bluuebunny/crossref_metadata_2025_split huggingface dataset:
Placental studies elucidate discrepancies between NIPT showing a structural chromosome aberration and a differently abnormal fetal karyotype
Authors: Van Opstal Diane , van Veen Stefanie , Joosten Marieke , Diderich Karin E.M. , Govaerts Lutgarde C.P. , Polak Joke , van Koetsveld Nicole , Boter Marjan , Go Attie T.J.I. , Papatsonis Dimitri N.M. , Prinsen Krista , Hoefsloot Lies H. , Srebniak Malgorzata I. 
Published: July 2019

AbstractObjectivePlacental cytogenetic studies may reveal the origin of discordant noninvasive prenatal testing (NIPT). We performed placental studies to elucidate discordances between NIPT showing a structural chromosome aberration and the fetus having a different chromosome aberration in three cases.MethodDiagnostic testing with genomic SNP microarray was performed in three cases with NIPT showing a duplication on 4q (case 1), a terminal deletion of 13q (case 2), and a terminal deletion of 15q (case 3). Placental studies involved SNP array analysis of cytotrophoblast and mesenchymal core of chorionic villi of four placental quadrants. Clinical follow‐up was performed as well.ResultsAmniotic fluid revealed a different structural chromosome aberration than predicted by NIPT: a terminal 2q deletion (case 1), a segmental uniparental isodisomy of 13q (case 2), and a terminal duplication of 15q and of 13q (case 3). Placental studies revealed the aberration detected with NIPT in the cytotrophoblast, whereas the fetal karyotype was confirmed in the placental mesenchymal core.ConclusionOur study shows that targeted cytogenetic investigations for confirmation of NIPT showing a microscopically visible structural chromosome aberration should be avoided, since another aberration, even a submicroscopic one or one involving another chromosome, may be present in the fetus.
High‐Quality Biobanks: Pivotal Assets for Reproducibility of OMICS‐Data in Biomedical Translational Research
Authors: Dollé Laurent , Bekaert Sofie 
Published: July 2019

AbstractHuman biospecimen samples (HBS) and associated data stored in biobanks (also called “biotrusts,” “biorepositories,” or “biodistributors”) are very critical resources for translational research. As HBS quality is decisive to the reproducibility of research results, biobanks are also key assets for new developments in precision medicine. Biobanks are more than infrastructures providing HBS and associated data. Biobanks have pioneered in identifying and standardizing sources of preanalytical variations in HBS, thus paving the way for the current biospecimen science. To achieve this milestone, biobankers have successively assumed the role of “detective,” and then “architect,” to identify new detrimental impact of preanalytical variables on the tissue integrity. While standardized methods in omics are required to be practiced throughout research communities, the accepted best practices and standards on biospecimen handling are generally not known nor applied by researchers. Therefore, it is mandatory to raise the awareness within omics communities regarding not only the basic concepts of collecting, storing, and utilizing HBS today, but also to suggest insights on biobanking in the cancer omics context.
Chain‐growth polymerization of azide–alkyne difunctional monomer: Synthesis of star polymer with linear polytriazole arms from a core
Authors: Gan Weiping , Cao Xiaosong , Shi Yi , Gao Haifeng 
Published: July 2019

ABSTRACTThis article reports a chain‐growth coupling polymerization of AB difunctional monomer via copper‐catalyzed azide–alkyne cycloaddition (CuAAC) reaction for synthesis of star polymers. Unlike our previously reported CuAAC polymerization of AB
n (n ≥ 2) monomers that spontaneously demonstrated a chain‐growth mechanism in synthesis of hyperbranched polymer, the homopolymerization of AB monomer showed a common but less desired step‐growth mechanism as the triazole groups aligned in a linear chain could not effectively confine the Cu catalyst in the polymer species. In contrast, the use of polytriazole‐based core molecules that contained multiple azido groups successfully switched the polymerization of AB monomers into chain‐growth mechanism and produced 3‐arm star polymers and multi‐arm hyperstar polymers with linear increase of polymer molecular weight with conversion and narrow molecular weight distribution, for example, Mw/Mn ~ 1.05. When acid‐degradable hyperbranched polymeric core was used, the obtained hyperstar polymers could be easily degraded under acidic environment, producing linear degraded arms with defined polydispersity. © 2019 Wiley Periodicals, Inc. J. Polym. Sci. 2020, 58, 84–90
Prediction of heavy precipitation in the eastern China flooding events of 2016: Added value of convection‐permitting simulations
Authors: Li Puxi , Guo Zhun , Furtado Kalli , Chen Haoming , Li Jian , Milton Sean , Field Paul R. , Zhou Tianjun 
Published: July 2019

AbstractDuring the period from June 30th to July 6th, 2016, a heavy rainfall event affected the middle and lower reaches of the Yangtze River valley in eastern China. The event was characterized by high‐intensity, long‐duration (lasted more than 6 days) precipitation and huge amounts (over 600.0 mm) of rainfall. The rainfall moved eastward from the Sichuan basin to the middle Yangtze River valley during the first 2 days, then Mei‐yu front formed and circulations became more “quasi‐stationary”. During the second‐phase, successive heavy rainfall systems occurred repeatedly over the same areas along the front, leading to widespread and catastrophic flooding. In this study, limited‐area convection‐permitting models (CPMs) covering all of eastern China, and global‐model simulations from the Met Office Unified Model are compared to investigate the added values of CPMs on the veracity of short‐range predictions of the heavy rainfall event. The results show that all the models can successfully simulate the accumulated amount and the evolution of this heavy rainfall event. However, the global model produces too much light rainfall (10.0 mm/day), fails to simulate the small‐scale features of both atmospheric circulations and precipitation, and tends to generate steady heavy rainfall over mountainous region. Afternoon precipitation is also excessively suppressed in global model. By comparison, the CPMs add some value in reproducing the spatial distribution of precipitation, the smaller‐scale disturbances within the rain‐bands, the diurnal cycle of precipitation and also reduce the spurious topographical rainfall, although there is a tendency for heavy rainfall to be too intense in CPMs.
Robust partial least squares path modeling
Authors: Schamberger Tamara , Schuberth Florian , Henseler Jörg , Dijkstra Theo K. 
Published: July 2019

AbstractOutliers can seriously distort the results of statistical analyses and thus threaten the validity of structural equation models. As a remedy, this article introduces a robust variant of Partial Least Squares Path Modeling (PLS) and consistent Partial Least Squares (PLSc) called robust PLS and robust PLSc, respectively, which are robust against distortion caused by outliers. Consequently, robust PLS/PLSc allows to estimate structural models containing constructs modeled as composites and common factors even if empirical data are contaminated by outliers. A Monte Carlo simulation with various population models, sample sizes, and extents of outliers shows that robust PLS/PLSc can deal with outlier shares of up to$$50\%$$50%without distorting the estimates. The simulation also shows that robust PLS/PLSc should always be preferred over its traditional counterparts if the data contain outliers. To demonstrate the relevance for empirical research, robust PLSc is applied to two empirical examples drawn from the extant literature.
Von unterkühlten Norddeutschen, gemütlichen Süddeutschen und aufgeschlossenen Großstädtern: Regionale Persönlichkeitsunterschiede in Deutschland
Authors: Obschonka Martin , Wyrwich Michael , Fritsch Michael , Gosling Samuel D. , Rentfrow P. Jason , Potter Jeff 
Published: July 2019

Zusammenfassung. Die geographische Psychologie befasst sich unter anderem mit Persönlichkeitsunterschieden von Regionen und Regionstypen, in denen Personen leben und handeln. Mittels solcher Forschung können regionale „Mentalitäten“ untersucht werden aus denen sich Forschungsfragen zu Entwicklungspfaden von Regionen und deren Populationen ableiten lassen. Während existierende psychologische Regionalforschung „psychologische Landkarten“ vor allem in den USA und Großbritannien erforschte, liefert die vorliegende Analyse eine Regionaluntersuchung für Deutschland auf kleinteiligem Raumniveau (97 deutsche Raumordnungsregionen). Basierend auf dem Big Five Modell der Persönlichkeit werden deutsche Daten der „The Big Five Project“-Studie ( N = 73756) präsentiert. Es werden regionale Persönlichkeitsunterschiedliche zwischen städtischen und ländlichen Regionen, Ost- und Westdeutschland, und Nord- und Süddeutschland getestet. Es finden sich insbesondere Hinweise für a) die empirische Validität einiger Stereotype (wie das der unterkühlten, rauen Norddeutschen, der gemütlichen Süddeutschen und der aufgeschlossenen Großstädter), b) systematische Migrationsmuster, und c) eine Köln-München Linie in der regionalen Verteilung von Neurotizismus. Die Effektstärken in den Regionalunterschieden sind in der Regel zwar gering, aber dennoch mit wichtigen Implikationen für zukünftige Forschung und Anwendungsgebiete.
Combined Effects of Equatorial Chorus Waves and High‐Latitude Z‐Mode Waves on Saturn's Radiation Belt Electrons
Authors: Yu J. , Li L.Y. , Cui J. , Cao J.B. , Wang J. 
Published: July 2019

AbstractIn this paper, we examined the combined effects of equatorial chorus waves and high‐latitude Z‐mode waves on the energy and pitch angle distribution of Saturn's radiation belt electrons. Our simulation results show that these two types of waves at different latitudes jointly control the fluxes of Saturn's radiation belt electrons, which is very different from the individual effects of each kind of waves. The presence of Z‐mode waves can efficiently inhibit the reversed energy spectrum of electrons driven by chorus waves, whereas the presence of chorus waves can further accelerate and scatter the relativistic electrons accelerated by Z‐mode waves toward the larger and smaller pitch angles. Our findings provide a new insight on how different types of waves at different latitudes jointly affect the radiation belt electron dynamics, including, but not limited to, Saturn.
Raptinal bypasses BAX, BAK, and BOK for mitochondrial outer membrane permeabilization and intrinsic apoptosis
Authors: Heimer Sina , Knoll Gertrud , Schulze-Osthoff Klaus , Ehrenschwender Martin 
Published: July 2019

AbstractMost antineoplastic chemotherapies eliminate cancer cells through activation of the mitochondria-controlled intrinsic apoptotic pathway. Therein, BAX, BAK, and/or BOK function as the essential pore-forming executioners of mitochondrial outer membrane permeabilization (MOMP). The activation threshold of BAX and BAK also correlates inversely with the required strength of an apoptotic stimulus to induce MOMP and thereby effectively determines a cell’s readiness to undergo apoptosis. Consequently, the ‘gatekeepers’ BAX and BAK emerged as therapeutic targets, but functional or genetic loss renders BAX/BAK-targeting strategies prone to fail. Here, we show that the small molecule Raptinal overcomes this limitation by triggering cytochrome c release in a BAX/BAK/BOK-independent manner. Raptinal exerts a dual cytotoxic effect on cancer cells by rapid activation of the intrinsic apoptotic pathway and simultaneous shutdown of mitochondrial function. Together with its efficacy to eliminate cancer cells in vivo, Raptinal could be useful in difficult-to-treat cancer entities harboring defects in the intrinsic apoptosis pathway.
Pptc7 is an essential phosphatase for promoting mammalian mitochondrial metabolism and biogenesis
Authors: Niemi Natalie M. , Wilson Gary M. , Overmyer Katherine A. , Vögtle F.-Nora , Myketin Lisa , Lohman Danielle C. , Schueler Kathryn L. , Attie Alan D. , Meisinger Chris , Coon Joshua J. , Pagliarini David J. 
Published: July 2019

AbstractMitochondrial proteins are replete with phosphorylation, yet its functional relevance remains largely unclear. The presence of multiple resident mitochondrial phosphatases, however, suggests that protein dephosphorylation may be broadly important for calibrating mitochondrial activities. To explore this, we deleted the poorly characterized matrix phosphatase Pptc7 from mice using CRISPR-Cas9 technology. Strikingly, Pptc7−/− mice exhibit hypoketotic hypoglycemia, elevated acylcarnitines and serum lactate, and die soon after birth. Pptc7−/− tissues have markedly diminished mitochondrial size and protein content despite normal transcript levels, and aberrantly elevated phosphorylation on select mitochondrial proteins. Among these, we identify the protein translocase complex subunit Timm50 as a putative Pptc7 substrate whose phosphorylation reduces import activity. We further find that phosphorylation within or near the mitochondrial targeting sequences of multiple proteins could disrupt their import rates and matrix processing. Overall, our data define Pptc7 as a protein phosphatase essential for proper mitochondrial function and biogenesis during the extrauterine transition.
Alternative splicing regulates stochastic NLRP3 activity
Authors: Hoss Florian , Mueller James L. , Rojas Ringeling Francisca , Rodriguez-Alcazar Juan F. , Brinkschulte Rebecca , Seifert Gerald , Stahl Rainer , Broderick Lori , Putnam Chris D. , Kolodner Richard D. , Canzar Stefan , Geyer Matthias , Hoffman Hal M. , Latz Eicke 
Published: July 2019

AbstractLeucine-rich repeat (LRR) domains are evolutionarily conserved in proteins that function in development and immunity. Here we report strict exonic modularity of LRR domains of several human gene families, which is a precondition for alternative splicing (AS). We provide evidence for AS of LRR domain within several Nod-like receptors, most prominently the inflammasome sensor NLRP3. Human NLRP3, but not mouse NLRP3, is expressed as two major isoforms, the full-length variant and a variant lacking exon 5. Moreover, NLRP3 AS is stochastically regulated, with NLRP3 ∆ exon 5 lacking the interaction surface for NEK7 and hence loss of activity. Our data thus reveals unexpected regulatory roles of AS through differential utilization of LRRs modules in vertebrate innate immunity.
Boosting NAD+ with a small molecule that activates NAMPT
Authors: Gardell Stephen J. , Hopf Meghan , Khan Asima , Dispagna Mauro , Hampton Sessions E. , Falter Rebecca , Kapoor Nidhi , Brooks Jeanne , Culver Jeffrey , Petucci Chris , Ma Chen-Ting , Cohen Steven E. , Tanaka Jun , Burgos Emmanuel S. , Hirschi Jennifer S. , Smith Steven R. , Sergienko Eduard , Pinkerton Anthony B. 
Published: July 2019

AbstractPharmacological strategies that boost intracellular NAD+ are highly coveted for their therapeutic potential. One approach is activation of nicotinamide phosphoribosyltransferase (NAMPT) to increase production of nicotinamide mononucleotide (NMN), the predominant NAD+ precursor in mammalian cells. A high-throughput screen for NAMPT activators and hit-to-lead campaign yielded SBI-797812, a compound that is structurally similar to active-site directed NAMPT inhibitors and blocks binding of these inhibitors to NAMPT. SBI-797812 shifts the NAMPT reaction equilibrium towards NMN formation, increases NAMPT affinity for ATP, stabilizes phosphorylated NAMPT at His247, promotes consumption of the pyrophosphate by-product, and blunts feedback inhibition by NAD+. These effects of SBI-797812 turn NAMPT into a “super catalyst” that more efficiently generates NMN. Treatment of cultured cells with SBI-797812 increases intracellular NMN and NAD+. Dosing of mice with SBI-797812 elevates liver NAD+. Small molecule NAMPT activators such as SBI-797812 are a pioneering approach to raise intracellular NAD+ and realize its associated salutary effects.
Nonlinear wavefront shaping with optically induced three-dimensional nonlinear photonic crystals
Authors: Liu Shan , Switkowski Krzysztof , Xu Chenglong , Tian Jie , Wang Bingxia , Lu Peixiang , Krolikowski Wieslaw , Sheng Yan 
Published: July 2019

AbstractGeneration of coherent light with desirable amplitude and phase profiles throughout the optical spectrum is a key issue in optical technologies. Nonlinear wavefront shaping offers an exceptional way to achieve this goal by converting an incident light beam into the beam (or beams) of different frequency with spatially modulated amplitude and phase. The realization of such frequency conversion and shaping processes critically depends on the matching of phase velocities of interacting waves, for which nonlinear photonic crystals (NPCs) with spatially modulated quadratic nonlinearity have shown great potential. Here, we present the first experimental demonstration of nonlinear wavefront shaping with three-dimensional (3D) NPCs formed by ultrafast-light-induced ferroelectric domain inversion approach. Compared with those previously used low-dimensional structures, 3D NPCs provide all spatial degrees of freedom for the compensation of phase mismatch in nonlinear interactions and thereby constitute an unprecedented system for the generation and control of coherent light at new frequencies.
Reduced marine phytoplankton sulphur emissions in the Southern Ocean during the past seven glacials
Authors: Goto-Azuma K. , Hirabayashi M. , Motoyama H. , Miyake T. , Kuramoto T. , Uemura R. , Igarashi M. , Iizuka Y. , Sakurai T. , Horikawa S. , Suzuki K. , Suzuki T. , Fujita K. , Kondo Y. , Hattori S. , Fujii Y. 
Published: July 2019

AbstractMarine biogenic sulphur affects Earth’s radiation budget and may be an indicator of primary productivity in the Southern Ocean, which is closely related to atmospheric CO2 variability through the biological pump. Previous ice-core studies in Antarctica show little climate dependence of marine biogenic sulphur emissions and hence primary productivity, contradictory to marine sediment records. Here we present new 720,000-year ice core records from Dome Fuji in East Antarctica and show that a large portion of non-sea-salt sulphate, which was traditionally used as a proxy for marine biogenic sulphate, likely originates from terrestrial dust during glacials. By correcting for this, we make a revised calculation of biogenic sulphate and find that its flux is reduced in glacial periods. Our results suggest reduced dimethylsulphide emissions in the Antarctic Zone of the Southern Ocean during glacials and provide new evidence for the coupling between climate and the Southern Ocean sulphur cycle.
Strong coupling of collective intermolecular vibrations in organic materials at terahertz frequencies
Authors: Damari Ran , Weinberg Omri , Krotkov Daniel , Demina Natalia , Akulov Katherine , Golombek Adina , Schwartz Tal , Fleischer Sharly 
Published: July 2019

AbstractSeveral years ago, strong coupling between electronic molecular transitions and photonic structures was shown to modify the electronic landscape of the molecules and affect their chemical behavior. Since then, this concept has evolved into a new field known as polaritonic chemistry. An important ingredient in the progress of this field was the demonstration of strong coupling with intra-molecular vibrations, which enabled the modification of processes occurring at the electronic ground-state. Here we demonstrate strong coupling with collective, inter-molecular vibrations occurring in organic materials in the low-terahertz region ($$\lesssim$$
≲
1012 Hz). Using a cavity filled with α-lactose molecules, we measure the temporal evolution and observe coherent Rabi oscillations, corresponding to a splitting of 68 GHz. These results take strong coupling into a new class of materials and processes, including skeletal polymer motions, protein dynamics, metal organic frameworks and other materials, in which collective, spatially extended degrees of freedom participate in the dynamics.
Inflammation triggers immediate rather than progressive changes in monocyte differentiation in the small intestine
Authors: Desalegn Girmay , Pabst Oliver 
Published: July 2019

AbstractBone marrow-derived circulating monocytes contribute to the replenishment and maintenance of the intestinal macrophage population. Intestinal monocytes undergo context-dependent phenotypic and functional adaptations to either maintain local immune balance or support intestinal inflammation. Here we use monocyte adoptive transfer to dissect the dynamics of monocyte-to-macrophage differentiation in normal and inflamed small intestine. We find that during homeostasis CCR2 and β7-integrin mediate constitutive homing of monocytes to the gut. By contrast, intestinal inflammation increases monocyte recruitment via CCR2, but not β7-integrin. In the non-inflamed intestine, monocytes gradually differentiate to express genes typically associated with tolerogenic macrophage functions. Conversely, immediately upon entry into the inflamed intestine, monocytes adapt a different expression pattern in a partly Trem-1-dependent manner. Our observations suggest that inflammation fundamentally changes the kinetics and modalities of monocyte differentiation in tissues.
Hydrophobic recognition allows the glycosyltransferase UGT76G1 to catalyze its substrate in two orientations
Authors: Yang Ting , Zhang Jinzhu , Ke Dan , Yang Wenxian , Tang Minghai , Jiang Jian , Cheng Guo , Li Jianshu , Cheng Wei , Wei Yuquan , Li Qintong , Naismith James H. , Zhu Xiaofeng 
Published: July 2019

AbstractDiets high in sugar are recognized as a serious health problem, and there is a drive to reduce their consumption. Steviol glycosides are natural zero-calorie sweeteners, but the most desirable ones are biosynthesized with low yields. UGT76G1 catalyzes the β (1–3) addition of glucose to steviol glycosides, which gives them the preferred taste. UGT76G1 is able to transfer glucose to multiple steviol substrates yet remains highly specific in the glycosidic linkage it creates. Here, we report multiple complex structures of the enzyme combined with biochemical data, which reveal that the enzyme utilizes hydrophobic interactions for substrate recognition. The lack of a strict three-dimensional recognition arrangement, typical of hydrogen bonds, permits two different orientations for β (1–3) sugar addition. The use of hydrophobic recognition is unusual in a regio- and stereo-specific catalysis. Harnessing such non-specific hydrophobic interactions could have wide applications in the synthesis of complex glycoconjugates.
Artificial cysteine-lipases with high activity and altered catalytic mechanism created by laboratory evolution
Authors: Cen Yixin , Singh Warispreet , Arkin Mamatjan , Moody Thomas S. , Huang Meilan , Zhou Jiahai , Wu Qi , Reetz Manfred T. 
Published: July 2019

AbstractEngineering artificial enzymes with high activity and catalytic mechanism different from naturally occurring enzymes is a challenge in protein design. For example, many attempts have been made to obtain active hydrolases by introducing a Ser → Cys exchange at the respective catalytic triads, but this generally induced a breakdown of activity. We now report that this long-standing dogma no longer pertains, provided additional mutations are introduced by directed evolution. By employing Candida antarctica lipase B (CALB) as the model enzyme with the Ser-His-Asp catalytic triad, a highly active cysteine-lipase having a Cys-His-Asp catalytic triad and additional mutations W104V/A281Y/A282Y/V149G can be evolved, showing a 40-fold higher catalytic efficiency than wild-type CALB in the hydrolysis of 4-nitrophenyl benzoate, and tolerating bulky substrates. Crystal structures, kinetics, MD simulations and QM/MM calculations reveal dynamic features and explain all results, including the preference of a two-step mechanism involving the zwitterionic pair Cys105−/His224+ rather than a concerted process.