bluuebunny/crossref_metadata_2025 huggingface dataset:
Umschriebene motorische Entwicklungsstörungen (UEMF)
Authors: Jaščenoka Julia , Petermann Franz
Published: November 2017

Zusammenfassung. Die umschriebene Entwicklungsstörung der motorischen Funktionen (UEMF) zählt zu den häufigsten Entwicklungsabweichungen des Kindesalters. Charakteristisch sind Defizite der Fein- und Grobmotorik, denen ursächlich keine sensorischen, neurologischen oder kognitiven Einschränkungen zugrunde liegen. Verschiedene Studien belegen, dass Kinder mit einer UEMF auch kognitive Defizite in der visuellen Wahrnehmung, in ihren Aufmerksamkeits- und Arbeitsgedächtnisleistungen aufweisen. Das Ziel ist es daher, den Einfluss dieser kognitiven Teilleistungsdefizite auf die Intelligenzleistungen von Kindern mit UEMF zu untersuchen und zu überprüfen, ob Kinder mit UEMF ein spezifisches Intelligenzprofil aufweisen. Die Datenbanken Web of Science und PubMed wurden entsprechend nach deutsch- und englischsprachigen Beiträgen für den Zeitraum 2007 bis 2017 durchsucht. Lediglich fünf Studien erfüllten die Auswahlkriterien. Die Ergebnisse deuten darauf hin, dass Kinder mit einer UEMF geringere Testleistungen im Gesamt-IQ aufweisen. Auf Skalenebene konnten insbesondere geringere Testleistungen in der Handlungsskala der WPPSI-III bzw. dem Wahrnehmungsgebundenen Logischen Denken der WISC-IV sowie in der Verarbeitungsgeschwindigkeit nachgewiesen werden. Die sprachlichen Leistungen der Kinder mit UEMF scheinen zumindest ab dem Grundschulalter unbeeinträchtigt. Testverfahren, die auf den Wechsler-Skalen basieren, stellen ein ökonomisches Instrument dar, um kognitive Leistungsdefizite orientierend im Zusammenhang mit einer UEMF abzubilden.
Wirksamkeitsüberprüfung einer kinderpsychiatrischen Eltern-Kind-Station unter klinischen Routinebedingungen
Authors: Krause Stefanie , Röttger Ulrike , Krauel Kerstin , Flechtner Hans-Henning
Published: November 2017

Zusammenfassung. Vor dem Hintergrund der komplexen Wechselwirkung zwischen der Entstehung und Aufrechterhaltung psychischer Störungen im Kindesalter einerseits und familiären Kontextbedingungen andererseits, bieten Eltern-Kind-Stationen die vielversprechende Möglichkeit das familiäre Umfeld intensiv in die kinderpsychiatrische Behandlung mit einzubeziehen. Um die Wirksamkeit dieser speziellen Therapieform zu untersuchen, wurden im Rahmen einer monozentrischen Fragebogenstudie unter klinischen Routinebedingungen im Ein-Gruppen-Prä-Post-Design anhand einer Stichprobe von 60 Familien die kindliche Symptombelastung (CBCL) und das elterliche Stresserleben (ESF) zu drei Zeitpunkten (Diagnostikblock, Beginn Therapieblock, Therapieende) erhoben. Während sich in der Wartezeit bis Therapiebeginn keine bedeutsamen Veränderungen zeigten, reduzierten sich im Verlauf der Behandlung sowohl die kindlichen Verhaltensauffälligkeiten als auch das elterliche Stresserleben signifikant. Damit liefern die vorliegenden Ergebnisse nicht nur einen Hinweis auf die therapeutische Effektivität kinderpsychiatrischer Eltern-Kind-Stationen, sondern untermauern bisherige Untersuchungen zur engen Verzahnung von kindlichen Verhaltensauffälligkeiten und elterlichen Stresserleben.
Advancing Climate Forecasting
Authors: Merryfield William , Doblas-Reyes Francisco , Ferranti Laura , Jeong Jee-Hoon , Orsolini Yvan , Saurral Ramiro , Scaife Adam , Tolstykh Mikhail , Rixen Michel
Published: November 2017

Better forecasts, new products: The World Climate Research Programme coordinates research aimed at improving and extending global climate forecasting capabilities.
Ticks parasitised feathered dinosaurs as revealed by Cretaceous amber assemblages
Authors: Peñalver Enrique , Arillo Antonio , Delclòs Xavier , Peris David , Grimaldi David A. , Anderson Scott R. , Nascimbene Paul C. , Pérez-de la Fuente Ricardo
Published: November 2017

Ticks are currently among the most prevalent blood-feeding ectoparasites, but their feeding habits and hosts in deep time have long remained speculative. Here, we report direct and indirect evidence in 99 million-year-old Cretaceous amber showing that hard ticks and ticks of the extinct new family Deinocrotonidae fed on blood from feathered dinosaurs, non-avialan or avialan excluding crown-group birds. A †Cornupalpatum burmanicum hard tick is entangled in a pennaceous feather. Two deinocrotonids described as †Deinocroton draculi gen. et sp. nov. have specialised setae from dermestid beetle larvae (hastisetae) attached to their bodies, likely indicating cohabitation in a feathered dinosaur nest. A third conspecific specimen is blood-engorged, its anatomical features suggesting that deinocrotonids fed rapidly to engorgement and had multiple gonotrophic cycles. These findings provide insight into early tick evolution and ecology, and shed light on poorly known arthropod–vertebrate interactions and potential disease transmission during the Mesozoic.
TRPM7 kinase activity is essential for T cell colonization and alloreactivity in the gut
Authors: Romagnani Andrea , Vettore Valentina , Rezzonico-Jost Tanja , Hampe Sarah , Rottoli Elsa , Nadolni Wiebke , Perotti Michela , Meier Melanie A. , Hermanns Constanze , Geiger Sheila , Wennemuth Gunther , Recordati Camilla , Matsushita Masayuki , Muehlich Susanne , Proietti Michele , Chubanov Vladimir , Gudermann Thomas , Grassi Fabio , Zierler Susanna
Published: November 2017

The melastatin-like transient-receptor-potential-7 protein (TRPM7), harbouring a cation channel and a serine/threonine kinase, has been implicated in thymopoiesis and cytokine expression. Here we show, by analysing TRPM7 kinase-dead mutant (Trpm7R/R) mice, that the enzymatic activity of the receptor is not essential for thymopoiesis, but is required for CD103 transcription and gut-homing of intra-epithelial lymphocytes. Defective T cell gut colonization reduces MHCII expression in intestinal epithelial cells. Mechanistically, TRPM7 kinase activity controls TGF-β-induced CD103 expression and pro-inflammatory T helper 17, but not regulatory T, cell differentiation by modulating SMAD2. Notably, we find that the TRPM7 kinase activity promotes gut colonization by alloreactive T cells in acute graft-versus-host disease. Thus, our results unravel a function of TRPM7 kinase in T cell activity and suggest a therapeutic potential of kinase inhibitors in averting acute graft-versus-host disease.
The transcript cleavage factor paralogue TFS4 is a potent RNA polymerase inhibitor
Authors: Fouqueau Thomas , Blombach Fabian , Hartman Ross , Cheung Alan C. M. , Young Mark J. , Werner Finn
Published: November 2017

TFIIS-like transcript cleavage factors enhance the processivity and fidelity of archaeal and eukaryotic RNA polymerases. Sulfolobus solfataricus TFS1 functions as a bona fide cleavage factor, while the paralogous TFS4 evolved into a potent RNA polymerase inhibitor. TFS4 destabilises the TBP–TFB–RNAP pre-initiation complex and inhibits transcription initiation and elongation. All inhibitory activities are dependent on three lysine residues at the tip of the C-terminal zinc ribbon of TFS4; the inhibition likely involves an allosteric component and is mitigated by the basal transcription factor TFEα/β. A chimeric variant of yeast TFIIS and TFS4 inhibits RNAPII transcription, suggesting that the molecular basis of inhibition is conserved between archaea and eukaryotes. TFS4 expression in S. solfataricus is induced in response to infection with the Sulfolobus turreted icosahedral virus. Our results reveal a compelling functional diversification of cleavage factors in archaea, and provide novel insights into transcription inhibition in the context of the host–virus relationship.
Loss of the molecular clock in myeloid cells exacerbates T cell-mediated CNS autoimmune disease
Authors: Sutton Caroline E. , Finlay Conor M. , Raverdeau Mathilde , Early James O. , DeCourcey Joseph , Zaslona Zbigniew , O’Neill Luke A. J. , Mills Kingston H. G. , Curtis Annie M.
Published: November 2017

The transcription factor BMAL1 is a core component of the molecular clock, regulating biological pathways that drive 24 h (circadian) rhythms in behaviour and physiology. The molecular clock has a profound influence on innate immune function, and circadian disruption is linked with increased incidence of multiple sclerosis (MS). However, the mechanisms underlying this association are unknown. Here we show that BMAL1 and time-of-day regulate the accumulation and activation of various immune cells in a CNS autoimmune disease model, experimental autoimmune encephalomyelitis (EAE). In myeloid cells, BMAL1 maintains anti-inflammatory responses and reduces T cell polarization. Loss of myeloid BMAL1 or midday immunizations to induce EAE create an inflammatory environment in the CNS through expansion and infiltration of IL-1β-secreting CD11b+Ly6Chi monocytes, resulting in increased pathogenic IL-17+/IFN-γ+ T cells. These findings demonstrate the importance of the molecular clock in modulating innate and adaptive immune crosstalk under autoimmune conditions.
High-resolution profiling of the gut microbiome reveals the extent of Clostridium difficile burden
Authors: Daquigan Ninalynn , Seekatz Anna Maria , Greathouse K. Leigh , Young Vincent B. , White James Robert
Published: November 2017

Microbiome profiling through 16S rRNA gene sequence analysis has proven to be a useful research tool in the study of C. difficile infection (CDI); however, CDI microbiome studies typically report results at the genus level or higher, thus precluding identification of this pathogen relative to other members of the gut microbiota. Accurate identification of C. difficile relative to the overall gut microbiome may be useful in assessments of colonization in research studies or as a prognostic indicator for patients with CDI. To investigate the burden of C. difficile at the species level relative to the overall gut microbiome, we applied a high-resolution method for 16S rRNA sequence assignment to previously published gut microbiome studies of CDI and other patient populations. We identified C. difficile in 131 of 156 index cases of CDI (average abundance 1.78%), and 18 of 211 healthy controls (average abundance 0.008%). We further detected substantial levels of C. difficile in a subset of infants that persisted over the first two to 12 months of life. Correlation analysis of C. difficile burden compared to other detected species demonstrated consistent negative associations with C. scindens and multiple Blautia species. These analyses contribute insight into the relative burden of C. difficile in the gut microbiome for multiple patient populations, and indicate that high-resolution 16S rRNA gene sequence analysis may prove useful in the development and evaluation of new therapies for CDI.
Protein Structure Insights into the Bilayer Interactions of the Saposin-Like Domain of Solanum tuberosum Aspartic Protease
Authors: Bryksa Brian C. , Yada Rickey Y.
Published: November 2017

Many plant aspartic proteases contain a saposin-like domain whose principal functions are intracellular sorting and host defence. Its structure is characterised by helical segments cross-linked by three highly conserved cystines. The present study on the saposin-like domain of Solanum tuberosum aspartic protease revealed that acidification from inactive to active conditions causes dimerisation and a strand-to-helix secondary structure transition independent of bilayer interaction. Bilayer fusion was shown to occur under reducing conditions yielding a faster shift to larger vesicle sizes relative to native conditions, implying that a lower level structural motif might be bilayer-active. Characterisation of peptide sequences based on the domain’s secondary structural regions showed helix-3 to be active (~4% of the full domain’s activity), and mutation of its sole positively charged residue resulted in loss of activity and disordering of structure. Also, the peptides’ respective circular dichroism spectra suggested that native folding within the full domain is dependent on surrounding structure. Overall, the present study reveals that the aspartic protease saposin-like domain active structure is an open saposin fold dimer whose formation is pH-dependent, and that a bilayer-active motif shared among non-saposin membrane-active proteins including certain plant defence proteins is nested within an overall structure essential for native functionality.
Age-dependent increase of oxidative stress regulates microRNA-29 family preserving cardiac health
Authors: Heid Johanna , Cencioni Chiara , Ripa Roberto , Baumgart Mario , Atlante Sandra , Milano Giuseppina , Scopece Alessandro , Kuenne Carsten , Guenther Stefan , Azzimato Valerio , Farsetti Antonella , Rossi Giacomo , Braun Thomas , Pompilio Giulio , Martelli Fabio , Zeiher Andreas M. , Cellerino Alessandro , Gaetano Carlo , Spallotta Francesco
Published: November 2017

The short-lived turquoise killifish Nothobranchius furzeri (Nfu) is a valid model for aging studies. Here, we investigated its age-associated cardiac function. We observed oxidative stress accumulation and an engagement of microRNAs (miRNAs) in the aging heart. MiRNA-sequencing of 5 week (young), 12–21 week (adult) and 28–40 week (old) Nfu hearts revealed 23 up-regulated and 18 down-regulated miRNAs with age. MiR-29 family turned out as one of the most up-regulated miRNAs during aging. MiR-29 family increase induces a decrease of known targets like collagens and DNA methyl transferases (DNMTs) paralleled by 5´methyl-cytosine (5mC) level decrease. To further investigate miR-29 family role in the fish heart we generated a transgenic zebrafish model where miR-29 was knocked-down. In this model we found significant morphological and functional cardiac alterations and an impairment of oxygen dependent pathways by transcriptome analysis leading to hypoxic marker up-regulation. To get insights the possible hypoxic regulation of miR-29 family, we exposed human cardiac fibroblasts to 1% O2 levels. In hypoxic condition we found miR-29 down-modulation responsible for the accumulation of collagens and 5mC. Overall, our data suggest that miR-29 family up-regulation might represent an endogenous mechanism aimed at ameliorating the age-dependent cardiac damage leading to hypertrophy and fibrosis.
Kiwifruit R2R3-MYB transcription factors and contribution of the novel AcMYB75 to red kiwifruit anthocyanin biosynthesis
Authors: Li Wenbin , Ding Zehong , Ruan Mengbin , Yu Xiaoling , Peng Ming , Liu Yifei
Published: November 2017

Red kiwifruit (Actinidia chinensis) is a popular fresh fruit with a high market value due to its unique color, caused by anthocyanin accumulation. The R2R3-MYB transcription factors (TFs) have important roles in plant development and anthocyanin metabolism. In this first comprehensive study of R2R3-MYBs in kiwifruit, a total of 93 R2R3-MYB genes, including five novel previously unannotated AcMYBs, were identified. Their phylogenic relationship, exon-intron structures, and conserved motifs were analyzed. Based on transcriptome data, 60 AcMYBs were expressed (FPKM > 1) across seven developmental stages of kiwifruit, revealing five expression patterns. One of the 5 newly identified R2R3 TFs, AcMYB75, showed an anthocyanin accumulation-linked expression pattern during fruit development. AcMYB75 localized to the nucleus and has an active transactivation domain, verifying it as a transcription factor. AcMYB75 protein specifically bound the promoter of the anthocyanin biosynthesis gene ANS in yeast one-hybrid system and in vivo. In 35 S:AcMYB75 Arabidopsis plants, anthocyanin significantly accumulated in leaves, and the expression of anthocyanin biosynthetic genes was greatly up-regulated. Together, these results suggest that AcMYB75 is involved in anthocyanin biosynthesis in kiwifruit. These findings will increase our understanding of AcMYBs involved in anthocyanin biosynthesis, and also benefit further functional characterization of R2R3-MYB genes in kiwifruit.
Highly-Sensitive Thin Film THz Detector Based on Edge Metal-Semiconductor-Metal Junction
Authors: Jeon Youngeun , Jung Sungchul , Jin Hanbyul , Mo Kyuhyung , Kim Kyung Rok , Park Wook-Ki , Han Seong-Tae , Park Kibog
Published: November 2017

Terahertz (THz) detectors have been extensively studied for various applications such as security, wireless communication, and medical imaging. In case of metal-insulator-metal (MIM) tunnel junction THz detector, a small junction area is desirable because the detector response time can be shortened by reducing it. An edge metal-semiconductor-metal (EMSM) junction has been developed with a small junction area controlled precisely by the thicknesses of metal and semiconductor films. The voltage response of the EMSM THz detector shows the clear dependence on the polarization angle of incident THz wave and the responsivity is found to be very high (~2,169 V/W) at 0.4 THz without any antenna and signal amplifier. The EMSM junction structure can be a new and efficient way of fabricating the nonlinear device THz detector with high cut-off frequency relying on extremely small junction area.
Genetic Pleiotropy between Nicotine Dependence and Respiratory Outcomes
Authors: Zhang Jushan , Peng Shouneng , Cheng Haoxiang , Nomura Yoko , Di Narzo Antonio Fabio , Hao Ke
Published: November 2017

Smoking is a major cause of respiratory conditions. To date, the genetic pleiotropy between smoking behavior and lung function/chronic obstructive pulmonary disease (COPD) have not been systematically explored. We leverage large data sets of smoking behavior, lung function and COPD, and addressed two questions, (1) whether the genetic predisposition of nicotine dependence influence COPD risk and lung function; and (2) the genetic pleiotropy follow causal or independent model. We found the genetic predisposition of nicotine dependence was associated with COPD risk, even after adjusting for smoking behavior, indicating genetic pleiotropy and independent model. Two known nicotine dependent loci (15q25.1 and 19q13.2) were associated with smoking adjusted lung function, and 15q25.1 reached genome-wide significance. At various suggestive p-value thresholds, the smoking adjusted lung function traits share association signals with cigarettes per day and former smoking, substantially greater than random chance. Empirical data showed the genetic pleiotropy between nicotine dependence and COPD or lung function. The basis of pleiotropic effect is rather complex, attributable to a large number of genetic variants, and many variants functions through independent model, where the pleiotropic variants directly affect lung function, not mediated by influencing subjects’ smoking behavior.
Amniotic fluid stem cell-derived vesicles protect from VEGF-induced endothelial damage
Authors: Sedrakyan S. , Villani V. , Da Sacco S. , Tripuraneni N. , Porta S. , Achena A. , Lavarreda-Pearce M. , Petrosyan A. , Soloyan H. , Filippo R. E. De , Bussolati B. , Perin L.
Published: November 2017

Injection of amniotic fluid stem cells (AFSC) delays the course of progression of renal fibrosis in animals with Alport Syndrome, enhancing kidney function and improving survival. The mechanisms responsible for these protective outcomes are still largely unknown. Here, we showed that vascular endothelial growth factor (VEGF) signaling within the glomeruli of Alport mice is strongly elevated early on in the disease, causing glomerular endothelial cell damage. Intraventricular injected AFSC that homed within the glomeruli showed strong modulation of the VEGF activity, particularly in glomerular endothelial cells. To investigate this phenomenon we hypothesized that extracellular vesicles (EVs) produced by the AFSC could be responsible for the observed renoprotection. AFSC derived EVs presented exosomal and stem cell markers on their surface membrane, including VEGFR1 and VEGFR2. EVs were able to modulate VEGF in glomerular endothelial cells by effectively trapping the excess VEGF through VEGFR1-binding preventing cellular damage. In contrast, VEGFR1/sVEGFR1 knockout EVs failed to show similar protection, thus indicating that VEGF trapping is a potentially viable mechanism for AFSC-EV mediated renoprotection. Taken together, our findings establish that EVs secreted by AFSC could target a specific signaling pathway within the glomerulus, thus representing a new potential glomerulus-specific targeted intervention.
Deep mutational scanning of S. pyogenes Cas9 reveals important functional domains
Authors: Spencer Jeffrey M. , Zhang Xiaoliu
Published: November 2017

RNA-guided endonucleases (RGENs) have invigorated the field of site-specific nucleases. The success of Streptococcus pyogenes Cas9 (SpCas9) has led to the discovery of several other CRISPR-associated RGENs. As more RGENs become available, it will be necessary to refine their activity before they can be translated into the clinic. With this in mind, we sought to demonstrate how deep mutational scanning (DMS) could provide details about important functional regions in SpCas9 and speed engineering efforts. Consequently, we developed a nuclease screening platform which could distinguish active Cas9 mutants. We screened a library of 1.9 × 107 with over 8500 possible non-synonymous mutations and inferred the effects of each mutation using DMS. We demonstrate that the RuvC and HNH domains are the least tolerant regions to mutation. In contrast, the Rec2 and PI domains tolerate mutation better than other regions. The mutation information defined in this work provides a foundation for further SpCas9 engineering. Together, our results demonstrate how DMS can be a powerful tool to uncover features important to RGEN function. Application of this approach to emerging RGENs should enhance their engineering and optimization for therapeutic and other applications.
Structures of PPARγ complexed with lobeglitazone and pioglitazone reveal key determinants for the recognition of antidiabetic drugs
Authors: Lee Min A , Tan Lingchen , Yang Huiseon , Im Yeong-Gwan , Im Young Jun
Published: November 2017

Peroxisome proliferator-activator receptor (PPAR) γ is a nuclear hormone receptor that regulates glucose homeostasis, lipid metabolism, and adipocyte function. PPARγ is a target for thiazolidinedione (TZD) class of drugs which are widely used for the treatment of type 2 diabetes. Recently, lobeglitazone was developed as a highly effective TZD with reduced side effects by Chong Kun Dang Pharmaceuticals. To identify the structural determinants for the high potency of lobeglitazone as a PPARγ agonist, we determined the crystal structures of the PPARγ ligand binding domain (LBD) in complex with lobeglitazone and pioglitazone at 1.7 and 1.8 Å resolutions, respectively. Comparison of ligand-bound PPARγ structures revealed that the binding modes of TZDs are well conserved. The TZD head group forms hydrogen bonds with the polar residues in the AF-2 pocket and helix 12, stabilizing the active conformation of the LBD. The unique p-methoxyphenoxy group of lobeglitazone makes additional hydrophobic contacts with the Ω-pocket. Docking analysis using the structures of TZD-bound PPARγ suggested that lobeglitazone displays 12 times higher affinity to PPARγ compared to rosiglitazone and pioglitazone. This structural difference correlates with the enhanced affinity and the low effective dose of lobeglitazone compared to the other TZDs.
Insight into the molecular recognition mechanism of the coactivator NCoA1 by STAT6
Authors: Russo Luigi , Giller Karin , Pfitzner Edith , Griesinger Christian , Becker Stefan
Published: November 2017

Crucial for immune and anti-inflammatory cellular responses, signal transducer and activator of transcription 6 (STAT6) regulates transcriptional activation in response to interleukin-4 and -13 -induced tyrosine phosphorylation by direct interaction with coactivators. The interaction of STAT6 with nuclear coactivator 1 (NCoA1) is mediated by a short region of the STAT6 transactivation domain that includes the motif LXXLL and interacts with the PAS-B domain of NCoA1. Despite the availability of an X-ray structure of the PAS-B domain/ Leu794-Gly814-STAT6 complex, the mechanistic details of this interaction are still poorly understood. Here, we determine the structure of the NCoA1257–385/STAT6783–814 complex using Nuclear Magnetic Resonance (NMR) and X-ray crystallography. The STAT6783–814 peptide binds with additional N-terminal amino acids to NCoA1257–385, compared to the STAT6794–814 peptide, explaining its higher affinity. Secondary and tertiary structures existing in the free peptide are more highly populated in the complex, suggesting binding by conformational selection.
Identification of insulin-sensitizing molecules acting by disrupting the interaction between the Insulin Receptor and Grb14
Authors: Gondoin Anaïs , Hampe Cornelia , Eudes Richard , Fayolle Cyril , Pierre-Eugène Cécile , Miteva Maria , Villoutreix Bruno O. , Charnay-Pouget Florence , Aitken David J. , Issad Tarik , Burnol Anne-Françoise
Published: November 2017

Metabolic diseases are characterized by a decreased action of insulin. During the course of the disease, usual treatments frequently fail and patients are finally submitted to insulinotherapy. There is thus a need for innovative therapeutic strategies to improve insulin action. Growth factor receptor-bound protein 14 (Grb14) is a molecular adapter that specifically binds to the activated insulin receptor (IR) and inhibits its tyrosine kinase activity. Molecules disrupting Grb14-IR binding are therefore potential insulin-sensitizing agents. We used Structure-Based Virtual Ligand Screening to generate a list of 1000 molecules predicted to hinder Grb14-IR binding. Using an acellular bioluminescence resonance energy transfer (BRET) assay, we identified, out of these 1000 molecules, 3 compounds that inhibited Grb14-IR interaction. Their inhibitory effect on insulin-induced Grb14-IR interaction was confirmed in co-immunoprecipitation experiments. The more efficient molecule (C8) was further characterized. C8 increased downstream Ras-Raf and PI3-kinase insulin signaling, as shown by BRET experiments in living cells. Moreover, C8 regulated the expression of insulin target genes in mouse primary hepatocytes. These results indicate that C8, by reducing Grb14-IR interaction, increases insulin signalling. The use of C8 as a lead compound should allow for the development of new molecules of potential therapeutic interest for the treatment of diabetes.
A novel paradigm to study interpersonal threat-related learning and extinction in children using virtual reality
Authors: Marusak Hilary A. , Peters Craig A. , Hehr Aneesh , Elrahal Farrah , Rabinak Christine A.
Published: November 2017

Disruptions in fear-extinction learning are centrally implicated in a range of stress-related disorders, including anxiety and posttraumatic stress disorder. Given that these disorders frequently begin in childhood/adolescence, an understanding of fear-extinction learning in children is essential for (1) detecting the source of developmental susceptibility, (2) identifying mechanisms leading to pathology, and (3) informing the development and/or more judicious application of treatments for youth. Here, we offer and validate a novel virtual reality paradigm to study threat-related learning and extinction in children that models real-world cues, environments, and fear-inducing events that children are likely to experience, and are linked to the development of fear- and stress-related pathologies. We found that our paradigm is well tolerated in children as young as 6 years, that children show intact fear and extinction learning, and show evidence of divergence in subjective, physiological, and behavioral measures of conditioned fear. The paradigm is available for use in 3-D and in 2-D (e.g., for the MRI scanner) upon request at www.tnp2lab.org.
Behavioral impairment in SHATI/NAT8L knockout mice via dysfunction of myelination development
Authors: Sumi Kazuyuki , Uno Kyosuke , Noike Hiroshi , Tomohiro Takenori , Hatanaka Yasumaru , Furukawa-Hibi Yoko , Nabeshima Toshitaka , Miyamoto Yoshiaki , Nitta Atsumi
Published: November 2017

We have identified SHATI/NAT8L in the brain of mice treated with methamphetamine. Recently, it has been reported that SHATI is N-acetyltransferase 8-like protein (NAT8L) that produces N-acetylaspatate (NAA) from aspartate and acetyl-CoA. We have generated SHATI/NAT8L knockout (Shati−/−) mouse which demonstrates behavioral deficits that are not rescued by single NAA supplementation, although the reason for which is still not clarified. It is possible that the developmental impairment results from deletion of SHATI/NAT8L in the mouse brain, because NAA is involved in myelination through lipid synthesis in oligodendrocytes. However, it remains unclear whether SHATI/NAT8L is involved in brain development. In this study, we found that the expression of Shati/Nat8l mRNA was increased with brain development in mice, while there was a reduction in the myelin basic protein (MBP) level in the prefrontal cortex of juvenile, but not adult, Shati−/− mice. Next, we found that deletion of SHATI/NAT8L induces several behavioral deficits in mice, and that glyceryltriacetate (GTA) treatment ameliorates the behavioral impairments and normalizes the reduced protein level of MBP in juvenile Shati−/− mice. These findings suggest that SHATI/NAT8L is involved in myelination in the juvenile mouse brain via supplementation of acetate derived from NAA. Thus, reduction of SHATI/NAT8L induces developmental neuronal dysfunction.
Monocyte gene expression in childhood obesity is associated with obesity and complexity of atherosclerosis in adults
Authors: Keustermans G. C. , Kofink D. , Eikendal A. , de Jager W. , Meerding J. , Nuboer R. , Waltenberger J. , Kraaijeveld A. O. , Jukema J. W. , Sels J. W. , Garssen J. , Prakken B. J. , Asselbergs F. W. , Kalkhoven E. , Hoefer I. E. , Pasterkamp G. , Schipper H. S.
Published: November 2017

Childhood obesity coincides with increased numbers of circulating classical CD14++CD16- and intermediate CD14++CD16+ monocytes. Monocytes are key players in the development and exacerbation of atherosclerosis, which prompts the question as to whether the monocytosis in childhood obesity contributes to atherogenesis over the years. Here, we dissected the monocyte gene expression profile in childhood obesity using an Illumina microarray platform on sorted monocytes of 35 obese children and 16 lean controls. Obese children displayed a distinctive monocyte gene expression profile compared to lean controls. Upon validation with quantitative PCR, we studied the association of the top 5 differentially regulated monocyte genes in childhood obesity with obesity and complexity of coronary atherosclerosis (SYNTAX score) in a cohort of 351 adults at risk for ischemic cardiovascular disease. The downregulation of monocyte IMPDH2 and TMEM134 in childhood obesity was also observed in obese adults. Moreover, downregulation of monocyte TMEM134 was associated with a higher SYNTAX atherosclerosis score in adults. In conclusion, childhood obesity entails monocyte gene expression alterations associated with obesity and enhanced complexity of coronary atherosclerosis in adults.
CO2 fixation in above-ground biomass of summer maize under different tillage and straw management treatments
Authors: Feng Qianqian , Xu Jing , Zhang Yayun , Li Xiaosha , Xu Jiaojiao , Han Huifang , Ning Tangyuan , Lal Rattal , Li Zengjia
Published: November 2017

This study was conducted to quantify the potential for CO2 fixation in the above-ground biomass of summer maize (Zea mays L.) under different tillage and residue retention treatments. The treatments were paired and included conventional tillage with straw removed (CT0), conventional tillage with straw retained (CTS), no-till with straw removed (NT0), no-till with straw retention (NTS), subsoiling with straw removed (SS0), and subsoiling with straw retained (SSS). The results indicated that NTS and SSS can enhance translocation of photosynthates to grains during the post-anthesis stage. SSS showed the highest total production (average of 7.8 Mg ha−1), carbon absorption by crop (Cd) (average of 9.2 Mg C ha−1), and total C absorption (Ct) (average of 40.4 Mg C ha−1); and NTS showed the highest contribution of post-anthesis dry matter translocation to grain yield (average of 74%). Higher CO2 emission intensity and CO2 fixation efficiency (CFE) were observed for straw retention treatments. In comparison with CTS, the mean CFE (%) over four years increased by 26.3, 19.0, 16.5, and 9.4 for NT0, SS0, NTS, and SSS, respectively. Thus, SSS and NTS systems offer the best options for removing CO2 from the atmosphere while enhancing crop productivity of summer maize in the North China Plain.
Quantitative Analysis of Inflammation in Orbital Fat of Thyroid-associated Ophthalmopathy Using MRI Signal Intensity
Authors: Higashiyama Tomoaki , Iwasa Maki , Ohji Masahito
Published: November 2017

We quantitatively analyzed inflammation in orbital fat from cases of thyroid-associated ophthalmopathy (TAO) using short-tau inversion recovery (STIR) sequences from magnetic resonance imaging. The signal intensity ratios (SIRs) of orbital fat as well as the superior rectus (SR), inferior rectus (IR), lateral rectus (LR), medial rectus (MR), and superior oblique (SO) muscles on STIR images were measured in 70 eyes from 70 treatment-naive TAO patients (active TAO group, 19 patients; inactive TAO group, 51 patients) and 20 eyes from 20 controls. The mean SIR in the active TAO group was significantly higher than that in the inactive TAO group and controls (P < 0.001). The SIR of orbital fat in all TAO patients was significantly (P < 0.001) positively correlated with that of the extraocular muscles: SR (r = 0.64), IR (r = 0.55), LR (r = 0.58), MR (r = 0.71), and SO (r = 0.65). The SIR of orbital fat had a significant positive correlation with the CAS (r = 0.53, P < 0.001). The measurements of SIRs in orbital fat may be useful in evaluating the activity in tissues of TAO patients.
A label-free fiber optic SPR biosensor for specific detection of C-reactive protein
Authors: Wang Wenjia , Mai Zhigang , Chen Yuzhi , Wang Jiaqi , Li Liang , Su Qingning , Li Xuejin , Hong Xueming
Published: November 2017

A highly sensitive and label-free fiber optic surface plasmon resonance (SPR) biosensor for specific detection of C-reactive protein (CRP) is proposed and demonstrated. We take dopamine as a cross-linking agent to immobilize the anti-CRP monoclonal antibody, which is an efficient and simple method for specific modification of the fiber optic SPR sensor. The modified sensor can successfully detect CRP specifically. We realize the fabrication of a disposable fiber optic SPR sensor for the CRP specific detection. Through optimizing the immobilization time of anti-CRP monoclonal antibody and the reaction time of antigen and antibody experimentally, the sensor shows a satisfactory linear response (R2 = 0.97) to CRP concentration within the range from 0.01 to 20 μg/ml. Moreover, the highest CRP sensitivity is obtained at 1.17 nm per lg (μg/ml). With the advantages of simple structure and easy fabrication, our sensor is convenient to be batch produced and controlled with good consistency, which is especially suitable for the fabrication of disposable biosensor. It makes sense that our detection can effectively avoid the cross pollution caused by repeated use of the sensor.
Cascaded gain-switching in the mid-infrared region
Authors: Luo Hongyu , Li Jianfeng , Zhu Chen , Lai Xue , Hai Yongchen , Liu Yong
Published: November 2017

In this report, we demonstrate mid-infrared dual-waveband (i.e., ~3 μm and ~2 μm) pulses from a cascaded gain-switched Ho3+-doped ZBLAN fiber laser by the use of hybrid pumping of 1150 nm CW and pulse LDs for the first time. Stable ~3 μm gain-switched pulses with the maximum output power 262.14 mW and shortest pulse duration of 0.824 μs were first gained at the repetition rate of 80 kHz and wavelength of 2928.5 nm. Then stable ~2 μm gain-switched pulses at 2068 nm were achieved at a switchable repetition rate between 40 kHz and 80 kHz. The maximum output power and shortest pulse duration were 75.23 mW and 0.787 μs, respectively (not simultaneously). Between them, there is a power-dependent μs-order time delay. This dual-waveband laser source has great potential in laser surgery, material processing.
Paper spray mass spectrometry for high-throughput quantification of nicotine and cotinine
Authors: Keating James E. , Minges John T. , Randell Scott H. , Glish Gary L.
Published: November 2017

The rapid release of new tobacco products requires high-throughput quantitative methods to support tobacco research.
Analysis of natural and synthetic folates in pharmaceuticals and foods: a review
Authors: Yin Shuo , Yang Yi , Li Yongxin , Sun Chengjun
Published: November 2017

This review is focused on the progress of sample pretreatment and analysis methods of natural and synthetic folates in pharmaceuticals and foods in the last decade.
Chemical amplification accelerates reactive oxygen species triggered polymeric degradation
Authors: Lee Sangeun , Stubelius Alexandra , Olejniczak Jason , Jang Hongje , Huu Viet Anh Nguyen , Almutairi Adah
Published: November 2017

Chemical amplification strategy is employed to accelerate degradation of ROS-responsive polymeric nanoparticles.
Perspectives of ruthenium(ii) polyazaaromatic photo-oxidizing complexes photoreactive towards tryptophan-containing peptides and derivatives
Authors: Estalayo-Adrián S. , Garnir K. , Moucheron C.
Published: November 2017

This review focuses on recent advances in the search for RuIIpolyazaaromatic complexes as molecular photoreagents for tryptophan-containing peptides and proteins, in view of future biomedical applications.
Tunable white-light emission by supramolecular self-sorting in highly swollen hydrogels
Authors: Zhao Qian , Chen Yong , Li Sheng-Hua , Liu Yu
Published: November 2017

Fluorescence-tunable hydrogels especially emitting white-light were achieved by swelling hydrogels in solutions containing two kinds of dyes.
Facile synthesis and the phase transition mechanism of fluoridated hydroxyapatite with a hierarchical architecture
Authors: Wang Liping , Wang Ming , Wang Yunli , Shao Yiran , Zhu Yingchun
Published: November 2017

The crystal growth process of FHA is investigated. The crystal orientation relationship is found to be [010]FHA//[001]DCPA and (001)FHA//(010)DCPA.
Photon-mediated hybridization of molecular vibrational states
Authors: Crum Vivian F. , Casey Shaelyn R. , Sparks Justin R.
Published: November 2017

The formation of polaritons with tunable contributions from the bonds of two different molecules is demonstrated in a microfluidic device.
Visible light driven plasmonic photochemistry on nano-textured silver
Authors: Walia Jaspreet , Guay Jean-Michel , Krupin Oleksiy , Variola Fabio , Berini Pierre , Weck Arnaud
Published: November 2017

Photooxidation of dodecanethiol on laser machined silver surfaces is achieved using low power visible light.
Dynamic equilibria in supported ionic liquid phase (SILP) catalysis: in situ IR spectroscopy identifies [Ru(CO)xCly]n species in water gas shift catalysis
Authors: Bauer Tanja , Stepic Robert , Wolf Patrick , Kollhoff Fabian , Karawacka Weronika , Wick Christian R. , Haumann Marco , Wasserscheid Peter , Smith David M. , Smith Ana-Sunčana , Libuda Jörg
Published: November 2017

Ru-based SILP systems efficiently catalyze the low-temperature water-gas shift reaction (WGSR).
Radiolytic stability ofN,N-dialkyl amide: effect on Pu(iv) complexes in solution
Authors: Drader J. A. , Boubals N. , Camès B. , Guillaumont D. , Guilbaud P. , Saint-Louis G. , Berthon L.
Published: November 2017

In situalpha radiolysis andex situgamma radiolysis of monoamide extractant: proposition of a degradation scheme.
A hydrolytically stable uranyl organic framework for highly sensitive and selective detection of Fe3+ in aqueous media
Authors: Liu Wei , Xie Jian , Zhang Linmeng , Silver Mark A. , Wang Shuao
Published: November 2017

A depleted uranium-based metal organic framework is synthesized and it exhibits highly sensitive and selective detection towards Fe3+ ions in aqueous media with an extremely low detection limit of 6.3 ppb.
Solar desalination coupled with water remediation and molecular hydrogen production: a novel solar water-energy nexus
Authors: Kim Seonghun , Piao Guangxia , Han Dong Suk , Shon Ho Kyong , Park Hyunwoong
Published: November 2017

A novel solar water-energy nexus technology is presented that combines the solar desalination of saline water and desalination-driven wastewater remediation coupled with the production of H2.
Synthesis of medium-chain carboxylic acids or α,ω-dicarboxylic acids from cellulose-derived platform chemicals
Authors: Li Xing-Long , Zhang Kun , Jiang Ju-Long , Zhu Rui , Wu Wei-Peng , Deng Jin , Fu Yao
Published: November 2017

Applying a M(OTf)n + Pd/C co-catalyst for the production of medium-chain carboxylic acids from carbohydrate derivatives by means of selective hydrodeoxygenation.
Synthesis of biologically active boron-containing compounds
Authors: Yang Fei , Zhu Mingyan , Zhang Jinyi , Zhou Huchen
Published: November 2017

A review focused on the synthetic methods of bioactive boron-containing compounds.
A saccharinate-bridged palladacyclic dimer with a Pd–Pd bond: experimental and molecular docking studies of the interaction with DNA and BSA and in vitro cytotoxicity against human cancer cell lines
Authors: Karami Kazem , Alinaghi Moloud , Amirghofran Zahra , Lipkowski Janusz , Momtazi-borojeni Amir Abbas
Published: November 2017

The synthesis, characterization and biological activities of a saccharinate-bridged palladacyclic dimer are reported in this work.
Synthesis and chemical transformation of Ni nanoparticles embedded in silica
Authors: Lynch Brian B. , Anderson Bryan D. , Kennedy W. Joshua , Tracy Joseph B.
Published: November 2017

Overcoating Ni nanoparticles with SiO2 etches, oxidizes, and embeds them in SiO2, which provides stability during oxidation and reduction.
The stimulation of GLP-1 secretion and delivery of GLP-1 agonists via nanostructured lipid carriers
Authors: Shrestha Neha , Bouttefeux Oriane , Vanvarenberg Kevin , Lundquist Patrik , Cunarro Juan , Tovar Sulay , Khodus Georgiy , Andersson Ellen , Keita Åsa V. , Gonzalez Dieguez Carlos , Artursson Per , Préat Véronique , Beloqui Ana
Published: November 2017

Dual-action nanostructured lipid carriers act as an oral carrier of the GLP-1 agonist and also stimulate endogenous GLP-1 secretion.
All-inorganic perovskite nanocrystal assisted extraction of hot electrons and biexcitons from photoexcited CdTe quantum dots
Authors: Mondal Navendu , De Apurba , Samanta Anunay
Published: November 2017

Harvesting of hot electrons and biexcitons from CdTe quantum dots by all-inorganic perovskite nanocrystals is demonstrated through femtosecond transient absorption measurements.
A colorimetric competitive displacement assay for the evaluation of catalytic peptides
Authors: Gest Anneliese M. M. , Aguiluz Erika M. , Mays Malik T. , Liu Xinyu , Neidhart Eliza K. , Witus Leah S.
Published: November 2017

An assay based on competitive dye displacement was adapted to detect the formation of aldol product in crude reaction mixtures, and was used to evaluate minimal peptide aldol catalysts.
Cyclic azole-homologated peptides from Marine sponges
Authors: Molinski Tadeusz F.
Published: November 2017

Azole-homologated peptides – marine natural products reviewed here for the first time – include potent protease inhibitors that offer challenging synthetic targets.
Effective macrophage delivery using RAFT copolymer derived nanoparticles
Authors: Montgomery K. S. , Davidson R. W. M. , Cao B. , Williams B. , Simpson G. W. , Nilsson S. K. , Chiefari J. , Fuchter M. J.
Published: November 2017

We use reversible addition fragmentation chain transfer (RAFT) polymerisation to prepare block copolymers that are subsequently assembled into nanoparticles. The prepared nanoparticles were extensively taken up by primary murine macrophages and are effective in the delivery of a cell impenetrable cargo.
A simple, modular synthesis of bifunctional peptide-polynorbornenes for apoptosis induction and fluorescence imaging of cancer cells
Authors: Xie Nan , Feng Ke , Shao Jianqun , Chen Bin , Tung Chen-Ho , Wu Li-Zhu
Published: November 2017

Bifunctional peptide-polynorbornenes were designed and fabricated via modular ROMP for mitochondrial-dependent apoptosis induction and fluorescence imaging of cancer cells.
Main-chain benzoxazine precursor block copolymers
Authors: Deliballi Zeynep , Kiskan Baris , Yagci Yusuf
Published: November 2017

A novel strategy for one-pot preparation of block copolymers of benzoxazine precursors with polyetheramines is described.
A polymer enhanced sulfur/graphene aerogel as a no-slurry cathode for lithium–sulfur batteries
Authors: Li Buyin , Xiao Qi , Luo Yuanzheng
Published: November 2017

We presented a facile no-slurry method to synthesize a three-dimensional polyvinylpyrrolidone–sulfur/graphene aerogel composite, which can be pressed into flexible sheets and directly used as a cathode without any additives.
Photocatalytic activity of NiS, NiO and coupled NiS–NiO for degradation of pharmaceutical pollutant cephalexin under visible light
Authors: Torki F. , Faghihian H.
Published: November 2017

Highly efficient visible light cephalexin degradation obtained by photocatalyst prepared by immobilization of NiS, and NiO on the Fe3O4@PPY support.
Poly(ethylene glycol) modified Mn2+ complexes as contrast agents with a prolonged observation window in rat MRA
Authors: Wu Changqiang , Yang Li , Chen Zhuzhong , Zhang Houbing , Li Danyang , Lin Bingbing , Zhu Jiang , Ai Hua , Zhang Xiaoming
Published: November 2017

PEGylated Mn2+ complexes show higher relaxivity and longer blood circulation time than free Mn2+ complexes.
Integrated analysis of solid-state NMR spectra and nuclear magnetic relaxation times for the phenol formaldehyde (PF) resin impregnation process into soft wood
Authors: Nishida Masakazu , Tanaka Tomoko , Miki Tsunehisa , Hayakawa Yoshio , Kanayama Kozo
Published: November 2017

Integrated analysis using a solid-state NMR method revealed that PF resin permeated not only lignin but also carbohydrate polymers.
Nano-composite of Co3O4and Cu with enhanced stability and catalytic performance for non-enzymatic electrochemical glucose sensors
Authors: Lin Xiaoyun , Wang Yanfang , He Wenhui , Ni Yongnian , Kokot Serge
Published: November 2017

A non-enzymatic glucose sensor (Co3O4–CuNPs/Pt) was successfully constructed by a dropping method and a potentiostatic deposition technology. This sensor was used successfully for the quantitative analysis of trace glucose in serum sample.
Addition of dihydrogen to a borylborenium center
Authors: Zheng Junhao , Li Zhen Hua , Wang Huadong
Published: November 2017

The reaction of a borylborenium cation with dihydrogen leads to the insertion of the borenium center to the H–H bond.
Highly efficient CH4 purification by LaBTB PCP-based mixed matrix membranes
Authors: Hua Yinying , Wang Haijun , Li Qianqian , Chen Guining , Liu Gongping , Duan Jingui , Jin Wanqin
Published: November 2017

A facilely prepared LaBTB-based mixed-matrix membrane shows great promise for efficient CH4 purification.
Defect chemistry and electrical properties of sodium bismuth titanate perovskite
Authors: Yang F. , Li M. , Li L. , Wu P. , Pradal-Velázquez E. , Sinclair D. C.
Published: November 2017

We review the diversity of the electrical behaviour of NBT induced by various defect mechanisms, including A-site Na or Bi non-stoichiometry, isovalent-substitution, and acceptor- and donor-doping.
Photocontrolled protein assembly for constructing programmed two-dimensional nanomaterials
Authors: Zhao Linlu , Li Yijia , Wang Tingting , Qiao Shanpeng , Li Xiumei , Wang Ruidi , Luo Quan , Hou Chunxi , Xu Jiayun , Liu Junqiu
Published: November 2017

A rapid and efficient strategy was developed to construct photocontrolled 2D protein nanosheets with an orderly arrangement.
Highly stretchable conductive thermoplastic vulcanizate/carbon nanotube nanocomposites with segregated structure, low percolation threshold and improved cyclic electromechanical performance
Authors: Kazemi Yasamin , Ramezani Kakroodi Adel , Ameli Amir , Filleter Tobin , Park Chul B.
Published: November 2017

We produced conductive thermoplastic vulcanizate composites that exhibit highly enhanced stretchability, low electrical percolation threshold, and improved electromechanical durability.