to generate this biochemical fuel locally when required in biomedical devices or enzymatic synthesis of valuable products.
Kinetically Controlled Sequential Growth of Surface‐Grafted Chiral Supramolecular Copolymers
Authors: Frisch Hendrik , Fritz Eva‐Corinna , Stricker Friedrich , Schmüser Lars , Spitzer Daniel , Weidner Tobias , Ravoo Bart Jan , Besenius Pol
Published: March 2016

We report a facile strategy to grow supramolecular copolymers on Au surfaces by successively exposing a surface‐anchored monomer to solutions of oppositely charged peptide comonomers. Charge regulation on the active chain end of the polymer sufficiently slows down the kinetics of the self‐assembly process to produce kinetically trapped copolymers at near‐neutral pH. We thereby achieve architectural control at three levels: The β‐sheet sequences direct the polymerization away from the surface, the height of the supramolecular copolymer brushes is well‐controlled by the stepwise nature of the alternating copolymer growth, and 2D spatial resolution is realized by using micropatterned initiating monomers. The programmable nature of the resulting architectures renders this concept attractive for the development of customized biomaterials or chiral interfaces for optoelectronics and sensor applications.
Amide (A)–thioamide (T) interconversions using Ph3SiSH (A to T) and Ph3SnOH (T to A) reagents
Authors: Arias‐Ugarte Renzo N , Sharma Hemant K , Pannell Keith H
Published: March 2016

Ph3SiSH transforms amides to thioamides and Ph3SnOH performs the reverse process, with the concomitant formation of Ph3SiOH (or Ph3SiOSiPh3) and Ph3SnSSnPh3, respectively. The chemistry is a delightful illustration of the oxophilicity of silicon compared to the thiophilicity of tin and occurs under relatively mild conditions, and for amide to thioamide transformation requires no amide activation. The chemistry is in accord with available data for Si(S)(O), Sn(O)(S) and C(O)(S) bond energies. Copyright © 2016 John Wiley & Sons, Ltd.
Eco‐friendly synthesis of benzoxazepine and malonamide derivatives in aqueous media
Authors: Babazadeh Mirzaagha , Hosseinzadeh‐Khanmiri Rahim , Zakhireh Solmaz
Published: March 2016

A special, efficient and reusable heterogeneous catalytic system is reported for the one‐pot three‐component synthesis of a series of malonamide and 2,3,4,5‐tetrahydrobenzo[b][1,4]oxazepine derivatives in the presence of a heterogeneous material composed of MCM‐48/H5PW10V2O40 in aqueous media and at room temperature. The products were identified using physical data (melting points) by comparison with those reported in the literature. Also, the structures of the new compounds were characterized by means of infrared, 1H NMR, 13C NMR and CHN analyses. Copyright © 2016 John Wiley & Sons, Ltd.
Biological screening and DNA nuclease activity of transition metal complexes of N2O2type of Knoevenagel condensate Schiff base
Authors: Pandiyan Rajakkani Paul , Raman Natarajan
Published: March 2016

A novel tetradentate N2O2 type of Knoevenagel condensate Schiff base, synthesized from 4‐amino‐2,3‐dimethyl‐1‐phenyl‐3‐pyrazolin‐5‐one (4‐aminoantipyrine) and 3‐(cinnamyl)‐pentane‐2,4‐dione, forms stable complexes with transition metal ions such as Cu(II), Co(II), Ni(II) and Zn(II). The structural features were derived from elemental analysis, molar conductance measurements, infrared, UV–visible, 1H NMR, 13C NMR, mass and electron paramagnetic resonance spectroscopies. These complexes show high conductance values, supporting their electrolytic nature. Spectroscopic and other analytical data of the complexes suggest square planar geometry. In vitro calf thymus DNA binding studies were performed by employing UV–visible absorption spectroscopy, viscometry and cyclic voltammetry. These techniques indicate that all the metal complexes bind to DNA via intercalation mode. Antimicrobial screening of the synthesized ligand and complexes was conducted against Gram‐positive bacteria, Gram‐negative bacteria and fungi. These complexes exhibit higher antimicrobial activities than the free Schiff base, as investigated using the minimum inhibitory concentration method. Gel electrophoresis reveals that these complexes also promote the cleavage of pUC18 plasmid DNA in the presence of activators. Copyright © 2016 John Wiley & Sons, Ltd.
Synthesis of a melamine‐cyclotriphosphazene derivative and its application as flame retardant on cotton gauze
Authors: Lv Meixiang , Yao Chunfeng , Yang Dingqiao , Zeng Heping
Published: March 2016

The halogen‐free flame retardance of natural fiber is an everlasting challenge due to the well‐known poor solubility of phosphazene in water. In this case, a new cyclotriphosphazene derivative (MCP) was synthesized. It was etherized hexamethylolmelamine (HMMM) and hexachloro‐cyclotriphosphazene (HCCP) by one pot reaction. It was characterized by1H NMR,13C NMR,31P NMR, FT‐IR, TGA, SEM, limited oxygen index (LOI) and vertical flame testing. The MCP has good solubility in water and thermosetting MCP has compact structure which can expand several times after burning. Cotton gauze was soaked in six different concentration of aqueous solutions of MCP (0 wt %, 5 wt %, 10 wt %, 15 wt %, 20 wt % and 25 wt %, respectively) to obtain the flame retardant cloth. The cloth was soaked in 20 wt % MCP solution had higher char yield and LOI. They had no any afterflame and afterglow, and gauze 2‐ gauze 5 cannot be burned out in 12s ignition time. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2016,133, 43555.
The behavior of natural rubber–epoxidized natural rubber–silica composites based on wet masterbatch technique
Authors: Wang Yueqiong , Liao Lusheng , Zhong Jieping , He Dongning , Xu Kui , Yang Changjin , Luo Yongyue , Peng Zheng
Published: March 2016

Natural rubber–epoxidized natural rubber–silica composites were prepared by the wet masterbatch technique and the traditional dry mixing method. Performances of the composites based on different preparation methods were investigated with a moving die rheometer, an electronic universal testing machine, a dynamic mechanical analyzer, a nuclear magnetic resonance crosslink density analyzer, a rubber processing analyzer (RPA), a scanning electron microscope (SEM), and a transmission electron microscope (TEM). The RPA, SEM, and TEM analyses indicated that silica has better dispersion, lower filler–filler interaction, and better filler–rubber interaction in compounds based on the wet masterbatch technique, leading to improvements in mechanical strength and the dynamic mechanical and compression properties of the composites. It also indicates that composites prepared by the wet masterbatch technique have shorter scorch time, faster curing velocity, and higher crosslink density. The composites prepared by the wet materbatch technique also have lower rolling resistance, which is an important property for their use as a green material for the tire industry. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43571.
Relationship between microstructure of lamellar graphene sheets and properties of polyimide/graphene nanocomposites film under different imidization stages
Authors: Ding Xin , Zhang Xian , Bao Chao , Tan Su , Zheng Kang , Chen Lin , Zhang Hui , Tian Xingyou
Published: March 2016

Herein, polyimide/graphene sheets (PI/GS) nanocomposite films with different GS distribution structures have been successfully obtained by controlling the imidization degrees, and the effect of the lamellar structure on the properties of PI film has been investigated. The results show that GS are gradually parallel to the surface of PI nanocomposite film with the increase of the imidization temperature, and 150 °C is the critical temperature, where the imidization rate is the fastest and the lamellar structure begins to form. Furthermore, with the drying temperature increasing, the corresponding thermal, electrical and mechanical properties of PI/GS nanocomposite films are significantly improved compared with that of pure PI films, which are ascribed to both the higher imidization degree and the lamellar GS structure. It is noteworthy that the formation process of the lamellar structure at different imidization stages can be directly observed by scanning electron microscope. Based on these results, a model has been proposed to explain the relationship between the lamellar structure and properties of PI composite film under different imidization stages, and the confinement of the thickness may be the most important factor for the formation of lamellar GS structure. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43575.
Risk of Herpes Zoster in Autoimmune and Inflammatory Diseases: Implications for Vaccination
Authors: Yun Huifeng , Yang Shuo , Chen Lang , Xie Fenglong , Winthrop Kevin , Baddley John W. , Saag Kenneth G. , Singh Jasvinder , Curtis Jeffrey R.
Published: March 2016

Objective

The herpes zoster (HZ) vaccine is recommended for adults in the US ages ≥60 years who do not have weakened immune systems. It is unclear how the risk of HZ varies according to age and disease conditions in younger patients with autoimmune or inflammatory (AI) diseases. This study was undertaken to evaluate the age‐stratified incidence of HZ in patients with AI diseases as compared to older adults for whom the HZ vaccine is currently recommended by the US Centers for Disease Control and Prevention.

Methods

Using linked data obtained from patients who were insured by US commercial and government health care plans during the period 2007–2010, 7 cohorts of patients with AI diseases were assembled: systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (PsO), ankylosing spondylitis (AS), and gout. Two comparator cohorts were also assembled as controls: adult patients with diabetes and adult subjects without AI diseases or diabetic conditions. HZ was identified using diagnostic codes. Age‐specific incidence rates (IRs) of HZ were calculated and compared to the IRs of HZ in control subjects ages 61–70 years who were without AI diseases or diabetic conditions.

Results

After review of the linked data, the following number of enrollment periods were identified: 8,395 for patients with SLE, 7,916 for patients with IBD, 50,646 for patients with RA, 2,629 for patients with PsA, 4,299 for patients with PsO, 1,019 for patients with AS, 58,934 for patients with gout, 214,631 for control patients with diabetes, and 330,727 for control subjects without AI diseases and diabetic conditions. The respective highest and lowest IRs of HZ during the study were 19.9 per 1,000 person‐years in the SLE cohort and 6.8 per 1,000 person‐years in the gout cohort, as compared to an IR of 5.3 per 1,000 person‐years in control subjects without AI diseases or diabetic conditions. The age‐specific IRs of HZ in patients with RA and those with SLE ages ≥40 years were 1.5–2 times greater than those observed in older healthy adults (IR 8.5 per 1,000 person‐years), for whom the vaccine is currently recommended.

Conclusion

SLE, IBD, and RA are AI diseases associated with a higher risk of HZ compared to that in older adults for whom vaccination is currently recommended, suggesting that individuals with these conditions who are as young as age 40 years could potentially benefit from the HZ vaccine.
Effect of Drug Therapy on Net Cholesterol Efflux Capacity of High‐Density Lipoprotein–Enriched Serum in Rheumatoid Arthritis
Authors: Ormseth Michelle J. , Yancey Patricia G. , Solus Joseph F. , Bridges S. Louis , Curtis Jeffrey R. , Linton MacRae F. , Fazio Sergio , Davies Sean S. , Roberts L. Jackson , Vickers Kasey C. , Kon Valentina , Michael Stein C. ,   the TETRAD Investigators
Published: March 2016

Objective

Patients with rheumatoid arthritis (RA) have an increased risk of coronary heart disease (CHD). Some RA therapies may modify this risk, but the underlying mechanisms are unclear. The cholesterol efflux capacity of high‐density lipoprotein (HDL) is associated with a reduced CHD risk in non‐RA populations; however, inflammation may impair the function of HDL. The aim of this study was to evaluate whether reduced inflammation resulting from treatment with methotrexate (MTX), adalimumab (ADA), or tocilizumab (TCZ) would increase the net cholesterol efflux capacity of HDL in patients with RA.

Methods

A longitudinal multicenter study repository (Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository) provided clinical information for and serum samples from 70 patients with RA before and 6 months after starting treatment with a new drug (MTX [n = 23], ADA [n = 22], or TCZ [n = 25]). Disease activity was measured using the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28‐ESR). The net cholesterol efflux capacity was measured in paired serum samples using THP‐1 macrophages, and total cellular cholesterol was measured by fluorometric assay.

Results

The DAS28‐ESR decreased with all treatments (P < 0.001). Net cholesterol efflux capacity was not significantly changed after 6 months of new RA therapy (mean ± SD 36.9 ± 17.3% units at baseline versus 38.0% ± 16.9% units at 6 months [P = 0.58]). However, change in net cholesterol efflux capacity was associated with change in the DAS28‐ESR (ρ = −0.25, P = 0.04). In a post hoc analysis of patients with impaired net cholesterol efflux capacity at baseline, treatment with TCZ resulted in significant improvement in net cholesterol efflux capacity (21.9 ± 14.7% units at baseline versus 31.3% ± 12.8% units at 6 months [P < 0.02]), but this was not observed with MTX or ADA.

Conclusion

Net cholesterol efflux capacity of HDL cholesterol did not change significantly after 6 months of new RA therapy, except in patients with impaired baseline cholesterol efflux capacity who were receiving TCZ. Change in disease activity was associated with change in the net cholesterol efflux capacity.
Perturbed Mucosal Immunity and Dysbiosis Accompany Clinical Disease in a Rat Model of Spondyloarthritis
Authors: Asquith Mark J. , Stauffer Patrick , Davin Sean , Mitchell Claire , Lin Phoebe , Rosenbaum James T.
Published: March 2016

Objective

The HLA–B27/β2‐microglobulin (β2m)–transgenic (Tg) rat is a leading model of B27‐associated spondyloarthritis (SpA), and the disease is dependent on the presence of intestinal bacteria. Previous studies have shown that adult HLA–B27/β2m–Tg rats have an altered intestinal microbiota. This study sought to better define the age‐dependent changes to both mucosal immune function and dysbiosis in this rat model of SpA.

Methods

Intestinal contents were collected from wild‐type and HLA–B27/β2m–Tg rats postweaning (ages 3 and 6 weeks), at disease onset (age 10 weeks), and after the establishment of disease (ages ≥16 weeks). The microbial community structure was determined by 16S ribosomal RNA sequencing and quantitative reverse transcription–polymerase chain reaction (qRT‐PCR). Mucosal and systemic Th1, Th17, and Treg cell responses were analyzed by flow cytometry, as was the frequency of IgA‐coated intestinal bacteria. Intestinal expression of inflammatory cytokines and antimicrobial peptides (AMPs) was determined by qRT‐PCR.

Results

An inflammatory cytokine signature and elevated AMP expression during the postweaning period preceded the development of clinical bowel inflammation and dysbiosis in HLA–B27/β2m–Tg rats. An early and sustained expansion of the Th17 cell pool was specifically observed in the cecal and colonic mucosa of HLA–B27/β2m–Tg rats. Strongly elevated intestinal colonization of Akkermansia muciniphila and an increased frequency of IgA‐coated fecal bacteria were significantly associated with expression of HLA–B27 and arthritis development.

Conclusion

HLA–B27/β2m expression in this rat model renders the host hyperresponsive to microbial antigens from infancy. Early activation of innate immunity and expansion of a mucosal Th17 signature are soon followed by dysbiosis in HLA–B27/β2m–Tg animals. The pathologic processes of perturbed mucosal immunity and dysbiosis strongly merit further study in both prediseased and diseased populations of patients with SpA.
Leveraging metadata to recommend keywords for academic papers
Authors: Blank Ido , Rokach Lior , Shani Guy
Published: March 2016

Users of research databases, such as CiteSeerX, Google Scholar, and Microsoft Academic, often search for papers using a set of keywords. Unfortunately, many authors avoid listing sufficient keywords for their papers. As such, these applications may need to automatically associate good descriptive keywords with papers. When the full text of the paper is available this problem has been thoroughly studied. In many cases, however, due to copyright limitations, research databases do not have access to the full text. On the other hand, such databases typically maintain metadata, such as the title and abstract and the citation network of each paper. In this paper we study the problem of predicting which keywords are appropriate for a research paper, using different methods based on the citation network and available metadata. Our main goal is in providing search engines with the ability to extract keywords from the available metadata. However, our system can also be used for other applications, such as for recommending keywords for the authors of new papers. We create a data set of research papers, and their citation network, keywords, and other metadata, containing over 470K papers with and more than 2 million keywords. We compare our methods with predicting keywords using the title and abstract, in offline experiments and in a user study, concluding that the citation network provides much better predictions.
Teaching with Wikipedia in a 21st‐century classroom: Perceptions of Wikipedia and its educational benefits
Authors: Konieczny Piotr
Published: March 2016

This article explores the current perception of Wikipedia in academia, focusing on both the reasons for its unpopularity among some and the reasons for its growing acceptance among others. First, the reasons that Wikipedia is still struggling to gain acceptance among many academics and higher education professionals are identified. These include common misconceptions about Wikipedia, doubts about its quality, uneasiness with the challenge that it poses to the traditional peer‐review system, and a lack of career‐enhancing motivations related to using Wikipedia. Second, the benefits of teaching with Wikipedia for educators, students, and the wider society, as discussed in the current teaching literature, are explored. Finally, the article presents an argument for using Wikipedia in a variety of ways to help students develop critical and academic writing skills.
One‐Pot Synthesis of Polysubstituted Benzenes through a N,N‐dimethyl‐4‐aminopyridine (DMAP)‐Catalyzed [4+2] Benzannulation of 1,3‐Bis(sulfonyl)butadienes and γ‐Substituted Allenoates
Authors: Chang Meijia , Wu Chengzhou , Zheng Jie , Huang You
Published: March 2016

A new strategy for the one‐pot synthesis of polysubstituted benzenes through a N,N‐dimethyl‐4‐aminopyridine (DMAP)‐catalyzed [4+2] benzannulation from readily prepared 1,3‐bis(sulfonyl)butadienes and γ‐substituted allenoates is described. This method provides a facile, metal‐free and general route to highly substituted benzenes under mild conditions in moderate‐to‐good yields with complete regioselectivity.
Mechanistic Study on Oxorhenium‐Catalyzed Deoxydehydration and Allylic Alcohol Isomerization
Authors: Wu Di , Zhang Yugen , Su Haibin
Published: March 2016

The reaction mechanism of 1,2×n‐deoxydehydration (DODH; n=1, 2, 3 …) reactions with 1‐butanol as a reductant in the presence of methyltrioxorhenium(VII) catalyst has been investigated by DFT. The reduced rhenium compound, methyloxodihydroxyrhenium(V), serves as the catalytically relevant species in both allylic alcohol isomerization and subsequent DODH processes. Compared with three‐step pathway A, involving [1,3]‐transposition of allylic alcohols, direct two‐step pathway B is an alternative option with lower activation barriers. The rate‐limiting step of the DODH reaction is the first hydrogen transfer in methyltrioxorhenium(VII) reduction. Moreover, the increase in the distance between two hydroxyl groups in direct 1,2×n‐DODH reactions for C4 and C6 diols results in a higher barrier height.
Asymmetric Total Synthesis of Propindilactone G, Part 3: The Final Phase and Completion of the Synthesis
Authors: Liang Xin‐Ting , You Lin , Li Yuan‐He , Yu Hai‐Xin , Chen Jia‐Hua , Yang Zhen
Published: March 2016

Two independent synthetic approaches were evaluated for the final phase of the asymmetric total synthesis of propindilactone G (1). The key steps that led to the completion of the asymmetric total synthesis included: 1) an intermolecular oxidative heterocoupling reaction of enolsilanes to link the core structure to the side chain; 2) an intermolecular Wittig reaction for the formation of the α,β,γ,δ‐unsaturated ester; and 3) a regio‐ and stereoselective OsO4‐catalyzed dihydroxylation of an α,β,γ,δ‐unsaturated enone, followed by an intramolecular lactonization reaction to afford the final product. These reactions enabled the synthesis of (+)‐propindilactone G in only 20 steps. As a consequence of our synthetic studies, the structure of (+)‐propindilactone G has been revised. Furthermore, the direct oxidative coupling strategy for ligation of the core of propindilactone G with its side chain may find application in the syntheses of other natural products and complex molecules.
Dopaminergic variants in siblings at high risk for autism: Associations with initiating joint attention
Authors: Gangi Devon N. , Messinger Daniel S. , Martin Eden R. , Cuccaro Michael L.
Published: March 2016

Younger siblings of children with autism spectrum disorder (ASD; high‐risk siblings) exhibit lower levels of initiating joint attention (IJA; sharing an object or experience with a social partner through gaze and/or gesture) than low‐risk siblings of children without ASD. However, high‐risk siblings also exhibit substantial variability in this domain. The neurotransmitter dopamine is linked to brain areas associated with reward, motivation, and attention, and common dopaminergic variants have been associated with attention difficulties. We examined whether these common dopaminergic variants, DRD4 and DRD2, explain variability in IJA in high‐risk (n = 55) and low‐risk (n = 38) siblings. IJA was assessed in the first year during a semi‐structured interaction with an examiner. DRD4 and DRD2 genotypes were coded according to associated dopaminergic functioning to create a gene score, with higher scores indicating more genotypes associated with less efficient dopaminergic functioning. Higher dopamine gene scores (indicative of less efficient dopaminergic functioning) were associated with lower levels of IJA in the first year for high‐risk siblings, while the opposite pattern emerged in low‐risk siblings. Findings suggest differential susceptibility—IJA was differentially associated with dopaminergic functioning depending on familial ASD risk. Understanding genes linked to ASD‐relevant behaviors in high‐risk siblings will aid in early identification of children at greatest risk for difficulties in these behavioral domains, facilitating targeted prevention and intervention. Autism Res 2016, 9: 1142–1150. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
When the right (Drug) should be left: Prenatal drug exposure and heterotaxy syndrome
Authors: van Veenendaal Nicole R. , Kusters Cynthia D.J. , Oostra Roelof‐Jan , Bergman Jorieke E.H. , Cobben Jan‐Maarten
Published: March 2016

Background

Recent studies reported an association between prenatal propylthiouracil exposure and birth defects, including abnormal arrangement across the left–right body axis, suggesting an association with heterotaxy syndrome.

Methods

This case–control and case‐finding study used data from 1981 to 2013 from the EUROCAT birth defect registry in the Northern Netherlands. First, we explored prenatal exposures in heterotaxy syndrome (cases) and Down syndrome (controls). Second, we describe the specific birth defects in offspring of mothers using propylthiouracil (PTU) prenatally.

RESULTS

A total of 66 cases with heterotaxy syndrome (incidence 12.1 per 100,000 pregnancies) and 783 controls with Down syndrome (143.3 per 100,000 pregnancies) were studied. No differences in intoxication use during pregnancy were found between cases and controls, including smoking (28.0% vs. 22.7%; p = 0.40), alcohol (14.0% vs. 26.9%; p = 0.052), and recreational drugs (0 vs. 0.3%; p = 1.00). We found an association between heterotaxy syndrome and prenatal drug exposure to follitropin‐alfa (5.6% vs. 1.1%; p = 0.04), and drugs used in nicotine dependence (3.7% vs. 0.2%; p = 0.02). Five mothers used PTU during pregnancy and gave birth to a child with trisomy 18, renal abnormalities, or hypospadias and cardiac defects.

Conclusion

This study identified follitropin‐alfa and drugs used in nicotine dependence as possible teratogens of heterotaxy syndrome. Our data suggest the possibility that there is an increased risk of birth defects (including renal, urological, and cardiac abnormalities) in children born among mothers taking PTU prenatally, but not for heterotaxy syndrome. Birth Defects Research (Part A) 106:573–579, 2016. © 2016 Wiley Periodicals, Inc.
Histone turnover and chromatin accessibility: Critical mediators of neurological development, plasticity, and disease
Authors: Wenderski Wendy , Maze Ian
Published: March 2016

In postmitotic neurons, nucleosomal turnover was long considered to be a static process that is inconsequential to transcription. However, our recent studies in human and rodent brain indicate that replication‐independent (RI) nucleosomal turnover, which requires the histone variant H3.3, is dynamic throughout life and is necessary for activity‐dependent gene expression, synaptic connectivity, and cognition. H3.3 turnover also facilitates cellular lineage specification and plays a role in suppressing the expression of heterochromatic repetitive elements, including mutagenic transposable sequences, in mouse embryonic stem cells. In this essay, we review mechanisms and functions for RI nucleosomal turnover in brain and present the hypothesis that defects in histone dynamics may represent a common mechanism underlying neurological aging and disease.
The evolving landscape of imprinted genes in humans and mice: Conflict among alleles, genes, tissues, and kin
Authors: Wilkins Jon F. , Úbeda Francisco , Van Cleve Jeremy
Published: March 2016

Three recent genome‐wide studies in mice and humans have produced the most definitive map to date of genomic imprinting (gene expression that depends on parental origin) by incorporating multiple tissue types and developmental stages. Here, we explore the results of these studies in light of the kinship theory of genomic imprinting, which predicts that imprinting evolves due to differential genetic relatedness between maternal and paternal relatives. The studies produce a list of imprinted genes with around 120–180 in mice and ∼100 in humans. The studies agree on broad patterns across mice and humans including the complex patterns of imprinted expression at loci like Igf2 and Grb10. We discuss how the kinship theory provides a powerful framework for hypotheses that can explain these patterns. Finally, since imprinting is rare in the genome despite predictions from the kinship theory that it might be common, we discuss evolutionary factors that could favor biallelic expression.
Generalized Student's t‐distribution mixtures for autoradiographic image spread modelling
Authors: Aykroyd Robert G.
Published: March 2016

In this paper, a new class of models for autoradiographic hot‐line data is proposed. The models, for which there is theoretical justification, are a linear combination of generalized Student's t‐distributions and have as special cases all currently accepted line‐spread models. The new models are used to analyse experimental hot‐line data and compared with the fit of current models. The data are from a line source labelled with iodine‐125 in a resin section of 0.6 m in thickness. It will be shown that a significant improvement in goodness of fit, over that of previous models, can be achieved by choosing from this new class of models. A single model from this class will be proposed that has a simple form made up of only two components, but which fits experimental data significantly better than previous models. A short sensitivity analysis indicates that estimation is reliable. The modelling approach, although motivated by and applied to autoradiography, is appropriate for any mixture modelling situation.
Efficient generation of smooth muscle cells from adipose‐derived stromal cells by 3D mechanical stimulation can substitute the use of growth factors in vascular tissue engineering
Authors: Parvizi Mojtaba , Bolhuis‐Versteeg Lydia A.M. , Poot André A. , Harmsen Martin C.
Published: March 2016

Occluding artery disease causes a high demand for bioartificial replacement vessels. We investigated the combined use of biodegradable and creep‐free poly (1,3‐trimethylene carbonate) (PTMC) with smooth muscle cells (SMC) derived by biochemical or mechanical stimulation of adipose tissue‐derived stromal cells (ASC) to engineer bioartificial arteries. Biochemical induction of cultured ASC to SMC was done with TGF‐β1 for 7d. Phenotype and function were assessed by qRT‐PCR, immunodetection and collagen contraction assays. The influence of mechanical stimulation on non‐differentiated and pre‐differentiated ASC, loaded in porous tubular PTMC scaffolds, was assessed after culturing under pulsatile flow for 14d. Assays included qRT‐PCR, production of extracellular matrix and scanning electron microscopy. ASC adhesion and TGF‐β1‐driven differentiation to contractile SMC on PTMC did not differ from tissue culture polystyrene controls. Mesenchymal and SMC markers were increased compared to controls. Interestingly, pre‐differentiated ASC had only marginal higher contractility than controls. Moreover, in 3D PTMC scaffolds, mechanical stimulation yielded well‐aligned ASC‐derived SMC which deposited ECM. Under the same conditions, pre‐differentiated ASC‐derived SMC maintained their SMC phenotype. Our results show that mechanical stimulation can replace TGF‐β1 pre‐stimulation to generate SMC from ASC and that pre‐differentiated ASC keep their SMC phenotype with increased expression of SMC markers.
Meta-analysis of the concordance of histological grade of breast cancer between core needle biopsy and surgical excision specimen
Authors: Knuttel F M , Menezes G L G , van Diest P J , Witkamp A J , van den Bosch M A A J , Verkooijen H M
Published: March 2016

Background

With the increasing use of neoadjuvant chemotherapy and minimally invasive ablative therapy in breast cancer, pretreatment assessment of tumour grade on core needle biopsy (CNB) is increasingly needed. However, grading on CNB is possibly less accurate than grading based on the surgical excision specimen. A systematic review and meta-analysis of the literature was conducted to derive a reliable estimate of the agreement in tumour grading between CNB and subsequent surgical excision.

Methods

Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) criteria, Embase, PubMed and the Cochrane Library were searched. Pooled proportions of agreement in grading between CNB and the excision specimen, Cohen's κ and percentages of overestimation and underestimation were calculated. Random-effects models were applied because of substantial heterogeneity, assessed by I2 test. Determinants of the level of agreement in grading were explored with meta-regression.

Results

Thirty-four articles were included in the systematic review (6029 patients) and 33 in the meta-analysis (4980 patients). Pooled agreement and κ were 71·1 (95 per cent c.i. 68·8 to 73·3) per cent and 0·54 (0·50 to 0·58) respectively. Underestimation and overestimation occurred in 19·1 (17·1 to 21·3) and 9·3 (7·7 to 11·4) per cent respectively. Meta-regression showed associations between agreement of histological type (positive association) and proportion of patients with oestrogen receptor-positive disease (negative association) and grade agreement.

Conclusion

Grading on CNB corresponds moderately with grading based on excision specimens, with underestimation in about one in five patients. Incorrect CNB tumour grading has limited clinical implications, as multiple factors influence decision-making for adjuvant systemic therapy.
An Expeditious Stereoselective Synthesis of (−)‐Pinidinone from Ethyl Acetoacetate
Authors: Damodar Kongara , Jun Jong‐Gab
Published: March 2016

An expeditious stereoselective synthesis of a naturally occurring 2,6‐disubstituted piperidine alkaloid, (−)‐pinidinone, has been accomplished with an overall yield of 31% in total eight steps. The synthesis involves ethyl acetoacetate as the starting material and the stereoselective α‐aminoallylation of aldehyde with (S)‐tert‐butanesulfinamide, allyl bromide, and indium and Grubbs’ olefin cross‐metathesis as the pivotal steps.
Various extraction methods for detection of bistrifluron residues in Asian pear using high‐performance liquid chromatography: application to dissipation patterns under open‐field conditions
Authors: Truong Lieu T. B. , Kim Sung Woo , Abd El‐Aty A. M. , Kabir Humayun , Rahman Musfiqur , Choi Jeong‐Heui , Shin Ho‐Chul , Kwon Chan‐Hyeok , Lee Kang‐Bong , Yoon Hae Jung , Shim Jae Han
Published: March 2016

The present study was carried out to develop an analytical method for the detection and quantification of bistrifluron, a benzoylphenylurea compound, in pear using high‐performance liquid chromatography with UV detection. Samples were extracted using conventional, AOAC and EN quick, easy, cheap, effective, rugged and safe ‘QuEChERS’ methods. As expected, conventional and EN‐QuEChERS methods gave higher recoveries than AOAC. In addition, interference around the analyte retention time was observed in the conventional method. Thus, the EN‐QuEChERS method was selected and validated by studying various parameters, including linearity, limit of detection, limit of quantification (LOQ), recovery and precision. Linearity was excellent, with a correlation coefficient of 0.9998. Recovery rates at three spiking levels (0.05, 0.2 and 1 mg/kg) ranged from 73.76 to 98.66%. Intra‐ and inter‐day precisions, expressed as relative standard deviations, were <6%. The LOQ of 0.05 mg/kg was considerably lower than the maximum residue limit (1 mg/kg) set by the Korean Ministry of Food and Drug Safety. The developed method was successfully applied to open‐field pear samples, in which the target analyte was slowly dissipated (55% decline) over 14 days with a half‐life of 10.19 days. Notably, the residue levels throughout the period of sample collection (14 days) were lower than the maximum residue limit, indicating that the residue was not hazardous for consumers. Copyright © 2016 John Wiley & Sons, Ltd.
A validated LC‐MS/MS method for the determination of canagliflozin, a sodium–glucose co‐transporter 2 (SGLT‐2) inhibitor, in a lower volume of rat plasma: application to pharmacokinetic studies in rats
Authors: Kobuchi Shinji , Yano Kyoka , Ito Yukako , Sakaeda Toshiyuki
Published: March 2016

Canagliflozin is a novel, orally selective inhibitor of sodium‐dependent glucose co‐transporter‐2 (SGLT2) for the treatment of patients with type 2 diabetes mellitus. In this study, a validated liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method for the quantitative analysis of canagliflozin in a lower volume of rat plasma (0.1 mL) was established and applied to a pharmacokinetic study in rats. Following liquid–liquid extraction by tert‐butyl methyl ether, chromatographic separation of canagliflozin was performed on a Quicksorb ODS (2.1 mm i.d. × 150 mm, 5 µm size) using acetonitrile–0.1% formic acid (90:10, v/v) as the mobile phase at a flow rate of 0.2 mL/min. The detection was carried out using an API 3200 triple‐quadrupole mass spectrometer operating in the positive electrospray ionization mode. Selected ion monitoring transitions of m/z = 462.0 [M + NH4]+ → 191.0 for canagliflozin and m/z = 451.2 [M + H]+ → 71.0 for empagliflozin (internal standard) were obtained. The validation of the method was investigated, and it was found to be of sufficient specificity, accuracy and precision. Canagliflozin in rat plasma was stable under the analytical conditions used. This validated method was successfully applied to assess the pharmacokinetics of canagliflozin in rats using 0.1 mL rat plasma. Copyright © 2016 John Wiley & Sons, Ltd.
Dopamine pathway gene variants may modulate cognitive performance in the DHS – Mind Study
Authors: Martelle Susan E. , Raffield Laura M. , Palmer Nichole D. , Cox Amanda J. , Freedman Barry I. , Hugenschmidt Christina E. , Williamson Jeff D. , Bowden Don W.
Published: March 2016

Background

There is an established association between type 2 diabetes and accelerated cognitive decline. The exact mechanism linking type 2 diabetes and reduced cognitive function is less clear. The monoamine system, which is extensively involved in cognition, can be altered by type 2 diabetes status. Thus, this study hypothesized that sequence variants in genes linked to dopamine metabolism and associated pathways are associated with cognitive function as assessed by the Digit Symbol Substitution Task, the Modified Mini‐Mental State Examination, the Stroop Task, the Rey Auditory‐Verbal Learning Task, and the Controlled Oral Word Association Task for Phonemic and Semantic Fluency in the Diabetes Heart Study, a type 2 diabetes‐enriched familial cohort (n = 893).

Methods

To determine the effects of candidate variants on cognitive performance, genetic association analyses were performed on the well‐documented variable number tandem repeat located in the 3' untranslated region of the dopamine transporter, as well as on single‐nucleotide polymorphisms covering genes in the dopaminergic pathway, the insulin signaling pathway, and the convergence of both. Next, polymorphisms in loci of interest with strong evidence for involvement in dopamine processing were extracted from genetic datasets available in a subset of the cohort (n = 572) derived from Affymetrix® Genome‐Wide Human SNP Array 5.0 and 1000 Genomes imputation from this array.

Results

The candidate gene analysis revealed one variant from the DOPA decarboxylase gene, rs10499695, to be associated with poorer performance on a subset of Rey Auditory‐Verbal Learning Task measuring retroactive interference (P = 0.001, β = −0.45). Secondary analysis of genome‐wide and imputed data uncovered another DOPA decarboxylase variant, rs62445903, also associated with retroactive interference (P = 7.21 × 10−7, β = 0.3). These data suggest a role for dopaminergic genes, specifically a gene involved in regulation of dopamine synthesis, in cognitive performance in type 2 diabetes.
Using Dynamic Risk to Enhance Conditional Release Decisions in Prisoners to Improve Their Outcomes
Authors: Serin Ralph C. , Gobeil Renée , Lloyd Caleb D. , Chadwick Nick , Wardrop Kaitlyn , Hanby Laura
Published: March 2016

Advances in criminal risk assessment have increased sufficiently that inclusion of valid risk measures to anchor assessments is considered a best practice in release decision‐making and community supervision by many paroling authorities and probation agencies. This article highlights how decision accuracy at several key stages of the offender's release and supervision process could be further enhanced by the inclusion of dynamic factors. In cases where the timing of release is discretionary and not legislated, the utilization of a validated decision framework can improve transparency and potentially reduce decision errors. In cases where release is by statute, there is still merit in using dynamic risk assessment and case analysis to inform the assignment of release conditions, thereby attending to re‐entry and public safety considerations. Finally, preliminary results from a recent study are presented to highlight the fact that community supervision outcomes may be improved by incorporating changes in dynamic risk into case planning and risk management, although this work requires replication with larger populations reflecting diverse groups of offenders. Nonetheless, these decision strategies have implications for both resource allocation and client outcomes, as outlined here. Copyright © 2016 John Wiley & Sons, Ltd.
New Frontiers for Conditional Release: Applying Lessons Learned from Other Offenders with Mental Illness
Authors: Gowensmith W. Neil , Peters Amanda J. , Lex Indira A. , Heng Anika K.S. , Robinson Kevin P. , Huston Benjamin A.
Published: March 2016

There is relatively little research in the literature on insanity acquittees as compared with the large number of studies focused on the supervision and treatment of probationers and parolees with mental illness. Ideally, the latter literature could be successfully applied to insanity acquittees discharged from an inpatient hospital on “conditional release.” This article describes the challenges faced by persons on conditional release as well as the gaps in extant conditional release literature. Then, five evidence‐based models for the supervision and/or treatment of probationers and parolees with mental illness are applied to a theoretical conditionally released population (mental health courts, forensic assertive community treatment teams, the risk–need–responsivity model, informed supervision practices, and HOPE probation). Benefits and limitations are noted, and recommendations for such crossover are given. Copyright © 2016 John Wiley & Sons, Ltd.
Chromosomes and clinical anatomy
Authors: Gardner Robert James McKinlay
Published: March 2016

Chromosome abnormalities may cast light on the nature of mechanisms whereby normal anatomy evolves, and abnormal anatomy arises. Correlating genotype to phenotype is an exercise in which the geneticist and the anatomist can collaborate. The increasing power of the new genetic methodologies is enabling an increasing precision in the delineation of chromosome imbalances, even to the nucleotide level; but the classical skills of careful observation and recording remain as crucial as they always have been. Clin. Anat. 29:540–546, 2016. © 2016 Wiley Periodicals, Inc.
Mammary tumor growth and metastasis are reduced in c‐Kit mutant Sash mice
Authors: He Licai , Zhu Zhenfeng , Chen Shang , Wang Yongping , Gu Haihua
Published: March 2016

Besides its well‐known function in allergic response, mast cell, one of the key immune cells present in tumor microenvironment, plays important roles in cancer progression. However, the functional role of mast cells in breast cancer development and metastasis is not well understood. To test the involvement of mast cells in breast cancer, we examined the effects of loss of mast cells on mammary tumor development by crossing the well‐known mast cell deficient mouse strain sash (KitW‐sh/W‐sh) with the mammary tumor transgenic mouse strain MMTV‐Polyoma Middle T antigen (PyMT). Although mammary tumor onset was not affected in the absence of mast cells, mammary growth and metastasis were reduced in PyMT/KitW‐sh/W‐sh mice compared with PyMT/wild‐type mice (WT). Histological and immunofluorescent analyses showed that tumors from PyMT/KitW‐sh/W‐sh mice showed largely differentiated morphology with reduced angiogenesis compared with MMTV‐PyMT/WT mice. Our results suggest that mast cells may promote breast cancer growth and metastasis. Agents that can block mast cells growth are potential new therapies to treat metastatic breast cancer.
Effect of ATRX and G‐Quadruplex Formation by the VNTR Sequence on α‐Globin Gene Expression
Authors: Li Yue , Syed Junetha , Suzuki Yuki , Asamitsu Sefan , Shioda Norifumi , Wada Takahito , Sugiyama Hiroshi
Published: March 2016

ATR‐X (α‐thalassemia/mental retardation X‐linked) syndrome is caused by mutations in chromatin remodeler ATRX. ATRX can bind the variable number of tandem repeats (VNTR) sequence in the promoter region of the α‐globin gene cluster. The VNTR sequence, which contains the potential G‐quadruplex‐forming sequence CGC(GGGGCGGGG)n, is involved in the downregulation of α‐globin expression. We investigated G‐quadruplex and i‐motif formation in single‐stranded DNA and long double‐stranded DNA. The promoter region without the VNTR sequence showed approximately twofold higher luciferase activity than the promoter region harboring the VNTR sequence. G‐quadruplex stabilizers hemin and TMPyP4 reduced the luciferase activity, whereas expression of ATRX led to a recovery in reporter activity. Our results demonstrate that stable G‐quadruplex formation by the VNTR sequence downregulates the expression of α‐globin genes and that ATRX might bind to and resolve the G‐quadruplex.