bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying National Cinema: A Case Study of the Irish Film Board 1993–2013
Authors: Flynn Roddy , Tracy Tony
Published: June 2016

This article sets out to reinvigorate national cinema studies in an Irish context through a quantitative analysis of films financed by the Irish Film Board between 1993 and 2013. In constructing and coding a database of titles produced with the aid of state finance during this period, the authors argue for a methodology that broadens the inductive approaches of textual analysis that have dominated discussions of Irish cinema to date. By establishing recurring genres, narrative patterns, themes and character types present in IFB-funded films during this period, this article demonstrates how the professional objectives of IFB personnel have shaped institutional funding outcomes.
Polymerase θ is a robust terminal transferase that oscillates between three different mechanisms during end-joining
Authors: Kent Tatiana , Mateos-Gomez Pedro A , Sfeir Agnel , Pomerantz Richard T
Published: June 2016

DNA polymerase θ (Polθ) promotes insertion mutations during alternative end-joining (alt-EJ) by an unknown mechanism. Here, we discover that mammalian Polθ transfers nucleotides to the 3’ terminus of DNA during alt-EJ in vitro and in vivo by oscillating between three different modes of terminal transferase activity: non-templated extension, templated extension in cis, and templated extension in trans. This switching mechanism requires manganese as a co-factor for Polθ template-independent activity and allows for random combinations of templated and non-templated nucleotide insertions. We further find that Polθ terminal transferase activity is most efficient on DNA containing 3’ overhangs, is facilitated by an insertion loop and conserved residues that hold the 3’ primer terminus, and is surprisingly more proficient than terminal deoxynucleotidyl transferase. In summary, this report identifies an unprecedented switching mechanism used by Polθ to generate genetic diversity during alt-EJ and characterizes Polθ as among the most proficient terminal transferases known.
Mycofactocin biosynthesis: modification of the peptide MftA by the radical S‐adenosylmethionine protein MftC
Authors: Khaliullin Bulat , Aggarwal Priyanka , Bubas Michael , Eaton Gareth R. , Eaton Sandra S. , Latham John A.
Published: June 2016

Mycofactocin is a putative, peptide derived, cofactor that is associated primarily with the Mycobacterium genera including the pathogen M. tuberculosis. The pathway consists of the three genes mftA, mftB, and mftC that encode for the peptide substrate, peptide chaperone, and a radical S‐adenosylmethionine protein (RS), respectively. Here, we show that the MftB acts as a peptide chaperone, binding MftA with a submicromolar KD (~ 100 nm) and MftC with a low micromolar KD (~ 2 μm). Moreover, we demonstrate that MftC is a radical S‐adenosylmethionine (SAM) enzyme. Finally, we show that MftC catalyzes the oxidative decarboxylation of the peptide MftA.
Solution structure and antiparasitic activity of scorpine‐like peptides from Hoffmannihadrurus gertschi
Authors: Flores‐Solis David , Toledano Yanis , Rodríguez‐Lima Oscar , Cano‐Sánchez Patricia , Ramírez‐Cordero Belen Ernestina , Landa Abraham , Rodríguez de la Vega Ricardo C. , del Rio‐Portilla Federico
Published: June 2016

Scorpine‐like peptides are two domain peptides found in different scorpion venoms displaying various antimicrobial, cytolytic, and potassium channel‐blocking activities. The relative contribution of each domain to their different activities remains to be elucidated. Here, we report the recombinant production, solution structure, and antiparasitic activity of Hge36, first identified as a naturally occurring truncated form of a Scorpine‐like peptide from the venom of Hoffmannihadrurus gertschi. We also show that removing the first four residues from Hge36 renders a molecule with enhanced potassium channel‐blocking and antiparasitic activities. Our results are important to rationalize the structure‐function relationships of a pharmacologically versatile molecular scaffold.
Identification and characterization of a bacterial hyaluronidase and its production in recombinant form
Authors: Messina Luciano , Gavira Jose A. , Pernagallo Salvatore , Unciti‐Broceta Juan D. , Sanchez Martin Rosario M. , Diaz‐Mochon Juan J. , Vaccaro Susanna , Conejero‐Muriel Mayte , Pineda‐Molina Estela , Caruso Salvatore , Musumeci Luca , Di Pasquale Roberta , Pontillo Angela , Sincinelli Francesca , Pavan Mauro , Secchieri Cynthia
Published: June 2016

Hyaluronidases (Hyals) are broadly used in medical applications to facilitate the dispersion and/or absorption of fluids or medications. This study reports the isolation, cloning, and industrial‐scale recombinant production, purification and full characterization, including X‐ray structure determination at 1.45 Å, of an extracellular Hyal from the nonpathogenic bacterium Streptomyces koganeiensis. The recombinant S. koganeiensis Hyal (rHyal_Sk) has a novel bacterial catalytic domain with high enzymatic activity, compared with commercially available Hyals, and is more thermostable and presents higher proteolytic resistance, with activity over a broad pH range. Moreover, rHyal_Sk exhibits remarkable substrate specificity for hyaluronic acid (HA) and poses no risk of animal cross‐infection.
Postprandial control of fatty acid transport proteins’ subcellular location is not dependent on insulin
Authors: Snook Laelie A. , Wright David C. , Holloway Graham P.
Published: June 2016

Fatty acid transport proteins rapidly translocate to the plasma membrane in response to various stimuli, including insulin, influencing lipid uptake into muscle. However, our understanding of the mechanisms regulating postprandial fatty acid transporter subcellular location remains limited. We demonstrate that the response of fatty acid transporters to insulin stimulation is extremely brief and not temporally matched in the postprandial state. We further show that high‐fat diet‐induced accumulation of fatty acid transporters on the plasma membrane can occur in the absence of insulin. Altogether, these data suggest that insulin is not the primary signal regulating fatty acid transporter relocation in vivo.
The relationship between eruptive activity, flank collapse, and sea level at volcanic islands: A long‐term (>1 Ma) record offshore Montserrat, Lesser Antilles
Authors: Coussens Maya , Wall‐Palmer Deborah , Talling Peter. J. , Watt Sebastian. F. L. , Cassidy Michael , Jutzeler Martin , Clare Michael A. , Hunt James. E. , Manga Michael , Gernon Thomas. M. , Palmer Martin. R. , Hatter Stuart. J. , Boudon Georges , Endo Daisuke , Fujinawa Akihiko , Hatfield Robert , Hornbach Matthew. J. , Ishizuka Osamu , Kataoka Kyoko , Le Friant Anne , Maeno Fukashi , McCanta Molly , Stinton Adam. J.
Published: June 2016

Hole U1395B, drilled southeast of Montserrat during Integrated Ocean Drilling Program Expedition 340, provides a long (>1 Ma) and detailed record of eruptive and mass‐wasting events (>130 discrete events). This record can be used to explore the temporal evolution in volcanic activity and landslides at an arc volcano. Analysis of tephra fall and volcaniclastic turbidite deposits in the drill cores reveals three heightened periods of volcanic activity on the island of Montserrat (∼930 to ∼900 ka, ∼810 to ∼760 ka, and ∼190 to ∼120 ka) that coincide with periods of increased volcano instability and mass‐wasting. The youngest of these periods marks the peak in activity at the Soufrière Hills volcano. The largest flank collapse of this volcano (∼130 ka) occurred toward the end of this period, and two younger landslides also occurred during a period of relatively elevated volcanism. These three landslides represent the only large (>0.3 km3) flank collapses of the Soufrière Hills edifice, and their timing also coincides with periods of rapid sea level rise (>5 m/ka). Available age data from other island arc volcanoes suggest a general correlation between the timing of large landslides and periods of rapid sea level rise, but this is not observed for volcanoes in intraplate ocean settings. We thus infer that rapid sea level rise may modulate the timing of collapse at island arc volcanoes, but not in larger ocean‐island settings.
Deformation in the mantle wedge associated with Laramide flat‐slab subduction
Authors: Behr Whitney M. , Smith Douglas
Published: June 2016

Laramide crustal deformation in the Rocky Mountains of the west‐central United States is often considered to relate to a narrow segment of shallow subduction of the Farallon slab, but there is no consensus as to how deformation along the slab‐mantle lithosphere interface was accommodated. Here we investigate deformation in mantle rocks associated with hydration and shear above the flat‐slab at its contact with the base of the North American plate. The rocks we focus on are deformed, hydrated, ultramafic inclusions hosted within diatremes of the Navajo Volcanic Field in the central Colorado Plateau that erupted during the waning stages of the Laramide orogeny. We document a range of deformation textures, including granular peridotites, porphyroclastic peridotites, mylonites, and cataclasites, which we interpret to reflect different proximities to a slab‐mantle‐interface shear zone. Mineral assemblages and chemistries constrain deformation to hydrous conditions in the temperature range ∼550–750°C. Despite the presence of hydrous phyllosilicates in modal percentages of up to 30%, deformation was dominated by dislocation creep in olivine. The mylonites exhibit an uncommon lattice preferred orientation (LPO) in olivine, known as B‐type LPO in which the a‐axes are aligned perpendicular to the flow direction. The low temperature, hydrated setting in which these fabrics formed is consistent with laboratory experiments that indicate B‐type LPOs form under conditions of high stress and high water contents; furthermore, the mantle wedge context of these LPOs is consistent with observations of trench‐parallel anisotropy in the mantle wedge above many modern subduction zones. Differential stress magnitudes in the mylonitic rocks estimated using paleopiezometry range from 290 to 444 MPa, and calculated effective viscosities using a wet olivine flow law are on the order of 1019−1023 Pa s. The high stress magnitudes, high effective viscosities, and high strains recorded in these rocks are consistent with models that invoke significant basal shear tractions as contributing to Laramide uplift and contraction in the continental interior.
Organochemical characteristics of carbonaceous materials as indicators of heat recorded on an ancient plate‐subduction fault
Authors: Kaneki S. , Hirono T. , Mukoyoshi H. , Sampei Y. , Ikehara M.
Published: June 2016

Coseismic shear stress and slip distance affect subduction‐related earthquake processes. They need to be understood to evaluate the earthquake's mechanism and the tsunami generation potential near trenches. The amount of frictional heat generated depends on the shear stress and slip distance, which are therefore able to be derived from the temperature recorded in the fault. Here we developed a new temperature proxy for carbonaceous materials by performing spectroscopic, thermogravimetric, and organic elemental analyses in conjunction with heating experiments. We found marked anomalies in the infrared and Raman spectra and atomic compositions of carbonaceous materials retrieved from the slip zone of an ancient megasplay fault in the Cretaceous Shimanto accretionary complex, Japan: the infrared spectra show extinction of aliphatic C–H bonding and very weak aromatic C=C bonding, and the Raman spectra show a slightly elevated ratio of disordered band intensity to graphitic band intensity and relatively low H/C and O/C ratios. These correlate well with the spectral and elemental features of host‐rock carbonaceous materials after heating to 600°C. Thus, we conclude that the slip zone experienced a temperature of 600°C during a past earthquake event, indicating coseismic slip of 2–9 m, which could have generated a large tsunami if the ruptures propagated to the seafloor.
Empirical estimates and theoretical predictions of the shorting factor for the THEMIS double‐probe electric field instrument
Authors: Califf S. , Cully C. M.
Published: June 2016

Double‐probe electric field measurements on board spacecraft present significant technical challenges, especially in the inner magnetosphere where the ambient plasma characteristics can vary dramatically and alter the behavior of the instrument. We explore the shorting factor for the Time History of Events and Macroscale Interactions during Substorms electric field instrument, which is a scale factor error on the measured electric field due to coupling between the sensing spheres and the long wire booms, using both an empirical technique and through simulations with varying levels of fidelity. The empirical data and simulations both show that there is effectively no shorting when the spacecraft is immersed in high‐density plasma deep within the plasmasphere and that shorting becomes more prominent as plasma density decreases and the Debye length increases outside the plasmasphere. However, there is a significant discrepancy between the data and theory for the shorting factor in low‐density plasmas: the empirical estimate indicates ~0.7 shorting for long Debye lengths, but the simulations predict a shorting factor of ~0.94. This paper systematically steps through the empirical and modeling methods leading to the disagreement with the intention of motivating further study on the topic.
Seafloor geodesy from repeated sidescan sonar surveys
Authors: DeSanto John B. , Sandwell David T. , Chadwell C. David
Published: June 2016

Accurate seafloor geodetic methods are critical to the study of marine natural hazards such as megathrust earthquakes, landslides, and volcanoes. We propose digital image correlation of repeated shipboard sidescan sonar surveys as a measurement of seafloor deformation. We test this method using multibeam surveys collected in two locales: 2500 m deep lightly sedimented seafloor on the flank of a spreading ridge and 4300 m deep heavily sedimented seafloor far from any plate boundary. Correlation of these surveys are able to recover synthetic displacements in the across‐track (range) direction accurate to within 1 m and in the along‐track (azimuth) direction accurate to within 1–10 m. We attribute these accuracies to the inherent resolution of sidescan data being better in the range dimension than the azimuth dimension. These measurements are primarily limited by the accuracy of the ship navigation. Dual‐frequency GPS units are accurate to ∼10 cm, but single‐frequency GPS units drift on the order of 1 m/h and are insufficient for geodetic application.
Can nudging be used to quantify model sensitivities in precipitation and cloud forcing?
Authors: Lin Guangxing , Wan Hui , Zhang Kai , Qian Yun , Ghan Steven J.
Published: June 2016

Efficient simulation strategies are crucial for the development and evaluation of high‐resolution climate models. This paper evaluates simulations with constrained meteorology for the quantification of parametric sensitivities in the Community Atmosphere Model version 5 (CAM5). Two parameters are perturbed as illustrating examples: the convection relaxation time scale (TAU), and the threshold relative humidity for the formation of low‐level stratiform clouds (rhminl). Results suggest that the fidelity of the constrained simulations depends on the detailed implementation of nudging and the mechanism through which the perturbed parameter affects precipitation and cloud. The relative computational costs of nudged and free‐running simulations are determined by the magnitude of internal variability in the physical quantities of interest, as well as the magnitude of the parameter perturbation. In the case of a strong perturbation in convection, temperature, and/or wind nudging with a 6 h relaxation time scale leads to nonnegligible side effects due to the distorted interactions between resolved dynamics and parameterized convection, while 1 year free‐running simulations can satisfactorily capture the annual mean precipitation and cloud forcing sensitivities. In the case of a relatively weak perturbation in the large‐scale condensation scheme, results from 1 year free‐running simulations are strongly affected by natural noise, while nudging winds effectively reduces the noise, and reasonably reproduces the sensitivities. These results indicate that caution is needed when using nudged simulations to assess precipitation and cloud forcing sensitivities to parameter changes in general circulation models. We also demonstrate that ensembles of short simulations are useful for understanding the evolution of model sensitivities.
Transferring measured discharge time series: Large‐scale comparison of Top‐kriging to geomorphology‐based inverse modeling
Authors: de Lavenne A. , Skøien J. O. , Cudennec C. , Curie F. , Moatar F.
Published: June 2016

Few methods directly transfer streamflow measurements for continuous prediction of ungauged catchments. Top‐kriging has been used mainly to predict the statistical properties of runoff but has been shown to outperform traditional regionalization approaches of rainfall‐runoff models. We applied the Top‐kriging approach across the Loire River basin and compared predictions to a geomorphology‐based approach. Whereas Top‐kriging uses spatial correlation, the other approach has the advantage of being more physically based by using a well‐known geomorphology‐based hydrological model (WFIUH) and its inversion. Both approaches require an equal degree of calibration and provide similar performances. We also demonstrate that the Ghosh distance, which considers the nested nature of catchments, can be used efficiently to calculate weights and to identify the suitability of gauged catchments for use as donor catchments. This result is particularly relevant for catchments with Strahler orders above five, i.e., where donor catchments are more strongly nested.
α‐synuclein conformational antibodies fused to penetratin are effective in models of Lewy body disease
Authors: Spencer Brian , Williams Stephanie , Rockenstein Edward , Valera Elvira , Xin Wei , Mante Michael , Florio Jazmin , Adame Anthony , Masliah Eliezer , Sierks Michael R.
Published: June 2016

Objective

Progressive accumulation of α‐synuclein (α‐syn) has been associated with Parkinson's disease (PD) and Dementia with Lewy body (DLB). The mechanisms through which α‐syn leads to neurodegeneration are not completely clear; however, the formation of various oligomeric species have been proposed to play a role. Antibody therapy has shown effectiveness at reducing α‐syn accumulation in the central nervous system (CNS); however, most of these studies have been conducted utilizing antibodies that recognize both monomeric and higher molecular weight α‐syn. In this context, the main objective of this study was to investigate the efficacy of immunotherapy with single‐chain antibodies (scFVs) against specific conformational forms of α‐syn fused to a novel brain penetrating sequence.

Method

We screened various scFVs against α‐syn expressed from lentiviral vectors by intracerebral injections in an α‐syn tg model. The most effective scFVs were fused to the cell‐penetrating peptide penetratin to enhance transport across the blood–brain barrier, and lentiviral vectors were constructed and tested for efficacy following systemic delivery intraperitoneal into α‐syn tg mice.

Result

Two scFVs (D5 and 10H) selectively targeted different α‐syn oligomers and reduced the accumulation of α‐syn and ameliorated functional deficits when delivered late in disease development; however, only one of the antibodies (D5) was also effective when delivered early in disease development. These scFVs were also utilized in an enzyme‐linked immunosorbent assay (ELISA) assay to monitor the effects of immunotherapy on α‐syn oligomers in brain and plasma.

Interpretation

The design and targeting of antibodies for specific species of α‐syn oligomers is crucial for therapeutic immunotherapy and might be of relevance for the treatment of Lewy body disease.
Microstructure and Mechanical Properties of Graphite Mold Casted TiZrAlV Alloy with Various Zr Contents
Authors: Liang Shunxing , Yin Lixia , Zheng Liyun , Ma Mingzhen , Liu Riping
Published: June 2016

Casting is an effective method to reduce costs which is a focus for Ti products. However, not all Ti alloys can be prepared by casting to reducing costs. To discuss whether the new TiZrAlV alloys are suitable for casting, microstructure and mechanical properties of graphite mold casted TiZrAlV alloys with various Zr contents are investigated. Results show that microstructure and mechanical properties of the TiZr‐based castings depend greatly on Zr contents. Furthermore, relations between tensile properties and microstructural parameters are also discussed. The synthesis result indicates that castings with 60 wt% and 75 wt% Zr have favorable formability and obdurability which are suitable for casting alloys. The current work will provide a reference for the design of TiZr‐ and even Ti‐based castings to reduce costs.
Improved Performance and Reliability of p‐i‐n Perovskite Solar Cells via Doped Metal Oxides
Authors: Savva Achilleas , Burgués‐Ceballos Ignasi , Choulis Stelios A.
Published: June 2016

Perovskite photovoltaics (PVs) have attracted attention because of their excellent power conversion efficiency (PCE). Critical issues related to large‐area PV performance, reliability, and lifetime need to be addressed. Here, it is shown that doped metal oxides can provide ideal electron selectivity, improved reliability, and stability for perovskite PVs. This study reports p‐i‐n perovskite PVs with device areas ranging from 0.09 cm2 to 0.5 cm2 incorporating a thick aluminum‐doped zinc oxide (AZO) electron selective contact with hysteresis‐free PCE of over 13% and high fill factor values in the range of 80%. AZO provides suitable energy levels for carrier selectivity, neutralizes the presence of pinholes, and provides intimate interfaces. Devices using AZO exhibit an average PCE increase of over 20% compared with the devices without AZO and maintain the high PCE for the larger area devices reported. Furthermore, the device stability of p‐i‐n perovskite solar cells under the ISOS‐D‐1 is enhanced when AZO is used, and maintains 100% of the initial PCE for over 1000 h of exposure when AZO/Au is used as the top electrode. The results indicate the importance of doped metal oxides as carrier selective contacts to achieve reliable and high‐performance long‐lived large‐area perovskite solar cells.
Hard Carbon Microtubes Made from Renewable Cotton as High‐Performance Anode Material for Sodium‐Ion Batteries
Authors: Li Yunming , Hu Yong‐Sheng , Titirici Maria‐Magdalena , Chen Liquan , Huang Xuejie
Published: June 2016

Sodium‐ion batteries (SIBs) have attracted more and more attention for scalable electrical energy storage due to the abundance and wide distribution of Na resources. However, the anode still remains a great challenge for the application of SIBs. Here the production of uniform hard carbon microtubes (HCTs) made from natural cotton through one simple carbonization process and their application as an anode are reported. The study shows that the electrochemical performance of the HCTs is seriously affected by the carbonization temperature due to the difference in their microstructure and heteroatomic content. The HCTs carbonized at 1300 °C deliver the highest reversible capacity of 315 mAh g−1 and good rate capability due to their unique tubular structure. This contribution not only provides a new approach for the preparation of hard carbon materials with unique tubular microstructure using natural inspiration, but it also deepens the fundamental understanding of the sodium storage mechanism.
Recurrent mutations of the exportin 1 gene (XPO1) and their impact on selective inhibitor of nuclear export compounds sensitivity in primary mediastinal B‐cell lymphoma
Authors: Jardin Fabrice , Pujals Anais , Pelletier Laura , Bohers Elodie , Camus Vincent , Mareschal Sylvain , Dubois Sydney , Sola Brigitte , Ochmann Marlène , Lemonnier François , Viailly Pierre‐Julien , Bertrand Philippe , Maingonnat Catherine , Traverse‐Glehen Alexandra , Gaulard Philippe , Damotte Diane , Delarue Richard , Haioun Corinne , Argueta Christian , Landesman Yosef , Salles Gilles , Jais Jean‐Philippe , Figeac Martin , Copie‐Bergman Christiane , Molina Thierry Jo , Picquenot Jean Michel , Cornic Marie , Fest Thierry , Milpied Noel , Lemasle Emilie , Stamatoullas Aspasia , Moeller Peter , Dyer Martin J.S , Sundstrom Christer , Bastard Christian , Tilly Hervé , Leroy Karen
Published: June 2016

Primary mediastinal B‐cell lymphoma (PMBL) is an entity of B‐cell lymphoma distinct from the other molecular subtypes of diffuse large B‐cell lymphoma (DLBCL). We investigated the prevalence, specificity, and clinical relevance of mutations of XPO1, which encodes a member of the karyopherin‐β nuclear transporters, in a large cohort of PMBL. PMBL cases defined histologically or by gene expression profiling (GEP) were sequenced and the XPO1 mutational status was correlated to genetic and clinical characteristics. The XPO1 mutational status was also assessed in DLBCL, Hodgkin lymphoma (HL) and mediastinal gray‐zone lymphoma (MGZL).The biological impact of the mutation on Selective Inhibitor of Nuclear Export (SINE) compounds (KPT‐185/330) sensitivity was investigated in vitro. XPO1 mutations were present in 28/117 (24%) PMBL cases and in 5/19 (26%) HL cases but absent/rare in MGZL (0/20) or DLBCL (3/197). A higher prevalence (50%) of the recurrent codon 571 variant (p.E571K) was observed in GEP‐defined PMBL and was associated with shorter PFS. Age, International Prognostic Index and bulky mass were similar in XPO1 mutant and wild‐type cases. KPT‐185 induced a dose‐dependent decrease in cell proliferation and increased cell‐death in PMBL cell lines harboring wild type or XPO1 E571K mutant alleles. Experiments in transfected U2OS cells further confirmed that the XPO1 E571K mutation does not have a drastic impact on KPT‐330 binding. To conclude the XPO1 E571K mutation represents a genetic hallmark of the PMBL subtype and serves as a new relevant PMBL biomarker. SINE compounds appear active for both mutated and wild‐type protein. Am. J. Hematol. 91:923–930, 2016. © 2016 Wiley Periodicals, Inc.
MED23‐associated refractory epilepsy successfully treated with the ketogenic diet
Authors: Lionel Anath C. , Monfared Nasim , Scherer Stephen W. , Marshall Christian R. , Mercimek‐Mahmutoglu Saadet
Published: June 2016

We report a new patient with refractory epilepsy associated with a novel pathogenic homozygous MED23 variant. This 7.5‐year‐old boy from consanguineous parents had infantile onset global developmental delay and refractory epilepsy. He was treated with the ketogenic diet at 2.5 years of age and became seizure free on the first day. He had microcephaly and truncal hypotonia. His brain MRI showed delayed myelination and thin corpus callosum. He was enrolled in a whole exome sequencing research study, which identified a novel, homozygous, likely pathogenic (c.1937A>G; p.Gln646Arg) variant in MED23. MED23 is a regulator of energy homeostasis and glucose production. Liver‐specific Med23‐knockout mice showed reduced liver gluconeogenesis and lower blood glucose levels compared to control mice. This is the first patient with documented refractory epilepsy caused by a novel homozygous pathogenic variant in MED23 expanding the phenotypic spectrum. Identification of the underlying genetic defect in MED23 sheds light on the possible mechanism of complete response to the ketogenic diet in this child. © 2016 Wiley Periodicals, Inc.
Prenatal diagnosis of Chudley–McCullough syndrome
Authors: Chapman Teresa , Perez Francisco A. , Ishak Gisele E. , Doherty Dan
Published: June 2016

Chudley–McCullough syndrome (CMS) is an autosomal‐recessive disorder characterized by a complex brain malformation and profound congenital sensorineural hearing loss. Postnatal brain imaging findings include ventriculomegaly, partial agenesis of corpus callosum, inferior cerebellar dysplasia, arachnoid cysts, and malformations of cortical development including frontal subcortical heterotopia and polymicrogyria. Prenatal diagnosis of CMS is important due to the markedly less severe neurodevelopmental prognosis compared to disorders with similar brain imaging findings. We report prenatal imaging features that help distinguish CMS from other disorders, including slit‐like frontal horns, agenesis of the corpus callosum, frontal subcortical heterotopia, arachnoid cysts, and cerebellar dysplasia. © 2016 Wiley Periodicals, Inc.
Trisomy 18: A survey of opinions, attitudes, and practices of neonatologists
Authors: Jacobs Adam P. , Subramaniam Akila , Tang Ying , Philips Joseph B. , Biggio Joseph R. , Edwards Rodney K. , Robin Nathaniel H.
Published: June 2016

We conducted a survey‐based study of the opinions, attitudes, and management practices of neonatologists across the United States regarding prenatally diagnosed Trisomy 18. The survey was designed based on previously validated surveys of severe fetal anomalies and collected demographic information on participants, as well as their attitudes, and management choices given a series of vignettes beginning in the prenatal period. The survey was sent to 3,143 American Academy of Pediatrics Section on Neonatal‐Perinatal Medicine members of which 409 (13%) completed the survey. While the response rate was rather low, our respondent pool was representative of the national neonatologist population. Respondents were predominately white (81%), married (88%), Christian (54%), had children (86%), and were pro‐choice in terms of abortion (68%). Eighty‐three percent (83%) of respondents thought that trisomy 18 is a lethal condition and 60% thought that treatment is futile. Seventy‐five percent (75%) expected that the best neurodevelopmental outcome in the case of infant survival would be profound intellectual disability. Regarding neonatal care, 95% stated that they would recommend palliative care only. Ninety‐five percent (95%) would never recommend or recommend only if asked full code resuscitation for a neonate with full trisomy 18, yet, 44% would comply partially or in full with a full code request for resuscitation measures. The demographic features that correlated most significantly with these responses were clinician race and years in practice. The attitudes toward and management of infants affected with trisomy 18 seem to be largely driven by parental attitudes and wishes. © 2016 Wiley Periodicals, Inc.
Fringes of the empire: Diet and cultural change at the Roman to post‐Roman transition in NW Iberia
Authors: López‐Costas Olalla , Müldner Gundula
Published: June 2016

A growing number of paleodiet investigations over recent years have begun to reveal the stark dietary differences that existed between regions of the Roman Empire, as well as significant changes in subsistence strategies after its fall. The present study explores the dietary changes at the Roman to post‐Roman (Germanic) transition in the Northwest Iberian Peninsula, in order to improve our understanding of the changes that occurred at end of the Roman Empire in different regions across Europe and to also consider the influence of climate had on them. The carbon and nitrogen stable isotope investigation in bone collagen from A Lanzada, NW Spain (100–700 AD), which was an important commercial, coastal settlement has been presented. A human sample of 59 individuals, 6 of them subadults, is compared with 31 faunal specimens, which include a number of marine fish. Isotope data for the terrestrial fauna reveal the influence of the sea on the local isotope baseline. Analysis of the human samples indicates a mixed marine‐terrestrial diet. A shift in mean human δ13C values from −16.7‰ to −14.3‰ provides clear evidence for a significant change in diet in the post‐Roman period, probably through the intensification of both marine resources exploitation and C4‐plant consumption (presumably millet). A deterioration of paleoenvironmental conditions, together with a poor socioeconomic situation and the arrival of new people, the Sueves, who brought a new political and socioeconomic system have been discussed as the main causes for the dietary modification in post‐Roman times.
In sickness and in death: Assessing frailty in human skeletal remains
Authors: Marklein Kathryn E. , Leahy Rachael E. , Crews Douglas E.
Published: June 2016

Stress plays an important role in the etiology of multiple morbid and mortal outcomes among the living. Drawing on health paradigms constructed among the living augments our evolving knowledge of relationships between stress and health. Therefore, elucidating relationships between stress and both chronic and acute skeletal lesions may help clarify our understanding of long‐term health trends in the past. In this study, we propose an index of “skeletal frailty,” based on models of frailty used to evaluate the life‐long effects of stress on health among living populations. Here, we assess the possible applicability of frailty to archaeological populations. The skeletal frailty index (SFI) is proposed as a methodological liaison between advances made by biological anthropologists studying relationships between stress and health among the living and bioarchaeologists studying stress and health among the dead. In a case study examining skeletal stress in Medieval London, the SFI is applied to nonmonastic (N = 60) and monastic (N = 74) samples. We used analysis of variance/analysis of covariance to compare SFI values between nonmonastic‐monastic groups, sexes, and age cohorts. Results indicate higher lifetime morbidity among monastic groups. These results complement previous bioarchaeological findings on the same London populations, wherein lower risks of mortality and longer lifespans were observed for monastic populations. SFI data reflect the morbidity‐mortality paradox observed in modern populations and accompany recent findings in bioarchaeology of variation in Medieval monastic and nonmonastic “health.” Ultimately, this study demonstrates the SFI's utility in bioarchaeology, through its application of commonly assessed skeletal biomarkers, its ease of applicability, and its potential usefulness for assessing changes in skeletal health over time and across specific geographies.
Mitochondrial DNA mutations increase in early stage Alzheimer disease and are inconsistent with oxidative damage
Authors: Hoekstra Jake G. , Hipp Michael J. , Montine Thomas J. , Kennedy Scott R.
Published: June 2016

Mitochondrial dysfunction and oxidative damage are commonly associated with early stage Alzheimer disease (AD). The accumulation of somatic mutations in mitochondrial DNA (mtDNA) has been hypothesized to be a driver of these phenotypes, but the detection of increased mutation loads has been difficult due to a lack of sensitive methods. We used an ultrasensitive next generation sequencing technique to measure the mutation load of the entire mitochondrial genome. Here, we report a significant increase in the mtDNA mutation frequency in the hippocampus of early stage AD, with the cause of these mutations being consistent with replication errors and not oxidative damage. Ann Neurol 2016;80:301–306
Platform Synthetic Lectins for Divalent Carbohydrate Recognition in Water
Authors: Carter Tom S. , Mooibroek Tiddo J. , Stewart Patrick F. N. , Crump Matthew P. , Galan M. Carmen , Davis Anthony P.
Published: June 2016

Biomimetic carbohydrate receptors (“synthetic lectins”) have potential as agents for biological research and medicine. However, although effective strategies are available for “all‐equatorial” carbohydrates (glucose, etc.), the recognition of other types of saccharide under natural (aqueous) conditions is less well developed. Herein we report a new approach based on a pyrene platform with polar arches extending from aryl substituents. The receptors are compatible with axially substituted carbohydrates, and also feature two identical binding sites, thus mimicking the multivalency observed for natural lectins. A variant with negative charges forms 1:2 host/guest complexes with aminosugars, with K1>3000 m−1 for axially substituted mannosamine, whereas a positively charged version binds the important α‐sialyl unit with K1≈1300 m−1.
Palladium‐Catalyzed Chemo‐ and Enantioselective C−O Bond Cleavage of α‐Acyloxy Ketones by Hydrogenolysis
Authors: Chen Jianzhong , Zhang Zhenfeng , Liu Delong , Zhang Wanbin
Published: June 2016

A chemoselective C−O bond cleavage of the ester alkyl side‐chain of α‐acyloxy ketones was realized for the first time by a highly efficient palladium‐catalyzed hydrogenolysis (S/C=6000, the highest catalytic efficiency by far). Furthermore, a kinetic resolution of α‐acyloxy ketones was first developed by enantioselective hydrogenolysis with good yields and up to 99 % ee.
Palladium Catalysis Enables Benzylation of α,α‐Difluoroketone Enolates
Authors: Yang Ming‐Hsiu , Hunt Jordan R. , Sharifi Niusha , Altman Ryan A.
Published: June 2016

A palladium‐catalyzed decarboxylative benzylation reaction of α,α‐difluoroketone enolates is reported, in which the key C(α)−C(sp3) bond is generated by reductive elimination from a palladium intermediate. The transformation provides convergent access to α‐benzyl‐α,α‐difluoroketone‐based products, and should be useful for accessing biological probes.
N‐Heterocyclic Carbene–Gold(I) Complexes Conjugated to a Leukemia‐Specific DNA Aptamer for Targeted Drug Delivery
Authors: Niu Weijia , Chen Xigao , Tan Weihong , Veige Adam S.
Published: June 2016

This report describes the synthesis and characterization of novel N‐heterocyclic carbene (NHC)–gold(I) complexes and their bioconjugation to the CCRF‐CEM‐leukemia‐specific aptamer sgc8c. Successful bioconjugation was confirmed by the use of fluorescent tags on both the NHC–AuI complex and the aptamer. Cell‐viability assays indicated that the NHC–AuI–aptamer conjugate was more cytotoxic than the NHC–gold complex alone. A combination of flow cytometry, confocal microscopy, and cell‐viability assays provided clear evidence that the NHC–AuI–aptamer conjugate was selective for targeted CCRF‐CEM leukemia cells.
Impact of Deuteration on the Assembly Kinetics of Transthyretin Monitored by Native Mass Spectrometry and Implications for Amyloidoses
Authors: Yee Ai Woon , Moulin Martine , Breteau Nina , Haertlein Michael , Mitchell Edward P. , Cooper Jonathan B. , Boeri Erba Elisabetta , Forsyth V. Trevor
Published: June 2016

It is well established that the formation of transthyretin (TTR) amyloid fibrils is linked to the destabilization and dissociation of its tetrameric structure into insoluble aggregates. Isotope labeling is used for the study of TTR by NMR, neutron diffraction, and mass spectrometry (MS). Here MS, thioflavin T fluorescence, and crystallographic data demonstrate that while the X‐ray structures of unlabeled and deuterium‐labeled TTR are essentially identical, subunit exchange kinetics and amyloid formation are accelerated for the deuterated protein. However, a slower subunit exchange is noted in deuterated solvent, reflecting the poorer solubility of non‐polar protein side chains in such an environment. These observations are important for the interpretation of kinetic studies involving deuteration. The destabilizing effects of TTR deuteration are rather similar in character to those observed for aggressive mutations of TTR such as L55P (associated with familial amyloid polyneuropathy).
Insertion of Isocyanides into N−Si Bonds: Multicomponent Reactions with Azines Leading to Potent Antiparasitic Compounds
Authors: Kishore Kranti G. , Ghashghaei Ouldouz , Estarellas Carolina , Mestre M. Mar , Monturiol Cristina , Kielland Nicola , Kelly John M. , Francisco Amanda Fortes , Jayawardhana Shiromani , Muñoz‐Torrero Diego , Pérez Belén , Luque F. Javier , Gámez‐Montaño Rocío , Lavilla Rodolfo
Published: June 2016

Trimethylsilyl chloride is an efficient activating agent for azines in isocyanide‐based reactions, which then proceed through a key insertion of the isocyanide into a N−Si bond. The reaction is initiated by N activation of the azine, followed by nucleophilic attack of an isocyanide in a Reissert‐type process. Finally, a second equivalent of the same or a different isocyanide inserts into the N−Si bond leading to the final adduct. The use of distinct nucleophiles leads to a variety of α‐substituted dihydroazines after a selective cascade process. Based on computational studies, a mechanistic hypothesis for the course of these reactions was proposed. The resulting products exhibit significant activity against Trypanosoma brucei and T. cruzi, featuring favorable drug‐like properties and safety profiles.
CuFeO2/tetrabutylammonium bromide catalyzes selective synthesis of 1,4‐disubstituted 1,2,3‐triazoles in neat water at room temperature
Authors: Hajipour Abdol R. , Karimzadeh Morteza , Fakhari Farzaneh , Karimi Hirbod
Published: June 2016

A completely green medium including water as a solvent and antiviral CuFeO2 as a catalyst is described for the synthesis of 1,4‐disubstituted 1,2,3‐triazoles. Excellent yields of products are obtained at room temperature. Cost effectiveness, high stability and high recyclability of CuFeO2 along with antiviral properties of the catalyst make it a unique catalyst for cycloadditions of phenylacetylene with a wide variety of aryl halides. Copyright © 2016 John Wiley & Sons, Ltd.
Nitrogen and phosphorous‐doped porous carbon xerogels as metal‐free catalysts for environmental catalytic peroxide oxidation of 4‐nitrophenol
Authors: Fathy Nady A. , Shouman Mona A. , Aboelenin Reham M. M.
Published: June 2016

This work reports an environmental benign porous carbon catalyst for the catalytic peroxide oxidation of 4‐nitrophenol (4‐NP) pollutant. Nitrogen and phosphorous‐doped carbon xerogels as metal‐free catalysts, which are namely as CX30, CX50 and CX75 with corresponding to initial concentrations of H3PO4 acid (30, 50 and 75 v/v %) were synthesized. Nitrogen gas adsorption measurements of the prepared carbon catalysts were performed at −196 °C, while Fourier transform infrared spectroscopy (FTIR) and high resolution scanning electron microscopy–energy dispersive X‐ray spectroscopy (SEM–EDS) analyses were examined for the sample of CX75 which appeared high catalytic performance. The effect of various factors such as temperature, catalyst loading, H2O2 dose and initial concentration of 4‐NP on the catalytic oxidation performance of the metal‐free catalysts was studied at pH = 4. Results revealed that the phosphoric acid activation of nitrogen‐doped resorcinol‐formaldehyde xerogel developed significant influence on the porosity and surface chemistry characteristics of the hereby catalysts. Increasing the concentration of H3PO4 enhances the microporosity at expense of mesoporosity yielding micro‐mesoporous carbons with surface area as high as 442 m2/g. EDS and FTIR analyses confirmed the presence of phosphorous‐ and nitrogen‐containing functional groups with high content of carbon and oxygen groups. During catalytic wet peroxide oxidation experiments, the CX75 catalyst exhibits complete decomposition 4‐NP (100%) within 60 min. Moreover, reusability experiments with this catalyst were run through three cycles and revealed high stability where up to 52.6% conversion of 4‐NP in the third recycle was occurred at 120 min. © 2016 Curtin University of Technology and John Wiley & Sons, Ltd.
Down‐Regulation of miR‐19a as a Biomarker for Early Detection of Silicosis
Authors: Yang Zhen , Li Qian , Yao Sanqiao , Zhang Ge , Xue Rong , Li Guoliang , Wang Yizheng , Wang Shixin , Wu Ruichang , Gao Hongsheng
Published: June 2016

The accumulated data indicate that there is significant genetic heterogeneity underlying the etiology of silicosis. Recent reports have revealed that microRNAs (miRNAs) play an important role in regulating pulmonary fibrosis. This study, therefore, aimed to identify some miRNAs as biomarkers for silicosis, and to explore the early diagnostic value of biomarkers for silicosis. Total RNAs were collected from the peripheral blood leukocytes of 23 silicosis patients and 23 healthy controls, the different miRNAs were screened using microarrays. The potential biomarker miRNAs were identified by quantitative real‐time polymerase chain reaction (qPCR) and receiver operating characteristic (ROC) curves. Eighteen differential miRNAs in leukocytes were up‐regulated and twenty differential miRNAs were down‐regulated in the silicosis group, compared with the control group. The expression levels of miR‐181a and miR‐19a were 0.8854 ± 0.1037 and 0.2929 ± 0.0342 by the relative quantitation method 2−△△CT of qPCR, respectively. The sensitivity and specificity for miR‐181a at a cut‐off value of 1.8917 were 70% and 75%, respectively, whereas, those for miR‐19a at a cut‐off value of 3.6828 were 95% and 95%, respectively. Thus, miR‐19a in peripheral blood leukocyte could be used as an effective biomarker for silicosis. Anat Rec, 299:1300–1307, 2016. © 2016 Wiley Periodicals, Inc.
Anatomical Basis of Dynamic Modulation of Tympanic Tension in the Water Monitor Lizard, Varanus salvator
Authors: Han Dawei , Young Bruce A.
Published: June 2016

Amphibious vertebrates, such as the water monitor (Varanus salvator), require anatomical and/or neural specializations to cope with pressure changes on the tympanic membrane when transiting between air and water. V. salvator has internally coupled ears which are distinguished by (patent) anatomical conduits through the skull linking the middle ear cavities on both sides of the head. We describe a small skeletal muscle in V. salvator which inserts onto the middle ear ossicle and the tympanic membrane. Laser doppler vibrometry demonstrates that contraction of this muscle both increases the vibrational velocity of the tympanic membrane and changes the waveform pattern of the tympanic displacement. The combined anatomical and functional results suggest that V. salvator is capable of actively modulating the tension of the tympanic membrane. Anat Rec, 299:1270–1280, 2016. © 2016 Wiley Periodicals, Inc.
Elevated CD14 (Cluster of Differentiation 14) and Toll‐Like Receptor (TLR) 4 Signaling Deteriorate Periapical Inflammation in TLR2 Deficient Mice
Authors: Rider Daniel , Furusho Hisako , Xu Shuang , Trachtenberg Alexander J. , Kuo Winston Patrick , Hirai Kimito , Susa Mako , Bahammam Laila , Stashenko Philip , Fujimura Akira , Sasaki Hajime
Published: June 2016

Apical periodontitis (periapical lesions) is an infection‐induced chronic inflammation in the jaw, ultimately resulting in the destruction of apical periodontal tissue. Toll‐like receptors (TLRs) are prominent in the initial recognition of pathogens. Our previous study showed that TLR4 signaling is proinflammatory in periapical lesions induced by a polymicrobial endodontic infection. In contrast, the functional role of TLR2 in regulation of periapical tissue destruction is still not fully understood. Using TLR2 deficient (KO), TLR2/TLR4 double deficient (dKO), and wild‐type (WT) mice, we demonstrate that TLR2 KO mice are highly responsive to polymicrobial infection‐induced periapical lesion caused by over activation of TLR4 signal transduction pathway that resulted in elevation of NF‐kB (nuclear factor kappa B) and proinflammatory cytokine production. The altered TLR4 signaling is caused by TLR2 deficiency‐dependent elevation of CD14 (cluster of differentiation 14), which is a co‐receptor of TLR4. Indeed, neutralization of CD14 strikingly suppresses TLR2 deficiency‐dependent inflammation and tissue destruction in vitro and in vivo. Our findings suggest that a network of TLR2, TLR4, and CD14 is a key factor in regulation of polymicrobial dentoalveolar infection and subsequent tissue destruction. Anat Rec, 299:1281–1292, 2016. © 2016 Wiley Periodicals, Inc.