bluuebunny/crossref_metadata_2025 huggingface dataset:
Sleep disordered breathing and daytime hypoventilation in a male with MECP2 mutation
Authors: Cacciatori Elena , Lelii Mara , Russo Silvia , Alari Valentina , Masciadri Maura , Guez Sophie , Patria Maria Francesca , Marchisio Paola , Milani Donatella
Published: September 2020

Rett syndrome (RTT, MIM * 312750) is an X‐linked neurodevelopmental disorder caused by pathogenic variants at the Xq28 region involving the gene methyl‐CpG‐binding protein 2 (MECP2, MIM * 300005). The spectrum of MECP2‐related phenotypes is wide and it ranges from asymptomatic female carriers to severe neonatal‐onset encephalopathy in males. Abnormal breathing represents one of the leading features, but today little is known about polysomnographic features in RTT females; no data are available about males. We report the case of a male of Moroccan origins with a MECP2 pathogenic variant and a history of encephalopathy and severe breathing disturbances in the absence of dysmorphic features. For the first time we describe in detail the polysomnographic characteristics of a MECP2‐mutated male and we show the relevance of severe central apneas, which may represent a new clinical clue to suggest the diagnosis. Moreover, we want to highlight the importance to maintain a high index of suspicion for MECP2‐related disorders in the presence of severe hypotonia, apneic crises, and respiratory insufficiency in males to permit an earlier diagnosis and the consequent definition of recurrence risk of the family and to avoid other useless and invasive exams.
TWAS pathway method greatly enhances the number of leads for uncovering the molecular underpinnings of psychiatric disorders
Authors: Chatzinakos Chris , Georgiadis Foivos , Lee Donghyung , Cai Na , Vladimirov Vladimir I. , Docherty Anna , Webb Bradley T. , Riley Brien P. , Flint Jonathan , Kendler Kenneth S. , Daskalakis Nikolaos P. , Bacanu Silviu‐Alin
Published: September 2020

Genetic signal detection in genome‐wide association studies (GWAS) is enhanced by pooling small signals from multiple Single Nucleotide Polymorphism (SNP), for example, across genes and pathways. Because genes are believed to influence traits via gene expression, it is of interest to combine information from expression Quantitative Trait Loci (eQTLs) in a gene or genes in the same pathway. Such methods, widely referred to as transcriptomic wide association studies (TWAS), already exist for gene analysis. Due to the possibility of eliminating most of the confounding effects of linkage disequilibrium (LD) from TWAS gene statistics, pathway TWAS methods would be very useful in uncovering the true molecular basis of psychiatric disorders. However, such methods are not yet available for arbitrarily large pathways/gene sets. This is possibly due to the quadratic (as a function of the number of SNPs) computational burden for computing LD across large chromosomal regions. To overcome this obstacle, we propose JEPEGMIX2‐P, a novel TWAS pathway method that (a) has a linear computational burden, (b) uses a large and diverse reference panel (33 K subjects), (c) is competitive (adjusts for background enrichment in gene TWAS statistics), and (d) is applicable as‐is to ethnically mixed‐cohorts. To underline its potential for increasing the power to uncover genetic signals over the commonly used nontranscriptomics methods, for example, MAGMA, we applied JEPEGMIX2‐P to summary statistics of most large meta‐analyses from Psychiatric Genetics Consortium (PGC). While our work is just the very first step toward clinical translation of psychiatric disorders, PGC anorexia results suggest a possible avenue for treatment.
Stabilisierung von Pentaphospholen als η5‐koordinierende Liganden
Authors: Riesinger Christoph , Balázs Gábor , Bodensteiner Michael , Scheer Manfred
Published: September 2020

Die elektrophile Funktionalisierung von [Cp*Fe(η5‐P5)] (1) ergibt die ersten Übergangsmetallkomplexe von Pentaphospholen (cyclo‐P5R). Die Silylierung von 1 mit [(Et3Si)2(μ‐H)][B(C6F5)4] führt zur Bildung der ionischen Spezies [Cp*Fe(η5‐P5SiEt3)][B(C6F5)4] (2), deren Folgereaktion mit H2O die Stammverbindung [Cp*Fe(η5‐P5H)][B(C6F5)4] (3) ergibt. Die Synthese eines kohlenstoffsubstituierten Derivates [Cp*Fe(η5‐P5Me)][X] ([X]−=[FB(C6F5)3]− (4 a), [B(C6F5)4]− (4 b)) kann durch die Methylierung von 1 durch Verwendung von [Me3O][BF4] und B(C6F5)3 oder einer Kombination aus MeOTf und [Li(OEt2)2][B(C6F5)4] ausgeführt werden. Die strukturelle Charakterisierung dieser Verbindungen zeigt eine leicht gewinkelte Struktur für den cyclo‐P5R‐Liganden. Detaillierte NMR‐spektroskopische Untersuchungen deuten auf ein hochdynamisches Verhalten hin und damit auf eine unterschiedliche Labilität für 2 und 3 in Lösung. DFT‐Rechnungen geben Aufschluss über die elektronische Struktur und die Bindungssituation dieser neuartigen Klasse von Verbindungen.
Stabilization of Pentaphospholes as η5‐Coordinating Ligands
Authors: Riesinger Christoph , Balázs Gábor , Bodensteiner Michael , Scheer Manfred
Published: September 2020

Electrophilic functionalisation of [Cp*Fe(η5‐P5)] (1) yields the first transition‐metal complexes of pentaphospholes (cyclo‐P5R). Silylation of 1 with [(Et3Si)2(μ‐H)][B(C6F5)4] leads to the ionic species [Cp*Fe(η5‐P5SiEt3)][B(C6F5)4] (2), whose subsequent reaction with H2O yields the parent compound [Cp*Fe(η5‐P5H)][B(C6F5)4] (3). The synthesis of a carbon‐substituted derivative [Cp*Fe(η5‐P5Me)][X] ([X]−=[FB(C6F5)3]− (4 a), [B(C6F5)4]− (4 b)) is achieved by methylation of 1 employing [Me3O][BF4] and B(C6F5)3 or a combination of MeOTf and [Li(OEt2)2][B(C6F5)4]. The structural characterisation of these compounds reveals a slight envelope structure for the cyclo‐P5R ligand. Detailed NMR‐spectroscopic studies suggest a highly dynamic behaviour and thus a distinct lability for 2 and 3 in solution. DFT calculations shed light on the electronic structure and bonding situation of this unprecedented class of compounds.
Water‐born 3D nanofiber mats using cost‐effective centrifugal spinning: comparison with electrospinning process: A complex study
Authors: Rihova Martina , Ince Ahmet Erdem , Cicmancova Veronika , Hromadko Ludek , Castkova Klara , Pavlinak David , Vojtova Lucy , Macak Jan M.
Published: September 2020

A comparison of the electrostatic and centrifugal spinning of poly(vinyl alcohol) and poly(vinyl pyrrolidone) is shown in terms of the resulting fiber morphology and the process conditions. Specific parameters of centrifugal spinning, such rotational speed of spinneret and the relative humidity, were extensively investigated in details. Morphologies and diameters of resulting fiber mats were investigated by a scanning electron microscopy and compared between the two spinning techniques. The results revealed that formation of fibers is mainly affected by the initial polymer concentrations (and resulting viscosities) of polymeric solutions, which is in line with previous reports. However, the key novel finding of this work is that increasing relative humidity during centrifugal spinning process leads to greatly reduced fiber diameters to the levels typical for electrospinning. The obtained comparison is discussed and clearly shows technological advantages of the centrifugal spinning over electrospinning, enabling quantitative production of fibers with same or similar diameters.
Nafion® reinforced with polyacrylonitrile/ZrO2 nanofibers for direct methanol fuel cell application
Authors: Sigwadi Rudzani , Mokrani Touhami , Dhlamini Simon , Msomi Phumlani Fortune
Published: September 2020

Nafion® membrane blended with polyacrylonitrile nanofibers decorated with ZrO2 was successfully fabricated. The composite membrane showed improved proton conductivity, swelling ratio, thermal and mechanical stability, reduced methanol crossover, and enhanced fuel cell efficiency. The nanocomposite membranes achieved a reduced methanol crossover of 5.465 × 10−8 cm2 S−1 compared to 9.118 × 10−7 cm2 S−1 of recast Nafion® membrane using a 5 M methanol solution at 80°C. The composite membrane also showed an ion conductivity of 1.84 compared to 0.25 S cm−1 recast Nafion® at 25°C. The composite membranes showed a peak power density of 68.7 mW·cm−2 at 25°C, these results show a promising composite membrane for fuel cell application.
Purity Assessment of Monosaccharides using Mass Balance Method
Authors: Lee Sunyoung , Kwon Ha‐Jeong
Published: September 2020

A mass balance method enables accurate determination of the purity of monosaccharides by incorporating the results obtained by various analytical techniques. High‐performance anion exchange chromatography with pulsed amperometric detection was used to quantify nonchromophoric impurities structurally related to the analyte. Organic acids as candidates of monosaccharide impurities were analyzed by ion chromatography with conductivity detection. Liquid chromatography with photodiode‐array UV detection was performed to detect other organic impurities. Karl‐Fischer coulometry with oven‐drying method was used to measure the water content in the samples. Finally, nonvolatile inorganic impurities were determined by thermal gravimetric analyses. The purities of the monosaccharides, glucose, galactose, fructose, and mannose, in kg/kg were (0.9983 ± 0.0004), (0.9962 ± 0.0005), (0.9999 ± 0.0004), and (0.9991 ± 0.0005), respectively. The mass balance method provides system of units (SI)‐traceable purity values, which can be applied to primary reference materials for assigning a certified value for the target monosaccharide in certified reference materials.
Development of a reversed‐phase high‐performance liquid chromatographic method for the determination of propranolol in different skin layers
Authors: Cunha‐Filho Marcilio , Rocha Jessika Layane , Duarte Natane C.B. , Sa‐Barreto Lívia L.
Published: September 2020

The aim of this work was to develop and validate an analytical method using HPLC for the determination of propranolol in the different layers of the skin to be used in kinetic studies of skin permeation. The development of the method was based on the suitability of the chromatogram, and the validation followed the international health regulation for bioanalytical methods. In addition, the method was tested in an in vitro permeation assay using porcine skin. The drug was determined using an RP‐C18 column at 30°C, a mobile phase comprising acidic aqueous phase:acetonitrile (75:25 v/v), at a flow rate of 1.0 mL min−1, and UV detection at 290 nm. The method was demonstrated to be selective against skin contaminants, linear in a wide range of concentrations (3–20 μg mL−1), sensitive enough to quantify less than 0.1% of the drug dosage in skin matrices, and precise regardless of analysis variations such as day of analysis, analyst, or equipment. In addition, the method presented a high drug extraction capacity greater than 90% for all skin layers (stratum corneum, hair follicle, and remaining skin). Finally, the method was successfully tested in skin permeation assays, proving its value in the development of topical formulations containing propranolol.
Neural correlates of verbal recognition memory in obese adults with and without major depressive disorder
Authors: Restivo Maria R. , Hall Geoffrey B. , Frey Benicio N. , McKinnon Margaret C. , Taylor Valerie H.
Published: September 2020

Background

Obesity and major depressive disorder (MDD) independently contribute to memory impairment. Little is known about shared neural mechanisms that may result in the cognitive impairment experienced by these populations. This study's aim was to determine how obesity impacts neural activity during a verbal recognition memory task in individuals both with and without MDD.

Methods

Functional magnetic resonance imaging was employed to examine whether differences in neural activation patterns would be seen across three groups during the Warrington's Recognition Memory Test. Three study groups are reported: 20 subjects with obesity but without MDD (bariatric controls), 23 subjects with past or current MDD and obesity, and 20 normal BMI controls (healthy controls).

Results

Three‐group conjunction analyses indicated that overlapping neural regions were activated during both encoding and retrieval processes across all groups. However, second‐level 2‐group t‐contrasts indicated that neural activation patterns differed when comparing healthy and bariatric controls, and when comparing bariatric controls and bariatric MDD participants.

Discussion

Results indicate that obesity in conjunction with MDD confers a subtle impact on neural functioning. Given high rates of obesity and MDD comorbidity, and the role of cognition on ability to return to premorbid level of functioning, this association should inform treatment decisions.
Expression profile and bioinformatics analysis of circular RNA in intestinal mucosal injury and repair after severe burns
Authors: Zhang Wenwen , Yan Hao , Deng Yuequ , Lou Jiaqi , Zhang Pan , Cui Qingwei , Sun Han , Tang Hao , Sun Yuan , Yang Juan , Li Dan , Sun Yong
Published: September 2020

Circular RNA (circRNA) is a novel noncoding RNA that is mostly found in humans and animals. Although the flux of circRNA research has increased in recent years, its precise function is still unclear. Some studies demonstrate that circRNAs can function as microRNA (miRNA) sponges involved in the regulation of competitive endogenous RNAs networks and play a crucial role in many biological processes. Other studies show that circRNAs play multiple biological roles in gastrointestinal diseases. However, the expression characteristics and function of circRNA in intestinal mucosal injury and repair after severe burn have not been reported. This study aims to screen differentially expressed circRNAs in intestinal mucosal injury and repair after severe burns and understand their underlying mechanisms. To test our hypothesis that circRNA may play a role in promoting repair in intestinal mucosa injury after severe burns, we collected the intestinal tissues of three severely burned mice and three pseudo‐scalded mice and evaluated the expression of circRNAs via microarray analysis. Quantitative real‐time polymerase chain reaction was also used to validate the circRNA microarray data by selecting six based on different multiples, original values, and p values. The host genes of all differentially expressed circRNAs and the downstream target genes of six selected DEcircRNAs were identified by Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway analysis. Meanwhile, we also created a circRNA‐miRNA‐mRNA network to predict the role and function of circRNAs in intestinal mucosal injury and repair after severe burns.
In Situ Self‐Supporting Cobalt Embedded in Nitrogen‐Doped Porous Carbon as Efficient Oxygen Reduction Electrocatalysts
Authors: Gao Yuan , Gong Xiaoman , Zhong Haihong , Li Dianqing , Tang Pinggui , Alonso‐Vante Nicolas , Feng Yongjun
Published: September 2020

A facile two‐step chemical route using cobalt ions coordinated with EDTA (CoII/EDTA chelate complex supported on glucose mixture), followed by the in situ pyrolysis process, from 500 to 900 °C, was developed to prepare Co embedded in N‐doped porous carbon hybrids (Co@C−T). The EDTA chelating agent served as both the N source and pore former. The physicochemical characterization results revealed that the pore structure, graphitization degree, and relative content of active centers, e. g., cobalt‐based components and nitrogen species, for Co@C−T electrocatalysts, were tailored by controlling the temperature of pyrolysis. The optimized material generated at 600 °C (Co@C‐600), showed an excellent oxygen reduction reaction activity with an onset potential of 0.91 V vs. RHE, and a half‐wave potential of 0.80 V vs. RHE. In addition, the Co@C‐600 catalyst showed superior durability and stability compared to the benchmark Pt/C.
Siloxyaluminate and Siloxygallate Complexes as Models for Framework and Partially Hydrolyzed Framework Sites in Zeolites and Zeotypes
Authors: Dombrowski James P. , Ziegler Micah S. , Phadke Neelay M. , Mansoor Erum , Levine Daniel S. , Witzke Ryan J. , Head‐Gordon Martin , Bell Alexis T. , Tilley T. Don
Published: September 2020

Anionic molecular models for nonhydrolyzed and partially hydrolyzed aluminum and gallium framework sites on silica, M[OSi(OtBu)3]4− and HOM[OSi(OtBu)3]3− (where M=Al or Ga), were synthesized from anionic chlorides Li{M[OSi(OtBu)3]3Cl} in salt metathesis reactions. Sequestration of lithium cations with [12]crown‐4 afforded charge‐separated ion pairs composed of monomeric anions M[OSi(OtBu)3]4− with outer‐sphere [([12]crown‐4)2Li]+ cations, and hydroxides {HOM[OSi(OtBu)3]3} with pendant [([12]crown‐4)Li]+ cations. These molecular models were characterized by single‐crystal X‐ray diffraction, vibrational spectroscopy, mass spectrometry and NMR spectroscopy. Upon treatment of monomeric [([12]crown‐4)Li]{HOM[OSi(OtBu)3]3} complexes with benzyl alcohol, benzyloxide complexes were formed, modeling a possible pathway for the formation of active sites for Meerwin–Ponndorf–Verley (MPV) transfer hydrogenations with Al/Ga‐doped silica catalysts.
A Photoclick‐Based High‐Throughput Screening for the Directed Evolution of Decarboxylase OleT
Authors: Markel Ulrich , Lanvers Pia , Sauer Daniel F. , Wittwer Malte , Dhoke Gaurao V. , Davari Mehdi D. , Schiffels Johannes , Schwaneberg Ulrich
Published: September 2020

Enzymatic oxidative decarboxylation is an up‐and‐coming reaction yet lacking efficient screening methods for the directed evolution of decarboxylases. Here, we describe a simple photoclick assay for the detection of decarboxylation products and its application in a proof‐of‐principle directed evolution study on the decarboxylase OleT. The assay was compatible with two frequently used OleT operation modes (directly using hydrogen peroxide as the enzyme's co‐substrate or using a reductase partner) and the screening of saturation mutagenesis libraries identified two enzyme variants shifting the enzyme's substrate preference from long chain fatty acids toward styrene derivatives. Overall, this photoclick assay holds promise to speed‐up the directed evolution of OleT and other decarboxylases.
Synthesis and Optoelectronic Properties of a Quinoxalino‐Phenanthrophenazine (QPP) Extended Tribenzotriquinacene (TBTQ)
Authors: Ueberricke Lucas , Punja Benke Bahiru , Kirschbaum Tobias , Hahn Sebastian , Rominger Frank , Bunz Uwe H. F. , Mastalerz Michael
Published: September 2020

A six‐step synthesis towards a tribenzotriquinacene (TBTQ) bearing three quinoxalinophenanthrophenazine (QPP) units is presented. The optoelectronic properties are investigated and the effect of the three‐dimensional arrangement of the individual QPP planes is examined using optical spectroscopy, electrochemical analysis and quantum‐chemical calculations.
Synthesis of Low‐Valent Dinuclear Group 14 Compounds with Element–Element Bonds by Transylidation
Authors: Mohapatra Chandrajeet , Darmandeh Heidar , Steinert Henning , Mallick Bert , Feichtner Kai‐Stephan , Gessner Viktoria H.
Published: September 2020

Dinuclear low‐valent compounds of the heavy main group elements are rare species owing to their intrinsic reactivity. However, they represent desirable target molecules due to their unusual bonding situations as well as applications in bond activations and materials synthesis. The isolation of such compounds usually requires the use of substituents that provide sufficient stability and synthetic access. Herein, we report on the use of strongly donating ylide‐substituents to access low‐valent dinuclear group 14 compounds. The ylides not only impart steric and electronic stabilization, but also allow facile synthesis via transfer of an ylide from tetrylene precursors of type RY2E to ECl2 (E=Ge, Sn; RY=TolSO2(PR3)C with R=Ph, Cy). This method allowed the isolation of dinuclear complexes amongst a germanium analogue of a vinyl cation, [(PhY)2GeGe(PhY)]+ with an electronic structure best described as a germylene‐stabilized GeII cation and a ylide(chloro)digermene [CyY(Cl)GeGe(Cl)CyY] with an unusually unsymmetrical structure.
Evaluation of the performance of catalytic oxidation of VOCs by a mixed oxide at a semi‐pilot scale†
Authors: Ribeiro Rita , Heymans Nicolas , Duprez Marie‐Eve , Cousin Renaud , Siffert Stéphane , Poupin Christophe , Thomas Diane , Decroly André , De Weireld Guy
Published: September 2020

Volatile organic compounds (VOCs) are one of the main contributors to air pollution. To reduce anthropogenic emissions, it is necessary to improve existing techniques such as catalytic oxidation through the development of new cost‐effective catalysts. Although many studies deal with the development and testing of new materials, most are performed at laboratory scale, of which only a few study mixtures of VOCs. To assess their viability for industrial applications, further tests are required, namely, mixture tests at intermediate scale in relevant environment and extrapolated on an industrial scale. In this work, the catalytic performance of a new mixed oxide Co‐Al‐Ce was investigated towards the oxidation of the n‐butanol and toluene on a semi‐pilot scale (TRL 4). Single component and mixture experiments were performed for several concentrations at a fixed flow rate. A commercial catalyst Pd/γ‐Al2O3 was used as the benchmark to evaluate the performance of the mixed oxide. The Co‐Al‐Ce catalyst enables complete oxidation of n‐butanol at the same temperature as the reference catalyst. Moreover, it provides a better selectivity for n‐butanol, while providing an equivalent one for the oxidation of toluene. In mixtures, the presence of n‐butanol promotes the oxidation of toluene for both catalysts but more significantly for the Co‐Al‐Ce catalyst. The presence of toluene inhibits the oxidation of n‐butanol for the Co‐Al‐Ce and promotes it for high conversions of n‐butanol for the Pd/γ‐Al2O3 catalyst.
Breast cancer treatment delays by socioeconomic and health care access latent classes in Black and White women
Authors: Emerson Marc A. , Golightly Yvonne M. , Aiello Allison E. , Reeder‐Hayes Katherine E. , Tan Xianming , Maduekwe Ugwuji , Johnson‐Thompson Marian , Olshan Andrew F. , Troester Melissa A.
Published: September 2020

Background

Breast cancer mortality is higher for Black and younger women. This study evaluated 2 possible contributors to disparities—time to treatment and treatment duration—by race and age.

Methods

Among 2841 participants with stage I‐III disease in the Carolina Breast Cancer Study, we identified groups of women with similar patterns of socioeconomic status (SES), access to care, and tumor characteristics using latent class analysis. We then evaluated latent classes in association with treatment delay (initiation >60 days after diagnosis) and treatment duration (in quartiles by treatment modality).

Results

Thirty‐two percent of younger Black women were in the highest quartile of treatment duration (versus 22% of younger White women). Black women experienced a higher frequency of delayed treatment (adjusted relative frequency difference [RFD], 5.5% [95% CI, 3.2%‐7.8%]) and prolonged treatment duration (RFD, 8.8% [95% CI, 5.7%‐12.0%]). Low SES was significantly associated with treatment delay among White women (RFD, 3.5% [95% CI, 1.1%‐5.9%]), but treatment delay was high at all levels of SES in Black women (eg, 11.7% in high SES Black women compared with 10.6% and 6.7% among low and high SES White women, respectively). Neither SES nor access to care classes were significantly associated with delayed initiation among Black women, but both low SES and more barriers were associated with treatment duration across both groups.

Conclusions

Factors that influence treatment timeliness persist throughout the care continuum, with prolonged treatment duration being a sensitive indicator of differences by race, SES, and care barriers.
Orthogonal Self‐Assembly of Cyclodextrin‐Decorated Noble Metal Nanoparticles via Photoresponsive Molecular Recognition in Aqueous Solution
Authors: Niehues Maximilian , Simke Julian , Ravoo Bart Jan
Published: September 2020

Control over the self‐assembly of mixed nanoparticles (NP) is a challenging but versatile concept for the bottom‐up fabrication of novel nanomaterials. Moreover, stimulus‐responsive self‐assembly is fundamental to the development of adaptive and intelligent materials. In this study, we demonstrate the orthogonal self‐assembly of cyclodextrin (CD) decorated noble metal NP. Utilizing the guest selectivity of αCD and γCD, divalent photoresponsive supramolecular crosslinkers were identified and applied in selective NP assembly. By design of specific crosslinkers, narcissistic as well as social self‐sorting of sub 10 nm metal NP was enabled. Irradiation experiments confirmed that the aggregation process is induced by photoresponsive host‐guest chemistry, which allows to form and dissolve the NP aggregates over several cycles and to photo‐initiate the NP aggregation. The molecular recognition as well as the specific response of CD‐functionalized NP show significant potential in the reversible self‐assembly of inorganic‐organic hybrid nanomaterials in aqueous solution.
Structural Changes Induced by Quinones: High‐Resolution Microwave Study of 1,4‐Naphthoquinone
Authors: Saxena Shefali , Panchagnula Sanjana , Sanz M. Eugenia , Pérez Cristóbal , Evangelisti Luca , Pate Brooks H.
Published: September 2020

1,4‐Naphthoquinone (1,4‐NQ) is an important product of naphthalene oxidation, and it appears as a motif in many biologically active compounds. We have investigated the structure of 1,4‐NQ using chirped‐pulse Fourier transform microwave spectroscopy and quantum chemistry calculations. The rotational spectra of the parent species, and its 13C and 18O isotopologues were observed in natural abundance, and their spectroscopic parameters were obtained. This allowed the determination of the substitution rs, mass‐weighted rm and semi‐experimental reSE structures of 1,4‐NQ. The obtained structural parameters show that the quinone moiety mainly changes the structure of the benzene ring where it is inserted, modifying the C−C bonds to having predominantly single or double bond character. Furthermore, the molecular electrostatic surface potential reveals that the quinone ring becomes electron deficient while the benzene ring remains a nucleophile. The most electrophilic areas are the hydrogens attached to the double bond in the quinone ring. Knowledge of the nucleophilic and electrophilic areas in 1,4‐NQ will help understanding its behaviour interacting with other molecules and guide modifications to tune its properties.
Human iPSC‐Derived Blood‐Brain Barrier Models: Valuable Tools for Preclinical Drug Discovery and Development?
Authors: Appelt‐Menzel Antje , Oerter Sabrina , Mathew Sanjana , Haferkamp Undine , Hartmann Carla , Jung Matthias , Neuhaus Winfried , Pless Ole
Published: September 2020

Translating basic biological knowledge into applications remains a key issue for effectively tackling neurodegenerative, neuroinflammatory, or neuroendocrine disorders. Efficient delivery of therapeutics across the neuroprotective blood‐brain barrier (BBB) still poses a demanding challenge for drug development targeting central nervous system diseases. Validated in vitro models of the BBB could facilitate effective testing of drug candidates targeting the brain early in the drug discovery process during lead generation. We here review the potential of mono‐ or (isogenic) co‐culture BBB models based on brain capillary endothelial cells (BCECs) derived from human‐induced pluripotent stem cells (hiPSCs), and compare them to several available BBB in vitro models from primary human or non‐human cells and to rodent in vivo models, as well as to classical and widely used barrier models [Caco‐2, parallel artificial membrane permeability assay (PAMPA)]. In particular, we are discussing the features and predictivity of these models and how hiPSC‐derived BBB models could impact future discovery and development of novel CNS‐targeting therapeutics. © 2020 The Authors.
Methods for Automated Single Cell Isolation and Sub‐Cloning of Human Pluripotent Stem Cells
Authors: Vallone Valeria Fernandez , Telugu Narasimha Swamy , Fischer Iris , Miller Duncan , Schommer Sandra , Diecke Sebastian , Stachelscheid Harald
Published: September 2020

Advances in human pluripotent stem cell (hPSC) techniques have led them to become a widely used and powerful tool for a vast array of applications, including disease modeling, developmental studies, drug discovery and testing, and emerging cell‐based therapies. hPSC workflows that require clonal expansion from single cells, such as CRISPR/Cas9‐mediated genome editing, face major challenges in terms of efficiency, cost, and precision. Classical sub‐cloning approaches depend on limiting dilution and manual colony picking, which are both time‐consuming and labor‐intensive, and lack a real proof of clonality. Here we describe the application of three different automated cell isolation and dispensing devices that can enhance the single‐cell cloning process for hPSCs. In combination with optimized cell culture conditions, these devices offer an attractive alternative compared to manual methods. We explore various aspects of each device system and define protocols for their practical application. Following the workflow described here, single cell−derived hPSC sub‐clones from each system maintain pluripotency and genetic stability. Furthermore, the workflows can be applied to uncover karyotypic mosaicism prevalent in bulk hPSC cultures. Our robust automated workflow facilitates high‐throughput hPSC clonal selection and expansion, urgently needed in the operational pipelines of hPSC applications. © 2020 The Authors.

Basic Protocol: Efficient automated hPSC single cell seeding and clonal expansion using the iotaSciences IsoCell platform

Alternate Protocol 1: hPSC single cell seeding and clonal expansion using the Cellenion CellenONE single‐cell dispenser

Alternate Protocol 2: hPSC single cell seeding and clonal expansion using the Cytena single‐cell dispenser

Support Protocol 1: Coating cell culture plates with Geltrex

Support Protocol 2: hPSC maintenance in defined feeder‐free conditions

Support Protocol 3: hPSC passaging in clumps

Support Protocol 4: Laminin 521 coating of IsoCell plates and 96‐well/384‐well plates

Support Protocol 5: Preparation of medium containing anti‐apoptotic small molecules

Support Protocol 6: 96‐ and 384‐well target plate preparation prior to single cell seeding

Support Protocol 7: Single cell dissociation of hPSCs

Support Protocol 8: IsoCell‐, CellenONE‐, and Cytena‐derived hPSC clone subculture and expansion
Oral nano‐curcumin on gingival inflammation in patients with gingivitis and mild periodontitis
Authors: Malekzadeh Meisam , Kia Seyed Javad , Mashaei Leila , Moosavi Mahdieh‐Sadat
Published: September 2020

Gingivitis can trigger gingival diseases such as periodontitis. Since the complete removal of microbial plaques by mechanical procedures is not conceivable in some conditions and also chemical mouthwashes have a lot of side effects, finding a new treatment strategy would be useful. In the present study, for the first time, the effects of oral nano‐curcumin on gingival inflammation in patients with gingivitis and mild periodontitis were assessed. Forty eight patients with gingivitis and mild periodontitis participated in this clinical trial. In one group the patients were treated with Sina curcumin capsules 80 mg and the other group received a placebo. Clinical parameters, including modified gingival index, papillary bleeding index, and plaque index were determined on days 0, 7, 14, and 28. There were no significant differences in age, sex, papillary bleeding index (PBI), and modified gingival index (MGI) between the two groups at baseline. There was a dropout of two patients (both from the placebo group). The MGI and PBI have a significantly decreasing trend in both case and control groups and the decreases were severe in the case group. The differences between PBI and MGI in the two groups were significant at 14 and 28 days. The plaque index did not significantly change in either group over the study period. The trend of changes in plaque index was not different between the two groups of the study. In the current study, no side effect was found in the patients. Oral nano‐curcumin has positive effects on the decrease of inflammation and gingival bleeding in patients with gingivitis and mild periodontitis. Nano‐curcumin capsules have a systemic target site with more bioavailability than topical forms.
Effects of quantitative trait locus MP3 on the number of panicles and rice productivity in nutrient‐poor soils of Madagascar
Authors: Takai Toshiyuki , Sakata Mitsukazu , Rakotoarisoa Njato M. , Razafinarivo Ny Toky , Nishigaki Tomohiro , Asai Hidetoshi , Ishizaki Takuma , Tsujimoto Yasuhiro
Published: September 2020

The majority of paddy fields in sub‐Saharan Africa (SSA) are characterized by nutrient‐poor soils. In such fields, tillering in rice (Oryza sativa L.) plants is severely restricted, which results in a reduced number of panicles and thus a decrease in grain yield. In this study, we evaluated the effects of a quantitative trait locus (QTL), associated with number of panicles and referred as MP3, on rice growth and grain yield in nutrient‐poor soils in Madagascar. We used a high‐yielding rice cultivar, Takanari, and its near‐isogenic line bearing the MP3 allele (NIL‐MP3). A pot experiment with various P application rates demonstrated vigorous tillering in NIL‐MP3 compared to Takanari from the early vegetative stage even under low P levels. This led to enlarged leaf area and thus increased biomass. We then conducted multiple field trials with a total of 12 experimental conditions using the two varieties. The experiments led to a range of grain yield from 1.3 to 4.1 t ha−1 and a range in number of panicles from 107 to 270 m−2. The results revealed that NIL‐MP3 produced a greater number of panicles and spikelets m−2 (19 and 12%, respectively) than Takanari across all 12 experiments. Grain yield increased in NIL‐MP3 under some experimental conditions. This study is the first of its kind to demonstrate that MP3 increased number of panicles and spikelets and grain yield in the nutrient‐poor and low‐yielding soils of SSA. Thus, we conclude that MP3 could become a prominent genetic resource for the improvement of rice yields in SSA.
Broader phenology of pollinator activity and higher plant reproductive success in an urban habitat compared to a rural one
Authors: Zaninotto Vincent , Raynaud Xavier , Gendreau Emmanuel , Kraepiel Yvan , Motard Eric , Babiar Olivier , Hansart Amandine , Hignard Cécile , Dajoz Isabelle
Published: September 2020

Urban habitat characteristics create environmental filtering of pollinator communities. They also impact pollinating insect phenology through the presence of an urban heat island and the year‐round availability of floral resources provided by ornamental plants.

Here, we monitored the phenology and composition of pollinating insect communities visiting replicates of an experimental plant assemblage comprising two species, with contrasting floral traits: Sinapis alba and Lotus corniculatus, whose flowering periods were artificially extended. Plant assemblage replicates were set up over two consecutive years in two different habitats: rural and densely urbanized, within the same biogeographical region (Ile‐de‐France region, France).

The phenology of pollination activity, recorded from the beginning (early March) to the end (early November) of the season, differed between these two habitats. Several pollinator morphogroups (small wild bees, bumblebees, honeybees) were significantly more active on our plant sets in the urban habitat compared to the rural one, especially in early spring and autumn. This resulted in different overall reproductive success of the plant assemblage between the two habitats. Over the course of the season, reproductive success of S. alba was always significantly higher in the urban habitat, while reproductive success of L. corniculatus was significantly higher in the urban habitat only during early flowering.

These findings suggest different phenological adaptations to the urban habitat for different groups of pollinators. Overall, results indicate that the broadened activity period of pollinating insects recorded in the urban environment could enhance the pollination function and the reproductive success of plant communities in cities.
Faunal input at host plants: Can camel thorn trees use nutrients imported by resident sociable weavers?
Authors: Prayag Kervin D. , du Toit Carla J. , Cramer Michael D. , Thomson Robert L.
Published: September 2020

“Islands of fertility” result from the focussing of water and nutrients around many shrub or tree species due to plants foraging for resources. Plant–animal feedbacks may amplify the development of such islands through environmental modification due to, for example, faunal deposition of nutrients and seeds. Fauna residing within vegetation clumps are likely to exert stronger feedbacks on their hosts than itinerant species. We studied the interaction between camel thorn trees (Vachellia erioloba) and the colonial nests of sociable weavers (Philetairus socius) in the Kalahari. We hypothesized that the accumulation of biological material below the nests will alter the nutrient status of the soil beneath the nest trees, in relation to unoccupied trees and the surrounding grassland. We also suggested that this association will have both positive and negative effects on the camel thorn trees. We found that soil concentrations of N, P, and K were, respectively, 4, 4.6, and 1.2 times higher below trees with nests compared to control trees, indicating faunal concentration of nutrients. Soil δ15N values were higher below trees with nests than below control trees without nests. Foliar δ15N values were also higher in nest trees than in control trees, showing the trees accessed faunally derived N. Furthermore, foliar biomass per diameter of terminal branches was 27% higher in nest trees, suggesting that trees respond to nutrient input from the weavers with increased growth. Large barren areas in the subcanopy vegetation directly beneath the colonies were attributed to decreased water infiltration rates, as a result of accumulation of organic matter due to continuous deposition of feces, possibly limiting competitive species from establishing in the subcanopy. On the other hand, canopy volume was reduced in trees with nests due to nests occupying large volumes within the canopy, and nests frequently causing branch fall, indicating costs associated with hosting weaver colonies. Synthesis: We found nutritional benefits to camel thorn trees when hosting sociable weaver colonies. These benefits can potentially overcome important environmental constraints, but these are partially offset by the resulting costs to the host trees.
Causal hypotheses accounting for correlations between decomposition rates of different mass fractions of leaf litter
Authors: Shipley Bill , Tardif Antoine
Published: September 2020

Whole‐leaf decomposition rates are the sum of the decomposition rates of each chemical fraction (water‐soluble, cellulose, hemicellulose, lignin), but the decomposition rates of each fraction show complicated patterns of covariation. What explains these patterns of covariation? After measuring the k values of each fraction in 42 different mixtures of tree leaf litters from five species, we tested three alternative causal hypotheses that have been proposed in the literature concerning these mixture interactions using structura equations modeling. All three hypotheses were rejected by the data. We then proposed a new hypothesis, in which rapid decomposition of the labile (water‐soluble) fraction stimulates the decomposition of lignin by white‐rot fungi and the decomposition of hemicellulose by brown‐rot fungi. A more rapid decomposition of hemicellulose then stimulates the decomposition of cellulose. This hypothesis is both consistent with known biology and with our data and is proposed as the most viable current hypothesis.
Frailty and the risk of all‐cause mortality and hospitalization in chronic heart failure: a meta‐analysis
Authors: Uchmanowicz Izabella , Lee Christopher S. , Vitale Cristiana , Manulik Stanisław , Denfeld Quin E. , Uchmanowicz Bartosz , Rosińczuk Joanna , Drozd Marcin , Jaroch Joanna , Jankowska Ewa A.
Published: September 2020

To estimate the risk of all‐cause mortality and hospitalization in frail patients with chronic heart failure (HF), a systematic search and meta‐analysis was carried out to identify all prospective cohort studies conducted among adults with HF where frailty was quantified and related to the primary endpoints of all‐cause mortality and/or hospitalization. Twenty‐nine studies reporting the link between frailty and all‐cause mortality in 18 757 patients were available for the meta‐analysis, along with 11 studies, with 13 525 patients, reporting the association between frailty and hospitalization. Frailty was a predictor of all‐cause mortality and hospitalization with summary hazard ratios (HRs) of 1.48 [95% confidence interval (CI): 1.31–1.65, P < 0.001] and 1.40 (95% CI: 1.27–1.54, P < 0.001), respectively. Summary HRs for all‐cause mortality among frail inpatients undergoing ventricular assist device implantation, inpatients hospitalized for HF, and outpatients were 1.46 (95% CI: 1.18–1.73, P < 0.001), 1.58 (95% CI: 0.94–2.22, P = not significant), and 1.53 (95% CI: 1.28–1.78, P < 0.001), respectively. Summary HRs for all‐cause mortality and frailty based on Fried's phenotype were 1.48 (95% CI: 1.03–1.93, P < 0.001) and 1.42 (95% CI: 1.05–1.79, P < 0.001) for inpatients and outpatients, respectively, and based on other frailty measures were 1.42 (95% CI: 1.12–1.72, P < 0.001) and 1.60 (95% CI: 1.43–1.77, P < 0.001) for inpatients and outpatients, respectively. Across clinical contexts, frailty in chronic HF is associated with an average of 48% and 40% increase in the hazard of all‐cause mortality and hospitalization, respectively. The relationship between frailty and all‐cause mortality is similar across clinical settings and comparing measurement using Fried's phenotype or other measures.
The effect of in‐session exposure in Fear‐Avoidance treatment of chronic low back pain: A randomized controlled trial
Authors: Ryum Truls , Hartmann Helge , Borchgrevink Petter , de Ridder Karin , Stiles Tore C.
Published: September 2020

Background

Treatment based on the Fear‐Avoidance (FA) model has been found to be effective with chronic low back pain (CLBP), and in‐vivo exposure of fear evoking movements is proposed as a key change mechanism. Exposure tasks may be conducted in the session (in‐session exposure; ISE), in other real‐life situations (between sessions exposure) as part of homework assignments, or both. Utilising a randomized, controlled dismantling study design, the aim of this study was to examine the unique effects of ISE in FA‐treatment of CLBP.

Methods

Patients (N = 90) with CLBP as primary medical complaints were randomized to receive six sessions of either (a) FA‐treatment with ISE (FA‐ISE) or (b) FA‐treatment without ISE (FA), allowing for between sessions exposure in both treatment groups. Patients were assessed with a large battery of outcome measures at four time‐points (pre‐treatment, post‐treatment, after a booster‐session and at 1‐year follow‐up) including pain intensity, pain catastrophising, self‐efficacy, physical performance and quality of life.

Results

Both treatment groups (FA‐ISE, FA) demonstrated statistically significant improvements on primary and most secondary outcomes, with mostly non‐significant between‐group differences.

Conclusions

No added benefit was found for the inclusion of ISE of feared movements in FA‐treatment for CLBP, delivered in a group format to participants with moderately elevated levels of fear‐avoidance beliefs. Clinical trials: NCT01158339.

Significance

This study adds to the existing research literature demonstrating FA‐treatment to be effective with CLBP, but further experimental studies are needed in order to examine under what circumstances ISE of feared movements may add to positive treatment outcomes.
Physiologic osteoclasts are not sufficient to induce skeletal pain in mice
Authors: de Clauser Larissa , Santana‐Varela Sonia , Wood John N , Sikandar Shafaq
Published: September 2020

Background

Increased bone resorption is driven by augmented osteoclast activity in pathological states of the bone, including osteoporosis, fracture and metastatic bone cancer. Pain is a frequent co‐morbidity in bone pathologies and adequate pain management is necessary for symptomatic relief. Bone cancer is associated with severe skeletal pain and dysregulated bone remodelling, while increased osteoclast activity and bone pain are also observed in osteoporosis and during fracture repair. However, the effects of altered osteoclast activity and bone resorption on nociceptive processing of bone afferents remain unclear.

Methods

This study investigates whether physiologic osteoclasts and resulting changes in bone resorption can induce skeletal pain. We first assessed correlation between changes in bone microarchitecture (through µCT) and skeletal pain using standardized behavioural phenotyping assays in a mouse model of metastatic bone cancer. We then investigated whether increased activity of physiologic osteoclasts, and the associated bone resorption, is sufficient to induce skeletal pain using mouse models of localized and widespread bone resorption following administration of exogenous receptor activator of nuclear factor kappa‐B ligand (RANKL).

Results

Our data demonstrates that mice with bone cancer exhibit progressive pain behaviours that correlate with increased bone resorption at the tumour site. Systemic RANKL injections enhance osteoclast activity and associated bone resorption, without producing any changes in motor function or pain behaviours at both early and late timepoints.

Conclusion

These findings suggest that activation of homeostatic osteoclasts alone is not sufficient to induce skeletal pain in mice.

Significance statement

The role of osteoclasts in peripheral sensitization of sensory neurones is not fully understood. This study reports on the direct link between oestrogen‐independent osteoclast activation and skeletal pain. Administration of exogenous receptor activator of nuclear factor kappa‐B ligand (RANKL) increases bone resorption, but does not produce pro‐nociceptive changes in behavioural pain thresholds. Our data demonstrates that physiologic osteoclasts are not essential for skeletal pain behaviours.
Surface and Electrochemical Characterization of a New Layered GC/Betaine/Pt Electrode and Investigation on its Performance as a Sensor for two B Complex Vitamins, B1 and B6: Preliminary Results
Authors: Contursi M. , Coviello D. , Ciriello R. , Guerrieri A. , Palmieri M. A. , Langerame F. , Bianco G. , Salvi A. M.
Published: September 2020

The electrochemical preparation of a novel composite glassy carbon/betaine/platinum (GC/BT/Pt) electrode with meso‐ nano Pt globules dispersed on the outer surface and betaine, as intermediate layer, electrodeposited on GC by Cyclic Voltammetry (CV) or Pulsed Potential (PP) techniques, is presented. Surface analysis by Scanning Electron Microscopy (SEM) and X‐ray Photoelectron Spectroscopy (XPS) confirms the strategic role of grafted betaine in modulating GC/BT‐ interaction sites and the range of potentials for adequate platinum CV electrodeposition. The GC/BT/Pt performance, concerning sensitivity, linearity, work potentials and repeatability tests with Flow Injection Analysis (FIA), was ascertained for the detection of vitamins B1 and B6.