bluuebunny/crossref_metadata_2025 huggingface dataset:
De novo unbalanced translocation (4p duplication/8p deletion) in a patient with autism, OCD, and overgrowth syndrome
Authors: Sagar Angela , Pinto Dalila , Najjar Fedra , Guter Stephen J. , Macmillan Carol , Cook Edwin H.
Published: April 2017

Chromosomal abnormalities, such as unbalanced translocations and copy number variants (CNVs), are found in autism spectrum disorders (ASDs) [Sanders et al. (2011) Neuron 70: 863–885]. Many chromosomal abnormalities, including sub microscopic genomic deletions and duplications, are missed by G‐banded karyotyping or Fragile X screening alone and are picked up by chromosomal microarrays [Shen et al. (2010) Pediatrics 125: e727–735]. Translocations involving chromosomes 4 and 8 are possibly the second most frequent translocation in humans and are often undetected in routine cytogenetics [Giglio et al. (2002) Circulation 102: 432–437]. Deletions of 4p16 have been associated with Wolf‐Hirschhorn syndrome while 4p16 duplications have been associated with an overgrowth syndrome and mild to moderate mental retardation [Partington et al. (1997) Journal of Medical Genetics 34: 719–728]. The 8p23.3 region contains the autism candidate gene DLGAP2, which can contribute to autism when disrupted [Marshall et al. (2008) The American Journal of Human Genetics 82: 477–488] . There has been a case report of a family with autism spectrum disorder (ASD), prominent obsessional behavior, and overgrowth in patients with der (8) t (4;8) p (16;23) [Partington et al. (1997)]. This is an independent report of a male patient with autism, obsessive compulsive disorder (OCD), attention‐deficit hyperactivity disorder (ADHD), and an overgrowth syndrome, whose de novo unbalanced translocation der (8) t (4;8) p (16.1→ter; 23.1→ter) was initially missed by routine cytogenetics but detected with SNP microarray, allowing higher resolution of translocation breakpoints.
Clinical and molecular characterization of a second family with the 12q14 microdeletion syndrome and review of the literature
Authors: Fischetto Rita , Palumbo Orazio , Ortolani Federica , Palumbo Pietro , Leone Maria Pia , Causio Francesco Andrea , Pesce Sabino , Digilio Maria Christina , Carella Massimo , Papadia Francesco
Published: April 2017

The 12q14 microdeletion syndrome is a rare condition characterized by low birth weight, failure to thrive, short stature, learning disabilities, and osteopoikilosis. To date, 20 cases of 12q14 deletion have been reported in the literature, displaying both phenotypic than genetic variability. We report on three familial cases, a mother and two brothers, with severe short stature. The mother and elder brother presented with osteopoikilosis while the younger brother had severe short stature and developmental delay. SNP array analysis revealed a 1.9 Mb heterozygous 12q14.2q14.3 deletion in all three patients encompassing 14 genes and 3 miRNAs. In addition, the younger brother carried a paternal 11q13.4 duplication including the SHANK2 gene. This latter patient was investigated for developmental delay and did not show osteopoikilosis, confirming the role of age in the clinical presentation of this condition. To the best of our knowledge, this is the second family described with the syndrome. Comparing the clinical and molecular data of our patients with those previously reported we performed a detailed genotype–phenotype correlation confirming the association between growth retardation and osteopoikilosis when the rearrangement includes both LEMD3 and HMGA2 genes. In addition, we suggest the XPOT, TBK1, WIF1 genes as candidates for the clinical features observed in our patients and discuss for the first time the possible involvement of some microRNAs, when deleted, in the etiology of the phenotypes in 12q14 microdeletion syndrome patients. We expect the interpretation of our findings to be useful both from a molecular point of view and for genetic counseling.
Vitamin D‐related genes are subjected to significant de novo mutation burdens in autism spectrum disorder
Authors: Li Jinchen , Wang Lin , Yu Ping , Shi Leisheng , Zhang Kun , Sun Zhong Sheng , Xia Kun
Published: April 2017

Vitamin D deficiency is a putative environmental risk factor for autism spectrum disorder (ASD). Besides, de novo mutations (DNMs) play essential roles in ASD. However, it remains unclear whether vitamin D‐related genes (VDRGs) carry a strong DNM burden. For the 943 reported VDRGs, we analyzed publicly‐available DNMs from 4,327 ASD probands and 3,191 controls. We identified 126 and 44 loss‐of‐function or deleterious missense mutations in the probands and the controls, respectively, representing a significantly higher DNM burden (p = 1.06 × 10−5; odds ratio = 2.11). Specifically, 18 of the VDRGs were found to harbor recurrent functional DNMs in the probands, compared with only one in the controls. In addition, we found that 108 VDRGs with functional DNMs in the probands were significantly more likely to exhibit haploinsufficiency and genic intolerance (p < 0.0078). These VDRGs were also significantly interconnected and co‐expressed, and also with other known ASD‐risk genes (p < 0.0014), thereby forming a functional network enriched in chromatin modification, transcriptional regulation, and neuronal function. We provide straightforward genetic evidences for the first time that VDRGs with a strong degree of DNM burden in ASD and DNMs of VDRGs could be involved in the mechanism underlying in ASD pathogenesis.
Orangutans, enamel defects, and developmental health: A comparison of Borneo and Sumatra
Authors: Skinner Mark F. , Skinner Matthew M.
Published: April 2017

Orangutans (Pongo sp.) show among the highest occurrence of three types of developmental enamel defect. Two are attributed to nutritional factors that reduce bone growth in the infant's face early in development. Their timing and prevalence indicate that Sumatra provides a better habitat than does Borneo. The third type, repetitive linear enamel hypoplasia (rLEH) is very common but its etiology is not understood. Our objective is to draw attention to this enigmatic, episodic stressor in the lives of orangutans. We are concerned that neglect of this possible marker of ill health may be contributing, through inaction, to their alarming decline in numbers. Width and depth of an LEH are considered proxies for duration and intensity of stress. The hypothesis that Bornean orangutans would exhibit relatively wider and deeper LEH was tested on 163 independent episodes of LEH from 9 Sumatran and 26 Bornean orangutans measured with a NanoFocus AG “µsurf Mobile Plus” scanner. Non‐normally distributed data (depths) were converted to natural logs. No difference was found in width of LEH among the two island taxa; nor are their differences in width or depth between the sexes. After controlling for significant differences in LEH depths between incisors and canines, defects are, contrary to prediction, significantly deeper in Sumatran than Bornean animals (median = 28, 18 µm, respectively). It is concluded that repetitive LEH records an unknown but significant stressor present in both Sumatra and Borneo, with an average periodicity of 6 months (or multiples thereof) that lasts about 6–8 weeks. It is worse in Sumatra. Given this patterning, shared with apes from a wide range of ecological and temporal sources, rLEH is more likely attributable to disease than to malnutrition.
Gezielte Spaltung von durch direktes Laserschreiben hergestellten Mikrostrukturen
Authors: Zieger Markus M. , Mueller Patrick , Quick Alexander S. , Wegener Martin , Barner‐Kowollik Christopher
Published: April 2017

Basierend auf einem neuartigen Photolack wurden 3D‐Mikrostrukturen durch direktes Laserschreiben (DLW) hergestellt, die gezielt und vollständig spaltbar sind. Die Netzwerke bestehen ausschließlich aus reversiblen Bindungen, die unter Bestrahlung eines Phenacylsulfid‐Vernetzers entstehen. In einer radikalfreien Stufenwachstumsreaktion zwischen den sich bildenden reaktiven Thioaldehyden und einer Thiol‐Komponente bilden sich Disulfidbrücken. Die Reaktion wurde in Lösung durch ESI‐MS nachgewiesen. Induziert wird die Spaltung durch einen Thiol‐Disulfidbrücken‐Austausch mit Dithiothreitol, der die geschriebenen Strukturen “löscht”. Die milde Spaltung des Disulfidbrücken‐Netzwerkes ist z. B. orthogonal zu Acrylat‐basierten DLW‐Strukturen. Um diesen Aspekt hervorzuheben, wurden DLW‐Strukturen hergestellt, die reversible Strukturelemente in nicht‐reversible Acrylat‐basierte Standardgerüste integrieren. Im Anschluss wurde die selektive Spaltung gezeigt. Die Erreichbarkeit hoher lateraler Auflösung wurde durch Anfertigen definierter Liniengitter mit Linienabständen bis 300 nm nachgewiesen.
Oxidation‐Initiated Cyclizations of Pentadienyl Ethers: An Alternative Entry to the Nazarov Reaction
Authors: Fradette Ryan J. , Kang Minkyu , West F. G.
Published: April 2017

Oxidation‐initiated Nazarov reactions of 1,4‐pentadien‐3‐yl ethers take place in the presence of DDQ. Termination by regioselective elimination preserves both stereocenters created during electrocyclization, providing cyclopentanone products bearing an exocyclic methylene unit. Use of catalytic DDQ with MnO2 as terminal oxidant is also described.
Enantioselective Chemo‐ and Biocatalysis: Partners in Retrosynthesis
Authors: Hönig Moritz , Sondermann Philipp , Turner Nicholas J. , Carreira Erick M.
Published: April 2017

Recent developments of stereoselective biocatalytic and chemocatalytic methods are discussed. The review provides a guide to the use of biocatalytic methods in the area of chemical synthesis with focused attention on retrosynthetic considerations and analysis. The transformations presented are organized according to bond disconnections and attendant synthetic methods. The review is expected to lead to better understanding of the characteristics and distinctions of the two complementary approaches. It depicts for researchers in bio‐ and chemocatalysis a road map of challenges and opportunities for the evolution (and at times revolution) in chemical synthesis.
An Oxygen‐Insensitive Hydrogen Evolution Catalyst Coated by a Molybdenum‐Based Layer for Overall Water Splitting
Authors: Garcia‐Esparza Angel T. , Shinagawa Tatsuya , Ould‐Chikh Samy , Qureshi Muhammad , Peng Xuyuan , Wei Nini , Anjum Dalaver H. , Clo Alain , Weng Tsu‐Chien , Nordlund Dennis , Sokaras Dimosthenis , Kubota Jun , Domen Kazunari , Takanabe Kazuhiro
Published: April 2017

For overall water‐splitting systems, it is essential to establish O2‐insensitive cathodes that allow cogeneration of H2 and O2. An acid‐tolerant electrocatalyst is described, which employs a Mo‐coating on a metal surface to achieve selective H2 evolution in the presence of O2. In operando X‐ray absorption spectroscopy identified reduced Pt covered with an amorphous molybdenum oxyhydroxide hydrate with a local structural order composed of polyanionic trimeric units of molybdenum(IV). The Mo layer likely hinders O2 gas permeation, impeding contact with active Pt. Photocatalytic overall water splitting proceeded using MoOx/Pt/SrTiO3 with inhibited water formation from H2 and O2, which is the prevailing back reaction on the bare Pt/SrTiO3 photocatalyst. The Mo coating was stable in acidic media for multiple hours of overall water splitting by membraneless electrolysis and photocatalysis.
Genomic Responses of Mouse Synovial Fibroblasts During Tumor Necrosis Factor–Driven Arthritogenesis Greatly Mimic Those in Human Rheumatoid Arthritis
Authors: Ntougkos Evangelos , Chouvardas Panagiotis , Roumelioti Fani , Ospelt Caroline , Frank‐Bertoncelj Mojca , Filer Andrew , Buckley Christopher D. , Gay Steffen , Nikolaou Christoforos , Kollias George
Published: April 2017

Objective

Aberrant activation of synovial fibroblasts is a key determinant in the pathogenesis of rheumatoid arthritis (RA). The aims of this study were to produce a map of gene expression and epigenetic changes occurring in this cell type during disease progression in the human tumor necrosis factor (TNF)–transgenic model of arthritis and to identify commonalities with human synovial fibroblasts.

Methods

We used deep sequencing to probe the transcriptome, the methylome, and the chromatin landscape of cultured mouse arthritogenic synovial fibroblasts at 3 stages of disease, as well as synovial fibroblasts stimulated with human TNF. We performed bioinformatics analyses at the gene, pathway, and network levels, compared mouse and human data, and validated selected genes in both species.

Results

We found that synovial fibroblast arthritogenicity was reflected in distinct dynamic patterns of transcriptional dysregulation, which was especially enriched in pathways of the innate immune response and mesenchymal differentiation. A functionally representative subset of these changes was associated with methylation, mostly in gene bodies. The arthritogenic state involved highly active promoters, which were marked by histone H3K4 trimethylation. There was significant overlap between the mouse and human data at the level of dysregulated genes and to an even greater extent at the level of pathways.

Conclusion

This study is the first systematic examination of the pathogenic changes that occur in mouse synovial fibroblasts during progressive TNF‐driven arthritogenesis. Significant correlations with the respective human RA synovial fibroblast data further validate the human TNF–transgenic mouse as a reliable model of the human disease. The resource of data generated in this work may serve as a framework for the discovery of novel pathogenic mechanisms and disease biomarkers.
Reactivity of Functionalized Ynamides with Tetracyanoethylene: Scope, Limitations and Optoelectronic Properties of the Adducts
Authors: Betou Marie , Durand Raphaël J. , Sallustrau Dr Antoine , Gousset Claire , Le Coz Erwann , Leroux Yann R. , Toupet Dr Loïc , Trzop Elzbieta , Roisnel Thierry , Trolez Yann
Published: April 2017

The reactivity of functionalized ynamides and arylynamines with tetracyanoethylene at room temperature was evaluated. In most cases, the corresponding 1,1,4,4‐tetracyanobutadienes (TCBDs) were obtained in good to excellent yields through a [2+2]‐cycloaddition/[2+2]‐retro‐electrocyclization sequence. The influence of diverse functional groups on the yield of the reaction was investigated, in particular concerning multiple ynamides. These TCBDs were characterized by various spectroscopic techniques and electrochemistry and X‐ray diffraction in some cases.
Halogen‐Free Synthesis of Carbamates from CO2 and Amines Using Titanium Alkoxides
Authors: Choi Jun‐Chul , Yuan Hao‐Yu , Fukaya Norihisa , Onozawa Syun‐ya , Zhang Qiao , Choi Seong Jib , Yasuda Hiroyuki
Published: April 2017

A direct synthesis of carbamates from amines and carbon dioxide in the presence of Ti(OR)4 (R=nBu (1), Me (2), Et (3), nPr (4)) was investigated. Aniline was reacted with titanium n‐butoxide (1) in the presence of carbon dioxide (5 MPa) to give the corresponding n‐butyl N‐phenylcarbamate (BPC) in nearly quantitative yield (99 %) within 20 min. Furthermore, 1 could be regenerated upon reaction with n‐butanol during water removal. The recovered 1 could then be reused in a subsequent reaction.
Preparation of Magnetically Recyclable Yolk/Shell FexOy/PdPt@CeO2 Nanoreactors with Enhanced Catalytic Activity
Authors: Yao Tongjie , Guan Chenchen , Zhang Junshuai , Zhang Xiao , Huang Xin , Wu Jie
Published: April 2017

Noble metal nanoparticles (NPs) have recently received considerable attention from researchers working in the field of catalysis. However, the development of new methods allowing these materials to reach their maximum catalytic properties remains challenging. Nanoreactors could lead to dramatic improvements in activity with the help of the intrinsic confinement effect. In this study, we designed a series of yolk/shell FexOy/PdPt@CeO2 composites, where the FexOy NPs acted as a movable core, allowing for the uniform distribution of the PdPt alloys on the inner surface of the CeO2 shell. The high porosity and existence of hollow voids in the CeO2 shell allowed these FexOy/PdPt@CeO2 composites to be used as nanoreactors in catalytic reactions. As well this confinement effect, we identified two structural features that led to enhanced catalytic activity, including (i) the replacement of monometallic NPs with a bimetallic PdPt alloy and (ii) the replacement of a chemically inert support with a reactive CeO2 shell. The resulting nanoassembled catalysts displayed higher activities toward the catalytic reduction of dyes than the reference samples. Moreover, these catalysts were readily recovered and reused because of the magnetic FexOy core.
Inhibition of polyglutamine aggregation by SIMILAR huntingtin N‐terminal sequences: Prospective molecules for preclinical evaluation in Huntington's disease
Authors: Burra Gunasekhar , Thakur Ashwani Kumar
Published: April 2017

The mutant huntingtin protein (mHtt) fragments with expanded polyglutamine sequence forms microscopically visible aggregates in neurons, a hallmark of Huntington's disease (HD). The aggregation process and aggregates are possible targets of therapeutic intervention in HD. Owing to the lack of treatment and cure, the patients die within 15–20 years after the disease onset. Therefore, discovering therapeutic molecules that may either inhibit the aggregation mechanism or downregulate the toxic effects of mHtt are highly needed. This study demonstrates the design and use of peptide inhibitors based on the role played by the N‐terminal seventeen amino acid sequence (NT17) of huntingtin fragment in its aggregation. Fug‐NT17 (Fugu), Xen‐NT17 (Xenopus), Dro‐NT17 (Drosophila), Aib‐NT17, and Pro‐NT17 sequences were tested for their ability to inhibit aggregation. Among them, the first three are the sequence variants of human NT17 from evolutionarily distant organisms and the latter two are the analogs of human NT17‐containing aminoisobutyric acid (Aib) and proline (Pro). Four out of five inhibited the aggregation of huntingtin fragment, NT17Q35P10K2 polypeptide. Data indicate that the physicochemical properties of the inhibitors play a crucial role in exhibiting the inhibitory effect. These inhibitors can be tested in cell and animal models for the preclinical evaluation in the treating of HD.
Stressing Escherichia coli to educate students about research: A CURE to investigate multiple levels of gene regulation
Authors: McDonough Janet , Goudsouzian Lara K. , Papaj Agllai , Maceli Ashley R. , Klepac‐Ceraj Vanja , Peterson Celeste N.
Published: April 2017

Course‐based undergraduate research experiences (CUREs) have been shown to increase student retention and learning in the biological sciences. Most CURES cover only one aspect of gene regulation, such as transcriptional control. Here we present a new inquiry‐based lab that engages understanding of gene expression from multiple perspectives. Students carry out a forward genetic screen to identify regulators of the stationary phase master regulator RpoS in the model organism Escherichia coli and then use a series of reporter fusions to determine if the regulation is at the level of transcription or the post‐transcription level. This easy‐to‐implement course has been run both as a 9‐week long project and a condensed 5–6 week version in three different schools and types of courses. A majority of the genes found in the screen are novel, thus giving students the opportunity to contribute to original findings to the field. Assessments of this CURE show student gains in learning in many knowledge areas. In addition, attitudinal surveys suggest the students are enthusiastic about the screen and their learning about gene regulation. In summary, this lab would be an appropriate addition to an intermediate or advanced level Molecular Biology, Genetics, or Microbiology curriculum. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(5):449–458, 2017.
Stabilization of Telomeric I‐Motif Structures by (2′S)‐2′‐Deoxy‐2′‐C‐Methylcytidine Residues
Authors: Aviñó Anna , Dellafiore María , Gargallo Raimundo , González Carlos , Iribarren Adolfo M. , Montserrat Javier , Eritja Ramon
Published: April 2017

G‐quadruplexes and i‐motifs are tetraplex structures present in telomeres and the promoter regions of oncogenes. The possibility of producing nanodevices with pH‐sensitive functions has triggered interest in modified oligonucleotides with improved structural properties. We synthesized C‐rich oligonucleotides carrying conformationally restricted (2′S)‐2′‐deoxy‐2′‐C‐methyl‐cytidine units. The effect of this modified nucleoside on the stability of intramolecular i‐motifs from the vertebrate telomere was investigated by UV, CD, and NMR spectroscopy. The replacement of selected positions of the C‐core with C‐modified residues induced the formation of stable intercalated tetraplexes at near‐neutral pH. This study demonstrates the possibility of enhancing the stability of the i‐motif by chemical modification.
Weight randomization test for the selection of the number of components in PLS models
Authors: Tran Thanh , Szymańska Ewa , Gerretzen Jan , Buydens Lutgarde , Afanador Nelson Lee , Blanchet Lionel
Published: April 2017

The selection of the optimal number of components remains a difficult but essential task in partial least squares (PLS). Randomization tests have the advantage of being automatic and they make use of the entire dataset, in contrary with the widely used cross‐validation approaches. Partial least squares modeling may include component(s) with a large amount of irrelevant data variation, and this might affect the model, depending on the assigned y‐loading (which is the regression coefficient in the latent domain). This has recently been indicated by us in the basic sequence framework with respect to the underlying theory of the PLS algorithm and presented to the chemometrics society. We will show in this work that this irrelevant data variation is the root cause of the difficulty in current methods for selecting the optimal number of components. For randomization tests, PLS models with nonsignificant components may result in false positive tests because of the incorrect assumption that “the components enter the model in a natural order”.

In this work, we introduce a new randomization test, weight randomization test, selection of the optimal number of components in PLS in light of the underlying theory of the PLS algorithm. In the proposed method the null distribution is well characterized and efficiently determined taking into account a newly defined model quality metric: the number of consecutive non‐significant components (CNC). We illustrate the effectiveness of weight randomization test in optimization of preprocessing as well as in classification models, where results are compared with the double cross‐validation procedure for the latter. This is an important step towards the full automation of PLS model development and routine updates.
Pre‐ejection period reactivity to reward is associated with anhedonic symptoms of depression among adolescents
Authors: Ahles Joshua J. , Mezulis Amy H. , Crowell Sheila E.
Published: April 2017

Pre‐ejection period (PEP) reactivity to reward has been posited as a specific index of behavioral approach and incentive motivation, suggesting it might be uniquely associated with the affective and motivational deficits of anhedonia. This study evaluated PEP reactivity to a reward task as a predictor of depressive symptoms among adolescents, examining global depressive symptoms as well as specific anhedonic and nonanhedonic symptoms clusters. Participants included 76 adolescents, ages 11–15 years (52% female). This study found marginal support for an association between PEP reactivity to reward and concurrent anhedonia symptoms, but no association with nonanhedonic or the global scale. Findings are discussed in terms of potential associations between peripheral psychophysiological measures and dopaminergic functioning and also the utility of this measure for future research on anhedonia.
Influence of bleaching and coloring on ethyl glucuronide content in human hair
Authors: Petzel‐Witt Silvana , Pogoda Werner , Wunder Cora , Paulke Alexander , Schubert‐Zsilavecz Manfred , Toennes Stefan W.
Published: April 2017

Ethyl glucuronide (EtG) is increasingly used in forensic toxicology as a marker for alcohol use in analyses of hair samples, especially in abstinence control. Some cosmetic treatments are considered to markedly reduce the EtG content. In view of especially many women with coloured hair the present study was performed to further investigate the effect of a variety of colouring procedures (bleaching, tinting, permanent and semi‐permanent dyeing, henna) on the EtG content.

Untreated hair samples (n = 12, EtG 13.9–64.7 pg/mg) were re‐analyzed (gas chromatography‐ negative chemical ionization mass spectrometry, 0.8 pg/mg quantification limit) after different treatment procedures. A decrease of the EtG content of at least 10% occurred in every case. The reduction in comparison to the untreated hair was expectedly high for permanent dyeing and bleaching with 18.1% of the initial content (median, range 0.0–50.9%) and 18.4% (0.0–46.7%), respectively. For henna this was 38.3% (0.0–83.0%), for tinting 70.4% (29.0–90.8%), for semi‐permanent dyeing 41.9% (0.0–77.4%). With permanent hair dye the EtG content was decreased to below 7 pg/mg in 10 of 12 cases, in 3 cases even below the LOD (0.2 pg/mg). Surprisingly henna treatment without oxidative component had a marked influence, EtG was below 2 pg/mg in 2 of 12 samples. The study showed that all tested coloration procedures markedly affected the deposited EtG content. Even temporary or henna coloration may have a marked effect. The present data support the recommendation to exclude hair samples with colour manipulations for analysis on the EtG content as a precaution in alcohol abstinence programs. Copyright © 2017 John Wiley & Sons, Ltd.
Epithelial–mesenchymal plasticity and circulating tumor cells: Travel companions to metastases
Authors: Francart Marie‐Emilie , Lambert Justine , Vanwynsberghe Aline M. , Thompson Erik W. , Bourcy Morgane , Polette Myriam , Gilles Christine
Published: April 2017

Epithelial–mesenchymal transitions (EMTs) associated with metastatic progression may contribute to the generation of hybrid phenotypes capable of plasticity. This cellular plasticity would provide tumor cells with an increased potential to adapt to the different microenvironments encountered during metastatic spread. Understanding how EMT may functionally equip circulating tumor cells (CTCs) with an enhanced competence to survive in the bloodstream and niche in the colonized organs has thus become a major cancer research axis. We summarize here clinical data with CTC endpoints involving EMT. We then review the work functionally linking EMT programs to CTC biology and deciphering molecular EMT‐driven mechanisms supporting their metastatic competence. Developmental Dynamics 247:432–450, 2018. © 2017 Wiley Periodicals, Inc.
Synthesis, Crystal Structures, and Properties of Zeolite‐Like T3(H3O)2[M(CN)6]2·uH2O (T = Co, Zn; M = Ru, Os)
Authors: Reguera Leslie , López Noeldris L. , Rodríguez‐Hernández Joelis , González Marlene , Hernandez‐Tamargo Carlos E. , Santos‐Carballal David , de Leeuw Nora H. , Reguera Edilso
Published: April 2017

We report the synthesis, crystal structures, and related properties of six new zeolite‐like hexacyanometallates of formula unit T3(H3O)2[M(CN)6]2·uH2O (T = Co2+, Zn2+; M = RuII, OsII). Their crystal structures were solved and refined from their X‐ray powder diffraction patterns in combination with the IR and UV/Vis/NIR spectroscopic data. The Co and Zn ions are coordinated tetrahedrally to the N atoms of four CN groups. The deconvolution of the overlapped UV/Vis/NIR spectral bands provided conclusive evidence of the tetrahedral coordination of the Co atoms. These materials have porous frameworks, which are characterized by a 3D array of TN4tetrahedral units linked to the MC6octahedral blocks in a 3:2 ratio. From the IR spectroscopy results, we found that all of the compounds reported here contain hydronium countercations. Two different structures in the same space group (R3c) were identified for the Co‐based materials. However, only a single phase was found for the Zn‐containing compounds. Density functional theory (DFT) modeling predicts hydrogen bonds between the hydronium ions and the CN groups at the surfaces of the pores. These materials were prepared through the hydrothermal recrystallization of the solids obtained from mixing ethanol solutions of H4[M(CN)6] with aqueous solutions of cobalt(II) nitrate and zinc nitrate. Our results illustrate the potential of the hydrothermal recrystallization technique for the preparation of metal hexacyanometallates with new structures and pore topologies that are not obtainable by the traditional precipitation method.
Recent Approaches to the Synthesis of Pyrimidine Derivatives
Authors: Mahfoudh Mafakher , Abderrahim Raoudha , Leclerc Eric , Campagne Jean‐Marc
Published: April 2017

The synthesis of pyrimidines is a very active area of research, due to the wide applicability of such compounds in pharmaceutical or coordination chemistry. The recent advances since the most recent reviews (2008/2009) are collected here, demonstrating the surge of creativity that this domain has experienced during the last seven years.
Cycloadditions of Donor–Acceptor Cyclopropanes and Nitriles
Authors: Pagenkopf Brian L. , Vemula Naresh
Published: April 2017

Lewis acid promoted cycloaddition reactions of donor–acceptor (DA) cyclopropanes are one of the well‐studied approaches for the construction of heterocyclic and carbocyclic frameworks. During our efforts to exploit this strategy for the synthesis and functionalization of carbohydrate‐derived systems, we discovered the cycloaddition of nitriles with DA cyclopropanes. This personal account details our contributions to the development of this cycloaddition. The reaction discovery, methods development, and application in total synthesis along with related examples from others are discussed herein.
11C‐Carbonylation through in Situ Generated 11C‐Benzoyl Chlorides with Tetrabutylammonium Chloride as Chloride Source
Authors: Dahl Kenneth , Nordeman Patrik
Published: April 2017

Aromatic 11C‐containing acids, amides, esters, and aldehydes were obtained through a novel 11C‐carbonylative reaction. In the two‐step process, aryl iodides are first reacted with 11CO and tetrabutylammonium chloride in a palladium‐mediated reaction to yield 11C‐benzoyl chlorides in situ. The crude mixture is then further treated with either a hydroxide, amine, alcohol, or a hydride in a second vial to furnish the final 11C‐carbonyl product. The monodentate ligand tri‐tert‐butylphosphonium tetrafluoroborate was proven to be crucial for obtaining high radiochemical yields (RCY). A wide range of 11C‐containing carbonyl compounds were successfully radiolabeled in moderate to excellent RCYs, ranging from 41–93 %. The synthetic retinoic acid tamibarotene was obtained in a RCY of 89 %, whereas the Boc‐protected procainamide was labelled in 68 % RCY, which is a significantly increase (2–3 fold) in RCY compared to other published methods.
Altered TERT promoter and other genomic regulatory elements: occurrence and impact
Authors: Heidenreich Barbara , Kumar Rajiv
Published: April 2017

Study of genetic alterations, inherited or acquired, that increase the risk or drive cancers and many other diseases had remained mostly confined to coding sequences of the human genome. Data from genome wide associations studies, development of the Encyclopedia of DNA Elements (ENCODE), and a spurt in detection of driver somatic mutations have shifted focus towards noncoding regions of the human genome. The majority of genetic variants robustly associated with cancers and other syndromes identified through genome wide studies are located within noncoding regulatory regions of the genome. Genome wide techniques have put an emphasis on the role of three‐dimensional chromosomal structures and cis‐acting elements in regulations of different genes. The variants within noncoding genomic regions can potentially alter a number of regulatory elements including promoters, enhancers, insulators, noncoding long RNAs and others that affect cancers and various diseases through altered expression of critical genes. With effect of genetic alterations within regulatory elements dependent on other partner molecules like transcription factors and histone marks, an understanding of such modifications can potentially identify extended therapeutic targets. That concept has been augmented by the detection of driver somatic noncoding mutations within the promoter region of the telomerase reverse transcriptase (TERT) gene in different cancers. The acquired somatic noncoding mutations within different regulatory elements are now being reported in different cancers with an increased regularity. In this review we discuss the occurrence and impact of germline and somatic alterations within the TERT promoter and other genomic regulatory elements.
The Inhibitory Effect of Nodakenin on Mast‐Cell‐Mediated Allergic Inflammation Via Downregulation of NF‐κB and Caspase‐1 Activation
Authors: Lee Na Young , Chung Kyung‐Sook , Jin Jong Sik , Lee Young‐Cheol , An Hyo‐Jin
Published: April 2017

Nodakenin, a coumarin isolated from the roots of Angelicae gigas, is effective for treating function control disorders, bacterial infections, pain, diarrhea, vitamin E deficiency, and for relaxation of the uterus. The aim of this study was to investigate the antiallergic related inflammatory effects in phorbol‐12‐myristate 13‐acetate plus calcium ionophore A23187 (PMACI)‐stimulated human mast cells (HMC‐1) or anaphylactic activity in a mouse model. Nodakenin inhibited the mRNA expression and production of pro‐inflammatory cytokines such as tumor necrosis factor (TNF)‐α, interleukin (IL)‐6, and IL‐1β in PMACI‐stimulated HMC‐1. We also studied the inhibitory effects of nodakenin on the nuclear translocation of nuclear factor kappa B (NF‐κB) and activation of caspase‐1, inhibitory κB kinase (IKK), and Akt in PMACI‐stimulated HMC‐1. However, mitogen‐activated protein kinase (MAPK) activation was not sufficient to abrogate the stimulus. In addition, administration of nodakenin at 20 mg/kg inhibited histamine release and protected mice against compound 48/80‐induced anaphylactic mortality. Furthermore, Nodakenin inhibited the mRNA expression and production of pro‐inflammatory cytokines and caspase‐1 activation in compound 48/80‐induced anaphylactic mice. These results suggest new insight that nodakenin may be a promising antiallergic related inflammatory agent for inflammatory disorders. J. Cell. Biochem. 118: 3993–4001, 2017. © 2017 Wiley Periodicals, Inc.
Dual Role of the Extracellular Domain of Human Mucin MUC1 in Metastasis
Authors: Syrkina M.S. , Maslakova A.A. , Potashnikova D.M. , Veiko V.P. , Vassetzky Y.S. , Rubtsov M.A.
Published: April 2017

Human mucin MUC1 plays an important role in cancer development. The increased level of this molecule expression during cancer cell progression induces metastasis and is associated with poor prognosis for patients. There is a large body of experimental data on the role of various functional domains of human mucin MUC1 in metastasis. While, the cytoplasmic domain determined to play a definitive role, the influence of extracellular domain on cancer cell invasiveness still remains unclear. The present paper reveals that the extracellular domain of MUC1 molecule consists of two functional subdomains—the region of tandem repeats (TR) and the region of irregular repeats (IR). We demonstrate the ability of each of these subdomains to alter the invasiveness of cancer cells. The presence of the MUC1 molecules containing TR subdomain (MUC1‐TR) on the surface of low‐invasive cancer cells leads to the increase in their transendothelial migration potency, while the addition of the IR subdomain to the MUC1‐TR molecule (MUC1‐IR‐TR) restores their natural low invasiveness. J. Cell. Biochem. 118: 4002–4011, 2017. © 2017 Wiley Periodicals, Inc.
Effects of hemoglobin variants HbJ Bangkok, HbE, HbG Taipei, and HbH on analysis of glycated hemoglobin via ion‐exchange high‐performance liquid chromatography
Authors: Zhang Xiu‐Ming , Wen Dong‐Mei , Xu Sheng‐Nan , Suo Ming‐Huan , Chen Ya‐Qiong
Published: April 2017

Background

To explore the effects of HbJ Bangkok, HbE, HbG Taipei, and α‐thalassemia HbH on the results of HbA1c assessment using ion‐exchange high‐performance liquid chromatography (IE‐HPLC).

Methods

We enrolled five patients in which the results of the IE‐HPLC HbA1c assay were inconsistent with the average levels of FBG. We performed hemoglobin capillary (Hb) electrophoresis using whole‐blood samples. We also sequenced the genes encoding Hb using dideoxy‐mediated chain termination and analyzed HbA1c using borate affinity HPLC (BA‐HPLC) and turbidimetric inhibition immunoassay (TINIA).

Results

Two patients had the HbJ Bangkok variant. Hb genotypes of these patients were β41‐42/βJ Bangkok and βN/βJ Bangkok, and the content of HbJ Bangkok was 93.9% and 52.4%, respectively. The remaining three patients had the following: HbE (βN/βE Hb genotype, 23.6% HbE content), HbG Taipei (βN/βG Taipei Hb genotype, 39.4% HbG Taipei content), and α‐thalassemia HbH (6.1% HbH content, 2.8% Hb Bart's content). In the patients with β‐thalassemia and HbJ Bangkok variants, the presence of the variants interfered with the results of HbA1c analyses using IE‐HPLC and TINIA; in the remaining four patients, there was interference with the results of HbA1c IE‐HPLC but not with the TINIA assay. There was no interference with BA‐HPLC HbA1c results.

Conclusions

HbJ Bangkok, HbE, HbG Taipei Hb, and α‐thalassemia HbH disease cause varying degrees of interference with the analysis of HbA1c using IE‐HPLC. In these patients, we suggest using methods free from such interference for the analysis of HbA1c and other indicators to monitor blood glucose levels.
A highly efficient method for extracting next‐generation sequencing quality RNA from adipose tissue of recalcitrant animal species
Authors: Sharma Davinder , Golla Naresh , Singh Dheer , Onteru Suneel K.
Published: April 2017

The next‐generation sequencing (NGS) based RNA sequencing (RNA‐Seq) and transcriptome profiling offers an opportunity to unveil complex biological processes. Successful RNA‐Seq and transcriptome profiling requires a large amount of high‐quality RNA. However, NGS‐quality RNA isolation is extremely difficult from recalcitrant adipose tissue (AT) with high lipid content and low cell numbers. Further, the amount and biochemical composition of AT lipid varies depending upon the animal species which can pose different degree of resistance to RNA extraction. Currently available approaches may work effectively in one species but can be almost unproductive in another species. Herein, we report a two step protocol for the extraction of NGS quality RNA from AT across a broad range of animal species.
The therapeutic potential of targeting the BRAF mutation in patients with colorectal cancer
Authors: Bahrami Afsane , Hesari AmirReza , Khazaei Majid , Hassanian Seyed Mahdi , Ferns Gordon A. , Avan Amir
Published: April 2017

Colorectal cancer is among the most lethal malignancies globally. BRAF is a member of the RAS/RAF/MEK/ERK signaling pathway. Its constitutive activation can result in increased cellular growth, development, invasion, and resistance to therapy. A mutation of the BRAF gene is present in 5–10% of metastatic colorectal cancers. BRAF mutations have been found to predict a lack of benefit to anti‐EGFR therapy in metastatic CRC. Furthermore, CRC containing the BRAF V600E mutation display an innate resistance to BRAF inhibitors. The mechanisms of cell resistance can be explained at least in part by ERK dependent and ERK in‐dependent pathway. Clinical trials evaluating the combinations of BRAF, PI3K, EGFR, and/or MEK inhibitors have revealed promising activity in BRAF mutant containing CRCs. There may be some benefit from future studies that focus on improving the efficacy of combined therapy in CRC with respect to the sustained effects. The aim of current review is to give an overview about the current status and prospective regarding the therapeutic potential of targeting BRAF mutant colorectal cancer.
Complex osteoclastogenic inductive effects of nicotine over hydroxyapatite
Authors: Costa‐Rodrigues Joao , Rocha Isabel , Fernandes Maria H.
Published: April 2017

Cigarette smoke is associated to pathological weakening of bone tissue, being considered an important playmaker in conditions such as osteoporosis and periodontal bone loss. In addition, it is also associated with an increased risk of failure in bone regeneration strategies. The present work aimed to characterize the effects of nicotine on human osteoclastogenesis over a hydroxyapatite substrate. Osteoclast precursors were maintained in the absence or presence of the osteoclastogenesis enhancers M‐CSF and RANKL, and were further treated with nicotine levels representative of the concentrations observed in the plasma and saliva of smokers. It was observed that nicotine at low concentrations elicit an increase in osteoclast differentiation, but only in the presence of M‐CSF and RANKL it was also able to significantly increase the resorbing ability of osteoclasts. A slight downregulation of NFkB pathway and an increase in the production of TNF‐α and, particularly PGE2, were involved in the observed effects of nicotine. At high concentrations, nicotine revealed cytotoxic effects, causing a decrease in cell density. In conclusion, nicotine at levels found in the plasma of the smokers, has the ability to act directly on osteoclast precursors, inducing its osteoclastogenic differentiation. The stimulatory behavior appears to be dependent on the stage of osteoclastic differentiation of the precursor cells, which means, in the absence of M‐CSF and RANKL, it only favors the initial stages of osteoclast differentiation, while in the presence of the growth factors, a significant increase in their resorbing ability is also achieved.
Can we truly rely on the urinary antigen test for the diagnosis? Legionella case report
Authors: Miyata Jun , Huh Ji Young , Ito Yukiko , Kobuchi Taketsune , Kusukawa Kazuko , Hayashi Hiroyuki
Published: April 2017

It is critical to diagnose and treat Legionella pneumonia (LP) immediately after infection because of the associated high mortality. The urine antigen test (UAT) is often used for the diagnosis of LP; however, it cannot detect the serogroups of all Legionella species. A detained medical history and several clinical findings such as liver enzyme elevation and hyponatremia are useful in diagnosis. Some specific types of Legionella are found in compost. Herein, we report a case of LP in which the patient's medical history and several clinical findings were useful for diagnosis.
Favorable effects of motivational interviewing and support in a patient with schizophrenia and alcohol abuse
Authors: Makuuchi Ayako , Takemoto Yasuhiko , Okamura Hiroshi , Nakane Takahiko , Namikawa Hiroki , Fukumoto Kazuo , Kobayashi Masanori , Kinuhata Shigeki , Morimura Mina , Hirohashi Kazuhiro , Hino Masayuki , Shuto Taichi
Published: April 2017

A 42‐year‐old man with schizophrenia was referred to our hospital after 2 weeks of worsening fatigue. His hemoglobin level was 2.8 g/dL owing to folic acid deficiency stemming from alcohol abuse and consumption of unbalanced meals. We induced behavioral changes in the patient by motivational interviewing. We had direct methodical conversations with medical staff involved with the patient as well as his family, and established new social support for him as well as public assistance. These have resulted in the patient maintaining a favorable lifestyle ever since.
A year‐round evidence‐based medicine‐learning course organized by medical students at Ehime University
Authors: Watanabe Haruka , Fujiwara Takashi , Kobayashi Naoto
Published: April 2017

To resolve the problem that evidence‐based medicine (EBM) courses are not sufficiently taught in Japanese medical schools, we organized a year‐round EBM‐learning course. This study was an observational study and was designed to evaluate the participants’ understanding of EBM using an original survey. The survey was given three times. In total, 18 students responded to our survey. Of those 18 students, six students answered both the first and the last surveys, and their mean score increased 1.17 of 4.00 (95% CI: 0.72‐1.65). These results suggest our course improved students’ ability to read clinical articles.
Isolated astasia caused by a localized infarction in the suprathalamic white matter
Authors: Takahashi Keiko , Osaka Akiyoshi , Tsuda Hiromasa , Ogasawara Hiroki
Published: April 2017

A 73‐year‐old woman with essential hypertension and diabetes mellitus abruptly developed astasia. There were no other neurological abnormalities. Cranial diffusion‐weighted magnetic resonance imaging demonstrated a localized infarction in the right‐sided suprathalamic white matter. Under antiplatelet agent and rehabilitation, the patient became asymptomatic within 4 days. This is a first reported case of isolated astasia due to a suprathalamic white matter infarction. We speculated that disruption of the connection from the ventrolateral nucleus of the thalamus to the posterior cingulate gyrus and/or supplementary motor area might cause astasia.
Lambert‐Eaton myasthenic syndrome with anti‐acetylcholine receptor antibody and anterior mediastinal tumor
Authors: Matsumoto Hideyuki , Ohtomo Gaku , Akahori Tsugumi , Hashida Hideji
Published: April 2017

This report describes the case of a 65‐year‐old male who complained of muscular weakness of the legs with easy fatigability. Blood and imaging examinations showed positive anti‐acetylcholine receptor antibody and an anterior mediastinal tumor (probably a thymic cyst), suggesting the diagnosis of myasthenia gravis (MG). However, neurological and electrophysiological examinations suggested the diagnosis of Lambert‐Eaton myasthenic syndrome (LEMS). We searched repeatedly for malignant tumors. Small cell lung cancer (SCLC) was found. Chemotherapy reduced the SCLC and improved the patient's clinical symptoms. On the basis of an accurate diagnosis of LEMS, we were able to detect SCLC and administer chemotherapy at an early stage. Anti‐P/Q‐type voltage‐gated calcium channel antibody was negative. In our case, MG and LEMS overlap syndrome in addition to MG should be differentiated. For the differentiation, the strict electrophysiological criteria of LEMS were useful.
Intractable otitis media as a diagnostic clue to antineutrophil cytoplasmic antibody‐associated vasculitis
Authors: Ishikawa Yukiko , Takeda Koichi , Akiyama Yoichiro , Matsumura Masami
Published: April 2017

Antineutrophil cytoplasmic antibody‐associated vasculitis (AAV) presents a variety of manifestations. Two patients with a history of intractable otitis media were diagnosed as having AAV. One was an 87‐year‐old woman who presented with cough, anorexia, and fever with a one‐year and four‐month history of otitis media, and the other was a 65‐year‐old woman with arthritis that appeared after the diagnosis of otitis media. The history of otitis media was a diagnostic clue to AAV in both patients. Diagnosis at the early localized stage is crucial to prevent irreversible status of AAV. Primary care physicians should be aware of the otological manifestation of AAV.